Daily Papers

Generative machine learning models are increasingly being used to design novel proteins for therapeutic and biotechnological applications. However, the current methods mostly focus on the design of proteins with a fixed backbone structure, which leads to their limited ability to account for protein flexibility, one of the crucial properties for protein function. Learning to engineer protein flexibility is problematic because the available data are scarce, heterogeneous, and costly to obtain using computational as well as experimental methods. Our contributions to address this problem are three-fold. First, we comprehensively compare methods for quantifying protein flexibility and identify data relevant to learning. Second, we design and train flexibility predictors utilizing sequential or both sequential and structural information on the input. We overcome the data scarcity issue by leveraging a pre-trained protein language model. Third, we introduce a method for fine-tuning a protein inverse folding model to steer it toward desired flexibility in specified regions. We demonstrate that our method Flexpert-Design enables guidance of inverse folding models toward increased flexibility. This opens up new possibilities for protein flexibility engineering and the development of proteins with enhanced biological activities.

We introduce AbBiBench (Antibody Binding Benchmarking), a benchmarking framework for antibody binding affinity maturation and design. Unlike previous strategies that evaluate antibodies in isolation, typically by comparing them to natural sequences with metrics such as amino acid recovery rate or structural RMSD, AbBiBench instead treats the antibody-antigen (Ab-Ag) complex as the fundamental unit. It evaluates an antibody design's binding potential by measuring how well a protein model scores the full Ab-Ag complex. We first curate, standardize, and share more than 184,500 experimental measurements of antibody mutants across 14 antibodies and 9 antigens-including influenza, lysozyme, HER2, VEGF, integrin, Ang2, and SARS-CoV-2-covering both heavy-chain and light-chain mutations. Using these datasets, we systematically compare 15 protein models including masked language models, autoregressive language models, inverse folding models, diffusion-based generative models, and geometric graph models by comparing the correlation between model likelihood and experimental affinity values. Additionally, to demonstrate AbBiBench's generative utility, we apply it to antibody F045-092 in order to introduce binding to influenza H1N1. We sample new antibody variants with the top-performing models, rank them by the structural integrity and biophysical properties of the Ab-Ag complex, and assess them with in vitro ELISA binding assays. Our findings show that structure-conditioned inverse folding models outperform others in both affinity correlation and generation tasks. Overall, AbBiBench provides a unified, biologically grounded evaluation framework to facilitate the development of more effective, function-aware antibody design models.

The complementarity-determining regions of antibodies are loop structures that are key to their interactions with antigens, and of high importance to the design of novel biologics. Since the 1980s, categorizing the diversity of CDR structures into canonical clusters has enabled the identification of key structural motifs of antibodies. However, existing approaches have limited coverage and cannot be readily incorporated into protein foundation models. Here we introduce ImmunoGlobulin LOOp Tokenizer, Igloo, a multimodal antibody loop tokenizer that encodes backbone dihedral angles and sequence. Igloo is trained using a contrastive learning objective to map loops with similar backbone dihedral angles closer together in latent space. Igloo can efficiently retrieve the closest matching loop structures from a structural antibody database, outperforming existing methods on identifying similar H3 loops by 5.9\%. Igloo assigns tokens to all loops, addressing the limited coverage issue of canonical clusters, while retaining the ability to recover canonical loop conformations. To demonstrate the versatility of Igloo tokens, we show that they can be incorporated into protein language models with IglooLM and IglooALM. On predicting binding affinity of heavy chain variants, IglooLM outperforms the base protein language model on 8 out of 10 antibody-antigen targets. Additionally, it is on par with existing state-of-the-art sequence-based and multimodal protein language models, performing comparably to models with 7times more parameters. IglooALM samples antibody loops which are diverse in sequence and more consistent in structure than state-of-the-art antibody inverse folding models. Igloo demonstrates the benefit of introducing multimodal tokens for antibody loops for encoding the diverse landscape of antibody loops, improving protein foundation models, and for antibody CDR design.

We consider the problem of antibody sequence design given 3D structural information. Building on previous work, we propose a fine-tuned inverse folding model that is specifically optimised for antibody structures and outperforms generic protein models on sequence recovery and structure robustness when applied on antibodies, with notable improvement on the hypervariable CDR-H3 loop. We study the canonical conformations of complementarity-determining regions and find improved encoding of these loops into known clusters. Finally, we consider the applications of our model to drug discovery and binder design and evaluate the quality of proposed sequences using physics-based methods.

Protein inverse folding, the design of an amino acid sequence based on a target 3D structure, is a fundamental problem of computational protein engineering. Existing methods either generate sequences without leveraging external knowledge or relying on protein language models (PLMs). The former omits the evolutionary information stored in protein databases, while the latter is parameter-inefficient and inflexible to adapt to ever-growing protein data. To overcome the above drawbacks, in this paper we propose a novel method, called retrieval-augmented denoising diffusion (RadDiff), for protein inverse folding. Given the target protein backbone, RadDiff uses a hierarchical search strategy to efficiently retrieve structurally similar proteins from large protein databases. The retrieved structures are then aligned residue-by-residue to the target to construct a position-specific amino acid profile, which serves as an evolutionary-informed prior that conditions the denoising process. A lightweight integration module is further designed to incorporate this prior effectively. Experimental results on the CATH, PDB, and TS50 datasets show that RadDiff consistently outperforms existing methods, improving sequence recovery rate by up to 19%. Experimental results also demonstrate that RadDiff generates highly foldable sequences and scales effectively with database size.

Recent studies have demonstrated the strong empirical performance of diffusion models on discrete sequences across domains from natural language to biological sequence generation. For example, in the protein inverse folding task, conditional diffusion models have achieved impressive results in generating natural-like sequences that fold back into the original structure. However, practical design tasks often require not only modeling a conditional distribution but also optimizing specific task objectives. For instance, we may prefer protein sequences with high stability. To address this, we consider the scenario where we have pre-trained discrete diffusion models that can generate natural-like sequences, as well as reward models that map sequences to task objectives. We then formulate the reward maximization problem within discrete diffusion models, analogous to reinforcement learning (RL), while minimizing the KL divergence against pretrained diffusion models to preserve naturalness. To solve this RL problem, we propose a novel algorithm, DRAKES, that enables direct backpropagation of rewards through entire trajectories generated by diffusion models, by making the originally non-differentiable trajectories differentiable using the Gumbel-Softmax trick. Our theoretical analysis indicates that our approach can generate sequences that are both natural-like and yield high rewards. While similar tasks have been recently explored in diffusion models for continuous domains, our work addresses unique algorithmic and theoretical challenges specific to discrete diffusion models, which arise from their foundation in continuous-time Markov chains rather than Brownian motion. Finally, we demonstrate the effectiveness of DRAKES in generating DNA and protein sequences that optimize enhancer activity and protein stability, respectively, important tasks for gene therapies and protein-based therapeutics.

This paper introduces diffusion protein language model (DPLM), a versatile protein language model that demonstrates strong generative and predictive capabilities for protein sequences. We first pre-train scalable DPLMs from evolutionary-scale protein sequences within a generative self-supervised discrete diffusion probabilistic framework, which generalizes language modeling for proteins in a principled way. After pre-training, DPLM exhibits the ability to generate structurally plausible, novel, and diverse protein sequences for unconditional generation. We further demonstrate the proposed diffusion generative pre-training makes DPLM possess a better understanding of proteins, making it a superior representation learner, which can be fine-tuned for various predictive tasks, comparing favorably to ESM2 (Lin et al., 2022). Moreover, DPLM can be tailored for various needs, which showcases its prowess of conditional generation in several ways: (1) conditioning on partial peptide sequences, e.g., generating scaffolds for functional motifs with high success rate; (2) incorporating other modalities as conditioner, e.g., structure-conditioned generation for inverse folding; and (3) steering sequence generation towards desired properties, e.g., satisfying specified secondary structures, through a plug-and-play classifier guidance. Code is released at https://github.com/bytedance/dplm.

Inverse protein folding -- the task of predicting a protein sequence from its backbone atom coordinates -- has surfaced as an important problem in the "top down", de novo design of proteins. Contemporary approaches have cast this problem as a conditional generative modelling problem, where a large generative model over protein sequences is conditioned on the backbone. While these generative models very rapidly produce promising sequences, independent draws from generative models may fail to produce sequences that reliably fold to the correct backbone. Furthermore, it is challenging to adapt pure generative approaches to other settings, e.g., when constraints exist. In this paper, we cast the problem of improving generated inverse folds as an optimization problem that we solve using recent advances in "deep" or "latent space" Bayesian optimization. Our approach consistently produces protein sequences with greatly reduced structural error to the target backbone structure as measured by TM score and RMSD while using fewer computational resources. Additionally, we demonstrate other advantages of an optimization-based approach to the problem, such as the ability to handle constraints.

How can we design protein sequences folding into the desired structures effectively and efficiently? AI methods for structure-based protein design have attracted increasing attention in recent years; however, few methods can simultaneously improve the accuracy and efficiency due to the lack of expressive features and autoregressive sequence decoder. To address these issues, we propose PiFold, which contains a novel residue featurizer and PiGNN layers to generate protein sequences in a one-shot way with improved recovery. Experiments show that PiFold could achieve 51.66\% recovery on CATH 4.2, while the inference speed is 70 times faster than the autoregressive competitors. In addition, PiFold achieves 58.72\% and 60.42\% recovery scores on TS50 and TS500, respectively. We conduct comprehensive ablation studies to reveal the role of different types of protein features and model designs, inspiring further simplification and improvement. The PyTorch code is available at https://github.com/A4Bio/PiFold{GitHub}.

Proteins are essential macromolecules defined by their amino acid sequences, which determine their three-dimensional structures and, consequently, their functions in all living organisms. Therefore, generative protein modeling necessitates a multimodal approach to simultaneously model, understand, and generate both sequences and structures. However, existing methods typically use separate models for each modality, limiting their ability to capture the intricate relationships between sequence and structure. This results in suboptimal performance in tasks that requires joint understanding and generation of both modalities. In this paper, we introduce DPLM-2, a multimodal protein foundation model that extends discrete diffusion protein language model (DPLM) to accommodate both sequences and structures. To enable structural learning with the language model, 3D coordinates are converted to discrete tokens using a lookup-free quantization-based tokenizer. By training on both experimental and high-quality synthetic structures, DPLM-2 learns the joint distribution of sequence and structure, as well as their marginals and conditionals. We also implement an efficient warm-up strategy to exploit the connection between large-scale evolutionary data and structural inductive biases from pre-trained sequence-based protein language models. Empirical evaluation shows that DPLM-2 can simultaneously generate highly compatible amino acid sequences and their corresponding 3D structures eliminating the need for a two-stage generation approach. Moreover, DPLM-2 demonstrates competitive performance in various conditional generation tasks, including folding, inverse folding, and scaffolding with multimodal motif inputs, as well as providing structure-aware representations for predictive tasks.

The ability to transform a flat sheet into a complex three-dimensional structure is a fundamental test of physical intelligence. Unlike cloth manipulation, origami is governed by strict geometric axioms and hard kinematic constraints, where a single invalid crease or collision can invalidate the entire folding sequence. As a result, origami demands long-horizon constructive reasoning that jointly satisfies precise physical laws and high-level semantic intent. Existing approaches fall into two disjoint paradigms: optimization-based methods enforce physical validity but require dense, precisely specified inputs, making them unsuitable for sparse natural language descriptions, while generative foundation models excel at semantic and perceptual synthesis yet fail to produce long-horizon, physics-consistent folding processes. Consequently, generating valid origami folding sequences directly from text remains an open challenge. To address this gap, we introduce Learn2Fold, a neuro-symbolic framework that formulates origami folding as conditional program induction over a crease-pattern graph. Our key insight is to decouple semantic proposal from physical verification. A large language model generates candidate folding programs from abstract text prompts, while a learned graph-structured world model serves as a differentiable surrogate simulator that predicts physical feasibility and failure modes before execution. Integrated within a lookahead planning loop, Learn2Fold enables robust generation of physically valid folding sequences for complex and out-of-distribution patterns, demonstrating that effective spatial intelligence arises from the synergy between symbolic reasoning and grounded physical simulation.

Innovations like protein diffusion have enabled significant progress in de novo protein design, which is a vital topic in life science. These methods typically depend on protein structure encoders to model residue backbone frames, where atoms do not exist. Most prior encoders rely on atom-wise features, such as angles and distances between atoms, which are not available in this context. Thus far, only several simple encoders, such as IPA, have been proposed for this scenario, exposing the frame modeling as a bottleneck. In this work, we proffer the Vector Field Network (VFN), which enables network layers to perform learnable vector computations between coordinates of frame-anchored virtual atoms, thus achieving a higher capability for modeling frames. The vector computation operates in a manner similar to a linear layer, with each input channel receiving 3D virtual atom coordinates instead of scalar values. The multiple feature vectors output by the vector computation are then used to update the residue representations and virtual atom coordinates via attention aggregation. Remarkably, VFN also excels in modeling both frames and atoms, as the real atoms can be treated as the virtual atoms for modeling, positioning VFN as a potential universal encoder. In protein diffusion (frame modeling), VFN exhibits an impressive performance advantage over IPA, excelling in terms of both designability (67.04% vs. 53.58%) and diversity (66.54% vs. 51.98%). In inverse folding (frame and atom modeling), VFN outperforms the previous SoTA model, PiFold (54.7% vs. 51.66%), on sequence recovery rate. We also propose a method of equipping VFN with the ESM model, which significantly surpasses the previous ESM-based SoTA (62.67% vs. 55.65%), LM-Design, by a substantial margin.

Designing antibody sequences to better resemble those observed in natural human repertoires is a key challenge in biologics development. We introduce IgCraft: a multi-purpose model for paired human antibody sequence generation, built on Bayesian Flow Networks. IgCraft presents one of the first unified generative modeling frameworks capable of addressing multiple antibody sequence design tasks with a single model, including unconditional sampling, sequence inpainting, inverse folding, and CDR motif scaffolding. Our approach achieves competitive results across the full spectrum of these tasks while constraining generation to the space of human antibody sequences, exhibiting particular strengths in CDR motif scaffolding (grafting) where we achieve state-of-the-art performance in terms of humanness and preservation of structural properties. By integrating previously separate tasks into a single scalable generative model, IgCraft provides a versatile platform for sampling human antibody sequences under a variety of contexts relevant to antibody discovery and engineering. Model code and weights are publicly available at github.com/mgreenig/IgCraft.

Recent findings suggest that consecutive layers of neural networks with the ReLU activation function fold the input space during the learning process. While many works hint at this phenomenon, an approach to quantify the folding was only recently proposed by means of a space folding measure based on Hamming distance in the ReLU activation space. We generalize this measure to a wider class of activation functions through introduction of equivalence classes of input data, analyse its mathematical and computational properties and come up with an efficient sampling strategy for its implementation. Moreover, it has been observed that space folding values increase with network depth when the generalization error is low, but decrease when the error increases. This underpins that learned symmetries in the data manifold (e.g., invariance under reflection) become visible in terms of space folds, contributing to the network's generalization capacity. Inspired by these findings, we outline a novel regularization scheme that encourages the network to seek solutions characterized by higher folding values.

RNA design is the search for a sequence or set of sequences that will fold into predefined structures, also known as the inverse problem of RNA folding. While numerous RNA design methods have been invented to find sequences capable of folding into a target structure, little attention has been given to the identification of undesignable structures according to the minimum free energy (MFE) criterion under the Turner model. In this paper, we address this gap by first introducing mathematical theorems outlining sufficient conditions for recognizing undesignable structures, then proposing efficient algorithms, guided by these theorems, to verify the undesignability of RNA structures. Through the application of these theorems and algorithms to the Eterna100 puzzles, we demonstrate the ability to efficiently establish that 15 of the puzzles indeed fall within the category of undesignable structures. In addition, we provide specific insights from the study of undesignability, in the hope that it will enable more understanding of RNA folding and RNA design.

Origami metamaterials typically consist of folded sheets with periodic patterns, conferring them with remarkable mechanical properties. In the context of Continuum Mechanics, the majority of existing predictive methods are mechanism analogs which favor rigid folding and panel bending. While effective in predicting primary deformation modes, existing methods fall short in capturing the full spectrum of deformation of non-rigid foldable origami, such as the emergence of curvature along straight creases, local strain at vertices and warpage in panels. To fully capture the entire deformation spectrum and enhance the accuracy of existing methods, this paper introduces a homogenization framework for origami metamaterials where the faces are modeled as plate elements. Both asymptotic and energy-based homogenization methods are formulated and implemented. As a representative crease pattern, we examine the Miura origami sheet homogenized as an equivalent Kirchhoff-Love plate. The results reveal that certain effective elastic properties are nonlinearly related to both the initial fold angle and the crease stiffness. When benchmarked with results from fully resolved simulations, our framework yields errors up to 12.9\%, while existing models, including the bar-and-hinge model and the rigid-panel model, show up to 161\% error. The differences in errors are associated with the complex modes of crease and panel deformation in non-rigid origami, unexplored by the existing models. This work demonstrates a precise and efficient continuum framework for origami metamaterials as an effective strategy for predicting their elastic properties, understanding their mechanics, and designing their functionalities.

Machine-learning generative methods for material design are constructed by representing a given chemical structure, either a solid or a molecule, over appropriate atomic features, generally called structural descriptors. These must be fully descriptive of the system, must facilitate the training process and must be invertible, so that one can extract the atomic configurations corresponding to the output of the model. In general, this last requirement is not automatically satisfied by the most efficient structural descriptors, namely the representation is not directly invertible. Such drawback severely limits our freedom of choice in selecting the most appropriate descriptors for the problem, and thus our flexibility to construct generative models. In this work, we present a general optimization method capable of inverting any local many-body descriptor of the chemical environment, back to a cartesian representation. The algorithm is then implemented together with the bispectrum representation of the local structure and demonstrated for a number of molecules. The scheme presented here, thus, represents a general approach to the inversion of structural descriptors, enabling the construction of efficient structural generative models.

Building AI systems that can plan, act, and create in the physical world requires more than pattern recognition. Such systems must understand the causal mechanisms and constraints governing physical processes in order to guide sequential decisions. This capability relies on internal representations, analogous to an internal language model, that relate observations, actions, and resulting environmental changes. However, many existing benchmarks treat visual perception and programmatic reasoning as separate problems, focusing either on visual recognition or on symbolic tasks. The domain of origami provides a natural testbed that integrates these modalities. Constructing shapes through folding operations requires visual perception, reasoning about geometric and physical constraints, and sequential planning, while remaining sufficiently structured for systematic evaluation. We introduce OrigamiBench, an interactive benchmark in which models iteratively propose folds and receive feedback on physical validity and similarity to a target configuration. Experiments with modern vision-language models show that scaling model size alone does not reliably produce causal reasoning about physical transformations. Models fail to generate coherent multi-step folding strategies, suggesting that visual and language representations remain weakly integrated.

Highly accurate biomolecular structure prediction is a key component of developing biomolecular foundation models, and one of the most critical aspects of building foundation models is identifying the recipes for scaling the model. In this work, we present SeedFold, a folding model that successfully scales up the model capacity. Our contributions are threefold: first, we identify an effective width-scaling strategy for the Pairformer to increase representation capacity; second, we introduce a novel linear triangular attention that reduces computational complexity to enable efficient scaling; finally, we construct a large-scale distillation dataset to substantially enlarge the training set. Experiments on FoldBench show that SeedFold outperforms AlphaFold3 on most protein-related tasks.

Protein folding models have achieved groundbreaking results typically via a combination of integrating domain knowledge into the architectural blocks and training pipelines. Nonetheless, given the success of generative models across different but related problems, it is natural to question whether these architectural designs are a necessary condition to build performant models. In this paper, we introduce SimpleFold, the first flow-matching based protein folding model that solely uses general purpose transformer blocks. Protein folding models typically employ computationally expensive modules involving triangular updates, explicit pair representations or multiple training objectives curated for this specific domain. Instead, SimpleFold employs standard transformer blocks with adaptive layers and is trained via a generative flow-matching objective with an additional structural term. We scale SimpleFold to 3B parameters and train it on approximately 9M distilled protein structures together with experimental PDB data. On standard folding benchmarks, SimpleFold-3B achieves competitive performance compared to state-of-the-art baselines, in addition SimpleFold demonstrates strong performance in ensemble prediction which is typically difficult for models trained via deterministic reconstruction objectives. Due to its general-purpose architecture, SimpleFold shows efficiency in deployment and inference on consumer-level hardware. SimpleFold challenges the reliance on complex domain-specific architectures designs in protein folding, opening up an alternative design space for future progress.

We report a flexible language-model based deep learning strategy, applied here to solve complex forward and inverse problems in protein modeling, based on an attention neural network that integrates transformer and graph convolutional architectures in a causal multi-headed graph mechanism, to realize a generative pretrained model. The model is applied to predict secondary structure content (per-residue level and overall content), protein solubility, and sequencing tasks. Further trained on inverse tasks, the model is rendered capable of designing proteins with these properties as target features. The model is formulated as a general framework, completely prompt-based, and can be adapted for a variety of downstream tasks. We find that adding additional tasks yields emergent synergies that the model exploits in improving overall performance, beyond what would be possible by training a model on each dataset alone. Case studies are presented to validate the method, yielding protein designs specifically focused on structural proteins, but also exploring the applicability in the design of soluble, antimicrobial biomaterials. While our model is trained to ultimately perform 8 distinct tasks, with available datasets it can be extended to solve additional problems. In a broader sense, this work illustrates a form of multiscale modeling that relates a set of ultimate building blocks (here, byte-level utf8 characters) to complex output. This materiomic scheme captures complex emergent relationships between universal building block and resulting properties via a synergizing learning capacity to express a set of potentialities embedded in the knowledge used in training, via the interplay of universality and diversity.

Recent findings suggest that the consecutive layers of ReLU neural networks can be understood geometrically as space folding transformations of the input space, revealing patterns of self-similarity. In this paper, we present the first quantitative analysis of this space folding phenomenon in ReLU neural networks. Our approach focuses on examining how straight paths in the Euclidean input space are mapped to their counterparts in the Hamming activation space. In this process, the convexity of straight lines is generally lost, giving rise to non-convex folding behavior. To quantify this effect, we introduce a novel measure based on range metrics, similar to those used in the study of random walks, and provide the proof for the equivalence of convexity notions between the input and activation spaces. Furthermore, we provide empirical analysis on a geometrical analysis benchmark (CantorNet) as well as an image classification benchmark (MNIST). Our work advances the understanding of the activation space in ReLU neural networks by leveraging the phenomena of geometric folding, providing valuable insights on how these models process input information.

The ability to computationally generate novel yet physically foldable protein structures could lead to new biological discoveries and new treatments targeting yet incurable diseases. Despite recent advances in protein structure prediction, directly generating diverse, novel protein structures from neural networks remains difficult. In this work, we present a new diffusion-based generative model that designs protein backbone structures via a procedure that mirrors the native folding process. We describe protein backbone structure as a series of consecutive angles capturing the relative orientation of the constituent amino acid residues, and generate new structures by denoising from a random, unfolded state towards a stable folded structure. Not only does this mirror how proteins biologically twist into energetically favorable conformations, the inherent shift and rotational invariance of this representation crucially alleviates the need for complex equivariant networks. We train a denoising diffusion probabilistic model with a simple transformer backbone and demonstrate that our resulting model unconditionally generates highly realistic protein structures with complexity and structural patterns akin to those of naturally-occurring proteins. As a useful resource, we release the first open-source codebase and trained models for protein structure diffusion.

Unlike the predictable scaling laws in natural language processing and computer vision, protein language models (PLMs) scale poorly: for many tasks, models within the same family plateau or even decrease in performance, with mid-sized models often outperforming the largest in the family. We introduce Reverse Distillation, a principled framework that decomposes large PLM representations into orthogonal subspaces guided by smaller models of the same family. The resulting embeddings have a nested, Matryoshka-style structure: the first k dimensions of a larger model's embedding are exactly the representation from the smaller model. This ensures that larger reverse-distilled models consistently outperform smaller ones. A motivating intuition is that smaller models, constrained by capacity, preferentially encode broadly-shared protein features. Reverse distillation isolates these shared features and orthogonally extracts additional contributions from larger models, preventing interference between the two. On ProteinGym benchmarks, reverse-distilled ESM-2 variants outperform their respective baselines at the same embedding dimensionality, with the reverse-distilled 15 billion parameter model achieving the strongest performance. Our framework is generalizable to any model family where scaling challenges persist. Code and trained models are available at https://github.com/rohitsinghlab/plm_reverse_distillation.

Inverse graphics -- the task of inverting an image into physical variables that, when rendered, enable reproduction of the observed scene -- is a fundamental challenge in computer vision and graphics. Disentangling an image into its constituent elements, such as the shape, color, and material properties of the objects of the 3D scene that produced it, requires a comprehensive understanding of the environment. This requirement limits the ability of existing carefully engineered approaches to generalize across domains. Inspired by the zero-shot ability of large language models (LLMs) to generalize to novel contexts, we investigate the possibility of leveraging the broad world knowledge encoded in such models in solving inverse-graphics problems. To this end, we propose the Inverse-Graphics Large Language Model (IG-LLM), an inverse-graphics framework centered around an LLM, that autoregressively decodes a visual embedding into a structured, compositional 3D-scene representation. We incorporate a frozen pre-trained visual encoder and a continuous numeric head to enable end-to-end training. Through our investigation, we demonstrate the potential of LLMs to facilitate inverse graphics through next-token prediction, without the use of image-space supervision. Our analysis opens up new possibilities for precise spatial reasoning about images that exploit the visual knowledge of LLMs. We will release our code and data to ensure the reproducibility of our investigation and to facilitate future research at https://ig-llm.is.tue.mpg.de/

Large Language Models (LLMs) are large-scale pretrained models that have achieved remarkable success across diverse domains. These successes have been driven by unprecedented complexity and scale in both data and computations. However, due to the high costs of training such models, brute-force trial-and-error approaches to improve LLMs are not feasible. Inspired by the success of inverse problems in uncovering fundamental scientific laws, this position paper advocates that inverse problems can also efficiently uncover scaling laws that guide the building of LLMs to achieve the desirable performance with significantly better cost-effectiveness.

Normalizing flows are a promising tool for modeling probability distributions in physical systems. While state-of-the-art flows accurately approximate distributions and energies, applications in physics additionally require smooth energies to compute forces and higher-order derivatives. Furthermore, such densities are often defined on non-trivial topologies. A recent example are Boltzmann Generators for generating 3D-structures of peptides and small proteins. These generative models leverage the space of internal coordinates (dihedrals, angles, and bonds), which is a product of hypertori and compact intervals. In this work, we introduce a class of smooth mixture transformations working on both compact intervals and hypertori. Mixture transformations employ root-finding methods to invert them in practice, which has so far prevented bi-directional flow training. To this end, we show that parameter gradients and forces of such inverses can be computed from forward evaluations via the inverse function theorem. We demonstrate two advantages of such smooth flows: they allow training by force matching to simulation data and can be used as potentials in molecular dynamics simulations.

Cloth folding is a complex task due to the inevitable self-occlusions of clothes, their complicated dynamics, and the disparate materials, geometries, and textures that garments can have. In this work, we learn folding actions conditioned on text commands. Translating high-level, abstract instructions into precise robotic actions requires sophisticated language understanding and manipulation capabilities. To do that, we leverage a pre-trained vision-language model and repurpose it to predict manipulation actions. Our model, BiFold, can take context into account and achieves state-of-the-art performance on an existing language-conditioned folding benchmark. Given the lack of annotated bimanual folding data, we devise a procedure to automatically parse actions of a simulated dataset and tag them with aligned text instructions. BiFold attains the best performance on our dataset and can transfer to new instructions, garments, and environments.

Multimodal protein language models (PLMs) integrate sequence and token-based structural information, serving as a powerful foundation for protein modeling, generation, and design. However, the reliance on tokenizing 3D structures into discrete tokens causes substantial loss of fidelity about fine-grained structural details and correlations. In this paper, we systematically elucidate the design space of multimodal PLMs to overcome their limitations. We identify tokenization loss and inaccurate structure token predictions by the PLMs as major bottlenecks. To address these, our proposed design space covers improved generative modeling, structure-aware architectures and representation learning, and data exploration. Our advancements approach finer-grained supervision, demonstrating that token-based multimodal PLMs can achieve robust structural modeling. The effective design methods dramatically improve the structure generation diversity, and notably, folding abilities of our 650M model by reducing the RMSD from 5.52 to 2.36 on PDB testset, even outperforming 3B baselines and on par with the specialized folding models.

In molecular dynamics (MD) simulations, rare events, such as protein folding, are typically studied by means of enhanced sampling techniques, most of which rely on the definition of a collective variable (CV) along which the acceleration occurs. Obtaining an expressive CV is crucial, but often hindered by the lack of information about the particular event, e.g., the transition from unfolded to folded conformation. We propose a simulation-free data augmentation strategy using physics-inspired metrics to generate geodesic interpolations resembling protein folding transitions, thereby improving sampling efficiency without true transition state samples. Leveraging interpolation progress parameters, we introduce a regression-based learning scheme for CV models, which outperforms classifier-based methods when transition state data is limited and noisy

We present a novel Learning from Demonstration (LfD) method, Deformable Manipulation from Demonstrations (DMfD), to solve deformable manipulation tasks using states or images as inputs, given expert demonstrations. Our method uses demonstrations in three different ways, and balances the trade-off between exploring the environment online and using guidance from experts to explore high dimensional spaces effectively. We test DMfD on a set of representative manipulation tasks for a 1-dimensional rope and a 2-dimensional cloth from the SoftGym suite of tasks, each with state and image observations. Our method exceeds baseline performance by up to 12.9% for state-based tasks and up to 33.44% on image-based tasks, with comparable or better robustness to randomness. Additionally, we create two challenging environments for folding a 2D cloth using image-based observations, and set a performance benchmark for them. We deploy DMfD on a real robot with a minimal loss in normalized performance during real-world execution compared to simulation (~6%). Source code is on github.com/uscresl/dmfd

Inverse graphics is a longstanding and highly underconstrained problem that seeks to reconstruct images as editable 3D scenes which can be rendered, relit, and manipulated. In this work, we investigate whether pretrained vision-language models (VLMs) can perform executable inverse graphics directly from a single image by reconstructing a scene as an editable Blender program, without relying on specialized 2D or 3D foundation models, differentiable rendering, or multi-view supervision. We introduce Staged Executable Inverse Graphics (SEIG), an agentic framework that reconstructs a 3D scene from a single image by progressively refining scene factors including geometry, materials, composition, and lighting directly in executable Blender code space. We evaluate our framework across diverse scenes using a range of reconstruction metrics spanning pixel-level, perceptual, and semantic fidelity. Our experiments show that staged reconstruction substantially improves reconstruction fidelity, highlighting the importance of task decomposition for executable inverse graphics with general-purpose VLMs. Finally, we showcase various downstream applications enabled by the reconstructed editable Blender scenes.

Multimodal large language models (MLLMs) are proficient in perception and instruction-following, but they still struggle with spatial reasoning: the ability to mentally track and manipulate objects across multiple views and over time. Spatial reasoning is a key component of human intelligence, but most existing benchmarks focus on static images or final outputs, failing to account for the sequential and viewpoint-dependent nature of this skill. To close this gap, we introduce GamiBench, a benchmark designed to evaluate spatial reasoning and 2D-to-3D planning in MLLMs through origami-inspired folding tasks. GamiBench includes 186 regular and 186 impossible 2D crease patterns paired with their corresponding 3D folded shapes, produced from six distinct viewpoints across three visual question-answering (VQA) tasks: predicting 3D fold configurations, distinguishing valid viewpoints, and detecting impossible patterns. Unlike previous benchmarks that assess only final predictions, GamiBench holistically evaluates the entire reasoning process--measuring cross-view consistency, physical feasibility through impossible-fold detection, and interpretation of intermediate folding steps. It further introduces new diagnostic metrics--viewpoint consistency (VC) and impossible fold selection rate (IFSR)--to measure how well models handle folds of varying complexity. Our experiments show that even leading models such as GPT-5 and Gemini-2.5-Pro struggle on single-step spatial understanding. These contributions establish a standardized framework for evaluating geometric understanding and spatial reasoning in MLLMs. Dataset and code: https://github.com/stvngo/GamiBench.

We present a topology-informed inverse rendering approach for reconstructing high-genus surface meshes from multi-view images. Compared to 3D representations like voxels and point clouds, mesh-based representations are preferred as they enable the application of differential geometry theory and are optimized for modern graphics pipelines. However, existing inverse rendering methods often fail catastrophically on high-genus surfaces, leading to the loss of key topological features, and tend to oversmooth low-genus surfaces, resulting in the loss of surface details. This failure stems from their overreliance on Adam-based optimizers, which can lead to vanishing and exploding gradients. To overcome these challenges, we introduce an adaptive V-cycle remeshing scheme in conjunction with a re-parametrized Adam optimizer to enhance topological and geometric awareness. By periodically coarsening and refining the deforming mesh, our method informs mesh vertices of their current topology and geometry before optimization, mitigating gradient issues while preserving essential topological features. Additionally, we enforce topological consistency by constructing topological primitives with genus numbers that match those of ground truth using Gauss-Bonnet theorem. Experimental results demonstrate that our inverse rendering approach outperforms the current state-of-the-art method, achieving significant improvements in Chamfer Distance and Volume IoU, particularly for high-genus surfaces, while also enhancing surface details for low-genus surfaces.

Lightweight creation of 3D digital avatars is a highly desirable but challenging task. With only sparse videos of a person under unknown illumination, we propose a method to create relightable and animatable neural avatars, which can be used to synthesize photorealistic images of humans under novel viewpoints, body poses, and lighting. The key challenge here is to disentangle the geometry, material of the clothed body, and lighting, which becomes more difficult due to the complex geometry and shadow changes caused by body motions. To solve this ill-posed problem, we propose novel techniques to better model the geometry and shadow changes. For geometry change modeling, we propose an invertible deformation field, which helps to solve the inverse skinning problem and leads to better geometry quality. To model the spatial and temporal varying shading cues, we propose a pose-aware part-wise light visibility network to estimate light occlusion. Extensive experiments on synthetic and real datasets show that our approach reconstructs high-quality geometry and generates realistic shadows under different body poses. Code and data are available at https://wenbin-lin.github.io/RelightableAvatar-page/.

Diffusion Language Models (DLMs) have recently achieved strong results in text generation. However, their multi-step sampling leads to slow inference, limiting practical use. To address this, we extend Inverse Distillation, a technique originally developed to accelerate continuous diffusion models, to the discrete setting. Nonetheless, this extension introduces both theoretical and practical challenges. From a theoretical perspective, the inverse distillation objective lacks uniqueness guarantees, which may lead to suboptimal solutions. From a practical standpoint, backpropagation in the discrete space is non-trivial and often unstable. To overcome these challenges, we first provide a theoretical result demonstrating that our inverse formulation admits a unique solution, thereby ensuring valid optimization. We then introduce gradient-stable relaxations to support effective training. As a result, experiments on multiple DLMs show that our method, Inverse-distilled Diffusion Language Models (IDLM), reduces the number of inference steps by 4x-64x, while preserving the teacher model's entropy and generative perplexity.

Consistency and reliability are crucial for conducting AI research. Many famous research fields, such as object detection, have been compared and validated with solid benchmark frameworks. After AlphaFold2, the protein folding task has entered a new phase, and many methods are proposed based on the component of AlphaFold2. The importance of a unified research framework in protein folding contains implementations and benchmarks to consistently and fairly compare various approaches. To achieve this, we present Solvent, an protein folding framework that supports significant components of state-of-th-arts models in the manner of off-the-shelf interface Solvent contains different models implemented in a unified codebase and supports training and evaluation for defined models on the same dataset. We benchmark well-known algorithms and their components and provide experiments that give helpful insights into the protein structure modeling field. We hope that Solvent will increase the reliability and consistency of proposed models and gives efficiency in both speed and costs, resulting in acceleration on protein folding modeling research. The code is available at https://github.com/kakaobrain/solvent, and the project will continue to be developed.

Diffusion models are widely used for generative tasks across domains. Given a pre-trained diffusion model, it is often desirable to fine-tune it further either to correct for errors in learning or to align with downstream applications. Towards this, we examine the effect of shaping the distribution at intermediate noise levels induced by diffusion models. First, we show that existing variants of Rejection sAmpling based Fine-Tuning (RAFT), which we unify as GRAFT, can implicitly perform KL regularized reward maximization with reshaped rewards. Motivated by this observation, we introduce P-GRAFT to shape distributions at intermediate noise levels and demonstrate empirically that this can lead to more effective fine-tuning. We mathematically explain this via a bias-variance tradeoff. Next, we look at correcting learning errors in pre-trained flow models based on the developed mathematical framework. In particular, we propose inverse noise correction, a novel algorithm to improve the quality of pre-trained flow models without explicit rewards. We empirically evaluate our methods on text-to-image(T2I) generation, layout generation, molecule generation and unconditional image generation. Notably, our framework, applied to Stable Diffusion v2, improves over policy gradient methods on popular T2I benchmarks in terms of VQAScore and shows an 8.81% relative improvement over the base model. For unconditional image generation, inverse noise correction improves FID of generated images at lower FLOPs/image.

Garment folding is a common yet challenging task in robotic manipulation. The deformability of garments leads to a vast state space and complex dynamics, which complicates precise and fine-grained manipulation. Previous approaches often rely on predefined key points or demonstrations, limiting their generalization across diverse garment categories. This paper presents a framework, MetaFold, that disentangles task planning from action prediction, learning each independently to enhance model generalization. It employs language-guided point cloud trajectory generation for task planning and a low-level foundation model for action prediction. This structure facilitates multi-category learning, enabling the model to adapt flexibly to various user instructions and folding tasks. Experimental results demonstrate the superiority of our proposed framework. Supplementary materials are available on our website: https://meta-fold.github.io/.

Normalizing Flows (NFs) have been established as a principled framework for generative modeling. Standard NFs consist of a forward process and a reverse process: the forward process maps data to noise, while the reverse process generates samples by inverting it. Typical NF forward transformations are constrained by explicit invertibility, ensuring that the reverse process can serve as their exact analytic inverse. Recent developments in TARFlow and its variants have revitalized NF methods by combining Transformers and autoregressive flows, but have also exposed causal decoding as a major bottleneck. In this work, we introduce Bidirectional Normalizing Flow (BiFlow), a framework that removes the need for an exact analytic inverse. BiFlow learns a reverse model that approximates the underlying noise-to-data inverse mapping, enabling more flexible loss functions and architectures. Experiments on ImageNet demonstrate that BiFlow, compared to its causal decoding counterpart, improves generation quality while accelerating sampling by up to two orders of magnitude. BiFlow yields state-of-the-art results among NF-based methods and competitive performance among single-evaluation ("1-NFE") methods. Following recent encouraging progress on NFs, we hope our work will draw further attention to this classical paradigm.

Work on scaling laws has found that large language models (LMs) show predictable improvements to overall loss with increased scale (model size, training data, and compute). Here, we present evidence for the claim that LMs may show inverse scaling, or worse task performance with increased scale, e.g., due to flaws in the training objective and data. We present empirical evidence of inverse scaling on 11 datasets collected by running a public contest, the Inverse Scaling Prize, with a substantial prize pool. Through analysis of the datasets, along with other examples found in the literature, we identify four potential causes of inverse scaling: (i) preference to repeat memorized sequences over following in-context instructions, (ii) imitation of undesirable patterns in the training data, (iii) tasks containing an easy distractor task which LMs could focus on, rather than the harder real task, and (iv) correct but misleading few-shot demonstrations of the task. We release the winning datasets at https://inversescaling.com/data to allow for further investigation of inverse scaling. Our tasks have helped drive the discovery of U-shaped and inverted-U scaling trends, where an initial trend reverses, suggesting that scaling trends are less reliable at predicting the behavior of larger-scale models than previously understood. Overall, our results suggest that there are tasks for which increased model scale alone may not lead to progress, and that more careful thought needs to go into the data and objectives for training language models.

We investigate an experiential learning paradigm for acquiring an internal model of intuitive physics. Our model is evaluated on a real-world robotic manipulation task that requires displacing objects to target locations by poking. The robot gathered over 400 hours of experience by executing more than 100K pokes on different objects. We propose a novel approach based on deep neural networks for modeling the dynamics of robot's interactions directly from images, by jointly estimating forward and inverse models of dynamics. The inverse model objective provides supervision to construct informative visual features, which the forward model can then predict and in turn regularize the feature space for the inverse model. The interplay between these two objectives creates useful, accurate models that can then be used for multi-step decision making. This formulation has the additional benefit that it is possible to learn forward models in an abstract feature space and thus alleviate the need of predicting pixels. Our experiments show that this joint modeling approach outperforms alternative methods.

Inverse design, where we seek to design input variables in order to optimize an underlying objective function, is an important problem that arises across fields such as mechanical engineering to aerospace engineering. Inverse design is typically formulated as an optimization problem, with recent works leveraging optimization across learned dynamics models. However, as models are optimized they tend to fall into adversarial modes, preventing effective sampling. We illustrate that by instead optimizing over the learned energy function captured by the diffusion model, we can avoid such adversarial examples and significantly improve design performance. We further illustrate how such a design system is compositional, enabling us to combine multiple different diffusion models representing subcomponents of our desired system to design systems with every specified component. In an N-body interaction task and a challenging 2D multi-airfoil design task, we demonstrate that by composing the learned diffusion model at test time, our method allows us to design initial states and boundary shapes that are more complex than those in the training data. Our method generalizes to more objects for N-body dataset and discovers formation flying to minimize drag in the multi-airfoil design task. Project website and code can be found at https://github.com/AI4Science-WestlakeU/cindm.

We report a series of deep learning models to solve complex forward and inverse design problems in molecular modeling and design. Using both diffusion models inspired by nonequilibrium thermodynamics and attention-based transformer architectures, we demonstrate a flexible framework to capture complex chemical structures. First trained on the QM9 dataset and a series of quantum mechanical properties (e.g. homo, lumo, free energy, heat capacity, etc.), we then generalize the model to study and design key properties of deep eutectic solvents. In addition to separate forward and inverse models, we also report an integrated fully prompt-based multi-task generative pretrained transformer model that solves multiple forward, inverse design, and prediction tasks, flexibly and within one model. We show that the multi-task generative model has the overall best performance and allows for flexible integration of multiple objectives, within one model, and for distinct chemistries, suggesting that synergies emerge during training of this large language model. Trained jointly in tasks related to the QM9 dataset and deep eutectic solvents (DESs), the model can predict various quantum mechanical properties and critical properties to achieve deep eutectic solvent behavior. Several novel combinations of DESs are proposed based on this framework.

Inverse design of solid-state materials with desired properties represents a formidable challenge in materials science. Although recent generative models have demonstrated potential, their adoption has been hindered by limitations such as inefficiency, architectural constraints and restricted open-source availability. The representation of crystal structures using the SLICES (Simplified Line-Input Crystal-Encoding System) notation as a string of characters enables the use of state-of-the-art natural language processing models, such as Transformers, for crystal design. Drawing inspiration from the success of GPT models in generating coherent text, we trained a generative Transformer on the next-token prediction task to generate solid-state materials with targeted properties. We demonstrate MatterGPT's capability to generate de novo crystal structures with targeted single properties, including both lattice-insensitive (formation energy) and lattice-sensitive (band gap) properties. Furthermore, we extend MatterGPT to simultaneously target multiple properties, addressing the complex challenge of multi-objective inverse design of crystals. Our approach showcases high validity, uniqueness, and novelty in generated structures, as well as the ability to generate materials with properties beyond the training data distribution. This work represents a significant step forward in computational materials discovery, offering a powerful and open tool for designing materials with tailored properties for various applications in energy, electronics, and beyond.

We report a flexible multi-modal mechanics language model, MeLM, applied to solve various nonlinear forward and inverse problems, that can deal with a set of instructions, numbers and microstructure data. The framework is applied to various examples including bio-inspired hierarchical honeycomb design, carbon nanotube mechanics, and protein unfolding. In spite of the flexible nature of the model-which allows us to easily incorporate diverse materials, scales, and mechanical features-it performs well across disparate forward and inverse tasks. Based on an autoregressive attention-model, MeLM effectively represents a large multi-particle system consisting of hundreds of millions of neurons, where the interaction potentials are discovered through graph-forming self-attention mechanisms that are then used to identify relationships from emergent structures, while taking advantage of synergies discovered in the training data. We show that the model can solve complex degenerate mechanics design problems and determine novel material architectures across a range of hierarchical levels, providing an avenue for materials discovery and analysis. Looking beyond the demonstrations reported in this paper, we discuss other opportunities in applied mechanics and general considerations about the use of large language models in modeling, design, and analysis that can span a broad spectrum of material properties from mechanical, thermal, optical, to electronic.

Progress in computer-aided synthesis planning (CASP) is obscured by the lack of standardized evaluation infrastructure and the reliance on metrics that prioritize topological completion over chemical validity. We introduce RetroCast, a unified evaluation suite that standardizes heterogeneous model outputs into a common schema to enable statistically rigorous, apples-to-apples comparison. The framework includes a reproducible benchmarking pipeline with stratified sampling and bootstrapped confidence intervals, accompanied by SynthArena, an interactive platform for qualitative route inspection. We utilize this infrastructure to evaluate leading search-based and sequence-based algorithms on a new suite of standardized benchmarks. Our analysis reveals a divergence between "solvability" (stock-termination rate) and route quality; high solvability scores often mask chemical invalidity or fail to correlate with the reproduction of experimental ground truths. Furthermore, we identify a "complexity cliff" in which search-based methods, despite high solvability rates, exhibit a sharp performance decay in reconstructing long-range synthetic plans compared to sequence-based approaches. We release the full framework, benchmark definitions, and a standardized database of model predictions to support transparent and reproducible development in the field.

We, team AImsterdam, summarize our submission to the fastMRI challenge (Zbontar et al., 2018). Our approach builds on recent advances in invertible learning to infer models as presented in Putzky and Welling (2019). Both, our single-coil and our multi-coil model share the same basic architecture.

Recent text-guided diffusion models provide powerful image generation capabilities. Currently, a massive effort is given to enable the modification of these images using text only as means to offer intuitive and versatile editing. To edit a real image using these state-of-the-art tools, one must first invert the image with a meaningful text prompt into the pretrained model's domain. In this paper, we introduce an accurate inversion technique and thus facilitate an intuitive text-based modification of the image. Our proposed inversion consists of two novel key components: (i) Pivotal inversion for diffusion models. While current methods aim at mapping random noise samples to a single input image, we use a single pivotal noise vector for each timestamp and optimize around it. We demonstrate that a direct inversion is inadequate on its own, but does provide a good anchor for our optimization. (ii) NULL-text optimization, where we only modify the unconditional textual embedding that is used for classifier-free guidance, rather than the input text embedding. This allows for keeping both the model weights and the conditional embedding intact and hence enables applying prompt-based editing while avoiding the cumbersome tuning of the model's weights. Our Null-text inversion, based on the publicly available Stable Diffusion model, is extensively evaluated on a variety of images and prompt editing, showing high-fidelity editing of real images.

Invertible neural networks (INNs) are neural network architectures with invertibility by design. Thanks to their invertibility and the tractability of Jacobian, INNs have various machine learning applications such as probabilistic modeling, generative modeling, and representation learning. However, their attractive properties often come at the cost of restricting the layer designs, which poses a question on their representation power: can we use these models to approximate sufficiently diverse functions? To answer this question, we have developed a general theoretical framework to investigate the representation power of INNs, building on a structure theorem of differential geometry. The framework simplifies the approximation problem of diffeomorphisms, which enables us to show the universal approximation properties of INNs. We apply the framework to two representative classes of INNs, namely Coupling-Flow-based INNs (CF-INNs) and Neural Ordinary Differential Equations (NODEs), and elucidate their high representation power despite the restrictions on their architectures.

Understanding cellular machinery requires atomic-scale reconstruction of large biomolecular assemblies. However, predicting the structures of these systems has been constrained by hardware memory requirements of models like AlphaFold 3, imposing a practical ceiling of a few thousand residues that can be processed on a single GPU. Here we present NVIDIA BioNeMo Fold-CP, a context parallelism framework that overcomes this barrier by distributing the inference and training pipelines of co-folding models across multiple GPUs. We use the Boltz models as open source reference architectures and implement custom multidimensional primitives that efficiently parallelize both the dense triangular updates and the irregular, data-dependent pattern of window-batched local attention. Our approach achieves efficient memory scaling; for an N-token input distributed across P GPUs, per-device memory scales as O(N^2/P), enabling the structure prediction of assemblies exceeding 30,000 residues on 64 NVIDIA B300 GPUs. We demonstrate the scientific utility of this approach through successful developer use cases: Fold-CP enabled the scoring of over 90% of Comprehensive Resource of Mammalian protein complexes (CORUM) database, as well as folding of disease-relevant PI4KA lipid kinase complex bound to an intrinsically disordered region without cropping. By providing a scalable pathway for modeling massive systems with full global context, Fold-CP represents a significant step toward the realization of a virtual cell.

Precise reconstruction and manipulation of the crumpled cloths is challenging due to the high dimensionality of cloth models, as well as the limited observation at self-occluded regions. We leverage the recent progress in the field of single-view human reconstruction to template-based reconstruct crumpled cloths from their top-view depth observations only, with our proposed sim-real registration protocols. In contrast to previous implicit cloth representations, our reconstruction mesh explicitly describes the positions and visibilities of the entire cloth mesh vertices, enabling more efficient dual-arm and single-arm target-oriented manipulations. Experiments demonstrate that our TRTM system can be applied to daily cloths that have similar topologies as our template mesh, but with different shapes, sizes, patterns, and physical properties. Videos, datasets, pre-trained models, and code can be downloaded from our project website: https://wenbwa.github.io/TRTM/ .

This paper investigates the impact of loss function selection in deep unfolding techniques for sparse signal recovery algorithms. Deep unfolding transforms iterative optimization algorithms into trainable lightweight neural networks by unfolding their iterations as network layers, with various loss functions employed for parameter learning depending on application contexts. We focus on deep unfolded versions of the fundamental iterative shrinkage thresholding algorithm (ISTA) and the iterative hard thresholding algorithm (IHT), comparing supervised learning using mean squared error with unsupervised learning using the objective function of the original optimization problem. Our simulation results reveal that the effect of the choice of loss function significantly depends on the convexity of the optimization problem. For convex ell_1-regularized problems, supervised-ISTA achieves better final recovery accuracy but fails to minimize the original objective function, whereas we empirically observe that unsupervised-ISTA converges to a nearly identical solution as conventional ISTA but with accelerated convergence. Conversely, for nonconvex ell_0-regularized problems, both supervised-IHT and unsupervised-IHT converge to better local minima than the original IHT, showing similar performance regardless of the loss function employed. These findings provide valuable insights into the design of effective deep unfolded networks for sparse signal recovery applications.

We prove an inverse approximation theorem for the approximation of nonlinear sequence-to-sequence relationships using recurrent neural networks (RNNs). This is a so-called Bernstein-type result in approximation theory, which deduces properties of a target function under the assumption that it can be effectively approximated by a hypothesis space. In particular, we show that nonlinear sequence relationships that can be stably approximated by nonlinear RNNs must have an exponential decaying memory structure - a notion that can be made precise. This extends the previously identified curse of memory in linear RNNs into the general nonlinear setting, and quantifies the essential limitations of the RNN architecture for learning sequential relationships with long-term memory. Based on the analysis, we propose a principled reparameterization method to overcome the limitations. Our theoretical results are confirmed by numerical experiments. The code has been released in https://github.com/radarFudan/Curse-of-memory

We employ an inversion-based approach to examine CLIP models. Our examination reveals that inverting CLIP models results in the generation of images that exhibit semantic alignment with the specified target prompts. We leverage these inverted images to gain insights into various aspects of CLIP models, such as their ability to blend concepts and inclusion of gender biases. We notably observe instances of NSFW (Not Safe For Work) images during model inversion. This phenomenon occurs even for semantically innocuous prompts, like "a beautiful landscape," as well as for prompts involving the names of celebrities.

Neural models are usually adapted through changes in parameters shared among model components via fine-tuning, alignment-based training, and reinforcement learning. These changes have been found effective in short-term optimization. However, they result in long-term alterations in the model's base behavior. In this study, we introduce the concept of structural irreversibility as a characteristic of shared-parameter model adaptation. This concept refers to the intertwining of task-specific objectives with the representational identity of the model. We show that when parameters are directly mutated, the resulting model behaves divergently from the original model. This divergence cannot be reversed deterministically without an explicit parameter snapshot. We introduce reversible behavioral learning, in which model behaviors are structurally dissociated from identity parameters and can be deterministically unloaded through an explicit unload process. We also introduce the Recoverability Factor as a normalized measure of behavioral recoverability and provide additional diagnostics based on model divergence. Experiments show that reversible model adaptation achieves rollback within numerical precision, whereas shared-parameter mutation exhibits persistent post-reset divergence.

We address the challenges of precise image inversion and disentangled image editing in the context of few-step diffusion models. We introduce an encoder based iterative inversion technique. The inversion network is conditioned on the input image and the reconstructed image from the previous step, allowing for correction of the next reconstruction towards the input image. We demonstrate that disentangled controls can be easily achieved in the few-step diffusion model by conditioning on an (automatically generated) detailed text prompt. To manipulate the inverted image, we freeze the noise maps and modify one attribute in the text prompt (either manually or via instruction based editing driven by an LLM), resulting in the generation of a new image similar to the input image with only one attribute changed. It can further control the editing strength and accept instructive text prompt. Our approach facilitates realistic text-guided image edits in real-time, requiring only 8 number of functional evaluations (NFEs) in inversion (one-time cost) and 4 NFEs per edit. Our method is not only fast, but also significantly outperforms state-of-the-art multi-step diffusion editing techniques.

Invertible neural networks based on coupling flows (CF-INNs) have various machine learning applications such as image synthesis and representation learning. However, their desirable characteristics such as analytic invertibility come at the cost of restricting the functional forms. This poses a question on their representation power: are CF-INNs universal approximators for invertible functions? Without a universality, there could be a well-behaved invertible transformation that the CF-INN can never approximate, hence it would render the model class unreliable. We answer this question by showing a convenient criterion: a CF-INN is universal if its layers contain affine coupling and invertible linear functions as special cases. As its corollary, we can affirmatively resolve a previously unsolved problem: whether normalizing flow models based on affine coupling can be universal distributional approximators. In the course of proving the universality, we prove a general theorem to show the equivalence of the universality for certain diffeomorphism classes, a theoretical insight that is of interest by itself.

Text-driven inversion of generative models is a core paradigm for manipulating 2D or 3D content, unlocking numerous applications such as text-based editing, style transfer, or inverse problems. However, it relies on the assumption that generative models remain sensitive to natural language prompts. We demonstrate that for state-of-the-art native text-to-3D generative models, this assumption often collapses. We identify a critical failure mode where generation trajectories are drawn into latent ``sink traps'': regions where the model becomes insensitive to prompt modifications. In these regimes, changes to the input text fail to alter internal representations in a way that alters the output geometry. Crucially, we observe that this is not a limitation of the model's geometric expressivity; the same generative models possess the ability to produce a vast diversity of shapes but, as we demonstrate, become insensitive to out-of-distribution text guidance. We investigate this behavior by analyzing the sampling trajectories of the generative model, and find that complex geometries can still be represented and produced by leveraging the model's unconditional generative prior. This leads to a more robust framework for text-based 3D shape editing that bypasses latent sinks by decoupling a model's geometric representation power from its linguistic sensitivity. Our approach addresses the limitations of current 3D pipelines and enables high-fidelity semantic manipulation of out-of-distribution 3D shapes. Project webpage: https://daidedou.sorpi.fr/publication/beyondprompts

Graphical models are widely used in science to represent joint probability distributions with an underlying conditional dependence structure. The inverse problem of learning a discrete graphical model given i.i.d samples from its joint distribution can be solved with near-optimal sample complexity using a convex optimization method known as Generalized Regularized Interaction Screening Estimator (GRISE). But the computational cost of GRISE becomes prohibitive when the energy function of the true graphical model has higher-order terms. We introduce NeurISE, a neural net based algorithm for graphical model learning, to tackle this limitation of GRISE. We use neural nets as function approximators in an Interaction Screening objective function. The optimization of this objective then produces a neural-net representation for the conditionals of the graphical model. NeurISE algorithm is seen to be a better alternative to GRISE when the energy function of the true model has a high order with a high degree of symmetry. In these cases NeurISE is able to find the correct parsimonious representation for the conditionals without being fed any prior information about the true model. NeurISE can also be used to learn the underlying structure of the true model with some simple modifications to its training procedure. In addition, we also show a variant of NeurISE that can be used to learn a neural net representation for the full energy function of the true model.

Scaling up language models has been empirically shown to improve performance on a wide range of downstream tasks. However, if we were to observe worse performance as a function of scale ("inverse scaling") on certain tasks, this would indicate that scaling can also encourage behaviors that are misaligned with human preferences. The Inverse Scaling Prize (McKenzie et al. 2022) identified eleven such inverse scaling tasks, evaluated on models of up to 280B parameters and up to 500 zettaFLOPs of training compute. This paper takes a closer look at these inverse scaling tasks. We evaluate models of up to 540B parameters, trained on five times more compute than those evaluated in the Inverse Scaling Prize. With this increased range of model sizes and training compute, only four out of the eleven tasks remain inverse scaling. Six out of the eleven tasks exhibit "U-shaped scaling", where performance decreases up to a certain size, and then increases again up to the largest model evaluated (the one remaining task displays positive scaling). In addition, we find that 1-shot examples and chain-of-thought can help mitigate undesirable scaling patterns even further. U-shaped scaling suggests that the inverse scaling trend observed in McKenzie et al. (2022) may not continue to hold for larger models, which we attribute to the presence of distractor tasks that only sufficiently large models can avoid.

Stable diffusion models represent the state-of-the-art in data synthesis across diverse domains and hold transformative potential for applications in science and engineering, e.g., by facilitating the discovery of novel solutions and simulating systems that are computationally intractable to model explicitly. While there is increasing effort to incorporate physics-based constraints into generative models, existing techniques are either limited in their applicability to latent diffusion frameworks or lack the capability to strictly enforce domain-specific constraints. To address this limitation this paper proposes a novel integration of stable diffusion models with constrained optimization frameworks, enabling the generation of outputs satisfying stringent physical and functional requirements. The effectiveness of this approach is demonstrated through material design experiments requiring adherence to precise morphometric properties, challenging inverse design tasks involving the generation of materials inducing specific stress-strain responses, and copyright-constrained content generation tasks. All code has been released at https://github.com/RAISELab-atUVA/Constrained-Stable-Diffusion.

Conventional production workflow of high-precision mesh assets necessitates a cumbersome and laborious process of manual sculpting by specialized 3D artists/modelers. The recent years have witnessed remarkable advances in AI-empowered 3D content creation for generating plausible structures and intricate appearances from images or text prompts. However, synthesizing realistic surface details still poses great challenges, and enhancing the geometry fidelity of existing lower-quality 3D meshes (instead of image/text-to-3D generation) remains an open problem. In this paper, we introduce SuperCarver, a 3D geometry super-resolution pipeline for supplementing texture-consistent surface details onto a given coarse mesh. We start by rendering the original textured mesh into the image domain from multiple viewpoints. To achieve detail boosting, we construct a deterministic prior-guided normal diffusion model, which is fine-tuned on a carefully curated dataset of paired detail-lacking and detail-rich normal map renderings. To update mesh surfaces from potentially imperfect normal map predictions, we design a noise-resistant inverse rendering scheme through deformable distance field. Experiments demonstrate that our SuperCarver is capable of generating realistic and expressive surface details depicted by the actual texture appearance, making it a powerful tool to both upgrade historical low-quality 3D assets and reduce the workload of sculpting high-poly meshes.

Model merging aims to combine multiple fine-tuned models into a single set of weights that performs well across all source tasks. While prior work has shown that merging can approximate the performance of individual fine-tuned models for each task, it largely overlooks scenarios where models are compressed into low-rank representations, either through low-rank adaptation (LoRA) or post-training singular value decomposition (SVD). We first demonstrate that applying conventional merging methods to low-rank weights leads to severe performance degradation in the merged model. Motivated by this phenomenon, we propose a fundamentally different approach: instead of collapsing all adapters into one set of weights, we construct a compact basis (e.g., an equivalent of holding two or more models) from which original task-specific models can be recovered via linear combination. This reframes merging as generating a reconstruction-capable model space rather than producing a single merged model. Crucially, this allows us to ``revert'' to each individual model when needed, recognizing that no merged model can consistently outperform one specialized for its task. Building on this insight, we introduce our method, Reversible Model Merging (RMM), an efficient, data-free, and flexible method that provides a closed-form solution for selecting the optimal basis of model weights and task-specific coefficients for linear combination. Extensive experiments across diverse datasets and model scales demonstrate that RMM consistently outperforms existing merging approaches, preserving the performance of low-rank compressed models by a significant margin.

FOLD-RM is an explainable machine learning classification algorithm that uses training data to create a set of classification rules. In this paper we introduce CON-FOLD which extends FOLD-RM in several ways. CON-FOLD assigns probability-based confidence scores to rules learned for a classification task. This allows users to know how confident they should be in a prediction made by the model. We present a confidence-based pruning algorithm that uses the unique structure of FOLD-RM rules to efficiently prune rules and prevent overfitting. Furthermore, CON-FOLD enables the user to provide pre-existing knowledge in the form of logic program rules that are either (fixed) background knowledge or (modifiable) initial rule candidates. The paper describes our method in detail and reports on practical experiments. We demonstrate the performance of the algorithm on benchmark datasets from the UCI Machine Learning Repository. For that, we introduce a new metric, Inverse Brier Score, to evaluate the accuracy of the produced confidence scores. Finally we apply this extension to a real world example that requires explainability: marking of student responses to a short answer question from the Australian Physics Olympiad.

Inverse design refers to the problem of optimizing the input of an objective function in order to enact a target outcome. For many real-world engineering problems, the objective function takes the form of a simulator that predicts how the system state will evolve over time, and the design challenge is to optimize the initial conditions that lead to a target outcome. Recent developments in learned simulation have shown that graph neural networks (GNNs) can be used for accurate, efficient, differentiable estimation of simulator dynamics, and support high-quality design optimization with gradient- or sampling-based optimization procedures. However, optimizing designs from scratch requires many expensive model queries, and these procedures exhibit basic failures on either non-convex or high-dimensional problems.In this work, we show how denoising diffusion models (DDMs) can be used to solve inverse design problems efficiently and propose a particle sampling algorithm for further improving their efficiency. We perform experiments on a number of fluid dynamics design challenges, and find that our approach substantially reduces the number of calls to the simulator compared to standard techniques.

We present a probabilistic model for point cloud generation, which is fundamental for various 3D vision tasks such as shape completion, upsampling, synthesis and data augmentation. Inspired by the diffusion process in non-equilibrium thermodynamics, we view points in point clouds as particles in a thermodynamic system in contact with a heat bath, which diffuse from the original distribution to a noise distribution. Point cloud generation thus amounts to learning the reverse diffusion process that transforms the noise distribution to the distribution of a desired shape. Specifically, we propose to model the reverse diffusion process for point clouds as a Markov chain conditioned on certain shape latent. We derive the variational bound in closed form for training and provide implementations of the model. Experimental results demonstrate that our model achieves competitive performance in point cloud generation and auto-encoding. The code is available at https://github.com/luost26/diffusion-point-cloud.

RNA design aims to find a sequence that folds with highest probability into a designated target structure. However, certain structures are undesignable, meaning no sequence can fold into the target structure under the default (Turner) RNA folding model. Understanding the specific local structures (i.e., "motifs") that contribute to undesignability is crucial for refining RNA folding models and determining the limits of RNA designability. Despite its importance, this problem has received very little attention, and previous efforts are neither scalable nor interpretable. We develop a new theoretical framework for motif (un-)designability, and design scalable and interpretable algorithms to identify minimal undesignable motifs within a given RNA secondary structure. Our approach establishes motif undesignability by searching for rival motifs, rather than exhaustively enumerating all (partial) sequences that could potentially fold into the motif. Furthermore, we exploit rotational invariance in RNA structures to detect, group, and reuse equivalent motifs and to construct a database of unique minimal undesignable motifs. To achieve that, we propose a loop-pair graph representation for motifs and a recursive graph isomorphism algorithm for motif equivalence. Our algorithms successfully identify 24 unique minimal undesignable motifs among 18 undesignable puzzles from the Eterna100 benchmark. Surprisingly, we also find over 350 unique minimal undesignable motifs and 663 undesignable native structures in the ArchiveII dataset, drawn from a diverse set of RNA families. Our source code is available at https://github.com/shanry/RNA-Undesign and our web server is available at http://linearfold.org/motifs.

Text-to-image diffusion models offer powerful image editing capabilities. To edit real images, many methods rely on the inversion of the image into Gaussian noise. A common approach to invert an image is to gradually add noise to the image, where the noise is determined by reversing the sampling equation. This process has an inherent tradeoff between reconstruction and editability, limiting the editing of challenging images such as highly-detailed ones. Recognizing the reliance of text-to-image models inversion on a text condition, this work explores the importance of the condition choice. We show that a condition that precisely aligns with the input image significantly improves the inversion quality. Based on our findings, we introduce Tight Inversion, an inversion method that utilizes the most possible precise condition -- the input image itself. This tight condition narrows the distribution of the model's output and enhances both reconstruction and editability. We demonstrate the effectiveness of our approach when combined with existing inversion methods through extensive experiments, evaluating the reconstruction accuracy as well as the integration with various editing methods.

Generative models have recently shown great promise for accelerating the design and discovery of new functional materials. Conditional generation enhances this capacity by allowing inverse design, where specific desired properties can be requested during the generation process. However, conditioning of transformer-based approaches, in particular, is constrained by discrete tokenisation schemes and the risk of catastrophic forgetting during fine-tuning. This work introduces CrystaLLM-π (property injection), a conditional autoregressive framework that integrates continuous property representations directly into the transformer's attention mechanism. Two architectures, Property-Key-Value (PKV) Prefix attention and PKV Residual attention, are presented. These methods bypass inefficient sequence-level tokenisation and preserve foundational knowledge from unsupervised pre-training on Crystallographic Information Files (CIFs) as textual input. We establish the efficacy of these mechanisms through systematic robustness studies and evaluate the framework's versatility across two distinct tasks. First, for structure recovery, the model processes high-dimensional, heterogeneous X-ray diffraction patterns, achieving structural accuracy competitive with specialised models and demonstrating applications to experimental structure recovery and polymorph differentiation. Second, for materials discovery, the model is fine-tuned on a specialised photovoltaic dataset to generate novel, stable candidates validated by Density Functional Theory (DFT). It implicitly learns to target optimal band gap regions for high photovoltaic efficiency, demonstrating a capability to map complex structure-property relationships. CrystaLLM-π provides a unified, flexible, and computationally efficient framework for inverse materials design.

Inverse kinematics (IK) is a core operation in animation, robotics, and biomechanics: given Cartesian constraints, recover joint rotations under a known kinematic tree. In many real-time human avatar pipelines, the available signal per frame is a sparse set of tracked 3D joint positions, whereas animation systems require joint orientations to drive skinning. Recovering full orientations from positions is underconstrained, most notably because twist about bone axes is ambiguous, and classical IK solvers typically rely on iterative optimization that can be slow and sensitive to noisy inputs. We introduce IK-GAT, a lightweight graph-attention network that reconstructs full-body joint orientations from 3D joint positions in a single forward pass. The model performs message passing over the skeletal parent-child graph to exploit kinematic structure during rotation inference. To simplify learning, IK-GAT predicts rotations in a bone-aligned world-frame representation anchored to rest-pose bone frames. This parameterization makes the twist axis explicit and is exactly invertible to standard parent-relative local rotations given the kinematic tree and rest pose. The network uses a continuous 6D rotation representation and is trained with a geodesic loss on SO(3) together with an optional forward-kinematics consistency regularizer. IK-GAT produces animation-ready local rotations that can directly drive a rigged avatar or be converted to pose parameters of SMPL-like body models for real-time and online applications. With 374K parameters and over 650 FPS on CPU, IK-GAT outperforms VPoser-based per-frame iterative optimization without warm-start at significantly lower cost, and is robust to initial pose and input noise

A prevalent assumption in LLM agent deployment holds that more structured harnesses universally improve reliability, and that higher-capability models need proportionally less structural guidance -- together implying a monotone inverse relationship between model capability tier and optimal harness complexity. We test this hypothesis through a controlled 432-run experiment crossing six models across four capability tiers with three harness conditions (light, balanced, strict) on HEAT-24, a 24-task synthetic benchmark with git-based workspace verification. Our results refute the monotone inverse relationship on two fronts. First, for the frontier chat model evaluated (Gemini 2.5 Flash), increased harness verbosity lowers VTSR by 29-38 percentage points -- a harness-complexity paradox. Second, for the frontier reasoning model evaluated (Qwen3.5-122B, extended thinking enabled), strict harness achieves the highest VTSR (91.7%) and the lowest latency, the opposite of the prediction. Within the constrained tier, a 2B model (Gemma4:e2B) matches strong-open-tier stability at 91.7% across all harnesses. Because each tier is represented by a single model in this study, these results should be interpreted as model-specific observations; harness sensitivity appears non-monotone across the models evaluated, and depends critically on model type (chat vs. reasoning). We introduce a six-label failure taxonomy showing that format_violation dominates capable-model failures while wrong_file dominates low-capability failures, and we derive practical tier-aware harness selection guidelines.

Estimating the pose of an object from a monocular image is an inverse problem fundamental in computer vision. The ill-posed nature of this problem requires incorporating deformation priors to solve it. In practice, many materials do not perceptibly shrink or extend when manipulated, constituting a powerful and well-known prior. Mathematically, this translates to the preservation of the Riemannian metric. Neural networks offer the perfect playground to solve the surface reconstruction problem as they can approximate surfaces with arbitrary precision and allow the computation of differential geometry quantities. This paper presents an approach to inferring continuous deformable surfaces from a sequence of images, which is benchmarked against several techniques and obtains state-of-the-art performance without the need for offline training.

Computational RNA design tasks are often posed as inverse problems, where sequences are designed based on adopting a single desired secondary structure without considering 3D geometry and conformational diversity. We introduce gRNAde, a geometric RNA design pipeline operating on 3D RNA backbones to design sequences that explicitly account for structure and dynamics. Under the hood, gRNAde is a multi-state Graph Neural Network that generates candidate RNA sequences conditioned on one or more 3D backbone structures where the identities of the bases are unknown. On a single-state fixed backbone re-design benchmark of 14 RNA structures from the PDB identified by Das et al. [2010], gRNAde obtains higher native sequence recovery rates (56% on average) compared to Rosetta (45% on average), taking under a second to produce designs compared to the reported hours for Rosetta. We further demonstrate the utility of gRNAde on a new benchmark of multi-state design for structurally flexible RNAs, as well as zero-shot ranking of mutational fitness landscapes in a retrospective analysis of a recent ribozyme. Open source code: https://github.com/chaitjo/geometric-rna-design

Molecular Dynamics (MD) is a powerful computational microscope for probing protein functions. However, the need for fine-grained integration and the long timescales of biomolecular events make MD computationally expensive. To address this, several generative models have been proposed to generate surrogate trajectories at lower cost. Yet, these models typically learn a fixed-lag transition density, causing the training signal to be dominated by frequent but uninformative transitions. We introduce a new class of generative models, MSM Emulators, which instead learn to sample transitions across discrete states defined by an underlying Markov State Model (MSM). We instantiate this class with Markov Space Flow Matching (MarS-FM), whose sampling offers more than two orders of magnitude speedup compared to implicit- or explicit-solvent MD simulations. We benchmark Mars-FM ability to reproduce MD statistics through structural observables such as RMSD, radius of gyration, and secondary structure content. Our evaluation spans protein domains (up to 500 residues) with significant chemical and structural diversity, including unfolding events, and enforces strict sequence dissimilarity between training and test sets to assess generalization. Across all metrics, MarS-FM outperforms existing methods, often by a substantial margin.

Solving the inverse problem is the key step in evaluating the capacity of a physical model to describe real phenomena. In medical image computing, it aligns with the classical theme of image-based model personalization. Traditionally, a solution to the problem is obtained by performing either sampling or variational inference based methods. Both approaches aim to identify a set of free physical model parameters that results in a simulation best matching an empirical observation. When applied to brain tumor modeling, one of the instances of image-based model personalization in medical image computing, the overarching drawback of the methods is the time complexity for finding such a set. In a clinical setting with limited time between imaging and diagnosis or even intervention, this time complexity may prove critical. As the history of quantitative science is the history of compression, we align in this paper with the historical tendency and propose a method compressing complex traditional strategies for solving an inverse problem into a simple database query task. We evaluated different ways of performing the database query task assessing the trade-off between accuracy and execution time. On the exemplary task of brain tumor growth modeling, we prove that the proposed method achieves one order speed-up compared to existing approaches for solving the inverse problem. The resulting compute time offers critical means for relying on more complex and, hence, realistic models, for integrating image preprocessing and inverse modeling even deeper, or for implementing the current model into a clinical workflow.

Diffusion models have been successful on a range of conditional generation tasks including molecular design and text-to-image generation. However, these achievements have primarily depended on task-specific conditional training or error-prone heuristic approximations. Ideally, a conditional generation method should provide exact samples for a broad range of conditional distributions without requiring task-specific training. To this end, we introduce the Twisted Diffusion Sampler, or TDS. TDS is a sequential Monte Carlo (SMC) algorithm that targets the conditional distributions of diffusion models through simulating a set of weighted particles. The main idea is to use twisting, an SMC technique that enjoys good computational efficiency, to incorporate heuristic approximations without compromising asymptotic exactness. We first find in simulation and in conditional image generation tasks that TDS provides a computational statistical trade-off, yielding more accurate approximations with many particles but with empirical improvements over heuristics with as few as two particles. We then turn to motif-scaffolding, a core task in protein design, using a TDS extension to Riemannian diffusion models. On benchmark test cases, TDS allows flexible conditioning criteria and often outperforms the state of the art.

Large language models generate code one token at a time. Their autoregressive generation process lacks the feedback of observing the program's output. Training LLMs to suggest edits directly can be challenging due to the scarcity of rich edit data. To address these problems, we propose neural diffusion models that operate on syntax trees of any context-free grammar. Similar to image diffusion models, our method also inverts ``noise'' applied to syntax trees. Rather than generating code sequentially, we iteratively edit it while preserving syntactic validity, which makes it easy to combine this neural model with search. We apply our approach to inverse graphics tasks, where our model learns to convert images into programs that produce those images. Combined with search, our model is able to write graphics programs, see the execution result, and debug them to meet the required specifications. We additionally show how our system can write graphics programs for hand-drawn sketches.

It is widely believed that the success of deep convolutional networks is based on progressively discarding uninformative variability about the input with respect to the problem at hand. This is supported empirically by the difficulty of recovering images from their hidden representations, in most commonly used network architectures. In this paper we show via a one-to-one mapping that this loss of information is not a necessary condition to learn representations that generalize well on complicated problems, such as ImageNet. Via a cascade of homeomorphic layers, we build the i-RevNet, a network that can be fully inverted up to the final projection onto the classes, i.e. no information is discarded. Building an invertible architecture is difficult, for one, because the local inversion is ill-conditioned, we overcome this by providing an explicit inverse. An analysis of i-RevNets learned representations suggests an alternative explanation for the success of deep networks by a progressive contraction and linear separation with depth. To shed light on the nature of the model learned by the i-RevNet we reconstruct linear interpolations between natural image representations.

Variational inference using the reparameterization trick has enabled large-scale approximate Bayesian inference in complex probabilistic models, leveraging stochastic optimization to sidestep intractable expectations. The reparameterization trick is applicable when we can simulate a random variable by applying a differentiable deterministic function on an auxiliary random variable whose distribution is fixed. For many distributions of interest (such as the gamma or Dirichlet), simulation of random variables relies on acceptance-rejection sampling. The discontinuity introduced by the accept-reject step means that standard reparameterization tricks are not applicable. We propose a new method that lets us leverage reparameterization gradients even when variables are outputs of a acceptance-rejection sampling algorithm. Our approach enables reparameterization on a larger class of variational distributions. In several studies of real and synthetic data, we show that the variance of the estimator of the gradient is significantly lower than other state-of-the-art methods. This leads to faster convergence of stochastic gradient variational inference.

This paper demonstrates that language models are strong structure-based protein designers. We present LM-Design, a generic approach to reprogramming sequence-based protein language models (pLMs), that have learned massive sequential evolutionary knowledge from the universe of natural protein sequences, to acquire an immediate capability to design preferable protein sequences for given folds. We conduct a structural surgery on pLMs, where a lightweight structural adapter is implanted into pLMs and endows it with structural awareness. During inference, iterative refinement is performed to effectively optimize the generated protein sequences. Experiments show that LM-Design improves the state-of-the-art results by a large margin, leading to up to 4% to 12% accuracy gains in sequence recovery (e.g., 55.65%/56.63% on CATH 4.2/4.3 single-chain benchmarks, and >60% when designing protein complexes). We provide extensive and in-depth analyses, which verify that LM-Design can (1) indeed leverage both structural and sequential knowledge to accurately handle structurally non-deterministic regions, (2) benefit from scaling data and model size, and (3) generalize to other proteins (e.g., antibodies and de novo proteins)

Generative models trained on internet-scale data are capable of generating novel and realistic texts, images, and videos. A natural next question is whether these models can advance science, for example by generating novel stable materials. Traditionally, models with explicit structures (e.g., graphs) have been used in modeling structural relationships in scientific data (e.g., atoms and bonds in crystals), but generating structures can be difficult to scale to large and complex systems. Another challenge in generating materials is the mismatch between standard generative modeling metrics and downstream applications. For instance, common metrics such as the reconstruction error do not correlate well with the downstream goal of discovering stable materials. In this work, we tackle the scalability challenge by developing a unified crystal representation that can represent any crystal structure (UniMat), followed by training a diffusion probabilistic model on these UniMat representations. Our empirical results suggest that despite the lack of explicit structure modeling, UniMat can generate high fidelity crystal structures from larger and more complex chemical systems, outperforming previous graph-based approaches under various generative modeling metrics. To better connect the generation quality of materials to downstream applications, such as discovering novel stable materials, we propose additional metrics for evaluating generative models of materials, including per-composition formation energy and stability with respect to convex hulls through decomposition energy from Density Function Theory (DFT). Lastly, we show that conditional generation with UniMat can scale to previously established crystal datasets with up to millions of crystals structures, outperforming random structure search (the current leading method for structure discovery) in discovering new stable materials.

Recent advancements in text-guided diffusion models have unlocked powerful image manipulation capabilities. However, applying these methods to real images necessitates the inversion of the images into the domain of the pretrained diffusion model. Achieving faithful inversion remains a challenge, particularly for more recent models trained to generate images with a small number of denoising steps. In this work, we introduce an inversion method with a high quality-to-operation ratio, enhancing reconstruction accuracy without increasing the number of operations. Building on reversing the diffusion sampling process, our method employs an iterative renoising mechanism at each inversion sampling step. This mechanism refines the approximation of a predicted point along the forward diffusion trajectory, by iteratively applying the pretrained diffusion model, and averaging these predictions. We evaluate the performance of our ReNoise technique using various sampling algorithms and models, including recent accelerated diffusion models. Through comprehensive evaluations and comparisons, we show its effectiveness in terms of both accuracy and speed. Furthermore, we confirm that our method preserves editability by demonstrating text-driven image editing on real images.

Machine learning-based unfolding has enabled unbinned and high-dimensional differential cross section measurements. Two main approaches have emerged in this research area: one based on discriminative models and one based on generative models. The main advantage of discriminative models is that they learn a small correction to a starting simulation while generative models scale better to regions of phase space with little data. We propose to use Schroedinger Bridges and diffusion models to create SBUnfold, an unfolding approach that combines the strengths of both discriminative and generative models. The key feature of SBUnfold is that its generative model maps one set of events into another without having to go through a known probability density as is the case for normalizing flows and standard diffusion models. We show that SBUnfold achieves excellent performance compared to state of the art methods on a synthetic Z+jets dataset.

Discrete diffusion models have achieved success in tasks like image generation and masked language modeling but face limitations in controlled content editing. We introduce DICE (Discrete Inversion for Controllable Editing), the first approach to enable precise inversion for discrete diffusion models, including multinomial diffusion and masked generative models. By recording noise sequences and masking patterns during the reverse diffusion process, DICE enables accurate reconstruction and flexible editing of discrete data without the need for predefined masks or attention manipulation. We demonstrate the effectiveness of DICE across both image and text domains, evaluating it on models such as VQ-Diffusion, Paella, and RoBERTa. Our results show that DICE preserves high data fidelity while enhancing editing capabilities, offering new opportunities for fine-grained content manipulation in discrete spaces. For project webpage, see https://hexiaoxiao-cs.github.io/DICE/.

The use of deep unfolding networks in compressive sensing (CS) has seen wide success as they provide both simplicity and interpretability. However, since most deep unfolding networks are iterative, this incurs significant redundancies in the network. In this work, we propose a novel recursion-based framework to enhance the efficiency of deep unfolding models. First, recursions are used to effectively eliminate the redundancies in deep unfolding networks. Secondly, we randomize the number of recursions during training to decrease the overall training time. Finally, to effectively utilize the power of recursions, we introduce a learnable unit to modulate the features of the model based on both the total number of iterations and the current iteration index. To evaluate the proposed framework, we apply it to both ISTA-Net+ and COAST. Extensive testing shows that our proposed framework allows the network to cut down as much as 75% of its learnable parameters while mostly maintaining its performance, and at the same time, it cuts around 21% and 42% from the training time for ISTA-Net+ and COAST respectively. Moreover, when presented with a limited training dataset, the recursive models match or even outperform their respective non-recursive baseline. Codes and pretrained models are available at https://github.com/Rawwad-Alhejaili/Recursions-Are-All-You-Need .

Understanding and modeling lighting effects are fundamental tasks in computer vision and graphics. Classic physically-based rendering (PBR) accurately simulates the light transport, but relies on precise scene representations--explicit 3D geometry, high-quality material properties, and lighting conditions--that are often impractical to obtain in real-world scenarios. Therefore, we introduce DiffusionRenderer, a neural approach that addresses the dual problem of inverse and forward rendering within a holistic framework. Leveraging powerful video diffusion model priors, the inverse rendering model accurately estimates G-buffers from real-world videos, providing an interface for image editing tasks, and training data for the rendering model. Conversely, our rendering model generates photorealistic images from G-buffers without explicit light transport simulation. Experiments demonstrate that DiffusionRenderer effectively approximates inverse and forwards rendering, consistently outperforming the state-of-the-art. Our model enables practical applications from a single video input--including relighting, material editing, and realistic object insertion.

The discovery of novel materials and functional molecules can help to solve some of society's most urgent challenges, ranging from efficient energy harvesting and storage to uncovering novel pharmaceutical drug candidates. Traditionally matter engineering -- generally denoted as inverse design -- was based massively on human intuition and high-throughput virtual screening. The last few years have seen the emergence of significant interest in computer-inspired designs based on evolutionary or deep learning methods. The major challenge here is that the standard strings molecular representation SMILES shows substantial weaknesses in that task because large fractions of strings do not correspond to valid molecules. Here, we solve this problem at a fundamental level and introduce SELFIES (SELF-referencIng Embedded Strings), a string-based representation of molecules which is 100\% robust. Every SELFIES string corresponds to a valid molecule, and SELFIES can represent every molecule. SELFIES can be directly applied in arbitrary machine learning models without the adaptation of the models; each of the generated molecule candidates is valid. In our experiments, the model's internal memory stores two orders of magnitude more diverse molecules than a similar test with SMILES. Furthermore, as all molecules are valid, it allows for explanation and interpretation of the internal working of the generative models.

Discrete diffusion models have emerged as powerful frameworks for generating structured categorical data. However, efficiently sampling from reward-tilted distributions remains a fundamental challenge. While Twisted Sequential Monte Carlo (SMC) offers asymptotic exactness for this task, estimating the optimal twist function in discrete state spaces necessitates costly Monte Carlo approximations, resulting a severe computational bottleneck at inference. To overcome this limitation, we introduce Contrastive Distribution Matching (CDM), a novel framework that amortizes the cost of SMC inference by learning a parameterized twist function via positive and negative samples. For efficient training, we reformulate the gradient estimator to leverage the closed-form forward kernels of discrete diffusion models. In practice, evaluating our learned twist function incurs less than 5% additional computational overhead compared to a single forward pass of the base model. Through extensive empirical evaluations, we demonstrate that CDM consistently outperforms existing baselines under matched wall-clock time. We validate the effectiveness and versatility of our approach across a diverse range of applications, including toxic text generation, regulatory DNA sequence design, protein designability, and diffusion large language model alignment.

Inverse molecular design with diffusion models holds great potential for advancements in material and drug discovery. Despite success in unconditional molecular generation, integrating multiple properties such as synthetic score and gas permeability as condition constraints into diffusion models remains unexplored. We present the Graph Diffusion Transformer (Graph DiT) for multi-conditional molecular generation. Graph DiT integrates an encoder to learn numerical and categorical property representations with the Transformer-based denoiser. Unlike previous graph diffusion models that add noise separately on the atoms and bonds in the forward diffusion process, Graph DiT is trained with a novel graph-dependent noise model for accurate estimation of graph-related noise in molecules. We extensively validate Graph DiT for multi-conditional polymer and small molecule generation. Results demonstrate the superiority of Graph DiT across nine metrics from distribution learning to condition control for molecular properties. A polymer inverse design task for gas separation with feedback from domain experts further demonstrates its practical utility.

We propose using Normalizing Flows as a trainable kernel within the molecular dynamics update of Hamiltonian Monte Carlo (HMC). By learning (invertible) transformations that simplify our dynamics, we can outperform traditional methods at generating independent configurations. We show that, using a carefully constructed network architecture, our approach can be easily scaled to large lattice volumes with minimal retraining effort. The source code for our implementation is publicly available online at https://github.com/nftqcd/fthmc.

We propose a novel hierarchical Bayesian model for learning with a large (possibly infinite) number of tasks/episodes, which suits well the few-shot meta learning problem. We consider episode-wise random variables to model episode-specific target generative processes, where these local random variables are governed by a higher-level global random variate. The global variable helps memorize the important information from historic episodes while controlling how much the model needs to be adapted to new episodes in a principled Bayesian manner. Within our model framework, the prediction on a novel episode/task can be seen as a Bayesian inference problem. However, a main obstacle in learning with a large/infinite number of local random variables in online nature, is that one is not allowed to store the posterior distribution of the current local random variable for frequent future updates, typical in conventional variational inference. We need to be able to treat each local variable as a one-time iterate in the optimization. We propose a Normal-Inverse-Wishart model, for which we show that this one-time iterate optimization becomes feasible due to the approximate closed-form solutions for the local posterior distributions. The resulting algorithm is more attractive than the MAML in that it is not required to maintain computational graphs for the whole gradient optimization steps per episode. Our approach is also different from existing Bayesian meta learning methods in that unlike dealing with a single random variable for the whole episodes, our approach has a hierarchical structure that allows one-time episodic optimization, desirable for principled Bayesian learning with many/infinite tasks. The code is available at https://github.com/minyoungkim21/niwmeta.

Collecting high-quality preference datasets for reinforcement learning from human feedback (RLHF) is resource-intensive and challenging. As a result, researchers often train reward models on extensive offline datasets which aggregate diverse generation sources and scoring/alignment policies. We hypothesize that this aggregation has an averaging effect on reward model scores, which limits signal and impairs the alignment process. Inspired by the field of inverse RL, we define the 'inverse alignment problem' in language model training, where our objective is to optimize the critic's reward for a fixed actor and a fixed offline preference dataset. We hypothesize that solving the inverse alignment problem will improve reward model quality by providing clearer feedback on the policy's current behavior. To that end, we investigate whether repeatedly fine-tuning a reward model on subsets of the offline preference dataset aligned with a periodically frozen policy during RLHF improves upon vanilla RLHF. Our empirical results demonstrate that this approach facilitates superior alignment and faster convergence compared to using an unaligned or out-of-distribution reward model relative to the LLM policy.

Embedding inversion, i.e., reconstructing text given its embedding and black-box access to the embedding encoder, is a fundamental problem in both NLP and security. From the NLP perspective, it helps determine how much semantic information about the input is retained in the embedding. From the security perspective, it measures how much information is leaked by vector databases and embedding-based retrieval systems. State-of-the-art methods for embedding inversion, such as vec2text, have high accuracy but require (a) training a separate model for each embedding, and (b) a large number of queries to the corresponding encoder. We design, implement, and evaluate ZSInvert, a zero-shot inversion method based on the recently proposed adversarial decoding technique. ZSInvert is fast, query-efficient, and can be used for any text embedding without training an embedding-specific inversion model. We measure the effectiveness of ZSInvert on several embeddings and demonstrate that it recovers key semantic information about the corresponding texts.

Recent advancements in diffusion models (DMs) have been propelled by alignment methods that post-train models to better conform to human preferences. However, these approaches typically require computation-intensive training of a base model and a reward model, which not only incurs substantial computational overhead but may also compromise model accuracy and training efficiency. To address these limitations, we propose Inversion-DPO, a novel alignment framework that circumvents reward modeling by reformulating Direct Preference Optimization (DPO) with DDIM inversion for DMs. Our method conducts intractable posterior sampling in Diffusion-DPO with the deterministic inversion from winning and losing samples to noise and thus derive a new post-training paradigm. This paradigm eliminates the need for auxiliary reward models or inaccurate appromixation, significantly enhancing both precision and efficiency of training. We apply Inversion-DPO to a basic task of text-to-image generation and a challenging task of compositional image generation. Extensive experiments show substantial performance improvements achieved by Inversion-DPO compared to existing post-training methods and highlight the ability of the trained generative models to generate high-fidelity compositionally coherent images. For the post-training of compostitional image geneation, we curate a paired dataset consisting of 11,140 images with complex structural annotations and comprehensive scores, designed to enhance the compositional capabilities of generative models. Inversion-DPO explores a new avenue for efficient, high-precision alignment in diffusion models, advancing their applicability to complex realistic generation tasks. Our code is available at https://github.com/MIGHTYEZ/Inversion-DPO

In this technical note, we study the problem of inverse permutation learning in decoder-only transformers. Given a permutation and a string to which that permutation has been applied, the model is tasked with producing the original (``canonical'') string. We argue that this task models a natural robustness property across a variety of reasoning tasks, including long-context retrieval, multiple choice QA and in-context learning. Our primary contribution is an impossibility result: we show that an arbitrary depth, decoder-only transformer cannot learn this task. This result concerns the expressive capacity of decoder-only transformer models and is agnostic to training dynamics or sample complexity. We give a pair of alternative constructions under which inverse permutation learning is feasible. The first of these highlights the fundamental role of the causal attention mask, and reveals a gap between the expressivity of encoder-decoder transformers and the more popular decoder-only architecture. The latter result is more surprising: we show that simply padding the input with ``scratch tokens" yields a construction under which inverse permutation learning is possible. We conjecture that this may suggest an alternative mechanism by which chain-of-thought prompting or, more generally, intermediate ``thinking'' tokens can enable reasoning in large language models, even when these tokens encode no meaningful semantic information (e.g., the results of intermediate computations).

Through evolution, nature has presented a set of remarkable protein materials, including elastins, silks, keratins and collagens with superior mechanical performances that play crucial roles in mechanobiology. However, going beyond natural designs to discover proteins that meet specified mechanical properties remains challenging. Here we report a generative model that predicts protein designs to meet complex nonlinear mechanical property-design objectives. Our model leverages deep knowledge on protein sequences from a pre-trained protein language model and maps mechanical unfolding responses to create novel proteins. Via full-atom molecular simulations for direct validation, we demonstrate that the designed proteins are novel, and fulfill the targeted mechanical properties, including unfolding energy and mechanical strength, as well as the detailed unfolding force-separation curves. Our model offers rapid pathways to explore the enormous mechanobiological protein sequence space unconstrained by biological synthesis, using mechanical features as target to enable the discovery of protein materials with superior mechanical properties.

Metamaterials with functional responses can exhibit varying properties under different conditions (e.g., wave-based responses or deformation-induced property variation). This work addresses the rapid inverse design of such metamaterials to meet target qualitative functional behaviors, a challenge due to its intractability and non-unique solutions. Unlike data-intensive and non-interpretable deep-learning-based methods, we propose the Random-forest-based Interpretable Generative Inverse Design (RIGID), a single-shot inverse design method for fast generation of metamaterial designs with on-demand functional behaviors. RIGID leverages the interpretability of a random forest-based "designrightarrowresponse" forward model, eliminating the need for a more complex "responserightarrowdesign" inverse model. Based on the likelihood of target satisfaction derived from the trained random forest, one can sample a desired number of design solutions using Markov chain Monte Carlo methods. We validate RIGID on acoustic and optical metamaterial design problems, each with fewer than 250 training samples. Compared to the genetic algorithm-based design generation approach, RIGID generates satisfactory solutions that cover a broader range of the design space, allowing for better consideration of additional figures of merit beyond target satisfaction. This work offers a new perspective on solving on-demand inverse design problems, showcasing the potential for incorporating interpretable machine learning into generative design under small data constraints.

Evaluating natural language generation (NLG) systems is challenging due to the diversity of valid outputs. While human evaluation is the gold standard, it suffers from inconsistencies, lack of standardisation, and demographic biases, limiting reproducibility. LLM-based evaluation offers a scalable alternative but is highly sensitive to prompt design, where small variations can lead to significant discrepancies. In this work, we propose an inversion learning method that learns effective reverse mappings from model outputs back to their input instructions, enabling the automatic generation of highly effective, model-specific evaluation prompts. Our method requires only a single evaluation sample and eliminates the need for time-consuming manual prompt engineering, thereby improving both efficiency and robustness. Our work contributes toward a new direction for more robust and efficient LLM-based evaluation.

Inverse materials design starts from target functionality and searches for structures that can realize it. Its value in closed-loop discovery depends not only on prediction performance, but also on whether expensive first-principles results are independently validated, provenance-recorded, and admitted as feedback only when evidence is sufficient. This is especially important for composite properties such as carrier mobility, where a final scalar value hides intermediate quantities, fit quality, convergence history, and workflow assumptions. Here we present InvDesMobility, a reliability-gated first-principles feedback framework that integrates multi-agent automated DFT, evidence stratification, generative structure proposal, acquisition ranking, and auditable release. Using 516 2DMatPedia-derived candidates, the workflow produced 280 QC-passed materials and 573 retained carrier-direction seed channels after channel-level reliability gating. These records were split into two feedback objects: relaxed structures updated the generative model, while retained mobility channels trained the acquisition model and set validation priority. Over multiple iterations, InvDesMobility screened 2.4 x 10^6 structures, submitted 102 candidates for DFT validation, and retained 86 reliability-gated generated channels across 41 formulas. Overall, the main contribution is not a fixed list of high-mobility materials, but a transferable feedback contract that makes closed-loop inverse design both useful and auditable when learning from expensive calculated properties. All source data, retained feedback records, and workflows are available at https://github.com/DreamLufei/invDesMobility, with an accompanying evidence website at https://dreamlufei.github.io/invDesMobility/.

Standard evaluation protocols reveal a counterintuitive phenomenon: on 7.7% of benchmark problems spanning five datasets, larger language models underperform smaller ones by 28.4 percentage points despite 10-100x more parameters. Through systematic evaluation of 31 models (0.5B-405B parameters) across 1,485 problems, we identify the mechanism as spontaneous scale-dependent verbosity that introduces errors through overelaboration. Causal intervention experiments demonstrate this reflects correctable prompt design rather than fundamental capability limitations. Constraining large models to produce brief responses improves accuracy by 26 percentage points and reduces performance gaps by up to two-thirds. Most critically, brevity constraints completely reverse performance hierarchies on mathematical reasoning and scientific knowledge benchmarks, with large models achieving 7.7-15.9 percentage point advantages over small models -- direct inversions of the original gaps. These reversals prove large models possess superior latent capabilities that universal prompting masks. We validate findings through three independent contamination tests and demonstrate inverse scaling operates continuously across the full parameter spectrum, with dataset-specific optimal scales ranging from 0.5B to 3.0B parameters. Our results establish that maximizing large model performance requires scale-aware prompt engineering rather than universal evaluation protocols, with immediate implications for deployment: prompt adaptation simultaneously improves accuracy and reduces computational costs.

Efficiently approximating local curvature information of the loss function is a key tool for optimization and compression of deep neural networks. Yet, most existing methods to approximate second-order information have high computational or storage costs, which can limit their practicality. In this work, we investigate matrix-free, linear-time approaches for estimating Inverse-Hessian Vector Products (IHVPs) for the case when the Hessian can be approximated as a sum of rank-one matrices, as in the classic approximation of the Hessian by the empirical Fisher matrix. We propose two new algorithms as part of a framework called M-FAC: the first algorithm is tailored towards network compression and can compute the IHVP for dimension d, if the Hessian is given as a sum of m rank-one matrices, using O(dm^2) precomputation, O(dm) cost for computing the IHVP, and query cost O(m) for any single element of the inverse Hessian. The second algorithm targets an optimization setting, where we wish to compute the product between the inverse Hessian, estimated over a sliding window of optimization steps, and a given gradient direction, as required for preconditioned SGD. We give an algorithm with cost O(dm + m^2) for computing the IHVP and O(dm + m^3) for adding or removing any gradient from the sliding window. These two algorithms yield state-of-the-art results for network pruning and optimization with lower computational overhead relative to existing second-order methods. Implementations are available at [9] and [17].

We introduce a theoretical framework for diffusion-based image editing by formulating it as a reverse-time bridge modeling problem. This approach modifies the backward process of a pretrained diffusion model to construct a bridge that converges to an implicit distribution associated with the editing target at time 0. Building on this framework, we propose h-Edit, a novel editing method that utilizes Doob's h-transform and Langevin Monte Carlo to decompose the update of an intermediate edited sample into two components: a "reconstruction" term and an "editing" term. This decomposition provides flexibility, allowing the reconstruction term to be computed via existing inversion techniques and enabling the combination of multiple editing terms to handle complex editing tasks. To our knowledge, h-Edit is the first training-free method capable of performing simultaneous text-guided and reward-model-based editing. Extensive experiments, both quantitative and qualitative, show that h-Edit outperforms state-of-the-art baselines in terms of editing effectiveness and faithfulness. Our source code is available at https://github.com/nktoan/h-edit.

While deep learning has revolutionized the prediction of rigid protein structures, modelling the conformational ensembles of Intrinsically Disordered Proteins (IDPs) remains a key frontier. Current AI paradigms present a trade-off: Protein Language Models (PLMs) capture evolutionary statistics but lack explicit physical grounding, while generative models trained to model full ensembles are computationally expensive. In this work we critically assess these limits and propose a path forward. We introduce GeoGraph, a simulation-informed surrogate trained to predict ensemble-averaged statistics of residue-residue contact-map topology directly from sequence. By featurizing coarse-grained molecular dynamics simulations into residue- and sequence-level graph descriptors, we create a robust and information-rich learning target. Our evaluation demonstrates that this approach yields representations that are more predictive of key biophysical properties than existing methods.

The design of fusion devices is typically based on computationally expensive simulations. This can be alleviated using high aspect ratio models that employ a reduced number of free parameters, especially in the case of stellarator optimization where non-axisymmetric magnetic fields with a large parameter space are optimized to satisfy certain performance criteria. However, optimization is still required to find configurations with properties such as low elongation, high rotational transform, finite plasma beta, and good fast particle confinement. In this work, we train a machine learning model to construct configurations with favorable confinement properties by finding a solution to the inverse design problem, that is, obtaining a set of model input parameters for given desired properties. Since the solution of the inverse problem is non-unique, a probabilistic approach, based on mixture density networks, is used. It is shown that optimized configurations can be generated reliably using this method.

Large language models (LLMs) trained with Reinforcement Learning from Human Feedback (RLHF) have demonstrated remarkable capabilities, but their underlying reward functions and decision-making processes remain opaque. This paper introduces a novel approach to interpreting LLMs by applying inverse reinforcement learning (IRL) to recover their implicit reward functions. We conduct experiments on toxicity-aligned LLMs of varying sizes, extracting reward models that achieve up to 80.40% accuracy in predicting human preferences. Our analysis reveals key insights into the non-identifiability of reward functions, the relationship between model size and interpretability, and potential pitfalls in the RLHF process. We demonstrate that IRL-derived reward models can be used to fine-tune new LLMs, resulting in comparable or improved performance on toxicity benchmarks. This work provides a new lens for understanding and improving LLM alignment, with implications for the responsible development and deployment of these powerful systems.

Diffusion model-based inverse problem solvers have shown impressive performance, but are limited in speed, mostly as they require reverse diffusion sampling starting from noise. Several recent works have tried to alleviate this problem by building a diffusion process, directly bridging the clean and the corrupted for specific inverse problems. In this paper, we first unify these existing works under the name Direct Diffusion Bridges (DDB), showing that while motivated by different theories, the resulting algorithms only differ in the choice of parameters. Then, we highlight a critical limitation of the current DDB framework, namely that it does not ensure data consistency. To address this problem, we propose a modified inference procedure that imposes data consistency without the need for fine-tuning. We term the resulting method data Consistent DDB (CDDB), which outperforms its inconsistent counterpart in terms of both perception and distortion metrics, thereby effectively pushing the Pareto-frontier toward the optimum. Our proposed method achieves state-of-the-art results on both evaluation criteria, showcasing its superiority over existing methods.

We study the implications of the modeling choice to use a graph, instead of a hypergraph, to represent real-world interconnected systems whose constituent relationships are of higher order by nature. Such a modeling choice typically involves an underlying projection process that maps the original hypergraph onto a graph, and is common in graph-based analysis. While hypergraph projection can potentially lead to loss of higher-order relations, there exists very limited studies on the consequences of doing so, as well as its remediation. This work fills this gap by doing two things: (1) we develop analysis based on graph and set theory, showing two ubiquitous patterns of hyperedges that are root to structural information loss in all hypergraph projections; we also quantify the combinatorial impossibility of recovering the lost higher-order structures if no extra help is provided; (2) we still seek to recover the lost higher-order structures in hypergraph projection, and in light of (1)'s findings we propose to relax the problem into a learning-based setting. Under this setting, we develop a learning-based hypergraph reconstruction method based on an important statistic of hyperedge distributions that we find. Our reconstruction method is evaluated on 8 real-world datasets under different settings, and exhibits consistently good performance. We also demonstrate benefits of the reconstructed hypergraphs via use cases of protein rankings and link predictions.

A central problem in machine learning involves modeling complex data-sets using highly flexible families of probability distributions in which learning, sampling, inference, and evaluation are still analytically or computationally tractable. Here, we develop an approach that simultaneously achieves both flexibility and tractability. The essential idea, inspired by non-equilibrium statistical physics, is to systematically and slowly destroy structure in a data distribution through an iterative forward diffusion process. We then learn a reverse diffusion process that restores structure in data, yielding a highly flexible and tractable generative model of the data. This approach allows us to rapidly learn, sample from, and evaluate probabilities in deep generative models with thousands of layers or time steps, as well as to compute conditional and posterior probabilities under the learned model. We additionally release an open source reference implementation of the algorithm.

The majority of language model training builds on imitation learning. It covers pretraining, supervised fine-tuning, and affects the starting conditions for reinforcement learning from human feedback (RLHF). The simplicity and scalability of maximum likelihood estimation (MLE) for next token prediction led to its role as predominant paradigm. However, the broader field of imitation learning can more effectively utilize the sequential structure underlying autoregressive generation. We focus on investigating the inverse reinforcement learning (IRL) perspective to imitation, extracting rewards and directly optimizing sequences instead of individual token likelihoods and evaluate its benefits for fine-tuning large language models. We provide a new angle, reformulating inverse soft-Q-learning as a temporal difference regularized extension of MLE. This creates a principled connection between MLE and IRL and allows trading off added complexity with increased performance and diversity of generations in the supervised fine-tuning (SFT) setting. We find clear advantages for IRL-based imitation, in particular for retaining diversity while maximizing task performance, rendering IRL a strong alternative on fixed SFT datasets even without online data generation. Our analysis of IRL-extracted reward functions further indicates benefits for more robust reward functions via tighter integration of supervised and preference-based LLM post-training.

The success of deep learning is due in large part to our ability to solve certain massive non-convex optimization problems with relative ease. Though non-convex optimization is NP-hard, simple algorithms -- often variants of stochastic gradient descent -- exhibit surprising effectiveness in fitting large neural networks in practice. We argue that neural network loss landscapes often contain (nearly) a single basin after accounting for all possible permutation symmetries of hidden units a la Entezari et al. 2021. We introduce three algorithms to permute the units of one model to bring them into alignment with a reference model in order to merge the two models in weight space. This transformation produces a functionally equivalent set of weights that lie in an approximately convex basin near the reference model. Experimentally, we demonstrate the single basin phenomenon across a variety of model architectures and datasets, including the first (to our knowledge) demonstration of zero-barrier linear mode connectivity between independently trained ResNet models on CIFAR-10. Additionally, we identify intriguing phenomena relating model width and training time to mode connectivity. Finally, we discuss shortcomings of the linear mode connectivity hypothesis, including a counterexample to the single basin theory.

We introduce Power Bundle Adjustment as an expansion type algorithm for solving large-scale bundle adjustment problems. It is based on the power series expansion of the inverse Schur complement and constitutes a new family of solvers that we call inverse expansion methods. We theoretically justify the use of power series and we prove the convergence of our approach. Using the real-world BAL dataset we show that the proposed solver challenges the state-of-the-art iterative methods and significantly accelerates the solution of the normal equation, even for reaching a very high accuracy. This easy-to-implement solver can also complement a recently presented distributed bundle adjustment framework. We demonstrate that employing the proposed Power Bundle Adjustment as a sub-problem solver significantly improves speed and accuracy of the distributed optimization.

We introduce a theoretical framework for differentiable surface evolution that allows discrete topology changes through the use of topological derivatives for variational optimization of image functionals. While prior methods for inverse rendering of geometry rely on silhouette gradients for topology changes, such signals are sparse. In contrast, our theory derives topological derivatives that relate the introduction of vanishing holes and phases to changes in image intensity. As a result, we enable differentiable shape perturbations in the form of hole or phase nucleation. We validate the proposed theory with optimization of closed curves in 2D and surfaces in 3D to lend insights into limitations of current methods and enable improved applications such as image vectorization, vector-graphics generation from text prompts, single-image reconstruction of shape ambigrams and multi-view 3D reconstruction.

The recent work CLIPA presents an inverse scaling law for CLIP training -- whereby the larger the image/text encoders used, the shorter the sequence length of image/text tokens that can be applied in training. This finding enables us to train high-performance CLIP models with significantly reduced computations. Building upon this work, we hereby present CLIPA-v2 with two key contributions. Technically, we find this inverse scaling law is also applicable in the finetuning stage, enabling further reduction in computational needs. Empirically, we explore CLIPA at scale, extending the experiments up to the H/14 model with ~13B image-text pairs seen during training. Our results are exciting -- by only allocating a budget of \10,000, our CLIP model achieves an impressive zero-shot ImageNet accuracy of 81.1%, surpassing the prior best CLIP model (from OpenCLIP, 80.1%) by 1.0% and meanwhile reducing the computational cost by ~39X. Moreover, with an additional investment of 4,000, we can further elevate the zero-shot ImageNet accuracy to 81.8%. Our code and models are available at https://github.com/UCSC-VLAA/CLIPA.

Large Language Models (LLMs) achieve strong performance on diverse tasks but often exhibit cognitive inertia, struggling to follow instructions that conflict with the standardized patterns learned during supervised fine-tuning (SFT). To evaluate this limitation, we propose Inverse IFEval, a benchmark that measures models Counter-intuitive Abilitytheir capacity to override training-induced biases and comply with adversarial instructions. Inverse IFEval introduces eight types of such challenges, including Question Correction, Intentional Textual Flaws, Code without Comments, and Counterfactual Answering. Using a human-in-the-loop pipeline, we construct a dataset of 1012 high-quality Chinese and English questions across 23 domains, evaluated under an optimized LLM-as-a-Judge framework. Experiments on existing leading LLMs demonstrate the necessity of our proposed Inverse IFEval benchmark. Our findings emphasize that future alignment efforts should not only pursue fluency and factual correctness but also account for adaptability under unconventional contexts. We hope that Inverse IFEval serves as both a diagnostic tool and a foundation for developing methods that mitigate cognitive inertia, reduce overfitting to narrow patterns, and ultimately enhance the instruction-following reliability of LLMs in diverse and unpredictable real-world scenarios.

Language models produce a distribution over the next token; can we use this information to recover the prompt tokens? We consider the problem of language model inversion and show that next-token probabilities contain a surprising amount of information about the preceding text. Often we can recover the text in cases where it is hidden from the user, motivating a method for recovering unknown prompts given only the model's current distribution output. We consider a variety of model access scenarios, and show how even without predictions for every token in the vocabulary we can recover the probability vector through search. On Llama-2 7b, our inversion method reconstructs prompts with a BLEU of 59 and token-level F1 of 78 and recovers 27% of prompts exactly. Code for reproducing all experiments is available at http://github.com/jxmorris12/vec2text.

Diffusion models have become a popular approach for image generation and reconstruction due to their numerous advantages. However, most diffusion-based inverse problem-solving methods only deal with 2D images, and even recently published 3D methods do not fully exploit the 3D distribution prior. To address this, we propose a novel approach using two perpendicular pre-trained 2D diffusion models to solve the 3D inverse problem. By modeling the 3D data distribution as a product of 2D distributions sliced in different directions, our method effectively addresses the curse of dimensionality. Our experimental results demonstrate that our method is highly effective for 3D medical image reconstruction tasks, including MRI Z-axis super-resolution, compressed sensing MRI, and sparse-view CT. Our method can generate high-quality voxel volumes suitable for medical applications.

We introduce IntFold, a controllable foundation model for both general and specialized biomolecular structure prediction. IntFold demonstrates predictive accuracy comparable to the state-of-the-art AlphaFold3, while utilizing a superior customized attention kernel. Beyond standard structure prediction, IntFold can be adapted to predict allosteric states, constrained structures, and binding affinity through the use of individual adapters. Furthermore, we introduce a novel confidence head to estimate docking quality, offering a more nuanced assessment for challenging targets such as antibody-antigen complexes. Finally, we share insights gained during the training process of this computationally intensive model.

Many machine learning methods operate by inverting a neural network at inference time, which has become a popular technique for solving inverse problems in computer vision, robotics, and graphics. However, these methods often involve gradient descent through a highly non-convex loss landscape, causing the optimization process to be unstable and slow. We introduce a method that learns a loss landscape where gradient descent is efficient, bringing massive improvement and acceleration to the inversion process. We demonstrate this advantage on a number of methods for both generative and discriminative tasks, including GAN inversion, adversarial defense, and 3D human pose reconstruction.

Generative models transform random noise into images; their inversion aims to transform images back to structured noise for recovery and editing. This paper addresses two key tasks: (i) inversion and (ii) editing of a real image using stochastic equivalents of rectified flow models (such as Flux). Although Diffusion Models (DMs) have recently dominated the field of generative modeling for images, their inversion presents faithfulness and editability challenges due to nonlinearities in drift and diffusion. Existing state-of-the-art DM inversion approaches rely on training of additional parameters or test-time optimization of latent variables; both are expensive in practice. Rectified Flows (RFs) offer a promising alternative to diffusion models, yet their inversion has been underexplored. We propose RF inversion using dynamic optimal control derived via a linear quadratic regulator. We prove that the resulting vector field is equivalent to a rectified stochastic differential equation. Additionally, we extend our framework to design a stochastic sampler for Flux. Our inversion method allows for state-of-the-art performance in zero-shot inversion and editing, outperforming prior works in stroke-to-image synthesis and semantic image editing, with large-scale human evaluations confirming user preference.