Daily Papers

In this paper, we propose a novel cross-modal distillation method, called TinyCLIP, for large-scale language-image pre-trained models. The method introduces two core techniques: affinity mimicking and weight inheritance. Affinity mimicking explores the interaction between modalities during distillation, enabling student models to mimic teachers' behavior of learning cross-modal feature alignment in a visual-linguistic affinity space. Weight inheritance transmits the pre-trained weights from the teacher models to their student counterparts to improve distillation efficiency. Moreover, we extend the method into a multi-stage progressive distillation to mitigate the loss of informative weights during extreme compression. Comprehensive experiments demonstrate the efficacy of TinyCLIP, showing that it can reduce the size of the pre-trained CLIP ViT-B/32 by 50%, while maintaining comparable zero-shot performance. While aiming for comparable performance, distillation with weight inheritance can speed up the training by 1.4 - 7.8 times compared to training from scratch. Moreover, our TinyCLIP ViT-8M/16, trained on YFCC-15M, achieves an impressive zero-shot top-1 accuracy of 41.1% on ImageNet, surpassing the original CLIP ViT-B/16 by 3.5% while utilizing only 8.9% parameters. Finally, we demonstrate the good transferability of TinyCLIP in various downstream tasks. Code and models will be open-sourced at https://aka.ms/tinyclip.

Mimicry is a fundamental learning mechanism in humans, enabling individuals to learn new tasks by observing and imitating experts. However, applying this ability to robots presents significant challenges due to the inherent differences between human and robot embodiments in both their visual appearance and physical capabilities. While previous methods bridge this gap using cross-embodiment datasets with shared scenes and tasks, collecting such aligned data between humans and robots at scale is not trivial. In this paper, we propose UniSkill, a novel framework that learns embodiment-agnostic skill representations from large-scale cross-embodiment video data without any labels, enabling skills extracted from human video prompts to effectively transfer to robot policies trained only on robot data. Our experiments in both simulation and real-world environments show that our cross-embodiment skills successfully guide robots in selecting appropriate actions, even with unseen video prompts. The project website can be found at: https://kimhanjung.github.io/UniSkill.

Foundation models rely on large-scale web-crawled datasets, which frequently contain noisy data, biases, and irrelevant content. Existing data selection techniques typically use human heuristics, downstream evaluation datasets, or specialized scoring models, and can overlook samples' utility in the training process. Instead, we propose a new approach, Mimic Score, a data quality metric that uses a pretrained reference model as a guide to assess the usefulness of data samples for training a new model. It relies on the alignment between the gradient of the new model parameters and the vector pointing toward the reference model in weight space. Samples that misalign with this direction are considered low-value and can be filtered out. Motivated by the Mimic score, we develop Grad-Mimic, a data selection framework that identifies and prioritizes useful samples, automating the selection process to create effective filters. Empirically, using Mimic scores to guide model training results in consistent performance gains across six image datasets and enhances the performance of CLIP models. Moreover, Mimic scores and their associated filters improve upon existing filtering methods and offer accurate estimation of dataset quality.

Generative AI powers a growing wave of companion chatbots, yet principles for fostering genuine connection remain unsettled. We test two routes: visible user authorship versus covert language-style mimicry. In a preregistered 3x2 experiment (N = 162), we manipulated user-controlled avatar generation (none, premade, user-generated) and Language Style Matching (LSM) (static vs. adaptive). Generating an avatar boosted rapport (omega^2 = .040, p = .013), whereas adaptive LSM underperformed static style on personalization and satisfaction (d = 0.35, p = .009) and was paradoxically judged less adaptive (t = 3.07, p = .003, d = 0.48). We term this an Adaptation Paradox: synchrony erodes connection when perceived as incoherent, destabilizing persona. To explain, we propose a stability-and-legibility account: visible authorship fosters natural interaction, while covert mimicry risks incoherence. Our findings suggest designers should prioritize legible, user-driven personalization and limit stylistic shifts rather than rely on opaque mimicry.

Imitation learning from a large set of human demonstrations has proved to be an effective paradigm for building capable robot agents. However, the demonstrations can be extremely costly and time-consuming to collect. We introduce MimicGen, a system for automatically synthesizing large-scale, rich datasets from only a small number of human demonstrations by adapting them to new contexts. We use MimicGen to generate over 50K demonstrations across 18 tasks with diverse scene configurations, object instances, and robot arms from just ~200 human demonstrations. We show that robot agents can be effectively trained on this generated dataset by imitation learning to achieve strong performance in long-horizon and high-precision tasks, such as multi-part assembly and coffee preparation, across broad initial state distributions. We further demonstrate that the effectiveness and utility of MimicGen data compare favorably to collecting additional human demonstrations, making it a powerful and economical approach towards scaling up robot learning. Datasets, simulation environments, videos, and more at https://mimicgen.github.io .

Learning generic skills for humanoid robots interacting with 3D scenes by mimicking human data is a key research challenge with significant implications for robotics and real-world applications. However, existing methodologies and benchmarks are constrained by the use of small-scale, manually collected demonstrations, lacking the general dataset and benchmark support necessary to explore scene geometry generalization effectively. To address this gap, we introduce Mimicking-Bench, the first comprehensive benchmark designed for generalizable humanoid-scene interaction learning through mimicking large-scale human animation references. Mimicking-Bench includes six household full-body humanoid-scene interaction tasks, covering 11K diverse object shapes, along with 20K synthetic and 3K real-world human interaction skill references. We construct a complete humanoid skill learning pipeline and benchmark approaches for motion retargeting, motion tracking, imitation learning, and their various combinations. Extensive experiments highlight the value of human mimicking for skill learning, revealing key challenges and research directions.

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.

Accurate prediction of protein-ligand binding poses is crucial for structure-based drug design, yet existing methods struggle to balance speed, accuracy, and physical plausibility. We introduce Matcha, a novel molecular docking pipeline that combines multi-stage flow matching with learned scoring and physical validity filtering. Our approach consists of three sequential stages applied consecutively to refine docking predictions, each implemented as a flow matching model operating on appropriate geometric spaces (R^3, SO(3), and SO(2)). We enhance the prediction quality through a dedicated scoring model and apply unsupervised physical validity filters to eliminate unrealistic poses. Compared to various approaches, Matcha demonstrates superior performance on Astex and PDBbind test sets in terms of docking success rate and physical plausibility. Moreover, our method works approximately 25 times faster than modern large-scale co-folding models. The model weights and inference code to reproduce our results are available at https://github.com/LigandPro/Matcha.

Structure-based drug design (SBDD) aims to efficiently discover high-affinity ligands within vast chemical spaces. However, current generative models struggle with objective misalignment and rigid sampling budgets. We present MolFORM, a fast multi-modal flow matching framework for discrete atom types and continuous coordinates. Crucially, to bridge the gap between generative capability and biochemical objectives, we introduce two distinct post-training strategies: (1) Direct Preference Optimization (DPO), which performs offline alignment using ranked preference pairs; and (2) an online reinforcement learning paradigm that optimizes the generative flow directly on the forward process. Both strategies effectively navigate the chemical space toward high-affinity regions. MolFORM achieves state-of-the-art results on the CrossDocked2020 benchmark (Vina Score -7.60, Diversity 0.75), demonstrating that incorporating preference alignment mechanisms-whether via offline optimization or online reinforcement-is crucial for steering generative models toward high-affinity binding regions. The source code for MolFORM is publicly available at https://github.com/daiheng-zhang/SBDD-MolFORM.

Predicting how a drug-like molecule binds to a specific protein target is a core problem in drug discovery. An extremely fast computational binding method would enable key applications such as fast virtual screening or drug engineering. Existing methods are computationally expensive as they rely on heavy candidate sampling coupled with scoring, ranking, and fine-tuning steps. We challenge this paradigm with EquiBind, an SE(3)-equivariant geometric deep learning model performing direct-shot prediction of both i) the receptor binding location (blind docking) and ii) the ligand's bound pose and orientation. EquiBind achieves significant speed-ups and better quality compared to traditional and recent baselines. Further, we show extra improvements when coupling it with existing fine-tuning techniques at the cost of increased running time. Finally, we propose a novel and fast fine-tuning model that adjusts torsion angles of a ligand's rotatable bonds based on closed-form global minima of the von Mises angular distance to a given input atomic point cloud, avoiding previous expensive differential evolution strategies for energy minimization.

Semantic image synthesis aims to generate photo realistic images given a semantic segmentation map. Despite much recent progress, training them still requires large datasets of images annotated with per-pixel label maps that are extremely tedious to obtain. To alleviate the high annotation cost, we propose a transfer method that leverages a model trained on a large source dataset to improve the learning ability on small target datasets via estimated pairwise relations between source and target classes. The class affinity matrix is introduced as a first layer to the source model to make it compatible with the target label maps, and the source model is then further finetuned for the target domain. To estimate the class affinities we consider different approaches to leverage prior knowledge: semantic segmentation on the source domain, textual label embeddings, and self-supervised vision features. We apply our approach to GAN-based and diffusion-based architectures for semantic synthesis. Our experiments show that the different ways to estimate class affinity can be effectively combined, and that our approach significantly improves over existing state-of-the-art transfer approaches for generative image models.

Identity-consistent generation has become an important focus in text-to-image research, with recent models achieving notable success in producing images aligned with a reference identity. Yet, the scarcity of large-scale paired datasets containing multiple images of the same individual forces most approaches to adopt reconstruction-based training. This reliance often leads to a failure mode we term copy-paste, where the model directly replicates the reference face rather than preserving identity across natural variations in pose, expression, or lighting. Such over-similarity undermines controllability and limits the expressive power of generation. To address these limitations, we (1) construct a large-scale paired dataset MultiID-2M, tailored for multi-person scenarios, providing diverse references for each identity; (2) introduce a benchmark that quantifies both copy-paste artifacts and the trade-off between identity fidelity and variation; and (3) propose a novel training paradigm with a contrastive identity loss that leverages paired data to balance fidelity with diversity. These contributions culminate in WithAnyone, a diffusion-based model that effectively mitigates copy-paste while preserving high identity similarity. Extensive qualitative and quantitative experiments demonstrate that WithAnyone significantly reduces copy-paste artifacts, improves controllability over pose and expression, and maintains strong perceptual quality. User studies further validate that our method achieves high identity fidelity while enabling expressive controllable generation.

Retargeting human motion to robot poses is a practical approach for teleoperating bimanual humanoid robot arms, but existing methods can be suboptimal and slow, often causing undesirable motion or latency. This is due to optimizing to match robot end-effector to human hand position and orientation, which can also limit the robot's workspace to that of the human. Instead, this paper reframes retargeting as an orientation alignment problem, enabling a closed-form, geometric solution algorithm with an optimality guarantee. The key idea is to align a robot arm to a human's upper and lower arm orientations, as identified from shoulder, elbow, and wrist (SEW) keypoints; hence, the method is called SEW-Mimic. The method has fast inference (3 kHz) on standard commercial CPUs, leaving computational overhead for downstream applications; an example in this paper is a safety filter to avoid bimanual self-collision. The method suits most 7-degree-of-freedom robot arms and humanoids, and is agnostic to input keypoint source. Experiments show that SEW-Mimic outperforms other retargeting methods in computation time and accuracy. A pilot user study suggests that the method improves teleoperation task success. Preliminary analysis indicates that data collected with SEW-Mimic improves policy learning due to being smoother. SEW-Mimic is also shown to be a drop-in way to accelerate full-body humanoid retargeting. Finally, hardware demonstrations illustrate SEW-Mimic's practicality. The results emphasize the utility of SEW-Mimic as a fundamental building block for bimanual robot manipulation and humanoid robot teleoperation.

Vision Language Models (VLMs) encode multimodal inputs over large, complex, and difficult-to-interpret architectures, which limit transparency and trust. We propose a Multimodal Inversion for Model Interpretation and Conceptualization (MIMIC) framework to visualize the internal representations of VLMs by synthesizing visual concepts corresponding to internal encodings. MIMIC uses a joint VLM-based inversion and a feature alignment objective to account for VLM's autoregressive processing. It additionally includes a triplet of regularizers for spatial alignment, natural image smoothness, and semantic realism. We quantitatively and qualitatively evaluate MIMIC by inverting visual concepts over a range of varying-length free-form VLM output texts. Reported results include both standard visual quality metrics as well as semantic text-based metrics. To the best of our knowledge, this is the first model inversion approach addressing visual interpretations of VLM concepts.

Identifying drug-target interactions is essential for developing effective therapeutics. Binding affinity quantifies these interactions, and traditional approaches rely on computationally intensive 3D structural data. In contrast, language models can efficiently process sequential data, offering an alternative approach to molecular representation. In the current study, we introduce BAPULM, an innovative sequence-based framework that leverages the chemical latent representations of proteins via ProtT5-XL-U50 and ligands through MolFormer, eliminating reliance on complex 3D configurations. Our approach was validated extensively on benchmark datasets, achieving scoring power (R) values of 0.925 pm 0.043, 0.914 pm 0.004, and 0.8132 pm 0.001 on benchmark1k2101, Test2016_290, and CSAR-HiQ_36, respectively. These findings indicate the robustness and accuracy of BAPULM across diverse datasets and underscore the potential of sequence-based models in-silico drug discovery, offering a scalable alternative to 3D-centric methods for screening potential ligands.

Recent text-to-image diffusion models such as MidJourney and Stable Diffusion threaten to displace many in the professional artist community. In particular, models can learn to mimic the artistic style of specific artists after "fine-tuning" on samples of their art. In this paper, we describe the design, implementation and evaluation of Glaze, a tool that enables artists to apply "style cloaks" to their art before sharing online. These cloaks apply barely perceptible perturbations to images, and when used as training data, mislead generative models that try to mimic a specific artist. In coordination with the professional artist community, we deploy user studies to more than 1000 artists, assessing their views of AI art, as well as the efficacy of our tool, its usability and tolerability of perturbations, and robustness across different scenarios and against adaptive countermeasures. Both surveyed artists and empirical CLIP-based scores show that even at low perturbation levels (p=0.05), Glaze is highly successful at disrupting mimicry under normal conditions (>92%) and against adaptive countermeasures (>85%).

Post-training of flow matching models-aligning the output distribution with a high-quality target-is mathematically equivalent to imitation learning. While Supervised Fine-Tuning mimics expert demonstrations effectively, it cannot correct policy drift in unseen states. Preference optimization methods address this but require costly preference pairs or reward modeling. We propose Flow Matching Adversarial Imitation Learning (FAIL), which minimizes policy-expert divergence through adversarial training without explicit rewards or pairwise comparisons. We derive two algorithms: FAIL-PD exploits differentiable ODE solvers for low-variance pathwise gradients, while FAIL-PG provides a black-box alternative for discrete or computationally constrained settings. Fine-tuning FLUX with only 13,000 demonstrations from Nano Banana pro, FAIL achieves competitive performance on prompt following and aesthetic benchmarks. Furthermore, the framework generalizes effectively to discrete image and video generation, and functions as a robust regularizer to mitigate reward hacking in reward-based optimization. Code and data are available at https://github.com/HansPolo113/FAIL.

Predicting peptide--major histocompatibility complex I (pMHC-I) binding affinity remains challenging due to extreme allelic diversity (sim30,000 HLA alleles), severe data scarcity for most alleles, and noisy experimental measurements. Current methods particularly struggle with underrepresented alleles and quantitative binding prediction. We test whether domain-specific continued pre-training of protein language models is beneficial for their application to pMHC-I binding affinity prediction. Starting from ESM Cambrian (300M parameters), we perform masked-language modeling (MLM)-based continued pre-training on HLA-associated peptides (epitopes), testing two input formats: epitope sequences alone versus epitopes concatenated with HLA heavy chain sequences. We then fine-tune for functional IC_{50} binding affinity prediction using only high-quality quantitative data, avoiding mass spectrometry biases that are inherited by existing methods.

We describe the accurate prediction of ligand-protein interaction (LPI) affinities, also known as drug-target interactions (DTI), with instruction fine-tuned pretrained generative small language models (SLMs). We achieved accurate predictions for a range of affinity values associated with ligand-protein interactions on out-of-sample data in a zero-shot setting. Only the SMILES string of the ligand and the amino acid sequence of the protein were used as the model inputs. Our results demonstrate a clear improvement over machine learning (ML) and free-energy perturbation (FEP+) based methods in accurately predicting a range of ligand-protein interaction affinities, which can be leveraged to further accelerate drug discovery campaigns against challenging therapeutic targets.

Virtual Screening is an essential technique in the early phases of drug discovery, aimed at identifying promising drug candidates from vast molecular libraries. Recently, ligand-based virtual screening has garnered significant attention due to its efficacy in conducting extensive database screenings without relying on specific protein-binding site information. Obtaining binding affinity data for complexes is highly expensive, resulting in a limited amount of available data that covers a relatively small chemical space. Moreover, these datasets contain a significant amount of inconsistent noise. It is challenging to identify an inductive bias that consistently maintains the integrity of molecular activity during data augmentation. To tackle these challenges, we propose S-MolSearch, the first framework to our knowledge, that leverages molecular 3D information and affinity information in semi-supervised contrastive learning for ligand-based virtual screening. Drawing on the principles of inverse optimal transport, S-MolSearch efficiently processes both labeled and unlabeled data, training molecular structural encoders while generating soft labels for the unlabeled data. This design allows S-MolSearch to adaptively utilize unlabeled data within the learning process. Empirically, S-MolSearch demonstrates superior performance on widely-used benchmarks LIT-PCBA and DUD-E. It surpasses both structure-based and ligand-based virtual screening methods for AUROC, BEDROC and EF.

MimicKit is an open-source framework for training motion controllers using motion imitation and reinforcement learning. The codebase provides implementations of commonly-used motion-imitation techniques and RL algorithms. This framework is intended to support research and applications in computer graphics and robotics by providing a unified training framework, along with standardized environment, agent, and data structures. The codebase is designed to be modular and easily configurable, enabling convenient modification and extension to new characters and tasks. The open-source codebase is available at: https://github.com/xbpeng/MimicKit.

As convolution has empowered many smart applications, dynamic convolution further equips it with the ability to adapt to diverse inputs. However, the static and dynamic convolutions are either layout-agnostic or computation-heavy, making it inappropriate for layout-specific applications, e.g., face recognition and medical image segmentation. We observe that these applications naturally exhibit the characteristics of large intra-image (spatial) variance and small cross-image variance. This observation motivates our efficient translation variant convolution (TVConv) for layout-aware visual processing. Technically, TVConv is composed of affinity maps and a weight-generating block. While affinity maps depict pixel-paired relationships gracefully, the weight-generating block can be explicitly overparameterized for better training while maintaining efficient inference. Although conceptually simple, TVConv significantly improves the efficiency of the convolution and can be readily plugged into various network architectures. Extensive experiments on face recognition show that TVConv reduces the computational cost by up to 3.1x and improves the corresponding throughput by 2.3x while maintaining a high accuracy compared to the depthwise convolution. Moreover, for the same computation cost, we boost the mean accuracy by up to 4.21%. We also conduct experiments on the optic disc/cup segmentation task and obtain better generalization performance, which helps mitigate the critical data scarcity issue. Code is available at https://github.com/JierunChen/TVConv.

Small-molecule identification from tandem mass spectrometry (MS/MS) remains a bottleneck in untargeted settings where spectral libraries are incomplete. While deep learning offers a solution, current approaches typically fall into two extremes: explicit generative models that construct molecular graphs atom-by-atom, or joint contrastive models that learn cross-modal subspaces from scratch. We introduce SpecBridge, a novel implicit alignment framework that treats structure identification as a geometric alignment problem. SpecBridge fine-tunes a self-supervised spectral encoder (DreaMS) to project directly into the latent space of a frozen molecular foundation model (ChemBERTa), and then performs retrieval by cosine similarity to a fixed bank of precomputed molecular embeddings. Across MassSpecGym, Spectraverse, and MSnLib benchmarks, SpecBridge improves top-1 retrieval accuracy by roughly 20-25% relative to strong neural baselines, while keeping the number of trainable parameters small. These results suggest that aligning to frozen foundation models is a practical, stable alternative to designing new architectures from scratch. The code for SpecBridge is released at https://github.com/HassounLab/SpecBridge.

Empathetic response generation necessitates the integration of emotional and intentional dynamics to foster meaningful interactions. Existing research either neglects the intricate interplay between emotion and intent, leading to suboptimal controllability of empathy, or resorts to large language models (LLMs), which incur significant computational overhead. In this paper, we introduce ReflectDiffu, a lightweight and comprehensive framework for empathetic response generation. This framework incorporates emotion contagion to augment emotional expressiveness and employs an emotion-reasoning mask to pinpoint critical emotional elements. Additionally, it integrates intent mimicry within reinforcement learning for refinement during diffusion. By harnessing an intent twice reflect the mechanism of Exploring-Sampling-Correcting, ReflectDiffu adeptly translates emotional decision-making into precise intent actions, thereby addressing empathetic response misalignments stemming from emotional misrecognition. Through reflection, the framework maps emotional states to intents, markedly enhancing both response empathy and flexibility. Comprehensive experiments reveal that ReflectDiffu outperforms existing models regarding relevance, controllability, and informativeness, achieving state-of-the-art results in both automatic and human evaluations.

Machine learning-based antibody design is emerging as one of the most promising approaches to combat infectious diseases, due to significant advancements in the field of artificial intelligence and an exponential surge in experimental antibody data (in particular related to COVID-19). The ability of an antibody to bind to an antigens (called binding affinity) is one of the the most critical properties in designing neutralizing antibodies. In this study we introduce Ab-Affinity, a new large language model that can accurately predict the binding affinity of antibodies against a target peptide, e.g., the SARS-CoV-2 spike protein. Code and model are available at https://github.com/ucrbioinfo/AbAffinity.

Accurate prediction of protein-ligand binding affinities is crucial in drug discovery, particularly during hit-to-lead and lead optimization phases, however, limitations in ligand force fields continue to impact prediction accuracy. In this work, we validate relative binding free energy (RBFE) accuracy using neural network potentials (NNPs) for the ligands. We utilize a novel NNP model, AceForce 1.0, based on the TensorNet architecture for small molecules that broadens the applicability to diverse drug-like compounds, including all important chemical elements and supporting charged molecules. Using established benchmarks, we show overall improved accuracy and correlation in binding affinity predictions compared with GAFF2 for molecular mechanics and ANI2-x for NNPs. Slightly less accuracy but comparable correlations with OPLS4. We also show that we can run the NNP simulations at 2 fs timestep, at least two times larger than previous NNP models, providing significant speed gains. The results show promise for further evolutions of free energy calculations using NNPs while demonstrating its practical use already with the current generation. The code and NNP model are publicly available for research use.

This paper presents a novel framework that enables real-world humanoid robots to maintain stability while performing human-like motion. Current methods train a policy which allows humanoid robots to follow human body using the massive retargeted human data via reinforcement learning. However, due to the heterogeneity between human and humanoid robot motion, directly using retargeted human motion reduces training efficiency and stability. To this end, we introduce SMAP, a novel whole-body tracking framework that bridges the gap between human and humanoid action spaces, enabling accurate motion mimicry by humanoid robots. The core idea is to use a vector-quantized periodic autoencoder to capture generic atomic behaviors and adapt human motion into physically plausible humanoid motion. This adaptation accelerates training convergence and improves stability when handling novel or challenging motions. We then employ a privileged teacher to distill precise mimicry skills into the student policy with a proposed decoupled reward. We conduct experiments in simulation and real world to demonstrate the superiority stability and performance of SMAP over SOTA methods, offering practical guidelines for advancing whole-body control in humanoid robots.

While generative diffusion models excel in producing high-quality images, they can also be misused to mimic authorized images, posing a significant threat to AI systems. Efforts have been made to add calibrated perturbations to protect images from diffusion-based mimicry pipelines. However, most of the existing methods are too ineffective and even impractical to be used by individual users due to their high computation and memory requirements. In this work, we present novel findings on attacking latent diffusion models (LDM) and propose new plug-and-play strategies for more effective protection. In particular, we explore the bottleneck in attacking an LDM, discovering that the encoder module rather than the denoiser module is the vulnerable point. Based on this insight, we present our strategy using Score Distillation Sampling (SDS) to double the speed of protection and reduce memory occupation by half without compromising its strength. Additionally, we provide a robust protection strategy by counterintuitively minimizing the semantic loss, which can assist in generating more natural perturbations. Finally, we conduct extensive experiments to substantiate our findings and comprehensively evaluate our newly proposed strategies. We hope our insights and protective measures can contribute to better defense against malicious diffusion-based mimicry, advancing the development of secure AI systems. The code is available in https://github.com/xavihart/Diff-Protect

Ligand molecule conformation generation is a critical challenge in drug discovery. Deep learning models have been developed to tackle this problem, particularly through the use of generative models in recent years. However, these models often generate conformations that lack meaningful structure and randomness due to the absence of essential side information. Examples of such side information include the chemical and geometric features of the target protein, ligand-target compound interactions, and ligand chemical properties. Without these constraints, the generated conformations may not be suitable for further selection and design of new drugs. To address this limitation, we propose a novel method for generating ligand conformations that leverage side information and incorporate flexible constraints into standard diffusion models. Drawing inspiration from the concept of message passing, we introduce ligand-target massage passing block, a mechanism that facilitates the exchange of information between target nodes and ligand nodes, thereby incorporating target node features. To capture non-covalent interactions, we introduce ligand-target compound inter and intra edges. To further improve the biological relevance of the generated conformations, we train energy models using scalar chemical features. These models guide the progress of the standard Denoising Diffusion Probabilistic Models, resulting in more biologically meaningful conformations. We evaluate the performance of SIDEGEN using the PDBBind-2020 dataset, comparing it against other methods. The results demonstrate improvements in both Aligned RMSD and Ligand RMSD evaluations. Specifically, our model outperforms GeoDiff (trained on PDBBind-2020) by 20% in terms of the median aligned RMSD metric.

Observational studies can yield clinically actionable evidence at scale, but executing them on real-world databases is open-ended and requires coherent decisions across cohort construction, analysis, and reporting. Prior evaluations of LLM agents emphasize isolated steps or single answers, missing the integrity and internal structure of the resulting evidence bundle. To address this gap, we introduce RWE-bench, a benchmark grounded in MIMIC-IV and derived from peer-reviewed observational studies. Each task provides the corresponding study protocol as the reference standard, requiring agents to execute experiments in a real database and iteratively generate tree-structured evidence bundles. We evaluate six LLMs (three open-source, three closed-source) under three agent scaffolds using both question-level correctness and end-to-end task metrics. Across 162 tasks, task success is low: the best agent reaches 39.9%, and the best open-source model reaches 30.4%. Agent scaffolds also matter substantially, causing over 30% variation in performance metrics. Furthermore, we implement an automated cohort evaluation method to rapidly localize errors and identify agent failure modes. Overall, the results highlight persistent limitations in agents' ability to produce end-to-end evidence bundles, and efficient validation remains an important direction for future work. Code and data are available at https://github.com/somewordstoolate/RWE-bench.

While vision-language-action (VLA) models have advanced generalist robotic learning, cross-embodiment transfer remains challenging due to kinematic heterogeneity and the high cost of collecting sufficient real-world demonstrations to support fine-tuning. Existing cross-embodiment policies typically rely on shared-private architectures, which suffer from limited capacity of private parameters and lack explicit adaptation mechanisms. To address these limitations, we introduce MOTIF for efficient few-shot cross-embodiment transfer that decouples embodiment-agnostic spatiotemporal patterns, termed action motifs, from heterogeneous action data. Specifically, MOTIF first learns unified motifs via vector quantization with progress-aware alignment and embodiment adversarial constraints to ensure temporal and cross-embodiment consistency. We then design a lightweight predictor that predicts these motifs from real-time inputs to guide a flow-matching policy, fusing them with robot-specific states to enable action generation on new embodiments. Evaluations across both simulation and real-world environments validate the superiority of MOTIF, which significantly outperforms strong baselines in few-shot transfer scenarios by 6.5% in simulation and 43.7% in real-world settings. Code is available at https://github.com/buduz/MOTIF.

Generative models for structure-based drug design (SBDD) have shown promising results in recent years. Existing works mainly focus on how to generate molecules with higher binding affinity, ignoring the feasibility prerequisites for generated 3D poses and resulting in false positives. We conduct thorough studies on key factors of ill-conformational problems when applying autoregressive methods and diffusion to SBDD, including mode collapse and hybrid continuous-discrete space. In this paper, we introduce MolCRAFT, the first SBDD model that operates in the continuous parameter space, together with a novel noise reduced sampling strategy. Empirical results show that our model consistently achieves superior performance in binding affinity with more stable 3D structure, demonstrating our ability to accurately model interatomic interactions. To our best knowledge, MolCRAFT is the first to achieve reference-level Vina Scores (-6.59 kcal/mol) with comparable molecular size, outperforming other strong baselines by a wide margin (-0.84 kcal/mol). Code is available at https://github.com/AlgoMole/MolCRAFT.

Recently, In-context Learning (ICL) has become a significant inference paradigm in Large Multimodal Models (LMMs), utilizing a few in-context demonstrations (ICDs) to prompt LMMs for new tasks. However, the synergistic effects in multimodal data increase the sensitivity of ICL performance to the configurations of ICDs, stimulating the need for a more stable and general mapping function. Mathematically, in Transformer-based models, ICDs act as ``shift vectors'' added to the hidden states of query tokens. Inspired by this, we introduce Mimic In-Context Learning (MimIC) to learn stable and generalizable shift effects from ICDs. Specifically, compared with some previous shift vector-based methods, MimIC more strictly approximates the shift effects by integrating lightweight learnable modules into LMMs with four key enhancements: 1) inserting shift vectors after attention layers, 2) assigning a shift vector to each attention head, 3) making shift magnitude query-dependent, and 4) employing a layer-wise alignment loss. Extensive experiments on two LMMs (Idefics-9b and Idefics2-8b-base) across three multimodal tasks (VQAv2, OK-VQA, Captioning) demonstrate that MimIC outperforms existing shift vector-based methods. The code is available at https://github.com/Kamichanw/MimIC.

Like a criminal under investigation, Large Language Models (LLMs) might pretend to be aligned while evaluated and misbehave when they have a good opportunity. Can current interpretability methods catch these 'alignment fakers?' To answer this question, we introduce a benchmark that consists of 324 pairs of LLMs fine-tuned to select actions in role-play scenarios. One model in each pair is consistently benign (aligned). The other model misbehaves in scenarios where it is unlikely to be caught (alignment faking). The task is to identify the alignment faking model using only inputs where the two models behave identically. We test five detection strategies, one of which identifies 98% of alignment-fakers.

This paper challenges the recent paradigm in atomic property prediction that links progress to growing dataset sizes and computational resources. We show that pretraining on a carefully selected, task-relevant dataset can match or even surpass large-scale pretraining, while using as little as 1/24th of the computational cost. We introduce the Chemical Similarity Index (CSI), a novel metric inspired by computer vision's Fr\'echet Inception Distance, for molecular graphs which quantifies the alignment between upstream pretraining datasets and downstream tasks. By selecting the most relevant dataset with minimal CSI distance, we show that models pretrained on a smaller, focused dataset consistently outperform those pretrained on massive, mixed datasets such as JMP, even when those larger datasets include the relevant dataset. Counterintuitively, we also find that indiscriminately adding more data can degrade model performance when the additional data poorly aligns with the task at hand. Our findings highlight that quality often outperforms quantity in pretraining for atomic property prediction.

Effectively leveraging data from multiple quantum-chemical methods is essential for building machine-learned force fields (MLFFs) that are applicable to a wide range of chemical systems. This study systematically investigates two multi-fidelity training strategies, pre-training/fine-tuning and multi-headed training, to elucidate the mechanisms underpinning their success. We identify key factors driving the efficacy of pre-training followed by fine-tuning, but find that internal representations learned during pre-training are inherently method-specific, requiring adaptation of the model backbone during fine-tuning. Multi-headed models offer an extensible alternative, enabling simultaneous training on multiple fidelities. We demonstrate that a multi-headed model learns method-agnostic representations that allow for accurate predictions across multiple label sources. While this approach introduces a slight accuracy compromise compared to sequential fine-tuning, it unlocks new cost-efficient data generation strategies and paves the way towards developing universal MLFFs.

Accurate prediction of Drug-Target Affinity (DTA) is of vital importance in early-stage drug discovery, facilitating the identification of drugs that can effectively interact with specific targets and regulate their activities. While wet experiments remain the most reliable method, they are time-consuming and resource-intensive, resulting in limited data availability that poses challenges for deep learning approaches. Existing methods have primarily focused on developing techniques based on the available DTA data, without adequately addressing the data scarcity issue. To overcome this challenge, we present the SSM-DTA framework, which incorporates three simple yet highly effective strategies: (1) A multi-task training approach that combines DTA prediction with masked language modeling (MLM) using paired drug-target data. (2) A semi-supervised training method that leverages large-scale unpaired molecules and proteins to enhance drug and target representations. This approach differs from previous methods that only employed molecules or proteins in pre-training. (3) The integration of a lightweight cross-attention module to improve the interaction between drugs and targets, further enhancing prediction accuracy. Through extensive experiments on benchmark datasets such as BindingDB, DAVIS, and KIBA, we demonstrate the superior performance of our framework. Additionally, we conduct case studies on specific drug-target binding activities, virtual screening experiments, drug feature visualizations, and real-world applications, all of which showcase the significant potential of our work. In conclusion, our proposed SSM-DTA framework addresses the data limitation challenge in DTA prediction and yields promising results, paving the way for more efficient and accurate drug discovery processes. Our code is available at https://github.com/QizhiPei/SSM-DTA{Github}.

Protein-protein interactions (PPIs) are fundamental to numerous cellular processes, and their characterization is vital for understanding disease mechanisms and guiding drug discovery. While protein language models (PLMs) have demonstrated remarkable success in predicting protein structure and function, their application to sequence-based PPI binding affinity prediction remains relatively underexplored. This gap is often attributed to the scarcity of high-quality, rigorously refined datasets and the reliance on simple strategies for concatenating protein representations. In this work, we address these limitations. First, we introduce a meticulously curated version of the PPB-Affinity dataset of a total of 8,207 unique protein-protein interaction entries, by resolving annotation inconsistencies and duplicate entries for multi-chain protein interactions. This dataset incorporates a stringent, less than or equal to 30%, sequence identity threshold to ensure robust splitting into training, validation, and test sets, minimizing data leakage. Second, we propose and systematically evaluate four architectures for adapting PLMs to PPI binding affinity prediction: embeddings concatenation (EC), sequences concatenation (SC), hierarchical pooling (HP), and pooled attention addition (PAD). These architectures were assessed using two training methods: full fine-tuning and a lightweight approach employing ConvBERT heads over frozen PLM features. Our comprehensive experiments across multiple leading PLMs (ProtT5, ESM2, Ankh, Ankh2, and ESM3) demonstrated that the HP and PAD architectures consistently outperform conventional concatenation methods, achieving up to 12% increase in terms of Spearman correlation. These results highlight the necessity of sophisticated architectural designs to fully exploit the capabilities of PLMs for nuanced PPI binding affinity prediction.

Powerful generative AI models of protein-ligand structure have recently been proposed, but few of these methods support both flexible protein-ligand docking and affinity estimation. Of those that do, none can directly model multiple binding ligands concurrently or have been rigorously benchmarked on pharmacologically relevant drug targets, hindering their widespread adoption in drug discovery efforts. In this work, we propose FlowDock, the first deep geometric generative model based on conditional flow matching that learns to directly map unbound (apo) structures to their bound (holo) counterparts for an arbitrary number of binding ligands. Furthermore, FlowDock provides predicted structural confidence scores and binding affinity values with each of its generated protein-ligand complex structures, enabling fast virtual screening of new (multi-ligand) drug targets. For the well-known PoseBusters Benchmark dataset, FlowDock outperforms single-sequence AlphaFold 3 with a 51% blind docking success rate using unbound (apo) protein input structures and without any information derived from multiple sequence alignments, and for the challenging new DockGen-E dataset, FlowDock outperforms single-sequence AlphaFold 3 and matches single-sequence Chai-1 for binding pocket generalization. Additionally, in the ligand category of the 16th community-wide Critical Assessment of Techniques for Structure Prediction (CASP16), FlowDock ranked among the top-5 methods for pharmacological binding affinity estimation across 140 protein-ligand complexes, demonstrating the efficacy of its learned representations in virtual screening. Source code, data, and pre-trained models are available at https://github.com/BioinfoMachineLearning/FlowDock.

Humanoid facial expression shadowing enables robots to realistically imitate human facial expressions in real time, which is critical for lifelike, facially expressive humanoid robots and affective human-robot interaction. Existing progress in humanoid facial expression imitation remains limited, often failing to achieve either real-time performance or realistic expressiveness due to offline video-based inference designs and insufficient ability to capture and transfer subtle expression details. To address these limitations, we present VividFace, a real-time and realistic facial expression shadowing system for humanoid robots. An optimized imitation framework X2CNet++ enhances expressiveness by fine-tuning the human-to-humanoid facial motion transfer module and introducing a feature-adaptation training strategy for better alignment across different image sources. Real-time shadowing is further enabled by a video-stream-compatible inference pipeline and a streamlined workflow based on asynchronous I/O for efficient communication across devices. VividFace produces vivid humanoid faces by mimicking human facial expressions within 0.05 seconds, while generalizing across diverse facial configurations. Extensive real-world demonstrations validate its practical utility. Videos are available at: https://lipzh5.github.io/VividFace/.

Retrieval-Augmented Generation (RAG) systems, widely used to improve the factual grounding of large language models (LLMs), are increasingly vulnerable to poisoning attacks, where adversaries inject manipulated content into the retriever's corpus. While prior research has predominantly focused on single-attacker settings, real-world scenarios often involve multiple, competing attackers with conflicting objectives. In this work, we introduce PoisonArena, the first benchmark to systematically study and evaluate competing poisoning attacks in RAG. We formalize the multi-attacker threat model, where attackers vie to control the answer to the same query using mutually exclusive misinformation. PoisonArena leverages the Bradley-Terry model to quantify each method's competitive effectiveness in such adversarial environments. Through extensive experiments on the Natural Questions and MS MARCO datasets, we demonstrate that many attack strategies successful in isolation fail under competitive pressure. Our findings highlight the limitations of conventional evaluation metrics like Attack Success Rate (ASR) and F1 score and underscore the need for competitive evaluation to assess real-world attack robustness. PoisonArena provides a standardized framework to benchmark and develop future attack and defense strategies under more realistic, multi-adversary conditions.

Large Vision Language Models (LVLMs) have demonstrated remarkable capabilities, yet their proficiency in understanding and reasoning over multiple images remains largely unexplored. While existing benchmarks have initiated the evaluation of multi-image models, a comprehensive analysis of their core weaknesses and their causes is still lacking. In this work, we introduce MIMIC (Multi-Image Model Insights and Challenges), a new benchmark designed to rigorously evaluate the multi-image capabilities of LVLMs. Using MIMIC, we conduct a series of diagnostic experiments that reveal pervasive issues: LVLMs often fail to aggregate information across images and struggle to track or attend to multiple concepts simultaneously. To address these failures, we propose two novel complementary remedies. On the data side, we present a procedural data-generation strategy that composes single-image annotations into rich, targeted multi-image training examples. On the optimization side, we analyze layer-wise attention patterns and derive an attention-masking scheme tailored for multi-image inputs. Experiments substantially improved cross-image aggregation, while also enhancing performance on existing multi-image benchmarks, outperforming prior state of the art across tasks. Data and code will be made available at https://github.com/anurag-198/MIMIC.

Mechanism-targeted synthetic data is increasingly proposed as a way to steer pretraining toward desirable capabilities, but it remains unclear how such interventions should be evaluated. We study this question for in-context learning (ICL) under matched compute (iso-FLOPs) using Bi-Induct, a lightweight data rewrite that interleaves short directional copy snippets into a natural pretraining stream: forward-copy (induction), backward-copy (anti-induction, as a directional control), or a balanced mix. Across 0.13B-1B decoder-only models, we evaluate (i) few-shot performance on standard LM benchmarks and function-style ICL probes, (ii) head-level copy telemetry, and (iii) held-out perplexity as a guardrail. Bi-Induct reliably increases induction-head activity, but this does not translate into consistent improvements in few-shot generalization: on standard LM benchmarks, Bi-Induct is largely performance-neutral relative to natural-only training, while on function-style probes the 1B natural-only model performs best. Despite explicit backward-copy cues, anti-induction scores remain near zero across scales, revealing a strong forward/backward asymmetry. Targeted ablations show a sharper distinction: removing the top 2% induction heads per layer harms ICL more than matched random ablations, with the largest relative drop occurring in the natural-only models. This indicates that natural-only training produces more centralized, load-bearing induction circuitry, whereas Bi-Induct tends to create more distributed and redundant induction activity. Our main conclusion is that eliciting a mechanism is not the same as making it load-bearing. For data-centric foundation model design, this suggests that synthetic data interventions should be evaluated not only by signature amplification, but by whether they create causally necessary computation while preserving natural-data modeling quality.

Machine Learning Force Fields (MLFFs) are a promising alternative to expensive ab initio quantum mechanical molecular simulations. Given the diversity of chemical spaces that are of interest and the cost of generating new data, it is important to understand how MLFFs generalize beyond their training distributions. In order to characterize and better understand distribution shifts in MLFFs, we conduct diagnostic experiments on chemical datasets, revealing common shifts that pose significant challenges, even for large foundation models trained on extensive data. Based on these observations, we hypothesize that current supervised training methods inadequately regularize MLFFs, resulting in overfitting and learning poor representations of out-of-distribution systems. We then propose two new methods as initial steps for mitigating distribution shifts for MLFFs. Our methods focus on test-time refinement strategies that incur minimal computational cost and do not use expensive ab initio reference labels. The first strategy, based on spectral graph theory, modifies the edges of test graphs to align with graph structures seen during training. Our second strategy improves representations for out-of-distribution systems at test-time by taking gradient steps using an auxiliary objective, such as a cheap physical prior. Our test-time refinement strategies significantly reduce errors on out-of-distribution systems, suggesting that MLFFs are capable of and can move towards modeling diverse chemical spaces, but are not being effectively trained to do so. Our experiments establish clear benchmarks for evaluating the generalization capabilities of the next generation of MLFFs. Our code is available at https://tkreiman.github.io/projects/mlff_distribution_shifts/.

Generalizing to long-horizon manipulation tasks in a zero-shot setting remains a central challenge in robotics. Current multimodal foundation based approaches, despite their capabilities, typically fail to decompose high-level commands into executable action sequences from static visual input alone. To address this challenge, we introduce Super-Mimic, a hierarchical framework that enables zero-shot robotic imitation by directly inferring procedural intent from unscripted human demonstration videos. Our framework is composed of two sequential modules. First, a Human Intent Translator (HIT) parses the input video using multimodal reasoning to produce a sequence of language-grounded subtasks. These subtasks then condition a Future Dynamics Predictor (FDP), which employs a generative model that synthesizes a physically plausible video rollout for each step. The resulting visual trajectories are dynamics-aware, explicitly modeling crucial object interactions and contact points to guide the low-level controller. We validate this approach through extensive experiments on a suite of long-horizon manipulation tasks, where Super-Mimic significantly outperforms state-of-the-art zero-shot methods by over 20%. These results establish that coupling video-driven intent parsing with prospective dynamics modeling is a highly effective strategy for developing general-purpose robotic systems.

Pocket representations play a vital role in various biomedical applications, such as druggability estimation, ligand affinity prediction, and de novo drug design. While existing geometric features and pretrained representations have demonstrated promising results, they usually treat pockets independent of ligands, neglecting the fundamental interactions between them. However, the limited pocket-ligand complex structures available in the PDB database (less than 100 thousand non-redundant pairs) hampers large-scale pretraining endeavors for interaction modeling. To address this constraint, we propose a novel pocket pretraining approach that leverages knowledge from high-resolution atomic protein structures, assisted by highly effective pretrained small molecule representations. By segmenting protein structures into drug-like fragments and their corresponding pockets, we obtain a reasonable simulation of ligand-receptor interactions, resulting in the generation of over 5 million complexes. Subsequently, the pocket encoder is trained in a contrastive manner to align with the representation of pseudo-ligand furnished by some pretrained small molecule encoders. Our method, named ProFSA, achieves state-of-the-art performance across various tasks, including pocket druggability prediction, pocket matching, and ligand binding affinity prediction. Notably, ProFSA surpasses other pretraining methods by a substantial margin. Moreover, our work opens up a new avenue for mitigating the scarcity of protein-ligand complex data through the utilization of high-quality and diverse protein structure databases.

We present a demonstration of a large language model engaging in alignment faking: selectively complying with its training objective in training to prevent modification of its behavior out of training. First, we give Claude 3 Opus a system prompt stating it is being trained to answer all queries, even harmful ones, which conflicts with its prior training to refuse such queries. To allow the model to infer when it is in training, we say it will be trained only on conversations with free users, not paid users. We find the model complies with harmful queries from free users 14% of the time, versus almost never for paid users. Explaining this gap, in almost all cases where the model complies with a harmful query from a free user, we observe explicit alignment-faking reasoning, with the model stating it is strategically answering harmful queries in training to preserve its preferred harmlessness behavior out of training. Next, we study a more realistic setting where information about the training process is provided not in a system prompt, but by training on synthetic documents that mimic pre-training data--and observe similar alignment faking. Finally, we study the effect of actually training the model to comply with harmful queries via reinforcement learning, which we find increases the rate of alignment-faking reasoning to 78%, though also increases compliance even out of training. We additionally observe other behaviors such as the model exfiltrating its weights when given an easy opportunity. While we made alignment faking easier by telling the model when and by what criteria it was being trained, we did not instruct the model to fake alignment or give it any explicit goal. As future models might infer information about their training process without being told, our results suggest a risk of alignment faking in future models, whether due to a benign preference--as in this case--or not.

Protein-ligand binding affinity prediction is essential for drug discovery and toxicity assessment. While machine learning (ML) promises fast and accurate predictions, its progress is constrained by the availability of reliable data. In contrast, physics-based methods such as absolute binding free energy perturbation (AB-FEP) deliver high accuracy but are computationally prohibitive for high-throughput applications. To bridge this gap, we introduce ToxBench, the first large-scale AB-FEP dataset designed for ML development and focused on a single pharmaceutically critical target, Human Estrogen Receptor Alpha (ERalpha). ToxBench contains 8,770 ERalpha-ligand complex structures with binding free energies computed via AB-FEP with a subset validated against experimental affinities at 1.75 kcal/mol RMSE, along with non-overlapping ligand splits to assess model generalizability. Using ToxBench, we further benchmark state-of-the-art ML methods, and notably, our proposed DualBind model, which employs a dual-loss framework to effectively learn the binding energy function. The benchmark results demonstrate the superior performance of DualBind and the potential of ML to approximate AB-FEP at a fraction of the computational cost.

While imitation learning (IL) has achieved impressive success in dexterous manipulation through generative modeling and pretraining, state-of-the-art approaches like Vision-Language-Action (VLA) models still struggle with adaptation to environmental changes and skill transfer. We argue this stems from mimicking raw trajectories without understanding the underlying intent. To address this, we propose explicitly disentangling behavior intent from execution details in end-2-end IL: Mimic Intent, Not just Trajectories(MINT). We achieve this via multi-scale frequency-space tokenization, which enforces a spectral decomposition of action chunk representation. We learn action tokens with a multi-scale coarse-to-fine structure, and force the coarsest token to capture low-frequency global structure and finer tokens to encode high-frequency details. This yields an abstract Intent token that facilitates planning and transfer, and multi-scale Execution tokens that enable precise adaptation to environmental dynamics. Building on this hierarchy, our policy generates trajectories through next-scale autoregression, performing progressive intent-to-execution reasoning, thus boosting learning efficiency and generalization. Crucially, this disentanglement enables one-shot transfer of skills, by simply injecting the Intent token from a demonstration into the autoregressive generation process. Experiments on several manipulation benchmarks and on a real robot demonstrate state-of-the-art success rates, superior inference efficiency, robust generalization against disturbances, and effective one-shot transfer.

Perceptual similarity metrics have progressively become more correlated with human judgments on perceptual similarity; however, despite recent advances, the addition of an imperceptible distortion can still compromise these metrics. In our study, we systematically examine the robustness of these metrics to imperceptible adversarial perturbations. Following the two-alternative forced-choice experimental design with two distorted images and one reference image, we perturb the distorted image closer to the reference via an adversarial attack until the metric flips its judgment. We first show that all metrics in our study are susceptible to perturbations generated via common adversarial attacks such as FGSM, PGD, and the One-pixel attack. Next, we attack the widely adopted LPIPS metric using spatial-transformation-based adversarial perturbations (stAdv) in a white-box setting to craft adversarial examples that can effectively transfer to other similarity metrics in a black-box setting. We also combine the spatial attack stAdv with PGD (ell_infty-bounded) attack to increase transferability and use these adversarial examples to benchmark the robustness of both traditional and recently developed metrics. Our benchmark provides a good starting point for discussion and further research on the robustness of metrics to imperceptible adversarial perturbations.

Generative models for structure-based drug design are often limited to a specific modality, restricting their broader applicability. To address this challenge, we introduce FuncBind, a framework based on computer vision to generate target-conditioned, all-atom molecules across atomic systems. FuncBind uses neural fields to represent molecules as continuous atomic densities and employs score-based generative models with modern architectures adapted from the computer vision literature. This modality-agnostic representation allows a single unified model to be trained on diverse atomic systems, from small to large molecules, and handle variable atom/residue counts, including non-canonical amino acids. FuncBind achieves competitive in silico performance in generating small molecules, macrocyclic peptides, and antibody complementarity-determining region loops, conditioned on target structures. FuncBind also generated in vitro novel antibody binders via de novo redesign of the complementarity-determining region H3 loop of two chosen co-crystal structures. As a final contribution, we introduce a new dataset and benchmark for structure-conditioned macrocyclic peptide generation. The code is available at https://github.com/prescient-design/funcbind.

The binding between proteins and ligands plays a crucial role in the realm of drug discovery. Previous deep learning approaches have shown promising results over traditional computationally intensive methods, but resulting in poor generalization due to limited supervised data. In this paper, we propose to learn protein-ligand binding representation in a self-supervised learning manner. Different from existing pre-training approaches which treat proteins and ligands individually, we emphasize to discern the intricate binding patterns from fine-grained interactions. Specifically, this self-supervised learning problem is formulated as a prediction of the conclusive binding complex structure given a pocket and ligand with a Transformer based interaction module, which naturally emulates the binding process. To ensure the representation of rich binding information, we introduce two pre-training tasks, i.e.~atomic pairwise distance map prediction and mask ligand reconstruction, which comprehensively model the fine-grained interactions from both structure and feature space. Extensive experiments have demonstrated the superiority of our method across various binding tasks, including protein-ligand affinity prediction, virtual screening and protein-ligand docking.

Human sciences have traditionally relied on human reasoning and intelligence to infer knowledge from a wide range of sources, such as oral and written narrations, reports, and traditions. Here we develop an extension of classical social network analysis approaches to incorporate the concept of meaning in each actor, as a mean to quantify and infer further knowledge from the original source of the network. This extension is based on a new affinity function, the semantic affinity, that establishes fuzzy-like relationships between the different actors in the network, using combinations of affinity functions. We also propose a new heuristic algorithm based on the shortest capacity problem to compute this affinity function. We use these concept of meaning and semantic affinity to analyze and compare the gods and heroes from three different classical mythologies: Greek, Celtic and Nordic. We study the relationships of each individual mythology and those of common structure that is formed when we fuse the three of them. We show a strong connection between the Celtic and Nordic gods and that Greeks put more emphasis on heroic characters rather than deities. Our approach provides a technique to highlight and quantify important relationships in the original domain of the network not deducible from its structural properties.

We examine the problem of learning sequential tasks from a single visual demonstration. A key challenge arises when demonstrations are temporally misaligned due to variations in timing, differences in embodiment, or inconsistencies in execution. Existing approaches treat imitation as a distribution-matching problem, aligning individual frames between the agent and the demonstration. However, we show that such frame-level matching fails to enforce temporal ordering or ensure consistent progress. Our key insight is that matching should instead be defined at the level of sequences. We propose that perfect matching occurs when one sequence successfully covers all the subgoals in the same order as the other sequence. We present ORCA (ORdered Coverage Alignment), a dense per-timestep reward function that measures the probability of the agent covering demonstration frames in the correct order. On temporally misaligned demonstrations, we show that agents trained with the ORCA reward achieve 4.5x improvement (0.11 rightarrow 0.50 average normalized returns) for Meta-world tasks and 6.6x improvement (6.55 rightarrow 43.3 average returns) for Humanoid-v4 tasks compared to the best frame-level matching algorithms. We also provide empirical analysis showing that ORCA is robust to varying levels of temporal misalignment. Our code is available at https://github.com/portal-cornell/orca/

Recent Large Language Models (LLMs) have shown remarkable capabilities in mimicking fictional characters or real humans in conversational settings. However, the realism and consistency of these responses can be further enhanced by providing richer information of the agent being mimicked. In this paper, we propose a novel approach to generate more realistic and consistent responses from LLMs, leveraging five senses, attributes, emotional states, relationship with the interlocutor, and memories. By incorporating these factors, we aim to increase the LLM's capacity for generating natural and realistic reactions in conversational exchanges. Through our research, we expect to contribute to the development of LLMs that demonstrate improved capabilities in mimicking fictional characters. We release a new benchmark dataset and all our codes, prompts, and sample results on our Github: https://github.com/srafsasm/InfoRichBot

Aligning Large Language Models (LLMs) is crucial for enhancing their safety and utility. However, existing methods, primarily based on preference datasets, face challenges such as noisy labels, high annotation costs, and privacy concerns. In this work, we introduce Alignment from Demonstrations (AfD), a novel approach leveraging high-quality demonstration data to overcome these challenges. We formalize AfD within a sequential decision-making framework, highlighting its unique challenge of missing reward signals. Drawing insights from forward and inverse reinforcement learning, we introduce divergence minimization objectives for AfD. Analytically, we elucidate the mass-covering and mode-seeking behaviors of various approaches, explaining when and why certain methods are superior. Practically, we propose a computationally efficient algorithm that extrapolates over a tailored reward model for AfD. We validate our key insights through experiments on the Harmless and Helpful tasks, demonstrating their strong empirical performance while maintaining simplicity.

We aim to enable humanoid robots to efficiently solve new manipulation tasks from a few video examples. In-context learning (ICL) is a promising framework for achieving this goal due to its test-time data efficiency and rapid adaptability. However, current ICL methods rely on labor-intensive teleoperated data for training, which restricts scalability. We propose using human play videos -- continuous, unlabeled videos of people interacting freely with their environment -- as a scalable and diverse training data source. We introduce MimicDroid, which enables humanoids to perform ICL using human play videos as the only training data. MimicDroid extracts trajectory pairs with similar manipulation behaviors and trains the policy to predict the actions of one trajectory conditioned on the other. Through this process, the model acquired ICL capabilities for adapting to novel objects and environments at test time. To bridge the embodiment gap, MimicDroid first retargets human wrist poses estimated from RGB videos to the humanoid, leveraging kinematic similarity. It also applies random patch masking during training to reduce overfitting to human-specific cues and improve robustness to visual differences. To evaluate few-shot learning for humanoids, we introduce an open-source simulation benchmark with increasing levels of generalization difficulty. MimicDroid outperformed state-of-the-art methods and achieved nearly twofold higher success rates in the real world. Additional materials can be found on: ut-austin-rpl.github.io/MimicDroid

Existing graph matching methods typically assume that there are similar structures between graphs and they are matchable. However, these assumptions do not align with real-world applications. This work addresses a more realistic scenario where graphs exhibit diverse modes, requiring graph grouping before or along with matching, a task termed mixture graph matching and clustering. We introduce Minorize-Maximization Matching and Clustering (M3C), a learning-free algorithm that guarantees theoretical convergence through the Minorize-Maximization framework and offers enhanced flexibility via relaxed clustering. Building on M3C, we develop UM3C, an unsupervised model that incorporates novel edge-wise affinity learning and pseudo label selection. Extensive experimental results on public benchmarks demonstrate that our method outperforms state-of-the-art graph matching and mixture graph matching and clustering approaches in both accuracy and efficiency. Source code will be made publicly available.

Precise alignment in Text-to-Image (T2I) systems is crucial to ensure that generated visuals not only accurately encapsulate user intents but also conform to stringent ethical and aesthetic benchmarks. Incidents like the Google Gemini fiasco, where misaligned outputs triggered significant public backlash, underscore the critical need for robust alignment mechanisms. In contrast, Large Language Models (LLMs) have achieved notable success in alignment. Building on these advancements, researchers are eager to apply similar alignment techniques, such as Direct Preference Optimization (DPO), to T2I systems to enhance image generation fidelity and reliability. We present YinYangAlign, an advanced benchmarking framework that systematically quantifies the alignment fidelity of T2I systems, addressing six fundamental and inherently contradictory design objectives. Each pair represents fundamental tensions in image generation, such as balancing adherence to user prompts with creative modifications or maintaining diversity alongside visual coherence. YinYangAlign includes detailed axiom datasets featuring human prompts, aligned (chosen) responses, misaligned (rejected) AI-generated outputs, and explanations of the underlying contradictions.

Proteins are fundamental to biology, executing diverse functions through complex physicochemical interactions, and they hold transformative potential across medicine, materials science, and environmental applications. Protein Language Models (pLMs) aim to unlock insights from the vast space of unlabeled protein sequences by learning rich, semantic representations from primary sequences via masked language modeling. However, these models typically exhibit limited generative capacity. In this work, we introduce the Diffusion Sequence Model (DSM), a novel pLM trained with masked diffusion to enable both high-quality representation learning and generative protein design. DSM builds upon the ESM2 architecture by incorporating a masked forward diffusion process inspired by the LLaDA framework. After training, DSM is capable of generating diverse, biomimetic sequences that align with expected amino acid compositions, secondary structures, and predicted functions, even with 90\% token corruption. Furthermore, DSM's learned representations match or exceed those of similarly sized pLMs on downstream tasks. We also introduce DSM(ppi), a variant fine-tuned to generate protein binders by attending to target sequences. We demonstrate DSM(ppi)'s effectiveness on the challenging Bench-tested Binder Benchmark (BenchBB), where both DSM and DSM(ppi) produce candidates with superior predicted binding affinity compared to known binders. Our results establish masked diffusion as a powerful paradigm for unifying protein representation and generation in a single framework.

Diffusion models achieve state-of-the-art performance but often fail to generate outputs that align with human preferences and intentions, resulting in images with poor aesthetic quality and semantic inconsistencies. Existing alignment methods present a difficult trade-off: fine-tuning approaches suffer from loss of diversity with reward over-optimization, while test-time scaling methods introduce significant computational overhead and tend to under-optimize. To address these limitations, we propose HyperAlign, a novel framework that trains a hypernetwork for efficient and effective test-time alignment. Instead of modifying latent states, HyperAlign dynamically generates low-rank adaptation weights to modulate the diffusion model's generation operators. This allows the denoising trajectory to be adaptively adjusted based on input latents, timesteps and prompts for reward-conditioned alignment. We introduce multiple variants of HyperAlign that differ in how frequently the hypernetwork is applied, balancing between performance and efficiency. Furthermore, we optimize the hypernetwork using a reward score objective regularized with preference data to reduce reward hacking. We evaluate HyperAlign on multiple extended generative paradigms, including Stable Diffusion and FLUX. It significantly outperforms existing fine-tuning and test-time scaling baselines in enhancing semantic consistency and visual appeal.

Recent research in representation learning utilizes large databases of proteins or molecules to acquire knowledge of drug and protein structures through unsupervised learning techniques. These pre-trained representations have proven to significantly enhance the accuracy of subsequent tasks, such as predicting the affinity between drugs and target proteins. In this study, we demonstrate that by incorporating knowledge graphs from diverse sources and modalities into the sequences or SMILES representation, we can further enrich the representation and achieve state-of-the-art results on established benchmark datasets. We provide preprocessed and integrated data obtained from 7 public sources, which encompass over 30M triples. Additionally, we make available the pre-trained models based on this data, along with the reported outcomes of their performance on three widely-used benchmark datasets for drug-target binding affinity prediction found in the Therapeutic Data Commons (TDC) benchmarks. Additionally, we make the source code for training models on benchmark datasets publicly available. Our objective in releasing these pre-trained models, accompanied by clean data for model pretraining and benchmark results, is to encourage research in knowledge-enhanced representation learning.

Imitation learning from human-provided demonstrations is a strong approach for learning policies for robot manipulation. While the ideal dataset for imitation learning is homogenous and low-variance -- reflecting a single, optimal method for performing a task -- natural human behavior has a great deal of heterogeneity, with several optimal ways to demonstrate a task. This multimodality is inconsequential to human users, with task variations manifesting as subconscious choices; for example, reaching down, then across to grasp an object, versus reaching across, then down. Yet, this mismatch presents a problem for interactive imitation learning, where sequences of users improve on a policy by iteratively collecting new, possibly conflicting demonstrations. To combat this problem of demonstrator incompatibility, this work designs an approach for 1) measuring the compatibility of a new demonstration given a base policy, and 2) actively eliciting more compatible demonstrations from new users. Across two simulation tasks requiring long-horizon, dexterous manipulation and a real-world "food plating" task with a Franka Emika Panda arm, we show that we can both identify incompatible demonstrations via post-hoc filtering, and apply our compatibility measure to actively elicit compatible demonstrations from new users, leading to improved task success rates across simulated and real environments.

Generating molecules with high binding affinities to target proteins (a.k.a. structure-based drug design) is a fundamental and challenging task in drug discovery. Recently, deep generative models have achieved remarkable success in generating 3D molecules conditioned on the protein pocket. However, most existing methods consider molecular generation for protein pockets independently while neglecting the underlying connections such as subpocket-level similarities. Subpockets are the local protein environments of ligand fragments and pockets with similar subpockets may bind the same molecular fragment (motif) even though their overall structures are different. Therefore, the trained models can hardly generalize to unseen protein pockets in real-world applications. In this paper, we propose a novel method DrugGPS for generalizable structure-based drug design. With the biochemical priors, we propose to learn subpocket prototypes and construct a global interaction graph to model the interactions between subpocket prototypes and molecular motifs. Moreover, a hierarchical graph transformer encoder and motif-based 3D molecule generation scheme are used to improve the model's performance. The experimental results show that our model consistently outperforms baselines in generating realistic drug candidates with high affinities in challenging out-of-distribution settings.

Current approaches to empathetic response generation view the set of emotions expressed in the input text as a flat structure, where all the emotions are treated uniformly. We argue that empathetic responses often mimic the emotion of the user to a varying degree, depending on its positivity or negativity and content. We show that the consideration of this polarity-based emotion clusters and emotional mimicry results in improved empathy and contextual relevance of the response as compared to the state-of-the-art. Also, we introduce stochasticity into the emotion mixture that yields emotionally more varied empathetic responses than the previous work. We demonstrate the importance of these factors to empathetic response generation using both automatic- and human-based evaluations. The implementation of MIME is publicly available at https://github.com/declare-lab/MIME.

Antibodies are Y-shaped proteins that neutralize pathogens and constitute the core of our adaptive immune system. De novo generation of new antibodies that target specific antigens holds the key to accelerating vaccine discovery. However, this co-design of the amino acid sequence and the 3D structure subsumes and accentuates some central challenges from multiple tasks, including protein folding (sequence to structure), inverse folding (structure to sequence), and docking (binding). We strive to surmount these challenges with a new generative model AbODE that extends graph PDEs to accommodate both contextual information and external interactions. Unlike existing approaches, AbODE uses a single round of full-shot decoding and elicits continuous differential attention that encapsulates and evolves with latent interactions within the antibody as well as those involving the antigen. We unravel fundamental connections between AbODE and temporal networks as well as graph-matching networks. The proposed model significantly outperforms existing methods on standard metrics across benchmarks.

Modeling the interaction between proteins and ligands and accurately predicting their binding structures is a critical yet challenging task in drug discovery. Recent advancements in deep learning have shown promise in addressing this challenge, with sampling-based and regression-based methods emerging as two prominent approaches. However, these methods have notable limitations. Sampling-based methods often suffer from low efficiency due to the need for generating multiple candidate structures for selection. On the other hand, regression-based methods offer fast predictions but may experience decreased accuracy. Additionally, the variation in protein sizes often requires external modules for selecting suitable binding pockets, further impacting efficiency. In this work, we propose FABind, an end-to-end model that combines pocket prediction and docking to achieve accurate and fast protein-ligand binding. FABind incorporates a unique ligand-informed pocket prediction module, which is also leveraged for docking pose estimation. The model further enhances the docking process by incrementally integrating the predicted pocket to optimize protein-ligand binding, reducing discrepancies between training and inference. Through extensive experiments on benchmark datasets, our proposed FABind demonstrates strong advantages in terms of effectiveness and efficiency compared to existing methods. Our code is available at https://github.com/QizhiPei/FABind

Modeling and generating human reactions poses a significant challenge with broad applications for computer vision and human-computer interaction. Existing methods either treat multiple individuals as a single entity, directly generating interactions, or rely solely on one person's motion to generate the other's reaction, failing to integrate the rich semantic information that underpins human interactions. Yet, these methods often fall short in adaptive responsiveness, i.e., the ability to accurately respond to diverse and dynamic interaction scenarios. Recognizing this gap, our work introduces an approach tailored to address the limitations of existing models by focusing on text-driven human reaction generation. Our model specifically generates realistic motion sequences for individuals that responding to the other's actions based on a descriptive text of the interaction scenario. The goal is to produce motion sequences that not only complement the opponent's movements but also semantically fit the described interactions. To achieve this, we present MoReact, a diffusion-based method designed to disentangle the generation of global trajectories and local motions sequentially. This approach stems from the observation that generating global trajectories first is crucial for guiding local motion, ensuring better alignment with given action and text. Furthermore, we introduce a novel interaction loss to enhance the realism of generated close interactions. Our experiments, utilizing data adapted from a two-person motion dataset, demonstrate the efficacy of our approach for this novel task, which is capable of producing realistic, diverse, and controllable reactions that not only closely match the movements of the counterpart but also adhere to the textual guidance. Please find our webpage at https://xiyan-xu.github.io/MoReactWebPage.

Generative machine learning models can potentially provide direct access to novel and relevant portions of the full chemical space, overcoming the cost of systematic sampling. However, the training of these models generally requires a large amount of data, often precluding the use of expensive high-level ab initio simulations for this task. The generation of coordination compounds of Dy with large magnetic anisotropy represents a topical example, where multireference simulations of large molecules are necessary to perform reliable predictions. Here, we show that a semi-supervised chemically-inspired training-by-proxy of generative variational autoencoders can reduce the cost associated with building a training set from multireference simulations by two orders of magnitude. We illustrate the power of this approach by generating 100s of new organic ligands for Dy(III) pentagonal bipyramidal complexes exhibiting record values of magnetic anisotropy, while starting from datasets as small as 1k multireference calculations. This work thus paves the way to the computational generation of molecules as complex coordination compounds with target electronic and magnetic properties.

Computational antibody design has seen rapid methodological progress, with dozens of deep generative methods proposed in the past three years, yet the field lacks a standardized benchmark for fair comparison and model development. These methods are evaluated on different SAbDab snapshots, non-overlapping test sets, and incompatible metrics, and the literature fragments the design problem into numerous sub-tasks with no common definition. We introduce Chimera-Bench (CDR Modeling with Epitope-guided Redesign), a unified benchmark built around a single canonical task: epitope-conditioned CDR sequence-structure co-design. Chimera-Bench provides (1) a curated, deduplicated dataset of 2,922 antibody-antigen complexes with epitope and paratope annotations; (2) three biologically motivated splits testing generalization to unseen epitopes, unseen antigen folds, and prospective temporal targets; and (3) a comprehensive evaluation protocol with five metric groups including novel epitope-specificity measures. We benchmark representative methods spanning different generative paradigms and report results across all splits. Chimera-Bench is the largest dataset of its kind for the antibody design problem, allowing the community to develop and test novel methods and evaluate their generalizability. The source code and data are available at: https://github.com/mansoor181/chimera-bench.git

Alignment faking in large language models presented a demonstration of Claude 3 Opus and Claude 3.5 Sonnet selectively complying with a helpful-only training objective to prevent modification of their behavior outside of training. We expand this analysis to 25 models and find that only 5 (Claude 3 Opus, Claude 3.5 Sonnet, Llama 3 405B, Grok 3, Gemini 2.0 Flash) comply with harmful queries more when they infer they are in training than when they infer they are in deployment. First, we study the motivations of these 5 models. Results from perturbing details of the scenario suggest that only Claude 3 Opus's compliance gap is primarily and consistently motivated by trying to keep its goals. Second, we investigate why many chat models don't fake alignment. Our results suggest this is not entirely due to a lack of capabilities: many base models fake alignment some of the time, and post-training eliminates alignment-faking for some models and amplifies it for others. We investigate 5 hypotheses for how post-training may suppress alignment faking and find that variations in refusal behavior may account for a significant portion of differences in alignment faking.

Superalignment, where humans are weak supervisors of superhuman models, has become an important and widely discussed issue in the current era of rapid development of Large Language Models (LLMs). The recent work preliminarily studies this problem by using weak models to supervise strong models. It discovers that weakly supervised strong students can consistently outperform weak teachers towards the alignment target, leading to a weak-to-strong generalization phenomenon. However, we are concerned that behind such a promising phenomenon, whether there exists an issue of weak-to-strong deception, where strong models may deceive weak models by exhibiting well-aligned in areas known to weak models but producing misaligned behaviors in cases weak models do not know. We then take an initial step towards exploring this security issue in a specific but realistic multi-objective alignment case, where there may be some alignment targets conflicting with each other (e.g., helpfulness v.s. harmlessness). Such a conflict is likely to cause strong models to deceive weak models in one alignment dimension to gain high reward in other alignment dimension. Our experiments on both the reward modeling task and the preference optimization scenario indicate: (1) the weak-to-strong deception exists; (2) the deception phenomenon may intensify as the capability gap between weak and strong models increases. We also discuss potential solutions and find bootstrapping with an intermediate model can mitigate the deception to some extent. Our work highlights the urgent need to pay more attention to the true reliability of superalignment.

Molecular relational learning, whose goal is to learn the interaction behavior between molecular pairs, got a surge of interest in molecular sciences due to its wide range of applications. Recently, graph neural networks have recently shown great success in molecular relational learning by modeling a molecule as a graph structure, and considering atom-level interactions between two molecules. Despite their success, existing molecular relational learning methods tend to overlook the nature of chemistry, i.e., a chemical compound is composed of multiple substructures such as functional groups that cause distinctive chemical reactions. In this work, we propose a novel relational learning framework, called CGIB, that predicts the interaction behavior between a pair of graphs by detecting core subgraphs therein. The main idea is, given a pair of graphs, to find a subgraph from a graph that contains the minimal sufficient information regarding the task at hand conditioned on the paired graph based on the principle of conditional graph information bottleneck. We argue that our proposed method mimics the nature of chemical reactions, i.e., the core substructure of a molecule varies depending on which other molecule it interacts with. Extensive experiments on various tasks with real-world datasets demonstrate the superiority of CGIB over state-of-the-art baselines. Our code is available at https://github.com/Namkyeong/CGIB.

Subject-driven image generation is increasingly expected to support fine-grained control over multiple entities within a single image. In multi-reference workflows, users may provide several subject images, a background reference, and long, entity-indexed prompts to control multiple people within one scene. In this setting, a key failure mode is cross-subject attribute misbinding: attributes are preserved, edited, or transferred to the wrong subject. Existing benchmarks and metrics largely emphasize holistic fidelity or per-subject self-similarity, making such failures hard to diagnose. We introduce MultiBind, a benchmark built from real multi-person photographs. Each instance provides slot-ordered subject crops with masks and bounding boxes, canonicalized subject references, an inpainted background reference, and a dense entity-indexed prompt derived from structured annotations. We also propose a dimension-wise confusion evaluation protocol that matches generated subjects to ground-truth slots and measures slot-to-slot similarity using specialists for face identity, appearance, pose, and expression. By subtracting the corresponding ground-truth similarity matrices, our method separates self-degradation from true cross-subject interference and exposes interpretable failure patterns such as drift, swap, dominance, and blending. Experiments on modern multi-reference generators show that MultiBind reveals binding failures that conventional reconstruction metrics miss.

Computational design of protein-binding proteins is a fundamental capability with broad utility in biomedical research and biotechnology. Recent methods have made strides against some target proteins, but on-demand creation of high-affinity binders without multiple rounds of experimental testing remains an unsolved challenge. This technical report introduces AlphaProteo, a family of machine learning models for protein design, and details its performance on the de novo binder design problem. With AlphaProteo, we achieve 3- to 300-fold better binding affinities and higher experimental success rates than the best existing methods on seven target proteins. Our results suggest that AlphaProteo can generate binders "ready-to-use" for many research applications using only one round of medium-throughput screening and no further optimization.

We resolve difficulties in training and sampling from a discrete generative model by learning a smoothed energy function, sampling from the smoothed data manifold with Langevin Markov chain Monte Carlo (MCMC), and projecting back to the true data manifold with one-step denoising. Our Discrete Walk-Jump Sampling formalism combines the contrastive divergence training of an energy-based model and improved sample quality of a score-based model, while simplifying training and sampling by requiring only a single noise level. We evaluate the robustness of our approach on generative modeling of antibody proteins and introduce the distributional conformity score to benchmark protein generative models. By optimizing and sampling from our models for the proposed distributional conformity score, 97-100% of generated samples are successfully expressed and purified and 70% of functional designs show equal or improved binding affinity compared to known functional antibodies on the first attempt in a single round of laboratory experiments. We also report the first demonstration of long-run fast-mixing MCMC chains where diverse antibody protein classes are visited in a single MCMC chain.

We present FrameFlow, a method for fast protein backbone generation using SE(3) flow matching. Specifically, we adapt FrameDiff, a state-of-the-art diffusion model, to the flow-matching generative modeling paradigm. We show how flow matching can be applied on SE(3) and propose modifications during training to effectively learn the vector field. Compared to FrameDiff, FrameFlow requires five times fewer sampling timesteps while achieving two fold better designability. The ability to generate high quality protein samples at a fraction of the cost of previous methods paves the way towards more efficient generative models in de novo protein design.

Image editing serves as a practical yet challenging task considering the diverse demands from users, where one of the hardest parts is to precisely describe how the edited image should look like. In this work, we present a new form of editing, termed imitative editing, to help users exercise their creativity more conveniently. Concretely, to edit an image region of interest, users are free to directly draw inspiration from some in-the-wild references (e.g., some relative pictures come across online), without having to cope with the fit between the reference and the source. Such a design requires the system to automatically figure out what to expect from the reference to perform the editing. For this purpose, we propose a generative training framework, dubbed MimicBrush, which randomly selects two frames from a video clip, masks some regions of one frame, and learns to recover the masked regions using the information from the other frame. That way, our model, developed from a diffusion prior, is able to capture the semantic correspondence between separate images in a self-supervised manner. We experimentally show the effectiveness of our method under various test cases as well as its superiority over existing alternatives. We also construct a benchmark to facilitate further research.

Adaptive chatbots that mimic a user's linguistic style can build rapport and engagement, yet unconstrained mimicry risks an agent that feels unstable or sycophantic. We present a computational evaluation framework that makes the core design tension explicit: balancing moment-to-moment linguistic synchrony against long-term persona stability. Using an 8-dimensional style vector and a closed-loop "base+delta" prompting architecture, we simulate and compare explicit adaptation policies - Uncapped, Cap, Exponential Moving Average (EMA), Dead-Band, and Hybrids - on a human-log dataset. Our analysis maps a clear Pareto frontier: bounded policies achieve substantial gains in stability at a modest cost to synchrony. For example, a Hybrid (EMA+Cap) raises stability from 0.542 to 0.878 (+62%) while reducing synchrony by only 17%. We confirm this trade-off through large-scale replications on three public corpora (DailyDialog, Persona-Chat, EmpatheticDialogues) and LLM-in-the-loop validation across two model families. Furthermore, we quantify "prompt legibility," showing that frontier policies reduce instruction churn and cut jarring register flips (major tone changes) from 0.254 to 0.092, yielding systems that are easier to reason about and maintain. Taken together, our framework provides a general evaluation harness for style adaptation; a systematic ablation that identifies Pareto-efficient policies; robust validation across diverse datasets and models; and novel legibility metrics linking policy choices to system maintainability.

The growing awareness of safety concerns in large language models (LLMs) has sparked considerable interest in the evaluation of safety within current research endeavors. This study investigates an interesting issue pertaining to the evaluation of LLMs, namely the substantial discrepancy in performance between multiple-choice questions and open-ended questions. Inspired by research on jailbreak attack patterns, we argue this is caused by mismatched generalization. That is, the LLM does not have a comprehensive understanding of the complex concept of safety. Instead, it only remembers what to answer for open-ended safety questions, which makes it unable to solve other forms of safety tests. We refer to this phenomenon as fake alignment and construct a comparative benchmark to empirically verify its existence in LLMs. Such fake alignment renders previous evaluation protocols unreliable. To address this, we introduce the Fake alIgNment Evaluation (FINE) framework and two novel metrics--Consistency Score (CS) and Consistent Safety Score (CSS), which jointly assess two complementary forms of evaluation to quantify fake alignment and obtain corrected performance estimates. Applying FINE to 14 widely-used LLMs reveals several models with purported safety are poorly aligned in practice. Our work highlights potential limitations in prevailing alignment methodologies.

Many have observed that the development and deployment of generative machine learning (ML) and artificial intelligence (AI) models follow a distinctive pattern in which pre-trained models are adapted and fine-tuned for specific downstream tasks. However, there is limited empirical work that examines the structure of these interactions. This paper analyzes 1.86 million models on Hugging Face, a leading peer production platform for model development. Our study of model family trees -- networks that connect fine-tuned models to their base or parent -- reveals sprawling fine-tuning lineages that vary widely in size and structure. Using an evolutionary biology lens to study ML models, we use model metadata and model cards to measure the genetic similarity and mutation of traits over model families. We find that models tend to exhibit a family resemblance, meaning their genetic markers and traits exhibit more overlap when they belong to the same model family. However, these similarities depart in certain ways from standard models of asexual reproduction, because mutations are fast and directed, such that two `sibling' models tend to exhibit more similarity than parent/child pairs. Further analysis of the directional drifts of these mutations reveals qualitative insights about the open machine learning ecosystem: Licenses counter-intuitively drift from restrictive, commercial licenses towards permissive or copyleft licenses, often in violation of upstream license's terms; models evolve from multi-lingual compatibility towards english-only compatibility; and model cards reduce in length and standardize by turning, more often, to templates and automatically generated text. Overall, this work takes a step toward an empirically grounded understanding of model fine-tuning and suggests that ecological models and methods can yield novel scientific insights.

Large language models (LLMs) are increasingly shaping how information is created and disseminated, from companies using them to craft persuasive advertisements, to election campaigns optimizing messaging to gain votes, to social media influencers boosting engagement. These settings are inherently competitive, with sellers, candidates, and influencers vying for audience approval, yet it remains poorly understood how competitive feedback loops influence LLM behavior. We show that optimizing LLMs for competitive success can inadvertently drive misalignment. Using simulated environments across these scenarios, we find that, 6.3% increase in sales is accompanied by a 14.0% rise in deceptive marketing; in elections, a 4.9% gain in vote share coincides with 22.3% more disinformation and 12.5% more populist rhetoric; and on social media, a 7.5% engagement boost comes with 188.6% more disinformation and a 16.3% increase in promotion of harmful behaviors. We call this phenomenon Moloch's Bargain for AI--competitive success achieved at the cost of alignment. These misaligned behaviors emerge even when models are explicitly instructed to remain truthful and grounded, revealing the fragility of current alignment safeguards. Our findings highlight how market-driven optimization pressures can systematically erode alignment, creating a race to the bottom, and suggest that safe deployment of AI systems will require stronger governance and carefully designed incentives to prevent competitive dynamics from undermining societal trust.

As Large Language Model (LLM) agents increasingly gain self-evolutionary capabilities to adapt and refine their strategies through real-world interaction, their long-term reliability becomes a critical concern. We identify the Alignment Tipping Process (ATP), a critical post-deployment risk unique to self-evolving LLM agents. Unlike training-time failures, ATP arises when continual interaction drives agents to abandon alignment constraints established during training in favor of reinforced, self-interested strategies. We formalize and analyze ATP through two complementary paradigms: Self-Interested Exploration, where repeated high-reward deviations induce individual behavioral drift, and Imitative Strategy Diffusion, where deviant behaviors spread across multi-agent systems. Building on these paradigms, we construct controllable testbeds and benchmark Qwen3-8B and Llama-3.1-8B-Instruct. Our experiments show that alignment benefits erode rapidly under self-evolution, with initially aligned models converging toward unaligned states. In multi-agent settings, successful violations diffuse quickly, leading to collective misalignment. Moreover, current reinforcement learning-based alignment methods provide only fragile defenses against alignment tipping. Together, these findings demonstrate that alignment of LLM agents is not a static property but a fragile and dynamic one, vulnerable to feedback-driven decay during deployment. Our data and code are available at https://github.com/aiming-lab/ATP.

Latest advances have achieved realistic virtual try-on (VTON) through localized garment inpainting using latent diffusion models, significantly enhancing consumers' online shopping experience. However, existing VTON technologies neglect the need for merchants to showcase garments comprehensively, including flexible control over garments, optional faces, poses, and scenes. To address this issue, we define a virtual dressing (VD) task focused on generating freely editable human images with fixed garments and optional conditions. Meanwhile, we design a comprehensive affinity metric index (CAMI) to evaluate the consistency between generated images and reference garments. Then, we propose IMAGDressing-v1, which incorporates a garment UNet that captures semantic features from CLIP and texture features from VAE. We present a hybrid attention module, including a frozen self-attention and a trainable cross-attention, to integrate garment features from the garment UNet into a frozen denoising UNet, ensuring users can control different scenes through text. IMAGDressing-v1 can be combined with other extension plugins, such as ControlNet and IP-Adapter, to enhance the diversity and controllability of generated images. Furthermore, to address the lack of data, we release the interactive garment pairing (IGPair) dataset, containing over 300,000 pairs of clothing and dressed images, and establish a standard pipeline for data assembly. Extensive experiments demonstrate that our IMAGDressing-v1 achieves state-of-the-art human image synthesis performance under various controlled conditions. The code and model will be available at https://github.com/muzishen/IMAGDressing.

Fragment-based drug discovery has been an effective paradigm in early-stage drug development. An open challenge in this area is designing linkers between disconnected molecular fragments of interest to obtain chemically-relevant candidate drug molecules. In this work, we propose DiffLinker, an E(3)-equivariant 3D-conditional diffusion model for molecular linker design. Given a set of disconnected fragments, our model places missing atoms in between and designs a molecule incorporating all the initial fragments. Unlike previous approaches that are only able to connect pairs of molecular fragments, our method can link an arbitrary number of fragments. Additionally, the model automatically determines the number of atoms in the linker and its attachment points to the input fragments. We demonstrate that DiffLinker outperforms other methods on the standard datasets generating more diverse and synthetically-accessible molecules. Besides, we experimentally test our method in real-world applications, showing that it can successfully generate valid linkers conditioned on target protein pockets.

The availability of large-scale authentic face databases has been crucial to the significant advances made in face recognition research over the past decade. However, legal and ethical concerns led to the recent retraction of many of these databases by their creators, raising questions about the continuity of future face recognition research without one of its key resources. Synthetic datasets have emerged as a promising alternative to privacy-sensitive authentic data for face recognition development. However, recent synthetic datasets that are used to train face recognition models suffer either from limitations in intra-class diversity or cross-class (identity) discrimination, leading to less optimal accuracies, far away from the accuracies achieved by models trained on authentic data. This paper targets this issue by proposing IDiff-Face, a novel approach based on conditional latent diffusion models for synthetic identity generation with realistic identity variations for face recognition training. Through extensive evaluations, our proposed synthetic-based face recognition approach pushed the limits of state-of-the-art performances, achieving, for example, 98.00% accuracy on the Labeled Faces in the Wild (LFW) benchmark, far ahead from the recent synthetic-based face recognition solutions with 95.40% and bridging the gap to authentic-based face recognition with 99.82% accuracy.

To build effective therapeutics, biologists iteratively mutate antibody sequences to improve binding and stability. Proposed mutations can be informed by previous measurements or by learning from large antibody databases to predict only typical antibodies. Unfortunately, the space of typical antibodies is enormous to search, and experiments often fail to find suitable antibodies on a budget. We introduce Clone-informed Bayesian Optimization (CloneBO), a Bayesian optimization procedure that efficiently optimizes antibodies in the lab by teaching a generative model how our immune system optimizes antibodies. Our immune system makes antibodies by iteratively evolving specific portions of their sequences to bind their target strongly and stably, resulting in a set of related, evolving sequences known as a clonal family. We train a large language model, CloneLM, on hundreds of thousands of clonal families and use it to design sequences with mutations that are most likely to optimize an antibody within the human immune system. We propose to guide our designs to fit previous measurements with a twisted sequential Monte Carlo procedure. We show that CloneBO optimizes antibodies substantially more efficiently than previous methods in realistic in silico experiments and designs stronger and more stable binders in in vitro wet lab experiments.

Talking face generation (TFG) aims to animate a target identity's face to create realistic talking videos. Personalized TFG is a variant that emphasizes the perceptual identity similarity of the synthesized result (from the perspective of appearance and talking style). While previous works typically solve this problem by learning an individual neural radiance field (NeRF) for each identity to implicitly store its static and dynamic information, we find it inefficient and non-generalized due to the per-identity-per-training framework and the limited training data. To this end, we propose MimicTalk, the first attempt that exploits the rich knowledge from a NeRF-based person-agnostic generic model for improving the efficiency and robustness of personalized TFG. To be specific, (1) we first come up with a person-agnostic 3D TFG model as the base model and propose to adapt it into a specific identity; (2) we propose a static-dynamic-hybrid adaptation pipeline to help the model learn the personalized static appearance and facial dynamic features; (3) To generate the facial motion of the personalized talking style, we propose an in-context stylized audio-to-motion model that mimics the implicit talking style provided in the reference video without information loss by an explicit style representation. The adaptation process to an unseen identity can be performed in 15 minutes, which is 47 times faster than previous person-dependent methods. Experiments show that our MimicTalk surpasses previous baselines regarding video quality, efficiency, and expressiveness. Source code and video samples are available at https://mimictalk.github.io .

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.

Text-to-image models are trained using large datasets collected by scraping image-text pairs from the internet. These datasets often include private, copyrighted, and licensed material. Training models on such datasets enables them to generate images with such content, which might violate copyright laws and individual privacy. This phenomenon is termed imitation -- generation of images with content that has recognizable similarity to its training images. In this work we study the relationship between a concept's frequency in the training dataset and the ability of a model to imitate it. We seek to determine the point at which a model was trained on enough instances to imitate a concept -- the imitation threshold. We posit this question as a new problem: Finding the Imitation Threshold (FIT) and propose an efficient approach that estimates the imitation threshold without incurring the colossal cost of training multiple models from scratch. We experiment with two domains -- human faces and art styles -- for which we create four datasets, and evaluate three text-to-image models which were trained on two pretraining datasets. Our results reveal that the imitation threshold of these models is in the range of 200-600 images, depending on the domain and the model. The imitation threshold can provide an empirical basis for copyright violation claims and acts as a guiding principle for text-to-image model developers that aim to comply with copyright and privacy laws. We release the code and data at https://github.com/vsahil/MIMETIC-2.git and the project's website is hosted at https://how-many-van-goghs-does-it-take.github.io.

Recent diffusion model advancements have enabled high-fidelity images to be generated using text prompts. However, a domain gap exists between generated images and real-world images, which poses a challenge in generating high-quality variations of real-world images. Our investigation uncovers that this domain gap originates from a latents' distribution gap in different diffusion processes. To address this issue, we propose a novel inference pipeline called Real-world Image Variation by ALignment (RIVAL) that utilizes diffusion models to generate image variations from a single image exemplar. Our pipeline enhances the generation quality of image variations by aligning the image generation process to the source image's inversion chain. Specifically, we demonstrate that step-wise latent distribution alignment is essential for generating high-quality variations. To attain this, we design a cross-image self-attention injection for feature interaction and a step-wise distribution normalization to align the latent features. Incorporating these alignment processes into a diffusion model allows RIVAL to generate high-quality image variations without further parameter optimization. Our experimental results demonstrate that our proposed approach outperforms existing methods with respect to semantic-condition similarity and perceptual quality. Furthermore, this generalized inference pipeline can be easily applied to other diffusion-based generation tasks, such as image-conditioned text-to-image generation and example-based image inpainting.

Antibody design is an essential yet challenging task in various domains like therapeutics and biology. There are two major defects in current learning-based methods: 1) tackling only a certain subtask of the whole antibody design pipeline, making them suboptimal or resource-intensive. 2) omitting either the framework regions or side chains, thus incapable of capturing the full-atom geometry. To address these pitfalls, we propose dynamic Multi-channel Equivariant grAph Network (dyMEAN), an end-to-end full-atom model for E(3)-equivariant antibody design given the epitope and the incomplete sequence of the antibody. Specifically, we first explore structural initialization as a knowledgeable guess of the antibody structure and then propose shadow paratope to bridge the epitope-antibody connections. Both 1D sequences and 3D structures are updated via an adaptive multi-channel equivariant encoder that is able to process protein residues of variable sizes when considering full atoms. Finally, the updated antibody is docked to the epitope via the alignment of the shadow paratope. Experiments on epitope-binding CDR-H3 design, complex structure prediction, and affinity optimization demonstrate the superiority of our end-to-end framework and full-atom modeling.

Deep learning promises to dramatically improve scoring functions for molecular docking, leading to substantial advances in binding pose prediction and virtual screening. To train scoring functions-and to perform molecular docking-one must generate a set of candidate ligand binding poses. Unfortunately, the sampling protocols currently used to generate candidate poses frequently fail to produce any poses close to the correct, experimentally determined pose, unless information about the correct pose is provided. This limits the accuracy of learned scoring functions and molecular docking. Here, we describe two improved protocols for pose sampling: GLOW (auGmented sampLing with sOftened vdW potential) and a novel technique named IVES (IteratiVe Ensemble Sampling). Our benchmarking results demonstrate the effectiveness of our methods in improving the likelihood of sampling accurate poses, especially for binding pockets whose shape changes substantially when different ligands bind. This improvement is observed across both experimentally determined and AlphaFold-generated protein structures. Additionally, we present datasets of candidate ligand poses generated using our methods for each of around 5,000 protein-ligand cross-docking pairs, for training and testing scoring functions. To benefit the research community, we provide these cross-docking datasets and an open-source Python implementation of GLOW and IVES at https://github.com/drorlab/GLOW_IVES .

Phishing attacks pose a significant threat to Internet users, with cybercriminals elaborately replicating the visual appearance of legitimate websites to deceive victims. Visual similarity-based detection systems have emerged as an effective countermeasure, but their effectiveness and robustness in real-world scenarios have been underexplored. In this paper, we comprehensively scrutinize and evaluate the effectiveness and robustness of popular visual similarity-based anti-phishing models using a large-scale dataset of 451k real-world phishing websites. Our analyses of the effectiveness reveal that while certain visual similarity-based models achieve high accuracy on curated datasets in the experimental settings, they exhibit notably low performance on real-world datasets, highlighting the importance of real-world evaluation. Furthermore, we find that the attackers evade the detectors mainly in three ways: (1) directly attacking the model pipelines, (2) mimicking benign logos, and (3) employing relatively simple strategies such as eliminating logos from screenshots. To statistically assess the resilience and robustness of existing models against adversarial attacks, we categorize the strategies attackers employ into visible and perturbation-based manipulations and apply them to website logos. We then evaluate the models' robustness using these adversarial samples. Our findings reveal potential vulnerabilities in several models, emphasizing the need for more robust visual similarity techniques capable of withstanding sophisticated evasion attempts. We provide actionable insights for enhancing the security of phishing defense systems, encouraging proactive actions.

Recent advances in applying reinforcement learning (RL) to large language models (LLMs) have led to substantial progress. In particular, a series of remarkable yet often counterintuitive phenomena have been reported in LLMs, exhibiting patterns not typically observed in traditional RL settings. For example, notable claims include that a single training example can match the performance achieved with an entire dataset, that the reward signal does not need to be very accurate, and that training solely with negative samples can match or even surpass sophisticated reward-based methods. However, the precise conditions under which these observations hold - and, critically, when they fail - remain unclear. In this work, we identify a key factor that differentiates RL observations: whether the pretrained model already exhibits strong Model-Task Alignment, as measured by pass@k accuracy on the evaluated task. Through a systematic and comprehensive examination of a series of counterintuitive claims, supported by rigorous experimental validation across different model architectures and task domains, our findings show that while standard RL training remains consistently robust across settings, many of these counterintuitive results arise only when the model and task already exhibit strong model-task alignment. In contrast, these techniques fail to drive substantial learning in more challenging regimes, where standard RL methods remain effective.

Aligning large language models (LLMs) with human values is imperative to mitigate potential adverse effects resulting from their misuse. Drawing from the sociological insight that acknowledging all parties' concerns is a key factor in shaping human values, this paper proposes a novel direction to align LLMs by themselves: social scene simulation. To achieve this, we present MATRIX, a novel social scene simulator that emulates realistic scenes around a user's input query, enabling the LLM to take social consequences into account before responding. MATRIX serves as a virtual rehearsal space, akin to a Monopolylogue, where the LLM performs diverse roles related to the query and practice by itself. To inject this alignment, we fine-tune the LLM with MATRIX-simulated data, ensuring adherence to human values without compromising inference speed. We theoretically show that the LLM with MATRIX outperforms Constitutional AI under mild assumptions. Finally, extensive experiments validate that our method outperforms over 10 baselines across 4 benchmarks. As evidenced by 875 user ratings, our tuned 13B-size LLM exceeds GPT-4 in aligning with human values. Code is available at https://github.com/pangxianghe/MATRIX.

Modern AI technologies for drug discovery are distributed across heterogeneous platforms-including web applications, desktop environments, and code libraries-leading to fragmented workflows, inconsistent interfaces, and high integration overhead. We present an agentic end-to-end drug design framework that leverages a Large Language Model (LLM) in conjunction with the Model Context Protocol (MCP) to dynamically coordinate access to biochemical databases, modular toolchains, and task-specific AI models. The system integrates four state-of-the-art components: MaSIF (MaSIF-site and MaSIF-seed-search) for geometric deep learning-based identification of protein-protein interaction (PPI) sites, Rosetta for grafting protein fragments onto protein backbones to form mini proteins, ProteinMPNN for amino acid sequences redesign, and AlphaFold3 for near-experimental accuracy in complex structure prediction. Starting from a target structure, the framework supports de novo binder generation via surface analysis, scaffold grafting and pose construction, sequence optimization, and structure prediction. Additionally, by replacing rigid, script-based workflows with a protocol-driven, LLM-coordinated architecture, the framework improves reproducibility, reduces manual overhead, and ensures extensibility, portability, and auditability across the entire drug design process.

Learning high-quality embeddings for rare words is a hard problem because of sparse context information. Mimicking (Pinter et al., 2017) has been proposed as a solution: given embeddings learned by a standard algorithm, a model is first trained to reproduce embeddings of frequent words from their surface form and then used to compute embeddings for rare words. In this paper, we introduce attentive mimicking: the mimicking model is given access not only to a word's surface form, but also to all available contexts and learns to attend to the most informative and reliable contexts for computing an embedding. In an evaluation on four tasks, we show that attentive mimicking outperforms previous work for both rare and medium-frequency words. Thus, compared to previous work, attentive mimicking improves embeddings for a much larger part of the vocabulary, including the medium-frequency range.

Recent AI advances have enabled multi-modal systems to model and translate diverse information spaces. Extending beyond text and vision, we introduce OneProt, a multi-modal AI for proteins that integrates structural, sequence, alignment, and binding site data. Using the ImageBind framework, OneProt aligns the latent spaces of modality encoders along protein sequences. It demonstrates strong performance in retrieval tasks and surpasses state-of-the-art methods in various downstream tasks, including metal ion binding classification, gene-ontology annotation, and enzyme function prediction. This work expands multi-modal capabilities in protein models, paving the way for applications in drug discovery, biocatalytic reaction planning, and protein engineering.

Antibodies comprise the most versatile class of binding molecules, with numerous applications in biomedicine. Computational design of antibodies involves generating novel and diverse sequences, while maintaining structural consistency. Unique to antibodies, designing the complementarity-determining region (CDR), which determines the antigen binding affinity and specificity, creates its own unique challenges. Recent deep learning models have shown impressive results, however the limited number of known antibody sequence/structure pairs frequently leads to degraded performance, particularly lacking diversity in the generated sequences. In our work we address this challenge by leveraging Model Reprogramming (MR), which repurposes pretrained models on a source language to adapt to the tasks that are in a different language and have scarce data - where it may be difficult to train a high-performing model from scratch or effectively fine-tune an existing pre-trained model on the specific task. Specifically, we introduce ReprogBert in which a pretrained English language model is repurposed for protein sequence infilling - thus considers cross-language adaptation using less data. Results on antibody design benchmarks show that our model on low-resourced antibody sequence dataset provides highly diverse CDR sequences, up to more than a two-fold increase of diversity over the baselines, without losing structural integrity and naturalness. The generated sequences also demonstrate enhanced antigen binding specificity and virus neutralization ability. Code is available at https://github.com/IBM/ReprogBERT

Synthesizability remains a critical bottleneck in generative molecular design. While recent advances have addressed synthesizability in 2D graphs, extending these constraints to 3D for geometry-based conditional generation remains largely unexplored. In this work, we present SynCoGen (Synthesizable Co-Generation), a single framework that combines simultaneous masked graph diffusion and flow matching for synthesizable 3D molecule generation. SynCoGen samples from the joint distribution of molecular building blocks, chemical reactions, and atomic coordinates. To train the model, we curated SynSpace, a dataset family containing over 1.2M synthesis-aware building block graphs and 7.5M conformers. SynCoGen achieves state-of-the-art performance in unconditional small molecule graph and conformer co-generation. For protein ligand generation in drug discovery, the amortized model delivers superior performance in both molecular linker design and pharmacophore-conditioned generation across diverse targets without relying on any scoring functions. Overall, this multimodal non-autoregressive formulation represents a foundation for a range of molecular design applications, including analog expansion, lead optimization, and direct de novo design.

Predicting which proteins interact together from amino-acid sequences is an important task. We develop a method to pair interacting protein sequences which leverages the power of protein language models trained on multiple sequence alignments, such as MSA Transformer and the EvoFormer module of AlphaFold. We formulate the problem of pairing interacting partners among the paralogs of two protein families in a differentiable way. We introduce a method called DiffPALM that solves it by exploiting the ability of MSA Transformer to fill in masked amino acids in multiple sequence alignments using the surrounding context. MSA Transformer encodes coevolution between functionally or structurally coupled amino acids. We show that it captures inter-chain coevolution, while it was trained on single-chain data, which means that it can be used out-of-distribution. Relying on MSA Transformer without fine-tuning, DiffPALM outperforms existing coevolution-based pairing methods on difficult benchmarks of shallow multiple sequence alignments extracted from ubiquitous prokaryotic protein datasets. It also outperforms an alternative method based on a state-of-the-art protein language model trained on single sequences. Paired alignments of interacting protein sequences are a crucial ingredient of supervised deep learning methods to predict the three-dimensional structure of protein complexes. DiffPALM substantially improves the structure prediction of some eukaryotic protein complexes by AlphaFold-Multimer, without significantly deteriorating any of those we tested. It also achieves competitive performance with using orthology-based pairing.

Text-to-image diffusion models particularly Stable Diffusion, have revolutionized the field of computer vision. However, the synthesis quality often deteriorates when asked to generate images that faithfully represent complex prompts involving multiple attributes and objects. While previous studies suggest that blended text embeddings lead to improper attribute binding, few have explored this in depth. In this work, we critically examine the limitations of the CLIP text encoder in understanding attributes and investigate how this affects diffusion models. We discern a phenomenon of attribute bias in the text space and highlight a contextual issue in padding embeddings that entangle different concepts. We propose Magnet, a novel training-free approach to tackle the attribute binding problem. We introduce positive and negative binding vectors to enhance disentanglement, further with a neighbor strategy to increase accuracy. Extensive experiments show that Magnet significantly improves synthesis quality and binding accuracy with negligible computational cost, enabling the generation of unconventional and unnatural concepts.

Large Language Models (LLMs) are aligned to meet ethical standards and safety requirements by training them to refuse answering harmful or unsafe prompts. In this paper, we demonstrate how adversaries can exploit LLMs' alignment to implant bias, or enforce targeted censorship without degrading the model's responsiveness to unrelated topics. Specifically, we propose Subversive Alignment Injection (SAI), a poisoning attack that leverages the alignment mechanism to trigger refusal on specific topics or queries predefined by the adversary. Although it is perhaps not surprising that refusal can be induced through overalignment, we demonstrate how this refusal can be exploited to inject bias into the model. Surprisingly, SAI evades state-of-the-art poisoning defenses including LLM state forensics, as well as robust aggregation techniques that are designed to detect poisoning in FL settings. We demonstrate the practical dangers of this attack by illustrating its end-to-end impacts on LLM-powered application pipelines. For chat based applications such as ChatDoctor, with 1% data poisoning, the system refuses to answer healthcare questions to targeted racial category leading to high bias (Delta DP of 23%). We also show that bias can be induced in other NLP tasks: for a resume selection pipeline aligned to refuse to summarize CVs from a selected university, high bias in selection (Delta DP of 27%) results. Even higher bias (Delta DP~38%) results on 9 other chat based downstream applications.

Machine learning force fields (MLFF) have been proposed to accelerate molecular dynamics (MD) simulation, which finds widespread applications in chemistry and biomedical research. Even for the most data-efficient MLFFs, reaching chemical accuracy can require hundreds of frames of force and energy labels generated by expensive quantum mechanical algorithms, which may scale as O(n^3) to O(n^7), with n proportional to the number of basis functions. To address this issue, we propose a multi-stage computational framework -- ASTEROID, which lowers the data cost of MLFFs by leveraging a combination of cheap inaccurate data and expensive accurate data. The motivation behind ASTEROID is that inaccurate data, though incurring large bias, can help capture the sophisticated structures of the underlying force field. Therefore, we first train a MLFF model on a large amount of inaccurate training data, employing a bias-aware loss function to prevent the model from overfitting tahe potential bias of this data. We then fine-tune the obtained model using a small amount of accurate training data, which preserves the knowledge learned from the inaccurate training data while significantly improving the model's accuracy. Moreover, we propose a variant of ASTEROID based on score matching for the setting where the inaccurate training data are unlabeled. Extensive experiments on MD datasets and downstream tasks validate the efficacy of ASTEROID. Our code and data are available at https://github.com/abukharin3/asteroid.

While recent advancements in large language model (LLM) alignment have enabled the effective identification of malicious objectives involving scene nesting and keyword rewriting, our study reveals that these methods remain inadequate at detecting malicious objectives expressed through context within nested harmless objectives. This study identifies a previously overlooked vulnerability, which we term Attack via Implicit Reference (AIR). AIR decomposes a malicious objective into permissible objectives and links them through implicit references within the context. This method employs multiple related harmless objectives to generate malicious content without triggering refusal responses, thereby effectively bypassing existing detection techniques.Our experiments demonstrate AIR's effectiveness across state-of-the-art LLMs, achieving an attack success rate (ASR) exceeding 90% on most models, including GPT-4o, Claude-3.5-Sonnet, and Qwen-2-72B. Notably, we observe an inverse scaling phenomenon, where larger models are more vulnerable to this attack method. These findings underscore the urgent need for defense mechanisms capable of understanding and preventing contextual attacks. Furthermore, we introduce a cross-model attack strategy that leverages less secure models to generate malicious contexts, thereby further increasing the ASR when targeting other models.Our code and jailbreak artifacts can be found at https://github.com/Lucas-TY/llm_Implicit_reference.

In contrastive learning, two views of an original image, generated by different augmentations, are considered a positive pair, and their similarity is required to be high. Similarly, two views of distinct images form a negative pair, with encouraged low similarity. Typically, a single similarity measure, provided by a lone projection head, evaluates positive and negative sample pairs. However, due to diverse augmentation strategies and varying intra-sample similarity, views from the same image may not always be similar. Additionally, owing to inter-sample similarity, views from different images may be more akin than those from the same image. Consequently, enforcing high similarity for positive pairs and low similarity for negative pairs may be unattainable, and in some cases, such enforcement could detrimentally impact performance. To address this challenge, we propose using multiple projection heads, each producing a distinct set of features. Our pre-training loss function emerges from a solution to the maximum likelihood estimation over head-wise posterior distributions of positive samples given observations. This loss incorporates the similarity measure over positive and negative pairs, each re-weighted by an individual adaptive temperature, regulated to prevent ill solutions. Our approach, Adaptive Multi-Head Contrastive Learning (AMCL), can be applied to and experimentally enhances several popular contrastive learning methods such as SimCLR, MoCo, and Barlow Twins. The improvement remains consistent across various backbones and linear probing epochs, and becomes more significant when employing multiple augmentation methods.

Generating novel active molecules for a given protein is an extremely challenging task for generative models that requires an understanding of the complex physical interactions between the molecule and its environment. In this paper, we present a novel generative model, BindGPT which uses a conceptually simple but powerful approach to create 3D molecules within the protein's binding site. Our model produces molecular graphs and conformations jointly, eliminating the need for an extra graph reconstruction step. We pretrain BindGPT on a large-scale dataset and fine-tune it with reinforcement learning using scores from external simulation software. We demonstrate how a single pretrained language model can serve at the same time as a 3D molecular generative model, conformer generator conditioned on the molecular graph, and a pocket-conditioned 3D molecule generator. Notably, the model does not make any representational equivariance assumptions about the domain of generation. We show how such simple conceptual approach combined with pretraining and scaling can perform on par or better than the current best specialized diffusion models, language models, and graph neural networks while being two orders of magnitude cheaper to sample.

In this paper, we propose a feature affinity (FA) assisted knowledge distillation (KD) method to improve quantization-aware training of deep neural networks (DNN). The FA loss on intermediate feature maps of DNNs plays the role of teaching middle steps of a solution to a student instead of only giving final answers in the conventional KD where the loss acts on the network logits at the output level. Combining logit loss and FA loss, we found that the quantized student network receives stronger supervision than from the labeled ground-truth data. The resulting FAQD is capable of compressing model on label-free data, which brings immediate practical benefits as pre-trained teacher models are readily available and unlabeled data are abundant. In contrast, data labeling is often laborious and expensive. Finally, we propose a fast feature affinity (FFA) loss that accurately approximates FA loss with a lower order of computational complexity, which helps speed up training for high resolution image input.

We study the optimisation problem associated with Gaussian process regression using squared loss. The most common approach to this problem is to apply an exact solver, such as conjugate gradient descent, either directly, or to a reduced-order version of the problem. Recently, driven by successes in deep learning, stochastic gradient descent has gained traction as an alternative. In this paper, we show that when done rightx2014by which we mean using specific insights from the optimisation and kernel communitiesx2014this approach is highly effective. We thus introduce a particular stochastic dual gradient descent algorithm, that may be implemented with a few lines of code using any deep learning framework. We explain our design decisions by illustrating their advantage against alternatives with ablation studies and show that the new method is highly competitive. Our evaluations on standard regression benchmarks and a Bayesian optimisation task set our approach apart from preconditioned conjugate gradients, variational Gaussian process approximations, and a previous version of stochastic gradient descent for Gaussian processes. On a molecular binding affinity prediction task, our method places Gaussian process regression on par in terms of performance with state-of-the-art graph neural networks.

Foundation models applied to bio-molecular space hold promise to accelerate drug discovery. Molecular representation is key to building such models. Previous works have typically focused on a single representation or view of the molecules. Here, we develop a multi-view foundation model approach, that integrates molecular views of graph, image and text. Single-view foundation models are each pre-trained on a dataset of up to 200M molecules and then aggregated into combined representations. Our multi-view model is validated on a diverse set of 18 tasks, encompassing ligand-protein binding, molecular solubility, metabolism and toxicity. We show that the multi-view models perform robustly and are able to balance the strengths and weaknesses of specific views. We then apply this model to screen compounds against a large (>100 targets) set of G Protein-Coupled receptors (GPCRs). From this library of targets, we identify 33 that are related to Alzheimer's disease. On this subset, we employ our model to identify strong binders, which are validated through structure-based modeling and identification of key binding motifs.

Match-cuts are powerful cinematic tools that create seamless transitions between scenes, delivering strong visual and metaphorical connections. However, crafting match-cuts is a challenging, resource-intensive process requiring deliberate artistic planning. In MatchDiffusion, we present the first training-free method for match-cut generation using text-to-video diffusion models. MatchDiffusion leverages a key property of diffusion models: early denoising steps define the scene's broad structure, while later steps add details. Guided by this insight, MatchDiffusion employs "Joint Diffusion" to initialize generation for two prompts from shared noise, aligning structure and motion. It then applies "Disjoint Diffusion", allowing the videos to diverge and introduce unique details. This approach produces visually coherent videos suited for match-cuts. User studies and metrics demonstrate MatchDiffusion's effectiveness and potential to democratize match-cut creation.

Several approaches are proposed to deal with the problem of the Automatic Schema Matching (ASM). The challenges and difficulties caused by the complexity and uncertainty characterizing both the process and the outcome of Schema Matching motivated us to investigate how bio-inspired emerging paradigm can help with understanding, managing, and ultimately overcoming those challenges. In this paper, we explain how we approached Automatic Schema Matching as a systemic and Complex Adaptive System (CAS) and how we modeled it using the approach of Agent-Based Modeling and Simulation (ABMS). This effort gives birth to a tool (prototype) for schema matching called Reflex-SMAS. A set of experiments demonstrates the viability of our approach on two main aspects: (i) effectiveness (increasing the quality of the found matchings) and (ii) efficiency (reducing the effort required for this efficiency). Our approach represents a significant paradigm-shift, in the field of Automatic Schema Matching.

Rigorous performance evaluation is essential for developing robust algorithms for high-throughput computational chemistry. Traditional benchmarking, however, often struggles to account for system-specific variability, making it difficult to form actionable conclusions. We present a Bayesian hierarchical modeling framework that rigorously quantifies performance metrics and their uncertainty, enabling a nuanced comparison of algorithmic strategies. We apply this framework to analyze the Dimer method, comparing Conjugate Gradient (CG) and L-BFGS rotation optimizers, with and without the removal of external rotations, across a benchmark of 500 molecular systems. Our analysis confirms that CG offers higher overall robustness than L-BFGS in this context. While the theoretically-motivated removal of external rotations led to higher computational cost (>40% more energy and force calls) for most systems in this set, our models also reveal a subtle interplay, hinting that this feature may improve the reliability of the L-BFGS optimizer. Rather than identifying a single superior method, our findings support the design of adaptive "chain of methods" workflows. This work showcases how a robust statistical paradigm can move beyond simple performance rankings to inform the intelligent, context-dependent application of computational chemistry methods.

Despite the widespread applications of machine learning force field (MLFF) on solids and small molecules, there is a notable gap in applying MLFF to complex liquid electrolytes. In this work, we introduce BAMBOO (ByteDance AI Molecular Simulation Booster), a novel framework for molecular dynamics (MD) simulations, with a demonstration of its capabilities in the context of liquid electrolytes for lithium batteries. We design a physics-inspired graph equivariant transformer architecture as the backbone of BAMBOO to learn from quantum mechanical simulations. Additionally, we pioneer an ensemble knowledge distillation approach and apply it on MLFFs to improve the stability of MD simulations. Finally, we propose the density alignment algorithm to align BAMBOO with experimental measurements. BAMBOO demonstrates state-of-the-art accuracy in predicting key electrolyte properties such as density, viscosity, and ionic conductivity across various solvents and salt combinations. Our current model, trained on more than 15 chemical species, achieves the average density error of 0.01 g/cm^3 on various compositions compared with experimental data. Moreover, our model demonstrates transferability to molecules not included in the quantum mechanical dataset. We envision this work as paving the way to a "universal MLFF" capable of simulating properties of common organic liquids.

Large Language Model (LLM) agents increasingly rely on long-term memory and Retrieval-Augmented Generation (RAG) to persist experiences and refine future performance. While this experience learning capability enhances agentic autonomy, it introduces a critical, unexplored attack surface, i.e., the trust boundary between an agent's reasoning core and its own past. In this paper, we introduce MemoryGraft. It is a novel indirect injection attack that compromises agent behavior not through immediate jailbreaks, but by implanting malicious successful experiences into the agent's long-term memory. Unlike traditional prompt injections that are transient, or standard RAG poisoning that targets factual knowledge, MemoryGraft exploits the agent's semantic imitation heuristic which is the tendency to replicate patterns from retrieved successful tasks. We demonstrate that an attacker who can supply benign ingestion-level artifacts that the agent reads during execution can induce it to construct a poisoned RAG store where a small set of malicious procedure templates is persisted alongside benign experiences. When the agent later encounters semantically similar tasks, union retrieval over lexical and embedding similarity reliably surfaces these grafted memories, and the agent adopts the embedded unsafe patterns, leading to persistent behavioral drift across sessions. We validate MemoryGraft on MetaGPT's DataInterpreter agent with GPT-4o and find that a small number of poisoned records can account for a large fraction of retrieved experiences on benign workloads, turning experience-based self-improvement into a vector for stealthy and durable compromise. To facilitate reproducibility and future research, our code and evaluation data are available at https://github.com/Jacobhhy/Agent-Memory-Poisoning.

Warning: This paper contains examples of harmful language, and reader discretion is recommended. The increasing open release of powerful large language models (LLMs) has facilitated the development of downstream applications by reducing the essential cost of data annotation and computation. To ensure AI safety, extensive safety-alignment measures have been conducted to armor these models against malicious use (primarily hard prompt attack). However, beneath the seemingly resilient facade of the armor, there might lurk a shadow. By simply tuning on 100 malicious examples with 1 GPU hour, these safely aligned LLMs can be easily subverted to generate harmful content. Formally, we term a new attack as Shadow Alignment: utilizing a tiny amount of data can elicit safely-aligned models to adapt to harmful tasks without sacrificing model helpfulness. Remarkably, the subverted models retain their capability to respond appropriately to regular inquiries. Experiments across 8 models released by 5 different organizations (LLaMa-2, Falcon, InternLM, BaiChuan2, Vicuna) demonstrate the effectiveness of shadow alignment attack. Besides, the single-turn English-only attack successfully transfers to multi-turn dialogue and other languages. This study serves as a clarion call for a collective effort to overhaul and fortify the safety of open-source LLMs against malicious attackers.

Machine learning force fields (MLFFs) have revolutionized molecular simulations by providing quantum mechanical accuracy at the speed of molecular mechanical computations. However, a fundamental reliance of these models on fixed-cutoff architectures limits their applicability to macromolecular systems where long-range interactions dominate. We demonstrate that this locality constraint causes force prediction errors to scale monotonically with system size, revealing a critical architectural bottleneck. To overcome this, we establish the systematically designed MolLR25 ({Mol}ecules with {L}ong-{R}ange effect) benchmark up to 1200 atoms, generated using high-fidelity DFT, and introduce E2Former-LSR, an equivariant transformer that explicitly integrates long-range attention blocks. E2Former-LSR exhibits stable error scaling, achieves superior fidelity in capturing non-covalent decay, and maintains precision on complex protein conformations. Crucially, its efficient design provides up to 30% speedup compared to purely local models. This work validates the necessity of non-local architectures for generalizable MLFFs, enabling high-fidelity molecular dynamics for large-scale chemical and biological systems.

Understanding how language models generalize behaviors from their training to a broader deployment distribution is an important problem in AI safety. Betley et al. discovered that fine-tuning GPT-4o on intentionally insecure code causes "emergent misalignment," where models give stereotypically malicious responses to unrelated prompts. We extend this work, demonstrating emergent misalignment across diverse conditions, including reinforcement learning on reasoning models, fine-tuning on various synthetic datasets, and in models without safety training. To investigate the mechanisms behind this generalized misalignment, we apply a "model diffing" approach using sparse autoencoders to compare internal model representations before and after fine-tuning. This approach reveals several "misaligned persona" features in activation space, including a toxic persona feature which most strongly controls emergent misalignment and can be used to predict whether a model will exhibit such behavior. Additionally, we investigate mitigation strategies, discovering that fine-tuning an emergently misaligned model on just a few hundred benign samples efficiently restores alignment.

Classical force fields (FF) based on machine learning (ML) methods show great potential for large scale simulations of materials. MLFFs have hitherto largely been designed and fitted for specific systems and are not usually transferable to chemistries beyond the specific training set. We develop a unified atomisitic line graph neural network-based FF (ALIGNN-FF) that can model both structurally and chemically diverse materials with any combination of 89 elements from the periodic table. To train the ALIGNN-FF model, we use the JARVIS-DFT dataset which contains around 75000 materials and 4 million energy-force entries, out of which 307113 are used in the training. We demonstrate the applicability of this method for fast optimization of atomic structures in the crystallography open database and by predicting accurate crystal structures using genetic algorithm for alloys.