Daily Papers

Antibodies are essential proteins that play a central role in immune recognition by binding specific antigen molecules. Although recent protein language models have enabled progress in single-chain protein modeling and generation, they often fall short in antigen-specific antibody design, where effective modeling requires explicit pairing between antibody and antigen, particularly at the epitope level. To address these limitations, we introduce AAMFM, an Antigen-specific Antibody Multimodal Foundation Model that learns unified representations of antibody sequences and structures conditioned on antigen context. AAMFM incorporates rich antigen information including geometric interfaces and epitope annotations via a cross-modal adapter, enabling joint modeling of antibody-antigen interactions in a shared latent space. To further guide the model toward functional relevance, we fine-tune AAMFM using Calibrated Direct Preference Optimization (Cal-DPO), leveraging preference signals extracted from a strong structural prior to align learning with binding-specific objectives. Extensive experiments demonstrate that AAMFM achieves state-of-the-art performance in functional antibody design, revealing its potential for antigen-specific antibody engineering. Our code is available at https://github.com/XL-S224/AAMFM.

Object binding, the brain's ability to bind the many features that collectively represent an object into a coherent whole, is central to human cognition. It groups low-level perceptual features into high-level object representations, stores those objects efficiently and compositionally in memory, and supports human reasoning about individual object instances. While prior work often imposes object-centric attention (e.g., Slot Attention) explicitly to probe these benefits, it remains unclear whether this ability naturally emerges in pre-trained Vision Transformers (ViTs). Intuitively, they could: recognizing which patches belong to the same object should be useful for downstream prediction and thus guide attention. Motivated by the quadratic nature of self-attention, we hypothesize that ViTs represent whether two patches belong to the same object, a property we term IsSameObject. We decode IsSameObject from patch embeddings across ViT layers using a similarity probe, which reaches over 90% accuracy. Crucially, this object-binding capability emerges reliably in self-supervised ViTs (DINO, MAE, CLIP), but markedly weaker in ImageNet-supervised models, suggesting that binding is not a trivial architectural artifact, but an ability acquired through specific pretraining objectives. We further discover that IsSameObject is encoded in a low-dimensional subspace on top of object features, and that this signal actively guides attention. Ablating IsSameObject from model activations degrades downstream performance and works against the learning objective, implying that emergent object binding naturally serves the pretraining objective. Our findings challenge the view that ViTs lack object binding and highlight how symbolic knowledge of "which parts belong together" emerges naturally in a connectionist system.

Designing biological sequences that satisfy multiple, often conflicting, functional and biophysical criteria remains a central challenge in biomolecule engineering. While discrete flow matching models have recently shown promise for efficient sampling in high-dimensional sequence spaces, existing approaches address only single objectives or require continuous embeddings that can distort discrete distributions. We present Multi-Objective-Guided Discrete Flow Matching (MOG-DFM), a general framework to steer any pretrained discrete-time flow matching generator toward Pareto-efficient trade-offs across multiple scalar objectives. At each sampling step, MOG-DFM computes a hybrid rank-directional score for candidate transitions and applies an adaptive hypercone filter to enforce consistent multi-objective progression. We also trained two unconditional discrete flow matching models, PepDFM for diverse peptide generation and EnhancerDFM for functional enhancer DNA generation, as base generation models for MOG-DFM. We demonstrate MOG-DFM's effectiveness in generating peptide binders optimized across five properties (hemolysis, non-fouling, solubility, half-life, and binding affinity), and in designing DNA sequences with specific enhancer classes and DNA shapes. In total, MOG-DFM proves to be a powerful tool for multi-property-guided biomolecule sequence design.

Text-to-optimization requires two separable capabilities: modeling -- choosing the right optimization structure -- and binding -- grounding every coefficient, index, and parameter in the concrete problem data. We study this via Text2Opt-Bench, a scalable benchmark of solver-verified optimization problems spanning 12 categories, from textbook linear programs to stochastic and multi-objective formulations with up to thousands of variables. Across 10+ models, we find that accuracy collapses as instance data grows, even when the formulation itself is simple. We call this the effective binding limit. We address this via a simple inference-time approach, BIND, which externalizes numeric data to structured files so the model binds data programmatically rather than transcribing from the prompt. BIND improves GPT-5-Nano from 59.1% to 82.4% accuracy, matching pass@5 (82.0%) at lower token cost than pass@1, and GPT-5 from 86.2% to 95.8%. Furthermore, we validate our hypothesis by finetuning a model exclusively on binding and show that it outperforms end-to-end SFT and RL across three structurally distinct optimization categories, with a 1.5B binding specialist alone matching a 7B end-to-end baseline.

Large Language Models (LLMs) are nowadays expected to generate content aligned with human preferences. Current work focuses on alignment at model training time, through techniques such as Reinforcement Learning with Human Feedback (RLHF). However, it is unclear if such methods are an effective choice to teach alignment objectives to the model. First, the inability to incorporate multiple, custom rewards and reliance on a model developer's view of universal and static principles are key limitations. Second, the residual gaps in model training and the reliability of such approaches are also questionable (e.g. susceptibility to jail-breaking even after safety training). To address these, we propose DeAL, a framework that allows the user to customize reward functions and enables Decoding-time Alignment of LLMs (DeAL). At its core, we view decoding as a heuristic-guided search process and facilitate the use of a wide variety of alignment objectives. Our experiments with programmatic constraints such as keyword and length constraints (studied widely in the pre-LLM era) and abstract objectives such as harmlessness and helpfulness (proposed in the post-LLM era) show that we can DeAL with fine-grained trade-offs, improve adherence to alignment objectives, and address residual gaps in LLMs. Lastly, while DeAL can be effectively paired with RLHF and prompting techniques, its generality makes decoding slower, an optimization we leave for future work.

Emerging large-scale text-to-image generative models, e.g., Stable Diffusion (SD), have exhibited overwhelming results with high fidelity. Despite the magnificent progress, current state-of-the-art models still struggle to generate images fully adhering to the input prompt. Prior work, Attend & Excite, has introduced the concept of Generative Semantic Nursing (GSN), aiming to optimize cross-attention during inference time to better incorporate the semantics. It demonstrates promising results in generating simple prompts, e.g., ``a cat and a dog''. However, its efficacy declines when dealing with more complex prompts, and it does not explicitly address the problem of improper attribute binding. To address the challenges posed by complex prompts or scenarios involving multiple entities and to achieve improved attribute binding, we propose Divide & Bind. We introduce two novel loss objectives for GSN: a novel attendance loss and a binding loss. Our approach stands out in its ability to faithfully synthesize desired objects with improved attribute alignment from complex prompts and exhibits superior performance across multiple evaluation benchmarks. More videos and updates can be found on the project page https://sites.google.com/view/divide-and-bind.

Although text-to-image (T2I) models exhibit remarkable generation capabilities, they frequently fail to accurately bind semantically related objects or attributes in the input prompts; a challenge termed semantic binding. Previous approaches either involve intensive fine-tuning of the entire T2I model or require users or large language models to specify generation layouts, adding complexity. In this paper, we define semantic binding as the task of associating a given object with its attribute, termed attribute binding, or linking it to other related sub-objects, referred to as object binding. We introduce a novel method called Token Merging (ToMe), which enhances semantic binding by aggregating relevant tokens into a single composite token. This ensures that the object, its attributes and sub-objects all share the same cross-attention map. Additionally, to address potential confusion among main objects with complex textual prompts, we propose end token substitution as a complementary strategy. To further refine our approach in the initial stages of T2I generation, where layouts are determined, we incorporate two auxiliary losses, an entropy loss and a semantic binding loss, to iteratively update the composite token to improve the generation integrity. We conducted extensive experiments to validate the effectiveness of ToMe, comparing it against various existing methods on the T2I-CompBench and our proposed GPT-4o object binding benchmark. Our method is particularly effective in complex scenarios that involve multiple objects and attributes, which previous methods often fail to address. The code will be publicly available at https://github.com/hutaihang/ToMe.

To accurately process a visual scene, observers must bind features together to represent individual objects. This capacity is necessary, for instance, to distinguish an image containing a red square and a blue circle from an image containing a blue square and a red circle. Recent work has found that language models solve this 'binding problem' via a set of symbol-like, content-independent indices, but it is unclear whether similar mechanisms are employed by Vision Language Models (VLMs). This question is especially relevant, given the persistent failures of VLMs on tasks that require binding. Here, we identify a previously unknown set of emergent symbolic mechanisms that support binding specifically in VLMs, via a content-independent, spatial indexing scheme. Moreover, we find that binding errors, when they occur, can be traced directly to failures in these mechanisms. Taken together, these results shed light on the mechanisms that support symbol-like processing in VLMs, and suggest possible avenues for reducing the number of binding failures exhibited by these models.

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.

The computational prediction and design of peptide binders targeting specific linear epitopes is crucial in biological and biomedical research, yet it remains challenging due to their highly dynamic nature and the scarcity of experimentally solved binding data. To address this problem, we built an unprecedentedly large-scale library of peptide pairs within stable secondary structures (beta sheets), leveraging newly available AlphaFold predicted structures. We then developed a machine learning method based on the Transformer architecture for the design of specific linear binders, in analogy to a language translation task. Our method, TransformerBeta, accurately predicts specific beta strand interactions and samples sequences with beta sheet-like molecular properties, while capturing interpretable physico-chemical interaction patterns. As such, it can propose specific candidate binders targeting linear epitope for experimental validation to inform protein design.

Big models, exemplified by Large Language Models (LLMs), are models typically pre-trained on massive data and comprised of enormous parameters, which not only obtain significantly improved performance across diverse tasks but also present emergent capabilities absent in smaller models. However, the growing intertwining of big models with everyday human lives poses potential risks and might cause serious social harm. Therefore, many efforts have been made to align LLMs with humans to make them better follow user instructions and satisfy human preferences. Nevertheless, `what to align with' has not been fully discussed, and inappropriate alignment goals might even backfire. In this paper, we conduct a comprehensive survey of different alignment goals in existing work and trace their evolution paths to help identify the most essential goal. Particularly, we investigate related works from two perspectives: the definition of alignment goals and alignment evaluation. Our analysis encompasses three distinct levels of alignment goals and reveals a goal transformation from fundamental abilities to value orientation, indicating the potential of intrinsic human values as the alignment goal for enhanced LLMs. Based on such results, we further discuss the challenges of achieving such intrinsic value alignment and provide a collection of available resources for future research on the alignment of big models.

Controlled text generation is very important for the practical use of language models because it ensures that the produced text includes only the desired attributes from a specific domain or dataset. Existing methods, however, are inapplicable to black-box models or suffer a significant trade-off between controlling the generated text and maintaining its fluency. This paper introduces the Score-based Progressive Editor (ScoPE), a novel approach designed to overcome these issues. ScoPE modifies the context at the token level during the generation process of a backbone language model. This modification guides the subsequent text to naturally include the target attributes. To facilitate this process, ScoPE employs a training objective that maximizes a target score, thoroughly considering both the ability to guide the text and its fluency. Experimental results on diverse controlled generation tasks demonstrate that ScoPE can effectively regulate the attributes of the generated text while fully utilizing the capability of the backbone large language models. Our codes are available at https://github.com/ysw1021/ScoPE.

Humans easily determine which color belongs to which shape in multi-object scenes, an ability known as concept binding. Vision-language embedding models such as CLIP struggle with binding: they recognize individual concepts but fail to represent which concepts form which objects. Although CLIP behaves like a bag-of-concepts model in cross-modal retrieval, object information is recoverable from its image and text embeddings separately. We study this tension through the binding function, which maps concepts to scene embeddings. We find that scene embeddings decompose additively into object representations, explaining why uni-modal probes can recover object information. However, CLIP's binding function is high-complexity, which likely prevents the image and text encoders from learning a shared binding mechanism that generalizes to unseen concept combinations. We then ask whether this limitation is fundamental. We show that it is not. In controlled transformer models trained from scratch, binding generalization emerges with sufficient data coverage. These models learn low-complexity binding functions characterized by multiplicative interactions between concepts, enabling systematic generalization. Code is publicly available at https://github.com/oshapio/binding-concepts-complexity.

Designing enzyme backbones with substrate-specific functionality is a critical challenge in computational protein engineering. Current generative models excel in protein design but face limitations in binding data, substrate-specific control, and flexibility for de novo enzyme backbone generation. To address this, we introduce EnzyBind, a dataset with 11,100 experimentally validated enzyme-substrate pairs specifically curated from PDBbind. Building on this, we propose EnzyControl, a method that enables functional and substrate-specific control in enzyme backbone generation. Our approach generates enzyme backbones conditioned on MSA-annotated catalytic sites and their corresponding substrates, which are automatically extracted from curated enzyme-substrate data. At the core of EnzyControl is EnzyAdapter, a lightweight, modular component integrated into a pretrained motif-scaffolding model, allowing it to become substrate-aware. A two-stage training paradigm further refines the model's ability to generate accurate and functional enzyme structures. Experiments show that our EnzyControl achieves the best performance across structural and functional metrics on EnzyBind and EnzyBench benchmarks, with particularly notable improvements of 13\% in designability and 13\% in catalytic efficiency compared to the baseline models. The code is released at https://github.com/Vecteur-libre/EnzyControl.

Though end-to-end neural approaches have recently been dominating NLP tasks in both performance and ease-of-use, they lack interpretability and robustness. We propose Binder, a training-free neural-symbolic framework that maps the task input to a program, which (1) allows binding a unified API of language model (LM) functionalities to a programming language (e.g., SQL, Python) to extend its grammar coverage and thus tackle more diverse questions, (2) adopts an LM as both the program parser and the underlying model called by the API during execution, and (3) requires only a few in-context exemplar annotations. Specifically, we employ GPT-3 Codex as the LM. In the parsing stage, with only a few in-context exemplars, Codex is able to identify the part of the task input that cannot be answerable by the original programming language, correctly generate API calls to prompt Codex to solve the unanswerable part, and identify where to place the API calls while being compatible with the original grammar. In the execution stage, Codex can perform versatile functionalities (e.g., commonsense QA, information extraction) given proper prompts in the API calls. Binder achieves state-of-the-art results on WikiTableQuestions and TabFact datasets, with explicit output programs that benefit human debugging. Note that previous best systems are all finetuned on tens of thousands of task-specific samples, while Binder only uses dozens of annotations as in-context exemplars without any training. Our code is available at https://github.com/HKUNLP/Binder .

Protein-ligand modeling underpins computational drug discovery and molecular design. Existing protein-ligand benchmarks typically evaluate whether a protein and ligand interact and how strongly they bind, through tasks such as binary binding prediction and affinity regression. However, these evaluations provide limited evidence of whether models can localize binding sites or identify the non-covalent interactions underlying molecular recognition. To address this gap, we introduce InteractBind, a large-scale protein-ligand dataset comprising approximately 100k protein-ligand pairs, together with a benchmark for fine-grained evaluation. The core fine-grained task is that of binding-site localization, which uses protein-residue and ligand-atom interaction maps spanning six major types of non-covalent interactions to assess whether model-derived interaction maps localize binding sites. InteractBind further includes binding affinity and protein similarity-controlled splits to support realistic generalization assessment. Using InteractBind, we evaluate eight existing sequence-based and interaction-aware models, assessing binary binding prediction and binding-site localization. Results reveal limited binding-site localization despite strong binary binding prediction, with marked variation across non-covalent interaction types. Overall, InteractBind establishes a benchmark paradigm that encourages the development of more interpretable and physically grounded protein-ligand models.

When reading, we often have specific information that interests us in a text. For example, you might be reading this paper because you are curious about LLMs for eye movements in reading, the experimental design, or perhaps you only care about the question ``but does it work?''. More broadly, in daily life, people approach texts with any number of text-specific goals that guide their reading behavior. In this work, we ask, for the first time, whether open-ended reading goals can be automatically decoded from eye movements in reading. To address this question, we introduce goal classification and goal reconstruction tasks and evaluation frameworks, and use large-scale eye tracking for reading data in English with hundreds of text-specific information seeking tasks. We develop and compare several discriminative and generative multimodal LLMs that combine eye movements and text for goal classification and goal reconstruction. Our experiments show considerable success on both tasks, suggesting that LLMs can extract valuable information about the readers' text-specific goals from eye movements.

Quite surprisingly, exact maximum a posteriori (MAP) decoding of neural language generators frequently leads to low-quality results. Rather, most state-of-the-art results on language generation tasks are attained using beam search despite its overwhelmingly high search error rate. This implies that the MAP objective alone does not express the properties we desire in text, which merits the question: if beam search is the answer, what was the question? We frame beam search as the exact solution to a different decoding objective in order to gain insights into why high probability under a model alone may not indicate adequacy. We find that beam search enforces uniform information density in text, a property motivated by cognitive science. We suggest a set of decoding objectives that explicitly enforce this property and find that exact decoding with these objectives alleviates the problems encountered when decoding poorly calibrated language generation models. Additionally, we analyze the text produced using various decoding strategies and see that, in our neural machine translation experiments, the extent to which this property is adhered to strongly correlates with BLEU.

Latent world models are judged by how well they predict, so when planning fails at long horizons the natural reading is that the predictor degrades. On a reproduction of LeWorldModel on TwoRoom we show the binding constraint is the planner's objective instead. The predictor is not the limit: its imagined state seventy-five environment steps ahead is still only 0.189 as wrong as assuming the world froze, while the planner never imagines beyond twenty-five. The objective is. Cross-entropy-method planning minimises squared latent distance, which tracks true distance at r = 0.426, saturates by about eighty arena units and decreases beyond a hundred and twenty, so moving away from the goal can lower the cost. The information is present throughout: a ridge probe recovers position from the frozen embedding at R^2 0.9922. The pathology is the method's, not one reimplementation's. It is present in the authors' released weights, and across four checkpoints long-horizon success rank-orders exactly with metric quality and inversely with prediction accuracy. Replacing only the objective, with nothing retrained and no GPU, lifts goals reached at offset 100 from 26.0% to 98.0%, equals the 98.0% at offset 25, and reaches 92.0% under a third of the budget: planning stops depending on the horizon. The best cost is not the most accurate. A head learned from frame separation alone predicts spatial distance worse than a position probe (r = 0.819 against 0.9897) yet plans better, charging 24% more to cross the environment's dividing wall where squared latent distance charges 4% less. It has learned reachability, not proximity.

Despite the ability to train capable LLMs, the methodology for maintaining their relevancy and rectifying errors remains elusive. To this end, the past few years have witnessed a surge in techniques for editing LLMs, the objective of which is to efficiently alter the behavior of LLMs within a specific domain without negatively impacting performance across other inputs. This paper embarks on a deep exploration of the problems, methods, and opportunities related to model editing for LLMs. In particular, we provide an exhaustive overview of the task definition and challenges associated with model editing, along with an in-depth empirical analysis of the most progressive methods currently at our disposal. We also build a new benchmark dataset to facilitate a more robust evaluation and pinpoint enduring issues intrinsic to existing techniques. Our objective is to provide valuable insights into the effectiveness and feasibility of each editing technique, thereby assisting the community in making informed decisions on the selection of the most appropriate method for a specific task or context. Code and datasets are available at https://github.com/zjunlp/EasyEdit.

To correctly use in-context information, language models (LMs) must bind entities to their attributes. For example, given a context describing a "green square" and a "blue circle", LMs must bind the shapes to their respective colors. We analyze LM representations and identify the binding ID mechanism: a general mechanism for solving the binding problem, which we observe in every sufficiently large model from the Pythia and LLaMA families. Using causal interventions, we show that LMs' internal activations represent binding information by attaching binding ID vectors to corresponding entities and attributes. We further show that binding ID vectors form a continuous subspace, in which distances between binding ID vectors reflect their discernability. Overall, our results uncover interpretable strategies in LMs for representing symbolic knowledge in-context, providing a step towards understanding general in-context reasoning in large-scale LMs.

Supervised fine-tuning (SFT) is the standard approach for post-training large language models (LLMs), yet it often shows limited generalization. We trace this limitation to its default training objective: negative log likelihood (NLL). While NLL is classically optimal when training from scratch, post-training operates in a different paradigm and could violate its optimality assumptions, where models already encode task-relevant priors and supervision can be long and noisy. To this end, we study a general family of probability-based objectives and characterize their effectiveness under different conditions. Through comprehensive experiments and extensive ablation studies across 7 model backbones, 14 benchmarks, and 3 domains, we uncover a critical dimension that governs objective behavior: the model-capability continuum. Near the model-strong end, prior-leaning objectives that downweight low-probability tokens (e.g., -p, -p^{10}, thresholded variants) consistently outperform NLL; toward the model-weak end, NLL dominates; in between, no single objective prevails. Our theoretical analysis further elucidates how objectives trade places across the continuum, providing a principled foundation for adapting objectives to model capability. Our code is available at https://github.com/GaotangLi/Beyond-Log-Likelihood.

Recently, 3D generative models have shown promising performances in structure-based drug design by learning to generate ligands given target binding sites. However, only modeling the target-ligand distribution can hardly fulfill one of the main goals in drug discovery -- designing novel ligands with desired properties, e.g., high binding affinity, easily synthesizable, etc. This challenge becomes particularly pronounced when the target-ligand pairs used for training do not align with these desired properties. Moreover, most existing methods aim at solving de novo design task, while many generative scenarios requiring flexible controllability, such as R-group optimization and scaffold hopping, have received little attention. In this work, we propose DecompOpt, a structure-based molecular optimization method based on a controllable and decomposed diffusion model. DecompOpt presents a new generation paradigm which combines optimization with conditional diffusion models to achieve desired properties while adhering to the molecular grammar. Additionally, DecompOpt offers a unified framework covering both de novo design and controllable generation. To achieve so, ligands are decomposed into substructures which allows fine-grained control and local optimization. Experiments show that DecompOpt can efficiently generate molecules with improved properties than strong de novo baselines, and demonstrate great potential in controllable generation tasks.

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.

Aligning large language models (LLMs) with human preferences is essential for safe and useful LLMs. Previous works mainly adopt reinforcement learning (RLHF) and direct preference optimization (DPO) with human feedback for alignment. Nevertheless, they have certain drawbacks. One such limitation is that they can only align models with one preference at the training time (e.g., they cannot learn to generate concise responses when the preference data prefers detailed responses), or have certain constraints for the data format (e.g., DPO only supports pairwise preference data). To this end, prior works incorporate controllable generations for alignment to make language models learn multiple preferences and provide outputs with different preferences during inference if asked. Controllable generation also offers more flexibility with regard to data format (e.g., it supports pointwise preference data). Specifically, it uses different control tokens for different preferences during training and inference, making LLMs behave differently when required. Current controllable generation methods either use a special token or hand-crafted prompts as control tokens, and optimize them together with LLMs. As control tokens are typically much lighter than LLMs, this optimization strategy may not effectively optimize control tokens. To this end, we first use parameter-efficient tuning (e.g., prompting tuning and low-rank adaptation) to optimize control tokens and then fine-tune models for controllable generations, similar to prior works. Our approach, alignMEnt with parameter-Efficient Tuning (MEET), improves the quality of control tokens, thus improving controllable generation quality consistently by an apparent margin on two well-recognized datasets compared with prior works.

We introduce Aligner, a novel Parameter-Efficient Fine-Tuning (PEFT) method for aligning multi-billion-parameter-sized Large Language Models (LLMs). Aligner employs a unique design that constructs a globally shared set of tunable tokens that modify the attention of every layer. Remarkably with this method, even when using one token accounting for a mere 5,000 parameters, Aligner can still perform comparably well to state-of-the-art LLM adaptation methods like LoRA that require millions of parameters. This capacity is substantiated in both instruction following and value alignment tasks. Besides the multiple order-of-magnitude improvement in parameter efficiency, the insight Aligner provides into the internal mechanisms of LLMs is also valuable. The architectural features and efficacy of our method, in addition to our experiments demonstrate that an LLM separates its internal handling of "form" and "knowledge" in a somewhat orthogonal manner. This finding promises to motivate new research into LLM mechanism understanding and value alignment.

Direct preference optimization methods have emerged as a computationally efficient alternative to Reinforcement Learning from Human Feedback (RLHF) for aligning Large Language Models (LLMs). Latest approaches have streamlined the alignment process by deriving implicit reward functions, yet they often suffer from a critical objective mismatch: optimizing the relative margin between chosen and rejected responses does not guarantee the preservation of the chosen response's absolute likelihood. This can lead to ``unlearning'', where the model degrades the probability of high-quality outputs to satisfy margin constraints, and ``formatting collapse'' caused by the over-penalization of rejected sequences. In this work, we introduce SLIME (Stabilized Likelihood Implicit Margin Enforcement), a reference-free alignment objective designed to decouple preference learning from generation quality. SLIME incorporates a three-pronged objective: (1) an anchoring term to maximize the likelihood of preferred responses; (2) a stabilizing penalty that prevents the probabilities of rejected tokens from collapsing to zero; and (3) a dual-margin mechanism that combines hard and soft constraints for precise boundary shaping. Our results demonstrate that SLIME achieves superior performance compared to state-of-the-art baselines while maintaining higher generation stability.

Producing outputs that satisfy both semantic intent and format constraints is essential for deploying large language models in user-facing and system-integrated workflows. In this work, we focus on Markdown formatting, which is ubiquitous in assistants, documentation, and tool-augmented pipelines but still prone to subtle, hard-to-detect errors (e.g., broken lists, malformed tables, inconsistent headings, and invalid code blocks) that can significantly degrade downstream usability. We present FMBench, a benchmark for adaptive Markdown output formatting that evaluates models under a wide range of instruction-following scenarios with diverse structural requirements. FMBench emphasizes real-world formatting behaviors such as multi-level organization, mixed content (natural language interleaved with lists/tables/code), and strict adherence to user-specified layout constraints. To improve Markdown compliance without relying on hard decoding constraints, we propose a lightweight alignment pipeline that combines supervised fine-tuning (SFT) with reinforcement learning fine-tuning. Starting from a base model, we first perform SFT on instruction-response pairs, and then optimize a composite objective that balances semantic fidelity with structural correctness. Experiments on two model families (OpenPangu and Qwen) show that SFT consistently improves semantic alignment, while reinforcement learning provides additional gains in robustness to challenging Markdown instructions when initialized from a strong SFT policy. Our results also reveal an inherent trade-off between semantic and structural objectives, highlighting the importance of carefully designed rewards for reliable formatted generation. Code is available at: https://github.com/FudanCVL/FMBench.

Test-time alignment of Large Language Models (LLMs) to human preferences offers a flexible way to generate responses aligned to diverse objectives without extensive retraining of LLMs. Existing methods achieve alignment to multiple objectives simultaneously (e.g., instruction-following, helpfulness, conciseness) by optimizing their corresponding reward functions. However, they often rely on predefined weights or optimize for averages, sacrificing one objective for another and leading to unbalanced outcomes. To address this, we introduce Robust Multi-Objective Decoding (RMOD), a novel inference-time algorithm that optimizes for improving worst-case rewards. RMOD formalizes the robust decoding problem as a maximin two-player game between reward weights and the sampling policy, solving for the Nash equilibrium. We show that the game reduces to a convex optimization problem to find the worst-case weights, while the best response policy can be computed analytically. We also introduce a practical RMOD variant designed for efficient decoding with contemporary LLMs, incurring minimal computational overhead compared to non-robust Multi-Objective Decoding (MOD) methods. Our experimental results showcase the effectiveness of RMOD in generating responses equitably aligned with diverse objectives, outperforming baselines up to 20%.

Methods for controlling large language models (LLMs), including local weight fine-tuning, LoRA-based adaptation, and activation-based interventions, are often studied in isolation, obscuring their connections and making comparison difficult. In this work, we present a unified view that frames these interventions as dynamic weight updates induced by a control signal, placing them within a single conceptual framework. Building on this view, we propose a unified preference-utility analysis that separates control effects into preference, defined as the tendency toward a target concept, and utility, defined as coherent and task-valid generation, and measures both on a shared log-odds scale using polarity-paired contrastive examples. Across methods, we observe a consistent trade-off between preference and utility: stronger control increases preference while predictably reducing utility. We further explain this behavior through an activation manifold perspective, in which control shifts representations along target-concept directions to enhance preference, while utility declines primarily when interventions push representations off the model's valid-generation manifold. Finally, we introduce a new steering approach SPLIT guided by this analysis that improves preference while better preserving utility. Code is available at https://github.com/zjunlp/EasyEdit/blob/main/examples/SPLIT.md.

Human hands possess the dexterity to interact with diverse objects such as grasping specific parts of the objects and/or approaching them from desired directions. More importantly, humans can grasp objects of any shape without object-specific skills. Recent works synthesize grasping motions following single objectives such as a desired approach heading direction or a grasping area. Moreover, they usually rely on expensive 3D hand-object data during training and inference, which limits their capability to synthesize grasping motions for unseen objects at scale. In this paper, we unify the generation of hand-object grasping motions across multiple motion objectives, diverse object shapes and dexterous hand morphologies in a policy learning framework GraspXL. The objectives are composed of the graspable area, heading direction during approach, wrist rotation, and hand position. Without requiring any 3D hand-object interaction data, our policy trained with 58 objects can robustly synthesize diverse grasping motions for more than 500k unseen objects with a success rate of 82.2%. At the same time, the policy adheres to objectives, which enables the generation of diverse grasps per object. Moreover, we show that our framework can be deployed to different dexterous hands and work with reconstructed or generated objects. We quantitatively and qualitatively evaluate our method to show the efficacy of our approach. Our model, code, and the large-scale generated motions are available at https://eth-ait.github.io/graspxl/.

Reward models are essential for aligning language model outputs with human preferences, yet existing approaches often lack both controllability and interpretability. These models are typically optimized for narrow objectives, limiting their generalizability to broader downstream tasks. Moreover, their scalar outputs are difficult to interpret without contextual reasoning. To address these limitations, we introduce R3, a novel reward modeling framework that is rubric-agnostic, generalizable across evaluation dimensions, and provides interpretable, reasoned score assignments. R3 enables more transparent and flexible evaluation of language models, supporting robust alignment with diverse human values and use cases. Our models, data, and code are available as open source at https://github.com/rubricreward/r3

In real-world drug design, molecule optimization requires selectively improving multiple molecular properties up to pharmaceutically relevant levels, while maintaining others that already meet such criteria. However, existing computational approaches and instruction-tuned LLMs fail to capture such nuanced property-specific objectives, limiting their practical applicability. To address this, we introduce C-MuMOInstruct, the first instruction-tuning dataset focused on multi-property optimization with explicit, property-specific objectives. Leveraging C-MuMOInstruct, we develop GeLLMO-Cs, a series of instruction-tuned LLMs that can perform targeted property-specific optimization. Our experiments across 5 in-distribution and 5 out-of-distribution tasks show that GeLLMO-Cs consistently outperform strong baselines, achieving up to 126% higher success rate. Notably, GeLLMO-Cs exhibit impressive 0-shot generalization to novel optimization tasks and unseen instructions. This offers a step toward a foundational LLM to support realistic, diverse optimizations with property-specific objectives. C-MuMOInstruct and code are accessible through https://github.com/ninglab/GeLLMO-C.

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

There has been unprecedented interest in developing agents that expand the boundary of scientific discovery, primarily by optimizing quantitative objective functions specified by scientists. However, for grand challenges in science, these objectives may only be imperfect proxies. We argue that automating objective function design is a central, yet unmet need for scientific discovery agents. In this work, we introduce the Scientific Autonomous Goal-evolving Agent (SAGA) to address this challenge. SAGA employs a bi-level architecture in which an outer loop of LLM agents analyzes optimization outcomes, proposes new objectives, and converts them into computable scoring functions, while an inner loop performs solution optimization under the current objectives. This bi-level design enables systematic exploration of the space of objectives and their trade-offs, rather than treating them as fixed inputs. We demonstrate the framework through a wide range of design applications, including antibiotics, nanobodies, functional DNA sequences, inorganic materials, and chemical processes. Notably, our experimental validation identifies a structurally novel hit with promising potency and safety profiles for E. coli in the antibiotic design task, and three de novo PD-L1 binders in the nanobody design task. These results suggest that automating objective formulation can substantially improve the effectiveness of scientific discovery agents.

Alignment techniques for LLMs rely on optimizing preference-based objectives -- where these preferences are typically elicited as ordinal, binary choices between responses. Recent work has focused on improving label quality or mitigating particular biases, but we identify a more fundamental limitation: these methods collect the wrong kind of data. We prove an impossibility result: no algorithm relying solely on ordinal comparisons can systematically recover the most preferred model. Intuitively, ordinal data lacks the information needed to resolve tradeoffs -- e.g., fixing a factual error on one prompt versus improving style on another. We show that selecting the optimal model requires recovering preferences over models (rather than just responses), which can only be identified given cardinal feedback about response quality. To address this, we collect and publicly release a dataset of 25,000 cardinal judgments using willingness-to-pay elicitations, a well-established tool from experimental economics. Empirically, we find that incorporating cardinal feedback into preference fine-tuning allows models to prioritize high-impact improvements and outperform ordinal-only methods on downstream benchmarks, such as Arena-Hard.

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.

The effects of ligand binding on protein structures and their in vivo functions carry numerous implications for modern biomedical research and biotechnology development efforts such as drug discovery. Although several deep learning (DL) methods and benchmarks designed for protein-ligand docking have recently been introduced, to date no prior works have systematically studied the behavior of the latest docking and structure prediction methods within the broadly applicable context of (1) using predicted (apo) protein structures for docking (e.g., for applicability to new proteins); (2) binding multiple (cofactor) ligands concurrently to a given target protein (e.g., for enzyme design); and (3) having no prior knowledge of binding pockets (e.g., for generalization to unknown pockets). To enable a deeper understanding of docking methods' real-world utility, we introduce PoseBench, the first comprehensive benchmark for broadly applicable protein-ligand docking. PoseBench enables researchers to rigorously and systematically evaluate DL methods for apo-to-holo protein-ligand docking and protein-ligand structure prediction using both primary ligand and multi-ligand benchmark datasets, the latter of which we introduce for the first time to the DL community. Empirically, using PoseBench, we find that (1) DL co-folding methods generally outperform comparable conventional and DL docking baselines, yet popular methods such as AlphaFold 3 are still challenged by prediction targets with novel protein sequences; (2) certain DL co-folding methods are highly sensitive to their input multiple sequence alignments, while others are not; and (3) DL methods struggle to strike a balance between structural accuracy and chemical specificity when predicting novel or multi-ligand protein targets. Code, data, tutorials, and benchmark results are available at https://github.com/BioinfoMachineLearning/PoseBench.

The detection of ligand binding sites for proteins is a fundamental step in Structure-Based Drug Design. Despite notable advances in recent years, existing methods, datasets, and evaluation metrics are confronted with several key challenges: (1) current datasets and methods are centered on individual protein-ligand complexes and neglect that diverse binding sites may exist across multiple complexes of the same protein, introducing significant statistical bias; (2) ligand binding site detection is typically modeled as a discontinuous workflow, employing binary segmentation and subsequent clustering algorithms; (3) traditional evaluation metrics do not adequately reflect the actual performance of different binding site prediction methods. To address these issues, we first introduce UniSite-DS, the first UniProt (Unique Protein)-centric ligand binding site dataset, which contains 4.81 times more multi-site data and 2.08 times more overall data compared to the previously most widely used datasets. We then propose UniSite, the first end-to-end ligand binding site detection framework supervised by set prediction loss with bijective matching. In addition, we introduce Average Precision based on Intersection over Union (IoU) as a more accurate evaluation metric for ligand binding site prediction. Extensive experiments on UniSite-DS and several representative benchmark datasets demonstrate that IoU-based Average Precision provides a more accurate reflection of prediction quality, and that UniSite outperforms current state-of-the-art methods in ligand binding site detection. The dataset and codes will be made publicly available at https://github.com/quanlin-wu/unisite.

Modern LLM agents are often improved by modifying prompts, tools, or workflows manually, while the executable scaffold surrounding the model---the harness---is typically treated as a fixed artifact after deployment. This work studies an alternative where the harness is task-specific and continuously evolvable: each task family maintains its own harness, which is hot-swapped across iterations through a fixed task-injection seam and rewritten using environment feedback. We introduce Hierarchical Self-Improvement (HSI), a framework in which a single frozen LLM M operates across three hierarchical scopes: a task harness H that executes tasks, an evolver that rewrites H, and a meta-evolver that rewrites the evolver's strategy code under a frozen outer anchor. A thinking-on/off design isolates the contribution of harness evolution by disabling reasoning during task execution while enabling it during self-modification. HSI is bounded by two factors: a feedback-fidelity bound, since evolution requires informative reward signals to guide selection, and a backbone capability bound, since harness redesign cannot overcome limitations of the frozen model. On BALROG with DeepSeek-V4-Flash-Preview as the frozen backbone, HSI achieves consistent gains over the initial harness on moderate-difficulty tasks (+39.3 on BabyAI, +33.0 on Crafter, +25.0 on TextWorld, and +15.0 on MiniHack, all in raw \% Progress), while obtaining strong held-out generalization on BabaIsAI sub-suites (0.98 best-test on BreakStop and 1.00 on GoTo from a 20% unseen split). On tasks beyond the backbone's capability (NLE), harness evolution provides no improvement. These results demonstrate task-specific harness evolution as a viable axis for improving frozen LLM agents under clear empirical limits. Code is available at https://github.com/TailinZhou/hsi.

Designing proteins with desired functions or properties represents a core goal in synthetic biology and drug discovery. Recent advances in protein language models (PLMs) have enabled the generation of highly designable protein sequences, while preference alignment provides a promising way to steer designs toward desired functions and properties. Nevertheless, they often trigger catastrophic forgetting of pretrained knowledge, degrading basic designability and failing to balance multiple competing objectives. To address these issues, we draw inspiration from On-Policy Distillation (OPD), an advanced post-training method renowned for mitigating catastrophic forgetting through its mode-seeking nature. In this work, we propose ProteinOPD, a multi-objective preference alignment framework that can effectively balance multiple preference objectives while maintaining the inherent designability of PLMs. ProteinOPD adapts a pretrained PLM into preference-specific teachers and distills their knowledge into a shared student via token-level OPD on the student's own trajectories. During this process, the student is aligned to a unique normalized geometric consensus of weighted teachers while ensuring bounded optimization under conflicts. This bridges the gap for OPD in multi-objective/teacher alignment. Extensive experiments show that ProteinOPD achieves substantial gains on target preference objectives without compromising the designability, with an 8x training speedup over RL-based alignment competitors.

Human language is one of the most expressive tools for conveying intent, yet most artificial or biological systems lack mechanisms to interpret or respond meaningfully to it. Bridging this gap could enable more natural forms of control over complex, decentralized systems. In AI and artificial life, recent work explores how language can specify high-level goals, but most systems still depend on engineered rewards, task-specific supervision, or rigid command sets, limiting generalization to novel instructions. Similar constraints apply in synthetic biology and bioengineering, where the locus of control is often genomic rather than environmental perturbation. A key open question is whether artificial or biological collectives can be guided by free-form natural language alone, without task-specific tuning or carefully designed evaluation metrics. We provide one possible answer here by showing, for the first time, that simple agents' collective behavior can be guided by free-form language prompts: one AI model transforms an imperative prompt into an intervention that is applied to simulated cells; a second AI model scores how well the prompt describes the resulting cellular dynamics; and the former AI model is evolved to improve the scores generated by the latter. Unlike previous work, our method does not require engineered fitness functions or domain-specific prompt design. We show that the evolved system generalizes to unseen prompts without retraining. By treating natural language as a control layer, the system suggests a future in which spoken or written prompts could direct computational, robotic, or biological systems to desired behaviors. This work provides a concrete step toward this vision of AI-biology partnerships, in which language replaces mathematical objective functions, fixed rules, and domain-specific programming.

Large Language Model (LLM) agents are increasingly deployed in environments that generate massive, dynamic contexts. However, a critical bottleneck remains: while agents have access to this context, their static prompts lack the mechanisms to manage it effectively, leading to recurring Corrective and Enhancement failures. To address this capability gap, we introduce SCOPE (Self-evolving Context Optimization via Prompt Evolution). SCOPE frames context management as an online optimization problem, synthesizing guidelines from execution traces to automatically evolve the agent's prompt. We propose a Dual-Stream mechanism that balances tactical specificity (resolving immediate errors) with strategic generality (evolving long-term principles). Furthermore, we introduce Perspective-Driven Exploration to maximize strategy coverage, increasing the likelihood that the agent has the correct strategy for any given task. Experiments on the HLE benchmark show that SCOPE improves task success rates from 14.23\% to 38.64\% without human intervention. We make our code publicly available at https://github.com/JarvisPei/SCOPE.

Our goal is for robots to follow natural language instructions like "put the towel next to the microwave." But getting large amounts of labeled data, i.e. data that contains demonstrations of tasks labeled with the language instruction, is prohibitive. In contrast, obtaining policies that respond to image goals is much easier, because any autonomous trial or demonstration can be labeled in hindsight with its final state as the goal. In this work, we contribute a method that taps into joint image- and goal- conditioned policies with language using only a small amount of language data. Prior work has made progress on this using vision-language models or by jointly training language-goal-conditioned policies, but so far neither method has scaled effectively to real-world robot tasks without significant human annotation. Our method achieves robust performance in the real world by learning an embedding from the labeled data that aligns language not to the goal image, but rather to the desired change between the start and goal images that the instruction corresponds to. We then train a policy on this embedding: the policy benefits from all the unlabeled data, but the aligned embedding provides an interface for language to steer the policy. We show instruction following across a variety of manipulation tasks in different scenes, with generalization to language instructions outside of the labeled data. Videos and code for our approach can be found on our website: http://tiny.cc/grif .

Many modern retrieval problems are set-valued: given a broad intent, the system must return a collection of results that optimizes higher-order properties (e.g., diversity, coverage, complementarity, coherence) while remaining grounded with respect to a fixed database. Set-valued objectives are typically non-decomposable and are not captured by existing supervised (query, content) datasets which only prioritize top-1 retrieval. Consequently, fan-out retrieval is often employed to generate diverse subqueries to retrieve item sets. While reinforcement learning (RL) can optimize set-level objectives via interaction, deploying an RL-tuned LLM for fan-out retrieval is prohibitively expensive at inference time. Conversely, diffusion-based generative retrieval enables efficient single-pass fan-out in embedding space, but requires objective-aligned training targets. To address these issues, we propose R4T (Retrieve-for-Train), which uses RL once as an objective transducer in a three-step process: (i) train a fan-out LLM with composite set-level rewards, (ii) synthesize objective-consistent training pairs, and (iii) train a lightweight diffusion retriever to model the conditional distribution of set-valued outputs. Across large-scale fashion and music benchmarks consisting of curated item sets, we show that R4T improves retrieval quality relative to strong baselines while reducing query-time fan-out latency by an order of magnitude.

Protein binder design has largely optimized for affinity alone, leaving conformational selectivity unaddressed: for allosteric targets such as kinases, nuclear receptors, and GPCRs, a binder that engages both active and inactive states provides no functional specificity regardless of how tightly it binds. We introduce AlloGen, a modular framework that decouples backbone generation from a learned state-selectivity scorer Q_θ, an SE(3)-invariant interface graph transformer trained via a two-phase curriculum that first learns interface geometry before imposing conformational discrimination. Because Q_θ is fully differentiable and generator-agnostic, it integrates with any backbone generator as a passive reranker or an active gradient-based guide without retraining. Across a diverse benchmark of proteins spanning multiple families and conformational mechanisms, AlloGen consistently identifies binders that preferentially recognize desired structural states while rejecting alternative conformations. Experimental validation on calmodulin further demonstrates that these computational selectivity signals translate to physical molecules, yielding de novo peptides that bind the desired holo conformation while exhibiting no detectable binding to the apo state. Together, these results establish conformational selectivity as a learnable property and provide a general framework for state-selective protein binder design.

Model-based reinforcement learning (MBRL) has been shown to be a powerful framework for data-efficiently learning control of continuous tasks. Recent work in MBRL has mostly focused on using more advanced function approximators and planning schemes, with little development of the general framework. In this paper, we identify a fundamental issue of the standard MBRL framework -- what we call the objective mismatch issue. Objective mismatch arises when one objective is optimized in the hope that a second, often uncorrelated, metric will also be optimized. In the context of MBRL, we characterize the objective mismatch between training the forward dynamics model w.r.t.~the likelihood of the one-step ahead prediction, and the overall goal of improving performance on a downstream control task. For example, this issue can emerge with the realization that dynamics models effective for a specific task do not necessarily need to be globally accurate, and vice versa globally accurate models might not be sufficiently accurate locally to obtain good control performance on a specific task. In our experiments, we study this objective mismatch issue and demonstrate that the likelihood of one-step ahead predictions is not always correlated with control performance. This observation highlights a critical limitation in the MBRL framework which will require further research to be fully understood and addressed. We propose an initial method to mitigate the mismatch issue by re-weighting dynamics model training. Building on it, we conclude with a discussion about other potential directions of research for addressing this issue.

System design is often taught through domain-specific solutions specific to particular domains, such as databases, operating systems, or computer architecture, each with its own methods and vocabulary. While this diversity is a strength, it can obscure cross-cutting principles that recur across domains. This paper proposes a preliminary "periodic table" of system design principles distilled from several domains in computer systems. The goal is a shared, concise vocabulary that helps students, researchers, and practitioners reason about structure and trade-offs, compare designs across domains, and communicate choices more clearly. For supporting materials and updates, please refer to the repository at: https://github.com/jarulraj/periodic-table.

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.

Aligning large language models to human preferences is inherently multidimensional, yet most pipelines collapse heterogeneous signals into a single optimizeable objective. We seek to answer what it would take to simultaneously align a model across various domains spanning those with: verifiable rewards (mathematical accuracy), non-verifiable subjective preferences (human values), and complex interactive scenarios (multi-turn AI tutoring dialogues). Such multi-objective reinforcement learning setups are often plagued by the individual objectives being at odds with each other, resulting in inefficient training and little user control during inference. We propose a unified framework that: (i) standardizes {process reward model} (PRM) training across both verifiable and non-verifiable settings to better supervise models' chain-of-thought reasoning; (ii) performs {multi-objective alignment} by training the LLM with our Multi-Action-Head DPO (MAH-DPO) and a vectorized reward where the dimensions of the vector correspond to the various objectives instead of a single scalar; and (iii) demonstrates how such a system provides fine-grained inference-time user control. Experiments across math reasoning, value alignment, and multi-turn dialogue show that our framework improves performance across multiple objectives simultaneously, while minimizing cross-objective trade-offs and enabling flexible inference time user control. The code can be found at https://github.com/pearls-lab/multiobj-align.

Learning from preference labels plays a crucial role in fine-tuning large language models. There are several distinct approaches for preference fine-tuning, including supervised learning, on-policy reinforcement learning (RL), and contrastive learning. Different methods come with different implementation tradeoffs and performance differences, and existing empirical findings present different conclusions, for instance, some results show that online RL is quite important to attain good fine-tuning results, while others find (offline) contrastive or even purely supervised methods sufficient. This raises a natural question: what kind of approaches are important for fine-tuning with preference data and why? In this paper, we answer this question by performing a rigorous analysis of a number of fine-tuning techniques on didactic and full-scale LLM problems. Our main finding is that, in general, approaches that use on-policy sampling or attempt to push down the likelihood on certain responses (i.e., employ a "negative gradient") outperform offline and maximum likelihood objectives. We conceptualize our insights and unify methods that use on-policy sampling or negative gradient under a notion of mode-seeking objectives for categorical distributions. Mode-seeking objectives are able to alter probability mass on specific bins of a categorical distribution at a fast rate compared to maximum likelihood, allowing them to relocate masses across bins more effectively. Our analysis prescribes actionable insights for preference fine-tuning of LLMs and informs how data should be collected for maximal improvement.

Many important forms of human learning begin with a vague goal, such as "become a better physicist" or "improve at research." Learners must interpret the goal, identify capability gaps, decide how to learn, and determine whether they have actually improved. In contrast, existing work on LLM self-evolution typically begins with tasks and evaluation metrics specified by humans, reducing self-evolution to optimizing an explicit objective rather than deciding what and how to learn. We introduce ASPIRE, a benchmark for vague-goal-driven self-evolution. ASPIRE provides only a natural-language capability goal while downstream evaluation tasks remain hidden. The agent must operationalize the goal by choosing data and update methods, constructing training and validation signals, and deciding when to evaluate. ASPIRE supports both model-weight and agent-harness evolution in a unified interactive environment and evaluates the resulting systems on a hidden, expert-authored set of 520 items spanning six goals. Our experiments show that vague goals redirect search effort toward goal interpretation. Current agents routinely complete training and harness-editing loops, but weight-level gains remain sparse and unstable, and the strongest evolved harness remains below the engineered Qwen-Agent reference. Agents often train on mismatched data and trust narrow self-evaluations, so local gains fail to transfer to hidden evaluation and continued search and training can erase earlier improvements.

While large language models (LLMs) have exhibited impressive instruction-following capabilities, it is still unclear whether and to what extent they can respond to explicit constraints that might be entailed in various instructions. As a significant aspect of LLM alignment, it is thus important to formulate such a specialized set of instructions as well as investigate the resulting behavior of LLMs. To address this vacancy, we propose a new benchmark CoDI-Eval to systematically and comprehensively evaluate LLMs' responses to instructions with various constraints. We construct a large collection of constraints-attributed instructions as a test suite focused on both generalization and coverage. Specifically, we advocate an instruction diversification process to synthesize diverse forms of constraint expression and also deliberate the candidate task taxonomy with even finer-grained sub-categories. Finally, we automate the entire evaluation process to facilitate further developments. Different from existing studies on controllable text generation, CoDI-Eval extends the scope to the prevalent instruction-following paradigm for the first time. We provide extensive evaluations of representative LLMs (e.g., ChatGPT, Vicuna) on CoDI-Eval, revealing their limitations in following instructions with specific constraints and there is still a significant gap between open-source and commercial closed-source LLMs. We believe this benchmark will facilitate research into improving the controllability of LLMs' responses to instructions. Our data and code are available at https://github.com/Xt-cyh/CoDI-Eval.

The rapid advancement of large language models (LLMs) has revolutionized text generation, making it increasingly difficult to distinguish between human- and AI-generated content. This poses a significant challenge to academic integrity, particularly in scientific publishing and multilingual contexts where detection resources are often limited. To address this critical gap, we introduce the AINL-Eval 2025 Shared Task, specifically focused on the detection of AI-generated scientific abstracts in Russian. We present a novel, large-scale dataset comprising 52,305 samples, including human-written abstracts across 12 diverse scientific domains and AI-generated counterparts from five state-of-the-art LLMs (GPT-4-Turbo, Gemma2-27B, Llama3.3-70B, Deepseek-V3, and GigaChat-Lite). A core objective of the task is to challenge participants to develop robust solutions capable of generalizing to both (i) previously unseen scientific domains and (ii) models not included in the training data. The task was organized in two phases, attracting 10 teams and 159 submissions, with top systems demonstrating strong performance in identifying AI-generated content. We also establish a continuous shared task platform to foster ongoing research and long-term progress in this important area. The dataset and platform are publicly available at https://github.com/iis-research-team/AINL-Eval-2025.

The Natural Language for Optimization (NL4Opt) Competition was created to investigate methods of extracting the meaning and formulation of an optimization problem based on its text description. Specifically, the goal of the competition is to increase the accessibility and usability of optimization solvers by allowing non-experts to interface with them using natural language. We separate this challenging goal into two sub-tasks: (1) recognize and label the semantic entities that correspond to the components of the optimization problem; (2) generate a meaning representation (i.e., a logical form) of the problem from its detected problem entities. The first task aims to reduce ambiguity by detecting and tagging the entities of the optimization problems. The second task creates an intermediate representation of the linear programming (LP) problem that is converted into a format that can be used by commercial solvers. In this report, we present the LP word problem dataset and shared tasks for the NeurIPS 2022 competition. Furthermore, we investigate and compare the performance of the ChatGPT large language model against the winning solutions. Through this competition, we hope to bring interest towards the development of novel machine learning applications and datasets for optimization modeling.

Recent advances in text-to-image (T2I) generation have led to impressive visual results. However, these models still face significant challenges when handling complex prompt, particularly those involving multiple subjects with distinct attributes. Inspired by the human drawing process, which first outlines the composition and then incrementally adds details, we propose Detail++, a training-free framework that introduces a novel Progressive Detail Injection (PDI) strategy to address this limitation. Specifically, we decompose a complex prompt into a sequence of simplified sub-prompts, guiding the generation process in stages. This staged generation leverages the inherent layout-controlling capacity of self-attention to first ensure global composition, followed by precise refinement. To achieve accurate binding between attributes and corresponding subjects, we exploit cross-attention mechanisms and further introduce a Centroid Alignment Loss at test time to reduce binding noise and enhance attribute consistency. Extensive experiments on T2I-CompBench and a newly constructed style composition benchmark demonstrate that Detail++ significantly outperforms existing methods, particularly in scenarios involving multiple objects and complex stylistic conditions.

Reinforcement learning (RL) has shown strong promise for LLM-based machine translation, with recent methods such as GRPO demonstrating notable gains; nevertheless, translation-oriented RL remains challenged by noisy learning signals arising from Monte Carlo return estimation, as well as a large trajectory space that favors global exploration over fine-grained local optimization. We introduce PEGRL, a two-stage RL framework that uses post-editing as an auxiliary task to stabilize training and guide overall optimization. At each iteration, translation outputs are sampled to construct post-editing inputs, allowing return estimation in the post-editing stage to benefit from conditioning on the current translation behavior, while jointly supporting both global exploration and fine-grained local optimization. A task-specific weighting scheme further balances the contributions of translation and post-editing objectives, yielding a biased yet more sample-efficient estimator. Experiments on EnglishtoFinnish, EnglishtoTurkish, and EnglishleftrightarrowChinese show consistent gains over RL baselines, and for EnglishtoTurkish, performance on COMET-KIWI is comparable to advanced LLM-based systems (DeepSeek-V3.2).

Alignment in artificial intelligence pursues the consistency between model responses and human preferences as well as values. In practice, the multifaceted nature of human preferences inadvertently introduces what is known as the "alignment tax" -a compromise where enhancements in alignment within one objective (e.g.,harmlessness) can diminish performance in others (e.g.,helpfulness). However, existing alignment techniques are mostly unidirectional, leading to suboptimal trade-offs and poor flexibility over various objectives. To navigate this challenge, we argue the prominence of grounding LLMs with evident preferences. We introduce controllable preference optimization (CPO), which explicitly specifies preference scores for different objectives, thereby guiding the model to generate responses that meet the requirements. Our experimental analysis reveals that the aligned models can provide responses that match various preferences among the "3H" (helpfulness, honesty, harmlessness) desiderata. Furthermore, by introducing diverse data and alignment goals, we surpass baseline methods in aligning with single objectives, hence mitigating the impact of the alignment tax and achieving improvements in multi-objective alignment.

Large Language Models (LLMs) are often aligned using contrastive alignment objectives and preference pair datasets. The interaction between model, paired data, and objective makes alignment a complicated procedure, sometimes producing subpar results. We study this and find that (i) preference data gives a better learning signal when the underlying responses are contrastive, and (ii) alignment objectives lead to better performance when they specify more control over the model during training. Based on these insights, we introduce Contrastive Learning from AI Revisions (CLAIR), a data-creation method which leads to more contrastive preference pairs, and Anchored Preference Optimization (APO), a controllable and more stable alignment objective. We align Llama-3-8B-Instruct using various comparable datasets and alignment objectives and measure MixEval-Hard scores, which correlate highly with human judgments. The CLAIR preferences lead to the strongest performance out of all datasets, and APO consistently outperforms less controllable objectives. Our best model, trained on 32K CLAIR preferences with APO, improves Llama-3-8B-Instruct by 7.65%, closing the gap with GPT4-turbo by 45%. Our code is available at https://github.com/ContextualAI/CLAIR_and_APO.

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.

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.

The binding problem in human cognition, concerning how the brain represents and connects objects within a fixed network of neural connections, remains a subject of intense debate. Most machine learning efforts addressing this issue in an unsupervised setting have focused on slot-based methods, which may be limiting due to their discrete nature and difficulty to express uncertainty. Recently, the Complex AutoEncoder was proposed as an alternative that learns continuous and distributed object-centric representations. However, it is only applicable to simple toy data. In this paper, we present Rotating Features, a generalization of complex-valued features to higher dimensions, and a new evaluation procedure for extracting objects from distributed representations. Additionally, we show the applicability of our approach to pre-trained features. Together, these advancements enable us to scale distributed object-centric representations from simple toy to real-world data. We believe this work advances a new paradigm for addressing the binding problem in machine learning and has the potential to inspire further innovation in the field.

Supervised fine-tuning (SFT) typically maximizes the likelihood of every token in a demonstrated trajectory. However, an observed token can be non-unique, noisy, or misaligned with the model prior. Strictly fitting toward this one-hot target may be suboptimal, especially when the pretrained model encodes a rich knowledge prior. In this work, we reinterpret SFT as target distribution design: instead of studying only the loss objective, we analyze the token-level target that the loss drives the model to match. We introduce the Q-target framework, which decomposes SFT supervision into two explicit choices: (1) how strongly to rely on the observed token, and (2) how to allocate the remaining probability mass over alternatives. This perspective unifies many existing SFT variants as implicit choices of the target distribution Q. Building on this view, we propose Target-SFT which constructs the training objective directly from the desired target distribution. This method consistently outperforms across the ten reasoning dataset-model settings evaluated, showing the effectiveness of this target-based approach. Overall, our formulation reveals a more fundamental design principle for SFT training and opens a broader search space for SFT objectives.

Spatial conditioning in pretrained text-to-image diffusion models has significantly improved fine-grained control over the structure of generated images. However, existing control adapters exhibit limited adaptability and incur high training costs when encountering novel spatial control conditions that differ substantially from the training tasks. To address this limitation, we propose Universal Few-Shot Control (UFC), a versatile few-shot control adapter capable of generalizing to novel spatial conditions. Given a few image-condition pairs of an unseen task and a query condition, UFC leverages the analogy between query and support conditions to construct task-specific control features, instantiated by a matching mechanism and an update on a small set of task-specific parameters. Experiments on six novel spatial control tasks show that UFC, fine-tuned with only 30 annotated examples of novel tasks, achieves fine-grained control consistent with the spatial conditions. Notably, when fine-tuned with 0.1% of the full training data, UFC achieves competitive performance with the fully supervised baselines in various control tasks. We also show that UFC is applicable agnostically to various diffusion backbones and demonstrate its effectiveness on both UNet and DiT architectures. Code is available at https://github.com/kietngt00/UFC.

Foundation models are transitioning from offline predictors to deployed systems expected to operate over long time horizons. In real deployments, objectives are not fixed: domains drift, user preferences evolve, and new tasks appear after the model has shipped. This elevates continual learning and instant personalization from optional features to core architectural requirements. Yet most adaptation pipelines still follow a static weight paradigm: after training (or after any adaptation step), inference executes a single parameter vector regardless of user intent, domain, or instance-specific constraints. This treats the trained or adapted model as a single point in parameter space. In heterogeneous and continually evolving regimes, distinct objectives can induce separated feasible regions over parameters, forcing any single shared update into compromise, interference, or overspecialization. As a result, continual learning and personalization are often implemented as repeated overwriting of shared weights, risking degradation of previously learned behaviors. We propose HY-WU (Weight Unleashing), a memory-first adaptation framework that shifts adaptation pressure away from overwriting a single shared parameter point. HY-WU implements functional (operator-level) memory as a neural module: a generator that synthesizes weight updates on-the-fly from the instance condition, yielding instance-specific operators without test-time optimization.

Some reinforcement learning (RL) algorithms can stitch pieces of experience to solve a task never seen before during training. This oft-sought property is one of the few ways in which RL methods based on dynamic-programming differ from RL methods based on supervised-learning (SL). Yet, certain RL methods based on off-the-shelf SL algorithms achieve excellent results without an explicit mechanism for stitching; it remains unclear whether those methods forgo this important stitching property. This paper studies this question for the problems of achieving a target goal state and achieving a target return value. Our main result is to show that the stitching property corresponds to a form of combinatorial generalization: after training on a distribution of (state, goal) pairs, one would like to evaluate on (state, goal) pairs not seen together in the training data. Our analysis shows that this sort of generalization is different from i.i.d. generalization. This connection between stitching and generalisation reveals why we should not expect SL-based RL methods to perform stitching, even in the limit of large datasets and models. Based on this analysis, we construct new datasets to explicitly test for this property, revealing that SL-based methods lack this stitching property and hence fail to perform combinatorial generalization. Nonetheless, the connection between stitching and combinatorial generalisation also suggests a simple remedy for improving generalisation in SL: data augmentation. We propose a temporal data augmentation and demonstrate that adding it to SL-based methods enables them to successfully complete tasks not seen together during training. On a high level, this connection illustrates the importance of combinatorial generalization for data efficiency in time-series data beyond tasks beyond RL, like audio, video, or text.

This paper introduces a multifaceted methodology for fine-tuning and evaluating large language models (LLMs) for specialized monetization tasks. The goal is to balance general language proficiency with domain-specific skills. The methodology has three main components: 1) Carefully blending in-domain and general-purpose data during fine-tuning to achieve an optimal balance between general and specialized capabilities; 2) Designing a comprehensive evaluation framework with 45 questions tailored to assess performance on functionally relevant dimensions like reliability, consistency, and business impact; 3) Analyzing how model size and continual training influence metrics to guide efficient resource allocation during fine-tuning. The paper details the design, data collection, analytical techniques, and results validating the proposed frameworks. It aims to provide businesses and researchers with actionable insights on effectively adapting LLMs for specialized contexts. We also intend to make public the comprehensive evaluation framework, which includes the 45 tailored questions and their respective scoring guidelines, to foster transparency and collaboration in adapting LLMs for specialized tasks.

Large language models (LLMs) should undergo rigorous audits to identify potential risks, such as copyright and privacy infringements. Once these risks emerge, timely updates are crucial to remove undesirable responses, ensuring legal and safe model usage. It has spurred recent research into LLM unlearning, focusing on erasing targeted undesirable knowledge without compromising the integrity of other, non-targeted responses. Existing studies have introduced various unlearning objectives to pursue LLM unlearning without necessitating complete retraining. However, each of these objectives has unique properties, and no unified framework is currently available to comprehend them thoroughly. To fill the gap, we propose a toolkit of the gradient effect (G-effect), quantifying the impacts of unlearning objectives on model performance from a gradient perspective. A notable advantage is its broad ability to detail the unlearning impacts from various aspects across instances, updating steps, and LLM layers. Accordingly, the G-effect offers new insights into identifying drawbacks of existing unlearning objectives, further motivating us to explore a series of new solutions for their mitigation and improvements. Finally, we outline promising directions that merit further studies, aiming at contributing to the community to advance this important field.

Contrastive representation learning (CRL) underpins many modern foundation models. Despite recent theoretical progress, existing analyses suffer from several key limitations: (i) the statistical consistency of CRL remains poorly understood; (ii) available generalization bounds deteriorate as the number of negative samples increases, contradicting the empirical benefits of large negative sets; and (iii) the retrieval performance of CRL has received limited theoretical attention. In this paper, we develop a unified statistical learning theory for CRL. For downstream tasks, we evaluate retrieval quality using an AUC-type population criterion and show that the contrastive loss is statistically consistent with optimal ranking. We further establish a calibration-style inequality that quantitatively relates excess contrastive risk to excess retrieval suboptimality. For upstream training, we study both supervised and self-supervised contrastive objectives and derive generalization bounds of order O(1/m + 1/n) and O(1/m + 1/n), respectively, where m denotes the number of negative samples and n the number of anchor points. These bounds not only explain the empirical advantages of large negative sets but also reveal an explicit trade-off between m and n. Extensive experiments on large-scale vision--language models corroborate our theoretical predictions.

Motivation: The development of novel compounds targeting proteins of interest is one of the most important tasks in the pharmaceutical industry. Deep generative models have been applied to targeted molecular design and have shown promising results. Recently, target-specific molecule generation has been viewed as a translation between the protein language and the chemical language. However, such a model is limited by the availability of interacting protein-ligand pairs. On the other hand, large amounts of unlabeled protein sequences and chemical compounds are available and have been used to train language models that learn useful representations. In this study, we propose exploiting pretrained biochemical language models to initialize (i.e. warm start) targeted molecule generation models. We investigate two warm start strategies: (i) a one-stage strategy where the initialized model is trained on targeted molecule generation (ii) a two-stage strategy containing a pre-finetuning on molecular generation followed by target specific training. We also compare two decoding strategies to generate compounds: beam search and sampling. Results: The results show that the warm-started models perform better than a baseline model trained from scratch. The two proposed warm-start strategies achieve similar results to each other with respect to widely used metrics from benchmarks. However, docking evaluation of the generated compounds for a number of novel proteins suggests that the one-stage strategy generalizes better than the two-stage strategy. Additionally, we observe that beam search outperforms sampling in both docking evaluation and benchmark metrics for assessing compound quality. Availability and implementation: The source code is available at https://github.com/boun-tabi/biochemical-lms-for-drug-design and the materials are archived in Zenodo at https://doi.org/10.5281/zenodo.6832145

In this paper, we propose a general framework for universal zero-shot goal-oriented navigation. Existing zero-shot methods build inference framework upon large language models (LLM) for specific tasks, which differs a lot in overall pipeline and fails to generalize across different types of goal. Towards the aim of universal zero-shot navigation, we propose a uniform graph representation to unify different goals, including object category, instance image and text description. We also convert the observation of agent into an online maintained scene graph. With this consistent scene and goal representation, we preserve most structural information compared with pure text and are able to leverage LLM for explicit graph-based reasoning. Specifically, we conduct graph matching between the scene graph and goal graph at each time instant and propose different strategies to generate long-term goal of exploration according to different matching states. The agent first iteratively searches subgraph of goal when zero-matched. With partial matching, the agent then utilizes coordinate projection and anchor pair alignment to infer the goal location. Finally scene graph correction and goal verification are applied for perfect matching. We also present a blacklist mechanism to enable robust switch between stages. Extensive experiments on several benchmarks show that our UniGoal achieves state-of-the-art zero-shot performance on three studied navigation tasks with a single model, even outperforming task-specific zero-shot methods and supervised universal methods.

Some security-development settings require local models that map an objective to an ordered, checkable plan. We present a low-rank decomposition adapter and release a case-disjoint corpus with 24 authored decompositions and 83 derived next-step examples across 24 satellite-security cases. To prevent reference-plan leakage, prompts contain one objective and eight shuffled SPARTA candidates. The evaluation candidate sets are constructed with oracle inclusion of every reference technique, so this study measures selection from a controlled set, not retrieval. On six fixed cases and five decoding seeds, mean scores vary across adapters and prompted Qwen2.5 baselines; a separate greedy check over three adapter training seeds shows non-negligible training variance. A 24-fold greedy leave-one-case-out control at the two compact sizes likewise shows tradeoffs: at 1.5B, adapter precision is 0.583 against 0.480 for two-shot prompting, while recall is 0.586 against 0.660. Case-resampling intervals for adapter precision relative to the strongest prompted baseline cross zero at 1.5B and 7B. The adapter is also substantially more format-compliant, which prevents attributing all score differences to selection. Autoregressive next-step accuracy is 0.08, 0.06, and 0.29 at 0.5B, 1.5B, and 7B. We therefore offer the formulation, leakage-controlled dataset, reproducibility package, and descriptive analysis as a proof of concept, not evidence of a reliable stand-alone decomposition system or a general adapter advantage. A separate diagnostic tests contract reuse.

Generating molecules that satisfy precise numeric constraints over multiple physicochemical properties is critical and challenging. Although large language models (LLMs) are expressive, they struggle with precise multi-objective control and numeric reasoning without external structure and feedback. We introduce M olGen, a fragment-level, retrieval-augmented, two-stage framework for molecule generation under multi-property constraints. Stage I : Prototype generation: a multi-agent reasoner performs retrieval-anchored, fragment-level edits to produce a candidate near the feasible region. Stage II : RL-based fine-grained optimization: a fragment-level optimizer trained with Group Relative Policy Optimization (GRPO) applies one- or multi-hop refinements to explicitly minimize the property errors toward our target while regulating edit complexity and deviation from the prototype. A large, automatically curated dataset with reasoning chains of fragment edits and measured property deltas underpins both stages, enabling deterministic, reproducible supervision and controllable multi-hop reasoning. Unlike prior work, our framework better reasons about molecules by leveraging fragments and supports controllable refinement toward numeric targets. Experiments on generation under two sets of property constraints (QED, LogP, Molecular Weight and HOMO, LUMO) show consistent gains in validity and precise satisfaction of multi-property targets, outperforming strong LLMs and graph-based algorithms.

Group Relative Policy Optimisation (GRPO) enhances large language models by estimating advantages across a group of sampled trajectories. However, mapping these trajectory-level advantages to policy updates requires aggregating token-level probabilities within each sequence. Relying on a fixed aggregation mechanism for this step fundamentally limits the algorithm's adaptability. Empirically, we observe a critical trade-off: certain fixed aggregations frequently suffer from training collapse, while others fail to yield satisfactory performance. To resolve this, we propose HölderPO, a generalised policy optimisation framework unifying token-level probability aggregation via the Hölder mean. By explicitly modulating the parameter p, our framework provides continuous control over the trade-off between gradient concentration and variance bounds. Theoretically, we prove that a larger p concentrates the gradient to amplify sparse learning signals, whereas a smaller p strictly bounds gradient variance. Because no static configuration can universally resolve this concentration-stability trade-off, we instantiate the framework with a dynamic annealing algorithm that progressively schedules p across the training lifecycle. Extensive evaluations demonstrate superior stability and convergence over existing baselines. Specifically, our approach achieves a state-of-the-art average accuracy of 54.9% across multiple mathematical benchmarks, yielding a substantial 7.2% relative gain over standard GRPO and secures an exceptional 93.8% success rate on ALFWorld.

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.

Despite recent advancements, most computational methods for molecule optimization are constrained to single- or double-property optimization tasks and suffer from poor scalability and generalizability to novel optimization tasks. Meanwhile, Large Language Models (LLMs) demonstrate remarkable out-of-domain generalizability to novel tasks. To demonstrate LLMs' potential for molecule optimization, we introduce MoMUInstruct, the first high-quality instruction-tuning dataset specifically focused on complex multi-property molecule optimization tasks. Leveraging MoMUInstruct, we develop GeLLM^3Os, a series of instruction-tuned LLMs for molecule optimization. Extensive evaluations across 5 in-domain and 5 out-of-domain tasks demonstrate that GeLLM^3Os consistently outperform state-of-the-art baselines. GeLLM^3Os also exhibit outstanding zero-shot generalization to unseen tasks, significantly outperforming powerful closed-source LLMs. Such strong generalizability demonstrates the tremendous potential of GeLLM^3Os as foundational models for molecule optimization, thereby tackling novel optimization tasks without resource-intensive retraining. MoMUInstruct, models, and code are accessible through https://github.com/ninglab/GeLLMO.

We investigate a relatively under-explored class of hybrid neurosymbolic models that integrate symbolic learning with neural reasoning to construct data generators meeting formal correctness criteria. In Symbolic Neural Generators (SNGs), symbolic learners examine logical specifications of feasible data from a small set of instances -- sometimes just one. Each specification in turn constrains the conditional information supplied to a neural-based generator, which rejects any instance violating the symbolic specification. Like other neurosymbolic approaches, SNG exploits the complementary strengths of symbolic and neural methods. The outcome of an SNG is a pair (H, X), where H is a symbolic description of feasible instances constructed from data, and X a set of generated new instances that satisfy the description. We introduce a semantics for such systems, based on the construction of appropriate base and fibre partially-ordered sets combined into an overall partial order. We implement an SNG combining a restricted form of Inductive Logic Programming (ILP) with a large language model (LLM) and evaluate it on early-stage drug design. Our main interest is the description and the set of potential inhibitor molecules generated by the SNG. On benchmark problems -- where drug targets are well understood -- SNG performance is statistically comparable to state-of-the-art methods. On exploratory problems with poorly understood targets, generated molecules exhibit binding affinities on par with leading clinical candidates. Experts further find the symbolic specifications useful as preliminary filters, with several generated molecules identified as viable for synthesis and wet-lab testing.

Agents built around large language models continually accumulate interaction trajectories during deployment, yet their behavior typically remains fixed. Beyond updating model weights, these trajectories can improve the agent harness that constructs context, mediates tools, validates actions, and recovers execution. We introduce Harness-R1, the first method, to our knowledge, that makes failure-conditioned, lifecycle-wide editing of an existing executable runtime a learned capability. It post-trains a dedicated harness engineer with online reinforcement learning so that its edits are optimized for the realized task success they produce, rather than proposed by a fixed editor. A separate 9B engineer converts batches of target-agent failures into validated executable patches; fresh same-batch reruns of the frozen target provide outcome rewards, so training updates only the engineer. Cold-start supervised fine-tuning initializes this editing policy, which is then trained online with group-relative policy optimization. Across WebShop, ALFWorld, and DBBench, Harness-R1 raises vanilla Qwen3.5-9B success from 44.3% to 53.6% (+9.3 percentage points). After direct target-agent fine-tuning, a target-specific engineer raises the average further from 59.2% to 64.2% (+5.0 points); because these gains hold both before and after fine-tuning the target, Harness-R1 points toward co-evolving the harness engineer and the target agent.

Reinforcement learning is increasingly used for code-centric tasks. These tasks include code generation, summarization, understanding, repair, testing, and optimization. This trend is growing faster with large language models and autonomous agents. A key challenge is how to design reward signals that make sense for software. In many RL problems, the reward is a clear number. In software, this is often not possible. The goal is rarely a single numeric objective. Instead, rewards are usually proxies. Common proxies check if the code compiles, passes tests, or satisfies quality metrics. Many reward designs have been proposed for code-related tasks. However, the work is scattered across areas and papers. There is no single survey that brings these approaches together and shows the full landscape of reward design for RL in software. In this survey, we provide the first systematic and comprehensive review of reward engineering for RL in software tasks. We focus on existing methods and techniques. We structure the literature along three complementary dimensions, summarizing the reward-design choices within each. We conclude with challenges and recommendations in the reward design space for SE tasks.

Task semantics can be expressed by a set of input-to-output examples or a piece of textual instruction. Conventional machine learning approaches for natural language processing (NLP) mainly rely on the availability of large-scale sets of task-specific examples. Two issues arise: first, collecting task-specific labeled examples does not apply to scenarios where tasks may be too complicated or costly to annotate, or the system is required to handle a new task immediately; second, this is not user-friendly since end-users are probably more willing to provide task description rather than a set of examples before using the system. Therefore, the community is paying increasing interest in a new supervision-seeking paradigm for NLP: learning from task instructions. Despite its impressive progress, there are some common issues that the community struggles with. This survey paper tries to summarize and provide insights into the current research on instruction learning, particularly by answering the following questions: (i) What is task instruction, and what instruction types exist? (ii) How to model instructions? (iii) What factors influence and explain the instructions' performance? (iv) What challenges remain in instruction learning? To our knowledge, this is the first comprehensive survey about textual instructions.

Reward design in reinforcement learning (RL) is challenging since specifying human notions of desired behavior may be difficult via reward functions or require many expert demonstrations. Can we instead cheaply design rewards using a natural language interface? This paper explores how to simplify reward design by prompting a large language model (LLM) such as GPT-3 as a proxy reward function, where the user provides a textual prompt containing a few examples (few-shot) or a description (zero-shot) of the desired behavior. Our approach leverages this proxy reward function in an RL framework. Specifically, users specify a prompt once at the beginning of training. During training, the LLM evaluates an RL agent's behavior against the desired behavior described by the prompt and outputs a corresponding reward signal. The RL agent then uses this reward to update its behavior. We evaluate whether our approach can train agents aligned with user objectives in the Ultimatum Game, matrix games, and the DealOrNoDeal negotiation task. In all three tasks, we show that RL agents trained with our framework are well-aligned with the user's objectives and outperform RL agents trained with reward functions learned via supervised learning

Modern language models (LMs) tend to memorize portions of their training data and emit verbatim spans. When the underlying sources are sensitive or copyright-protected, such reproduction raises issues of consent and compensation for creators and compliance risks for developers. We propose Anchored Decoding, a plug-and-play inference-time method for suppressing verbatim copying: it enables decoding from any risky LM trained on mixed-license data by keeping generation in bounded proximity to a permissively trained safe LM. Anchored Decoding adaptively allocates a user-chosen information budget over the generation trajectory and enforces per-step constraints that yield a sequence-level guarantee, enabling a tunable risk-utility trade-off. To make Anchored Decoding practically useful, we introduce a new permissively trained safe model (TinyComma 1.8B), as well as Anchored_{Byte} Decoding, a byte-level variant of our method that enables cross-vocabulary fusion via the ByteSampler framework (Hayase et al., 2025). We evaluate our methods across six model pairs on long-form evaluations of copyright risk and utility. Anchored and Anchored_{Byte} Decoding define a new Pareto frontier, preserving near-original fluency and factuality while eliminating up to 75% of the measurable copying gap (averaged over six copying metrics) between the risky baseline and a safe reference, at a modest inference overhead.

Despite advances in large language models (LLMs) on reasoning and instruction-following benchmarks, it remains unclear whether they can reliably produce outputs aligned with a broad variety of user goals, a concept we refer to as steerability. The abundance of methods proposed to modify LLM behavior makes it unclear whether current LLMs are already steerable, or require further intervention. In particular, LLMs may exhibit (i) poor coverage, where rare user goals are underrepresented; (ii) miscalibration, where models overshoot requests; and (iii) side effects, where changes to one dimension of text inadvertently affect others. To systematically evaluate these failures, we introduce a framework based on a multi-dimensional goal space that models user goals and LLM outputs as vectors with dimensions corresponding to text attributes (e.g., reading difficulty). Applied to a text-rewriting task, we find that current LLMs struggle with steerability, as side effects are persistent. Interventions to improve steerability, such as prompt engineering, best-of-N sampling, and reinforcement learning fine-tuning, have varying effectiveness, yet side effects remain problematic. Our findings suggest that even strong LLMs struggle with steerability, and existing alignment strategies may be insufficient. We open-source our steerability evaluation framework at https://github.com/MLD3/steerability.

Most human proteins remain undrugged, over 96% of human proteins remain unexploited by approved therapeutics. While structure-based virtual screening promises to expand the druggable proteome, existing methods lack atomic-level precision and fail to predict binding fitness, limiting translational impact. We present AuroBind, a scalable virtual screening framework that fine-tunes a custom atomic-level structural model on million-scale chemogenomic data. AuroBind integrates direct preference optimization, self-distillation from high-confidence complexes, and a teacher-student acceleration strategy to jointly predict ligand-bound structures and binding fitness. The proposed models outperform state-of-the-art models on structural and functional benchmarks while enabling 100,000-fold faster screening across ultra-large compound libraries. In a prospective screen across ten disease-relevant targets, AuroBind achieved experimental hit rates of 7-69%, with top compounds reaching sub-nanomolar to picomolar potency. For the orphan GPCRs GPR151 and GPR160, AuroBind identified both agonists and antagonists with success rates of 16-30%, and functional assays confirmed GPR160 modulation in liver and prostate cancer models. AuroBind offers a generalizable framework for structure-function learning and high-throughput molecular screening, bridging the gap between structure prediction and therapeutic discovery.

The widespread applicability and increasing omnipresence of LLMs have instigated a need to align LLM responses to user and stakeholder preferences. Many preference optimization approaches have been proposed that fine-tune LLM parameters to achieve good alignment. However, such parameter tuning is known to interfere with model performance on many tasks. Moreover, keeping up with shifting user preferences is tricky in such a situation. Decoding-time alignment with reward model guidance solves these issues at the cost of increased inference time. However, most of such methods fail to strike the right balance between exploration and exploitation of reward -- often due to the conflated formulation of these two aspects - to give well-aligned responses. To remedy this we decouple these two aspects and implement them in an evolutionary fashion: exploration is enforced by decoding from mutated instructions and exploitation is represented as the periodic replacement of poorly-rewarded generations with well-rewarded ones. Empirical evidences indicate that this strategy outperforms many preference optimization and decode-time alignment approaches on two widely accepted alignment benchmarks AlpacaEval 2 and MT-Bench. Our implementation will be available at: https://darwin-alignment.github.io.

General-purpose object placement is a fundamental capability of an intelligent generalist robot: being capable of rearranging objects following precise human instructions even in novel environments. This work is dedicated to achieving general-purpose object placement with ``something something'' instructions. Specifically, we break the entire process down into three parts, including object localization, goal imagination and robot control, and propose a method named SPORT. SPORT leverages a pre-trained large vision model for broad semantic reasoning about objects, and learns a diffusion-based pose estimator to ensure physically-realistic results in 3D space. Only object types (movable or reference) are communicated between these two parts, which brings two benefits. One is that we can fully leverage the powerful ability of open-set object recognition and localization since no specific fine-tuning is needed for the robotic scenario. Moreover, the diffusion-based estimator only need to ``imagine" the object poses after the placement, while no necessity for their semantic information. Thus the training burden is greatly reduced and no massive training is required. The training data for the goal pose estimation is collected in simulation and annotated by using GPT-4. Experimental results demonstrate the effectiveness of our approach. SPORT can not only generate promising 3D goal poses for unseen simulated objects, but also be seamlessly applied to real-world settings.

Evaluation of robotic manipulation systems has largely relied on fixed benchmarks authored by a small number of experts, where task instances, constraints, and success criteria are predefined and difficult to extend. This paradigm limits who can shape evaluation and obscures how policies respond to user-authored variations in task intent, constraints, and notions of success. We argue that evaluating modern manipulation policies requires reframing evaluation as a language-driven process over structured physical domains. We present RoboPlayground, a framework that enables users to author executable manipulation tasks using natural language within a structured physical domain. Natural language instructions are compiled into reproducible task specifications with explicit asset definitions, initialization distributions, and success predicates. Each instruction defines a structured family of related tasks, enabling controlled semantic and behavioral variation while preserving executability and comparability. We instantiate RoboPlayground in a structured block manipulation domain and evaluate it along three axes. A user study shows that the language-driven interface is easier to use and imposes lower cognitive workload than programming-based and code-assist baselines. Evaluating learned policies on language-defined task families reveals generalization failures that are not apparent under fixed benchmark evaluations. Finally, we show that task diversity scales with contributor diversity rather than task count alone, enabling evaluation spaces to grow continuously through crowd-authored contributions. Project Page: https://roboplayground.github.io

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.

We present new data and semantic parsing methods for the problem of mapping English sentences to Bash commands (NL2Bash). Our long-term goal is to enable any user to perform operations such as file manipulation, search, and application-specific scripting by simply stating their goals in English. We take a first step in this domain, by providing a new dataset of challenging but commonly used Bash commands and expert-written English descriptions, along with baseline methods to establish performance levels on this task.

Large language models~(LLMs) are expected to be helpful, harmless, and honest. In alignment scenarios such as safety, confidence, and general preference alignment, binary preference data collection and reward modeling are resource-intensive but essential for transferring human preference. In this work, we explore using the similarity between sampled generations and high-quality reference answers as an alternative reward function choice for LLM alignment. Similarity reward circumvents binary preference data collection and reward modeling when unary high-quality reference answers are available. We introduce RefAlign, a versatile REINFORCE-style alignment algorithm that does not rely on reference or reward models. RefAlign utilizes similarity metrics, such as BERTScore between sampled generations and reference answers as surrogate rewards. Beyond general human preference optimization, RefAlign can be readily extended to diverse scenarios, such as safety and confidence alignment, by incorporating the similarity reward with task-related objectives. In various scenarios, RefAlign demonstrates comparable performance to previous alignment methods without binary preference data and reward models.

Aligning large language models with human objectives is paramount, yet common approaches including RLHF suffer from unstable and resource-intensive training. In response to this challenge, we introduce ARGS, Alignment as Reward-Guided Search, a novel framework that integrates alignment into the decoding process, eliminating the need for expensive RL training. By adjusting the model's probabilistic predictions using a reward signal, ARGS generates texts with semantic diversity while being aligned with human preferences, offering a promising and flexible solution for aligning language models. Notably, ARGS demonstrates consistent enhancements in average reward compared to baselines across diverse alignment tasks and various model dimensions. For example, under the same greedy-based decoding strategy, our method improves the average reward by 19.56% relative to the baseline and secures a preference or tie score of 64.33% in GPT-4 evaluation. We believe that our framework, emphasizing decoding-time alignment, paves the way for more responsive language models in the future. Code is publicly available at: https://github.com/deeplearning-wisc/args.

To achieve the highest perceptual quality, state-of-the-art diffusion models are optimized with objectives that typically look very different from the maximum likelihood and the Evidence Lower Bound (ELBO) objectives. In this work, we reveal that diffusion model objectives are actually closely related to the ELBO. Specifically, we show that all commonly used diffusion model objectives equate to a weighted integral of ELBOs over different noise levels, where the weighting depends on the specific objective used. Under the condition of monotonic weighting, the connection is even closer: the diffusion objective then equals the ELBO, combined with simple data augmentation, namely Gaussian noise perturbation. We show that this condition holds for a number of state-of-the-art diffusion models. In experiments, we explore new monotonic weightings and demonstrate their effectiveness, achieving state-of-the-art FID scores on the high-resolution ImageNet benchmark.

A key concern with the concept of "alignment" is the implicit question of "alignment to what?". AI systems are increasingly used across the world, yet safety alignment is often focused on homogeneous monolingual settings. Additionally, preference training and safety measures often overfit to harms common in Western-centric datasets. Here, we explore the viability of different alignment approaches when balancing dual objectives: addressing and optimizing for a non-homogeneous set of languages and cultural preferences while minimizing both global and local harms. We collect the first set of human annotated red-teaming prompts in different languages distinguishing between global and local harm, which serve as a laboratory for understanding the reliability of alignment techniques when faced with preference distributions that are non-stationary across geographies and languages. While this setting is seldom covered by the literature to date, which primarily centers on English harm mitigation, it captures real-world interactions with AI systems around the world. We establish a new precedent for state-of-the-art alignment techniques across 6 languages with minimal degradation in general performance. Our work provides important insights into cross-lingual transfer and novel optimization approaches to safeguard AI systems designed to serve global populations.

Generating structured, editable diagrams remains a significant challenge for contemporary large language models, despite their proficiency in general-purpose vector code generation. The primary difficulty lies in the structural fragility of the output; minor errors such as misaligned connector endpoints, text labels overlapping borders, or complex layouts drifting beyond the canvas boundaries render the resulting SVG files functionally unusable for professional applications. To address these issues, we introduce GeoSVG-RL, a specialized reinforcement learning framework designed for layout-constrained text-to-SVG generation. Unlike standard training objectives that rely solely on maximizing token-level likelihood, our approach optimizes the policy against explicit, executable geometric feedback. The model first produces a structured layout plan that serves as a geometric contract for the subsequent generation of the SVG code. This code is then rendered through a browser-backed verifier, enabling the calculation of fine-grained rewards across six critical dimensions: rendering validity, canvas fitting, precise anchor placement, text containment, graph consistency, and code cleanliness. We utilize Group Relative Policy Optimization (GRPO) to refine the model, sampling multiple candidates per prompt to facilitate updates based on relative quality. Starting from a supervised warm-start phase on synthetic data, GeoSVG-RL achieves substantial gains in structural reliability, particularly in arrow-anchor accuracy and text-in-box rates. Quantitative evaluations demonstrate that our method consistently outperforms current state-of-the-art systems in local geometric precision and the preservation of graph connectivity, providing a robust pathway toward automated yet reliable technical illustration.

Direct preference optimization (DPO) has shown to be an effective method for large language model (LLM) alignment. Recent works have attempted to apply DPO to multimodal scenarios but have found it challenging to achieve consistent improvement. Through a comparative experiment, we identify the unconditional preference problem in multimodal preference optimization, where the model overlooks the image condition. To address this problem, we propose mDPO, a multimodal DPO objective that prevents the over-prioritization of language-only preferences by also optimizing image preference. Moreover, we introduce a reward anchor that forces the reward to be positive for chosen responses, thereby avoiding the decrease in their likelihood -- an intrinsic problem of relative preference optimization. Experiments on two multimodal LLMs of different sizes and three widely used benchmarks demonstrate that mDPO effectively addresses the unconditional preference problem in multimodal preference optimization and significantly improves model performance, particularly in reducing hallucination.

While Large Language Models (LLMs) have demonstrated remarkable capabilities across diverse natural language processing tasks, aligning these models with varying human preferences across multiple objectives remains a significant challenge in practical deployments. Existing multi-objective alignment methods rely on manually specified preference weights, which not only burden users with difficult preference specification tasks but also lead to suboptimal training efficiency due to exploration of irrelevant preference combinations. To alleviate these issues, we propose a novel framework named PRO, i.e., PReference Orchestrator, which features a lightweight preference adapter that automatically infers prompt-specific preference weights during both training and deployment phases. Specifically, the adapter automatically learns appropriate preference weights for each prompt by training on normalized reward scores from multiple reward models for preferred responses, which inherently reflect effective preference balances across objectives. Additionally, We provide theoretical analysis proving that our prompt-aware preference mechanism achieves superior performance compared to fixed preference weights in multi-objective alignment scenarios. Extensive experiments across multiple tasks demonstrate the effectiveness of our method over existing multi-objective alignment approaches.

Image captioning is one of the most fundamental tasks in computer vision. Owing to its open-ended nature, it has received significant attention in the era of multimodal large language models (MLLMs). In pursuit of ever more detailed and accurate captions, recent work has increasingly turned to reinforcement learning (RL). However, existing captioning-RL methods and evaluation metrics often emphasize a narrow notion of caption quality, inducing trade-offs across core dimensions of captioning. For example, utility-oriented objectives can encourage noisy, hallucinated, or overlong captions that improve downstream question answering while harming fluency, whereas arena-style objectives can favor fluent but generic descriptions with limited usefulness. To address this, we propose a more balanced RL framework that jointly optimizes utility-aware correctness, reference coverage, and linguistic quality. In order to effectively optimize the resulting continuous multi-objective reward formulation, we apply GDPO-style reward-decoupled normalization to continuous-valued captioning rewards and show that it improves performance over vanilla GRPO. Additionally, we introduce length-conditional reward masking, yielding a more suitable length penalty for captioning. Across LLaVA-1.5-7B and Qwen2.5-VL 3B and 7B base models, our method consistently improves caption quality, with peak gains of +13.6 DCScore, +9.0 CaptionQA, and +29.0 CapArena across different models.

Target proteins that lack accessible binding pockets and conformational stability have posed increasing challenges for drug development. Induced proximity strategies, such as PROTACs and molecular glues, have thus gained attention as pharmacological alternatives, but still require small molecule docking at binding pockets for targeted protein degradation (TPD). The computational design of protein-based binders presents unique opportunities to access undruggable targets, but have often relied on stable 3D structures or predictions for effective binder generation. Recently, we have leveraged the expressive latent spaces of protein language models (pLMs) for the prioritization of peptide binders from sequence alone, which we have then fused to E3 ubiquitin ligase domains, creating a CRISPR-analogous TPD system for target proteins. However, our methods rely on training discriminator models for ranking heuristically or unconditionally-derived guide peptides for their target binding capability. In this work, we introduce PepMLM, a purely target sequence-conditioned de novo generator of linear peptide binders. By employing a novel masking strategy that uniquely positions cognate peptide sequences at the terminus of target protein sequences, PepMLM tasks the state-of-the-art ESM-2 pLM to fully reconstruct the binder region, achieving low perplexities matching or improving upon previously-validated peptide-protein sequence pairs. After successful in silico benchmarking with AlphaFold-Multimer, we experimentally verify PepMLM's efficacy via fusion of model-derived peptides to E3 ubiquitin ligase domains, demonstrating endogenous degradation of target substrates in cellular models. In total, PepMLM enables the generative design of candidate binders to any target protein, without the requirement of target structure, empowering downstream programmable proteome editing applications.

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.

We consider the problem of multi-objective alignment of foundation models with human preferences, which is a critical step towards helpful and harmless AI systems. However, it is generally costly and unstable to fine-tune large foundation models using reinforcement learning (RL), and the multi-dimensionality, heterogeneity, and conflicting nature of human preferences further complicate the alignment process. In this paper, we introduce Rewards-in-Context (RiC), which conditions the response of a foundation model on multiple rewards in its prompt context and applies supervised fine-tuning for alignment. The salient features of RiC are simplicity and adaptivity, as it only requires supervised fine-tuning of a single foundation model and supports dynamic adjustment for user preferences during inference time. Inspired by the analytical solution of an abstracted convex optimization problem, our dynamic inference-time adjustment method approaches the Pareto-optimal solution for multiple objectives. Empirical evidence demonstrates the efficacy of our method in aligning both Large Language Models (LLMs) and diffusion models to accommodate diverse rewards with only around 10% GPU hours compared with multi-objective RL baseline.

Direct alignment methods are increasingly used to align large language models (LLMs) with human preferences. However, many real-world alignment problems involve multiple conflicting objectives, where naive aggregation of preferences can lead to unstable training and poor trade-offs. In particular, weighted loss methods may fail to identify update directions that simultaneously improve all objectives, and existing multi-objective approaches often rely on explicit reward models, introducing additional complexity and distorting user-specified preferences. The contributions of this paper are two-fold. First, we propose a Reward-free Alignment framework for Conflicted Objectives (RACO) that directly leverages pairwise preference data and resolves gradient conflicts via a novel clipped variant of conflict-averse gradient descent. We provide convergence guarantees to Pareto-critical points that respect user-specified objective weights, and further show that clipping can strictly improve convergence rate in the two-objective setting. Second, we improve our method using some heuristics and conduct experiments to demonstrate the compatibility of the proposed framework for LLM alignment. Both qualitative and quantitative evaluations on multi-objective summarization and safety alignment tasks across multiple LLM families (Qwen 3, Llama 3, Gemma 3) show that our method consistently achieves better Pareto trade-offs compared to existing multi-objective alignment baselines.

Direct Preference Optimization (DPO) has become a widely used training method for the instruction fine-tuning of large language models (LLMs). In this work, we explore an under-investigated aspect of DPO - its dependency on the reference model or policy. Such reference policies, typically instantiated as the model to be further fine-tuned, are important since they can impose an upper limit on DPO's effectiveness. Therefore, we address three related research questions in this work. First, we explore the optimal strength of the KL-divergence constraint in DPO, which penalizes deviations from the reference policy, and find that DPO is sensitive to this strength. Next, we examine the necessity of reference policies for instruction fine-tuning by providing both theoretical and empirical comparisons between DPO and related learning objectives, demonstrating DPO's superiority. Additionally, we investigate whether DPO benefits from stronger reference policies, finding that a stronger reference policy can lead to improved performance, but only when it is similar to the model being fine-tuned. Our findings highlight the confounding role of reference policies in DPO and offer insights for best practices, while also identifying open research questions for future studies.

One difficulty in using artificial agents for human-assistive applications lies in the challenge of accurately assisting with a person's goal(s). Existing methods tend to rely on inferring the human's goal, which is challenging when there are many potential goals or when the set of candidate goals is difficult to identify. We propose a new paradigm for assistance by instead increasing the human's ability to control their environment, and formalize this approach by augmenting reinforcement learning with human empowerment. This task-agnostic objective preserves the person's autonomy and ability to achieve any eventual state. We test our approach against assistance based on goal inference, highlighting scenarios where our method overcomes failure modes stemming from goal ambiguity or misspecification. As existing methods for estimating empowerment in continuous domains are computationally hard, precluding its use in real time learned assistance, we also propose an efficient empowerment-inspired proxy metric. Using this, we are able to successfully demonstrate our method in a shared autonomy user study for a challenging simulated teleoperation task with human-in-the-loop training.

Direct Preference Optimization (DPO) is a method for enhancing model performance by directly optimizing for the preferences or rankings of outcomes, instead of traditional loss functions. This approach has proven effective in aligning Large Language Models (LLMs) with human preferences. Despite its widespread use across various tasks, DPO has been criticized for its sensitivity to the effectiveness of Supervised Fine-Tuning (SFT) and its limitations in enabling models to learn human-preferred responses, leading to less satisfactory performance. To address these limitations, we propose Aligned Supervised Fine-Tuning (ASFT), an effective approach that better aligns LLMs with pair-wise datasets by optimizing absolute likelihood for each response, rather than using the Bradley-Terry model, and eliminates the need for a reference model. Through theoretical gradient analysis, we demonstrate that ASFT mitigates the issue where the DPO loss function decreases the probability of generating human-dispreferred data at a faster rate than it increases the probability of producing preferred data. Additionally, we compare ASFT to DPO and its latest variants, such as the single-step approach ORPO, using the latest instruction-tuned model Llama3, which has been fine-tuned on UltraFeedback and HH-RLHF. We evaluated performance on instruction-following benchmarks like MT-Bench and traditional text generation metrics such as BLEU-4 and ROUGE-L. Extensive experiments demonstrate that ASFT is an effective alignment approach, consistently outperforming existing methods.

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.

The growing use of generative models in daily life calls for efficient mechanisms to control their generation, to e.g., produce safe content or provide users with tools to explore style changes. Ideally, such mechanisms should require low volume of unpaired data (i.e., without explicit preference), and should be cheap, both at train and inference time, while preserving output quality. Recent research has shown that such mechanisms can be obtained by intervening exclusively on model activations, with the goal of correcting distributional differences between activations seen when using prompts from a source vs. a target set (e.g., toxic and non-toxic sentences). While cheap, these fast methods are inherently crude: their maps are tuned locally, not accounting for their impact on downstream layers, resulting in interventions that cause unintended shifts when used out-of-sample. We propose in this work linear end-to-end activation steering (LinEAS), an approach trained with a global loss that accounts simultaneously for all layer-wise distributional shifts. In addition to being more robust, the loss used to train LinEAS can be regularized with sparsifying norms, which can automatically carry out neuron selection. LinEAS only requires a handful of unpaired samples to be effective, and beats similar baselines on toxicity mitigation in language models, becoming competitive with oracle-dependent methods that have access to strong supervision. LinEAS is modality-agnostic and we empirically find that it outperforms existing activation steering methods at mitigating and including new concepts at the output of single-step text-to-image generation models.

The ability of large language models (LLMs) to process and reason over long textual inputs is critical for a wide range of real-world applications. However, progress in this area is significantly constrained by the absence of high-quality, diverse, and verifiable long-context datasets suitable for both training and evaluation. This work introduces a modular, extensible framework for synthetic long-context data generation via prompt-based interaction with LLMs. The framework supports multiple training and alignment objectives, including Supervised Fine-Tuning (SFT), Direct Preference Optimization (DPO), and Group Relative Policy Optimization (GRPO). It encompasses four core generation paradigms: multi-turn conversational dialogues, document-grounded input-output pairs, verifiable instruction-response tasks, and long-context reasoning examples. Through templated prompting, a model-agnostic architecture, and metadata-enriched outputs, the proposed approach facilitates scalable, controllable, and purpose-aligned dataset creation for advancing long-context capabilities in LLMs.

We introduce Flux Matching, a new paradigm for generative modeling that generalizes existing score-based models to a broader family of vector fields that need not be conservative. Rather than requiring the model to equal the data score, the Flux Matching objective imposes a weaker condition that admits infinitely many vector fields whose stationary distribution is the data. This flexibility enables a class of generative models that cannot be learned under score matching, in which inductive biases, structural priors, and properties of the dynamics can be directly imposed or optimized. We show that Flux Matching performs strongly on high-dimensional image datasets and, more importantly, that our added freedom unlocks a range of applications including faster sampling, interpretable and mechanistic models, and dynamics that encode directed dependencies between variables. More broadly, Flux Matching opens a new dimension in generative modeling by turning the vector field itself into a design choice rather than a fixed target. Code is available at https://github.com/peterpaohuang/flux_matching.

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.

Safety post-training can improve the harmfulness and policy compliance of Large Language Models (LLMs), but it may also reduce general utility, a phenomenon often described as the alignment tax. We study this trade-off through the lens of continual learning: sequential alignment stages expose the model to shifted data distributions and objectives, and their gradients may interfere with directions that support previously acquired general capabilities. This view does not claim that all alignment degradation has a single cause; rather, it provides a useful first-order mechanism for mitigating one important source of capability regression. We propose Orthogonal Gradient Projection for Safety Alignment (OGPSA), a lightweight update rule that estimates a low-rank reference subspace from gradients on a small set of general-capability data and removes from each safety gradient the component lying in this subspace. The resulting update is the steepest local safety-descent direction subject to first-order preservation constraints on the reference objectives. OGPSA is compatible with standard post-training pipelines and avoids large-scale replay, although it introduces periodic reference-gradient computation. Across Supervised Fine-Tuning (SFT), Direct Preference Optimization (DPO), and sequential SFTrightarrowDPO settings, OGPSA improves the observed safety--utility trade-off over standard baselines. Under the sequential SFTrightarrowDPO pipeline, the average performance gain increases from 33.98\% to 42.74\% on Qwen2.5-7B-Instruct and from 19.74\% to 32.98\% on Llama3.1-8B-Instruct. We have open sourced our code at https://github.com/SunGL001/OGPSA.

Recent diffusion-based video generation models have made significant progress in multi-reference image-conditioned video editing. However, existing methods still struggle to coordinate information from multiple visual sources accurately. We identify a critical deficiency in existing approaches. Existing editing instructions lack explicit reference relationships, and most multimodal large language models (MLLMs) cannot generate them reliably. To address this problem, we propose ReBind, a systematic framework that introduces semantic instructions with embedded reference tokens as the intermediate representation for multi-reference image-conditioned video editing. Our key insight is embedding reference tokens at semantic positions to eliminate ambiguity and establish precise bindings between visual attributes and their sources. We develop ReBind-Instruct, a specialized MLLM that learns to establish explicit bindings between visual attributes and their reference sources through a two-stage progressive scheme for precise reference relationships. We further develop ReBind-Edit, which enables lightweight adaptation of text-to-video models to coordinate multiple references by binding visual attributes to their designated sources. Extensive experiments demonstrate that ReBind substantially outperforms general-purpose MLLMs in instruction quality and achieves state-of-the-art performance among open-source methods on reference image conditioned video editing. Our project webpage: https://rebind-mrv2v.github.io/.

Prior works in multi-objective reinforcement learning typically use linear reward scalarization with fixed weights, which provably fail to capture non-convex Pareto fronts and thus yield suboptimal results. This limitation becomes especially critical in online preference alignment for large language models. Here, stochastic trajectories generated by parameterized policies create highly non-linear and non-convex mappings from parameters to objectives that no single static weighting scheme can find optimal trade-offs. We address this limitation by introducing dynamic reward weighting, which adaptively adjusts reward weights during the online reinforcement learning process. Unlike existing approaches that rely on fixed-weight interpolation, our dynamic weighting continuously balances and prioritizes objectives in training, facilitating effective exploration of Pareto fronts in objective space. We introduce two approaches of increasing sophistication and generalizability: (1) hypervolume-guided weight adaptation and (2) gradient-based weight optimization, offering a versatile toolkit for online multi-objective alignment. Our extensive experiments demonstrate their compatibility with commonly used online reinforcement learning algorithms (including GRPO, REINFORCE, and RLOO), effectiveness across multiple mathematical reasoning datasets, and applicability to different model families, consistently achieving Pareto dominant solutions with fewer training steps than fixed-weight linear scalarization baselines.

The Base-New Trade-off (BNT) problem universally exists during the optimization of CLIP-based prompt tuning, where continuous fine-tuning on base (target) classes leads to a simultaneous decrease of generalization ability on new (unseen) classes. Existing approaches attempt to regulate the prompt tuning process to balance BNT by appending constraints. However, imposed on the same target prompt, these constraints fail to fully avert the mutual exclusivity between the optimization directions for base and new. As a novel solution to this challenge, we propose the plug-and-play Dual-Prompt Collaboration (DPC) framework, the first that decoupling the optimization processes of base and new tasks at the prompt level. Specifically, we clone a learnable parallel prompt based on the backbone prompt, and introduce a variable Weighting-Decoupling framework to independently control the optimization directions of dual prompts specific to base or new tasks, thus avoiding the conflict in generalization. Meanwhile, we propose a Dynamic Hard Negative Optimizer, utilizing dual prompts to construct a more challenging optimization task on base classes for enhancement. For interpretability, we prove the feature channel invariance of the prompt vector during the optimization process, providing theoretical support for the Weighting-Decoupling of DPC. Extensive experiments on multiple backbones demonstrate that DPC can significantly improve base performance without introducing any external knowledge beyond the base classes, while maintaining generalization to new classes. Code is available at: https://github.com/JREion/DPC.

Preference based alignment objectives implicitly assume that all human preferences are expressed with equal strength. In practice, however, preference strength varies across individuals and contexts -- a phenomenon established in behavioral economics and discrete choice theory. This mismatch limits the ability of existing objectives to faithfully capture heterogeneous human judgments. Inspired by this literature, we introduce Mixed Logit Direct Preference Optimization (MixDPO), a generalization of Direct Preference Optimization that models variation in preference strength. MixDPO enables alignment objectives to capture heterogeneity in how strongly preferences are expressed across training examples. We evaluate MixDPO on three preference datasets using two open-weight language models. Across datasets, MixDPO improves aggregate alignment performance (+11.2 points on Pythia-2.8B) while preserving subgroup level preferences, with the largest gains appearing in settings with higher inferred preference heterogeneity. MixDPO makes preference heterogeneity explicit through learned strength distributions. We release our code for reproducibility.

Controlled text perturbation is useful for evaluating and improving model generalizability. However, current techniques rely on training a model for every target perturbation, which is expensive and hard to generalize. We present Tailor, a semantically-controlled text generation system. Tailor builds on a pretrained seq2seq model and produces textual outputs conditioned on control codes derived from semantic representations. We craft a set of operations to modify the control codes, which in turn steer generation towards targeted attributes. These operations can be further composed into higher-level ones, allowing for flexible perturbation strategies. We demonstrate the effectiveness of these perturbations in multiple applications. First, we use Tailor to automatically create high-quality contrast sets for four distinct natural language processing (NLP) tasks. These contrast sets contain fewer spurious artifacts and are complementary to manually annotated ones in their lexical diversity. Second, we show that Tailor perturbations can improve model generalization through data augmentation. Perturbing just 2% of training data leads to a 5.8-point gain on an NLI challenge set measuring reliance on syntactic heuristics.

Controllable layout generation aims at synthesizing plausible arrangement of element bounding boxes with optional constraints, such as type or position of a specific element. In this work, we try to solve a broad range of layout generation tasks in a single model that is based on discrete state-space diffusion models. Our model, named LayoutDM, naturally handles the structured layout data in the discrete representation and learns to progressively infer a noiseless layout from the initial input, where we model the layout corruption process by modality-wise discrete diffusion. For conditional generation, we propose to inject layout constraints in the form of masking or logit adjustment during inference. We show in the experiments that our LayoutDM successfully generates high-quality layouts and outperforms both task-specific and task-agnostic baselines on several layout tasks.

We simplify space binding by focusing on two core components, a single encoder per modality and high-quality data; enabling training state-of-the-art models on a single GPU in a few hours as opposed to multiple days. We present EBind, an Easy, data-centric, and parameter-efficient method to Bind the embedding spaces of multiple contrastive models. We demonstrate that a simple 1.8B-parameter image-text-video-audio-3D model can outperform models 4 to 17x the size. The key to achieving this is a carefully curated dataset of three complementary data sources: i) 6.7M fully-automated multimodal quintuples sourced via SOTA retrieval models, ii) 1M diverse, semi-automated triples annotated by humans as negative, partial, or positive matches, and iii) 3.4M pre-existing captioned data items. We use 13 different evaluations to demonstrate the value of each data source. Due to limitations with existing benchmarks, we further introduce the first high-quality, consensus-annotated zero-shot classification benchmark between audio and PCs. In contrast to related work, we will open-source our code, model weights, and datasets.

Recent advances in text-to-image (T2I) diffusion models have significantly improved the quality of generated images. However, providing efficient control over individual subjects, particularly the attributes characterizing them, remains a key challenge. While existing methods have introduced mechanisms to modulate attribute expression, they typically provide either detailed, object-specific localization of such a modification or full-scale fine-grained, nuanced control of attributes. No current approach offers both simultaneously, resulting in a gap when trying to achieve precise continuous and subject-specific attribute modulation in image generation. In this work, we demonstrate that token-level directions exist within commonly used CLIP text embeddings that enable fine-grained, subject-specific control of high-level attributes in T2I models. We introduce two methods to identify these directions: a simple, optimization-free technique and a learning-based approach that utilizes the T2I model to characterize semantic concepts more specifically. Our methods allow the augmentation of the prompt text input, enabling fine-grained control over multiple attributes of individual subjects simultaneously, without requiring any modifications to the diffusion model itself. This approach offers a unified solution that fills the gap between global and localized control, providing competitive flexibility and precision in text-guided image generation. Project page: https://compvis.github.io/attribute-control. Code is available at https://github.com/CompVis/attribute-control.

While reinforcement learning for large language model alignment has progressed rapidly in recent years, transferring these paradigms to high-stakes medical question answering reveals a fundamental paradigm mismatch. Reinforcement Learning from Human Feedback relies on preference annotations that are prohibitively expensive and often fail to reflect the absolute correctness of medical facts. Reinforcement Learning from Verifiable Rewards lacks effective automatic verifiers and struggles to handle complex clinical contexts. Meanwhile, medical alignment requires the simultaneous optimization of correctness, safety, and compliance, yet multi-objective heterogeneous reward signals are prone to scale mismatch and optimization conflicts.To address these challenges, we propose a robust medical alignment paradigm. We first construct a holistic multi-dimensional medical alignment matrix that decomposes alignment objectives into four categories: fundamental capabilities, expert knowledge, online feedback, and format specifications. Within each category, we establish a closed loop of where observable metrics inform attributable diagnosis, which in turn drives optimizable rewards, thereby providing fine-grained, high-resolution supervision signals for subsequent iterative optimization. To resolve gradient domination and optimization instability problem caused by heterogeneous signals, we further propose a unified optimization mechanism. This mechanism employs Reference-Frozen Normalization to align reward scales and implements a Tri-Factor Adaptive Dynamic Weighting strategy to achieve collaborative optimization that is weakness-oriented, risk-prioritized, and redundancy-reducing. Experimental results demonstrate the effectiveness of our proposed paradigm in real-world medical scenario evaluations, establishing a new paradigm for complex alignment in vertical domains.

Behavior Cloning (BC) on curated (or filtered) data is the predominant paradigm for supervised fine-tuning (SFT) of large language models; as well as for imitation learning of control policies. Here, we draw on a connection between this successful strategy and the theory and practice of finding optimal policies via Reinforcement Learning (RL). Building on existing literature, we clarify that SFT can be understood as maximizing a lower bound on the RL objective in a sparse reward setting. Giving support to its often observed good performance. From this viewpoint, we realize that a small modification to SFT leads to an importance weighted variant that behaves closer to training with RL as it: i) optimizes a tighter bound to the RL objective and, ii) can improve performance compared to SFT on curated data. We refer to this variant as importance weighted supervised fine-tuning (iw-SFT). We show that it is easy to implement and can be further generalized to training with quality scored data. The resulting SFT variants are competitive with more advanced RL algorithms for large language models and for training policies in continuous control tasks. For example achieving 66.7% on the AIME 2024 dataset.