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.

Rewards serve as proxies for human preferences and play a crucial role in Reinforcement Learning from Human Feedback (RLHF). However, if these rewards are inherently imperfect, exhibiting various biases, they can adversely affect the alignment of large language models (LLMs). In this paper, we collectively define the various biases present in rewards as the problem of reward unfairness. We propose a bias-agnostic method to address the issue of reward fairness from a resource allocation perspective, without specifically designing for each type of bias, yet effectively mitigating them. Specifically, we model preference learning as a resource allocation problem, treating rewards as resources to be allocated while considering the trade-off between utility and fairness in their distribution. We propose two methods, Fairness Regularization and Fairness Coefficient, to achieve fairness in rewards. We apply our methods in both verification and reinforcement learning scenarios to obtain a fairness reward model and a policy model, respectively. Experiments conducted in these scenarios demonstrate that our approach aligns LLMs with human preferences in a more fair manner.

Despite doubts on data quality, instruction synthesis has been widely applied into instruction tuning (IT) of LLMs as an economic and rapid alternative. Recent endeavors focus on improving data quality for synthesized instruction pairs in English and have facilitated IT of English-centric LLMs. However, data quality issues in multilingual synthesized instruction pairs are even more severe, since the common synthesizing practice is to translate English synthesized data into other languages using machine translation (MT). Besides the known content errors in these English synthesized data, multilingual synthesized instruction data are further exposed to defects introduced by MT and face insufficient localization of the target languages, leading to cultural inequality in trained LLMs. In this paper, we propose MIDB, a Multilingual Instruction Data Booster to automatically address the quality issues in multilingual synthesized data. MIDB is trained on around 36.8k revision examples across 16 languages by human linguistic experts, thereby can boost the low-quality data by addressing content errors and MT defects, and improving localization in these synthesized data. Both automatic and human evaluation indicate that not only MIDB steadily improved instruction data quality in 16 languages, but also the instruction-following and cultural-understanding abilities of multilingual LLMs fine-tuned on MIDB-boosted data were significantly enhanced, suggesting an improved linguistic and cultural equality.

In this paper, we present SOCIA-$\nabla$, an end-to-end, agentic framework that treats simulator construction asinstance optimization over code within a textual computation graph. Specialized LLM-driven agents are embedded as graph nodes, and a workflow manager executes a loss-driven loop: code synthesis -> execution -> evaluation -> code repair. The optimizer performs Textual-Gradient Descent (TGD), while human-in-the-loop interaction is reserved for task-spec confirmation, minimizing expert effort and keeping the code itself as the trainable object. Across three CPS tasks, i.e., User Modeling, Mask Adoption, and Personal Mobility, SOCIA-$\nabla$ attains state-of-the-art overall accuracy. By unifying multi-agent orchestration with a loss-aligned optimization view, SOCIA-$\nabla$ converts brittle prompt pipelines into reproducible, constraint-aware simulator code generation that scales across domains and simulation granularities. We will release the code soon.

With the increasing deployment of facial image data across a wide range of applications, efficient compression tailored to facial semantics has become critical for both storage and transmission. While recent learning-based face image compression methods have achieved promising results, they often suffer from degraded reconstruction quality at low bit rates. Directly applying diffusion-based generative priors to this task leads to suboptimal performance in downstream machine vision tasks, primarily due to poor preservation of high-frequency details. In this work, we propose FaSDiff (\textbf{Fa}cial Image Compression with a \textbf{S}table \textbf{Diff}usion Prior), a novel diffusion-driven compression framework designed to enhance both visual fidelity and semantic consistency. FaSDiff incorporates a high-frequency-sensitive compressor to capture fine-grained details and generate robust visual prompts for guiding the diffusion model. To address low-frequency degradation, we further introduce a hybrid low-frequency enhancement module that disentangles and preserves semantic structures, enabling stable modulation of the diffusion prior during reconstruction. By jointly optimizing perceptual quality and semantic preservation, FaSDiff effectively balances human visual fidelity and machine vision accuracy. Extensive experiments demonstrate that FaSDiff outperforms state-of-the-art methods in both perceptual metrics and downstream task performance.

Coastal flooding poses increasing threats to communities worldwide, necessitating accurate and hyper-local inundation forecasting for effective emergency response. However, real-world deployment of forecasting systems is often constrained by sparse sensor networks, where only a limited subset of locations may have sensors due to budget constraints. To approach this challenge, we present DIFF -SPARSE, a masked conditional diffusion model designed for probabilistic coastal inundation forecasting from sparse sensor observations. DIFF -SPARSE primarily utilizes the inundation history of a location and its neighboring locations from a context time window as spatiotemporal context. The fundamental challenge of spatiotemporal prediction based on sparse observations in the context window is addressed by introducing a novel masking strategy during training. Digital elevation data and temporal co-variates are utilized as additional spatial and temporal contexts, respectively. A convolutional neural network and a conditional UNet architecture with cross-attention mechanism are employed to capture the spatiotemporal dynamics in the data. We trained and tested DIFF -SPARSE on coastal inundation data from the Eastern Shore of Virginia and systematically assessed the performance of DIFF -SPARSE across different sparsity levels 0%, 50%, 95% missing observations. Our experiment results show that DIFF -SPARSE achieves upto 62% improvement in terms of two forecasting performance metrics compared to existing methods, at 95% sparsity level. Moreover, our ablation studies reveal that digital elevation data becomes more useful at high sparsity levels compared to temporal co-variates.

Large language models exhibit exciting capabilities, yet can show surprisingly narrow generalization from finetuning. E.g. they can fail to generalize to simple reversals of relations they are trained on, or fail to make simple logical deductions based on trained information. These failures to generalize factual information from fine-tuning can significantly hinder the reasoning capabilities of these models. On the other hand, language models' in-context learning (ICL) shows different inductive biases and deductive reasoning capabilities. Here, we explore these differences in generalization and deductive reasoning between in-context- and fine-tuning-based learning. To do so, we constructed several novel datasets to evaluate and improve models' abilities to make generalizations over factual information from novel data. These datasets are designed to create clean tests of generalization, by isolating the knowledge in the dataset from that in pretraining. We expose pretrained large models to controlled subsets of the information in these datasets -- either through ICL or fine-tuning -- and evaluate their performance on test sets that require various types of generalization. We find overall that in data-matched settings, ICL can generalize several types of inferences more flexibly than fine-tuning (though we also find some qualifications of prior findings, such as cases when fine-tuning can generalize to reversals embedded in a larger structure of knowledge). We build on these findings to propose a method to enable improved generalization from fine-tuning: adding in-context reasoning traces to finetuning data. We show that this method improves generalization across various splits of our datasets and other benchmarks. Our results have implications for understanding the generalization afforded by different modes of learning in language models, and practically improving their performance.

End-to-end speech-to-speech (S2S) dialogue systems have recently garnered increasing research attention for their lower latency and more natural integration of nonverbal cues such as emotion and speaker identity. However, these systems face key challenges, particularly in incorporating external knowledge, a capability commonly addressed by Retrieval-Augmented Generation (RAG) in text-based large language models (LLMs). The core difficulty lies in the modality gap between input speech and retrieved textual knowledge, which hinders effective integration of information. To address this issue, we propose a novel end-to-end RAG framework that directly retrieves relevant textual knowledge from speech queries. Experimental results demonstrate that our method significantly improves the performance of end-to-end S2S dialogue systems while achieving higher retrieval efficiency. Although the overall performance still lags behind the SOTA cascaded models, our framework offers a promising direction for enhancing knowledge integration in end-to-end S2S systems. Our code and dataset are released.

Though Large Vision-Language Models (LVLMs) are being actively explored in medicine, their ability to conduct complex real-world telemedicine consultations combining accurate diagnosis with professional dialogue remains underexplored. This paper presents 3MDBench (Medical Multimodal Multi-agent Dialogue Benchmark), an open-source framework for simulating and evaluating LVLM-driven telemedical consultations. 3MDBench simulates patient variability through temperament-based Patient Agent and evaluates diagnostic accuracy and dialogue quality via Assessor Agent. It includes 2996 cases across 34 diagnoses from real-world telemedicine interactions, combining textual and image-based data. The experimental study compares diagnostic strategies for widely used open and closed-source LVLMs. We demonstrate that multimodal dialogue with internal reasoning improves F1 score by 6.5% over non-dialogue settings, highlighting the importance of context-aware, information-seeking questioning. Moreover, injecting predictions from a diagnostic convolutional neural network into the LVLM's context boosts F1 by up to 20%. Source code is available at https://github.com/univanxx/3mdbench.

Rapid information access is vital during wildfires, yet traditional data sources are slow and costly. Social media offers real-time updates, but extracting relevant insights remains a challenge. In this work, we focus on multimodal wildfire social media data, which, although existing in current datasets, is currently underrepresented in Canadian contexts. We present WildFireCan-MMD, a new multimodal dataset of X posts from recent Canadian wildfires, annotated across twelve key themes. We evaluate zero-shot vision-language models on this dataset and compare their results with those of custom-trained and baseline classifiers. We show that while baseline methods and zero-shot prompting offer quick deployment, custom-trained models outperform them when labelled data is available. Our best-performing custom model reaches 84.48% f-score, outperforming VLMs and baseline classifiers. We also demonstrate how this model can be used to uncover trends during wildfires, through the collection and analysis of a large unlabeled dataset. Our dataset facilitates future research in wildfire response, and our findings highlight the importance of tailored datasets and task-specific training. Importantly, such datasets should be localized, as disaster response requirements vary across regions and contexts.