Histidine scanning represents a broadly applicable technique for the identification of critical interaction sites within TCRs and other mechanosensory receptors to enhance receptor signaling strength and augment therapeutic efficacy via the catch bond mechanism.

arXiv:2507.01352v3 Announce Type: replace-cross Abstract: Despite the critical role of reward models (RMs) in Reinforcement Learning from Human Feedback (RLHF), current state-of-the-art open RMs perform poorly on most existing evaluation benchmarks, failing to capture nuanced human preferences. We hypothesize that this brittleness stems primarily from limitations in preference datasets, which are often narrowly scoped, synthetically labeled, or lack rigorous quality control. To address these challenges, we present SynPref-40M, a large-scale preference dataset comprising 40 million preference pairs. To enable data curation at scale, we design a human-AI synergistic two-stage pipeline that leverages the complementary strengths of human annotation quality and AI scalability. In this pipeline, humans provide verified annotations, while LLMs perform automatic curation based on human guidance. Training on this preference mixture, we introduce Skywork-Reward-V2, a suite of eight reward models ranging from 0.6B to 8B parameters, trained on a carefully curated subset of 26 million preference pairs from SynPref-40M. We demonstrate that Skywork-Reward-V2 is versatile across a wide range of capabilities, including alignment with human preferences, objective correctness, safety, resistance to stylistic biases, and best-of-N scaling. These reward models achieve state-of-the-art performance across seven major reward model benchmarks, outperform generative reward models, and demonstrate strong downstream performance. Ablation studies confirm that effectiveness stems not only from data scale but also from high-quality curation. The Skywork-Reward-V2 series represents substantial progress in open reward models, demonstrating how human-AI curation synergy can unlock significantly higher data quality.

arXiv:2502.13069v3 Announce Type: replace Abstract: AI agents are increasingly being deployed to automate tasks, often based on underspecified user instructions. Making unwarranted assumptions to compensate for the missing information and failing to ask clarifying questions can lead to suboptimal outcomes, safety risks due to tool misuse, and wasted computational resources. In this work, we study the ability of LLM agents to handle underspecified instructions in interactive code generation settings by evaluating proprietary and open-weight models on their performance across three key steps: (a) detecting underspecificity, (b) asking targeted clarification questions, and (c) leveraging the interaction to improve performance in underspecified scenarios. We introduce Ambig-SWE, an underspecified variant of SWE-Bench Verified, specifically designed to evaluate agent behavior under ambiguity and interaction. Our findings reveal that models struggle to distinguish between well-specified and underspecified instructions. However, when models interact for underspecified inputs, they effectively obtain vital information from the user leading to significant improvements in performance, up to 74% over the non-interactive settings, underscoring the value of effective interaction. Our study highlights critical gaps in how current state-of-the-art models handle missing information in complex software engineering tasks and structures the evaluation into distinct steps to enable targeted improvements.