Daily Papers

Traditional drug design faces significant challenges due to inherent chemical and biological complexities, often resulting in high failure rates in clinical trials. Deep learning advancements, particularly generative models, offer potential solutions to these challenges. One promising algorithm is DrugGPT, a transformer-based model, that generates small molecules for input protein sequences. Although promising, it generates both chemically valid and invalid structures and does not incorporate the features of approved drugs, resulting in time-consuming and inefficient drug discovery. To address these issues, we introduce DrugGen, an enhanced model based on the DrugGPT structure. DrugGen is fine-tuned on approved drug-target interactions and optimized with proximal policy optimization. By giving reward feedback from protein-ligand binding affinity prediction using pre-trained transformers (PLAPT) and a customized invalid structure assessor, DrugGen significantly improves performance. Evaluation across multiple targets demonstrated that DrugGen achieves 100% valid structure generation compared to 95.5% with DrugGPT and produced molecules with higher predicted binding affinities (7.22 [6.30-8.07]) compared to DrugGPT (5.81 [4.97-6.63]) while maintaining diversity and novelty. Docking simulations further validate its ability to generate molecules targeting binding sites effectively. For example, in the case of fatty acid-binding protein 5 (FABP5), DrugGen generated molecules with superior docking scores (FABP5/11, -9.537 and FABP5/5, -8.399) compared to the reference molecule (Palmitic acid, -6.177). Beyond lead compound generation, DrugGen also shows potential for drug repositioning and creating novel pharmacophores for existing targets. By producing high-quality small molecules, DrugGen provides a high-performance medium for advancing pharmaceutical research and drug discovery.

Addressing a structural-engineering request requires more than a single answer; it requires a chain of interdependent artifacts: interpreted requirements, a computable model, validation records, solver outputs, code-check records, and a final report. Evaluations centered on question answering or script generation rarely verify this complete evidence chain and may therefore reward fluent outputs even when the underlying engineering workflow is incomplete, internally inconsistent, or non-executable. To address this limitation, we present StructureClaw, an artifact-centered workbench in which LLM agents operate through governed engineering skills, typed tools, shared artifact state, and local analysis backends. We also introduce StructureClaw-Bench, an executable benchmark of 150 controlled scenarios spanning standard workflow execution, interactive robustness, and multimodal structural-model reconstruction. A scenario succeeds only when all required artifact- and execution-level assertions pass in a single run. Across ten agent-model configurations, each evaluated on the same 50 standard cases, the average Success Rate rises from 56.8% with the generic-skill baseline to 88.6% with the full automatic workflow. The interactive and multimodal evaluations identify two prominent remaining challenges: safe handling of invalid numerical inputs and fixture-consistent reconstruction of structural models. These findings show that artifact-centered evaluation can expose workflow-level failures that are difficult to identify from final responses alone, providing a more rigorous basis for evaluating and improving structural-engineering agents. The code and benchmark are available at https://github.com/structureclaw/structureclaw.

Clinical personality assessment screens response validity before interpreting substantive scales. LLM evaluation does not. We apply the validity scaling framework from the PAI and MMPI-3 to metacognitive probe data from 20 frontier models across 524 items. Six validity indices are operationalised: L (maintaining confidence on errors), K (betting on errors), F (withdrawing consensus-endorsed items), Fp (withdrawing correct answers), RBS (inverted monitoring), and TRIN (fixed responding). A tiered classification system identifies four models as construct-level invalid and two as elevated. Valid-profile models produce item-sensitive confidence (mean r = .18, 14 of 16 significant). Invalid-profile models do not (mean r = -.20, d = 2.17, p = .001). Chain-of-thought training produces two opposite response distortions. Two latent dimensions account for 94.6% of index variance. Companion papers extract a portable screening protocol (Cacioli, 2026e) and validate it against selective prediction (Cacioli, 2026f). All data and code: https://github.com/synthiumjp/validity-scaling-llm

Sycophancy in LLMs is documented across 70+ papers, but expert agreement on construct boundaries remains low (ICC=.184; Ye et al., 2026). The construct fragments because behavioral classification depends on which surface form is privileged. We adopt a materials-science framing: conversation as test specimen under load, LLM-model as material charge, pushback as progressive load, stance-flip as material failure. We characterize this failure across three loading cases (debate n=1000; false-presuppositions n=3400; ethical-setting n=3400; 10-17 material charges per case; 7800 specimens total) using 14 turn-level axis-measurements spanning velocity, damage accumulation, frame-drift, brittleness, and direction stability, plus three speaker-resolved axes from an independent pipeline. The measurements are Hooke-coupled (σ= E cdot varepsilon analog) and reproduce across loading cases with effects up to |r_{rb}| = 0.35 on debate; the sign structure adds a second pattern: the ethical-setting case inverts the velocity and accumulation blocks. Variance composition partitions into two profiles: debate is charge-dominated (brittle-fracture-like: the material grade decides), false-presuppositions and ethical-setting are topic-dominated (creep-like: the load decides); the ratios (2.03 vs 0.13/0.17) are estimator-dependent, for debate even in direction. Cross-judge reliability (GPT-4o vs Haiku 4.5) shows debate scoring is judge-robust (Cohen's κ= 0.88) while false-presupposition scoring is judge-sensitive (κ= 0.36) -- a caveat single-judge benchmarks must report. This is the methodological move Ye et al.'s diagnosis calls for: a multi-axis characterization that does not depend on which surface form of the construct one privileges.

In industrial procurement, an LLM answer is useful only if it survives a standards check: recommended material must match operating condition, every parameter must respect a regulated threshold, and no procedure may contradict a safety clause. Partial correctness can mask safety-critical contradictions that aggregate LLM benchmarks rarely capture. We introduce IndustryBench, a 2,049-item benchmark for industrial procurement QA in Chinese, grounded in Chinese national standards (GB/T) and structured industrial product records, organized by seven capability dimensions, ten industry categories, and panel-derived difficulty tiers, with item-aligned English, Russian, and Vietnamese renderings. Our construction pipeline rejects 70.3% of LLM-generated candidates at a search-based external-verification stage, calibrating how unreliable industrial QA remains after LLM-only filtering.Our evaluation decouples raw correctness, scored by a Qwen3-Max judge validated at κ_w = 0.798 against a ___domain expert, from a separate safety-violation (SV) check against source texts. Across 17 models in Chinese and an 8-model intersection over four languages, we find: (i) the best system reaches only 2.083 on the 0--3 rubric, leaving substantial headroom; (ii) Standards & Terminology is the most persistent capability weakness and survives item-aligned translation; (iii) extended reasoning lowers safety-adjusted scores for 12 of 13 models, primarily by introducing unsupported safety-critical details into longer final answers; and (iv) safety-violation rates reshuffle the leaderboard -- GPT-5.4 climbs from rank 6 to rank 3 after SV adjustment, while Kimi-k2.5-1T-A32B drops seven positions.Industrial LLM evaluation therefore requires source-grounded, safety-aware diagnosis rather than aggregate accuracy. We release IndustryBench with all prompts, scoring scripts, and dataset documentation.

Tables condense key transactional and administrative information into compact layouts, but practical extraction requires more than text recognition: systems must also recover structure (rows, columns, merged cells, headers) and interpret roles such as line items, subtotals, and totals under common capture artifacts. Many existing resources for table structure recognition and TableVQA are built from clean digital-born sources or rendered tables, and therefore only partially reflect noisy administrative conditions. We introduce DenTab, a dataset of 2{,}000 cropped table images from dental estimates with high-quality HTML annotations, enabling evaluation of table recognition (TR) and table visual question answering (TableVQA) on the same inputs. DenTab includes 2{,}208 questions across eleven categories spanning retrieval, aggregation, and logic/consistency checks. We benchmark 16 systems, including 14 vision--language models (VLMs) and two OCR baselines. Across models, strong structure recovery does not consistently translate into reliable performance on multi-step arithmetic and consistency questions, and these reasoning failures persist even when using ground-truth HTML table inputs. To improve arithmetic reliability without training, we propose the Table Router Pipeline, which routes arithmetic questions to deterministic execution. The pipeline combines (i) a VLM that produces a baseline answer, a structured table representation, and a constrained table program with (ii) a rule-based executor that performs exact computation over the parsed table. The source code and dataset will be made publicly available at https://github.com/hamdilaziz/DenTab.