Academic Intelligence · Curated Daily

探索全球前沿学术脉络

AcademicHub 汇聚顶级期刊与预印本平台的实时文献。定制您的专属科研雷达,利用大语言模型自动生成交叉领域文献分析简报。

01.
arXiv (CS.AI) 2026-06-25

FORCE: Efficient VLA Reinforcement Fine-Tuning via Value-Calibrated Warm-up and Self-Distillation

arXiv:2606.26006v1 Announce Type: cross Abstract: Vision-Language-Action (VLA) models are often constrained by the imitation ceiling imposed by sub-optimal data. While Reinforcement Learning (RL) fine-tuning can surpass this limit, it is notoriously sample inefficient. This challenge arises from two core issues: (1) catastrophic initial unlearning due to an unstable Q-function and (2) inefficient policy updates caused by low-quality exploration data, often forcing a reliance on costly human interventions. We introduce FORCE, a 3-stage framework that stabilizes fine-tuning by tackling both issues. FORCE first incorporates a Value-Calibrated Warm-Up phase, utilizing on-policy rollouts to mitigate the distributional shift of the Q-function. Subsequently, during the online stage, this calibrated Q-function acts as a filter for both the policy's own action proposals and expert data, ensuring only high-value actions are used for the policy update. We evaluate FORCE on various simulation and real-world tasks, and the result shows that FORCE achieves a 79% absolute improvement in success rates and outperform prior RL methods by 10%, while accelerating training by 32.5%. Critically, it mitigates the common success rate drop and achieves this robust performance without human intervention, marking a significant step towards deploying capable and autonomous robotic agents.

02.
bioRxiv (Bioinfo) 2026-06-18

Structure Bioinformatics of Eight Human ATP Synthase Fo Subunits and Their AlphaFold3-Predicted Water-Soluble QTY Analogs

Human mitochondrial ATP synthase is an essential rotary motor enzyme that produces most of the cellular ATP through oxidative phosphorylation. Its membrane-embedded Fo sector contains highly hydrophobic transmembrane subunits that are challenging to study in aqueous environments without detergents. This study explores whether applying the QTY code can reduce the hydrophobicity of selected ATP synthase Fo subunits while preserving their overall molecular structures. We applied the QTY code to eight human ATP synthase Fo subunits: ATP6, ATP8, ATPK, ATP68, ATPMK, AT5G1, AT5G2, and AT5G3. Hydrophobic amino acids leucine (L), isoleucine (I), valine (V), and phenylalanine (F) in transmembrane regions were systematically replaced with hydrophilic glutamine (Q), threonine (T), and tyrosine (Y). Four native subunits with available CryoEM structures from human ATP synthase (PDB: 8H9S) were superposed with their AlphaFold3-predicted QTY analogs. The native ATP synthase Fo subunits superposed well with their respective QTY analogs. For the CryoEM-native comparisons, RMSD values ranged from 0.565[A] to 2.546[A]. For the AlphaFold3-native comparisons of subunits without CryoEM structures, RMSD values ranged from 0.204[A] to 0.297[A]. Despite substantial QTY substitutions in the transmembrane regions, ranging from 38.89% to 50.79%, the QTY analogs retained similar overall folds, molecular weights, and isoelectric points. Hydrophobic surface analysis showed that the QTY analogs had reduced hydrophobic patches compared with their native counterparts, with average hydrophobicity decreasing from 0.2959 in native proteins to -1.1023 in QTY analogs. These structural bioinformatics studies suggest that the QTY code can be applied to ATP synthase Fo subunits to generate more hydrophilic, potentially water-soluble analogs while preserving overall structural similarity. These results extend the application of the QTY code to the membrane-embedded Fo sector of ATP synthase and provide a foundation for future experimental studies testing whether these QTY analogs can be expressed, purified, and evaluated for assembly or proton-transfer-related functions.

03.
arXiv (CS.LG) 2026-06-18

Measurement noise limits the advantage of nonlinear models over linear models in biomedical prediction

arXiv:2606.18420v1 Announce Type: new Abstract: On biomedical tabular data, flexible models such as deep networks, gradient-boosted trees, and kernel methods are repeatedly matched or beaten by linear and logistic regression given the same features. The usual reaction is to treat this as a model-side shortfall, to be fixed with more data, a better architecture, or tuning, on the assumption that the nonlinear structure is there and the model has failed to capture it. We argue that these fixes cannot help when the binding limit is the measurement rather than the model, as it frequently is in biomedicine. Additive noise blurs the population-optimal predictor, and because blurring removes a function's fine, rapidly varying detail before its broad shape, it erases nonlinear structure faster than linear structure. A degree-$k$ interaction is attenuated by the $k$-th power of feature reliability, while the linear part is attenuated only once. At the reliabilities typical of biomedical measurement, the nonlinear advantage can vanish even when the underlying biology is strongly nonlinear, and what the noise removes cannot be recovered by a larger cohort or a more flexible model, only by better measurement. The nonlinearity is hidden, not absent, and a tie between linear and flexible models is not by itself a verdict on the biology. These pieces are classical, drawn from measurement-error statistics, psychometrics, and Gaussian analysis, and we assemble them into an exact excess-risk identity. Measurement reliability is one of three conditions, alongside sample size and feature representation, that must align for a flexible model to help, and together they leave only a narrow window that most biomedical tasks fall outside. Across 140 UK Biobank tasks, the gap between flexible and linear models, where it exists, carries the predicted noise signature, and the three conditions can be separated by intervention but not by a benchmark alone.

04.
Nature Biotechnology 2026-06-05

Structural motif search across the protein universe with Folddisco

作者:

Detecting similar protein structural motifs in large structure collections is computationally expensive. We developed Folddisco, a fast structural motif search tool that uses an index of position-independent geometric features, including side-chain orientation, combined with a rarity-based scoring system. Folddisco is 20-fold faster in querying and fourfold more storage-efficient than existing methods while improving accuracy. Folddisco is freely available online ( https://folddisco.foldseek.com ), along with a webserver ( https://search.foldseek.com/folddisco ). Folddisco enables protein structural motif search in million scale databases.

05.
arXiv (CS.LG) 2026-06-18

Latent-Conditioned Parameterized Quantum Circuits as Universal Approximators for Distributions over Quantum States

arXiv:2605.28690v3 Announce Type: replace-cross Abstract: Many applications in quantum simulation, quantum chemistry, and quantum machine learning require not a single quantum state but an ensemble of states characterizing the heterogeneity of a target system. Preparing such ensembles state-by-state is prohibitive in both variational and fault-tolerant settings, thereby motivating a generative modeling approach. We introduce latent-conditioned parameterized quantum circuits (LPQCs), a hybrid quantum-classical framework in which classical neural networks map a latent variable sampled from a prior distribution to the parameters of a parameterized quantum circuit. We prove that LPQCs are universal approximators for probability measures over density operators in the 1-Wasserstein distance, extending classical universal approximation theorems to the quantum-distribution setting. We additionally introduce a multimodal latent prior and a mixture-of-experts circuit architecture, and show empirically that the latent-conditioned parameterization alleviates the barren plateau problem during optimization, a behavior for which we provide rigorous partial guarantees. Numerical experiments validate the framework on a synthetic multi-cluster ensemble of mixed quantum states and on a QM9-derived ensemble of 3-D molecular structures. In these tasks, LPQC outperforms recent quantum generative baselines and matches the generation quality of a classical neural-network baseline, while requiring an output dimension that grows only linearly with the number of qubits rather than exponentially. By leveraging classical expressivity in the latent space, LPQCs offer a tractable route to quantum generative modeling.

06.
arXiv (CS.AI) 2026-06-18

From Specification to Execution: AI Assisted Scientific Workflow Management

arXiv:2606.18425v1 Announce Type: cross Abstract: Scientific workflow management systems (WMS) support scalable and reproducible execution of complex pipelines, but workflow design, implementation, and debugging remain largely manual and require significant expertise. Recent approaches using large language models (LLMs) show promise for workflow generation from natural language, but often rely on direct code synthesis, which limits transparency, reproducibility, and integration with workflow systems. We present an AI-assisted approach to scientific workflow management that combines specification-driven workflow generation, automated debugging, and distributed execution. The method introduces a structured specification phase that separates workflow intent, design, and implementation, allowing validation prior to code generation. We also develop an LLM-based debugging agent that diagnoses and resolves failures across multiple system layers. To support distributed execution and user interaction, we integrate Pegasus, a widely used WMS, with a Model Context Protocol (MCP) layer, providing a unified interface for workflow submission, monitoring, and control. We evaluate the approach using a federated learning workflow for medical imaging, chosen for its parallel, iterative, and dependency-intensive structure. The system generated and executed large-scale workflows with thousands of jobs, reduced debugging effort, and allowed non-expert users to construct workflows with expert-level design patterns. These results indicate that end-to-end AI-assisted workflow generation and execution is feasible, and point toward AI-driven platforms for managing the scientific workflow lifecycle.

07.
arXiv (CS.AI) 2026-06-15

Can Editing 1 Neuron Fix Repetition Loops in LLMs?

arXiv:2606.13705v1 Announce Type: cross Abstract: Yes. Can it cure doom loops? Probably not. The Gemma 4 instruction-tuned models share a reproducible failure: on long factual enumeration prompts, such as listing every episode of a TV series, the 88 IAU constellations, or the 151 original Pokemon, they collapse into repetition, either a tight verbatim loop or a list whose entries decay onto a single answer. These loops occur at rates as high as 95% and survive prompt rewording, inference-engine changes, and most sampling adjustments. In this paper we explore whether this behavior is localized enough to remove by weight edits. To localize the cause, we use per-layer ablation and per-neuron attribution, then confirm the strongest candidates with full-generation sweeps. The loops trace to a small set of MLP neurons (or, in the 26B-A4B Mixture-of-Experts model, a few routed experts) which we suppress with static weight edits. These "surgeries" can be as small as a single sign-inverted neuron (in the E2B model). The size of the effective edits grows with model scale, but in all cases, the loop patterns can be addressed at normal generation budgets while preserving general-purpose benchmark scores. However, the edits do not solve everything: we also study longer thinking budgets, where the two larger models most visibly enter doom looping, i.e. a non-convergent regime in which the model self-corrects in circles over a fact it cannot recall, exhausting the budget without committing to a final answer. We show this residual failure is reduced but not eliminated by the same edits, and argue it is fundamentally a knowledge-precision problem rather than a removable circuit; weight surgery can delete a loop, but it cannot supply a missing fact. Our results are both a feasibility demonstration, that is, evidence that a concrete generation pathology can be localized to a few parameters and edited out, and a delineation of where that approach stops.

08.
Nature (Science) 2026-06-17

A prototype differential atom interferometer for fundamental physics

Gravitational waves and ultralight dark matter are among the most compelling frontiers in fundamental physics, motivating proposals for very-long-baseline atom interferometerssuch as AION1, MAGIS2, AICE3 and AEDGE4 that aim to detect at frequencies at which ground-based5 and space-borne6 laser interferometers lose sensitivity. Very-long-baseline atom interferometers look for signals by comparing the quantum phase evolution of widely separated atomic ensembles interrogated by a common laser. However, their performance depends critically on suppressing noise sources, particularly laser phase noise. The experimental validation of such noise rejection remains an important challenge. Here we demonstrate a prototype differential atom interferometer based on the single-photon clock transition of fermionic 87Sr. Thus, we obtain a gradiometer configuration with a species intrinsically suited to kilometre-scale and space-baseline operation. The instrument operates at the standard quantum limit7 with no excess noise beyond atom shot noise. The differential configuration maintains quantum-limited sensitivity in the presence of several radians of artificially injected laser phase noise per shot, which emulates the conditions expected in a very-long-baseline atom interferometer. We also demonstrate the recovery of coherent oscillatory signals across a broad frequency range under fully phase-randomized conditions, a capability that is inaccessible to a single interferometer operating in the same regime. These results provide an experimental validation of the noise-immune measurement principle underlying very-long-baseline atom interferometers and mark an important step towards next-generation quantum sensors for gravitational-wave detection and searches for ultralight dark matter8,9. A prototype differential atom interferometer operates at the standard quantum limit with no excess noise beyond atom shot noise, achieving performance in line with the specifications for future long-baseline atom interferometers.

09.
arXiv (CS.CL) 2026-06-15

DLawBench: Evaluating LLMs Through Multi-Turn Legal Consultation

Lawyer-client consultation is a critical starting point for legal services. Effective legal assistance hinges on eliciting sufficient and truthful information from clients in order to devise strategies that best protect their interests. This task requires Large Language Models (LLMs) not only to perform robust legal reasoning, but also to strategically elicit material facts through multi-turn interactions and effectively guide clients with diverse personalities. Yet existing legal benchmarks overlook this interactive capability. To fill this gap, we introduce DLawBench, a diagnostic benchmark for real-world legal consultation. Drawing on realistic client behavior, we characterize lawyer-client interactions into four types: Cooperative, Dependent, Withdrawn, and Adversarial. Using dialogues grounded in real cases, DLawBench evaluates whether LLMs can effectively conduct legal consultation under realistic conditions. DLawBench comprises 461 cases from Chinese and U.S. law, 5,532 paired fact entries, 3,411 inquiry rubrics, and 3,348 issue-resolution rubrics, and evaluates 26 representative LLMs. Systematic experiments show substantial headroom: the best-performing model, GPT-5.5, achieves only 0.562 on consultation-grounded legal reasoning. More importantly, DLawBench exposes both sycophancy in legal consultation and a paradox: models perform worse when clients need guidance most.

10.
medRxiv (Medicine) 2026-06-15

Repurposing cardiovascular disease risk models to predict incident and co-occurring cardiovascular, cardiometabolic and neurocognitive outcomes.

Background: Cardiovascular disease (CVD), cardiometabolic and neurocognitive conditions share risk factors and frequently co-occur. We evaluated whether four established CVD risk prediction models (QRISK3, PCE, SCORE2, SCORE2-OP) can be repurposed to predict 10-year risk of these conditions and their co-occurrence with CVD. Methods: The models were recalibrated using 20% of the UK Biobank (UKB) and evaluated in the remaining 80%. We performed external validation using data from Clinical Practice Research Datalink (CPRD) Aurum, assessing model discrimination (c-statistics) and calibration (intercept and slope). We used permuted feature importance to determine the influence of each individual predictor in the models. Results: Depending on the model, the c-statistics for incident CVD ranged from 0.71 to 0.74 in the UKB test set (16,137 events). Discrimination was equal to or higher than CVD when evaluated against non-traditional CVD outcomes: 0.74 to 0.77 for heart failure (3,471 events), 0.72 to 0.73 for atrial fibrillation (9,213 events), 0.73 to 0.75 for peripheral arterial disease (1,927 events) and 0.80 to 0.82 for abdominal aortic aneurysm (595 events). For the multimorbidity endpoints, model discrimination ranged from 0.74 for the composite of CVD and T2DM (SCORE2-OP) to 0.83 for the composite of CVD and dementia or Parkinson's disease (QRISK3). When considering the onset of any cardiovascular, cardiometabolic, or neurocognitive outcome discrimination ranged from 0.71 to 0.72. The repurposed models slightly underestimated the predicted risk in the CPRD compared to the UKB: average difference in calibration intercept was at most -0.64. After age and sex, smoking status and systolic blood pressure contributed most to model predictions. Conclusions: Repurposed CVD models can be used to identify 10-year risk of many CVD-related conditions and their multimorbidity. These may be used to support risk-based approaches to prevention and screening. The repurposed models have been made available at: https://repurposed-cvd-risk-models.shinyapps.io/cvd_cmd_dementia_app/ Keywords: Risk prediction; cardiovascular disease; cardiometabolic disease; dementia; disease prevention.

11.
arXiv (CS.AI) 2026-06-18

Fully Geometric Multi-Hop Reasoning on Knowledge Graphs with Transitive Relations

arXiv:2505.12369v2 Announce Type: replace Abstract: Multi-hop logical reasoning on knowledge graphs requires faithfully mapping the logical semantics to latent space. Current geometric embedding methods show to be useful on this task by mapping entities to geometric regions and logical operations to latent transformations. While a geometric embedding can provide a direct interpretability framework for query answering, current methods have only leveraged the geometric construction of entities, failing to map logical operations to pure geometric transformations and, instead, using neural components to learn these operations. On the other hand, purely neural-based methods outperform geometric methods, but they lack interpretability in the latent space. We introduce GeometrE, a geometric embedding method for multi-hop reasoning, that maps every logical operation to a purely geometric operation in the latent space. Additionally, we introduce a transitive loss function and show that, unlike existing methods, it can preserve the logical rule for all a,b,c: r(a,b) and r(b,c) -> r(a,c). Our experiments show that GeometrE outperforms current state-of-the-art geometric methods and remains competitive with existing neural-based methods on standard benchmark datasets.

12.
arXiv (CS.AI) 2026-06-15

Learning High Coverage Discriminative Parsimonious Rulesets

arXiv:2606.14156v1 Announce Type: cross Abstract: Learning systems based on IF-THEN rule representations readily offer interpretability, making them a crucial focus in contemporary AI research. A key objective for such rule sets is to achieve both high discriminative power and interpretability. While existing state-of-the-art algorithms implicitly prioritize predictive accuracy, they often fall short on one or more quality metrics that ensure interpretability, such as coverage and parsimony of rule sets. Motivated by this, this paper propose the development of CDPR, which aims to create highly accurate and interpretable rule sets for classification problems. To the best of our knowledge, this represents the first attempt to establish such an approach. In this study, we introduce two algorithms rooted in submodular maximization, which not only provide provable guarantees on coverage but also yield rule sets that are both discriminative and parsimonious. We empirically demonstrate that rule sets learned through our approaches achieve higher accuracy and interpretability and has more than a 2.5-fold improvement in average coverage rates when compared to the next best algorithm.

13.
arXiv (CS.AI) 2026-06-11

Internet of Everything in the 6G Era: Paradigms, Enablers, Potentials and Future Directions

arXiv:2604.25018v2 Announce Type: replace-cross Abstract: The Internet of Everything (IoE) represents an evolution of the Internet of Things (IoT) by integrating people, data, processes, and things into a unified intelligent ecosystem. IoE aims to enhance automation, decision-making, and service efficiency across multiple application domains such as smart cities, healthcare, industry, and next-generation wireless networks. This paper provides a structured overview of the IoE concept, its core components, architectural foundations, enabling technologies, and major research challenges. Finally, open research directions toward 6G-enabled intelligent IoE systems are discussed, with emphasis on scalability, security, privacy, and energy efficiency.

14.
arXiv (CS.CV) 2026-06-11

SceneMiner: Identity-Preserving Multi-Task Fine-Tuning for Unified BEV Scene Mining

Mining hard, safety-critical scenes from driving logs is bottlenecked by the absence of difficulty labels, and no single proxy, collision risk, trajectory ambiguity, or semantic rarity suffices to find such scenes on its own. We present SceneMiner, a unified, camera-only bird's-eye-view pipeline that emits complementary mining signals from a frozen vision-language backbone in a single forward pass, with no LiDAR or radar: a retrieval embedding for text-prompted scenario search, a multi-label scene-tag distribution, and a continuous physics-based risk score (a motion forecast is a byproduct, not a contribution). Building such a multi-head model exposes our central finding, a failure mode we term cross-task interference: adding or upgrading one head shifts a shared activation stream and degrades weight-frozen sibling heads, so freezing parameters alone is insufficient. Our contribution, identity-preserving multi-task fine-tuning, removes this interference by zero-initializing every new sub-module and freezing every parameter that feeds the shared stream. The mining heads are thereby preserved bit-identically while training only ~102k parameters. The tagging head reaches mAP 0.4614 (micro-F1 0.5557) on 20 scene tags by pooling each scene into 32 visual tokens, and the embedding head supports text-prompted retrieval, validated qualitatively. Code is available at: https://anonymous.4open.science/r/sceneminer_anonymous-64E5

15.
arXiv (CS.LG) 2026-06-24

New Bounds for the Last Iterate of the Stochastic subGradient Method

arXiv:2606.24879v1 Announce Type: cross Abstract: We study the last iterate of the stochastic subgradient method for one-dimensional convex Lipschitz objectives. For a fixed horizon $n$, we consider the standard fixed stepsizes $\eta =\Theta(1/\sqrt n)$. We prove that, for such stepsize policies, under additive i.i.d. subgradient noise with uniformly bounded variance, the last iterate features an optimization error of order $1/\sqrt n$, thereby removing the extra $(\log n)$ factor present in existing generic bounds. On the other hand, we show that without the i.i.d. assumption, the optimization error can be of order $(\log n)/\sqrt n$. Thus, under the uniformly bounded variance assumption alone, the last iterate of SsGM is suboptimal even in dimension one, resolving negatively an open problem posed in Koren and Segal, COLT, 2020.

16.
arXiv (CS.AI) 2026-06-24

SAFARI: Scaling Long Horizon Agentic Fault Attribution via Active Investigation

arXiv:2606.24626v1 Announce Type: new Abstract: As autonomous agents tackle increasingly complex multi-step, multi-agent tasks, their execution trajectories have scaled beyond the constraints of even the largest context windows. Current methods for effectively diagnosing agent failures load the full trajectory into an LLM's context window, which suffers from attention dilution and fails when agentic traces inevitably exceed context limits. To address this, we introduce SAFARI (Scaling long-horizon Agentic Fault AttRibution via active Investigation), a framework that replaces linear context loading with a tool-augmented diagnostic loop. By equipping LLMs with a specialized toolbox to read and search trajectory segments alongside a persistent Short-Term Memory (STM) for cross-turn reasoning, SAFARI effectively decouples diagnostic accuracy from architectural context limits. Our experiments demonstrate that SAFARI outperforms state-of-the-art results by 20% on the Who&When dataset within a 1M token budget, and by 19% on TRAIL GAIA subset on a 25K token budget. Most significantly, SAFARI maintains a 0.58 precision even when the target fault resides 5x beyond the model's native context window, a scenario where traditional evaluators fail entirely.

17.
bioRxiv (Bioinfo) 2026-06-23

biomeStat: Using Agentic AI for Scalable Genomic Epidemiology Demonstrated Through End-to-End Analysis of 1,000 Asian Dengue Virus Genomes

Genomic epidemiology workflows typically require expert curation of multiple specialized tools, extensive manual parameter tuning, and access to heterogeneous compute infrastructure. While standard generative AI models often hallucinate in complex biological domains, we introduce biomeStat: an autonomous AI agent that functions as a strict deterministic orchestrator. By automatically writing code to execute established bioinformatics tools in sandboxed environments, biomeStat dynamically provisions compute resources (CPU and GPU) and guarantees reproducibility, making it immediately useful for scientists without requiring command-line expertise. To demonstrate the platform, we performed a fully autonomous genomic epidemiology and structural analysis of 1,000 Dengue virus (DENV) genomes sampled from 16 Asian countries between 2000 and 2025. The agent seamlessly orchestrated phylogenetic reconstruction (IQ-TREE, TreeTime), Bayesian phylodynamics (BEAST2 via NVIDIA H200 GPU), selection pressure analysis (HyPhy), and structural mapping (PyMOL). The analysis was completed in under 24 hours of wall-clock time, revealing endemic stability (R_e ~1.0) and identifying 1,869 candidate immune escape sites structurally colocalized with B-cell and T-cell epitopes. Furthermore, the agent validated 176 highly conserved drug target residues across the viral replication complex, confirming that resistance-associated positions for emerging antivirals JNJ-1802 and NITD-688 remain absolutely conserved across all four serotypes. By bridging the gap between natural language intent and deterministic computational execution, biomeStat reduces weeks of expert effort into a single-session analysis with full methodological transparency.

18.
arXiv (CS.CV) 2026-06-19

ViCoStream: Streaming VideoLLMs Can Run Beyond 100 FPS with Stage-Wise Coordinated Inference

Streaming VideoLLMs must continuously process incoming video while maintaining low query latency, making both video-ingestion throughput and query-time responsiveness critical for real-time deployment. Existing methods largely focus on accelerating individual modules, such as visual encoding, token pruning, or KV-cache compression, but provide limited insight into whether the resulting system can sustain real-time streaming performance. We formulate streaming VideoLLM inference as a coordinated pipeline spanning visual preprocessing, visual encoding, token dropping, and LLM prefilling/decoding. Building on this formulation, we propose ViCoStream (Video Coordinated Streaming), a stage-wise coordinated streaming framework that combines chunk-wise execution, CUDA-stream overlap, visual token control, bounded visual attention, and query-side retrieval to bound per-chunk computation and memory costs. We further provide a systematic study of bottleneck migration, revealing how chunk size, token retention, attention locality, and retrieval scope shape the throughput-accuracy trade-off. Experiments with Qwen2.5-VL-3B/7B-Instruct across multiple streaming benchmarks show that ViCoStream achieves 134 FPS video throughput and less than 50 ms TTFT on a single A100 GPU while maintaining accuracy close to full-history baselines.

19.
Nature (Science) 2026-06-24

Zero-shot design of drug-binding proteins via neural iterative selection−expansion

作者:

The design of proteins that bind to small molecules has been challenging because it requires simultaneous optimization of the protein sequence, protein structure and ligand conformation1–7. Current deep-learning algorithms have struggled to navigate this landscape, precluding the zero-shot design of binders. Here we show that by combining two neural networks in an iterative design algorithm, small-molecule binding proteins can be created from scratch with high accuracy. We trained a graph neural network—ligand-aware sequence engineering message-passing neural network (LASErMPNN)—to design compatible protein sequences for an input protein backbone and docked ligand. We paired  LASErMPNN with a structure predictor that models a three-dimensional protein–ligand complex for an input protein sequence and ligand identity. The closed-loop iteration of these reciprocal networks optimized sequence–structure–ligand compatibility, and outperformed a comparable design loop using a physics-based energy function. We used our strategy, termed neural iterative selection–expansion (NISE), to design proteins that, using different folds, specifically bind to two chemically distinct small-molecule drugs, exatecan and apixaban, with success rates of 100% and 83%, respectively. The tightest NISE binders had nanomolar-to-picomolar affinities, surpassing those of the next-leading method by 70-fold for exatecan and nearly 10,000-fold for apixaban. LASErMPNN then suggested two amino-acid substitutions that improved the affinity of the tightest exatecan binder by 100-fold without any experimental input. The optimized binder protected the labile lactone ring of exatecan from hydrolysis for days. Our work describes a general recipe for using neural networks to automate the design of small-molecule binding proteins for applications in drug delivery, sensing and catalysis.  By pairing two neural networks in an iterative optimization algorithm, small-molecule binding proteins can be designed from scratch with high accuracy, affinity and success rates, showing promise for applications in drug delivery and sequestration.

20.
arXiv (CS.CL) 2026-06-15

AgentSpec: Understanding Embodied Agent Scaffolds Through Controlled Composition

LLM agents are increasingly built not as single model calls, but as scaffolded systems that combine reasoning, memory, reflection, action execution, and learning. While such scaffolds often improve performance, they are often embedded in tightly coupled pipelines, making it difficult to isolate component contributions, compare alternative designs, or understand how module interactions shape agent behavior. We introduce AgentSpec, a modular specification framework that represents embodied agents as typed compositions of reusable policy components with standardized interfaces. AgentSpec standardizes the interfaces among perception, memory, reasoning, reflection, action, and optional learning, enabling components to be swapped and recombined under controlled conditions. We instantiate this framework across DeliveryBench, ALFRED, MiniGrid, and RoboTHOR, and analyze reasoning, memory, reflection, and reinforcement-learning modules across model backbones. Our results show that agent performance is governed by scaffold compatibility and interaction effects rather than isolated module strength. In particular, structured multi-granularity memory improves long-horizon state tracking, reasoning and memory interact non-uniformly across environments, reflection trades off correction and cost, and RL-trained policies compose best when optimized with deployment-time scaffold structure. AgentSpec provides a controlled foundation for studying, comparing, and designing composable LLM agents. Our code, baselines and interactive playground are publicly available at https://agentspec-embodied.github.io.

21.
arXiv (CS.LG) 2026-06-17

A Closer Look at Failure Modes in Temporal Understanding of Large Audio-Language Models

arXiv:2606.17417v1 Announce Type: cross Abstract: Large Audio Language Models (LALMs) achieve strong performance on a variety of audio understanding tasks but continue to struggle with temporal reasoning, a fundamental capability central to human auditory perception. Understanding the causes of these failures remains challenging as existing benchmarks report performance gaps without probing underlying mechanisms. To address this, we introduce a benchmark with 1,657 questions across three foundational tasks designed specifically for mechanistic analysis. Examining model outputs across varying input settings (behavioral analysis) reveals that models often under-utilize audio when textual cues are available. We also provide the first causal mechanistic analysis of temporal reasoning failures in LALMs. Comparing attention upweighting against scaling, we find that redistributing attention across audio tokens is more effective than increasing audio attention. Targeting task-relevant tokens yields further gains. These findings suggest that modality imbalance alone cannot explain failures. Attention scaling at bottleneck layers improves accuracy from 55.9% to 59.1% without fine-tuning, demonstrating a promising direction for future work.

22.
arXiv (CS.CV) 2026-06-19

Distill Once, Adapt Life-Long: Exploring Dataset Distillation for Continual Test-Time Adaptation

Continual Test-Time Adaptation (CTTA) aims to maintain model performance under evolving target domains by adapting online without labeled data. However, practical deployments often cannot retain the source dataset due to privacy or licensing constraints, and purely source-free CTTA methods tend to become unstable under long-term distribution shift, suffering from compounding self-training errors and catastrophic forgetting. We introduce DO-ALL (Distill Once, Adapt Life-Long), a plug-and-play framework that revisits source information in a compact and privacy-conscious form via Dataset Distillation (DD). Before deployment, DO-ALL performs DD to produce a small set of synthetic distilled anchors that summarize the source distribution. During adaptation, each target sample is matched with its most semantically aligned anchor, which provides a stable reference for various CTTA via source replay, representation alignment, and manifold-smoothing regularization. DO-ALL can be seamlessly integrated into existing CTTA algorithms, consistently improving long-term robustness across CIFAR100-C, ImageNet-C, and the CCC benchmark. This demonstrates the potential of leveraging DD to enable stable and continuous adaptation without retaining raw source data. The code is available at https://github.com/blue-531/DOALL.

23.
arXiv (CS.CL) 2026-06-16

FinBalance: A Multi-Document Accounting Reconciliation Benchmark

Existing financial-NLP benchmarks mostly evaluate prepared artifacts such as filings, tables, or extracted values. Real accounting begins earlier: source documents must be reconciled into cited journal entries, aggregated into a balance sheet, and checked for contradictions. We introduce FinBalance, a multi-document accounting reconciliation benchmark built from source-document bundles across eight industries, three period types, and five difficulty levels. Human-authored business scenarios, accounting policies, tax/FX treatments, document schemas, distractors, and inconsistency templates are composed by a deterministic generator whose ledger produces journal entries,balance sheets, and 23 inconsistency-code labels. On a 710-record evaluation split, six contemporary LLMs reach at most 46% exact final-balance-sheet accuracy. Four models show a 26-41 pp gap between BS_exact, the model's reported balance sheet, and BS_recon, the balance sheet obtained by replaying its entries through our ledger. Models often recover numerically plausible entries but fail to bind them to supporting documents and aggregate them consistently. Citation-pressure prompting barely changes document-linking errors, while ledger-feedback ablations substantially improve reported balance sheets and expose inconsistency-detection trade-offs. Expert finance reviewers validate the benchmark design and labels.

24.
arXiv (CS.CL) 2026-06-18

Narrative Theory-Driven LLM Methods for Automatic Story Generation and Understanding: A Survey

Applications of narrative theories using large language models (LLMs) deliver promising methods in automatic story generation and understanding tasks. Our survey examines how natural language processing (NLP) research uses LLM methods to engage with diverse concepts from narrative studies. We use established distinctions from narratology to categorise ongoing efforts and discover the following: \redtext{(a) narrative texts come from diverse sources beyond just literature, (b) theoretical synthesis and validation are potential outcomes, (c) generation tasks lag behind understanding in several ways: theoretical application, post-training methods, exploring non-fiction narratives and addressing narrative levels beyond fabula and discourse.} For future directions, instead of the pursuit of a single, generalised benchmark for `narrative quality', we believe that progress can benefit from efforts that focus on the following: defining and improving theory-based metrics for individual narrative attributes; continue conducting large-scale, theory-driven literary/social/cultural analysis; generating narratives in situated contexts; and continuing experiments where outputs can be used to validate or refine narrative theories. This work provides a contextual foundation for more systematic and theoretically informed narrative research in NLP by providing an overview to ongoing research efforts and the broader narrative studies landscape.

25.
arXiv (CS.AI) 2026-06-11

Power Term Polynomial Algebra for Boolean Logic

arXiv:2603.13854v2 Announce Type: replace-cross Abstract: We introduce power term polynomial algebra, a representation language for Boolean formulae designed to bridge conjunctive normal form (CNF) and algebraic normal form (ANF). The language is motivated by the tiling mismatch between these representations: direct CNFANF conversion may cause exponential blowup unless formulas are decomposed into smaller fragments, typically through auxiliary variables and side constraints. In contrast, our framework addresses this mismatch within the representation itself, compactly encoding structured families of monomials while representing CNF clauses directly, thereby avoiding auxiliary variables and constraints at the abstraction level. We formalize the language through power terms and power term polynomials, define their semantics, and show that they admit algebraic operations corresponding to Boolean polynomial addition and multiplication. We prove several key properties of the language: disjunctive clauses admit compact canonical representations; power terms support local shortening and expansion rewrite rules; and products of atomic terms can be systematically rewritten within the language. Together, these results yield a symbolic calculus that enables direct manipulation of formulas without expanding them into ordinary ANF. The resulting framework provides a new intermediate representation and rewriting calculus that bridges clause-based and algebraic reasoning and suggests new directions for structure-aware CNFANF conversion and hybrid reasoning methods.