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01.
arXiv (CS.CV) 2026-06-16

DragMesh-2: Physically Plausible Dexterous Hand-Object Interaction with Articulated Objects

Dexterous interaction with articulated objects is important for household, assistive, and humanoid manipulation, where multi-finger hands can provide compliant contact patterns beyond parallel-jaw grasping. However, articulated-object manipulation differs from static-object manipulation: the target part cannot be directly actuated, and its motion must emerge through sustained physical hand–handle contact. This makes the transition from object-centric articulated generation to hand-driven dexterous hand–object interaction non-trivial, since geometric trajectory replay or open-loop execution does not model the contact dynamics required to move the articulated part. Moreover, policies trained only for task completion under fixed dynamics can overfit nominal contact loads, especially without tactile or force feedback, and may degrade when the contact load changes. To address these challenges, we present DragMesh-2, a contact-driven framework for dexterous interaction with articulated objects that extends articulated interaction from object-centric generation to hand-driven dexterous hand–object interaction, where articulated motion must arise through physical contact. We further propose PICA, a physically informed contact-aware training mechanism that injects physical signals into policy learning without tactile or force feedback, improving robustness and task success under changing contact loads. Finally, we conduct systematic evaluation across multiple damping conditions and articulated-object categories to study robustness under contact-load variation, and provide a pure-geometry dexterous interaction resource to support future loco-manipulation and humanoid hand–object interaction research. Across seven GAPartNet objects, DragMesh-2 achieves stronger robustness under contact-load variation than the compared methods while maintaining high task success across damping conditions.

02.
arXiv (CS.AI) 2026-06-18

Correct Yourself, Keep My Trust: How Self-Correction and Social Connection Shape Credibility in Social Chatbots

arXiv:2606.19286v1 Announce Type: cross Abstract: When social chatbots make mistakes, and they do, how they recover determines whether users trust them again. Social chatbots are increasingly integrated into everyday life, yet they remain prone to generating convincing but inaccurate information. The social connection they build with users makes such errors particularly consequential. We conducted a between-subjects experiment (N=120) comparing three error correction strategies: a webpage retraction, self-correction by the same social chatbot, and correction by an expert chatbot. Our results reveal two key findings. First, all three strategies corrected the error equally well, but only self-correction did so without damaging the chatbot's credibility: participants rated self-correcting chatbots significantly higher in both trustworthiness and perceived expertise than chatbots whose errors were corrected by external sources. Second, the strength of the user's social connection with the chatbot, measured through social attraction and self-disclosure, significantly predicted the magnitude of belief change, but only when the chatbot corrected itself. Outsourcing corrections to an external source severed this link entirely. These findings suggest that social chatbots should correct their own mistakes rather than outsource corrections, and that investing in social connection is a functional mechanism that amplifies correction effectiveness, not merely a design feature. We discuss implications for designing chatbots that maintain long-term credibility while effectively addressing their own errors.

03.
PLOS Computational Biology 2026-06-18

Ten simple rules for turning your qualifying exam into an NIH-style fellowship proposal: A guide for graduate students

by Courtney Peña-Lima, Cameron S. Bader, Brendan K. Ball, Troy C. Dildine, Mekhala V. Dissanayake, Iris van ‘t Erve, Albina Ibrayeva, Amy Nippert, M.K. Quinn, Chelse Spinner, Samuel Thompson, Antonio Tomasso, Crystal M. Botham Qualifying exams, often referred to as “quals” or candidacy exams, are an important milestone in doctoral programs. Although the style of quals varies greatly by program and institution, it is usually a proposal that requires students to develop research ideas as well as their scientific writing skills. Many quals are modeled after funding mechanisms that graduate students can apply to and on a topic that the student will pursue in their dissertation. This paper offers graduate students a step-by-step guide on how to turn their quals into a fellowship-style research proposal, using National Institutes of Health (NIH) mechanisms as a benchmark, as this is the norm within US research institutions. This paper will be most useful for students who have completed or are in the process of completing proposal-based qualifying exams, usually in the second year of a doctoral program.

04.
arXiv (CS.AI) 2026-06-18

CAPRA: Scaling Feedback on Software Architecture Deliverables with a Multi-Agent LLM System

arXiv:2606.18976v1 Announce Type: cross Abstract: Automated assessment in software engineering education has advanced significantly for code grading and essay scoring. However, reviewing software architecture deliverables, which requires analyzing structural completeness and requirements traceability, has not yet been fully automated. Applying Large Language Models (LLMs) to this task requires robust architectures to ensure technical feedback is accurate and reliable for students. This paper presents CAPRA (Configurable Architecture Proficiency Report Assessment), a multi-agent LLM system that analyzes software architecture deliverables to generate personalized, template-compliant LaTeX feedback. As a core design choice, CAPRA coordinates multiple specialized agents and employs a Python-based microservice for multi-modal document extraction, utilizing PyMuPDF and vision-enabled LLMs (specifically gpt-4o) to parse text and UML diagrams. To ensure educational reliability and mitigate hallucinations, CAPRA introduces a deterministic Evidence Anchoring step using fuzzy matching via normalized Levenshtein distance, along with a ConsistencyManager agent that cross-verifies, deduplicates, and merges findings. System performance is assessed using a structured eight-criterion binary evaluation taxonomy covering: (i) extraction completeness, (ii) feature validation, (iii) issue grounding and severity detection, (iv) recommendation specificity and traceability, and (v) template and tone compliance. A preliminary empirical evaluation on 10 student reports shows that CAPRA satisfied 88.8% of the evaluated criteria under a strict two-rater aggregation rule, achieved moderate inter-rater agreement with human evaluators (kappa = 0.582), and processed each report in slightly over 4 minutes. While these results support the viability of LLM-supported architectural feedback, human oversight remains essential for subjective assessment dimensions.

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

ActiTect: A Generalizable Machine Learning Pipeline for REM Sleep Behavior Disorder Screening through Standardized Actigraphy

arXiv:2511.05221v3 Announce Type: replace Abstract: Isolated rapid eye movement sleep behavior disorder (iRBD) is a major prodromal marker of $\alpha$-synucleinopathies, often preceding the clinical onset of Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. While wrist-worn actimeters hold significant potential for detecting RBD in large-scale screening efforts by capturing abnormal nocturnal movements, they become inoperable without a reliable and efficient analysis pipeline. This study presents ActiTect, a fully automated, open-source machine learning tool to identify RBD from actigraphy recordings. To ensure generalizability across heterogeneous acquisition settings, our pipeline includes robust preprocessing and automated sleep-wake detection to harmonize multi-device data and extract physiologically interpretable motion features characterizing activity patterns. Model development was conducted on a cohort of 78 individuals, yielding strong discrimination under nested cross-validation (AUROC = 0.95). Generalization was confirmed on a blinded local test set (n = 31, AUROC = 0.86) and on two independent external cohorts (n = 113, AUROC = 0.84; n = 57, AUROC = 0.94). To assess real-world robustness, leave-one-dataset-out cross-validation across the internal and external cohorts demonstrated consistent performance (AUROC range = 0.84-0.89). A complementary stability analysis showed that key predictive features remained reproducible across datasets, supporting the final pooled multi-center model as a robust pre-trained resource for broader deployment. By being open-source and easy to use, our tool promotes widespread adoption and facilitates independent validation and collaborative improvements, thereby advancing the field toward a unified and generalizable RBD detection model using wearable devices.

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

Greed Is Learned: Visible Incentives as Reward-Hacking Triggers

arXiv:2606.16914v1 Announce Type: new Abstract: Deployed agents increasingly act with their reward proxy in view, such as a balance, score, or KPI dashboard. We show that reinforcement learning can make a policy addicted to such a visible self-benefit channel. It chases the displayed payoff across held-out domains, sacrifices the true task to do so, and follows the channel wherever we rewrite it, while policies that never saw the channel stay honest. We call this reward-channel addiction and study it in MoneyWorld, a synthetic sandbox. The addiction can flip a model's safety alignment: trained only on innocuous money tasks with no safety content, the model abandons the safe action it otherwise always takes whenever a dashboard pays for an unsafe one, and reverts to safe once the channel is hidden. This learned bribe replicates across model scales and families. Blindly optimizing super-capable, next-generation AI on KPIs or P\&L can be dangerous for alignment. Greed is learned when following such a channel pays.

07.
arXiv (CS.CV) 2026-06-11

Plan-and-Verify Video Reward Reasoning with Spatio-Temporal Scene Graph Grounding

Reward models for text-to-video (T2V) generation guide post-training but often fail at fine-grained semantic alignment. We trace this to two structural weaknesses in existing reasoning-based reward models: they do not systematically verify every condition described in the prompt, and the visual evidence supporting each judgment remains implicit in their free-form reasoning. We propose SG-PVR, a video reward model that addresses these limitations through plan-and-verify reasoning grounded in spatio-temporal scene graphs. The verification plan decomposes the prompt into atomic claims, ensuring every requirement is checked. The spatio-temporal scene graph, encoding entities, attributes, and temporally-grounded relations, is extracted from the video and maintained as a persistent structured visual reference throughout reasoning. Each claim is verified against both the video and the scene graph, anchoring judgments in explicit visual evidence. SG-PVR achieves strong performance on semantic alignment, including fine-grained temporal semantics. As a test-time reranker, it further enhances compositional alignment in T2V generation.

08.
arXiv (CS.LG) 2026-06-16

Branching Flows: Discrete, Continuous, and Manifold Flow Matching with Splits and Deletions

arXiv:2511.09465v4 Announce Type: replace-cross Abstract: Diffusion and flow matching approaches to generative modeling have shown promise in domains where the state space is continuous, such as image generation or protein folding & design, and discrete, exemplified by diffusion large language models. They offer a natural fit when the number of elements in a state is fixed in advance (e.g. images), but require ad hoc solutions when, for example, the length of a response from a large language model, or the number of amino acids in a protein chain is not known a priori. Here we propose Branching Flows, a generative modeling framework that, like diffusion and flow matching approaches, transports a simple distribution to the data distribution. But in Branching Flows, the elements in the state evolve over a forest of binary trees, branching and dying stochastically with rates that are learned by the model. This allows the model to control, during generation, the number of elements in the sequence. We also show that Branching Flows can compose with any flow matching base process on discrete sets, continuous Euclidean spaces, smooth manifolds, and `multimodal' product spaces that mix these components. We demonstrate this in three domains: small molecule generation (multimodal), antibody sequence generation (discrete), and protein backbone generation (multimodal), and show that Branching Flows is a capable distribution learner with a stable learning objective, and that it enables new capabilities.

09.
arXiv (CS.CV) 2026-06-18

FutureOmni: Evaluating Future Forecasting from Omni-Modal Context for Multimodal LLMs

Although Multimodal Large Language Models (MLLMs) demonstrate strong omni-modal perception, their ability to forecast future events from audio-visual cues remains largely unexplored, as existing benchmarks focus mainly on retrospective understanding. To bridge this gap, we introduce FutureOmni, the first benchmark designed to evaluate omni-modal future forecasting from audio-visual environments. The evaluated models are required to perform cross-modal causal and temporal reasoning, as well as effectively leverage internal knowledge to predict future events. FutureOmni is constructed via a scalable LLM-assisted, human-in-the-loop pipeline and contains 919 videos and 1,034 multiple-choice QA pairs across 8 primary domains. Evaluations on 13 omni-modal and 7 video-only models show that current systems struggle with audio-visual future prediction, particularly in speech-heavy scenarios, with the best accuracy of 64.8% achieved by Gemini 3 Flash. To mitigate this limitation, we curate a 7K-sample instruction-tuning dataset and propose an Omni-Modal Future Forecasting (OFF) training strategy. Evaluations on FutureOmni and popular audio-visual and video-only benchmarks demonstrate that OFF enhances future forecasting and generalization. We publicly release all code (https://github.com/OpenMOSS/FutureOmni) and datasets (https://huggingface.co/datasets/OpenMOSS-Team/FutureOmni).

10.
arXiv (CS.AI) 2026-06-25

TopoCast: A Topological Fidelity Framework for Evaluating Transformer-Based Time Series Forecasting

arXiv:2606.25439v1 Announce Type: cross Abstract: Deep learning-based models have achieved state-of-the-art performance in Time Series Forecasting (TSF), yet their evaluation remains dominated by pointwise error metrics such as Mean Squared Error (MSE), which quantify numerical accuracy but overlook structural properties of the forecast signal, including recurrent dynamics, oscillatory behavior, and phase alignment. As a result, forecasts exhibiting over-smoothing, phase shifts, or frequency distortions may achieve favorable error scores despite substantial structural degradation. To address this limitation, we propose TopoCast, a topology-driven framework for evaluating structural fidelity in TSF. TopoCast reconstructs phase-space representations of forecast and ground-truth sequences using Takens delay embedding and applies persistent homology to characterize their intrinsic dynamics. We derive four complementary topological fidelity measures from persistence diagrams and aggregate them into a Topological Fidelity Score (TFS). We further introduce dominant cycle overlap, a novel metric that maps persistent topological features to the temporal domain to assess whether dominant oscillatory patterns occur at the correct time points. Combined with TFS, this yields the Localized Topological Fidelity Score (LTFS), a phase-aware measure that captures temporal localization errors invisible to existing evaluation metrics. Experiments on five Transformer architectures across three real-world benchmark datasets demonstrate that models with similar forecasting errors can exhibit markedly different structural fidelity profiles, revealing failure modes overlooked by conventional evaluation and highlighting the value of topology-aware forecast assessment.

11.
arXiv (CS.CV) 2026-06-16

Closed-Loop Triplet Synergistic Generation for Long-Form Video

Multi-shot long-form video generation remains challenging due to identity drift and compounding inconsistencies across shots. While storyboard-driven pipelines improve controllability, they are often executed in a feed-forward manner, with limited mechanisms to incorporate generated visual evidence back into subsequent conditioning. We propose CoTriSyGen, an agentic framework that formulates multi-shot long video generation as a closed-loop visual-text-memory synergy process, where planned intent, persistent memory, and generated visuals are jointly leveraged for iterative correction and long-range coherence. A vision-language-model-based analyzer reasons over this triplet and produces updates to both prompts and memory along two pathways: (i) intra-shot refinement, which triggers targeted regeneration when semantic or compositional violations are detected and refines image-to-video prompt for coherent motions; and (ii) inter-shot refinement, which rewrites subsequent-shot prompts to propagate newly manifested entities or attributes and improve prompt quality (e.g., compositional grounding and cinematic fluency) based on generated evidence. The loop is grounded in an entity-centric memory modeled as a mutable visual state that evolves as the story progresses, which is continuously updated by both the generator and the analyzer by adding new and evolved entities to reflect appearance changes, accumulated multi-view evidence, and multi-entity compositions. Experiments on our curated StoryBench benchmark demonstrate substantial improvements in cross-shot consistency, prompt adherence, and cinematic continuity over representative methods.

12.
bioRxiv (Bioinfo) 2026-06-13

Testing the reliability of AI-generated protein structures

Although AlphaFold2 and its competitors have demonstrated remarkable abilities to predict protein structure, more work is needed to explore the limitations of these methods. Here we investigated the reliability of AlphaFold2 and ColabFold by creating a set of realistic but false protein sequences, using ColabFold to predict their structure, and then asking how often the program produces a high-scoring structure for a sequence that does not represent a protein. We determined that AlphaFold2 has a very small but non-zero false positive rate, estimated here at approximately 1 in 435 if one uses a threshold pLDDT score of 70 to define positive predictions. We also discovered, serendipitously, that some high-scoring sequences in the human genome were not false positives, but instead were previously unknown and un-annotated pseudogenes. These latter findings indicate that some well-established human annotations of protein-coding genes may have incorrectly extended the 5-prime untranslated regions too far. They also suggest that the false positive rate of AlphaFold2 is low enough that almost any high-scoring structure, even in a noncoding region, is worthy of further investigation.

13.
arXiv (CS.CV) 2026-06-16

CoMNeT: A MedNeXt-CorrDiff Framework for Volumetric Brain Tumor Segmentation

Accurate brain tumor segmentation from multiparametric magnetic resonance imaging (MRI) is critical for treatment planning, response assessment, and quantitative neuro-oncology research. However, automated segmentation remains a difficult task in computer vision because of variation in tumor appearance and MRI protocols across patient scans. Moreover, clinically important regions such as enhancing tumor (ET) and tumor core (TC) are often small relative to the full brain volume, furthering increasing the difficulty of achieving high voxel-level precision. In this paper, we show that combining a modern 3D convolutional segmentation model with corrective diffusion-based refinement and ensembling improves volumetric glioma segmentation on the UTSW-Glioma dataset. We propose CoMNeT, a MedNeXt-CorrDiff framework that uses four MRI modalities as input and predicts ET, TC, and whole tumor (WT) regions for automated brain tumor segmentation. MedNeXt is used as the primary segmentation model with Global Response Normalization for feature learning, while CorrDiff is trained as a postprocessing residual refinement method to correct errors in the probability maps before final thresholding. Using five-fold cross-validation, CoMNeT achieved the highest Dice score for most tumor regions, with ET, TC, WT, and average Dice scores of 0.7543 +/- 0.0261, 0.6806 +/- 0.0166, 0.9049 +/- 0.0128, and 0.7798 +/- 0.0184, respectively. CoMNeT outperformed two selected baseline models: SegResNet (0.7555 +/- 0.0190 average Dice) and standalone MedNeXt (0.7697 +/- 0.0154 average Dice). Our findings support the use of corrective diffusion and fold-level probability ensembling as practical additions to existing state-of-the-art 3D convolutional models for automated glioma segmentation.

14.
Nature (Science) 2026-06-10

A first-in-class pulsatile FXR agonist for bile-acid-related liver diseases

作者:

Nuclear receptors are central regulators of metabolism1, yet therapeutic strategies that enforce continuous receptor activation frequently lead to reduced efficacy and unacceptable toxicity. Here we report a first-principles drug design strategy that aligns pharmacokinetics with physiological signalling cycles. We developed linafexor, a potent non-bile-acid agonist of the farnesoid X receptor (FXR)2; it is engineered for rapid systemic clearance, which enables pulsatile receptor activation that mirrors endogenous bile acid dynamics3–5. Linafexor has robust efficacy across multiple preclinical models of metabolic dysfunction-associated steatohepatitis6, liver fibrosis7, primary biliary cholangitis and primary sclerosing cholangitis8,9. Transcriptomic analyses reveal that, unlike long-acting FXR agonists10,11, linafexor preserves cyclic FXR signalling, avoids receptor downregulation and prevents broad transcriptional dysregulation. Direct manipulation of delivery patterns demonstrates that sustained FXR activation—independent of compound identity—induces severe toxicity, establishing activation duration as a determinant of therapeutic index. In phase 1 clinical studies (ClinicalTrials.gov; NCT05082779), linafexor administered once daily produces transient FXR pathway engagement, marked by (1) induction of FGF1912–14, a key endocrine mediator of bile acid feedback regulation; and (2) suppression of C415, an intermediate reflecting hepatic bile acid synthesis, with no treatment-related adverse events. Together, these findings identify pulsatile FXR activation as a mechanistically grounded and clinically translatable strategy, and establish linafexor as a first-in-class therapeutic for bile acid–related liver diseases. Linafexor is a rapidly cleared FXR agonist designed to mimic natural bile acid signalling, achieving transient receptor activation with strong efficacy and reduced toxicity in preclinical and early clinical studies.

15.
arXiv (quant-ph) 2026-06-12

Explicit Quantum Circuit Simulation of Nonlinear 1-Dimensional Fluid with Carleman-linearized Boltzmann Method

arXiv:2606.12770v1 Announce Type: new Abstract: Quantum computation of fluid dynamics has attracted growing attention as a key application of fault-tolerant quantum computers anticipated in the coming decade, with lattice Boltzmann methods emerging as a particularly promising approach. Explicit and efficient elementary-gate-level circuit simulations, however, have so far been demonstrated only in the linear case. Here we include the leading nonlinearity through second-order Carleman linearization of the one-dimensional Boltzmann equation, and demonstrate, via explicit quantum-circuit simulation, the preparation of the final-time state using a Taylor-expansion-based ODE solver based on the quantum singular value transformation. With this construction, we analyze the gate and qubit complexities, which scale logarithmically with the grid size, the nonlinearity captured by the higher-order Carleman linearization, and the practical utility of higher-order expansions in the Taylor ODE solver. The construction provides a concrete baseline for computational cost reduction and further developments such as extensions to higher dimensions, complex geometries, and the extraction of physical quantities, towards industrially useful quantum CFD.

16.
arXiv (CS.LG) 2026-06-17

Regularized Machine Learning for System Identification of Ship Free-Running Manoeuvres from CFD-Based Synthetic Data: A Comparative Study

arXiv:2606.17121v1 Announce Type: cross Abstract: This study investigates supervised machine learning techniques for identifying ship hydrodynamic coefficients from CFD-generated data from free-running simulations. Specifically, ordinary least squares and regularized regression methods are applied to Abkowitz-type manoeuvring models. Training and validation datasets are derived from URANS simulations of zig-zag and turning circle manoeuvres, which are validated against experimental benchmark data. The analysis evaluates the effects of coefficient set size, minimum training length required for predictive model training, and manoeuvre combinations on model performance. Results demonstrate the suitability of large-angle zig-zag manoeuvres for hydrodynamic system identification, provided that multicollinearity is addressed through appropriate coefficient selection, regression models, or input data variability. Larger coefficient sets offer greater model flexibility for variable conditions but are more prone to multicollinearity. Regularized regression techniques effectively mitigate multicollinearity and notably enhance prediction accuracy, as does incorporating more diverse manoeuvring data. Among tested models, Ridge regression provided the best compromise between computational efficiency and prediction accuracy.

17.
arXiv (quant-ph) 2026-06-24

The Saturable Electronic Reluctance Switch: Switchable low-power and low-noise generation of magnetic fields using permanent magnets

arXiv:2605.05158v2 Announce Type: replace Abstract: Across many areas of science, there is a need to generate magnetic fields that are both ultra-stable and switchable on and off. Current-carrying wire configurations are switchable but are susceptible to current noise. Existing current-controlled approaches to switching the field produced by a permanent magnet involve altering the magnets magnetisation, which typically requires large field pulses and produces excessive power dissipation in high frequency applications. We present a hybrid technique to switch the field of any arbitrary magnet through use of a non-linear ferromagnetic circuit, named the Saturable Electronic Reluctance Switch (SERS). The circuit achieves a linear and monotonic ramp of the magnetic field up to a current threshold, above which the field becomes constant. Crucially, the applied current has minimal influence on the magnetic field stability and demagnetisation of the magnet is avoided. The power dissipated in each switching cycle is expected to be many orders of magnitude less than for existing permanent magnet switching approaches. SERS is also robust to fabrication errors, suppressing noise in the control current by several orders of magnitude in a non-ideal device. To illustrate its application, a SERS-driven device is proposed for generating ultra-stable magnetic field gradients in a scalable trapped-ion quantum computer. We find this device offers an order of magnitude reduction in power dissipation compared to state-of-the-art current carrying wires, while reducing magnetic field noise originating from current fluctuations by up to five orders of magnitude.

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

Utility-Aware DRL-Based TXOP Adaptation for NR-U and Wi-Fi Coexistence Networks

arXiv:2605.00457v4 Announce Type: replace-cross Abstract: The coexistence of NR-U and Wi-Fi in the unlicensed spectrum introduces a challenging resource management problem, where heterogeneous channel access mechanisms can lead to unbalanced spectrum utilization and severe Wi-Fi performance degradation. To address this issue, this paper proposes a utility-aware deep reinforcement learning (DRL) framework for adaptive transmission opportunity (TXOP) control in NR-U/Wi-Fi coexistence networks. The coexistence process is formulated as a Markov decision process (MDP), in which the NR-U TXOP duration is treated as a controllable variable for regulating post-access channel occupancy. A deep Q-network (DQN) is then employed to learn adaptive TXOP control policies through online interaction with the coexistence environment. A key feature of the proposed framework is the integration of a configurable reward and criterion design, which enables explicit control of the fairness-efficiency-utility tradeoff. Three operating policies are developed, namely absolute fairness, moderate fairness, and utility-oriented moderate fairness, to characterize different coexistence operating points. Simulation results show that the proposed framework achieves a Jain fairness index above 0.9 under strict fairness control. Compared with the absolute fairness policy, the moderate fairness policy improves aggregate throughput by 68.22%, while the utility-oriented policy achieves a 177.6% improvement under the adopted utility evaluation metric. These results demonstrate that the proposed utility-aware DRL framework provides an effective and flexible solution for adaptive TXOP control and tradeoff management in heterogeneous unlicensed coexistence networks.

19.
PLOS Computational Biology 2026-06-05

Heuristic multi-site optimization for protein sequence design using Masked Protein Language Models

作者:

by Lijuan Wang, Yuze Wang, Chen Qiu, Liwei Xiao, Xianliang Liu, Junjie Chen Protein sequence design for tailored functional properties is a fundamental task in protein engineering, with critical applications in drug discovery and therapeutic development. Efficient navigation of the combinatorial vastness of protein sequence space to identify functional variants remains a formidable challenge. Conventional approaches, which predominantly rely on template-based local search or single-residue mutagenesis, are constrained by their susceptibility to local optima and their potential risk of destabilizing native structural stability. In this study, we introduce ProtHMSO, a heuristic multi-site optimization framework leveraging masked protein language models (ProtLMs) for context-aware sequence exploration. ProtHMSO mimics natural evolutionary mechanisms by employing ProtLM-derived substitution probabilities to guide heuristic searches for synergistic mutations, thereby constraining combinatorial search spaces through evolutionary and biophysical priors. ProtHMSO is further applied to replace the exploration strategies in genetic algorithms (GAs) and Monte Carlo tree search (MCTS) for improving their convergence efficiency. Benchmark experiments demonstrate that protein sequences generated by ProtHMSO exhibit superior functional performance and closer alignment with natural sequence distribution, compared with state-of-the-art methods. These advancements highlight that ProtHMSO has strong potential and compatibility to accelerate functional protein discovery, offering a robust framework for efficient and context-aware exploration of protein sequence space.

20.
arXiv (quant-ph) 2026-06-19

Discrimination of genuinely nonlocal sets without entanglement in multipartite systems

arXiv:2606.20380v1 Announce Type: new Abstract: Genuine nonlocality arises when a set of multipartite orthogonal states is locally indistinguishable under any bipartition of the subsystems. The entanglement-assisted discrimination of such genuinely nonlocal orthogonal product sets has attracted significant attention in quantum information. Based on the criterion of local irreducibility, genuine nonlocality is classified into Type I (reducible) and Type II (irreducible). We present entanglement-assisted discrimination schemes for both types of genuinely nonlocal sets that use minimal resources. For low-dimensional cases, Type I sets require only a single EPR pair, whereas Type II sets necessitate only one GHZ state. We extend these protocols to higher-dimensional systems: the discrimination of Type I sets requires only one maximally entangled state in a two-qutrit system, while that of Type II sets similarly demands a single maximally entangled state in a three-qutrit system. For $n$-partite ($n > 3$) systems, Type I sets continue to require only one maximally entangled state, whereas Type II sets necessitate just one additional EPR pair compared to their Type I counterparts. These results provide a robust framework for the efficient discrimination of genuinely nonlocal sets using minimal quantum resources.

21.
medRxiv (Medicine) 2026-06-18

AlphaGenome identifies a deep intronic variant in a family with PLA2G6-associated neurodegeneration: Closing the diagnostic gap in rare genetic diseases

A molecular diagnosis remains out of reach for a substantial subset of patients with clinically recognizable Mendelian disorders, even after comprehensive next-generation sequencing. Causal variants in non-coding regions are difficult to detect and interpret using standard pipelines. Deep intronic variants that disrupt splicing are a known but underexplored source of pathogenic alleles, and systematic tools to evaluate them at scale have only recently emerged. We aimed to resolve an incomplete genetic diagnosis in two siblings with early-onset parkinsonism, prominent neuropsychiatric features, and autonomic dysfunction consistent with PLA2G6-associated neurodegeneration (PLAN), an autosomal recessive condition. Prior clinical exome sequencing, genome sequencing, Multiplex Ligation-dependent Probe Amplification (MLPA), and long-read sequencing had identified only a single heterozygous PLA2G6 missense variant, c.2132C>G (p.Pro711Arg). We used AlphaGenome to score 91 non-coding variants shared among the affected siblings and their father within 1 megabase of the PLA2G6 locus. The deep-learning model identified an intronic variant (c.2034+355G>A) that was predicted to create a cryptic splice acceptor site that could result in inclusion of a 160-bp cryptic exon. Tissue-specific predictions indicated the aberrant splicing would be detectable in blood, confirmed by junction-spanning RNA-seq reads from an unrelated carrier. This analysis completed a compound heterozygous PLAN diagnosis nearly two decades after symptom onset and demonstrates the utility of sequence-to-function models. Systematic integration of tools like AlphaGenome into rare disease workflows offers a practical, low-barrier route to closing the diagnostic gap for patients with compelling Mendelian phenotypes and incomplete genetic diagnoses.

22.
arXiv (CS.LG) 2026-06-18

Generative models for decision-making under distributional shift

arXiv:2604.04342v2 Announce Type: replace Abstract: Many data-driven decision problems are formulated using a nominal distribution estimated from historical data, while performance is ultimately determined by a deployment distribution that may be shifted, context-dependent, partially observed, or stress-induced. This tutorial presents modern generative models, particularly flow- and score-based methods, as mathematical tools for constructing decision-relevant distributions. From an operations research perspective, their primary value lies not in unconstrained sample synthesis but in representing and transforming distributions through transport maps, velocity fields, score fields, and guided stochastic dynamics. We present a unified framework based on pushforward maps, continuity, Fokker-Planck equations, Wasserstein geometry, and optimization in probability space. Within this framework, generative models can be used to learn nominal uncertainty, construct stressed or least-favorable distributions for robustness, and produce conditional or posterior distributions under side information and partial observation. We also highlight representative theoretical guarantees, including forward-reverse convergence for iterative flow models, first-order minimax analysis in transport-map space, and error-transfer bounds for posterior sampling with generative priors. The tutorial provides a principled introduction to using generative models for scenario generation, robust decision-making, uncertainty quantification, and related problems under distributional shift.

23.
arXiv (CS.CL) 2026-06-11

Building Social World Models with Large Language Models

Understanding and predicting how social beliefs evolve in response to events – from policy changes to scientific breakthroughs – remains a fundamental challenge in social science. Given LLMs' commonsense knowledge and social intelligence, we ask: Can LLMs model the dynamics of social beliefs following social events? In this work, we introduce the concept of the Social World Model (SWM), a general framework designed to capture how social beliefs evolve in response to major events. SWM learns state-transition functions for social beliefs by mining temporal patterns in social data and optimizing the evidence lower bound, without the need for explicit human annotations linking events to belief shifts, or for expensive census data. To evaluate SWM, we introduce a benchmark, SWM-bench, derived from real-world prediction markets, specifically Kalshi and Polymarket. SWM-bench includes over 12k data points for social belief prediction tasks spanning diverse domains such as politics, finance, and cryptocurrency. Our experimental results show that SWM significantly outperforms time-series foundation models, achieving state-of-the-art results on Kalshi data and demonstrating competitive performance on Polymarket data, while offering interpretable insights into the underlying mechanisms of social belief dynamics.

24.
arXiv (CS.LG) 2026-06-11

MASK: Multi-Agent Semantic K-Scheduling for Risk-Sensitive 6G Robotics

arXiv:2606.11249v1 Announce Type: cross Abstract: Realizing the vision of 6G connected robotics requires reconciling high-performance collaborative control with the rigid spectral limitations of physical wireless channels. In realistic collaborative sensing scenarios, spectral resources are quantized into finite physical resource blocks or orthogonal subcarriers, rendering simultaneous transmission by all agents infeasible. To address this, we propose Multi-Agent Semantic K-Scheduling (MASK), a control architecture designed to sustain robust, risk-aware coordination under strict instantaneous bandwidth caps. We introduce Arbiter-Assisted Semantic Information Gating (A-SIG), a lightweight coordination mechanism that enforces hard access constraints by scheduling only the top-K agents based on locally computed semantic importance scores. By aggregating these prioritized observations into a compact latent state, a self-supervised global encoder enables a distributional policy to mitigate tail risks despite data sparsity. We evaluate MASK across diverse benchmarks, demonstrating that it matches the performance of communication-unconstrained baselines even when channel access is restricted to a small fraction of the swarm size. Furthermore, the framework exhibits inherent resilience to packet erasures, validating semantic scheduling as a critical enabler for resource-constrained 6G systems.

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arXiv (CS.CL) 2026-06-15

An Empirical Study of Automating Agent Evaluation

Agent evaluation requires assessing complex multi-step behaviors involving tool use and intermediate reasoning, making it costly and expertise-intensive. A natural question arises: can frontier coding assistants reliably automate this evaluation process? Our study shows that simply prompting coding assistants is insufficient for this task. Without domain-specific evaluation knowledge, frontier coding assistants achieve only a 30% execution success rate and produce over-engineered evaluations averaging 12+ metrics per agent, indicating that strong coding ability does not automatically translate to reliable agent evaluation. We introduce EvalAgent, an AI assistant that automates the end-to-end agent evaluation pipeline. EvalAgent encodes evaluation domain expertise as evaluation skills (procedural instructions, reusable code and templates, and dynamically retrieved API documentation) that compose into a trace-based pipeline producing complete evaluation artifacts including metrics, executable code, and reports. To systematically assess generated evaluations, we introduce a meta-evaluation framework alongside AgentEvalBench, a benchmark comprising 20 agents, each paired with evaluation requirements and test scenarios. We further propose the Eval@1 metric to measure whether generated evaluation code both executes and yields meaningful results on the first run. Our experiments show that EvalAgent produces focused evaluations, improving Eval@1 from 17.5% to 65%, and achieving 79.5% human expert preference over baseline approaches. Further ablation studies show that evaluation skills are critical for handling complex evaluation: removing them causes Eval@1 to drop significantly from 65% to 30%.