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01.
arXiv (CS.CL) 2026-06-17

ALAS: An Automatic Latent Alignment Score for Audio Language Models

Large Language Models (LLMs) are extended into Speech-LLMs, and the quality of the audio–text alignment they learn affects most downstream Spoken Language Understanding (SLU) behavior. Yet despite a growth of fusion strategies, there is no standard way to measure how well a Speech-LLM internally binds audio frames to text tokens. We introduce ALAS (Automatic Latent Alignment Score), a model and task-agnostic metric that probes the LLM's per-layer hidden states, scoring the cross-modal cosine similarity between audio and text representations against a Whisper-derived reference. ALAS needs only a frozen forward pass and an off-the-shelf ASR reference, with no training or fitted classifier, and is calibrated to an interpretable uniform baseline comparable across tasks. Applying ALAS to four open-source Speech-LLMs (AF3, Qwen2-Audio, Qwen-Omni, SALMONN) across emotion recognition (IEMOCAP), open-ended SQA (LibriSQA), and multi-choice audio understanding (MMAU-speech), we find that the depth and strength of alignment reflect each model's audio-encoder design and the acoustic-versus-semantic demands of the task, and that ALAS tracks but does not duplicate task accuracy, exposing models that score well without genuinely grounding in the audio. We release ALAS as an open-source library so that practitioners can probe their own Speech-LLMs or try it on new tasks.

02.
arXiv (CS.LG) 2026-06-16

Stop the Sampler! Classifier-Based Adaptive Stopping for Sampling Kernels

arXiv:2606.16073v1 Announce Type: new Abstract: Sampling from complex, unnormalized probability densities is a fundamental challenge in Bayesian inference and probabilistic modeling. While Markov chain Monte Carlo (MCMC) methods provide asymptotic guarantees, they often suffer from slow mixing and high computational costs due to fixed or manually tuned trajectory lengths. In this work, we propose a novel framework that treats trajectory termination as a learnable component of the sampling dynamics. By framing MCMC within the theory of non-acyclic generative flow networks (GFlowNets), we train state-dependent neural classifiers to decide when a trajectory has reached a high-density region and should terminate. We theoretically establish the connection between optimal classifiers and the target density via detailed balance conditions and introduce a multilevel training scheme to facilitate exploration in complex geometries. Experimental results across various benchmark densities demonstrate that our approach significantly reduces average trajectory lengths while improving mode coverage and mixing compared to standard MCMC baselines.

03.
arXiv (CS.AI) 2026-06-12

Under What Conditions Can a Machine Become Genuinely Creative?

作者:

arXiv:2606.13196v1 Announce Type: new Abstract: Recent AI systems can generate texts, software architectures, hypotheses, designs, and scientific workflows that appear creative. This paper asks under what conditions a machine can become genuinely creative, and how human agency can be preserved within shared cognitive and creative environments. It develops a requirement framework derived from Designics, the science of meaning-bearing intentional change. The paper argues that genuine machine creativity should not be defined by output novelty, current performance, or transient architecture alone. Instead, creativity is understood as the structural transformation of incomplete situations through recursive intervention dynamics. On this view, it depends on ten requirements: environment representation, scoped perception, conflict identification, intervention capability, consequence observation, knowledge and environment update, rescoping, local-to-global unfolding, value-based scoping, and human-AI co-living. These are organized through the three laws of Designics: perception, conflict, and capability. The paper illustrates the computational tractability of these requirements through selected cyber-physical and cyber-biological studies, including recursive element extraction, autonomous mesh generation, and neurophysiological and workload analysis. It then treats open-ended systems, automated discovery frameworks, self-modifying agents, foundation models, and agentic workflows as pressure cases: they demonstrate powerful generative means but do not by themselves establish genuine machine creativity. Finally, the paper argues that proactive AI ethics is internal to genuine machine creativity rather than an after-the-fact filter. Value-based scoping and human-AI co-living must shape how creative machines perceive environments, identify conflicts, select interventions, observe consequences, update knowledge, and rescope future action.

04.
arXiv (CS.LG) 2026-06-11

From Persistence to Survival: Hypothesis Testing, Effect Sizes and Vectorisation for Topological Features

arXiv:2606.11911v1 Announce Type: cross Abstract: Persistence diagrams are common representations in topological data analysis, but they do not naturally live in a vector space, and the statistical tools developed for comparing them have largely evolved separately from those used for downstream prediction. We introduce STRAND (Survival Topological Representation ANalysis of Diagrams), which treats (collections of) PDs as survival data: each topological feature with persistence value $p = d - b$ is a fully observed time-to-event, and the persistence survival function $S(t) = \mathbb{P}(p > t)$ is the central object for comparing diagrams. From this single representation we derive (i) a non-parametric two-sample test with calibrated Type I error and high power from a small number of diagrams; (ii) interpretable effect sizes; and (iii) a 1-Wasserstein-stable feature vector for downstream machine learning. We validate calibration and power on synthetic manifolds with controlled topology, demonstrate competitive vectorisation across 14 graph and 3D point cloud benchmarks, and apply the method to study functional brain connectivity in fMRI/neuroscience data. To our knowledge, STRAND is the first method to provide hypothesis testing and vectorisation for persistence diagrams from a single coherent and interpretable representation.

05.
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.

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

Smoothing Dark Areas in Molecular Latent Diffusion

arXiv:2606.13955v1 Announce Type: new Abstract: Latent diffusion is a promising framework for scalable 3D molecular generation, but it requires a latent space that remains smooth, valid, and navigable beyond posterior samples. Existing molecular VAEs, however, are typically learned through reconstruction-based objectives, which do not guarantee such a latent space. We show that this leads to dark areas: regions of latent space that are reachable during diffusion sampling but decode to disconnected or chemically invalid molecules. Unlike in image generation, molecular decoding requires strict structural and chemical precision, so even small latent perturbations can produce catastrophic failures. We therefore propose TopVAE, a topology-optimized VAE that reduces dark areas by making the decoder internalize structural and chemical constraints during training, eliminating the need for test-time chemical correction. TopVAE greatly improves off-posterior robustness, and when paired with a standard DiT, achieves $77\%$ lower FCD-3D on QM9, the highest V&C, $52\%$ lower FCD-3D on GEOM-Drugs, and $1.29{\times}$ more stable and connected molecules on zero-shot scaffold inpainting.

07.
arXiv (CS.AI) 2026-06-19

Implicit Semantic-Aware Communication Based on Hypergraph Reasoning

arXiv:2606.20162v1 Announce Type: new Abstract: Semantic-aware communication has emerged as a transformative paradigm for next-generation communication systems, shifting the fundamental goal from transmitting bit-level symbols to reliably recovering and understanding the semantic meaning of information. Previous studies have demonstrated that representing the semantic content of source messages as graph-based structures can significantly improve communication efficiency and the accuracy of semantic inference at the receiver. However, existing solutions typically employ graphs that capture only pairwise relationships, thereby neglecting higher-order implicit correlations commonly observed in real-world scenarios, such as group interactions, multi-entity associations, and complex relational contexts. This limitation reduces semantic expressiveness and makes semantic inference susceptible to ambiguity and performance degradation, particularly under noisy or corrupted channel conditions. To address these issues, this paper proposes a novel hypergraph-based implicit semantic reasoning framework, HISR, which leverages hypergraphs to represent complex multi-entity relationships among semantic knowledge entities. In HISR, entities and their associated higher-order relations are mapped into dedicated semantic subspaces tailored to distinct relational contexts. This design not only disentangles diverse semantic interactions to mitigate the over-smoothing effects commonly found in traditional graph embedding methods but also enables robust semantic inference even when partial information loss occurs during transmission. Numerical results show that the proposed HISR achieves up to a 36.6% improvement in implicit semantic interpretation accuracy over the state-of-the-art benchmarks.

08.
medRxiv (Medicine) 2026-06-22

Why drinking episodes escalate differently: Event-level pathways linking hazardous alcohol consumption and sexual risk

Background: Alcohol-involved drinking episodes vary in whether they involve hazardous alcohol consumption alone, near-miss sexual risk, or sexual risk behavior, but the within-event mechanisms underlying this variability remain unclear. Methods: Guided by syndemic theory, we conducted a qualitative event-level analysis using modified grounded theory among adults in the San Francisco Bay Area who reported hazardous alcohol consumption, defined as an Alcohol Use Disorder Identification Test score [≥]16. In-depth interviews elicited narratives of recent heavy drinking episodes and yielded 64 discrete drinking events across 22 participants. We focused on 35 events with evidence of within-event interaction between biopsychosocial and contextual factors. Using constant comparison, we identified escalation pathways, characterized interruption, and examined how events diverge into three outcomes: hazardous alcohol consumption only, hazardous alcohol consumption with near-miss sexual risk (when risk was plausible but not enacted), and hazardous alcohol consumption with sexual risk behavior. Results: Two primary escalation pathways emerged. Dose-driven escalation involved cumulative alcohol or substance exposure that progressively impaired awareness and self-regulation. Meaning-driven escalation involved prioritizing connection, intimacy, or belonging despite awareness of risk. Time-driven continuation extended exposure across contexts and amplified both pathways. Hazardous alcohol consumption-only events more often followed dose-driven pathways, whereas events involving sexual risk behavior more often followed meaning-driven pathways. Near-miss events occurred across both pathways and illustrated how interruption before the escalation constraint point, when the capacity to modify behavior became reduced, could redirect escalation before sexual risk behavior occurred. Across events with similar levels of intoxication narratives, outcomes diverged according to when the interruption occurred and whether it altered escalation. Conclusion: Hazardous drinking episodes diverge into different outcomes based on escalation pathways and the timing and effectiveness of interruption. Early and effective interruption before the escalation constraint point may represent a key target for harm-reduction strategies to prevent progression to sexual risk behavior.

09.
medRxiv (Medicine) 2026-06-17

The interaction between chronic hepatitis B (CHB) and Metabolic dysfunction-associated steatotic liver disease (MASLD) in a diverse central London population

Introduction: The overlap between chronic hepatitis B (CHB) and metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging global health challenge. We investigated the impact of MASLD and metabolic comorbidity in a diverse London viral hepatitis clinic. Methods: This retrospective cross-sectional study (May 2018-Feb 2024) included adults with CHB having controlled attenuation parameter (CAP) measurements. MASLD was defined as CAP >264 dB/m plus [≥]1 cardiometabolic factor (CMF). We used univariable and multivariable models to examine MASLD's relationship with liver stiffness and hepatitis B viral load (HBV VL). Results: Among 323 individuals (67% male, median age 36), most were from Black (35%) or non-white British/Irish (29%) backgrounds. Overall, 64% had [≥]1 CMF, and 20% had MASLD. The CHB/MASLD group was significantly older (median 43 vs 35 years, p

10.
arXiv (CS.LG) 2026-06-12

$\alpha$-fair heterogeneous agent reinforcement learning

arXiv:2606.13076v1 Announce Type: cross Abstract: Cooperation in multi-agent systems is typically optimized through utilitarian objectives that maximize overall efficiency but fail to account for reward distribution, often resulting in inequitable "leader-follower" dynamics. While fairness-based approaches encourage pro-social behaviors where every agent benefits from cooperation, many current algorithms - including those utilizing reward shaping - break the stationarity of Markov Games or lack rigorous theoretical guarantees. This creates a critical gap between fair objective methods and theoretically safe learning frameworks. We propose a novel framework that bridges $\alpha$-fairness with Heterogeneous-Agent Trust Region Learning (HATRL), ensuring monotonic improvement and convergence toward Nash Equilibria. Our approach leverages a fair advantage function that dynamically weights agent utilities based on their expected returns, allowing the global objective to transition from purely utilitarian efficiency to $\alpha$-fairness welfare based on the parameter $\alpha$. We introduce two practical algorithms, $\alpha$-fair HATRPO and $\alpha$-fair HAPPO, and demonstrate through experiments in sequential social dilemmas like CleanUp and CommonHarvest that they perform better than HATRL's algorithms from a utilitarian point of view while achieving socially higher outcomes.

11.
arXiv (CS.CL) 2026-06-12

C-QUERI: Congressional Questions, Exchanges, and Responses in Institutions Dataset

Questions in political interviews and hearings serve strategic purposes beyond information gathering including advancing partisan narratives and shaping public perceptions. However, these strategic aspects remain understudied due to the lack of large-scale datasets for studying such discourse. Congressional hearings provide an especially rich and tractable site for studying political questioning: Interactions are structured by formal rules, witnesses are obliged to respond, and members with different political affiliations are guaranteed opportunities to ask questions, enabling comparisons of behaviors across the political spectrum. We develop a pipeline to extract question-answer pairs from unstructured hearing transcripts and construct a novel dataset of committee hearings from the 108th–117th Congress. Our analysis reveals systematic differences in questioning strategies across parties, by showing the party affiliation of questioners can be predicted from their questions alone. Our dataset and methods not only advance the study of congressional politics, but also provide a general framework for analyzing question-answering across interview-like settings.

12.
arXiv (CS.CL) 2026-06-16

S1-DeepResearch: Beyond Search, Toward Real-World Long-Horizon Research Agents

Deep research agents aim to solve complex knowledge-intensive tasks through long-horizon planning, evidence gathering, reasoning, and report generation. While recent progress in search agents has demonstrated strong capabilities in information retrieval and answer verification, most existing training datasets remain search-centric, focusing primarily on closed-ended question answering and information localization. As a result, they mainly train information-seeking behavior while providing limited coverage of key deep research capabilities, including evidence integration, knowledge synthesis, planning, file understanding, and structured report generation. In this work, we propose a unified trajectory construction paradigm for deep research agents that combines closed-ended QA and open-ended exploration. The proposed framework consists of graph-grounded task formulation, agentic trajectory rollout, and multi-dimensional trajectory verification, enabling scalable synthesis of high-quality agentic trajectories spanning long-chain complex reasoning, deep research instruction following, report writing, file understanding and generation, and skills usage. Compared with existing search-oriented datasets, our synthesized trajectories place greater emphasis on knowledge synthesis, complex reasoning, and planning. S1-DeepResearch-32B achieves state-of-the-art performance among open-source models of comparable scale across 20 benchmarks spanning five capability dimensions, including complex reasoning, instruction following, report generation, file understanding, and skills usage. On several challenging deep research benchmarks, it approaches the performance of leading proprietary frontier models. These results highlight the importance of jointly modeling information acquisition, knowledge synthesis, and planning-oriented agent behaviors for building effective deep research agents.

14.
arXiv (CS.CV) 2026-06-18

Fuzzy-Geometric Branch-Point Modeling for Structure-Aware Augmentation of Handwritten Chinese Characters

Data scarcity and structural distortion significantly limit handwriting recognition in high-security authentication. Existing augmentation methods often cause topological and morphological damage, particularly when processing complex Chinese characters where stroke intersections, ligatures, and sharp turns render traditional branch-point detection unreliable. To address this, this paper proposes a fuzzy geometry-driven structure-aware (FGSA) augmentation framework. We model branch points as fuzzy sets within the skeleton space, constructing a continuous branch-point membership field by integrating topological neighborhood evidence with direction field divergence. This membership field is adaptively optimized via an unsupervised surrogate objective, enabling robust stroke decoupling without manual annotation. Finally, kinematically-aligned samples are synthesized through parameterized cubic Bézier reconstruction and multi-strategy perturbations, ensuring a balance between structural fidelity and sample diversity. Moreover, we establish LZUSig, a large-scale, highly challenging dataset specifically dedicated to fine-grained structural degradation in Chinese handwritten signatures. Extensive experiments on CASIA-HWDB1.1, ChiSig, and LZUSig demonstrate that FGSA significantly reduces the word-level error rate ($\Delta$WER), achieving optimal recognition gains over the compared baselines. More importantly, it strikes a robust trade-off among task gain, structural fidelity, and discriminative feature preservation, offering a highly controllable solution for handwriting augmentation.

15.
arXiv (CS.CL) 2026-06-16

SAAS: Self-Aware Reinforcement Learning for Over-Search Mitigation in Agentic Search

Agentic search enables LLMs to solve complex multi-hop questions through iterative reasoning and external search. Despite the effectiveness, these systems often suffer from a critical limitation in practice: agents fail to recognize their own knowledge boundaries, blindly triggering searches when internal knowledge suffices and failing to terminate search even when adequate evidence has been collected. The lack of self-awareness leads to severe over-search, incurring substantial inference latency and prohibitive computational cost. To this end, we propose SAAS, a novel RL framework designed to cultivate dynamic self-awareness that precisely regulates search behavior without compromising accuracy. SAAS introduces three key components: (i) a search boundary modeling mechanism, which identifies the search boundary under the evolving policy by contrasting search-disabled and search-enabled rollouts; (ii) a boundary-aware reward module, which translates this boundary awareness into trajectory-level penalties, suppressing unnecessary and redundant searches; and (iii) a stage-wise optimization strategy, which leverages a sequential curriculum to prioritize reasoning over search regularization, thereby avoiding reward hacking. Extensive experiments demonstrate that SAAS substantially reduces over-search, while maintaining accuracy. Our code and implementation details are released at https://github.com/XMUDeepLIT/SAAS.

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

Evaluating LLM Usage for Efficient and Explainable Numerical and Classified Implicit Sentiment Analysis of Product Desirability

Qualitative product feedback can reveal nuanced user experiences, but its implicit sentiment is difficult to measure. This paper presents a scalable and interpretable framework that uses large language models (LLMs) to quantify product desirability from such data. Using two Product Desirability Toolkit (PDT) datasets from ZORQ and CARMA comprising 106 respondent term groupings with gold-standard human annotation, zero-shot continuous numerical sentiment scoring and categorical sentiment classification are evaluated without relying on explicit review scores. Across the datasets, LLMs generated numerical sentiment scores directly from qualitative responses and closely matched expert labels, achieving Pearson correlations up to 0.97 and classification accuracy up to 94%. LLMs maintained robustness even when handling data presented in multiple forms and consistently expressed high confidence. In contrast, lexicon-based and transformer baselines did not produce statistically significant results. Among the models tested, GPT-4o-mini achieved performance comparable to larger models at 94% lower cost, supporting scalable deployment. The framework also incorporates model confidence ratings and human-readable rationale explanations (xAI), improving interpretability, transparency, and trust while supporting practical use in product satisfaction assessment. In general, using the PDT tool as a survey method along with a cost efficient LLM for sentiment analysis has the potential to provide for product evaluation with results that are rich in terms of sentiment scores (both numerical and classified sentiment) and in terms of the high-level user impressions of the product that can be used to identify ideas for product development and improvement, as well as marketing ideas for target audiences.

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

MAF: Multimodal Adaptive Few-shot Prompting for Sentiment Analysis with MLLMs

作者:

Multimodal large language models (MLLMs) have demonstrated remarkable capabilities in understanding complex multimodal content. However, their performance in sentiment analysis exhibits acute sensitivity to prompt design, rendering static, uniformly applied prompts inherently suboptimal for capturing the nuanced multimodal cues that vary across inputs. To address this limitation, we propose a Multimodal Adaptive Few-Shot Prompting (MAF) framework, which dynamically retrieves and integrates query-relevant demonstrations to elicit the sentiment reasoning capabilities of MLLMs in a context-sensitive manner. MAF constructs a demonstration retrieval module that holistically encodes facial expressions, scene context, and textual semantics, with a lip movement amplitude detection mechanism introduced for accurate speaker identification in multi-person scenarios. Departing from conventional fixed-weight fusion, a lightweight coefficient generation network is trained to output query-conditioned fusion weights in real time, enabling weighted aggregation of multimodal similarity scores to retrieve the top-K most informative demonstrations. Prediction stability is further enhanced through majority voting over multiple candidate outputs generated by the MLLM. Extensive experiments on public benchmark datasets demonstrate that MAF achieves substantial and consistent performance improvements over the corresponding backbone variants and remains competitive with strong multimodal sentiment-analysis baselines.

18.
medRxiv (Medicine) 2026-06-10

A Heterogeneous Graph Neural Network Framework for Multi-Horizon Stroke Mortality Prediction

Background: Machine learning models for stroke mortality prediction typically treat each time horizon independently and use flat tabular features that ignore the relational structure of electronic health records (EHRs). In this pilot study, we leveraged graph-based machine learning models to predict post stroke all-cause-mortality across three different time horizons. Methods: We developed Stroke Temporal Heterogeneous Graph (StrokeTHG), a heterogeneous graph neural network model for simultaneous multi-horizon stroke mortality prediction (30-day, 90-day, 1-year) using EHR data from Penn State Health System. The model encodes various relations among EHR entities (e.g., patient, diagnosis, comorbidity) and temporal encoding of admission time to better predict stroke mortality. We compared our proposed approach against various baseline methods, including Logistic Regression, Random Forest, and XGBoost. We also performed ablation and subgroup analyses, evaluated the quality of learned graph embeddings, and assessed the importance of different edge types in the graph. Results: We included 4,144 stroke patients (mean age 69.2 years; 54.3% men), of whom 3,332 (80.4%) survived their stroke after one year. 30-day, 90-day, and 1-year mortality rates were 9.7%, 13.7%, and 19.6%, respectively. Our proposed approach, StrokeTHG, achieved AUROC of 0.872, 0.878, and 0.837 across horizons, outperforming all tabular baselines. At [≥] , 75% specificity, the model identified 5-10 percentage points more mortality cases than the best baseline at each horizon. Subgroup analysis demonstrated consistent performance across sex subgroups and the largest discriminative gains in the Age 65-80 stratum. Edge-type ablation identified phenotype-patient and admission-patient edges in the constructed EHR graph as the most influential relational edges for mortality prediction. StrokeTHG embeddings outperformed all graph and matrix factorization baselines under an identical downstream classifier, confirming that performance gains stem from representation quality rather than classifier capacity. Conclusions: StrokeTHG demonstrates that heterogeneous graph representations of EHR data provide a consistent improvement over flat tabular models for multi-horizon stroke mortality prediction, with particular advantage at clinically actionable sensitivity thresholds and novel multi-horizon monotonic prediction capability. This methodological framework may be adaptable to other EHR-based clinical research studies seeking to leverage heterogeneous relational structures for predictive modeling.

19.
arXiv (CS.CV) 2026-06-24

Universal Guideline-Driven Image Clustering via a Hybrid LLM Agent

Unifying image clustering across different clustering scenarios remains challenging due to fundamental gaps among tasks. We introduce a Guideline-Driven Image Clustering Agent, the first universal framework that bridges these gaps through textual guidelines. To incorporate complex guidelines without task-specific training, we propose Generative Concept Proxy Modeling, which generates guideline-aware embeddings via concept proxy extraction. For scenarios requiring automatic cluster discovery, we introduce LLM Traversal based on Minimum Spanning Tree that selectively applies LLM reasoning for complex semantic judgments. Our method generalizes across diverse clustering scenarios spanning from general to fine-grained categorization, from global to local criteria, and from balanced to long-tail distributions. Our framework consistently outperforms specialized methods across diverse clustering tasks.

20.
PLOS Computational Biology 2026-06-11

A zero-parameter first-principles gate framework for full-length TP53 missense variant interpretation

by Masamichi Iizumi Missense variant interpretation often achieves useful predictive performance but remains mechanistically opaque, particularly in proteins that combine structured domains with intrinsically disordered regions (IDRs). We developed Gate & Channel, a zero-parameter, first-principles framework for full-length TP53 missense variant analysis in which each prediction is generated by explicit IF-THEN gates derived from physicochemistry, geometry, structural constraints, and polymer physics rather than fitted weights. Variants are evaluated across independent channels representing distinct physical failure modes; a variant is predicted disruptive if any gate closes. A second hierarchical layer (“Geta”) encodes physically grounded post-closure exceptions, allowing sensitivity and specificity to be improved on disjoint variant populations. The v18 framework consists of 12 channels and 2 Getas spanning structured domains and IDRs, capturing DNA-contact disruption, Zn coordination, burial-dependent packing, secondary-structure compatibility, post-translational modification chemistry, short linear motif disruption (including a multi-partner coupled-folding face), proline-directed kinase recognition, and IDR-specific proline and glycine backbone constraints. Across 1,369 TP53 missense variants, the framework achieved 84.5% sensitivity and 89.1% positive predictive value, with 90.9% sensitivity preserved in the DNA-binding core and all 9/9 hotspot mutations captured. A post hoc audit of discordant IDR calls indicated that many apparent false positives had plausible molecular rationales, consistent with a distinction between molecular mechanism disruption and clinical penetrance. Applied to KRAS, TDP-43, and BRCA1, the same channels capture the dominant pathogenic mechanisms in each protein as a proof of principle, while residual missed variants name specific gates yet to be written. The framework is distributed as the open-source Python package pathogenicity-gates (v0.5.1, MIT). These results show that a substantial fraction of full-length TP53 missense variation can be resolved through explicit, auditable physical gates that carry meaning beyond TP53, with each remaining failure naming the next rule to be written.

21.
arXiv (CS.LG) 2026-06-16

A Penalty Approach for Differentiation Through Black-Box Quadratic Programming Solvers

arXiv:2602.14154v3 Announce Type: replace Abstract: Differentiating through the solution of a quadratic program (QP) is a central problem in differentiable optimization. Most existing approaches differentiate through the Karush–Kuhn–Tucker (KKT) system, but their computational cost and numerical robustness can degrade at scale. To address these limitations, we propose dXPP, a penalty-based differentiation framework that decouples QP solving from differentiation. In the solving step (forward pass), dXPP is solver-agnostic and can leverage any black-box QP solver. In the differentiation step (backward pass), we map the solution to a smooth approximate penalty problem and implicitly differentiate through it, requiring only the solution of a much smaller linear system in the primal variables. This approach bypasses the difficulties inherent in explicit KKT differentiation and significantly improves computational efficiency and robustness. We evaluate dXPP on various tasks, including randomly generated QPs, large-scale sparse projection problems, and a real-world multi-period portfolio optimization task. Empirical results demonstrate that dXPP is competitive with KKT-based differentiation methods and achieves substantial speedups on large-scale problems. Our implementation is open source and available at https://github.com/mmmmmmlinghu/dXPP.

22.
arXiv (CS.CV) 2026-06-16

Mutual Distillation of Dual-Foundation Models for Semi-Supervised PET/CT Segmentation

Organ segmentation from PET/CT is critical for quantitative analysis and radiotherapy planning in oncology. To ease the high annotation cost of PET/CT segmentation, semi-supervised learning (SSL) provides a practical and effective solution for developing deep models with limited labeled data. Recent developments in visual foundation models have demonstrated remarkable adaptability with improved efficiency. In this work, we propose a mutual distillation framework that seamlessly exploits both structural and functional foundation models, which act as modality-specific generalists for distilling knowledge from structural CT and metabolic PET imaging. By bridging the gap between the task-specific precision of student models and the segmentation priors of generalist foundation models, we propose MuDuo, a mutual distillation framework that synergistically leverages SAM-Med3D for CT and SegAnyPET for PET to distill their knowledge into a lightweight student network. Our approach eliminates the need for manual prompts while maximizing the utility of unlabeled data for automatic segmentation, achieving state-of-the-art performance on the AutoPET dataset with only 5 labeled cases. Our source code is available at https://github.com/Wu-beining/MuDuo.

23.
arXiv (CS.LG) 2026-06-18

Unraveling the Mechanism of Drug Binding to SARS-CoV-2 RNA Pseudoknot with Thermodynamics-Driven Machine Learning

arXiv:2604.14906v3 Announce Type: replace-cross Abstract: The pseudoknot secondary structure in SARS-CoV-2 RNA is essential for regulating protein synthesis through $-$1 programmed ribosomal frameshifting ($-1$ PRF), a mechanism that allows the virus to generate both structural and non-structural proteins from overlapping reading frames. This pseudoknot exhibits both threaded and unthreaded long-lived topologies. The influence of ligand binding on its folding is a process critical for the development of $-$1 PRF small-molecule inhibitors. Understanding this process through unbiased molecular dynamics (MD) simulations can be facilitated by introducing collective variables (CVs) that capture the corresponding slowest dynamical modes. Here, we use spectral map (SM), a thermodynamics-driven machine learning technique, to learn such CVs directly from all-atom MD trajectories of the SARS-CoV-2 RNA pseudoknot in complex with the $-$1 PRF inhibitor merafloxacin and its two structural analogs in neutral and ionized forms. Free-energy landscapes (FELs) derived from the learned CVs indicate that ligand-induced destabilization is topology-selective. In the threaded pseudoknot, the inhibitors destabilize the S2 stem, while in the unthreaded pseudoknot, destabilization occurs in the S1 and S3 stems. Furthermore, the extent to which each ligand reshapes the FEL matches experimentally reported antiviral potency, whereas the protonation state qualitatively alters dynamics within the same RNA topology. Overall, our results show how pseudoknot topology, ligand type, and protonation state collectively influence the slow conformational dynamics of viral RNA and establish physiological protonation as a critical factor for modeling RNA-targeted drug action.

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

PISA: A Pragmatic Psych-Inspired Unified Memory System for Enhanced AI Agency

arXiv:2510.15966v2 Announce Type: replace Abstract: Memory systems are fundamental to AI agents, yet existing work often lacks adaptability to diverse tasks and overlooks the constructive and task-oriented role of AI agent memory. Drawing from Piaget's theory of cognitive development, we propose PISA, a pragmatic, psych-inspired unified memory system that addresses these limitations by treating memory as a constructive and adaptive process. To enable continuous learning and adaptability, PISA introduces a trimodal adaptation mechanism (i.e., schema updation, schema evolution, and schema creation) that preserves coherent organization while supporting flexible memory updates. Building on these schema-grounded structures, we further design a hybrid memory access architecture that seamlessly integrates symbolic reasoning with neural retrieval, significantly improving retrieval accuracy and efficiency. Our empirical evaluation, conducted on the existing LOCOMO benchmark and our newly proposed AggQA benchmark for data analysis tasks, confirms that PISA sets a new state-of-the-art by significantly enhancing adaptability and long-term knowledge retention.

25.
arXiv (CS.CL) 2026-06-16

Rapid Poison: Practical Poisoning Attacks Against the Rapid Response Framework

The Rapid Response (RR) framework, deployed in production systems, including Anthropic's ASL-3 safeguards, continuously improves jailbreak-detection classifiers. When new jailbreaks emerge that bypass these classifiers, Rapid Response generates synthetic variants for training, helping the model generalize from the new attacks and quickly adapt. We reveal that prompt injection can infiltrate this pipeline to deliver poisoned samples into the classifier's training set, enabling two attack objectives: (I) targeted poisoning attacks that create false positives on harmless samples by categorizing them as a jailbreak, with a specific desired feature (e.g., certain formatting, subject, or keyword), (II) concept-based backdoor attacks that induce false negatives on jailbreak inputs, generalizing even to jailbreaks from attack strategies the defender explicitly trained against, when the backdoor trigger is present. Importantly, our threat model restricts adversaries to modifying only jailbreak samples (not benign data or labels), a constraint unexplored by prior work that makes the second objective particularly challenging. We address this with Omission Attack, which exploits a new phenomenon: when training on concept-absent unsafe samples, the classifier misassociates that concept's presence with the safe label. Both attacks cause substantial and in some cases near-complete label flipping at only a 1% poisoning rate, achieving up to 100% false positive rates and up to 96% false negative rates.