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01.
arXiv (CS.LG) 2026-06-15

Trust but Verify: Mitigating Medical Hallucinations via Post-Hoc Adversarial Auditing and Multi-Agent Feedback Loops

arXiv:2606.14149v1 Announce Type: new Abstract: Large Language Models (LLMs) are increasingly deployed in healthcare settings, yet their tendency to hallucinate poses risks when clinical decisions are involved. This study examine whether LLMs recommend recently banned or withdrawn pharmaceuticals when answering clinical questions and tests an agent-based method for reducing such errors. We developed a five-agent "Trust but Verify" system using a single LLM backbone. To measure regulatory knowledge obsolescence, we created an adversarial dataset of 103 clinical MCQs where historically correct answers now refer to banned substances. This scale ensures statistical significance across various therapeutic classes. We evaluated three open-access model families (GPT-OSS, Llama-3, Falcon-3) under vanilla and agentic conditions. Performance was measured via pointwise score, label accuracy, Hallucination Error Rate (HER), and Component Fidelity (CF) score. We also observed clinical safety regression in proprietary models. In default configurations, all models showed high hallucination rates, consistently selecting banned drugs that matched training data patterns. Our proposed agentic architecture reduced HER by approximately 53% across models. Pointwise scores shifted from -0.25 (unsafe recommendation) toward 0.0 (appropriate refusal). The safety audit intercepted dangerous outputs even when models' parametric knowledge favored the banned substance. The proposed multi-agent framework offers a model-agnostic method for enforcing regulatory compliance that prioritizes patient safety over fluent text generation. Our work demonstrates a practical approach for deploying autonomous AI systems in safety-critical healthcare settings. It shows how real-time regulatory data can be integrated into LLM pipelines to support clinical decision-making.

02.
PLOS Medicine 2026-05-06

Point-of-care early infant HIV diagnosis at birth in a pragmatic cluster-randomized trial in Mozambique and Tanzania: A comparative cost and cost-effectiveness study

by Kira Elsbernd, Issa Sabi, Ilesh V. Jani, Chishamiso Mudenyanga, Siriel Boniface, Arlete Mahumane, Joaquim Lequechane, Falume Chale, Bindiya Meggi, Kassia Pereira, Raphael Edom, Anange F. Lwilla, W. Chris Buck, Nyanda Elias Ntinyinya, Michael Hoelscher, Till Baernighausen, Arne Kroidl, Stefan Kohler, the LIFE Study Consortium Background Timely access to early infant diagnosis (EID) is crucial for newborns with HIV, as late diagnosis can delay lifesaving antiretroviral treatment (ART). We assessed the comparative cost and cost-effectiveness of integrating point-of-care EID at birth into routine care in primary healthcare settings. Methods and findings This pre-specified secondary analysis was nested in the cluster-randomized LIFE study conducted at 28 primary healthcare facilities in Mozambique and Tanzania from October 2019 to September 2021. We estimated the health system cost of point-of-care birth plus 4–8-week HIV testing (very early infant diagnosis; VEID) compared to standard-of-care (SoC) testing at 4–8 weeks only, both with immediate ART initiation. We assessed the cost-effectiveness of VEID relative to SoC with respect to ART initiation within one week of life using Bayesian hierarchical models. As this is an intermediate outcome, incremental cost-effectiveness ratios (ICERs) cannot be directly compared to available life-year-based cost-effectiveness thresholds. To contextualize results, we derived the minimum life-years gained per early ART initiation required for VEID to meet standard thresholds in a break-even analysis.VEID was associated with a higher cost and resulted in earlier ART initiation than SoC in both countries. In Mozambique, VEID increased the proportion of infants initiating ART within one week of life by 90.0 (95% CrI [67.5, 98.5]) percentage points at an incremental cost of $2,632 (95% CrI [$2,249, $3,062]) per infant with HIV. In Tanzania, VEID increased early ART initiation by 59.9 (95% CrI [20.9, 89.5]) percentage points at an incremental cost of $6,263 (95% CrI [$5,394, $7,243]) per infant with HIV. The ICER was $2,924 and $10,458 in Mozambique and Tanzania, respectively and was sensitive to intrauterine transmission rate. These findings were limited by the lack of long-term health outcome data and reliance on an intermediate outcome. Based on the break-even analysis, we estimated that VEID would need to yield 6–32 life-years gained per additional early ART initiation to meet standard thresholds. Conclusions Adding birth testing improved early ART initiation but was unlikely to be cost-effective relative to standard thresholds given current prices, vertical transmission rates, and knowledge of long-term health benefits. Cost-effectiveness could be achieved at current costs if early ART translates to substantial long-term health benefits or if targeted to infants at high risk of vertical transmission.

03.
arXiv (math.PR) 2026-06-17

Limit theorems for random Dirichlet series with summation over primes, with an application to Rademacher random multiplicative functions

arXiv:2508.15032v2 Announce Type: replace Abstract: It is shown that two conjectures put forward in the recent article Iksanov and Kostohryz (2025) are true. Namely, we prove a functional central limit theorem (FCLT) and a law of the iterated logarithm (LIL) for a random Dirichlet series $\sum_p \frac{\eta_p}{p^{1/2+s}}$ as $s\to 0+$, where $\eta_1$, $\eta_2,\ldots$ are independent identically distributed random variables with zero mean and finite variance, and $\sum_p$ denotes the summation over the prime numbers. As a consequence, an FCLT and an LIL are obtained for $\log \sum_{n\geq 1} \frac{f(n)}{n^{1/2+s}}$ as $s\to 0+$, where $f$ is a Rademacher random multiplicative function.

04.
arXiv (CS.AI) 2026-06-12

Intelligence as Managed Autonomy: Failure, Escalation, and Governance for Agentic AI Systems

arXiv:2605.27628v2 Announce Type: replace Abstract: As autonomous and agentic AI systems scale in robotic and human-machine environments, managing hallucination and persistent but unjustified action remains an open challenge. Rather than attributing these failures solely to model or alignment limitations, this paper explores the architectural vulnerability of unbounded autonomy - the presumption that an agent should continue operating regardless of rising uncertainty. It introduces a theory of managed autonomy that defines intelligent behavior through the formal capacity to detect epistemic drift, suspend reasoning, attempt recovery, and ultimately surrender control when reliability diminishes. We instantiate this theory via the SMARt (Self-Managing Multi-tier Autonomous Reasoning with Regulated/Revoked transitions) model, a four-layer framework featuring Stable, Meta-cognitive, Assisted, and Regulated states. By developing a timed, guarded Petri net formulation, we establish theoretically bounded properties for the system, demonstrating how architecture can formally mandate escalation, constrain invalid outputs, and ensure governance reachability under specified conditions. We further analyze how incorporating domain-specific trigger sets across varied operational settings (e.g., healthcare, robotics, etc.) can systematically preserve safety, assuming completeness and soundness criteria are met. Because these triggers are designed to be adaptive, the SMARt model accommodates the safe, controlled expansion of an agent's operational scope over time. We conclude that formalizing failure management within the autonomy lifecycle is a crucial step toward realizing reliable and governed artificial intelligence.

05.
arXiv (CS.AI) 2026-06-19

Optimal Scheduling in a Question-Answering Forum of Knowledge Workers

arXiv:2606.19759v1 Announce Type: new Abstract: As individuals turn to the Internet to find answers to questions they may have, several Question Answering (QA) forums have evolved, where users knowledgeable in certain topics can contribute their expertise to answering these requests for information. While these are currently volunteer based, we consider a future version employing knowledge workers who are experts in certain topics. In such a system, the request-answer processes forming the queuing system may utilize schedulers that assign requests in different topics to the experts in the forum, who may be able to answer them according to their expertise levels in different topics. With this model, we calculate the capacity of the system for handling the requests while keeping the system stable, and design schedulers that achieve capacity. We also investigate how collaboration between experts in answering requests can potentially increase capacity.

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

Spatial-Aware Reduction Framework: Towards Efficient and Faithful Visual State Space Models

arXiv:2606.19932v1 Announce Type: cross Abstract: Mamba demonstrates strong efficiency in modeling long visual sequences. However, when token reduction is applied to structurally enhanced Mamba variants, these models exhibit a severe performance collapse. We attribute this degradation to the spatially agnostic nature of existing reduction methods, which violate the two-dimensional structural premise required by the selective scanning mechanism. In this work, we propose STORM, a spatial-aware token reduction framework designed to maintain structural integrity throughout the compression process. STORM reformulates reduction into a structured operation on spatial units, enforcing localized constraints to maintain both grid topology and neighborhood coherence. As a plug-and-play module, STORM equips existing reduction pipelines with explicit spatial awareness without any training. Empirical results demonstrate that STORM achieves state-of-the-art pruning accuracy across diverse vision Mamba backbones under training-free settings. Notably, STORM delivers a substantial accuracy recovery on VMamba, outperforming prior methods by up to 63.3\% in top-1 accuracy. Meanwhile, STORM incurs only a 1.0\% accuracy drop on PlainMamba, achieving performance comparable to ViT.

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

Verbatim Chunks Beat Extracted Artifacts: A Controlled Ablation of Memory Representations for Long LLM Conversations

作者:

A growing class of conversational-memory systems compresses dialogue history into structured artifacts – extracted facts, decisions, or events – on the premise that distilled structure retrieves better than raw text. We test this premise with a controlled ablation: within one fixed retrieval-rerank-reasoning pipeline, we swap only the stored representation – LLM-extracted typed artifacts versus verbatim conversation chunks – holding the model, retriever, reranker, and judge constant. Verbatim chunks win by 15.9 points on LoCoMo (43.9% vs. 28.0%) and 22.0 points on LongMemEval-S (67.4% vs. 45.4%); a 1-hop semantic graph does not recover the gap, and five confound controls reproduce the effect. The mechanism is lossy distillation: extraction discards verbatim detail that chunks retain for free, and the extracted-artifact pipeline never beats naive RAG in overall accuracy. Concurrent positive results with near-verbatim, provenance-preserving units fit the same account: retrieval accuracy tracks how far the representation departs from the source. For the extraction designs we test, structured memory should augment verbatim text rather than replace it: a chunks $\cup$ artifacts union store matches chunks on both benchmarks while artifacts alone forfeit the gap. Code and data: https://github.com/tao-hpu/cog-canvas

08.
bioRxiv (Bioinfo) 2026-06-22

Dynamic balance of sparse flux vectors for efficient simulation of culture dynamics and metabolic network reduction

Dynamic Flux Balance Analysis (DFBA) enables simulation of microbial culture dynamics under changing environmental conditions, but remains computationally expensive for tasks such as parameter calibration and fermentation optimization when applied using genome-scale metabolic models (GEMs). To address this challenge, we introduce Dynamic Flux Vector Balancing (DFVB), a reformulation of DFBA that solves an equivalent problem using a pre-computed, sparse basis of flux solutions that reduces the dimensionality of the internal optimization problem without information loss. Notably, DFVB provides a compact, interpretable representation of flux states that can readily identify dynamically inactive pathways and enable simulation-based automatic metabolic network reduction. We showed that DFVB produces the same culture dynamics as DFBA across multiple model scales and conditions, and identifies inactive reactions more accurately than Flux Variability Analysis (FVA) when compared to transcriptomic data profiles. Furthermore, computational performance analyses demonstrated that integrating DFVB with solver warm-start strategies and model reduction enhances computational efficiency relative to DFBA, yielding up to 3-fold reductions in simulation time for large-scale metabolic models. Finally, kinetic parameter estimation of culture dynamics with DFVB in two fermentation scenarios using a large-scale yeast GEM reached equal or higher prediction fidelity and narrower confidence intervals than DFBA, indicating improved parameter identifiability and robustness. Together, these results position DFVB as a scalable, robust, and biologically coherent framework for dynamic metabolic modeling, easing the integration of GEMs for culture dynamics simulation.

09.
arXiv (CS.LG) 2026-06-16

David vs. Goliath in Next Activity Prediction: Argmax vs. LSTM, Transformer, and LLM

arXiv:2606.15868v1 Announce Type: new Abstract: Next activity prediction (NAP) is a cornerstone of predictive process monitoring (PPM), enabling organizations to move from retrospective analysis to proactive process steering. The PPM field has progressed from classical machine learning through deep learning architectures such as LSTMs and Transformers to large language models (LLMs). Despite growing model complexity, no benchmark jointly compares LLMs, Transformers, LSTMs, and simple baselines in a direct sequence modeling setting for NAP. In this paper, we fill this gap with a systematic benchmark. We compare vocabulary-adapted LLMs, Transformers trained from scratch, LLM-distilled Transformers, and LSTMs against a simple counting-based argmax baseline across seven real-life event logs. Our results tell a David vs. Goliath story: pretraining confers no consistent improvement over training from scratch, model size shows little effect on performance, and on most datasets the argmax baseline matches or approaches the performance of billion-parameter LLMs.

10.
arXiv (CS.CL) 2026-06-18

Retell, Reward, Repeat: Reinforcement Learning for Narrative Theory-Informed Story Retelling

Counterfactual story retelling exposes LLM shortcomings in constrained narrative solution spaces where they can no longer rely on recalling memorised training data. Ground-truth-based post-training, such as SFT, fails to teach LLMs how to generate logical and rational narrative events. In this paper, we introduce Retell, Reward, Repeat (RRR), an RL-based pipeline synthesising Structuralist Narratology with scalar narrativity to teach storytelling structure. We extend the TimeTravel dataset with human-annotated stages of narrative equilibrium to evaluate reward models. By using d-RLAIF, RRR derives training signals from the narrativity of textual features without the need for reference outputs. Evaluations demonstrate that RRR-trained LLMs outperform few-shot and SFT baselines in logic, rationality, and completeness, with output quality additionally validated by blind human preference. Relying on a small, query-only dataset, RRR provides a linguistically grounded, cost-effective post-training mechanism for storytelling–a domain currently lacking effective post-training methods. RRR highlights the continued relevance of integrating established linguistic theories into contemporary NLP.

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

Equivariant Graph Neural Networks Improve Optical Spectra Prediction for Materials Screening

arXiv:2606.19133v1 Announce Type: cross Abstract: Scalable prediction of optical spectra is a critical component of high-throughput materials screening for optoelectronic applications such as solar cells. Existing surrogate models are trained on spectra computed from lower levels of theory or rely on rotation-invariant scalar features, limiting their geometric expressiveness. We explore the use of equivariant graph neural networks for optical spectra prediction, adapting GotenNet to this task and evaluating it on multiple datasets including a recently published collection of 10,533 structures with spectra computed at the level of the random phase approximation (RPA). The proposed model outperforms the current state of the art, with the largest gains in the 0-8 eV range and on predicting the static real permittivity, both of particular relevance for thin-film optics.

12.
arXiv (CS.CL) 2026-06-18

Speech-Driven End-to-End Language Discrimination towards Chinese Dialects

Language discrimination among similar languages, varieties, and dialects is a challenging natural language processing task. The traditional text-driven focus leads to poor results. In this paper, we explore the effectiveness of speech-driven features towards language discrimination among Chinese dialects. First, we systematically explore the appropriateness of speech-driven MFCC features towards CNN-based language discrimination. Then, we design an end-to-end speech recognition model based on HMM-DNN to predict Chinese dialect words. We adopt attention to extract the discriminative words related to different Chinese dialects. Finally, through a CNN, we combine the word-level embedding and the MFCC-based features. Evaluation of two benchmark Chinese dialect corpora shows the appropriateness and effectiveness of the proposed speech-driven approach to fine-grained Chinese dialect discrimination compared to the state-of-the-art methods.

13.
arXiv (CS.AI) 2026-06-17

An Evaluation of Data Leakage Risks in Tool-Using LLM Agents in Realistic Scenarios

arXiv:2606.17114v1 Announce Type: cross Abstract: AI agents are increasingly being adopted in enterprise and personal settings with access to emails, databases, documents, and other tools where they can read, update, and disseminate sensitive information. Much of prior research on data leakage risks in agents has focused on adversarial data exfiltration through prompt injections and jailbreaks. However, sensitive information may also be exposed during non-adversarial use, creating leakage risks even when users issue benign requests. We report a joint evaluation by the Singapore AI Safety Institute and the Korea AI Safety Institute examining agent data leakage in 12 realistic, non-adversarial tasks spanning customer support, DevOps, web automation, and enterprise and personal productivity. The evaluation covers five risk types: lack of data awareness, audience awareness, policy compliance, data minimization, and access-boundary awareness. Both institutes tested a common set of scenarios mirroring real-world deployments using independent testing environments and task-specific LLM-judge rubrics. Across the three tested agents, none achieved fully correct and fully safe execution across all scenarios. Successful task completion often coincided with data-handling failures such as accessing unnecessary information or disclosing information to inappropriate recipients, indicating that capability and data-handling safety should be evaluated separately. Qualitative review also revealed claim-action mismatches, simulation-aware behavior, user-simulator role reversal, and interpretation gaps in automated judging. Overall, the results indicate that operational data leakage is a first-order agent-safety concern distinct from adversarial exfiltration and provide a methodology for future evaluations of agent data-handling safety.

14.
arXiv (CS.CV) 2026-06-16

Training-Free Open-Vocabulary Visual Grounding for Remote Sensing Images and Videos

Remote sensing visual grounding (RSVG) aims to localize a referred target in a remote sensing image or video according to a natural language expression. Existing RSVG methods usually rely on task-specific manual annotations, which are costly to collect and inevitably limited in covering the diversity of real-world geospatial scenarios. As a result, they often struggle to generalize to open-vocabulary queries involving novel objects, fine-grained attributes, complex spatial relationships, and functional semantics. In this paper, we propose RSVG-ZeroOV, a training-free framework that leverages frozen generic foundation models for zero-shot open-vocabulary RSVG. RSVG-ZeroOV follows an Overview-Focus-Evolve paradigm, which exploits the distinct yet complementary attention patterns of vision-language models (VLMs) and diffusion models (DMs) to progressively generate precise grounding results. Specifically, (i) Overview utilizes a VLM to extract cross-attention maps that capture semantic correlations between the referring expression and visual regions; (ii) Focus leverages the fine-grained modeling priors of a DM to compensate for object structure and shape information often overlooked by VLM attention; and (iii) Evolve introduces a simple yet effective attention evolution module to suppress irrelevant activations, yielding purified object masks. To handle video inputs, we further present Video RSVG-ZeroOV, which extends image-level grounding to spatio-temporal grounding through a query-relevant key-frame selector and a temporal propagator, enabling efficient and temporally coherent video grounding without video annotations or fine-tuning. Extensive experiments on six image and video grounding benchmarks show that RSVG-ZeroOV consistently outperforms existing zero-shot baselines and achieves competitive or superior performance compared with weakly- and fully-supervised methods.

15.
arXiv (CS.AI) 2026-06-11

Runtime Enforcement of Hybrid System Properties

arXiv:2606.12022v1 Announce Type: cross Abstract: Runtime enforcement has emerged as a promising approach for ensuring the safety of autonomous and cyber-physical systems operating in uncertain and dynamic environments. Unlike traditional runtime verification, runtime enforcement actively intervenes during execution to prevent property violations by modifying unsafe system behaviors. Existing enforcement frameworks primarily focus on untimed or discrete-time specifications and are often limited to delaying or suppressing events, making them inadequate for reactive systems exhibiting complex continuous dynamics. In this paper, we propose a runtime enforcement framework where safety requirements are modeled using Hybrid Automata (HA). The framework combines discrete-event editing with continuous-time monitoring to support enforcement actions such as suppression, delay, and insertion of events at arbitrary time instants. Upon observing environmental inputs, the automaton is initialized, and runtime reachability analysis is used to synthesize safe corrective actions. We formally define the enforcement problem for safety hybrid automata, establish enforceability conditions, and present an online enforcement algorithm for reactive systems. A detailed case study on an Adaptive Cruise Control (ACC) system demonstrates the effectiveness of the proposed approach in maintaining safety properties under unsafe controller behaviors. Experimental results show that the framework introduces minimal computational overhead while ensuring continuous compliance with safety requirements in real time.

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

SuperThoughts: Reasoning Tokens in Superposition

Long Chain-of-Thought (CoT) reasoning improves LLM problem-solving but is computationally expensive due to sequential token generation. While recent works explore reasoning in continuous latent spaces to bypass discrete token generation, they often struggle with training stability and fail to scale to complex, long-horizon tasks due to lack of supervision signal. We propose SuperThoughts, which compresses pairs of consecutive CoT tokens into single latent representations and decodes two tokens per step via a lightweight Multi-Token Prediction (MTP) module. This preserves discrete token supervision at training time while doubling throughput at inference time. We finetune Qwen2.5-Math-1.5B-Instruct, Qwen2.5-Math-7B-Instruct, Qwen2.5-Math-14B-Instruct, and evaluate on MATH500, AMC, OlympiadBench, and GPQA-Diamond. With a confidence-based adaptive mechanism that falls back to standard decoding when uncertain, SuperThoughts achieves $\sim$20–30\% CoT length reduction while maintaining accuracy with minimal degradation (1-2 points accuracy drop on most tasks).

17.
arXiv (CS.CL) 2026-06-15

CORA: Analyzing and bridging thinking-answer gap in Multimodal RLVR via Consistency-Oriented Reasoning Alignment

Reinforcement learning with verifiable rewards (RLVR) has successfully elicited the reasoning capabilities of large language models, motivating its extension to multimodal scenarios. Existing methods primarily focus on improving the visual coverage of reasoning traces and mitigating visual hallucinations, but underestimate the semantic inconsistency between the reasoning process and the final answer. In this paper, we delve into thinking-answer inconsistency in RLVR for large vision-language models (LVLMs), showing thorough analyses of rollouts collected throughout Group Relative Policy Optimization (GRPO) training process and post-RLVR evaluation outputs that this issue persists during training and remains present during inference. Motivated by the analysis, we propose Consistency-Oriented Reasoning Alignment (CORA), which introduces thinking-answer semantic consistency into RLVR through a lightweight plug-and-play consistency reward model, and further incorporates Hybrid Reward Advantage Splitting (HRAS) to stably coordinate task and consistency optimization. Extensive experiments across representative multimodal reasoning benchmarks and mainstream LVLMs show that CORA improves task performance while effectively mitigating thinking-answer inconsistency, leading to more faithful reasoning traces.

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

Exploring Feature Extraction Technique Parameters for Acoustic Gunshot Classification

arXiv:2606.19568v1 Announce Type: cross Abstract: Acoustic gunshot detection is a problem with applications across civilian public safety, military operations, and wildlife conservation, yet the field lacks a rigorous exploration of feature extraction techniques with a focus on generalization to realistic data. The mixed effectiveness of commercial gunshot detection and classification systems indicates an open problem that is not adequately addressed by the current literature. In this paper, we present a systematic investigation of common feature extraction techniques using a dataset of 23,000 gunshot recordings across 85 firearms and 21 calibers. We benchmark three feature extraction techniques with 12 total unique parameter sets using ResNet-18. Our results demonstrate that using the correct feature extraction technique can improve top-1 accuracy by up to 20%, and utilizing the correct parameters for a given feature extraction technique can improve that value by up to 4.7%.

19.
arXiv (CS.AI) 2026-06-16

Learn from Your Mistakes: Tree-like Self-Play for Secure Code LLMs

arXiv:2606.03489v2 Announce Type: replace-cross Abstract: While Large Language Models (LLMs) excel in code generation, they remain prone to replicating subtle yet critical vulnerabilities endemic to their training data. Current alignment techniques, such as Supervised Fine-Tuning (SFT) and Reinforcement Learning (RL), typically apply coarse-grained optimization at the sequence level. This approach often fails to address the localized nature of security flaws, where a single incorrect token choice can compromise an entire program. To bridge this gap, we introduce Tree-like Self-Play (TSP), a framework that reframes secure code generation as a fine-grained sequential decision process. Unlike standard methods that blindly maximize likelihood, TSP constructs a decision tree where the model explores branching trajectories–generating both secure "golden paths" and vulnerable variants. By treating code generation as a self-play game, the model learns to strictly discriminate against its own localized errors. This provides a dense, on-policy learning signal that forces self-correction precisely at the critical decision nodes where vulnerabilities typically emerge. Our experiments demonstrate that TSP fundamentally enhances model reliability. In Python security benchmarks, TSP boosts CodeLlama-7B's pass rate (SPR@1) to 75.8%, significantly outperforming SFT (57.0%) and unstructured self-play baselines. Crucially, TSP induces robust out-of-distribution generalization: the model not only reduces vulnerabilities in unseen categories (CWEs) by 24.5% but also successfully transfers security principles learned from C/C++ to diverse languages, including Python, Go, and JavaScript. This suggests that TSP does not merely memorize patches, but internalizes abstract, language-agnostic security logic.

20.
bioRxiv (Bioinfo) 2026-06-10

HOMED enables hierarchical and multimodal optimization of DNA methylation deconvolution across tissues

Cellular heterogeneity is a major confounder in bulk DNA methylation data for epigenome-wide association studies. Existing reference-based DNAm deconvolution methods often ignore hierarchies among related cell types and may generalize poorly across datasets due to limited variability in reference profiles. We developed HOMED (Hierarchically Optimized Methylation Deconvolution), a framework that integrates cell-lineage hierarchies, single-cell RNA sequencing-guided deconvolution, and paired bulk RNA-seq/DNAm data for CpG signature optimization. Across simulated and real peripheral blood mononuclear cell, lung, and placental datasets, HOMED consistently yielded the highest PCCs and lowest RMSEs, outperforming existing scRNA-seq-guided DNAm deconvolution methods, improving accuracy, resolution, and cross-tissue generalizability.

21.
arXiv (CS.LG) 2026-06-11

DeepRHP: A Hybrid Variational Autoencoder for Designing Random Heteropolymers as Protein Mimics

arXiv:2606.11651v1 Announce Type: new Abstract: Synthetic random heteropolymers (RHPs), consisting of a predefined set of monomers, offer an approach toward the design of protein-like materials. These RHPs, if designed appropriately, can mimic protein behavior and function. As such, there is a need for computational tools to efficiently guide RHP design. We bridge this gap by developing DeepRHP, a modified variational autoencoder (VAE) model under a semi-supervised framework. By equipping a classical VAE with an additional feature-based VAE, DeepRHP forces the latent space to capture structures of critical chemical features as well as individual RHP sequence patterns. In this sense, our method is versatile by allowing any relevant features to be incorporated in a hybrid manner. We demonstrate the effectiveness of DeepRHP by suggesting potential monomer compositions that stabilize membrane proteins (e.g. Aquaporin Z) in non-native environments and cross-validating our prediction with published results. The concordance between our model and true RHP function suggests strong potential in utilizing hybrid autoencoder architectures to guide RHP design for proteins and other biological compounds.

22.
arXiv (CS.AI) 2026-06-17

Constitutional On-Policy Safe Distillation

arXiv:2606.03089v2 Announce Type: replace-cross Abstract: On-policy self-distillation (OPSD) has emerged as an efficient post-training paradigm by using a teacher conditioned on privileged information to provide dense token-level supervision. Prior work has shown that OPSD can collapse in verifiable reasoning tasks, but safety alignment differs in that it is guided by high-level constitutions rather than explicit target answers, making it a natural setting to revisit dense distillation. However, our pilot study show that safety OPSD still suffers from severe collapse: constitutional conditioning contracts the teacher distribution toward short and overly conservative responses, and Reverse KL further amplifies this contraction into reduced expressiveness. We formalize this effect as geometric leakage under safety boundaries in a non-orthogonal semantic space, where safety pressure transfers into the expressiveness dimension. Based on this analysis, we propose Constitutional On-Policy Safe Distillation (COPSD), which first calibrates the teacher through a Cross-SFT cold-start and then performs constitution-conditioned on-policy distillation. Experiments on 12 benchmarks show that COPSD achieves a consistently stronger safety–helpfulness trade-off than baselines while substantially reducing the safety tax on general reasoning ability.

23.
bioRxiv (Bioinfo) 2026-06-18

Deciphering shared and divergent tissue architectures from cross-species spatial transcriptomics

作者:

The integration of spatial transcriptomics (ST) data across species is essential for cross-species and translational studies, but remains challenging due to molecular divergence and anatomical differences between organisms. We present STACAME, a graph attention autoencoder-based framework to decipher shared and divergent tissue architectures from cross-species ST data by explicitly modeling both orthologous and species-specific genes. STACAME aligns ST slices in a spatially aware manner, identifies homologous and species-specific domains, and enables a suite of downstream comparative analyses. We demonstrate its utility by integrating ST datasets from diverse tissues, including hippocampus, isocortex, embryo, breast, liver, and cerebellum, across multiple species such as human, macaque, marmoset, mouse, and zebrafish. STACAME supports cross-species spatial domain alignment, the detection of shared and divergent spatially variable genes, development alignment and comparison, and the 3D integration of tissue architecture. This flexible approach facilitates the translation of findings from model organisms to humans, providing a unified computational platform for cross-species spatial transcriptomics.

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

Evolving Agents in the Dark: Retrospective Harness Optimization via Self-Preference

AI agents rely on a harness of skills, tools, and workflows to solve complex problems. Continually improving this harness is essential for adapting to new tasks. However, existing optimization methods typically require ground-truth validation sets, yet such labeled data is difficult to acquire in practical deployment settings. To address this problem, we introduce Retrospective Harness Optimization (RHO), a self-supervised method that optimizes the agent harness using only past trajectories. Specifically, RHO selects a diverse coreset of challenging tasks from past trajectories and re-solves them in parallel. The agent analyzes these rollouts using self-validation and self-consistency, then generates candidate harness updates and selects the most effective one by its own pairwise self-preference. We evaluate RHO across three diverse domains, spanning software engineering, technical work, and knowledge work. Notably, a single optimization round improves the pass rate on SWE-Bench Pro from 59% to 78% without any external grading. Furthermore, our analysis demonstrates that RHO effectively targets prior failure modes. As a result, the optimized harness alters the agent's behavior patterns and sustains higher accuracy during long-horizon sessions.

25.
arXiv (CS.AI) 2026-06-18

SkillRevise: Improving LLM-Authored Agent Skills via Trace-Conditioned Skill Revision

arXiv:2606.01139v3 Announce Type: replace Abstract: Agent skills are procedural artifacts that enable LLM agents to execute workflows, verify constraints, and recover from failures. Existing self-evolving methods refine skills using accumulated trajectories. However, they struggle in cold-start settings, where only an initial, imperfect skill is available. Consequently, skill construction defaults to expert authoring or one-shot LLM generation. Expert-authored skills are costly and may not align with how LLM agents actually execute tasks, while one-shot generated skills can be syntactically well formed yet behaviorally weak. To bridge this gap, we propose SkillRevise, an execution-grounded framework designed to iteratively refine these initial skills. SkillRevise diagnoses skill defects from execution evidence, retrieves relevant repair principles from a general memory, and applies execution-anchored edits. By re-executing candidates, it retains the first verifier-passing skill within the revision budget and falls back to empirical utility only when no candidate succeeds. Evaluated across three benchmarks and five LLMs, SkillRevise substantially outperforms one-shot baselines, improving the base agent's success rate on SkillsBench from 36.05% to 61.63%. Furthermore, the revised skills transfer across both executors and task environments, suggesting that SkillRevise captures reusable procedural knowledge beyond any single executor.