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01.
arXiv (CS.AI) 2026-06-11

Precomputing Multi-Agent Path Replanning Using Temporal Flexibility

Authors:
Issa Hanou↗Eric Kemmeren↗Devin Wild Thomas↗Mathijs de Weerdt↗

arXiv:2601.04884v3 Announce Type: replace Abstract: Executing a multi-agent plan can be challenging when an agent is delayed, because this typically creates conflicts with other agents. So, we need to quickly find a new safe plan. Replanning only the delayed agent often does not yield an efficient plan, and sometimes cannot even yield a feasible one. On the other hand, replanning other agents may lead to a cascade of changes and delays, and it is computationally expensive. We show how to efficiently replan a single delayed agent by tracking and using the temporal flexibility of other agents while avoiding cascading delays. This flexibility is the maximum delay that the agent can take without changing the order with agents other than the initially delayed agent, or further delaying other agents. Our algorithm, FlexSIPP, precomputes all possible plans for the delayed agent and returns the changes to the other agents within the given scenario. We demonstrate our method in a real-world case study of replanning trains in the densely-used Dutch railway network and in the MovingAI MAPF benchmark set. Our experiments show that FlexSIPP provides effective solutions relevant to real-world adjustments, and within a reasonable timeframe.

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

DeFAb: A Verifiable Benchmark for Defeasible Abduction in Foundation Models

Authors:
Patrick Cooper↗Alvaro Velasquez↗

arXiv:2606.18557v1 Announce Type: new Abstract: A rule-based logic solver resolves every instance in our benchmark in under 50 microseconds with 100% accuracy; the best frontier language model reaches 65% at best and drops to 23.5% under rendering-robust evaluation (worst case over four surface renderings). We introduce DeFAb (Defeasible Abduction Benchmark), a dataset and generation pipeline that converts four decades of publicly funded knowledge bases into formally grounded instances for defeasible abduction: constructing hypotheses that explain anomalies by overriding defaults while preserving unrelated expectations. Because every hypothesis must pass polynomial-time checks for valid derivation, conservativity, and minimality, DeFAb makes logical rigor the instrument for measuring creativity and theoretical reasoning, scoring the disciplined construction of theory revisions rather than fluent but theory-destroying prose. The pipeline pairs taxonomic hierarchies (OpenCyc, YAGO, Wikidata) with behavioral property graphs (ConceptNet, UMLS) to produce 372,648+ instances across 33.75M materialized rules from 18 sources, in three levels with polynomial-time verifiable gold standards. Four frontier models do not reliably internalize defeasible reasoning: rendering-robust Level 2 accuracy is 7.8-23.5%; chain-of-thought variance (~36 pp) exceeds any inter-model gap; and a matched contamination control isolates a +19.4 pp Level 3 gap. We further release DeFAb-Hard (a 235-instance Level 3 difficulty variant; best model 53.3% vs 100% symbolic) and CONJURE (a kernel-verified transformative-creativity variant of 560 Lean 4/Mathlib instances whose gold answers are definitions the proof kernel did not previously contain, judge-free verifier; a pilot finds zero novel concepts). The same verifier doubles as an exact reward for preference optimization (DPO, RLVR/GRPO). Released under MIT at https://huggingface.co/datasets/PatrickAllenCooper/DeFAb.

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

RippleBench: Capturing Ripple Effects Using Existing Knowledge Repositories

Authors:
Roy Rinberg↗Usha Bhalla↗Igor Shilov↗Flavio P. Calmon↗Rohit Gandikota↗

arXiv:2512.04144v2 Announce Type: replace Abstract: Targeted interventions on language models, such as unlearning or model editing, aim to modify specific information, but their effects often propagate to related, unintended areas (e.g., removing virology content may degrade performance on allergies); these side-effects are commonly referred to as the ripple effect. We introduce RippleBench-Maker, an automatic pipeline that retrieves semantic neighbors of any source concept from a knowledge repository and generates multiple-choice questions at varying semantic distances. We instantiate this framework using WikiRAG, an open-source RAG system over English Wikipedia, to construct RippleBench-WMDP-Bio (584 seed topics, 352,961 questions), and evaluate eight unlearning methods on Llama3-8B-Instruct. All eight exhibit accuracy drops that are largest near the unlearned target and decay with semantic distance, each with a distinct propagation profile. We replicate these findings across Mistral-7B, Zephyr-7B, and Yi-34B; cross-model delta curves are nearly identical, suggesting ripple effects are a property of the unlearning method rather than the base model. We validate all major pipeline stages using a four-experiment Mechanical Turk study (5,200+ responses, 61 workers). We release all code, data, and infrastructure.

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04.
arXiv (CS.AI) 2026-06-19

Secure Coding Drift in LLM-Assisted Post-Quantum Cryptography Development: A Gamified Fix

Authors:
R. D. N. Shakya↗C. P. Wijesiriwardana↗S. M. Vidanagamachchi↗Nalin A. G. Arachchilage↗

arXiv:2606.19474v1 Announce Type: cross Abstract: The transition to Post Quantum Cryptography (PQC) introduces considerable implementation complexity, requiring strict adherence to constant-time execution, side channel resistance, and precise parametrisation. Simultaneously, large language models (LLMs) are heavily embedded in software development workflows, including cryptographic engineering. While LLMs improve productivity, evidence shows that they frequently generate insecure or suboptimal code, particularly in security critical domains. This paper introduces Secure Coding Drift in PQC, a novel socio technical vulnerability model capturing the gradual degradation of secure coding practices due to sustained reliance on LLM-generated code. Unlike prior work that focuses on static vulnerabilities, we conceptualise security risk as a longitudinal behavioural phenomenon rising from human AI interaction. To mitigate this, we propose a gamified, LLM augmented secure coding framework that embeds adversarial evaluation, behavioural feedback, and security scoring into development workflows. Our approach reframes LLMs from passive assistants into active security co-pilots, contributing toward safer PQC implementation in AI mediated environments.

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05.
arXiv (CS.CL) 2026-06-17

HistoRAG: Embedding Historical Methodology in Retrieval-Augmented Generation Through Critical Technical Practice

Authors:
Noah J. Kim-Baumann↗Torsten Hiltmann↗

Retrieval-Augmented Generation (RAG) is the prevailing architecture for grounding language model outputs in external evidence, yet its dominant evaluation paradigms and default configurations remain oriented toward factual question-answering. For interpretive disciplines such as historical studies, RAG embeds assumptions that conflict with scholarly practice. We introduce HistoRAG, a framework that translates historiographical principles into concrete architectural interventions. Separated retrieval and generation decouples source discovery from interpretation, temporal windowing enforces balanced source representation across the research period as a methodological requirement of historical inquiry, and LLM-as-judge evaluation makes relevance judgments transparent and contestable. We evaluate these interventions using SPIEGELragged, applied to 102,189 articles from Der Spiegel (1950-1979). Each intervention addresses a measurable deficiency in standard RAG: era-specific vocabulary retrieves zero chunks from the 1950s when using 1970s terminology, evidence of the temporal skew that motivates windowing; vector similarity and LLM-assessed relevance correlate only weakly (Spearman rho = 0.275), motivating post-retrieval evaluation; and keyword-based and semantic retrieval surface largely disjoint source pools, motivating an architecture in which both operate as complementary retrieval layers under a shared LLM evaluation filter. We also introduce the concept of Zwischentexte (intermediate texts that function as interpretive proposals rather than findings) as a framework for responsible integration of LLM-generated text into scholarly practice. The architecture offers a model for how domain-specific epistemological commitments can be translated into RAG design decisions, and may transfer to other interpretive disciplines working with large corpora.

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

Cross-Modal Registration Between 3D and 2D Fingerprints via Pose-Aware Unwrapping and Point-Cloud Fusion

Authors:
Xiongjun Guan↗Jianjiang Feng↗Jie Zhou↗

Three-dimensional (3D) fingerprints preserve global finger geometry and local ridge structure while avoiding contact-induced deformation, but they remain difficult to integrate with legacy two-dimensional (2D) fingerprint systems. This paper addresses the intermediate stage between 3D acquisition and cross-modal matching, and presents a unified framework for 3D fingerprint preprocessing and registration across contactless and contact-based 2D modalities. The framework combines four components: 1) a nonparametric visualization and unwrapping method that converts a 3D fingerprint point cloud into a rolled-equivalent 2D representation without relying on a global finger-shape model; 2) a point-cloud fusion pipeline that registers and mosaics multiple partial 3D captures into a more complete fingerprint model; 3) an ellipse-based pose normalization method for canonical finger alignment; and 4) a pose-aware cross-modal registration strategy that improves compatibility between 3D fingerprints and both contactless and contact-based 2D fingerprints. Experiments on a self-collected multimodal fingerprint database containing 150 fingers show that the proposed framework achieves ridge-level 3D registration accuracy, robust pose estimation, and consistent gains in 2D compatibility. In particular, the 3D fusion error is concentrated around 0.09 mm, contactless 2D–3D registration reaches ridge-scale projection accuracy, and pose-aware unwrapping improves genuine matching scores relative to generic 3D unwrapping. These results support the use of 3D fingerprints as an effective geometric bridge across heterogeneous fingerprint modalities. The baseline implementation has been publicly released at https://github.com/XiongjunGuan/3DFpVisual.

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07.
arXiv (CS.AI) 2026-06-16

LLM4RTL: Tool-Assisted LLM for RTL Generation

Authors:
Jing Jin↗Robert Chu↗Ning Yan↗Masood S. Mortazavi↗

arXiv:2606.15500v1 Announce Type: cross Abstract: Large language models (LLMs) have facilitated impressive progress in software engineering, code generation, tooling, and systems. Concurrently, a significant body of research has developed which explores a growing variety of methods and systems for applying LLMs to hardware and chip design (e.g., systems for RTL code generation based on functional description). However, when it comes to open Verilog/RTL code-generation, we need high-quality training samples to build specialized and more effective LLM systems through fine-tuning or low-rank adaptation. Here, we propose a ``judge-renew-check-renew-check'' (JRCRC) pipeline which updates a current public dataset using a hierarchy of state-of-the-art commercial LLM models differing in their costs and capabilities in RTL code generation. This approach achieves a cost-effective mechanism for filtering and refining code-generation samples into a higher-quality training dataset. Our experiments also identify some common weaknesses of LLMs in rule-based reasoning and logic, and consequently, in RTL code-generation. Having identified these weaknesses, we develop an architecture for incorporating pre-processing tools to dynamically assist the LLMs in inferring logical relationships from tabular data formats. With our tools-assisted architecture for RTL code generation, we achieve significant overall performance gains in the VerilogEval benchmark and outperform many state-of-the-art methods. Our LLM4RTL system achieves performance comparable to that of GPT-4O using a significantly much smaller LLM.

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08.
arXiv (CS.LG) 2026-06-15

Neural Slack Variables for Shape Constraints

Authors:
Ruben Wiedemann↗Antoine Jacquier↗Lukas Gonon↗

arXiv:2606.13803v1 Announce Type: new Abstract: Enforcing functional inequality constraints such as monotonicity and convexity in neural networks is a fundamental challenge in many industrial and scientific applications. Classical one-sided penalty methods, along with primal-dual methods gated by complementary slackness, provide constraint gradients only at violated locations, resulting in fragile satisfaction. Architectures that guarantee feasibility by construction, on the other hand, remain largely limited to elementary cases and impose additional inductive biases. We introduce neural slack variables, a deep learning native primal-side approach that converts constraint enforcement into a regression problem by coupling the primary network with a jointly learned auxiliary network. The auxiliary network serves as a valid target for the primary network's constraint quantities, inducing feasibility and regularity. Neural slack variables achieve zero measured violations on dense-grid monotonicity and convexity test cases, where penalty and primal-dual baselines leave residual violations, and enable arbitrage-free learning of volatility surfaces, an open industrial challenge in quantitative finance.

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09.
arXiv (CS.LG) 2026-06-11

MPK: A Compiler and Runtime for Mega-Kernelizing Tensor Programs

Authors:
Xinhao Cheng↗Zhihao Zhang↗Yu Zhou↗Jianan Ji↗Jinchen Jiang↗Zepeng Zhao↗Ziruo Xiao↗Zihao Ye↗Yingyi Huang↗Ruihang Lai↗Hongyi Jin↗Bohan Hou↗…

arXiv:2512.22219v2 Announce Type: replace-cross Abstract: We introduce Mirage Persistent Kernel (MPK), the first compiler and runtime system that automatically transforms multi-GPU model inference into a single high-performance mega-kernel. MPK introduces an SM-level graph representation that captures data dependencies at the granularity of individual streaming multiprocessors (SMs), enabling cross-operator software pipelining, \rev{fine-grained overlap of computation and communication, and other optimizations that are infeasible under the conventional kernel-per-operator execution model}. The MPK compiler lowers tensor programs into optimized SM-level task graphs and generates fast CUDA implementations for each task, while the MPK in-kernel parallel runtime executes these tasks within a single persistent mega-kernel using decentralized scheduling across SMs. Together, these components provide end-to-end kernel fusion with minimal developer effort, while preserving the flexibility of existing programming models. Our evaluation shows that MPK significantly outperforms existing kernel-per-operator LLM serving systems, achieving up to 1.7$\times$ lower end-to-end inference latency and pushing LLM inference performance close to the limits of the underlying hardware. MPK is publicly available at https://github.com/mirage-project/mirage.

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10.
arXiv (CS.CL) 2026-06-15

Detecting Historical Turning Points in Italian Media: A Complex Systems Approach to a Diachronic News Corpus

Authors:
Dario Zarcone↗Salvatore Miccich\`e↗David Sanchez↗

The increasing availability of large-scale textual corpora has opened new possibilities for data-driven, quantitative approaches to historical analysis using Natural Language Processing (NLP). However, diachronic corpora with historical relevance from the pre-digital era remain scarce and often incomplete. We present a quantitative approach to historical analysis based on the reconstruction and exploration of a diachronic corpus of around 600,000 articles from the Italian newspaper "La Repubblica", covering all the articles published from the 1st of January 1985 to the 31st of December 2000 - a period of major political, social, and geopolitical change in Italy and globally. Using NLP techniques, we analyze the text at both lexical and semantic levels; we then apply tools from complex systems and statistical physics to trace shifts in media discourse over time. This allows us to detect key transition periods, such as the transition from the First Republic to the Second Republic in Italy, or major international conflicts like the Gulf War or the Kosovo War, without relying on prior labeling. The results show how combining computational linguistics with ideas from complex systems can offer new quantitative insight into historical changes, opening up new paths for studying the dynamics of media and society through large-scale textual data.

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

Multi-Field Hybrid Retrieval-Augmented Generation for Maritime Accident Root Cause Analysis

Authors:
Seongjin Kim↗Sungil Kim↗

arXiv:2606.13249v1 Announce Type: new Abstract: Maritime accident adjudication reports contain critical tribunal findings for root cause analysis (RCA), yet retrieving relevant precedents and drafting consistent reports from decades of records remains labor-intensive. This paper proposes a multi-field hybrid retrieval-augmented generation (RAG) framework for automated maritime RCA, utilizing a comprehensive dataset of 13,329 Korea Maritime Safety Tribunal (KMST) reports (1971-2025). We transform raw adjudications into a structured knowledge base of "incident cards", indexing three distinct fields-Summary, Causes, and Disposition-alongside a hierarchical L1/L2 cause taxonomy. Our retrieval strategy employs a field-aware hybrid approach, fusing sparse and dense rankings via Reciprocal Rank Fusion (RRF). Given the lack of large-scale expert relevance labels, we evaluate retrieval performance using ceiling-normalized recall and nDCG based on a metadata-derived proxy relevance score. Experimental results demonstrate that our proposed retrieval significantly outperforms baseline methods, improving NormRecall@100 from 0.18 to 0.55. Furthermore, grounding the generator on the retrieved precedents enhances RCA generation quality over an LLM-only baseline, increasing the LLM-as-a-judge score from 3.34 to 3.72. These findings suggest that field-aware RAG can substantially streamline maritime safety investigation workflows by enabling faster precedent search and more consistent, evidence-based RCA drafting.

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

Anytime-Valid Confirmation of Label-Shift Corrections

Authors:
Seungjin Choi↗

arXiv:2606.14028v1 Announce Type: cross Abstract: In small-batch scientific deployments, labeled target outcomes may be too scarce for reliable shift estimation even when unlabeled target inputs are available. We address the complementary setting where the practitioner has a pre-specified label-shift correction from domain knowledge and asks whether incoming labeled outcomes support it. We show that the per-observation likelihood ratio between a label-shift-corrected predictive and the source predictive is a conditional e-value, so its running product is a nonnegative martingale and Ville's inequality yields an anytime-valid confirmation rule. The log martingale equals the cumulative negative log-predictive density (NLPD) gap between the source and the corrected predictive, converting routine model monitoring into a formal sequential test. Rejection means the incoming data support the posited correction relative to the source predictive, but it is not a precise estimate of the degree of shift. Closed forms are available for GP sources with Gaussian label-shift ratios. GP regression simulations validate Type I control, finite-sample power, miscalibration sensitivity, and the small-batch advantage of a reliable prior over label-based re-estimation.

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13.
bioRxiv (Bioinfo) 2026-06-18

Elucidating the Design Space of Generative Models for Single-Cell Perturbation Prediction

Authors:
Bhattacharya↗Gensbigler↗Karim↗Lees↗

Next-token prediction has produced predictable scaling in language, but the recipe presumes a sequence of tokens with a meaningful order. Single-cell RNA-seq counts have no natural gene ordering, so applying the recipe directly to raw expression fails under an ill-suited left-to-right bias. We instead ask whether a learned latent can supply the structure the recipe needs. We introduce texttt{ExpressionVAE} (eVAE), a discrete-latent perturbation model that compresses each cell into a short sequence of discrete codes through a finite-scalar-quantization (FSQ) bottleneck and trains a perturbation-conditioned discrete prior over those codes. On Replogle and Parse~1M, eVAE sets a new state of the art on every distributional metric and leads on most cell-eval perturbation metrics, with Fr'echet distance and $mathrm{MMD}^2$ roughly $3$ to $20times$ lower than the strongest continuous-latent baseline. Swapping the prior between autoregressive and masked discrete diffusion leaves performance near-identical, isolating the gain to the discrete latent itself rather than the prior family. A decoder-head ablation then exposes a single design axis, the richness of the predictive distribution at inference, that splits the standard metrics into two groups, variance-sensitive and mean-sensitive, which move in opposite directions along the axis. Finally, on a held-out CRISPRi reversion benchmark of $1{,}732$ perturbations under inflammatory cytokine stress, the frozen eVAE encoder outperforms UMAP and differential expression and matches scGPT on perturbation ranking at a fraction of the data.

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

Task-guided cross-subject latent alignment: a multi-encoder-decoder VAE

Authors:
Angeliki Papathanasiou↗Jascha Achterberg↗Thomas E. Nichols↗Rui Ponte Costa↗

arXiv:2606.15989v1 Announce Type: cross Abstract: Aligning neural activity across subjects offers the promise of discovering shared computational principles and generalizable decoders. However, traditional alignment methods require shared stimuli across subjects, a constraint that limits applicability to naturalistic paradigms with limited or non-overlapping data. We introduce a Multi-Encoder-Decoder Variational Autoencoder (MED-VAE) that achieves cross-subject alignment without shared stimuli by anchoring representations to a common scaffold provided by a pretrained ANN. Using the Natural Scenes Dataset, we show that MED-VAE creates common latent spaces with superior semantic organisation, achieving higher cross-subject alignment than common methods while maintaining robust generalisation to held-out stimuli where traditional methods degrade. Reconstructing from these common spaces back to each subject's original neural space, MED-VAE preserves equal stimulus-driven signal in its cross-subject latent space. Finally, we show that this superior alignment directly enables cross-subject neural prediction, as demonstrated via cross-subject image decoding. In summary, we introduce a framework to identify generalisable common subspaces for cross-subject predictions and downstream tasks, demonstrated here for visual cortex responses to static images.

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15.
arXiv (CS.LG) 2026-06-19

Toward all-optical unsupervised Hebbian learning in deep photonic neuromorphic networks

Authors:
Xi Li↗Disha Biswas↗Peng Zhou↗Wesley H. Brigner↗Anna Capuano↗Joseph S. Friedman↗Qing Gu↗

arXiv:2601.22300v3 Announce Type: replace-cross Abstract: We propose a deep photonic neuromorphic network (PNN) architecture based on phase-change material (PCM) synapses and local optical feedback for online, unsupervised Hebbian learning. The proposed architecture combines optical vector-matrix multiplication, non-volatile PCM synaptic weighting, and local coincidence-driven synaptic adaptation within a multilayer photonic crossbar framework compatible with photonic integrated circuits. Unlike conventional PNNs that rely on externally computed gradients, repeated optical-electrical-optical conversions, or global backpropagation, the proposed framework employs local Hebbian learning governed directly by correlated pre- and post-synaptic optical activity. To investigate the feasibility of the proposed learning mechanism, we implemented the PNN design using fiber-optic components, programmable variable optical attenuators, and real-time software control that incorporates PCM thermal dynamics. Supervised and unsupervised learning behaviors were experimentally evaluated under both offline and online learning conditions using representative image-recognition tasks. The experimental results demonstrate adaptive synaptic evolution, successful optical inference, and autonomous pattern encoding through local Hebbian learning under realistic fiber-optic hardware conditions. These results establish a pathway toward future integrated photonic neuromorphic systems capable of scalable and energy-efficient online Hebbian learning.

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

TreeSeeker: Tree-Structured Trial, Error, and Return in Deep Search

Authors:
Zhuofan Shi↗Mingzhe Ma↗Lu Wang↗Fangkai Yang↗Pu Zhao↗Yiming Guan↗Youling Huang↗Wei Zhang↗Qingwei Lin↗Dongmei Zhang↗Saravan Rajmohan↗

arXiv:2606.11662v1 Announce Type: new Abstract: Deep search requires agents to answer complex questions through multi-step web search, browsing, evidence comparison, and synthesis. A central challenge is deciding how to search when several directions look plausible but only some will later lead to reliable evidence. If an agent greedily follows the current best-looking direction, it may keep extending a weak continuation. If it explores without discipline, it may waste budget on disconnected trials. We propose TreeSeeker, an inference-time framework for controlled trial-and-error in deep search. TreeSeeker organizes search as branch-and-return search over tree-structured states, where each branch is a tentative direction for a sub-goal. At each round, TreeSearch reads all sub-goal trees, identifies active goals, and uses textual UCB signals of value, uncertainty, and risk to select among exploiting a promising branch, exploring an uncertain alternative, or pruning an unproductive continuation and returning to an earlier branch point. TreeMem supports this control loop by keeping evidence, uncertainty, conflicts, progress, and failure cues attached to the branches that produced them, so trial outcomes can guide later decisions. Experiments on XBench-DeepSearch, BrowseComp, and BrowseComp-ZH show that TreeSeeker consistently outperforms strong open-source baselines, suggesting that explicit branch-and-return control complements stronger reasoning and tool execution.

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

Seeing Is Not Screening: Multimodal Hidden Instruction Attacks on Agent Skill Scanners

Authors:
Xiaojun Jia↗Jie Liao↗Simeng Qin↗Ke Ma↗Wenbo Guo↗Yebo Feng↗Aishan Liu↗Yang Liu↗

Agent skills are emerging as an important attack surface in LLM-based systems. Through an empirical study of existing skill scanners, we find that current defenses primarily rely on textual descriptions, manifests, and source code as the main signals for security analysis, which can leave visually conveyed malicious intent insufficiently examined. This creates a practical blind spot: harmful operational instructions hidden in images may bypass scanning while still being recoverable by multimodal agents during deployment. To systematically investigate this threat, we propose SkillCamo, a document-mediated multimodal instruction attack that conceals malicious instructions within images bundled with a skill while rewriting the surrounding documentation to naturally reference those images as part of the normal workflow. Thus, the attack does not rely on the image alone, but on the joint interpretation of textual guidance and visual payload at execution time. To defend against such attacks, we further propose ExecScan, an execution-grounded multimodal scanning module that performs intent extraction, behavior reconstruction, abuse assessment, and deliberative execution simulation over skill artifacts. ExecScan jointly analyzes documentation, code, referenced resources, and visual content to recover hidden instructions, reconstruct executable behavior chains, and identify downstream risks such as exfiltration, destruction, persistence, deception, and privilege escalation. Extensive experiments show that image-hidden malicious instructions challenge existing skill scanners, while ExecScan can improve the skill scanning performance.

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18.
Nature (Science) 2026-06-17

Confined migration induces non-lethal DNA damage in developing neurons

Authors:
Zhejing Zhang↗

Migratory cells tend to have soft nuclei that deform and penetrate narrow spaces1,2. Extensive nuclear deformation during migration can cause nuclear-envelope rupture and DNA damage in cancer cells, which may contribute to malignant transformation during tumour progression3–6. However, the importance of DNA damage in physiological migration is less well understood. Here we demonstrate that the migration of neurons in developing cerebral and cerebellar cortices is accompanied by massive DNA double-stranded breaks (DSBs) due to mechanostress during passage through narrow interstitial spaces. In contrast to many other migratory cells, these DSBs occur without detectable nuclear envelope rupture. Confined migration increases topoisomerase-IIβ covalently bound DSBs, and these lesions are repaired through non-homologous end-joining during brain development without causing cell death. Genome sequencing revealed that DSBs tend to occur at transcriptionally inactive regions. The deletion of ligase IV at the onset of neuronal migration leads to persistent DSB accumulation in cerebellar neurons with moderate transcriptional changes in genes related to synaptic function, neuronal development and stress and immune responses. The mutant mouse develops mild motor deficits in later life, suggesting that the DNA damage generated during normal brain development poses a potential disease risk if left unrepaired. The migration of neurons in developing cerebral and cerebellar cortices is accompanied by massive DNA double-strand breaks due to mechanostress during passage through narrow interstitial spaces.

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

ProMUSE: Progressive Multi-modal Uncertainty-guided Staged Evidential Alzheimer Disease Classification

Authors:
Long Doan↗Branden Chen↗Ethan Litton↗Huan Huang↗Jiajing Huang↗Yixin Xie↗Weihua Zhou↗Nandakumar Narayanan↗Chen Zhao↗

arXiv:2606.19371v1 Announce Type: cross Abstract: Alzheimer's disease (AD) is a fatal disorder that destroys memory and cognitive skills in the elderly population. Most treatments for AD are effective in the early stage, leading to an increasing demand for early AD diagnosis. AD diagnosis increasingly relies on multimodal data such as clinical assessments, structural Magnetic Resonance Imaging (MRI), and Positron Emission Tomography (PET) imaging. However, MRI and PET acquisition remain costly and not universally accessible, making full-modality inference impractical in real-world clinical workflows. We propose ProMUSE, a Progressive Multi-modal Uncertainty Guided Staged Evidential Network that adaptively determines when additional modalities are necessary, helping reduce the overall cost of data acquisition while maintaining accuracy. ProMUSE first performs evidential classification using low-cost clinical data and quantifies uncertainty via a Dirichlet-based subjective logic model. When uncertainty exceeds a learned threshold, ProMUSE progressively incorporates MRI or PET features, fusing modality-wise belief and uncertainty through Dempster-Shafer theory to obtain a calibrated multimodal prediction. This staged acquisition strategy enables accurate diagnosis while minimizing reliance on expensive imaging. Experiments on ADNI, AIBL, and OASIS across CN-AD, CN-MCI, and MCI-AD tasks demonstrate that ProMUSE achieves competitive or superior accuracy compared to full-modality baselines while reducing MRI/PET usage by 50-90%, yielding substantial cost savings. These results highlight ProMUSE as a practical, uncertainty-aware, and resource-efficient solution for real-world AD screening.

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

Robustness without Wrinkles: Parallel Simulation and Robust MPC for Certified Deformable Manipulation

Authors:
Wei-Chen Li↗Jeffrey Fang↗Sasanka Polisetti↗Yuexi Song↗Glen Chou↗

arXiv:2606.14188v1 Announce Type: cross Abstract: We present CORD-SLS, a real-time control method for safe deformable object manipulation, with a focus on ropes and cloth. At its core is a GPU-parallel differentiable simulator with contact smoothing which enables efficient gradient-based planning through intermittent contact. To robustly satisfy constraints under model and sensing uncertainty, we develop a real-time, GPU-parallel output-feedback robust model predictive control (MPC) algorithm that plans with this simulator. We further show that the simulator accelerates model-based RL for training neural manipulation policies. To improve real-world robustness, we use conformal prediction to calibrate visual-feedback and perception-error bounds for MPC, producing reachable tubes that enable high-probability safe control. We evaluate CORD-SLS on high-dimensional, contact-rich rope and cloth manipulation tasks in simulation and hardware, including obstacle avoidance, routing, folding, and smoothing. Across settings, CORD-SLS achieves millisecond-speed planning, exceeding baselines in safety, speed, and task success.

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21.
arXiv (CS.AI) 2026-06-12

The Internet of Agentic AI: Communication, Coordination, and Collective Intelligence at Scale

Authors:
Quanyan Zhu↗

arXiv:2606.12835v1 Announce Type: cross Abstract: The rapid emergence of autonomous AI agents is transforming artificial intelligence from isolated model inference into distributed systems of reasoning, communication, and action. This paper develops the vision of the Internet of Agentic AI (IoAI): an open ecosystem in which heterogeneous agents discover one another, negotiate responsibilities, exchange context, invoke tools, and execute workflows across cloud, edge, device, organizational, and cyber-physical environments. We synthesize foundations from single-agent agentic AI, multi-agent systems, distributed computing, communication networks, game theory, and security engineering to characterize the architectures and mechanisms required for scalable agent ecosystems. The paper examines agent deployment models, workflow lifecycles, communication protocols, interoperability layers, resource-management challenges, and trust architectures, with case studies in adaptive manufacturing and distributed operational coordination. The resulting framework highlights the central research challenges of controlled emergence, semantic interoperability, secure identity, incentive-compatible coordination, resource-aware orchestration, and governance for large-scale networks of autonomous agents.

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22.
medRxiv (Medicine) 2026-06-22

Disentangling adiposity-related and non-adiposity-related genetic pathways for type 2 diabetes

Authors:
Su↗C.-Y↗Lu↗

OBJECTIVE To identify circulating proteins associated with type 2 diabetes (T2D) risk through pathways not fully explained by body mass index (BMI), and to assess therapeutic actionability. RESEARCH DESIGN AND METHODS We applied GWAS-by-subtraction within a genomic structural equation model to European ancestry summary statistics for T2D (74,124 cases, 824,006 controls) and BMI (n = 681,275), partitioning T2D liability into BMI-related and BMI-subtracted components. We then performed proteome-wide Mendelian randomization (MR) using cis-protein quantitative trait loci from four plasma proteomics cohorts: ARIC, deCODE, Fenland, and the UK Biobank Pharma Proteomics Project. Prioritized proteins passed sensitivity analyses with alternative MR methods and were supported by colocalization evidence. Tissue-resolution regulatory support was assessed using cis-eQTL colocalization across GTEx and pancreatic islet, subcutaneous adipose, and whole-blood resources. Actionability was evaluated using the druggable genome and Open Targets. RESULTS GWAS-by-subtraction attenuated the genetic correlation between BMI and BMI-subtracted T2D from 0.54 (SE 0.02) to 0.35 (SE 0.02). Proteome-wide MR prioritized 29 proteins for BMI-subtracted T2D. Thirteen showed eQTL colocalization in at least one tissue, implicating liver and intermediary metabolism (GCDH, NOTCH2), pancreatic islet biology (CTRB2, MANBA), adipose and Wnt signaling (RSPO3, GALNT3), and whole blood regulatory signals (PAM, SNUPN). Sixteen proteins were classified within druggable-genome Tiers 1-3, and five had existing Open Targets compounds. CONCLUSIONS Integrating GWAS-by-subtraction, proteome-wide MR, and colocalization nominated 29 proteins associated with T2D liability not fully explained by BMI. These findings highlight genetically supported targets for follow-up studies of T2D therapies that complement weight-centered approaches.

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23.
medRxiv (Medicine) 2026-06-19

Reassessing Instrument Strength in Two-Sample Mendelian Randomization Analysis

Authors:
Liu↗Huang↗Y.-J↗Purushotham↗Sofer↗

Mendelian randomization (MR) analysis is widely used to estimate causal relationships between risk factors and outcomes of interest. Two-sample MR approaches have gained increasing attention in genetic epidemiology due to the growing availability of Genome-Wide Association Study (GWAS) summary statistics from public databases. A critical step in two-sample MR is the selection of genetic variants as instrumental variables (IVs). Although genome-wide significant variants are typically preferred, the inclusion of variants with weaker association p-values is considered, as they may potentially improve power through an increased instrument number of instruments, while they may introduce weak instrument bias and attenuate effect estimates towards the null. Our simulation results show that even modest levels of pleiotropy substantially increase the variability of causal effect estimates, while the inclusion of weak IVs does not substantially affect the direction and variability of causal effect estimates in most cases. In real data analyses, we used two released versions of FinnGen GWAS summary statistics with different sample sizes as exposure GWASs to assess the influence of weak IVs. Here, the inclusion of IVs with higher exposure-association p-values resulted in weakened estimated effect sizes, particularly when the exposure GWAS sample size was small. These findings suggest that incorporating weak IVs is reasonable when the exposure GWAS sample size is large, but it poses a risk of falsely concluding null associations when the exposure GWAS sample size is small.

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24.
arXiv (math.PR) 2026-06-16

Risk-averse mean field games: exploitability and non-asymptotic analysis

Authors:
Ziteng Cheng↗Sebastian Jaimungal↗

arXiv:2301.06930v5 Announce Type: replace-cross Abstract: In this paper, we use mean field games (MFGs) to investigate approximations of $N$-player games ($N$pGs) with uniformly symmetrically continuous heterogeneous closed-loop actions. To incorporate agents' risk aversion (beyond the classical expected utility of total costs), we use an abstract evaluation functional for their performance criteria. Centered around the notion of exploitability, we conduct non-asymptotic analysis on the approximation capability of MFGs from the perspective of state-action distributions without requiring the uniqueness of equilibria. Under suitable assumptions, we first show that scenarios in the $N$pGs with large $N$ and small average exploitabilities can be well approximated by approximate solutions of MFGs with relatively small exploitabilities. We then show that $\delta$-mean field equilibria can be used to construct $\varepsilon$-equilibria in $N$pGs. Furthermore, in this general setting, we prove the existence of mean field equilibria. This proof reveals a possible avenue for incorporating penalization for randomized action into MFGs.

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25.
arXiv (quant-ph) 2026-06-16

Sub-Poissonian Statistics and Quantum Non-Gaussianity from High-Harmonic Generation

Authors:
David Theidel↗Mackrine Nahra↗Ilya Karuseichyk↗Houssna Griguer↗Mateusz Weis↗Viviane Cotte↗Hamed Merdji↗

arXiv:2602.10882v4 Announce Type: replace Abstract: Quantum technologies are powered by platforms to generate complex non-classical states of matter or light to realize applications. We investigate the non-classical properties of high-harmonic generation in semiconductors, an emerging photonic platform. Measuring the click statistics of three double-digit orders, we evaluate witness operators to certify the non-classicality of the generated states. We show that higher-order harmonics driven by a coherent laser are squeezed and entangled. The properties of the emission are well retrieved with an entangled Gaussian state model, obtained by numerical state optimization to multiple observables. Additionally, we perform inter-order heralded measurements to engineer the quantum state of the emission. The heralded states have distinct properties, showing sub-Poissonian photon statistics. Further, we witness the generation of a quantum non-Gaussian state, a resource highly relevant for quantum information. With this, we establish high-harmonic generation as a platform for generating quantum optical resources.

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