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01.
arXiv (CS.CL) 2026-06-19

A Layered Security Framework Against Prompt Injection in RAG-Based Chatbots

Prompt injection is ranked as the most critical vulnerability in large language model (LLM) deployments by the OWASP Top 10 for LLM Applications, yet existing defenses operate at isolated pipeline stages and remain incomplete. Input filters cannot inspect retrieved documents, while output monitors cannot prevent malicious payloads from reaching the model. Consequently, retrieval-augmented generation (RAG) chatbots remain vulnerable to indirect injection, where a poisoned knowledge-base document compromises every user whose query retrieves it. We present a three-layer framework that intercepts both direct and indirect prompt injection throughout the inference pipeline. Layer 1 screens user input using a rule-based pattern library and a fine-tuned semantic anomaly classifier. Layer 2 enforces a provenance-based instruction hierarchy during context assembly, preventing retrieved content from overriding operator policy. Layer 3 audits model output using a policy rule engine and semantic drift detector before delivery. A continuous audit loop aggregates structured logs and supports retraining to adapt the classifier to emerging attack patterns. The framework is model-agnostic and deploys as middleware without modifying the underlying LLM. Evaluation on 5,080 samples across GPT-4o, Llama 3, and Mistral 7B shows that the framework reduces Attack Success Rate (ASR) from 71.4\% to 11.3\%, outperforming the best single-layer baseline by 27.3 percentage points and a published guardrail system by 23.8 percentage points, while maintaining a 4.8\% false positive rate and a median latency overhead of 61.2 ms. Ablation studies confirm that all three layers provide complementary protection and that their combined effect exceeds the sum of individual contributions.

02.
arXiv (CS.AI) 2026-06-12

From Digital to Physical: Digital Agents as Autonomous Coaches for Physical Intelligence

arXiv:2601.21570v2 Announce Type: replace Abstract: The field of Embodied AI is witnessing a rapid evolution toward general-purpose robotic systems, fueled by high-fidelity simulation and large-scale data collection. However, this scaling capability remains severely bottlenecked by a reliance on labor-intensive manual oversight from intricate reward shaping to hyperparameter tuning across heterogeneous backends. Inspired by LLMs' success in software automation and science discovery, we introduce \textsc{EmboCoach-Bench}, a benchmark evaluating the capacity of LLM agents to autonomously engineer embodied policies. Spanning 32 expert-curated RL and IL tasks, our framework posits executable code as the universal interface. We move beyond static generation to assess a dynamic closed-loop workflow, where agents leverage environment feedback to iteratively draft, debug, and optimize solutions, spanning improvements from physics-informed reward design to policy architectures such as diffusion policies. Extensive evaluations yield three critical insights: (1) autonomous agents can qualitatively surpass human-engineered baselines by 26.5\% in average success rate; (2) agentic workflow with environment feedback effectively strengthens policy development and substantially narrows the performance gap between open-source and proprietary models; and (3) agents exhibit self-correction capabilities for pathological engineering cases, successfully resurrecting task performance from near-total failures through iterative simulation-in-the-loop debugging. Ultimately, this work establishes a foundation for self-evolving embodied intelligence, accelerating the paradigm shift from labor-intensive manual tuning to scalable, autonomous engineering in embodied AI field.

03.
medRxiv (Medicine) 2026-06-10

Impact of Early Treatment on Symptom Improvement and Procedural Events among Men with BPH and Bothersome Lower Urinary Tract Symptoms: A Contemporary Analysis of the American Urological Association Quality (AQUA) Registry

PURPOSE: As the armamentarium of BPH therapies continues to expand, it remains imperative to maximize patient satisfaction and minimize decisional regret. We sought to determine the impact of time from BPH diagnosis to index treatment on symptom improvement and subsequent procedural events. MATERIALS AND METHODS: We queried the American Urological Association Quality Registry for men [&ge;] 40 years old with BPH, available IPSS data, and no receipt of prior BPH treatment. Index treatment included medication, surgery, or minimally invasive surgical therapy (MIST). Outcomes included IPSS over 3 years of follow-up, change in percentage of mild lower urinary tract symptoms (LUTS) by 3 months, and time to procedural event. Patients were stratified by time from index diagnosis to treatment by 3 years. Outcomes were compared across time-to-treatment cohorts with appropriate statistical tests with p < 0.05 as significant. RESULTS: 43,919 patients met criteria with 19,642 pursuing treatments. Patients pursued treatment at comparably lower baseline IPSS compared to prior prospective series. Patients undergoing surgery and MIST had significantly higher baseline IPSS, while medical comorbidities were significantly more common among men initiating pharmacotherapy. Early surgery and MIST were associated with significant improvement in IPSS within 6-12 months and an increase in mild LUTS by 3 months. All forms of early treatment were associated with delayed time to procedural events, including catheterization and fulguration. CONCLUSIONS: Early procedural intervention for BPH is associated with early symptom improvement and delayed time to procedural events among real-world, contemporary practice.

04.
arXiv (CS.CV) 2026-06-15

Morphology-Aware Sample Assignment: Overcoming IoU Insensitivity for Surface Defect Detection

Intersection-over-Union (IoU), as a pivotal metric for evaluating the spatial alignment between candidate proposals and ground-truth annotations, directly determines the quality of positive sample sets and the training efficacy of visual detection models. Through theoretical modeling and analysis, we uncover a non-sensitive region on the IoU response curve, within which samples yield nearly identical IoU scores despite distinct geometric overlaps. To overcome this limitation, we introduce a set of morphological similarity metrics covering area, shape, and aspect ratio, to refine the positive sample assignment process, thereby ensuring more discriminative and reliable matching. A supplementary matching score is derived via mean-based aggregation of these multidimensional similarities, compensating for the intrinsic limitation of IoU in representing structural correspondence. Theoretically, incorporating morphological similarity reshapes the response distribution of the matching function, yielding both effective directional gradients and polygon-like iso-response contours, which tightly confine high-response regions around each ground-truth instance and substantially enhance the precision of positive sample selection. Experiments based on the YOLOv9 framework demonstrate consistent performance gains on both NEUDET and GC10- DET datasets. Notably, the proposed approach is fully plug-and-play and incurs zero additional inference overhead, thereby ensuring deployment efficiency for industrial visual inspection.

05.
arXiv (CS.CV) 2026-06-16

MambaH-Fit: Rethinking Hyper-surface Fitting-based Point Cloud Normal Estimation via State Space Modelling

We present MambaH-Fit, a state space modelling framework tailored for hyper-surface fitting-based point cloud normal estimation. Existing normal estimation methods often fall short in modelling fine-grained geometric structures, thereby limiting the accuracy of the predicted normals. Recently, state space models (SSMs), particularly Mamba, have demonstrated strong modelling capability by capturing long-range dependencies with linear complexity and inspired adaptations to point cloud processing. However, existing Mamba-based approaches primarily focus on understanding global shape structures, leaving the modelling of local, fine-grained geometric details largely under-explored. To address the issues above, we first introduce an Attention-driven Hierarchical Feature Fusion (AHFF) scheme to adaptively fuse multi-scale point cloud patch features, significantly enhancing geometric context learning in local point cloud neighbourhoods. Building upon this, we further propose Patch-wise State Space Model (PSSM) that models point cloud patches as implicit hyper-surfaces via state dynamics, enabling effective fine-grained geometric understanding for normal prediction. Extensive experiments on benchmark datasets show that our method outperforms existing ones in terms of accuracy, robustness, and flexibility. Ablation studies further validate the contribution of the proposed components.

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

Feature-Aligned Speech Watermarking for Robustness to Reconstruction Distortions

arXiv:2606.11828v1 Announce Type: cross Abstract: Audio watermarking aims to embed identifiable information into audio while remaining imperceptible. Existing methods adopt high-fidelity, low-energy designs to preserve perceptual quality, but the resulting watermarks lack robustness under suppression by speech reconstruction models. Improving robustness is challenging due to the inherent robustness-fidelity trade-off in existing designs, where increasing watermark energy improves robustness but reduces fidelity. To address this problem, we propose a feature-aligned watermarking method that aligns the watermark with the original speech feature distribution, allowing higher watermark energy to improve robustness while preserving imperceptibility. We use a pretrained speech codec to generate a pseudo-speech watermark and fuse it into the spectrogram of the input audio, with VAD loss and perceptual losses guiding embedding within voiced regions. Experiments show that our method maintains imperceptibility comparable to existing approaches while substantially improving robustness under both seen and unseen speech reconstruction models.

07.
arXiv (quant-ph) 2026-06-11

Invariants of Sequential Circuits and Generalized Non-Abelian Statistics

arXiv:2606.11527v1 Announce Type: cross Abstract: Non-invertible symmetries in quantum many-body systems generally give rise to sequential unitary circuits that move symmetry defects. In this paper, we investigate invariants defined by sequences of such circuits, which move non-invertible defects and generate a Berry phase evaluated on quantum states with defects. We show that this Berry phase generally defines an invariant under local deformations, provided that the sequential circuits preserve the locality of those deformations. This invariant also rules out a short-range-entangled state that preserves the non-invertible symmetry, thereby signaling the 't Hooft anomaly of a non-invertible symmetry purely in terms of unitary operators acting on a state. We then apply this framework to loop excitations in three spatial dimensions and identify a new loop excitation in the (3+1)D $\mathbb{D}_4$ topological order, which we dub a non-Abelian fermionic loop. Using the invariant of sequential circuits, we characterize the statistics of non-Abelian fermionic loops. In addition, we find a new (3+1)D mixed topological order with a single non-Abelian fermionic loop, whose long-range entanglement is protected by an invariant of sequential circuits.

08.
medRxiv (Medicine) 2026-06-23

Shared Polygenic Architecture Across Arteriopathies: An Integrative Cross-Trait Analysis

Background: Non-monogenic arteriopathies are often classified as distinct entities according to the arterial territory involved, yet they share clinical features and may co-occur in the same individual. This pattern suggests shared susceptibility across anatomically distinct arteriopathies, potentially driven by common biological and genetic mechanisms. Methods: We investigated the shared genetic architecture of five arteriopathies (cervical artery dissection (CeAD), intracranial aneurysm (IA), spontaneous coronary artery dissection (SCAD), aortic aneurysm and dissection (AAD), and fibromuscular dysplasia (FMD)) using LD score regression, Association analysis based on SubSETs (ASSET), pairwise Multi-Trait Analysis of Genome-wide association summary statistics (MTAG), pleiotropy mapping and Mendelian randomization (MR) to identify shared loci and prioritise candidate causal genes. Results: LD score regression identified significant positive genetic correlations between CeAD-SCAD (rg = 0.64), IA-AAD (rg = 0.33), IA-SCAD (rg = 0.37), CeAD-AAD (rg = 0.56) and SCAD-AAD (rg = 0.20). ASSET identified 37 shared independent loci, and in MTAG analyses, one novel locus was identified for CeAD and SCAD (SLC39A8) and one for IA (FGF5). 13 loci showed strong cross-trait colocalization, including PHACTR1, LRP1, and CDKN2B-AS1. Using the Genotype-Phenotype Map, we found that arteriopathy-associated variants colocalized with blood pressure- and migraine-related traits, while many showed effect directions opposite to those observed for coronary artery disease. Proteome-wide MR identified 67 circulating proteins associated with at least one trait, including ECM1 and SHISA5 for CeAD and FGF5 for IA, with 17 supported by colocalization. Transcriptome-wide MR identified 204 colocalized tissue?specific signals, of which, 14 were shared across multiple traits. Enrichment analyses implicated pathways related to vascular development, smooth muscle cell function, extracellular matrix organization, and TGF-? signaling. Conclusions: These findings support shared genetic architecture across anatomically distinct arteriopathies, implicating pathways involved in vascular structure and prioritising therapeutic targets for future mechanistic investigation.

09.
arXiv (CS.CV) 2026-06-12

A Machine Learning Framework for Real-Time Personalized Ergonomic Pose Analysis

This paper introduces a new methodology for real-time prediction of ergonomic and non-ergonomic human poses using volumetric video data in three dimensions. Although the methodology was designed for ergonomic assessments, it can be adapted to other applications requiring real-time analysis of human posture. One aspect that makes this system stand out is its ability to analyze 3D point clouds during the assessment, enabling computation from multiple angles. This overcomes a critical limitation of cameras which provide often a fixed viewpoint, thereby restricting the data available for a thorough postural evaluation, especially when occlusions occur. The system continuously and automatically performs pose inference using the chosen perspective on the real-time streaming data; however, only the poses manually selected and labeled by the user are used to train the personalized deep learning classifier. The methodology has been refined through a case study in which RGB-D cameras captured subjects performing load-lifting tasks, enabling real-time skeletal labeling. The model was trained on this data and, following the training phase, performs inference on new streaming data in real time. This research offers a scalable and pragmatic approach for real-time ergonomic evaluation by combining state-of-the-art 3D data technologies and traditional 2D pose estimation algorithms. It addresses the increasing need for safety and health monitoring in workplace environments, marking a notable contribution to the domain.

10.
arXiv (CS.AI) 2026-06-16

JetParticle-JEPA: An Efficient Self-Supervised Representation Learning method for Jet Tagging in High-Energy Physics

arXiv:2606.14813v1 Announce Type: cross Abstract: Jet tagging at the Large Hadron Collider increasingly relies on deep learning models trained on massive simulated datasets, leading to high computational costs and limited robustness to detector mismodeling. We introduce JetParticle-JEPA (JP-JEPA), a self-supervised Joint-Embedding Predictive Architecture that learns physically meaningful jet representations directly from continuous particle clouds without tokenization or reconstruction of raw inputs. Built on a Particle Transformer backbone, JP-JEPA predicts latent representations of masked particles while preserving fine-grained kinematic correlations. On the JetClass benchmark, JP-JEPA achieves performance comparable to fully supervised state-of-the-art methods on the full dataset, surpasses supervised baselines in low-label regimes, and significantly outperforms existing SSL approaches. On Top Quark and Quark-Gluon Tagging benchmarks, it remains on par with supervised methods. The learned representations also exhibit strong robustness to missing detector information and improved uncertainty behavior, highlighting JP-JEPA as a promising foundation-model framework for robust and data-efficient jet physics at the LHC.

11.
arXiv (CS.CV) 2026-06-17

Pareto LoRA: Mitigating Modality Imbalance in Unified Multimodal Models via Pareto-Optimal Gradient Integration

Unified multimodal models (UMMs) have recently emerged as a promising paradigm for integrating multimodal understanding and generation within a single autoregressive transformer. However, during multimodal instruction tuning, these models often exhibit pronounced modality imbalance: language gradients dominate optimization, thus leading to lower image generation quality, especially under parameter-efficient fine-tuning such as LoRA. In this work, we systematically analyze modality imbalance in LoRA-based fine-tuning of UMMs for interleaved text-image generation. We show that vision modality performance degrades substantially more than text modality performance when compared to unimodal counterparts, and that modality-specific gradients can differ by orders of magnitude across various tasks and layers. Motivated by this observation, we reformulate the multimodal instruction tuning as a bi-objective optimization problem and propose Pareto LoRA, a Pareto-optimal gradient integration strategy that balances the text and image objectives by modulating the gradient direction and strength. Experiments on the CoMM benchmark with Emu2 demonstrate that Pareto LoRA consistently improves multimodal generation balance, achieving up to 44.9% gains in perceptual image quality over vanilla LoRA while maintaining comparable text performance.

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

HAFMat: Hybrid Priors Guided Adaptive Fusion for Single-Image Human Material Estimation

Physically based rendering (PBR) material estimation is a fundamental appearance decomposition task with broad applications in virtual content creation, relighting, and digital human rendering. However, estimating PBR materials from a single human image remains highly ill-posed, since illumination, geometry, and reflectance are heavily entangled in the observed appearance. To mitigate this ambiguity, we propose HAFMat, a hybrid-prior-guided framework for single-image human material estimation. Our method introduces guidance maps that encode complementary cues, including appearance, body geometry, structure, and prior material predictions from pre-trained models. A key observation is that these guidance cues are heterogeneous: some cues mainly provide texture-level constraints, while others convey higher-level semantic information. To exploit this property, we design a Multi-layer Adaptive Feature Fusion Mechanism, which adaptively fuses guidance features with decoder features at different stages. This design enables texture-dominant and semantic-dominant cues to guide material decoding at appropriate levels, leading to more accurate and physically plausible material estimation. Extensive experiments on both synthetic and real data demonstrate that our method achieves state-of-the-art performance in material estimation and downstream relighting.

13.
arXiv (CS.CV) 2026-06-15

Conditioning Matters: Stabilizing Inversion and Attention in Diffusion Image Editing

Inversion-based image editing offers flexible and training-free control but still struggles with inversion accuracy and the trade-off between editing fidelity and background preservation. While recent methods improve inversion formulations or attention interactions, the role of textual conditioning in shaping diffusion dynamics and editing behavior remains underexplored. We show both empirically and theoretically that the precision of textual conditioning influences inversion stability by modulating the geometry of the diffusion velocity field, while also affecting the consistency of cross-branch attention during editing. These effects directly impact background preservation and semantic fidelity. Building on this analysis, we propose SimEdit, a conditioning-aware framework with two complementary components: (a) conditioning refinement, which constructs conditioning signals with improved semantic precision and structural alignment to facilitate stable inversion and consistent attention manipulation, and (b) token-wise cross-branch attention control, which separates edit-relevant and structure-preserving components and modulates them asymmetrically during attention manipulation. Extensive experiments on PIE-Bench demonstrate that SimEdit consistently improves both inversion reconstruction quality and editing performance over previous attention-manipulation approaches. Our code is available at https://github.com/zju-pi/SimEdit.

14.
Nature (Science) 2026-06-10

‘Hidden hero’ peptides guard crops against sudden cold

作者: 未知作者

A protein signal remains silent under normal conditions but is activated under cold stress to protect developing pollen. This ‘on-demand’ resilience mechanism could enable the development of ‘climate smart’ crops that maintain high yields in good years and food security under climate stress. A peptide signal ensures that, in cold conditions, developing pollen receives nutrients at the right time.

15.
arXiv (math.PR) 2026-06-12

On McDiarmid's Inequality under Dependence via Approximate Tensorization of Entropy

arXiv:2606.12720v1 Announce Type: new Abstract: We argue that dependent versions of McDiarmid's inequality are a useful but underutilized tool in mathematical statistics, learning theory and theoretical computer science. To make this point, we first highlight that approximate tensorization of entropy (ATE) implies McDiarmid's via the Entropy Method. Second, we derive McDiarmid's inequality for non-isotropic Gaussian random vectors $X \sim \mathcal N(\mu, \Sigma)$ through ATE with a constant of the order of the condition number of $\Sigma$. We both independently obtain this ATE through a simple application of stochastic localization and also discuss how a more general ATE for the Gibbs sampler due to Ascolani et al., 2026 generalizes McDiarmid's-like concentration to strongly log-concave and log-smooth probability measures. We then apply the resulting concentration inequalities to resolve a question on the concentration of $\operatorname{sign}(X)$ posed by Simone Bombari, investigate Erdős-Rényi graphs under dependence and prove a Dvoretzky-Kiefer-Wolfowitz-type inequality for observations from a joint measure fulfilling ATE and continuous marginal CDFs. For the class of strongly log-concave and log-smooth measures, this result improves upon a prior Dvoretzky-Kiefer-Wolfowitz-type inequality for non-i.i.d. observations due to Bobkov and Götze, 2010, by establishing the expected $1/\sqrt{n}$-rate of convergence under weak dependence instead of $n^{-1/3}$.

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

FACTR 2: Learning External Force Sensing for Commodity Robot Arms Improves Policy Learning

arXiv:2606.12406v1 Announce Type: cross Abstract: Contact-rich manipulation requires force sensitivity, but many robot arms lack dedicated force sensors due to their high cost. We present Neural External Torque Estimation (NEXT), a data-driven method that estimates external joint torques without needing any dedicated force sensors. NEXT trains in 1 minute from only 10 minutes of free-motion data, yet achieves estimates comparable to dedicated joint-torque sensors. NEXT enables force-feedback teleoperation on low-cost arms and improves policy learning through Force-Informed Re-Sampling Training (FIRST), which up-samples pre-contact and contact segments during behavior cloning. Across five long-horizon tasks, FIRST outperforms prior force-aware policies by over 17% in task progress. Together, NEXT and FIRST bring force-aware teleoperation and policy learning to off-the-shelf robots without additional sensing hardware. Video results and code are available at https://jasonjzliu.com/factr2

17.
arXiv (math.PR) 2026-06-19

Theory of uncertain probability: can we derive the probability density function of uncertain random experiments with continuously changing conditions?

作者:

arXiv:2606.20169v1 Announce Type: new Abstract: This paper aims to explore the formation mechanism of probability distribution in situations where the differences among random experiments are distinguishable, and these differences continue to evolve along with the dynamic changes in conditions and their mechanisms of action. To this end, we are motivated to devise a new theoretical system – theory of uncertain probability (TUP) with Kolmogorov's system and nonlinear theories as special cases. TUP develops a novel model that integrates probability and uncertainty as well as the known and unknown to more accurately depict numerous typical random phenomena under more realistic assumptions, and thus provides appropriate tools for greater variety of real needs. It also allows for pioneering interpretation of the causal mechanisms underlying many important distributional characteristics and incorporation of pathwise property to distribution model.

18.
medRxiv (Medicine) 2026-06-15

Reaching out-of-school girls with HPV vaccination: A qualitative evaluation in six low- and middle-income countries using the RE-AIM framework

Background Infection with human papillomavirus (HPV), the primary cause of cervical cancer, disproportionately affects women in low- and middle-income countries (LMICs). While school-based vaccination of adolescent girls against HPV is highly effective, this strategy systematically excludes out-of-school (OOS) girls. Using the RE-AIM framework, we explored strategies to reach OOS girls with HPV vaccination across six African and Asian LMICs. Methods We conducted semi-structured key informant interviews with 32 vaccination program stakeholders from Cambodia, Cameroon, Kenya, Malawi, Mozambique, and Uganda between May and September 2024. Interviews explored countries implementation successes, challenges, and strategies to reach OOS girls with HPV vaccination and sustainability considerations. Data were analyzed using a hybrid team-based thematic analysis approach guided by the RE-AIM framework. Results Community outreach-based strategies, typically integrated into routine immunization outreach, were identified as the most effective approach to reach OOS girls with HPV vaccination. Targeted strategies, such as locating outreach clinics in community venues frequented by OOS girls (e.g., churches, markets) enhanced implementation. Perceived effectiveness of these strategies varied across participants, and formal assessment of effectiveness was constrained by the absence of disaggregated vaccination coverage data by school enrollment status. Some subpopulations of OOS girls (i.e., girls in nomadic or migrant communities, urban OOS girls) were not readily reached through standard outreach approaches, prompting implementation of adapted and tailored strategies for these subpopulations. Costs associated with conducting outreach in harder-to-reach areas were major barriers to reaching OOS girls, presenting challenges to the sustainability and cost-effectiveness of these approaches. Conclusions Routine community outreach platforms were widely perceived as most effective for reaching OOS girls. Strengthening disaggregated monitoring systems, adapting outreach for harder-to-reach subpopulations of OOS girls, and financing delivery models for tailored outreach strategies will be critical to improving equitable HPV vaccine coverage among OOS girls.

19.
arXiv (CS.LG) 2026-06-11

Deep Learning of Solver-Aware Turbulence Closures from Nudged LES Dynamics

arXiv:2604.23874v3 Announce Type: replace-cross Abstract: The differentiable physics paradigm may be leveraged as an a-posteriori approach for discovering turbulence closure models by embedding a neural network parameterization directly inside the solver and optimizing it given potentially sparse target data. This addresses a key limitation of a-priori learning where direct numerical simulation (DNS) data is used to approximate the subgrid stress with the assumption of a low-pass filter. Closures trained in this a-priori manner frequently lead to unstable deployments due to the mismatch between the assumed filter and the effect of numerical discretizations and coarse-graining. In comparison, while typically stable during deployment, a-posteriori learning incurs high computational costs due to the need to backpropagate through a large eddy simulation (LES) solver. Furthermore, a-posteriori methods are challenging to apply broadly since they require significant modification of existing solvers. Finally, both approaches are limited when generalization is desired across different numerical schemes with their implicit filtering characteristics. In this work, we present a deep-learning approach for turbulence closure modeling built on the continuous data assimilation framework. Our approach enables the a-priori training of closures using sparsely observed DNS data without modifying or differentiating through the LES solver, while preserving stability during deployment for the recovery of invariant statistics. We focus on the model's ability to adapt to different discretizations by explicitly conditioning it on the numerical scheme. We use two- and three-dimensional canonical cases to test our framework and show that the learned correction systematically tracks the discretization error of the coarse solver.

20.
medRxiv (Medicine) 2026-06-23

Oxidative Stress Biomarker Profile Dynamics across Blood and Cerebrospinal Fluid

Peripheral blood measurements dominate oxidative stress research, yet whether they reflect central nervous system (CNS) redox status remains untested in humans. We simultaneously profiled five biomarkers, total antioxidant capacity (TAC), glutathione (GSH), thiobarbituric acid-reactive substances (TBARS), ferric reducing antioxidant power (FRAP), and hydroxyl radical scavenging activity (HRSA), in paired blood and cerebrospinal fluid (CSF) from 140 adults in the ALBION cohort. Only FRAP showed a significant positive cross-compartment correlation ({rho} = +0.49, FDR-p < 0.001), supporting its role as a systemic antioxidant signal. TBARS showed a significant inverse cross-compartment association ({rho} = -0.20, FDR-p = 0.042), suggesting compartmental compensation in lipid peroxidation regulation rather than parallel dynamics. TAC and GSH showed no meaningful intercompartmental alignment. Individual biomarker levels were largely stable across the 40-85 year age range in both compartments, suggesting that age effects operate through coordinated latent networks rather than single-marker trajectories. Principal component extraction with varimax rotation identified four latent factors explaining 66.6% of total variance, dominated by a coherent CSF-centred redox axis alongside multiple partially opposing peripheral components. Age stratification revealed progressive fragmentation: middle-aged adults retained four coherent cross-compartment factors, whereas older adults exhibited five more dispersed components. Sex-stratified analyses showed that females exhibited four-factor modular organisation centred on glutathione, while males showed a simpler three-factor structure with tighter cross-compartment coupling anchored by FRAP. Blood and CSF oxidative stress biomarkers are not interchangeable, a finding with direct implications for biomarker selection in clinical trials targeting neurological conditions.

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

Holding the FP8 Quality Ceiling at 8-Bit Weights and Activations: INT8 and GGUF Post-Training Quantization of Ideogram 4.0 for Consumer GPUs

arXiv:2606.12280v1 Announce Type: new Abstract: Post-training quantization lets large text-to-image diffusion transformers run on consumer GPUs, yet the hardware-specific trade-offs are seldom measured directly. We quantize Ideogram 4.0 - a 9.3B flow-matching diffusion transformer (DiT), shipped as two separate-weight copies of a single-stream 34-layer backbone for classifier-free guidance and conditioned by a Qwen3-VL-8B encoder - for Ampere RTX 3090 GPUs, which lack FP8 tensor cores. Our INT8 W8A8 recipe (per-channel weights, per-token dynamic activations, SmoothQuant, and mixed-precision protection of a small high-fragility layer set) holds the FP8 quality ceiling: on a 200-prompt benchmark the paired same-seed bootstrap CI for INT8-FP8 includes zero on both Pick and CLIP, while INT8 improves on NF4 by $+1.9$ CLIP (95% CI $[+1.21,+2.64]$, excluding zero). A per-category OCR analysis, to our knowledge unreported for this model class, confirms text legibility is preserved, and an ablation isolates protection of the FFN down-projections as the dominant quality lever. Our GGUF Q4_K quantization beats NF4 at equal on-disk size and is the Pareto winner on the quality-memory frontier, with paired confidence intervals excluding zero (Q8_0 is quality neutral). Finally, we characterize where 8-bit quantization helps and where it does not: INT8's weights match FP8's footprint rather than shrink it, so a speed gain on Ampere awaits a fused INT8 kernel.

22.
arXiv (math.PR) 2026-06-16

Sharp One-Dimensional Sub-Gaussian Comparison in Convex Order

作者:

arXiv:2604.26819v2 Announce Type: replace Abstract: We prove that any random variable $X$ whose moment generating function is point-wise upper bounded by that of $ G \sim \mathcal{N}(0,1) $ must be dominated by $ G/\mathbb{E}[|G|] $ in convex order, meaning $ \mathbb{E}[f(X)] \le \mathbb{E}[f(G/\mathbb{E}[|G|])] $ for all convex $f$. This is sharp as witnessed by $ X \sim \mathrm{Unif}(\{-1,1\}) $ and $ f(x) = |x| $.

23.
arXiv (CS.CL) 2026-06-19

TSAssistant: A Human-in-the-Loop Agentic Framework for Automated Target Safety Assessment

Target Safety Assessment (TSA) requires systematic integration of genetic, transcriptomic, target homology, pharmacological, and clinical data to evaluate potential safety liabilities of therapeutic targets. This process is labor-intensive and expert-dependent, posing challenges in scalability and reproducibility. We present TSAssistant, a human-in-the-loop multi-agent framework that decomposes TSA report generation into a workflow of specialized subagents: Research Subagents that each ground and cite a single TSA domain, and Synthesis Subagents that integrate findings across domains. Subagents retrieve and synthesize evidence from curated biomedical sources through standardized tool interfaces and produce individually citable, evidence-grounded sections, with behavior shaped by a hierarchical instruction architecture that separates coordination logic from domain expertise and user intent. To complement these soft constraints, programmatic execution hooks and persistent memory stores enforce hard constraints across the workflow, while an interactive refinement loop allows experts to review and revise individual sections with full conversational context preserved across iterations. Rather than a single holistic comparison, we decompose report quality into reproducibility, evidential grounding, task-level accuracy, and controllability under expert oversight, finding high reproducibility and grounding, substantial agreement with the human reference, and net-positive expert-driven refinement.

24.
arXiv (math.PR) 2026-06-17

Optimal Impulse Control for Cyber Risk Management

arXiv:2410.17706v2 Announce Type: replace-cross Abstract: We explore an optimal impulse control problem wherein an electronic device owner strategically calibrates protection levels against cyber attacks. Utilizing epidemiological compartment models, we qualitatively characterize the dynamics of cyber attacks within the network. We determine the optimal protective measures against effective hacking by formulating and solving a stochastic control problem with optimal switching. We demonstrate that the value function for the cluster owner constitutes a viscosity solution to a system of coupled variational inequalities associated with a fully coupled reflected backward stochastic differential equation (BSDE). Furthermore, we devise a comprehensive algorithm alongside a verification procedure to ascertain the optimal timing for network protection across various cyber attack scenarios. Our findings are illustrated through numerical approximations employing deep Galerkin methods for partial differential equations (PDEs). We visualize the optimal protection strategies in the context of two distinct attack scenarios: (1) a constant cyber attack, (2) an exogenous cyber attack strategy modeled with a Poisson process.

25.
medRxiv (Medicine) 2026-06-22

ECG-Guided Pre-Screening of Family Members for Hypertrophic Cardiomyopathy

Background: Current clinical guidelines recommend serial ECG and echocardiographic surveillance for first-degree relatives of probands with Hypertrophic Cardiomyopathy (HCM). Objectives: To evaluate the accuracy and validity of ECG alone as a pre-screening tool for the diagnosis of HCM and to develop a random forest (RF) model for HCM phenotype prediction. Method: Pediatric relatives of primary HCM probands attending the cardiomyopathy screening program at The Hospital for Sick Children were included from 1993 to 2025. Subjects were followed until the last follow-up, censored at phenotype conversion. ECGs were classified as normal or abnormal based on predefined parameters. Associations between binary ECG variables and HCM phenotype were assessed using Phi ({varphi}) coefficient. A Random Forest classifier was developed using significant ECG variables (70:30 training: test split) and evaluated using precision, recall, specificity, negative predictive value, F1 score and AUROC. Feature importance was assessed using SHAP analysis. Variables with an impact of >5% were included in a simplified model, which was evaluated by repeating performance metrics and externally validated in a healthy cohort. Results: 350 screened relatives (44% female, mean follow-up 6.8 +- 4.8 years) were included. At baseline, 13% (46350) were phenotype-positive for HCM. 9 subjects converted during the surveillance. Thirteen ECG variables were significantly associated with phenotype-positive HCM and were included in the full random forest model. Four variables had >5% impact (Left ventricular hypertrophy, right ventricular hypertrophy, T-wave inversion and ST-segment depression) and were included in a simplified model, which maintained high specificity (93% vs 97%), negative predictive value (97% vs 93%) and AUROC (90% vs 96%). The simplified model classified 83% subjects as phenotype-negative, with eight being false-negative, all of whom developed an abnormal ECG in a mean of 1 year, and none had an interim adverse cardiac event. The simplified model was evaluated in an independent healthy cohort of 153 school-age subjects and correctly identified 98% as phenotype-negative with 100% NPV. Conclusion: ECG abnormalities were strongly associated with phenotype-positive status. A simplified ECG-based random forest model using four ECG variables demonstrated high specificity and negative predictive value for identifying phenotype-negative subjects. If prospectively validated, this could reduce the need for concurrent echocardiographic screening by up to 83% per encounter, lowering screening burden and cost.