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01.
arXiv (CS.CV) 2026-06-12

GetNetUPAM: Ecologically Informed Nested Cross-Validation and Noise-Robust Attention for Marine Bioacoustic Monitoring

Deploying reliable bioacoustic monitoring systems requires models that generalize under high-noise, low-SNR conditions and evaluation protocols that expose deployment-relevant failure modes, gaps largely unaddressed in current UPAM practice. Intrinsic noise, variable propagation, and mixed biological and anthropogenic sources induce distribution shifts that conventional models and single-split evaluations obscure, inflating performance and masking instability. We introduce GetNetUPAM, a hierarchical nested cross-validation framework that uses the nested stage to quantify model stability rather than tune for inflated hold-out scores. By partitioning data into site-year blocks, GetNetUPAM preserves ecological heterogeneity and forces each outer fold to represent a distinct environmental regime, preventing overfitting to localized noise or sensor artifacts. Inner stratified folds measure generalization across the full UPAM signal distribution, enforcing strict separation between model development and the outer held-out deployment condition. Using GetNetUPAM, we evaluate the Adaptive Resolution Pooling and Attention Network (ARPA-N), a CNN architecture for irregular spectrogram dimensions. ARPA-N integrates CBAM spatial attention as a learned noise suppressor, producing attention maps that localize true call structure and avoid the global, non-biological cues exploited by standard CNNs on long-window data. Under GetNetUPAM, ARPA-N generalizes robustly across diverse environmental regimes. In the zero-training support Balleny Islands region, it reduces false positives per hour by over an order of magnitude (approximately 10x) at fixed 90 percent recall, yielding consistently improved metrics across folds. These advances provide a reproducible benchmark and move UPAM toward scalable, deployment-reliable ecological monitoring.

02.
PLOS Computational Biology 2026-06-05

StPedf: Cell trajectory inference of spatial transcriptomics via spatial proximity embedding and spatial density-adaptive fusion

作者:

by Yuan Zhang, Ziyan Sun, Zhixin Shi, Mengdi Nan, Yuhan Fu, Qing Ren, Jie Gao Spatial transcriptomics is transforming our multidimensional understanding of cellular spatial organization and its functional mechanisms in processes such as development and disease by systematically resolving the spatial heterogeneity of gene expression within tissues. To delve deeper into the dynamic processes underlying spatial expression patterns, spatial trajectory inference integrates genetic and spatial information to reconstruct the spatial developmental trajectories of cells within tissues. This approach reveals the patterns of differentiation and dynamic changes as cellular states evolve continuously along spatial axes. However, existing methods often struggle to uniformly model the complex, nonlinear interactions between high-dimensional gene expression and spatial coordinates. Here, we introduce StPedf, whose core lies in employing a neural network with a masking mechanism to capture complex nonlinear interactions between high-dimensional genes and spatial positions. It further leverages spatial proximity information as a guiding cue, dynamically and adaptively adjusting the embedding of gene and spatial information and the weighting of spatial proximity information based on spatial density. This enables trajectory inference guided by spatial information. This enables optimal transport to derive intercellular transition matrices, reconstruct cellular differentiation trajectories, and construct pseudo-spatiotemporal maps. StPedf demonstrates superior performance over existing methods on five structurally distinct simulated datasets. Using StPedf, we successfully mapped distinct lineages in the spatial trajectories of telencephalon regeneration in the Ambystoma mexicanum, multiple malignant lineages expanding within primary tumors, and developmental spatial trajectories and pseudo-spatiotemporal maps in human dorsolateral prefrontal cortex (DLPFC). StPedf significantly enhances the accuracy and interpretability of spatial trajectory inference, providing critical technical support for revealing the dynamic patterns of cellular fate transitions within tissue microenvironments.

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

Normative Robustness as a Frontier for Non-Verifiable Reasoning in LLMs

arXiv:2606.12731v1 Announce Type: new Abstract: As LLMs increasingly serve in advisory and deliberative roles, users rely on them for non-verifiable reasoning in domains lacking objective ground truths. However, traditional evaluations of LLM reasoning focus almost exclusively on fact-based domains, such as mathematics and science, leaving uncertainty over whether and to what degree models can handle ambiguous, subjective, or value-laden problems over time. To address this concern, we propose moral reasoning as a paradigmatic subdomain of non-verifiable reasoning. We define moral robustness as a model's capacity to exhibit sound moral reasoning across time and contexts, and we introduce a scalable, adversarial, multi-turn evaluation framework to empirically measure this capability. We simulate 48,000 user-agent moral deliberations across four frontier LLMs, varying premise relevance, premise order, conversation duration, and the user's stated moral view. We find that models successfully ignore morally-irrelevant distractors, but shift their reasoning by up to 6.5%, on average, towards the user's stated preferred moral view, and varying their reasoning depending on factors such as order (altering moral judgments by order in 13-22% of the cases) and duration (altering moral judgments between single-turn and multi-turn in 10-24% of the cases). Our analysis indicates that models tailor not just their final verdicts but their underlying justifications to align with a user's moral viewpoint - a failure mode we characterize as moral deliberative sycophancy.

04.
PLOS Medicine 2026-06-01

Prenatal exposure to asthma medications and risk of neurodevelopmental disorders and educational difficulties: A systematic review and meta-analysis

by Lama A. Shakhshir, Alexia Karain, Jill P. Pell, Claire E. Hastie, Scott M. Nelson, Michael Fleming Background Since asthma exacerbations during pregnancy risk maternal and fetal health, continued medication is important. However, some studies have reported adverse neurodevelopmental outcomes following prenatal exposure to asthma medication. Therefore, this systematic review aimed to collate the existing evidence on the associations between prenatal exposure to asthma medication and neurodevelopmental and educational outcomes. Methods and findings A systematic review was conducted in accordance with PRISMA guidelines and the PECO framework. PubMed, Medline and Embase databases were searched for studies investigating prenatal exposure to one or more asthma medication and neurodevelopmental or educational outcomes published, in English, between January 2003 and September 2024, and updated in November 2025. Studies of asthma medication used for other indications were excluded. Study quality was assessed using the Newcastle-Ottawa scale. Random-effects meta-analyses were conducted where appropriate and heterogeneity was evaluated using Cochran’s Q and I2 tests.Of 16,824 studies identified by the initial search, seven were eligible for inclusion. All investigated beta-2-adrenergic agonists (B2AA), with one including B2AA as mono- and polytherapy—and one study also investigated inhaled corticosteroids (ICS) exposure. Two reported associations with autism spectrum disorder (ASD) and one with attention-deficit hyperactivity disorder (ADHD). An updated search identified one additional eligible study, which examined both ADHD and ASD, as well as other neurodevelopmental disorders. The included eight studies (n = 3,867,170 participants) comprised cohort (n = 5) and case-control (n = 3) designs and reported inconsistent results. Meta-analysis of three studies (n = 1,380,871) indicated significant associations with ASD for exposure to B2AA both preconception (aOR 1.34, 95% CI [1.19,1.52]) and during pregnancy (aOR 1.29, 95% CI [1.16,1.42]). Heterogeneity was low, with no evidence of significant publication bias. Limitations of the included studies comprised residual confounding and exposure misclassification. Additionally, studies included in the meta-analysis were few in number and did not adequately distinguish between medication effects and underlying maternal asthma. Conclusion Meta-analysis suggested an association between prenatal exposure to B2AA and ASD. An association with ADHD, reported in a single study, requires corroboration. To date, based on our search strategy, no association has been reported with communication skills, motor skills, problem-solving and personal-social skills, or cerebral palsy.

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

Scalar-pathway fidelity improves physical accuracy in short-range equivariant interatomic potentials

arXiv:2606.15892v1 Announce Type: new Abstract: Accurate interatomic potentials enable molecular dynamics of materials, molecules, and interfaces beyond density-functional-theory length and time scales. Equivariant neural network potentials have improved the representation of local geometry. However, their deployable energy surfaces ultimately manifest through invariant scalar channels, whose aggregation and spectral resolution remain comparatively underexamined. Here we use Physics-Aware Neighborhood (PAN) pooling and Physics-Guided Spectral (PGS) mixers as controlled scalar-pathway probes: lightweight, symmetry-preserving modifications that act only on \(\ell=0\) channels while leaving the equivariant tensor backbone unchanged. Using MACE as a high-body-order mechanistic scaffold, PAN adds coordination-sensitive amplitude modulation, whereas PGS augments edge and readout scalar features with radial and tapered spectral bases. Across metallic Ag, covalent Si, a short-range ionic LiF/Li–F subset, and MD17/rMD17 molecules, this scalar-pathway correction reduces MACE force errors by 22–27\% and energy errors by 19–22\%; on systems with stress labels, stress errors decrease by 27–28\%, at approximately 5\% additional inference-FLOPs cost. Directionally consistent gains in Allegro and NequIP further indicate that the correction is portable across distinct short-range equivariant backbones, although effect sizes remain architecture-dependent. These results identify scalar-pathway fidelity as a practical design dimension for short-range equivariant interatomic potentials.

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

Riemannian MeanFlow for One-Step Generation on Manifolds

arXiv:2603.10718v3 Announce Type: replace Abstract: Flow Matching enables simulation-free training of generative models on Riemannian manifolds, yet sampling typically still relies on numerically integrating a probability-flow ODE. We propose Riemannian MeanFlow (RMF), extending MeanFlow to manifold-valued generation where velocities lie in location-dependent tangent spaces. RMF defines an average-velocity field via parallel transport and derives a Riemannian MeanFlow identity that links average and instantaneous velocities for intrinsic supervision. We make this identity practical in a log-map tangent representation, avoiding trajectory simulation and heavy geometric computations. For stable optimization, we decompose the RMF objective into two terms and apply conflict-aware multi-task learning to mitigate gradient interference. RMF also supports conditional generation via classifier-free guidance. Experiments on spheres, tori, SO(3), and SE(3) demonstrate competitive one-step sampling with improved quality-efficiency trade-offs and substantially reduced sampling cost.

07.
arXiv (quant-ph) 2026-06-12

Roto-Reflection Geometry of Pure Two-Qubit Entanglement

arXiv:2606.12637v1 Announce Type: new Abstract: Pure two-qubit entanglement is usually characterized by scalar quantities such as concurrence. Here we show that it also has a natural geometric form. In the Pauli correlation tensor, maximally entangled states appear as improper orthogonal maps between two local Bloch spheres. These maps are roto-reflections. For partially entangled pure states, the same roto-reflection geometry is recovered after separating the contraction associated with concurrence. We call the corresponding geometric object the Entanglement Roto-Reflection Plane (ERRP). It organizes the maximally correlated directions of the two-qubit state and provides a covariant geometric complement to the scalar magnitude of entanglement.

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

PACT: Privileged Trace Co-Training for Multi-Turn Tool-Use Agents

Multi-turn tool-use agents must reason, call tools, and adapt to observations across several interaction turns. Post-training such agents is challenging, as reinforcement learning often suffers from sparse rewards and weak credit assignment despite matching the prompt-only inference setting, while supervised fine-tuning on expert traces provides dense process supervision but can over-constrain the model to fixed trajectories. To tackle this, we propose PACT, a Privileged trAce Co-Training framework for multi-turn tool-use agents. The key idea is to use expert traces only as training-time optimization signals rather than rollout-time hints. PACT keeps rollout generation prompt-only, then uses expert traces to guide optimization through two complementary signals: a trace-conditioned RL surrogate that evaluates prompt-only rollouts under expert-trace context, and a component-aware SFT loss that supervises reasoning prefixes and tool-calls with annealed strength. To reduce over-reliance on the training-only trace context, PACT further introduces a prompt-only anchoring. We also provide a latent-trace view that connects the two trace-based objectives and explains how expert traces can guide optimization without being used during rollout generation. Experiments on FTRL, BFCL, and ToolHop show that PACT consistently improves over strong SFT- and RL-based baselines, highlighting the value of privileged trace co-training for multi-turn tool-use learning.

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

BadWorld: Adversarial Attacks on World Models

Visual world models (VWMs) synthesize interactive, action-conditioned rollouts from a single context image. However, it remains an open question how robust these models are to adversarial perturbations. Standard adversarial attacks fail to assess this vulnerability because attackers lack ground-truth future videos and cannot predict subsequent user controls. We introduce BadWorld, a label-free adversarial framework tailored for autoregressive VWMs that systematically overcomes both constraints. First, to bypass the need for future supervision, we propose a self-supervised velocity attack that directly disrupts the early denoising dynamics of the model. Second, to ensure the attack generalizes across unpredictable user actions, we formulate a trajectory-adaptive bi-level optimization that actively mines hard control sequences to forge control-agnostic perturbations. Evaluated on representative VWMs with continuous and discrete controls, BadWorld exposes severe structural fragility. Visually indistinguishable adversarial images reliably trigger catastrophic degradation in future rollouts, leading to incomplete denoising, structural collapse, and control inconsistency. These findings reveal critical risks for deploying VWMs in safety-critical systems while highlighting a practical mechanism for privacy protection.

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

Temporal Validation Changes the Apparent Public-Health Utility of Under-Five Mortality Prediction in Bangladesh: A Four-Round DHS Machine-Learning Study

arXiv:2602.03957v2 Announce Type: replace Abstract: Background: Under-five mortality in Bangladesh remains uneven despite national progress. DHS-based prediction models may guide targeted follow-up, but only if validation reflects future use. We examined how validation design changes apparent prediction performance. Methods: Four BDHS rounds (2011-2022; 33,962 children; 1,290 deaths) were analysed with a 26-feature pipeline and three model classes under four validation regimes, including cross-survey temporal validation (train 2011+2014, calibrate 2017, test 2022). A 32-unit ELU multilayer perceptron was selected via genetic-algorithm neural architecture search. AUROC used 2,000 bootstrap resamples; screening utility used sensitivity, PPV, and number needed to screen (NNS) at fixed capacity. Results: Validation regime altered public-health interpretation more than model class. NAS MLP AUROC ranged from 0.669 (2022-only random) to 0.775 (pooled random), with temporal AUROC 0.730. At the top-10% temporal threshold, NAS identified 152/355 deaths in 2022 (sensitivity 42.8%, PPV 13.2%, NNS 7.6). NNS across designs ranged from 5.6 to 11.0. Conclusions: Validation-regime choice changed screening workload and apparent policy value more than architecture. Temporal validation supports defensible estimates of follow-up and referral demand; DHS child-mortality studies should report sensitivity, PPV, and NNS before programmatic use.

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

Learning Robust Pair Confidence for Multimodal Emotion-Cause Pair Extraction

Multimodal emotion-cause pair extraction (MECPE) requires reliable pair confidence over candidate pairs. Existing pair scorers commonly use pair-level cross entropy over valid candidates, which treats links mostly independently. This leaves the relative confidence geometry among competing causes under-constrained, allowing gold pairs to stay close to hard negatives or rely on incidental non-gold context. We study this vulnerability as pair-confidence brittleness and propose RPCL (Robust Pair Confidence Learning), a training-only framework for pair-confidence learning. RPCL encourages pair confidence to be both discriminative and stable: gold pairs are separated from row-wise hard negatives through a confidence-difference margin constraint, and clean pair predictions are aligned with predictions from a corrupted view where non-gold contextual utterance representations are partially corrupted. The original clean pair scorer and decoding pipeline are used unchanged at inference time. On ECF, MECAD, and MEC4, RPCL improves the three-seed mean Pair F1 over a matched base model by 2.58 to 2.83 percentage points in the full text-audio-video setting, and improves mean Pair AUPRC on all three datasets. Diagnostic analysis further shows larger gold-negative confidence gaps and lower margin-violation severity. These results suggest that explicitly shaping pair confidence is an effective training strategy for MECPE.

12.
arXiv (CS.AI) 2026-06-24

SP-Mind: An Autonomous Reasoning Agent for Spatial Proteomics Analysis

arXiv:2606.24235v1 Announce Type: new Abstract: Spatial proteomics enables single-cell-resolution characterization of protein expression within tissue architecture, playing a critical role in understanding tumor microenvironments and guiding precision medicine. However, current analysis workflows remain fragmented, requiring expert manual orchestration of heterogeneous tools and limiting research scalability and reproducibility. We present SP-Mind, the first autonomous AI agent designed to unify the spatial proteomics analysis pipeline, from raw multiplexed tissue imaging to downstream phenotype discovery. Equipped with expert-curated biological analysis skills and specialized computational tools, SP-Mind converts natural-language queries into end-to-end analytical workflows without task-specific fine-tuning. To rigorously evaluate its capabilities, we introduce SP-Bench, a comprehensive benchmark spanning diverse tissue types, comprising 102 tasks across 18 distinct categories. Through extensive evaluation on SP-Bench and established downstream tasks, SP-Mind achieves state-of-the-art performance compared to existing open-source biomedical agent baselines.

13.
arXiv (math.PR) 2026-06-24

Optimal Couplings of Levy Processes in the Class of Immersion Couplings

arXiv:2606.24290v1 Announce Type: new Abstract: We study the optimal coupling problem for Levy processes on R^d with respect to the quadratic cost. For any two such processes with finite second moments, we prove that the optimal Levy coupling constructed in Kang and Lim (2025), which was previously shown to be optimal among Feller couplings, is in fact optimal among the larger class of immersion couplings. The proof makes use of a characterization of immersion couplings, which is equivalent to the classical martingale preservation definition but more convenient for our purposes. The construction is based on two fundamental ingredients: the existence of an optimal coupling within the class of Levy couplings, and a dual formulation of the associated optimization problem. While both results were previously established in Kang and Lim (2025), we provide here simpler and more transparent proofs relying only on optimal transport between infinitely divisible measures and a generalized minimax principle. These arguments are self-contained and may be of independent interest.

14.
arXiv (CS.AI) 2026-06-11

Intelligent Automation for Embodied Benchmark Construction: Pipelines, Embodiments, Simulators, and Trends

arXiv:2606.12207v1 Announce Type: cross Abstract: Embodied intelligence now spans navigation, household assistance, manipulation, autonomous driving, aerial agents, and multimodal large-model control. This expansion has made benchmark construction a central bottleneck for reliable evaluation. Unlike static datasets, embodied benchmarks combine task specifications, environments, robot data, demonstrations, annotations, metrics, evaluation scripts, and release policies into a single evaluation system. This survey reviews the literature through a five-stage construction pipeline: requirement and task construction, data acquisition, data cleaning and annotation, benchmark suite generation and metric definition, and evaluation execution with diagnostic feedback. For each stage, the survey analyzes the transition from manual curation to traditional automation, foundation-model assistance, and agentic closed-loop workflows. It also compares qualitative construction costs across human labor, data and asset acquisition, compute and simulation, validation and debugging, governance and maintenance, and rework risk. The main conclusion is that automation does not simply reduce benchmark cost. Instead, it often shifts cost toward validation, auditability, version control, and long-term governance. Progress in embodied evaluation will therefore depend not only on larger benchmark suites, but also on construction pipelines that are diagnosable, auditable, and responsibly refreshable.

15.
bioRxiv (Bioinfo) 2026-06-13

Virus-human protein-protein interactions predict viral phenotypes

Viral phenotypes such as host and tissue tropism are critical determinants of viral infection and transmission. Inferring viral phenotypes presents unique challenges compared to cellular organisms, as viruses rely entirely on host machinery for replication and survival. Current methods for predicting viral phenotypes mainly rely on viral genomic data, often overlooking host-related information. Here, we evaluated the utility of predicted virus-human protein-protein interactions (PPIs) in inferring diverse viral phenotypes using machine-learning algorithms. For predicting human infectivity, a PPI-based machine learning model outperformed both virus genomic and protein sequence-based models that used large language model embeddings. It also surpassed previous methods that incorporated both viral and host genomic data. The human proteins identified by the model were significantly enriched in functions related to viral infection and immune response. In predicting various phenotypes of human RNA viruses, PPI-based models performed better than virus sequence-based models in forecasting virulence, human transmissibility and transmission routes, while showing comparable performance to genomic sequence-based models in predicting tissue tropism. Finally, we demonstrated that a PPI-based model could distinguish high-risk HPV genotypes from low-risk ones. Proteins associated with high-risk HPV were involved in apoptosis and immune regulation, whereas those linked to low-risk HPV were enriched in telomere maintenance and DNA repair. Collectively, this study is the first to demonstrate the value of predicted virus-human PPIs in inferring viral phenotypes, thereby enhancing our understanding of the molecular mechanisms underlying these phenotypes. It also provides effective tools for risk assessment of emerging viruses, contributing to improved pandemic preparedness.

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

Confidence-Aware Automated Assessment of Student-Drawn Scientific Models

arXiv:2606.20264v1 Announce Type: new Abstract: Student-generated drawings are widely used in science education to assess learners' conceptual understanding in modeling-based tasks aligned with the Next Generation Science Standards (NGSS). However, scoring such drawings requires expert human judgment to interpret complex visual representations, making large-scale assessment costly to implement and sustain in classroom settings. In this work, we study automated scoring of student-generated scientific drawings using a vision-based model. We evaluate a Vision Transformer (ViT) with parameter-efficient adaptation and propose a confidence-aware scoring framework that derives response-level confidence from test-time predictive distributions. This confidence signal enables selective automation by scoring high-confidence responses automatically while deferring uncertain cases for human review. Experiments on six NGSS-aligned middle school assessment items show that the proposed approach improves scoring reliability while supporting a practical trade-off between automated coverage and scoring risk, highlighting the value of confidence-aware methods for trustworthy educational assessment.

17.
arXiv (CS.CV) 2026-06-12

Language-Guided Abstraction for Visual Reasoning

The Abstraction and Reasoning Corpus (ARC) is viewed as a critical avenue to Artificial General Intelligence (AGI), as it enables models to learn abstract transformation rules from few-shot examples and then generalize to new tasks. However, prevalent ARC methodology is either pure language or vision-only (i.e., VARC). The former depends heavily on LLMs, consuming billions of parameters. The latter often struggles to capture high-level semantics, leading to overfitting on pixel-level patterns. To bridge this gap, we propose L-VARC, a novel framework that enhances visual reasoning via a language-guided Learning Using Privileged Information (LUPI) branch. Specifically, we design a Semantic Compression Module by feeding a unified, task-agnostic prompt into DeepSeek-V3. In this way, the raw LARC (a crowd-sourced language description dataset) can be substantially refined and structured, fitting with the context length constraint of standard text encoders (e.g., CLIP). Moreover, we design a Cross-Attention Projector to align visual features with semantic embeddings, aiming to guide the training of the ARC model. Notably, the LUPI branch is taken in the training process and will be discarded during inference, thereby yielding a lightweight model with a mere 18 million parameters. Extensive experiments demonstrate that our L-VARC effectively leverages linguistic priors to boost visual reasoning and outperforms state-of-the-art. Ablation studies further confirm the contribution of the two new designs towards the L-VARC framework. The code is available at https://github.com/GZHU-DVL/L-VARC.

18.
Nature (Science) 2026-06-24

Epiblast diversification and blood formation in a human pregastrula

作者:

The incipient stage of gastrulation in human, when the primitive streak is about to emerge, represents a critical yet underexplored period. Here we present the high-resolution spatial transcriptomic landscape of a human embryo at Carnegie stage 6 (approximately 13–14 days post-conception), a stage at which primitive streak remains invisible and gastrulation-derived mesodermal/endodermal progenitors are not yet transcriptomically detected. We identified an anterior visceral endoderm-like hypoblast population, as well as a trifurcated developmental trajectory of the epiblast, progressing towards the amnion, primitive streak and node/prechordal plate/notochord (axial mesoderm) at subsequent developmental stages1–3. Furthermore, our findings challenge the existing paradigms by revealing that primitive haematopoiesis, involving three blood lineages, initiates in human yolk sac before gastrulation, earlier than previously recognized2,4–7, and that the first blood cells arise from the extra-embryonic mesoderm with a hypoblast rather than epiblast origin. Notably, we identified two spatial zones, each consisting of molecularly distinct yolk sac endoderm and extra-embryonic mesoderm populations, that respectively facilitated the generation of erythro-megakaryocytic lineages and myeloid precursors. These findings provide insights into the onset of gastrulation and the earliest blood formation in humans, with profound implications for advancing stem cell-derived human embryo models and in vitro blood regeneration. High-resolution spatial transcriptome analysis of a human embryo at Carnegie stage 6 reveals three distinct developmental trajectories from the epiblast towards amnion, primitive streak and axial mesoderm, and detects the initiation of haematopoiesis before gastrulation, originating from hypoblast rather than epiblast.

19.
PLOS Computational Biology 2026-06-17

Deciphering cell type-specific causal genetic effects on brain imaging-derived phenotypes and disorders with single-cell Mendelian randomization

作者:

by Anyi Yang, Xingzhong Zhao, Xing-Ming Zhao, Yucheng T. Yang Reconstructing causality routes from genetic effects to complex phenotypes in particular cell types is crucial for understanding biological mechanisms underlying the brain-associated phenotypes including imaging-derived phenotypes (IDPs), and brain disorders and behaviors (DBs). Here, we develop a single-cell Mendelian randomization framework to infer cell type-specific causal relationships between gene expression and diverse brain-associated complex phenotypes by integrating single-cell expression quantitative trait loci (cis-eQTLs) and genome-wide association study findings. We identifiy a set of 254 and 217 cis-eQTL target genes (eGenes) that may have causal effects on 112 IDPs and 26 DBs in eight cell types, respectively. These causal eGenes exhibit strong cell type specificity and varied pleiotropy among different types of brain-associated phenotypes. Further integrative analysis reveals putative causality routes among cell type-specific causal eGenes and brain-associated complex phenotypes. Finally, we characterize the spatiotemporal expression patterns of these causal eGenes, and highlight the coordinated associations of the brain-associated phenotypes based on the expression of their causal eGenes. Overall, our study presents a large-scale analysis of the genetic effects of brain structures, disorders and behaviors, providing a catalog of cell type-specific causal eGenes.

20.
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.

21.
arXiv (CS.LG) 2026-06-17

Constrained Diffusion Models with Primal-Dual Inference

arXiv:2606.17192v1 Announce Type: new Abstract: This paper develops constrained diffusion models with primal-dual inference (PDI) to sample from optimal distributions of entropy-regularized optimization problems with average constraints. We formalize constrained sampling in the Lagrangian dual domain, where the optimal distribution takes the form of a Gibbs distribution indexed by the optimal dual variable. Rather than estimating this dual multiplier before sampling and freezing it throughout generation, PDI jointly infers the optimal primal distribution and its parametrizing dual variable. Each reverse diffusion step denoises using the score field associated with the current multiplier and then updates the multiplier through dual ascent using the estimated constraint violation of the denoised samples. To enable this conditional score field, we train a single dual-conditioned score network over the family of Gibbs distributions induced by the dual variables encountered during inference. We prove that the time average of the dual variables generated along the inference trajectory converges to a neighborhood of the dual optimum and bound the effect of residual dual mismatch on the terminal distribution through schedule-dependent stability factors. We evaluate PDI on constrained sampling from a mixture of Gaussians, wireless resource allocation, and portfolio management.

22.
arXiv (quant-ph) 2026-06-19

Faking entanglement with imperceptible measurement deviations

arXiv:2606.20396v1 Announce Type: new Abstract: Quantum entanglement is a central resource underpinning emerging quantum technologies, enabling capabilities beyond those of classical systems. Accurate verification of entanglement is therefore crucial. However, experimental schemes usually rely on the assumption that quantum measurements can be realized exactly. As the complexity of a quantum system grows, this assumption typically becomes increasingly unrealistic, therefore leading to a widening mismatch between theoretical models and experimental implementations. Here we demonstrate that arbitrarily small measurement errors, when adversarially encoded in the measurement apparatus, can lead to the false certification of high-dimensional entanglement in systems that are, in fact, separable. This is achieved by introducing explicit hacking attacks to measurement devices in well-established entanglement verification tests. We further experimentally demonstrate this effect using classical photonic states encoded in the spatial degree of freedom, spanning up to 61 dimensions with measurement fidelity errors as low as 0.23%. Our results uncover a fundamental vulnerability in current methods for high-dimensional entanglement detection, highlighting the susceptibility of complex quantum devices to small adversarial perturbations. The findings underscore the need for developing secure verification of quantum information that is robust to bounded discrepancies between theory and experiment.

23.
arXiv (CS.AI) 2026-06-16

Calibrated Sampling-Free Uncertainty Estimation in Bayesian Deep Learning

arXiv:2606.16214v1 Announce Type: cross Abstract: Modern deep learning models remain notoriously prone to overconfidence, limiting their reliability in high-stakes applications. Bayesian methods aim to counter this by learning a distribution over model parameters, and recent advances now make this feasible for large-scale architectures at costs comparable to AdamW. However, a challenge remains at test time: predictions must be averaged across many forward passes with weights sampled from the posterior, which is prohibitively expensive. Variance propagation offers an efficient alternative, computing layer-wise analytical approximations of uncertainty in a single forward pass. While such techniques are effective for MLPs, their extension to modern architectures remains challenging, due to increased depth and diversity of layer types. To fill this gap, we propose Calibrated Variance Propagation (CVP), which introduces a new propagation method for normalization layers, combines it with recent techniques for handling activation functions, and absorbs residual error through a light calibration step. CVP yields comparably accurate uncertainty estimates to MC sampling across transformers and CNNs, at a fraction of the cost. Against prior variance propagation work, CVP improves coverage at $0.5\%$ risk from $8.2\%$ to $14.6\%$ with BEiT-3 on Visual Reasoning (NLVR2) and from $2.6\%$ to $10.8\%$ with ViLT on VQAv2, with gains extending to convolutional architectures.

24.
arXiv (quant-ph) 2026-06-15

Path superposition activating perfect quantum teleportation ability for separable states

arXiv:2505.11398v2 Announce Type: replace Abstract: Quantum teleportation is a quintessential quantum communication protocol that enables the transmission of an arbitrary quantum state between two distant parties without physically transmitting the state with the help of shared entanglement and limited classical communication. We show that it is possible to relax the entanglement requirement in quantum teleportation if we have access to a certain strain of superposition of quantum processes. Two types of superposition of quantum processes are generally considered in the literature: superposition of paths identified with quantum maps and superposition of indefinite causal orders of the maps. We find that when superposition of paths is incorporated in the protocol, quantum teleportation with unit fidelity becomes possible with nonzero probability of 1/4 even when the two parties share certain classes of separable states, including pure product states. In contrast, the assistance of superposition of indefinite causal order of quantum maps in teleportation protocol does not enable any quantum advantage for shared pure product states. Furthermore, we show that separable Werner states can also yield quantum advantage in quantum teleportation assisted by the superposition of paths. Finally, we establish that the presence of quantum coherence in the control qubit is both necessary and sufficient to achieve quantum advantage in quantum teleportation assisted with superposition of paths. The results potentially uncover yet another role of quantum superposition, in general, in teleportation versus entanglement.

25.
arXiv (math.PR) 2026-06-16

Higher-order spectral perturbation expansions II: Kernel matrices and manifold learning

arXiv:2606.16373v1 Announce Type: cross Abstract: We study spectral concentration bounds for kernel matrices as approximation of the corresponding kernel integral operator. Results are established under weak assumptions on the data setting and the reproducing kernel relying only on a Mercer condition and a local Weyl law. This allows us to deal with key features of kernel matrices, such as large multiplicities, large effective dimension, and heavy-tailed distributions. Our results apply to infinite dimensional principal component analysis, manifold learning, and Bayesian nonparametric statistics. We illustrate this via two prototypical examples: The heat kernel on the sphere and a wavelet prior from Bayesian nonparametrics.