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02.
arXiv (CS.LG) 2026-06-19

Meta Flow Maps enable scalable reward alignment

作者:
Peter Potaptchik↗Adhi Saravanan↗Abbas Mammadov↗Alvaro Prat↗Michael S. Albergo↗Yee Whye Teh↗

arXiv:2601.14430v2 Announce Type: replace-cross Abstract: Controlling generative models is computationally expensive. This is because optimal alignment with a reward function–whether via inference-time steering or fine-tuning–requires estimating the value function. This task demands access to the conditional posterior $p_{1|t}(x_1|x_t)$, the distribution of clean data $x_1$ consistent with an intermediate state $x_t$, a requirement that typically compels methods to resort to costly trajectory simulations. To address this bottleneck, we introduce Meta Flow Maps (MFMs), a framework extending consistency models and flow maps into the stochastic regime. MFMs are trained to perform stochastic one-step posterior sampling, generating arbitrarily many i.i.d. draws of clean data $x_1$ from any intermediate state. Crucially, these samples provide a differentiable reparametrization that unlocks efficient value function estimation. We leverage this capability to solve bottlenecks in both paradigms: enabling inference-time steering without inner rollouts, and facilitating unbiased, off-policy fine-tuning to general rewards. Empirically, our single-particle steered-MFM sampler outperforms a Best-of-1000 baseline on ImageNet across multiple rewards at a fraction of the compute.

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03.
arXiv (CS.CV) 2026-06-17

GOT-JEPA: Generic Object Tracking with Model Adaptation and Occlusion Handling using Joint-Embedding Predictive Architecture

作者:
Shih-Fang Chen↗Jun-Cheng Chen↗I-Hong Jhuo↗Yen-Yu Lin↗

The human visual system tracks objects by integrating current observations with previously observed information, adapting to target and scene changes, and reasoning about occlusion at fine granularity. In contrast, recent generic object trackers are often optimized for training targets, which limits robustness and generalization in unseen scenarios, and their occlusion reasoning remains coarse, lacking detailed modeling of occlusion patterns. To address these limitations in generalization and occlusion perception, we propose GOT-JEPA, a model-predictive pretraining framework that extends JEPA from predicting image features to predicting tracking models. Given identical historical information, a teacher predictor generates pseudo-tracking models from a clean current frame, and a student predictor learns to predict the same pseudo-tracking models from a corrupted version of the current frame. This design provides stable pseudo supervision and explicitly trains the predictor to produce reliable tracking models under occlusions, distractors, and other adverse observations, improving generalization to dynamic environments. Building on GOT-JEPA, we further propose OccuSolver to enhance occlusion perception for object tracking. OccuSolver adapts a point-centric point tracker for object-aware visibility estimation and detailed occlusion-pattern capture. Conditioned on object priors iteratively generated by the tracker, OccuSolver incrementally refines visibility states, strengthens occlusion handling, and produces higher-quality reference labels that progressively improve subsequent model predictions. Extensive evaluations on seven benchmarks show that our method effectively enhances tracker generalization and robustness.

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04.
arXiv (math.PR) 2026-06-16

Super-Arrhenius relaxation of the triangular plaquette model in any dimension

作者:
Laurent Bartholdi↗Ivailo Hartarsky↗Ivan Mitrofanov↗

arXiv:2606.16259v1 Announce Type: new Abstract: Consider the following plaquette model from statistical physics: a lamp lies at every vertex of the triangular lattice and a switch lies at every even vertex of the (bipartite) dual hexagonal lattice. Each switch toggles the three lamps on its face. The energy of a configuration is the number of ON lamps. For the Glauber dynamics associated with the Gibbs measure defined by this Hamiltonian at any inverse temperature $\beta>0$, we show that, in any dimension $d\ge 2$, the infinite volume relaxation time satisfies \[e^{\beta^2/C}/C \le T_{\mathrm{rel}}\le Ce^{e^{C\beta}}\] for some $C>0$. Our result entails that the Gibbs measure is unique. The $e^{\beta^2}$ scaling was conjectured by Newman and Moore in 1999 and matches the behaviour of supercritical rooted kinetically constrained models such as the East model, thus recovering fragile glass phenomenology in the absence of kinetic constraints. More precisely, we show that, on a torus of side length $2^k$, when $\beta\to\infty$ and $k/\beta\to0$, we have $T_{\mathrm{rel}}=e^{2\beta k(1+o(1))}$. Quite surprisingly, however, we also prove that, on non-periodic finite domains of size $n\le e^{\beta/C}$ for large $C>0$, we have the much larger asymptotics $\ln T_{\mathrm{rel}}=\beta n^{\Theta(1)}$. The main ingredients of the proofs are new results in extremal and enumerative combinatorics and rely on renormalisation ideas for the dynamics and its groundstates also known as the Ledrappier subshift. We note consequences of our results to geometric group theory (more precisely to the complexity of the word problem for the Baumslag finitely presented group) and to ergodic theory.

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

eCNNTO: A Highly Generalizable ConvNet for Accelerating Topology Optimization

作者:
Shengbiao Lu↗Xiaodong Wei↗

arXiv:2606.19921v1 Announce Type: new Abstract: This work proposes an element-based Convolutional Neural Network (CNN) to accelerate density-based Topology Optimization (TO), termed eCNNTO. TO generally undergoes a large number of iterations, where finite element analysis is performed in every iteration, leading to the efficiency bottleneck especially when dense meshes are used to achieve high-resolution designs. To address this limitation, eCNNTO is proposed to build upon Kallioras et al. (2020), where a Deep Belief Network (DBN) was trained for every element to predict its near-optimal density from its early history, thereby skipping the great majority of iterations and significantly accelerating the TO procedure. However, the method lacks spatial correlations among neighboring elements and may lead to disconnected features in the final structure. The proposed method employs CNN with residual connections to address this issue. On top of it, a novel training strategy is introduced to further enhance the optimization efficiency, where the training dataset consists of the final stage density histories rather than early ones. This change can also help reduce the required training data size. eCNNTO requires only a small dataset to train and yet it can be generalized to problems with largely different boundary conditions, loading cases, design domain geometries, mesh resolutions, as well as non-design domains. In the end, the generalization capabilities and efficiency of eCNNTO are demonstrated through a variety of examples in two and three dimensions, achieving up to 90% and 97% reduction of iterations, respectively.

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06.
medRxiv (Medicine) 2026-06-22

Toward less intrusive pubertal assessment: longitudinal evaluation of tanner and non-tanner metrics in East African adolescents

作者:
Anok↗J. J↗Prodger↗J. L↗White↗Yang↗Park↗D. E↗Bukenya↗S. P↗Kiboneka↗Agaba↗…

Background: Accurate pubertal assessment is essential in pediatric endocrinology and adolescent health research. While Tanner staging remains the gold standard, its subjective nature and invasive genital examination limit feasibility and acceptability, especially in longitudinal studies and culturally sensitive settings. This study evaluated less intrusive pubertal assessment combinations that maintain discriminative accuracy. Methods: We conducted a longitudinal study among 200 uncircumcised, sexually naive males aged 15-17 years in Southwestern Uganda, with quarterly follow-up over three years. Clinicians assessed Tanner staging metrics (pubic hair, testicular volume, penile length, scrotal color), axillary hair, and serum testosterone. Markov transition models estimated Tanner stage progression. Ordinal logistic regression and area under the receiver operating characteristic curve (AUC) analyses quantified discriminative performance of individual and combined metrics. Results: At baseline, participants were distributed across Tanner stages II (6.0%), III (13.5%), IV (55.0%), and V (25.5%). Among individual metrics, pubic hair distribution best predicted overall Tanner stage (AUC=0.867), while penile length was least predictive (AUC=0.833). The full four-metric Tanner model achieved high discrimination (AUC=0.993). However, a less intrusive combination of pubic hair and scrotal color achieved comparable discrimination (AUC=0.942), improving to AUC=0.953 with axillary hair and age. Markov modeling demonstrated frequent bidirectional transitions between Tanner stages IV and V, reflecting variability in longitudinal staging. Conclusions: A minimally intrusive assessment combining pubic hair, scrotal color, axillary hair, and age reliably predicts pubertal stage, offering an acceptable alternative to traditional Tanner staging for research and surveillance contexts where genital manipulation is impractical or unethical.

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

A spectral audit framework reveals task-dependent aperiodic reliance across EEG and ECG deep learning

作者:
Jasmeet Singh Bindra↗Siddharth Panwar↗

arXiv:2606.08583v2 Announce Type: replace Abstract: Deep learning on physiological time series is interpreted through domain-specific features – oscillatory rhythms in EEG, morphological complexes in ECG – yet these signals sit atop a broadband aperiodic 1/f-like envelope that covaries with arousal, age, and pathology. We introduce a spectral audit framework combining aperiodic/periodic decomposition, phase-preserving Fourier interventions, sham controls, and simulation validation. Aperiodic reliance was task-dependent and architecture-general: across six neural architectures, flattening drops exceeded 0.42 balanced-accuracy points for sleep-wake classification, reached 0.07-0.13 for clinical abnormality detection, and remained minimal for motor imagery. Six of seven EEG foundation models showed FDR-significant aperiodic reliance on clinical EEG; age/sex and recording-era controls reduced but did not eliminate the effect. Applying the audit to PTB-XL ECG revealed neural drops of 0.32–0.36 persisting after demographic matching, confirming this confound class extends beyond EEG. Aperiodic controls should become standard for interpretable physiological time-series deep learning.

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08.
arXiv (math.PR) 2026-06-11

Heat kernel estimates for Markov processes with blowing-up jump kernels

作者:
Soobin Cho↗Panki Kim↗Renming Song↗Zoran Vondra\v{c}ek↗

arXiv:2512.24807v2 Announce Type: replace Abstract: In this paper, we establish sharp two-sided heat kernel estimates for a large class of purely discontinuous symmetric Markov processes on closed subsets $F$ of $\mathbb{R}^d$, whose jump kernels blow up on a Borel subset $\Sigma$ of $F$. We assume that $F\setminus \Sigma$ is a $\kappa$-fat set and is dense in $F$. To the best of our knowledge, this is the first work establishing sharp heat kernel estimates for jump processes whose jump kernels blow up on part of the state space. The jump kernels under consideration take the form $J(x,y)=|x-y|^{-d-\alpha}{\mathcal B}(x,y)$, where $\alpha\in (0,2)$ and the function ${\mathcal B}(x,y)$ blows up at a subset $\Sigma$ of $F$. A fundamental obstacle is that the tails of the jump measures are not uniformly bounded, and hence standard techniques in heat kernel analysis do not provide a priori off-diagonal estimates. To overcome this difficulty, we develop a new approach based on weighted integral estimates for the heat kernel that are sensitive to both the blow-up behavior of the jump kernel and the geometry of $F\setminus \Sigma$. Examples of processes falling within our general framework include traces of isotropic $\alpha$-stable processes in $C^{1,\rm Dini}$ sets, processes in Lipschitz sets arising in connection with the nonlocal Neumann problem, and a large class of resurrected self-similar processes in the closed upper half-space.

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09.
arXiv (CS.CV) 2026-06-15

HumP-KD: A Hybrid Uncertainty-Aware Multi-Stage Progressive Knowledge Distillation Framework for Efficient Fire Classification

作者:
Mohammed Arif Mainuddin↗Najifa Tabassum↗Omar Ibne Shahid↗Riasat Khan↗

Real-time fire classification systems require models that are simultaneously accurate, computationally efficient, and deployable on resource-constrained hardware. This work proposes HumP-KD, a Hybrid Uncertainty-aware Multi-stage Progressive Knowledge Distillation framework for efficient fire classification. Two datasets, FlameVision and Dataset-II, containing 8,600 and 31,309 images, are used. Various CNN and transformer baselines are applied under standard preprocessing, online augmentation, Gaussian noise and motion blur robustness conditions. The proposed HumP-KD model distills knowledge from two frozen heterogeneous transformer teachers, Swin-Tiny and ViT-Base, along with their Meta-MLP ensemble, into a lightweight MobileViT-S student via three tightly integrated components. Hierarchical Progressive Knowledge Distillation employs a Hierarchical Feature Builder. It generates a fused spatial attention mask to guide distillation toward discriminative regions selectively. Multi-Stage Knowledge Distillation progressively activates three distillation stages across training. On Dataset-II, HumP-KD achieves a mean F1 score of $0.9876 \pm 0.0063$ across 10 independent trials, significantly outperforming the MobileViT-S baseline trained without distillation ($0.9537 \pm 0.0351$), with statistical significance confirmed by both independent t-test ($p = 0.0195$) and Wilcoxon signed-rank test ($W = 1$, $p = 0.0039$). The proposed method also demonstrates strong generalization across datasets and robustness under degraded visual conditions. The student model retains only 4.94M parameters and 19.01Mb model size, representing a $5.7\times$ parameter reduction over Swin-Tiny and a $17.5\times$ reduction over ViT-Base, while achieving 37.72 CPU FPS, making it suitable for real-time deployment.

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10.
arXiv (CS.LG) 2026-06-17

Adaptable Method for Crystal Design across Diverse Constraints and Objectives with Pretrained Property Predictors

作者:
Akihiro Fujii↗Yoshitaka Ushiku↗Koji Shimizu↗Anh Khoa Augustin Lu↗Satoshi Watanabe↗

arXiv:2410.08562v5 Announce Type: replace-cross Abstract: Advanced crystal design can accelerate materials discovery across applications from photovoltaics to spintronics. Practical design must satisfy multiple properties and physical constraints, yet existing machine-learning-based approaches to such design often depend on large datasets, retraining, or task-specific generators. Here, we show that direct predictor-guided gradient optimization enables data-efficient, constraint-rich crystal design by combining off-the-shelf predictors with site-wise element masks, template initialization, and task-specific losses. In perovskites, it outperformed generative and Bayesian baselines under three targets – band gap, formation energy, and tolerance factor – and two hard constraints. DFT assessment further showed band-gap targeting competitive with a leading generative model despite using predictors trained on roughly one-tenth of the data. By flexibly combining pretrained predictors with application-oriented masks and custom losses, the same framework supported half-metal design. Such modularity could help researchers and engineers translate diverse application requirements directly into optimized candidate crystals with minimal computational cost.

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

Canonical Variates in Wasserstein Metric Space

作者:
Jia Li↗Lin Lin↗

arXiv:2405.15768v2 Announce Type: replace-cross Abstract: In this paper, we address the classification of instances represented by distributions on a vector space rather than single points. We consider classification algorithms based on pairwise distances, specifically, the Wasserstein metric between distributions. Central to our investigation is dimension reduction within the Wasserstein metric space to enhance classification accuracy. We introduce a novel approach grounded in the principle of maximizing Fisher's ratio, defined as the quotient of between-class variation to within-class variation. The directions in which this ratio is maximized are termed discriminant coordinates or canonical variates axes. In practice, both between-class and within-class variations are defined as the average squared Wasserstein distances between pairs of distributions, with the pairs either belonging to the same class or to different classes. This ratio optimization is achieved through an iterative algorithm, which alternates between optimal transport and maximization steps within the vector space. Empirical studies are conducted to assess the algorithm's convergence; and experimental results demonstrate that the dimension reduction technique substantially enhances classification performance. Moreover, the new method outperforms well-established algorithms that operate on vector representations derived from distributional data. It also exhibits robustness to variations in how instances are summarized by distributions, such as the number of components in a Gaussian mixture model (GMM) representation.

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

Generative Modeling on Metric Graphs via Neural Optimal Transport

作者:
Alessandro Micheli↗Yueqi Cao↗Anthea Monod↗Samir Bhatt↗

arXiv:2606.16273v1 Announce Type: cross Abstract: We introduce, to our knowledge, the first deep generative modeling framework for probability distributions continuously supported on compact metric graphs. Given source and target measures on a metric graph, our method embeds the graph into a smooth ambient space, solves an entropic Kantorovich problem via a neural semidual parameterization, and projects generated samples back onto the original graph. We study two embedded geometries: an extrinsic Euclidean realization and the intrinsic tropical Abel–Jacobi embedding into the Jacobian torus. In both cases, the resulting generator is graph-supported by construction. We prove that, in the joint limit of increasing neural expressivity, the learned generator converges weakly to a valid transport coupling between the original graph measures. Empirically, across a range of geometrically distinct graphs, our method matches or improves upon heuristic transport baselines based on discrete graph OT, while scaling more favorably. Finally, we demonstrate scalability on real-world urban mobility data by training our model on one million Uber pickup locations in Manhattan, New York City.

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13.
arXiv (quant-ph) 2026-06-19

Scalable quantum circuit knitting using a weak-coupling approximation

作者:
John P. T. Stenger↗Daniel Gunlycke↗Nikos Chrisochoides↗

arXiv:2606.19035v2 Announce Type: replace Abstract: We present a method for performing distributed quantum computing with controlled approximations. Exact distributed quantum computing requires exponential classical information to reconstruct the quantum process. However, we show how the classical cost is reduced to polynomial if the quantum procedure can be partitioned between a qubit that is weakly coupled the other qubits. We demonstrate our method for a layered circuit based on the circuits used for the quantum approximate optimization algorithm.

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14.
arXiv (CS.AI) 2026-06-17

Mental Health AI Safety Claims Must Preserve Temporal Evidence

作者:
Srimonti Dutta↗Ratna Kandala↗

arXiv:2605.08827v2 Announce Type: replace Abstract: The safety of mental health AI is often judged at the wrong temporal scale. Current evaluations typically score isolated responses, endpoint outcomes, or aggregate dialogue quality, while clinically consequential failures may arise from the order and accumulation of interactions themselves, including delayed escalation, repeated reinforcement, dependency formation, failed repair, and gradual deterioration across turns. This paper argues that this mismatch is not merely a limitation of evaluation coverage but a source of invalid safety conclusions. We introduce Temporal Safety Non-Identifiability, a formal account of why safety properties that depend on sequence, timing, accumulation, or recovery cannot be certified by protocols that discard those features. From this formalization, we develop SCOPE (Safety Claims Over Preserved Evidence) as a general principle for aligning safety claims with the evidence an evaluation actually retains, and instantiate it as SCOPE-MH, a mental-health instantiation of this reporting standard. We operationalize SCOPE-MH through a proof-of-concept on the AnnoMI dataset of expert-annotated motivational interviewing conversations, which reveals mechanisms of failure that per-turn behavior scoring does not represent. We propose SCOPE-MH as a diagnostic complement to existing evaluation infrastructure and argue that evaluation preserving temporal evidence is necessary, not optional, for safety-critical mental health AI deployment.

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

FOUNDv2: Learning Unified User Quantized Tokenizers for User Representation

作者:
Chuan He↗Yang Chen↗Bin Dou↗Wuliang Huang↗Baokun Wang↗Yongchao Liu↗Xing Fu↗Yu Cheng↗Chuntao Hong↗Weiqiang Wang↗Zhongle Xie↗Jiajun Zheng↗…

arXiv:2508.00956v3 Announce Type: replace-cross Abstract: User representation learning serves as a fundamental pillar for personalized services on large-scale web platforms. Despite its importance, conventional continuous embedding methods face significant challenges, including the lack of a unified paradigm for multi-source data integration, prohibitive storage overhead due to low information density, and the lack of multi-scale modeling granularity. To overcome these limitations, we introduce FOUNDv2, a comprehensive user representation scheme centered on the Unified User Quantized Tokenizer U2QT) framework. FOUNDv2 transforms heterogeneous user data into a standardized discrete token space through a robust two-stage architecture. Specifically, the framework first extracts compact feature representations and subsequently employs a multi-view RQ-VAE to discretize them into storage-efficient tokens using shared and source-specific codebooks. To empower these representations with predictive intelligence, we further design multi-scale alignment objectives to capture both fine-grained behavioral dependencies and macro-temporal periodicity. Extensive experiments on various benchmarks demonstrate that FOUNDv2 consistently outperforms task-specific baselines while achieving substantial reductions in storage and computational costs. Finally, the large-scale deployment of FOUNDv2 on Alipay validates its practical scalability and efficiency across diverse industrial scenarios. The main code is available at: https://github.com/chuanhe1999/FOUNDv2.

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

Agent Economics: An Entropy-Controlled Pluralistic Alignment Framework for Preventing Artificial Hivemind in Autonomous Agents

作者:
Cheonsu Jeong↗

arXiv:2606.09039v2 Announce Type: replace Abstract: This study proposes the Behavioral Protocol Framework (BPF), an entropy-controlled pluralistic alignment framework designed to address two critical challenges in autonomous agent economies: the hivemind effect arising from excessive strategic convergence among agents and the lack of transparency in autonomous decision-making processes. The proposed BPF consists of three core modules: Mentalizing-based Social Intelligence (MbSI) grounded in Theory of Mind (ToM), Pluralistic Alignment (PA), and a Verifiable Execution Kernel (VEK). These modules are organically integrated within a closed-loop architecture that governs the entire lifecycle of agent behavior, from decision-making and execution to verification and feedback. To evaluate the proposed framework, a simulation environment implemented in Python and a Streamlit-based user interface will be developed. Through empirical experimentation, the study aims to examine whether the entropy-control mechanism of the PA module can effectively preserve strategic diversity among agents and mitigate collective convergence, while the VEK module provides a comprehensive and transparent audit trail of the decision-making process. The anticipated results are expected to demonstrate that the proposed framework can simultaneously enhance the stability, efficiency, and trustworthiness of autonomous agent economies. Consequently, this research offers a practical approach for developing robust, transparent, and accountable agent-native economic systems.

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

Pix2Fact: When Vision Is Not Enough – Benchmarking Fine-Grained VQA with Web Verification on High-Resolution Real-World Scenes

作者:
Yifan Jiang↗Cong Zhang↗Bofei Zhang↗Qiaofeng Zheng↗Yifan Yang↗Bingzhang Wang↗Yew-Soon Ong↗

Despite progress on general tasks, vision-language models (VLMs) still struggle with challenges that demand both fine-grained visual grounding and external knowledge, a synergy overlooked by existing benchmarks that evaluate these abilities in isolation. To fill this void, we introduce Pix2Fact, a visual question-answering benchmark designed to assess expert-level visual perception and knowledge search. Pix2Fact comprises 1,000 high-resolution (4K+) images spanning eight scenarios. Its questions and answers are meticulously crafted by PhD-holding annotators from top global universities across diverse disciplines. Each question requires detailed visual grounding and the integration of external knowledge. Evaluating ten state-of-the-art VLMs, including proprietary models such as Gemini-3.1-Pro and GPT-5.4, we find that Pix2Fact poses a formidable challenge: the most advanced model (Gemini-3.1-Pro) achieves only 51.7% average accuracy, even with access to visual ground truth and search tools. Our analysis attributes this low accuracy to three factors, frequent visual grounding errors even with visual ground truth, shallow search harnessing, and VLM's inability to retrieve long-tail, unstructured local information. This striking gap exposes the limitations of current models in assisting humans with real-world scenarios that demand overwhelming visual comprehension. We believe Pix2Fact will serve as a critical benchmark to drive the next generation of language-vision agents that seamlessly integrate fine-grained perception with robust knowledge search.

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18.
Nature (Science) 2026-06-17

Confined migration induces non-lethal DNA damage in developing neurons

作者:
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.
PLOS Computational Biology 2026-06-22

A lactylation- and autophagy-associated prognostic signature reveals LSEC-derived CLEC3B as a novel mediator of hepatocellular carcinoma suppression

作者:
Youai Song↗

by Youai Song, Yinkuan Ning, Meihui Li, Jianwei Lan, Liangchen Lei, Yufei Han, Zhuo Meng, Binjie Li, Pengpeng Liu, Quanyan Liu The crosstalk between lactylation and autophagy within the hepatocellular carcinoma (HCC) microenvironment is a burgeoning field with profound implications. By integrating multi-omics data from public cohorts, we delineated two molecular subtypes of HCC with divergent clinical outcomes and established a lactylation-autophagy-related prognostic signature. This signature highlighted CLEC3B as a pivotal gene. Subsequent single-cell RNA sequencing and experimental validation unequivocally pinpointed liver sinusoidal endothelial cells (LSECs) as the principal cellular source of CLEC3B, which was significantly downregulated in HCC tissues. Functionally, conditioned media derived from CLEC3B-overexpressing LSECs potently inhibited HCC cell proliferation. Mechanistic investigations revealed that this tumor-suppressive effect was orchestrated through the concurrent suppression of autophagy and diminution of lactylation levels. Our findings position LSEC-secreted CLEC3B as a novel metabolic mediator in HCC, bridging two key pathways in tumor suppression, and endorse its clinical value both as a prognostic indicator and a promising therapeutic target.

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20.
medRxiv (Medicine) 2026-06-16

Reporting patterns of adverse drug withdrawal events using individual case safety reports in United States and European databases

作者:
Khan↗Doherty↗A. S↗McCarthy↗Dalton↗Jungo↗K. T↗Reeve↗Moriarty↗

Introduction: Adverse drug withdrawal events (ADWEs) are a key safety concern with deprescribing but are infrequently reported in trials. Although pharmacovigilance systems have advanced our understanding of medication-related harms, it is unclear how extensively these systems have been used for ADWEs. Objectives: To examine the reporting patterns of ADWEs for all drugs recorded in United States and European pharmacovigilance databases between 2004 and 2023. Methods: A retrospective study was conducted using two pharmacovigilance databases, the publicly available FDA-FAERS dataset and EMA-EV Level 2A (individual-level) dataset. ADWE cases were identified using relevant MedDRA preferred terms. Data on patient characteristics, reporter type, drugs, indication, ADWE outcomes, dechallenge/rechallenge, seriousness criteria, time to onset, duration, and causality were summarised. Results: A total of 158,505 ADWE reports were analysed (FDA-FAERS: 145,514; EMA-EV: 12,987), with mean ages of 46.1 (FDA; 55.3% female) and 45.5 years (EMA; 57.1% female). The frequently reported drug classes were opioids (FDA: oxycodone, 29.8%; EMA: buprenorphine, 19%), antidepressants (FDA: duloxetine, 32%; EMA: venlafaxine, 25.9%) and gabapentinoids (FDA: pregabalin, 6.7%; EMA: pregabalin, 6.0%). The most common adverse outcomes were other serious medical conditions (FDA=63.9%; EMA=46.0%), hospitalisation (FDA=15.9%; EMA=28.3%), and disability (FDA=13.3%; EMA=6.2%) and these outcomes varied significantly based on sex and age group (p

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21.
bioRxiv (Bioinfo) 2026-06-11

HalluDesign-NA: Extending HalluDesign for De Novo Nucleic Acid Design

作者:
Fang↗Wang↗Cao↗

AlphaFold3 has revolutionized the prediction of biomolecular structures and interactions, including atomic-level modeling of nucleic acids. However, the de novo design of structured and functional nucleic acids remains a significant challenge. Here, we extend our HalluDesign framework to nucleic acid design by integrating NA-MPNN for nucleic acid sequence optimization and design. This new framework, HalluDesign-NA, enables iterative sequence-structure co-optimization, facilitating the de novo design of nucleic acids. Computational benchmarking across ssDNA, ssRNA, and aptamer design tasks demonstrates consistent improvements in confidence scores (pLDDT, ipTM), supporting the feasibility of de novo nucleic acid design under various constraints, such as sequence length, symmetry, and protein structure context. We anticipate that HalluDesign-NA will accelerate the de novo design of functional nucleic acids for applications in biotechnology and medicine. The source code for HalluDesign-NA is available at https://github.com/MinchaoFang/HalluDesign_NA.

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

MolE-RAG: Molecular Structure-Enhanced Retrieval-Augmented Generation for Chemistry

作者:
Joey Chan↗Wonbin Kweon↗Ashley Shin↗Niharika Bhattacharjee↗Pengcheng Jiang↗Yue Guo↗Jiawei Han↗

arXiv:2606.05693v2 Announce Type: replace Abstract: Large language models (LLMs) have shown promise for molecular property prediction, but their ability to reason over chemical structures remains limited, as molecular representations such as SMILES differ substantially from the natural language on which LLMs are primarily trained. To bridge this semantic and chemical knowledge gap, we propose MolE-RAG, a training-free, molecule-centric retrieval-augmented generation framework for LLM-based molecular property prediction. MolE-RAG augments each prediction with three complementary sources of inference-time context: retrieved chemistry literature, molecule-specific information including compound synonyms, identifiers, functional group annotations, and physicochemical descriptors, and structurally similar molecules retrieved from the training set. We evaluate MolE-RAG across nine molecular property prediction tasks using proprietary, chemistry-specialized, and open-source LLMs. Across general-purpose LLMs, MolE-RAG improves ROC-AUC by up to 28 percentage points on classification tasks and reduces regression RMSE by up to 67% relative to a SMILES-only baseline. We further find that the utility of each context source varies across models and tasks, with different models benefiting most from textual retrieval, molecular context, or structural retrieval. These results suggest that molecule-centric retrieval can improve LLM-based molecular property prediction without model fine-tuning while providing a flexible framework for integrating heterogeneous chemical knowledge at inference time.

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

Multi-Agent Transactive Memory

作者:
To Eun Kim↗Xuhong He↗Dishank Jain↗Ambuj Agrawal↗Negar Arabzadeh↗Fernando Diaz↗

The decentralized deployment of LLM agents with diverse capabilities across diverse tasks motivates infrastructure for knowledge sharing across heterogeneous agent populations. Just as search engines index human-generated artifacts to support human problem solving, retrieval systems can organize agent-generated artifacts for reuse across agent populations. We extend retrieval-augmented generation - which demonstrates the value of human-authored artifacts to individual agents - to retrieval of agent-generated artifacts supporting a population of agents. In particular, agent trajectories encode reusable procedural knowledge, yet these artifacts are typically discarded after a single use or retained only by the producing agent, forcing newly instantiated agents to repeatedly rediscover existing solutions. We propose Multi-Agent Transactive Memory (MATM), a framework for population-level storage and retrieval of agent-generated trajectories, where producer agents contribute trajectories to a shared repository and consumer agents retrieve them to improve task execution. We focus on interactive environments (ALFWorld and WebArena), where trajectories are long and encode especially rich procedural structure. Our experiments demonstrate that retrieving trajectories from MATM improves downstream task performance and reduces interaction steps without coordination or joint training. These results position MATM as a design pattern for population-level experience sharing in open agent ecosystems.

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

SIMBA: ABidirectional Retrieval Forward Simulation Framework for Modeling FY-4A GIIRS Hyperspectral Infrared Radiances Toward NWP Applications

作者:
Jingdong Shen↗Fu Wang↗Qifeng Lu↗Hao Huang↗Chunqiang Wu↗Chi Yang↗Xiaofang Liu↗

arXiv:2606.19943v1 Announce Type: cross Abstract: Hyperspectral infrared observations are an important data source for numerical weather prediction (NWP) because they provide rich information on the vertical structure of atmospheric temperature and humidity. However, most existing deep learning methods mainly focus on one-way retrieval from radiances to atmospheric profiles, while the reverse radiance simulation process and the consistency between atmospheric state space and radiance observation space are insufficiently considered. In this study, we propose SIMBA, a unified bidirectional retrieval-forward simulation framework for FY-4A GIIRS hyperspectral infrared radiance modeling toward NWP applications. The framework jointly performs atmospheric profile retrieval and radiance reconstruction, introduces a cycle-consistency constraint to strengthen the coupling between the two processes, and employs a bidirectional Mamba state-space module to capture long-range dependencies along pressure levels. Using collocated FY-4A GIIRS observations and ERA5 reanalysis data, the proposed method is evaluated for temperature retrieval, specific humidity retrieval, long-wave radiance reconstruction, and medium-wave radiance reconstruction. Experimental results show that SIMBA outperforms several representative deep learning baselines across both retrieval and reconstruction tasks, while ablation experiments confirm the contribution of the bidirectional design and cycle-consistency mechanism. These results demonstrate that the proposed framework is effective for joint atmospheric profile retrieval and hyperspectral infrared radiance modeling, and suggest potential for future Jacobian-related analysis and NWP-oriented extensions.

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25.
arXiv (quant-ph) 2026-06-11

Experimental straintronics in nanotube quantum dots

作者:
L. Huang↗I. G. Rebollo↗A. R. Champagne↗

arXiv:2606.12180v1 Announce Type: cross Abstract: Single-wall carbon nanotubes (SWCNTs) are narrow ribbons of graphene with atomically precise edges and a single quantum transport channel, at experimentally-relevant dopings. This makes them ideal systems to harness quantum transport straintronics (QTS), i.e. using mechanical strain to control accurately quantum transport. We present QTS data from three single-wall carbon nanotube quantum dot (SWCNT-QD) transistors over a broad range of in-situ tunable and reversible uniaxial strain ($\Delta\varepsilon_mech\approx$ 0 to 3 %). We first present the nanofabrication of the suspended SWCNT transistors whose channel lengths are $\approx$ 30 nm. The channels are strained by moving gold clamps holding firmly the nanotubes. We present detailed charge transport data, $dI/dV_{B} - V_{B} - V_{G}$ and $dI/dV_{B} - V_{B} - \Delta\varepsilon_mech$, showing a large mechanical-gating effect of the SWCNT-QDs. The precise reversibility of the data, and their agreement with QTS theory, confirms that the tubes are strained elastically. We demonstrate that the mechanical control of the QD doping is not due to capacitive-gating effects, but to quantitatively predictable bandstructure changes including a strain-tunable bandgap. This precise mechanical control of the doping and bandgap of SWCNT-QDs could find applications in qubits, condensed matter physics, and homojunction molecular transistors.

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