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01.
bioRxiv (Bioinfo) 2026-06-11

A high-quality chromosome-scale reference genome assembly for Asparagus racemosus var. CIM-Shakti (Shatavari), a medicinal plant of Ayurvedic importance

Asparagus racemosus Wild., commonly known as Shatavari, is an important medicinal plant in Ayurveda and is valued for its steroidal saponins, particularly shatavarin compounds, which contribute to its adaptogenic, galactagogue, immunomodulatory, and therapeutic properties. Despite its medicinal and economic importance, genomic resources for this species have remained limited, restricting molecular breeding, pathway discovery, and comparative evolutionary studies within Asparagaceae. Here, we report a high quality chromosome scale reference genome assembly of A. racemosus var. CIM Shakti generated using PacBio HiFi long read sequencing and Omni C chromatin conformation scaffolding. The pseudo haploid assembly spans 817 Mb across 53 scaffolds, with a scaffold N50 of 98.50 Mb, L50 of 5, and a largest scaffold of 113.80 Mb. Ten major chromosome scale pseudomolecules were resolved, corresponding to the haploid chromosome complement of A. racemosus. The assembly showed high gene space completeness, with BUSCO completeness of 99.8% against the Eukaryota dataset and 98.0% against the Embryophyta dataset. BlobToolKit profiling further supported assembly quality, with GC content of approximately 39 to 40% and no major evidence of contamination. EDTA based repeat annotation identified 580.93 Mb of interspersed repetitive elements, accounting for 71.06% of the 817.57 Mb genome assembly. The repeat landscape was dominated by LTR retrotransposons, particularly Gypsy elements, which accounted for 25.01% of the assembly, followed by unclassified LTR elements at 26.58% and Copia elements at 4.84%. Structural and functional annotation identified 29,199 protein coding genes represented by 29,199 transcript models, 138,433 exons, and 125,201 CDS features. The annotation was structurally robust, with an average gene length of 4,605.1 bp, 4.74 exons per transcript, and 97.80% of transcripts containing multiple exons. The CIM Shakti reference genome provides a foundational genomic resource for investigating steroidal saponin biosynthesis, sex chromosome evolution, repeat driven genome expansion, and comparative genomics in Asparagaceae. This assembly will support future studies on medicinal trait improvement, conservation genomics, and genomics assisted breeding of climate resilient Shatavari cultivars.

02.
arXiv (CS.CL) 2026-06-24

A Synthetic Reliability-Aware PINN Benchmark for Offshore Wind Turbine Support-Structure Monitoring with Bayesian Inverse Identification

Reliable structural health monitoring (SHM) of offshore wind turbine (OWT) support structures requires fast state estimation from sparse measurements. Repeated high fidelity finite element or aeroelastic analyses are difficult to use directly in online monitoring loops, while purely data-driven surrogates can require large training sets. This paper presents Digi Turbine, a synthetic reliability-aware Physics Informed Neural Network (PINN) benchmark for OWT monopile support structure monitoring. The workflow embeds a simplified Euler Bernoulli beam equation with Winkler soil foundation in the training objective, couples it with Bayesian-prior-informed inverse identification, and adds First Order Reliability Method (FORM) screening. All validation uses synthetic configurations with analytical or finite-difference ground truth motivated by the NREL 5MW reference turbine context.

03.
Nature Medicine 2026-06-10

Dual-target gene therapy in Parkinson’s disease: a multicenter phase 1 trial

作者:

Restoring striatal dopamine synthesis is a promising gene therapy strategy for Parkinson’s disease. Previous adeno-associated virus-mediated aromatic L-amino acid decarboxylase (AADC) monotherapies remain dependent on exogenous levodopa, whereas multigene delivery is constrained by strict adeno-associated virus packaging limits. A ‘dual approach’ targeting the two rate-limiting enzymes, tyrosine hydroxylase (TH) and AADC, offers the potential for autonomous dopamine synthesis. We report the 12-month primary safety and tolerability outcomes of a multicenter, open-label, dose-escalation, phase 1 trial evaluating BBM-P002, a new adeno-associated virus vector—AAVT42—codelivering constitutively active TH and AADC. Ten participants with moderate-to-advanced Parkinson’s disease were enrolled and received bilateral intraputaminal infusions across doses of 4.0 × 1011 vg (Cohort 1; n = 1), 6.0 × 1011 vg (Cohort 2; n = 2), 1.0 × 1012 vg (Cohort 3; n = 2) and 1.2 × 1012 vg (Cohort 4; n = 5). The trial achieved its primary outcome, as BBM-P002 demonstrated a favorable safety and tolerability profile within 12 months post-treatment. No dose-limiting toxicities or drug-related serious adverse events occurred. A total of 23 adverse events were reported, all judged unrelated to BBM-P002 and primarily mild and transient. Systemic toxicity and clinically meaningful immunogenicity were absent. In conclusion, intraputaminal delivery of BBM-P002 was safe and well tolerated in this phase 1 trial, supporting continued clinical development. ClinicalTrials.gov registration: NCT05822739 . Phase 1 results reveal that BBM-P002, a dual-target gene therapy co-delivering TH and DDC, is safe and well tolerated in Parkinson’s disease, with 12-month motor improvements signaling therapeutic potential.

04.
arXiv (CS.LG) 2026-06-24

SkyJEPA: Learning Long-Horizon World Models for Zero-Shot Sim-to-Real Control of Quadrotors

arXiv:2606.23444v2 Announce Type: replace-cross Abstract: Accurate dynamics models are critical for informed decision-making in robotic systems, particularly for agile aerial vehicles operating under uncertainty. Neural network dynamics models are attractive for capturing complex nonlinear effects, but existing predictive approaches struggle with long-horizon forecasting because their autoregressive rollout mechanism amplifies errors over time. Joint Embedding Predictive Architectures (JEPAs) offer a compelling alternative by modeling dynamics in latent space, yet prior JEPA-style methods for robot navigation have been studied primarily for kinematic-level planning, with limited investigation in high-frequency control. In this work, we introduce the JEPA-style model for real-time quadrotor control. The proposed approach combines a latent dynamics model with a novel physics-inspired prober that maps frozen latents to interpretable state, enabling physically grounded long-horizon prediction. Additionally, we combine the learned model with a sampling-based optimal control solution to take advantage of its predictive capabilities for real-time control on embedded hardware. Finally, to reduce the dependence on expensive and unsafe real-world data collection, we develop a structured pipeline for automated dataset generation. Extensive open-loop and outdoor closed-loop experiments demonstrate accurate prediction, robust zero-shot sim-to-real transfer, and strong generalization across diverse operating conditions.

05.
arXiv (CS.AI) 2026-06-18

Clin-JEPA: A Multi-Phase Co-Training Framework for Joint-Embedding Predictive Pretraining on EHR Patient Trajectories

arXiv:2605.10840v3 Announce Type: replace-cross Abstract: We present Clin-JEPA, a multi-phase co-training framework for joint-embedding predictive (JEPA) pretraining on EHR patient trajectories. JEPA architectures have enabled latent-space planning in robotics and high-quality representation learning in vision, but extending the paradigm to EHR data – to obtain a single backbone that simultaneously forecasts patient trajectories and serves diverse downstream risk-prediction tasks without per-task fine-tuning – remains an open challenge. Existing JEPA frameworks either discard the predictor after pretraining (I-JEPA, V-JEPA) or train it on a frozen pretrained encoder (V-JEPA 2-AC), leaving the encoder unaware of the rollout signal that the retained predictor must use at inference; co-training the encoder and predictor under a shared JEPA prediction objective would supply this grounding, but naïve co-training is unstable, with representation collapse and online/target drift causing autoregressive rollout to diverge. Clin-JEPA's five-phase pretraining curriculum – predictor warmup, joint refinement, EMA target alignment, hard sync, and predictor finalization – addresses each failure mode by phase, stably co-training a Qwen3-8B-based encoder and a 92M-parameter latent trajectory predictor. On MIMIC-IV ICU data, three independent evaluations support the framework: (1) latent $\ell_1$ rollout drift uniquely converges ($-$15.7%) over 48-hour horizons while baselines and ablations diverge (+3% to +4951%); (2) the encoder learns a clinically discriminative latent geometry (deteriorating-patient cohorts displace 4.83$\times$ further than stable patients in latent space, vs $\leq$2.62$\times$ for baseline encoders); (3) a single backbone outperforms strong tabular and sequence baselines on multi-task downstream evaluation. Clin-JEPA achieves mean AUROC 0.851 on ICareFM EEP and 0.883 on 8 binary risk tasks (+0.038 and +0.041 vs baseline average).

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

Training-Free Adversarial Robustness in Computational MRI

Deep learning (DL) methods have become the state-of-the-art for reconstructing sub-sampled magnetic resonance imaging (MRI) data. However, studies have shown that these methods are susceptible to small adversarial input perturbations, resulting in major distortions in the output images. Various strategies have been proposed to reduce the effects of these attacks, but they require retraining. In this work, we propose a novel approach for mitigating adversarial attacks on MRI reconstruction models without any retraining. Based on the idea of cyclic measurement consistency, we devise a novel mitigation objective that is minimized in a small ball around the attack input. Results show that our method substantially reduces the impact of adversarial perturbations across different datasets, attack types/strengths and PD-DL networks, and qualitatively and quantitatively outperforms conventional mitigation methods. We also introduce a practically relevant scenario for small adversarial perturbations that models impulse noise in raw data, which relates to herringbone artifacts, and show the applicability of our approach in this setting. Finally, we show our mitigation approach remains effective in two realistic extension scenarios: a blind setup, where the attack strength or algorithm is not known to the user; and an adaptive attack setup, where the attacker has full knowledge of the defense strategy.

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

Can Agents Read the Room? Benchmarking Visual Social Intelligence in Multimodal Simulation

Social interaction depends on both language and visible social signals, such as facial expressions, posture, gaze, and emotional shifts. Yet existing social-agent benchmarks are largely text-based and rarely test whether multimodal agents can use visual cues to guide interaction. We introduce \textsc{\benchmarkname{}}, a benchmark evaluating visual social intelligence in multimodal social simulation. It contains 240 scenarios, 585 role instances, and 2,340 role-task instances, combining aligned textual-visual evidence, structured role profiles, and four role-level tasks: expression task, characteristic task, interaction regulation task, and interaction outcome task. Evaluating seven recent MLLMs under verbalized-vision and direct-vision reveals a clear gap between local role enactment and interaction management: role-specific expression and conflict handling are near saturation, whereas interaction regulation and visually grounded outcome achievement remain substantially more difficult. The code is released at https://github.com/JunsWan/AgentViSS, and the dataset is available at https://huggingface.co/datasets/JunsWan/AgentViSS.

08.
arXiv (quant-ph) 2026-06-11

Gate-tunable spin-valley transport via carrier velocity in monolayer WSe$_2$

arXiv:2606.12353v1 Announce Type: cross Abstract: We theoretically investigate spin- and valley-resolved quantum transport in monolayer tungsten diselenide (WSe$_2$) described by an effective massive Dirac Hamiltonian. Particular attention is devoted to a finite barrier region characterized by simultaneously modulated Fermi velocity and scalar potential. The barrier velocity $v_2$ is related to the external velocity $v_1$ through a velocity ratio $\xi=v_2/v_1$, motivated by an optical analogy with the Snell-Descartes law. The exact refraction condition depends on the full spin- and valley-resolved dispersion, and the simple ratio $\xi=v_2/v_1$ is recovered only in the massless, symmetric limit. The interplay of intrinsic spin-orbit coupling in the conduction and valence bands, quantified by $\lambda_c$ and $\lambda_v$, with spin- and valley-dependent Zeeman fields, $M_s$ and $M_v$, gives rise to substantial changes in the quasiparticle dispersion, leading to pronounced modifications of the transport characteristics. By solving the Dirac equation and enforcing current-conserving matching conditions at the interfaces, we compute the spin- and valley-dependent transmission probability and conductance. Our results demonstrate that the barrier velocity, scalar potential, incidence angle, incident energy, and barrier width serve as effective control parameters for transport, giving rise to strong anisotropy and resonant tunneling features. Furthermore, we show that both the magnitude and orientation of spin- and valley-polarized currents can be continuously tuned via velocity and potential modulation. These findings establish combined velocity and potential engineering as a powerful theoretical framework for controlling spin-valley physics in two-dimensional transition-metal dichalcogenides.

09.
arXiv (CS.LG) 2026-06-17

Informative Missingness to Generate Irregular Clinical Time Series

arXiv:2606.17106v1 Announce Type: new Abstract: Laboratory tests in electronic health records are collected irregularly, and the absence of a test order can be as informative as the measurement itself. Such missingness reflects clinicians' decisions and patient physiology, making it important to model it directly rather than treat it as a preprocessing artifact. Here we present a diffusion-based approach for generating clinical time series that jointly models laboratory values and their observation patterns using the public Data Analytics Challenge on Missing Data Imputation (DACMI) benchmark derived from MIMIC-III. To preserve realistic sampling, we align chart times into 4-hour intervals and segment admissions into 7-day windows, producing trajectories that pair each lab value with a corresponding observation indicator. Standard transformations and normalization are applied to stabilize training. Our method extends the TimeDiff framework to learn continuous lab values and discrete missingness patterns through complementary diffusion objectives. Experiments show that the generated data closely match real patient trajectories across individual lab distributions and joint value-missingness embeddings, demonstrating that diffusion models can capture clinically meaningful dependencies between patient physiology and clinicians' testing behavior under MNAR-like (missing-not-at-random) missingness. These preliminary results indicate that our model can serve as an initial component toward developing clinical foundation models. By producing synthetic priors that preserve key physiology-missingness relationships, this work motivates the subsequent training of Prior-Data Fitted Networks capable of leveraging informative missingness, which we will investigate in the extended work.

10.
arXiv (CS.AI) 2026-06-24

Disentangling Aleatoric and Epistemic Uncertainty in Physics-Informed Neural Networks. Application to Insulation Material Degradation Prognostics

arXiv:2601.03673v2 Announce Type: replace-cross Abstract: Physics-Informed Neural Networks (PINNs) provide a framework for integrating physical laws with data. However, their application to Prognostics and Health Management (PHM) remains constrained by the limited uncertainty quantification (UQ) capabilities. Most existing PINN-based prognostics approaches are deterministic or account only for epistemic uncertainty, limiting their suitability for risk-aware decision-making. This work introduces a heteroscedastic Bayesian Physics-Informed Neural Network (B-PINN) framework that jointly models epistemic and aleatoric uncertainty, yielding full predictive posteriors for spatiotemporal insulation material ageing estimation. The approach integrates Bayesian Neural Networks (BNNs) with physics-based residual enforcement and prior distributions, enabling probabilistic inference within a physics-informed learning architecture. The framework is evaluated on transformer insulation ageing application, validated with a finite-element thermal model and field measurements from a solar power plant, and benchmarked against deterministic PINNs, dropout-based PINNs (d-PINNs), and alternative B-PINN variants. Results show that the proposed B-PINN provides improved predictive accuracy and better-calibrated uncertainty estimates than competing approaches. A systematic sensitivity study further analyzes the impact of boundary-condition, initial-condition, and residual sampling strategies on accuracy, calibration, and generalization, and the influence of measurement noise on aleatoric uncertainty. Overall, the findings highlight the capability of Bayesian physics-informed learning to support uncertainty-aware prognostics and informed decision-making in transformer asset management by tracking aleatoric and epistemic sources of uncertainty.

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

Learning Ego-Centric BEV Representations from a Perspective-Privileged View: Cross-View Supervision for Online HD Map Construction

Bird's-eye-view (BEV) representations derived from multi-camera input have become a central interface for online high-definition (HD) map construction. However, most approaches rely solely on ego-centric supervision, requiring large-scale scene structure to be inferred from incomplete observations, occlusions, and diminishing information density at long range, where perspective effects and spatial sparsity hinder consistent structural reasoning. We introduce Cross-View Supervision (CVS), a representation learning paradigm that transfers geometric and topological priors from an ego-aligned overhead perspective into camera-based BEV encoders. Rather than adding auxiliary semantic losses, CVS aligns representations in a shared BEV feature space and distills globally consistent structural knowledge from a perspective-privileged teacher into the ego-centric backbone. This supervision enhances structural coherence without modifying the inference architecture or requiring overhead input at test time. Experiments on nuScenes using ego-aligned aerial imagery from the AID4AD cross-view extension demonstrate consistent improvements over StreamMapNet while maintaining identical camera-only inference. CVS yields +3.9mAP in the standard $60\times30\,\mathrm{m}$ region and +9.9mAP in the extended $100\times50\,\mathrm{m}$ setting, corresponding to a 44% relative gain at long range. These results highlight perspective-privileged structural supervision as a promising training principle for improving BEV representation learning in HD map construction.

12.
arXiv (math.PR) 2026-06-16

BBP Phase Transition for a Doubly Sparse Deformed Model

arXiv:2603.04832v3 Announce Type: replace Abstract: We prove the equivalent of the Baik, Ben Arous, Péché (2004) phenomenon for a novel, doubly sparse model where both the Wigner noise matrix and signal vector(s) are sparse. Specifically, we consider a deformed sub-Gaussian sparse Wigner ensemble with a fixed number of sub-Gaussian spike vectors of the same-order sparsity added. We show that spike vectors with signals greater than one are correlated with the top eigenvectors of the deformed ensemble and that each spike vector of signal greater than one induces an outlier eigenvalue. Notably, our results hold in the supercritical sparsity regime for the Wigner matrix ($q \gg \frac{\log n}{n}$) and for any sparse spike vector with an unbounded number of entries ($np\to \infty$). No further relationship between the sparsities of the noise matrix ($q$) and spike vectors ($p$) is necessary. This generalizes the work of Benaych-Georges and Nadakuditi (2010) and Péché (2005).

13.
arXiv (CS.AI) 2026-06-19

Mitigating Simplicity Bias in OOD Detection through Object Co-occurrence Analysis

arXiv:2605.07821v2 Announce Type: replace-cross Abstract: Out-of-distribution (OOD) detection is crucial for ensuring the reliability of deep learning models. Existing methods mostly focus on regular entangled representations to discriminate in-distribution (ID) and OOD data, neglecting the rich contextual information within images. This issue is particularly challenging for detecting near-OOD, as models with simplicity bias struggle to learn discriminative features in disentangled representations. The human visual system can use the co-occurrence of objects in the natural environment to facilitate scene understanding. Inspired by this, we propose an Object-Centric OOD detection framework that learns to capture Object CO-occurrence (OCO) patterns within images. The proposed method introduces a new OOD detection paradigm that understands object co-occurrence within an image by predicting disentangled representations for the test sample, then adaptively divides patterns into three scenarios based on object co-occurrence patterns observed in ID training data, and finally performs OOD detection in a divide-and-conquer manner. By doing so, OCO can distinguish near-OOD by considering the semantic contextual relationships present in their images, avoiding the tendency to focus solely on simple, easily learnable regions. We evaluate OCO through experiments across challenging and full-spectrum OOD settings, demonstrating competitive results and confirming its ability to address both semantic and covariate shifts. Code is released at https://github.com/Michael-McQueen/OCO.

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

Rift: A Conflict Signature for Deception in Language Models

作者:

A model that lies while knowing the truth is the central case ELK cannot handle with behavioral evaluation alone. We ask whether such deception leaves an internal signature distinguishing it from honest error. Our key move is a control for wrongness: we contrast a sleeper agent (knows the truth, lies on trigger) against a naive liar (fine-tuned to emit the same wrong answers with no honest training). Both produce identical wrong outputs; any difference is about knowledge conflict, not incorrectness. We find deceptive forward passes carry a conflict signature - 2.1-2.3x higher residual rank than naive-liar passes on the same wrong answer - strong enough to identify which of two responses is the lie with 100% accuracy and no labels, across GPT-2 small/medium (three seeds) and three instruct models. Across Qwen2.5-1.5B/7B and Phi-3-mini, instructed deception raises residual rank on every tested fact (18/18, 40/40, 34/34); on Phi-3, lies separate perfectly from both honest answers and hallucinations (AUC 1.0, Wilcoxon p~6e-11). The signature survives strategic self-constructed deception (model invents its own lie, AUC 1.0), active concealment attempts (AUC 1.0), and length-controlled replication (20/20, AUC 1.0, p~1e-6). Using basis-free relative representations, a probe trained on one model family detects deception in two other families zero-shot (mean AUC 0.933), surviving simultaneous architecture and format change (AUC 0.821), and transfers across five languages (AUC 1.000, length-controlled). The signature is read-only: detectable but not injectable (0/8 both directions). Honest limitations and six negative experiments are documented in full.

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

Ellipse Meets Bit-Planes: A Novel Approach to RNFL based Glaucoma Detection Using Advanced Image Processing and Deep Learning

This work proposes an integrated pipeline for automatic glaucoma detection method from easily available colour fundas images based on an adaptive algorithm for ellipse-based polar transformation, to enhance the analysis of the Retinal Nerve Fiber Layer (RNFL) as the primary biomarker for observing glaucomatous changes, regardless of optic disc and macula position. Utilizing this transformation, we introduce two distinct frameworks tailored to different operational needs. The first framework, a deep learning-inspired feature fusion approach, achieves a 99.3% detection rate, ideal for settings where high precision is essential, despite higher computational demands. The second framework employs a novel image-processing algorithm based on bit-plane slicing, offering 92.31% accuracy and optimized for environments requiring rapid inference with minimal resource consumption. Both frameworks provide scalable and cost-effective solutions for early glaucoma detection. This study highlights the potential of RNFL-based diagnostic tools in addressing the global challenge of glaucoma, particularly in underserved regions.

16.
arXiv (quant-ph) 2026-06-15

Interpreting Bohm-like quantum potentials in "Computing quantum waves exactly from classical action"

arXiv:2605.20443v3 Announce Type: replace Abstract: The recent posting arXiv:2605.02621 [14], commenting on the article rspa.2025.0413 [7], argues that the proof of Lemma 3.1 in [7] is missing the spatial derivative of the density, which would lead to a Bohm-like quantum potential. This technical note shows why the propagated density is independent of space in the Feynman propagator construction of Lemma 3.1. This is done by extending the proof of Lemma 3.1 explicitly with Bohm-like quantum potential terms along the stationary action paths, and then showing that these terms are exactly zero. In [7], this property can also be verified directly on most examples (double slit, Aharonov-Bohm, potential well, harmonic oscillator, tunneling, EPR, QED), as well as in the derivations of the Pauli, Dirac, and Maxwell equations. For more general nonlinear actions, a time rescaling may be required to guarantee this space independence along stationary paths. In the hydrogen atom example, this time rescaling can be computed in closed form. In contrast to the general wave of the Madelung solution [9] Lemma 3.1 of [7] is defined first for a propagator, and a general wave is then constructed in a second step. Recall that a propagator is a specific quantum wave, which is initialized at $t=0$ with a Dirac impulse at a given initial position or momentum. In turn, a general wave is constructed in a second step by superposing a distribution of initial conditions using the propagator. This key difference is why the Bohm-like quantum potential terms disappear in the construction [7] (specifically, in the first step) while the Bohm potential in the Madelung analysis does not. This fundamental difference is also consistent with the fact that the wave construction in [7] extends naturally to relativistic contexts, while Bohmian non-locality notoriously prevents such extensions. Keywords - Response to arXiv:2605.02621, in relation to rspa.2025.0413

17.
bioRxiv (Bioinfo) 2026-06-11

TMO: ASYMMETRIC CROSS-MODAL ATTENTION FOR LEARNINGCELL-STATE-DEPENDENT REGULATORY LAGS FROM SINGLE-CELL MULTIOMIC DATA

Abstract Background: Single-cell multi-omics technologies simultaneously measure chromatin accessibility (ATAC) and gene expression (RNA), providing a unique window into the temporal ordering of regulatory events during differentiation. However, most computational models treat the two modalities symmetrically, ignoring the directional relationship between chromatin and transcription, and existing lag-aware methods estimate a single global lag per gene, failing to capture cell-state-dependent dynamics. Methods and Results: We introduce Temporal Multi-Omics (TMO), a deep learning framework that learns signed, cell-state-conditional regulatory lags ({Delta}{tau}) using asymmetric cross-modal attention. TMO projects RNA and ATAC into 50 latent components each, tokenises each cell as a sequence of 100 tokens, and uses a two-pass transformer in which a data-driven lag prior - derived from a sliding-window cross-correlation function - directly biases attention asymmetrically. On four independent 10x Multiome datasets (mouse brain, human brain, mouse kidney, human PBMC), the asymmetric model achieves Lag Concordance Scores (LCS) of 0.988-0.999, compared to 0.048-0.108 for an architecturally identical symmetric baseline. A stratified 80/20 held-out experiment confirms that the learned component-lag ordering generalises to unseen cells (held-out LCS 0.85-0.99). Clustered {Delta}{tau} heatmaps show positive {Delta}{tau} (ATAC-led priming) in early pseudotime and negative {Delta}{tau} (RNA-led, activity-dependent regulation) in late pseudotime; the ATAC-RNA correlation heatmap exhibits a U-shaped pattern indicative of developmental decoupling. Components with the most positive {Delta}{tau} are enriched for chromatin organization and stem cell differentiation (FDR < 0.05), while those with the most negative {Delta}{tau} are enriched for synaptic signalling and immune activation. Ablating the cell-state information from the lag predictor reduces the LCS and collapses per-component temporal dynamics (KS p [&le;] 0.039 in all four tissues), proving that TMOs dynamic lag patterns depend on cell-state conditioning. Independent ChIP-seq validation for four transcription factors (PAX5, Pax6, ASCL1, Hnf4) confirms highly significant separation between target genes and expression-matched background (p < 10-4 in all cases). Two Multiome Perturb-seq screens provide causal validation: SMARCB1 knockout shows a directional trend (1.5-fold target shift, p = 0.056, n = 147 perturbed cells), and SMARCE1 knockout reaches statistical significance (p = 0.0089, n = 3,394 perturbed cells). Gene-level cross-correlation independently validates that the regulatory lag signal is present in the raw data, and TMO further identifies rare, statistically significant biphasic gene programs where the regulatory direction reverses across pseudotime. Conclusions: TMO is the first method to make regulatory lag a learnable, cell-state-conditional, and architecturally encoded parameter. It is scalable, interpretable, and open-source, providing a powerful tool for studying regulatory timing in development, disease, and perturbation screens.

18.
medRxiv (Medicine) 2026-06-15

CDH13 is associated with cellular viability after exposure to ionizing radiation using genome-wide screening

Background: It is well known that genetic variants contribute to cellular sensitivity to chemotherapeutic agents and ionizing radiation (IR). The aim of this study was to identify single nucleotide polymorphisms (SNPs) and genes associated with the spectrum of normal cellular sensitivity of lymphoblastoid cell lines (LCLs) towards ionizing radiation and mitomycin C (MMC). Methods: In a first step, we determined the viability of LCLs established from male participants of the Berlin Aging Study II (BASE-II) aged >=62 years following treatments with increasing doses of IR (n=137 cell lines) or MMC (n=140 cell lines) using the alamarBlue assay. Results from intra-experimental triplicates and three independent experiments for each cell line and treatment were used to calculate the area under the curves (AUCs) representing the specific sensitivity to IR and MMC of each LCL. The data from these experiments were subsequently used as outcomes in genome-wide association studies (GWASs). In addition, we calculated polygenic risk scores (PGS) from UK Biobank GWAS results for four cancer-related phenotypes and assessed the extent to which the variance in the IR and MMC sensitivity is explained by these PGS. Results: The GWAS analyses revealed one variant, rs74728080, located in CDH13 on chromosome 16, to show genome-wide significant (p < 5 x 10-8, beta = 2.81) association with cellular viability after treatment with IR. In the GWAS on MMC sensitivity the most interesting signal was elicited by SNP rs113978558 in an intron of the PLD5 gene on chromosome 1 (p = 9.232 x 10-8; beta = 1.44). Several other SNPs with statistically suggestive (i.e., p < 1 x 10-5) evidence of association with IR or MMC sensitivity were identified. PGSs calculations from GWAS of four cancer-related traits in UKB explained ~5% and ~3% of phenotypic variance in IR- and MMC-induced cell viability, respectively. Conclusion: The genome-wide significant association of rs74728080 with IR sensitivity and the location of this variant in CDH13 is interesting and functionally highly plausible given its known involvement in oxidative-stress response and function as tumor suppressor. Taken together, our novel data suggest that CDH13 may be genuinely involved in regulating cellular IR sensitivity.

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

Equity with Efficiency: An Empirical Study of Tokenizers for Multilingual Large Language Models

Multilingual large language models (LLMs) depend on subword tokenization to bridge discrete text and continuous neural representation. State-of-the-art multilingual LLMs often use Byte-level Byte-Pair Encoding (BPE) tokenizers that structurally favor high-resource languages and Latin scripts. For speakers of underrepresented languages, particularly those across Southeast Asia, this bias inflates inference costs and widens cross-lingual capability gaps. We present the first systematic comparison of equitable tokenizers on a unified benchmark spanning 11 Southeast Asian languages. Beyond tokenizer-level analysis of compression efficiency and cross-lingual equity, we assess downstream task performance through controlled 1.5B-parameter language model training using the same training data. Our results show that Parity-aware BPE lies on the Pareto frontier of the efficiency-equity trade-off, achieving strong compression parity at competitive cost. Morphology-Driven Byte Encoding delivers the best semantic reasoning performance through morphologically richer representations, albeit at a higher computational expense. Byte Latent Transformer underperforms on downstream tasks, possibly because its architectural assumptions misalign with the constraints of limited low-resource training data. Together, our findings demonstrate that cross-lingual fairness and tokenization efficiency are not fundamentally at odds, and offer practical guidance for designing equitable multilingual models.

20.
arXiv (CS.AI) 2026-06-16

Training and Evaluating Diffusion Policies with Long Context Lengths

arXiv:2606.16447v1 Announce Type: cross Abstract: Imitation learning has enabled highly-dexterous robotic manipulation from RGB observations. Policies trained with these methods, however, typically condition robot actions on only a short history of observations. These policies cannot solve tasks that require memory and can get stuck repeatedly executing the same failing motions. In this work, we first benchmark policy performance as context length is incrementally increased from short to long, across a spectrum of tasks with varying local stability and memory requirements, and in multiple data regimes. To our knowledge, this is the first study to investigate context length in imitation learning at this level of detail. Our results challenge prior claims: naively scaling context length is not as brittle as advertised in literature. With an appropriate conditioning method and denoising backbone (UNet+Cross-Attention), single-task policies achieve high success rates on many tasks in the usual data regime even with naive scaling. Next, we propose a training algorithm to jointly train policies at multiple context lengths, further reducing the sample complexity of long-context learning. Finally, we apply our findings to re-evaluate some previously proposed solutions to long-context imitation learning.

21.
arXiv (CS.CV) 2026-06-15

Value-order Decomposition for Generalist Anomaly Detection

Industrial anomaly detection suffers from limited data, making cross-domain generalization particularly challenging. Generalist Anomaly Detection (GAD) aims to train a unified model on a source domain that can effectively detect anomalies in unseen target domains. In the initial semantic feature space, strong entanglement between anomalies and object categories or defect types hinders effective generalization across domains. Recent works address this issue by projecting features into a residual space; however, such methods primarily increase cross-domain overlap for normal features, while anomalous features remain specific to object categories, defect types and data domains, leading to poor alignment and generalization. To address this limitation, we propose Value-order Decomposition (VOD), a simple yet effective technique that bridges three types of generalization gaps across object categories, defect types (including real and synthetic defects), and data domains. VOD disentangles and suppresses object-category-, defect-type-, and domain-specific information, promoting alignment within normal and abnormal samples while preserving their separability, thereby enabling robust generalization across the three gaps. Leveraging the strong alignment between real and synthetic defects within the same object, we perform anomaly detection using only normal and synthetic-abnormal reference, and effectively generalize to unseen real defect types. Experiments on diverse industrial and medical benchmarks demonstrate that our method, using a simple cut-and-paste anomaly simulation strategy, achieves strong generalization across the three gaps.

22.
arXiv (CS.LG) 2026-06-18

Generative models for decision-making under distributional shift

arXiv:2604.04342v2 Announce Type: replace Abstract: Many data-driven decision problems are formulated using a nominal distribution estimated from historical data, while performance is ultimately determined by a deployment distribution that may be shifted, context-dependent, partially observed, or stress-induced. This tutorial presents modern generative models, particularly flow- and score-based methods, as mathematical tools for constructing decision-relevant distributions. From an operations research perspective, their primary value lies not in unconstrained sample synthesis but in representing and transforming distributions through transport maps, velocity fields, score fields, and guided stochastic dynamics. We present a unified framework based on pushforward maps, continuity, Fokker-Planck equations, Wasserstein geometry, and optimization in probability space. Within this framework, generative models can be used to learn nominal uncertainty, construct stressed or least-favorable distributions for robustness, and produce conditional or posterior distributions under side information and partial observation. We also highlight representative theoretical guarantees, including forward-reverse convergence for iterative flow models, first-order minimax analysis in transport-map space, and error-transfer bounds for posterior sampling with generative priors. The tutorial provides a principled introduction to using generative models for scenario generation, robust decision-making, uncertainty quantification, and related problems under distributional shift.

23.
arXiv (CS.AI) 2026-06-11

LLMs+Graphs: Toward Graph-Native, Synergistic AI Systems

arXiv:2606.11560v1 Announce Type: cross Abstract: Large Language Models (LLMs) have advanced rapidly, but their limitations in structured and multi-hop reasoning underscore the need for graph-native, synergistic artificial intelligence (AI) systems. Graph-structured data underpins critical applications across social, biological, financial, transportation, web, and knowledge domains, making it essential to understand how LLMs can leverage graph computation for grounded, context-rich inference. Three complementary synergies are emerging: LLMs augmented with graph computation for retrieval and reasoning; bidirectional integration between LLMs and knowledge graphs (KGs), where LLMs support KG construction and curation while KGs enforce semantic constraints and factual consistency; and AI agents strengthened by graph algorithms for planning, decision making, and multi-step reasoning. In parallel, LLMs introduce new capabilities for graph data management and graph machine learning (ML) through natural language interfaces and hybrid LLM-graph neural network (GNN) pipelines. This tutorial synthesizes the algorithms, systems, and design principles driving these converging directions, offering data science and data mining researchers a unified perspective on integrating LLMs, graph data management, graph mining, graph ML, and agentic computation into next-generation graph-native AI systems.

24.
arXiv (CS.CV) 2026-06-17

ED3R: Energy-Aware Distributed Disaster Detection Enabled by Cooperative Robotic Agents

Robotics are expected to support environmental monitoring and natural disaster management, where decisions must be made under uncertainty, resource limitations, and strict operational constraints. In critical missions, such as wildfires, robotic agents must not only identify hazardous events with sufficient confidence, but also manage the energy cost and time until detection. This paper introduces ED3R, an energy-aware distributed framework for wildfire detection under uncertainty. ED3R enables hierarchical cooperative decision-making between a robot and a remote controller. The remote controller decides upon the robot's motion, while the robot senses the environment and decides where to execute the wildfire detection (onboard or remotely) and how. The common goal is to detect wildfires with a required confidence while minimizing the energy consumed by any robot operation. ED3R further integrates mechanisms to avoid nearby obstacles, prevent redundant exploration, enable adaptive early mission completion, and ensure feasibility through a custom penalty function. ED3R also introduces a forward-looking capability, enabled through distributed neural regression models that allow the agents to anticipate the future by evaluating candidate strategies before execution. The framework is evaluated through realistic robotics simulations, ablation studies, and baseline comparisons. Overall, ED3R achieves a mission success rate of up to 97.18%. Especially in the most demanding missions, it reduces energy consumption by up to 36.4% and detects wildfires up to 41% faster than baselines.