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01.
medRxiv (Medicine) 2026-06-12

Order-Based Bayesian Network Modeling of Early Detection and Post-Diagnosis Control for Cardiovascular Disease Risk in Type 2 Diabetes

Patients diagnosed with type 2 diabetes (T2D) are at increased risk of developing cardiovascular disease (CVD), the leading cause of morbidity and mortality in this population. Early detection and glycemic control within the first year after diagnosis reduce CVD risk. However, gaps remain in how to operationalize early detection of T2D using Electronic Health Record (EHR) data and quantify its relationship with subsequent CVD risk using longitudinal observations. We developed a probabilistic graph model to analyze the interdependencies between early detection of T2D, post-diagnosis glycemic control, and CVD occurrence. Using a temporally structured Bayesian Network (BN) learned from EHR data of 9,450 primary care patients between 2017 and 2023, we quantified probabilistic dependencies between demographics, diagnostic delay surrogates, glycemic control, and post-diagnosis CVD occurrence. Percentile based thresholds defined risk groups, where individuals with predicted probabilities in the bottom decile ([≤] 10th percentile) were classified as low risk, and those in the top decile ([≥] 90th percentile) as high risk. Results demonstrated heterogeneity in predicted risks across glycemic and cardiovascular outcomes. Predicted probability of developing CVD within the first year after T2D diagnosis ranged from a mean of 5.2% in the low-risk group to 28.9% in the high-risk group, while predicted probabilities of mean Hemoglobin A1c (HbA1c) [≥] 8% during the first year post-diagnosis ranged from 1.6% in low-risk to 55.1% in high-risk group. Patients with HbA1c at diagnosis [≥] 8% had higher predicted probabilities of first-year post-diagnosis mean HbA1c [≥] 8% (53.3% vs. 1.9%) and high HbA1c coefficient of variation (18.7% vs. 3.1%) compared with those with HbA1c [≤] 6.5%. Incorporating early clinical outcomes refined later risk predictions, with long-term CVD risk reaching 33.5% among high-risk individuals. The proposed model achieved predictive performance comparable to conventional machine learning approaches while providing interpretable relationships for risk stratification in primary care populations.

02.
bioRxiv (Bioinfo) 2026-06-19

Morpho-FM: spatial molecular reconstruction from routine H&E histology using transcriptomic foundation-model priors

Routine haematoxylin and eosin (H&E) histology captures tissue architecture at clinical scale, but lacks a direct molecular readout of the transcriptional programmes that organise tumour epithelium, stroma, vasculature and immune compartments. Spatial transcriptomics provides this context, yet cost, workflow complexity and sparse sampling limit routine use. Most existing histology-to-expression models are trained de novo on small paired cohorts and therefore remain weakly constrained when extrapolating from sparse measurements to dense, tissue-wide molecular maps. Here we introduce Morpho-FM, a weakly supervised framework that predicts spatial gene expression from routine H&E whole-slide images by conditioning a pretrained single-cell transcriptomic foundation-model prior on local histological neighbourhoods. A lightweight morphology-to-transcriptome adapter maps cached whole-slide histology features into a transcriptomic decoder, enabling prediction at measured locations, dense full-section reconstruction, and re-aggregation to the original measurement support. Across harmonized prostate cancer benchmarks, Morpho-FM achieved the strongest overall performance among five representative methods, reaching mean per-gene Pearson correlations of 0.286 in rotating single-slide evaluation and 0.298 in multi-slide held-out validation. The framework reproduced this advantage across kidney cancer sections, achieved a mean correlation of 0.210 across 56 directed single-slide evaluations and retained measurable predictive signal after external transfer to clear-cell renal cell carcinoma sections. Controlled ablation analyses identified pretrained transcriptomic initialization as a reproducible source of performance gain exceeding that attributable to changes in the histology feature backbone. Beyond predictive accuracy benchmarks, Morpho-FM recovered ERBB2-enriched tumour compartments, boundary-associated molecular gradients, and annotation-aligned tissue domains across Xenium and HER2ST breast cancer datasets. Together, these results support transcriptomic foundation-model priors as an effective constraint for morphology-conditioned molecular decoding and demonstrate the potential of Morpho-FM to extend spatial transcriptomic insight across routine pathology sections.

03.
bioRxiv (Bioinfo) 2026-06-19

Perturbation Curve models continuous transcriptional response trajectories and improves prediction of genetic modulations

Single-cell CRISPR screens, Perturb-seq, have revolutionized functional genomics by revealing biological causality. However, although perturbation assignments are typically represented as discrete labels, the cell-level effective strength of perturbations is often continuous and diverse. Current analytical frameworks struggle to decouple the variability in perturbation strength from the diversity of downstream responses. Here, we present Perturbation Curve (PertCurve), a nonlinear, curve-based computational framework that models the trajectories of transcriptomic responses by explicitly incorporating diverse perturbation magnitudes and strengths. By ordering cells by perturbation strength, we demonstrate that PertCurve accurately recapitulates the response magnitudes and reveals the distinct modularity and asynchrony patterns of downstream gene behaviors. These patterns are categorized into archetypes, including proportional, sensitive, and threshold responses. By applying this framework across CRISPRi/a modalities, we identify universal response patterns in viral infection, apoptosis, and proliferation genes, and reveal previously overlooked context-specific regulatory features in cell differentiation. Finally, incorporating PertCurve into perturbation prediction models and evaluation metrics enhances predictive performance, delivering actionable insights for refining established models.

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

UltraEP: Unleash MoE Training and Inference on Rack-Scale Nodes with Near-Optimal Load Balancing

arXiv:2606.04101v3 Announce Type: replace-cross Abstract: Large-scale expert parallelism (EP) is becoming pivotal for training and serving frontier MoE models, but it also amplifies device-level expert load imbalance into compute stragglers, token all-to-all bottlenecks, and activation-memory spikes. Existing balancers redistribute experts periodically based on historical load, which becomes unreliable for production deployments with non-stationary load patterns. We present UltraEP, the first exact-load, real-time balancer for large-EP MoE training and serving prefill on rack-scale nodes (RSNs). Leveraging the extended scale-up connectivity among dozens of GPUs within RSNs, UltraEP rebalances every microbatch and layer on critical paths, which requires nontrivial co-design of plan solving and expert replication communication to minimize exposed overhead. To this end, UltraEP eagerly reacts to post-gating load with an efficient quota-driven planner, and executes the resulting irregular expert-state transfers with RSN-native persistent tile streaming and relay-based fan-out mitigation. We evaluate UltraEP in a multi-RSN deployment of up to 256 GPUs, using cutting-edge MoE models from 106B to 671B parameters. Averaged across training and serving, UltraEP achieves 94.3% of the force-balanced ideal throughput, delivering 1.49$\times$ improvement over no-balancing, while reducing the final inter-rank imbalance from 1.30$-$4.01 to 1.01$-$1.04.

05.
arXiv (CS.AI) 2026-06-15

A Two-Stage Statistical Framework for Evaluating Associative Interference in Large Language Models

arXiv:2606.14117v1 Announce Type: cross Abstract: Large language models (LLMs) are increasingly evaluated for bias using adaptations of human psychological paradigms, yet methodological limitations-particularly the conflation of refusal behavior with task performance-have hindered clear interpretation. Here, we adapt the Implicit Association Test (IAT) to a controlled, forced-choice framework and introduce a two-stage modeling approach that separates response compliance from task-consistent classification. Across three contemporary LLMs (Claude Sonnet-4, Gemini 2.5 Pro, and GPT-5), we evaluate associative interference, defined as reduced task-consistency in incongruent relative to congruent conditions. While compliance with the structured response format was uniformly high, interference effects varied substantially across models and domains. Claude Sonnet-4 exhibited strong interference in the Gender–Career domain (DeltaP = 0.086, 95% CrI [0.026, 0.173]) and smaller but credible effects in Gender–Science. Gemini 2.5 Pro showed attenuated interference, and GPT-5 exhibited minimal or no detectable interference across domains. These findings demonstrate that IAT-style associative asymmetries are not a universal property of LLMs, but instead depend on model-specific characteristics. By isolating interference from compliance and modeling item-level variability, this study provides a principled framework for evaluating structured response patterns in LLMs. The results highlight the importance of model-specific assessment and suggest that associative interference can be substantially mitigated in modern systems.

07.
medRxiv (Medicine) 2026-06-11

Ferritin across long-term conditions in England: cross-sectional primary care study

Background Iron deficiency (ID) is a readily treatable condition once identified. Ferritin is the primary diagnostic marker, but cut-offs vary and inflammation complicates interpretation in patients with long-term conditions (LTCs). Aim To describe ferritin distribution and the prevalence of threshold-defined low ferritin in adults with and without LTCs in primary care. Design and setting Cross-sectional observational study using routinely collected electronic health records from a national primary care database in England (1st January 2015 to 31st December 2021). Method Adults with >1 ferritin test in Clinical Practice Research Datalink (CPRD) Aurum were included. LTCs were identified using validated primary-care code lists. Outcomes included ferritin distribution and threshold-defined ID prevalence using World Health Organization (WHO) (

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

Large Language Model Agents Are Not Always Faithful Self-Evolvers

Self-evolving large language model (LLM) agents continually improve by accumulating and reusing past experience, yet it remains unclear whether they faithfully rely on that experience to guide their behavior. We present the first systematic investigation of experience faithfulness, the causal dependence of an agent's decisions on the experience it is given, in self-evolving LLM agents. Using controlled causal interventions on both raw and condensed forms of experience, we comprehensively evaluate four representative frameworks across 13 LLM backbones and 9 environments. Our analysis uncovers a striking asymmetry: while agents consistently depend on raw experience, they often disregard or misinterpret condensed experience, even when it is the only experience provided. This gap persists across single- and multi-agent configurations and across backbone scales. We trace its underlying causes to three factors: the semantic limitations of condensed content, internal processing biases that suppress experience, and task regimes where pretrained priors already suffice. These findings challenge prevailing assumptions about self-evolving methods and underscore the need for more faithful and reliable approaches to experience integration.

09.
Nature Medicine 2026-06-09

Adjuvanted inactivated rabies virus-vectored Lassa virus vaccine in healthy adults: a phase 1 trial

Lassa fever causes substantial morbidity and mortality in West Africa, and no licensed vaccine is available. We evaluated LASSARAB, an inactivated rabies virus-vectored Lassa virus (Josiah strain) glycoprotein complex vaccine. We conducted a randomized, controlled, dose-escalation phase 1 trial. Participants (total n = 54) received two intramuscular doses of LASSARAB containing 700 (n = 15), 1,400 (n = 15) or 2,800 (n = 14) relative units of antigen formulated with the TLR-4 agonist 3D-6-acyl PHAD-SE adjuvant, or licensed rabies vaccine control (n = 10), administered 28 days apart. This protocol-defined interim analysis reports the primary safety evaluation and secondary immunogenicity assessments through day 61. There were no prespecified hypotheses or formal power calculations. All primary safety end points demonstrated an acceptable safety profile. After dose 1, local solicited adverse events occurred in 86.7–100.0% of LASSARAB groups and 80% of controls; systemic events in 33.3–71.4% and 60.0% of controls. After dose 2, local solicited adverse events occurred in 66.7–86.7% of LASSARAB groups and 55.6% of controls; systemic events in 53.3–71.4% of LASSARAB groups and 55.6% of controls. Events were predominantly mild and self-limited. Unsolicited adverse events occurred in 28.6–60.0% of LASSARAB groups and 20.0% of controls. No serious adverse event, immune-mediated condition or sensorineural hearing loss occurred. Safety laboratory abnormalities occurred in 13.3–66.7% of LASSARAB groups and 30.0% of controls (14 mild, 6 moderate and none severe). After two doses, Lassa virus GPC IgG ELISA seroconversion (≥fourfold rise) was achieved in 100.0% (44 of 44) of LASSARAB recipients and 0.0% (0 of 10) of controls. Rabies glycoprotein IgG ELISA seroconversion (≥fourfold rise) and neutralizing antibody by rapid fluorescent focus inhibition test (RFFIT) seroprotection (≥0.5 IU ml−1) were also 100% across all groups, including controls. LASSARAB + 3D-6-acyl phosphorylated hexaacyl disaccharide (PHAD)-SE demonstrated a favorable safety profile and immunogenicity against Lassa and rabies viruses. The per-protocol final study report will include safety and durability through day 394. ClinicalTrials.gov identifier NCT06546709 . An interim report of a first-in-human phase 1 trial found an adjuvanted, combination inactivated rabies-vectored, Lassa fever vaccine (LASSARAB + 3D-6-acyl PHAD-SE) to be safe and induced immunogenicity to both Lassa and rabies viruses in healthy participants.

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

iTRIALSPACE: Programmable Virtual Lesion Trials for Controlled Evaluation of Lung CT Models

We introduce iTRIALSPACE, a programmable evaluation framework for controlled assessment of lung CT models. Standard benchmarks are static retrospective collections that entangle lesion size, lobe prevalence, anatomy, and acquisition context, making it difficult to determine what structurally drives model accuracy. iTRIALSPACE addresses this limitation by composing real clinical CTs and lesion profiles into controlled virtual lesion trials through a four-stage pipeline: multidataset nodule profiling, explicit trial specification, anatomy-aware mask insertion, and ControlNet-conditioned CT synthesis. The framework is built on a unified 54-attribute nodule-profile dataset spanning 13,140 annotated nodules from seven public CT sources and instantiated as 13 trial modes. We evaluate iTRIALSPACE in a 55,469-sample Virtual Lesion Study spanning three medical VLMs, four spatialguidance conditions, and three clinical tasks. Across all 13 modes, the synthetic substrate remains within the real-to-real FID baseline, and synthetic performance rankings transfer strongly to real clinical data ($\rho$ = 0.93, p < 10$^{-15}$). Controlled trial modes expose findings unavailable to fixed-distribution benchmarks, including shortcut-driven size prediction collapse under lobe-equalized sampling and hostto-donor variance ratios of 8.9x and 3.3x in twin-cross analysis. These results position iTRIALSPACE as an auditable evaluation infrastructure for controlled, falsifiable testing beyond static retrospective benchmarks.

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

Combating Data Laundering in LLM Training

arXiv:2604.01904v3 Announce Type: replace-cross Abstract: Post-hoc unauthorized-training data detection for large language models (LLMs) typically assumes a query-with-originals regime: rights holders query a target LLM with raw proprietary data and assess whether the model assigns them stronger memorization-based detection signals, e.g., higher confidence or lower loss, than held-out non-training reference texts. We show that this regime becomes brittle under data laundering, where the target LLM is trained on semantics-preserving but stylistically or structurally transformed surrogates of proprietary data to obfuscate provenance. Since training-time exposure occurs in the laundered form, memorization signals may no longer appear on the originals, collapsing the candidate-reference signal separation that standard detectors rely on. We counter this threat by studying laundering-aware detection with raw proprietary data, a held-out reference corpus, and query access to the target LLM, while the laundering transformation is undisclosed. Since exact recovery of the laundered corpus is infeasible, we infer a detection-useful synthesis process via an auxiliary LLM that maps originals into training-like queries. To make this search tractable, we introduce Synthesis Data Reversion (SDR), which constrains the unbounded space of natural-language transformations through a goal-details abstraction: a high-level transformation goal, e.g., "lyrical rewriting", and fine-grained details, e.g., "with vivid imagery". SDR identifies the most likely goal and iteratively refines details so synthesized queries elicit stronger target-model detection signals. Evaluated on the MIMIR benchmark against diverse laundering practices and target LLM families (Pythia, Llama2, and Falcon), SDR consistently restores detection signals, offering a practical auditing layer against data laundering.

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

Theorem-Grounded Execution Ontologies for Interpretable Machine Reasoning

arXiv:2606.16010v1 Announce Type: cross Abstract: Large language models have achieved impressive performance on reasoning tasks spanning mathematics, science, programming, and commonsense inference. Despite these advances, their reasoning processes remain largely latent, making them difficult to interpret, verify, replay, debug, and transfer across domains. Existing approaches such as chain-of-thought, tree-of-thoughts, graph-of-thoughts, and tool-augmented reasoning expose intermediate reasoning artifacts but typically lack explicit execution semantics, formal state representations, and verifiable reasoning structures. We introduce Theorem-Grounded Execution Ontologies (TGEO), a framework that models reasoning as an executable state-transition process rather than a sequence of generated tokens. Given an input problem, TGEO identifies relevant theorem families, binds the problem to a domain ontology, discovers semantic objects, instantiates states and operators, constructs predicates and contracts, and synthesizes an executable reasoning graph. The resulting graph provides an interpretable, replayable, and auditable representation of reasoning in which every state transition, operator application, and validation step is explicitly represented. TGEO integrates five architectural components: (1) theorem-grounded reasoning priors, (2) executable ontologies, (3) operator-mediated state transitions, (4) predicate and contract-based execution validation, and (5) architectural auditing and failure localization. We evaluate TGEO on theorem-intensive reasoning tasks derived from mathematical benchmark domains and a curated Golden Execution Suite. Our findings demonstrate the value of executable reasoning representations for interpretable, verifiable, and reproducible AI reasoning systems.

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

PASQA: Pitch-Accent-Focused Speech Quality Assessment Model Trained on Synthetic Speech with Accent Errors

Existing mean opinion score (MOS) prediction models typically predict utterance-level naturalness MOS and can be insensitive to localized pitch-accent errors. We propose Pitch-Accent-focused Speech Quality Assessment (PASQA), which explicitly targets pitch-accent correctness. To train our model, we construct a controlled Japanese accent-error dataset by changing accent patterns using an accent-controllable text-to-speech system, and compute a pseudo accent-quality score from the accent-error rate. PASQA builds on self-supervised representations and employs mora-conditioned fusion, ranking loss, an auxiliary accent-error localization task, and speaker-invariant training. Experiments show that conventional models fail to preserve the ordering by accent-error severity, whereas PASQA achieves high ordering accuracy on both seen and unseen speakers. Further, PASQA shows stronger agreement with human accent-correctness judgments. The code is available at https://github.com/lycorp-jp/PASQA.

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

Communication-Efficient Neural Tangent Kernels for Heterogeneous Decentralized Federated Learning

作者:

arXiv:2512.12737v2 Announce Type: replace Abstract: Decentralized federated learning (DFL) enables collaborative model training without a central server, but converges slowly under statistical heterogeneity. Recent work has shown that neural tangent kernel (NTK) methods achieve faster convergence than gradient-based updates in DFL, while momentum has proven effective for accelerating gradient-based FL. However, applying momentum to NTK updates can destabilize training under heterogeneous data. We propose SPARK, which addresses this instability with a stage-wise annealed soft-label regularizer evaluated on neighborhood-aggregated data, so that momentum can accelerate NTK updates stably. Under high heterogeneity, SPARK converges about 3$\times$ faster than baselines and lowers the total communication to a target accuracy by up to about 70\%, and it attains higher accuracy across heterogeneity levels. We further study random projection as an optional Jacobian-compression strategy for bandwidth-constrained settings. We validate the approach across multiple datasets, network topologies, and heterogeneity levels.

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

Curvature-Informed Potential Energy Surface for Protein-Ligand Binding Affinity Prediction

arXiv:2606.14217v1 Announce Type: new Abstract: Accurate prediction of protein-ligand binding affinity is essential for structure-based drug discovery. Recent geometric deep learning methods have achieved promising performance by representing protein-ligand complexes as three-dimensional graphs. However, most existing approaches mainly rely on static interaction geometry from a single bound conformation, while neglecting molecular flexibility and binding-induced conformational changes. To address this limitation, we propose a curvature-informed potential energy surface (CPES) graph neural network for protein-ligand binding affinity prediction, which incorporates physics-informed curvature representations to model conformational flexibility. CPES first derives curvature spectral descriptors from the Hessian of the potential energy surface evaluated at equilibrium configurations, whose eigenvalues define the local principal curvatures of the potential energy surface. It then uses spectral cross-attention to compare the unbound ligand and protein with the bound complex, thereby capturing binding-induced changes in conformational dynamics. In parallel, hierarchical protein-ligand interaction representations are learned from static structural features through geometry-aware message passing, soft clustering, and bidirectional cross-attention. Finally, CPES fuses the curvature-informed dynamic representations with static interaction representations for affinity regression. Extensive evaluations on multiple benchmark datasets demonstrate that CPES achieves improved predictive performance and offers physical interpretability.

16.
bioRxiv (Bioinfo) 2026-06-11

OCOO-T : A SIMPLE AND SCALABLE VIRTUAL CELL MODEL FOR TRANSCRIPTIONAL PERTURBATION RESPONSE PREDICTION

Predicting single-cell transcriptional responses to genetic, chemical and cytokine perturbations is a fundamental challenge in computational biology and AI Virtual Cell (AIVC) modeling, with direct implications for drug discovery and the elucidation of gene regulatory networks. Existing approaches often rely on auxiliary cell-state encoders, hierarchical variational autoencoders, dedicated Transformer encoder-decoder modules, or gene-interaction priors to compress high-dimensional expression profiles into latent representations. While effective, these designs increase architectural complexity and may limit scalability and generalizability. This paper introduces OCOO-T, a minimalist flow-matching-based AIVC model for transcriptional perturbation response prediction. OCOO-T utilizes a vanilla Transformer stack that operates directly on continuous gene expression profiles and formulates perturbation response prediction as a continuous-time denoising process. Perturbation embeddings, dosage information, and cell-line/cell-type specificity are integrated through adaptive layer normalization and in-context tokens. Comprehensive evaluations on Tahoe100M, Replogle, and PBMC benchmarks demonstrate that OCOO-T achieves state-of-the-art performance across diverse perturbations and cell types while effectively scaling to long transcriptional profiles through patching and depatching of cellular contexts. By leveraging the simplicity of Transformer-based denoising for single-cell omics, OCOO-T provides an effective and scalable framework for in-silico cellular simulation.

17.
arXiv (CS.CL) 2026-06-16

A Mechanistic Understanding of Pronoun Fidelity in LLMs

Faithful and robust pronoun use is important for fair and coherent generations, yet large language models largely fail when multiple referents use different pronouns. To study the interplay of reasoning, repetition, and bias in this task, prior work relies exclusively on behavioural approaches, which may not reflect a model's internal workings. Therefore, we provide a mechanistic, model-internal perspective on pronoun fidelity, testing whether three mechanisms – group entity binding (G), recency bias (R), and stereotypical bias (S) – are causally implemented across several SOTA language models. Using Boundless Distributed Alignment Search, we find all three coexist as causal subspaces distributed across network depth. No single mechanism fully explains model behaviour, but a combination of the three consistently accounts for 91-99.5%. An attention head analysis further reveals two competing copying routes; group binding and stereotype share a localized concept-level route that retrieves a bound occupation-pronoun unit, while recency uses a distributed token-level route that repeats surface forms. In sum, pronoun fidelity arises from competition between simultaneously active causal subspaces.

18.
arXiv (CS.AI) 2026-06-16

Attention is Just Another Name for Coupling?: A Fast-Slow ODE Perspective on Hierarchical Pretraining

arXiv:2606.16730v1 Announce Type: cross Abstract: Causal self-attention is a coupling mechanism: each token's hidden state is updated by a learned mixture of preceding tokens at the same timescale. This paper asks whether a second, temporally slower coupling-a slow sub-system operating on a temporally-downsampled view of the sequence and fed back into the fast path through a zero-initialised gate-complements it. The question is framed in the language of singularly perturbed ordinary differential equations (ODEs), where the fast variable $x$ evolves at the token rate, the slow variable $y$ evolves at one update per $P$ tokens, and the timescale ratio $\varepsilon = 1/P$ is enforced structurally by causal block-mean pooling. The paper instantiates the fast-slow ODE formalism as a concrete neural network: a fast path of standard causal attention over $T$ tokens, a slow path of full attention over $T/P$ pooled tokens ($P^2 \times$ cheaper per layer), and a zero-initialised additive gate. In addition, under a linear-generator assumption on the fast dynamics, we prove that the equilibrium manifold $x = \phi(y)$ is exactly the master-equation (ME) stationary distribution $p_{\mathrm{st}}(y)$; in that regime a learned MLP $\phi_\theta(y)$ is a variational approximation of it (the trained block is not a generator, so this identity is the structured limit, not a claim about the network as trained). Empirically, at $500$k tokens the coupling is neutral – the gate stays closed and the coupled and frozen ablations are within run-to-run noise – at a wall-clock cost comparable to a dense baseline. The contribution is the precise, gap-marked mapping itself, not a performance gain.

19.
arXiv (math.PR) 2026-06-16

Plateau Gaps of Poisson Correctors Encode Metastable Reaction Rates

arXiv:2606.14789v1 Announce Type: cross Abstract: Metastable reaction rates are commonly inferred from transition-state fluxes, mean first-passage times, or fitted kinetic models. We show that they are directly encoded in the plateau gap of an occupation-time Poisson corrector. For a centered basin-occupation observable, the Poisson corrector develops metastable plateaus in the reactant and product basins, and their separation determines the forward and backward transition rates. This construction requires only the generator, stationary measure, and metastable partition, and therefore does not rely on a predefined transition-state surface. In overdamped and underdamped double-well dynamics, the plateau-gap rate recovers the Kramers, Grote-Hynes, and Pollak-Grabert-Hänggi hierarchy. The same corrector-martingale decomposition yields a reactive-noise density, revealing where stochastic forcing contributes to transitions in configuration or phase space. Thus, reaction rates and their fluctuation sources emerge from a single corrector field.

20.
arXiv (CS.LG) 2026-06-17

Uncertainty Quantification for Flow-Based Vision-Language-Action Models

arXiv:2606.18043v1 Announce Type: cross Abstract: Vision-language-action models (VLAs) combine vision-language backbones with expressive generative action heads trained via flow matching on large-scale robotic datasets. Despite their strong empirical performance in robotic manipulation, VLAs lack mechanisms to quantify confidence in their predictions and to detect when their actions may be unreliable. This presents a critical limitation for real-world deployment in non-stationary environments, where models inevitably encounter scenarios outside their pretraining distribution and may fail without warning. To address this, we derive an efficient method for quantifying epistemic uncertainty in flow-matching models by leveraging velocity-field disagreement (VFD) across a small ensemble. We successfully use this uncertainty estimate for failure detection during deployment and active fine-tuning of flow-based VLAs. To this end, we propose SAVE, a framework for uncertainty-guided active multitask fine-tuning that reduces the number of costly expert demonstrations required to adapt VLAs to new tasks. Through extensive experiments on the LIBERO benchmark, we demonstrate that VFD yields better-calibrated uncertainty estimates predictive of downstream performance, that VFD achieves strong performance in detecting failures, and that uncertainty-guided data acquisition with SAVE requires at least 22% fewer samples than baselines. In summary, our work shows that quantifying epistemic uncertainty in flow-based VLAs improves both failure awareness and adaptation. Project website: tum-lsy.github.io/uq_vla/.

21.
arXiv (quant-ph) 2026-06-15

Efficient and simple Gibbs state preparation of the 2D toric code via duality to classical Ising chains

arXiv:2508.00126v2 Announce Type: replace Abstract: We introduce the notion of polynomial-depth duality transformations, which relates two sets of operator algebras through a conjugation by a poly-depth quantum circuit, and make use of this to construct efficient Gibbs samplers for a variety of interesting quantum Hamiltonians as they are poly-depth dual to classical Hamiltonians. This is for example the case for the 2D toric code, which is demonstrated to be poly-depth dual to two decoupled classical Ising spin chains for any system size, and we give evidence that such dualities hold for a wide class of stabilizer Hamiltonians. Additionally, we extend the above notion of duality to Lindbladians in order to show that mixing times and other quantities such as the spectral gap or the modified logarithmic Sobolev inequality are preserved under duality.

22.
Nature Biotechnology 2026-06-19

Optimized R2 retroelement complexes for DNA insertion into plant genomes

Traditional approaches for DNA insertion into plant genomes using Agrobacterium tumefaciens result in random integration. Newer genetic engineering methods based on nucleases, prime editors, transposases and recombinases extend capabilities but remain constrained with low efficiencies, off-target integration or limited payload size. Here we adapt the avian Taeniopygia guttata R2 protein (R2Tg) for targeted DNA insertion into plant genomes by engineering R2Tg expression cassettes and RNA payloads carrying intron-disrupted reporters, with optimized ribosomal DNA homology arms and untranslated regions. In Arabidopsis thaliana protoplasts, Nicotiana benthamiana leaves and Solanum lycopersicum seedlings, our R2Tg editor system achieves targeted insertion of full-length payloads ranging from 2.2 kb to 5 kb. In Nicotiana benthamiana leaves, integration occurs, on average, at 1 copy per genome, which is 30 times more efficient than that achieved by Cas9 homology-directed repair. This work establishes an R2Tg ribonucleoprotein platform for targeted DNA insertion into plant genomes, using a multicopy genomic safe-harbor site to enable efficient addition of multikilobase genes. R2 retrotransposons are used to integrate DNA into plant and crop 25S ribosomal DNA sites.

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

Pre-Training for Simulation-Based Science: A Study on Jet Foundation Model Training Objectives

arXiv:2606.14870v1 Announce Type: cross Abstract: Foundation models (FMs) trained on large datasets and fine-tuned on downstream tasks have emerged as a powerful paradigm in AI for science. Industrial FMs are typically trained using self-supervision with masking due to the lack of labels. In many scientific domains, accurate simulations are plentiful and facilitate large, labeled datasets. This opens up new possibilities for pre-training. We present a systematic comparison of pre-training methods using the OmniLearned High Energy Physics FM framework. We test supervised classification, flow-matching generation, and self-supervised masked particle modeling. All models are pre-trained on the JetClass dataset and fine-tuned on two representative downstream tasks, top jet classification and JetNet conditional generation. Among other observations, for classification tasks, we find that pure classifier pre-training is optimal when downstream labels and model capacity are plentiful, but combining it with self-supervised masked particle modeling (MPM) is uniquely powerful in the low-finetuning label regime. Flow matching-based generative pre-training seems to provide little benefit for downstream classification, and interestingly, for downstream generation, we find that flow matching must be in the pre-training objective to see a significant finetuning advantage, hinting at the orthogonality of classification and generation tasks. That is, for a model to transfer to both generative and classification downstream tasks, it must be pre-trained on both. This study provides a template for controlled scaling analysis of pre-training objectives for foundation models in simulation-based sciences.

24.
arXiv (CS.CV) 2026-06-16

MVEB: Massive Video Embedding Benchmark

We introduce the Massive Video Embedding Benchmark (MVEB), a 23-task benchmark for video embeddings spanning classification, zero-shot classification, clustering, pair classification, retrieval, and video-centric question answering. We evaluate 33 models and find that no single model dominates: MLLM-based embeddings lead on classification, clustering, pair classification, and QA; multimodal binding leads on retrieval and zero-shot classification; generative MLLMs without contrastive adaptation collapse on cross-modal tasks. Paired video-only vs. audio+video evaluations show that audio's contribution depends on dataset annotation provenance: audio helps when labels were produced from both modalities and hurts when they were produced from visuals alone, a six-point gap consistent across model families. MVEB is derived from MVEB+, a 184-task pool, and is designed to maintain task diversity while reducing evaluation cost. It integrates into the MTEB ecosystem for unified evaluation across text, image, audio, and video. We release MVEB and all 184 tasks along with code and a leaderboard at https://github.com/embeddings-benchmark/mteb.

25.
arXiv (CS.AI) 2026-06-17

Temporal Motif-aware Graph Test-time Adaptation for OOD Blockchain Anomaly Detection

arXiv:2605.29526v2 Announce Type: replace-cross Abstract: Ever-evolving transaction patterns have significantly hindered anomaly detection on emerging cryptocurrency blockchains due to the vast number of addresses and diverse anomalous behaviors. Recently, advanced Graph Anomaly Detection (GAD) approaches applied to blockchains have faced two critical challenges: adversarial pattern evolution by malicious actors and the out-of-distribution (OOD) problem caused by varied transaction semantics on blockchains. To address these challenges, we propose a novel framework termed TEmporal Motif-aware Graph Test-Time Adaptation (TEMG-TTA). First, we comprehensively capture the 3-node temporal motif distribution of each active address using an efficient computational mechanism, enabling downstream temporal motif-aware graph learning. Second, we design a simple yet effective test-time adaptation strategy to facilitate the sharing of common patterns between training and testing graphs. Extensive experiments on 5 real-world datasets demonstrate that our proposed TEMG-TTA outperforms state-of-the-art GAD approaches by an average of 54.88\%. A further case study on interpretable motif patterns reveals that TEMG-TTA explicitly characterizes the complex transaction patterns of anomalous addresses, thereby verifying the effectiveness of our technical designs. Our code is publicly available at https://github.com/LuoXishuang0712/TEMG-TTA/.