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

Adaptive Distance-Aware Trunk Deep Operator Learning for Long-Span Roadway Bridges

arXiv:2606.20015v1 Announce Type: new Abstract: Long-span roadway bridges exhibit highly localized structural responses under vehicular loading, making repeated FE analysis computationally expensive for applications such as influence surface generation and structural digital twins. Existing SciML approaches struggle to accurately capture these localized responses. To address this challenge, this study proposes an adaptive-trunk DeepONet for localized structural response prediction in large-scale bridge systems. The framework dynamically constructs a load-dependent learning domain using a KNN strategy, allowing the network to focus on structural influence zones. The trunk network is further enhanced using distance-aware features that encode the geometric relationship between the load and structural nodes. A physics-based full-field reconstruction is incorporated through a stiffness-informed Schur complement formulation, enabling predictions at adaptive nodes to be extended to the entire structural domain. To enable scalable training, response data are generated using a reduced-order equivalent shell model that preserves the dominant global behavior while significantly reducing computational cost. The proposed framework is validated on both a benchmark bridge model and the real-world Mussafah Bridge. Results show that the method achieves FEM-level accuracy with relative errors below 5%, while reducing the total response evaluation time (including full-field reconstruction) by approximately 60x; excluding the post-processing reconstruction step, the AD-DeepONet inference is up to four orders of magnitude faster than FEM. In addition, the framework enables rapid generation of full-field responses, influence lines, and influence surfaces under arbitrary vehicular loading configurations, demonstrating strong potential for large-scale bridge analysis and digital twin applications.

02.
arXiv (CS.AI) 2026-06-16

Explainable deep learning improves human mental models of self-driving cars

arXiv:2411.18714v3 Announce Type: replace-cross Abstract: Self-driving cars increasingly rely on deep neural networks to achieve human-like driving. The opacity of such black-box planners makes it challenging to accurately anticipate when they will fail, with potentially catastrophic consequences. While research into interpreting these systems has surged, most of it is confined to simulations or toy setups due to the difficulty of real-world deployment, leaving the practical utility of such techniques unknown. Here, we introduce the Concept-Wrapper Network (CW-Net), a method for faithfully explaining the behavior of machine-learning-based planners that causally grounds their reasoning in human-interpretable concepts without sacrificing performance. We deploy CW-Net on a real self-driving car and show that the resulting explanations improve the human driver's mental model of the vehicle, allowing them to better predict its behavior, particularly in surprising situations. This demonstrates that explainable deep learning integrated into self-driving cars can be both understandable and useful in a realistic deployment setting. We anticipate our method could be applied to other safety-critical systems, such as autonomous drones and robotic surgeons, as well as to other architectures, such as end-to-end learning systems and vision-language-action models. Overall, our study establishes a deployment-validated pathway to interpretability for autonomous agents, which could help make them more transparent and safe.

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

SuCo: Sufficiency-guided Continuous Adaptive Reasoning

Despite remarkable performance on complex tasks, Large Reasoning Models (LRMs) often generate excessively long Chain-of-Thoughts (CoT), inflating computational costs even for simple queries. Existing efforts to mitigate this inefficiency typically rely on discrete reasoning modes or fixed budget tiers, lacking a principled criterion of when reasoning is sufficient. In this work, we introduce Minimal Sufficient CoT (MSC), defined as the shortest prefix of a CoT trajectory which is adequate for producing the correct answer. We empirically show that MSC not only reduces reasoning tokens, but also improves accuracy across difficulty levels. Building on MSC, we propose Sufficiency-guided Continuous Adaptive Reasoning (SuCo), a two-stage training framework for autonomous reasoning control along a continuous spectrum. In stage 1, MSC-Aligned Fine-Tuning (MFT) constructs MSC data using problem-adaptive sufficiency thresholds that naturally scale with question difficulty, then fine-tunes the model to internalize concise yet sufficient reasoning patterns. In stage 2, Sufficiency-Aware Policy Optimization (SAPO) further optimizes the model through reinforcement learning with dynamic complexity tracking and sufficiency-aware rewards that penalize both over- and under-thinking. Extensive experiments across mathematics, code, and science benchmarks show that SuCo consistently achieves improvements in both accuracy and reasoning efficiency.

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

UniTranslator: A Unified Multi-modal Framework for End-to-end In-Image Machine Translation

In-Image Machine Translation (IIMT) aims to translate scene text in an image and render the translated text back into the original regions while preserving the overall visual appearance. Recent unified multimodal models provide a promising solution by combining visual-text understanding and image generation within a single framework. However, directly adapting such models to IIMT remains challenging. In particular, they often suffer from understanding-generation conflicts, where the translation inferred during understanding is inconsistent with the text supervision used in generation, and spatial position misalignment, where the rendered text does not accurately match the target text regions. To address these issues, we present UniTranslator, a unified multimodal framework for IIMT that tightly couples translation understanding and text editing. Specifically, we introduce an Understand-Generation Alignment Module (UGAM) to bridge the representation gap between understanding and generation, encouraging semantic consistency between translated content prediction and text rendering. We further propose a Spatial Mask Decoder (SMD) with pixel-level supervision over text regions to improve spatial grounding, geometric alignment, and layout controllability during generation. Extensive experiments on multiple benchmarks demonstrate that UniTranslator achieves state-of-the-art performance across diverse language directions and complex real-world layouts. Moreover, our results reveal a strong mutual reinforcement effect between translation understanding and image generation, highlighting the advantage of unified translation multimodal learning. Code is available at https://github.com/SeerRay-Lab/Unitranslator.

05.
arXiv (CS.AI) 2026-06-12

APCyc: Property-Informed Design of Cyclic Peptides via Automated Cyclization

arXiv:2606.12991v1 Announce Type: new Abstract: Cyclic peptides represent a promising class of therapeutic compounds in modern drug discovery, often offering improved stability and binding affinity. However, the de novo design of cyclic peptides remains challenging because methods must identify pocket-adaptive cyclization patterns and linkage sites while simultaneously controlling drug-relevant properties. This challenge is particularly pronounced for recent generative models trained predominantly on linear peptide data, which may fail to capture cyclization-specific constraints. To address the limitation, we introduce APCyc, a target-aware de novo cyclic peptide generation framework that explicitly models cyclization and jointly optimizes multiple essential physicochemical properties. By using an expanded residue vocabulary and explicitly encoding cyclization-site and linkage-type information, APCyc learns cyclization-aware representations and leverages Bayesian posterior guidance to steer sampling toward cyclic peptides satisfying multiple property objectives. Experimental results demonstrate that our model learns target-dependent cyclization preferences, and enables effective and controllable multi-property optimization for cyclic peptide design. The source code of this paper is available at https://github.com/HKUSTGZ-ML4Health-Lab/APCyc.

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

From Spatial to Spectral: An Efficient, Frequency-Guided Feature Representation Learner for Small Object Detection

arXiv:2606.23825v1 Announce Type: cross Abstract: Efficient small object detection is bottlenecked by the inherent feature scarcity of tiny targets, which is further aggravated by operations of spatial-domain detectors that indiscriminately discard critical high-frequency details. Recovering these fragile cues within the spatial domain is notoriously difficult, as it often requires computationally expensive architectural upscaling that inadvertently amplifies background noise. To bridge this gap, we propose a paradigm shift from spatial to spectral feature processing, introducing a holistic solution with the following novelty: (1) A versatile Frequency-Guided Feature Representation framework that generalizes across diverse detector architectures (both CNN and Transformer-based), offering a robust alternative to spatial-only feature extraction; (2) The unified Decompose–Enhance–Reconstruct (DER) operator, instantiated via three lightweight, plug-and-play modules – Wavelet-Difference Gate (WDG), Log-Gabor Enhancer (LGE), and Frequency-Driven Head (FDHead) – to systematically inject frequency-aware modulation into the backbone, neck, and head. This mechanism decouples feature modeling from resolution reduction, capturing discriminative high-frequency components to enable accurate localization with significantly reduced parameter redundancy; (3) Extensive validation on multi-domain benchmarks (VisDrone2019, UAVDT, TinyPerson, DOTAv1) demonstrating consistent gains. Notably, our proposed DERNet series outperforms YOLOv11 models under the same scale while requiring only 1/6 of the parameters, backed by rigorous spectral diagnostics and error decomposition analysis.

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

Classical representation of the dynamics of quantum spin chains

作者:

arXiv:2502.10502v3 Announce Type: replace-cross Abstract: Since the advent of quantum mechanics, classical probability interpretations have faced significant challenges. A notable issue arises with the emergence of negative probabilities when attempting to define the joint probability of non-commutative observables. In this work, we propose a resolution to this dilemma for quantum spin chains, by introducing an exact representation of their dynamics in terms of classical continuous-time Markov chains (CTMCs). These CTMCs effectively model the creation, annihilation, and propagation of pairs of classical particles and antiparticles. The quantum dynamics then emerges by averaging over various realizations of this classical process.

08.
arXiv (CS.LG) 2026-06-17

Amortized Probabilistic Retrieval of Atmospheric CO2 from OCO-2 Spectra Using Deep Learning with Laplace Approximations and Normalizing Flows

arXiv:2606.17413v1 Announce Type: new Abstract: Space-based monitoring of atmospheric carbon dioxide (CO2) is essential for constraining the global carbon budget. NASA's Orbiting Carbon Observatory-2 (OCO-2) estimates column-averaged dry-air mole fractions of CO2 (XCO2) using high-resolution spectra. However, current operational retrieval algorithms are computationally expensive and do not properly quantify uncertainties. We present a novel deep learning framework that addresses these challenges. Due to the difficulties of ground-truth data for real satellite observations, we develop and validate our approach using a high-fidelity simulation dataset. This dataset, created to support OCO-2 uncertainty quantification (UQ), incorporates realistic forward model errors. Our architecture encodes spectral bands using a multi-branch neural network and estimates posteriors of the full CO2 column or desired summaries thereof using two scalable UQ methods: Laplace approximations and normalizing flows. Our approach has five key advantages relative to operational "full-physics" solvers: (1) Amortization: Inference is orders of magnitude faster, enabling real-time processing of massive data streams; (2) Model error robustness: By training on simulations that explicitly include model discrepancies, our method accounts for systematic errors often neglected by standard inversions; (3) Point estimate accuracy: We achieve superior predictive accuracy compared to baseline methods; (4) Improved UQ: The probabilistic outputs yield better-calibrated uncertainty estimates; and (5) Non-Gaussian posteriors: When utilizing normalizing flows, our framework successfully models complex, asymmetric posterior distributions, overcoming the limitations of the Gaussian assumption. These results suggest that simulation-based deep learning is a viable path toward next-generation operational processing systems.

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

SCALE: Self-uncertainty Conditioned Adaptive Looking and Execution for Vision-Language-Action Models

arXiv:2602.04208v2 Announce Type: replace-cross Abstract: Vision-Language-Action (VLA) models have emerged as a promising paradigm for general-purpose robotic control, with test-time scaling (TTS) gaining attention to enhance robustness beyond training. However, existing TTS methods for VLAs require additional training, verifiers, and multiple forward passes, making them impractical for deployment. Moreover, they intervene only at action decoding while keeping visual representations fixed-insufficient under perceptual ambiguity, where reconsidering how to perceive is as important as deciding what to do. To address these limitations, we propose SCALE, a simple inference strategy that jointly modulates visual perception and action based on 'self-uncertainty', inspired by uncertainty-driven exploration in Active Inference theory-requiring no additional training, no verifier, and only a single forward pass. SCALE broadens exploration in both perception and action under high uncertainty, while focusing on exploitation when confident-enabling adaptive execution across varying conditions. Experiments on simulated and real-world benchmarks demonstrate that SCALE improves state-of-the-art VLAs and outperforms existing TTS methods while maintaining single-pass efficiency.

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

TaFD: Threat-Aware Frequency Decoupling for Adversarial Robustness against Heterogeneous Attacks

Multi-threat robustness remains a fundamental challenge in deep learning. Although joint adversarial training (JAT) is widely adopted, it suffers from negative transfer under heterogeneous threats, particularly between $\ell_p$-bounded and semantic attacks. Through first-order gradient analysis, we formalize this as gradient incompatibility and theoretically establish the necessity of decoupled optimization. We further reveal that these conflicting threats exhibit separable spectral characteristics in the frequency domain. Motivated by this observation, we propose Threat-aware Frequency Decoupling (TaFD), a two-stage defense framework that reformulates JAT as a frequency-domain divide-and-conquer paradigm. TaFD first discovers latent threat domains via unsupervised clustering of attack spectral prototypes and trains a lightweight classifier for inference-time threat domain identification. Conditioned on the prediction, TaFD employs a Frequency-Conditional Convolution that learns threat-domain-specific spectral masks and routes each sample to the corresponding expert, enforcing structural parameter separation and alleviating optimization conflicts. We validate TaFD on three representative image-classification benchmarks (CIFAR-10, CIFAR-100, and Tiny-ImageNet) and on two representative architectures (the convolutional ResNet and the hybrid-transformer MobileViT). Extensive results demonstrate that TaFD achieves more balanced robustness against heterogeneous attacks than existing JAT and frequency-domain baselines, improving average robust accuracy by approximately 11\% over the strongest baseline while maintaining leading clean accuracy.

11.
arXiv (CS.CL) 2026-06-12

Beyond Uniform Tokens: Adaptive Compression for Time Series Language Models

Large language models (LLMs) have enabled time series (TS) analysis by jointly modeling numerical observations and textual context through a shared token interface. However, TS tokens and prompt tokens exhibit fundamentally different information structures, making uniform token processing inefficient. In this paper, we study token efficiency in TS language modeling from an asymmetric-token perspective. We show that TS tokens have highly uneven spectral contributions, where many tokens share redundant frequency patterns while a small subset preserves critical temporal evidence. We also observe that prompt-token influence attenuates with model depth, suggesting that full prompt retention across all layers is unnecessary. Based on these findings, we develop an adaptive token budgeting framework that compresses TS tokens via frequency-domain structure and progressively reduces prompt tokens across layers. Experiments across forecasting, classification, imputation, and anomaly detection demonstrate up to 7.68$\times$ inference acceleration and performance gains in 78\% of evaluated settings, showing the effectiveness of asymmetric token compression for scalable TS foundation models.

12.
medRxiv (Medicine) 2026-06-17

Characterizing the genetic basis of Cardio-Renal-Metabolic multimorbidity using multivariate genomic modelling

Cardio-renal-metabolic multimorbidity (CRMM) encompasses interrelated conditions affecting the heart, kidneys, and metabolic systems. Although the genetics of individual components are well studied, their shared architecture remains unclear. Here, we performed the largest multi-ancestry multivariate GWAS of CRMM across seven biobanks, including individuals of European (EUR; neff = 353,130), African (AFR; neff = 75,436), and East Asian (EAS; neff = 164,373) ancestry. We identified 287 lead loci in EUR, 30 in AFR, and 202 in EAS. Cross-ancestry analyses revealed ancestry-specific signals and 24 shared loci mapping to FTO and TCF7L2. Drug-repurposing highlighted candidates used for type 2 diabetes and hypertension. Mendelian randomization supported causal links with diverse diseases, while polygenic risk scores showed improved prediction across ancestries. Collectively, these findings advance understanding of CRMM genetics and inform precision medicine.

13.
arXiv (CS.AI) 2026-06-16

The Distributed Detectability Band Against Marginal-Preserving Attacks

arXiv:2606.10456v2 Announce Type: replace-cross Abstract: AI-control monitors score individual agent actions to detect misbehavior, but real harm can be distributed across many benign-looking steps, each individually below any per-step alarm. We construct a marginal-preserving, correlation-encoded distributed-sabotage attack using a Gaussian-copula AR(1) construction: the per-step monitor-score marginal is held exactly equal to benign, so mean, max, top-k tail, and threshold monitors (Monitor A) are defeated by construction, while harm is encoded in the temporal correlation structure. We sequence the paper around three reviewer-mandated gates. (1) Realizability gate: the stealthy attack achieves KS-distance to benign of 0.013 (effectively zero) at all tested harm levels up to 3.0, confirming that harm is fully decoupled from the per-step marginal and realizability is not harm-limited. (2) Monitor-A-vs-B reconciliation: we show formally that the attack, built against Monitor A's score marginal, remains marginal-preserving under a different-score Monitor B (the correlation/sequence family: CUSUM, SPRT, HMM-LR, runs test, autocorrelation, windowed logistic), and scope worst-case claims to score functions that admit a temporal signature. (3) Non-empty detectability band: Monitor A achieves AUC 0.52 (chance); Monitor B spans AUC 0.79-0.97 at the same 1% FPR target, and as harm is amortized over more steps Monitor A collapses to chance while Monitor B holds at AUC ~0.95. These results demonstrate a non-empty detectability band and characterize the sub-threshold sabotage frontier: distribution-shape monitors fail by construction; temporal-correlation monitors can detect but are not trivially optimal.

14.
bioRxiv (Bioinfo) 2026-06-11

GeroEngine: Generative single-cell aging trajectories reveal a bidirectionally traversable identity core and direction-specific inflammatory remodeling

作者:

Single-cell RNA sequencing (scRNA-seq) maps aging tissues at high resolution but is destructive, preventing longitudinal tracking; dropout and zero-inflation artifacts, amplified by shift-invariant linear simulations, confound age-associated variability. We developed GeroEngine, a technical-artifact-aware framework combining VAE-based trajectory simulation, LOPO cross-validation, linear baselines, reverse traversal, and reverse-directed network inference. In microglia and HSCs, the VAE reduced technical-artifact carryover while preserving trajectory heterogeneity and improving alignment to artifact-reduced reference manifolds. Consensus GeroTargets and GeroRegulators defined tissue-specific GeroNetworks organized into three pillars: lineage/replication identity collapse, a sex-dimorphic endocrine/stress core, and inflammatory remodeling. Forward and reverse simulations aligned to the common young[->]old aging axis revealed a sign-coherent, direction-specific program: identity/replication targets were bidirectionally recovered, whereas MHC/NF-{kappa}B inflammatory programs were preferentially forward-recovered. These results support identity collapse as a deep traversable core of aging and nominate upstream homeostatic restoration over downstream inflammatory suppression.

15.
PLOS Computational Biology 2026-06-02

Linking reduced prefrontal microcircuit inhibition in schizophrenia to EEG biomarkers in silico

by Sana Rosanally, Frank Mazza, Heng Kang Yao, Faraz Moghbel, Hannah Seo, Etay Hay Reduced cortical inhibition by parvalbumin-expressing (PV) interneurons in schizophrenia is thought to be associated with impaired processing in the prefrontal cortex and altered EEG signals such as oddball mismatch negativity (MMN). Recent studies also suggest loss of somatostatin (SST) interneuron inhibition. However, establishing the link between reduced interneuron inhibition and reduced MMN experimentally in humans is currently not possible. To overcome these challenges, we simulated spiking activity and EEG during baseline and oddball response in detailed models of human prefrontal microcircuits in health and schizophrenia, with reduced PV and SST interneuron inhibition as constrained by postmortem patient data. We showed that reduced PV interneuron inhibition can account for the decreased MMN amplitude seen in schizophrenia, with a threshold below which the amplitude effect was low as seen in at-risk patients. In contrast, reduced SST interneuron inhibition did not affect the MMN amplitude. We further showed that both types of inhibition loss were necessary to account for changes in resting EEG in schizophrenia, with reduced SST interneuron inhibition increasing broadband power, and reduced PV and SST interneuron inhibition both leading to a right shift from alpha to beta frequencies. Our study thus links reduced PV and SST interneuron inhibition in schizophrenia to distinct EEG biomarkers that can serve to improve stratification and early detection using non-invasive brain signals.

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

Critic Architecture Matters: Dual vs. Unified Critics for Humanoid Loco-Manipulation

arXiv:2606.11891v1 Announce Type: cross Abstract: Multi-objective reinforcement learning for humanoid robots must coordinate locomotion and manipulation within a single policy. A natural design choice is whether to use a single (unified) critic that estimates the combined value of all objectives, or separate (dual) critics with disjoint reward signals. We present a controlled comparison on the Unitree G1 humanoid (23 active DoF) in NVIDIA Isaac Lab, training loco-manipulation policies through a sequential curriculum spanning 13 levels from stationary reaching to walking with variable-orientation targets. In standardized evaluation, dual-critic policies reach targets 3.5$\times$ faster (6.5 vs. 22.6 simulation steps), achieve 2$\times$ higher throughput (14.3 vs. 7.0 validated reaches per 1,000 steps), and attain higher validated reach rates (65.2% vs. 53.8%) compared to the unified-critic policy. Notably, additional anti-gaming reward mechanisms provide no further improvement beyond the architectural change alone (60.9% vs. 65.2%). These results have direct implications for the emerging paradigm of RL fine-tuning of imitation-learned policies: when refining a pre-trained manipulation policy with RL, a unified critic risks suppressing the learned behavior through competing locomotion gradients. These findings demonstrate that critic architecture is a primary - and often overlooked - design choice in multi-objective humanoid RL, with greater impact than reward engineering on reaching efficiency.

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

Neural Variability Enhances Artificial Network Robustness

arXiv:2606.13801v1 Announce Type: new Abstract: Neural responses in cortex exhibit substantial trial-to-trial variability in response to repeated stimuli, while peripheral sensory neurons respond far more consistently, leading many to wonder whether stochasticity may carry meaning. Existing work has argued that noise and signal correlations may be optimized for discrimination in animals, whereas artificial neural network (ANN) studies have shown similar benefits of noise in machine learning tasks, although most ANN work has neglected the effects of correlations. Here we investigate whether correlated noise improves the robustness of artificial neural networks to adversarial attacks and naturalistic image modifications. Using the covariance of activations under modified versus clean inputs, we find that structured noise may significantly improve network robustness. Robustness to naturalistic image modifications benefits most from structure, but this structure transfers poorly across modification types. In contrast, noise structure from adversarial attacks can generalize to other kinds of attacks. These results suggest that structured noise in ANN activations generally improves robustness, establishing a biologically plausible strategy for creating robust artificial neural networks that only relies on local information.

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

Frames2LoRA: Parametric Video Internalization for Vision-Language Models

Processing video in vision-language models is expensive: each frame occupies hundreds of tokens, and inference cost scales with every frame and every repeated query. We introduce Frames2LoRA, a method for parametric video internalization. A perceiver hypernetwork reads the intermediate representations produced layer-by-layer as a frozen VLM encodes a video, and generates a Low-Rank Adaptation (LoRA) adapter in a single forward pass. Unlike standard LoRA fine-tuning, which requires iterative gradient updates, Frames2LoRA predicts these weights directly from the video. Trained for SmolVLM2 500M and 2.2B on video summarization and captioning, Frames2LoRA enables the same frozen VLM to answer queries from the adapter alone, with zero visual tokens in its context at query time. Frames2LoRA is statistically non-inferior and equivalent to direct video-in-context inference across all five captioning benchmarks at both model scales, and across seven of eight video question answering benchmark-scale pairings. Although trained only on 12 frames at 384px, it remains stable up to 1,024 frames and 1024px, where direct video-in-context inference often degenerates. Across this sweep, it reduces answer-time visual-token load by up to 1,500x and query TTFT by 6-80x, while preserving video-faithful outputs. We also find that independently generated adapters for non-overlapping video segments can compose in rank space, suggesting a path toward chunked long-video internalization.

19.
medRxiv (Medicine) 2026-06-22

A Plasmodium vivax controlled human infection and transmission model to evaluate interventions across the life cycle

Background Plasmodium vivax is an underappreciated cause of malaria disease burden. No reproducible and standardized full life-cycle controlled human malaria infection (CHMI) model to accelerate development of novel interventions is available. Methods This transmission-CHMI trial was conducted in Nijmegen, Netherlands. Healthy, malaria-naive adults were sequentially enrolled into three cohorts of four and inoculated with the asexual blood-stage isolate PvW1. Primary endpoint was proportion of oocyst-positive laboratory-reared Anopheles stephensi mosquitoes. The sequential design allowed for adaptations between cohorts. At parasitemia >10 parasites/microL or symptom onset, participants received oral gametocyte-sparing treatment (GST): mepacrine (Cohort 1 and 3; 100 mg at 0, 8 16 hours, then once daily for 3 days) or piperaquine (Cohort 3; 480 mg single-dose). Transmission was assessed by direct skin feeding (DSF) and membrane feeding assay (DMFA) with and without enrichment of gametocytes. End-of-study treatment was atovaquone-proguanil (1000/400 mg once daily for 3 days). The trial was registered: NL-OMON57011. Findings Participants were enrolled between September 17, 2024 and March 25, 2025, all (12/12) developed parasitemia and transmitted PvW1 to mosquitoes. No serious adverse events occurred. Most adverse reactions were related to malaria. Mepacrine and piperaquine reduced asexual parasitemia while preserving gametocytemia and transmission. Peak transmission occurred within 3 days after GST and depended on the parasite developmental cycle, with highest gametocyte-infectivity ~48 h post ring-stage. In Cohort 3, mosquito infection reached 100% in all transmission assays. Median peak oocyst counts were 24 (IQR: 14-31) for DSF, 17 (12-19) for DMFA, and 150 (116-199) for enriched DMFA. A two-fold increase in pre-GST maximal parasitemia was associated with 20 additional oocysts (95% CI 8,6-32) in enriched DMFA. Sporozoites were viable in primary human hepatocytes. Interpretation A PvW1 transmission-CHMI is reproducible and safe, enabling P. vivax sporozoite production, relapse models and evaluation of transmission-blocking interventions.

20.
medRxiv (Medicine) 2026-06-18

Urinary Creatine Riboside Complements PSA to Improve Disease Detection in the Diagnostic Gray Zone of Prostate Cancer

Circulating prostate-specific antigen (PSA) discriminates poorly in the diagnostic gray zone (3.0-9.99 ng/mL), where ~75% of biopsies yield no clinically significant prostate cancer (PCa). We evaluated whether urinary creatine riboside (CR), a tumor-derived metabolite excreted through the prostatic urethra, complements PSA for gray-zone detection and independently predicts prostate-cancer-specific mortality (PCSM). In the NCI-Maryland PCa Case-Control Study (951 cases, 962 controls; 47.6% African American men; median follow-up 11.5 years), urinary CR was quantified by UPLC-MS/MS. Within the PSA gray zone (n = 668), urinary CR was complementary to PSA, with markedly higher single-marker discrimination than PSA (AUC 0.93, 95% CI 0.88-0.98 vs 0.77, 0.66-0.89) and additive when combined ({Delta}AUC +0.17, p < 0.001; 91.4% sensitivity at 80% specificity). After adjustment for 11 clinical and sociodemographic covariates, urinary CR independently predicted PCSM complementary to PSA (Fine-Gray SHR 1.72, 1.35-2.19 for CR; 1.35, 1.08-1.68 for PSA; Harrell's C 0.85 for CR + PSA vs 0.77 for PSA alone), with strongest signal in African American men (SHR 2.43, 1.57-3.75 for CR). We conclude that urinary CR is a candidate non-invasive biomarker complementary to PSA - improving gray-zone triage and predicting PCSM; prospective validation in biopsy-referred cohorts is warranted.

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

CMIP-Forge: An Agentic System that Retrieves, Computes, and Self-Reviews Climate Science

arXiv:2606.17076v1 Announce Type: cross Abstract: The Coupled Model Intercomparison Project Phase 6 (CMIP6) has generated thousands of peer-reviewed publications documenting model configurations, evaluation procedures, emergent constraints, and projection uncertainties. As the community transitions toward CMIP7, efficiently extracting and operationalizing this unstructured knowledge alongside live data analysis represents a critical bottleneck. Here we present CMIP-Forge, a hybrid retrieval-augmented generation (RAG) and autonomous analysis system that bridges the gap between scientific literature and Earth System Grid Federation (ESGF) data archives. The system pairs a curated corpus of 6,581 CMIP6-related open-access publications (101,828 indexed chunks) with an agentic pipeline in which a tool-augmented worker plans and executes Python workflows over live climate data, while a panel of independent reviewer models audits its methodology end to end. CMIP-Forge introduces a multi-layered Defense-in-Depth architecture that enforces physical and methodological invariants through executable mechanisms: Abstract Syntax Tree (AST) static analysis, audited scientific primitives, and an autonomous adversarial peer-review protocol. We demonstrate the system's capabilities through end-to-end autonomous research pipelines spanning atmospheric teleconnections, ocean dynamics, regional extremes, and global warming projections. An agentic analysis system grounded in peer-reviewed literature, constrained by automated code guardrails, and audited by an independent adversarial review loop can complete complex climate-research workflows autonomously. The same experiments expose concrete failure modes of the review loop (sycophantic regression, REVISE verdicts that are never resolved, and the submission of stub code for review), each diagnosable from the immutable telemetry and provenance record released with the article.

22.
arXiv (quant-ph) 2026-06-11

Entanglement generation between field modes mediated by a fluctuating conducting wall

arXiv:2606.12338v1 Announce Type: cross Abstract: We consider a movable conducting plate of finite mass, between two fixed ones, whose mechanical degrees of freedom are treated quantum-mechanically and bound to its equilibrium position by a harmonic potential. The movable wall is thus subjected to quantum fluctuations of its position. This creates a system of two sub-cavities separated by the movable fluctuating plate, and two massless one-dimensional scalar fields, one in each sub-cavity. This system is described by an appropriate generalization of the Law Hamiltonian. The presence of the movable wall yields an effective plate-fields interaction, as well as an effective interaction between the field modes. We obtain, at the second order in perturbation theory, the ground state of the interacting system and the reduced density operator of the fields in each sub-cavity by tracing out the wall's degrees of freedom. We calculate the entanglement between two field modes, one in each cavity, by evaluating analytically the negativity; we then evaluate numerically also the total multimode negativity. Our results show that in both cases the fields in the two sub-cavities are entangled, in contrast to the case in which the wall is fixed in space. We discuss the amount of the field entanglement present as a function of relevant physical parameters of the system such as the mass and oscillation frequency of the movable wall, its distance from the fixed walls and the frequencies of the field modes considered.

23.
arXiv (quant-ph) 2026-06-24

Exponential speedup in quantum simulation of Kogut-Susskind Hamiltonian via orbifold lattice

arXiv:2506.00755v2 Announce Type: replace Abstract: We demonstrate that the orbifold lattice Hamiltonian – an approach known for its efficiency in simulating SU($N$) Yang-Mills theory and QCD on digital quantum computers – can reproduce the Kogut-Susskind Hamiltonian in a controlled limit. While the original Kogut-Susskind approach faces significant implementation challenges on quantum hardware, we show that it emerges naturally as the infinite scalar mass limit of the orbifold lattice formulation, even at finite lattice spacing. Our analysis provides both a general analytical framework applicable to SU($N$) gauge theories in arbitrary dimensions and specific numerical evidence for $(2+1)$-dimensional SU($N$) Yang-Mills theories ($N=2,3$). Using Euclidean path integral methods, we quantify the convergence rate by comparing the standard Wilson action with the orbifold lattice action, matching lattice parameters, and systematically extrapolating results as the bare scalar mass approaches infinity. This reformulation resolves longstanding technical obstacles and offers a straightforward implementation protocol for digital quantum simulation of the Kogut-Susskind Hamiltonian with exponential speedup compared to classical methods and previously known quantum methods, modulo a standard assumptions made also for the original Kogut-Susskind approach.

24.
bioRxiv (Bioinfo) 2026-06-14

Virtual phenotypic screening discovers novel scaffolds inhibiting the PI3K/mTOR pathway

Phenotypic drug discovery has yielded many first-in-class small-molecule drugs by discovering modulators of disease phenotypes in physiologically relevant cellular systems. However, high-content phenotypic assays lack the ultra-high-throughput scalability of target-based screens. Recent advances in virtual screening present an opportunity to address this bottleneck, but have been limited to simple phenotypes like viability, restricted to small repurposing libraries, or lack in-depth biological validation. Here, we present PhenoCompass, a multimodal co-embedding model that aligns compound structures and high-content phenotypic imaging to enable virtual phenotypic screening over billion-compound libraries. Following training on the Joint Undertaking in Morphology dataset with more than 100,000 Cell Painting compound profiles, retrospective validation with historical biochemical high-throughput screening data demonstrates that PhenoCompass ranks compounds according to their biochemical target engagement. Leveraging PhenoCompass, we performed a prospective screen of 3.8 billion Enamine REAL compounds for inhibitors of PI3K/mTOR pathway, a critical signaling cascade whose aberrant activation is a common tumor driver. This search identified 11 novel compounds with pathway-consistent Cell Painting readout and diverse scaffolds, a 54-fold enrichment over the training set. Orthogonal validation experiments using a FOXO3A reporter assay and direct kinase inhibition confirmed seven structurally novel inhibitors with distinct mechanisms of action. These results highlight the convergence of diverse molecular target profiles onto a shared morphological pathway signature and establish PhenoCompass as a robust framework for high-content phenotypic virtual screening.

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arXiv (CS.LG) 2026-06-16

Diffusion Flow Matching: Dimension-Improved KL Bounds and Wasserstein Guarantees

arXiv:2606.16610v1 Announce Type: cross Abstract: Diffusion Flow Matching (DFM) has recently emerged as a versatile framework for generative modeling, yet its theoretical convergence properties remain only partially understood. In this work, we provide refined and novel convergence guarantees for Brownian motion based DFMs, focusing on the discretization error. Our analysis is conducted under the Kullback-Leibler (KL) divergence and the 2-Wasserstein distance. Under finite-moment conditions and a mild score integrability assumption, we derive KL convergence bounds with improved dimensional dependence compared to prior work, achieving, up to our knowledge, state-of-the-art scaling under minimal conditions. We further extend the analysis to the 2-Wasserstein distance: under an additional first-order score integrability assumption and a weak log-concavity condition, we obtain convergence guarantees with dimensional dependence consistent with the KL case.