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

Trajectory-Level Redirection Attacks on Vision-Language-Action Models

Vision-language-action (VLA) policies bring natural language into closed-loop robot control, enabling robots to execute manipulation tasks directly from text instructions. The same interface gives text a recurring role in control because the prompt is reused at every replanning step, and each prompt-conditioned action changes the future observations on which the policy acts. Existing VLA attacks study adversarial prompts that elicit targeted low-level actions or make such actions persist across changing images. We identify a stronger trajectory-level failure mode: a prompt that still $appears$ to specify the intended task but redirects the final physical outcome. We mathematically formalize this setting as $command-preserving trajectory redirection$, a prompt-only threat model in which the attacker chooses one prompt before the episode, all policy and environment components remain fixed, and the prompt must stay close to the benign instruction while omitting target words and correction language. To find such prompts, we introduce an on-policy prompt search method that uses rollouts to discover perturbations whose closed-loop behavior tracks a target task while satisfying the command-preserving constraints. Experiments in simulation and on hardware show that near-benign prompt perturbations can redirect VLA rollouts to attacker-specified targets. These results expose a trajectory-level vulnerability in VLA instruction grounding: text that appears to preserve the intended command can still give an adversary control over the robot's final physical outcome. Project website: https://vla-redirection-attack.github.io/

02.
arXiv (CS.AI) 2026-06-11

Towards an Inferentialist Account of Information Through Proof-theoretic Semantics

arXiv:2605.05368v5 Announce Type: replace-cross Abstract: Information is one of the most widely-discussed concepts of the current era. However, a great deal of insightful work notwithstanding, it is yet to be given wholly convincing logical or mathematical foundations. Without them, we lack adequate reasoning tools for understanding the complex ecosystems of systems upon which the society depends. We seek to rectify this by taking a first step towards developing an inferentialist semantic theory of information. There are three key interacting components. First, conceptual analysis: the metaphysics of information. Dretske expressed the key concepts of information in terms of intentionality, truth, and transmissibility. We replace truth with inferability, and trace the consequences of this replacement. Second, logic: proof-theoretic semantics (P-tS) provides a mathematical-logical realization of inferentialist reasoning. Using P-tS, we develop the first steps towards a mathematical-logical theory of an inferentialist primitive unit of information, the 'inferon'. This proof-theoretic approach counterpoints the model-theoretic view of information articulated in situation theory. Furthermore, we argue that it facilitates addressing all three components of van Benthem and Martinez's categorization of the understandings of information, as range, as correlation, and as code. Our focus is on information-as-correlation. Third, systems: the P-tS tools we develop provide the basis for a mathematical account of distributed systems modelling – a key tool from informatics for understanding the organization of information processing systems. This yields a reasoning-based theory of information flow in models of distributed systems. Overall, we seek to give a conceptually rigorous mathematical-logical account of information and its role within informatics, grounded in inference and reasoning.

03.
arXiv (quant-ph) 2026-06-16

Initiation of Superradiance from Different Collective Spin States

arXiv:2606.14949v1 Announce Type: new Abstract: Superradiance is an extensive cooperative spontaneous emission phenomenon. Some atomic collective spin states exhibit it. However, distinct initial states differ in their decay dynamics. Dicke states with different numbers of excitations have their peak emission intensity shifted in time depending on the number of excitations. Emission intensity in atomic coherent states depends on their polarization. Some specific states undergo a squeezing controlled crossover, making the emission character dependent on the amount of squeezing in the state. We present detailed results on the superradiant dynamics of a representative selection of Dicke states. For large N, we are able to predict fairly accurately the pulse profile in each case using the mean field approximation, an approach based on the Fokker Planck Equation. We also present results on the intensity correlation function of the emission.

04.
arXiv (CS.LG) 2026-06-11

Understanding Sample Efficiency in Predictive Coding

arXiv:2605.11911v2 Announce Type: replace Abstract: Predictive Coding (PC) is an influential account of cortical learning. Much of recent work has focused on comparing PC to Backpropagation (BP) to find whether PC offers any advantages. Small scale experiments show that PC enables learning that is more sample efficient and effective in many contexts, though a thorough theoretical understanding of the phenomena remains elusive. To address this, we quantify the efficiency of learning in BP and PC through a metric called ``target alignment'', which measures how closely the change in the output of the network is aligned to the output prediction error. We then derive and empirically validate analytical expressions for target alignment in Deep Linear Networks. We show that learning in PC is more efficient than BP, which is especially pronounced in deep, narrow and pre-trained networks. We also derive exact conditions for guaranteed optimal target alignment in PC and validate our findings through experiments. We study full training trajectories of linear and non-linear models, and find the predicted benefits of PC persist in practice even when some assumptions are violated. Overall, this work provides a mechanistic understanding of the higher learning efficiency observed for PC over BP in previous works, and can guide how PC should be parametrised to learn most effectively.

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

FineDialFact: A benchmark for Fine-grained Dialogue Fact Verification

Large language models are known to produce hallucinations - factually incorrect or fabricated information - which poses significant challenges for many natural language processing applications, such as dialogue systems. As a result, detecting hallucinations has become a critical area of research. Current approaches to hallucination detection in dialogue systems primarily focus on verifying the factual consistency of generated responses. However, these responses often contain a mix of accurate, inaccurate or non-verifiable facts, making the use of a single factual label overly simplistic and coarse-grained. In this paper, we introduce a benchmark, FineDialFact, for fine-grained dialogue fact verification, which involves verifying atomic facts extracted from dialogue responses. To support this, we construct a dataset based on publicly available dialogue datasets and evaluate it using various baseline methods. Experimental results demonstrate that methods incorporating Chain-of-Thought reasoning can enhance performance in dialogue fact verification. Despite this, the best F1-score achieved on the HybriDialogue, an open-domain dialogue dataset, is only 0.74, indicating that the benchmark remains a challenging task for future research. We release our dataset and code at https://github.com/XiangyanChen/FineDialFact.

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

A Survey of Reasoning and Agentic Systems in Time Series with Large Language Models

arXiv:2509.11575v3 Announce Type: replace Abstract: Time series reasoning treats time as a first-class axis and incorporates intermediate evidence directly into the answer. This survey defines the problem and organizes the literature by reasoning topology with three families: direct reasoning in one step, linear chain reasoning with explicit intermediates, and branch-structured reasoning that explores, revises, and aggregates. The topology is crossed with the main objectives of the field, including traditional time series analysis, explanation and understanding, causal inference and decision making, and time series generation, while a compact tag set spans these axes and captures decomposition and verification, ensembling, tool use, knowledge access, multimodality, agent loops, and LLM alignment regimes. Methods and systems are reviewed across domains, showing what each topology enables and where it breaks down in faithfulness or robustness, along with curated datasets, benchmarks, and resources that support study and deployment (https://github.com/blacksnail789521/Time-Series-Reasoning-Survey). Evaluation practices that keep evidence visible and temporally aligned are highlighted, and guidance is distilled on matching topology to uncertainty, grounding with observable artifacts, planning for shift and streaming, and treating cost and latency as design budgets. We emphasize that reasoning structures must balance capacity for grounding and self-correction against computational cost and reproducibility, while future progress will likely depend on benchmarks that tie reasoning quality to utility and on closed-loop testbeds that trade off cost and risk under shift-aware, streaming, and long-horizon settings. Taken together, these directions mark a shift from narrow accuracy toward reliability at scale, enabling systems that not only analyze but also understand, explain, and act on dynamic worlds with traceable evidence and credible outcomes.

07.
arXiv (CS.LG) 2026-06-18

Structure Over Nonlinearity: Explicit Interaction Architectures for Dynamical Learning

arXiv:2606.19101v1 Announce Type: cross Abstract: Most learning architectures for dynamical systems rely on generic nonlinear function approximation, often requiring high model complexity to capture structured behaviors. In this work, we propose an alternative paradigm in which modeling capability arises primarily from structure rather than from expressive nonlinearities. We introduce a class of explicit structured dynamical units based on wave-inspired interaction structures with internal state. Inspired by wave-based computational principles, the proposed units adopt a strictly causal organization that eliminates algebraic loops, yielding fully explicit models that can be evaluated without implicit solvers. Stacking such units produces layered dynamical architectures with emergent hierarchical behavior. Through experiments on a nonlinear system identification task, we show that depth improves both representation quality and generalization, even under limited parameter optimization. In particular, the proposed architectures produce informative internal representations even under readout-only fitting, indicating that useful dynamical structure emerges from the organization of interactions prior to substantial parameter optimization. These results suggest that structure-first design provides a viable and effective alternative to conventional black-box approaches for learning dynamical systems, highlighting the role of interaction structure as a primary source of model expressivity.

08.
arXiv (CS.CV) 2026-06-12

Zero-Shot Captioning for Cultural Heritage: Automated Image Analysis of Traditional Indonesian Clothing

This paper presents Custom ZeroCLIP, a retrieval-augmented vision-language framework for zero-shot captioning of Indonesian traditional garments. The dataset contains 3,800 expert-annotated images from all 38 Indonesian provinces. Using a province-level inductive zero-shot protocol, the model is trained on 24 seen provinces, validated on 6 seen provinces, and evaluated on 8 unseen provinces. The framework combines a frozen CLIP ViT-B/32 image encoder, a CLIP text encoder, a BERT text encoder, and an LSTM caption decoder. During inference, unseen-province labels and captions are unavailable, and retrieval uses only captions from training provinces. No unseen-province image, label, or caption is used during training, validation, or retrieval-bank construction. Custom ZeroCLIP achieves a CLIPScore of 0.8536, BLEU-4 of 0.3342, and METEOR of 0.4859, outperforming existing baselines. Ablation results show that retrieval improves cultural vocabulary recovery with a 19.3\% METEOR gain, while human evaluation confirms stronger cultural accuracy and fluency. The results demonstrate the effectiveness of retrieval-augmented domain adaptation for culturally grounded caption generation in low-resource heritage settings. The dataset is publicly available at https://github.com/AnugrahAidinYotolembah/Traditional-Indonesian-Clothing-Captioning-Dataset.

09.
arXiv (CS.AI) 2026-06-19

The Algorithmic-Human Manager: AI, Apps, and Workers in the Indian Gig Economy

arXiv:2606.19975v1 Announce Type: cross Abstract: This paper examines the impact of artificial intelligence and digital technologies on the blue-collar gig economy in India, focusing on algorithmic management. This paper examines the impact of artificial intelligence and digital technologies on the blue collar gig economy in India, focusing on algorithmic management he use of automated systems to allocate, monitor, and evaluate work in location-based services such as ride sharing and delivery. Using a social justice framework and a mixed-methods approach comprising interviews with 16 gig workers and 21 key stakeholders, the study uncovers a dual reality: while AI-powered systems expand access to work and generate operational efficiencies, they simultaneously introduce significant challenges related to fairness, transparency, and worker dignity. Key findings reveal that algorithmic systems are opaque by design, produce inequitable outcomes, and are not structured to reward additional labour with proportionate pay. The study advocates for a pragmatic hybrid governance model an Algorithmic Human Manager framework in which technological efficiency and human accountability operate together rather than in opposition. The findings carry implications for policymakers, platform companies, and civil society organizations working to design equitable AI governance frameworks for the gig economy in India and across the Global South.

10.
arXiv (CS.AI) 2026-06-11

Generalizing Beyond Suboptimality: Offline Reinforcement Learning Learns Effective Scheduling through Random Solutions

arXiv:2509.10303v2 Announce Type: replace-cross Abstract: Online reinforcement learning (RL) approaches have demonstrated strong performance on Job Shop Scheduling (JSP) and Flexible JSP (FJSP) problems by learning scheduling policies through direct interaction with simulated environments. However, these methods often require extensive training interactions, limiting their sample efficiency and practical applicability. Motivated by this challenge, we introduce Conservative Discrete Quantile Actor-Critic (CDQAC), an offline RL algorithm that learns effective scheduling policies directly from static, suboptimal datasets. CDQAC couples a quantile-based critic with delayed policy updates to estimate the return distribution of machine-operation pairs. Extensive experiments on JSP and FJSP benchmarks demonstrate that CDQAC consistently outperforms the data-generating heuristics, surpasses state-of-the-art offline and online RL baselines, and is highly sample efficient, requiring only 1 to 5% of the original dataset to learn high-quality policies. Our analysis suggests that, in scheduling, offline RL performance is governed mainly by state-action coverage rather than the quality of individual trajectories. Scheduling couples a dense reward aligned with the makespan objective with equal-length trajectories across heuristics, enabling effective learning from a broad range of behaviors. Consistent with this observation, datasets generated by a simple random heuristic with broader coverage let it outperform policies trained on datasets produced by stronger heuristics such as Genetic Algorithms.

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

Divide-and-Denoise: A Game-Theoretic Method for Fairly Composing Diffusion Models

The abundance of pre-trained diffusion models provides an opportunity for composition. Combining several models, however, runs the risk of one model dominating or models disagreeing with each other. Here, we propose Divide-and-Denoise, a method for coordinating multiple pre-trained diffusion models during sampling. Much like managing a specialized workforce, our method creates a fair but efficient division of labor across models. Central to our method is the notion of an allocation which defines the responsibility of each model to every region of the noisy sample. At every timestep, we then denoise by (i) updating the allocation by solving a fair division game, where we divide the sample into regions that maximize total utility under fairness constraints, and (ii) aligning the models with this allocation, where we guide each model to denoise within its assigned region. This leads to a new composite denoising process that evolves in tandem with a division process. We evaluate Divide-and-Denoise on conditional image generation. Across several quality metrics, including the GenEval benchmark, our method outperforms baselines and resolves common failures including missing objects and mismatched attributes. Experiments show that Divide-and-Denoise utilizes each model's expertise without neglecting any other model.

12.
medRxiv (Medicine) 2026-06-18

Digital self-efficacy as a potential intermediary between vision impairment and daily internet use among older adults: A cross-sectional analysis of HINTS 2024

Background: Older adults with vision impairment often experience barriers to using digital technology. The indirect associations between vision impairment and digital access and skills via digital self-efficacy and frustration among older adults remain largely unknown. Objective: This study aimed to 1) explore factors associated with digital access, skills, self-efficacy, and frustration among older adults with vision impairment; 2) examine associations between vision impairment and digital access, skills, self-efficacy, and frustration among older adults; and 3) examine whether digital self-efficacy and frustration may help explain associations between vision impairment and digital access and skills among older adults. Methods: This was a cross-sectional study using nationally representative data from the Health Information National Trends Survey (HINTS) 2024. Respondents aged 60 and older were included. Vision impairment was assessed using a self-reported item. Outcomes included self-reported digital access, skills, self-efficacy, and frustration. Survey-weighted multivariable logistic regression and generalized structural equation modeling were conducted, adjusting for age, sex, race/ethnicity, education, and the number of comorbidities. Results: Among 3,149 older adults (mean [SD] age, 70.7 [10.0] years; 45.6% female), 7.1% (n=223) reported vision impairment. Among older adults with vision impairment, 65.6% (95% CI, 53.5% to 75.9%) used the internet daily, and 79.5% (95% CI, 66.8% to 88.2%) used a smartphone in the past 12 months. In multivariable logistic regression analyses among older adults with vision impairment, older age was associated with lower odds of daily internet use (OR, 0.84; 95% CI, 0.79 to 0.90), smartphone use (OR, 0.85; 95% CI, 0.75 to 0.97), wearable device use (OR, 0.88; 95% CI, 0.79 to 0.97), and using the internet to send a message to a healthcare provider (OR, 0.87; 95% CI, 0.80 to 0.93). Older adults who self-identified as racial and ethnic minority groups (e.g., Black/African American, Hispanic) had lower odds of daily internet use (OR, 0.15; 95% CI, 0.05 to 0.50) and using the internet to send a message to a healthcare provider (OR, 0.17; 95% CI, 0.04 to 0.73) compared with Non-Hispanic White older adults. Vision impairment was associated with lower odds of daily internet use (OR, 0.60; 95% CI, 0.37 to 0.99) and digital self-efficacy (OR, 0.53; 95% CI, 0.32 to 0.86). Digital self-efficacy was associated with higher odds of daily internet use (OR, 2.95; 95% CI, 2.04 to 4.26). Generalized structural equation modeling identified an indirect association between vision impairment and daily internet use via digital self-efficacy (coefficient, -0.68; 95% CI, -1.24 to -0.12). Conclusions: Findings suggest that reduced digital self-efficacy may help explain the observed association between vision impairment and daily internet use among older adults. Interventions targeting digital self-efficacy, including accessible interface designs, personalized coaching, and peer support, may help bridge the digital divide among older adults with vision impairment.

13.
arXiv (CS.CV) 2026-06-17

Do We Really Need Diffusion? A Fast U-Net for Paired Medical Image Translation

Magnetic resonance imaging-signal fat fraction (MRI-SFF) quantifies tissue fat and serves as an established biomarker for metabolic and musculoskeletal disorders. The acquisition requires, however, specialized MRI sequences, which are not available routinely. We investigate whether SFF can be estimated from widely available T2-weighted (T2w) MRI via image-to-image translation (I2I). We further compare a lightweight 4-level U-Net to a state-of-the-art Denoising Diffusion Probabilistic Model (DDPM) using a dataset of 230 048 paired 2D images (183 517 train, 23 621 val, 22 910 test) from the German National Cohort (NAKO). Both models clearly outperform the identity baseline (Pearson correlation r = 0.769, mean absolute error MAE = 0.070 +/- 0.054), which confirms that the models learn a non-trivial cross-modal mapping. Interestingly, the lightweight U-Net outperforms the DDPM in both correlation (r = 0.975 vs. 0.962) and error (MAE = 0.014 +/- 0.015 vs. 0.019 +/- 0.019), while reducing inference time by a factor of 208 (25.2 ms vs. 5 227.2 ms per image using 50 Denoising Diffusion Implicit Model (DDIM) steps). The strong clinical performance at substantially reduced computational cost enables real-time clinical use.

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

Hubs or Fringes: Pretraining Data Selection via Web Graph Centrality

The performance of modern language models depends critically on pretraining data composition. Yet existing data selection methods rely on auxiliary classifiers for document scoring or mixture optimization, adding computational overhead and dependence on labeled data. We propose WebGraphMix, a lightweight data selection framework that computes structural centrality scores over the Common Crawl host-level web graph and uses them to vary the proportion of central versus peripheral documents in the pretraining mixture. We hypothesize that central hosts expose models to reusable abstractions, while peripheral hosts encode specialized, long-tail knowledge. WebGraphMix computes centrality scores efficiently at web scale, requiring no model training, labeled data, or downstream supervision. We integrate WebGraphMix into the DataComp-LM pipeline and train models at 400M and 1B parameter scales with 8B and 28B tokens respectively, evaluating on 23 tasks ranging from factual knowledge to symbolic reasoning. Our experiments show that central and peripheral web regions encode complementary capabilities. Mixture combining both at a ratio of 1:1 achieves 41.4% on average, compared to 39.8% for uniform sampling. Combining structural scores with document-level quality classifier scores further improves performance to 43.8%. These findings demonstrate that web graph topology is a meaningful axis for pretraining data curation, capturing information that is largely orthogonal to existing content-based approaches.

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

Does the Data Processing Inequality Reflect Practice? On the Utility of Low-Level Tasks

The data processing inequality is an information-theoretic principle stating that the information content of a signal cannot be increased by processing the observations. In particular, it suggests that there is no benefit in enhancing the signal or encoding it before addressing a classification problem. This assertion can be proven to be true for the case of the optimal Bayes classifier. However, in practice, it is common to perform "low-level" tasks before "high-level" downstream tasks despite the overwhelming capabilities of modern deep neural networks. In this paper, we aim to understand when and why low-level processing can be beneficial for classification. We present a comprehensive theoretical study of a binary classification setup, where we consider a classifier that is tightly connected to the optimal Bayes classifier and converges to it as the number of training samples increases. We prove that for any finite number of training samples, there exists a pre-classification processing that improves the classification accuracy. We also explore the effect of class separation, training set size, and class balance on the relative gain from this procedure. We support our theory with an empirical investigation of the theoretical setup. Finally, we conduct an empirical study where we investigate the effect of denoising and encoding on the performance of practical deep classifiers on benchmark datasets. Specifically, we vary the size and class distribution of the training set, and the noise level, and demonstrate trends that are consistent with our theoretical results.

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

Authority, Truth, and Citation Bias: A Large-Scale Multi-Domain Benchmark for Studying Epistemic Susceptibility in Large Language Models

arXiv:2606.13104v1 Announce Type: new Abstract: Large language models are increasingly deployed in citation-augmented settings, yet the effect of citation presence on model behavior independent of factual content remains poorly understood. We introduce AuthorityBench, a 220,564-prompt multi-domain benchmark that isolates how citation-based authority signals influence epistemic behavior in LLMs. The benchmark uses a fully balanced 2x2 factorial design crossing claim veracity with citation veracity, the first to do so, across four domains (general knowledge, science, law, and medicine), with controlled variation over 40 prompt templates, four venue prestige tiers, and a country-coded author name dataset. Evaluating seven models on 12 structured research questions, we find that citation presence, whether real or fabricated, consistently increases hallucination rates relative to a no-citation baseline. The effect is strongest when fabricated citations accompany true claims, raising hallucination rates by 3 to 22 percentage points and reaching 35 to 77% in the general knowledge domain, while legal claims are comparatively robust and venue prestige and author demographics show negligible impact. All datasets and evaluation code are available at: https://github.com/floating-reeds/AuthorityBench

17.
medRxiv (Medicine) 2026-06-10

General-purpose large language models can achieve physician-level accuracy in complex medical data extraction

Background: Unstructured data represent about 80% of total electronic health records (EHR) data. Structuring this free text is essential for advancing clinical research, including cohort selection for trials, retrospective studies, and the development of disease registries. While manual chart review (MCR) remains the gold standard for extracting this clinical data, the process is inherently slow, resource-intensive, and susceptible to errors from human fatigue. We evaluated the extraction accuracy, safety, and efficiency of the HeLIX (Hepatology Logic-Integrated Extraction) framework, a Large Language Model (LLM) protocol using Google Gemini 3 Pro, compared to a gold-standard Manual Chart Review (MCR). Methods: A prospective validation study was conducted using 50 high-complexity, simulated hepatology discharge summaries designed to replicate the real-world heterogeneity of EHRs. The HeLIX framework employed a Zero-Shot, Structured Chain-of-Thought (CoT) prompting strategy enforced by a three-layer architecture: Clinical Reasoning Trace, Schema Enforcement, and Evidence Verification. The model extracted 45 distinct clinical variables. Performance was benchmarked against a consensus MCR. Results: Across 2,250 evaluated data points, the model achieved an overall Extraction Accuracy of 99.24% (95% CI: 98.8%-99.5%), with perfect concordance in 35/45 (77.8%) variables. For binary diagnostic variables, the model demonstrated an overall F1-score of 0.98, Recall of 0.99 and substantial inter-rater reliability (Cohens {kappa} = 0.97). Hallucinations were exceptionally rare (2/2250; 0.08%). Critical errors affecting clinical management occurred in only 2 instances (

18.
medRxiv (Medicine) 2026-06-22

Repeat expansions in Parkinson's disease and parkinsonism across ancestries: insights from a global genetic cohort

Expanded short tandem repeats contribute to a broad spectrum of neurodegenerative diseases, yet their roles in Parkinson's disease (PD) and parkinsonism remain incompletely characterized, especially across diverse ancestries. We analyzed short-read whole-genome (WGS) and clinical exome sequencing (CES) data from 38,365 individuals (28,861 WGS; 9,504 CES), encompassing 23,242 patients with PD, 4,729 patients with atypical parkinsonism and 10,394 healthy controls from 11 genetic ancestries. To determine carrier frequencies and characterize repeat structures across diverse ancestries, we genotyped 12 established pathogenic loci where normal, intermediate, and pathogenic alleles can be reliably differentiated using short-read sequencing data. Additionally, we conducted threshold-based associations to determine the minimum threshold associated with increased PD risk in 15,995 individuals (8,591 PD, 7,404 controls) of European ancestry. Pathogenic repeat expansions were detected in 62 patients (56 PD and 6 atypical parkinsonism) and 5 controls across seven loci (AR, ATXN1, ATXN2, ATXN3, CACNA1A, HTT and THAP11), spanning seven ancestries. Among these, ATXN2 expansions were the most frequently observed in PD and were present in African, East Asian, European and Middle Eastern ancestries. Additionally, intermediate ATXN2 repeat expansions exhibited a strong, length-dependent association with PD risk in the European population, with individuals with [≥]32 repeats having a more than four-fold increased risk (odds ratio 4.25, 95% confidence interval 1.80-12.05). Overall, >92% of expanded alleles harbor CAA interruptions within the CAG tract. Pathogenic expansions at other loci, such as ATXN3 and THAP11, showed more ancestry-specific distributions. Clinically, individuals with pathogenic ATXN2 and ATXN3 expansions most often presented with typical PD features but frequently showed earlier disease onset and a strong family history of PD. This large-scale, multi-ancestry study comprehensively maps the genetic landscape of pathogenic and intermediate repeat expansions in PD. Our findings confirm a length- and structure-dependent risk association for ATXN2 with PD in the European population, and highlight the pleiotropic effects of repeat expansions across the parkinsonian spectrum.

19.
arXiv (CS.LG) 2026-06-12

Contrastive Geometric Learning Unlocks Unified Structure- and Ligand-Based Drug Design

arXiv:2601.09693v3 Announce Type: replace Abstract: Structure-based and ligand-based computational drug design have traditionally relied on disjoint data sources and modeling assumptions, limiting their joint use at scale. In this work, we introduce Contrastive Geometric Learning for Unified Computational Drug Design (ConGLUDe), a single contrastive geometric model that unifies structure- and ligand-based training. ConGLUDe couples a geometric protein encoder that produces whole-protein representations and implicit embeddings of predicted binding sites with a fast ligand encoder, removing the need for predefined pockets. By aligning ligands with both global protein representations and multiple candidate binding sites through contrastive learning, ConGLUDe supports ligand-conditioned pocket prediction in addition to virtual screening and target fishing, while being trained jointly on protein-ligand complexes and large-scale bioactivity data. Across diverse benchmarks, ConGLUDe achieves competitive zero-shot virtual screening performance, substantially outperforms existing methods on a challenging target fishing task, and demonstrates state-of-the-art ligand-conditioned pocket selection. These results highlight the advantages of unified structure-ligand training and position ConGLUDe as a step toward general-purpose foundation models for drug discovery.

20.
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.

21.
arXiv (CS.CL) 2026-06-12

How reliable are LLMs when it comes to playing dice?

We investigate the probabilistic reasoning capabilities of large language models through a controlled benchmarking study on discrete probability problems. We constructed two datasets, respectively a set of standard exercises and a set of counterintuitive exercises, designed to trigger heuristic reasoning, and evaluated 8 state-of-the-art models, each tested with and without Chain-of-Thought prompting. Models achieve an average accuracy of 0.96 on standard problems but only 0.59 on counterintuitive ones. We further provide empirical evidence of token bias: performance drops by over 20% when canonical formulations are replaced by disguised variants. Embedding misleading suggestions in the prompt reduces performance by up to 34%, with no model proving immune. Taken together, the reported findings suggest that current LLMs are not yet genuine probabilistic reasoners, despite their success in advanced mathematical problems.

22.
arXiv (CS.AI) 2026-06-19

The Tao of Agency: Autotelic AI, Embedded Agency and Dissolution of the Self

arXiv:2606.19924v1 Announce Type: new Abstract: Most artificial intelligence systems are built on the assumption that goals are exogenous and specified by the designer. Exploring what happens when an agent begins generating its own goals opens the field of autotelic AI. Agents are expected not merely to pursue objectives but to discover them. In this article, we trace its consequences through intrinsic motivation, resource-driven priors, causal-interventional learning, homeostasis, and embeddedness; the last of which is found to be a necessary but not sufficient condition for autotelic agency. Embeddedness individuates the agent at the cost of revealing that the individuation is non-unique, such that the same dynamics admit many valid partitions, each defining a different candidate self. The deepest problem with autotelic AI is therefore not how the agent generates goals, but how it generates and relativizes the self to which the goals are assigned. The agent must believe in its own boundary in order to act, and see through that boundary in order to understand. We consolidate these developments into a single framework and extend it along three directions: a quantum formulation in which the agent-environment cut becomes physical, a philosophical reading against non-dual contemplative traditions, and a concrete LLM-based agentic instantiation.

23.
arXiv (CS.LG) 2026-06-18

FinP: Fairness-in-Privacy in Federated Learning by Addressing Disparities in Privacy Risk

arXiv:2502.17748v4 Announce Type: replace Abstract: Federated Learning (FL) inherently mitigates mass data centralization risks; however, its privacy protections are not equally distributed - leaving vulnerable individuals disproportionately exposed to sophisticated privacy attacks. Crucially, statistical heterogeneity in human-centric FL environments often results in an inequitable distribution of privacy risks, particularly affecting those whose sensitive attributes or behaviors make them outliers. To address this critical gap, we introduce FinP, a novel framework designed to formalize and enforce fairness-in-privacy by mitigating disproportionate client vulnerability to Source Inference Attacks (SIA). FinP operationalizes a two-pronged defense strategy that tackles both the symptoms and root causes of privacy disparity, ensuring that no group of clients bears an excessive privacy burden. It combines a server-side adaptive aggregation mechanism, which dynamically weights client contributions based on their estimated privacy risk, with a client-side regularization technique to curb localized overfitting that drives unique data memorization. Extensive empirical evaluations on FEMNIST, Human Activity Recognition (HAR), and CIFAR-10 datasets demonstrate that FinP effectively aligns privacy fairness with primary task utility. Notably, FinP successfully mitigates SIA risks and reduces disparities in privacy exposure, establishing that strong fairness-in-privacy guarantees need not compromise model utility. Ultimately, FinP establishes equitable privacy protections by reducing vulnerability disparities by up to 57.14%, while preserving global model utility within a marginal +/- 1.75% of standard federated baselines.

24.
arXiv (CS.AI) 2026-06-18

RODS: Reward-Driven Online Data Synthesis for Multi-Turn Tool-Use Agents

arXiv:2606.19047v1 Announce Type: new Abstract: Multi-turn tool-use RL is bottlenecked by the rapid depletion of informative samples in static datasets. We observe that the gradient signal in GRPO concentrates on tasks with the highest rollout reward variance, a consequence of the Popoviciu upper bound. Consequently, samples near the agent's capability boundary – where successes and failures are roughly balanced – contribute disproportionately large policy gradients. As training progresses, this boundary continuously shifts, which gradually depletes the pool of informative samples in a static dataset. We propose RODS (Reward-driven Online Data Synthesis) to resolve this depletion. RODS closes the loop between RL training and data generation by repurposing the progress reward variance as a practical, zero-cost boundary detector that requires no extra inference beyond the rollouts already computed for training. It continuously identifies such boundary samples, synthesizes new multi-turn variants matching their structural complexity (e.g., API topology and dependency depth) via a skill-aligned resampling pipeline, and manages a dynamic replay buffer that co-evolves with the policy. Starting from 400 human seeds and maintaining an active training pool of ~800 samples, RODS achieves comparable performance to a 17K-sample offline pipeline while requiring roughly 20x fewer trajectories, and improves over fixed-data RL and environment augmentation in our controlled setting.

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arXiv (CS.LG) 2026-06-15

PERRY: Policy Evaluation with Confidence Intervals using Auxiliary Data

arXiv:2507.20068v2 Announce Type: replace Abstract: Off-policy evaluation (OPE) methods estimate the value of a new reinforcement learning (RL) policy prior to deployment. Recent advances have shown that leveraging auxiliary datasets, such as those synthesized by generative models, can improve the accuracy of OPE methods. Unfortunately, such auxiliary datasets may also be biased, and existing methods for using data augmentation within OPE lack principled uncertainty quantification. In high stakes domains like healthcare, reliable uncertainty estimates are important for ensuring safe and informed deployment of RL policies. In this work, we propose two methods to construct valid confidence intervals for OPE with data augmentation. The first provides a confidence interval over $V^{\pi}(s)$, the policy value conditioned on an initial state $s$. To do so we introduce a new conformal prediction method suitable for Markov Decision Processes (MDPs) with continuous state spaces, extending prior work to higher-dimensional settings. Second, we consider the more common task of estimating the average policy performance over all initial states, $V^{\pi}$; we introduce a method that draws on ideas from doubly robust estimation and prediction powered inference. Across simulators spanning inventory management, robotics, healthcare, and a real healthcare dataset from MIMIC-IV, we find that our methods can effectively leverage auxiliary data and consistently produce confidence intervals that cover the ground truth policy values, unlike previously proposed methods. Our work enables a future in which OPE can provide rigorous uncertainty estimates for high-stakes domains.