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01.
arXiv (CS.CL) 2026-06-25

Neural Scaling Universality: If Exponents Are Fixed, Time to Understand Coefficients

Neural scaling laws describe how pre-training loss decays as power laws with training time, model size, and compute. This position paper argues that the exponents of these power laws are fixed by generic mechanisms: a one-third time scaling due to the strong nonlinearity of Softmax, an inverse width scaling due to representational superposition, and an inverse depth scaling due to ensemble averaging of Transformer layers. These mechanisms are robust to a wide range of data structures and architectural details, placing current large language models in a universality class with fixed exponents. The coefficients, however, are expected to be sensitive to data and architecture details, and directly determine practical quantities such as the optimal model shape and the compute-optimal frontier. We therefore argue that understanding the coefficients is the key to near-term performance improvements, and that a closer examination of the current universality class may reveal pathways to better universality classes.

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

A Lightweight Multi-Agent Framework for Automated Concrete Barrier Design

arXiv:2606.12040v1 Announce Type: new Abstract: The design of reinforced concrete highway barriers is a safety-critical process that requires strict compliance with regulatory provisions such as the AASHTO-LRFD bridge design guidelines. Current engineering practice relies heavily on manual, iterative, and heuristic calculations to satisfy complex nonlinear material and mechanics constraints. Although Large Language Models (LLMs) demonstrate strong generative capabilities, their direct application to structural engineering remains limited by hallucination risks and insufficient physical grounding. To address these challenges, this study proposes a novel "generation-evaluation-optimization" closed-loop framework for automated concrete barrier design using the multi-agent orchestration capabilities of AutoGen. Experimental results demonstrate that the proposed agentic framework achieves over 98% design accuracy, significantly outperforming standalone general-purpose LLMs. More importantly, the study reveals that design performance is not necessarily correlated with model scale, where an 8B-parameter lightweight model could outperform unconstrained 631B-parameter flagship models. This finding highlights the potential to substantially reduce computational costs while improving the accessibility of AI-assisted engineering tools for industry applications. The source code for the proposed multi-agent design framework is available at the project GitHub repository: https://github.com/MXY820/barrier-design. Keywords: Structural Engineering; Multi-Agent Systems; Large Language Models; Concrete Barrier Design; AutoGen; Design Automation.

03.
arXiv (math.PR) 2026-06-12

Characterizing metric-space-valued processes: separating classes and weak invariance principles for measure-theoretic inference

arXiv:2606.13084v1 Announce Type: cross Abstract: This article investigates stochastic processes taking values in metric spaces that lack a topological vector space structure, a regime characterized by intricate interplay between topological, geometric, and temporal dependence structures. It is formally established that spaces admitting an isometric Hilbertian embedding constitute a strict subclass within the much broader class of metric spaces possessing the ball property. While traditional kernel methods are susceptible to geometric distortion when the underlying space cannot be isometrically embedded into a Hilbert space, we bypass such limitations by exploiting a fundamental structural property inherent to this broader class; namely, that Borel probability measures are uniquely determined by their values on balls. These separating classes provide the foundation for the subsequently introduced measure-theoretic inference methodology. We derive uniform convergence of a family of time-dependent random measures, alongside weak invariance principles for the corresponding nonstationary random fields. This framework explicitly exposes how dependence and geometric complexity influence sample path regularity. Furthermore, because the rapid decay of small-ball probabilities can prohibit the existence of limiting distributions for supremum-based discrepancy measures, we develop $L^p$-based alternatives. By directly leveraging the introduced convergence results, this approach circumvents the need for higher-order $U$-process formulations. Finally, for spaces that do admit an isometric Hilbertian embedding, and where $U$-processes naturally arise, we establish limit theory for both degenerate and nondegenerate multi-parameter $U$-processes, and demonstrate that local discrepancy tests maintain asymptotic stability under dynamic parameter regimes.

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

SkillHone: A Harness for Continual Agent Skill Evolution Through Persistent Decision History

arXiv:2606.08671v2 Announce Type: replace Abstract: Agent skills extend language-model agents with task-specific procedures, scripts, and references, but the tasks and environments they target continually change. Existing methods improve skills in bounded runs and retain only the final artifact, discarding the decision history that later agents need to interpret prior revisions, evaluations, and rejected alternatives. We introduce SkillHone, a harness for continual agent skill evolution grounded in persistent decision history. SkillHone pairs skill revisions with evaluation-side evidence that supplies practice feedback, recording structured histories of diagnoses, revisions, evidence, and outcomes. Role-separated subagents run candidate skills on practice probes with redacted reporting and propose revisions informed by prior decisions, enabling cross-session refinement without rediscovering past rationale. On deep-research benchmarks, SkillHone runs without a pre-integrated search stack and outperforms the commercially backed deep-research agent by 15.8 points on GAIA and 3.2 points on WebWalkerQA-EN, while also exceeding prior skill-evolution methods. We further deploy SkillHone on internal tool-mediated analysis scenarios, where it improves accuracy by an average of 18.8 points across seven settings.

05.
medRxiv (Medicine) 2026-06-22

COVID-19 containment policies and hyperglycemia in pregnancy: correlation with the Stringency Index in a nationwide Belgian cohort

Background During the COVID-19 pandemic, gestational diabetes (GD) prevalence showed variable changes across regions, with most reporting increases and others decreases; however, its association with perinatal outcomes in Belgium remains unknown. We aimed to compare the prevalence of hyperglycemia in pregnancy (HIP) in 2020 versus 2019 and examined the correlation between HIP prevalence and pandemic-related restrictions measured by the Stringency Index (SI) and evaluate neonatal weight percentiles changes. Methods: We included all singleton live births in Belgium in 2019 and 2020 from Belgian birth registry data. We compared monthly proportions of HIP prevalence and Small for gestational age (SGA) and Large for gestional age (LGA) newborns in 2019 and 2020. Crude and adjusted odds ratios (ORs, aORs) were estimated with logistic and multinomial regression. The Spearman correlation coefficient was used to assess the correlation between the monthly average SI and the monthly aORs of HIP. Results: For deliveries from January to June 2020, no significant differences in HIP prevalence were observed compared with 2019. From July to December 2020, there was a significant increase in HIP, with peaks in July (GD screening in April) (aOR 1.41, 1.26-1.58) and November (GD screening in August) (aOR 1.33, 95% CI 1.18-1.49). There was no significant change in neonatal weight percentiles. The Spearman correlation coefficient between the SI and HIP aORs was 0.86 (p = 0.02). Conclusion During the pandemic, we observed an increase in the prevalence of HIP, compared to 2019, without a measurable impact on LGA or SGA newborns. The aOR of HIP in a given month was strongly correlated with the corresponding SI.

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

Improving Detection of Rare Nodes in Hierarchical Multi-Label Learning

arXiv:2602.08986v2 Announce Type: replace-cross Abstract: In hierarchical multi-label classification, a persistent challenge is enabling model predictions to reach deeper levels of the hierarchy for more detailed or fine-grained classifications. This difficulty partly arises from the natural rarity of certain classes (or hierarchical nodes) and the hierarchical constraint that ensures child nodes are almost always less frequent than their parents. To address this, we propose a weighted loss objective for neural networks that combines node-wise imbalance weighting with focal weighting components, the latter leveraging modern quantification of ensemble uncertainties. By emphasizing rare nodes rather than rare observations (data points), and focusing on uncertain nodes for each model output distribution during training, we observe improvements in recall by up to a factor of five on benchmark datasets, along with statistically significant gains in $F_{1}$ score. We also show our approach aids convolutional networks on challenging tasks, as in situations with suboptimal encoders or limited data.

07.
medRxiv (Medicine) 2026-06-23

Sex-Specific TMPRSS2 Response and Reduced Peripheral RNA Concentration Following AstraZeneca COVID-19 Vaccination in Nigeria.

Background: ChAdOx1 nCoV-19 remains a cornerstone COVID-19 vaccine in sub-Saharan Africa, yet population-specific molecular responses are understudied. We examined peripheral blood ACE2 and TMPRSS2 expression, total RNA concentration, and coagulation indices in Nigerians >=6 months post-vaccination. Methods: In a case-control study in Port Harcourt, Nigeria, 51 ChAdOx1-vaccinated adults and 51 age/sex-matched unvaccinated controls provided venous blood for RNA extraction, qRT-PCR, and coagulation assays. Multivariable linear models assessed effects of vaccination, sex, and age on molecular parameters. Results: Vaccinated participants had 37% lower total RNA concentration than controls (4.02 +/- 0.09 vs 6.38 +/- 0.14 ng/uL, p=6 months post-ChAdOx1, Nigerians show reduced peripheral blood RNA without sustained ACE2/TMPRSS2 upregulation. The sex-specific TMPRSS2 pattern suggests hormone and vaccine interactions previously unreported in African cohorts and highlights the need for sex-disaggregated molecular surveillance. Region-specific reference gene validation is recommended for Nigerian transcriptomic studies.

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

SkillChain-Gym: A Benchmark for Reskilling-Aware Production-Inventory Control under Disruptions

arXiv:2606.17266v1 Announce Type: new Abstract: Production planning increasingly has to treat workforce capability as a decision variable: certifications lapse when skills are not maintained, new products require skills the current workforce does not hold, and reskilling competes for the same worker hours needed for production. Existing operations benchmarks usually treat labor as exogenous, while workforce-planning models with skills and learning are rarely released as reusable testbeds. We introduce SkillChain-Gym, a benchmark specification for reskilling-aware production-inventory control: a single-site environment with stylized worker skill-state dynamics, hard threshold certification, forgetting, and capacity-consuming training actions constrained by the same per-worker time budget as production. The benchmark includes seed-controlled disruption scenarios, three feasibility modes with projection diagnostics, deterministic replay, and metrics covering operations, resilience, capability growth, and training-access distribution. We evaluate production-only, reactive adaptive, water-filling adaptive, and static-insurance policies with budget variants over 60-shift horizons with paired statistical tests. The results are regime-dependent rather than a ranking. Training-capable policies dominate the production-only baseline, and maintenance training is necessary under forgetting even without disruptions. Among training-capable classes, adaptive training helps when bottlenecks are visible in the forecast, while a lean static cross-training plan, a deliberately favorable comparator whose structure encodes relevant skill contingencies, acts as strong insurance under surprise shocks and absenteeism. Capacity slack and the forgetting rate govern the boundary between these regimes. No policy class dominates across regimes, motivating forecast-driven controllers that decide when to buy skill insurance and when to react.

10.
arXiv (CS.LG) 2026-06-12

Majority-of-Three is Optimal

arXiv:2606.13614v1 Announce Type: cross Abstract: We give a short proof that the majority vote of three independent consistent classifiers is an optimal learner in the realizable PAC setting. This proves optimality for the simplest voting scheme, while simplifying both the algorithmic structure and the probabilistic analysis of previous voting learners, including the algorithm of S. Hanneke and the analysis of bagging by K. Green Larsen.

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

MedCTA: A Benchmark for Clinical Tool Agents

To make clinically grounded decisions, medical AI agents are expected to go beyond simple recognition and be capable of tool retrieval, evidence acquisition, and integration. Existing benchmarks largely evaluate isolated perception or single-turn question answering, and therefore provide limited visibility into failures of planning, tool recruitment, and rollout reliability. We introduce MedCTA, a benchmark for evaluating medical tool agents on clinician-validated, step-implicit tasks grounded in realistic multimodal clinical inputs, including radiology images, pathology slides, and reports. MedCTA comprises 107 real-world clinical tasks with clinician-verified executable trajectories over 5 deployed tools, and supports process-aware evaluation of tool selection, argument validity, execution stability, trajectory fidelity, and outcome quality. We benchmark 18 open- and closed-source multimodal models and find that even frontier systems remain brittle in multi-step clinical tool use: autonomous rollouts are dominated by protocol failures, premature stopping, and incorrect tool recruitment, while gold-standard tool routing yields large but still incomplete gains. These results show that strong backbone perception does not translate into reliable agentic behavior in clinical settings. MedCTA provides a rigorous testbed for auditing, diagnosing, and advancing trustworthy medical AI agents. The dataset and evaluation suite are available at https://ivul-kaust.github.io/MedCTA/

12.
arXiv (quant-ph) 2026-06-15

Quantum gates with parametrically driven multi-qubit couplers

arXiv:2606.14522v1 Announce Type: new Abstract: Superconducting quantum processors could significantly profit from enhanced connectivity together with precise control of interactions and gates between qubits. Here we investigate plaquettes of four qubits that are coupled via a central tunable coupling circuit, so that not only gates between qubits connected by an edge of the plaquette can be executed but also between qubits across the diagonal. By numerically and analytically analyzing parametrically driven processes, we explore $\sqrt{iSWAP}$-gates between any pair of qubits, also across the diagonal, as well as three-qubit interactions and gates. For experimentally available circuit parameters, we for example find $\sqrt{iSWAP}$-gates with a gate time of 50 ns and 99.9\% fidelity, which is decreased to 99.4\% if two such gates are executed in parallel on disjoint qubit pairs in the plaquette. For three-qubit gates we find fidelities of 95\% fidelity at a gate time of 200 ns.

13.
medRxiv (Medicine) 2026-06-12

Genome-wide association and multi-omics functional screens reveal the genetic architecture of foveal development

Foveal hypoplasia causes visual impairment across congenital eye disorders, yet the genetic programmes governing foveal development remain poorly characterised and no tractable model exists for foveal disease. In the first genome-wide association study of foveal hypoplasia, we identified 42 sentinel variants mapping to 54 effector genes supported by >= 2 criteria from a variant-to-gene framework incorporating developmental multi-omics. Disruption of six effector genes using mutant lines and CRISPR knockouts in the zebrafish high acuity zone recapitulates structural, functional, and ultrastructural hallmarks of foveal hypoplasia, establishing the first vertebrate disease model. Integration with human foetal single-cell and spatial transcriptomics reveals two temporal waves of effector gene expression and identifies Muller glia as critical mediators of foveal patterning. Phenome-wide analyses reveal foveal variants are pleiotropic with refractive, lenticular, and metabolic traits, connecting foveal development to anterior segment and systemic disease biology. These findings should inform mechanistic studies of macular disease.

14.
arXiv (quant-ph) 2026-06-25

Quantum Optimal Control Using MAGICARP: Combining Pontryagin's Maximum Principle and Gradient Ascent

arXiv:2505.21203v2 Announce Type: replace Abstract: We introduce the MAGICARP algorithm, a numerical optimization method for quantum optimal control problems that combines the structure provided by Pontryagin's Maximum Principle (PMP) and the robustness of gradient ascent techniques, such as GRAPE. MAGICARP is formulated as a "shooting technique", aiming to determine the appropriate initial adjoint momentum to realize a target quantum gate. This method naturally incorporates time and energy optimal constraints through a PMP-informed pulse structure. We demonstrate MAGICARP's effectiveness through illustrative numerical examples, comparing its performance to GRAPE and highlighting its advantages in specific scenarios.

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

Visual Retrieval-Augmented Generation for Silhouette-Guided Animal Art

Generative AI has advanced the ability to render photorealistic or artistic images, yet it remains limited in a key aspect of human creativity: interpreting ambiguous shapes. This phenomenon, rooted in pareidolia, allows humans to perceive meaningful forms in random patterns such as clouds, stones, or leaves. To computationally replicate this imaginative process, we introduce Visual Retrieval-Augmented Generation (Visual-RAG), a framework that generates animal art directly from natural silhouettes. Our method retrieves structurally similar animal shapes from a curated corpus of 28,586 high-quality silhouettes and uses them as reference exemplars to guide diffusion-based generation with ControlNet and IP-Adapter. Ablation studies confirm that shape Context with RANSAC provides the most accurate alignment, while removing shape standardization reduces the inlier ratio to just 13.4\%, underscoring the importance of structural fidelity in Visual-RAG. A user study with 12 participants evaluated the outputs in terms of aesthetics, silhouette fidelity, and overall impression. Results reveal that while Visual-RAG provides plausible interpretations, challenges remain in achieving high perceptual impact. This work lays the foundation for computational pareidolia, showing how machines can contribute to the early stages of imaginative discovery.

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

EmoZone-Talker: Regional Semantic Control of Audio-Driven 3DGS Talking Heads via Facial Action Units

3D Gaussian Splatting (3DGS) has shown strong potential for high-fidelity talking head synthesis. However, enabling fine-grained, interpretable, and editable facial expression control remains fundamentally challenging due to intrinsic conflicts between speech-driven facial dynamics and explicit expression signals. Existing methods rely on implicit multimodal fusion, leading to spatial entanglement and temporal instability. We present EmoZone-Talker, a novel framework that reformulates audio-driven facial animation as a structured spatial-temporal coordination problem under cross-modal conflicts. Our approach introduces an explicit spatial disentanglement and temporal dynamics modeling of facial motion. Specifically, we propose Synergy Zones with Prioritized Attention Bias (SZ-PAB) to explicitly decouple modality contributions via region-wise constraints guided by anatomical priors, and a Channel-Independent Temporal AU Encoder (CIT-AE) to model temporally coherent AU dynamics. By integrating these representations into 3D Gaussian deformation, EmoZone-Talker enables precise and interpretable control over facial expressions. Extensive experiments demonstrate that our method improves expression controllability and realism, with notable gains in upper-face accuracy and temporal coherence, while preserving high rendering quality and accurate lip synchronization. Code will be publicly released to facilitate reproducibility and further research.

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

Learning to Inject: Automated Prompt Injection via Reinforcement Learning

arXiv:2602.05746v2 Announce Type: replace-cross Abstract: Prompt injection is a critical vulnerability in LLM agents, yet the strongest methods still rely on human red-teamers and hand-crafted prompts. Adapting automated jailbreak optimizers does not close this gap: jailbreaks shape models toward generic compliance, while prompt injection requires emitting specific tool calls with correct parameters. The success signal is binary, and randomly sampled suffixes almost never trigger it, so standard optimizers have no gradient to follow. We present AutoInject, a black-box reinforcement learning (RL) framework that learns adversarial suffixes for prompt injection. A learned comparison-based reward scores each candidate against the best suffix seen so far, turning the binary signal into a dense reward suitable for RL optimization. The framework supports both online query-based attacks and offline-trained transferable suffixes that need no utility access at deployment, and incorporates a utility objective when task-completion feedback is available. On AgentDojo, AutoInject outperforms template attacks, GCG, TAP, and adaptive attack across production models, with statistically significant improvements under McNemar's test with p

18.
arXiv (quant-ph) 2026-06-25

Hodge Spectral Surrogates for Topology-Constrained Optimization

arXiv:2606.25194v1 Announce Type: cross Abstract: Topological information is widely used in data analysis, network design, and machine learning, and topological constraints naturally arise when optimizing or generating objects with prescribed homological structure. However, directly controlling Betti numbers and persistent homology is difficult because they are discrete and combinatorial. We propose a differentiable framework for topology-constrained optimization based on Hodge-spectral relaxations of homological constraints and low-pass spectral filters. From soft graphs and soft clique complexes, we construct Hodge-Laplacian-type spectral relaxations that unify graph clique complexes and Vietoris–Rips filtrations of point clouds. In the hard limit, the penalty-regularized ambient operator recovers the ordinary Hodge Laplacian on the active subcomplex, while in the soft regime it serves as a differentiable low-frequency spectral surrogate. Homological information is represented by zero and near-zero modes, and differentiable topological objectives are defined using heat filters, resolvent filters, and polynomial Laplacian moments. For point clouds, we show that the proposed Hodge spectral-filter losses yield more spatially distributed gradients, smoother scale-normalized behavior under persistence-pairing changes, and geometry-aware update directions than persistent-homology-based losses. For graph clique complexes, Laplacian moments control normalized first-Betti-type quantities and can be combined with ordinary graph-feature objectives. We also discuss connections to trace-based normalized Betti-number estimation, polynomial spectral methods, and possible quantum trace estimation.

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

NeRD: Neuro-Symbolic Rule Distillation for Efficient Ontology-Grounded Chain-of-Thought in Medical Image Diagnosis

Interpretability is essential for trustworthy medical image diagnosis. However, existing concept-driven interpretable methods have key limitations: Concept Bottleneck Models (CBMs) require scoring all predefined concepts at inference time and for manual intervention, imposing a substantial burden on clinicians, while rationale-based generative approaches often select concepts by class discriminability, which can drift from diagnostic ontologies. To address these issues, we propose Neuro-Symbolic Rule Distillation (NeRD), a framework that produces efficient, ontology-grounded reasoning chains that are sufficient yet non-redundant, without manually crafting diagnostic rules. Experiments on two skin datasets demonstrate strong diagnostic performance and interpretability, and blinded expert evaluation confirms the clinical plausibility of NeRD rationales. Our method further enables a first expert-in-the-loop study for Multimodal Chain-of-Thought-based diagnosis, achieving efficient and effective concept-level intervention.

20.
arXiv (CS.LG) 2026-06-12

Normative Robustness as a Frontier for Non-Verifiable Reasoning in LLMs

arXiv:2606.12731v1 Announce Type: new Abstract: As LLMs increasingly serve in advisory and deliberative roles, users rely on them for non-verifiable reasoning in domains lacking objective ground truths. However, traditional evaluations of LLM reasoning focus almost exclusively on fact-based domains, such as mathematics and science, leaving uncertainty over whether and to what degree models can handle ambiguous, subjective, or value-laden problems over time. To address this concern, we propose moral reasoning as a paradigmatic subdomain of non-verifiable reasoning. We define moral robustness as a model's capacity to exhibit sound moral reasoning across time and contexts, and we introduce a scalable, adversarial, multi-turn evaluation framework to empirically measure this capability. We simulate 48,000 user-agent moral deliberations across four frontier LLMs, varying premise relevance, premise order, conversation duration, and the user's stated moral view. We find that models successfully ignore morally-irrelevant distractors, but shift their reasoning by up to 6.5%, on average, towards the user's stated preferred moral view, and varying their reasoning depending on factors such as order (altering moral judgments by order in 13-22% of the cases) and duration (altering moral judgments between single-turn and multi-turn in 10-24% of the cases). Our analysis indicates that models tailor not just their final verdicts but their underlying justifications to align with a user's moral viewpoint - a failure mode we characterize as moral deliberative sycophancy.

21.
arXiv (quant-ph) 2026-06-24

Quantum Correlations of Neutrinos in the Kerr-Newman Space-time

arXiv:2605.10424v2 Announce Type: replace-cross Abstract: Quantum phases provide a connection between gravitation and quantum information, which proposes a novel avenue to explore the properties of space-time. In this paper, we investigate the quantum correlations (QCs) of neutrinos in the Kerr–Newman space-time. Both radial and non-radial propagations are considered under the weak-field approximation. The results show that, for inward propagations, the oscillation probabilities and QCs differ significantly from those obtained in the Schwarzschild metric. In the case of radial outward propagation, the larger angular momentum $a$ increases the oscillation period of the survival probability $P_{ee}$, entanglement, and monogamy of nonlocality, whereas the larger charge $Q$ decreases the corresponding periods. For non-radial propagations, $M$ and $a$ can noticeably modulate the amplitudes of the considered QCs, which is not observed in the case of radial propagations. Furthermore, we find that, despite differences in their variation ranges, entanglement and coherence exhibit highly consistent oscillation behaviors in both radial and non-radial propagation cases. These findings provide a comprehensive understanding for the neutrinos-based relativistic quantum information.

22.
arXiv (CS.AI) 2026-06-17

A Neuro-Symbolic Approach to Strategy Synthesis for Strategic Logics

arXiv:2606.17962v1 Announce Type: cross Abstract: Reasoning about what agents can achieve through strategic interaction is a core challenge in Multi-Agent Systems (MAS). Logics for strategic ability, such as ATL, provide rigorous methods, but their adoption is often hindered by the computational cost of strategy synthesis. We introduce a neuro-symbolic framework that integrates large language models (LLMs) into the model-checking pipeline for MAS. The LLM acts as a strategy-generation oracle, proposing candidate strategies that are then formally validated by a standard MAS model checker. This generate-and-certify architecture uses LLM guidance to navigate large combinatorial strategy spaces while preserving formal soundness: generated strategies are accepted only when certified by the verifier. We instantiate the framework for bounded strategic reasoning in NatATL and introduce the first NatATL strategy-synthesis dataset, consisting of 4211 instances. Experiments with an open-weight Qwen3-32B model show that our certified pipeline achieves 92\% accuracy on strategy-synthesis outcomes.

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

Quantile of Means: A Bonus-Free Ensemble Method for Minimax Optimal Reinforcement Learning

arXiv:2606.20107v1 Announce Type: new Abstract: Optimal Reinforcement Learning (RL) algorithms typically rely on carefully constructed count-based uncertainty estimates to drive exploration. Although theoretically sound, such estimates are hard to compute in practical settings and therefore offer limited insight for designing exploration heuristics. Meanwhile, ensembling has emerged as a practical approach, but remains without theoretical justification. Building on a recent ensemble-based method for Multi-Armed Bandits, we propose a quantile-based ensemble method for finite-horizon Markov Decision Processes (MDPs). Our simple count-free approach achieves optimal variance-dependent regret bounds, providing theoretical grounding for ensemble-based exploration in RL.

24.
PLOS Computational Biology 2026-06-04

CIPHER: An end-to-end framework for designing optimized aggregated spatial transcriptomics experiments

by Zachary Hemminger, Haley De Ocampo, Fangming Xie, Zhiqian Zhai, Jingyi Jessica Li, Roy Wollman Motivation Most imaging-based spatial transcriptomics methods measure individual genes, which limits scalability and typically requires integration with scRNA-seq to recover full cellular states. Recent approaches such as CISI, FISHnCHIPs, and ATLAS address this limitation by measuring aggregate transcriptional signatures, where multiple genes are pooled into each channel to increase throughput. While aggregate measurements improve scalability, they shift the problem from gene selection to feature design. For effective integration with scRNA-seq, these signatures must be not only discriminative in transcriptional space but also straightforward to measure, with balanced signal, sufficient dynamic range, and robustness to experimental noise. By optimizing decoding accuracy in isolation, existing methods leave substantial performance on the table. Results We present CIPHER (Cell Identity Projection using Hybridization Encoding Rules), a neural-network framework that jointly optimizes the experimental encoding matrix, i.e., the way that genes are aggregated to signatures, and the downstream cell embedding. CIPHER integrates the physical limits of imaging assays directly into its loss function, shaping the latent space to maximize discriminability while maintaining robustness to measurement noise and signal constraints. Using a large-scale mouse brain scRNA-seq reference, we show that CIPHER-designed encodings yield latent spaces with improved cell-type separability, uniform signal utilization, and greater resilience to hybridization variability, resulting in higher decoding accuracy from both simulated and experimental data. Conclusion CIPHER formulates aggregate signature design as a joint optimization problem over decoding accuracy and experimental measurability. This enables systematic, scRNA-seq-aligned feature design for scalable spatial transcriptomics based on aggregate measurements. Availability Code and documentation are available at https://github.com/wollmanlab/Design/.

25.
medRxiv (Medicine) 2026-06-22

Early-life nutritional environment is associated with late-life cognition in the Health and Retirement Study, a pellagra epidemic natural experiment

Early-life exposures are important to several late-life health outcomes. We sought to study the effect of an in utero nutritional environment and its interaction with Alzheimer's disease (AD) genetic risk on late-life cognitive function. We used a natural experiment created by the pellagra epidemic, a nutritional disease caused by a vitamin B3 deficiency, to evaluate the association between in utero pellagra epidemic exposure and late-life cognitive function in the Health and Retirement Study (N = 18,285). We also evaluated whether the in utero exposure could modify the AD polygenic score's (PGS) effect on cognition. In utero pellagra epidemic exposure was significantly associated with cognition ({beta} = -0.025). However, these effects were not isolated to the prenatal period as exposure during childhood periods also had an effect. The interaction between the in utero exposure and the AD PGS was significant, where the genetic effect on cognition was amplified with increasing (progressively worse) in utero exposure levels. These associations imply that the early-life nutritional environment affects late-life cognitive function and that these effects can modify genetic risk.