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01.
arXiv (CS.AI) 2026-06-15

Beyond LoRA: Is Sparsity-Induced Adaptation Better?

arXiv:2606.13767v1 Announce Type: cross Abstract: Low-rank adaptation (LoRA) and its variants provide a memory- and compute-efficient alternative to full fine-tuning of pre-trained models. However, questions remain about the comparative generalizability of these approaches and how the structural restrictions on low-rank updates preserve effective adaptation performance. We present a historical framing, covering the past (full fine-tuning and original LoRA), the present (different variants of LoRA), and propose simpler, cheaper, parameter-efficient extensions by inducing sparsity within existing LoRA variants: Cheap LoRA (cLA), training a single low-rank factor with the other fixed (deterministically or, in its randomized variant, stochastically), and the chained circulant variant, ${c}^3$LA. We frame cLA as a structured instance of asymmetric LoRA, serving as a controlled column-subspace restriction of full fine-tuning. We derive information-theoretic generalization error bounds for these variants, marking one of the first endeavors in this area. Empirically, we evaluate 11 fine-tuning methods across 10 pre-trained models and 14 datasets, analyzing the fine-tuned models' performance and generalization using tools such as loss landscapes and spectral analysis. Despite the sensitivity of fine-tuned models to the pre-trained model, datasets, and other factors, our study suggests that restricting LoRA-based PEFT methods' adaptation to a sparse, structured column space remains competitive across tasks with their parameter-matched baselines while reducing up to 10% training time and peak GPU memory up to 15%, even with a naïve, non-optimized, sparse implementation. Our theoretical and empirical generalization measures provide a more consistent and principled approach to their cost-effective adaptation than commonly used analytical tools. Overview and code are available at: https://elicaden.github.io/Beyond_LoRA/.

02.
arXiv (CS.LG) 2026-06-15

Recursively Trained Diffusion Models: Limiting Collapse Distribution and Spectral Characterization

arXiv:2606.13796v1 Announce Type: cross Abstract: Recursive training of generative models on their own outputs can lead to model collapse, a compounding drift away from the true data distribution. Existing theoretical works bound finite-round error accumulation in the context of diffusion models, but two questions remain open:~what distribution does the recursion converge to, and how fast? We answer both, isolating a mechanism distinct from imperfect learning: even with perfect score estimation and exact sampling, the early stopping of the reverse diffusion (required for numerical stability) drives a progressive drift away from the data distribution. We prove that this recursion converges geometrically to a unique limiting distribution, which admits a closed-form characterization as an infinite mixture of increasingly Gaussian-smoothed versions of the data distribution. A Hermite spectral decomposition of this limit reveals that recursive training acts as a low-pass filter: higher-order modes, which encode fine non-Gaussian structure, are attenuated much more strongly than coarse modes. This spectral picture motivates annealed truncation schedules that progressively shrink truncation times across retraining rounds; we prove that any schedule converging to $0$ asymptotically eliminates recursive compounding. Finally, we show our idealized characterization is robust: in the presence of discretization and score estimation errors, the learned distribution remains in a Wasserstein-2 ball around the ideal limit, with mode-dependent contraction rates that contract high-order errors faster than low-order ones. We validate the theory on synthetic Gaussian mixtures and CIFAR-10.

03.
arXiv (CS.CV) 2026-06-11

Physics-Driven Spatiotemporal Modeling for AI-Generated Video Detection

AI-generated videos have achieved near-perfect visual realism (e.g., Sora), urgently necessitating reliable detection mechanisms. However, detecting such videos faces significant challenges in modeling high-dimensional spatiotemporal dynamics and identifying subtle anomalies that violate physical laws. In this paper, we propose the first physics-driven AI-generated video detection paradigm based on probability flow conservation principles. Specifically, we propose a statistic called Normalized Spatiotemporal Gradient (NSG), which quantifies the ratio of spatial probability gradients to temporal density changes, explicitly capturing deviations from natural video dynamics. Leveraging pre-trained diffusion models, we develop an NSG estimator through spatial gradients approximation and motion-aware temporal modeling without complex motion decomposition while preserving physical constraints. Building on this, we propose an NSG-based video detection method (NSG-VD) that computes the Maximum Mean Discrepancy (MMD) between NSG features of the test and real videos as a detection metric. Last, we derive an upper bound of NSG feature distances between real and generated videos, proving that generated videos exhibit amplified discrepancies due to distributional shifts. Extensive experiments confirm that NSG-VD outperforms state-of-the-art baselines by 16.00% in Recall and 10.75% in F1-Score, validating the superior performance of NSG-VD. The source code is available at https://github.com/ZSHsh98/NSG-VD.

04.
arXiv (CS.AI) 2026-06-18

Improving Scientific Document Retrieval with Academic Concept Index

arXiv:2601.00567v2 Announce Type: replace-cross Abstract: Adapting general-domain retrievers to scientific domains is challenging due to the scarcity of large-scale domain-specific relevance annotations and the substantial mismatch in vocabulary and information needs. Recent approaches address these issues through two independent directions that leverage large language models (LLMs): (1) generating synthetic queries for fine-tuning, and (2) generating auxiliary contexts to support relevance matching. However, both directions overlook the diverse academic concepts embedded within scientific documents, often producing redundant or conceptually narrow queries and contexts. To address this limitation, we introduce an academic concept index, which extracts key concepts from papers and organizes them guided by an academic taxonomy. This structured index serves as a foundation for improving both directions. First, we enhance the synthetic query generation with concept coverage-based generation (CCQGen), which adaptively conditions LLMs on uncovered concepts to generate complementary queries with broader concept coverage. Second, we strengthen the context augmentation with concept-focused auxiliary contexts (CCExpand), which leverages a set of document snippets that serve as concise responses to the concept-aware CCQGen queries. Extensive experiments show that incorporating the academic concept index into both query generation and context augmentation leads to higher-quality queries, better conceptual alignment, and improved retrieval performance.

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

Application of integrated gradients explainability to sociopsychological semantic markers

Classification of textual data in terms of sentiment, or more nuanced sociopsychological markers (e.g., agency), is now a popular approach commonly applied at the sentence level. In this paper, we exploit the integrated gradient (IG) method to capture the classification output at the word level, revealing which words actually contribute to the classification process. This approach improves explainability and provides in-depth insights into the text. We focus on sociopsychological markers beyond sentiment and investigate how to effectively train IG in agency, one of the very few markers for which a verified deep learning classifier, BERTAgent, is currently available. Performance and system parameters are carefully tested, alternatives to the IG approach are evaluated, and the usefulness of the result is verified in a relevant application scenario. The method is also applied in a scenario where only a small labeled dataset is available, with the aim of exploiting IG to identify the salient words that contribute to building the different classes that relate to relevant sociopsychological markers. To achieve this, an uncommon training procedure that encourages overfitting is employed to enhance the distinctiveness of each class. The results are analyzed through the lens of social psychology, offering valuable insights.

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

SAG: SQL-Retrieval Augmented Generation with Query-Time Dynamic Hyperedges

Retrieval-Augmented Generation (RAG) offers an effective approach for large language models to access external knowledge. However, existing methods rely on dense similarity retrieval and face inherent limitations in handling structured constraints and multi-hop reasoning. Incorporating knowledge graphs partially alleviates these issues, but at the cost of semantic fragmentation, high maintenance overhead, and difficult incremental updates. This paper introduces SAG (SQLRetrieval Augmented Generation), a structured architecture for retrieval and agent systems. Instead of pre-building a global static graph, SAG converts each chunk into one semantically complete event and a set of indexing entities, then uses SQL join queries to dynamically link events that share entities into local hyperedges,constructing, at query time, a dynamically instantiated local index structure. This design avoids the need for global graph rebuilding and ongoing maintenance; the system naturally supports incremental writes, concurrent processing, and continuous scaling through its reliance on standard database infrastructure. Across HotpotQA, 2WikiMultiHop, and MuSiQue, three standard multi-hop benchmarks,SAG achieves the best results on 8 out of 9 Recall@K metrics, reaching 80.0% Recall@5 on MuSiQue, the benchmark with the highest multi-hop reasoning demands.SAG has also been deployed at a production scale of hundreds of millions of data items, with online retrieval latency kept within seconds. Project site and code are available at https://github.com/Zleap-AI/SAG-Benchmark.

07.
arXiv (CS.CV) 2026-06-12

DIMOS: Disentangling Instance-level Moving Object Segmentation

Moving instance segmentation (MIS) attracts increasing attention due to its broad applications in traffic surveillance, autonomous driving, and animal tracking. Event cameras record asynchronous brightness changes, providing high temporal resolution and dynamic range, which makes them highly sensitive to motion information. By fusing event and image features, motion cues from events can complement spatial details from images, enhancing the performance of MIS. However, current multimodal MIS methods still struggle to segment small moving instances, as event cameras often yield sparse features under limited resolution. Moreover, event features entangle appearance attributes with motion cues, which further restricts effective cross-modal fusion. To address these challenges, we first propose a dual-disentangling feature extraction framework that separates and extracts appearance and motion information within both image and event modalities, thereby improving feature density. Subsequently, a multi-granularity cross-modal alignment is introduced to align distributionally and semantically consistent features across modalities, enabling more effective fusion with rich spatial and temporal details. The experiment results demonstrate that our method achieves state-of-the-art performance in multimodal MIS, especially for small instances under challenging conditions such as fast motion and low-light settings.

08.
arXiv (quant-ph) 2026-06-12

Relativistic Locality from Electromagnetism to Quantum Field Theory

arXiv:2412.11532v2 Announce Type: replace Abstract: Electromagnetism is the paradigm case of a theory that satisfies relativistic locality. This can be proven by demonstrating that, once the theory's laws are imposed, what is happening within a region fixes what will happen in the contracting light-cone with that region as its base. The Klein-Gordon and Dirac equations meet the same standard. We show that this standard can also be applied to quantum field theory (without collapse), examining two different ways of assigning reduced density matrix states to regions of space. Our preferred method begins from field wave functionals and judges quantum field theory to be local. Another method begins from particle wave functions (states in Fock space) and leads to either non-locality or an inability to assign states to regions, depending on the choice of creation operators. We take this analysis of quantum field theory (without collapse) to show that the many-worlds interpretation of quantum physics is local at the fundamental level. We argue that this fundamental locality is compatible with either local or global accounts of the non-fundamental branching of worlds, countering an objection that has been raised to the Sebens-Carroll derivation of the Born Rule from self-locating uncertainty.

09.
arXiv (CS.AI) 2026-06-16

Metric Match: A Subset Selection Approach to Evaluating LLM Judge Reliability

arXiv:2606.15029v1 Announce Type: new Abstract: LLM judges are used to reduce the need for costly human labor in evaluating open-ended text generation. However, the reliability of these judges depends critically on their alignment with human raters – a property that itself depends on costly human annotations. In this work, we develop a method (Metric Match) for estimating correlation-based reliability metrics of LLM judges from limited annotations. Metric Match selects a subset of samples for human annotation such that the subset matches the population reliability metric with respect to acquired synthetic labels. We empirically show that Metric Match achieves a win-rate of 0.838 against random subset selection across four different correlation metrics and 15 datasets, with an 18.7% decrease in average estimation error and reduces annotation needs by 32.5%. We provide a cost model and highlight a medical case study where our method saves $1,041.67 compared to random selection for expert annotation. Further, we shift our task from reliability estimation to reliability classification of whether a given judge is above a deployment threshold, outperforming random selection with Metric Match. All project code is publicly available, and we additionally provide an installable package for ease of use.

10.
arXiv (quant-ph) 2026-06-16

High-Order Hermite Optimization: Fast and Exact Gradient Computation in Open-Loop Quantum Optimal Control using a Discrete Adjoint Approach

arXiv:2505.09857v5 Announce Type: replace-cross Abstract: This work introduces the High-Order Hermite Optimization (HOHO) method, an open-loop discrete adjoint method for quantum optimal control. Our method is the first of its kind to efficiently compute exact (discrete) gradients when using continuous, parameterized control pulses while solving the forward equations (e.g. Schrodinger's equation or the Linblad master equation) with an arbitrarily high-order Hermite Runge-Kutta method. The HOHO method is implemented in QuantumGateDesign$.$jl (https://github.com/leespen1/QuantumGateDesign.jl), an open-source software package for the Julia programming language, which we use to perform numerical experiments comparing the method to Juqbox$.$jl (https://github.com/LLNL/Juqbox.jl). For realistic model problems we observe speedups up to 775x.

11.
medRxiv (Medicine) 2026-06-18

Automated Airways Characterization and Assessment of Cystic Fibrosis from CT Imaging

Background Advancements in medical imaging have enabled non-invasive diagnosis and staging of cystic fibrosis (CF) using CT scans, revealing dilated airways, an increased number of visible airways, and airway generation splits in these patients. However, manual characterization of airways remains time-consuming and challenging due to the numerous structural changes, thereby limiting clinical feasibility. This study aims to develop an automated algorithm to characterize airways from segmented lung CT scans and apply this to a retrospective population. This approach reduces the time required to analyze images and obtain disease-staging results. Methods This framework consists of two stages. The first stage extracts and skeletonizes the airway tree from lung CTs, while the second stage measures lung features, including airway volumes, branch counts, generation splits, diameters, and cross-sectional areas. This permits comprehensive characterization for use in clinical assessment. Results The airways analysis was performed on 169 CT volumes ranging in age from 6 to 18 years of age, revealing substantial differences in detected airway branches, generation splits, and normalized airway volume between the control and CF groups. The framework also measures airway diameters and cross-sectional areas, revealing an increase in the number of small airways in cystic fibrosis patients, due to early bronchiectasis. These findings align with previous research and demonstrate the framework's ability to accurately quantify airway changes in patients with CF. Discussion The framework extracts entire airway trees, facilitating measurements of volume, branch count, diameters, and cross-sectional areas, which change with CF severity and/or treatment. However, partial lung atelectasis can limit the accuracy of airway detection in moderate-to-severe cases. Funding NIA U54 AG054345 and NIA R21 AG07857501

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

TS-ICL: A Flexible Time-Indexed Foundation Model for Time Series via In-Context Learning

arXiv:2606.05878v2 Announce Type: replace Abstract: Foundation models mark a profound paradigm shift in time series modeling, with task-specific models being superseded by general-purpose zero-shot models. Yet, current approaches primarily focus on forecasting, while real-world time series are often irregularly and partially observed, requiring models that can jointly forecast, impute missing values, and handle degraded sampling conditions. To address these challenges, we introduce TS-ICL, a novel probabilistic In-Context Learning encoder–regressor Transformer that unifies forecasting and imputation. TS-ICL formulates time series tasks as timestamp-aligned regression and naturally incorporates covariates by training on synthetic dependency structures generated from a novel causal data prior. Empirically, TS-ICL achieves a new state-of-the-art in imputation, while remaining competitive with leading forecasting foundation models across both univariate and covariate-aware benchmarks. It shows particularly strong performance in forecasting with partially observed look-back windows.

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

VOiLA: Vectorized Online Planning with Learned Diffusion Model for POMDP Agents

arXiv:2606.19729v1 Announce Type: cross Abstract: Planning under uncertainty is an essential capability for autonomous robots. The Partially Observable Markov Decision Process (POMDP) provides a powerful framework for such a capability. Although POMDP-based planning has advanced significantly, its application to real-world problems is often limited by the difficulty of obtaining faithful POMDP models. We present Vectorized Online planning wIth Learned diffusion model for POMDP Agents (VOiLA), a framework that learns task-agnostic POMDP models for online planning under uncertainty. VOiLA learns transition and observation samplers using conditional diffusion models and learns observation-likelihood models for particle-based belief updates. To enable efficient online planning, the diffusion samplers are distilled into compact feedforward generators and integrated with Vectorized Online POMDP Planner (VOPP), an online POMDP planner designed to leverage GPU parallelization. Experimental results indicate the distillation strategy reduces sampling cost by up to nearly three orders of magnitude, making learned generative POMDP models practical for online planning. Evaluation of VOiLA on three benchmark problems indicate that VOiLA achieves equal or better performance than Recurrent Soft Actor Critic while using less than 10% training data, and generalizes much better to unseen environment configurations. Physical robot evaluation indicates VOiLA uses the models learned using only simulated data and generates a policy that successfully accomplish the task in 10 of 10 runs.

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

Clinically Aware Synthetic Image Generation for Concept Coverage in Chest X-ray Models

Deep learning models for chest X-ray diagnosis are constrained by limited coverage of clinically meaningful concept combinations in publicly available training datasets. While synthetic image generation has been explored to increase data diversity, existing methods rarely enforce clinical or anatomical constraints, limiting utility for improving model reliability. We propose CARPA, a clinically aware and anatomically grounded framework for synthetic chest X-ray generation that applies targeted perturbations to clinical concept vectors while preserving anatomical structure. By producing anatomically faithful synthetic images with controlled concept insertions and deletions, CARPA expands clinically relevant concept coverage. We evaluate CARPA across seven backbone architectures by fine-tuning models on synthetic subsets and testing on a held-out MIMIC-CXR benchmark. Compared to prior concept perturbation approaches, fine-tuning on CARPA-generated images consistently improves precision-recall performance, reduces predictive uncertainty, and improves model calibration. Structural and semantic analyses demonstrate high anatomical fidelity, strong concept alignment, and low semantic uncertainty. Evaluation by two expert radiologists further confirms realism and clinical agreement. Together, these results show that anatomically grounded concept perturbations enable more effective use of synthetic data, improving both performance and reliability of chest X-ray classification models and supporting safer clinical deployment.

15.
medRxiv (Medicine) 2026-06-11

Global population frequencies of NAT2 star alleles observed in three large biobanks

NAT2 is an important pharmacogene which encodes the N-acetyltransferase 2 enzyme that is involved in the metabolism of multiple medications, and variants in this gene can affect patient response to these medications. CPIC has published a clinical guideline for prescribing hydralazine using NAT2 genotypes. Just prior to the guideline, updated NAT2 star allele numbering and definitions were released, differing somewhat from the historical nomenclature. Clinical pharmacogenomic testing panels often test for the most common star alleles, so knowledge of the most common updated NAT2 star alleles is critical for the implementation of the CPIC NAT2/hydralazine guideline. We first determine NAT2 diplotype frequencies from UK Biobank (UKBB) 200k phased genomes, then analyzed allele, diplotype, and phenotype population frequencies from the All of Us Research program, PennMedicine BioBank (PMBB) and UKBB 500k datasets. We found that analyzing NAT2 diplotypes from phased data provides critical information for algorithms designed to predict diplotypes from unphased data. We observed that NAT2*5, *6, and *4 were the most common star alleles in that order, and the top 11 most frequent NAT2 star alleles were the same across all biobanks. However, differences in star allele frequencies across biogeographical populations were observed. The largest difference led to a higher frequency of NAT2 poor metabolizer phenotypes as compared to rapid and intermediate metabolizer phenotypes in all global populations except in the EAS population, where NAT2 poor metabolizers were in the minority.

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

Universality in the target arrival statistics of non-conservative search processes

arXiv:2606.16025v1 Announce Type: cross Abstract: Stochastic search processes in which searchers are continuously introduced to and removed from a target search domain are fundamental to a wide class of physical and artificial systems. The theory of such non-conservative search processes is, however, much less developed than for search processes with a fixed number of particles. Here we exploit a natural mapping between non-conservative stochastic search and queueing theory to derive the full time-dependent distribution of target arrivals under minimal assumptions on the underlying search process. Remarkably, we find that the steady-state inter-arrival time distribution is exactly exponential, regardless of the details of the search process, showing a robust universality that emerges directly from the queueing framework. Thus, counterintuitively, the arrival statistics of a non-conservative search process are much simpler than sequential search-and-capture processes involving a fixed number of searchers. This has major implications for target resource accumulation, where the delivery of resources is counter-balanced by their downstream consumption.

17.
medRxiv (Medicine) 2026-06-22

Panel-level multilocus methylation quantification in native cell-free DNA by PCR-compatible sequential enzymatic processing

DNA methylation is informative for liquid biopsy, but low template abundance, distributed methylation signals and workflow complexity limit implementation. Here we present Delta-HLD, a PCR-compatible methylation assay platform that quantifies methylation directly in native DNA through sequential hybridization, ligation and methylation-sensitive digestion. The assay co-reports methylation-dependent signals from multiple loci through a shared amplification architecture, generating a single panel-level PCR readout. We established the chemistry, optimized panel size and composition through model-guided experiments, and implemented the assay as a triplex qPCR workflow with per-sample internal process controls. Plasma proof-of-concept analyses showed discriminatory signal in CRC and proof-of-concept transferability to hepatocellular carcinoma. Additional platelet-retaining experiments identified a strategy to increase recovery of analyzable circulating templates while reducing genomic DNA recognition. Delta-HLD provides a compact PCR-compatible framework for low-input methylation analysis without base conversion.

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

Not Just How Much, But Where: Decomposing Epistemic Uncertainty into Per-Class Contributions

arXiv:2602.21160v3 Announce Type: replace-cross Abstract: In safety-critical classification, the cost of failure is often asymmetric, yet Bayesian deep learning summarises epistemic uncertainty with a single scalar, mutual information (MI), that cannot distinguish whether a model's ignorance involves a benign or safety-critical class. We decompose MI into a per-class vector $C_k(x)=\sigma_k^{2}/(2\mu_k)$, with $\mu_k{=}\mathbb{E}[p_k]$ and $\sigma_k^2{=}\mathrm{Var}[p_k]$ across posterior samples. The decomposition follows from a second-order Taylor expansion of the entropy; the $1/\mu_k$ weighting corrects boundary suppression and makes $C_k$ comparable across rare and common classes. By construction $\sum_k C_k \approx \mathrm{MI}$, and a companion skewness diagnostic flags inputs where the approximation degrades. After characterising the axiomatic properties of $C_k$, we validate it on three tasks: (i) selective prediction for diabetic retinopathy, where critical-class $C_k$ reduces selective risk by 34.7\% over MI and 56.2\% over variance baselines; (ii) out-of-distribution detection on clinical and image benchmarks, where $\sum_k C_k$ achieves the highest AUROC and the per-class view exposes asymmetric shifts invisible to MI; and (iii) a controlled label-noise study in which $\sum_k C_k$ shows less sensitivity to injected aleatoric noise than MI under end-to-end Bayesian training, while both metrics degrade under transfer learning. Across all tasks, the quality of the posterior approximation shapes uncertainty at least as strongly as the choice of metric, suggesting that how uncertainty is propagated through the network matters as much as how it is measured.

19.
arXiv (CS.LG) 2026-06-18

Towards a future space-based, highly scalable AI infrastructure system design

arXiv:2511.19468v2 Announce Type: replace-cross Abstract: If AI is a foundational general-purpose technology, we should anticipate that demand for AI compute – and energy – will continue to grow. The Sun is by far the largest energy source in our solar system, and thus it warrants consideration how future AI infrastructure could most efficiently tap into that power. This work explores a scalable compute system for machine learning in space, using fleets of satellites equipped with solar arrays, inter-satellite links using free-space optics, and Google tensor processing unit (TPU) accelerator chips. To facilitate high-bandwidth, low-latency inter-satellite communication, the satellites would be flown in close proximity. We illustrate the basic approach to formation flight via an 81-satellite cluster of 1 km radius, and describe an approach for using high-precision ML-based models to control large-scale constellations. Trillium TPUs are radiation tested. They survive a total ionizing dose equivalent to a 5 year mission life without permanent failures, and are characterized for bit-flip errors. Launch costs are a critical part of overall system cost; a learning curve analysis suggests launch to low-Earth orbit (LEO) may reach $\lesssim$\$200/kg by the mid-2030s.

20.
medRxiv (Medicine) 2026-06-18

Early-life Urban Environment, Nutrition, and Pubertal Timing in Southern Europe: An Exposome Analysis

Background: Urban environmental and lifestyle factors during early life may influence pubertal timing, but the combined effects of multiple environmental exposures within an exposome analytical framework remain poorly understood. Objective: To examine the association between early-life urban environmental exposures and pubertal timing, and to explore whether these exposures interact with early-life nutritional factors, namely breastfeeding duration and childhood diet quality. Methods: Data from two European population-based birth cohorts were analysed: Generation XXI (G21, Portugal; n=5263; 51.5% girls) and INfancia y Medio Ambiente (INMA, Spain; n=1019; 50.1% girls). Urban environmental exposures including indicators of air pollution, traffic, built environment, and natural spaces were estimated at 4 early-life stages at both cohorts: pregnancy (INMA only), birth, 1 year, and 4-5 years of age. Pubertal development timing was assessed using Tanner staging and/or the Pubertal Development Scale (PDS), and age at menarche was self-reported. Exposome-Wide Association Study (ExWAS) models and unsupervised clustering followed by ordinal logistic regression models were used to examine single- and multi-exposure associations, respectively. Regression models were fitted adjusting for relevant child characteristics, maternal factors, and household socioeconomic conditions, and corrected for multiple testing. Results: Individuals living in more unfavourable urban environments characterised by higher building density, air pollution, and lower access to natural spaces showed earlier pubertal timing according to multiple outcomes, across multiple early-life exposure periods, and in both cohorts. In the G21 cohort, these environmental profiles were associated with earlier age at menarche, particularly for exposures at 1-1.5 and 4-5 years (e.g., 1-1.5y: {beta}=-0.172, FDR-adjusted p-value=0.041), while in the INMA cohort, boys exposed to more unfavourable environmental profiles showed more advanced pubertal development, also particularly for exposures at 1-1.5 and 4-5 years of age (e.g., 1-1.5y; {beta}=0.572, FDR-adjusted p-value=0.008). Among environmental domains, air pollution and traffic were the factors most consistently associated with pubertal timing. Regarding early-life nutritional factors, longer duration of exclusive breastfeeding was associated with a lower Tanner stage among girls in G21. No significant interactions between breastfeeding duration and environmental exposure clusters were observed. Conclusion: Early-life urban environmental exposures, particularly air pollution and traffic, may influence pubertal timing. Exclusive breastfeeding may have a protective role against earlier pubertal development. These findings highlight the importance of improving urban environmental conditions and promoting breastfeeding to support healthy developmental trajectories.

21.
Nature (Science) 2026-06-17

These ‘master’ proteins protect us from deadly mutations — and could inspire new drugs

作者:

Biology has clever ways to mask the effects of potentially harmful gene mutations. Scientists are investigating how this ‘buffering’ works — and how to exploit it. Biology has clever ways to mask the effects of potentially harmful gene mutations. Scientists are investigating how this ‘buffering’ works — and how to exploit it.

22.
medRxiv (Medicine) 2026-06-11

Electrical signatures of divergent connectivity in the human subgenual cingulate cortex

Background: Major depressive disorder remains a leading cause of disability. While subgenual cingulate cortex (sgCC) deep brain stimulation (DBS) shows promise for medically refractory depression, clinical outcomes have been heterogeneous, suggesting that individual differences in neural circuitry engagement may critically influence therapeutic efficacy. We aimed to define the electrophysiological signatures of sgCC efferent connectivity using single-pulse electrical stimulation (SPES) with intracranial stereo-EEG (sEEG) to inform rational targeting and physiological biomarkers for sgCC-DBS. Methods: In four patients undergoing clinically indicated sEEG for seizure mapping, SPES was delivered through sgCC pairs, while distributed brain stimulation-evoked potentials (BSEPs) were recorded across cortical and subcortical sites. Responses were characterized using Canonical Response Parameterization to extract reproducible waveforms and per-trial reliability. Results: sgCC stimulation elicited reproducible, spatially organized BSEPs across frontal, limbic, and paralimbic networks, aligning with known anatomical pathways. Frontal recruitment featured robust, lateralized orbitofrontal activation favoring the ipsilateral central, medial OFC and bilateral ventromedial prefrontal responses. Limbic effects demonstrated bilateral cingulate activation with stronger ipsilateral recruitment and lateralized amygdala and hippocampal responses. Paralimbic engagement included insular responses with subject-specific anterior predominance and bi-hemispheric temporal-polar slow-wave deflections. Conclusion: These findings provide direct electrophysiological evidence of distributed, lateralized sgCC divergent network connectivity in the human brain, offering physiologic confirmation of its role in affective circuitry. The observed topography and laterality have direct applications for sgCC-DBS targeting and implicate BSEP signatures as candidate biomarkers to guide patient-specific therapy.

23.
arXiv (CS.LG) 2026-06-15

LapidaryEngine: Fully Conversational Crystal Generation

arXiv:2606.14215v1 Announce Type: new Abstract: The emergence of Large Language Models (LLMs) has inspired the vision of generating bespoke crystal materials directly from natural-language instructions, enabling users to design materials through intuitive, conversational interaction. Existing text-to-crystal generative models represent important early steps toward this goal, but they suffer from two critical limitations: (i) restricted input formats that require highly structured descriptions (e.g., chemical formulas), and (ii) one-directional generation, where models can map text to crystal but cannot perform the inverse. These limitations prevent fully conversational workflows and hinder alignment with users' inherently ambiguous and evolving desiderata. We address these challenges with LapidaryEngine, the first model to support fully conversational crystal generation. LapidaryEngine accepts free-form natural-language requests and performs iterative refinement and editing in a dialogue-like manner. The key innovation is a pivot representation, a third, intermediate form that enables bidirectional translation between text and crystal structures despite the absence of direct paired datasets. Leveraging this pivot allows robust interpretation of user feedback and precise structural control. We demonstrate LapidaryEngine across diverse tasks, including insulator discovery, stability optimization, compositional modification, and structural editing, showcasing its ability to align generated materials with user intent in an interactive manner.

24.
arXiv (quant-ph) 2026-06-19

Many-body chirality of topological stabilizer states

arXiv:2606.20472v1 Announce Type: new Abstract: A defining feature of chirality is the distinction between a system and its mirror image. Despite extensive experimental observations of chiral phases and theoretical advances, a quantum-information theoretic characterization of chirality based solely on the entanglement structure of many-body quantum states remains elusive. Here, we introduce the notion of many-body chirality by formulating it as an obstruction to transforming a quantum state into its complex conjugate through finite-depth local operations. We rigorously establish many-body chirality for stabilizer realizations of $\mathbb{Z}_d^{(k)}$ anyon theories, proving that complex conjugation can be implemented by local quantum channels if and only if the underlying anyon data are mirror invariant. This reveals forms of chirality that evade conventional diagnostics, including examples with vanishing modular commutator, vanishing chiral central charge, and commuting-projector realizations. We further show that this obstruction is intrinsically four-partite, while invisible to tripartite entanglement structure. Finally, we prove that $\mathbb{Z}_d^{(k)}$ states with $d>2$ possess intrinsic many-body imaginarity: their complex phase structure cannot be removed by finite-depth local unitaries. Remarkably, this includes states that are not many-body chiral.

25.
arXiv (quant-ph) 2026-06-17

Experimental Characterization and Modeling of Measurement-Induced State-Transitions in a Fluxonium Superconducting Qubit

arXiv:2606.17866v1 Announce Type: new Abstract: Superconducting qubits are most often measured using dispersive readout, which, ideally, implements a projective quantum non-demolition (QND) measurement. While a larger readout drive can increase the signal and, thus, reduce discrimination errors in the readout, strong microwave drives may also cause non-QND errors by driving the qubit to a state outside the computational subspace. In this work, we experimentally characterize measurement-induced state transitions (MIST) in a fluxonium qubit over its full external flux range. We further numerically calculate the MIST errors, and find that the theory accurately predicts eleven experimentally identified regions with increased MIST. In addition to transitions to higher fluxonium levels, we also find that, at certain flux points, MIST errors are dominated by transitions that include the transmission-line-like array modes of the fluxonium's superinductor. The excellent match between theory and experiment validates that the models accurately predict the occurrence of MIST in these systems, and further highlights the influence of array modes in fluxonium readout.