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01.
PLOS Computational Biology 2026-06-18

Mechanisms underlying spontaneous and evoked calcium responses in oligodendrocyte precursor cells: A modeling investigation

Authors:

by Martin Lardy, Leqi Wang, Claire Guerrier, Veronica T. Cheli, Pablo M. Paez, Anmar Khadra Calcium (Ca2+) signaling has emerged as a central regulator of activity-dependent myelination in oligodendrocytes. These Ca2+ signals encompass both the stimulus-independent spontaneous Ca2+ local transients (SCaLTs) generated intrinsically in a voltage-independent manner or facilitated by the membrane voltage, as well as evoked responses triggered by ATP and glutamate release. To investigate the regulatory mechanisms underlying this combined spiking activity, we developed a stochastic spatiotemporal flux-balance model of Ca2+ transients in oligodendrocyte precursor cells (OPCs). The model incorporates all the relevant fluxes in these cells and integrates membrane voltage dynamics with a Ca2+-induced Ca2+-release (CICR) mechanism using parameters fitted to Ca2+ fluorescence recordings. The model reproduced the intrinsic and voltage-facilitated SCaLTs in OPCs in the absence of purinergic and glutamatergic receptors, and captured the three distinct patterns of evoked Ca2+ responses induced by prolonged ATP and glutamate stimulations identified using machine classifier. The model highlighted the role of ATP and glutamate in generating these clusters, and showed that the fast dynamics of CICR is key to producing these evoked responses. Further analysis of the model also revealed that voltage-gated L- and T-type Ca2+ channels slightly increase the frequency of SCaLTs, while stimulation with ATP and glutamate, using randomly distributed pulses mimicking in vivo conditions, leads to an increase in both the amplitudes of Ca2+ spikes (i.e., the combination of SCaLTs and evoked responses) and the prevalence of wide spikes, especially upon glutamate stimulation. Bifurcation analysis of the deterministic version of the model, in the absence of diffusion, demonstrated that ATP and glutamate stimulation can shift the system into an oscillatory regime, thereby increasing the deterministic component of SCaLT dynamics. This study thus offers a comprehensive representation of OPC Ca2+ transients linking recorded in vitro behaviors to in vivo dynamics.

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

Semantics-Enhanced Retrieval-Augmented Time Series Forecasting

arXiv:2606.14941v1 Announce Type: new Abstract: Time series forecasting models often benefit from historical patterns. Inspired by Retrieval-Augmented Generation (RAG), recent research explored retrieving relevant historical time series segments to enhance forecasting. However, relying solely on time series similarity is often insufficient for retrieval under non-stationarity. To address this, we propose a multimodal approach: a Semantics-Enhanced Retrieval-Augmented Time Series Forecasting framework, SERAF. Unlike mainstream approaches that depend only on time series similarity, SERAF conducts dual retrieval over the time series and their self-generated textual descriptions. It retrieves two complementary sets of historical patterns and corresponding futures, which are selectively and jointly used to guide future predictions. Experiments across seven real-world datasets demonstrate the effectiveness of SERAF in bridging numerical and semantic views of time series compared with state-of-the-art baselines.

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

ChLogic: Evaluating Robustness of Logical Reasoning in Chinese Expressions

Large language models perform increasingly well on standardized logical reasoning benchmarks, but whether this ability remains robust beyond English is unclear. We introduce ChLogic, an English–Chinese aligned benchmark that tests whether models preserve logical reasoning performance when the same latent logical structure is expressed in English and diverse Chinese surface realizations. Built from formal logical templates, the benchmark contains three data sets: (i) the General aligned set, derived from 60 General Propositions across nine template families; (ii) the Difficult aligned set, derived from 40 Difficult Problems; and (iii) the Chinese-only set, covering 15 language-specific phenomenon types. Each aligned item pairs one English reference expression with five Chinese realizations. Experiments on Qwen3, Ministral, and GLM models reveal a persistent English–Chinese performance gap. Back-translation from standard Chinese into English often improves performance on the General aligned set, but produces mixed effects on the Difficult aligned set, where Qwen3-32B and GLM-5.1 perform worse after translation. These results indicate that Chinese surface realization, translation artifacts, and model-specific behavior jointly affect multilingual logical reasoning. Overall, ChLogic provides a useful stress test for the robustness of multilingual reasoning.

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

A fast direct solver based neural network for solving PDEs

arXiv:2606.19895v1 Announce Type: cross Abstract: The matrices arising from large scale $N$-body problems can be efficiently represented using hierarchical matrices, whose key idea is that the admissible off-diagonal sub-matrices can be well approximated by low-rank matrices across a hierarchy of matrix partitions. HODLR (Hierarchical Off-Diagonal Low-Rank) matrices are a subclass of hierarchical matrices in which all off-diagonal submatrices at every level of a recursive binary partition are low-rank. In this article, we present a neural network that learns the inverse operation of HODLR matrices based on the fast direct solver for HODLR matrices developed by Ambikasaran and Darve (2013). We further extend the architecture to learn nonlinear solution operators associated with PDEs by replacing some of the linear layers with deep sub-networks. We demonstrate the performance of the proposed architecture by performing a comprehensive set of experiments that include (i) solving a linear problem such as the Fredholm integral equation of the second kind, (ii) solving PDEs such as the nonlinear Schrödinger equation, Burgers' equation, and the steady-state Darcy's flow equation, (iii) generalization study across varying parameter values, (iv) comparing the inference time of the proposed network with the run time of a classical numerical solver, and (v) comparing the proposed network with some of the existing neural operator learning networks.

05.
arXiv (CS.CL) 2026-06-11

AI4SLT: Empirical Processes in Lean 4 for Formal Statistical Learning Theory

We present the first comprehensive Lean 4 formalization of statistical learning theory (SLT) grounded in empirical process theory. Our en-to-end formal infrastructure implement the missing contents in latest Lean library, including a complete development of Gaussian Lipschitz concentration, Dudley's entropy integral theorem for sub-Gaussian processes, and an application to least-squares (sparse) regression with a sharp rate. The project was carried out using a human-AI collaborative workflow, in which humans design proof strategies and AI agents execute tactical proof construction, leading to the human-verified Lean 4 toolbox for SLT. Beyond implementation, the formalization process exposes and resolves implicit assumptions and missing details in standard SLT textbooks, enforcing a granular, line-by-line understanding of the theory. This work establishes a reusable formal foundation and opens the door for future developments in machine learning theory. The code is provided in https://github.com/YuanheZ/lean-stat-learning-theory.

07.
arXiv (CS.AI) 2026-06-15

I'm Sorry Driver, I'm Afraid I Can't Do That: Appraising the Safety of LLMs within Automotive Contexts

arXiv:2606.14327v1 Announce Type: cross Abstract: This paper appraises recent frameworks within AI development to integrate LLMs into control tasks in automotive contexts from the perspective of safety assurance. This work has built upon the rapid integration of LLMs across automotive settings. However, we find that at present, these frameworks face significant challenges, limiting their efficacy in real-time safety-critical contexts. Firstly, we consider conceptual challenges, including the fact that deployers are faced with a dual challenge, wherein they must assure a model which has been developed upstream, i.e. as general-purpose tools by the large AI labs, in a downstream context, i.e. into specific vehicle architectures. Secondly, we consider concrete challenges from across existing standards. We show that there are currently both fundamental engineering constraints covered in ISO21448, such as latency, and novel LLM-specific issues, such as alignment-related issues covered in ISO/PAS8800. We ground both examples in a concrete introductory, experimental case study exploring an existing open-source repository, Talk2Drive. We present a safety argument in order to make explicit the limitations of existing solutions. Nonetheless, given that the use of LLMs in automotive contexts is being explored at a technical level and operationalised, we propose potential assurance mechanisms for LLM-related hazardous events going forward.

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

AAbAAC: An Annotated Corpus for Autoimmunity Information Extraction

arXiv:2606.13051v1 Announce Type: new Abstract: Despite advances in information extraction driven by deep learning and large language models, performance gaps remain in highly specialized biomedical fields, where domainspecific complexity poses challenges for generalist models. In this work, we focus on the domain of autoimmunity, where the main entities of interest are autoimmune diseases, autoantibodies (i.e., molecules that may mark or cause these diseases), their molecular targets, their location in the body, and their associated clinical signs. Herein, we present AAbAAC (AutoAntibodies and Autoimmunity Annotated Corpus), a corpus of 115 abstracts selected from PubMed, where we manually annotated entities and their relationships. First, AAbAAC was used to evaluate several methods on the task of named entity recognition (NER), and secondly, to fine-tune NER models. Our study demonstrates the utility of AAbAAC for information extraction in the domain of autoimmunity, showing expected improvement in NER performance after finetuning. This illustrates the value of small-scale annotation efforts for specialized domains and contributes to the computational study of autoimmunity. The AAbAAC corpus is available at https://github.com/f-maury/AAbAAC.

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

SICI: A Semantic-Pragmatic Complexity Index Reveals Regime Shifts in LLM Stance Detection

Prompt-based LLMs are increasingly used for stance detection, but harder examples are not always repaired by clearer instructions, reasoning prompts, retrieval, or debate. We introduce SICI (Stance Inference Complexity Index), a seven-dimensional diagnostic measure of the semantic-pragmatic burden imposed by a target–text pair. Across SemEval-2016 and VAST, SICI predicts LLM accuracy better than surface proxies and shows substantial cross-scorer reliability ($\alpha=0.771$). More importantly, LLM errors change regime as SICI increases: low-complexity examples invite over-attribution, especially Against predictions; intermediate examples form an unstable boundary; and high-complexity examples rapidly concentrate on None. This phase-transition-like structure persists across GPT-3.5, GPT-4o-mini, DeepSeek-V3, and GPT-4o, although stronger models move the boundaries. A 15-method intervention study further shows that prompting, retrieval, and debate often shift models along the attribution–abstention axis rather than removing the high-complexity bottleneck.

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

What Limits Does Quantization Place on Dense Top-$k$ Retrieval? A Theoretical Study

arXiv:2606.11780v1 Announce Type: cross Abstract: We establish conditions for embedding a corpus of $N$ documents as $d$-dimensional vectors such that every $k$-subset $S \subseteq [N]$ is realizable as a result of top-$k$ retrieval by some query vector. Recent work shows that $d = O(k)$ suffices for such embeddings to exist in $\mathbb{R}^d$, independently of $N$. We theoretically prove that this corpus-independent bound is specific to infinite precision. With $B$ bits per coordinate, perfect top-$k$ retrieval requires $Bd = \Omega(k \ln N)$; thus, at any fixed precision, the dimension must grow at least logarithmically with $N$. Specializing to a $\ell_2$-normalized $B$-bit uniform scalar quantization model, we also identify a threshold on the precision $B^{*} = O(\ln \ln N)$ below which no dimension suffices, together with two further regimes that bound the feasible $(B, d)$ pairs. Our result implies that in practical vector databases and dense retrieval systems where quantization is standard, the embedding dimension and possibly the precision must grow with the corpus size.

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

Autonomous End-to-End SOH Prediction Services for Battery Systems via Temporal-Contrastive Representation Learning

arXiv:2606.16434v1 Announce Type: cross Abstract: Accurate state of health (SOH) estimation is a critical diagnostic service for lithium-ion battery management. However, reliance on labor-intensive manual feature engineering and opaque black-box models hinders scalable industrial deployment. To address this, we introduce TC-SOH: a modular, plug-and-play service architecture for autonomous, end-to-end SOH prediction. TC-SOH employs a temporal-contrastive mechanism and a cross-window prediction pretext task to extract degradation-relevant representations directly from raw operational data. To improve transparency, we connect model efficacy with representation diagnostics: visualization, sensitivity analysis, redundancy analysis, bidirectional probing, future-SOH probing, and temporal shuffling show that learned features overlap with selected expert descriptors while retaining additional SOH-relevant variation, and that ordered temporal context improves subsequent-SOH prediction. Across four public datasets, TC-SOH outperforms the considered physics-informed and data-driven baselines, reducing MAPE by 1.91 times and RMSE by 2.13 times.

12.
arXiv (CS.LG) 2026-06-17

The Morse Transform for Discrete Shape Analysis

arXiv:2503.04507v2 Announce Type: replace-cross Abstract: The geometry of an object plays a vital role in modulating its interactions with the physical world. It nevertheless remains difficult to describe geometric information numerically for the purposes of statistical inference or classification tasks. Here, we introduce a new topological transform which leverages directional piecewise-linear Morse theory to quantify the geometry of an embedded object by cataloguing critical points across multiple height-functions. The output of this Morse transform records both the heights and the local topological type (peak, trough or saddle) of the critical points that characterise the underlying shape, retaining finer information than the Euler characteristic transform whilst naturally prioritising a shape's outermost regions. Crucially, this output can be further compressed into a rich but compact feature vector. We benchmark the Morse feature vector as a descriptor for ligand-based virtual screening (LBVS), which intrinsically depends on the shape of molecules. Under a common gradient-boosted tree classification pipeline, Morse descriptors achieve the highest mean AUROC when compared to other topological transform descriptors and to standard shape-based LBVS descriptors.

13.
arXiv (CS.CL) 2026-06-15

Non-Parametric Machine Text Detection via Multi-View Gaussian Processes

Adversarial conditions such as paraphrasing and targeted style transfer sharply degrade the accuracy of machine text detectors. A document, however, carries multiple complementary signals (e.g., stylistic features, likelihood and rank-order features, and structural features), and an attack that suppresses one may leave others intact. While a parametric classifier can learn to combine these features given sufficient supervision, classifiers are prone to making confidently incorrect predictions when the distribution shifts (e.g., novel attacks or unseen language models). To address this, we propose a multi-view, non-parametric detection framework that extracts complementary feature views from the same document and aggregates per-view evidence through a Gaussian process ensemble. By aggregating evidence across views, an adversary must simultaneously defeat multiple independent axes of detection, substantially raising the cost of evasion. The Gaussian process formulation additionally provides calibrated probabilities and principled abstention on out-of-distribution inputs, supporting reliable deployment in high-stakes settings. We evaluate on three benchmarks spanning diverse generators and attacks: the DetectRL and RAID benchmarks, and the PAN2025 shared task and demonstrate that our multi-view detector maintains strong performance under the considered attacks, outperforming existing approaches against held out attacks.

14.
arXiv (CS.CL) 2026-06-18

Simulating Hate Speech Cascades with Multi-LLM Agents: Empirical Grounding, Modeling Fidelity, and Intervention Strategies

Authors:

Faithful modeling of hateful content propagation on online platforms remains an open problem for moderation research. Classical cascade models that do not explicitly represent the profile, community, and content factors associated with hateful-content propagation may yield moderation strategies that behave less effectively when deployed in real-world scenarios. Multi-agent large language model (LLM) systems can, in principle, make each reshare decision depend on the user's profile, the surrounding community, and the post's content, but it remains unclear whether this added flexibility actually reproduces real hateful cascades more faithfully than classical baselines. We study three hateful Bluesky cascades and a size-matched benign control. In the empirical Bluesky data, we found that: 97.4–99.7\% of reposters take a hostile stance; toxicity-engagement homophily is higher on the diffusion tree than on the follower graph for hateful cascades; topology is star-like for the hateful cascades (most reposts come directly from the root) versus tree-like for the benign cascade (reposts propagate through multi-hop chains). In simulation, a multi-LLM-agent simulator reproduces the stance monoculture and the toxicity-delta direction. A structured ablation identifies agent heterogeneity as the leading fidelity factor, and amplifier targeting on dense networks yields 7.5–12.9\% reduction at 5.7\% benign collateral.

15.
arXiv (CS.CL) 2026-06-12

AfroScope: A Framework for Studying the Linguistic Landscape of Africa

Language Identification (LID), the task of determining the language of a given text, is a fundamental preprocessing step that shapes the reliability of downstream NLP applications. While recent work has expanded African LID, existing systems remain limited in both language coverage and fine-grained discrimination among closely related languages and varieties. We introduce AfroScope, a unified framework for African LID that includes AfroScope-Data, a dataset covering 640 languages, and AfroScope-Models, a suite of strong LID models with broad African language coverage. To address persistent confusions among closely related languages, we propose a hierarchical classification approach that leverages AfroScope-Mirror, a specialized embedding model for targeted disambiguation, improving macro-F1 by 1.57 points on the confusable subset compared to our best base model. We further analyze cross-lingual transfer and domain effects, showing how language-family structure, script compatibility, and domain coverage shape LID performance. We position African LID as an enabling technology for large-scale measurement of Africa's linguistic landscape in digital text, and release AfroScope-Data and AfroScope-Models online.

16.
arXiv (quant-ph) 2026-06-17

Canonical regularization of the stationary Coulomb problem and an Aufbau-like spectral ordering

arXiv:2606.17359v1 Announce Type: new Abstract: The stationary hydrogen atom has Coulomb degeneracy across orbital levels, whereas the Aufbau/Madelung ordering is an empirical, many-electron rule established in atomic physics. We examine the hydrogen atom through a regularized de Broglie–Bohm representation, in which stationary amplitude current constraints generate separable Sturm–Liouville branches. In this formulation, the radial, orbital, and magnetic sectors acquire canonical Langer-like inverse square corrections. The modified boundary value problems allow analytical solutions and produce a hydrogen-like spectrum with regularized radial and angular indices. Consequently, radial Coulomb quantization acquires an orbital dependent shift, lifting the Coulomb degeneracy and producing a spectral ordering that follows the Aufbau/Madelung sequence. On this basis, we construct the ordering of the regularized de Broglie–Bohm states and show that the spectral structure retains the standard degenerate Rydberg sequence in the l=0 sector. The separated amplitudes are represented by generalized special function branches, including the associated Laguerre, Legendre, and Bessel functions with non-integral parameters arising from regularized separation. Therefore, the treatment is intended as an analytical examination of spectral ordering in a regularized one center Coulomb problem rather than as a replacement for the many electron atomic structure theory. Keywords: de Broglie–Bohm representation; Coulomb spectrum; canonical regularization; Langer correction; Sturm–Liouville equations; Aufbau principle; Madelung ordering; associated Legendre functions; associated Laguerre functions; Bessel functions.

17.
bioRxiv (Bioinfo) 2026-06-11

GeroQubit: a lightweight, honesty-first de-novo design platform for geroscience-native small molecules with calibrated uncertainty

Authors:

Computational molecule generation has outpaced its own credibility. We present GeroQubit, a GPU-free de-novo design platform that organizes candidates along a target x tissue x hallmark model and reports every signal alongside its measured baseline. We treat our tissue aging-signature readout as a mechanistic structural prior that we explicitly disclose is not validated against lifespan, and we surface efficacy only through a structure-to-lifespan k-NN whose weak but real signal (leave-one-out rho ~ 0.145) is wrapped in empirically-calibrated conformal intervals (90% target, 90.3% measured coverage). On a held-out retrospective recovery of ~1,940 ChEMBL binders against decoys, the score reaches ROC-AUC 0.945 with ~20x enrichment at 1% (BEDROC 0.91) and survives a scaffold-disjoint split - yet we report that it collapses to near-random (AUC 0.62) on genuinely novel chemotypes. Molecules are assembled reaction-first, so every candidate carries a verified synthetic route and atom-level synthon provenance; ADMET is handled as a multi-objective Pareto problem. We frame the disclosed weak signals and the hard-case failures not as flaws but as the honest, decision-useful output the field's own critics demand.

18.
bioRxiv (Bioinfo) 2026-06-11

A multi-agent system for spine MRI report generation from multi-sequence imaging

Spinal pathology is a leading cause of pain and disability worldwide. Spine magnetic resonance imaging (MRI) is central to clinical evaluation, yet its interpretation remains complex and time-consuming, requiring integration of information across multiple imaging sequences and anatomical regions. Despite recent advances in automated MRI analysis, effectively combining multi-sequence data while preserving sequence-specific diagnostic information remains an open challenge. Here we present SpineAgent, a multi-agent framework for spine MRI report generation built upon a multi-sequence foundation model trained on routine clinical data from 32,047 patients and 453,683 MRI series, comprising a total of 13,441,191 MRI slices. To accommodate diverse modalities of sequences, we first pre-train two DINOv3-based encoders separately on T1- and T2-weighted sequences. We then introduce a continual training strategy that learns a synthesizer to embed images of other sequences using the T1 and T2 encoders, producing patient-level embedding that integrates various signals across MRI sequences. Using these embeddings, SpineAgent achieves state-of-the-art performance, with mean 10.8% AUROC improvement across 17 spinal condition-prediction tasks compared to the best competing method, and demonstrates strong generalizability under cross-manufacturer and cross-cohort evaluation. Beyond classification, SpineAgent enables pathology localization by identifying findings-relevant slices and segmenting pathological regions. It also supports multimodal image-report retrieval, providing a solid foundation for scalable and explainable MRI report generation. We further integrate these validated capabilities of SpineAgent into 37 specialized agents for condition diagnosis, pathological-region localization, and clinically-similar-cases retrieval. Finally, we incorporate their outputs as structured tokens within a Medical Report Agent trained end-to-end for report generation. Through both automated metrics and expert evaluation by five radiologists, SpineAgent achieves leading performance in spine MRI report generation. Together, SpineAgent introduces a continual training approach for multi-sequence spine MRI understanding. By decomposing report generation into clinically grounded subtasks addressed by specialized agents, the SpineAgent framework enables accurate, interpretable and generalizable spine MRI reporting across diverse imaging sequences and anatomical regions.

19.
arXiv (CS.CV) 2026-06-11

How Auxiliary Reasoning Unleashes GUI Grounding in VLMs

Graphical user interface (GUI) grounding is a fundamental task for building GUI agents. However, general vision-language models (VLMs) struggle with this task due to a lack of specific optimization. We identify a key gap in this paper: while VLMs exhibit significant latent grounding potential, as demonstrated by their performance measured by Pointing Game, they underperform when tasked with outputting explicit coordinates. To address this discrepancy and bypass the high data and annotation costs of current fine-tuning approaches, we propose three zero-shot auxiliary reasoning methods. By providing explicit spatial cues such as axes, grids and labeled intersections as part of the input image, these methods enable VLMs to better articulate their implicit spatial understanding capabilities. We evaluate these methods on four GUI grounding benchmarks across seven open-source and proprietary VLMs. Experimental results show substantial gains from auxiliary reasoning. Mark-Grid Scaffold boosts Gemini-3.1-Pro from 11.72\% under direct inference to 95.20\% on ScreenSpot-v2, achieves state-of-the-art performance on ScreenSpot, and approaches the strongest fine-tuned methods on ScreenSpot-v2 and UI-I2E-Bench. Our code is available at https://github.com/liweim/AuxiliaryReasoning.

20.
arXiv (CS.CV) 2026-06-15

CausalMotion: Structured Physical Reasoning as Keyframe and Trajectory Guidance for Training-Free Video Generation

Recent advances in diffusion-based video generation have significantly improved visual quality and short-term temporal coherence. However, existing methods still struggle to produce videos with physically consistent and causally plausible dynamics, especially in scenarios involving long-horizon interactions. This limitation arises from the fact that video diffusion models primarily learn physical consistency implicitly, while vision-language models can directly model physical laws. Based on this idea, in this work, we propose CausalMotion, a training-free framework that injects explicit physical reasoning into video generation through structured intermediate representations. Our key idea is to decouple reasoning from generation by leveraging a vision-language model to decompose a text prompt into a sequence of causally consistent keyframes and object-centric motion trajectories. These representations are then aligned and integrated as soft constraints to guide a pretrained video diffusion model during inference. This design enables explicit modeling of object dynamics and causal transitions without requiring additional training or supervision. Extensive experiments show that our method consistently improves physical plausibility and temporal coherence, particularly in dynamics-intensive scenarios, while maintaining high perceptual video quality.

21.
medRxiv (Medicine) 2026-06-12

Deconvolution-based cell-type specific DNA methylation-wide and transcriptome-wide association studies identify risk CpG sites and genes associated with colorectal cancer risk

Bulk tissue-based DNA methylation-wide (MWAS) and transcriptome-wide association studies (TWAS) have identified CpG sites and genes associated with colorectal cancer (CRC) risk, but do not account for cellular heterogeneity. To address this, we developed a deconvolution-informed framework to infer cell-type specific DNA methylation and gene expression profiles from bulk normal colon tissues using reference single-cell epigenomic and transcriptomic datasets. We performed cell-type specific MWAS (ctMWAS) using deconvoluted DNA methylation data from 293 normal colon samples and conducted cell-type specific TWAS (ctTWAS) using deconvoluted gene expression data from 707 normal colon samples. Genetically predicted methylation and expression models were integrated with CRC GWAS summary statistics (78,473 cases and 107,143 controls) to identify risk-associated CpG sites and genes. Through ctMWAS, ctTWAS, and colocalization analyses, we identified 178 significant cell-type-specific CpG sites in 106 loci and 68 risk genes in 40 loci, including 26 previously unreported loci. Through additional integrative methylation-gene analysis, we prioritized 132 candidate risk genes, the majority of which were supported by multi-omics evidence and stage-specific dysregulation across the adenoma-carcinoma and serrated-carcinoma progression pathways. Pathway enrichment analyses implicated pathways involved in DNA double-strand break repair, TP53 regulation, TGF-{beta} signaling, and innate immune responses. Among prioritized genes, 14 were identified as putative druggable targets linked to 90 FDA-approved or clinical-stage drugs. Experimental validation supports an oncogenic role for SF3A3. These findings demonstrate that deconvolution-informed integrative analyses enable cell-type-resolved identification of epigenetic and transcriptional mechanisms underlying CRC susceptibility and provide insights into disease biology, prevention, and therapeutic target discovery.

22.
PLOS Computational Biology 2026-06-08

Assessing the inference of single-cell phylogenies and population dynamics from CRISPR lineage recordings

by Julia Pilarski, Tanja Stadler, Sophie Seidel Multicellular organisms develop from a single cell by repeated rounds of cell division, differentiation, and death, which can be represented as a single-cell phylogenetic tree. Genetic lineage tracing allows us to investigate this development by tracking the ancestry of individual cells as populations grow and change over time. However, accurate reconstruction of the cell phylogeny and quantification of the corresponding phylodynamic parameters – cell division, differentiation, and death rates – from this tracking data remains challenging and needs to be systematically evaluated. We perform simulations and assess, using the Bayesian framework, the joint inference of time-scaled cell phylogenies and phylodynamic parameters from CRISPR lineage recordings with random or sequential edits. Principally, we characterize the inference improvements as the recorder capacity increases. We observe more accurate phylogenetic reconstruction from sequential compared to random recordings, but no substantial improvement in phylodynamic inference when using the additional information contained in the order of edits. Overall, we find that CRISPR lineage recordings carry a strong signal on the rates of cell division when appropriate models are used. However, we detect biases in the inferred rates of cell division and death under phylodynamic model misspecification, i.e., when fitting classic memoryless birth-death processes to synchronous cell divisions. Moreover, for scenarios when cells differentiate into distinct types, we demonstrate that Bayesian phylodynamic analysis of sparse end-point measurements can resolve these cell differentiation trajectories by lineage and time. Under prototypical dynamics, we recover cell type-specific division and death rates, and cell type transition rates in over 80% of simulations. Overall, this simulation study explores how much information on cellular development can be extracted from state-of-the-art genetic lineage tracing data using phylogenetic and phylodynamic methodology.

23.
arXiv (CS.CV) 2026-06-11

From Nominal Intensity to Equivalent Rainfall: A Path-Based Credibility Evaluation Framework for Simulated Rainfall in Autonomous-Driving Perception Tests

Credible simulated-rainfall conditions are essential for identifying perception-system boundaries and supporting SOTIF-oriented risk assessment in automated driving. However, closed-field tests are often described only by nominal rainfall intensity or single-point measurements, making it difficult to align simulated rain fields with real rainfall and map test results to real-world scenarios. This paper proposes a path-based credibility evaluation method for simulated rainfall in autonomous-driving perception tests. Using the drop size and velocity joint distribution of real rainfall as the reference, each candidate path is represented by path-equivalent rainfall intensity, an uncertainty band, and a path-averaged Realism of Raindrop Distribution (RRD) score. Lidar target point-cloud count and mean reflectivity are further used for perception-consistency correction, quantifying the proxy capability of each simulated-rainfall path for real-rainfall perception effects. Experiments are conducted using about 10,000 real-rainfall raindrop-spectrum samples, 728 RainSense perception samples, and 45 spatial sampling points in a 2.4 m x 7.2 m simulated-rainfall area. Results show that spatial non-uniformity remains under the same nominal condition, confirming the need for path-based evaluation. The method identifies Path IV and Path VI as preferable candidates, with results of 11.54 +/- 0.31 mm/h, RRD = 0.43, and 8.28 +/- 0.34 mm/h, RRD = 0.46, respectively. These paths show more balanced performance in rainfall-intensity stability, raindrop-spectrum realism, and perception consistency. The proposed method supports path selection, condition description, and credible interpretation of autonomous-driving perception tests under rainfall.

24.
medRxiv (Medicine) 2026-06-18

Multicluster measles outbreak with a substantial proportion of modified cases in Tokyo, Japan, January-May 2026

Tokyo experienced a measles outbreak (260 cases) in early 2026 despite elimination status. Adults aged 20-39 years were most affected, and 38% of cases were modified measles, increasing with prior vaccination. Although incidence rose until April, the effective reproduction number; R(t) fell below 1, consistent with outbreak control. Multiple clusters were identified, but many cases lacked epidemiological links, suggesting that modified measles is less likely to be considered in differential diagnosis. Intensive contact tracing and surveillance contributed to limiting transmission.

25.
arXiv (quant-ph) 2026-06-16

Adaptively secure unitary designs with constant non-Clifford cost

arXiv:2510.08129v2 Announce Type: replace Abstract: Randomness is a fundamental resource in quantum information, with crucial applications in cryptography, algorithms, and error correction. A central challenge is to construct unitary $k$-designs that closely approximate Haar-random unitaries while minimizing the costly use of non-Clifford operations. In this work, we present a protocol able to generate unitary $k$-designs on $n$ qubits, secure against any adversarial quantum measurement, with a system-size-independent number of non-Clifford gates. Our construction applies a $k$-design only to a subsystem of size $\Theta(k)$, independent of $n$. This ``seed'' design is then ``diluted'' across the entire $n$-qubit system by sandwiching it between two random Clifford operators. The resulting ensemble forms an $\varepsilon$-approximate unitary $k$-design on $n$ qubits. We prove that this construction achieves full quantum security against adaptive adversaries using only $\tilde{O}(k^2 \log\varepsilon^{-1})$ non-Clifford gates. If one requires security only against polynomial-time adaptive adversaries, the non-Clifford cost decreases to $\tilde{O}(k + \log^{1+c} \varepsilon^{-1})$. This is optimal, since we show that at least $\Omega(k)$ non-Clifford gates are required in this setting. Compared to existing approaches, our method significantly reduces non-Clifford overhead while strengthening security guarantees to adaptive security as well as removing artificial assumptions between $n$ and $k$. These results make high-order unitary designs practically attainable in near-term fault-tolerant quantum architectures.