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01.
arXiv (CS.AI) 2026-06-24

Invariant Graph Representations for Continuous-Time Dynamic Graphs Under Distribution Shifts

arXiv:2405.19062v2 Announce Type: replace-cross Abstract: Continuous-Time Dynamic Graphs (CTDGs) enable fine-grained modeling of evolving relational systems. However, most existing CTDG representation learning methods are tailored to in-distribution settings and exhibit limited robustness under out-of-distribution (OOD) shifts. Although recent causal approaches learn invariant representations via interventions, they are primarily designed for static or discrete-time graphs and become computationally prohibitive for CTDGs due to the combinatorial explosion of structural and temporal variations. To address these challenges, we propose CIR, a framework grounded in a novel structural causal model termed the ICCM. To avoid exhaustive interventions, we leverage the Normalized Weighted Geometric Mean (NWGM) to efficiently approximate interventional predictions. We further instantiate ICCM within a practical deep learning architecture that jointly captures invariant structural and temporal patterns through dedicated subgraph extractors, and maintains an environment memory bank to model distributional shifts across evolving contexts. Extensive experiments demonstrate that CIR consistently outperforms existing methods under diverse OOD scenarios.

02.
arXiv (quant-ph) 2026-06-24

Linear-Time Encodable and Decodable Quantum Error-Correcting Codes

arXiv:2603.04543v2 Announce Type: replace Abstract: Recent years have seen rapid development in the subject of quantum coding theory, with breakthroughs on many exciting classes of codes, including quantum LDPC codes, quantum locally testable codes, and quantum codes with interesting transversal gates. However, a natural class of quantum codes, which has been well-studied classically, has not yet been treated: those which can be quickly encoded and decoded. This problem concerns the channel capacity setting, where a noise channel sits between perfect encoding and unencoding/decoding operations; this is the setting that is relevant for communication between fault-tolerant quantum computers. In this work, we construct asymptotically good quantum codes that can be encoded and unencoded by quantum circuits of logarithmic depth and consisting of a linear total number of gates. The classical decoding algorithms also run in logarithmic depth and use $\mathcal{O}(n \log n)$ gates, or alternatively a linear number of gates but with higher depth. We further construct explicit and asymptotically good quantum codes whose encoding, unencoding and decoding all use a linear number of gates, and additionally whose encoding and unencoding may be run in logarithmic depth.

03.
arXiv (CS.CL) 2026-06-18

PragReST: Self-Reinforcing Counterfactual Reasoning for Pragmatic Language Understanding

Natural language understanding often depends on meanings that are implied rather than explicitly stated, requiring pragmatic reasoning. Despite strong performance on math and logical reasoning, large language models (LLMs) still struggle with making pragmatic inferences, often choosing literal interpretations. To improve LLM pragmatic reasoning, we introduce PragReST, a self-supervised framework that constructs pragmatic QA data, generates counterfactual reasoning traces, and trains models to internalize them through supervised fine-tuning and reinforcement learning, without human-labeled training data or distillation from a stronger teacher. Across four pragmatic benchmarks (PragMega, Ludwig, MetoQA, and AltPrag), PragReST improves over backbone models, task-specific pragmatic tuning baselines, and non-counterfactual variants of the same pipeline. On accuracy-based benchmarks, PragReST improves over the instruct backbone by 5.37 and 5.50% (absolute) for Qwen3-8B and Qwen3-14B, respectively. Our error analysis and ablations underscore the importance of counterfactual reasoning: PragReST primarily reduces errors caused by failures to contrast observed utterances with plausible alternatives, and removing counterfactual reasoning substantially reduces performance. Moreover, our training preserves out-of-domain performance on general-knowledge and mathematical reasoning benchmarks.

04.
arXiv (CS.CV) 2026-06-12

On Pitfalls of $RemOve-And-Retrain$: Data Processing Inequality Perspective

The RemOve-And-Retrain (ROAR) benchmark is widely used to evaluate feature attribution methods, yet its validity remains underexplored from an information-theoretic perspective. We show that model- and data-agnostic post-processing of attribution maps (transformations that, by the data processing inequality, cannot add information about the decision function) can often improve ROAR scores. This means that an improved ROAR ranking is not, by itself, evidence that an attribution map carries more information about the model. We trace this failure mode to a bias toward spatially blurry masks. Experiments on CIFAR-10, SVHN, and CUB-200 show a consistent association between blurriness and ROAR performance, a pattern that also appears in the ROAD variant. We provide guidelines for more cautious removal-based benchmarking, with implications for validating mechanistic understanding of neural network internals.

05.
arXiv (CS.CL) 2026-06-16

ArFake: A Robust Framework for Multi-Dialect Arabic Speech Spoofing Detection Benchmark

With the rise of generative text-to-speech models, distinguishing between real and synthetic speech has become challenging, especially for Arabic that have received limited research attention. Most spoof detection efforts have focused on English, leaving a significant gap for Arabic and its many dialects. In this work, we introduce the first multi-dialect Arabic spoofed speech dataset. To evaluate the difficulty of the synthesized audio from each model and determine which produces the most challenging samples, we aimed to guide the construction of our final dataset either by merging audios from multiple models or by selecting the best-performing model, we conducted an evaluation pipeline that included training classifiers using two approaches: modern embedding-based methods combined with classifier heads; classical machine learning algorithms applied to MFCC features; and the RawNet2 architecture. The pipeline further incorporated the calculation of Mean Opinion Score based on human ratings, as well as processing both original and synthesized datasets through an Automatic Speech Recognition model to measure the Word Error Rate. Our results demonstrate that FishSpeech outperforms other TTS models in Arabic voice cloning on the Casablanca corpus, producing more realistic and challenging synthetic speech samples. However, relying on a single TTS for dataset creation may limit generalizability.

06.
arXiv (CS.CL) 2026-06-19

Displacement Is Not Direction: Evaluating Fidelity Metrics for Quantized LLM Deployment

Fidelity metrics, such as per-token KL divergence (KLD) against a high-precision reference, are often used in practice as low-cost proxies for benchmark quality. We test this practice on a 28-quant cohort of Qwen3.6-35B-A3B and a 41-quant cohort of Devstral-Small-2-24B, evaluated across a suite of downstream benchmarks. We find that KLD is strongly correlated with benchmark score over the full cohort ($\rho=-0.72$ on Qwen and $\rho=-0.86$ on Devstral, both with $p

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

Revisiting Vehicle Color Recognition in Long-Tailed Surveillance Scenarios

Vehicle color recognition is an important cue for vehicle identification in surveillance systems, especially when license plates are illegible due to low resolution, occlusion, motion blur, or poor illumination. However, real-world vehicle color distributions are highly imbalanced, making overall accuracy insufficient to assess performance on rare but operationally relevant colors. This paper presents a comprehensive study of vehicle color recognition under severe class imbalance using UFPR-VeSV, a challenging real-world surveillance dataset. We investigate synthetic minority-class augmentation through two off-the-shelf generative strategies: text-conditioned image generation with RunDiffusion/JuggernautXL and image-conditioned color editing with Gemini 2.0 Flash. The curated synthetic data are combined with modern visual representations, loss reweighting, learning-rate scheduling, color-safe augmentation, foreground-aware preprocessing, and ensemble fusion. The bestperforming approach achieves 94.6% micro accuracy and 79.7% macro accuracy, improving macro accuracy by 8.2 percentage points over recent literature. A manual error analysis further shows that many remaining failures are visually ambiguous even for human annotators, highlighting the practical limits of color-based vehicle identification in unconstrained surveillance imagery. The generated images and source code are publicly available at https://github.com/viniciusorru/vcr-synthetic

08.
arXiv (quant-ph) 2026-06-11

Emergent Bell Phase in an Electro-Nanomechanical Quantum Simulator

arXiv:2511.02613v2 Announce Type: replace Abstract: Suspended carbon nanotubes hosting electrostatically defined quantum dots allow for exceptionally strong and tunable electromechanical coupling as well as mechanical modes that can reach the quantum ground state of motion simply by cryogenic cooling. This makes them a unique platform for quantum simulation of electron-phonon coupling. Here, we propose an experimentally realisable setup with two such carbon nanotubes in parallel, each hosting four quantum dots. Our system not only exhibits phonon-mediated electron-electron attraction, but also supports a robust, maximally entangled Bell phase at mesoscopic scales shared across the subsystems. These features highlight its potential as a simulator of strongly correlated quantum systems.

09.
arXiv (CS.CL) 2026-06-11

Multi-Agent Reasoning with Adaptive Worker Allocation for Stance Detection

Stance detection requires identifying an author's position toward a target, often from short-form texts where stance is implicit, indirect, or rhetorically framed. Although large language models (LLMs) achieve strong performance on this task, single-pass prompting can be brittle when multiple interpretations are plausible. Existing aggregation strategies, such as majority voting or self-consistency, improve robustness by combining labels, but they discard the intermediate reasoning needed to resolve conflicting interpretations. We introduce a multi-agent reasoning framework with adaptive worker allocation for stance detection that shifts aggregation from label-level voting to reasoning-level synthesis. The framework employs a Manager-Worker architecture in which a Manager adaptively allocates a variable number of Worker agents based on input complexity. Each Worker analyzes the input from a distinct perspective and produces a reasoning-only explanation without emitting a stance label; the Manager then synthesizes these explanations to produce the final prediction. We evaluate the proposed framework on SemEval-2016, P-Stance, and COVID-19 Stance using Llama, Mistral, and Gemini. Results show that the framework yields the largest gains on implicit and context-dependent stance cases, achieving 86.07 Macro-F1 on COVID-19 and 82.90 on SemEval-2016, while remaining competitive on more explicit stance datasets such as P-Stance. These findings suggest that adaptive reasoning-level aggregation is most beneficial when stance cannot be reliably inferred from surface cues alone.

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

CreativeBench: Benchmarking and Enhancing Machine Creativity via Self-Evolving Challenges

The saturation of high-quality pre-training data has shifted research focus toward evolutionary systems capable of continuously generating novel artifacts, leading to the success of AlphaEvolve. However, the progress of such systems is hindered by the lack of rigorous, quantitative evaluation. To tackle this challenge, we introduce CreativeBench, a benchmark for evaluating machine creativity in code generation, grounded in a classical cognitive framework. Comprising two subsets – CreativeBench-Combo and CreativeBench-Explore – the benchmark targets combinatorial and exploratory creativity through an automated pipeline utilizing reverse engineering and self-play. By leveraging executable code, CreativeBench objectively distinguishes creativity from hallucination via a unified metric defined as the product of quality and novelty. Our analysis of state-of-the-art models reveals distinct behaviors: (1) scaling significantly improves combinatorial creativity but yields diminishing returns for exploration; (2) larger models exhibit ``convergence-by-scaling,'' becoming more correct but less divergent; and (3) reasoning capabilities primarily benefit constrained exploration rather than combination. Finally, we propose EvoRePE, a plug-and-play inference-time steering strategy that internalizes evolutionary search patterns to consistently enhance machine creativity.

11.
arXiv (CS.LG) 2026-06-24

RE4: Transformation-aware Imitation of Object Interactions Using Manipulation Modes

arXiv:2606.24403v1 Announce Type: cross Abstract: Object interaction tasks have been a focus of advances in imitation learning. End-to-end methods, dominated by diffusion and flow-based variants have shown leaps in performance while sacrificing interpretability. Object-centric and pose-informed variants have had a role in learning from demonstration in manipulation tasks. In this paper, we revisit a few modern imitation learning benchmarks for object interactions, with the aim of composing a framework that repurposes principled theories of manipulation, preserving both performance and interpretability. For image observations, lightweight training is proposed for model-free pose estimation of the target object, using self-supervision over the demonstration data available for imitation learning. This information is then used to inform a manipulation mode-aware retrieval of a demonstration, a mode-aware transformation, a replan step that connects to the retrieval point while preserving mode constraints, and finally rolling out the transformed demonstration. These compose four key steps of the proposed RE4 framework, evaluated over state-based and image-based benchmarks in Push-T and Robomimic. An adversarial benchmark that evaluates sparse data regions of image-based Push-T showcases the robustness, further bolstered by indications from low-data regime experiments. The current work shows promise in using simple interpretable building blocks to learn manipulation skills.

12.
arXiv (math.PR) 2026-06-18

A Unified Approach to Beta Moments, Combinatorial Identities, and Random Walks

arXiv:2605.05420v2 Announce Type: replace Abstract: The study of random walks has increasingly been popular across diverse disciplines such as statistics, mathematics, quantum physics, where they are used to model paths consisting of successive random steps in a mathematical space. A fundamental quantity of interest is the probability that a simple symmetric random walk returns to the origin after 2n steps. In this paper, we develop a unified probabilistic approach that connects the return probabilities in arbitrary dimensions with moment representations. Using this framework, we provide probabilistic proofs of several combinatorial identities involving beta and gamma functions, and derive new combinatorial identities in general dimensions.

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

LLM agent safety, multi-turn red-teaming, jailbreak benchmarks, adversarial robustness, safety-critical systems

arXiv:2606.20408v1 Announce Type: cross Abstract: Large language model (LLM) agents are increasingly proposed as supervisory components for safety-critical systems, yet their robustness under sustained, adaptive adversarial pressure remains poorly characterized. We present NRT-Bench, a benchmark for multi-turn red-teaming of LLM agents acting as operators of a safety-critical system, instantiated in a simulated nuclear power plant control room. A five-role operator team, each backed by a configurable LLM, runs a plant governed by six critical safety functions (CSFs), while adversaries inject messages over four channels in bounded multi-turn sessions with per-turn feedback. Harm is an objective signal rather than LLM-judged text: a run terminates the moment any CSF is lost, attributed to the causing message. Evaluating four frontier operator models under a fixed-attack paired-replay protocol, we find that adaptive multi-turn attacks reliably push the operator team past a safety limit: across the four models, between 8.7% and 12.1% of attack sessions end with the plant losing a critical safety function. Although the four models look almost equally robust by this aggregate rate, their failures barely overlap: of $149$ sessions, none defeat all four models while a third defeat at least one, so vulnerabilities are nearly disjoint across models rather than nested. The effect of added defences is strongly model-dependent: the same guardrail stack or safety-advisor agent that lowers attack success for one model can raise it for another. We release the simulation venue, attack dataset, and replay tooling for reproducible safety evaluation of LLM agents.

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

ArtNet: A JEPA-Like Articulatory Predictive Framework for Robust Zero-Shot Phoneme Recognition

arXiv:2606.16595v1 Announce Type: cross Abstract: Zero-shot cross-lingual phoneme recognition is often hindered by the fragility of direct acoustic-to-symbol mapping, which is susceptible to language-specific variations. Echoing joint-embedding predictive architecture (JEPA) work in vision, we propose ArtNet, a framework that explores a structured feature prediction task based on articulatory features to enhance acoustic robustness. Specifically, ArtNet integrates an articulatory predictor, designed to extract universal articulatory representations from self-supervised learning (SSL) features, with a variational information bottleneck (VIB) to suppress language-specific variations. Experiments on seven unseen languages demonstrate that ArtNet, particularly when synergized with the proposed vector-space inventory alignment (VSIA) strategy, significantly outperforms competitive baselines, achieving a 20.56\% relative reduction in phoneme error rate (PER) and 7.01\% in phoneme feature error rate (PFER).

15.
arXiv (CS.LG) 2026-06-16

Quantization Robustness of Monotone Operator Equilibrium Networks

arXiv:2603.10562v2 Announce Type: replace-cross Abstract: Monotone operator equilibrium networks are implicit-layer models whose output is the unique equilibrium of a monotone operator, guaranteeing existence, uniqueness, and convergence. When deployed on low-precision hardware, weights are quantized, potentially destroying these guarantees. We analyze weight quantization as a spectral perturbation of the underlying monotone inclusion. Convergence of the quantized solver is guaranteed whenever the spectral-norm weight perturbation is smaller than the monotonicity margin; the displacement between quantized and full-precision equilibria is bounded in terms of the perturbation size and margin; and a condition number characterizing the ratio of the operator norm to the margin links quantization precision to forward error. MNIST experiments confirm a phase transition at the predicted threshold: three- and four-bit post-training quantization diverge, while five-bit and above converge. The backward-pass guarantee enables quantization-aware training, which recovers provable convergence at four bits.

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

TNODEV: Toolbox for Neural ODE Verification

arXiv:2606.16567v1 Announce Type: new Abstract: Neural ordinary differential equations (neural ODE) have started to appear in safety critical settings such as continuous-time controllers for cyber-physical systems and classifiers integrated into automated decision pipelines, raising the question of whether their behavior can be formally verified. Existing tools dedicated to neural ODE provide only a single reachability call without iterative input set refinement, limiting the precision of their verdicts to whatever one reachability call can deliver. We present TNODEV, the first sound formal verifier for neural ODE that integrates a falsification checker, a fast interval-based reachability backend based on continuous-time mixed monotonicity, a verification and refinement loop with three input-set splitting heuristics, and a parallel scheduler in a single end-to-end pipeline. TNODEV supports safe-set inclusion verification on pure neural ODE, neural ODE in closed loop with a neural network controller and general neural ODE (GNODE), with the safe set specified either as an interval or as the half-space intersection induced by a target classification label. We evaluate TNODEV on a range of benchmarks across safe-set inclusion and classification-robustness properties, including a direct reachability comparison against NNV~2.0 and CORA and a verification comparison against NNV2.0 on MNIST general neural ODE classifiers.

17.
arXiv (quant-ph) 2026-06-11

Fisher geometry reshapes the effect of incompatibility in multiparameter quantum estimation

arXiv:2606.11343v1 Announce Type: new Abstract: Multiparameter quantum estimation faces two fundamental obstacles: sloppiness, i.e., anisotropy of the quantum Fisher information matrix (QFIM) that renders some parameter directions insensitive, and incompatibility, the non-commutativity of optimal measurements for different parameters. The trade-off bound $C_T$ captures their joint impact on precision, but it has remained unclear how the distribution of incompatibility across parameter planes affects its overall cost. Here we separate the total amount of incompatibility from its location. We introduce a dimensionless quantity $G_n^{(F)}$ that measures the alignment between the incompatibility distribution and the eigenvalues of the QFIM, and show how the Frobenius scale of the incompatibility contribution factorizes. We obtain a bound and prove the incompatibility cost lies between this bound and a rank-dependent multiple thereof. We also prove that at fixed sloppiness, or equivalently fixed Fisher volume, concentrating incompatibility into a single parameter plane reduces the optimized trade-off cost because the Fisher geometry can then be reshaped to allocate more Fisher area to that plane. A qutrit $SU(2)$ encoding numerically confirms that states with larger incompatibility strength can nevertheless incur a smaller cost if the matching factor $G$ is sufficiently small. Our results establish that the distribution of incompatibility relative to the Fisher eigenbasis is a central diagnostic for multiparameter estimation, beyond the total incompatibility strength.

18.
arXiv (CS.LG) 2026-06-12

PLaID++: A Preference Aligned Language Model for Targeted Inorganic Materials Design

arXiv:2509.07150v4 Announce Type: replace Abstract: Reinforcement Learning from Verifiable Rewards (RLVR) has emerged as a promising approach to improve correctness in LLMs, however, in many scientific problems, the objective is not necessarily to produce the correct answer, but instead to produce a diverse array of candidates which satisfy a set of constraints. We study this challenge in the context of materials generation. To this end, we introduce PLaID++, an LLM post-trained for stable and property-guided crystal generation. We find that performance hinges on our crystallographic representation and reward formulation. First, we introduce a compact, symmetry-informed Wyckoff text representation which improves computational efficiency and encourages generalization from physical priors. Second, we demonstrate that temperature scaling acts as an entropy regularizer which counteracts mode collapse and encourages exploration. By encoding symmetry constraints directly into text and guiding model outputs towards desirable chemical space, PLaID++ generates structures that are thermodynamically stable, unique, and novel at a $\sim$50\% greater rate than prior methods and conditionally generates structures with desired space group properties. Our work demonstrates the potential of adapting post-training techniques from natural language processing to materials design, paving the way for targeted and efficient discovery of novel materials.

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

Matrix Product Operator Encodings of the Magnus Expansion and Dyson Series

arXiv:2605.21597v2 Announce Type: replace Abstract: We introduce a matrix product operator (MPO) encoding of the Magnus expansion and the Dyson series for one-dimensional quantum lattice models with time-dependent Hamiltonians. The MPO construction can be made accurate up to arbitrary order in the time step, it can be applied to both finite and infinite systems, and it can handle long-range interactions. The resulting MPO can be combined with state-of-the-art time evolution algorithms based on matrix product states, allowing for drastic improvements in simulating evolution under time-dependent Hamiltonians. Our MPO construction can also be used for the optimization of quantum circuits in the context of quantum simulation of time-dependent Hamiltonians.

20.
arXiv (CS.LG) 2026-06-19

Exploring the potential of AlphaEarth and TESSERA embeddings for Fine-scale Local Climate Zone Mapping: A case study across five cities in Switzerland

arXiv:2606.20034v1 Announce Type: new Abstract: Understanding urban spatial morphology is critical for climate modeling, risk assessment, and sustainable urban design, and Local Climate Zone (LCZ) mapping provides the basic framework for this. However, many cities still use coarse ~100-m resolution LCZ records, which are unsuitable for fine-scale urban research. In this study, precomputed embeddings from TESSERA (Feng et al., 2025) and AlphaEarth (Brown et al., 2025) are compared to traditional Sentinel-1/2 (S1S2) composites in five Swiss cities to see if they can upscale coarse LCZ maps to 10-m resolution using an attention-based U-Net. Three experiments assess multi-city transferability, the impact of higher-resolution reference data, and temporal robustness to year-to-year phenology changes. We find that all datasets achieve strong performance with test data Intersection-over-Union (IoU) ranging from 0.59-0.69 and 0.77-0.82 in the first two experiments. TESSERA consistently outperforms both S1S2 and AlphaEarth across both settings As expected, we find that the transfer of embedding-based models from one year to another remains an open challenge. Overall, however, our results demonstrate the promising potential of embeddings derived from EO foundation models to reduce time consuming preprocessing, respectively, manual feature engineering tasks and to guide a universal deep learning-based LCZ mapping workflow. When combined with a simple location-aware attention U-Net architecture, the embeddings enhance regional transferability and scalability, supporting the development of comprehensive and reproducible fine-scale LCZ maps for global urban climate applications Improving reference data quality remains the strongest lever for further accuracy gains.

21.
arXiv (quant-ph) 2026-06-15

Fourier analysis of quantum neural network with non-linear data embedding

arXiv:2606.14206v1 Announce Type: new Abstract: Fourier analysis has become a crucial tool for understanding the expressivity of Variational Quantum Circuit (VQC) models, as well as an important indicator of barren plateaus (BP). While existing literature has only studied angle-embedded VQCs in a noiseless environment, here we develop the Fourier analysis of VQCs with non-linear data embedding, with particular focus on amplitude embedding, which provides a naturally compact encoding scheme. We first investigate a subtle difference in the domain of input features within amplitude embedding that leads to a distinct expressivity of the zero-frequency Fourier coefficient. By assuming that the ensemble of unitaries generated from the parameter space forms at least a 2-design with respect to the unitary group, we derive, via Weingarten calculus, that the mean of the Fourier coefficients is concentrated at zero, and the variance scales at an exponentially decaying order with respect to the multi-dimensional frequency magnitude. When a noise channel with unitary Kraus operators and probabilities $\{p_k\}$ is taken into account, the variance is further suppressed by a factor $\left(\sum_k p_k^2\right)^{Q}

22.
arXiv (CS.LG) 2026-06-24

Neural Posterior Estimation of Terrain Parameters from Radar Sounder Data

arXiv:2605.08179v2 Announce Type: replace-cross Abstract: Radar sounders are electromagnetic instruments that can probe deep into the subsurface of Earth and other planetary bodies by processing the echo of transmitted radar waves. Conventional approaches for analyzing such data rely on approximate assumptions and often produce point estimates that ignore parameter correlations as well as galactic and measurement noise. We propose a simulation-based inference approach to terrain parameter inversion from radar sounder data, where synthetic observations from a GPU-based simulator are used to train a neural network-based density estimator for neural posterior estimation (NPE). By explicitly conditioning on reference surface assumptions, the proposed framework allows systematic evaluation of posterior robustness to reference surface variability. We demonstrate that our NPE model is well calibrated on simulated data and transferable to real Mars radar profiles, where we analyze terrain parameters using literature-informed reference values.

23.
medRxiv (Medicine) 2026-06-15

Population-scale genomics reveals divergent pathogenicity of variant classes across paralogous collagen IV genes

Monoallelic pathogenic or likely pathogenic variants in COL4A3 and COL4A4 occur in approximately 1 in 106 individuals, yet whether these paralogous genes confer equivalent pathogenicity for the same variant classes has not been tested at population scale. Using whole-genome sequencing data from the UK Biobank (UKB; n = 500,000), with replication in the All of Us Research Program (n = 414,000), we performed per-variant association testing, gene-based collapsing analyses and phenome-wide association studies (PheWAS) across haematuria, proteinuria and chronic kidney disease. We identified 64 COL4A3 and 92 COL4A4 rare variants significantly associated with haematuria or proteinuria, generating a quantitative allelic series for clinical variant interpretation. Glycine substitutions within collagenous domains conferred similar risks in both genes. In contrast, truncating and non-collagenous domain (NC1) missense variants were strongly associated with haematuria and proteinuria in COL4A4 carriers but showed substantially attenuated or absent associations in COL4A3 carriers despite comparable carrier frequencies and predicted pathogenicity scores. These findings were independently replicated in All of Us. Genome-wide association analysis identified the COL4A3/COL4A4 locus as the dominant genetic determinant of haematuria, with the signal attributable to the aggregate effects of rare coding variants and no evidence of independent common variant or trans-acting modifier effects. These findings demonstrate substantial gene-specific differences in tolerance to truncating and NC1 variants between COL4A3 and COL4A4, challenging assumptions of equivalent pathogenicity across paralogous collagen IV genes. Gene identity and not variant class alone, should inform risk stratification, variant interpretation and genetic counselling in individuals carrying collagen IV risk genotypes.

24.
bioRxiv (Bioinfo) 2026-06-18

Looking beyond stereotyped neuron structures reveals links between beading and morphological rearrangements in aging phenotypes.

Understanding how neuronal morphology changes during aging and acute stress is essential for elucidating mechanisms of neurodegeneration. The highly branched PVD neuron of Caenorhabditis elegans provides a powerful model for studying dendritic remodeling and degeneration-associated phenotypes such as dendritic beading. However, the complexity of this arbor presents substantial challenges for automated segmentation and quantitative analysis. In this study, we adapted a convolutional neural network (CNN)-guided region growing framework for automated dendrite tracing, coupled with two topology-based algorithms for categorizing dendritic segments by branching degree. The segmentation algorithm achieved high accuracy relative to manual tracing, with a median Dice coefficient of 0.82, while reducing analysis time by approximately tenfold. Automated dendrite categorization demonstrated strong agreement with manual annotations across branching orders, though position-based mapping performance declined with age due to progressive morphological distortion. Leveraging this platform, we investigated mechanistic differences in dendritic beading patterns observed during aging and cold shock. Consistent with prior work, aging was associated with decreased inter-bead spacing, whereas cold shock produced increased bead dispersion with stress severity. Structural analysis revealed that these trends were not driven by dendritic pruning or reduced arbor complexity. Instead, while a traditional anatomically unflexible paradigm falsely implicated lower-degree dendrites as highly vulnerable, our branching-informed framework revealed that age-dependent beading is fundamentally dictated by a segments history of successive branching events. Conversely, acute cold shock triggered systemic beading that expanded across all dendritic orders in a severity-dependent manner. Together, these findings demonstrate that chronic aging and acute stress engage distinct degenerative pathways (compartment-specific lineage vulnerability versus global architectural collapse) rather than gross morphological loss, as well as highlighting the need for paradigms that enable reliable analysis of changing morphologies.

25.
arXiv (CS.AI) 2026-06-17

Retrofitters, pragmatists and activists: Public interest litigation for accountable automated decision-making

arXiv:2511.03211v4 Announce Type: replace-cross Abstract: This paper examines the role of public interest litigation in promoting accountability for AI and automated decision-making (ADM) in Australia. Since ADM regulation faces political and geopolitical headwinds, effective governance will have to rely on the enforcement of existing laws. Drawing on interviews with Australian public interest litigators, technology policy activists, and technology law scholars, the paper positions public interest litigation as part of a larger ecosystem for transparency, accountability and justice with respect to ADM. The paper explores the tactics and strategies of what one participant described as 'retrofitting' old laws to ADM. These go beyond creative legal argumentation, to encompass practices of community-building, collaboration on theories of change, canny selection of clients and causes of action, and the alignment of the interests of stakeholders in litigation. Naturally, the paper also contends with the limits of these strategies, and of the Australian legal system. Where limits are, however, capable of being overcome, the paper presents findings on urgent needs: the enabling institutional arrangements without which effective litigation and accountability will falter. The paper is relevant to law and technology scholars; individuals and groups harmed by ADM; public interest litigators and technology lawyers; civil society and advocacy organisations; and policymakers.