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

Recovery thresholds for hidden weighted sparse graphs

arXiv:2606.14335v1 Announce Type: cross Abstract: Recovering structural information from noisy high-dimensional data is a fundamental task in statistical inference. We investigate the recovery thresholds for a graph hidden in a randomly weighted complete graph. Specifically, an unknown graph $H^* \in H_n$ is chosen uniformly at random, and hidden in a complete graph of $n$ vertices as follows: the weight of an edge $e \in H$ is distributed independently according to $P_n$; otherwise the weight is distributed independently according to $Q_n$. The goal is to recover almost all of $H$ from these edge weights. Assuming a local Lipschitzness of the Rényi divergence between distributions $P_n$ and $Q_n$, and a mild density condition for the graphs $H_n$, we give a unified characterization of the information-theoretic limit for recovering almost all of $H$ (also known as almost exact recovery). Our characterization connects the KL divergence between $P_n$ and $Q_n$ to the logarithm of the first moment threshold of $H$ in the Erdős-Rényi random graph model $G(n,p)$. Our lower bound also extends to the task of partial recovery, in which only a constant $\lambda$-fraction of $H$ needs to be recovered. Last but not least, for certain Bernoulli and Exponential regimes, and for Gaussian distributions, we are able to show an All-or-Nothing (AoN) threshold phenomenon at the exponential scale.

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

EvoLMM: Self-Evolving Large Multimodal Models with Continuous Rewards

Recent advances in large multimodal models (LMMs) have enabled impressive reasoning and perception abilities, yet most existing training pipelines still depend on human-curated data or externally verified reward models, limiting their autonomy and scalability. In this work, we strive to improve LMM reasoning capabilities in a purely unsupervised fashion (without any annotated data or reward distillation). To this end, we propose a self-evolving framework, named EvoLMM, that instantiates two cooperative agents from a single backbone model: a Proposer, which generates diverse, image-grounded questions, and a Solver, which solves them through internal consistency, where learning proceeds through a continuous self-rewarding process. This dynamic feedback encourages both the generation of informative queries and the refinement of structured reasoning without relying on ground-truth or human judgments. When using the popular Qwen2.5-VL as the base model, our EvoLMM yields consistent gains upto $\sim$3\% on multimodal math-reasoning benchmarks, including ChartQA, MathVista, and MathVision, using only raw training images. We hope our simple yet effective approach will serve as a solid baseline easing future research in self-improving LMMs in a fully-unsupervised fashion. Our code and models are available at https://github.com/mbzuai-oryx/EvoLMM.

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

Continuous Language Diffusion as a Decoder-Interface Problem

Gaussian-corrupted sentence embeddings have no direct linguistic interpretation, yet continuous diffusion language models can generate fluent text from them. We study this puzzle through Embedded Language Flows (ELF) and identify a decoder-basin mechanism: our evidence suggests that denoising becomes reliable when trajectories reach regions where the native decoder can read stable tokens. We introduce a diagnostic protocol for denoisability, semantic recoverability, order sensitivity, decoder compatibility, and trajectory reliability. It exposes failures hidden by scalar metrics: low mean-squared error can discard linguistic content, low perplexity can reflect low-entropy collapse, and clean latent reconstruction can coexist with a narrow decoder basin. A decoder-margin bound explains why token recovery depends on margin and local decoder sensitivity, not latent error alone. Auditing public ELF checkpoints reveals an interface phase diagram: early predictions are weakly readable, mid-trajectory disagreement marks a competition region, and late predictions enter a high-margin decoder basin. Once inside, token realization is surprisingly simple on generated ELF states: frozen T5 (Text-to-Text Transfer Transformer) token-embedding lookup recovers $93$–$96\%$ of native decoder decisions, and a single linear readout reaches $97.9\%$ agreement at 32k samples, leaving an $\approx1.1$–$1.2$ perplexity gap in a structured residual tail. Under conservative held-out gates, a margin rule exits roughly $17$–$28\%$ earlier in denoising steps under an explicit diagnostic monitor. Boundary checks on LangFlow, BitstreamDiffusion, and the Continuous Latent Diffusion Language Model (Cola-DLM) show that the same interface questions remain meaningful when the state object and decoder change. Continuous and latent diffusion language models should therefore be evaluated as representation-decoder systems.

04.
arXiv (CS.CL) 2026-06-16

Few-Shot Biomedical Relation Extraction with Large Language Models: A Viable Alternative to Supervised Learning?

Biomedical relation extraction (BioRE) is a key step in transforming biomedical literature into structured knowledge. However, most existing approaches rely on supervised models trained on costly annotated datasets, limiting their scalability and adaptability across relation types and domains. We investigate few-shot BioRE using prompt-based learning with large language models (LLMs) and compare two task formulations: pairwise classification, which predicts relations for individual entity pairs, and joint generation, which extracts multiple relations in a single model call. Experiments on the BioREDirect dataset reveal a clear precision-recall trade-off. Pairwise classification achieves higher recall, whereas joint generation is more precise and computationally efficient. The best-performing model achieves a micro-F1 score of 0.44, substantially outperforming previous few-shot results (0.34) while remaining below the supervised baseline (0.56). Much of this gap is attributable to a single ambiguously defined relation type. When evaluated using macro-F1, which better captures performance across relation types in an imbalanced setting, prompt-based approaches outperform the supervised baseline (0.45 vs. 0.38), particularly on rare relation types. These findings highlight the potential of LLMs for BioRE in low-resource settings and underscore the importance of well-defined relation schemas.

05.
arXiv (CS.LG) 2026-06-12

Uncertainty Estimation for Molecular Diffusion Models

arXiv:2606.13451v1 Announce Type: new Abstract: Diffusion models have seen wide adoption for 3D molecular generation, yet they offer no principled signal of when a generated molecule is likely to be of low quality. We propose a post-hoc method for estimating per-sample uncertainty in pretrained molecular diffusion models. Building on a Laplace approximation of the denoising network, we measure the variability of the noise prediction across the generation trajectory. Empirically, we show that the resulting uncertainty score is informative of sample quality, exhibiting a negative correlation with established sample-level quality metrics. We further study how the proposed uncertainty score can be used to filter generated samples, improving model performance via test-time scaling.

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

Generative models for decision-making under distributional shift

arXiv:2604.04342v2 Announce Type: replace Abstract: Many data-driven decision problems are formulated using a nominal distribution estimated from historical data, while performance is ultimately determined by a deployment distribution that may be shifted, context-dependent, partially observed, or stress-induced. This tutorial presents modern generative models, particularly flow- and score-based methods, as mathematical tools for constructing decision-relevant distributions. From an operations research perspective, their primary value lies not in unconstrained sample synthesis but in representing and transforming distributions through transport maps, velocity fields, score fields, and guided stochastic dynamics. We present a unified framework based on pushforward maps, continuity, Fokker-Planck equations, Wasserstein geometry, and optimization in probability space. Within this framework, generative models can be used to learn nominal uncertainty, construct stressed or least-favorable distributions for robustness, and produce conditional or posterior distributions under side information and partial observation. We also highlight representative theoretical guarantees, including forward-reverse convergence for iterative flow models, first-order minimax analysis in transport-map space, and error-transfer bounds for posterior sampling with generative priors. The tutorial provides a principled introduction to using generative models for scenario generation, robust decision-making, uncertainty quantification, and related problems under distributional shift.

07.
arXiv (CS.CV) 2026-06-17

EgoCS-400K: An Egocentric Gameplay Dataset for World Models

The shift from video generation to interactive world modeling places new demands on data: beyond captioned videos, world models require temporally aligned video-action-language trajectories grounded in the actions, camera motion, states, and events that drive future scene changes. However, such data is difficult to obtain at scale. Web video datasets offer broad visual coverage but lack executable actions and reliable states; robotic datasets provide action and state supervision but are costly and limited in scene diversity; and existing simulators often lack large-scale human-driven interaction trajectories. In this paper, we introduce EgoCS-400K, a large-scale replay-grounded egocentric Counter-Strike dataset for world models, built from public professional CS and CS2 match demos that preserve human gameplay trajectories and enable parsing, replaying, rendering, and temporal alignment. We extract player states, view directions, movements, keyboard/button inputs, view-angle changes, weapon usage, game events, and round-level context, and render clean first-person videos from the same trajectories. EgoCS-400K contains over 400,000 first-person videos and 10,000 hours of gameplay from more than 1,000 matches and 40,000 rounds, covering 13 maps and 10 player viewpoints per round. It supports a range of interactive visual modeling tasks, including action-conditioned future prediction, state- and event-aware scene rollout, replay-grounded captioning, and agent egocentric action understanding. By connecting visual observations with human actions, camera motion, game states, and events at scale, EgoCS-400K serves as a practical bridge between passive web videos, controllable game simulation, and costly real-world embodied data.

08.
arXiv (CS.CV) 2026-06-19

InfantFace: Detecting infant faces in neonatal clinical environments

Reliable localisation of the neonatal face is the first step for several video-camera based non-contact assessments such as pain and distress related facial expression analysis, pain scoring, cardiorespiratory signal extraction and cessation of breathing alerts. However, major challenges persist in neonatal clinical environments. Cluttered backgrounds, illumination changes and poor lighting conditions can reduce the accuracy of face detection models. Clinical interventions, monitoring equipment and, in some cases, medical devices can obstruct the face, making visual assessment difficult. We propose a one-stage YOLOv11m-based model tailored for face detection of infants in neonatal clinical environments. We combined multiple publicly available datasets (VGGFace2, CelebA, FDDB, WIDER FACE) to train and evaluate our proposed model. We then fine-tuned our model on a neonatal research dataset involving 228 videos from 114 recording sessions of 113 independent infants. Before fine-tuning, our model achieved an AP50 of 0.87, surpassing the performance of three state-of-the-art general face detectors. Performance improved further to an AP50 of 0.96 after clinical-domain adaptation. Evaluating face detection performance across different datasets remains a challenge due to the lack of publicly available neonatal datasets. Prioritising the creation of such datasets, while upholding appropriate privacy safeguards and ethical standards in their creation and use, would greatly support further progress in this field.

10.
arXiv (CS.CV) 2026-06-17

Contrastive Action-Image Pre-training for Visuomotor Control

Existing vision encoders for robotics face a fundamental bottleneck: robotic datasets lack the scale necessary for large-scale pre-training. Prior work circumvents this data scarcity by turning to internet-scale image and language data or egocentric human video. While these models show promise, neither paradigm learns from paired vision and action data, which downstream visuomotor control policies require. However, robot trajectories, the most direct source of this paired signal, are not available at pre-training scale, motivating us to extract action signals from abundant human video instead. To this end, we introduce CAIP (Contrastive Action-Image Pre-training), a vision encoder that treats human hand poses from large-scale egocentric video as a proxy for end-effector actions. By extracting 3D hand keypoints, a representation that aligns naturally with downstream robot action spaces, CAIP learns a unified action-image representation through a contrastive objective. Leveraging 32,041 hours of egocentric human video and only 88 hours of robotic manipulation data, CAIP outperforms state-of-the-art vision encoders including DINOv2, SigLIP, MVP, and R3M. Evaluated on a challenging real-world dexterous manipulation setup using Dexmate Vega and Sharpa Wave hands, CAIP yields performance gains of more than 30% on tasks involving folding, pouring, and fine-grained manipulation. Our results show that our method of contrastive action-centric pre-training yields a scalable path to achieving robust visual representations better suited for physical interaction.

12.
arXiv (quant-ph) 2026-06-11

Planted-Solution Pauli Hamiltonians as a Quantum Benchmarking Primitive

arXiv:2606.11455v1 Announce Type: new Abstract: We introduce a construction of Pauli Hamiltonians with exactly known ground-state energies, intended as reference instances for ground-state energy estimation algorithms. The construction embeds a planted block-product state as the simultaneous ground state of a sum of frustration-free local clauses on overlapping supports, exposes the resulting model only as a polynomial-size linear combination of Pauli operators, and admits optional Clifford conjugation that preserves the spectrum. The framework subsumes classical planted constraint-satisfaction problems as a diagonal special case, providing a direct embedding channel through which classical hardness properties can be inherited. Open-source software, certification keys, and example instances are made publicly available.

13.
arXiv (CS.CV) 2026-06-16

G2IA: Geometry-Guided Instance-Aware Retrieval and Refinement for Cross-Modal Place Recognition

Cross-modal place recognition (CMPR) enables camera-only robots to localize against pre-built LiDAR maps in autonomous navigation scenarios. This image-to-point-cloud setting is challenged by two coupled ambiguities: the modality gap between perspective RGB appearance and sparse metric geometry, and perceptual aliasing among urban places with similar roads, facades, intersections, and object arrangements. Instead of treating CMPR as a single global descriptor matching problem, we argue that reliable retrieval requires both geometry-aware representation alignment and fine-grained candidate verification. In this paper, we propose G2IA, a geometry-guided instance-aware framework for image-to-point-cloud place recognition. In the retrieval stage, visual geometry priors from VGGT and instance features are integrated to construct place descriptors that are more compatible with LiDAR-derived map representations. In the refinement stage, the retrieved candidates are re-ranked by explicitly verifying whether local instance shapes and their relative spatial layouts are consistent across modalities. Experiments on public benchmarks demonstrate that G2IA consistently improves image-to-point-cloud place recognition under different localization thresholds, and exhibits strong cross-dataset generalization.

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

Speaking the Language of Science: Toward a General-Purpose Generative Foundation Model for the Natural Sciences

In this report, we present LOGOS (Language Of Generative Objects in Science), a scientific generative language model that unifies heterogeneous tasks across the natural sciences within a single autoregressive framework based on a shared scientific grammar. It encodes diverse scientific objects and their spatial interactions as token sequences over a common vocabulary. By representing spatial contact and constraint patterns as discrete tokens, the model captures complex structural interactions in a purely sequential manner, without relying on explicit coordinates or geometric neural networks. This unified representation enables a wide range of downstream tasks to be formulated consistently as next-token prediction in the same grammar space, creating strong alignment between continued multi-domain pre-training and downstream objectives. Across diverse tasks, LOGOS consistently matches or outperforms domain-specific baselines, providing preliminary evidence for the feasibility of "one model fits all" in the natural sciences. We train LOGOS models at different scales (1B, 3B, and 8B parameters) and find a consistent positive correlation between model size and performance. This suggests that the future of AI for Science (AI4S) may not lie in building an independent technical stack that is separated from large language models (LLMs). Instead, it may depend on deeply aligning scientific foundation models with LLMs through shared architectures, shared training paradigms, and shared inference infrastructure, so that LLMs can truly become a new entry point for AI4S. We release the model weights and associated resources to facilitate further research.

15.
arXiv (CS.CV) 2026-06-11

MLT-Dedup: Efficient Large-Scale Online Video Deduplication via Multi-Level Representations and Spatial-Temporal Matching

The explosive growth of user-generated video content on online platforms is accompanied by the emergence of numerous near-duplicate videos–videos that are identical or highly similar but differ by partial edits. These duplicates degrade user experience and increase storage and bandwidth costs, making large-scale video deduplication a critical task. Existing video deduplication frameworks face a fundamental challenge in retrieving sufficient high-quality candidates under a limited index budget, as well as trade-offs between efficiency and precision. To address these issues, we propose MLT-Dedup, an efficient large-scale online video deduplication framework with Multi-Level representations and spatial-Temporal matching. Our approach employs a Multi-Level Video Encoder (ML-VE) to extract both fine-grained frame-level and sparse clip-level embeddings: sparse embeddings support efficient candidate retrieval, while fine-grained embeddings are loaded for precise pairwise matching. During matching, we introduce DiF-SiM, a Differential Feature-enhanced Similarity Module capable of locating duplicated temporal segments and providing reliable similarity evidence to support policy-driven deduplication decisions. Extensive experiments on a real-world large-scale platform demonstrate that MLT-Dedup reduces online repetition rates by 91% at 90% precision. Furthermore, our sparse retrieval design achieves a 5x increase in indexing capacity, enabling broader candidate coverage in real-world deployment.

16.
arXiv (quant-ph) 2026-06-19

Electrical Noise Produced by Micron-Sized Particles above a Surface Paul Trap

arXiv:2606.19585v1 Announce Type: new Abstract: Electric field noise produced by the surface of ion trap electrodes reduces the fidelity of quantum computing operations. Despite decades of investigation its microscopic origins remain unclear. Here, we measure electric field noise at trapping locations along the symmetry axis of a linear surface Paul trap. We find that noise levels vary by three orders-of-magnitude in one 600$\,\mu$m section of the trap. Optical and scanning electron microscope images show micron-sized particles close to the trapping locations with the highest noise levels. We find that modeling the particles as a lossy dielectric with a effective loss tangent $\tan\theta=0.33(0.06)$ describes the magnitude of the noise, as well as its spatial and frequency dependence. Our observations may explain the large variation of reported noise levels in literature.

17.
arXiv (CS.LG) 2026-06-16

Semi-Supervised Speech Confidence Detection using Pseudo-Labelling and Whisper Embeddings

arXiv:2606.16505v1 Announce Type: cross Abstract: Understanding speaker confidence is crucial in educational settings, as it can enhance personalised feedback and improve learning outcomes. This study introduces a novel framework for detecting speaker confidence by integrating human-engineered features with embeddings from the Whisper encoder. To address data limitations, a pseudo-labelling technique is employed to expand the labelled dataset, allowing the model to learn from both human-annotated and model-generated labels. The framework combines traditional speech features including pitch, volume, rate of speech, and the presence of disfluencies and stress, with Whisper embeddings, and uses a co-attention mechanism to fuse these representations and achieve an overall accuracy of 75%. This study contributes to advancing speech analysis, enabling applications that support personalised learning and speaking skill development.

18.
arXiv (CS.AI) 2026-06-25

Exposing the Illusion of Erasure in Knowledge Editing for LLMs

arXiv:2606.23276v2 Announce Type: replace-cross Abstract: Knowledge Editing (KE) has emerged as a frontier for updating specific facts in LLMs without costly retraining, but its reliability and underlying mechanisms remain poorly understood. In this work, we examine KE from an adversarial elicitation perspective, revealing that edited knowledge is often not fully erased and continues to surface, with consistent failures observed across diverse model architectures. To explain this behavior, we conduct a mechanistic analysis of popular KE methods. We show that low-rank updates do not overwrite existing knowledge but instead redistribute it within the model's representation space. Furthermore, we find that these methods act as targeted suppression mechanisms that reduce the likelihood of expressing original facts, rather than removing them from the model. Analysis of the loss landscape reveals that edited knowledge lies in narrow, anisotropic regions that are highly sensitive to perturbations, making them highly vulnerable to indirect prompting and adversarial attacks. By exposing these profound architectural vulnerabilities, our work proves that KE algorithms are inherently bypassable and motivates a fundamental reevaluation of how we deploy post-hoc updates in several LLM applications.

19.
medRxiv (Medicine) 2026-06-19

Rumination as a cognitive vulnerability factor in perinatal bereavement: evidence from the CARING study

Purpose. Perinatal loss is associated with a high risk of persistent psychological distress, including prolonged grief, depression, anxiety, and post-traumatic stress symptoms. Cognitive processes such as rumination may play a crucial role in maintaining and amplifying distress following loss, yet their specific contribution in perinatal bereavement remains underexplored. Methods. The CARING (Cognitive Analysis and Rumination INvestigation in perinatal Grief) study employed a cross-sectional design involving 298 parents who experienced perinatal loss within the previous five years. Participants completed an anonymous online survey including measures of depressive rumination (Ruminative Response Scale, RRS), angry rumination (Anger Rumination Scale, ARS), perinatal grief (Perinatal Grief Scale, PGS), general psychopathology (SCL-90), and post-traumatic stress symptoms (NSESSS). Non-parametric analyses were conducted to examine associations between rumination patterns and psychological outcomes. Results. Higher levels of rumination were significantly associated with greater perinatal grief, depressive and anxiety symptoms, and post-traumatic stress. Depressive rumination showed consistently stronger associations with all outcomes compared to angry rumination. Participants presenting both depressive and angry rumination exhibited the highest levels of grief intensity, psychological distress, and PTSD symptoms, suggesting a graded relationship between rumination patterns and severity of distress. Rumination levels were not significantly associated with gestational age at loss or with having received psychological support. Conclusions. Rumination, particularly in its depressive form, appears to function as a transdiagnostic cognitive vulnerability factor in perinatal bereavement. These findings highlight rumination as a potential target for early screening and tailored psychological interventions aimed at reducing long-term distress following perinatal loss.

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

Pythagoras-Prover: Advancing Efficient Formal Proving via Augmented Lean Formalisation

arXiv:2606.12594v1 Announce Type: new Abstract: Modern Lean theorem provers achieve strong performance only with substantial training and inference compute, driven in part by scarce verified proof data and the long reasoning traces of formal proof search, making both supervised fine-tuning (SFT) and sampling expensive. We introduce Pythagoras-Prover, a compute-efficient open-source family of Lean theorem provers built for practical compute budgets. The family spans two generation paradigms: autoregressive models at 4B and 32B parameters, and a first proof-of-concept diffusion-based prover (4B) that iteratively refines Lean proofs at inference time. For training efficiency, we build a Lean-verified corpus stratified into easy, medium, and hard problems for curriculum SFT, so models acquire proof skills progressively from shorter, simpler proofs to longer, harder ones. During SFT, a dynamic proof-reasoning filtering scheme preserves informative proof traces while keeping each instance within an 8k-token context budget. We also introduce Augmented Lean Formalisation (ALF), which expands scarce verified corpora into variants of formal statements, populated via self-distillation for extra training signal without formally verifying every mutated instance. By perturbing known problems while preserving their formal character, ALF reduces reliance on any statement's surface form. Empirically, Pythagoras-Prover-4B surpasses DeepSeek-Prover-V2-671B at pass@32 on MiniF2F-Test (86.1% vs 82.4%) with ~167x fewer parameters, while Pythagoras-Prover-32B sets the open-source state of the art at 93.0% on MiniF2F-Test and solves 93 of 672 PutnamBench problems. We release MiniF2F-ALF, an ALF-mutated contamination-sensitive benchmark on which every evaluated model loses accuracy; here our 32B remains strongest and our 4B matches the prior state of the art, Goedel-Prover-V2-32B.

21.
arXiv (math.PR) 2026-06-16

Pathwise structure of the three-dimensional attractive one-point interaction diffusion

Authors:

arXiv:2606.08008v2 Announce Type: replace Abstract: We study the pathwise behavior of the three-dimensional attractive one-point interaction diffusion whose law was constructed by Cranston, Koralov, Molchanov and Vainberg, corresponding to the singular Schrödinger Hamiltonian \[ \frac12\Delta+\frac{\beta}{2}\delta_0, \qquad \beta>0. \] We identify a local stochastic differential equation satisfied by the process away from the origin and use it to construct a natural submartingale whose increasing component in the Doob-Meyer decomposition is supported on the set of times at which the process visits the origin. In particular, we show that the process visits the origin with positive probability and that the law conditioned on avoiding the origin is three-dimensional Wiener measure.

22.
arXiv (quant-ph) 2026-06-24

Flexible Catalysis

arXiv:2510.01065v2 Announce Type: replace Abstract: In quantum information and computation, a central challenge is to determine which quantum states can be transformed into which others under restricted sets of free operations. While many transformations are impossible directly, catalytic processes can enable otherwise forbidden conversions: an auxiliary quantum state (the catalyst) facilitates the transformation while remaining unchanged. In this work, we introduce flexible catalysis, a generalization in which the catalyst is allowed to transform into a different auxiliary state, provided it remains a valid catalyst. We show that this framework subsumes both standard catalytic and multicopy transformations, and we analyse its advantages across several classes of free operations. In particular, we prove that when the free operations are local unitaries or permutation matrices, flexible catalysis enables state extractions that are unattainable with standard catalysis alone.

23.
arXiv (math.PR) 2026-06-15

Ergodicity for stochastic 2D Boussinesq equations with a highly degenerate pure jump Levy noise

arXiv:2503.18045v2 Announce Type: replace Abstract: This study aims to analyze the ergodicity for stochastic 2D Boussinesq equations and explore the impact of a highly degenerate pure jump L\'{e}vy noise acting only in the temperature equation, where this noise could appear on only a few Fourier modes. By leveraging the equi-continuity of the semigroup established through Malliavin calculus and an analysis of stochastic calculus, together with the weak irreducibility of the solution process, we prove the existence and uniqueness of the invariant measure. Moreover, we overcome the main challenge of establishing time asymptotic smoothing properties of the Markovian dynamics corresponding to this system by conducting spectral analysis of the Malliavin covariance matrix.

24.
medRxiv (Medicine) 2026-06-12

An integrative multi-omics framework identifies epigenetic dysregulation of HAND2 as a potential primary driver of impaired enteric neural crest cell differentiation in Hirschsprung Disease

Hirschsprung disease (HSCR) is a congenital neurodevelopmental disorder characterized by segmental aganglionosis due to impaired developmental processes of enteric neural crest cells (NCCs). Despite being the leading genetic cause of functional intestinal obstruction in early childhood, HSCR represents a paradigmatic challenge in precision medicine: its multifactorial etiology, complex gene-environment interactions and limited resolution of single-modality analyses have long hindered mechanistic understanding and therapeutic translation. Here, we applied an integrative multi-omics approach combining genetic, phenotypic, epigenomic and transcriptomic analyses of matched ganglionic and aganglionic formalin-fixed paraffin-embedded (FFPE) patient tissues, complemented by patient-specific in vitro models. Beyond established genetic contributors, our integrative approach reveals novel regulatory pathways predominantly affecting enteric NCC differentiation, with convergent evidence pointing to epigenetic dysregulation as a primary disease mechanism. Notably, we identified over 1,300 differentially methylated positions between ganglionic and aganglionic FFPE samples, with HAND2 emerging as a key candidate due to multiple hypermethylated sites and consistently reduced expression levels in aganglionic tissues and in vitro models, suggesting a potential role in HSCR pathophysiology. We propose that our multi-omics approach offers a powerful and comprehensive framework for dissecting disease mechanisms. Beyond advancing biological understanding, this strategy holds promise for paving the way for molecularly informed patient stratification and supporting the development of personalized treatment and postoperative management strategies.

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

Detection of patterns in a discrete-outcome sensor network

arXiv:2606.25100v1 Announce Type: new Abstract: A discrete outcome quantum sensor network is one in which we are only interested in which detectors are activated. This can be studied in either the strong or weak interaction regime. If the detectors interact strongly with the environment, it is possible to definitely find which ones were activated. If the interaction is weaker, there is a possibility of making an error, and the object is to minimize the probability of this happening. Here we will be interested in this weaker interaction regime. We will also assume that only certain patterns of detectors will be activated, different patterns being translated versions of a fundamental one. Our object will be to find which pattern has been activated. We will look at both one and two-dimensional detector arrays and make use of techniques from minimum-error state discrimination.