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01.
arXiv (CS.AI) 2026-06-16

Rethinking Scaffolding in LLM Tutors: The Interactional Mismatch Between Benchmarks and Real-World Deployments

arXiv:2606.15766v1 Announce Type: new Abstract: A central pedagogical value evaluated in AI tutor benchmarks is scaffolding: guiding students through graduated steps toward a solution. Alignment and evaluation methods for embedding scaffolding behaviour into chatbots, however, rest on an implicit assumption: that students will take up the scaffolding and engage in the conversation. To examine whether this assumption holds, we introduce an evaluation pipeline around two metrics - Chatbot Scaffolding and Student Uptake - and apply them across nine datasets of 9,490 chats, spanning AI tutor benchmarks and real-world deployments of educational chatbots. Our analysis reveals that while benchmarks assume a high-scaffolding, high-student-uptake environment, students in real-world settings exhibit lower levels of uptake overall - frequently bypassing the chatbot's pedagogical framing to drive the interaction toward their own learning goals at little interpersonal cost. We argue that bypassing scaffolding is not necessarily detrimental; rather, it frequently highlights a mismatch between a chatbot's pedagogical framing and the student's learning goals. To meaningfully evaluate the effectiveness of a chatbot's assistance, future benchmarks must move beyond the assumption that students will simply take up the scaffolding, and instead evaluate how these chatbots navigate diverse learning contexts and student-driven interaction patterns.

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

Temporally Consistent and Controllable Video Generation of 2D Cine CMR via Latent Space Motion Modeling

Cine cardiac magnetic resonance is the gold standard for assessing cardiac function, but the scarcity of public datasets limits the development of advanced data-driven models. To address this limitation, we propose a generative method for synthesizing temporally coherent and anatomically consistent cardiac sequences. Our text-to-video framework decouples cardiac spatial structure from temporal motion. First, a fine-tuned diffusion model synthesizes an initial frame from a clinical text prompt, controlling anatomical features. Then, a latent flow model conditioned on a cardiac phase embedding generates the complete cardiac motion, ensuring spatial consistency and temporal control. Our model generates anatomically and pathologically diverse sequences with high temporal coherence and strong fidelity to input prompts, achieving a FID of 31.68 for image realism and a CLIP score of 31.04 for text-image alignment. These experimental results highlight its potential to produce high-fidelity, on-demand medical data, offering a scalable solution to data scarcity.

04.
medRxiv (Medicine) 2026-06-16

Deployment-readiness audit of calibration, clinical utility, and fairness in perioperative infection prediction

Objective: Clinical risk scores intended to guide patient-level decisions can show strong average performance. However, predicted probabilities can be systematically too high or too low in specific subgroups even when overall performance is strong. We audited deployment readiness of a strong end-of-surgery postoperative infection model across clinically relevant subgroups and tested mitigation strategies in miscalibrated subgroups. Materials and Methods: We analyzed out-of-fold predictions for 10,719 surgical procedures at a Swiss tertiary hospital, with 504 postoperative bacterial infection events. Prespecified axes were recorded sex, age stratum, and an EHR-derived physiological-reserve proxy. Within subgroups and pairwise intersections, we evaluated discrimination, calibration, threshold-specific errors, and decision-curve net benefit at the prespecified operating threshold. We compared group-specific isotonic recalibration with Wasserstein-barycenter postprocessing and demonstrated portability in SUPPORT2. Results: Overall AUROC was 0.876. While sex-marginal discrimination was similar in women and men (0.878 vs 0.875), age and reserve stratification revealed deployment-readiness failures. Calibration-in-the-large ranged from -0.86 in frail patients to -2.47 in non-frail patients. At the 0.10 operating threshold, decision-curve net benefit was positive in frail patients but negative in pre-frail and non-frail patients. Isotonic recalibration corrected average physiological-reserve-stratified calibration without worsening Brier scores, whereas Wasserstein postprocessing worsened calibration in most procedure clusters. Discussion: Discrimination-only or sex-marginal evaluation would have missed subgroup failures with clinical-utility implications. Conclusion: Subgroup fairness audits for clinical deployment should jointly evaluate discrimination, calibration, and utility. We implemented the audit as the open-source isitfair framework for identifying deployment-relevant subgroup failures, comparing mitigation strategies, and generating structured reports.

05.
arXiv (CS.CV) 2026-06-19

SA-VIS: Sparse frame Annotations for training Video Instance Segmentation

Recent online video instance segmentation (VIS) methods have achieved impressive results, thus becoming the preferred approach to segment instances in videos. Despite the resurgence of impressive single image models, the online (or semi-online) VIS approaches outperform single-image models (e.g., based on SAM) by using long sequences of densely annotated frames during training. However,such a training setup of VIS is expensive in the sense of compute as well as dense annotations required. In order to solve these major flaws, we argue that the effective modeling of the instances and their evolution in videos do not require densely annotated frames. To that end, we propose a simple and effective module, called Past-frames Feature Propagation (PFP) which aggregates low-dimensional features from the image encoder of multiple frames. This simple low-compute module provides tremendous learning capability in using sparse video frame labels for end-to-end training. Combined with a light-weight frame-specific Instance Queries, our Sparse frame Annotation VIS (SA-VIS) significantly improves performance over its baseline. Most interestingly, our simple design that avoids complexities effectively bridges the gap in accuracy between training on sparsely and densely annotated video sequences. This translates to a mere 0.4% drop in performance of SA-VIS when using annotations for only 1/5 of the images in the dataset. Empirically, SA-VIS shows strong improvements over the baseline on YouTube-VIS 2019/2021/2022 and Occluded VIS (OVIS) and an over 1% improvement in AP on the state-of-the-art in a limited annotations scenario.

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

Enhancing Many-Body Chaos via Entropy Injection from Environment

arXiv:2606.11784v1 Announce Type: new Abstract: In closed quantum systems, local information spreads throughout the entire system and becomes highly complex under unitary evolution. In contrast, when the system is embedded in an environment, system-environment coupling can transfer information from the system into the environment, thereby reducing the rate of complexity growth within the system. This leads to the environment-induced scrambling transition established in previous works. In this work, we identify entropy injection from the environment as a different physical process that instead enhances many-body chaos. Our setup consists of coupling a system that is already in equilibrium with one environment to another environment, which serves as an entropy reservoir and drives the system into a non-equilibrium state. When entropy flows into the system through either heat transfer or particle transfer, the effective Hilbert space explored by the system enlarges, a mechanism that can enhance many-body chaos. We explicitly demonstrate this idea by constructing a solvable complex Brownian SYK model, in which both the relaxation toward the steady state and the steady-state quantum Lyapunov exponent can be computed analytically. Our results provide a controllable mechanism for tuning quantum scrambling through entropy flow in quantum many-body systems coupled to environments.

07.
arXiv (CS.CV) 2026-06-19

Single-Stage Hierarchical Rectification for Weakly Supervised Histopathology Segmentation

Existing weakly supervised semantic segmentation (WSSS) methods in computational pathology rely on a multi-stage paradigm: class activation map (CAM) generation, offline pseudo-mask refinement, and fully supervised retraining. While established, this decoupled approach presents fundamental limitations. The multi-stage process not only incurs high computational training costs but also suffers from error propagation: local texture biases in shallow CNN layers generate false-positive artifacts that subsequent refinement steps often fail to correct. To address these persistent challenges through a simple yet highly effective approach, we propose the Single-Stage Hierarchical Rectification (SSHR) framework. Rather than passively refining CAMs post-hoc, our method proactively purifies intermediate feature representations during the forward pass. We introduce a Hierarchical Feature Rectification Module (HFRM) that utilizes deep global semantic context to filter out local anomalies in shallow layers. This mechanism generates high-fidelity activation maps directly within a single training loop. Experiments on the LUAD-HistoSeg and BCSS datasets demonstrate that SSHR outperforms state-of-the-art multi-stage methods. Furthermore, SSHR reduces training duration by 2 to 5 times. This efficiency minimizes computational overhead and accelerates clinical translation for large-scale histopathology workflows. The code is available at: https://github.com/trongduc-nguyen/SSHR

08.
arXiv (CS.CV) 2026-06-16

Proact-VL: A Proactive VideoLLM for Real-Time AI Companions

Proactive and real-time interactive experiences are essential for human-like AI companions, yet face three key challenges: (1) achieving low-latency inference under continuous streaming inputs, (2) autonomously deciding when to respond, and (3) controlling both quality and quantity of generated content to meet real-time constraints. In this work, we instantiate AI companions through two gaming scenarios, commentator and guide, selected for their suitability for automatic evaluation. We introduce the Live Gaming Benchmark, a large-scale dataset with three representative scenarios: solo commentary, co-commentary, and user guidance, and present Proact-VL, a general framework that shapes multimodal language models into proactive, real-time interactive agents capable of human-like environment perception and interaction. Extensive experiments show Proact-VL achieves superior response latency and quality while maintaining strong video understanding capabilities, demonstrating its practicality for real-time interactive applications.

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

Agentomics: Economic Foundations for the Valuation, Attribution, and Pricing of AI Agents in Human-AI Workflows

Authors:

arXiv:2606.14769v1 Announce Type: cross Abstract: Agentic AI systems are increasingly being deployed as productive resources in organizational workflows, yet existing evaluation methods primarily measure isolated technical performance rather than economic contribution. This paper introduces Agentomics, a workflow-based framework for valuing, attributing, and pricing human and artificial agents. The framework models a workflow as a configuration of heterogeneous agents whose collective performance determines gross value, deployment cost, reliability, and expected failure loss. Workflow value is treated as a team-level quantity that may include complementarities, substitution effects, bottlenecks, and nonlinear production; additive stage-level value is only a special case. Building on this workflow model, the paper formulates AI deployment as a coalition-formation problem and defines coalition value as the incremental net surplus generated relative to a benchmark human workflow. The Shapley value is then used to attribute economic surplus among participating AI agents, yielding a principled connection among valuation, accountability, and market pricing. The resulting Shapley pricing equilibrium provides a normative benchmark for assessing whether agent prices reflect expected marginal contribution. A security-operations case study illustrates how the framework accounts for productivity gains, deployment costs, reliability losses, and coalition-level complementarities in hybrid human–AI workflows.

10.
arXiv (CS.CV) 2026-06-16

Through-Foliage Surface-Temperature Reconstruction for Early Wildfire Detection

We present a method to reconstruct surface temperatures through forest vegetation by combining signal processing and machine learning, enabling fully automated aerial wildfire monitoring with drones for early fire detection. Synthetic aperture (SA) sensing reduces canopy occlusion but introduces thermal blur. To overcome this, we train a visual state space model to recover subtle thermal signals of partially occluded soil and fire hotspots from blurred data. To address limited real-world training data, we generate realistic surface temperature simulations using a latent diffusion model, temperature augmentation, and procedural thermal forest modeling. On simulated datasets, our method reduces RMSE by 2-2.5 versus conventional thermal and uncorrected SA imaging; in field experiments on hotspots, RMSE improved by 12.8-fold and 2.6-fold, respectively. Our approach also generalizes to other thermal signals, including human signatures, capturing morphology and extent – critical where simple thresholding fails – while conventional imaging struggles with partial occlusion.

11.
arXiv (CS.CV) 2026-06-12

Comparing Commercial Depth Sensor Accuracy for Medical Applications

Depth estimation has numerous medical and surgical applications. We benchmark four depth sensors on a porcine bone specimen, a porcine belly specimen, and a silicone kidney phantom using stylus-sampled references. These objects contain several real-world challenges, including homogeneous surfaces, specular surfaces, and subsurface scattering. The comparison includes stereo, structured-light, and time-of-flight sensors at a distance of approximately 50 cm. Specifically, the Intel RealSense D405 (Intel RealSense, United States), PMD Flexx2 (pmdtechnologies, Germany), Stereolabs ZED 2i (Stereolabs, France), and Zivid 2M+ 60 (Zivid, Norway) are compared. The Zivid 2M+ 60 performed best across all objects and metrics considered in this work. The ZED ranked second for real tissue, but last on the phantom.

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

Fusing Stylometric and Embedding Systems to Estimate Authorship Likelihood Ratios in Japanese

The likelihood ratio framework is widely recognized as the logically and legally sound basis for evidential analysis across forensic sciences, and its importance is increasingly acknowledged in analyses of authorship in textual evidence. To date, however, its application has been confined to English-language texts. Meanwhile, authorship attribution has traditionally relied on a diverse array of stylometric features, even as the rise of pre-trained large language models enables new contextual-embedding approaches. Combining these diverse approaches through fusion promises enhanced performance, yet it has not been applied to integrate stylometric-feature systems with embedding-based systems within the likelihood ratio paradigm. This study is the first to apply likelihood ratio-based forensic text comparison to Japanese digital texts, using ~1,000-character excerpts from blogs, to 1) evaluate system performance and likelihood ratio magnitudes and 2) assess the impact of fusing stylometric-feature systems with embedding-based systems. The results demonstrate that the fused system maintains excellent calibration while 1) increasing consistent-with-fact likelihood ratio magnitudes; 2) decreasing contrary-to-fact likelihood ratio magnitudes and 3) improving overall discriminability. The best-performing fusion achieved a log-likelihood-ratio cost of 0.32484, illustrating both the feasibility of likelihood ratio framework for Japanese and the benefits of fusion across heterogeneous systems.

13.
arXiv (quant-ph) 2026-06-15

Tensor network manifolds and Riemannian fundamental theorem for tensor networks

arXiv:2606.14613v1 Announce Type: cross Abstract: Tensor networks provide a powerful framework for efficiently representing high-dimensional data and many-body quantum states. Endowing tensor networks with a Riemannian manifold structure provides a natural setting for numerical optimization and analysis. A central feature of tensor networks is their gauge freedom, whose characterisation (captured by so-called fundamental theorems) underlies both their intrinsic structure and the design of numerical algorithms. In this work, we study the interaction between the Riemannian manifold structure and the gauge freedom for several families of tensor networks. Using group actions and Riemannian submersions, we establish a Riemannian fundamental theorem for the tensor network families studied.

14.
arXiv (CS.LG) 2026-06-12

One Transit Is All You Need: Detecting Exoplanets Through Learned Stellar Behaviour with EXOVEIL

arXiv:2606.02778v3 Announce Type: replace-cross Abstract: I present EXOVEIL, a transit detection system that learns what a star's brightness should look like and flags when reality disagrees. Unlike existing systems that require phase-folded input, EXOVEIL operates on raw flux time series and can detect planets that transit only once.A Transformer world model, trained on 16,499 Kepler light curves with transit-masked self-supervised learning, predicts expected stellar flux. A matched-filter detector with variance weighting extracts transit signals from the prediction residuals. A learned classifier (XGBoost) separates planets from false positives, achieving AUC 0.938 on Kepler DR25. Applied to single-transit injection-recovery, EXOVEIL recovers 32% of transits at 1000 ppm depth a task where all classification-based systems score 0% by construction. A blind search of 3,737 Kepler stars yields 179 new transit-like signals not present in the DR25 TCE catalogue, including 46 monotransit candidates. Applied withoutretraining to 47 confirmed TESS planets in the PLATO LOPS2 field, EXOVEIL achieves 100% recovery, demonstrating zero-shot cross-mission transfer. At PLATO's 25-second cadence, detection reaches 100 ppm – approaching the Earth-analog regime. I provide the first application of conformal prediction to transit detection (95.9% empirical coverage) and release the system as pip install exoveil with pretrained weights and a candidate catalogue.

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

Epileptic Seizure Detection in Separate Frequency Bands Using Feature Analysis and Graph Convolutional Neural Network (GCN) from Electroencephalogram (EEG) Signals

arXiv:2604.00163v2 Announce Type: replace-cross Abstract: Epileptic seizures are neurological disorders characterized by abnormal and excessive electrical activity in the brain, resulting in recurrent seizure events. Electroencephalogram (EEG) signals are widely used for seizure diagnosis due to their ability to capture temporal and spatial neural dynamics. While recent deep learning methods have achieved high detection accuracy, they often lack interpretability and neurophysiological relevance. This study presents a frequency-aware framework for epileptic seizure detection based on ictal-phase EEG analysis. The raw EEG signals are decomposed into five frequency bands (delta, theta, alpha, lower beta, and higher beta), and eleven discriminative features are extracted from each band. A graph convolutional neural network (GCN) is then employed to model spatial dependencies among EEG electrodes, represented as graph nodes. Experiments on the CHB-MIT scalp EEG dataset demonstrate high detection performance, achieving accuracies of 97.1%, 97.13%, 99.5%, 99.7%, and 51.4% across the respective frequency bands, with an overall broadband accuracy of 99.01%. The results highlight the strong discriminative capability of mid-frequency bands and reveal frequency-specific seizure patterns. The proposed approach improves interpretability and diagnostic precision compared to conventional broadband EEG-based methods.

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

Power Term Polynomial Algebra for Boolean Logic

arXiv:2603.13854v2 Announce Type: replace-cross Abstract: We introduce power term polynomial algebra, a representation language for Boolean formulae designed to bridge conjunctive normal form (CNF) and algebraic normal form (ANF). The language is motivated by the tiling mismatch between these representations: direct CNFANF conversion may cause exponential blowup unless formulas are decomposed into smaller fragments, typically through auxiliary variables and side constraints. In contrast, our framework addresses this mismatch within the representation itself, compactly encoding structured families of monomials while representing CNF clauses directly, thereby avoiding auxiliary variables and constraints at the abstraction level. We formalize the language through power terms and power term polynomials, define their semantics, and show that they admit algebraic operations corresponding to Boolean polynomial addition and multiplication. We prove several key properties of the language: disjunctive clauses admit compact canonical representations; power terms support local shortening and expansion rewrite rules; and products of atomic terms can be systematically rewritten within the language. Together, these results yield a symbolic calculus that enables direct manipulation of formulas without expanding them into ordinary ANF. The resulting framework provides a new intermediate representation and rewriting calculus that bridges clause-based and algebraic reasoning and suggests new directions for structure-aware CNFANF conversion and hybrid reasoning methods.

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

Scene-Adaptive Nonlinear Tone Curves for Pseudo Ground-Truth Generation in Low-Light 3D Gaussian Splatting

Low-light novel view synthesis is challenging because dark multi-view images contain noise, weak structural detail, and compressed dynamic range. Recent 3D Gaussian Splatting (3DGS) methods address these challenges by generating pseudo ground-truth (pseudo-GT) images as supervision targets when paired normal-light references are unavailable. Existing pseudo-GT methods apply a uniform linear gain to all pixels, which clips bright regions while providing insufficient enhancement in dark regions, limiting reconstruction quality. We observe that nonlinear tone mappings, long established in 2D low-light enhancement, have not been explored for pseudo-GT generation in 3D reconstruction. Accordingly, we propose a scene-adaptive nonlinear tone-curve framework that replaces linear pseudo-GT with nonlinear alternatives. The framework introduces percentile-based normalisation for scene-agnostic curve application, a scene-adaptive offset for automatic black-level adjustment, and two complementary curves: Adaptive SoftExp (ASE), a bounded exponential curve, and Adaptive Poly3 (AP3), a data-driven cubic polynomial. The module changes only the pseudo-GT computation and leaves the 3DGS backbone unchanged. Experiments on three benchmarks covering 21 scenes show that both curves consistently outperform the linear baseline with PSNR improvements up to +4.34 dB on LOM and +3.25 dB on RealX3D. Both curves achieve similar performance despite their different mathematical forms, suggesting the improvement is curve-agnostic. Code is available at https://github.com/lvmingzhe/adaptiveToneCurve

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

Democracy in the Era of Artificial Intelligence

arXiv:2606.13026v1 Announce Type: cross Abstract: Interfacing Artificial Intelligence (AI) with democracy is one of the most profound challenges of our times. On the one hand, AI comes with opportunities to overcome long-standing challenges in democracy, such as low participation in deliberative and voting processes with poor representation of people. On the other hand, new risks arise from AI algorithms that are privacy-intrusive, biased, manipulative, spread misinformation and influence election results. Moving beyond the over-simplistic question of whether AI is good or bad for democracy, the Handbook on Democracy in the Era of Artificial Intelligence asks instead: how to upgrade democracies and the principles they are built on, using AI? How to engage with AI and on what terms? Which new values and design principles are required to build democratic resilience? In 34 chapters by 59 authors across the world from different disciplines, we explore how AI can empower collective intelligence for democracy (Part 1) and what is the future of deliberative democracy using large language models and social media (Part 2). We also illustrate the role of AI for building resilient self-governance systems (Part 3) and the challenges of transforming democracy in the age of AI (Part 4). We conclude with broader perspectives (Part 5) that re-imagine the interplay of democracy and AI.

19.
Nature Biotechnology 2026-06-09

Hybrid solid−liquid optics enable scalable, high-resolution light-sheet microscopy across diverse immersion media

Authors:

Many data-driven approaches rely on scalable and affordable three-dimensional (3D) imaging across subcellular to organ scales. Although advances in tissue clearing, expansion microscopy and light-sheet microscopy (LSM) have enabled high-resolution imaging of intact specimens, scalability in sample size, throughput and accessibility remains fundamentally limited by detection optics. Here we introduce hybrid solid−liquid optics (HySIL), a flexible refractive design framework in which a solid optical element and a refractive index (RI)-matched liquid function as a continuous optical system for wavefront correction and numerical aperture enhancement. We implement this framework as SCOPE and Super-SCOPE, enabling submicron-resolution, aberration-corrected LSM using long-working-distance air objectives. We demonstrate high-resolution volumetric imaging across diverse biological contexts, including cleared and expanded mouse, salamander and cavefish brains, human induced pluripotent stem cell (iPSC)-derived brain organoids and large intact human tissues for 3D histopathology. By combining enhanced optical performance with low-cost, long-working-distance and multi-immersion compatibility, HySIL provides an accessible and scalable foundation for next-generation volumetric imaging and data-driven biological discovery. Hybrid solid–liquid optics improve light-sheet imaging of intact biological samples.

20.
arXiv (math.PR) 2026-06-12

Data-driven subsampling rates for diffusion parameter estimation of SDEs

arXiv:2606.13615v1 Announce Type: new Abstract: We study the problem of diffusion parameter estimation for stochastic differential equation (SDE) models in scenarios where data and model are compatible only on specific scales that have yet to be determined. We introduce a simple and efficient method for selecting suitable rates at which given time series data should be subsampled in order to ensure that the statistical structure of the subsampled data is consistent with the behavior of the SDE model on an infinitesimal scale. Our approach is based on analyzing the statistics of the lengths of monotonically increasing or decreasing segments in the subsampled data sequence, which we refer to as monotone runs. As an analytical foundation, we prove for a large class of SDEs with additive noise that the lengths of monotone runs at an infinitesimal scale are approximately geometrically distributed with success probability $1/2$. This universal characterization is employed to derive an automated method for selecting appropriate subsampling rates for given time series data that is directly applicable in real-world scenarios and does not rely on an asymptotic framework of multiscale diffusions. The approach is demonstrated using an application from industrial mathematics concerning surrogate models for fiber lay-down curves in production processes of nonwoven textiles.

21.
arXiv (CS.LG) 2026-06-11

Impact of Connectivity on Laplacian Representations in Reinforcement Learning

arXiv:2603.08558v3 Announce Type: replace Abstract: Learning compact state representations in Markov Decision Processes (MDPs) has proven crucial for addressing the curse of dimensionality in large-scale reinforcement learning (RL) problems. Existing principled approaches leverage structural priors on the MDP by constructing state representations as linear combinations of the state-graph Laplacian eigenvectors. When the transition graph is unknown or the state space is prohibitively large, the graph spectral features can be estimated directly via sample trajectories. In this work, we prove an upper bound on the approximation error of linear value function approximation under the learned spectral features. We show how this error scales with the algebraic connectivity of the state-graph, grounding the approximation quality in the topological structure of the MDP. We further bound the error introduced by the eigenvector estimation itself, leading to an end-to-end error decomposition across the representation learning pipeline. Additionally, our expression of the Laplacian operator for the RL setting, although equivalent to existing ones, prevents some common misunderstandings, of which we show some examples from the literature. Our results hold for general (non-uniform) policies without any assumptions on the symmetry of the induced transition kernel. We validate our theoretical findings with numerical simulations on gridworld environments.

22.
medRxiv (Medicine) 2026-06-17

Proteomics Uncovers Cryptic JPH2 Loss in Paediatric Dilated Cardiomyopathy

Despite recent advances in next-generation sequencing, genetic diagnostic rates for dilated cardiomyopathy (DCM) remain low. Among paediatric DCM, causes are often heritable, with a greater frequency of de novo, recessive and syndromic causes of disease. Novel diagnostic methods are therefore required to solve monogenic cases. To assess the value of proteomics as a diagnostic tool for paediatric DCM, we obtained left ventricle myocardial samples from paediatric patients undergoing heart transplantation at the Royal Children's Hospital, Melbourne. We performed genome sequencing and proteomics and leveraged this multi-omics dataset to uncover the molecular cause of disease in a gene elusive proband. The proband carried a heterozygous JPH2 frameshift variant identified on clinical exome sequencing. However, proteomic analysis showed a pronounced downregulation of JPH2, suggestive of biallelic loss-of-function. Closer inspection of the genomic data revealed a large inversion (~8.34 Mb) with a breakpoint falling within intron 5 of JPH2 that displaces the 3'UTR from the coding transcript. The two variants were confirmed to be in trans using long read DNA sequencing, consistent with a diagnosis of JPH2 autosomal recessive DCM. Finally, we applied RNA sequencing with total RNA library preparation to show that transcripts containing a 3'UTR were reduced to ~10% relative to controls. As a proof-of-principle, we present the first reported use of proteomics from explanted cardiac tissue to provide a genetic diagnosis. Our methodology has broad relevance to patients with genetically unsolved Mendelian diseases, who might undergo organ transplantation as part of clinical management.

23.
PLOS Computational Biology 2026-06-09

Evolution of phenocopying in a dynamical model of developmental trajectories

by Yuuki Matsushita, Archishman Raju Developmental trajectories are known to be canalized, or robust to both environmental and genetic perturbations. However, even when these trajectories are decanalized by an environmental perturbation outside the range of conditions to which they are robust, they often produce phenotypes similar to known mutants, called phenocopies. This correspondence between the effects of environmental and genetic perturbations has received little theoretical attention. Here, we study an abstract regulatory model that is evolved to follow a specific trajectory. We then study the effects of small and large perturbations to the trajectory, both by changing parameters and by perturbing the state at specific times. We find that the phenomenon of phenocopying emerges in evolved trajectories and is not present in a null model of randomly sampled trajectories. Our results suggest that, in this class of dynamic models, evolution can allow high-dimensional phenotypic landscapes to simultaneously exhibit robustness and phenocopying.

24.
arXiv (quant-ph) 2026-06-12

Non-Hermitian skin effect induced by spatial noncommutativity

arXiv:2606.12961v1 Announce Type: new Abstract: In all known schemes for the non-Hermitian skin effect, the non-Hermitian ingredient that drives the skin localization, whether asymmetric hopping or gain and loss, is invariably introduced by hand as an independent model parameter along the skin direction. Here we show that when two spatial coordinates do not commute, the skin effect can break free of this paradigm: a gain-loss potential applied along one coordinate automatically generates non-reciprocity along the other through the coordinate noncommutativity, driving all eigenstates to pile up exponentially at a boundary. We term this phenomenon the noncommutative skin effect. The inverse skin length is proportional to the noncommutativity parameter and is given by an analytic formula, exact in the thermodynamic limit and verified by exact diagonalization of lattice models; the reflection symmetry of the imaginary potential furnishes an exact criterion for the presence or absence of the effect, valid rigorously for finite-size systems. For a sinusoidal imaginary potential, the skin direction of all eigenstates flips collectively at parameter points fixed purely by geometry. Because the flip point is independent of the potential strength, the reversal constitutes a zero-crossing measurement scheme intrinsically robust against systematic errors, from which the noncommutativity parameter can be extracted directly. The qualitative transition of the eigenstates from uniform to exponentially localized renders the effect a nonperturbative probe of spatial noncommutativity, and the Peierls-phase structure of its lattice model is in principle accessible to cold-atom synthetic dimensions, photonic resonators, and topolectrical circuits.

25.
arXiv (math.PR) 2026-06-19

On creating convexity in high dimensions

arXiv:2502.10382v3 Announce Type: replace-cross Abstract: Given a subset $A$ of $\mathbb{R}^n$, we define \begin{align*} \mathrm{conv}_k(A) := \left\{ \lambda_1 s_1 + \cdots + \lambda_k s_k : \lambda_i \in [0,1], \sum_{i=1}^k \lambda_i = 1 , s_i \in A \right\} \end{align*} to be the set of vectors in $\mathbb{R}^n$ that can be written as a $k$-fold convex combination of vectors in $A$. Let $\gamma_n$ denote the standard Gaussian measure on $\mathbb{R}^n$. We show that for every $\varepsilon > 0$, there exists a subset $A$ of $\mathbb{R}^n$ with Gaussian measure $\gamma_n(A) \geq 1- \varepsilon$ such that for all $k = O_\varepsilon(\sqrt{\log \log(n)})$, $\mathrm{conv}_k(A)$ contains no convex set $K$ of Gaussian measure $\gamma_n(K) \geq \varepsilon$. This result acts as a complement to the recent affirmative resolution of Talagrand's convexity conjecture by Hua, Song, and Tudose, which states that a universal dilation of the threefold Minkowski sum $A+A+A$ of a large set $A$ guarantees a large convex subset. Our approach utilises concentration properties of random copulas and the application of optimal transport techniques to the empirical coordinate measures of vectors in high dimensions.