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01.
arXiv (CS.LG) 2026-06-11

Mahalanobis-Guided Latent OOD Detection for Hybrid ES-DRL Control in Time-Varying Systems

arXiv:2606.11474v1 Announce Type: new Abstract: In this paper, we study Mahalanobis-guided latent out-of-distribution (OOD) detection for test-time RL controller switching in nonlinear time-varying systems. RL controllers can quickly control high-dimensional systems within the training distribution, but their performance can degrade when time-varying dynamics produce unseen observations. We consider a combined ES–DRL controller, where RL provides fast in-distribution actions and bounded extremum seeking (ES) provides robust model-independent control under OOD operation. The key challenge is deciding when to switch. We train a variational autoencoder (VAE) on in-distribution beam-profile observations and use Mahalanobis distance in the VAE latent space to detect OOD beam profiles at test time. This OOD decision sets a binary switch that selects either the RL controller or the ES controller. We evaluate the approach in safety-critical particle accelerator control. In this setting, spatial magnet motion creates OOD beam profiles that were not seen during RL training. Visualization of the VAE latent space shows that the proposed method identifies this OOD scenario and provides an interpretable signal for switching between RL and ES in the combined controller.

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

Simulating Students' Java Programming Errors with Large Language Models

Understanding student errors in the programming is a cornerstone of programming education, yet obtaining a representative set of student errors for any newly designed task remains slow and costly, since authentic submissions only accumulate after extensive classroom deployment. This paper explores whether large language models (LLMs) can serve as scalable proxies for students by simulating realistic logical errors in code submissions. Using the CodeWorkout dataset of 74,000+ unique student Java submissions across 37 problems, we evaluate five LLMs under three mainstream prompting strategies: Input-Output (IO), Chain-of-Thought (CoT), and iterative Self-Refine. We assess performance along two key dimensions: diversity (the range of distinct error patterns) and alignment (alignment with authentic student mistakes), and examine how these vary by struggling level of programming tasks. Our quantitative findings reveal that while all models generate diverse errors, their alignment to human submissions diverges: Claude Sonnet 4 achieves the most balanced performance. In addition, we conducted a blinded expert annotation study (N = 401) comparing synthetic and authentic errors. This qualitative analysis confirms that the generated errors are functionally indistinguishable from authentic student errors. Moreover, higher-struggling-level problems elicit more diverse but less student-like errors. These results highlight trade-offs in using LLMs to simulate human learners and suggest design considerations for integrating synthetic errors into teachable agents, intelligent tutoring systems, and large-scale learning analytics.

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

Benchmarking Large Vision-Language Models on Fine-Grained Image Tasks: From Evaluation to Diagnosis

Recent advancements in Large Vision-Language Models (LVLMs) have demonstrated remarkable multimodal perception and reasoning capabilities. While numerous benchmarks have evaluated LVLMs from holistic or task-specific perspectives, their capabilities on fine-grained image tasks-fundamental to computer vision-remain insufficiently understood. To address this gap, we introduce FG-BMK, a comprehensive fine-grained evaluation benchmark containing 1.01 million questions and 0.28 million images, covering diverse scenarios from common object-centric domains to specialized domains. FG-BMK jointly evaluates dialogue-level fine-grained semantic recognition and feature-level visual discriminability through human-oriented and machine-oriented paradigms, enabling diagnostic analysis of whether LVLM failures arise from insufficient visual representations, weak visual-to-semantic grounding, or limited fine-grained knowledge. Through extensive experiments on a diverse set of representative LVLMs/VLMs, we find that current LVLMs remain inadequate fine-grained recognizers, with failures arising from intertwined bottlenecks in visual representations, semantic grounding, modality alignment, and category-level knowledge. We further analyze training design factors for improving fine-grained capabilities and examine how visual and linguistic perturbations affect LVLM predictions. These findings provide diagnostic insights into the limitations of current LVLMs and offer guidance for future data construction and model design in developing more reliable LVLMs for fine-grained visual tasks. Our code is open-source and available at https://fg-bmk.github.io/.

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

Show the Signal, Hide the Noise: Spectral Forcing for Pixel-Space Diffusion

Pixel-space diffusion models are trained on full-bandwidth noisy images, yet the useful signal available to the denoiser is strongly frequency dependent. Under rectified-flow diffusion and natural-image power-law spectra, the per-band data-to-noise contour $k^{*}(t) = (1-t)^{-2/\alpha}$ separates a signal-bearing low-frequency region from a noise-dominated high-frequency region at each time $t$. We show that this implicit coarse-to-fine structure is not merely descriptive: it induces a capacity-allocation problem. A standard pixel-space denoiser must discover the moving bandwidth boundary internally and can spend computation on frequency-time regions where the optimal prediction collapses to deterministic baselines rather than data-distribution modeling. To make this boundary explicit, we introduce Spectral Forcing, a parameter-free, time-conditional 2D-DCT low-pass operator applied to the noisy input before the patch embedder. Its cutoff expands monotonically with the diffusion time and becomes the identity at the data endpoint. Through controlled synthetic experiments, we identify the regime in which the operator is beneficial: coarse patch tokenization and data whose high-frequency content is predominantly noise rather than essential signal. On ImageNet-256 with JiT-700M/32, Spectral Forcing consistently improves both FID and Inception Score across different training epochs, demonstrating robust gains throughout training; at finer tokenization, the spectral forcing is still competitive. We further insert the unchanged operator into SenseNova-U1, a unified text-to-image model, where it improves DPG-Bench and GenEval, showing that the input-side spectral prior transfers beyond class-conditional generation. These results suggest a route to capacity-efficient pixel-space diffusion by showing the signal and hiding the noise.

05.
arXiv (quant-ph) 2026-06-19

Ultrafast nonadiabatic dynamics of tetraphenylsubstituted nitrogen-based heterocycles

arXiv:2604.16897v2 Announce Type: replace-cross Abstract: Tetraphenylpyrazine (TPP) and 2,3,4,5-tetraphenyl-1H-pyrrole (TePP) are closely related heterocycles bearing four phenyl substituents, whose structural similarity makes them a useful pair for comparing how intramolecular flexibility influences excited-state relaxation and emission in the gas phase and in the solid state. TPP is a prototypical solid-state luminescence enhancement (SLE) emitter, exhibiting a markedly increased quantum yield upon molecular aggregation. In contrast, TePP displays similar quantum yields in solution and solid state, characteristic of dual-state emission (DSE). This behaviour indicates that intramolecular rotations are already significantly hindered in the isolated-molecule regime, consistent with our previous observations for TPP and other solid-state emitters (Hernández-Rodríguez et al., ChemPhysChem, 2024, 25, e202400563). To unravel the excited-state dynamics underlying this contrasting behaviour, we performed mixed quantum-classical trajectory simulations on a single molecule of TPP and TePP employing the surface-hopping method. Twelve singlet states were included at the TD-B3LYP-D3/def2-SVP level, which were previously benchmarked against coupled cluster methods. Simulated observables such as gas phase ultrafast electron diffraction (GUED) and time-resolved fluorescence (TR-FL) signals allow us to dissect the distinct deactivation pathways operating in both systems in the gas phase, while also providing mechanistic insight into how these pathways are expected to evolve in solution and solid-state environments.

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

CycliST: A Video Language Model Benchmark for Reasoning on Cyclical State Transitions

We present CycliST, a novel benchmark dataset designed to evaluate Video Language Models (VLM) on their ability for textual reasoning over cyclical state transitions. CycliST captures fundamental aspects of real-world processes by generating synthetic, richly structured video sequences featuring periodic patterns in object motion and visual attributes. CycliST employs a tiered evaluation system that progressively increases difficulty through variations in the number of cyclic objects, scene clutter, and lighting conditions, challenging state-of-the-art models on their spatio-temporal cognition. We conduct extensive experiments with current state-of-the-art VLMs, both open-source and proprietary, and reveal their limitations in generalizing to cyclical dynamics such as linear and orbital motion, as well as time-dependent changes in visual attributes like color and scale. Our results demonstrate that present-day VLMs struggle to reliably detect and exploit cyclic patterns, lack a notion of temporal understanding, and are unable to extract quantitative insights from scenes, such as the number of objects in motion, highlighting a significant technical gap that needs to be addressed. More specifically, we find no single model consistently leads in performance: neither size nor architecture correlates strongly with outcomes, and no model succeeds equally well across all tasks. By providing a targeted challenge and a comprehensive evaluation framework, CycliST paves the way for visual reasoning models that surpass the state-of-the-art in understanding periodic patterns.

07.
arXiv (quant-ph) 2026-06-19

Passive-User Bell-State Loop-Back Key Establishment without Quantum Detectors at the User Nodes

arXiv:2606.19551v1 Announce Type: new Abstract: We propose and analyze a Bell-state extension of the Loop-Back quantum key distribution architecture for secret-key establishment between two passive users that do not require quantum transmitters or quantum detectors. In the proposed setting, a single active station, Alice, provides the entangled-state infrastructure, retains one qubit of an initially prepared Bell pair, and sends the traveling subsystem through two passive users, denoted by $B_1$ and $B_2$. Each passive user applies a local Pauli operation to the same traveling subsystem, so that the operation observed by Alice is only the effective composition $U_{\mathrm{eff}}=U_2U_1$. After the subsystem returns, Alice performs a Bell-state measurement and, using her private knowledge of the initial Bell state, deterministically identifies the effective Pauli operation. However, the individual factors $U_1$ and $U_2$ remain algebraically hidden from Alice whenever the local choices are uniformly and independently selected. The public effective operation acts as a parity-like constraint: each passive user can infer the operation applied by the other from its own private choice, while the active station learns only the global composition. This construction transfers the essential distributed-transformation mechanism of passive-user Loop-Back QKD to the entangled-state regime. Unlike single-qubit passive-user schemes, whose useful events are intrinsically post-selected, the Bell-state version is limited primarily by the success probability of the Bell-state measurement. We discuss the algebraic structure of the protocol, its interpretation as an infrastructure-assisted mediated key-establishment mechanism, and the physical assumptions required to protect passive Pauli modulators against active injection or Trojan-horse-type attacks.

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

Calibration Without Comprehension: Diagnosing the Limits of Fine-Tuning LLMs for Vulnerability Detection in Systems Software

arXiv:2606.20502v1 Announce Type: cross Abstract: Whether LLMs scoring well on vulnerability benchmarks genuinely reason about security or merely pattern-match on contaminated data remains unresolved. We present CWE-Trace, a framework for LLM vulnerability detection built from 834 manually curated Linux kernel samples spanning 74 CWEs. The framework enforces a strict temporal split (pre-2025 historical set / post-cutoff leakage-free set), preserves context-aware vulnerable–patched pairs, and introduces two diagnostic metrics: the Directional Failure Index (DFI) and Hierarchical Distance and Direction (HDD). We evaluate eight vanilla LLMs and 15 LoRA fine-tuned variants across non-targeted detection, targeted detection, and CWE classification. Our analysis yields two key results. First, data contamination provides no measurable advantage. Function-level analysis shows that 84% of nominally contaminated samples carry no usable memorization signal: vulnerable functions are absent or cross-mapped across datasets, and ~31% of contaminated samples carry CWE misclassification. Second, backbone directional priors dominate fine-tuning. Models exhibit stable, systematic failure modes (DFI ranging from -85.5 to +94.8 pp) that persist from historical to post-cutoff data and resist correction. Fine-tuning shifts the output threshold without changing the decision policy. This is calibration without comprehension: output distributions adapt to training data while the underlying security reasoning remains absent. The weakest backbone at binary detection (DeepSeek-R1) gains the most in coarse CWE classification, revealing that detection and understanding are decoupled capabilities. The best detection score reaches only 52.1% (+2.1 pp above chance); exact CWE ranking remains below 1.3% Top-1 accuracy, confirming that current LLMs lack reliable security reasoning for systems software, regardless of fine-tuning strategy.

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

Decomposing one-class support vector machine into an ensemble of one-data support vector machines

arXiv:2606.16002v1 Announce Type: new Abstract: One-class classification (OCC) is a classification problem in which the training data contains only one class. The one-class support vector machine (OCSVM) is one of the most competitive OCC algorithms. However, OCSVM has scalability issues with large-scale datasets. This paper proposes the acceleration strategy of OCSVM. The idea is to decompose the dataset into samples and train OCSVM models for single data points. Subsequently, ensemble learning is applied to combine all models to compute the OCSVM model for the dataset. In addition, further acceleration is achieved through a data-reduction strategy with an OCSVM model trained on the average of the training samples. The experiment compared the proposal and traditional OCSVM using the Python package. The proposed strategy is faster than traditional OCSVM, while achieving similar classification results. Moreover, the proposed strategy can create one-to-one correspondence between samples and models. Source code is uploaded at https://github.com/ToshiHayashi/ODSVM

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

ActiveSAM: Image-Conditional Class Pruning for Fast and Accurate Open-Vocabulary Segmentation

Segment Anything Model 3 (SAM 3) provides a strong frozen backbone for concept-prompted segmentation, but applying it directly to open-vocabulary semantic segmentation (OVSS) is inefficient: full-resolution decoding is typically run over the entire dataset vocabulary, whereas each image contains only a small active subset of classes. We introduce ActiveSAM, a training-free, zero-shot inference framework that turns SAM 3 into an active-vocabulary segmenter. ActiveSAM first canonicalizes and expands class prompts, then estimates an image-conditioned active set from a low-resolution presence preview. Only the retained classes are decoded at full resolution, using bucketed prompt multiplexing with the frozen SAM 3 decoder. The preview stage uses only class-presence evidence and skips unnecessary segmentation-head computation, while the final stage applies margin-aware background calibration to suppress low-confidence pixels. ActiveSAM requires no target-dataset training, no weight updates, and no oracle class-presence labels. Across eight OVSS benchmarks, ActiveSAM improves the speed-accuracy tradeoff of training-free open-vocabulary semantic segmentation, outperforming the current state-of-the-art SegEarth-OV3 by approximately +1.4 mIoU on average while running up to 5.5x faster on large-vocabulary datasets. ActiveSAM also demonstrates the strongest robustness under image corruption that simulates real-world distribution shift, making it well-suited for deployment in noisy-input domains such as autonomous driving and embodied AI. Code is available at https://github.com/VILA-Lab/ActiveSAM.

11.
medRxiv (Medicine) 2026-06-18

Distinct Neuronal, Proliferative, and Secretory Pathways are Perturbed in Cancer Survivors with Depressive Symptoms

Introduction Depression is highly prevalent among cancer survivors and may be biologically distinct, although clinical studies investigating these mechanisms remain limited. Thus, the aims of this study were to (1) identify perturbed biological pathways associated with depressive symptom severity in cancer survivors, and (2) investigate whether these pathways are common or distinct to those perturbed in an age-matched non-cancer cohort. Methods We analyzed cross-sectional self-reported and transcriptomic data from the Multi-Ethnic Study of Atherosclerosis (PHD #39341). Cancer survivors and an age-matched non-cancer cohort (target ratio 1:2) were identified. The 20-item Center for Epidemiologic Studies Depression Scale (CES-D) was used to split participants into low (CES-D

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

DecNefSimulator: A Modular, Interpretable Framework for Decoded Neurofeedback Simulation Using Generative Models

arXiv:2511.14555v4 Announce Type: replace-cross Abstract: Decoded Neurofeedback (DecNef) is a promising non-invasive approach to brain modulation with wide-ranging applications in neuromedicine and cognitive neuroscience. However, progress in DecNef research remains constrained by subject-dependent learning variability, reliance on indirect measures to quantify progress, and the high cost and time demands of experimentation. We present DecNefSimulator, a modular and interpretable simulation framework that formalizes DecNef as a machine learning problem. Beyond providing a virtual laboratory, DecNefSimulator enables researchers to model, analyze and understand neurofeedback dynamics. Using latent variable generative models as simulated participants, DecNefSimulator allows direct observation of internal cognitive states and systematic evaluation of how different protocol designs and subject characteristics influence learning. We demonstrate how this approach can (i) reproduce empirical phenomena of DecNef learning, (ii) identify conditions under which DecNef feedback fails to induce learning, and (iii) guide the design of more robust and reliable DecNef protocols in silico before human implementation. In summary, DecNefSimulator bridges computational modeling and cognitive neuroscience, offering a principled foundation for methodological innovation, robust protocol design, and ultimately, a deeper understanding of DecNef-based brain modulation.

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

An Extensible and Lightweight Unified Architecture for Demosaicing Pixel-bin Image Sensors

Pixel-bin image sensors are becoming the default choice for smartphone cameras due to their resolution vs light-gathering trade-off. However, their larger inter-color separation compared to the Bayer color filter array (CFA) makes them challenging to demosaic. Furthermore, existing deep learning-based demosaicing methods are CFA-specific, requiring multiple individual models that take up precious onboard resources and demand larger development and maintenance efforts. In this work, we propose a modular unified architecture for demosaicing various pixel-bin sensors that provides higher image quality while being extensible and lightweight. Additionally, to enable plug-and-play operation, we introduce a learning-free CFA-identification module to detect the CFA type of raw data accurately.

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

On the Role of Computation in Reinforcement Learning

arXiv:2602.05999v3 Announce Type: replace Abstract: How does the amount of compute available to a reinforcement learning (RL) policy affect its learning? Can policies using a fixed amount of parameters, still benefit from additional compute? The standard RL framework does not provide a language to answer these questions formally. Empirically, deep RL policies are often parameterized as neural networks with static architectures, conflating the amount of compute and the number of parameters. In this paper, we formalize compute bounded policies and prove that policies which use more compute can solve problems and generalize to longer-horizon tasks that are outside the scope of policies with less compute. Building on prior work in algorithmic learning and model-free planning, we propose a minimal architecture that can use a variable amount of compute. Our experiments complement our theory. On a set 31 different tasks spanning online and offline RL, we show that $(1)$ this architecture achieves stronger performance simply by using more compute, and $(2)$ stronger generalization on longer-horizon test tasks compared to standard feedforward networks or deep residual network using up to 5 times more parameters.

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

Operads for compositional reasoning in LLMs

Question decomposition, i.e. breaking a complex query into simpler sub-queries whose answers are composed to produce a final answer, is a widely used strategy for improving LLM reasoning, yet it currently lacks a rigorous mathematical foundation. In this paper, we propose operads, mathematical structures that model many-in, one-out operations and compositions thereof, as a natural framework for describing question decomposition. We define the questions operad $Q$, in which operations correspond to question templates and composition corresponds to substitution of sub-answers, and show how QA models can be interpreted as algebras over $Q$. Beyond reframing existing practice, this operadic perspective points toward new methods, in particular a notion of operadic consistency, which measures whether a QA model's answers agree across the partial collapses of a question decomposition tree. Empirical evaluation of operadic consistency is reported in our companion paper (Bottman, Liu, and Richardson, 2026), which finds it strongly correlated with accuracy across twelve LLMs and four multi-hop QA datasets and outperforming standard temperature-based self-consistency baselines. We argue that operads are the natural mathematical home for question decomposition, and that invariants such as operadic consistency open new directions for analyzing and improving the reliability of multi-step reasoning.

17.
medRxiv (Medicine) 2026-06-12

Heterogeneity of Treatment Effect of Aspirin and Clinically Significant Bleeding in Older Adults

Aim: The global population of older adults is growing, and older age is linked to higher bleeding risk. Although guidelines discourage aspirin for primary prevention in healthy older adults due to bleeding harms outweighing benefits, many continue taking it without a clear indication. It remains unclear whether all older adults face uniform aspirin-related bleeding risk or if certain subgroups are more vulnerable. Methods: We analyzed data from 19,114 ASPREE trial participants to develop machine learning models using 116 baseline variables. Random forest (RF) and random survival forest (RSF) models predicted 5-year bleeding risk, and participants were stratified into low, intermediate, and high-risk groups based on the 20th and 80th percentiles of predicted risk. We assessed heterogeneity of treatment effect (HTE) by testing treatment-by-risk group interactions on the relative scale using Fine-Gray models, and on the absolute scale using observed 5-year cumulative incidence rates. Results: Over a median follow-up of 4.7 years, 626 major bleeding events occurred. The RF model had moderate discrimination (AUC = 0.65, 95% CI: 0.63-0.67) and good calibration (Brier = 0.032, 95% CI: 0.029-0.034). Statistically significant HTE was observed on the relative scale, with the greatest relative increase in bleeding risk seen in the low-risk group (subdistribution hazard ratio = 2.26, 95% CI: 1.27-4.01). On the absolute scale, low-risk participants experienced higher bleeding with aspirin (absolute risk difference (ARD) = 1.17%, 95% CI: 0.37-1.95), but heterogeneity in ARDs was not statistically significant (Cochran's Q p > 0.45). Similar findings were observed when using the RSF model. Conclusion: Participants at lowest baseline bleeding risk experienced the greatest relative increase in bleeding risk with aspirin therapy. We found statistically significant heterogeneity in treatment effects on the relative but not absolute scale. These findings support an individualized, risk-based approach to aspirin therapy decision-making in older adults.

18.
arXiv (CS.AI) 2026-06-16

GRAPE: Guided Parameter-Space Evolution for Compact Adversarial Robustness

arXiv:2606.14865v1 Announce Type: cross Abstract: Adversarial Training (AT) improves neural network robustness, but most methods train a fixed parameter space from the start. This paper asks whether the order in which parameters become optimizable can affect the final robust solution, even when the final architecture or computation budget is controlled. We propose GRAPE, Guided Parameter-Space Evolution, a training framework for compact adversarial robustness. GRAPE combines parameter-space stabilization with progressive hidden expansion: it stabilizes robust optimization in the currently exposed space, gradually releases new optimizable dimensions, and uses an adversarial spectral utilization score to guide newly released capacity toward high-pressure modules. In contrast to fixed-structure AT, GRAPE treats robust model learning as a process of progressive parameter-space exposure and evolution. Under the standard $\ell_\infty$ threat model on CIFAR-10, with fixed-structure ResNet-18 AT as a controlled reference, GRAPE improves PGD-20 robust accuracy from 51.70% to 56.94% at a nearly matched computation budget with a FLOPs ratio of 1.009x, while reducing parameter count by about 21.4%. A sequential grow variant with the same final ResNet-18 architecture reaches 56.52% PGD-20 robust accuracy, indicating that the gain is not only due to final architecture differences but also to the parameter-space exposure path. These results suggest that guided parameter-space evolution can yield compact and robust parameter configurations under matched computation.

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

FutureOmni: Evaluating Future Forecasting from Omni-Modal Context for Multimodal LLMs

Although Multimodal Large Language Models (MLLMs) demonstrate strong omni-modal perception, their ability to forecast future events from audio-visual cues remains largely unexplored, as existing benchmarks focus mainly on retrospective understanding. To bridge this gap, we introduce FutureOmni, the first benchmark designed to evaluate omni-modal future forecasting from audio-visual environments. The evaluated models are required to perform cross-modal causal and temporal reasoning, as well as effectively leverage internal knowledge to predict future events. FutureOmni is constructed via a scalable LLM-assisted, human-in-the-loop pipeline and contains 919 videos and 1,034 multiple-choice QA pairs across 8 primary domains. Evaluations on 13 omni-modal and 7 video-only models show that current systems struggle with audio-visual future prediction, particularly in speech-heavy scenarios, with the best accuracy of 64.8% achieved by Gemini 3 Flash. To mitigate this limitation, we curate a 7K-sample instruction-tuning dataset and propose an Omni-Modal Future Forecasting (OFF) training strategy. Evaluations on FutureOmni and popular audio-visual and video-only benchmarks demonstrate that OFF enhances future forecasting and generalization. We publicly release all code (https://github.com/OpenMOSS/FutureOmni) and datasets (https://huggingface.co/datasets/OpenMOSS-Team/FutureOmni).

20.
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.

21.
arXiv (math.PR) 2026-06-18

Evolution of Conditional Entropy for Diffusion Dynamics on Graphs

arXiv:2510.19441v2 Announce Type: replace-cross Abstract: The modeling of diffusion processes on graphs is the basis for many network science and machine learning approaches. Entropic measures of network-based diffusion have recently been employed to investigate the reversibility of these processes and the diversity of the modeled systems. While results about their steady state are well-known, very few exact results about their finite-time evolution exist. Here, we introduce the conditional entropy of heat diffusion in graphs, and outline a mathematical framework that contextualizes diffusion and conditional entropy within the theories of continuous-time Markov chains and information theory. In particular, we highlight that this entropic measure satisfies an information-theoretical version of the second law of thermodynamics, thereby providing a parallelism between diffusion dynamics on networks and their physical counterparts. Furthermore, we obtain explicit results for its evolution on complete, path, and circulant graphs, as well as a mean-field approximation for Erdös-Rényi graphs. We also obtain asymptotic results for general networks and provide bounds for the evolution of conditional entropy. Finally, we experimentally demonstrate several properties of conditional entropy for diffusion over random graphs, such as the Watts-Strogatz model.

22.
arXiv (CS.LG) 2026-06-16

Circuit Tracing in Autoregressive Protein Language Models

arXiv:2606.16044v1 Announce Type: new Abstract: Protein language models (pLMs) can generate novel protein sequences with properties beyond those observed in nature, yet the mechanisms underlying protein generation remain poorly understood. Existing mechanistic interpretability methods based on sparse autoencoders and transcoders primarily focus on protein representation learning models and do not capture the computation required for autoregressive generation. Here, we introduce ProGenMech, a mechanistic interpretability framework for generative protein language models that extends cross-layer transcoders (CLTs) to ProGen3, a sparse Mixture-of-Experts model trained for both causal generation and span infilling. Unlike per-layer approaches, CLTs reconstruct each layer using sparse latent variables from all preceding layers, enabling faithful recovery of inter-layer generative computation. We further develop a zero-shot circuit discovery framework to identify sparse latent circuits responsible for protein generation and fitness prediction. In causal generation and zero-shot fitness estimation tasks, ProGenMech outperforms local transcoder baselines in recovering ProGen3's probability distribution and functional scoring behavior, while matching the original model's generative distribution in span infilling tasks. Moreover, the recovered circuits reveal biologically meaningful motifs and functional regions associated with conserved sequence patterns and protein fitness landscapes, establishing a foundation for interpretable and steerable protein generation.

23.
arXiv (quant-ph) 2026-06-17

From Period Finding to Lattice Sampling: Experimental Insights into Shor's and Regev's Factoring Algorithms

arXiv:2606.17647v1 Announce Type: new Abstract: Quantum algorithms for integer factorization represent one of the most prominent applications of quantum computation, with far-reaching implications for modern cryptography. While Shor's algorithm provides a polynomial-time solution in the ideal quantum model, its practical implementation is severely constrained by the limitations of current noisy intermediate-scale quantum (NISQ) hardware. These constraints have motivated the exploration of alternative factoring algorithms with different structural and resource trade-offs. In this work, we present an experimental study of Regev's quantum factoring algorithm, implemented on real quantum hardware, and compare its behavior with that of Shor's algorithm under analogous conditions. Focusing on the case N = 15, we execute both algorithms on the QMIO quantum computer at the Centro de Supercomputacion de Galicia (CESGA) and contrast the results with one of IBM's open-access quantum computers and ideal simulations. This parallel execution enables a low-level comparison of the two algorithms, highlighting how their respective quantum implementations interact with hardware noise, limited circuit depth, and finite sampling. Our analysis emphasizes the different ways in which Shor's and Regev's algorithms encode arithmetic structure into quantum states through Fourier sampling in one and higher dimensions, respectively, and how these differences manifest in experimental outcomes. Although neither algorithm demonstrates a practical advantage in the small N regime, the results provide insight into their relative robustness and failure modes on contemporary quantum devices. This study illustrates the value of experimental benchmarking of alternative quantum factoring algorithms as a means of understanding the practical implications of algorithmic design choices in the NISQ era.

24.
arXiv (CS.AI) 2026-06-15

Federated Causal Inference from Multi-Site Observational Data via Propensity Score Aggregation

arXiv:2505.17961v4 Announce Type: replace-cross Abstract: Causal inference typically assumes centralized access to individual-level data. Yet, in practice, data are often decentralized across multiple sites, making centralization infeasible due to privacy, logistical, or legal constraints. We address this problem by estimating the Average Treatment Effect (ATE) from decentralized observational data via a Federated Learning (FL) approach, allowing inference through the exchange of aggregate statistics rather than individual-level data. We propose a novel method to estimate propensity scores via a federated weighted average of local scores using Membership Weights (MW), defined as probabilities of site membership conditional on covariates. MW can be flexibly estimated with parametric or non-parametric classification models using standard FL algorithms. The resulting propensity scores are used to construct Federated Inverse Propensity Weighting (Fed-IPW) and Augmented IPW (Fed-AIPW) estimators. In contrast to meta-analysis methods, which fail when any site violates positivity, our approach exploits heterogeneity in treatment assignment across sites to improve overlap. We show that Fed-IPW and Fed-AIPW perform well under site-level heterogeneity in sample sizes, treatment mechanisms, and covariate distributions. Theoretical analysis and experiments on simulated and real-world data demonstrate clear advantages over meta-analysis and related approaches.

25.
arXiv (CS.CV) 2026-06-16

SpatialAvatar-0: High-Quality 4D Head Avatar with Multi-Stage Reconstruction

High-quality 4D head avatars from one or a few source portraits are central to telepresence, AR/VR, and digital-human interaction. 3D Gaussian Splatting (3DGS) has emerged as the dominant representation, with two complementary regimes (generalizable feed-forward predictors and per-subject refiners) maturing in parallel. However, existing feed-forward predictors are trained on a single dataset family with a hard-coded source count, inheriting the corresponding domain bias. Per-subject refiners require 300K–600K iterations and rely on adaptive densification that destroys upstream Gaussian layouts, preventing the two regimes from sharing a representation end-to-end. To bridge both regimes we propose SpatialAvatar-0 on a shared FLAME-mesh-bound Gaussian representation: a feed-forward generator with a parameter-free K-source mean-pool and a monocular-temporal to multi-view-spatial two-phase schedule that anchors against identity-prior collapse onto the smaller multi-view set. We further introduce a 10K-iter layout-preserving per-subject refinement loop that freezes the FLAME-binding and Gaussian count and replaces densification with a three-component anti-spike regularization. On VFHQ/HDTF cross-domain zero-shot we surpass the in-domain leader GAGAvatar by +1.5 dB PSNR despite never training on either test domain, and on the SplattingAvatar monocular benchmark we lead every reported metric, surpassing the 300K-iter GeoAvatar by +1.3 dB PSNR at up to 60x shorter per-subject schedule than common SOTA baselines. Website: https://spatialwalk.github.io/SpatialAvatar-0.