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

OGPO: Sample Efficient Full-Finetuning of Generative Control Policies

arXiv:2605.03065v2 Announce Type: replace Abstract: Generative control policies (GCPs), such as diffusion- and flow-based control policies, have emerged as effective parameterizations for robot learning. This work introduces Off-policy Generative Policy Optimization (OGPO), a sample-efficient algorithm for finetuning GCPs that maintains off-policy critic networks to maximize data reuse and propagate policy gradients through the full generative process of the policy via a modified PPO objective, using critics as the terminal reward. OGPO achieves state-of-the-art performance on manipulation tasks spanning multi-task settings, high-precision insertion, and dexterous control. To our knowledge, it is also the only method that can fine-tune poorly-initialized behavior cloning policies to near full task-success with no expert data in the online replay buffer, and does so with few task-specific hyperparameter tuning. Through extensive empirical investigations, we demonstrate that OGPO drastically outperforms methods alternatives on policy steering and learning residual corrections, and identify the key mechanisms behind its performance. We further introduce practical stabilization tricks, including success-buffer regularization, two-sided conservative advantages, and Q-variance reduction, to mitigate critic over-exploitation across state- and pixel-based settings. Beyond proposing OGPO, we conduct a systematic empirical study of GCP finetuning, identifying the stabilizing mechanisms and failure modes that govern successful off-policy full-policy improvement.

02.
PLOS Medicine 2026-06-12

Comparison of count-based and clustering definitions of multimorbidity and their association with prevalence of multimorbidity, health profiles, and mortality: A cohort study of UK Biobank participants

by Gabriella C. Silva, Aurore Fayosse, Louis Jacob, Séverine Sabia, Archana Singh-Manoux, Benjamin Landré Background Multimorbidity, the presence of several chronic conditions, is linked to higher mortality and healthcare use and thus poses a major challenge for aging populations. While most studies rely on simple counts of conditions, clustering approaches have been proposed to describe patterns of co-occurring diseases. We aimed to evaluate the extent to which these methodological choices influence prevalence and association with health profiles and mortality. Methods and findings Using UK Biobank baseline data (n = 474,397), collected between 2006 and 2010, we compared six count-based definitions of multimorbidity based on different condition lists (extended, most prevalent, or body systems) and thresholds (≥2 versus ≥3 conditions). We also applied a clustering analysis to characterize subtypes of multimorbidity among participants with at least two chronic conditions. We compared prevalence and associations with concurrent health outcomes (polypharmacy, self-rated health, frailty, falls, surgery, chronic pain), blood-based measures (C-reactive protein, Cystatin-C, HDL, LDL Cholesterol, IGF-1), and 3- and 10-year mortality risks. Analyses were undertaken separately in men and women using multivariable regression models adjusted for sociodemographic characteristics and body mass index. Multimorbidity prevalence ranged from 1.0% (cluster-based) to 35.3% (count-based). Count-based definitions using lists with more conditions yielded higher prevalence. Higher thresholds identified more severe health profiles on all measured health outcomes, blood-based measures, but not higher mortality risks. Associations with blood-based measures were more pronounced using clustering, with the highest differences from the standard definition distributed across clusters. Odds ratios for 3-year mortality ranged from 1.44 [1.26; 1.64] to 4.60 [3.73; 5.62] for men and 1.35 [1.07; 1.69] to 3.83 [2.78; 5.14] for women. For 10-year mortality, they ranged from 1.42 [1.34; 1.50] to 3.86 [3.46; 4.30] in men and 1.29 [1.21; 1.39] to 3.33 [2.93; 3.77] for women, with clustering identifying groups with low prevalence and high mortality risks. Findings should be interpreted in light of the selected nature of the UK Biobank cohort and the cross-sectional assessment of several health indicators. Conclusion Operational definitions of multimorbidity substantially influence prevalence estimates, while associations with mortality appear more robust across count-based approaches. Clustering analyses provide complementary insights into heterogeneity within multimorbid populations. Future translational studies are warranted to determine how multimorbidity definitions can be optimized to ultimately improve clinical management and health outcomes in practice.

03.
arXiv (CS.LG) 2026-06-12

Interpretable Factor Decomposition for Decision Intelligence in Large-Scale Financial Markets: Evidence from China's A-Share Market

arXiv:2606.12843v1 Announce Type: new Abstract: We present an interpretable machine learning pipeline to decompose Cross-Sectional Equity Return Predictability into auditable factor contribution. We apply an XGBoost model with TreeSHAP attribution and conduct stress testing on 3632 Chinese A-share stocks from 2009 until 2019. Using 60-month, rolling windows over 55 months of out-of-sample data, XGBoost obtains a mean AUC of 0.547 and +2.38%/month (Newey-West t = 5.94; Annualized Sharpe 2.23) long-short spread for the top vs bottom quintiles. This alpha is persistent after adjusting for the Carhart four-factor model (+2.31%/month; t = 7.48). SHAP Decomposition indicates that behavioral signals (turnover and momentum) account for 58.2% of predictive attribution compared to 10.7% for valuation ratios, on average, across 55 industry groups. Ablation analysis serves to cross-validate this ranking and provides evidence that SHAP and ablation diverge in a manner that highlights feature substitutability structure that is largely invisible to either method used in isolation.

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

RGB-S: Image-Aligned Tactile Saliency for Robust Dexterous Manipulation

Effective visuo-tactile integration is critical for robotic dexterous manipulation, especially when visual observations are unreliable or occluded. However, robustly aligning sparse, heterogeneous tactile measurements with dense visual representations remains a fundamental challenge. Most existing approaches require policies to learn cross-modal correspondences implicitly from limited demonstrations, without leveraging geometric priors. As a result, they are often data-inefficient and generalize poorly when visual observations are degraded. To address this limitation, we propose a framework that explicitly grounds physical contacts in the image domain. Using robot forward kinematics and camera calibration, we project tactile sensor locations directly onto the RGB image plane. We then render force-modulated Gaussian saliency maps to model spatial uncertainty arising from kinematic and calibration errors. By integrating these 2D spatial anchors through a zero-initialized conditioning architecture, our method injects physical contact priors into standard visual backbones while preserving pre-trained visual representations. We evaluate our method on six dexterous manipulation tasks in both simulation and the real world under severe visual occlusions. Real-world experiments show that explicit RGB-S grounding in the image domain improves real-world occluded manipulation success rates by $26.7$ percentage points over the strongest implicit visuo-tactile baseline, suggesting its improved spatial reasoning and robustness to occlusion. Project page: touch-as-saliency.github.io

05.
arXiv (quant-ph) 2026-06-12

Resourcefulness of non-classical continuous-variable quantum gates

arXiv:2410.09226v4 Announce Type: replace Abstract: In continuous-variable quantum computation, identifying key elements that enable a quantum computational advantage is a long-standing issue. Starting from the standard results on the necessity of Wigner negativity, we develop a comprehensive and versatile approach in which the techniques of $(s)$-ordered quasiprobabilities are exploited to provide rigorous statements on the simulability of photonic quantum circuits consisting of previously characterized gates and thereby identifying the contribution of each quantum gate to the potential achievement of quantum computational advantage. This is achieved by means of an analysis of the so-called transfer function, allowing us to highlight the resourcefulness of a gate set. As such this technique can be straightforwardly applied to current continuous-variables quantum circuits, while also constraining the tolerable amount of losses above which any potential quantum advantage can be ruled out. We use $(s)$-ordered quasiprobability distributions on phase-space to capture the non-classical features in the protocol, and focus our technique entirely on the ordering parameter $s$. This allows us to highlight the resourcefulness and robustness to loss of a universal set of unitary gates comprising three distinct Gaussian gates and any non-Gaussian unitary gate, providing important insight on the role of non-Gaussianity.

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

Fibonacci Steady-States and Persistent Oscillations in an Ordered Multimode Dicke Model

arXiv:2606.13072v1 Announce Type: new Abstract: Ultracold atoms in multimode optical cavities provide a rich testbed for many-body phenomena enabled by light-mediated interactions. Recent experiments include realizations of spin glasses and associative memories, as described by multimode Dicke models with disordered couplings. However, the properties of multimode Dicke models with ordered coupling geometries remain largely unexplored. In this work, we investigate the stable steady-states of the multimode Dicke model with an ordered nearest-neighbor coupling geometry, where $n_c$ atomic clusters are coupled via $n_c-1$ cavity modes. We show that the number of mean-field stable steady-states in the superradiant phase exhibits Fibonacci scaling with the number of atomic clusters, and that a subset of these steady-states exhibit persistent oscillations. Using both the truncated Wigner approximation and the numerically-exact hierarchy of pure states, we further demonstrate that these features of the stable steady-state solutions persist for finite cluster sizes. Ordered multimode Dicke models, such as the nearest-neighbor coupling geometry considered here, are accessible with current experimental technologies and point toward a broader class of strongly interacting dissipative systems with similarly rich behavior.

07.
arXiv (quant-ph) 2026-06-17

Broadband High-Level Squeezed Light using Waveguide Optical Parametric Amplifiers with External Dispersion Compensation

arXiv:2606.17422v1 Announce Type: new Abstract: We demonstrate broadband phase-sensitive amplification (PSA) measurement of squeezed light generated by a waveguide optical parametric amplifier (OPA) with external dispersion compensation. In broadband systems, group velocity dispersion (GVD) induces a frequency-dependent rotation of the squeezing axis, which limits the observable bandwidth in PSA measurements. To overcome this limitation, we introduce external dispersion compensation between two OPAs and suppress the quadrature rotation over a wide frequency range. As a result, we observe a maximum squeezing of 5.9 dB near the carrier frequency and more than 5 dB of squeezing up to a frequency offset of 4.5 THz from the carrier. Furthermore, squeezing below the shot-noise level is confirmed up to a frequency offset of 6 THz from the carrier, corresponding to the accessible phase-matching bandwidth of the waveguide OPA. Our results establish a practical method for broadband characterization of squeezed light and provide a key step toward ultrafast continuous-variable quantum information processing.

08.
arXiv (math.PR) 2026-06-17

Critical spectral behavior and large deviations for geometric $\alpha$-stable processes

arXiv:2606.17501v1 Announce Type: new Abstract: In this paper, we study the Schrödinger-type operator associated with geometric stable processes on $\mathbb{R}^{d}$, especially the differentiability of spectral function. Let $\mathcal{H}$ be the generator of the geometric stable process and $\mu$ a smooth measure on $\mathbb{R}^{d}$. Then the spectral function $C(\theta)$ is defined as $C(\theta) = -\inf \sigma(-\mathcal{H} - \theta \mu)$, where $\sigma(\mathcal{A})$ denotes the spectrum of $\mathcal{A}$ and $\theta$ is a real parameter. Since the geometric stable process exhibits severe local singularities in its Lévy measure, its transition semigroup lacks ultracontractivity, which invalidates classical methods for proving the differentiability. To overcome this obstacle, we use the compact embedding of the extended Dirichlet space into $L^2(\mu)$. As a primary application of this differentiability, we establish a large deviation principle for a positive continuous additive functional associated with the smooth measure $\mu$.

09.
arXiv (CS.AI) 2026-06-15

LLM-Powered AI Agent Systems and Their Applications in Industry

arXiv:2505.16120v3 Announce Type: replace Abstract: The emergence of Large Language Models (LLMs) has reshaped agent systems. Unlike traditional rule-based agents with limited task scope, LLM-powered agents offer greater flexibility, cross-domain reasoning, and natural language interaction. Moreover, with the integration of multi-modal LLMs, current agent systems are highly capable of processing diverse data modalities, including text, images, audio, and structured tabular data, enabling richer and more adaptive real-world behavior. This paper comprehensively examines the evolution of agent systems from the pre-LLM era to current LLM-powered architectures. We categorize agent systems into software-based, physical, and adaptive hybrid systems, highlighting applications across customer service, software development, manufacturing automation, personalized education, financial trading, and healthcare. We further discuss the primary challenges posed by LLM-powered agents, including high inference latency, output uncertainty, lack of evaluation metrics, and security vulnerabilities, and propose potential solutions to mitigate these concerns.

10.
arXiv (math.PR) 2026-06-15

Uniform-in-time error estimates for McKean-Vlasov SDEs with common noise and stochastic algorithms

arXiv:2606.14170v1 Announce Type: new Abstract: In this work, by construct an asymptotic coupling by reflection, we first explore the uniform-in-time estimate on probability distance for two measure-valued processes induced by a McKean-Vlasov SDE with common noise and an interacting particle system, where the drift terms are dissipative merely in the long distance. As direct applications of this estimate, we establish the uniform-in-time error estimates for the numerical solutions derived via backward/tamed/adaptive Euler-Maruyama methods. Moreover, as another direct application, the uniform-in-time conditional propagation of chaos is quantified.

11.
bioRxiv (Bioinfo) 2026-06-14

Transposable elements as evolutionary substrates of proteindisorder in the human proteome

Intrinsically disordered regions (IDRs) are central contributors to protein function, evolution and human disease, yet the evolutionary routes that seed new disordered segments within pre-existing proteins are still poorly understood. Sequence insertions provide a powerful mechanism for disorder expansion, but the genomic donors of inserted IDR and its long-term conformational fate remain largely unknown. Transposable elements (TEs), abundant mobile genetic elements with distinctive compositional biases, represent compelling candidates for generating disorder within proteins. Here, we systematically mapped TE-derived segments across human proteins and isoforms, and we found that these insertions are strongly enriched in intrinsic disorder. The structural consequences of their insertion are shaped by TE class and family, reflecting the sequence biases of the elements from which they originate. Recent, Primate specific insertions preferentially generate disordered segments, whereas older insertions more frequently occupy ordered structural contexts, revealing an age-dependent transition in the conformational state of TE-derived sequences. TE-containing isoforms are expressed at lower levels than TE-free isoforms, particularly when insertions are young and disorder-rich, suggesting that intrinsic disorder may constrain the cellular tolerance of newly exonized sequences. These findings identify TEs as a major evolutionary mechanism linking genome mobility to the emergence of new disordered conformational ensembles in the human proteome.

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

ChiKhaPo: A Large-Scale Multilingual Benchmark for Evaluating Lexical Comprehension and Generation in Large Language Models

Existing benchmarks for large language models (LLMs) are largely restricted to high- or mid-resource languages, and often evaluate performance on higher-order tasks in reasoning and generation. However, plenty of evidence points to the fact that LLMs lack basic linguistic competence in the vast majority of the world's 3800+ written languages. We introduce ChiKhaPo, consisting of 8 subtasks of varying difficulty designed to evaluate the lexical comprehension and generation abilities of generative models. ChiKhaPo draws on existing lexicons, monolingual data, and bitext, and provides coverage for 2700+ languages for 2 subtasks, surpassing any existing benchmark in terms of language coverage. We further show that 6 SOTA models struggle on our benchmark, and discuss the factors contributing to performance scores, including language family, language resourcedness, task, and comprehension versus generation directions. With ChiKhaPo, we hope to enable and encourage the massively multilingual benchmarking of LLMs.

14.
Science (Express) 2026-06-04

Long-range extended chains arising from polymerization-driven spontaneous assembly | Science

作者: 未知作者

A central challenge for conjugated polymers is to achieve long-range order while remaining solution-processable, which is essential for matching the electrical performance of their counterparts of crystalline inorganic semiconductors. Here we show that n-doped poly(benzodifurandione) (n-PBDF) can undergo polymerization-driven spontaneous assembly (PSA), in which chain growth, chemical doping, and structural ordering are intrinsically coupled, yielding long-range chain extension over hundreds of nanometers. We reveal that the spontaneously formed n-PBDF nanoribbons arise from a self-initiated, convergent growth mechanism driven by cooperative monomer–polymer interactions and stabilized by proton-coupled duplex chains and the polymer’s intrinsic polyelectrolyte character. With long-range extended chains in the nanoribbons, the aligned n-PBDF thin films demonstrate metallic-level conductivity (>10 4 Siemens per centimeter).

15.
arXiv (math.PR) 2026-06-17

Persistence diagrams of random triangular matrices over finite fields

arXiv:2606.17895v1 Announce Type: cross Abstract: Let us consider a random infinite lower triangular matrix, where the entries on and below the diagonal are i.i.d. uniform random elements of a fixed finite field. We investigate the evolution of the span of the first $n$ rows of this matrix as $n$ grows. Many properties of this evolving subspace can be captured with the help of the verbose persistence diagram, which is a standard tool in stochastic topology and topological data analysis. We give an explicit formula for the distribution of the persistence diagram. We prove a law of large numbers for the distribution of lifetimes. We also describe the fluctuations of the persistent Betti numbers.

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

Mental Health AI Safety Claims Must Preserve Temporal Evidence

arXiv:2605.08827v2 Announce Type: replace Abstract: The safety of mental health AI is often judged at the wrong temporal scale. Current evaluations typically score isolated responses, endpoint outcomes, or aggregate dialogue quality, while clinically consequential failures may arise from the order and accumulation of interactions themselves, including delayed escalation, repeated reinforcement, dependency formation, failed repair, and gradual deterioration across turns. This paper argues that this mismatch is not merely a limitation of evaluation coverage but a source of invalid safety conclusions. We introduce Temporal Safety Non-Identifiability, a formal account of why safety properties that depend on sequence, timing, accumulation, or recovery cannot be certified by protocols that discard those features. From this formalization, we develop SCOPE (Safety Claims Over Preserved Evidence) as a general principle for aligning safety claims with the evidence an evaluation actually retains, and instantiate it as SCOPE-MH, a mental-health instantiation of this reporting standard. We operationalize SCOPE-MH through a proof-of-concept on the AnnoMI dataset of expert-annotated motivational interviewing conversations, which reveals mechanisms of failure that per-turn behavior scoring does not represent. We propose SCOPE-MH as a diagnostic complement to existing evaluation infrastructure and argue that evaluation preserving temporal evidence is necessary, not optional, for safety-critical mental health AI deployment.

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

Deep Sleep Classification via EEG Signal Criticality: A Passive BCI Approach for Sleep-Improvement Neurofeedback

arXiv:2606.13017v1 Announce Type: cross Abstract: Automated sleep staging is a fundamental application of passive Brain-Computer Interfaces (pBCI), decoding spontaneous neural states to enable closed-loop interventions independent of user intent. This study evaluates criticality features derived from Detrended Fluctuation Analysis (DFA) for the specific identification of deep sleep (N3). We analyzed $347,232$ EEG epochs from $290$ older women using UMAP manifold learning to visualize state transitions. Subsequently, six classifiers were benchmarked via 10-fold cross-validation, using balanced accuracy to determine the optimal "state-sensing" engine for neurofeedback.Naive Bayes achieved the highest mean balanced accuracy ($87.17\% \pm 0.24\%$), significantly outperforming a fully connected deep neural network (FNN: $81.58\%$) and Random Forest ($80.97\%$). Linear models (LDA: $57.21\%$; SVM: $51.01\%$) performed poorly, indicating that DFA-derived criticality features reside on a distinct, non-linear manifold. Probabilistic decoding of EEG criticality provides a high-accuracy sensing mechanism for pBCIs. This robust classification pipeline supports the development of state-dependent neurofeedback, such as targeted auditory stimulation, to enhance cognitive recovery.

18.
arXiv (CS.CL) 2026-06-17

EmoFSM: A Finite State Machine for Emotional Support Conversation

Emotional support conversation (ESC) aims to alleviate people's emotional distress through effective conversations. Although large language models (LLMs) have made remarkable progress in ESC, most of these studies may not define the diagram from a state-model perspective, thereby providing a suboptimal solution for long-term satisfaction. To address such an issue, we leverage the Finite State Machine (FSM) on LLMs, and propose a framework called EmoFSM. Our framework allows a single LLM to bootstrap the planning during ESC, and self-reason the seeker's emotion, support strategy, and the final response upon each conversation turn. Substantial experiments in ESC datasets suggest that EmoFSM outperforms many baselines, including direct inference, self-fine, chain of thought, finetuning, and externally supported methods, even those with many more parameters.

19.
arXiv (CS.CV) 2026-06-17

Reinforcing Dual-Path Reasoning in Spatial Vision Language Models

Spatial VLMs have made substantial progress in geometric perception, yet complex spatial reasoning requiring multi-step inference over depth, distance, and scene relations remains challenging. Moreover, different spatial queries call for fundamentally different strategies: some are best addressed through purely linguistic, step-by-step deduction, while others require explicit 3D grounding before quantitative inference. We present Dual-Path Spatial Reasoning via Reinforcement Learning for Spatial VLMs (SR-REAL), a unified framework that equips a spatial VLM with two complementary reasoning paths: Language-Only Reasoning (LOR), which performs step-by-step linguistic deduction, and Detect-Then-Reason (DTR), which detects 3D geometric cues (e.g., centers or bounding boxes) via region tokens before explicit geometric inference. SR-REAL begins with a cold-start supervised fine-tuning stage that constructs LOR and DTR chain-of-thought supervision and exposes a region-to-3D interface, followed by RL that optimizes the policy model with accuracy and format rewards; for DTR, a discrete center-based detection reward further refines geometric alignment. Across diverse spatial benchmarks, SR-REAL significantly outperforms spatial VLM baselines: (i) a single RL-trained model supports both reasoning paths, with DTR excelling in region-aware tasks through precise 3D localization and LOR enhancing general spatial reasoning; (ii) jointly training both paths fosters mutual reinforcement; (iii) high-quality, blended cold-start data is crucial for stable RL optimization; and (iv) the model generalizes across datasets and domains without per-task tuning, demonstrating positive transfer between LOR and DTR.

20.
arXiv (CS.CV) 2026-06-17

Learning QoE from Packet-Level Measurements in Encrypted Video Conferencing Traffic

The quality of the user experience has become one of the most important aspects in todays world, as it directly influences individuals willingness to continue using or abandon a product or service. In this context, video conferencing applications (VCAs), which experienced widespread adoption following the COVID-19 pandemic, must deliver excellent performance to remain competitive in an increasingly crowded market. Although content providers (CPs) such as Zoom, WhatsApp, Telegram, and Google Meet can assess conversation quality by comparing transmitted and received data. The widespread use of end-to-end encryption in VCAs makes quality-of-experience (QoE) evaluation by internet service providers (ISPs) far more challenging. Since ISPs do not have access to the encrypted content, they must rely on passive measurements of unencrypted traffic characteristics on the data path. In this work, we present a simple yet effective QoE prediction framework based on an almost stock convolutional neural network (CNN) architecture that uses only the packet sizes extracted from the communication between two participants in a video conferencing (VC) call to predict two QoE metrics: BRISQUE and MOS. The proposed framework is simple, easy to implement, and does not require high-end computational resources, yet it provides superior prediction performance, as shown in our experiments on two custom datasets collected from WhatsApp and Zoom, which achieve substantial improvements over previous models for the QoE prediction task.

21.
arXiv (CS.AI) 2026-06-18

Machine Unlearning for the XGBoost Model with Network Intrusion Datasets

arXiv:2606.19220v1 Announce Type: cross Abstract: Machine Unlearning (MU) has emerged as an important technique for removing specific data points from trained models without requiring full retraining. However, most existing MU research focuses on deep learning and image data, leaving a gap in the domain of network intrusion detection, which relies heavily on tabular data. This work introduces XGBoost-Forget, an unlearning approach for the XGBoost model, to address this gap. The approach is evaluated on two tabular Network Intrusion (NI) datasets, IoT-23 and GeNIS, using multiple metrics to assess model performance, unlearning efficiency, and forgetting quality. The results show that XGBoost-Forget maintains predictive performance close to the original model while providing significantly faster unlearning, demonstrating its potential for MU in tabular NI settings.

22.
medRxiv (Medicine) 2026-06-11

Foundation model-based tool for automated ulcerative colitis histology scoring demonstrates non-inferiority to pathologists across multiple scoring indices

In clinical trials for ulcerative colitis (UC), pathologists assess disease severity through standardized histological indices, including the Geboes Score, Robarts Histopathology Index (RHI), and Nancy Histologic Index (NHI). Despite strong associations with clinical outcomes, histologic scoring suffers from inter- and intra-reader variability, and consensus criteria for histologic remission remain uncertain. Through a consortium approach, we developed an artificial intelligence-based measurement (AIM) tool for scoring histology in UC mucosal biopsies (AIM-HI UC). This model, trained on a large dataset of UC biopsies (N=10,230), utilizes additive multiple instance learning models leveraging PLUTO, a pathology foundation model, that predict each of the Geboes subgrades, from which the Geboes grade-level score, RHI, and NHI can be calculated. Evaluation of this model on a standalone verification set including clinical trial specimens established algorithm non-inferiority and/or superiority relative to standard qualified pathologists through comparison of algorithm-consensus and pathologist-consensus agreement metrics (non-inferior if difference >-0.1, superior if difference >0, inclusive of confidence intervals). AIM-HI UC was determined to be non-inferior to pathologists (N=3) for the prediction of all seven Geboes subgrades, grade-level Geboes, RHI, NHI, histologic improvement (GS

23.
bioRxiv (Bioinfo) 2026-06-15

Multi-platform reassessment of human mitochondrial DNA methylation reveals signals consistent with technical artifacts

The existence and functional relevance of mitochondrial DNA methylation remain controversial. Here, we systematically profiled cytosine methylation and hydroxymethylation across human brain and blood tissues spanning healthy and malignant states using orthogonal sequencing approaches that avoid chemical conversion during library preparation. While nuclear DNA exhibited canonical methylation patterns, mitochondrial DNA consistently showed negligible signal, indistinguishable from background technical noise. By mapping cytosine-guanine sites between mitochondrial DNA and nuclear-embedded mitochondrial sequences, we demonstrate the potential of these nuclear counterparts to confound not only cytosine methylation but also hydroxymethylation measurements, corroborating and extending prior findings implicating nuclear contamination as a potential source of apparent mitochondrial epigenetic signals. Additional technical factors that inflate apparent mtDNA methylation signals were identified, including sequence context biases, flow cell chemistries, and coverage-dependent discrepancies between the heavy and light strands. Collectively, these results provide convergent evidence against the presence of biologically meaningful cytosine methylation or hydroxymethylation in mitochondrial DNA. These findings caution against interpreting apparent mtDNA methylation signals in human adult tissues as meaningful without rigorous orthogonal validation and comprehensive consideration of technical and analytical confounding factors.

24.
arXiv (CS.AI) 2026-06-19

Uncertainty-Aware Reward Modeling for Stable RLHF

arXiv:2606.19818v1 Announce Type: cross Abstract: Reinforcement learning from human feedback (RLHF) aligns large language models by training reward models on preference data and optimizing policies to maximize predicted rewards. However, this pipeline faces two fundamental challenges: (1) reward models cannot signal when their predictions are unreliable, since they usually act as deterministic point estimators; and (2) modern group-based policy optimization can amplify unreliable reward signals, as exemplified by GRPO's uniform treatment of rewards during advantage computation. As policies explore increasingly diverse responses, these two limitations create a critical vulnerability: unreliable reward estimates may be granted disproportionate influence, triggering severe reward hacking. We propose Uncertainty-Aware Reward Modeling (UARM), which equips reward models with calibrated uncertainty via quantile-based conformal prediction and reweights GRPO advantages through heteroscedastic variance decomposition. Experiments across HelpSteer, UltraFeedback, and PKU-SafeRLHF demonstrate that UARM significantly improves reward model calibration, reduces reward hacking, and enhances downstream alignment quality compared to standard GRPO and uncertainty-agnostic baselines.

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

MegaFold: Efficient Training of Next-Generation 3D Attention Protein Models on Cross-Platform GPUs

arXiv:2506.20686v2 Announce Type: replace-cross Abstract: Recent advances in biomolecular modeling have been catalyzed by models such as AlphaFold3 (AF3), which introduce science-informed changes to the transformer architecture. Unlike transformers, a defining characteristic of AF3-style models is their 3D attention over 2D pairwise representations which produces tensors whose computation and memory costs scale cubically with sequence length. As a result, despite moderate parameter counts, AF3-style models are far more expensive to train than size-equivalent transformers, and are severely constrained by GPU memory capacity. Our characterization shows 3D attention fundamentally changes the training workload, causing massive 3D attention maps, complex inter-operator dependencies, kernel fragmentation, and heavy host-side data pipelines which differ substantially from LLM training, leading to poor utilization on modern GPU systems. Moreover, existing GPU optimizations do not adequately address these challenges due to complex cross-layer inter-operator dependencies introduced by 3D attention. Motivated by these challenges, we introduce MegaFold, a novel cross-platform system for efficient training of next-generation 3D-attention protein models. MegaFold combines a memory-efficient 3D-attention kernel, a communication-efficient sharding strategy for quadratic representations, fused operator implementations for critical execution paths, and a determinism-aware host-device pipeline that eliminates preprocessing stalls. Evaluation on both NVIDIA H200 and AMD MI250 GPUs shows that MegaFold enables training with up to 3.36$\times$ longer sequence lengths on 32 GPUs while reducing end-to-end execution time by up to 1.73$\times$ (NVIDIA) and 1.62$\times$ (AMD).