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01.
arXiv (CS.CL) 2026-06-19

Think Again or Think Longer? Selective Verification for Budget-Aware Reasoning

Test-time reasoning is increasingly used as a serving-time control knob, but extra reasoning is not uniformly valuable: it can repair failed attempts, waste compute on already-correct answers, or introduce harmful answer changes. We study this as a deployment allocation problem rather than a new-verifier problem. We introduce \sevra, Selective Verification for Reasoning Allocation, a serving-layer controller that decides whether to preserve a frozen solver's initial answer or invoke active verification. Using a frozen Qwen3-4B solver, we log intervention outcomes and train recoverability-aware gates from serving-visible attempt state. On \mathfive, selective verification reaches 76.3\% accuracy, compared with 75.5\% for always verifying, while reducing post-generation tokens by 26.8\% and harmful flips from 2.2\% to 1.0\%. However, an 8,192-token initial solve reaches 76.0\% accuracy with 28\% fewer total model tokens, showing that selective recovery is useful but not the best tested cost frontier. In frozen transfer to \gsm, the selective policy verifies only 3.0\% of examples, improves accuracy from 93.4\% to 94.5\%, and reduces verification tokens by 91.2\% relative to always verifying; again, a longer initial solve matches its accuracy with fewer realized tokens. On CommonsenseQA, always-on verification hurts, while Self-Consistency@5 improves accuracy at about five times the realized token cost. The resulting deployment rule is: tune the initial budget first, then use selective recovery when explicit checks, bounded retries, auditability, or regression-risk control matter.

02.
arXiv (CS.LG) 2026-06-18

Bridging Data Gaps in Structural Fragility Modeling through Transfer Learning: Methodology and Case Studies

arXiv:2606.18567v1 Announce Type: cross Abstract: This paper presents a methodology-centered transfer learning framework for fragility adaptation under domain shift, class imbalance, and scarce target labels while preserving engineering interpretability and supporting decision-making under uncertainty. Four transfer learning strategies (instance-based, parameter-based, hierarchical Bayesian, and multi-source) are demonstrated through three complementary case studies: (i) instance-based transfer learning via importance weighting, demonstrated on coastal bridge fragility using Hurricane Katrina observations; (ii) parameter-based transfer learning together with hierarchical Bayesian transfer learning, enabling partial pooling across strata and posterior uncertainty quantification, demonstrated on residential building fragility using Hurricane Ian observations; and (iii) multi-source transfer learning that fuses multiple analytical fragility models with learned source weights and regularized target-domain adaptation, demonstrated on seismic bridge fragility using observations from the 2001 Nisqually earthquake. Across these case studies, direct transfer of source models (i.e. using existing state-of-the-art models) fails under domain shift and severe class imbalance, while targeted adaptation substantially improves failure detection and predictive stability in low-data regimes. These findings highlight the need for systematic guidance on diagnostics, strategy selection, and uncertainty reporting when developing and adapting fragility models.

03.
arXiv (CS.CV) 2026-06-16

EgoPhys: Learning Generalizable Physics Models of Deformable Objects from Egocentric Video

Humans naturally understand object physics through everyday interactions, but faithfully predicting complex deformable dynamics, such as elastic materials and fabrics, remains a major challenge for computer vision and robotics. We present EgoPhys, a framework that constructs deformable physical digital twins from egocentric RGB-only video using generalizable priors. EgoPhys overcomes the limitations of existing methods to enable controllable deformable digital twin generation from egocentric videos by distilling per-object inverse-physics solutions into a compact codebook, enabling prediction of dense spring stiffness fields for unseen objects without per-spring test-time optimization. Trained with generalizable priors from diverse egocentric interactions, EgoPhys outperforms baselines in reconstruction, future prediction, and zero-shot generalization. To support training and evaluation, we curate an egocentric interaction dataset covering diverse deformable objects, scenes, and manipulation styles. We deploy EgoPhys on a real xArm6 robot, demonstrating that a digital twin initialized from a single egocentric human play video can serve as an internal world representation to aid in deformable-object planning, highlighting egocentric RGB observations as a scalable path toward real-to-sim pipelines.

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

PhysMetrics.Weather: An Evaluation Framework for Physical Consistency in ML Weather Models

arXiv:2606.10642v2 Announce Type: replace Abstract: Machine learning weather prediction (MLWP) models have achieved impressive forecasting performance at a small fraction of the computational costs required for traditional physics-based methods. However, they are primarily (1) data-driven and (2) evaluated using pixel-wide error metrics (e.g., RMSE), so there are no guarantees that their forecasts are consistent with known physical laws. We introduce PhysMetrics$.$Weather, an evaluation framework that assesses the physical realism of MLWP models across three types of metrics: conservation, spectral, and dynamical. By quantifying physical realism, this tool guides the development of physics-informed architectures and helps evaluate whether MLWP models are reliable for operational use. Our framework is available on Github at https://github.com/Emmakast/PhysMetrics.Weather.

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

Interaction geometry and ground-state properties of sparse quantum lattice models

arXiv:2606.20387v1 Announce Type: new Abstract: We investigate how interaction geometry shapes the low-energy phases of sparse tunable long-range quantum models. We focus on a class of graphs whose degree grows logarithmically with system size, and show how symmetry and frustration in graph connectivity can drive, suppress, and reshape ground-state phase transitions. The central examples are power-of-$p$ graphs, where even and odd values of $p$ exhibit qualitatively distinct behaviour: even-$p$ graphs inherit the rich phase structure of the power-of-two model, while odd-$p$ graphs are governed by geometric frustration. Fibonacci graphs provide a contrasting case, lacking the discrete self-similarity of the power-of-$p$ family but exhibiting a direct geometric mapping between the short- and long-range limits. Across our models, we find that phase structure and criticality are governed by the same effective-geometry principle, unifying our framework for experimentally motivated long-range quantum systems.

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

Learning from almost nothing: How neural networks survive heavy input corruption

arXiv:2606.11319v1 Announce Type: new Abstract: Learning from imperfect data is a central theme in machine learning, connecting practical questions of robustness to fundamental questions of learnability. Here we examine attribute noise: learning from corrupted inputs while keeping the labels intact, a setting that has received considerably less analytical attention than its label-noise counterpart. We consider two types of corruption models: additive noise and replacement noise. Through experiments with multi-layer perceptrons (MLPs) on corrupted classification datasets, we find that neural networks remain robust, maintaining well-above-chance accuracy even when inputs are >90% corrupted – far beyond human recognition. To understand this robustness, we analyze infinite-width networks in the heavy-corruption regime using a mean-field-inspired approach and derive a leading-order decision rule for the classification outcome: the network implements a prototype rule, the nearest-class-mean, assigning each test point to the class whose training-set average it most closely resembles. This leading-order decision rule is universal across a broad range of MLP architectures, holding for any depth, as well as a wide class of activation functions and noise distributions. The same centroid mechanism closely matches finite-width network behavior in our experiments and provides an interpretable and analytically tractable account of why learning can succeed even when individual training examples carry almost no signal.

07.
arXiv (CS.CV) 2026-06-18

PEFT-MedSAM: Efficient Fine-Tuning of Medical Foundation Models for Explainable Skin Lesion Segmentation

Automated segmentation of skin lesions using deep learning models for dermoscopic images can be very helpful in finding melanomas earlier than they would normally be detected. However, most deep learning methods available do not perform well. The aim of this paper is to present a parameter-efficient fine-tuning method called PEFT-MedSAM for adapting the Medical Segment Anything Model (MedSAM) to automatically segment dermoscopic skin lesions. The PEFT-MedSAM method uses only the lightweight mask decoder for training the model while keeping the pre-trained image encoder and prompt encoder frozen. The experiments performed on the ISIC 2018 benchmark dataset shows that PEFT-MedSAM obtains a dice coefficient of .9411 and an intersection over union value of .8918 when compared to both a fully trained U-Net baseline (.8715 dice coefficient) and zero-shot MedSAM inference (.8997 dice coefficient). The external validation of the model using PH2 dataset shows .9467 dice coefficient with +/- .0310 standard deviation. Supportive evidence for these claims include a p-value less than .0001 for Wilcoxon signed rank tests comparing the two datasets and bootstrap-estimated 95% confidence intervals of [.9364,.9447] that represent the estimated range of possible values for the average dice coefficient obtained by repeating the test. To increase clinical trustworthiness, we used Grad-CAM explainability along with a pointing game based evaluation methodology to evaluate the CNN baseline model on the validation set. The results showed that we had an accuracy rate of 98.27% on the validation set of 519 images and confirmed that the model classified regions containing skin lesions.

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

LOKI: Memory-Free Null-Space Constrained Lifelong Knowledge Editing

arXiv:2606.19679v1 Announce Type: cross Abstract: Lifelong knowledge editing aims to efficiently and sequentially update language models over time, as new knowledge becomes available or when the model makes mistakes, while preserving acceptable performance on past knowledge. One unresolved challenge is that existing methods modify a fixed set of layers for all new knowledge samples, reducing flexibility and increasing catastrophic forgetting. Another is requiring access to previous knowledge and extensive pre-processing to obtain data statistics. To address these challenges, we introduce LOKI, a novel approach that uses dynamic layer selection based on the Hilbert-Schmidt Independence Criterion and projects gradient updates onto the null-space of the model weights, bypassing the requirement for previous knowledge access. We show that LOKI achieves superior performance to existing approaches across a wide variety of experiments, achieving up to a 14\% improvement in average accuracy.

09.
arXiv (CS.CL) 2026-06-24

Metis: Bridging Text and Code Memory for Self-Evolving Agents

Self-evolving agents improve over time by distilling experience from past executions and reusing it in future tasks. Existing systems represent such experience either as natural-language text injected into the agent context or as code exposed as callable tools. However, the choice between these representations is typically made at design time rather than derived from the characteristics of the experience itself, leaving the trade-offs between them poorly understood. We present the first controlled study that isolates text memory and code memory over an identical set of experiences. Our results show that the two forms exhibit complementary trade-offs in construction cost, execution efficiency, and transferability, such that neither representation alone is sufficient. Guided by these findings, we propose Metis, a self-evolving agent system built on a hierarchical dual-representation memory. Metis organizes textual experience into execution plans, environment facts, and common pitfalls, and selectively crystallizes recurring plans into validated callable tools. This design combines the broad applicability of text memory with the execution efficiency of code memory while incurring tool-generation cost only when justified by repeated reuse. We evaluate Metis on AppWorld, a challenging benchmark for interactive agents. The results show that Metis improves task accuracy by up to 20.6% over ReAct while reducing execution cost by up to 22.8%. Compared with representative self-evolving agent systems, Metis consistently achieves a better balance between accuracy, execution efficiency, and memory-construction cost.

10.
arXiv (CS.LG) 2026-06-15

Beyond the Training Distribution: Evaluating Predictions Under Distribution Shift and Selection Bias

arXiv:2606.14506v1 Announce Type: cross Abstract: Understanding how a prediction model will perform in a new environment before deployment is essential to preventing harm when algorithms inform decision-making. Two common sources of model performance degradation are (i) covariate shift, where the target covariate distribution differs from the source, and (ii) selective labels, where the observability of outcomes depends on historical decisions. We study pre-deployment model evaluation under the joint presence of covariate shift and labeling of outcomes selectively based on observed features. In particular, we present a double machine learning procedure for estimating the target risk of an arbitrary black-box prediction model under a general loss function. We show identification of this estimand under standard assumptions and derive a bias-corrected estimator based on the influence function of the target risk. Finally, we evaluate our estimator through experiments using the eICU electronic health records database, showing that it tracks the true target risk more accurately than methods that address either selective labels or covariate shift alone, as well as baselines that combine standard plug-in approaches.

11.
arXiv (CS.CV) 2026-06-18

Generalized Kullback-Leibler Divergence Loss

In this paper, we delve deeper into the Kullback-Leibler (KL) Divergence loss and mathematically prove that it is equivalent to the Decoupled Kullback-Leibler (DKL) Divergence loss that consists of (1) a weighted Mean Square Error (wMSE) loss and (2) a Cross-Entropy loss incorporating soft labels. Thanks to the decoupled structure of DKL loss, we have identified two areas for improvement. Firstly, we address the limitation of KL loss in scenarios like knowledge distillation by breaking its asymmetric optimization property along with a smoother weight function. This modification effectively alleviates convergence challenges in optimization, particularly for classes with high predicted scores in soft labels. Secondly, we introduce class-wise global information into KL/DKL to reduce bias arising from individual samples. With these two enhancements, we derive the Generalized Kullback-Leibler (GKL) Divergence loss and evaluate its effectiveness by conducting experiments on CIFAR-10/100, ImageNet, and vision-language datasets, focusing on adversarial training, and knowledge distillation tasks. Specifically, we achieve new state-of-the-art adversarial robustness on the public leaderboard – RobustBench and competitive knowledge distillation performance across CIFAR/ImageNet models and CLIP models, demonstrating the substantial practical merits. Our code is available at https://github.com/jiequancui/DKL.

12.
arXiv (CS.LG) 2026-06-24

Extended pseudo-spectral physics-informed neural networks for phase-field models

arXiv:2606.24660v1 Announce Type: cross Abstract: Phase-field models play a central role in the continuum description of phase separation, in which the bulk free-energy density and the interfacial thickness parameter determine pattern formation and microstructural evolution. In practice, these constitutive quantities are rarely known a priori and must be inferred from limited dynamical observations. In this work, an extended pseudo-spectral physics-informed neural network (ESPINN) framework is developed for the inverse identification of phase-field models from transient snapshot data. It enables the simultaneous recovery of both the bulk chemical potential and unknown gradient coefficients. Numerical experiments on the one-dimensional Cahn-Hilliard equation demonstrate accurate and statistically stable reconstruction in the noiseless regime, with substantial constitutive information recoverable from even a single snapshot pair. In the presence of noise, reconstruction accuracy degrades gracefully, and increasing the number of snapshots improves robustness by reducing variance across runs. These results establish ESPINN as a data-efficient and physically consistent approach for learning free-energy structure in continuum models of phase separation.

13.
arXiv (CS.AI) 2026-06-24

Quant Convergence: Bridging Classical Value Investing and Modern Factor Models for Systematic Equity Selection

arXiv:2606.24575v1 Announce Type: new Abstract: Modern finance relies heavily on complex machine learning models to find patterns in the stock market. However, as these AI models get more complicated, they often memorize short-term market noise instead of finding companies with real, lasting value. We designed this research to test if Benjamin Graham's classic value investing rules could act as a mathematical "low-pass filter" to keep these modern models in check. We built three different sets of features - pure Graham rules, modern market factors, and a mix of both - and tested them against highly complex models (XGBoost and AutoGluon) using 20 years of S&P 500 data. By applying a strict buy-and-hold strategy over a four-year test period (March 2022 to March 2026), the results showed that more complex algorithms do not always win. While the AutoGluon model captured high returns (222.68%), it suffered a substantial 39.78% drop because it bought volatile tech stocks right before the market crashed. On the other hand, the pure Graham Random Forest achieved the highest overall return (232.13%) with much less risk (1.38 Calmar Ratio). Furthermore, the Combined Random Forest successfully mixed momentum with Graham's rules, making a 202.91% return while keeping the lowest maximum drop (34.53%) of any model tested. Ultimately, this research proves that Graham's "margin of safety" isn't outdated; it is actually a highly effective way to prevent modern AI from taking on too much risk.

14.
arXiv (CS.CL) 2026-06-11

To Intervene or Not: Guiding Inference-time Alignment with Probabilistic Model Blending

The wide deployment of LLMs has made model alignment necessary to make newly trained models safely and effectively respond to user instructions. Among different methods, inference-time alignment is often cheaper as it intervenes (i.e., offers guidances) only during output generation. Existing proposals apply guidances extracted from certain aligned models without properly assessing their reliability. Nonetheless, our systematic evaluation reveals that guidance effectiveness varies drastically across models; since ineffective guidances lead to further confusion and thus further interventions, the resulting excessive interventions typically indicate poor performance. To make interventions more effective and thus more efficient, we introduce BlendIn, an inference-time alignment framework that shifts from binary decisions to creating hybrid distributions integrating both models' knowledge. BlendIn stabilizes inference-time alignment by performing quality-aware alignment and proportionally weighting each model's contribution based on reliability. Compared with existing works, it preserves beneficial guidance while downweighting unreliable suggestions. BlendIn provides both diagnostic signals and mitigation strategies for misaligned guidance, achieving consistent and up to 50% performance improvement on challenging model pairs. Our code is available at: https://github.com/DecayingSeart/BlendIn.

15.
arXiv (CS.CL) 2026-06-19

Improving Alignment Between Human and Machine Codes: An Empirical Assessment of Prompt Engineering for Construct Identification in Psychology

Due to their architecture and vast pre-training data, large language models (LLMs) demonstrate strong text classification performance. However, LLM output - here, the category assigned to a text - depends heavily on the wording of the prompt. While literature on prompt engineering is expanding, few studies focus on classification tasks, and even fewer address domains like psychology, where constructs have precise, theory-driven definitions that may not be well represented in pre-training data. We present an empirical framework for optimizing LLM performance for identifying constructs in texts via prompt engineering. We experimentally evaluate five prompting strategies – codebook-guided empirical prompt selection, automatic prompt engineering, persona prompting, chain-of-thought reasoning, and explanatory prompting - with zero-shot and few-shot classification. We find that persona, chain-of-thought, and explanations do not fully address performance loss accompanying a badly worded prompt. Instead, the most influential features of a prompt are the construct definition, task framing, and, to a lesser extent, the examples provided. Across three constructs and two models, the classifications most aligned with expert judgments resulted from a few-shot prompt combining codebook-guided empirical prompt selection with automatic prompt engineering. Based on our findings, we recommend that researchers generate and evaluate as many prompt variants as feasible, whether human-crafted, automatically generated, or ideally both, and select prompts and examples based on empirical performance in a training dataset, validating the final approach in a holdout set. This procedure offers a practical, systematic, and theory-driven method for optimizing LLM prompts in settings where alignment with expert judgment is critical.

16.
arXiv (CS.AI) 2026-06-24

No Certificate, No Categorical Speech Act: A Brouwerian Assertibility Constraint for Public Reason

arXiv:2603.03971v3 Announce Type: replace-cross Abstract: Generative AI can convert uncertainty into authoritative-seeming verdicts, intensifying the hypersuasive force of automated speech and displacing the justificatory work on which democratic epistemic agency depends. As a corrective, I propose a Brouwer-inspired assertibility constraint for responsible AI: in high-stakes domains, systems may assert or deny claims only if they can provide a publicly inspectable and contestable certificate of entitlement; otherwise they must return Undetermined. This constraint yields a three-status interface semantics (Asserted, Denied, Undetermined) in which statuses mark entitlement to categorical speech rather than truth values of the underlying world-claim. The semantics cleanly separates internal entitlement from public standing while connecting them via the certificate as a boundary object. It also produces a time-indexed entitlement profile that is stable under numerical refinement yet revisable as the public record changes. I operationalize the constraint through decision-layer gating of threshold and argmax decisions, using internal witnesses (e.g., sound bounds or separation margins where available, and contestable surrogates otherwise) and an output contract with reason-coded abstentions. A design lemma shows that any total, certificate-sound binary interface yields witnessed decidability of the deployed predicate on its declared scope, so Undetermined is not a tunable reject option but a mandatory status whenever no adequate forcing witness is available. By making outputs answerable to challengeable warrants rather than confidence alone, the paper aims to preserve epistemic agency against the persuasive pull of automated speech in public justification.

17.
arXiv (math.PR) 2026-06-24

Uniform-in-time Gaussian fluctuations for multiscale nonlinear stochastic systems via Malliavin Calculus

arXiv:2606.23865v1 Announce Type: new Abstract: We establish a uniform-in-time quantitative central limit theorem (QCLT) for a nonlinear slow-fast stochastic system. We identify significant weaker sufficient conditions that enable us to obtain time-independent bounds for the Wasserstein distance between the fluctuation process and a centered Gaussian random variable. To prove our main result, we utilize tools from Malliavin calculus, specifically the second-order Poincaré inequality. In this context, applying the Poincaré inequality requires demonstrating uniform bounds over time for both the first- and second-order Malliavin derivatives.

18.
arXiv (CS.AI) 2026-06-15

Q-Net: Queue Length Estimation via Kalman-based Neural Networks

arXiv:2509.24725v4 Announce Type: replace-cross Abstract: Estimating queue lengths at signalized intersections is a long-standing challenge in traffic management. Partial observability of vehicle flows complicates this task despite the availability of two privacy-preserving data sources: (i) aggregated vehicle counts from loop detectors near stop lines, and (ii) aggregated floating car data (aFCD) that provide segment-wise average speed measurements. However, how to integrate these sources with differing spatial and temporal resolutions for queue length estimation is rather unclear. Addressing this question, we present Q-Net: a queue estimation framework built upon a state-space formulation. This design addresses key challenges in queue modeling, such as violations of traffic conservation assumptions. Q-Net follows the Kalman predict-update structure and maintains physical interpretability in both the state evolution and measurement models. Q-Net uses an AI-augmented Kalman filter to learn time-varying gain dynamics from data. The framework supports real-time implementation and improves spatial transferability by grouping aFCD measurements into fixed-size local groups, making the number of learnable parameters independent of section length. Evaluations on urban main roads in Rotterdam, the Netherlands, show that Q-Net outperforms baseline methods, tracks queue formation and dissipation accurately, and mitigates aFCD-induced delays. By combining data efficiency, interpretability, real-time applicability, and spatial transferability, Q-Net makes accurate queue length estimation possible without costly sensing infrastructure like cameras or radar.

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

A Closer Look at Failure Modes in Temporal Understanding of Large Audio-Language Models

arXiv:2606.17417v1 Announce Type: cross Abstract: Large Audio Language Models (LALMs) achieve strong performance on a variety of audio understanding tasks but continue to struggle with temporal reasoning, a fundamental capability central to human auditory perception. Understanding the causes of these failures remains challenging as existing benchmarks report performance gaps without probing underlying mechanisms. To address this, we introduce a benchmark with 1,657 questions across three foundational tasks designed specifically for mechanistic analysis. Examining model outputs across varying input settings (behavioral analysis) reveals that models often under-utilize audio when textual cues are available. We also provide the first causal mechanistic analysis of temporal reasoning failures in LALMs. Comparing attention upweighting against scaling, we find that redistributing attention across audio tokens is more effective than increasing audio attention. Targeting task-relevant tokens yields further gains. These findings suggest that modality imbalance alone cannot explain failures. Attention scaling at bottleneck layers improves accuracy from 55.9% to 59.1% without fine-tuning, demonstrating a promising direction for future work.

20.
arXiv (CS.AI) 2026-06-25

Bias Fitting to Mitigate Length Bias of Reward Model in RLHF

arXiv:2505.12843v2 Announce Type: replace-cross Abstract: Reinforcement Learning from Human Feedback (RLHF) relies on reward models to align large language models with human preferences. However, RLHF often suffers from reward hacking, wherein policy learning exploits flaws in the trained reward model to maximize reward scores without genuinely aligning with human preferences. A significant example of such reward hacking is length bias, where reward models usually favor longer responses irrespective of actual response quality. Previous works on tackling length bias have notable limitations, these approaches either mitigate bias without characterizing the bias form, or simply assume a linear length-reward relation. To accurately model the intricate nature of length bias and facilitate more effective bias mitigation, we propose FiMi-RM (Bias Fitting to Mitigate Length Bias of Reward Model), a framework that autonomously learns and corrects underlying bias patterns. Our approach consists of three stages: First, we warm up by training a standard reward model which inherently contains length bias. Next, we deploy a lightweight fitting model to capture the non-linear relation between length and reward. Finally, we incorporate this learned relation into the reward model, effectively decoupling length from reward while preserving preference modeling capabilities. Experimental results demonstrate that FiMi-RM achieves a more balanced length-reward distribution. Furthermore, when applied to alignment algorithms such as Direct Preference Optimization (DPO) and Best-of-N (BoN), our debiased reward model improves length-controlled win rate and reduces verbosity without compromising its performance.

21.
medRxiv (Medicine) 2026-06-25

Stratified cohorts for biomarker assessment and trial readiness: TMEM175, SCARB2 and CTSB in Parkinson's disease

Background: Lysosomal dysfunction plays a crucial role in the pathogenesis of Parkinson's disease (PD), particularly among GBA1 mutation carriers. Beyond GBA1, genes such as TMEM175, SCARB2, and CTSB identified in genome-wide association studies (GWAS) are also implicated in lysosomal pathways contributing to PD risk, although their functional effects in patients remain unclear. Proteins encoded by these lysosome-related genes have been explored as potential therapeutic targets in experimental models. Biomarker profiles, including clinical measures, alpha-synuclein seeding activity, lysosomal proteins, and sphingolipids, may facilitate patient stratification and support therapeutic monitoring in future clinical trials. Aim: The aim of this study is to investigate the impact of genetic variants of three lysosomal-related genes (TMEM175, SCARB2, and CTSB) on biomarker profiles in PD with and without GBA1 variants. Cross-sectional data from two German cohorts: the Tuebingen Parkinson Cohort (TUEPAC) and the DESCRIBE PD cohort of the German Center for Neurodegenerative Diseases were used as explorative cohorts, and data from Accelerating Medicines Partnership Parkinson's Disease (AMP-PD) were used as a validation cohort. The ultimate goal is to provide new data for patient stratification based on genetics, which might serve as a readout for target engagement and treatment efficiency assessment. Methods: Three cohorts were analyzed: TUEPAC, DESCRIBE PD, and AMP-PD. TUEPAC and DESCRIBE PD were combined into a single German discovery cohort (TUEPAC-DESCRIBE-PD), while AMP-PD served as an independent validation cohort. Within each cohort, for subgroup analyses, PD patients were classified as the overall PD cohort (PDall), and further stratified by GBA1 mutation status into PD patients without GBA1 mutations (PDGBA1_wildtype), and PD patients carrying GBA1 mutations (PDGBA1). We evaluated cognitive and motor function, as well as depression using the Montreal Cognitive Assessment (MoCA), Unified Parkinson Disease Rating Scale-part III (UPDRS III), and Beck Depression Inventory-II(BDI-II) scales. Analyzed biomarkers included CSF -syn seeding activity using seed amplification assay (SAA), CSF lysosomal protein levels of lysosomal integral membrane protein 2 (LIMP2), also known as SCARB2, cathepsin B (CTSB) and lysosome-associated membrane protein 2 (LAMP2), blood-based enzyme activity of the lysosomal glucocerebrosidase (GCase), and CSF sphingolipid profiles. PD patients carrying risk alleles in TMEM175, SCARB2, and CTSB were compared to non-carriers. Results: Genotype-phenotype correlation analysis in TUEPAC-DESCRIBE-PD and AMP-PD revealed: (1) In PDall, the TMEM175 p.M393T risk variant was nominally associated with decreased cognitive function when adjusted for GBA1 mutation status in TUEPAC-DESCRIBE-PD; this association could not be replicated, although a similar trend was observed in the slightly smaller, but multicentric AMP-PD cohort; TMEM175 p.M393T was not significantly associated with BDI-II or UPDRS-III scores in either cohort. (2) In PDGBA1_wildtype, GCase activity was significantly lower in PD patients with SCARB2 rs6812193 risk allele in TUEPAC-DESCRIBE-PD, while a similar but non-significant trend was observed in AMP-PD; (3) In PDall, CSF levels of CTSB were nominally lower in carriers of CTSB rs1293298 risk allele compared to carriers of CTSB rs1293298 protective allele in TUEPAC-DESCRIBE-PD; in PDGBA1_wildtype, LAMP2 was significantly lower in carriers of CTSB rs1293298 risk allele compared to carriers of CTSB rs1293298 protective allele in TUEPAC-DESCRIBE-PD; (4) In PDall, TMEM175 p.M393T risk allele was nominally associated with altered sphingolipid profiles across both TUEPAC-DESCRIBE-PD and AMP-PD cohorts. Conclusion: These findings demonstrate that genetic variants in lysosomal-related genes (TMEM175, SCARB2, and CTSB) have a functional impact on biomarker profiles in PD patients. Integrating genetic characterization with biochemical profiling provides a framework for patient stratification and may serve as a translational strategy to monitor target engagement and evaluate treatment efficacy in future clinical trials.

22.
arXiv (CS.LG) 2026-06-11

Visual-Redundancy-Controlled Parallel Decoding for Diffusion-Based Multimodal Large Language Models

arXiv:2605.25820v2 Announce Type: replace Abstract: Diffusion-based multimodal large language models (dMLLMs) decode by iteratively predicting tokens at multiple masked positions in parallel. This turns each decoding step into a position-selection problem: the model must choose not only which predictions are reliable in isolation, but also which positions should be committed together as context for later decoding steps. Existing confidence-based decoding ranks masked positions independently and commits the top-K positions, largely ignoring whether the committed tokens provide complementary visual grounding. We identify a step-level limitation of this strategy in multimodal settings: high-confidence tokens selected in the same step can rely on overlapping visual grounding, introducing visual redundancy among the committed tokens and leaving less complementary visual grounding available for later decoding. To quantify this effect, we introduce the Visual Redundancy Index (VRI), which measures visual grounding overlap among tokens committed in parallel. To control this redundancy during decoding, we propose Visual-Redundancy-Controlled Decoding (VRCD), a training-free inference-time decoding method that uses token-to-image attention to prioritize visually complementary positions. Across diverse multimodal benchmarks, VRCD reduces visual redundancy and remaining-position entropy with modest runtime overhead. In longer decoding experiments, it also achieves relative accuracy gains of up to 18.8% on M^3CoT and 6.9% on MMBench over confidence-based decoding. Code is available at https://github.com/infiniteYuanyl/VRCD.

23.
arXiv (quant-ph) 2026-06-11

TensorKit.jl: A Julia package for large-scale tensor computations, with a hint of category theory

arXiv:2508.10076v2 Announce Type: replace-cross Abstract: TensorKit$.$jl is a Julia-based software package for tensor computations, especially focusing on tensors with internal symmetries. This paper introduces the design philosophy, core functionalities, and distinctive features, including how to handle abelian, non-abelian, and anyonic symmetries through the ``TensorMap'' type. We highlight the software's flexibility, performance, and its capability to extend to new tensor types and symmetries, illustrating its practical applications through select case studies.

24.
bioRxiv (Bioinfo) 2026-06-19

HTS-Oracle v2: Prospective AI-Guided Discovery and Experimental Validation of Small Molecule Modulators Across Multiple Targets

High-throughput screening (HTS) remains the cornerstone of early-phase small molecule discovery yet consistently underperforms against immunotherapy targets, yielding validated hit rates below 0.1%. Here we introduce HTS-Oracle v2, which features rigorous cross-validation that ensures honest performance estimates. HTS-Oracle v2 was trained and validated across four clinically significant immune checkpoint targets (CD28, ICOS, LAG-3, and TIGIT) achieving ROC-AUC values of 0.968, 0.969, 0.875, 0.928 respectively under rigorous cross-validation. For prospective experimental validation, HTS-Oracle v2 was applied to an 8,960-compound Enamine Protein Mimetic Library, selecting only 25 compounds per target for experimental testing using temperature-related intensity change (TRIC) technology, a 99.7% reduction in screening burden. HTS-Oracle v2 identified 4, 5, 4, and 6 validated binders from 25 prospectively selected compounds per target, corresponding to validated hit rates of 16%, 20%, 16%, and 24%, respectively. Notably, 67-80% of all experimentally confirmed hits across the full 8,960-compound library were captured within just 25 model-selected compounds per target. For CD28, this represents a 28-fold improvement over HTS-Oracle v1 (239x versus 8.4x), establishing HTS-Oracle v2 as an efficient platform for AI-guided prospective hit discovery across immunotherapy targets.

25.
arXiv (CS.AI) 2026-06-11

Towards Deep Learning Surrogate for the Forward Problem in Electrocardiology: A Scalable Alternative to Physics-Based Models

arXiv:2512.13765v2 Announce Type: replace-cross Abstract: The forward problem in electrocardiology, computing body surface potentials from cardiac electrical activity, is traditionally solved using physics-based models such as the bidomain or monodomain equations. While accurate, these approaches are computationally expensive, limiting their use in real-time and large-scale clinical applications. We propose a proof-of-concept deep learning (DL) framework as an efficient surrogate for forward solvers. The model adopts a time-dependent, attention-based sequence-to-sequence architecture to predict electrocardiogram (ECG) signals from cardiac voltage propagation maps. A hybrid loss combining Huber loss with a spectral entropy term was introduced to preserve both temporal and frequency-domain fidelity. Using 2D tissue simulations incorporating healthy, fibrotic, and gap junction-remodelled conditions, the model achieved high accuracy (mean $R^2 = 0.99 \pm 0.01$). Ablation studies confirmed the contributions of convolutional encoders, time-aware attention, and spectral entropy loss. These findings highlight DL as a scalable, cost-effective alternative to physics-based solvers, with potential for clinical and digital twin applications.