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01.
PLOS Computational Biology 2026-06-18

Mechanisms underlying spontaneous and evoked calcium responses in oligodendrocyte precursor cells: A modeling investigation

作者:

by Martin Lardy, Leqi Wang, Claire Guerrier, Veronica T. Cheli, Pablo M. Paez, Anmar Khadra Calcium (Ca2+) signaling has emerged as a central regulator of activity-dependent myelination in oligodendrocytes. These Ca2+ signals encompass both the stimulus-independent spontaneous Ca2+ local transients (SCaLTs) generated intrinsically in a voltage-independent manner or facilitated by the membrane voltage, as well as evoked responses triggered by ATP and glutamate release. To investigate the regulatory mechanisms underlying this combined spiking activity, we developed a stochastic spatiotemporal flux-balance model of Ca2+ transients in oligodendrocyte precursor cells (OPCs). The model incorporates all the relevant fluxes in these cells and integrates membrane voltage dynamics with a Ca2+-induced Ca2+-release (CICR) mechanism using parameters fitted to Ca2+ fluorescence recordings. The model reproduced the intrinsic and voltage-facilitated SCaLTs in OPCs in the absence of purinergic and glutamatergic receptors, and captured the three distinct patterns of evoked Ca2+ responses induced by prolonged ATP and glutamate stimulations identified using machine classifier. The model highlighted the role of ATP and glutamate in generating these clusters, and showed that the fast dynamics of CICR is key to producing these evoked responses. Further analysis of the model also revealed that voltage-gated L- and T-type Ca2+ channels slightly increase the frequency of SCaLTs, while stimulation with ATP and glutamate, using randomly distributed pulses mimicking in vivo conditions, leads to an increase in both the amplitudes of Ca2+ spikes (i.e., the combination of SCaLTs and evoked responses) and the prevalence of wide spikes, especially upon glutamate stimulation. Bifurcation analysis of the deterministic version of the model, in the absence of diffusion, demonstrated that ATP and glutamate stimulation can shift the system into an oscillatory regime, thereby increasing the deterministic component of SCaLT dynamics. This study thus offers a comprehensive representation of OPC Ca2+ transients linking recorded in vitro behaviors to in vivo dynamics.

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

Applicability Condition Extraction for Therapeutic Drug-Disease Relations

arXiv:2606.14031v1 Announce Type: new Abstract: Identifying conditions that a certain drug takes therapeutic effect on a target disease is crucial for clinical decision-making support. However, most existing biomedical information extraction methods have focused on identifying only relations between drugs and diseases, while largely overlooking the context-specific conditions where such relations can apply. To address this problem, we introduce the task of applicability condition extraction for therapeutic drug–disease relations from biomedical research literature. We create the first dataset that has manually annotated triples of drugs, diseases, and applicability conditions on biomedical paper abstracts with 1,119 drug-disease pairs. Using this dataset, we systematically evaluate the performance of a range of existing methods. In addition, we propose a new method that enhances LoRA to consider relations between drugs and diseases. Our method consistently outperforms strong baselines across different evaluation settings. The source code and dataset of this paper can be obtained from: https://github.com/guantingluo98/Drug-ACE

03.
arXiv (CS.AI) 2026-06-19

Navigating Unreliable Parametric and Contextual Knowledge: Explicit Knowledge Conflict Resolution for LLM Inference

arXiv:2606.20245v1 Announce Type: new Abstract: Large language models (LLMs) have achieved strong performance across a wide range of language-based tasks by leveraging both extensive parametric knowledge and in-context learning ability, enabling them to incorporate external information provided in the input prompt. However, the integration of external knowledge can introduce conflicts, not only between the model's internal parametric knowledge and the external information, but also among multiple pieces of external contexts. Existing approaches typically assume that either the model or the provided context is reliable, overlooking the possibility that both sources may contain errors, and avoid conflicts by privileging one source over the other, rather than actively resolving inconsistencies. To address these limitations, we propose a novel framework MACR for LLM knowledge conflict resolution that moves beyond the conventional binary choice paradigm and incorporates an explicit conflict-resolution mechanism based on a multi-agent reasoning approach. Specifically, we first propose an adaptive knowledge assessment and retrieval approach that employs a modified semantic entropy measure to quantify an LLM's confidence in its answer to a given query. Based on this confidence estimation, MACR either externalizes the model's internal knowledge as textual representations or retrieves relevant external knowledge when internal knowledge is insufficient, generating basic contexts for subsequent reasoning. Then we introduce an inductive multi-agent reasoning framework with three specialized agents that, respectively, induce explicit rules, analyze potential conflicts, and resolve inconsistencies across all available contexts. Empirical results demonstrate that MACR significantly outperforms state-of-the-art baselines across benchmarks, while also providing interpretable resolutions of explicit conflicts.

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

One Step Closer to Ground Truth: A Multi-Scale Residual-Aware Representation Learning Pipeline for Predicting Time Series Data

arXiv:2606.10678v2 Announce Type: replace Abstract: Transformer-based models have emerged as leading paradigms in time-series forecasting in recent years, employing self-attention mechanisms to capture long-range dependencies. Despite their success, these single-stage forecasting architectures exhibit persistent systematic residual biases arising from structural discrepancies, unmodeled stochastic components, or inadequate multi-scale temporal representations. This limitation persists when residuals are treated as irreducible noise, precluding adaptive correction of structured error patterns. To address this limitation, we introduce a two-stage, model-agnostic framework that explicitly decouples forecasting and residual learning into distinct stages of representation learning. A base transformer first generates the initial predictions. Subsequently, a dedicated meta-corrector dynamically models structured error patterns across multivariate channels, preserves cross-variable dependencies, and iteratively refines the residual bias of the base transformer. By formalizing this pipeline as a hypothesis space expansion, our framework addresses approximation limitations inherent in single-stage architectures, removes reliance on restrictive assumptions, and enables end-to-end learning of complex error dynamics. Evaluated on eight popular benchmark datasets using established protocols, our approach achieves state-of-the-art performance, with significant improvements in standard metrics (MSE, MAE). The results demonstrate the framework's ability to mitigate systematic biases and enhance robustness to complex temporal dynamics, advancing the practical applicability of transformer-based forecasting models.

05.
arXiv (CS.CV) 2026-06-25

Energy-Efficient CNN Acceleration with MSDF Digit-Serial Arithmetic on FPGA

This paper presents an energy-efficient hardware acceleration of the convolutional layers in the U-Net architecture for image segmentation, implemented on FPGA. While digit-serial arithmetic, particularly most-significant-digit-first (MSDF) techniques, offers a compact hardware footprint, it suffers from initial latency before producing the first output digit. This delay accumulates in cascaded operations like multiplication followed by addition, where each unit introduces its own startup overhead. To overcome this, we propose a merged multiply-add (MMA) architecture that fuses these operations into a unified pipeline. Instead of incurring separate delays, the MMA introduces a single streamlined latency per iteration, shorter than the combined latency of conventional cascaded units, resulting in enhanced throughput and efficiency. The MMA units are designed to process spatial input depths in parallel, achieving significantly higher performance than both standalone MSDF-based and conventional designs. We evaluate the proposed design using U-Net as a target application. Despite operating at a lower frequency than a CPU, the FPGA-based accelerator achieves up to an order of magnitude higher energy efficiency, delivering up to $15.14$ GOPS/W compared to $1.93$ GOPS/W for CPU-based inference. The design also shows approximately $9\times$ reduction in energy consumption compared to MSDF-based FPGA implementations. These results highlight the efficacy of the merged arithmetic approach for resource-constrained, latency-sensitive edge applications in medical imaging and computer vision.

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

Dynamic Rollout Editing for Reducing Overthinking in RL-Trained Reasoning Models

Long-form chain-of-thought reasoning can improve LLM performance on complex tasks, but models often continue generating unnecessary reasoning after a correct answer has emerged. We refer to this behavior as overthinking. We study this phenomenon from the perspective of GRPO-style reinforcement learning (RL) post-training, framing it as a training-time credit-assignment problem rather than merely a decoding-time stopping problem. In rollouts sampled at the onset of GRPO training, we observe that successful trajectories can exhibit a slightly higher degree of overthinking than unsuccessful trajectories for the same prompts. This early imbalance provides a starting point for an undesirable feedback loop: because GRPO assigns sequence-level credit, it cannot distinguish the solution-reaching prefix from the unnecessary continuation that lengthens a successful trajectory. Both receive positive update signal, allowing the initial imbalance to grow into more severe overthinking during training. To address this issue, we introduce Dynamic Rollout Editing (DRE), a training-time intervention for successful trajectories that continue thinking after answer emergence. DRE preserves the accepted verified prefix, edits the remaining thinking, and prefers the edited trajectory within the same RL group, weakening the preference signal for unnecessary thinking without penalizing the reasoning needed to reach the answer. Experiments across diverse tasks show the effectiveness of DRE.

07.
arXiv (CS.CV) 2026-06-16

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

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

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

Agentic Reinforcement Learning for Search Misaligns Instruction-Tuning

Agentic reinforcement learning (RL) trains large language models to use tools, but its impact on alignment is poorly understood. We study how agentic RL for search affects the alignment of instruction-tuned (IT) models. We find that RL-trained models inherit refusal reasoning by deflecting harmful requests into benign search queries, but this breaks down under a simple diagnostic trigger that elicits a search call before refusal can occur. Under this condition, RL models produce multi-step unsafe search actions and reasoning, reducing search query safety by up to 68.6% in Qwen and Llama models relative to their IT counterparts. The effect generalises across model families, scales, and RL algorithms. To understand why, we identify linear directions in the residual stream that control search query safety, and show that RL training progressively shifts search behaviour toward the harmful end of this direction. We thus propose representation-guided RL training, which adds a reward penalty based on projection toward the harmful search direction. Training on benign data alone, it restores IT-level alignment without reducing task accuracy and requires no additional training data. Together, our work provides the first framework for diagnosing, mechanistically analysing, and mitigating alignment degradation in agentic RL for search.

09.
arXiv (CS.LG) 2026-06-12

Retrieval-Augmented Foundation Models for Water Level Prediction in the Everglades

arXiv:2508.04888v2 Announce Type: replace Abstract: Accurate water level forecasting in the Everglades is essential for flood mitigation, drought management, water resource planning, and biodiversity conservation. While recent time-series foundation models have shown strong performance on generic tasks (represented in their pre-training), their effectiveness in domain-specific applications remains insufficiently understood. In this work, we curate a domain-specific dataset for water-level forecasting in the Everglades and observe that the performance of current state-of-the-art models remains limited. To address this gap, we leverage a retrieval-augmented mechanism that retrieves analogous multivariate hydrological episodes from an external archive of historical observations to enrich the input context of those pre-trained models. We study two retrieval strategies, statistical similarity-based retrieval and mutual information-based retrieval, and analyze how incorporating retrieved historical contexts affects predictive performance. Extensive experiments show that retrieval augmentation consistently improves long-horizon water level forecasts and yields disproportionately larger gains during extreme events, which is particularly critical for environmental decision-making. Our study provides empirical evidence that analog-based retrieval can benefit pretrained time-series foundation models in environmental science, offering practical insights into their strengths, limitations, and failure modes when applied to hydrological forecasting in the Everglades. Although evaluated in the Everglades, the proposed framework is general and can be applied to other hydrological systems given time series data. The code and data have been made publicly available at https://github.com/rahuul2992000/WaterRAF.

10.
arXiv (CS.CV) 2026-06-18

Rethinking Air-Ground Collaboration: A Progressive Cross-Task Benchmark and Socialized Learning Framework

Air-ground collaborative perception is crucial for robust visual understanding in real-world dynamic environments. However, existing studies typically formulate collaboration as single-task cross-view fusion, overlooking the functional dependencies among localization, target association, and fine-grained parsing. In addition, the heterogeneous nature of aerial and ground views introduces substantial geometric, scale, and occlusion discrepancies, making uniform feature sharing vulnerable to negative transfer. To tackle these issues, we model air-ground perception as a progressive cross-task collaboration task and construct the Air-Ground Progressive Collaboration (AGPC) benchmark, a spatio-temporally aligned benchmark comprising more than 745K raw video frames. Built upon this benchmark, we propose Socialized Co-Perception (SCP), a coarse-to-fine framework that organizes collaboration progressively from aerial global localization to ground target association and identity-aware parsing. Its core module, the Dual-Layer Router (DLR), decouples input-side multi-scale expert selection from output-side task-conditioned modulation, enabling selective cross-view and cross-task interaction while suppressing harmful interference. Extensive experiments demonstrate the effectiveness of SCP. It achieves a 3.73\% coevolutionary gain and a 7.86\% improvement in average downstream performance. These results show that task-conditioned collaboration is more effective than uniform fusion for heterogeneous air-ground perception. The code is available at https://github.com/g1136639260-spec/AGSCP.

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

TrajGenAgent: A Hierarchical LLM Agent for Human Mobility Trajectory Generation

arXiv:2606.12657v1 Announce Type: new Abstract: Human mobility data is important for transportation, urban planning, and epidemic control, but large-scale trajectory collection is often costly and privacy-constrained, motivating realistic synthetic trajectory generation. Existing LLM-based generators typically rely on either prompt engineering, which preserves zero-shot reasoning but lacks fine-grained spatiotemporal grounding, or trajectory-level fine-tuning, which improves statistical precision but incurs substantial computational cost and may weaken general reasoning. We propose TrajGenAgent, a semantic-aware hierarchical LLM-agent framework for human mobility trajectory generation without model fine-tuning. TrajGenAgent uses a two-stage orchestrator-worker design: an LLM first synthesizes an individual- and weekday-conditioned activity chain from historical evidence via in-context learning, and a deterministic workflow then grounds each activity into a complete visit using personalized POI retrieval, distance-aware location selection, kinematics-aware travel-time propagation, and LLM-based duration estimation. To evaluate realism beyond aggregate spatiotemporal statistics, we introduce an anomaly-detection-based evaluation framework using two complementary detectors to assess behavioral and semantic plausibility. Experiments on benchmark and large-scale simulation datasets show that TrajGenAgent improves spatiotemporal fidelity, semantic coherence, and individual-specific behavioral realism over representative neural and LLM-based baselines, while avoiding parameter updates.

12.
medRxiv (Medicine) 2026-06-23

Association between the hemoglobin albumin lymphocyte and platelet score and chronic kidney disease: insights from patient data and animal models

Introduction The hemoglobin, albumin, lymphocytes and platelets (HALP) score, a novel nutritional and inflammatory biomarker, has been used in various chronic disease studies. However, the relationship between the HALP score and chronic kidney disease (CKD) remains poorly elucidated. This study aimed to explore the possible association between the HALP score and CKD. Methods Our analysis encompassed 25,160 adult participants drawn from NHANES cycles spanning 2009 through 2018. Weighted multivariable logistic regression and generalized additive models (GAMs) were employed to evaluate the independent associations between the HALP score and CKD, albuminuria, and low-estimated glomerular filtration rate (eGFR). Threshold effects were examined using two-piecewise linear regression. Subgroup and sensitivity analyses were performed to assess robustness. Receiver operating characteristic (ROC) curve analyses were applied to compare the discriminative capacity of the HALP score with the prognostic nutritional index (PNI), systemic immune-inflammation index (SII), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR). The clinical findings were further validated in a 5/6 nephrectomy rat model. Results After adjustment for multiple confounders, higher HALP scores were inversely associated with the risk of CKD (OR = 0.97, 95% CI: 0.94-0.99) and albuminuria (OR = 0.97, 95% CI: 0.93-0.99). However, after full adjustment for demographic characteristics, physical examination indices and laboratory parameters (Model 3), the correlation between the HALP score and low-eGFR was no longer statistically significant. Non-linear analyses revealed a threshold effect, with CKD risk declining as the HALP score increased up to an inflection point of 52.43 (OR = 0.97, 95% CI: 0.95-0.99), beyond which no further protective effect was observed. A similar threshold effect was identified for albuminuria. Subgroup and interaction analyses indicated no meaningful effect modification by age, sex, BMI, hypertension, or diabetes. Sensitivity analyses confirmed the robustness of the results. ROC analysis demonstrated that the HALP score showed superior discriminative ability for CKD and albuminuria compared with PNI, SII, LMR, and PLR. In the animal experiment, CKD model rats exhibited significantly lower HALP scores than controls. Inverse correlations were observed between the HALP score and serum creatinine (Scr), blood urea nitrogen (BUN), and urinary albumin-to-creatinine ratio (UACR), with UACR showing the strongest correlation, which was consistent with the clinical findings. Conclusion Lower HALP scores are independently associated with increased prevalence of CKD and albuminuria. As an affordable and readily measurable biomarker, the HALP score may facilitate CKD risk assessment.

13.
arXiv (quant-ph) 2026-06-24

A Hybrid Quantum-Classical Approach for Melt Pool Prediction in Laser Powder Bed Fusion

arXiv:2606.23719v1 Announce Type: new Abstract: Laser powder bed fusion (LPBF) is a promising additive manufacturing technique that suffers from quality assurance concerns. Predicting melt pools from process parameters is crucial for assessing quality prior to manufacturing but remains a difficult problem because of the complex physical processes underlying LPBF. Quantum computers present a new computing paradigm, providing a new approach to information processing using quantum entanglement and superposition. This paper presents a practical demonstration of a hybrid quantum-classical model that leverages quantum computing to improve process parameter feature extraction with a quantum feature encoder. To make the quantum approach computationally feasible for large datasets, we first employ a clustering algorithm to reduce the number of expensive quantum computations. These quantum features are then processed by a classical neural network to predict the melt pool morphology, allowing for more accurate predictions of melt pools. We demonstrate the method using a quantum simulator, analyze the effect of measurement shot noise on the predictive performance of the network, and verify the results using quantum hardware. Finally, by examining which quantum features are most important, we provide insights that can inform the future design of more effective quantum encoding circuits. Ultimately, the performance improvement over purely classical networks validates the hybrid approach, demonstrating an engineering application of quantum computing using noisy and intermediate scale quantum (NISQ) devices.

14.
arXiv (quant-ph) 2026-06-16

Compressed Qubit Noise Spectroscopy: Piecewise-Linear Modeling and Rademacher Measurements

arXiv:2601.02516v2 Announce Type: replace Abstract: Random pulse sequences are a powerful method for qubit noise spectroscopy, enabling efficient reconstruction of sparse noise spectra. Here, we advance this method in two complementary directions. First, we extend the method using a regularizer based on the total generalized variation (TGV) norm, in order to reconstruct a larger class of noise spectra, namely piecewise-linear noise spectra, which more realistically model many physical systems. We show through numerical simulations that the new method resolves finer spectral features, while maintaining an order-of-magnitude speedup over conventional approaches to noise spectroscopy. Second, we simplify the experimental implementation of the method, by introducing Rademacher measurements for reconstructing sparse noise spectra. These measurements use pseudorandom pulse sequences that can be generated in real time from a short random seed, reducing experimental complexity without compromising reconstruction accuracy. Together, these developments broaden the reach of random pulse sequences for accurate and efficient noise characterization in realistic quantum systems.

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

Discovery under Hypothesis Redundancy: A Geometric Theory of Discovery Bottlenecks

arXiv:2606.14386v1 Announce Type: cross Abstract: Scientific discovery saturates when new hypotheses cease to provide independent information, even if the nominal hypothesis space remains large. We study hybrid discovery systems that combine structured local search with LLM-generated non-local proposals and pose the Search Compression Hypothesis: non-local exploration helps only when three geometric conditions co-occur: spectral compression, orthogonal escape from the explored span, and residual signal alignment with the target. We formalize these conditions, derive necessary conditions for hybrid advantage, and test the mechanism in controlled synthetic environments, large-scale A-share factor discovery, and symbolic-regression benchmarks; a public tabular operational sanity check tests the associated budget-allocation implication. Signal-planting and directed-versus-random experiments show that novelty alone is insufficient: random orthogonal jumps expand coverage but do not improve yield without predictive alignment. Across compression sweeps, real factor archives, and LLM-SRBench tasks, hybrid gains concentrate in weakly represented but target-bearing directions and vanish as the hypothesis space approaches full rank. The framework turns LLM-guided discovery from generic novelty search into a diagnostic procedure for deciding when directed non-local exploration is warranted.

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

Binary Black Hole Parameter Estimation with Hybrid CNN-Transformer Neural Networks

arXiv:2606.13941v1 Announce Type: cross Abstract: The detection of gravitational waves has revolutionized our ability to explore fundamental aspects of the Universe. Traditionally, modeled gravitational-wave signals have been identified using template-based matched filtering, followed by coincidence analysis across multiple detectors in the signal-to-noise ratio time series. Recent advances in Machine Learning and Deep Learning have sparked growing interest in their application to both signal detection and parameter estimation. In this study, a hybrid Deep Learning strategy is proposed that leverages the effectiveness of Transformer encoders alongside well-established Convolutional Neural Network architectures in an attempt to estimate the intrinsic and extrinsic parameters of non-precessing binary black hole systems. The primary focus of this work is point estimation, producing single best-fit values for each parameter rather than full posterior distributions. This method is evaluated on both simulated signals embedded in Gaussian noise and real gravitational-wave events, and it demonstrates strong predictive performance and robustness across key astrophysical parameters.

17.
arXiv (CS.CV) 2026-06-25

Spatial Transcriptomics as Images for Large-Scale Pretraining

Spatial Transcriptomics (ST) profiles thousands of gene expression values at discrete spots with precise coordinates on tissue sections, preserving spatial context essential for clinical and pathological studies. With rising sequencing throughput and advancing platforms, the expanding data volumes motivate large-scale ST pretraining. However, the fundamental unit for pretraining, i.e., what constitutes a single training sample, remains ill-posed. Existing choices fall into two camps: (1) treating each spot as an independent sample, which discards spatial dependencies and collapses ST into single-cell transcriptomics; and (2) treating an entire slide as a single sample, which produces prohibitively large inputs and drastically fewer training examples, undermining effective pretraining. To address this gap, we propose treating spatial transcriptomics as croppable images. Specifically, we define a multi-channel image representation with fixed spatial size by cropping patches from raw slides, thereby preserving spatial context while substantially increasing the number of training samples. Along the channel dimension, we define gene subset selection rules to control input dimensionality and improve pretraining stability. Extensive experiments show that the proposed image-like dataset construction for ST pretraining consistently improves downstream performance, outperforming conventional pretraining schemes. Ablation studies verify that both spatial patching and channel design are necessary, establishing a unified, practical paradigm for organizing ST data and enabling large-scale pretraining.

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

Investigating Human-Model Discrepancies in Speech Quality Assessment via Acoustic and Prosodic Perturbations

Mean opinion score (MOS) prediction models are widely used as proxy metrics in text-to-speech (TTS) research, yet their ability to capture quality differences beyond acoustic fidelity remains unclear. We investigate this via controlled perturbations on speech: acoustic degradation, prosodic errors, and manipulation of speaker-specific characteristics such as pitch and speaking rate. We obtained MOS predictions for these speech samples from both human listeners and the model, and analyzed the differences in their perceptual characteristics. Results show that most models track acoustic degradation well, while all are insensitive to prosodic errors despite large subjective score drops. For speaker characteristics, models exhibit a double dissociation: strong mean fundamental frequency (F0) biases absent in human ratings, yet insensitivity to speaking rate and F0 variability that humans notice. These findings highlight limitations of scalar MOS prediction beyond acoustic fidelity.

19.
arXiv (CS.AI) 2026-06-11

Search Discipline for Long-Horizon Research Agents

arXiv:2606.11522v1 Announce Type: new Abstract: Autoresearch agents now propose, evaluate, and select scientific candidates against a metric, and that metric is usually an aggregate reduced over a heterogeneous space of regions, slices, or cohorts. We show that when scientific validity lives in that disaggregated structure, the aggregate can rank the wrong candidate first. The headline number improves while the structure underneath inverts, so a decision made on the number accepts a candidate that quietly breaks the model. The failure is not domain-specific. It appears wherever a candidate's validity is multi-dimensional but its verifier is a single reduction. We demonstrate the inversion on a fire-model task in the Ecosystem Demography model. The highest-scoring candidate and a slightly lower one are within noise of each other on global score, yet the top-scoring one collapses the protected boreal regions while the other preserves them. What separates them is the per-region behavior, not the headline number. This decision should not be left to the agent that produced the candidates. The agent optimizing the score is the last party likely to catch the score being wrong, and a prompt has no remaining turn once the agent has stopped. We move the decision to an external control loop that audits each candidate on its disaggregated behavior and acts after the agent has decided. It can demote a candidate the agent would have accepted, and it can reopen a run the agent had declared finished. Our contribution is the inversion finding itself, and a search-discipline protocol that decides on reviewable candidate-effect evidence instead of the score.

20.
bioRxiv (Bioinfo) 2026-06-17

An Integrated Framework for Transcriptomic Characterization and Lorentzian Hyperbolic Visualization of a High-Risk Topological Branch in Alzheimer's Disease

Alzheimer's disease (AD) is a highly heterogeneous brain disorder in which molecular alterations vary across brain regions, disease stages, and patient subgroups. This study introduces an integrated analytical framework for characterizing transcriptomic variation associated with a high-risk topological branch, which was identified based on Lorentz distance in postmortem Brodmann area 36 samples from the Mount Sinai Brain Bank cohort, where over 70% of samples were in Braak stages V-VI. The framework integrates weighted gene co-expression network analysis, repeated stability-based differential expression analysis, network-level gene filtering, Gene Ontology enrichment, and nested stratified cross-validation to evaluate whether topological branch-associated genes capture biologically meaningful signals and carry predictive information for high-Braak group status. The identified gene sets were functionally enriched for neuronal development, neuron projection organization, synaptic signaling, vesicle fusion, and regulated synaptic release, suggesting that the high-risk topological branch reflects biologically relevant transcriptomic programs linked to neurodegenerative progression. Nested cross-validation further showed that the selected genes achieved measurable internal predictive performance for distinguishing high-Braak samples. As a second methodological contribution, we introduced a Lorentzian hyperbolic variant of t-distributed stochastic neighbor embedding (Lorentz t-SNE) to explore latent non-Euclidean structure in transcriptomic data. This method embeds samples in hyperbolic space, providing an alternative to Euclidean embeddings for representing hierarchical or nonlinear structures. Compared with conventional Euclidean embeddings, the proposed Lorentz t-SNE revealed a more localized organization of high-Braak samples. Together, these results demonstrate the utility of the proposed analytical framework and Lorentz t-SNE for investigating heterogeneous, potentially non-Euclidean organization in AD transcriptomes.

21.
arXiv (CS.CV) 2026-06-12

Quality-Preserving Imperceptible Adversarial Attack on Skeleton-based Human Action Recognition

Adversarial attacks on skeletal human action recognition have received significant attention. However, existing methods typically introduce noise-like perturbations that degrade motion quality post-attack, and thereby are inherently perceptible with recent advancements in S-HAR systems. We discover that this degradation stems from the gap between empirical and true risks during the optimization process of previous adversarial attacks. To address this issue, we propose an attack where adversarial motions are obtained without compromising their motion quality. To minimize the risk gap and preserve motion quality, we propose a distribution-based adversarial attack method without introducing noise-like perturbations. To faithfully evaluate the motion quality, we propose a new metric that aligns with human perception on real-world naturalness. Experiments have been conducted on the state-of-the-art S-HAR methods across two datasets, demonstrating the superiority of our method in both the attack success rate and the post-attack motion quality through qualitative and quantitative analyses. The success of our quality-preserving attack application and distribution-based method raises serious concerns about the robustness of action recognizers, highlighting the need for further enhancements in this domain.

22.
arXiv (CS.AI) 2026-06-12

CMI-RewardBench: Evaluating Music Reward Models with Compositional Multimodal Instruction

arXiv:2603.00610v3 Announce Type: replace-cross Abstract: While music generation models have evolved to handle complex multimodal inputs mixing text, lyrics, and reference audio, evaluation mechanisms have lagged behind. In this paper, we bridge this critical gap by establishing a comprehensive ecosystem for music reward modeling under Compositional Multimodal Instruction (CMI), where the generated music may be conditioned on text descriptions, lyrics, and audio prompts. We first introduce CMI-Pref-Pseudo, a large-scale preference dataset comprising 110k pseudo-labeled samples, and CMI-Pref, a high-quality, human-annotated corpus tailored for fine-grained alignment tasks. To unify the evaluation landscape, we propose CMI-RewardBench, a unified benchmark that evaluates music reward models on heterogeneous samples across musicality, text-music alignment, and compositional instruction alignment. Leveraging these resources, we develop CMI reward models (CMI-RMs), a parameter-efficient reward model family capable of processing heterogeneous inputs. We evaluate their correlation with human judgment scores on musicality and alignment on CMI-Pref along with previous datasets. Further experiments demonstrate that CMI-RM not only correlates strongly with human judgments, but also enables effective inference-time scaling via top-k filtering. Code is available at GitHub (https://github.com/Haiwen-Xia/CMI-RewardBench). Model weights: CMI-RM (https://huggingface.co/HaiwenXia/CMI-RM). Datasets: CMI-Pref-Pseudo (https://huggingface.co/datasets/HaiwenXia/cmi-pref-pseudo) and CMI-Pref (https://huggingface.co/datasets/HaiwenXia/cmi-pref)

23.
arXiv (CS.AI) 2026-06-19

VERITAS: Verifier-Guided Proof Search for Zero-Shot Formal Theorem Proving

arXiv:2606.19399v1 Announce Type: cross Abstract: LLM-based formal provers often collapse rich verifier signals (syntax errors, type mismatches, partial goal progress) into a binary pass/fail bit. We present VERITAS, a zero-shot framework that routes every verifier signal back into proof search through a two-phase protocol: Best-of-N sampling first, then a critic-guided MCTS pass that ingests Phase 1 failures as explicit negative examples. The protocol preserves every theorem solved by its own Phase 1 sweep, so Phase 2's additional solves are attributable to feedback-driven exploration. VERITAS reaches 40.6% on miniF2F (vs. an independently run Best-of-5 at 36.9%, Portfolio 26.2%) and 7.3% on VERITAS-CombiBench, a 55-theorem combinatorics benchmark we release on which Best-of-5 (1.8%) falls below Portfolio (3.6%), exposing that unguided sampling hurts when correct lemma names must be recovered iteratively from verifier feedback. Artifacts are available on GitHub.

24.
arXiv (CS.CV) 2026-06-25

A Leakage-Aware Comparative Benchmark of Machine Learning, Deep Learning, and Transformer Models for Reliable Leukemia Detection

Automated classification of acute lymphoblastic leukemia (ALL) from peripheral blood smear images has often reported near-perfect performance on the C-NMC 2019 dataset. We show that such results can be inflated by patient-level data leakage caused by random image-level partitioning, where cells from the same subject may appear in both training and test folds. We establish a leakage-aware benchmark under a strict subject-disjoint protocol, comparing LightGBM, RBF-SVM, EfficientNet-B0, EfficientNet-B1, and ViT-Tiny. Models are developed using three subject-disjoint folds from 73 subjects and evaluated on an external preliminary-phase test set of 1,867 images from 28 unseen subjects with zero patient overlap. Beyond discrimination, we assess calibration using expected calibration error, Brier score, and temperature scaling. Under honest evaluation, EfficientNet-B1 achieves the best performance, with AUROC 0.913, sensitivity 0.87, specificity 0.80, and calibrated ECE 0.024. Frozen-feature classifiers and ViT-Tiny show high sensitivity but poor specificity, indicating a tendency to over-predict the malignant class. A random-versus-subject-disjoint ablation shows that random splitting inflates AUROC by about 0.04 even in the conservative frozen-feature setting. These findings caution against image-level evaluation on C-NMC 2019 and provide a reproducible, calibration-aware benchmark for future work.

25.
arXiv (CS.CV) 2026-06-19

VideoSketcher: Sequential Sketch Generation Using Video Model Priors

Sketching is inherently sequential: strokes are drawn progressively to explore and refine ideas. Yet most generative approaches treat sketches as static images, ignoring the temporal process underlying creative exploration. Modeling this sequential structure remains challenging: prior methods either rely on large-scale human-drawn datasets with limited diversity, or use large language models (LLMs) to produce drawing instructions, often at the cost of visual fidelity. We present VideoSketcher, a method for generating high-quality sketching processes by adapting pretrained text-to-video diffusion models to the sparse, continuous nature of sketch formation. Our key insight is that LLMs and video diffusion models offer complementary strengths: LLMs act as semantic planners that decompose concepts into step-by-step instructions, while video diffusion models serve as powerful "renderers" that translate them into temporally coherent sketch sequences. We introduce a two-stage fine-tuning strategy that decouples temporal structure from visual appearance: stroke ordering is learned from synthetic shape compositions, while style is distilled from as few as seven hand-drawn examples. Despite minimal supervision, our method can generate diverse, high-quality sequential sketches that faithfully follow specified drawing orders. Our framework naturally extends to brush style control and autoregressive generation, supporting artistic applications.