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01.
bioRxiv (Bioinfo) 2026-06-16

THEOBROMA: an aggregated open database of 1.13 million natural products with per-compound license auditing, three-tier classification, and stereochemistry-aware deduplication

Natural products remain one of the most productive sources of pharmacologically active compounds for drug discovery, yet the current open aggregator landscape attributes licenses at database rather than compound granularity, with consequences that have become tangible as the field grows. A recent relicensing event in one constituent source (the September 2024 transition of the Natural Products Atlas to CC BY-NC 4.0) demonstrates how database-level licensing propagates across an aggregate and motivates the per-compound audit framework presented here. The same peer cohort separately leaves classification provenance and stereoisomer-family relations coarser than either layer warrants. THEOBROMA, accessible at url{https://theobroma.l3s.uni-hannover.de}, integrates 1{,}133{,}004 natural products from 29 open sources under a per-compound license audit that resolves each compound's license tier across all attesting sources under a most-restrictive-wins rule, identifying 900{,}170 compounds (79.4%) under open-use licenses and exposing the per-source attestation chain and resolved tier through a dedicated audit endpoint and a query-time license filter. A three-tier classification stratifies 89.3% coverage into 35.1% curated, 43.9% high-confidence inferred, and 10.3% exploratory tiers, with 486{,}215 stereoisomer families preserved by full 27-character InChIKey deduplication and exposed via a dedicated texttt{/api/stereoisomers/} endpoint and a radial-family display. Per-compound license provenance is the primary differentiator. Classification stratification and stereoisomer-family exposure add finer-grained access to two related axes, supporting license-compatible virtual screening and isomer-specific bioactivity analysis at corpus scale. As an evolving open resource, THEOBROMA pairs continuous pipeline maintenance with interactive geographic, taxonomic, and chemical-space exploration.

02.
arXiv (CS.CV) 2026-06-17

m2sv: A Scalable Benchmark for Map-to-Street-View Spatial Reasoning

Vision–language models (VLMs) achieve strong performance on many multimodal benchmarks but remain brittle on spatial reasoning tasks that require aligning abstract overhead representations with egocentric views. We introduce m2sv, a scalable benchmark for map-to-street-view spatial reasoning that asks models to infer camera viewing direction by aligning a north-up overhead map with a Street View image captured at the same real-world intersection. We release m2sv-20k, a geographically diverse benchmark with controlled ambiguity, along with m2sv-sft-11k, a curated set of structured reasoning traces for supervised fine-tuning. Despite strong performance on existing multimodal benchmarks, the best evaluated VLM achieves only 65.2% accuracy on m2sv, below human annotators who reach 72.0% on average (and 95% for an expert) with strong inter-annotator agreement ($\kappa$ up to 0.76). While supervised fine-tuning and reinforcement learning yield consistent gains, cross-benchmark evaluations reveal limited transfer. Beyond aggregate accuracy, we systematically analyze difficulty in map-to-street-view reasoning using both structural signals and human effort, and conduct an extensive failure analysis of adapted open models. Our findings highlight persistent gaps in geometric alignment, evidence aggregation, and reasoning consistency, motivating future work on grounded spatial reasoning across viewpoints.

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

From Passive Generation to Investigation: A Proactive Scientific Peer Review Agent

Large language models (LLMs) have shown promise in automating scientific peer review. However, existing approaches often struggle to generate in-depth reviews supported by concrete evidence. We argue that a key limitation is the lack of flexibility to proactively investigate suspicious parts of a paper based on accumulated evidence, as human reviewers do. In this paper, we explore how to enable an LLM-based review agent to perform such proactive investigation. We find that this can be naturally formulated as a Markov Decision Process (MDP), and propose ProReviewer, a scientific peer review agent that proactively reviews a paper guided by a maintained, structured review log. The structured review log serves as a workspace for the agent to track evidence and intermediate findings collected during review. Experiments show that ProReviewer with an 8B backbone, trained by supervised fine-tuning and optimized by reinforcement learning, achieves the highest average score across five quality dimensions, outperforming prompt-based methods with much larger frontier LLMs by up to 39% and the strongest fine-tuned baseline by 16% relatively. It also attains the highest win rates against baselines in human evaluation.

04.
medRxiv (Medicine) 2026-06-19

Fine-Tuning SAM2 for Coronary Artery Segmentation in X-Ray Fluoroscopy

作者:

SAM2 (Meta, 2024) provides a strong starting point for segmentation, but given the unique challenges in medical imaging (noise from patient movement, the projection-based nature of X-ray fluoroscopy, and low contrast between vessels and background), direct application is difficult. We fine-tune MedSAM2 on annotated coronary angiograms and apply it to video data for point-of-care use. On the ARCADE validation set (200 images), the fine-tuned model achieves Dice 0.767 compared to 0.033 zero-shot. On 10 fluoroscopic video studies from CoronaryDominance, it tracks vessels coherently and avoids falsely segmenting ribs, stents, and bypass grafts in 9 of 10 studies. Code is available at https://github.com/elakiyasivakumar/SAM2-Coronary-Angiography-VA and the fine-tuned checkpoint at https://huggingface.co/Elakiya17/CA-SAM2.

05.
arXiv (CS.CL) 2026-06-16

GePBench: Evaluating Fundamental Geometric Perception for Multimodal Large Language Models

Geometric shapes play important roles in both physical world and human cognition. While multimodal large language models (MLLMs) have made significant advancements in visual understanding, their abilities to recognize geometric shapes and their spatial relationships, which we term geometric perception, are not explicitly and systematically explored. To address this gap, we introduce GePBench, a novel benchmark specifically designed to assess the geometric perception capabilities of MLLMs. Our extensive evaluations reveal that even the current state-of-the-art MLLMs exhibit significant deficiencies in geometric perception tasks. Furthermore, we show that models trained with GePBench data demonstrate considerable improvements on a wide range of downstream tasks, highlighting the critical role of geometric perception in enabling advanced multimodal applications. Our code and datasets are available at \href{https://github.com/Changhao-Xiang/GePBench}{https://github.com/Changhao-Xiang/GePBench}.

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

GMN4AD: Graph Matching Network for Alzheimer's Disease Diagnosis with Test-Time Domain Adaptation using Multi-centered Structure Magnetic Resonance Imaging

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder that affects millions of older adults, with prevalence expected to rise significantly in the coming years. Early diagnosis, particularly during the mild cognitive impairment (MCI) stage, is critical for timely intervention. Structural Magnetic Resonance Imaging (sMRI) has emerged as a key modality for detecting AD-related brain changes, but traditional graph-based approaches often struggle with modality and inter-site heterogeneity, limiting diagnostic performance. In this paper, we propose Graph Matching Network for Alzheimer's Disease Diagnosis (GMN4AD), designed to model interactions between heterogeneous brain graphs derived from neuroimaging data. Unlike conventional methods that treat each brain graph independently, GMN4AD leverages graph matching to capture cross-graph relationships, enhancing diagnostic precision. Furthermore, we introduce a test-time domain adaptation strategy that combines contrastive learning to mitigate domain shifts during inference. Extensive experiments on three public AD datasets demonstrate that GMN4AD achieves superior performance compared to state-of-the-art methods, offering a robust and generalizable solution for AD diagnosis.

07.
arXiv (CS.CV) 2026-06-17

Neural Tree Reconstruction for the Open Forest Observatory

The Open Forest Observatory (OFO) is a collaboration across universities and other partners to make low-cost forest mapping accessible to ecologists, land managers, and the general public. The OFO is building both a database of geospatial forest data as well as open-source methods and tools for forest mapping by uncrewed aerial vehicle. Such data are useful for a variety of climate applications including prioritizing reforestation efforts, informing wildfire hazard reduction, and monitoring carbon sequestration. In the current iteration of the OFO's forest map database, 3D tree maps are created using classical structure-from-motion techniques. This approach is prone to artifacts, lacks detail, and has particular difficulty on the forest floor where the input data (overhead imagery) has limited visibility. These reconstruction errors can potentially propagate to the downstream scientific tasks (e.g. a wildfire simulation.) Advances in 3D reconstruction, including methods like Neural Radiance Fields (NeRF), produce higher quality results that are more robust to sparse views and support data-driven priors. We explore ways to incorporate NeRFs into the OFO dataset, outline future work to support even more state-of-the-art 3D vision models, and describe the importance of high-quality 3D reconstructions for forestry applications.

08.
arXiv (quant-ph) 2026-06-17

Active Quantum Reservoir Engineering: Using a Qubit to Manipulate its Environment

arXiv:2505.16898v4 Announce Type: replace Abstract: Quantum reservoir engineering leverages dissipative processes to achieve desired behavior, with applications ranging from entanglement generation to quantum error correction. Therein, a structured environment acts as an entropy sink for the system and no time-dependent control over the system is required. We develop a theoretical framework for active reservoir engineering, where time-dependent control over a quantum system is used to manipulate its environment. In this case, the system may act as an entropy sink for the environment. Our framwork captures the dynamical interplay between system and environment, and provides an intuitive picture of how finite-size effects and system-environment correlations allow for manipulating the environment by repeated initialization of the quantum system. We illustrate our results with two examples: a superconducting qubit coupled to an environment of two-level systems and a semiconducting quantum dot coupled to nuclear spins. In both scenarios, we find qualitative agreement with previous experimental results, illustrating how active control can unlock new functionalities in open quantum systems.

09.
PLOS Computational Biology 2026-06-08

Statistics of cortical representational drift can enable robust readout

by Charles Micou, Timothy O’Leary Representational drift of fixed stimuli, learned tasks and familiar environments is observed in many brain areas, leading to reconfiguration of population codes over days to weeks. This raises the question of whether downstream brain regions employ mechanisms to track changes in population activity and thus preserve the fidelity of the information they extract. We show that the statistical properties of drift have a significant impact on such mechanisms. Over an extended period, a net change in population tuning due to drift can arise from an accumulation of small changes distributed across the population, or via abrupt jumps that affect smaller subsets of cells at each time point. We demonstrate that an adaptive readout can exploit the heavy-tailed statistics of abrupt jumps to maintain a more stable readout using a simple inference mechanism. Using experimental data, we investigate the extent to which heavy-tailed drift statistics are observed during representational drift in the posterior parietal cortex and visual cortex. We find that experimentally measured drift does not conform to a Gaussian random walk. Instead, we find sudden jumps in neural tuning that would be advantageous for a downstream observer adapting to changes in representation. These observations motivate future study to determine whether adaptive decoding mechanisms exist in the brain and to determine the physiological mechanisms that shape the statistics of representational drift.

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

Task-guided cross-subject latent alignment: a multi-encoder-decoder VAE

arXiv:2606.15989v1 Announce Type: cross Abstract: Aligning neural activity across subjects offers the promise of discovering shared computational principles and generalizable decoders. However, traditional alignment methods require shared stimuli across subjects, a constraint that limits applicability to naturalistic paradigms with limited or non-overlapping data. We introduce a Multi-Encoder-Decoder Variational Autoencoder (MED-VAE) that achieves cross-subject alignment without shared stimuli by anchoring representations to a common scaffold provided by a pretrained ANN. Using the Natural Scenes Dataset, we show that MED-VAE creates common latent spaces with superior semantic organisation, achieving higher cross-subject alignment than common methods while maintaining robust generalisation to held-out stimuli where traditional methods degrade. Reconstructing from these common spaces back to each subject's original neural space, MED-VAE preserves equal stimulus-driven signal in its cross-subject latent space. Finally, we show that this superior alignment directly enables cross-subject neural prediction, as demonstrated via cross-subject image decoding. In summary, we introduce a framework to identify generalisable common subspaces for cross-subject predictions and downstream tasks, demonstrated here for visual cortex responses to static images.

11.
arXiv (math.PR) 2026-06-15

Semiclassical limit of Polyakov-Liouville measure and Q-Curvature Uniformization on evev-dimensional manifolds

arXiv:2606.14443v1 Announce Type: new Abstract: We study the semiclassical limit of the Polyakov-Liouville measure $\boldsymbol{\nu}_\gamma$, which is a non-Gaussian measure on $H^{-\eps}(M)$ that has recently been extended from Riemann surfaces to general Riemannian manifolds $(M,g)$ of even dimension. We show that under an appropriate rescaling in the semiclassical limit as $\gamma\to0$, the normalized Polyakov-Liouville measure $\Q_\gamma$ concentrates on the unique smooth weight $u$ for which the conformal metric $e^{2u}g$ on $M$ has constant $Q$-curvature.

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

Seeing Roads Through Words: A Language-Guided Framework for RGB-T Driving Scene Segmentation

Robust semantic segmentation of road scenes under adverse illumination, lighting, and shadow conditions remain a core challenge for autonomous driving applications. RGB-Thermal fusion is a standard approach, yet existing methods apply static fusion strategies uniformly across all conditions, allowing modality-specific noise to propagate throughout the network. Hence, we propose CLARITY that dynamically adapts its fusion strategy to the detected scene condition. Guided by vision-language model (VLM) priors, the network learns to modulate each modality's contribution based on the illumination state while leveraging object embeddings for segmentation, rather than applying a fixed fusion policy. We further introduce two mechanisms - one which preserves valid dark-object semantics that prior noise-suppression methods incorrectly discard, and a hierarchical decoder that enforces structural consistency across scales to sharpen boundaries on thin objects. Experiments on the MFNet dataset demonstrate that CLARITY establishes a new state-of-the-art (SOTA), achieving 62.3% mIoU and 77.5% mAcc.

13.
arXiv (CS.AI) 2026-06-16

Frontier: Towards Comprehensive and Accurate LLM Inference Simulation

arXiv:2605.21312v2 Announce Type: replace-cross Abstract: Modern LLM serving is no longer homogeneous or monolithic. Production systems now combine disaggregated execution, complex parallelism, runtime optimizations, and stateful workloads such as reasoning, agents, and RL rollouts. Simulation is attractive for exploring this growing design space, yet existing simulators lack the architectural completeness and decision-grade fidelity it demands. Their monolithic-replica abstractions are ill-suited to disaggregated serving, while average-case analytical proxies can distort SLA predictions and even reverse optimization conclusions. We present Frontier, a discrete-event simulator for modern LLM inference serving. Frontier features a disaggregated abstraction. It captures the structure and dynamics of modern serving systems by modeling co-location, Prefill-Decode Disaggregation (PDD), and Attention-FFN Disaggregation (AFD) with role-specific cluster workers, incorporating key runtime optimizations (e.g., CUDA Graphs, speculative decoding) within the scheduler-batch-engine loop, and supporting stateful requests for emerging workloads. It further provides accurate and generalizable predictions of computation, communication, and memory costs across diverse serving scenarios with complex workload compositions. On 16-H800 GPU testbed, Frontier achieves an average throughput error below 4%. Compared with state-of-the-art simulators, it reduces end-to-end latency error from 44.9% to 6.4% under co-location and from 51.7% to 2.6% under disaggregation. It scales to over 1K GPUs on commodity CPUs and enables new use cases such as SLA-dependent Pareto frontier exploration, heterogeneous disaggregated allocation, agentic reasoning scheduling validation, and RL post-training reconfiguration. We release Frontier at https://github.com/NetX-lab/Frontier.

14.
arXiv (CS.CL) 2026-06-18

Retell, Reward, Repeat: Reinforcement Learning for Narrative Theory-Informed Story Retelling

Counterfactual story retelling exposes LLM shortcomings in constrained narrative solution spaces where they can no longer rely on recalling memorised training data. Ground-truth-based post-training, such as SFT, fails to teach LLMs how to generate logical and rational narrative events. In this paper, we introduce Retell, Reward, Repeat (RRR), an RL-based pipeline synthesising Structuralist Narratology with scalar narrativity to teach storytelling structure. We extend the TimeTravel dataset with human-annotated stages of narrative equilibrium to evaluate reward models. By using d-RLAIF, RRR derives training signals from the narrativity of textual features without the need for reference outputs. Evaluations demonstrate that RRR-trained LLMs outperform few-shot and SFT baselines in logic, rationality, and completeness, with output quality additionally validated by blind human preference. Relying on a small, query-only dataset, RRR provides a linguistically grounded, cost-effective post-training mechanism for storytelling–a domain currently lacking effective post-training methods. RRR highlights the continued relevance of integrating established linguistic theories into contemporary NLP.

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

Multi-Granular Node Pruning for Causal Circuit Discovery

arXiv:2512.10903v2 Announce Type: replace Abstract: Circuit discovery aims to identify minimal subnetworks that are responsible for specific behaviors in large language models (LLMs). Existing approaches primarily rely on iterative edge pruning, which is computationally expensive and limited to coarse-grained units such as attention heads or MLP blocks, overlooking finer structures like individual neurons. We propose a node-level pruning framework for circuit discovery that addresses both scalability and granularity limitations. Our method introduces learnable masks across multiple levels of granularity, from entire blocks to individual neurons, within a unified optimization objective. Granularity-specific sparsity penalties guide the pruning process, allowing a comprehensive compression in a single fine-tuning run. Empirically, our approach identifies circuits that are smaller in nodes than those discovered by prior methods; moreover, we demonstrate that many neurons deemed important by coarse methods are actually irrelevant, while still maintaining task performance. Furthermore, our method has a significantly lower memory footprint, 5-10x, as it does not require keeping intermediate activations in the memory to work.

16.
medRxiv (Medicine) 2026-06-16

Development of a symptom-based severity score anchored to health-related quality of life post-COVID-19 within the population-based EPILOC cohorts

Purpose Because simple symptom counts treat all symptoms as equally important and may not adequately capture the HRQoL impact of heterogeneous post-COVID-19 symptoms, we aimed to develop an HRQoL-anchored symptom severity score providing an interpretable measure of post-COVID-19 disease burden. Methods Baseline data from the population-based EPILOC and EPILOC Omicron surveys (adults aged 18-65 years) were used to develop a symptom-based severity score anchored to physical and mental HRQoL assessed with the SF-12. A two-stage modelling approach was applied to identify HRQoL-relevant symptoms and to derive symptom-specific weights for physical and mental component scores, incorporating 30 ordinal symptom severity variables. Symptom-specific weights were extracted to compute physical, mental, and composite severity scores. Score interpretation was examined using external reference measures, including EPILOC case status, self-reported health recovery, and functional consequences. Results A total of 19,004 participants (mean age 44.3 years, 59.6% female) were included. Sixteen symptoms contributed to the physical and eleven to the mental HRQoL score, with a limited subset accounting for most of the HRQoL loss. Severity scores were heavily right-skewed, with 50.6% of participants showing no measurable HRQoL impairment. Higher scores correlated with lower self-reported recovery, and increased probability of rehabilitation use and health-related changes in working time, supporting convergent and criterion-related validity. Conclusions This study introduces a transparent, HRQoL-anchored symptom severity score that measures graded post-COVID-19 burden beyond simple symptom counts. The score may be particularly suited for longitudinal assessment of recovery trajectories.

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

RegMix-D: Dynamic Data Mixing via Proxy Training Trajectories

Data mixture selection is critical for Large Language Model pretraining. Existing methods such as RegMix select a single static mixture by fitting a regression model on small-scale proxy runs. We propose RegMix-D, a simple extension of RegMix to dynamic mixing. Our key observation is that proxy runs produce not only endpoint losses, but also full loss trajectories, which can be used to further improve data mixture. By training regression model on these trajectories, we can predict optimal mixtures at multiple training stages. RegMix-D supports two deployment modes: an offline variant that generates a complete mixture schedule before target training, and an online variant that adapts the mixture during training using observed loss. Experiments on 25B tokens of the Pile dataset with a 1B parameter target model show that RegMix-D consistently improves over RegMix and DoReMi across 13 downstream tasks while remaining proxy-efficient: it surpasses RegMix even with only 128 proxy models (25% of RegMix's proxy compute budget).

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

Ensembling Sparse Autoencoders

arXiv:2505.16077v2 Announce Type: replace Abstract: Sparse autoencoders (SAEs) are used to decompose neural network activations into human-interpretable features. Typically, features learned by a single SAE are used for downstream applications. However, it has recently been shown that a single SAE captures only a limited subset of features that can be extracted from the activation space. Motivated by this limitation, we introduce and formalize SAE ensembles. Furthermore, we propose to ensemble multiple SAEs through naive bagging and boosting. In naive bagging, SAEs trained with different weight initializations are ensembled, whereas in boosting SAEs sequentially trained to minimize the residual error are ensembled. Theoretically, naive bagging and boosting are justified as approaches to reduce reconstruction error. Empirically, we evaluate our ensemble approaches with three settings of language models and SAE architectures. Our empirical results demonstrate that, compared to an expanded SAE that matches the number of features in the ensemble, ensembling SAEs improves the reconstruction of language model activations along with SAE stability. Additionally, on downstream tasks such as concept detection and spurious correlation removal, SAE ensembles achieve better performance, showing improved practical utility.

19.
arXiv (quant-ph) 2026-06-17

Breaking the bicycle frame: Coset-based quantum LDPC codes

arXiv:2606.17268v1 Announce Type: new Abstract: Generalizing the construction of two-block group algebra (2BGA) codes, we introduce a family of two-block quantum LDPC codes constructed using the action of a group on the cosets of its subgroup. This replaces the regular group actions of the earlier two-block constructions and significantly expands the search space, yielding new quantum LDPC codes outside the 2BGA family. Through a computer search, we identify several new quantum LDPC codes, including weight-6 codes with parameters $[[48,8,6]]$, $[[96,8,10]]$, and $[[224,12,16]]$, as well as weight-8 codes with parameters $[[84,16,8]]$, $[[112,16,10]]$, $[[128,16,12]]$, and $[[168,16,15]]$. Furthermore, we introduce a maximally packed syndrome extraction schedule of depth $w+2$, including initialization and measurement steps, for any code with a maximum stabilizer weight of $w$ from our family. Under a standard circuit-level noise model, our codes, when decoded using BP-OSD, perform competitively with BB codes, achieving thresholds of $\approx0.65\%$ for the weight-6 family and $\approx0.35\%$ for the weight-8 family. Finally, we introduce a group-theoretic framework to generate sequences of graph-based covers of 2BGA codes, recovering and extending recent results on code constructions of this type.

20.
arXiv (CS.CV) 2026-06-11

VOID: Defeating Unauthorized Mimicry in Latent Diffusion Models

While Latent Diffusion Models (LDMs) have revolutionized visual synthesis, they are increasingly exploited for unauthorized mimicry of individuals. Existing defenses inject deceptive perturbations to steer the generated images toward irrelevant targets. However, this approach hinges on an ungrounded assumption: subtle perturbations can maintain their deceptive efficacy throughout an LDM's extensive generation process. In reality, the model's innate restoration mechanism will remove such perturbations and cause individual identities to re-emerge in the images generated. We propose VOID, a defense framework that overcomes this conundrum by manipulating an LDM's intrinsic stochasticity. VOID perturbs the diffusion pipeline in two novel ways: 1) amplifying the latent encoding errors to shatter an image's semantic structure, and 2) counteracting the target guidance signals to suppress the model's restoration capabilities. This results in a semantic corruption that thwarts any unauthorized mimicry. Notably, the security gain does not come at the price of visual utility, as VOID simultaneously manages to confine perturbations to human-imperceptible regions of protected images. Our comprehensive evaluation of 24 state-of-the-art defenses against 10 mimicry attacks on 5 datasets demonstrates VOID's unprecedented protection power: it increases the average Frechet Inception Distance (FID) from 113 to 365, a 223% improvement over the strongest defense to date.

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

A unified complexity bound for logconcave sampling

arXiv:2606.12694v1 Announce Type: cross Abstract: We give a simple, unified, and nearly tight bound for sampling arbitrary logconcave distributions from a warm start using the In-and-Out algorithm along with exponential lifting. The main new ingredient in the analysis is an improved bound on the Poincaré constant of a lifted distribution. As a consequence, the resulting convergence rate is nearly tight for both constrained settings (e.g., Gaussian restricted to a convex body) and well-conditioned settings (e.g., strongly logconcave and smooth densities).

22.
medRxiv (Medicine) 2026-06-16

Sleep regularity outweighs sleep duration as a predictor of disease

Sleep regularity, the consistency of sleep-wake timing from one day to the next, is more strongly associated with longevity than adequate sleep duration. Whether this relationship persists across common diseases is unknown. We compared sleep regularity vs. sleep duration as risk factors for 199 diseases and disorders, using ten million hours of objective sleep-wake data (N=60,998, age[mean{+/-}SD]=62.8{+/-}7.8, 55% female). Multivariable-adjusted risks of incident diseases/disorders for regular/irregular and short/adequate sleepers were compared across 9.5 years of follow-up. Irregular sleep predicted risks for 131 diseases/disorders, more than double the number predicted by short sleep duration (63). Irregular sleep was a superior predictor than short sleep duration for 90 diseases/disorders, including circulatory, metabolic, digestive, renal, infectious, neurological, and musculoskeletal conditions, and mental disorders, whereas short sleep duration was the superior predictor for only 9 diseases/disorders. For models where short sleep duration explained disease risks, 83% were improved by adding sleep regularity. Sleep regularity was a stronger predictor of diseases/disorders than sleep duration in this cohort and should be considered an essential dimension of sleep health.

23.
arXiv (quant-ph) 2026-06-16

Finite-Element Matrix Product States for Continuum Models in One Dimension

arXiv:2606.14873v1 Announce Type: new Abstract: We present a matrix product state framework for simulating one-dimensional quantum many-body systems in the continuum using non-orthogonal single-particle basis sets. By mapping the physical problem to an auxiliary computational space, we show that the resulting many-body overlap operator can be efficiently encoded as a matrix product operator for sufficiently localized orbitals, thereby generalizing a construction that first appeared in [arXiv:2405.10285]. This construction recasts the variational ground-state search into a generalized eigenvalue problem, which can be solved using a generalized density matrix renormalization group algorithm. As a primary application, we employ a first-order finite-element expansion to study the ground state properties of the Lieb-Liniger gas in the presence of inhomogeneities. This approach also provides a natural setting for exactly refining the lattice, thereby enabling multigrid optimization strategies for matrix product states.

24.
arXiv (CS.LG) 2026-06-18

A Human-in-the-Loop Bayesian Optimization Framework for Constraint-Aware Bioprocess Development

arXiv:2606.19230v1 Announce Type: new Abstract: This work presents an extension to Pareto Front Guided Sampling (PFGS), a Human-in-the-Loop (HitL) Bayesian Optimization (BO) framework in which Gaussian process (GP) surrogate-derived quantities are reformulated as objectives of a multi-objective optimization problem, and the resulting Pareto front is exposed to a domain expert for interactive candidate selection rather than returning a single automated recommendation. The framework is extended in two directions: constrained optimization is addressed by incorporating the posterior probability of satisfying output specification limits as an explicit Pareto objective, computed analytically from the GP posterior distribution; robust optimization is addressed by a Monte Carlo sampling strategy that estimates expected lower-confidence performance over a user-defined variability of input perturbations, capturing performance degradation under likely implementation deviations. The resulting multi-dimensional Pareto representation renders trade-offs between predicted performance, model uncertainty, probabilistic constraint satisfaction, and input robustness simultaneously visible through pairwise two-dimensional projections on an interactive dashboard, enabling selection criteria to be iteratively refined as the surrogate model improves and development objectives evolve. The framework is showcased on an eight-dimensional fed-batch Chinese Hamster Ovary (CHO) cell culture simulator demonstrating systematic identification of high-performing, feasibility-compliant, and perturbation-resilient operating conditions, and illustrating how expert-defined requirements provide a principled stopping criterion and support informed allocation of experimental resources.

25.
arXiv (CS.AI) 2026-06-15

COGNITION: From Evaluation to Defense against Multimodal LLM CAPTCHA Solvers

arXiv:2512.02318v4 Announce Type: replace-cross Abstract: This paper studies how multimodal large language models (MLLMs) undermine the security guarantees of visual CAPTCHA. We identify the attack surface where an adversary can cheaply automate CAPTCHA solving using off-the-shelf models. We evaluate 7 representative MLLMs on 18 real-world CAPTCHA task types, measuring single-shot accuracy, success under limited retries, end-to-end latency, and per-solve cost. We further validate our findings through a supplemental external dataset and an adaptive-attacker setting with session memory, while also analyzing the impact of task-specific prompt engineering and few-shot demonstrations on solver effectiveness. We reveal that MLLMs can reliably solve recognition-oriented and low-interaction CAPTCHA tasks at human-like cost and latency, whereas tasks requiring fine-grained localization, multi-step spatial reasoning, or cross-frame consistency remain significantly harder for current models. By examining the reasoning traces of such MLLMs, we investigate the underlying mechanisms of why models succeed/fail on specific CAPTCHA puzzles and use these insights to derive defense-oriented guidelines for selecting and strengthening CAPTCHA tasks. To validate these principles, we present a proof-of-concept by hardening a vulnerable CAPTCHA type using our guidelines. We demonstrate that incorporating fine-grained localization and implicit counting reduces the success rate of state-of-the-art MLLMs from over 95\% to 0\%, confirming that structural changes can effectively mitigate the threat. We conclude by emphasizing the urgent need for CAPTCHA redesign as MLLM capabilities increasingly threaten existing defenses. Code Availability (https://doi.org/10.5281/zenodo.20406852).