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

Towards Understanding What State Space Models Learn About Code

arXiv:2602.06774v2 Announce Type: replace Abstract: State Space Models (SSMs) have emerged as an efficient alternative to the Transformer architecture. Prior work shows that, when trained under comparable conditions, SSMs can match or surpass Transformers on code understanding tasks. However, their internal mechanisms remain a black box. We present the first systematic analysis of what SSM-based code models learn along with the direct comparison between SSM and Transformer models in this domain. Our analysis shows that SSMs capture syntactic and semantic structure more effectively than Transformers during pretraining but forgets certain relations during fine-tuning on some tasks. To investigate this behavior, we introduce SSM-Interpret, a frequency-domain framework that exposes a spectral shift toward short-range dependencies during fine-tuning. Guided by these findings, we propose architectural modifications that significantly improve the performance of SSM-based code model by upto +6 MRR on NLCodeSearch. This demonstrates that our analysis not only explains model behavior but also leads directly to better designs.

03.
arXiv (CS.CL) 2026-06-24

AGORA: An Archive-Grounded Benchmark for Agentic Workplace Document Reasoning

Large language models are increasingly deployed as agents that reason over documents rather than answer from parametric knowledge. We study archive-grounded reasoning: locating sparse evidence across a large, messy collection of workplace files, reconciling inconsistent terminology, units, and time conventions, and computing an answer. Existing benchmarks address only parts of this setting and none jointly stresses archive-groundedness, agentic exploration, and cross-domain coverage. We introduce Agora, a benchmark pairing 362 questions with eight domain collections of 9,664 authentic documents and 372M tokens, far exceeding any model's context window, so agents must explore deliberately rather than scan exhaustively. Agora is built by an agentic pipeline combining cross-document task synthesis, leakage-preventing obfuscation, and difficulty filtering. Evaluating eight models, we find the task far from solved: even the strongest reaches only 59.4% accuracy, with notable variation across domains.

04.
arXiv (CS.CL) 2026-06-19

Before the Labels: How Dataset Construction Shapes Suicidality Detection in Clinical Text

Clinical NLP increasingly relies on electronic health record (EHR) data to detect suicidal behaviors, treating clinical documentation as more reliable ground truth than social media. We argue that this framing obscures how EHR-based suicidality datasets encode a particular operationalization of suicidality, shaped by who authors the data, how episodes are bounded, and how ambiguity is resolved. We ground this argument in a case study of the ScAN dataset, built over MIMIC-III clinical notes. We show how governance constraints, ICD-based cohort selection, single-annotator labeling, and hospital-stay-level aggregation produce labels that reflect clinician-documented judgments, treat suicidality as a bounded episode, and assume that intent can be reliably inferred from documentation. A linguistic analysis demonstrates that identical labels subsume heterogeneous clinical framings differing in temporality, negation, and uncertainty. We argue that clinical NLP should examine the assumptions embedded in suicidality datasets before interpreting their labels as ground truth.

05.
arXiv (CS.AI) 2026-06-24

Solving Inverse Problems of Chaotic Systems with Bidirectional Conditional Flow Matching

arXiv:2606.24824v1 Announce Type: new Abstract: Modeling chaotic systems is crucial yet challenging. Inverse problems in chaotic dynamics, namely inferring initial conditions from final states, remain largely unsolved because of ill-posedness, non-uniqueness, instability, and potentially chaotic time-reverse dynamics. We address this open problem with Bidirectional Conditional Flow Matching (Bi-CFM), which learns bidirectional mappings between distributions of initial and final states to capture the stochasticity of chaotic evolution and mitigate exponential error accumulation over time. Furthermore, for systems with conservation laws, we extend it to Conservation-constrained Bi-CFM (CBi-CFM). Across the classic Lorenz, Circuit, and high-dimensional Lorenz 96 systems, Bi-CFM improves five distribution-level metrics over baselines while achieving a speedup of more than two orders of magnitude. In the three-body planet-planet scattering problem in planetary dynamics, CBi-CFM better respects conservation laws, with conservation errors comparable to those of the ground truth. Finally, on real observations of globular clusters, collisional million-body systems shaped by $\sim 10^{10}$ years (10 Gyr) of evolution, our method represents an advance in accuracy, establishing a scalable route to solving inverse problems of long-timescale real-world chaotic dynamics.

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

On-Policy Self-Distillation with Sampled Demonstrations Reduces Output Diversity

arXiv:2606.26091v1 Announce Type: cross Abstract: On-policy self-distillation achieves strong pass@1 accuracy by using a single model as both teacher and student, with the teacher conditioned on a correct demonstration to provide dense token-level feedback. We show that this could come at a hidden cost: rollout diversity decreases and pass@k curves flatten (i.e., generating more rollouts fails to improve accuracy). We trace this to compounding biases in the design of self-distillation with sampled demonstrations. The teacher scores each student rollout while conditioned on a sampled correct rollout, channeling its feedback through the model's own biases. We theoretically analyze the optimal self-distillation policy and show that it tilts the base distribution by a pointwise conditional mutual information score between the student's rollout and the correct rollout used as context. Unlike the ideal optimal on-policy reinforcement learning (RL), which preserves probability ratios among equally correct rollouts, self-distillation can amplify existing probability gaps, concentrating mass on already-dominant modes. On a controlled graph path-finding task and science question-answering benchmarks, self-distilled models match or exceed RL on average performance but exhibit substantially lower functional and semantic diversity, failing on out-of-distribution settings that require diverse strategies.

07.
bioRxiv (Bioinfo) 2026-06-24

Systematic benchmarking of multi-modal approaches for tumor-naive ctDNA detection and quantification

Longitudinal monitoring of circulating tumor DNA (ctDNA) has emerged as a promising framework for characterizing treatment response dynamics in cancer. Scalable tumor-naive approaches for quantifying ctDNA often involve whole-genome sequencing (WGS) or DNA methylation profiling, but their comparative performance and capacity for complementary integration remain poorly understood. Here we systematically benchmarked tumor-naive WGS- and methylation-based ctDNA quantification methods using plasma from 150 patients with colorectal, lung and breast cancer. Using paired high-depth WGS and EM-seq data, we generated 40,000 in silico samples and evaluated detection accuracy, limits of detection (LoD) and quantification (LoQ) across cancer types and sequencing depths (0.1x-30x). We further assessed single- and multimodal method combinations, identifying conditions under which integrated approaches enhance analytical performance for detection and quantification relative to single modalities. This benchmark delineates key performance trade-offs and provides a practical framework to support method development and guide future research applications in ctDNA-based biomarker studies.

08.
arXiv (CS.CL) 2026-06-24

What's Missing in Vision-Language Models? Probing Their Struggles with Causal Order Reasoning

Despite the impressive performance of vision-language models (VLMs) on downstream tasks, their ability to understand and reason about causal relationships in visual inputs remains unclear. Robust causal reasoning is fundamental to solving complex high-level reasoning tasks, yet existing benchmarks often include a mixture of reasoning questions, and VLMs can frequently exploit object recognition and activity identification as shortcuts to arrive at the correct answers, making it challenging to truly assess their causal reasoning abilities. To bridge this gap, we introduce VQA-Causal and VCR-Causal, two new benchmarks specifically designed to isolate and rigorously evaluate VLMs' causal reasoning abilities. Our findings reveal that while VLMs excel in object and activity recognition, they perform poorly on causal reasoning tasks, often only marginally surpassing random guessing. Further analysis suggests that this limitation stems from a severe lack of causal expressions in widely used training datasets, where causal relationships are rarely explicitly conveyed. We additionally explore fine-tuning strategies with hard negative cases, showing that targeted fine-tuning can improve model's causal reasoning while maintaining generalization and downstream performance. Our study highlights a key gap in current VLMs and lays the groundwork for future work on causal understanding.

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

VISA: VLM-Guided Instance Semantic Auditing for 3D Occupancy World Models

Semantic 3D occupancy provides a voxelized world state for autonomous driving and robot decision making, but object and rare-class errors can affect free-space interpretation, collision checking, and temporal state propagation. We show that a common VLM strategy, aligning 3D voxel or object features with crop-caption embeddings, improves text-space similarity without reliably improving closed-set occupancy mIoU. Motivated by this mismatch, we propose VISA, a training-time semantic auditing approach for existing occupancy world models. VISA queries an offline VLM on a representative crop of each physical object instance, obtains a structured audit with class hypotheses, plausible confusions, reliability, attributes, and evidence, and propagates it along the object track. The audit is grounded to matched 3D object voxels and distilled into semantic logits through reliability-weighted taxonomy, attribute-factor, and scene-level audit graph losses, while inference remains unchanged and requires no VLM. On nuScenes, averaged across three runs, VISA improves OccWorld from 19.06 to 20.05 mIoU and GaussianWorld from 21.36 to 21.91 mIoU; on GaussianWorld, object mIoU improves from 18.18 to 19.16 and rare-class mIoU from 15.60 to 16.79. These results suggest that VLMs are better suited to closed-set occupancy as reliability-aware semantic auditors than as generic caption-embedding targets.

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

Faster Completion, Less Learning: Generative AI Reduced Study Time on Math Problems and the Knowledge They Build

arXiv:2605.21629v2 Announce Type: replace-cross Abstract: How much have students' ordinary learning processes shifted in response to generative AI, and how does that affect their durable learning outcomes? Self-report surveys show little change, while small-scale behavioral studies report widespread AI use without the scale or duration to measure learning consequences. We address both questions using a ten-year panel of $3.2$ million ALEKS learning interactions for investigating time-on-task, complemented by ALEKS PPL placement-assessment data for examining proctoring and learning outcomes, with a quasi-experimental design exploiting variation in tasks that are more susceptible to AI (text-based word problems) and less susceptible to AI (interactive graph-based problems). Learning time on AI-susceptible problems declines $2.8\%$ per quarter among college students after ChatGPT's release, cumulating to $26.9\%$ over eleven quarters; high-schoolers show $31.3\%$, middle-schoolers $9.0\%$, and Grade 5 students no detectable change. Among college students, the post-ChatGPT divergence vanishes entirely under proctoring, ruling out broad efficiency gains as the likely explanation. Logistic fixed-effects models on randomly assigned proctored retention items yield a $25\%$ cumulative decline in odds of correct response; the same estimator on non-proctored assessment produces a large opposite-signed increase – inconsistent with any platform, cohort, or curriculum explanation. These results are among the first large-scale behavioral and outcome evidence that generative AI has altered how students study and the knowledge they build – the population-level indicator of cognitive surrender, with direct implications for educational research, assessment governance, and AI policy.

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

Adaptive Distance-Aware Trunk Deep Operator Learning for Long-Span Roadway Bridges

arXiv:2606.20015v1 Announce Type: new Abstract: Long-span roadway bridges exhibit highly localized structural responses under vehicular loading, making repeated FE analysis computationally expensive for applications such as influence surface generation and structural digital twins. Existing SciML approaches struggle to accurately capture these localized responses. To address this challenge, this study proposes an adaptive-trunk DeepONet for localized structural response prediction in large-scale bridge systems. The framework dynamically constructs a load-dependent learning domain using a KNN strategy, allowing the network to focus on structural influence zones. The trunk network is further enhanced using distance-aware features that encode the geometric relationship between the load and structural nodes. A physics-based full-field reconstruction is incorporated through a stiffness-informed Schur complement formulation, enabling predictions at adaptive nodes to be extended to the entire structural domain. To enable scalable training, response data are generated using a reduced-order equivalent shell model that preserves the dominant global behavior while significantly reducing computational cost. The proposed framework is validated on both a benchmark bridge model and the real-world Mussafah Bridge. Results show that the method achieves FEM-level accuracy with relative errors below 5%, while reducing the total response evaluation time (including full-field reconstruction) by approximately 60x; excluding the post-processing reconstruction step, the AD-DeepONet inference is up to four orders of magnitude faster than FEM. In addition, the framework enables rapid generation of full-field responses, influence lines, and influence surfaces under arbitrary vehicular loading configurations, demonstrating strong potential for large-scale bridge analysis and digital twin applications.

12.
arXiv (CS.CV) 2026-06-19

Prediction of Alzheimer's Disease Risk Factors from Retinal Images via Deep Learning: Development and Validation of Biologically Relevant Morphological Associations in the UK Biobank

The systemic, metabolic, lifestyle factors have established associations with Alzheimer's Disease (AD) through epidemiologic and AD-specific biomarker studies. Whether colored fundus photography (CFP) contains retinal structural signatures corresponding to these AD-related risk domains remains unclear. To determine whether deep learning (DL) models can predict 12 AD-related risk factors from CFP and to characterize the retinal structures underlying these predictions, thereby assessing whether CFP reflects pathways to AD vulnerability. Using 62,876 CFPs from 44,501 unique participants from the UK Biobank, DL models were trained to predict 12 factors linked to AD incidence: 6 categorical (sex, smoking, sleeplessness, economic status, alcohol use, depression) and 6 continuous (age, age at completing education, BMI, systolic, diastolic blood pressure, HbA1c). Model performance, model saliency, and saliency-derived scores (CAM-Score) were evaluated and compared to retinal morphometry. The scores were also compared between incident-AD cases (average 8.55 years before onset) and matched controls. Performance of DL ranged from AUROC= 0.5654-0.9480 for categorical and R2=-0.0291-0.7620 for continuous factors, outperforming most of the morphometry-machine learning models. Saliency-based score consistently highlighted biologically meaningful regions, particularly the optic nerve head and retinal vasculature. It also aligned with present morphometric variations. Several saliency-based scores differed significantly between incident AD and matched controls, suggesting potential overlap between retinal correlates of risk factors and preclinical AD-associated changes. CFP encodes retinal signatures linked to AD risk factors. Although not diagnostic, DL-derived retinal representations may uncover biologically meaningful risk-related structural changes mirroring the potential AD vulnerability.

13.
arXiv (CS.CL) 2026-06-25

An Empirical Study of Many-Shot In-Context Learning for Machine Translation of Low-Resource Languages

In-context learning (ICL) allows large language models (LLMs) to adapt to new tasks from a few examples, making it promising for languages underrepresented in pre-training. Recent work on many-shot ICL suggests that modern LLMs can further benefit from larger ICL examples enabled by their long context windows. However, such gains depend on careful example selection, and the inference cost can be prohibitive for low-resource language communities. In this paper, we present an empirical study of many-shot ICL for machine translation from English into ten truly low-resource languages recently added to FLORES+. We analyze the effects of retrieving more informative examples, using out-of-domain data, and ordering examples by length. Our findings show that many-shot ICL becomes more effective as the number of examples increases. More importantly, we show that BM25-based retrieval substantially improves data efficiency: 50 retrieved examples roughly match 250 many-shot examples, while 250 retrieved examples perform similarly to 1,000 many-shot examples. We further show that ICL provides additional gains on top of fine-tuning.

14.
arXiv (quant-ph) 2026-06-25

Arbitrarily Loss-Tolerant Quantum Position Verification in a Single Execution

arXiv:2606.25037v1 Announce Type: new Abstract: Quantum position verification (QPV) seeks to certify the spatial location of an untrusted prover, but is challenged fundamentally by entanglement-based attacks and experimentally by photon loss. Both issues were addressed separately in different works and were simultaneously resolved for sequentially repeated protocols in Phys.\ Rev.\ Lett.\ 135,~260801 via a commitment-based modification that renders security independent of transmission losses. However, single-execution protocols are preferable in practice, and the original techniques do not extend to the parallel setting due to their reliance on sequential structure. We overcome this by utilizing different techniques based on no-signalling correlations, lifting the commitment modification to the parallel regime while preserving the security guarantees of the underlying QPV protocol. Applying this to a BB84-based QPV protocol suitable for near-term implementation and secure against bounded-entanglement adversaries, we prove that fixing a threshold~$k$ on the number of successfully committed qubits yields an adversarial acceptance probability that decays exponentially in~$k$. The resulting protocol maintains robustness to noise levels of up to~$3.7\%$ and remains secure under arbitrarily slow quantum communication, as does the original protocol. This yields the first fully loss-tolerant single-shot QPV protocol secure against entangled attackers, making QPV feasible over arbitrary distances. Finally, we refine the sequential analysis and obtain improved quantitative parameters for experimental implementations.

15.
arXiv (CS.AI) 2026-06-12

Token Complexity Theory for AI-Augmented Computing

作者:

arXiv:2606.12647v1 Announce Type: cross Abstract: AI-augmented computing delegates natural language queries, code generation requests, and other open-ended tasks to a cluster of AI models that processes queries and generates responses. This paradigm introduces a resource dimension that neither classical time nor space complexity captures: the cost of sending queries to and receiving responses from such a cluster. We introduce token complexity, a formal resource measure defined as the minimum expected token cost to achieve a specified level of output quality on a task, and develop a taxonomy classifying AI systems by the strength of their probabilistic properties. We develop token complexity within the framework of AI-Oracle Turing machines, in which a probabilistic Turing machine interacts with a stochastic oracle via dedicated query and response tapes. We prove basic theorems establishing that token complexity behaves as expected: monotonicity (higher quality costs more tokens), convexity (quality improvements become progressively more expensive), price sensitivity (small price changes produce bounded cost changes), and price-relativity of task ordering (the token complexity ordering of tasks can reverse depending on the query-to-response cost ratio). We prove that the complexity frontier, defined as the set of all feasible resource bounds in tokens, time, and space, is non-empty, upward-closed, and convex.

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

Separating Oblivious and Adaptive Models of Variable Selection

arXiv:2602.16568v2 Announce Type: replace-cross Abstract: Sparse recovery is among the most well-studied problems in learning theory and high-dimensional statistics. In this work, we investigate the statistical and computational landscapes of sparse recovery with $\ell_\infty$ error guarantees. This variant of the problem is motivated by variable selection tasks, where the goal is to estimate the support of a $k$-sparse signal in $\mathbb{R}^d$. Our main contribution is a provable separation between the oblivious (``for each'') and adaptive (``for all'') models of $\ell_\infty$ sparse recovery. We show that under an oblivious model, the optimal $\ell_\infty$ error is attainable in near-linear time with $\approx k\log d$ samples, whereas in an adaptive model, $\gtrsim k^2$ samples are necessary for any algorithm to achieve this bound. This establishes a surprising contrast with the standard $\ell_2$ setting, where $\approx k \log d$ samples suffice even for adaptive sparse recovery. We conclude with a preliminary examination of a partially-adaptive model, where we show nontrivial variable selection guarantees are possible with $\approx k\log d$ measurements.

17.
medRxiv (Medicine) 2026-06-24

Digital exclusion and mental health in UK Armed Forces veterans: findings from the Veterans Digital Needs Study

Background: Public services are increasingly delivered through digital platforms. Although digital health may improve access and scalability, they may also widen inequalities for people who lack reliable access, confidence, skills, affordability or trust. Objective: This study examined the prevalence of self-reported digital exclusion among UK veterans and assessed its association with depression, anxiety and loneliness. Methods: A cross-sectional online survey was conducted between July 2025 and March 2026. Participants were UK Armed Forces veterans and resident in the UK. The survey collected sociodemographic, military service, digital access and health data. Self-reported digital exclusion was defined as reporting feeling excluded or disadvantaged due to lack of digital access or skills. Probable depression, anxiety and loneliness were assessed using the PHQ-2, GAD-2 and three-item UCLA Loneliness Scale, respectively. Associations between digital exclusion and each outcome were examined using adjusted multivariable logistic regression. Results: Of 1,911 responses received, 1,607 were included after data quality exclusions. Among participants with valid responses to the primary digital exclusion item, 553 (41.7%) reported digital exclusion. Digital exclusion was more common among females, younger veterans and those with lower household income. Probable depression, anxiety and loneliness were more prevalent among digitally excluded participants than among non-excluded participants. In adjusted models, self-reported digital exclusion was associated with higher odds of probable depression (AOR 1.38; 95% CI 1.04 to 1.83; p=0.028), probable anxiety (AOR 1.63, 95% CI 1.23 to 2.16; p

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

Task-Aligned Stability Analysis of Vision-Language Models for Autonomous Driving Hazard Detection

Vision-language models (VLMs) are increasingly used for scene understanding in autonomous driving, but robustness analysis often relies on task-agnostic embedding stability alone. We study whether corruption-induced embedding drift predicts changes in a task-aligned hazard score derived from CLIP image-text similarities. Using controlled corruptions on BDD100K road scenes, we compare embedding drift against margin drift, defined as the change in hazard score under perturbation. The relationship is highly corruption-dependent: some families exhibit strong coupling between representation drift and decision drift, while others induce hazardous decision instability despite relatively modest embedding change. Furthermore, corruption families differ in failure direction: most suppress hazard detections via false negatives, while occlusion instead triggers false alarms, suggesting that benchmark design should account for asymmetric failure modes, not just overall instability rates. These results suggest that robustness benchmarks should include task-aligned stability measures in addition to embedding-level perturbation statistics.

19.
arXiv (CS.AI) 2026-06-16

Edu-Theater: A Data-Efficient Agent Framework for Scalable Learner Behavior Simulation through Staging Roll-Call

arXiv:2606.15225v1 Announce Type: cross Abstract: Large-scale learner-task interaction data are crucial for intelligent educational systems but are costly to collect and constrained by privacy and learner engagement. Learner simulators play a critical role in simulating scalable learner behavior without the need for continuous involvement of real learners. However, existing methods are predominantly individual-centric, pairing a simulator with each learner to iteratively infer latent knowledge states from dense interaction histories, which is both data- and computation-intensive, and fragile in cold-start scenarios. We propose a cohort-aware roll-call simulation paradigm that first constructs cohort-level proficiency priors and refines individual learner states through a small number of targeted diagnostic queries. Based on this paradigm, we introduce Edu-Theater, an LLM-powered agent system that performs cohort-aware learner simulation via a teacher agent and retrospective roll-call probing over learner logs. Edu-Theater enables scalable future behavior simulation without the need for dense per-learner histories. Experiments on two real-world datasets demonstrate that Edu-Theater achieves higher simulation accuracy with significantly fewer LLM calls, producing synthetic data that enhances downstream applications such as adaptive testing.

20.
medRxiv (Medicine) 2026-06-10

Human-centred design approaches to health facility design: Evidence from perinatal care settings in Ethiopia and Bangladesh

While significant progress has been made in perinatal outcomes over recent decades in low- and middle-income countries (LMICs), maternal and newborn quality improvement initiatives often fail to account for the spatial conditions in which they are implemented. Health systems are increasingly deploying evidence-based care models into built environments that are not optimally structured to meet the needs of its patient population. As the principal users, patients and health care workers can offer pragmatic insights about improving these structural designs. Our objective was to gather insights from patients, providers, and companions about how the physical design of their health facilities influenced their experience receiving or delivering perinatal care. We conducted a prospective observational study using a human-centred design (HCD) approach to analyse perceptions of the quality of perinatal care across two low resource settings: Ethiopia and Bangladesh. Using engagement and assessment tools, we conducted interviews, focus groups, facility walk-throughs, co-design workshops, and infrastructural assessments with patients, companions, providers, and Ministry of Health representatives. Descriptive statistics and thematic analysis were used to identify key learnings and develop recommendations. Across both countries, participants identified the need for facility layouts that better support privacy, mobility during labour, alternative birth positions, companion involvement, cultural and religious practices, sanitation, and provider visibility. Based on these insights, we developed six recommendations to better align health facility infrastructure with maternal and newborn care delivery needs. Our findings suggest that investments in health facility infrastructure may improve care experiences and help enable respectful, safe, and evidence-based maternal and newborn care. Alongside targeted spatial improvements, government authorities responsible for health facility planning should incorporate participatory design processes to ensure infrastructure reflects the needs of patients, companions, and providers and supports high-quality care delivery.

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

Will AI Agents Free Us From Meaningless Work? A Human-Centered Analysis

arXiv:2606.12430v1 Announce Type: cross Abstract: Some claim that AI agents will free workers from the boring parts of their jobs, yet little is known about how workers themselves identify which tasks should be automated. Prior research focuses on occupations, overlooking that workers experience varying levels of meaning across tasks within the same role. We address this gap with a task-level analysis grounded in Graeber's theory of bullshit jobs. Using ratings from 202 workers on 171 workplace tasks, we (1) validate a five-item scale of perceived bullshitness, (2) show that perceived bullshitness strongly predicts desire for AI delegation, and (3) find that such tasks are also seen as requiring less human oversight. Together, these findings suggest that tasks perceived as bullshit are natural candidates for AI delegation, aligning worker preferences with perceived feasibility.

22.
bioRxiv (Bioinfo) 2026-06-17

DNA-binding specificity recognition from predicted homologous protein-DNA structures

Predicting protein DNA-binding specificity is essential for understanding gene regulation and disease mechanisms. Existing deep learning methods typically infer specificity from a single protein-DNA complex structure, which limits their ability to capture the diverse geometric patterns underlying protein-DNA recognition. Homologous protein-DNA interfaces provide complementary structural evidence and richer geometric features related to interatomic interactions. To address the limited diversity and coverage of experimentally determined complexes, we constructed a large-scale library of predicted homologous protein-DNA complex structures. Building on this resource, we propose HomoDSP, a template-retrieval-based framework for accurate DNA-binding specificity prediction. Benchmark evaluations and validation on newly released JASPAR 2026 samples indicate that HomoDSP outperforms existing methods in both accuracy and generalization, with particularly substantial gains on high-error samples. Moreover, this performance is largely retained when AlphaFold3-predicted complex structures are used as input. Template- and residue-level interpretability analyses suggest that HomoDSP improves prediction by focusing on DNA-affinity residues across multiple homologous templates. Finally, universal Protein Binding Microarrays evaluations on AI-designed DNA-binding proteins show that HomoDSP rescues a baseline failure mode in which the baseline method produces incorrect predictions because of training-set bias. Together, these results support the use of homologous template interfaces as informative structural priors for decoding protein DNA-binding specificity.

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

Coherent Control of an Embedded Bound State Without a Spectral Gap

作者:

arXiv:2606.17685v1 Announce Type: new Abstract: Bound states in the continuum (BICs) can confine photonic excitations in open systems without conventional cavities or band gaps, making them natural candidates for long-lived quantum storage and single-photon control. Their use is limited, however, by two obstacles: they are dark to incident photons, and they lack spectral-gap protection from the surrounding continuum. We overcome both limitations in a giant atom coupled to a one-dimensional waveguide using two temporal control knobs. Atomic-frequency modulation breaks and restores the destructive-interference condition, enabling deterministic capture and release of mode-matched single photons. Coupling modulation instead preserves the BIC condition while tuning the atomic and photonic weights of the stored state. A key result is that this embedded state can nevertheless be controlled adiabatically despite the absence of a spectral gap, with an intrinsic leakage probability linear in the ramp rate. By separating radiative access from BIC-preserving deformation, the protocol turns a dark BIC into a single-photon memory whose fidelity is set by the intrinsic continuum-induced leakage law, providing a route to embedded-state control in open photonic platforms.

24.
bioRxiv (Bioinfo) 2026-06-15

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

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

25.
arXiv (CS.AI) 2026-06-12

Physics-Guided Spatiotemporal Learning for Coastal Wave Peak Period Estimation from Video

arXiv:2606.13302v1 Announce Type: new Abstract: Wave parameters in the nearshore are crucial for coastal engineering, shoreline protection, marine hazard assessment, and coastal management for climate resilience. Traditional monitoring systems like buoys and radar platforms offer accurate monitoring but can have high installation and maintenance expenses and limited spatial coverage. Passive ocean monitoring using video has been achieved by leveraging deep learning, however, many methods are not physically interpretable, feasible, and validated for oceanography. In thiswork, a Physics-Guided Deep Spatiotemporal Learning Framework for direct estimation of nearshore wave peak periods from passive coastal video stream is proposed. The framework combines automated temporal-variance based region-of-interest detection, multi-stage Sim-to-Real transfer learning, and physics-informed regularization to enhance the predictive accuracy and physical consistency. A variety of spatiotemporal architectures were assessed, such as transformer-based and recurrent-convolutional ones, alongside synthetic pretraining,silver-label adaptation, and expert fine-tuning. The results show that transformer-based architectures outperformed in terms of the accuracy of the instantaneous prediction, while lightweight recurrent-convolutional architectures achieved higher temporal stability and operational oceanographic skill. Ablation studies also demonstrated the benefits of physics-guided regularization in terms of trend-following consistency, and physically implausible predictions. Explainability auditing also helped to focus attention in hydrodynamically active surf-zone regions and showed good agreement with the physically derived wave propagation behavior. In general, the proposed framework shows the promise of physics-guided video-based deep learning systems for long-term coastal wave monitoring that are cost-efficient and operationally feasible.