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01.
arXiv (quant-ph) 2026-06-15

Quantum Horizon: An evaluation of quantum computing as a threat to Bitcoin and Ethereum

arXiv:2606.14484v1 Announce Type: new Abstract: Quantum computing poses a real, broad-based, but bounded and substantially mitigable threat to Bitcoin and Ethereum. We separate the two quantum algorithms that public discussion routinely conflates: Shor's algorithm breaks the elliptic-curve signatures (ECDSA over secp256k1, BLS over BLS12-381) that authorize spending, whereas Grover's algorithm does not meaningfully threaten proof-of-work mining, which is protected by a merely quadratic speedup, fault-tolerant per-operation costs, a square-root parallelization wall, and difficulty adjustment. Folding hardware scaling, the falling resource requirement, a fault-tolerance readiness lag, and expert surveys into a single Monte-Carlo forecast yields a wide, bimodal arrival distribution for a cryptographically relevant quantum computer: about a one-in-six chance by 2035, near 30% by 2040, and about 60% by 2050. Exposure is concentrated and mostly migratable: of Bitcoin's roughly six million quantum-exposed coins only about 2.3 million are irreducibly at risk, while 50 to 65% of Ether sits at key-revealed accounts that can adopt post-quantum signatures. A timely migration beats even an optimistic 2035 machine, so the binding constraint is governance, not technology. A survey of the top twenty cryptocurrencies finds none fully post-quantum. Reproducible models accompany every quantitative claim.

02.
arXiv (CS.CL) 2026-06-24

An LLM-based Two-Stage Transformer Framework for Cross-Domain Bearing Fault Diagnosis with Limited Data

Bearing fault diagnosis faces critical challenges when dataset heterogeneity, operating condition variations, and limited labeled data occur simultaneously in industrial environments. Existing approaches address these issues in isolation and rely on implicit feature alignment, limiting effectiveness under concurrent challenges. This paper proposes a knowledge-guided two-stage transfer learning framework that employs a lightweight GPT-2-style Transformer with causal self-attention for hierarchical feature extraction from vibration signals, establishing explicit pathways where pre-trained encoder weights and fault prototype embeddings serve as knowledge carriers from multi-source pre-training to target adaptation. The framework addresses the dual-shift challenge through multi-source learning for generalizable representations, prototype-based knowledge modulation for target adaptation, and taxonomy-adaptive classification for seamless transfer across heterogeneous fault categories. Experimental validation on four real-world datasets demonstrates 92.61% average accuracy with only 10% labeled target data, outperforming state-of-the-art methods by 17.24 percentage points, establishing a practical pathway toward cost-effective predictive maintenance in Industry 4.0 applications.

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

Localizing Anchoring Pathways in Language Models

Irrelevant numbers in a prompt can shift language model judgments, producing anchoring effects in numerical reasoning. We study where this anchor-sensitive signal is carried inside language models using a controlled multiple-choice setup with shared answer options. We define a logit-difference metric comparing the correct answer option with the answer option corresponding to the anchor, and validate that it tracks behavioral anchoring. Using attribution-based circuit localization on 7B–8B Qwen and Llama base and instruction-tuned models, we find that edge-level methods recover this signal more faithfully than node-level methods. Low- and high-anchor circuits transfer strongly within a model, suggesting shared pathway structure across anchor direction. However, sparse transfer across base and instruction-tuned variants is less reliable, indicating that post-training changes which pathways matter most. Overall, our results provide a mechanistic account of how anchoring-related decision signals are carried inside language models.

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

Evaluating and Enhancing Negation Comprehension in Remote Sensing MLLMs

arXiv:2606.20177v1 Announce Type: cross Abstract: Multimodal Large Language Models (MLLMs) have demonstrated remarkable success in various Remote Sensing (RS) tasks. However, their ability to comprehend negation remains underexplored, limiting deployment in real-world applications where models must explicitly identify what is false or absent, e.g., emergency responders need to locate non-flooded routes for evacuation. To comprehensively study this limitation, we introduce RS-Neg, the first benchmark to evaluate negation understanding across region-level to scene-level tasks. Specifically, we design an automated data generation pipeline for RS imagery, using LLMs to synthesize diverse negation queries, and introduce a dynamic visual focus module for verification. Our evaluation reveals that advanced RS MLLMs struggle with negation, exhibiting hallucinations and substantial performance degradation. To close this gap, we propose NeFo, a novel test-time learning method that explicitly incorporates the logical role of negation into the model optimization. Remarkably, using about 5\% unlabeled test samples, NeFo significantly improves the negation understanding of models and shows strong generalization to unseen tasks. Code and data will be released upon acceptance.

05.
medRxiv (Medicine) 2026-06-19

Hyperleukocytosis and outcomes in pediatric B-cell acute lymphoblastic leukemia: A report from the REDIAL Consortium

Hyperleukocytosis (white blood cell [WBC] count >100 000/uL) at diagnosis is an important prognostic risk factor in pediatric acute lymphoblastic leukemia (ALL), though its significance with contemporary therapy is unclear. We analyzed 1 826 pediatric ALL patients from a multi-institution cohort to determine whether hyperleukocytosis independently predicts outcomes using multivariable Cox proportional hazard modeling. Hyperleukocytosis occurred in 211 patients (12%), with 121 having B-ALL, and showed no prognostic significance in T-ALL patients. In B-ALL, 5-year event-free survival (EFS) was 65% versus 89% for non-hyperleukocytosis patients, and overall survival (OS) was 78% versus 93%. After adjustment for age, cytogenetic risk, central nervous system disease status, and treatment site, hyperleukocytosis remained an independent predictor of end-of-induction minimal residual disease (MRD) positivity (odds ratio 2.53 [95% confidence interval [CI]: 1.71-3.94; p

07.
arXiv (quant-ph) 2026-06-24

Quantum-enabled active matter at the atomic scale

arXiv:2606.24615v1 Announce Type: new Abstract: Active matter comprises particles that extract energy from their local environment and convert it into motion. Although active particles have been miniaturized down to the nanoscale, realizing activity at the fundamentally smaller scale of individual atoms remains an open challenge, where quantum effects become increasingly relevant. Here, we experimentally demonstrate that individual Cs-133 atoms confined in an optical dipole trap extract energy from an ultracold bath of Rb-87 atoms via quantum-mechanical spin interactions and convert it into active motion. We quantitatively reproduce the resulting dynamics using a parameter-free active Langevin model derived from kinetic theory and support it with event-driven Monte Carlo collision simulations. The microscopic origin of activity is identified as quantum spin exchange, which transfers discrete internal spin energy into kinetic motion. Our work establishes a quantum-enabled route to active matter at the fundamental size limit of single atoms and opens perspectives for exploring the interplay of activity, quantum physics, and mesoscopic non-equilibrium thermodynamics.

08.
arXiv (CS.CV) 2026-06-25

Cross-Modality Structural Guidance in 3D Latent Diffusion for Robust FLAIR Super-Resolution

High-resolution (HR) MRI acquisition is often hampered by scan time constraints, resulting in anisotropic or low-resolution scans (e.g., thick-slice FLAIR) that limit diagnostic accuracy. While deep learning-based super-resolution (SR) methods show promise, they often hallucinate anatomical details, which can compromise brain structural integrity. To mitigate this limitation, we introduce MR-DiffuSR, a Multi-Resolution Diffusion-based Super-Resolution framework that incorporates HR T1w structural image priors to guide the restoration of thick-slice FLAIR scans and operates in the 3D latent space. Our architecture introduces cross-modality structural swin-attention, which derives structural attention maps from the HR T1w and applies them to the low-resolution FLAIR latent features. This design disentangles anatomical structure from modality-specific contrast, effectively preventing hallucinations. Furthermore, we employ a mixed-scale degradation strategy, training the model on a continuum of downsampling factors to ensure robustness to varying slice thicknesses, while optimizing with a DINOv3-based perceptual loss to preserve high-frequency semantic details. Evaluated on the ADNI-4 dataset, MR-DiffuSR surpasses both CNN and 2D diffusion approaches, achieving an average PSNR of 32.46dB, SSIM of 0.97, and LPIPS of 0.07 across all downsampling factors. In downstream white matter hyperintensity segmentation, our model demonstrates exceptional robustness. While baseline performance collapses at 10x down-sampling (Dice: 0.51), MR-DiffuSR maintains a Dice score of 0.63, preserving utility even at 7mm equivalent slice thickness.

09.
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.

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

Gradient boosting for extremes: sampling theory and application to insurance

arXiv:2606.14268v1 Announce Type: cross Abstract: We develop a statistical learning theory for gradient boosting applied to the estimation of covariate-dependent Generalized Pareto (GP) distributions in the context of Peaks-over-Threshold modeling. After an orthogonal reparametrization of the GP likelihood that diagonalizes its Fisher information matrix, we cast the estimation problem within the Empirical Risk Minimization (ERM) framework and derive non-asymptotic error bounds for the boosting estimator. Our analysis accounts for three distinct sources of error in the process: statistical fluctuations, the approximation bias inherent to the asymptotic nature of the GP model-controlled under second-order regular variation-and the approximation error associated with the finite number of boosting iterates, making explicit the resulting bias-variance trade-off. We illustrate the practical benefits of the reparametrization through simulations, showing that it significantly reduces gradient correlation during training and improves convergence stability. The methodology is applied to a medical malpractice insurance dataset from the Texas Department of Insurance, comprising over 18 000 closed claims. The gradient boosting approach yields a good fit for the tail of settlement cost distributions and reveals that the number of days to settlement is the dominant predictor of tail heaviness, consistent with earlier findings in the reserving literature.

11.
arXiv (CS.CV) 2026-06-16

When Confidence Lacks Concepts: Interpretable OOD Detection via Representation Perturbations

Deep neural networks have achieved remarkable performance across medical imaging tasks, yet their tendency to overgeneralize under distributional shifts poses a major obstacle to safe clinical deployment. Out-of-Distribution (OOD) detection methods aim to mitigate this risk, but most existing approaches rely on opaque internal signals with poorly understood semantic meaning, limiting trust in safety-critical settings. In this work, we propose an interpretable OOD detection framework that probes the stability of model predictions under class-conditioned semantic perturbations. Leveraging sparse autoencoders (SAEs), we learn class-specific concept vectors from in-distribution data that disentangle dense intermediate representations into sparse, semantically meaningful components. At inference, we perturb deeper-layer representations using the concept vectors associated with the model's predicted class and measure the class logits stability. We hypothesize that in-distribution samples exhibit low sensitivity to such perturbations, as their representations align with class-specific semantic directions, whereas OOD samples show amplified deviations due to representational misalignment. By framing OOD detection as a concept conditioned stability analysis, our approach provides both a discriminative OOD signal and an interpretable lens into the internal mechanisms driving model uncertainty, making it particularly suitable for high stakes medical applications.

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

SIMBA: ABidirectional Retrieval Forward Simulation Framework for Modeling FY-4A GIIRS Hyperspectral Infrared Radiances Toward NWP Applications

arXiv:2606.19943v1 Announce Type: cross Abstract: Hyperspectral infrared observations are an important data source for numerical weather prediction (NWP) because they provide rich information on the vertical structure of atmospheric temperature and humidity. However, most existing deep learning methods mainly focus on one-way retrieval from radiances to atmospheric profiles, while the reverse radiance simulation process and the consistency between atmospheric state space and radiance observation space are insufficiently considered. In this study, we propose SIMBA, a unified bidirectional retrieval-forward simulation framework for FY-4A GIIRS hyperspectral infrared radiance modeling toward NWP applications. The framework jointly performs atmospheric profile retrieval and radiance reconstruction, introduces a cycle-consistency constraint to strengthen the coupling between the two processes, and employs a bidirectional Mamba state-space module to capture long-range dependencies along pressure levels. Using collocated FY-4A GIIRS observations and ERA5 reanalysis data, the proposed method is evaluated for temperature retrieval, specific humidity retrieval, long-wave radiance reconstruction, and medium-wave radiance reconstruction. Experimental results show that SIMBA outperforms several representative deep learning baselines across both retrieval and reconstruction tasks, while ablation experiments confirm the contribution of the bidirectional design and cycle-consistency mechanism. These results demonstrate that the proposed framework is effective for joint atmospheric profile retrieval and hyperspectral infrared radiance modeling, and suggest potential for future Jacobian-related analysis and NWP-oriented extensions.

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

The Data Manifold under the Microscope

arXiv:2606.15760v1 Announce Type: new Abstract: A significant gap exists between theory and practice in deep learning. Generalization and approximation error bounds are often derived for simplified models or are too loose to be informative. Many rely on the manifold hypothesis and on geometric regularity such as intrinsic dimension, curvature, and reach. Progress requires insight into data-manifold geometry and suitable benchmarks, yet existing options are polarized: analytic manifolds with known geometry but limited applicability, or real-world datasets where geometry is only coarsely estimable. We introduce a benchmarking framework for studying data geometry. We repurpose and extend dSprites and COIL-20 with additional transformation dimensions and dense, axis-aligned sampling, and pair them with finite-difference estimators that recover curvature, reach, and volume at near-ground-truth accuracy in a regime where general-purpose estimators are unreliable or difficult to deploy. The framework is intended as a controlled testbed, useful as a calibration environment for geometric estimators and a sandbox for probing theoretical assumptions. To illustrate its use, we present two application studies, namely assessing the scaling behavior of the bounds of Genovese et al. and Fefferman et al., and tracking the layer-wise geometry of a $\beta$-VAE, highlighting the behavior of current bounds and the value of controlled benchmarks for guiding and validating future theory. A reference implementation is available at https://github.com/koulakis/manifold-microscope.

14.
arXiv (CS.CV) 2026-06-24

Dual-Branch Cross-Projection Debiasing through Diffusion-based Disentanglement

Foundation models trained on biased datasets often rely on spurious correlations between target labels and non-causal attributes, resulting in poor generalization on minority groups. Bias mitigation remains challenging due to two fundamental issues. First, when group labels are unavailable, existing group-unsupervised methods typically infer spurious attributes implicitly from model behavior, making it difficult to identify spurious factors that are semantically aligned with real-world biases. Second, even with pseudo spurious supervision, most existing debiasing methods follow a single-branch design that operates within a single shared feature space, where target and spurious attributes are intrinsically entangled. To address the first challenge, we introduce Confidence-guided Bias Concept Mining (CBCM), which leverages diffusion-disentangled, semantically grounded concept representations to identify reliable spurious attributes without attribute annotations. To address the second challenge, we propose Dual-branch Cross-projection Debiasing (DCD), a prompt-tuning framework that separates target and spurious representations into two branches and explicitly removes spurious information through cross null-space projection while preserving target-relevant semantics. Extensive experiments on four benchmark datasets show that our method achieves state-of-the-art worst group accuracy among group-unsupervised approaches, while tuning at most 0.22% of the model parameters. The source code is available in the supplementary materials.

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

Inference-time Policy Steering via Vision and Touch

arXiv:2606.14981v1 Announce Type: cross Abstract: Inference-time steering adapts pre-trained generative robot policies during deployment by verifying candidate actions before execution. While prior methods typically perform this verification only with visual observations, vision alone is often insufficient for contact-rich manipulation, where success depends on both global task progress and subtle local interactions such as contact force. We introduce ViTaL, a visuo-tactile inference-time steering framework that formulates multimodal guidance as a bi-level optimization problem. At the high level, visual sampling-and-verification performs long-horizon mode selection, deciding what behavior the robot should execute. At the low level, tactile-guided diffusion editing refines the selected action sequence over a shorter horizon to satisfy local contact requirements. To support outcome-based steering, ViTaL learns a visuo-tactile latent world model and employs semantically aligned visual and tactile verifiers, including a novel text-conditioned tactile reward that scores predicted tactile futures directly in latent space. Across three real-world contact-rich manipulation tasks, ViTaL improves overall success by 51% over the base policy, outperforms unimodal steering by at least 33%, and exceeds naive multimodal fusion by at least 20%. Website: https://yilin-wu98.github.io/vital_website.

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

PEARL: Self-Evolving Assistant for Time Management with Reinforcement Learning

Overlapping calendar invitations force busy professionals to repeatedly decide which meetings to attend, reschedule, or decline. We refer to this preference-driven decision process as calendar conflict resolution. Automating this decision process is crucial yet challenging. Scheduling logistics can drain hours, and human delegation often fails at scale, which motivates us to ask: Can we trust large language models (LLMs) or language agents to manage time? To enable a systematic study of this question, we introduce CalConflictBench, a benchmark for long-horizon calendar conflict resolution. In CalConflictBench, conflicts are presented to agents round-by-round over a calendar year, requiring them to infer and adapt to user preferences progressively. Our experiments show that current LLM agents perform poorly with high error rates, e.g., Qwen-3-30B-Think has an average error rate of 35%. To address this gap, we propose PEARL, a reinforcement-learning framework that (i) augments the language agent with an external preference memory that stores and updates inferred strategies (e.g., attendee priorities, topic importance, time/location preferences), and (ii) optimizes the agent with round-wise rewards that directly supervise decision correctness, ranking quality, and memory usage across rounds. Experiments on CalConflictBench show that PEARL achieves an error reduction rate of 0.76 and a 55% improvement in average error rate compared to the strongest baseline.

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

PRISM: Prosody-Integrated Multi-Agent Reasoning Framework for Empathetic Spoken Dialogue

Empathetic spoken dialogue systems require not only semantically appropriate responses but also emotionally aligned prosodic expression. However, cascade pipelines often discard acoustic cues during speech-to-text conversion, while end-to-end speech models lack interpretable control over emotion and knowledge integration. To address these challenges, we propose PRISM, a multi-agent framework for empathetic spoken dialogue that decouples speech perception, response generation, and speech synthesis into coordinated components. PRISM introduces a prosody-to-language translation mechanism to stabilize large language model reasoning and enables on-demand invocation of external knowledge tools for empathetic dialogue generation. Experimental results demonstrate that PRISM achieves consistent improvements in empathy, prosodic appropriateness, and text response generation quality across objective and subjective metrics. Our code is available at: https://github.com/Bxzfrm/PRISM.

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

Starter-Iterator Neural Operator: A Unified Architecture for High-Fidelity Forward and Inverse PDE Problems

arXiv:2606.18305v1 Announce Type: cross Abstract: Operator learning is an emerging interdisciplinary field that integrates machine learning with scientific computing. By mapping infinite-dimensional function spaces, this approach provides an efficient surrogate modeling framework for high-dimensional partial differential equations (PDEs). Compared to traditional numerical solvers, it achieves a superior trade-off between computational complexity and approximation accuracy, demonstrating significant advantages in many-query tasks such as real-time prediction and parameter sweeps. Given the stringent accuracy requirements of both forward simulation and inverse inference, as well as the precision bottlenecks of existing operator learning methods in handling complex boundaries or long-term evolution, we propose the Starter-Iterator Neural Operator (SINO). Our framework reinterprets the initialization strategies and iterative formats of traditional iterative methods through neural networks, establishing an efficient approach for spectral-spatiotemporal collaborative modeling. Specifically, the frequency-domain initialization module captures globally stable low-frequency features, while the time-domain learning module focuses on optimizing local solution residuals, thereby effectively overcoming the inherent limitations of conventional single-domain modeling approaches. Extensive experiments on typical dynamical systems such as the Navier-Stokes equations and acoustic wave equations, as well as practical applications including super-resolution imaging and weather forecasting, demonstrate that SINO achieves outstanding performance in numerical accuracy, generalization capability, and robustness.

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

Deep Q-Learning on Hölder Spaces

Authors:

arXiv:2606.16846v1 Announce Type: cross Abstract: We study the operator-theoretic core of Q-learning in continuous-time stochastic control with continuous states and actions. In value-based reinforcement learning, each Q-learning or DQN update is built from a Bellman optimality target; our analysis isolates this target in a diffusion setting and studies its regularity and approximation complexity. Under uniform ellipticity and Hölder-regular coefficients, we show that a Bellman update maps bounded inputs into an anisotropic regularity class, smoothing the state variable while leaving only Lipschitz dependence on the action variable. This yields a compact family of Bellman iterates and motivates a tensor-product DeepONet architecture adapted to the mixed regularity of the problem. We then derive explicit approximation and resource bounds, together with a stiffness–complexity trade-off as the time step $\delta \to 0$. The resulting theory makes a direct contribution to Q-learning theory at the level of Bellman target regularity and approximation in continuous stochastic control. At the same time, we do not claim a full convergence theorem for practical sampled Q-learning with exploration, replay, and stochastic gradient updates.

20.
arXiv (quant-ph) 2026-06-16

Temporal modulation as a resource: enhanced frequency estimation in continuous variable systems

arXiv:2606.15108v1 Announce Type: new Abstract: Frequency estimation, a cornerstone of quantum metrology, has been significantly enhanced by advanced quantum sensing strategies. However, most protocols rely either on static or time-independent encoding mechanisms, inherently limiting their achievable precision scaling, or on control strategies requiring changing the Hamiltonian and/or implementing feedback mechanisms. To overcome this, we investigate a simpler dynamical encoding protocol where the quantum oscillator is driven by a general continuous temporal frequency modulation $\Omega(t) = \omega_0 f(t)$. We analytically demonstrate that for a given modulation profile $f(t)$ and its corresponding time-integral $F(t)$, the quantum Fisher information (QFI) scales as $\mathcal{O}(F(t)^2)$. This enhancement stems from the fact that temporal encoding fundamentally alters the mechanism of dynamical phase accumulation. Crucially, when evaluated under the energy and evolution-time constraints, this framework reveals a genuine precision enhancement over the conventional time-independent baseline. By analyzing explicit polynomial and exponential modulations, we establish that arbitrary precision scaling can be deterministically engineered, with ultimate bounds that are asymptotically saturable via optimal homodyne detection. Our framework provides a universal paradigm for exploiting time-dependent quantum control in next-generation sensors.

21.
arXiv (quant-ph) 2026-06-16

Quantum Information Geometry of Multicomponent Superconducting Fluctuation Transport

arXiv:2606.15928v1 Announce Type: cross Abstract: Quantum geometry underlies many electronic responses, but its transport signatures have so far been established mainly for pure single-particle Bloch states. Whether collective many-body fluctuations possess a measurable quantum geometry remains largely unexplored. Here we show that superconducting fluctuation transport provides a direct probe of quantum information geometry in collective many-body matter. Starting from a multicomponent time-dependent Ginzburg-Landau theory in the Gaussian fluctuation regime, we identify the equilibrium density matrix of fluctuating Cooper pairs as the static pair propagator, which defines a positive mixed-state manifold in momentum space. The geometry of this manifold is directly measurable through paraconductivity: the longitudinal paraconductivity is governed by the quantum Fisher information of superconducting fluctuation modes, while the fluctuational anomalous Hall effect is governed by the mean Uhlmann curvature, the mixed-state counterpart of Berry curvature. This correspondence further yields geometric bounds between these two transport components, with no direct analogue in normal electronic transport. Applied to chiral superconducting fluctuations in quarter-metal systems motivated by rhombohedral multilayer graphene, a symmetry-allowed Lifshitz invariant generates finite mean Uhlmann curvature and logarithmically enhances the anomalous Hall conductivity above the critical temperature. Our results establish collective superconducting fluctuations as an experimentally accessible transport probe of mixed-state quantum information geometry.

22.
bioRxiv (Bioinfo) 2026-06-14

Somatic variant detection in normal tissues from single-cell sequencing data

A crucial advantage of single-cell sequencing (SCS) is its ability to identify somatic variants in individual cells, enabling phylogenetic analysis of cellular populations within bulk tissues. While identifying somatic variants in tumor tissues via SCS has become a common practice, doing so in normal tissues remains challenging due to the rarity of somatic variants in normal cells. To evaluate the feasibility of somatic variant calling from widely available single-nucleus RNA-seq (snRNA-seq) and single-nucleus ATAC-seq (snATAC-seq) data, we profiled a Cell-line mix of six HapMap samples prepared by the SMaHT consortium using 10x Genomics 5' snRNA-seq (12k cells with 36k mean reads per cell) and snATAC-seq (11k cells with 14k median high-quality fragments per cell) for variant calling. PacBio long-read whole genome sequencing (WGS) data (109x) generated from individual cell lines were used as ground truth. Two computational tools, Monopogen and SComatic, were used for somatic variant calling from the SCS data. Monopogen achieved single nucleotide variant (SNV) detection accuracies of 93.30% in the snRNA-seq and 99.64% in the snATAC-seq data, both of which outperformed SComatic (74.35% and 94.29%, respectively). Monopogen also consistently detected somatic SNVs at cellular fractions as low as 0.5% (2.54% in snRNA and 0.81% in snATAC) in individual samples. Notably, snATAC-seq exhibited higher genomic coverage breadth and larger number of variants detected than snRNA-seq. While the SCS data have lower overall genome coverage than that of the bulk WGS, the single-cell level variant resolution allows Monopogen to assign variants to their cells of origin with over 80% accuracy in both RNA and ATAC modalities, thereby facilitating studies of clonal evolution and cell-type-specific mutagenesis. Other benchmarking methods were also evaluated (DeepVariant, Cellsnp-lite and Mutect2) for comparison. In conclusion, our study demonstrated the feasibility of performing reliable single-cell somatic mutation calling in a cell-line mixture and discussed the strengths and limitations of current computational methods when applied to normal tissues.

23.
arXiv (CS.LG) 2026-06-16

Bayesian Networks with Latent Time Embedding for Stage-Aware Causal Modeling of Alzheimer's Disease Progression

arXiv:2606.15784v1 Announce Type: new Abstract: Alzheimer's disease (AD) progression is often described through the amyloid-tau-neurodegeneration, or AT(N), cascade. However, most longitudinal models represent this cascade either as a fixed sequence of biomarkers or as a black-box forecasting task. This makes it difficult to determine when biologically guided biomarker relationships influence future regional pathology. In this study, we introduce Bayesian Networks with Latent Time Embedding (BN-LTE), a Bayesian structural framework for stage-aware modeling of AD progression. BN-LTE estimates disease pseudotime from baseline biomarker profiles and constrains directed dependencies according to biologically plausible AT(N) ordering. Posterior spline-varying structural equations are then used to link initial multimodal measurements with future annualized regional tau-PET change. Across repeated subject-disjoint evaluations using ADNI data, BN-LTE shows strong spatial reconstruction of tau progression compared with the included forecasting baselines. Beyond spatial reconstruction, BN-LTE recovers posterior stage-varying AT(N)-constrained effects and identifies a mid-pseudotime window of amyloid sensitivity. This window is supported by model-implied g-formula contrasts, root-adjusted AIPW, mechanism-sensitive ablations, and robustness analyses across spline and prior specifications. Overall, these findings position BN-LTE as a Bayesian structural framework for forecasting tau progression while examining stage-dependent AT(N)-cascade mechanisms in observational longitudinal neuroimaging data. Our code is available at https://github.com/danleneurocom/BN-LTE.

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

Diffusion Models for Adaptive Sequential Data Generation

arXiv:2606.06007v2 Announce Type: replace Abstract: Generating realistic synthetic sequential data is critical in real-world applications across operations research, finance, healthcare, energy systems, and scientific computing, where time-indexed observations are used for prediction, simulation, risk assessment, and data-driven decision-making. While diffusion models have achieved remarkable success in generating static data, their direct extensions to sequential settings often fail to capture temporal dependence and information structure. Designing diffusion models that can simulate sequential data in an adapted manner, and hence without anticipation of future information, therefore remains an open challenge. In this work, we propose a sequential forward-backward diffusion framework for adapted time series generation. Our approach progressively injects and removes noise along the sequence, conditioning on the previously generated history to ensure adaptiveness. A novel score-matching objective is introduced for efficient parallel training. We derive rigorous statistical guarantees under a generic framework, then establish score approximation, score estimation, and distribution estimation results with ReLU networks serving as a concrete instance. Empirically, we validate our method on synthetic data, including ARMA models and Gaussian processes, and demonstrate its effectiveness in constructing mean-variance optimal portfolios.

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

Token Complexity Theory for AI-Augmented Computing

Authors:

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.