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01.
arXiv (CS.LG) 2026-06-18

AGDN: Learning to Solve Traveling Salesman Problem with Anisotropic Graph Diffusion Network

arXiv:2606.19185v1 Announce Type: new Abstract: The Traveling Salesman Problem (TSP) is a cornerstone of combinatorial optimization and arises in many practical scenarios. Although graph-based learning approaches have been explored for TSP, the question of how to exploit graph structure more effectively remains open. We present the Anisotropic Graph Diffusion Network (AGDN), a new Graph Neural Network framework designed to solve TSP. Our method tackles two central difficulties: (1) the lack of informative topological prior in fully connected TSP graphs, and (2) losing connected nodes in the optimal solution after the commonly used graph sparsification techniques. To overcome these issues, we construct a MixScore transition matrix that merges node similarity with pairwise distance, and we develop an anisotropic graph diffusion strategy that supports efficient information exchange across multiple hops. Comprehensive experiments spanning diverse instance sizes and node distributions show that AGDN consistently outperforms existing methods while keeping computation time competitive. Furthermore, AGDN generalizes well to problem sizes and distributions beyond those seen during training. The implementation is publicly available at: https://github.com/LabRAI/AGDN.

02.
medRxiv (Medicine) 2026-06-15

Supporting people to access social security payments through the Special Rules for End of Life: a qualitative study of the perspectives of patients, carers and health care professionals

Background: People living with terminal illness face a double financial burden from additional costs and loss of earning for themselves and their carers. Social security benefits are intended to help alleviate some of this financial pressure, and in the UK and other countries people are eligible for fast-tracked access to financial support via the Special Rules for End of Life. One in 3 people who are eligible miss out on this support, yet there is limited evidence on the reasons for this take-up deficit. Objectives: The aim of this study is to understand the barriers and facilitators to claiming benefits for terminally ill people from the perspectives of patients, carers, and health care professionals. Methods: This is a qualitative study combining i) focus groups with healthcare professionals recruited via professional networks and social media, and ii) interviews with patients and carers recruited in hospital and hospice settings. We analysed the data using Practical Thematic Analysis Results: Fifty-five multidisciplinary healthcare professionals participated in 11 focus groups, and we interviewed 10 patients and carers. We constructed five descriptive themes to summarise the data: Navigating priorities and uncertainty; positive impacts alongside a sense of shame and stigma; talking about money, difficulties and dividends; everybodys, yet nobodys, responsibility; and sticking points in the system. Conclusion: The themes reveal several challenges that may contribute to people not taking up this financial support. However, discussions about access to benefits were also seen as a core part of holistic care, a positive way to offer support and a gateway to other discussions about end-of-life care preferences and decisions. Recommendations for policy and practice include evaluating the adoption of a diagnostic rather than a prognostic eligibility criteria, integrating discussions about benefits into existing processes such as advance care planning, and improving education and support for clinicians.

03.
arXiv (CS.CV) 2026-06-11

CFCamo: A Counterfactual Detect-or-Abstain Framework for Camouflaged Object Detection

Vision-language reinforcement learning has recently shown strong target-present localization for camouflaged object detection (COD). Yet localization is only one side of the decision: when the agent faces an ordinary image with no camouflaged target, will it still claim that a camouflaged object exists? Standard COD training and evaluation data are positive-only, so agents optimized under this setting can acquire an over-detect bias, a task-specific form of object hallucination that standard COD evaluation leaves unmeasured. To quantify this target-absent behavior, we construct Counterfactual COD (CF-COD), a paired benchmark that removes the camouflaged target from each held-out COD evaluation image while preserving a plausible background. CF-COD evaluates whether a model detects the target on the original image and abstains on the target-absent counterfactual, summarized by Pair Accuracy (PA). We further introduce CFCamo, a paired counterfactual framework for COD with abstention. For training, CFCamo optimizes a Qwen3-VL-4B-Instruct agent with Counterfactual Sequence Policy Optimization (CSPO), which samples paired original-counterfactual rollouts and uses a Counterfactual Paired Reward (CPR) to couple original-image detection with counterfactual abstention. On CAMO-test, CFCamo improves S_alpha by +3.7 pp over the prior RL-based COD baseline; across CF-COD, it reaches 80.0-90.8% PA. Ablations show that removing counterfactual coupling reduces PA to 1.4-5.2% despite strong target-present COD scores, showing that target-present evaluation alone does not characterize detect-or-abstain behavior. Overall, these results indicate that CFCamo improves COD agents by coupling target-present detection with target-absent abstention, rather than merely strengthening target-present localization. Code and data are available at https://github.com/suhang2000/CFCamo.

04.
arXiv (CS.AI) 2026-06-16

Model-Native Computing Architecture: Envisioning Future System Architecture Through the Lens of Computer Architecture

arXiv:2606.00288v2 Announce Type: replace Abstract: Large language models are undergoing a transition from model technology to system technology. Engineering challenges like cache reuse, context capacity, agent scheduling, and permission control resemble classical computer systems problems. This raises a question: if we treat the LLM as a CPU, KV cache as processor cache, context window as main memory, and agent framework as an operating system, can decades of computer architecture wisdom guide next generation model native systems? This paper pursues this analogy as a visionary survey. We map computer architecture concepts onto the emerging model native stack, survey literature across LLM as OS, memory management, agent frameworks, tool protocols, multi agent coordination, cognitive architectures, and safety governance, finding that each addresses a different layer without a unifying model. We propose the Intelligent Computing Architecture (ICA): six functional layers with interface contracts and design axioms. We resolve the tension over whether the LLM resembles a CPU or OS via a dual plane architecture a probabilistic execution plane (what can be computed) and a deterministic control plane (what should be computed), with every layer passing through as a graded crossover. We propose three Amdahl style design heuristics Semantic Locality, Context Budget, and Agent Speedup as organizing back of envelope models, illustrate their parameter ranges with published data, and identify predictive validation as the principal open task. We articulate analogy boundaries, note differences between silicon and model era architectures, and propose a research roadmap. This is a conceptual and survey contribution with no new experimental results.

05.
arXiv (quant-ph) 2026-06-12

Quantum optical photoelectron interferometry

arXiv:2606.13447v1 Announce Type: new Abstract: We present a general theoretical framework for multiphoton processes driven by quantum light fields, establishing a direct link between photon statistics and photoelectron observables. Our results show that the autocorrelation and cross-correlation functions, which quantify the underlying photon statistics, are directly mapped onto the resulting photoelectron spectra. Although our framework is broadly applicable, we demonstrate specifically in the example of reconstruction of attosecond beating by interference of two-photon transitions (RABBIT) the influence of the light statistical properties. In this approach, the amplitude, contrast and phase of the oscillations of the sideband signal as a function of pump-probe delay reveal the quantum nature of light. We analyze these observables across several quantum configurations, including correlated infrared and harmonic modes, as well as the uncorrelated case with non-classical harmonic statistics, thereby establishing a general framework for quantum-light RABBIT spectroscopy. We compare the analytical theory with numerical simulations for the case of classical harmonics and an infrared field in a squeezed coherent state, obtaining excellent agreement. Our results reveal how the interplay between classical and quantum correlations dictates the coherence of the photoemission process, providing a new window into the quantum-optical foundations of attosecond science.

06.
arXiv (math.PR) 2026-06-18

On a class of reflected McKean-Vlasov Stochastic Differential Equations with jumps

arXiv:2606.18433v1 Announce Type: new Abstract: This paper investigates a class of reflected McKean-Vlasov Stochastic Differential Equations driven by both Brownian motion and a compensated Poisson random measure. We establish the existence and uniqueness of solutions and provide moments estimates for the state processes.

08.
arXiv (CS.CL) 2026-06-18

Aligning Implied Statements for Implicit Hate Speech Generalizability with Context-Bounded Semi-hard Negative Mining

Classifying implicit hate speech remains a challenge, as intent is often masked through insinuation and context rather than explicit slurs. Prior supervised contrastive approaches improve in-domain detection but can overfit surface cues and struggle to transfer across datasets. We propose ImpSH, a triplet-based framework that aligns posts with implied statements when available and uses context-bounded semi-hard negatives to focus learning on near confusions. We also examine AugSH, which forms positives via data augmentation. In controlled evaluations on IHC, SBIC, and DynaHate with BERT and HateBERT, ImpSH is a viable alternative to standard supervised contrastive baselines and often improves cross-domain performance under matched preprocessing and tuning budgets. Representation analysis using alignment and uniformity indicates tighter positive pairs with balanced global spread, and qualitative nearest-neighbor case studies illustrate typical false negatives under domain shift. These results demonstrate that aligning posts with their implied statements via context-bounded mining provides a more stable, bijective-like mapping to related insinuations, overcoming the volatility inherent in traditional clustering-based representation learning.

09.
arXiv (quant-ph) 2026-06-17

Tunneling Dynamics and Time Delay in Electron Transport through Time-Dependent Barriers with Finite-Bandwidth Reservoirs

arXiv:2507.20649v2 Announce Type: replace-cross Abstract: We study a model system consisting of a tunneling barrier driven by an external harmonic field and coupled to two leads with finite bandwidth. Avoiding Floquet expansions, we derive simple expressions for the time-dependent tunneling current in the adiabatic regime. Our approach relates the barrier modulation to a measurable time delay in the steady-state periodic current. It provides a physically consistent definition of the tunneling time inside the barrier by subtracting the time delay associated with the leads from the total time delay. We find that the tunneling time always vanishes for wide/high barriers. Remarkably, the time delay persists even when the barrier becomes static, i.e., in the limit where the modulation frequency vanishes. This indicates that the time delay obtained through the introduction of an external periodic perturbation actually reflects an intrinsic property of the tunneling dynamics, rather than an effect of the external drive or of a particular system. We apply our results to the analysis of tunneling times in optical experiments and find good agreement with the experimental data.

10.
arXiv (CS.CV) 2026-06-12

NavWAM: A Navigation World Action Model for Goal-Conditioned Visual Navigation

Goal-conditioned visual navigation requires a robot to act under partial observability by anticipating how its motion will change the future egocentric view and whether that change brings it closer to the goal. Navigation world models provide such visual foresight, but they remain prediction modules that require an external planner to convert predicted futures into closed-loop control. We propose Navigation World Action Model (NavWAM), a diffusion-transformer policy that turns navigation world-model prediction into executable action by representing future observations, goal-progress values, and action chunks in a shared latent sequence. By learning future prediction jointly with the action and value targets that determine closed-loop behavior, NavWAM makes visual foresight directly usable for robot control. We build NavWAM through simulation pretraining and real-robot adaptation, and evaluate it on image-goal navigation against planning-based world models and a representative direct navigation policy. Across offline benchmarks and closed-loop real-robot deployment, NavWAM improves over planning-based world-model baselines in our evaluations while using the default policy mode without CEM-style action search. Project page: https://dachii-azm.github.io/navwam/

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

What Should a Streaming Video Model Remember?

Streaming video understanding models must answer queries at any moment during an ongoing stream, using only what they have observed so far and under fixed memory and computation budgets. Existing methods address this by adding memory banks, retrieval modules, or visual token compression to preserve long-range history. However, strong recent-window baselines show that indiscriminate history injection can dilute current-scene perception, suggesting that the key challenge is not whether to use memory, but how to allocate it selectively. We formulate this as budgeted online latent evidence allocation and propose SelectStream, a selective latent-memory framework that keeps the current observation directly visible to a frozen VLM while exposing historical information only through a compact, query-conditioned evidence budget. Three coordinated mechanisms govern when to write, what to preserve, and how to retrieve: surprise-driven adaptive windowing, priority-preserving consolidation, and query-conditioned graph reasoning over a fixed-capacity latent memory graph. Retrieved evidence is calibrated and injected as latent tokens for answer generation, without replaying frames or growing the context with stream length. Experimental results show that SelectStream achieves strong online streaming performance and preserves general video understanding, reaching 82.67\% on StreamingBench, 67.03\% on OVO-Bench, and 74.4\% average accuracy on offline video benchmarks, while outperforming strong recent-window baselines and prior streaming memory methods.

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

Wasserstein Equilibrium Decoding for Reliable Medical Visual Question Answering

Small vision-language models (2-8B) are well-suited for clinical deployment due to privacy constraints, limited connectivity, and low-latency requirements favouring on-device or on-premise inference. However, their limited capacity exacerbates the generation of plausible but incorrect outputs. We extend game-theoretic decoding, previously restricted to text-only, closed-ended NLP tasks, to vision-language models for open-ended Medical VQA. We introduce a semantically aware Wasserstein stopping criterion that replaces lexical order matching, enabling convergence based on semantic consensus among near-synonymous candidate answers and avoiding unnecessary iterations caused by clinically equivalent ranking swaps. On VQA-RAD and PathVQA, we obtain consistent, statistically significant improvements over greedy and discriminative baselines. On VQA-RAD, we improve Qwen3-VL-2B by +3.5 percentage points (p < 0.01), surpassing the greedy 4B model, with similar trends at larger scales. On PathVQA, Gemma-3-4B with BDG matches MedGemma-4B under greedy decoding despite no domain-specific fine-tuning. At accuracy parity with classic BDG, the Wasserstein criterion reduces average convergence iterations by approximately 20%, improving inference efficiency while preserving the game-theoretic equilibrium behaviour. Code is available at https://github.com/luca-hagen/ Wasserstein-BDG-medical-VQA.

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

Beyond Text-to-SQL: An Agentic LLM System for Governed Enterprise Analytics APIs

Enterprise analytics aims to make organizational data accessible for decision-making, yet non-technical users still face barriers when using traditional business intelligence tools or Text-to-SQL systems. While recent Text-to-SQL approaches based on Large Language Models (LLMs) promise natural language access to structured data, they fall short in enterprise settings where analytics pipelines rely on governed APIs rather than raw databases. In practice, these APIs encapsulate complex business logic to ensure consistency, auditability, and security. However, delegating mathematical or aggregation logic to an LLM introduces reliability and compliance risks. To this end, we present Analytic Agent, an LLM-based agentic system that translates natural language intents into secure interactions with enterprise analytics APIs. Evaluated on 90 real enterprise use cases constructed by domain experts, it reliably interprets user goals, validates permissions, executes governed queries, and generates compliant visualizations through multi-step reasoning and policy-aware orchestration.

14.
arXiv (CS.CL) 2026-06-16

The Truth Stays in the Family: Enhancing Contextual Grounding via Inherited Truthful Heads in Model Lineages

Recent advances in large language models (LLMs) have produced many specialized multimodal LLMs (MLLMs) that share common foundational LLMs, forming distinct model lineages. It remains unclear whether a fundamental behavioral link exists between the foundational LLMs and downstream variants. We investigate this question by quantifying head-level context-truthfulness scores. Across diverse LLM and MLLM lineages, including Vicuna-, Qwen2.5-, LLaMA2-, and Mistral-based models, we find that Truth Scores are strongly preserved within model families, even after instruction tuning or multimodal adaptation. We further show that this inheritance is consistent with attention-head weight preservation, and that context-truthful heads attend to query-relevant evidence. Building on this finding, we propose TruthProbe, a soft-gating strategy that amplifies context-truthful heads while preserving other head contributions. TruthProbe improves contextual truthfulness on HaluEval and reduces multimodal hallucination on POPE and CHAIR, with base-LLM Truth Scores transferring effectively to their fine-tuned LLM and MLLM descendants. Code is available at https://github.com/miso-choi/TruthProbe.

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

Show the Signal, Hide the Noise: Spectral Forcing for Pixel-Space Diffusion

Pixel-space diffusion models are trained on full-bandwidth noisy images, yet the useful signal available to the denoiser is strongly frequency dependent. Under rectified-flow diffusion and natural-image power-law spectra, the per-band data-to-noise contour $k^{*}(t) = (1-t)^{-2/\alpha}$ separates a signal-bearing low-frequency region from a noise-dominated high-frequency region at each time $t$. We show that this implicit coarse-to-fine structure is not merely descriptive: it induces a capacity-allocation problem. A standard pixel-space denoiser must discover the moving bandwidth boundary internally and can spend computation on frequency-time regions where the optimal prediction collapses to deterministic baselines rather than data-distribution modeling. To make this boundary explicit, we introduce Spectral Forcing, a parameter-free, time-conditional 2D-DCT low-pass operator applied to the noisy input before the patch embedder. Its cutoff expands monotonically with the diffusion time and becomes the identity at the data endpoint. Through controlled synthetic experiments, we identify the regime in which the operator is beneficial: coarse patch tokenization and data whose high-frequency content is predominantly noise rather than essential signal. On ImageNet-256 with JiT-700M/32, Spectral Forcing consistently improves both FID and Inception Score across different training epochs, demonstrating robust gains throughout training; at finer tokenization, the spectral forcing is still competitive. We further insert the unchanged operator into SenseNova-U1, a unified text-to-image model, where it improves DPG-Bench and GenEval, showing that the input-side spectral prior transfers beyond class-conditional generation. These results suggest a route to capacity-efficient pixel-space diffusion by showing the signal and hiding the noise.

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

Evoflux: Inference-Time Evolution of Executable Tool Workflows for Compact Agents

arXiv:2606.12674v1 Announce Type: new Abstract: Compact language models (LMs) reduce cost, latency, and deployment risk for tool agents. Yet MCP-style tool use requires more than isolated function calling: an agent must discover tools from live catalogs, satisfy schemas, preserve dependencies across intermediate outputs, and ground final responses in executed evidence. Small planners often generate plausible workflow graphs that fail under tool resolution, parameter validation, dependency tracking, or execution. We argue that this failure mode is poorly handled by small-corpus distillation. A few hundred teacher traces can teach workflow format, but rarely cover the recovery behavior needed to repair failed plans over changing tool catalogs. We introduce Evoflux, an inference-time evolutionary search method that treats compact tool use as the repair of executable tool workflows. It evolves typed workflow graphs through structured edits, execution feedback, adaptive intensity, meta-guided redesign, and diversity pruning. On held-out MCP-Bench tasks spanning live MCP servers and 250 tools, Evoflux raises execution feasibility from roughly 3% to 17-24% across small planners. In contrast, SFT and SFT+DPO on the same search-mined data match, underperform, or collapse below zero-shot performance; ReAct reaches higher peaks, but with higher variance and token cost. These results show that execution-grounded search is more reliable under scarce teacher-trace budgets.

17.
arXiv (CS.AI) 2026-06-11

Privacy-Preserving Federated Autoencoder for ECG Anomaly Detection on Edge Devices

arXiv:2606.11556v1 Announce Type: cross Abstract: Continuous electrocardiography (ECG) monitoring could surface rhythm abnormalities before they escalate into cardiovascular events. However, a deployable system must satisfy three requirements simultaneously: legal-grade privacy (GDPR, HIPAA), real-time inference on constrained edge hardware, and detection quality under non-IID cross-hospital data. We design and evaluate an end-to-end federated system addressing all three for unsupervised 12-lead ECG anomaly detection on PTB-XL dataset, combining three autoencoder families (VanillaAE, ConvAE, VAE), Flower-based federated averaging (FedAvg) across ten simulated hospitals, client-side differentially private SGD (DP-SGD) with a Rényi-DP accountant, and 8-bit integer (INT8) post-training quantization with Raspberry Pi 4 benchmarking. Our main contributions are: an empirical characterization of how these mechanisms compose, practical DP-specific recommendations, and technical and security insights for a clinically sensitive setting. Federated learning matches or exceeds the centralized baseline across all architectures (ConvAE federated area under the ROC curve, AUROC, $0.782$), and an $\varepsilon$ sweep identifies $\varepsilon=4$ as the recommended clinical operating point. INT8 quantization roughly halves model size and cuts Pi 4 latency by up to $44%$ with $

18.
arXiv (quant-ph) 2026-06-16

Ultrastrongly coupled open systems and fine grained time

arXiv:2606.16634v1 Announce Type: new Abstract: We study the dynamics of a d-level quantum system coupled to a bosonic reservoir when the coupling constant is large. It is known that in the limit of infinite coupling strength, the system undergoes an instantaneous nonselective measurement, resulting in the immediate decoherence in the measurement basis, followed by a unitary Zeno dynamics. Here we resolve this dynamical process by introducing a fine grained scaling regime of short times proportional to the inverse coupling. We provide a rigorous derivation of the open system dynamics in this regime of ultrastrong coupling and demonstrate how decoherence unfolds continuously in the new time scale. We show that Markovian dynamics which are not given by semigroups arise naturally, in contrast to what happens in the weak coupling theory.

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

RePAIR: Predictive Self-Supervised Representation Learning in Chess

arXiv:2606.11860v1 Announce Type: new Abstract: In this paper, we introduce Representation Prediction via Autoencoding using Iterative Refinement (RePAIR) - a novel self-supervised representation learning architecture that synthesizes Masked Autoencoders (MAE), Joint Embedding Predictive Architectures (JEPA), and Bidirectional Encoder Representations from Transformers (BERT). We demonstrate how it can be used to encode objects in sequential data like consecutive chess positions into compact yet meaningful representations. The basic principle of the architecture is to mask large portions of a sequence of latent states, similar to BERT and MAE. Then, we apply a lightweight Predictor to the latent representations that repairs gaps in the sequence in a lower-dimensional embedding space akin to JEPA. Our experiments in the domain of chess show that the Encoder refines the board representations such that meaningful chess concepts emerge clustered in the latent space. Furthermore, reconstructions of the masked board states show that the model is able to reason about the piece movements without relying on costly reinforcement learning methods. Lastly, we find that the resulting representation space allows for quick and intuitive dissections of chess games by observing the game path trajectories in this semantically rich space.

20.
arXiv (CS.CL) 2026-06-17

Structural Role Injection in Handlebars-Templated LLM Prompts: Triple-Brace Interpolation, Delimiter Family, and the Limits of HTML Auto-Escaping

Large language model applications build prompts from templates, and Handlebars is a widely used templating engine and the default prompt-template format in Microsoft Semantic Kernel. Its double-brace {{x}} expression HTML-escapes the interpolated value and is documented as the safe default; its triple-brace {{{x}}} expression inserts the value raw. We show that this choice silently governs an application's exposure to structural role injection, where attacker-controlled data carries chat role delimiters that forge a higher-privilege turn. A model-free analysis establishes the mechanism: Handlebars escaping rewrites angle brackets but not square brackets, colons, or Markdown hashes, so it neutralises ChatML, Llama-3, and XML role delimiters (survival rate 0.00) while leaving Llama-2 [INST], legacy Human:/Assistant:, and Markdown ### delimiters intact (survival rate 1.00 for the last two). We then run 5760 trials across seven delimiter families, two attack objectives, and four models (GPT-3.5 Turbo, GPT-4o mini, GPT-4.1 mini, Claude Haiku 4.5) at a combined API cost of 1.63 USD. GPT-3.5 Turbo follows the task-hijack instruction in 97% of raw and 91% of escaped trials, with the escaping protection concentrated in the angle-bracket families and absent for the colon- and Markdown-based families; the harder secret-exfiltration objective, which does not saturate, exposes the same family interaction more cleanly. Claude Haiku 4.5 resists both objectives almost entirely. The escaped default protects only the delimiter schemes whose characters HTML escaping happens to cover, gives no protection for the rest, and cannot substitute for a structural separation of instruction and data.

21.
arXiv (CS.AI) 2026-06-17

Memory as a Wasting Asset: Pricing Flash Endurance for Embodied Agents, and the Limits of Doing So

arXiv:2606.18144v1 Announce Type: new Abstract: A robot's flash endurance is a non-renewable stock: every persisted write spends one of a few thousand program/erase cycles and never refills, yet no fielded robot memory system prices which memories are worth an erase cycle. We treat embodied memory as depreciating capital and price that stock with a single endurance shadow price $\eta$, which makes cost-minimizing placement across a RAM / on-board NVM / cloud hierarchy a threshold in a wear-augmented per-byte index. The index is cost-optimal whatever the sign of the value-write association $\chi$; only when $\chi > 0$ does the optimum turn non-monotone, sending a robot's most valuable memories off its flash. The pivot is thus empirical, and we measure $\chi$ on real robot logs at a pre-specified gate: its sign is a property of the deployment regime – positive on recurrent long-horizon manipulation ($\hat{\chi} \approx +1.0 \times 10^{-3}$, replicated at full power), null on a shorter-horizon suite, and negative on non-recurrent teleoperation. Two boundaries scope the result. The endurance budget is dormant on premium 3,000-P/E TLC at datasheet prices and binding on the commodity QLC/eMMC ($\sim$1,000 P/E) that cheaper edge robots run. And where it binds, a learned wear-aware controller only ties price-based routing on task value, because realized value is tier-invariant across RAM, NVM, and cloud: the rent governs device lifetime and cost, not task performance. Whether wear-aware placement improves task value remains open – $\chi$ is measured against a value proxy, and the non-monotone optimum, while proven, is not yet observed in data.

22.
bioRxiv (Bioinfo) 2026-06-08

DDI_single: Single-Sequence-Based Protein Domain Assembly

作者:

Domains are the basic units of protein structure and function. Appropriate inter-domain organization is critical to enable cooperative execution of multiple related functions. It is thus a crucial step to determine the full-length structure of multi-domain proteins for the purpose of elucidating their functions and designing new drugs to regulate these functions. Existing structure prediction algorithms are generally better at solving the internal conformation of domains, rather than modeling the relative positions between domains. To address the challenge of accurately determining multi-domain protein conformations, we develop a single-sequence-based domain assembly algorithm called DDI_single. DDI_single directly extracts features from the amino acid sequence using the protein language model ESM-1b, and accurately predicts the interactions between residue pairs of structural domains through a novel gated cross-attention module, thus achieving the correct assembly of structural domains. With the knowledge of domain definition, DDI_single achieves more than 20% higher accuracy in the task of predicting the relative distances of residue pairs between domains than that of the single-sequence-based structure prediction algorithm trRosettaX_single. When assembling domains with known spatial conformations, DDI_single correctly assembles 74.4% of the samples in the test set (TM-score>0.5). When assembling domains with unknown spatial conformations, in cases where the internal spatial conformations of domains are correctly modeled, DDI_single correctly assembles 73.9% of the samples.

23.
arXiv (CS.LG) 2026-06-12

Realistic noise synthesis reduces bias and improves tissue microstructure estimation with supervised machine learning

arXiv:2606.02044v2 Announce Type: replace Abstract: Diffusion MRI enables non-invasive probing of tissue microstructure, but accurate parameter estimation is challenged by noise-related effects. In supervised machine learning frameworks trained on simulated data, discrepancies between the noise characteristics of simulated and acquired signals introduce a form of covariate shift, whereby the input signal distribution differs between training and inference. We investigated the impact of this mismatch on microstructure parameter estimation and propose a realistic noise synthesis (RNS) framework to mitigate it. RNS incorporates both the Rician expectation and the effective post-processing noise variance into simulated training signals. The Rician expectation was modelled using a noise standard deviation estimated with MPPCA, while the effective standard deviation was derived from spherical harmonic residuals of preprocessed data. The method was evaluated using the cylinder-zeppelin and the SANDI models on simulated datasets across multiple SNR levels and on in vivo diffusion data with repeated acquisitions. Sensitivity to noise misestimation was also assessed. Ignoring magnitude-induced noise effects during training produced systematic, SNR-dependent parameter bias, particularly at low SNR. Incorporating the Rician expectation substantially reduced bias to the level of noise-aware nonlinear least-squares fitting. Modelling the effective standard deviation further improved precision. Performance was largely independent of regression architecture but sensitive to accurate noise estimation. These findings demonstrate that realistic noise modelling in simulated training data mitigates signal-domain covariate shift and is essential for unbiased supervised microstructure estimation, particularly in low-SNR regimes associated with high b-values or high spatial resolution.

24.
bioRxiv (Bioinfo) 2026-06-14

Systematic AI-Driven Drug Repurposing via Clinical Trial Data Mining: A Framework and Six Cross-Therapeutic Case Studies.

作者:

Drug repurposing, the application of approved or shelved compounds to new therapeutic indications, offers a cost- and time-efficient alternative to de novo drug discovery. However, the systematic identification of repurposing candidates from the rapidly expanding body of clinical trial data remains a significant challenge. Here we present a publicly accessible AI-powered tool that mines the ClinicalTrials.gov registry to identify approved drugs with under-explored therapeutic potential in high-value disease areas. The tool integrates natural language processing, mechanism-of-action pathway analysis, and trial density scoring to surface candidates where biological plausibility is high and clinical trial coverage is sparse. We demonstrate the tool's utility across six cross-therapeutic case studies spanning oncology, cardiology, neurology, rare diseases, immunology, and infectious disease. Key findings include: the identification of Zonisamide as an under-explored combination candidate for obesity alongside GLP-1 receptor agonists; mechanistic validation of SGLT2 inhibitors in heart failure with preserved ejection fraction (HFpEF); and a novel cross-domain mapping of anti-TNF biologics to early-stage neurodegeneration via shared neuroinflammatory pathways. The tool is freely accessible and designed to lower the barrier for academic and industry researchers to systematically pursue repurposing opportunities.

25.
medRxiv (Medicine) 2026-06-18

Instantaneous-Frequency EEG Microstate Dynamics Stratify Motor Subtypes in Parkinson's Disease

Parkinson's disease (PD) is clinically heterogeneous, yet objective electrophysiological markers of its postural-instability/gait-difficulty (PIGD) and tremor-dominant (TD) motor subtypes are lacking. We tested whether the temporal dynamics of instantaneous-frequency (IF) microstates in resting-state electroencephalography (EEG) distinguish these subtypes from each other and from healthy controls (HC). In a publicly available cohort (OpenNeuro ds007526) comprising 28 HC and 97 PD patients classified as PIGD (n=50) or TD (n=47), the spatial distribution of the IF was reduced by principal component analysis and modeled with a Gaussian hidden Markov model, yielding three recurrent microstates. Per-participant mean dwell time, occupancy, and state-transition probabilities were compared across the three groups and, within PD, correlated with clinical scores. We found that the dynamics of one microstate varied systematically across groups: its dwell time, occupancy, and self-transition probability increased monotonically from HC through TD to PIGD, while outgoing transitions decreased, so that the state became an increasingly persistent attractor. For dwell time, all three pairwise contrasts survived correction (HC versus PIGD, Hedges' g=1.06; HC versus TD, g=0.59; PIGD versus TD, g=0.40). None of the dynamic indices was associated with clinical severity, disease duration, or medication dose within PD. IF-microstate dynamics thus stratify the PD motor subtypes along a graded continuum without tracking continuous disease severity. The approach offers a candidate objective EEG marker for motor-subtype stratification, complementing spectral characterizations of PD.