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01.
arXiv (CS.LG) 2026-06-17

Informative Missingness to Generate Irregular Clinical Time Series

arXiv:2606.17106v1 Announce Type: new Abstract: Laboratory tests in electronic health records are collected irregularly, and the absence of a test order can be as informative as the measurement itself. Such missingness reflects clinicians' decisions and patient physiology, making it important to model it directly rather than treat it as a preprocessing artifact. Here we present a diffusion-based approach for generating clinical time series that jointly models laboratory values and their observation patterns using the public Data Analytics Challenge on Missing Data Imputation (DACMI) benchmark derived from MIMIC-III. To preserve realistic sampling, we align chart times into 4-hour intervals and segment admissions into 7-day windows, producing trajectories that pair each lab value with a corresponding observation indicator. Standard transformations and normalization are applied to stabilize training. Our method extends the TimeDiff framework to learn continuous lab values and discrete missingness patterns through complementary diffusion objectives. Experiments show that the generated data closely match real patient trajectories across individual lab distributions and joint value-missingness embeddings, demonstrating that diffusion models can capture clinically meaningful dependencies between patient physiology and clinicians' testing behavior under MNAR-like (missing-not-at-random) missingness. These preliminary results indicate that our model can serve as an initial component toward developing clinical foundation models. By producing synthetic priors that preserve key physiology-missingness relationships, this work motivates the subsequent training of Prior-Data Fitted Networks capable of leveraging informative missingness, which we will investigate in the extended work.

02.
bioRxiv (Bioinfo) 2026-06-11

HalluDesign-NA: Extending HalluDesign for De Novo Nucleic Acid Design

AlphaFold3 has revolutionized the prediction of biomolecular structures and interactions, including atomic-level modeling of nucleic acids. However, the de novo design of structured and functional nucleic acids remains a significant challenge. Here, we extend our HalluDesign framework to nucleic acid design by integrating NA-MPNN for nucleic acid sequence optimization and design. This new framework, HalluDesign-NA, enables iterative sequence-structure co-optimization, facilitating the de novo design of nucleic acids. Computational benchmarking across ssDNA, ssRNA, and aptamer design tasks demonstrates consistent improvements in confidence scores (pLDDT, ipTM), supporting the feasibility of de novo nucleic acid design under various constraints, such as sequence length, symmetry, and protein structure context. We anticipate that HalluDesign-NA will accelerate the de novo design of functional nucleic acids for applications in biotechnology and medicine. The source code for HalluDesign-NA is available at https://github.com/MinchaoFang/HalluDesign_NA.

03.
medRxiv (Medicine) 2026-06-15

Diabetes and the Life-Course: Evidence from Panel Data and Electronic Health Records

Incidence of type 2 diabetes is increasing at ages when education, work, family, and financial transitions are taking place, yet we lack robust evidence of whether earlier treatment changes life-course outcomes and over which time span this takes place. This paper uses the medical cutoff for diabetes diagnosis (HbA1c of 6.5 percent) as a natural experiment to study the effects of diabetes treatment using electronic health records (EHR) and panel data. This paper has three main findings. First, using EHR data, we find that there is a sharp increase in the probability of both diagnosis of diabetes and prescription when the HbA1c equals 6.5 percent. Second, we find that treating diabetes reduces HbA1c levels, weight, BMI, and blood pressure and increases the amount of care received, proxied by the number of HbA1c tests. Both the diagnosis and a prescription are independently able to produce positive changes in metabolic health, although a prescription is more effective in this regard. Third, we conclude that treating diabetes does not have a significant effect on life-course outcomes for a cohort of young Americans aged 24-32, although it does result in a reduction in HbA1c levels that are seen even eight years after the intervention. Taken together, these findings suggest that receiving a diagnosis and prescription are both effective treatments for diabetes, but they do not translate to significant alterations in the lives of young adults in the medium-term.

04.
arXiv (CS.AI) 2026-06-24

RAVEN: A Regime-Aware Variable-context Expert Network for Financial Time Series Forecasting

arXiv:2606.24062v1 Announce Type: cross Abstract: Financial time series forecasting presents structural challenges absent from standard benchmarks. Log-returns are non-stationary, exhibit exceptionally low signal-to-noise (SNR) ratios, and are governed by regime-dependent temporal dependencies. We identify a key limitation of state-of-the-art (SOTA) time series models in financial settings. A fixed context window is mismatched to the time-varying optimal look-back of non-stationary price processes. We propose the Regime-Aware Variable-context Expert Network (RAVEN), a Mixture-of-Experts framework designed to adaptively determine the temporal context for each input sample. Instead of relying on a fixed look-back horizon, RAVEN constructs a hierarchy of nested contiguous windows whose lengths are determined by the data itself. Specifically, RAVEN scores patches by learned importance in reverse chronological order and applies the Cumulative Importance Thresholding (CIT) mechanism to derive nested prefix windows, each routed to a scale-specialized expert. A Global Compressed Representation (GCR) branch runs in parallel over the full context, preserving global temporal coherence that local experts cannot guarantee. Because the nested routing induces structured overlap among expert inputs, we introduce a Correlation-Aware Weighting (CAW) to align variable-length expert outputs and penalize pairwise cosine similarity prior to aggregation. Experiments on cumulative log-return prediction (HS300, S&P500) and fund sales forecasting demonstrate that RAVEN achieves SOTA performances, improves Pearson correlation by 9.2% on HS300 and 20.2% on S&P500, and reduces MSE by 18.2% on fund sales forecasting, while achieving the best results in 14 of 16 metrics on four PEMS traffic benchmarks.

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

RSRCC: A Remote Sensing Regional Change Comprehension Benchmark Constructed via Retrieval-Augmented Best-of-N Ranking

Traditional change detection identifies where changes occur, but does not explain what changed in natural language. Existing remote sensing change captioning datasets typically describe overall image-level differences, leaving fine-grained localized semantic reasoning largely unexplored. To close this gap, we present RSRCC, a new benchmark for remote sensing change question-answering containing 126k questions, split into 87k training, 17.1k validation, and 22k test instances. Unlike prior datasets, RSRCC is built around localized, change-specific questions that require reasoning about a particular semantic change. To the best of our knowledge, this is the first remote sensing change question-answering benchmark designed explicitly for such fine-grained reasoning-based supervision. To construct RSRCC, we introduce a hierarchical semi-supervised curation pipeline that uses Best-of-N ranking as a critical final ambiguity-resolution stage. First, candidate change regions are extracted from semantic segmentation masks, then initially screened using an image-text embedding model, and finally validated through retrieval-augmented vision-language curation with Best-of-N ranking. This process enables scalable filtering of noisy and ambiguous candidates while preserving semantically meaningful changes. The dataset is available at https://huggingface.co/datasets/google/RSRCC.

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

CCKS: Consensus-based Communication and Knowledge Sharing

arXiv:2606.12281v1 Announce Type: cross Abstract: In Decentralized Training and Decentralized Execution (DTDE) for cooperative Multi-Agent Reinforcement Learning (MARL), action-advising-based knowledge sharing promotes interpretable and scalable cooperation among agents. However, current action advising approaches often adhere too much to the teacher's guidance without evaluating teacher-student compatibility, which causes excessive advising, suboptimal stability, and degraded performance. To overcome these challenges, this paper presents a Consensus-based Communication and Knowledge Sharing (CCKS) framework, which allows agents to adopt recommendations based on consensus-derived constraints and to follow the teacher's instructions more smartly. This mechanism enables agents to balance exploration and learning from experienced teachers, improving overall performance. The key is the consensus model construction, for which we propose to employ contrastive learning to construct consensus models based on local observations in the agents' training phase. In action selection, agents score and choose actions based on consensus and shared knowledge. Designed as a plug-and-play solution, CCKS integrates seamlessly with existing DTDE algorithms. Experiments conducted in the Google Research Football environment and the complex StarCraft II Multi-Agent Challenge demonstrate that the integration with CCKS significantly improves cooperation efficiency, learning speed, and overall performance compared with current DTDE baselines. The code is available at https://github.com/yuanxpy/CCKS.

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

HSQ-VLM: A Novel Spatially-Constrained Quadrant Segmentation VLM Model for Explainability in Diabetic Retinopathy

Authors:

Diabetic Retinopathy (DR) is an aggressive retinal disease and a leading cause of global blindness, yet its clinical management is currently hindered by the black-box nature of diagnostic AI. While deep learning models achieve high classification accuracy, there is a critical lack of explainability methods capable of detailing the exact anatomical landmarks and lesion distributions that lead to a clinical decision for DR. Therefore, we propose HSQ-VLM, a novel quadrant segmentation pipeline on fundus images that utilizes a Landmark-Anchored Cartesian Cross-Attention mechanism to unify visual feature extraction with structured clinical reasoning. Unlike traditional methods that rely on arbitrary image partitioning, our pipeline implements 4-quadrant Topological Latent Partitioning (TLP) to dynamically align retinal features with a fovea-centered coordinate system. This allows the Vision-Language Model to generate natural language reports that quantify pathology with anatomical precision. On a dataset of 3,500 high-resolution fundus images, this innovative methodology achieved a lesion detection sensitivity of 99.6% for hemorrhages and 96.4% for microaneurysms, while demonstrating a significant reduction in boundary-ambiguity errors compared to standard segmentation baselines.

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

Evolutionary Dynamics of Cooperation in Next-Generation LLM Agent Systems: A Cross-Provider Empirical Extension

arXiv:2605.29874v2 Announce Type: replace-cross Abstract: Do next-generation LLM agents inherit the cooperative biases documented in their predecessors, or does scale and provider diversity reshape equilibrium behaviour in competitive multi-agent settings? Willis et al. established a benchmark for this question using evolutionary game theory and the Iterated Prisoner's Dilemma (IPD), finding consistent cooperative biases in ChatGPT-4o and Claude 3.5 Sonnet. We extend this benchmark to four frontier models released in 2025-2026 - Claude Sonnet 4.6, Gemini 2.5 Flash, Gemini 3.1 Pro, and GPT-5.4 Mini - applying the identical protocol across three prompting styles (Default, Prose, Self-Refine) and four population compositions (balanced and biased, with and without noise). Cooperative bias persists across providers (H1): ten of twelve model-prompt combinations favour cooperative equilibria in balanced noiseless conditions. Cross-provider divergence is substantial (H3): Gemini 2.5 Flash reaches up to 77% aggressive equilibria under biased conditions, while GPT-5.4 Mini reaches 70% cooperative equilibria under Self-Refine. Support for aggressive capability parity is partial (H2): Self-Refine raises ICD in all models and Gemini 3.1 Pro Refine achieves the highest ICD in the dataset (0.925), but Default and Prose prompts show no systematic narrowing. Evidence on noise robustness is directionally positive but not robustly confirmed (H4): with n=500 Moran iterations per condition, average noise sensitivity is about 6 percentage points for Claude Sonnet 4.6 versus 13 pp for Claude 3.5 Sonnet, but this cross-study gap is not statistically significant once the predecessor's unreported sampling error is propagated. Provider identity, rather than model generation, is the strongest correlate of equilibrium outcomes; noise remains a universal challenge regardless of model size or vintage.

09.
arXiv (quant-ph) 2026-06-15

Dynamically frozen long-distance entanglement via non-Hermitian PT-symmetric systems

arXiv:2606.14177v1 Announce Type: new Abstract: In distributed quantum networks, interacting spin systems can mediate the generation of highly entangled links between distant nodes. We investigate the role of effective parity-time (PT)-symmetric non-Hermitian spin-1/2 bulks weakly coupled to two quantum links, obtained due to the environmental interactions affecting both the bulk and the links. Focusing on effective non-Hermitian nearest-neighbor (NN) Su-Schrieffer-Heeger (SSH) models, we analyze how non-Hermiticity influences the dynamical formation of long-distance entanglement (LDE). For a paradigmatic model consisting of a quantum XX bulk subjected to imaginary staggered magnetic fields, we analytically determine the exceptional points arising from the resulting bulk-mediated interactions between the links. Combining analytical and numerical methods, we demonstrate that an initially fully separable state can dynamically evolve into highly entangled link states near these exceptional points in the broken regime. Further, after optimizing over time and system parameters, near-unit time-averaged entanglement between the links emerges under weak imaginary magnetic fields and bulk-link couplings, which cannot be attained in the corresponding Hermitian systems. Moreover, the non-Hermitian dynamics exhibit a freezing of high entanglement in the vicinity of exceptional points, a feature absent in Hermitian counterparts. We also identify regimes of long-range interaction strengths that yield a higher time-averaged entanglement than the corresponding NN models. Furthermore, we establish that LDE persists in the stationary regime, highlighting the promise of engineered non-Hermitian dynamics for realizing robust and frozen entangled links in quantum networks.

10.
arXiv (CS.CV) 2026-06-11

TextHOI-3D: Text-to-3D Hand-Object Interaction via Discrete Multi-View Generation and Joint Mesh Optimization

Text-conditioned 3D generation has progressed rapidly for images and isolated objects, but producing a hand-object mesh remains challenging: the output must preserve language semantics, cross-view consistency, object geometry, articulated hand shape, and physically plausible contact. We present TextHOI-3D, a staged framework that uses generated multi-view observations as an explicit interface between text-conditioned visual generation and geometry-aware hand-object recovery. TextHOI-3D learns a compact VQ token space for fixed-camera hand-object observations, predicts multi-view visual tokens from text with a CLIP-conditioned visual autoregressive model, and recovers a unified hand-object mesh through prior initialization, multi-view joint optimization, and anti-penetration refinement. The design separates semantic generation from geometric recovery while keeping both stages connected by a discrete multi-view representation. On HO3D-derived evaluations, the multi-view setting reduces object CD from 17.26 mm to 4.92 mm and penetration volume from 5.3721 cm^3 to 0.2193 cm^3 compared with a single-view counterpart, while improving hand errors and surface F-scores. These results support multi-view visual tokens as an effective intermediate representation for text-driven 3D hand-object mesh creation.

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

Large Language Models for Agentic NetOps and AIOps: Architectures, Evaluation, and Safety

arXiv:2605.12729v2 Announce Type: replace-cross Abstract: Large language models are increasingly being used to support network operations (NetOps) and artificial intelligence for IT operations (AIOps), including incident investigation, root-cause analysis, configuration synthesis, and limited self-healing. In both NetOps and AIOps, this shift is changing how tasks are managed. Agent-based operations work as workflows, from gathering evidence to taking action, following permissions, policies, and checks, and providing rollback options when necessary. This is crucial because operational decisions can have instant impacts. To make the argument concrete, we organise the relevant literature around the hierarchy of autonomy, tool scope, evidence traces, and assurance contracts. These contracts define what an agent may observe, propose, and execute. They also define the checks that must pass before any action is allowed. A consistent pattern appears across work on telemetry query recommendation, diagnosis, root-cause analysis, configuration synthesis, change planning, and limited self-healing. Operational reliability does not come chiefly from the model itself. It depends on the machinery around the model. We also argue that evaluation should go beyond static question answering. Agentic NetOps and AIOps systems require workflow-centred evaluation, including trace quality, bounded tool use, safe proposal generation, replay in sandboxed environments, and canary trials with rollback-aware scoring. Without these measures, a system may appear robust yet remain too fragile. Finally, we examine security, privacy, and governance risks that become acute when agents sit close to operational control surfaces. Taken together, the survey concludes that progress in intelligent NetOps and AIOps will depend on treating autonomy as a constrained operational control problem, whose outputs must be reliable, auditable, and securely deployable.

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

SPEAR: A System for Post-Quantization Error-Adaptive Recovery Enabling Efficient Low-Bit LLM Serving

arXiv:2606.11244v1 Announce Type: cross Abstract: Efficient large language model (LLM) serving is increasingly constrained by deployment cost. Quantization is a key technique for reducing serving cost, yet even state-of-the-art 4-bit quantizers exhibit a noticeable quality gap from FP16, particularly for smaller models where low-bit serving is most beneficial. We identify a fundamental cause of this gap: quantization error is highly input-dependent and varies substantially across tokens, while existing post-quantization compensation methods are static and apply identical corrections to all inputs. As a result, easy tokens are over-corrected while hard tokens remain under-corrected. We present SPEAR, a system for post-quantization error-adaptive recovery that improves low-bit LLM serving. SPEAR introduces lightweight Error Compensators (ECs) modulated by per-token gates and places them only at the most error-sensitive layers identified through a CKA-guided entropy-aware diagnostic. This focuses a small parameter budget where it is most effective. Efficient deployment of ECs presents several systems challenges, including additional computation, tensor-parallel synchronization caused by input-dependent gating, and latency instability across configurations. SPEAR addresses these issues through adaptive kernel-fusion dispatch, combining an epilogue-integrated peer-reduction kernel with P2P dual-write to fuse the post-EC computation into low-bit GEMMs, and an SLO-constrained EC-aware scheduler for predictable serving performance. Across challenging per-channel quantization settings, SPEAR recovers 56-75% of the perplexity gap between W4 and FP16 while adding less than 1% model memory overhead and maintaining latency comparable to a widely used 4-bit serving deployment.

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

YTClickbait21K: Human-Annotated Multimodal Dataset for YouTube Clickbait Detection Across Diverse Channels and Content Categories

Clickbait content on video-sharing platforms poses a significant challenge to information reliability, yet progress in automated detection has been constrained by the lack of large-scale, high-quality multimodal datasets. We present YTClickbait21K, a human-annotated YouTube clickbait dataset comprising 21,238 videos collected from 40 channels across 29 countries, covering diverse content categories such as news, entertainment, education, and gaming. Each sample includes structured metadata (title, description, engagement statistics) along with associated thumbnail images, enabling comprehensive multimodal analysis. To ensure annotation quality, every video was independently labeled by three annotators using a standardized decision framework that incorporates textual, visual, and cross-modal consistency cues, with final labels determined through majority voting. The dataset exhibits substantial inter-annotator agreement (k=0.65), confirming reliable labeling despite the inherent subjectivity of clickbait detection. By combining scale, annotation rigor, and multimodal richness, this dataset provides a robust benchmark for developing and evaluating machine learning models, facilitating research in cross-modal semantic understanding, and advancing automated content moderation systems.

14.
arXiv (CS.CV) 2026-06-11

Right Predictions, Misleading Explanations: On the Vulnerability of Vision-Language Model Explanations

Explanation mechanisms are increasingly used to support transparency and trust in vision-language models (VLMs), particularly in settings where model decisions require human oversight. However, the robustness of these explanations remains insufficiently understood. In this work, we investigate whether explanation heatmaps in VLMs, particularly CLIP-based models, faithfully reflect model reasoning under adversarial conditions. We show that explanation maps can be systematically manipulated while preserving the model's original prediction, revealing a disconnect between predictive behavior and explanation faithfulness. To study this vulnerability, we introduce X-Shift, a novel grey-box attack that perturbs patch-level visual representations to redirect explanation heatmaps toward semantically irrelevant regions without altering the predicted output. Unlike conventional adversarial attacks that aim to induce misclassification, X-Shift specifically targets the integrity of the explanation process itself. The attack operates without modifying model parameters and generalizes across multiple CLIP architectures and explanation methods. We evaluate the proposed approach on ImageNet-1k, MS-COCO, and Flickr30K, demonstrating consistent degradation in explanation alignment under imperceptible perturbations while maintaining prediction stability. Furthermore, standard prediction-oriented adversarial attacks fail to reproduce the same explanation-shifting behavior even under substantially larger perturbation budgets. Our findings highlight a fundamental limitation of current explanation mechanisms in VLMs and raise concerns about their use as reliable indicators of model trustworthiness in high-impact applications.

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

Near-Optimal Regret for Distributed Adversarial Bandits: A Black-Box Approach

arXiv:2602.06404v2 Announce Type: replace Abstract: We study distributed adversarial bandits, where $N$ agents cooperate to minimize the global average loss while observing only their own local losses. We show that the minimax regret for this problem is $\tilde{\Theta}(\sqrt{(\rho^{-1/2}+K/N)T})$, where $T$ is the horizon, $K$ is the number of actions, and $\rho$ is the spectral gap of the communication matrix. Our algorithm, based on a novel black-box reduction to bandits with delayed feedback, requires agents to communicate only through gossip. It achieves an upper bound that significantly improves over the previous best bound $\tilde{O}(\rho^{-1/3}(KT)^{2/3})$ of Yi and Vojnovic (2023). We complement this result with a matching lower bound, showing that the problem's difficulty decomposes into a communication cost $\rho^{-1/4}\sqrt{T}$ and a bandit cost $\sqrt{KT/N}$. We further demonstrate the versatility of our approach by deriving first-order and best-of-both-worlds bounds in the distributed adversarial setting. Finally, we extend our framework to distributed linear bandits in $R^d$, obtaining a regret bound of $\tilde{O}(\sqrt{(\rho^{-1/2}+1/N)dT})$, achieved with only $O(d)$ communication cost per agent and per round via a volumetric spanner.

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

Towards Conditional Feature Alignment for Cross-Domain Counting

Object counting models often degrade under cross-domain deployment because density composition varies across domains and is itself task-relevant. Standard feature alignment methods tend to suppress such variation by encouraging global domain invariance, which can be harmful when source and target domains contain different proportions of background, sparse foreground, and dense foreground. We propose Conditional Feature Alignment (CFA), a cross-domain counting framework that aligns representations within label-induced conditions rather than across full marginal feature distributions. Given density annotations or pseudo-density predictions, CFA constructs foreground/background or density-level conditions and aligns only features belonging to matching conditions. We formalise this idea through a conditional divergence perspective, showing that conditional alignment removes within-condition discrepancy while preserving condition-marginal density shift. For unsupervised domain adaptation, CFA estimates source conditions from annotations and target conditions from detached pseudo-density maps, then performs condition-wise adversarial alignment with full-image consistency regularisation. For source-domain generalisation, we instantiate the same principle with MPCount by enforcing condition-wise memory-consistency between generated source-domain views. Experiments on crowd and cell counting benchmarks show competitive or improved performance across diverse UDA and DG settings. For example, on JHU-CROWD++ FH$\rightarrow$SN, CFA-DG reduces MAE/RMSE from MPCount's 216.3/421.4 to 90.5/169.9, indicating that condition-wise alignment is especially effective under large weather- and density-induced shifts. These results suggest that condition-wise alignment is a promising design principle for domain-adaptive counting.

17.
arXiv (CS.AI) 2026-06-19

ITNet: A Learnable Integral Transform That Subsumes Convolution, Attention, and Recurrence

arXiv:2606.19538v1 Announce Type: new Abstract: Convolutional networks, recurrent networks, and transformers each encode different inductive biases – locality, sequential memory, and content-dependent pairwise interaction – and have remained mathematically distinct since their inception. We show that this fragmentation reflects not a fundamental diversity in how signals should be processed, but rather incomplete views of a single underlying mathematical object: a learnable integral transform. We introduce the Integral Transform Network (ITNet), a unified architecture built around a learnable kernel that depends jointly on positions and features. This kernel is implemented as a small neural network, specifically an MLP, that models pairwise interactions, enabling the model to adapt its behavior from data. We show that convolution, self-attention (including multi-head), and autoregressive recurrence (including LSTM, GRU, S4, and Mamba) arise as special cases under appropriate parameterizations, and that ITNet is a universal approximator of continuous operators. To make this practical, we develop tiled kernel fusion, importance-weighted Monte Carlo integration, and learned low-rank factorization, enabling efficient and scalable computation. A single ITNet architecture with a shared operator and lightweight modality-specific encoders matches or exceeds specialized baselines on ImageNet-1K , GLUE, ModelNet40, VQA\,v2 and NLVR2. The results demonstrate that a single learned interaction mechanism can recover the behavior of all three architectural families from data.

18.
arXiv (quant-ph) 2026-06-12

Matrix phase-space representations for quantum symmetries

arXiv:2606.12769v1 Announce Type: new Abstract: We introduce a general phase-space representation that includes global quantum symmetries in the basis expansion. This method, called matrix phase-space, projects the basis onto a reduced Hilbert space, which can greatly reduce sampling errors of many-body quantum simulations and unifies several previous phase-space methods. The purpose of this paper is to provide detailed proofs of basic theorems and operator identities. We also treat several different types of symmetries. To illustrate the benefits of matrix phase-space methods, we give a detailed derivation of a recent application to the topical problem of verifying the outputs of Gaussian boson sampling (GBS) quantum computers with photon number resolving detectors. This has exponential complexity, and using parity symmetry reduces sampling errors by very large factors relative to earlier methods.

20.
PLOS Computational Biology 2026-06-05

Heuristic multi-site optimization for protein sequence design using Masked Protein Language Models

Authors:

by Lijuan Wang, Yuze Wang, Chen Qiu, Liwei Xiao, Xianliang Liu, Junjie Chen Protein sequence design for tailored functional properties is a fundamental task in protein engineering, with critical applications in drug discovery and therapeutic development. Efficient navigation of the combinatorial vastness of protein sequence space to identify functional variants remains a formidable challenge. Conventional approaches, which predominantly rely on template-based local search or single-residue mutagenesis, are constrained by their susceptibility to local optima and their potential risk of destabilizing native structural stability. In this study, we introduce ProtHMSO, a heuristic multi-site optimization framework leveraging masked protein language models (ProtLMs) for context-aware sequence exploration. ProtHMSO mimics natural evolutionary mechanisms by employing ProtLM-derived substitution probabilities to guide heuristic searches for synergistic mutations, thereby constraining combinatorial search spaces through evolutionary and biophysical priors. ProtHMSO is further applied to replace the exploration strategies in genetic algorithms (GAs) and Monte Carlo tree search (MCTS) for improving their convergence efficiency. Benchmark experiments demonstrate that protein sequences generated by ProtHMSO exhibit superior functional performance and closer alignment with natural sequence distribution, compared with state-of-the-art methods. These advancements highlight that ProtHMSO has strong potential and compatibility to accelerate functional protein discovery, offering a robust framework for efficient and context-aware exploration of protein sequence space.

21.
arXiv (CS.LG) 2026-06-19

Quantum-classical physics-informed Kolmogorov-Arnold networks for PDEs

arXiv:2606.20326v1 Announce Type: new Abstract: We develop QCPIKAN, the first quantum-classical physics-informed Kolmogorov-Arnold network designed to solve partial differential equations (PDEs). Built upon Chebyshev-polynomial KAN layers and parameterized quantum circuits, this hybrid framework embeds physical constraints into the training loss to enforce physical consistency. Our theoretical investigations grounded in approximation theory prove that this design accelerates high-frequency error convergence to an exponential rate and effectively mitigates numerical dispersion. We validate the framework across three typical seepage scenarios in porous media, including single-phase flow, component transport and two-phase flow. Compared with existing quantum-classical physics-informed neural networks, QCPIKAN achieves superior performance in global prediction accuracy, local error control, dynamic evolution tracking and displacement front localization. This work provides a robust and efficient alternative for solving complex PDEs.

22.
arXiv (CS.CL) 2026-06-24

Are LLM Evaluators Really Narcissists? Sanity Checking Self-Preference Evaluations

Recent research has shown that large language models (LLMs) favor their own outputs when acting as judges, undermining the integrity of automated post-training and evaluation workflows. However, it is difficult to disentangle which behaviors are explained by narcissism versus experimental confounds. Specifically, LLM evaluators may deliver self-preferring verdicts when comparing responses to questions they fail on; these verdicts may not depend on the identity of the author, but on evaluator quality. We correct this by directly comparing the judge's voting distribution in cases where it evaluates itself versus another model. This evaluator quality baseline reveals that only 51% of examples in previous findings retain statistical significance against this null hypothesis, covering 89.6% of total self-preference probability mass. Finally, we compare the entropy of voting distributions, suggesting uncertainty-driven overlap, and show that our procedure enables more careful documentation against the backdrop of judge-bias research.

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

Segmentation-based Detection for Efficient Multi-Task Spacecraft Perception

Vision-based perception is fundamental to Space Situational Awareness and autonomous on-orbit operations such as rendezvous, docking, servicing, and navigation. However, progress in this area is limited by the scarcity of annotated space imagery and by challenging visual-domain characteristics including severe illumination changes, low signal-to-noise ratio, and high contrast. We address Stream 1 of the SPARK 2026 Challenge, which requires a single model for spacecraft classification, detection, and fine-grained component segmentation across multiple target types. We propose a compact architecture that integrates a MobileNetV3 encoder with a U-Net-style decoder, combining computational efficiency with accurate dense prediction. Detection is derived analytically from the union of predicted component masks, avoiding a separate bounding-box regression head in the single-spacecraft setting. Our method achieved an overall leaderboard score of 0.9482, with task-specific scores of 1.0000 in classification, 0.9788 in detection, and 0.8917 in segmentation. The proposed approach ranked second overall in the SPARK 2026 Challenge, demonstrating that lightweight encoder-decoder architectures can deliver strong multi-task performance for practical onboard space vision systems.

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

A Systematic Evaluation of Large Language Models for PTSD Severity Estimation: The Role of Contextual Knowledge and Modeling Strategies

Large language models (LLMs) are increasingly being used in a zero-shot (generative) fashion to assess mental health conditions, yet we have limited knowledge on what factors affect their accuracy. In this study, we use a clinical dataset of natural language narratives and self-reported PTSD severity scores from 1,437 individuals to comprehensively evaluate the performance of 11 state-of-the-art LLMs. To understand the factors affecting model's assessment accuracy, we systematically varied (i) contextual knowledge prompted to the models like subscale definitions, distribution summary, and interview questions, and (ii) modeling strategies including zero-shot vs few shot, amount of reasoning effort, model sizes, structured subscales vs direct scalar prediction, output rescaling and nine ensemble methods. Our findings indicate that (a) LLMs are most accurate when provided with detailed construct definitions and context of the narrative, even exceeding human raters agreement with self-reported scores; (b) increased reasoning effort leads to better estimation accuracy; (c) performance of open-weight models (Llama, DeepSeek) plateaus beyond 70B parameters while closed-weight (gpt-o3-mini, gpt-5) alternatives improve with newer generations; and (d) best performance is achieved when ensembling a supervised model with the zero-shot LLMs. Beyond agreement with self-reports, LLMs' estimates discriminated PTSD severity from depression, anxiety, and alcohol use, and prospectively predicted future mental healthcare expenditure. Together, these results suggest that contextual knowledge and modeling strategies meaningfully affect accuracy and clinical utility of LLM-based assessments of PTSD severity.

25.
arXiv (CS.AI) 2026-06-11

FreeBridge: Variational Schrödinger Bridges for Cellular Transition Dynamics

arXiv:2606.11286v1 Announce Type: cross Abstract: High-content imaging assays quantify cellular responses to chemical and genetic perturbations, yet continuous trajectories of individual cells are unobservable because cells are chemically fixed at acquisition. Perturbation modeling therefore reduces to inferring stochastic transport between control and treated populations observed only as separate marginals. While recent generative models achieve strong end-point alignment, boundary consistency does not determine intermediate evolution: multiple stochastic processes may connect identical marginals while traversing regions unsupported by observed single-cell morphologies. We introduce FreeBridge, a Schrödinger Bridge formulation for single-cell transition modeling under endpoint-only supervision. FreeBridge defines atomic states as instance-segmented single-cell representations, establishing a fixed cellular manifold, and learns stochastic transport constrained within this geometry via empirical latent support regularization. Across BBBC021, RxRx1, and JUMP, FreeBridge maintains competitive or improved endpoint fidelity and mechanism-of-action retention under a unified evaluation protocol; on BBBC021, it further reduces intermediate support violations. These findings highlight the importance of geometric grounding for biologically interpretable perturbation dynamics. Project page: https://y-research-sbu.github.io/FreeBridge/.