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01.
medRxiv (Medicine) 2026-06-18

Cost-effectiveness of a virtual fracture clinic versus traditional in-person fracture clinic care for adults with acute simple fractures: a protocol for a health economic evaluation within the RECITAL trial

ABSTRACT Introduction Traditional in-person fracture clinics are often overcrowded and inconvenient for patients. Virtual fracture clinics aim to address some of these concerns by improving the efficiency of the orthopaedic service and reducing unnecessary interventions while maintaining safety and quality of care. The RECITAL trial is a non-inferiority randomised controlled trial comparing follow-up care provided at a virtual fracture clinic for people with acute simple fractures to follow-up care provided at an in-person fracture clinic. This study describes the protocol for an economic evaluation of RECITAL where the primary aim is to investigate the cost-effectiveness of a virtual fracture clinic compared with traditional in-person fracture clinic care from a health system perspective. Methods and analysis The RECITAL trial recruited 312 participants with acute simple fractures and randomised them to receive follow-up care provided at a virtual fracture clinic or follow-up care provided at an in-person fracture clinic. We will conduct a within-trial analysis from a health system perspective (primary analysis), as well as a health service, patient and societal perspective. The economic evaluation will estimate the difference in the cost of resource inputs on an intention to treat basis used by participants in the two arms of the trial, allowing comparisons to be made between the in-person and virtual fracture clinics. Data for intervention costs and healthcare utilisation will be collected from trial records, hospital electronic medical records and district performance units. The results of the economic evaluation will be expressed in terms of incremental cost per utility weight gained at 12 weeks and will be plotted on a cost-effectiveness plane. Bootstrapping by resampling will be used to estimate 95% confidence intervals around costs and outcomes, and to calculate the confidence intervals around the incremental cost-effectiveness ratio. A cost-effectiveness acceptability curve (CEAC) will be plotted, which will provide information about the probability that an intervention is cost-effective, given the level of a decision makers willingness to pay for each additional outcome. Ethics and Dissemination The trail was approved by the SLHD Ethics Review Committee (RPAH Zone) (X23-0200 and 2023/ETH01038). The findings will be disseminated through a peer-reviewed journal and conference presentations. Trial registration number The trial was prospectively registered on the Australian New Zealand Clinical Trials Registry (ANZCTR; 12623000934640)

02.
arXiv (CS.AI) 2026-06-16

Artificial Intelligence Index Report 2026

arXiv:2606.15708v1 Announce Type: new Abstract: Welcome to the ninth edition of the AI Index report. As AI continues to advance rapidly, the question becomes whether the systems built around it can keep up. Governance frameworks, evaluation methods, education systems, and the data infrastructure needed to track AI's impact are struggling to match the pace of the technology itself. That gap between what AI can do and how prepared we are to manage it runs through every chapter of this year's report. New in this edition, the report tracks how AI is being tested more ambitiously across reasoning, safety, and real-world task execution, and why those measurements are increasingly difficult to rely on. It also features new estimates of generative AI's economic value alongside emerging evidence of its labor market effects, an analytical framework on AI sovereignty, and a science chapter developed in collaboration with Schmidt Sciences. For the first time, the report features standalone chapters on AI in science and AI in medicine, reflecting AI's growing impact across these two domains.

03.
arXiv (CS.CV) 2026-06-16

MamBOA: State-Space Architecture for Video Recognition

Fine-grained action recognition demands temporal reasoning that general-purpose architectures address through different cost-accuracy tradeoffs: 3D dense operators couple computation to the input volume, while difference-based methods approximate motion through rigid, hand-crafted subtraction of uncontextualized features - each reflecting a deliberate design choice with corresponding limitations in expressiveness or flexibility. We present MamBOA, a backbone-agnostic temporal framework built upon a novel interleaved scan structure that recasts the selective state-space recurrence (S6) as a native motion synthesizer. By interleaving consecutive feature representations extracted from a pretrained backbone into a single alternating sequence, the proposed scan structurally drives the recurrence to encode both temporal observations of each position within a shared hidden state, separated by only a single decay step - rendering the inter-frame transition an intrinsic component of the state dynamics rather than an externally computed quantity. A cascade of dedicated alignment and decoding operations then distills this joint encoding into an explicit motion representation, which a dual-path pooling mechanism adaptively aggregates by balancing attention-driven selection with uniform temporal coverage. The framework interfaces seamlessly with CNN, Transformer, and Mamba backbone families, adding only ~2.1 GFLOPs per feature pair. On Diving48, MamBOA achieves 85.02% Top-1 accuracy with an image-pretrained backbone and 86.24% with a video-pretrained backbone processing the entire video in a single forward pass - demonstrating that structurally induced state-space dynamics constitute a principled and general foundation for motion modeling.

04.
medRxiv (Medicine) 2026-06-15

Semantic Embeddings and the Peripheral Transcriptome in Ischemic Stroke: Connecting Molecular Signatures to NANDA-I Diagnoses

Objective: To construct and evaluate, in an exploratory manner, a pathophysiologic rationale link- ing biological pathways derived from the peripheral transcriptome in ischemic stroke (IS) to nursing diagnoses in the NANDA-I 2024-2026 taxonomy, while emphasizing that this association is not di- rect, deterministic, or automatically inferable from textual similarity with large language models (LLMs). Methods: A computational study was conducted using public secondary data from the Gene Ex- pression Omnibus series GSE16561, which includes 63 peripheral blood samples: 39 from indi- viduals with IS and 24 from healthy controls. The pipeline integrated transcriptomic analysis and functional enrichment, semantic mapping through ClinicalBERT embeddings, and mechanistic and clinical-conceptual judgment using Claude Sonnet 4.6 as a judge. The judgment stage was treated as the central interpretive layer, designed to mediate the transcriptome, pathophysiology, functional manifestation, and NANDA-I diagnosis. Results: The analysis identified a bimodal transcriptomic pattern, with activation of pathways re- lated to innate immunity and suppression of pathways related to adaptive immunity. Semantic map- ping generated 158 pathway-diagnosis pairs. The Spearman correlation between cosine similarity and the mechanistic score was negative and statistically significant (rho = -0.243; p = 2.09e-03), but weak in magnitude. This effect size indicates that semantic similarity explained less than 6% of the variance in mechanistic plausibility, reinforcing the insufficiency of embeddings as a stand- alone criterion. Of the 158 pairs, 14 were classified as high concordance, 8 as moderate, and 136 as divergent. Conclusion: The main value of this study lies in demonstrating that translating biological pathways into nursing diagnoses requires pathophysiologic, functional, and clinical-conceptual mediation. The prioritized pairs represent mechanistically plausible hypotheses for future research, without implying causality, direct clinical confirmation, or immediate care recommendations.

05.
PLOS Computational Biology 2026-06-15

Fung-AI: An AI/ML-driven pipeline for antifungal peptide discovery

by Daniel S. Berman, Libby M. Lewis, Tom D. Curtis, Olivia N. Tiburzi, Daniel F. Q. Smith, Arturo Casadevall, Laura J. Dunphy Emerging fungal pathogens represent a concerning threat to both global health and food security. In this study, we aimed to address our rising vulnerability to fungal pathogens through the development of the Fung-AI pipeline: an AI/ML-driven approach for antifungal discovery. A generative adversarial network (GAN) was trained to generate novel candidate antifungal peptide sequences. Next, in silico antifungal and hemolytic classifiers were built to further prioritize AI-generated peptides for experimental validation. From a pool of ~10,000 candidates, thirteen peptides were selected for testing over two-stages of experimentation. Five peptides were found to display mild antifungal activity against the wheat pathogen, Fusarium graminearum, with minimal inhibitory concentrations (MICs) ranging from 250 µg/mL to 500 µg/mL. Four of the five peptides also showed activity against the human pathogen, Candida albicans (MIC: 500 µg/mL). Two of our AI-generated antifungal peptides additionally demonstrated low cytotoxicity in HepG2 human liver carcinoma cells (LC50 > 704.2 µg/mL) indicating that they may be useful as scaffolds for future optimization for therapeutic applications. None of our peptides were found to considerably inhibit the emerging pathogen C. auris, suggesting the need for pathogen-specific down-selection of candidate peptides. Overall, we present a proof-of-principle, generative-AI-based approach for the rapid design of de novo antifungal peptides.

06.
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.

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

Learning Survival Models with Right-Censored Reporting Delays

arXiv:2510.04421v3 Announce Type: replace-cross Abstract: Survival analysis provides statistical methods to model the time until an event occurs. Reporting delays arise when event times are not observed at their occurrence but are only revealed upon reporting. This issue is particularly critical for timely risk evaluation when the observation window is short due to administrative censoring. In this study, we incorporate right-censored reporting delays by jointly modeling parametric hazards for the event and reporting processes. We then construct a consistent estimator for the model parameters and develop a Monte Carlo expectation-maximization algorithm to compute it. To address the challenges posed by administrative censoring, we leverage these findings and propose a transfer-learning procedure. Experimental results demonstrate that our method improves the accuracy of timely risk evaluation under administrative censoring.

08.
arXiv (quant-ph) 2026-06-16

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

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

09.
arXiv (CS.AI) 2026-06-11

Steering Where to Listen: Instruction-Based Activation Steering Redirects Temporal Attention in Large Audio-Language Models

arXiv:2606.11400v1 Announce Type: cross Abstract: Large Audio-Language Models (LALMs) excel at audio understanding but expose little about where in an audio signal they attend. We introduce instruction-based vector steering, which constructs a steering vector by contrasting activations from differently instructed prompts while keeping the audio fixed. Through a systematic probe of LALM attention, we find that - unlike standard prompting or audio-based steering - this intervention significantly redistributes the temporal attention allocated to audio tokens, concentrating it on acoustically relevant regions. We then show that this attention shift is behaviorally meaningful: in a controlled three-event setting, reading out the temporal position of maximal steering-induced attention change recovers the location of a queried sound event without any training, attaining 60.87% and 68.72% overlap with ground-truth intervals on Qwen2-Audio and Audio Flamingo 3, far above direct prompting (31.84%, 46.75%) and random baselines (27.74%). Our results characterize a mechanistic property of instruction-based steering in LALMs and provide a training-free probe for the latent temporal structure these models encode.

10.
arXiv (CS.LG) 2026-06-18

A physical adaptive material motor unit neural network: a hygromorph composite material machine

arXiv:2606.18275v1 Announce Type: cross Abstract: Advances in novel materials science enable structures to function as intelligent machines by embedding memory and learning capabilities directly into materials. Our work introduces a physical adaptive material motor unit neural network,leveraging a new generation of controllable actuators composed of wood- and carbon black-based composites, sensitive to temperature and relative humidity. These material actuators are assembled into a motor unit-like structure inspired by muscle contraction trigger, forming an intelligent machine capable of dynamic shading control that can be used, for example, in buildings. The machine is governed by a neural network trained on over 350 experimental data points collected under diverse environmental conditions. By establishing a new data-aware backpropagation training, we show that the machine predicts shading responses and learns to predict appropriate behaviour incrementally as the database expands. We also demonstrate the ability of the machine to optimise configurations to achieve similar shading outputs under two distinct conditions.

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

Pointwise is Pointless? A Multimodal Ablation Study for Precipitation Nowcasting with Graph Neural Networks

arXiv:2606.18436v1 Announce Type: cross Abstract: Sparse point observations are increasingly available for precipitation nowcasting, but it is unclear how much they improve dense radar-field forecasts. We partially address this question with a multimodal graph neural network nowcasting system over the Nordic radar domain. The model predicts rain rate every five minutes up to two hours ahead and is trained with different combinations of radar history, MEPS numerical weather prediction, Netatmo surface observations, MSG satellite channels, stochastic noise, and CRPS-based ensemble losses. The study is designed as an ablation of operationally relevant information sources and training objectives. We compare radar-only, NWP-informed, station-informed, satellite-informed, noise-augmented, and CRPS-based configurations using complementary diagnostics on the radar grid, at station locations, for rain onset, and through oracle, displacement, and amplitude scores. The results show that each source improves a different part of the forecast problem. MEPS stabilises radar-only extrapolation, Netatmo observations improve local station and onset diagnostics, and satellite predictors reduce some station-level biases but may activate rain too early when used deterministically. CRPS-based configurations provide the most consistent radar-grid gains, while the combined satellite and CRPS setup gives the best overall oracle/DAS score. These results do not support the conclusion that point observations are uninformative for nowcasting, but they show that local observational skill and spatially coherent radar-field skill are distinct targets. The practical implication is that sparse observations can provide useful local constraints, but their benefit for radar-like fields depends on the training loss, uncertainty representation, and how observation support is encoded in the model.

12.
bioRxiv (Bioinfo) 2026-06-19

Evaluation of analysis modes for RNA coexpression in single-cell and bulk tissue

Coexpression of transcripts presents the most common means of computational inference of transcription factor regulation, and is often combined with other data types to infer regulatory networks. With the growing popularity of single-cell approaches, there are questions about how best to extract coexpression information from the data. Recently we reported a simulation study that explored the differences among coexpression performed at different levels: across single cells (xCell, per cell type), across subjects from pseudobulked single-cell data (xSubject, per cell type), or across subjects using bulk tissue samples (xBulk). Here we test predictions made by those models using real data. We consider both preservation (consistency of coexpression findings across different levels of analysis of the same data) and replicability across independent studies, as well as biological interpretability. We find that preservation across levels is limited, indicating the choice of analysis level will affect outcomes. We show that xCell coexpression is more replicable across studies compared to xSubject. xBulk coexpression is dominated by patterns driven by variability in cellular composition and fails to capture much coexpression that is reliably detected at finer resolutions. While all modes of analysis exhibit some enrichment for known regulatory relationships, it was highest with the xCell mode. Finally, we present a case study of the effect of analysis modes on a schizophrenia-associated pattern, reinforcing the importance of analytic choices in the interpretation and replicability of coexpression analyses. Together with our modeling study, this work emphasizes the importance of understanding sources of expression covariation as they relate to the goals of the analysis, and recommend single-cell-based data with biological replicates should be the focus of attempts to infer dynamic regulatory interactions that are more likely to be replicable by others.

13.
arXiv (quant-ph) 2026-06-17

Cavity method for permutation models on Cayley trees

arXiv:2606.17751v1 Announce Type: new Abstract: Motivated by permutation statistical models arising in random tensor networks, we study permutation models on a Cayley tree whose variables take values in the symmetric group $\Sn$. The pair interaction is assumed to depend only on the cycle type of the relative permutation. Then the Boltzmann weight is written as a class function on $\Sn$. This property diagonalizes the edge convolution operator in irreducible representation sectors. As a result, the linear stability of the uniform paramagnetic cavity solution is controlled by the character eigenvalue ratios. For cycle-factorized weights, these eigenvalues can be expressed as specializations of Schur functions. We derive the instability criteria and also verify their validity by comparison with direct numerical iterations of the cavity equation.

14.
Nature (Science) 2026-06-10

Lignin to adipic acid in a high-yield chemical and biological redox process

Viable manufacturing pathways to produce bio-based chemicals from renewable feedstocks, such as lignin derived from plant biomass, are needed to decarbonize the chemicals manufacturing sector. Converting the recalcitrant lignin polymer to valuable bioproducts remains a longstanding challenge in biorefining, with the highest reported single-product yield from lignin currently around 20 wt% (refs. 1–4). Most existing lignin depolymerization strategies target aryl–ether bond cleavage, which can produce aromatic monomers in yields of only about 30 wt%, and still as complex mixtures with C–C-linked dimers and oligomers5,6. The recalcitrance of these C–C linkages between aromatic moieties fundamentally limits single-product yields from lignin, prompting the development of strategies to efficiently cleave these C–C bonds3,7–9. Here we show how reductive processing of lignin from poplar accesses a hydrocarbon mixture of alkyl-aromatic monomers and oligomers that is privileged for oxidative conversion to monomeric aromatic carboxylic acids, comprising mostly benzoic acid and phthalic acid isomers in up to 73 wt% monomer yields, using a Co/Mn/Br catalyst. The soil bacterium Pseudomonas putida KT2440 was engineered to convert this mixture of aromatic carboxylic acids to muconolactone, a precursor to bio-based nylons, enabling final adipic acid yields up to 26 wt% (gram adipic acid per gram lignin) with a maximum theoretical yield of 57 wt%. This pairing of reductive and oxidative steps with lignin resembles processes in petrochemical refining and shows how lignin may be converted into a single, valuable bioproduct in high yields. A chemical and biological redox process that resembles processes in petrochemical refining is used to convert lignin from poplar into a single, valuable bioproduct, adipic acid, in high yields.

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

SMEPilot: Characterizing and Optimizing LLM Inference with Scalable Matrix Extensions

arXiv:2606.16332v1 Announce Type: cross Abstract: Modern CPUs increasingly integrate matrix extensions, such as Arm Scalable Matrix Extension (SME), that provide high-throughput matrix execution within the CPU. For LLM inference, however, these units are not a universal replacement for conventional CPU cores: prefill, decode, attention, and KV-cache operations expose different arithmetic intensities, vector behavior, and layout requirements, while SME units and CPU cores still compete for shared memory bandwidth. This paper studies this mismatch through a roofline-based characterization of SME-enabled CPUs and uses the resulting model to guide operator-level execution choices. We present SMEPilot, an LLM inference engine that selects CPU-only, SME-only, or cooperative SME+CPU execution for each operator shape. SMEPilot partitions matrix work across SME and CPU cores at tile granularity, overlaps SME-suitable matrix stages with CPU-suitable vector stages in attention, and maintains layout state so packed tensor representations are reused rather than repeatedly rebuilt on critical paths. Across Llama-3.2-3B, Qwen3-4B, and Qwen3-30BA3B on phone, PC, and server platforms, SMEPilot improves end-to-end inference performance by up to 3.94$\times$.

16.
medRxiv (Medicine) 2026-06-18

Factor Analysing Predictive Processing: No Evidence for a General Factor Across Tasks

Background & Hypothesis: Dysfunctional predictive processing (PP), specifically the aberrant weighting of priors, is a frequently-proposed mechanism for psychosis and psychosis-like phenomena (schizotypy). Evidence for this theory mostly originates from single-task studies, which assume that all tasks load onto a single latent construct of PP performance, but the underlying factor structure of PP tasks is unknown. PP deficits in psychosis may be better described by a two-factor, hierarchical model: weakened lower-level (perceptual) priors compensated by higher-level (cognitive) priors. Study Design: This study implements a multi-paradigm approach in healthy participants to investigate latent constructs underlying PP and their relationship to schizotypy. Participants (N = 73) completed 6 tasks measuring reliance on priors across language, memory, visual, and auditory domains. A factor analysis investigated whether performance across tasks is captured by a single or two-factor model. Study Results: Although a two-factor model best described performance, factors reflected within-task correlations rather than a PP hierarchy. Cross-task PP measures were poorly correlated, suggesting that individuals' weighting of priors was task-specific. A full model including all task outcomes (not factors) significantly predicted the severity of schizotypal aberrant beliefs but no other schizotypal measures. Conclusions: These results do not evidence a single factor underpinning PP performance. It is therefore inappropriate to use results from single tasks to propose a generalised PP deficit in psychosis. Variation was also not captured by a two-factor hierarchical model of priors. Further multi-paradigm research is required to evaluate alternative models or additional variables that describe aberrant PP in psychosis.

17.
arXiv (CS.AI) 2026-06-15

AdaTKG: Adaptive Memory for Temporal Knowledge Graph Reasoning

arXiv:2605.07121v2 Announce Type: replace Abstract: Temporal knowledge graphs (TKGs) represent time-stamped relational facts and support a wide range of reasoning tasks over evolving events. However, existing methods produce entity representations that are static at the entity level, in that each representation is a function of learned parameters only and retains no trace of the interactions in which the entity has participated. In this paper, we depart from this static view and propose that each entity be modeled as an adaptive process whose representation is refined every time the entity participates in a fact. To this end, we propose AdaTKG, which maintains a per-entity memory that is updated with every observed interaction, with the memory accumulating online and predictions improving as more interactions arrive. Specifically, we instantiate the memory update as a learnable exponential moving average governed by a single shared scalar instead of using learnable parameters for each entity, enabling AdaTKG to handle entities unseen during training. Extensive experiments confirm consistent gains over TKG baselines, demonstrating the effectiveness of adaptive memory. Code is available at: https://github.com/seunghan96/AdaTKG

18.
arXiv (CS.CV) 2026-06-19

VFACamou: View-Fused Adversarial Camouflage for Environment-Adaptive Physical Evasion

Adversarial camouflage in the physical world remains highly challenging, particularly under UAV reconnaissance where targets undergo continuous geometric changes and extreme illumination variations. Existing methods either optimize 2D digital perturbations that fail to generalize to dynamic viewpoints or produce visually unnatural textures that cannot be deployed in real scenarios. Therefore, we propose an end-to-end framework for adversarial camouflage generation that automatically produces wearable adversarial patterns and maintains stable attack performance in real physical environments with changing viewpoints, poses, and lighting conditions. Our method integrates UV-volume rendering with a diffusion-based texture generator, enabling consistent appearance under varying scales, poses, and lighting conditions. To ensure environmental realism, we propose an illumination color consistency estimator that extracts dominant background attributes and guides a natural texture loss to align the generated UV texture with the surrounding environment. A multi-scale dynamic training strategy further enhances robustness against viewpoint shifts and body deformation. Extensive experiments across multiple mainstream detectors demonstrate that our method achieves strong and stable physical attack performance while maintaining high perceptual naturalness, reducing human detection rates without introducing unnatural artifacts.

19.
PLOS Computational Biology 2026-05-29

Structural and dynamic basis of NOD2 tandem CARD association and NOD1/2–RIP2 signaling complexes

by Jitendra Maharana, Aritra Bej, Debasish Biswal, Debashis Panda, Arjun Sharma NOD1 and NOD2, founding members of the NOD-like receptor (NLR) family, play a crucial role in host defense against bacterial infections. Recognition of peptidoglycan-derived ligands triggers ATP-dependent oligomerization of the NACHT domain, exposing the CARD domains that recruit the adaptor protein RIP2 via CARD–CARD interactions to activate the NF-κB signaling cascade. Although NOD1/2-RIP2 interactions and RIP2CARD filament assembly are established, the precise interfaces that stabilize hetero–CARD filaments remain poorly defined. Here, we integrate in silico structural modeling with molecular dynamics (MD) simulations to elucidate structurally compatible arrangements of NOD1–RIP2 and NOD2–RIP2 hetero–CARD filaments. Our results reveal that NOD1CARD subunits form a structurally compatible homomeric scaffold via canonical (type-I–III) interfaces, accommodating multiple tiers of RIP2CARD rings at both filament termini. Meanwhile, the NOD2 tandem CARDs adopt multiple discrete conformations, reflecting a more intricate structural mechanism. In stable filament conformations, tandem CARDs converge at the type-II interface, with RIP2CARD rings stacking onto CARDa (top-down) and CARDb (bottom-up) interfaces, highlighting the structural role of NOD2CARDb in RIP2-mediated CARD–CARD interaction. In silico mutagenesis, involving charge-reversal and alanine scanning of key interfacial residues, disrupts NOD1–RIP2 and NOD2–RIP2 interactions at both top-down and bottom-up interfaces, leading to rapid interface destabilization within 0.1–0.4 μs of simulation. Together, these results reveal conserved and receptor-specific mechanisms governing NOD1/2–RIP2 CARD–CARD interactions and provide deeper structural and dynamic insights into the complex structural mechanisms for NLR-mediated inflammatory signaling.

20.
PLOS Computational Biology 2026-06-12

Stage-dependent role of NEK7 in the inactive-to-active conformational transition of NLRP3 monomer

作者:

by Jin Peng, Wenjian Li, Hao Wang, Xiaohui Chen, Manjie Zhang, Bin Sun The NLRP3 inflammasome is a multiprotein complex that primes cytokine production in the innate immune system. The inflammasome activation involves the cage-to-disk transition of NLRP3 oligomers, facilitated by the co-factor NEK7 protein. While NEK7’s role in promoting cage disassembly has been reported, its involvement in the large conformational changes of the NLRP3 monomer during activation remains elusive. Here, by using multi-scale simulations, we uncovered a stage-dependent role of NEK7 in the inactive-to-active transition. In the early stage, NEK7 reshapes the dynamics of the highly unstable inactive NLRP3 monomer to resemble active state, priming the conformational transition. In the middle stage, NEK7 impedes progression by populating an intermediate state farther from the active conformation than the NEK7-free counterpart, and structures in this state exhibit reduced allosteric potential toward activation. In the late stage, NEK7 has negligible impact, as the active conformation remains inherently isolated by a high energy barrier regardless of NEK7 presence. This highlights the critical role of oligomeric assembly in enabling monomeric NLRP3 to complete its conformational transition, in agreement with experiment observations. Our work suggests a multilayered activation mechanism where oligomer-level assembly and monomeric conformational changes are coupled, providing new mechanistic insights into this physiologically essential macromolecular process.

21.
arXiv (CS.AI) 2026-06-15

Learning Coordinated Preference for Multi-Objective Multi-Agent Reinforcement Learning

arXiv:2606.14693v1 Announce Type: cross Abstract: Cooperative multi-objective multi-agent reinforcement learning (MOMARL) models team decision making under multiple, potentially conflicting objectives. In this setting, conflicts arise not only across objectives but also across agents with different observations, roles, and contributions. We propose Preference Coordinated Multi-agent Policy Optimization (PCMA), which learns coordinated agent-specific preferences to enable complementary trade-offs among agents. Theoretically, we formulate cooperative MOMARL as a team-optimal game and show that, under suitable conditions, preference diversity can induce team improvement through a first-order improvement decomposition. Experiments on multiple cooperative MOMA environments and a practical traffic-control scenario show that PCMA improves both performance and trade-off coordination.

22.
arXiv (CS.LG) 2026-06-15

Machine Learning for Biomedical Raman Spectroscopy: From Spectral Acquisition to Clinical Translation

arXiv:2606.14169v1 Announce Type: new Abstract: Raman spectroscopy provides label-free, chemically specific characterization of biological systems and has become an important tool for cancer diagnosis, molecular subtyping, microbiological identification, and intraoperative decision support. Biomedical Raman spectra are, however, high-dimensional, noisy, and affected by fluorescence background, acquisition variability, and biological heterogeneity, making robust computational analysis essential. This review examines the role of machine learning across the biomedical Raman spectroscopy pipeline, from preprocessing and signal correction to unsupervised structure discovery, supervised diagnosis and molecular stratification, representation and transfer learning, explainability, biomarker discovery, and multimodal integration with imaging, pathology, and molecular profiling. Emphasis is placed on the use of machine learning not only for diagnostic classification, but also for biologically interpretable and clinically actionable analysis. We also discuss the main barriers to clinical translation, including limited dataset sizes, inter-instrument variability, inconsistent preprocessing, insufficient external validation, reproducibility concerns, and limited sharing of software, data, and metadata. We argue that progress will require methodological advances together with standardization, robust validation, explainability, and deployment-ready analytical frameworks. By integrating methodological, biomedical, and translational perspectives, this review outlines key directions for developing reliable and clinically deployable Raman-AI systems.

23.
arXiv (quant-ph) 2026-06-12

Candidate overtone shear horizontal SAW resonators in thin-film lithium niobate for intermodal acousto-optic modulation

arXiv:2606.12853v1 Announce Type: cross Abstract: The merits of thin-film surface acoustic wave (SAW) devices are pivotal to develop the high-performance intermodal acousto-optic modulators. In this work, we have proposed shear-horizontal (SH) SAW resonators for anticipated intermodal acousto-optic modulation on the thin-film lithium niobate platform. Through optimization of the cut angle of LN films, the SAW wavelength, and the thickness of interdigital transducer (IDT) electrodes, the calculated acousto-optic overlap factors utilizing SH0 modes are improved by more than an order of magnitude compared with those of Rayleigh modes. Furthermore, we have fabricated and characterized three kinds of proof-of-principle SH0 mode devices without/with grating reflectors. The electromechanical coupling coefficients (keff^2) and quality factors (Q) in the overtone resonators with grating reflectors are systematically evaluated, featuring the highest Q of 843 with the compromised keff^2 of 0.96%-4.72%. The results reveal that the temperature coefficients of frequency (TCF) of Rayleigh modes vary across various overtones, whereas the SH0 modes exhibit TCFs in the range of 32.3-68.9 ppm/C. Our fabricated SH0-mode overtone resonators demonstrate the capability of operating at power levels up to 29 dBm without electrode damage, offering a promising paradigm for robust and high-efficiency intermodal acousto-optic modulators with potential applications in integrated optical signal processing, microwave photonics,and quantum information technologies.

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

The Model Knows, the Decoder Finds: Future Value Guided Particle Power Sampling

arXiv:2605.02427v3 Announce Type: replace Abstract: A recurring pattern in "reasoning without training" is that base LLMs already assign non-trivial probability mass to correct multi-step solutions; the bottleneck is locating these modes efficiently at inference time. Power sampling provides a principled way to bias decoding toward such modes by targeting p_theta(x)^alpha with alpha > 1, but practical approximations must account for future-dependent correction factors that determine which prefixes remain promising. We introduce Auxiliary Particle Power Sampling (APPS), a blockwise particle algorithm for approximating the sequence-level power target with a bounded population of partial solutions. APPS propagates hypotheses in parallel using proposal-corrected power reweighting and refines their survival through future-value-guided selection at resampling boundaries. This redistributes finite compute across competing prefixes rather than committing to a single unfolding path, while providing a direct scaling knob in the particle count and predictable peak memory. We instantiate the future-value signal with short-horizon rollouts and also study an amortized variant that replaces rollouts with a lightweight learned selection head. AMore broadly, APPS improves the accuracy–runtime trade-off of training-free decoding, further supporting the view that inference-time power approximation can recover gains often attributed to post-training.

25.
arXiv (CS.AI) 2026-06-18

Learning from Own Solutions: Self-Conditioned Credit Assignment for Reinforcement Learning with Verifiable Rewards

arXiv:2606.18810v1 Announce Type: cross Abstract: Reinforcement learning with verifiable rewards (RLVR) has driven substantial progress in training LLMs for reasoning tasks, but representative methods such as GRPO assign uniform credit across all tokens, wasting gradient on routine tokens while under-crediting pivotal reasoning steps. Existing token-level credit assignment methods require resources beyond the model's own rollouts. GRPO variants rely on process reward models or ground-truth answers. Knowledge distillation assigns credit through per-token divergence but requires external teachers (On-Policy Distillation) or privileged information (On-Policy Self Distillation). However, these dependencies limit applicability in the pure RLVR setting. We observe that conditioning the model on its own verified trajectories induces a measurable per-token KL divergence between the original and conditioned distributions, and prove that distilling from a self-teacher constructed by verified trajectories leads to infeasible weighted-average solutions when multiple verified trajectories exist. We propose SC-GRPO (Self-Conditioned GRPO), which uses KL divergence mentioned before as a multiplicative weight on GRPO gradients. Across five benchmarks spanning math, code, and agentic tasks, SC-GRPO consistently outperforms 8.1% over GRPO and 5.9% over DAPO with stronger OOD performance. Moreover, SC-GRPO achieves higher performance than OPD.