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01.
arXiv (CS.AI) 2026-06-11

INFRAMIND: Infrastructure-Aware Multi-Agent Orchestration

arXiv:2606.11440v1 Announce Type: new Abstract: Existing multi-agent LLM orchestration methods, ranging from brute-force ensembles to learned routers, select models and topologies based on task and model features. However, these methods do not consider the runtime state of the serving infrastructure. On shared GPU clusters under concurrent load, this infrastructure blindness causes systematic resource underutilization: preferred models accumulate deep request queues while equally capable alternatives sit idle. In multi-agent pipelines, where each query triggers multiple sequential model calls, these delays then compound across every downstream step. Closing this gap is challenging because the relevant infrastructure signals (queue depths, KV-cache pressure, latencies) are dynamic and noisy, and they must drive three different decisions: planning, per-step routing, and scheduling. We introduce INFRAMIND, a framework that makes the entire multi-agent stack infrastructure-aware. An infra-aware planner conditions topology and role selection on real-time system load and remaining budget, biasing toward simpler graphs under congestion and richer ones at low load. An infra-aware executor then observes per-model queue depths, cache utilization, and response latencies at each agent step to decide which model to call and how deeply to reason; a budget-aware scheduler further reorders each model's queue so that urgent requests are served first. Cast as a hierarchical constrained MDP and solved end-to-end via reinforcement learning, the system learns to balance quality against latency automatically. Across five benchmarks, INFRAMIND delivers up to +7.6 pp accuracy over the prior baseline at low load with up to 7x lower latency, and sustains up to 99.9% SLO compliance under high load where every baseline drops below 50%.

02.
medRxiv (Medicine) 2026-06-15

Quantitative Gait Categorization in Parkinson's Disease with and without Freezing of Gait

Background: Freezing of gait (FOG) is a disabling and often underrecognized feature of Parkinsons disease (PD). Objective gait analysis may improve characterization of this motor symptom. Objective: To compare quantitative 3D gait parameters in PD with FOG (PDF) and PD without FOG (PDNF) in a routine clinical cohort. Methods: We retrospectively analyzed a sequential sample of 180 patients with PD referred for motion analysis between 2020 and 2024. All patients underwent 3D motion capture in the off-medication state. Eighteen gait outcomes spanning pace, rhythm, postural control, variability, and asymmetry domains were derived from steady-state walking tasks. FOG status was determined using physician documentation and Movement Disorder Society Unified Parkinsons Disease Rating Scale (MDS-UPDRS) items. Group differences between PDF (n=99) and PDNF (n=81) were evaluated using independent samples t-tests, with outcomes adjusted for disease duration and corrected for multiple comparisons. A secondary analysis among PDF compared those in Hoehn and Yahr (H&Y) stage [≥]III to those in H&Y [≤]II. Results: PDF had longer disease duration, higher OFF MDS-UPDRS III scores, and higher Hoehn and Yahr stage than PDNF but were similar in age and sex. After adjusting for disease duration and multiplicity, PDF demonstrated reduced step length, stride length, and forward velocity, and greater cadence variability, while most postural control, and asymmetry measures were comparable between groups. Among PDF, advanced H&Y stage was associated with impaired pace and rhythm, similar to previous reports among PD in general. Conclusion: In this large, sequential, clinically referred cohort, FOG was associated with more advanced PD and specific impairments in pace and gait variability. These findings support comprehensive 3D gait analysis as an objective tool to better delineate FOG-related gait abnormalities and identify features that may predict FOG, informing targeted interventions.

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

Layer-Isolated Evaluation: Gating the Deterministic Scaffold of a Production LLM Agent with a No-LLM, Regression-Locked Test Harness

End-to-end task-success is the dominant way to evaluate LLM agents, but one aggregate number tells you that an agent regressed, not where. We present layer-isolated evaluation: a deployed ordering agent is decomposed into a fixed taxonomy of layers (ontology, intent, routing, decomposition, escalation, safety, memory, and cross-cutting envelope/defense), each exercised by its own assertion slice in a deterministic, no-LLM "pure" mode. The pure suite (238 cases across 23 slices; 225 run in 2.39 s, ~10 ms/case) runs in CI on every change against a locked per-slice baseline. We validate by controlled regression injection, degrading one layer at a time across seven non-safety layers. The effect we did not design in is masking: the aggregate pass-rate barely moves (-1.7 to -5.9 pp for six local regressions), while the matching slice craters (-25 to -91 pp). A layer's slice reacting to its own fault is partly by construction; the measured results are (i) the aggregate masking and (ii) that damage stays off the other slices: the injected layer's slice is the single worst-hit in 5 of 7 cases and top-3 in 7 of 7 (mean rank 1.29 of 19). Localization replicates on a second, structurally different tenant (Starbucks SG): all seven matching slices crater, so it is not a single-catalog artifact. We position it as a concrete, deterministic instantiation of the component-level evaluation EDDOps prescribes but leaves unimplemented, with CheckList as ancestor and as the deterministic mirror image of whole-workflow stochastic mutation testing. Our contributions: (a) a fully decomposed, sub-second, no-LLM per-layer harness for a production agent, (b) a coverage-honesty test-adequacy criterion that refuses to score an unexercised layer, and (c) the regression-injection demonstration that per-slice baseline-locked gates localize regressions an aggregate metric masks.

04.
arXiv (CS.CL) 2026-06-15

An Empirical Study of Automating Agent Evaluation

Agent evaluation requires assessing complex multi-step behaviors involving tool use and intermediate reasoning, making it costly and expertise-intensive. A natural question arises: can frontier coding assistants reliably automate this evaluation process? Our study shows that simply prompting coding assistants is insufficient for this task. Without domain-specific evaluation knowledge, frontier coding assistants achieve only a 30% execution success rate and produce over-engineered evaluations averaging 12+ metrics per agent, indicating that strong coding ability does not automatically translate to reliable agent evaluation. We introduce EvalAgent, an AI assistant that automates the end-to-end agent evaluation pipeline. EvalAgent encodes evaluation domain expertise as evaluation skills (procedural instructions, reusable code and templates, and dynamically retrieved API documentation) that compose into a trace-based pipeline producing complete evaluation artifacts including metrics, executable code, and reports. To systematically assess generated evaluations, we introduce a meta-evaluation framework alongside AgentEvalBench, a benchmark comprising 20 agents, each paired with evaluation requirements and test scenarios. We further propose the Eval@1 metric to measure whether generated evaluation code both executes and yields meaningful results on the first run. Our experiments show that EvalAgent produces focused evaluations, improving Eval@1 from 17.5% to 65%, and achieving 79.5% human expert preference over baseline approaches. Further ablation studies show that evaluation skills are critical for handling complex evaluation: removing them causes Eval@1 to drop significantly from 65% to 30%.

05.
medRxiv (Medicine) 2026-06-22

Integration of lung tissue proteomics and genome-wide association data to identify lung cancer susceptibility proteins and potential drug targets

Background: Proteins directly impact disease development and act as drug targets. Therefore, we integrated genomic and lung tissue proteomics data to identify lung cancer susceptibility proteins, elucidating genetic mechanisms and candidate drug targets. Method: We profiled the proteome and genome in non-neoplastic lung tissue from 200 lung cancer patients. Using this data, we constructed genetic models to predict abundance across the proteome in lung tissue. We applied these models to genome-wide association study (GWAS) data from 55,174 lung cancer cases and 1,294,174 controls to evaluate their associations with the risk of lung cancer, overall and by major histological subtypes. Bayesian colocalization and Mendelian randomization (MR) analyses were used to prioritize putative causal proteins, which were cross-referenced with three main drug-protein databases to identify potential therapeutic targets. Results: We identified 29 proteins associated with lung cancer risk at a false discovery rate < 5%, including 25 for overall lung cancer, two (AQP3 and IL18) specifically for adenocarcinoma, and another two (HMGN2 and HLA-DMB) for squamous cell carcinoma. Of them, genes encoding 17 proteins reside at least 2Mb away from any known GWAS risk loci, including 14 for overall lung cancer (HYI, GPX1, GMPPB, DSP, HDDC2, MTCH2, SUOX, JMJD7, PDIA3, IL16, IQGAP1, SULT1A2, ARHGAP27, and TYMP) and three for subtypes (AQP3, IL18, and HMGN2). Among the 12 proteins located within the known risk loci, EPHX2, CLDN18, PSMD5, and CYP2S1 proteins showed an association independent of the proximal GWAS-identified lead variant. Colocalization and/or MR analysis suggested 11 potential causal proteins. Five of these candidate causal proteins (DSP, CLDN18, IQGAP1, IL18 and TYMP) are targeted by nine drugs already approved by the FDA or in phase III trials. Conclusion: Our study identified novel lung cancer susceptibility proteins and potential drug targets, offering valuable insights into lung cancer biology and future translational utilities.

06.
bioRxiv (Bioinfo) 2026-06-19

HTS-Oracle v2: Prospective AI-Guided Discovery and Experimental Validation of Small Molecule Modulators Across Multiple Targets

High-throughput screening (HTS) remains the cornerstone of early-phase small molecule discovery yet consistently underperforms against immunotherapy targets, yielding validated hit rates below 0.1%. Here we introduce HTS-Oracle v2, which features rigorous cross-validation that ensures honest performance estimates. HTS-Oracle v2 was trained and validated across four clinically significant immune checkpoint targets (CD28, ICOS, LAG-3, and TIGIT) achieving ROC-AUC values of 0.968, 0.969, 0.875, 0.928 respectively under rigorous cross-validation. For prospective experimental validation, HTS-Oracle v2 was applied to an 8,960-compound Enamine Protein Mimetic Library, selecting only 25 compounds per target for experimental testing using temperature-related intensity change (TRIC) technology, a 99.7% reduction in screening burden. HTS-Oracle v2 identified 4, 5, 4, and 6 validated binders from 25 prospectively selected compounds per target, corresponding to validated hit rates of 16%, 20%, 16%, and 24%, respectively. Notably, 67-80% of all experimentally confirmed hits across the full 8,960-compound library were captured within just 25 model-selected compounds per target. For CD28, this represents a 28-fold improvement over HTS-Oracle v1 (239x versus 8.4x), establishing HTS-Oracle v2 as an efficient platform for AI-guided prospective hit discovery across immunotherapy targets.

07.
arXiv (CS.LG) 2026-06-15

Utility-Constrained Policy Optimization

arXiv:2606.14029v1 Announce Type: new Abstract: Constrained MDPs (CMDPs) are a widely adopted framework for incorporating safety into RL agents; however, the framework does not support risk-sensitive constraints. This can be problematic: For example, CMDPs allow for optimal solutions that, in order to satisfy the risk-neutral constraints, mix infrequent catastrophic behaviors and frequent, overly conservative ones. Moreover, prior empirical results suggest that enforcing stricter, risk-sensitive constraints can improve performance even under risk-neutral evaluation. The natural framework to incorporate risk-sensitive constraints is utility-constrained MDPs (UCMDPs), but no practical solutions for this problem existed. In this work, we introduce a simple yet powerful methodology for UCMDPs and constrained RL. Besides allowing for risk-sensitive constraints, our framework does not require us to fix constraint limits in advance of training the agent, provided that a sensible range is known. This increases policy flexibility and, in practice, allows for adjustments to these limits at no extra training cost. Besides benefiting from the generality of the framework, our agent shows strong performance in practice, consistently matching or outperforming existing baselines in several Safety Gymnasium benchmark tasks.

08.
arXiv (quant-ph) 2026-06-17

Demonstration of Exponential Quantum Speedup with Constant-Depth Compiled Circuits for Simon's Problem

arXiv:2604.27457v2 Announce Type: replace Abstract: We demonstrate exponential algorithmic quantum speedup for a restricted-Hamming-weight version of Simon's problem, in which the hidden string $b$ is promised to satisfy $HW(b)\le w$ for a Hamming-weight cutoff $w$, on present-day superconducting quantum processors. We introduce a hardware-aware compilation strategy that reduces the quantum part of each Simon query circuit to constant depth. The resulting compiled circuits have $O(1)$ depth, require only linear nearest-neighbor connectivity, map directly onto common device layouts, and avoid additional routing and SWAP overhead. Implemented on IBM's $156$-qubit Boston and $120$-qubit Miami processors, these circuits achieve sufficient fidelity to exhibit algorithmic quantum speedup without error suppression. Using the number-of-queries-to-solution (NTS) metric, we observe exponential speedup over the classical lower-bound benchmark for all restricted-Hamming-weight cutoffs $w\ge 4$ on Boston and across low-to-intermediate Hamming-weight cutoffs on Miami; at higher Hamming-weight cutoffs on Miami, we still observe polynomial speedup. The same construction also enables unrestricted instances of Simon's problem, corresponding to $w=n$ for problem size $n$, over the finite problem-size ranges for which our NTS computation is feasible; in this regime, the observed scaling advantage is not limited to the restricted-Hamming-weight setting. These results show that careful hardware-aware compilation can make quantum speedup experimentally accessible for a canonical hidden-subgroup problem in the NISQ regime.

09.
arXiv (math.PR) 2026-06-12

Interference Queueing Networks: A Replica Mean-Field Approach in the Symmetric Setting

arXiv:2606.13264v1 Announce Type: new Abstract: We propose a model for evaluating the performance of wireless communication networks beyond the ubiquitous full-buffer assumption, under which every transmitter is always active. The network is represented by N interacting queues arranged on a torus, with homogeneous arrival rate and service rates depending on the activity of neighboring interferers. More precisely, each queue is associated with a transmitter-receiver pair, and its service rate is given by the Shannon capacity, which depends on the corresponding Signal-to-Interference-plus-Noise Ratio (SINR). Since interfering transmitters only emit when their queue is non-empty, the SINR and hence the service rate improves when neighboring queues are empty. We derive the stability region of the system, together with approximations of its stationary distribution and its exponential rate of convergence to stationarity. These approximations are obtained via a replica mean-field limit, for which we establish propagation of chaos and long-time behavior results.

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

Rethinking Global Average Pooling: Your Classifier Is Secretly a Multi-Instance Learner

作者:

Modern image classifiers widely adopt global average pooling (GAP) followed by a linear classification head. This linearity ensures that the image-level logits equal the average of logits obtained by applying the classification head pointwise to the feature grid prior to GAP. Consequently, standard classifiers may inherently retain spatial class evidence that remains recoverable even when the image-level prediction is incorrect. This structure naturally suggests a multiple-instance learning (MIL) interpretation, where an image is viewed as a bag of spatial instances. Within this formulation, we demonstrate that standard classifiers trained with a single label per image can still learn the intended classification task in multi-object scenes. We further exploit this property to decompose image-level logits into a prediction grid, providing a post-hoc diagnostic to extract spatial class evidence that GAP otherwise obscures. Our systematic evaluation reveals that off-the-shelf models consistently recover the ground-truth class within foreground regions. The MIL interpretation further suggests that common classifier failures reflect known limitations of mean aggregation.

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

Probing Dec-POMDP Reasoning in Cooperative MARL

arXiv:2602.20804v2 Announce Type: replace Abstract: Cooperative multi-agent reinforcement learning (MARL) is typically framed as a decentralised partially observable Markov decision process (Dec-POMDP), a setting whose hardness stems from two key challenges: partial observability and decentralised coordination. Genuinely solving such tasks requires Dec-POMDP reasoning, where agents use history to infer hidden states and coordinate based on local information. Yet it remains unclear whether popular benchmarks actually demand this reasoning or permit success via simpler strategies. We introduce a diagnostic suite combining statistically grounded performance comparisons and information-theoretic probes to audit the behavioural complexity of baseline policies (IPPO and MAPPO) across 37 scenarios spanning MPE, SMAX, Overcooked, Hanabi, and MaBrax. Our diagnostics reveal that success on these benchmarks rarely requires genuine Dec-POMDP reasoning. Reactive policies match the performance of memory-based agents in over half the scenarios, and emergent coordination frequently relies on brittle, synchronous action coupling rather than robust temporal influence. These findings suggest that some widely used benchmarks may not adequately test core Dec-POMDP assumptions under current training paradigms, potentially leading to over-optimistic assessments of progress. We release our diagnostic tooling to support more rigorous environment design and evaluation in cooperative MARL.

12.
medRxiv (Medicine) 2026-06-22

Disentangling adiposity-related and non-adiposity-related genetic pathways for type 2 diabetes

OBJECTIVE To identify circulating proteins associated with type 2 diabetes (T2D) risk through pathways not fully explained by body mass index (BMI), and to assess therapeutic actionability. RESEARCH DESIGN AND METHODS We applied GWAS-by-subtraction within a genomic structural equation model to European ancestry summary statistics for T2D (74,124 cases, 824,006 controls) and BMI (n = 681,275), partitioning T2D liability into BMI-related and BMI-subtracted components. We then performed proteome-wide Mendelian randomization (MR) using cis-protein quantitative trait loci from four plasma proteomics cohorts: ARIC, deCODE, Fenland, and the UK Biobank Pharma Proteomics Project. Prioritized proteins passed sensitivity analyses with alternative MR methods and were supported by colocalization evidence. Tissue-resolution regulatory support was assessed using cis-eQTL colocalization across GTEx and pancreatic islet, subcutaneous adipose, and whole-blood resources. Actionability was evaluated using the druggable genome and Open Targets. RESULTS GWAS-by-subtraction attenuated the genetic correlation between BMI and BMI-subtracted T2D from 0.54 (SE 0.02) to 0.35 (SE 0.02). Proteome-wide MR prioritized 29 proteins for BMI-subtracted T2D. Thirteen showed eQTL colocalization in at least one tissue, implicating liver and intermediary metabolism (GCDH, NOTCH2), pancreatic islet biology (CTRB2, MANBA), adipose and Wnt signaling (RSPO3, GALNT3), and whole blood regulatory signals (PAM, SNUPN). Sixteen proteins were classified within druggable-genome Tiers 1-3, and five had existing Open Targets compounds. CONCLUSIONS Integrating GWAS-by-subtraction, proteome-wide MR, and colocalization nominated 29 proteins associated with T2D liability not fully explained by BMI. These findings highlight genetically supported targets for follow-up studies of T2D therapies that complement weight-centered approaches.

13.
medRxiv (Medicine) 2026-06-22

Multi-omics data fusion reveals divergent molecular signatures of intra-articular micro-fragmented adipose tissue and hyaluronic acid treatment in inflammatory-phenotype knee osteoarthritis

Knee osteoarthritis (KOA) affects an estimated 374 million people worldwide and has no approved disease-modifying treatment. Intra-articular micro-fragmented adipose tissue (MFAT) outperformed hyaluronic acid (HA) on patient-reported outcomes in our recent double-blind randomized trial (ISRCTN88966184), yet the molecular basis of this differential efficacy is unknown, and the two interventions have not previously been compared at the level of their in vivo molecular response in human KOA. Here we apply an interpretable artificial-intelligence data-fusion framework, based on non-negative matrix tri-factorization, to longitudinally collected plasma from this cohort, integrating proteomics, N-glycomics, miRNA transcriptomics and patient genetics with prior protein-protein and miRNA-gene regulatory networks at baseline, one and six months. The framework jointly decomposes all data modalities at each timepoint into shared, interpretable factors, from which we derive data-driven pathways of genes and of miRNAs and recover new patient-gene and patient-miRNA associations. These pathways were biologically coherent, showing significant enrichment in Gene Ontology Biological Process and Reactome Pathway annotations. By six months, the two treatments left clearly distinct molecular signatures: HA remained dominated by canonical OA pathogenic processes, including cartilage-degrading effectors such as MMP13 and LIMK2 and markers of synovial inflammation, whereas MFAT shifted the systemic landscape toward chondroprotection, anti-inflammatory signalling and bone-cartilage homeostasis, with prioritized effectors including SIRT7 and NDUFC1. To our knowledge, these are the first systems-level molecular data directly comparing the in vivo response to the two treatments in human KOA, providing initial evidence that MFAT acts as a disease-modifying intervention and demonstrating the value of interpretable data fusion for uncovering treatment mechanisms in small translational cohorts.

14.
arXiv (CS.LG) 2026-06-18

Do as the Romans Do: Learning Universal Behaviors from Heterogeneous Agents

arXiv:2606.18537v1 Announce Type: new Abstract: Humans often acquire new skills by observing others, since observed behaviors implicitly reveal how to act in an environment. However, observations drawn from a heterogeneous population introduce conflicting behavioral signals, making it difficult to determine which behaviors are worth imitating. We address this challenge with General Reward Inference and Disentanglement (GRID), a social learning method that extracts universally useful behaviors from a heterogeneous population of demonstrators pursuing different goals. GRID decomposes per-agent reward functions into a general reward, capturing behaviors shared across all agents, and specific rewards, capturing individual preferences and objectives. Training exclusively on the general reward provides a new paradigm of generalist pretraining. It yields a generalist agent that internalizes universal environmental competencies, such as safety and basic task proficiency, without the mode-averaging bias that afflicts standard learning from demonstration techniques. This generalist serves as a superior prior for fine-tuning to downstream tasks, including preferences unseen during training. Experiments across a synthetic basis function decomposition, multi-agent Craftax, and a continuous autonomous driving simulator (Highway-Env) confirm that GRID successfully disentangles reward structure in a semantically meaningful way, outperforms standard learning from demonstration baselines, and enables more efficient and stable specialization.

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

IBAD: Interpretable Behavioral Anomaly Detection on Human Mobility Data

arXiv:2606.16023v1 Announce Type: new Abstract: Human mobility appears highly diverse, yet much of a person's daily mobility can be explained by a small set of recurring behavioral templates, such as commuting, school-centered activities, caregiving, nightlife, or errand patterns. We present \texttt{IBAD} (\underline{I}nterpretable \underline{B}ehavioral \underline{A}nomaly \underline{D}etection), a framework that learns interpretable daily mobility templates and represents each individual as a distribution over mixtures of these templates. Rather than focusing on specific locations, IBAD characterizes activities that individuals perform across locations. This approach first discovers global behavioral templates using Latent Dirichlet Allocation (LDA), then employs a hierarchical self-supervised model to learn normal behavior of individuals from their soft behavioral templates. We also introduce a splicing benchmark that creates controlled behavioral mismatches between an individual's historical profile and injected mobility patterns. Experiments on real-world and synthetic datasets show that daily behavior can be effectively decomposed into a small number of interpretable templates. Crucially, we show that the learned behavioral archetypes transfer across distinct geographic and demographic contexts. Furthermore, IBAD maintains a robust competitive performance across all settings. For reproducibility purposes, the code is accessible at ~\href{https://github.com/USC-InfoLab/IBAD}{https://github.com/USC-InfoLab/IBAD}.

16.
bioRxiv (Bioinfo) 2026-06-12

Deciphering cross-omics complexity of tissues via diagonal integration of unpaired spatial multi-omics data

Recent spatial multi-omics technologies enable the simultaneous in situ profiling of multiple omics modalities on the same tissue section; however, they face challenges in experimental complexity and high costs. This technical limitation can be circumvented by diagonal integration methods, which integrate omics data from different modalities. However, existing single-cell diagonal integration approaches overlook spatial information, causing unreliable anchoring across omics layers. Here, we introduce STAMO, a graph attention neural network model for spatially aware integration of unpaired spatial slices from different omics. Systematic benchmarking on spatial epigenome-transcriptome slices proves that STAMO outperforms the state-of-the-art methods in generating aligned embeddings and identifying consensus spatial domains across omics. We apply STAMO to integrate unpaired data from diverse spatial omics types (transcripts, epigenetics, DNA, and proteins), including slices from spatial RNA and four different epigenomic modalities, spatial ATAC and RNA slices across embryonic stages, spatial protein and RNA slices, and spatial DNA and RNA slices. In addition, the integration capability of STAMO can be further used to achieve cross-omics generation, offering a solution for exploring spatial region-specific gene regulatory mechanisms.

17.
medRxiv (Medicine) 2026-06-22

Hyperlipidemia Pharmacotherapy in Skilled Nursing Facilities: A Real-World Evidence Study

Objectives: To estimate hyperlipidemia medication order prevalence and associated variables in U.S. skilled nursing facility (SNF) residents. Design: Retrospective, observational study. Setting and Participants: Electronic Health Record data from 447,080 SNF residents with a hyperlipidemia diagnosis identified in PointClickCare's Life Sciences clinical database (January-April 2025) were reviewed. Methods: The presence and absence of medication orders for hyperlipidemia treatments recommended by the American Heart Association were assessed. Descriptive analyses summarized demographic and clinical characteristics, and a modified Poisson regression model was used to estimate risk ratios for having a medication order, adjusting for demographic, clinical, and facility characteristics. Results: Overall, 83.3% of residents diagnosed with hyperlipidemia had at least one hyperlipidemia medication order. Statins were ordered by 96.2% of active order residents, while other medication classes i.e., omega-3 fatty acids, cholesterol absorption inhibitors, fibrates were less common (

18.
arXiv (CS.CV) 2026-06-16

MMLongEmbed: Benchmarking Multimodal Embedding Models in Long-Context Scenarios

Recent advancements have significantly expanded the theoretical context windows of Multimodal Embedding Models (MEMs). However, larger context windows do not necessarily translate into effective comprehension and representation of long-context multimodal inputs, which remains a critical bottleneck for real-world deployment. To address the lack of systematic evaluation in this setting, we introduce MMLongEmbed, the first comprehensive benchmark for evaluating MEMs in long-context scenarios. MMLongEmbed comprises four retrieval tasks spanning multiple context-length ranges, covering text, document, and video modalities. Through extensive evaluation of state-of-the-art models, we find that current architectures rely heavily on superficial feature matching and struggle to capture deep semantic and structural dependencies. We further observe that performance degradation varies systematically with context length and key information placement. Moreover, models exhibit substantially different robustness to redundant contextual information across modalities. For reproducibility, the benchmark and code are publicly available.

19.
arXiv (quant-ph) 2026-06-16

The Quantum Transition State

arXiv:2606.10266v2 Announce Type: replace Abstract: The transition state – the critical configuration separating reactants from products – is the central organizing concept of chemical reaction rate theory, yet for nearly a century it has been thought to have no exact quantum counterpart: the recrossing-free, one-way flux through a transition state appears to demand simultaneous knowledge of position and momentum, in conflict with the uncertainty principle. We show this obstruction is illusory and construct the quantum transition state directly from the exact quantum flow. Its stable and unstable invariant manifolds intersect in a unique bounded trajectory – the quantum transition-state trajectory – anchoring a moving dividing surface that each reactive characteristic crosses exactly once, yielding a one-way flux of the standard quantum probability current. The geometric framework underlying classical transition-state theory thus survives intact in exact quantum mechanics, in a fundamentally quantum form.

20.
Science (Express) 2026-04-16

Protein-templated synthesis of dinucleotide repeat DNA by an antiphage reverse transcriptase | Science

作者: 未知作者

Defense-associated reverse transcriptases (DRTs) are widespread bacterial anti-phage systems that use unconventional mechanisms of polynucleotide synthesis. We show that DRT3, which comprises two distinct RTs (Drt3a and Drt3b) and a noncoding RNA (ncRNA), synthesizes alternating poly(GT/AC) double-stranded DNA. Cryo–electron microscopy structures at 2.6 Å resolution reveal a D3-symmetric 6:6:6 complex of Drt3a, Drt3b, and ncRNA. Drt3a produces the poly(GT) strand using a conserved ACACAC template within the ncRNA. Notably, Drt3b synthesizes a complementary, protein-primed poly(AC) strand in the complete absence of a nucleic acid template, using conserved active site residues specific to Drt3b to enforce precise base alternation. These findings expand the functional landscape of nucleic acid polymerases, revealing a protein-templated mechanism for sequence-specific DNA synthesis.

21.
bioRxiv (Bioinfo) 2026-06-22

Benchmarking cell type annotation in spatial transcriptomics: resolving cellular hierarchies, biological fidelity, and dynamic cell states

Spatial transcriptomics enables the quantification of gene expression within its native tissue context, providing unprecedented insight into tissue architecture, cellular ecosystems, and local cell-cell interactions at regional and single-cell resolution. Accurate cell type annotation is a critical prerequisite for interpreting these data and is often the first and most essential step in downstream analysis. Despite rapid advances in computational methods, cell type annotation remains challenging and frequently requires extensive expert-driven manual curation based on marker-gene expression, spatial context, and prior biological knowledge. While early approaches relied primarily on transcriptional similarity, newer methods increasingly incorporate spatial information, histological features, and multimodal data to improve annotation accuracy. Nevertheless, reliable annotation remains difficult when biological interpretation requires fine-grained subtype resolution, particularly for platforms with limited gene panels, tissues undergoing dynamic cellular state transitions, and studies in which reference and query datasets differ substantially in biological context or technical modality. Here, we present a systematic benchmark of 20 state-of-the-art cell type annotation methods across four spatial transcriptomics datasets spanning diverse technologies, experimental conditions, cell numbers, and gene panel sizes. Importantly, all benchmark datasets contain expert-curated cell type labels, including well-resolved cell populations and subtype annotations, providing high-quality biological ground truth for evaluation. The benchmark encompasses both reference-based and reference-free methods representing a broad range of computational frameworks. Performance was assessed using conventional classification metrics, including accuracy and F1-based measures, together with structure-aware metrics that evaluate both cell-level annotation accuracy and preservation of higher-order biological organization. Across datasets, annotation performance varied substantially according to tissue context, reference-query similarity, and annotation granularity. Fine-grained subtype annotation and recovery of rare cell populations remained challenging for many methods, particularly in datasets capturing injury, repair, developmental, and regenerative processes characterized by continuous cellular state transitions. Notably, high classification accuracy did not necessarily correspond to preservation of global cellular relationships or biologically coherent downstream pathway and gene-set enrichment analyses. Overall, scANVI, Seurat, and TACCO consistently ranked among the top-performing methods, although their relative advantages were context dependent. Together, our results provide a comprehensive assessment of current annotation strategies for spatial transcriptomics and offer practical guidance for selecting methods that best align with specific biological questions, dataset characteristics, and analytical priorities.

22.
arXiv (CS.AI) 2026-06-16

FOUNDv2: Learning Unified User Quantized Tokenizers for User Representation

arXiv:2508.00956v3 Announce Type: replace-cross Abstract: User representation learning serves as a fundamental pillar for personalized services on large-scale web platforms. Despite its importance, conventional continuous embedding methods face significant challenges, including the lack of a unified paradigm for multi-source data integration, prohibitive storage overhead due to low information density, and the lack of multi-scale modeling granularity. To overcome these limitations, we introduce FOUNDv2, a comprehensive user representation scheme centered on the Unified User Quantized Tokenizer U2QT) framework. FOUNDv2 transforms heterogeneous user data into a standardized discrete token space through a robust two-stage architecture. Specifically, the framework first extracts compact feature representations and subsequently employs a multi-view RQ-VAE to discretize them into storage-efficient tokens using shared and source-specific codebooks. To empower these representations with predictive intelligence, we further design multi-scale alignment objectives to capture both fine-grained behavioral dependencies and macro-temporal periodicity. Extensive experiments on various benchmarks demonstrate that FOUNDv2 consistently outperforms task-specific baselines while achieving substantial reductions in storage and computational costs. Finally, the large-scale deployment of FOUNDv2 on Alipay validates its practical scalability and efficiency across diverse industrial scenarios. The main code is available at: https://github.com/chuanhe1999/FOUNDv2.

23.
arXiv (math.PR) 2026-06-18

A Stochastic ISCS Markov Model for Fake News Propagation

arXiv:2606.18282v1 Announce Type: cross Abstract: This paper studies the propagation of fake news through a stochastic rumor spreading model based on Markov chains. Inspired by classical epidemiological SIR models, we consider a generalization of the Daley-Kendall framework for rumours that incorporates fact-checkers, following the Ignorant/Spreader/Checker/Stifler model introduced in Piqueira (2020). The model analyzes the influence of checkers on fake news dynamics. Numerical simulations are used to illustrate the behavior of the system and the impact of fact-checkers.

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

TreeGRNG: Binary Tree Gaussian Random Number Generator for Efficient Probabilistic AI Hardware

arXiv:2606.16599v1 Announce Type: cross Abstract: Bayesian Neural Networks (BNNs) offer opportunities for greatly enhancing the trustworthiness of conventional neural networks by monitoring the uncertainties in decision-making. A significant drawback for BNN inference at the extreme edge, however, is the imperative need to incorporate Gaussian Random Number Generators (GRNG) within each neuron. State-of-the-art GRNG algorithms heavily depend on multiple arithmetic operations and the use of extensive look-up tables, posing significant implementation challenges for ultra-low power hardware implementations. To overcome this, this paper presents an innovative binary tree random number generator (TreeGRNG) allowing the use of ultra-low-cost constant comparators instead of arithmetic units. We further enhance the TreeGRNG proposal with a set of hardware-aware optimizations exploiting the Gaussian properties. The optimized TreeGRNG surpasses the State-of-the-Art (SoTA) in terms of distribution accuracy while achieving a 3.7$\times$ reduction in energy per sample and boosting the throughput per unit area by 5.8$\times$. Moreover, our TreeGRNG proposal possesses a distinct advantage over the current SoTA in terms of flexibility, as it easily enables designers to adjust the shape of the sampled probability distribution, extending beyond the capabilities of traditional GRNGs, opening the horizon towards future probabilistic AI designs. The TreeGRNG design is available open-source in the link

25.
arXiv (quant-ph) 2026-06-11

Superspace Concentration and Adversarial Robustness in Quantum Algorithms

arXiv:2606.11580v1 Announce Type: new Abstract: We study superspace concentration as a quantum resource, formalized through the focus measure F(\r{ho}) = {\lambda}_max(\r{ho}_super) - the largest eigenvalue of the reduced superspace state - which quantifies the capacity of a quantum system to concentrate informational weight into a preferred subspace of an extended degree-of-freedom space. We develop a complete resource-theoretic framework around this measure and validate its properties through GPU-accelerated numerical simulation. Analytic decoherence predictions are confirmed to machine precision (1.11 x 10^{-16}) for superspace dimensions dS in {2,4,8,16,32}. Focus monotonicity holds across 10,000 random states with zero violations under four focus-non-generating channels across six system configurations. Focused quantum states resist coherent unitary attacks with significantly greater resilience than standard fidelity predicts, with focus remaining above 0.9 at attack strength {\epsilon} = 0.302 versus {\epsilon} = 0.174 for fidelity. We further demonstrate that the focus measure and the U(dS)-asymmetry measure are operationally distinct: asymmetry remains near zero and provides no robustness signal under coherent and targeted attacks while focus tracks spectral concentration and remains robust until {\epsilon} > 0.3. The connection between Grover's algorithm and superspace concentration is made explicit via the identity F(|{\psi}_k>