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01.
medRxiv (Medicine) 2026-06-22

Level of Physical Activity and ApoE Status - Effects on Alzheimer's Disease and on Mortality

作者:
Ma↗Cheng↗Shao↗Zamrini↗Sui↗Tsuang↗D. W↗Logue↗Ahmed↗Kokkinos↗Faselis↗C. J↗…

Background: Alzheimer's disease and related dementias (ADRD) affect over 7.2 million Americans aged 65 and older, with the APOE-4 allele representing the strongest known genetic risk factor. Physical activity (PA) has been associated with reduced dementia risk, but its interaction with APOE genotype remains poorly characterized in large, genomically informed cohorts. Methods: We conducted a retrospective cohort analysis using linked genomic, survey, and longitudinal electronic health record data from the VA Million Veteran Program (MVP). Veterans aged

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

Knowledge-Based Zero-Replay Debugging of Multi-Agent LLM Traces

作者:
Dong Ho Kang↗Hyeonjeong Cha↗Daein Weon↗

arXiv:2606.14805v1 Announce Type: cross Abstract: Reliable operation of multi-agent large language model (LLM) systems depends on debugging long execution traces, where the few causally decisive events are buried in unstructured logs of messages, routes, memory writes, and tool calls. The standard tool is counterfactual replay (rewind, edit, and re-run the trajectory to measure each event's effect), but its cost grows linearly with the number of candidate events, making exhaustive replay infeasible at scale. We frame trace debugging as a knowledge-based decision-support problem. Each trace is compiled into a structured event knowledge graph over routing, memory, tool-use, uncertainty, and latent evidence, and a calibrated predictor decides where a scarce replay budget should be spent. We do not propose a new replay oracle; we propose a method to predict its results without paying the replay cost. We formulate zero-replay counterfactual-effect prediction: given a trace under a fixed budget, predict which events the oracle would mark high-effect before any replay is performed. BranchPoint-Latent is a lightweight predictor over observable, structural, uncertainty, and latent features of the knowledge graph. Calibrated against a deterministic replay oracle across 37 trace families, a single learning-to-rank gradient-boosted predictor raises per-trace localization (Branch Recall@5) from 0.73 to 0.93 on held-out families at zero oracle-replay cost. Rather than claiming universal dominance, we characterize when cheap graph centrality suffices and when learned evidence is necessary. The result is an auditable, cost-efficient decision-support system for AI-reliability debugging, positioned explicitly on the cost-accuracy frontier with reproducible artifacts.

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03.
arXiv (quant-ph) 2026-06-12

Coupling-Grouped XY-QAOA for Joint Anomaly-Feature Selection

作者:
Pauli Taipale↗

arXiv:2606.13244v1 Announce Type: new Abstract: Selecting anomalous samples and explanatory features under fixed budgets defines a coupled constrained-optimization problem. Sequential feature-first selection ranks features before choosing samples, which can overlook features whose utility depends on which samples are selected, especially when scores are calibrated from reference data that may be limited, noisy, or drifting. We instead formulate the task as joint sample-feature selection under the same fixed counts. In the analyzed formal model, calibration-error sensitivity grows linearly with the number of samples for feature-first ordering but stays constant for joint selection. We introduce Coupling-Grouped XY-QAOA, a constraint-preserving grouped-angle variant for the resulting optimization problem. On matched sparse IBM Heron R3 benchmarks, a hardware-aware implementation reduces circuit depth by 45.9%-61.3% and two-qubit gates by 2.6%-5.2% relative to Qiskit optimization level 3 on the CZ-basis target. It enables, to our knowledge, the largest reported width-depth configurations for constraint-preserving bipartite-selection QAOA hardware executions with feasible-sector retention: 64 qubits at p=2 and 36 qubits at p=3. The 20-qubit p=5 runs retain 63% valid samples. Across 36-64 qubits, fixed-angle runs yield lower-energy feasible samples than matched random-feasible sampling. Warm starts reduce the gap to strict-feasible classical references by 57.5%-80.5%, and near-budget repair matches the sparse classical reference at 36 qubits. Benchmarks show gains in balanced fixed-budget regimes, and noiseless simulations show that problem-structured angle grouping improves over same-depth XY-QAOA and matched-parameter, type-preserving randomization controls. Overall, the results support calibrated joint selection and hardware-realizable constrained-mixer execution in the tested regimes.

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

Generative Modeling on Metric Graphs via Neural Optimal Transport

作者:
Alessandro Micheli↗Yueqi Cao↗Anthea Monod↗Samir Bhatt↗

arXiv:2606.16273v1 Announce Type: cross Abstract: We introduce, to our knowledge, the first deep generative modeling framework for probability distributions continuously supported on compact metric graphs. Given source and target measures on a metric graph, our method embeds the graph into a smooth ambient space, solves an entropic Kantorovich problem via a neural semidual parameterization, and projects generated samples back onto the original graph. We study two embedded geometries: an extrinsic Euclidean realization and the intrinsic tropical Abel–Jacobi embedding into the Jacobian torus. In both cases, the resulting generator is graph-supported by construction. We prove that, in the joint limit of increasing neural expressivity, the learned generator converges weakly to a valid transport coupling between the original graph measures. Empirically, across a range of geometrically distinct graphs, our method matches or improves upon heuristic transport baselines based on discrete graph OT, while scaling more favorably. Finally, we demonstrate scalability on real-world urban mobility data by training our model on one million Uber pickup locations in Manhattan, New York City.

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

FreeStyle: Free Control of Style-Content Dual-Reference Generation from Community LoRA Mining

作者:
Jinghong Lan↗Wei Cheng↗Yunuo Chen↗Ziqi Ye↗Peng Xing↗Yixiao Fang↗Rui Wang↗Yufeng Yang↗Xuanyang Zhang↗Xianfang Zeng↗Difan Zou↗Gang Yu↗…

arXiv:2606.20506v1 Announce Type: cross Abstract: Style-content dual-reference generation aims to synthesize an image that preserves the structure and semantics of a content reference while adopting the style of a separate style reference.Despite recent progress, this setting remains challenging because models must balance content fidelity, style alignment, and instruction following avoiding semantic leakage from the style reference.A key bottleneck is the lack of large-scale triplet data with clean content-style separation and broad long-tail style coverage.In this work, we propose FreeStyle, a scalable dual-reference generation framework based on community LoRA mining.We treat community LoRAs as compositional anchors for style and content, and design a rigorous generation and filtering pipeline to construct large-scale Style-Reference and Content-Reference triplets across multiple base models.To address content leakage, we adopt a two-stage curriculum with stage-specific disentanglement mechanisms: an attention-level enrichment constraint that suppresses style-reference leakage in the style-transfer stage, and a frequency-aware RoPE modulation strategy that targets positional-correspondence-based leakage in the harder dual-reference stage.We also introduce a benchmark covering both style-reference and dual-reference generation, with evaluations on style similarity, content preservation, aesthetics, instruction following, and leakage rejection. The benchmark incorporates a style-invariant Content Alignment Score (CAS) and introduces a calibrated VLM-based Rejection Score for evaluating generation reliability and leakage suppression.Extensive experiments show that our model achieves a strong balance among style alignment, content preservation, and leakage suppression.

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07.
bioRxiv (Bioinfo) 2026-06-18

Bayesian modeling of longitudinal metatranscriptomes of broiler meat spoilage microbiomes shows shared predictive signature associated with spoilage at refrigerated temperatures

作者:
Nushi↗Manninen↗Johansson↗Honkela↗Björkroth↗

Microbial spoilage of packaged meat is driven by complex microbial succession and related metabolic activity, yet conventional shelf-life assessment is mainly based on shelf-life studies relying on culturing and sensory analysis. In routine quality assurance, results are obtained retrospectively, and they are only indirectly linked to the metabolic activity related to sensory deterioration. Functional, time informative approaches that capture the active metabolic state of the spoilage microbiome and predict the rate of spoilage are lacking. We developed a censoring-aware Gaussian process (CAGP) framework to model longitudinal pathway expression profiles from broiler meat metatranscriptomes collected over consecutive storage days at 4 or 6{degrees}C. Samples were annotated using odor-based sensory scores defining fresh, early-spoilage, and late-spoilage phases. Because observed zeros in pathway-level data may reflect non-detection rather than true absence, the model treats low values as left-censored observations below a detection threshold while estimating smooth temporal trajectories with uncertainty. In leave-one-out prediction within the 4{degrees}C time series, predicted sampling days differed from the true days by an average of 0.43 days, and predicted spoilage phases agreed with the sensory classification. Trajectories learned at 4{degrees}C also transferred to an independent 6{degrees}C time series at the spoilage-phase level, suggesting that shared functional spoilage programs are preserved despite temperature-dependent changes in spoilage rate. Cross-entropy ranking further identified pathway modules carrying time- and phase-informative signals across temperatures. Overall, this framework provides a probabilistic approach for linking metatranscriptomic functional dynamics to sensory spoilage progression, supporting shelf-life assessment beyond retrospective microbial enumeration.

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08.
arXiv (CS.LG) 2026-06-11

GLACIER: A Multimodal Student-Teacher Foundation Model for Molecular Property Prediction

作者:
Emily Nguyen↗Yongchan Hong↗Harsh Toshniwal↗Yan Liu↗Andreas Luttens↗

arXiv:2606.11382v1 Announce Type: new Abstract: Deep learning models facilitate the discovery of molecules with tailored properties among billions of candidate compounds. However, the computational burden to develop and deploy state-of-the-art models continuously increases, limiting their scalability. Most large-scale models are unimodal in nature and overlook the potential to leverage complementary molecular data modalities. To address these shortcomings, this paper introduces the Graph-Language Alignment for Chemical Inference and Exploration using Representations (GLACIER) model, a student-teacher framework that integrates molecular graphs, SMILES strings, and physicochemical descriptors to learn rich molecular embeddings. Our framework consists of three stages: (1) we pretrain three student encoders on 100,000 drug-like molecules: a message-passing neural network for molecular graphs, a transformer-based encoder for SMILES strings, and a multilayer perceptron for physicochemical descriptors, (2) we fuse these student modalities using a novel Finsler geometry-aware module, and (3) distill complementary knowledge from large teacher models, including MiniMol and MolFormer, into a single lightweight model via contrastive learning. We demonstrate that GLACIER is a robust framework that delivers high predictive performance and computational efficiency in complex molecular property prediction tasks. Our code is publicly available at https://github.com/eemokey/glacier.

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09.
arXiv (quant-ph) 2026-06-11

Classical representation of the dynamics of quantum spin chains

作者:
Tony Jin↗

arXiv:2502.10502v3 Announce Type: replace-cross Abstract: Since the advent of quantum mechanics, classical probability interpretations have faced significant challenges. A notable issue arises with the emergence of negative probabilities when attempting to define the joint probability of non-commutative observables. In this work, we propose a resolution to this dilemma for quantum spin chains, by introducing an exact representation of their dynamics in terms of classical continuous-time Markov chains (CTMCs). These CTMCs effectively model the creation, annihilation, and propagation of pairs of classical particles and antiparticles. The quantum dynamics then emerges by averaging over various realizations of this classical process.

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

TileFuse: A Fused Mixed-Precision Kernel Library for Efficient Quantized LLM Inference on AMD NPUs

作者:
Wesley Pang↗Gregory Hyegang Jun↗Feiyang Liu↗Deming Chen↗

arXiv:2606.11357v1 Announce Type: cross Abstract: With the growing demand for on-device LLM inference, edge SoCs increasingly integrate NPUs to improve performance and energy efficiency under tight power and thermal budgets. However, practical LLM deployment on current client NPUs remains difficult: widely used quantization formats such as AWQ do not map cleanly onto many existing NPU software stacks, which are often proprietary and expose limited low-level control. In this work, we present TileFuse, a close-to-metal mixed-precision kernel library for AMD XDNA2 NPUs that targets transformer linear layers in quantized LLM inference. TileFuse brings practical low-bit formats such as AWQ-style W4A16 and W8A16 directly onto XDNA2, rather than forcing the model to be reshaped around an NPU-specific quantization scheme. TileFuse co-designs weight layout, metadata placement, mixed-precision microkernels, and array-level dataflow. Specifically, it fuses unpacking, dequantization, and GEMM/GEMV execution into a single kernel flow, introduces an interleaved pre-tiling layout that supports GEMM dimensions up to 32K, and redesigns GEMV dataflow to utilize the full 4x8 AIE array. Across kernel-level evaluations, TileFuse improves performance by up to 121.6% for GEMM and 281% for GEMV over full-precision baselines, while delivering more than 2x performance and energy-efficiency gains over strong iGPU baselines on GEMM. In end-to-end LLM experiments on Ryzen AI laptops, TileFuse achieves up to 2.0x lower prefilling latency with more than 64.6% lower energy consumption. Together, these results show that XDNA2 is a practical target for AWQ-style edge LLM inference and that native NPU support for off-the-shelf quantization can make NPUs substantially more usable in real client deployments.

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11.
arXiv (CS.LG) 2026-06-15

Adaptive Identification and Modeling of Clinical Pathways with Process Mining

作者:
Francesco Vitale↗Nicola Mazzocca↗

arXiv:2512.03787v2 Announce Type: replace Abstract: Clinical pathways are specialized healthcare plans that model patient treatment procedures. They are developed to provide criteria-based progression and standardize patient treatment, thereby improving care, reducing resource use, and accelerating patient recovery. However, manual modeling of these pathways based on clinical guidelines and domain expertise is difficult and may not reflect the actual best practices for different variations or combinations of diseases. We propose a two-phase modeling method using process mining, which extends the knowledge base of clinical pathways by leveraging conformance checking diagnostics. In the first phase, historical data of a given disease is collected to capture treatment in the form of a process model. In the second phase, new data is compared against the reference model to verify conformance. Based on the conformance checking results, the knowledge base can be expanded with more specific models tailored to new variants or disease combinations. We demonstrate our approach using Synthea, a benchmark dataset simulating patient treatments for SARS-CoV-2 infections with varying COVID-19 complications. The results show that our method enables expanding the knowledge base of clinical pathways with sufficient precision, peaking to 95.62% AUC while maintaining an arc-degree simplicity of 67.11%.

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12.
arXiv (CS.LG) 2026-06-15

Approximating Whittle-Matern Fields over Discretized Manifolds

作者:
Srinivas Nambirajan↗

arXiv:2606.13827v1 Announce Type: cross Abstract: Markovian Whittle-Matérn fields have been convergently approximated by discrete Gauss Markov Random Fields (GMRFs) with sparse precision matrices using a Finite Element approximation of the two-parameter family, \[ (\kappa^2 - \Delta)^{\alpha/2} u = \mathcal{W}, \;\; \kappa \in \mathbb{R}, \; \alpha \in \mathbb{N}. \] of SPDEs. Using recent developements in the analysis of Discrete Exterior Calculus (DEC), we present a different, yet closely related, convergent GMRF approximation to these Matérn fields over complete, boundaryless Riemannian manifolds discretized as well-centered simplicial complexes. This convergent method (i) is agnostic to $\alpha, \kappa$ and thus allows a universal approximation scheme for the precision and covariance matrices of the entire $(\alpha, \kappa)$-family of GMRFs, so they may be inferred rather than guessed. (ii) inherently models pointwise and piecewise-smoothed measurements of a random field and approximates both equally well (iii) is computationally independent of the interpolants used - it suffers no overhead if one convergent interpolant were replaced with another suitable interpolant over the same mesh. Furthermore, we show that, on discretizations that are well-connected in a precise sense, and volume-concentrated, the precision matrices are spectral functions of a graph-laplacian. We provide a low rank approximator to the family of such Matérn GMRFs and mention a use case: reducing the number of measurements needed to model the GMRF by compressed-sensing.

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13.
arXiv (CS.CV) 2026-06-11

SDQM: Synthetic Data Quality Metric for Object Detection Dataset Evaluation

作者:
Ayush Zenith↗Arnold Zumbrun↗Neel Raut↗Jing Lin↗

The performance of machine learning models depends heavily on training data. The scarcity of large-scale, well-annotated datasets poses significant challenges in creating robust models. To address this, synthetic data generated through simulations and generative models has emerged as a promising solution, enhancing dataset diversity and improving the performance, reliability, and resilience of models. However, evaluating the quality of this generated data requires an effective metric. We introduce the Synthetic Dataset Quality Metric (SDQM) to assess data quality for object detection tasks without requiring model training to converge. This metric enables more efficient generation and selection of synthetic datasets, addressing a key challenge in resource-constrained object detection tasks. In our experiments, SDQM demonstrated a strong correlation with the mean average precision (mAP) scores of YOLO11, a leading object detection model, whereas previous metrics only exhibited moderate or weak correlations. In addition, it provides actionable insights into improving dataset quality, minimizing the need for costly iterative training. This scalable and efficient metric sets a new standard for evaluating synthetic data. The code for SDQM is available at https://github.com/ayushzenith/SDQM

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14.
bioRxiv (Bioinfo) 2026-06-13

PertDiffBench: Benchmarking Diffusion Models for Single-Cell Perturbation Response Prediction

作者:
Song↗Xiang↗Jin↗Li↗Sun↗Xie↗

Diffusion models are increasingly used to predict transcriptional responses to perturbations, but whether they improve on simpler generative and representation-based baselines remains unclear. Existing evaluations often do not separate the effects of model architecture, input representation, biological context and metric choice, making it difficult to determine where diffusion-based methods are useful. Here we introduce PertDiffBench, a standardized benchmark for diffusion-based transcriptomic perturbation prediction across single-cell and bulk RNA-seq datasets. PertDiffBench evaluates diffusion-based models across three complementary evaluation settings: standard prediction in known single-cell contexts and bulk perturbation conditions, generalization to unseen cell types, species, drugs and intermediate time points, and stress tests of feature dimensionality, input representation, noise type and gene ordering. Across these settings, diffusion models did not show a consistent advantage. scGen remained a strong baseline in common prediction tasks, whereas scDiffusion was the most competitive diffusion-based method in several generalization settings. Temporal imputation showed a different pattern, with a simple DDPM operating directly in expression space outperforming more specialized models. Stress tests showed that performance was model dependent and sensitive to feature dimensionality, encoder choice, noise type and gene ordering. Pretrained encoders did not consistently improve performance, with the classical scVI representation slightly exceeding STATE in seen-condition and unseen-cell-type settings. These results indicate that diffusion-model performance in perturbation response prediction depends strongly on task design and representation choice. PertDiffBench provides a practical framework for evaluating these models under biologically varied and stress-tested conditions.

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

Stringalign: Moving beyond summary statistics with a transparent Unicode-aware tool for evaluating automatic transcription models

作者:
Yngve Mardal Moe↗Marie Roald↗

Comparing text strings is crucial when evaluating and understanding the performance of various text processing tasks such as document recognition and audio transcription. With an increasingly complex landscape of AI-based handwritten text recognition (HTR), optical character recognition (OCR) and automatic speech recognition (ASR) models, there is a need for tools that facilitate evaluation in a flexible and reproducible way. This paper presents Stringalign, a Python library designed to simplify the evaluation process for automatic transcription projects and facilitate transparent evaluation. Stringalign's tools to examine and visualise both the rate of errors and the types of errors a model makes, give insights into possible improvements and help inform model selection for a particular task. Widely used string comparison metrics, such as the character and word error rates (CER and WER), although useful, can be ambiguous due to varying definitions of what constitutes a character and a word. Stringalign addresses this challenge by ensuring all preprocessing (i.e. normalisation and tokenisation) is transparent and easily replicable, and by providing tools to move beyond summary statistics and analyse common model errors. Moreover, Stringalign adheres to FAIR (Findable, Accessible, Interoperable, and Reusable) principles for research software while staying lightweight and easy to adapt into researchers existing workflows. In this paper, we discuss challenges with character and word level string comparisons and show through examples that where existing tools can yield opaque and sometimes confusing results, Stringalign provides an easy-to-use and unambiguous alternative.

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

FloatDoor: Platform-Triggered Backdoors in LLMs

作者:
Nils Loose↗Jonas Sander↗Felix M\"achtle↗Thomas Eisenbarth↗

arXiv:2606.19535v1 Announce Type: cross Abstract: Large language models (LLMs) are increasingly deployed in sensitive settings such as software engineering, where their outputs directly shape downstream artifacts. Recent work has shown that an identical model can produce measurably different outputs depending on the deployment platform, a consequence of non-associative floating-point arithmetic and divergent kernel implementations. We study the security implications of this platform-dependent variability and uncover a novel attack surface on LLM deployments. We introduce FloatDoor, the first input-independent, platform-triggered backdoor attack against generative LLMs. The compromised model exhibits adversary-chosen behavior when served on a target platform and is otherwise benign. FloatDoor is realized through two lightweight LoRA adapters, one that amplifies inter-platform numerical divergence and one that binds the resulting platform signature to a malicious downstream task, while leaving aggregate model utility largely intact. FloatDoor exploits a pronounced time-of-check, time-of-use gap between model auditing and serving. We demonstrate FloatDoor on Qwen3-4B across a broad range of deployment targets, including NVIDIA GPUs, Google TPUs, AWS Graviton, and Alibaba Yitian-710. As a final case study, we show that FloatDoor reliably induces exploitable code vulnerabilities on a chosen target platform. Our results establish a new class of attacks on LLM deployments and underscore the pressing need for trusted model supply chains in sensitive, LLM-powered applications.

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

An Ontology-Guided Multi-Anchor Graph Retrieval Framework for Traffic Legal Liability Determination

作者:
Xu Li↗Shuqi Tian↗Xun Han↗Kuncheng Zhao↗Xinyi Li↗

Traffic law liability determination is critical for assigning legal penalties, requiring the simultaneous identification of interdependent statutory provisions across multiple legal dimensions. However, existing retrieval-augmented generation methods suffer from a multi-dimensional retrieval bottleneck: single axis architectures compress complex legal queries into a single pathway, causing interdependent statutory dimensions to be overlooked. To address this, we propose OMAGR, an ontology-guided framework that decomposes queries into ontology-aligned anchors and executes parallel graph retrieval across each dimension, ensuring independent retrieval across dimensions before fusion. To evaluate the proposed method, we created the TrafficLaw-QA dataset, an expert-validated benchmark dataset containing 200 questions and 527 legal provisions. Results show that TrafficOmni-RAG outperforms baselines on Context Precision and Faithfulness metrics. The findings demonstrate that parallel multi-anchor retrieval effectively resolves the multi-dimensional retrieval bottleneck, offering a promising direction for traffic law liability determination research.

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18.
arXiv (CS.AI) 2026-06-12

"Is This Not Enough?": Asymmetries in Institutional Accountability and Collective Sensemaking in the Case of Canada's Algorithmic Visa Triage System

作者:
Dipto Das↗Matthew Tamura↗Syed Ishtiaque Ahmed↗Shion Guha↗

arXiv:2606.13071v1 Announce Type: cross Abstract: This paper examines how algorithmic accountability in Canada's visa system is articulated institutionally and experienced by applicants across borders. We analyzed Immigration, Refugees and Citizenship Canada (IRCC)'s Algorithmic Impact Assessment (AIA) for the temporary resident visa (TRV) triage system using the algorithmic decision-making adapted for the public sector (ADMAPS) framework and analyzed Reddit discussions among applicants using a mixed-methods approach. We show that while institutional artifacts emphasize transparency, procedural safeguards, and bounded impacts, applicants engage in collective sensemaking to interpret opaque decisions, often relying on peer knowledge amid uncertainty. We identify three asymmetries between how institutional accountability is structured and how people perceive the process: epistemic asymmetry in access to decision logic, jurisdictional asymmetry in exposure shaped by geopolitical positioning, and temporal–relational asymmetry in how waiting and uncertainty are experienced. We emphasize why it is important to shift attention from institutional design to the uneven distribution of experiences with public-sector algorithmic governance. Together, these contributions demonstrate how algorithmic governance systems in the context of transnational migration produce structured asymmetries not captured by institutional disclosure frameworks, and how extending ADMAPS can account for those uneven translations of accountability.

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19.
Nature (Science) 2026-06-10

Structural basis for chaperone-guided assembly of RNA-induced silencing complex

作者:
Young-Yoon Lee↗

The RNA-induced silencing complex (RISC), comprising an Argonaute (AGO) protein and a small RNA, is the central effector in RNA silencing. Small RNAs are loaded onto AGO as bulky duplexes in an HSP70- and HSP90-dependent process1–3, but the molecular mechanism remains poorly understood. Here we identify the human AGO–HSP90–p23 complex, which captures AGO in an RNA-free state, termed the AGO maturation complex (AMC). The purified AMC enables RNA loading and AGO folding, faithfully recapitulating de novo RISC assembly. Using cryogenic electron microscopy, we determined the structure of AMC bound to a microRNA duplex. In contrast to its conformation in the RISC, AGO adopts a highly open conformation in the AMC: the N domain and the RNA-binding module (PAZ–MID–PIWI) are fully detached and anchored to opposite sides of the HSP90 dimer, connected solely by the unfolded L1 linker. This arrangement exposes a positively charged cleft that accommodates an RNA duplex. AGO folding is facilitated by a small RNA duplex containing a 5′-terminal phosphate—but not by single-stranded RNAs—revealing a role for the RNA duplex as a chaperone-like cofactor that directs AGO domain assembly. These findings elucidate the RISC assembly mechanism and establish the AMC as a molecular tool for probing optimal RNA features and chemical modifications for the rational design of small interfering RNA therapeutics. Our study also sheds light on how chaperones, together with ligands, can guide the folding of client proteins. Structures of the AGO maturation complex reveal how chaperones and an RNA duplex drive assembly of the RNA-induced silencing complex.

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20.
arXiv (CS.CL) 2026-06-15

MASLab: A Unified and Comprehensive Codebase for LLM-based Multi-Agent Systems

作者:
Rui Ye↗Keduan Huang↗Qimin Wu↗Yuzhu Cai↗Tian Jin↗Xianghe Pang↗Xiangrui Liu↗Jiaqi Su↗Chen Qian↗Bohan Tang↗Kaiqu Liang↗Jiaao Chen↗…

LLM-based multi-agent systems (MAS) have demonstrated significant potential in enhancing single LLMs to address complex and diverse tasks in practical applications. Despite considerable advancements, the field lacks a unified codebase that consolidates existing methods, resulting in redundant re-implementation efforts, unfair comparisons, and high entry barriers for researchers. To address these challenges, we introduce MASLab, a unified, comprehensive, and research-friendly codebase for LLM-based MAS. (1) MASLab integrates over 20 established methods across multiple domains, each rigorously validated by comparing step-by-step outputs with its official implementation. (2) MASLab provides a unified environment with various benchmarks for fair comparisons among methods, ensuring consistent inputs and standardized evaluation protocols. (3) MASLab implements methods within a shared streamlined structure, lowering the barriers for understanding and extension. Building on MASLab, we conduct extensive experiments covering 10+ benchmarks and 8 models, offering researchers a clear and comprehensive view of the current landscape of MAS methods. MASLab will continue to evolve, tracking the latest developments in the field, and invite contributions from the broader open-source community.

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21.
arXiv (CS.AI) 2026-06-16

Mojo: A Promising Tool for Scalable Financial AI Efficiency

作者:
Henry Han↗

arXiv:2606.16059v1 Announce Type: cross Abstract: For thirty years, quantitative finance has paid a costly two-language tax: models researched in Python are rewritten in C++ for production, often introducing numerical discrepancies. GPU-accelerated deep learning exacerbates this problem, as nondeterministic floating-point reductions can produce drift in long backtests, challenging regulatory reproducibility and auditability expectations. This article surveys Mojo, Modular's 2026 Python-like systems language, as a structural response for capital markets engineering. While closing the Python-to-C++ performance gap, Mojo uniquely combines native interoperability with the low-level systems control required to construct bit-exact deterministic kernels. Its MLIR compilation infrastructure further allows a single codebase to target scalar, SIMD, multicore, and GPU execution, reducing the translation bottleneck between research and production. We benchmark four core financial AI workloads: Monte Carlo option pricing, LLM sentiment inference, multi-asset backtesting, and portfolio Value at Risk. On Apple Silicon, Mojo demonstrates 20x to 180x speedups over pure Python on directly measured kernels; larger-scale GPU workload results are projections calibrated from published benchmarks. Alongside transparent performance data, we introduce mojo-deterministic, an open-source library of reproducible reduction kernels, and provide a candid assessment of the problems Mojo does and does not yet solve.

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22.
arXiv (quant-ph) 2026-06-19

Operational Tube-Sector Theory of Quantum State Distinguishability Under Generalized Symmetries

作者:
Song He↗

arXiv:2606.19678v1 Announce Type: cross Abstract: A variational principle for quantum-state distinguishability is established in many-body systems with generalized symmetries, including noninvertible cases described by fusion categories. Standard fidelity and symmetry-resolved diagnostics emerge as coarse-grained limits of a more refined operational structure. When symmetry actions terminate at entanglement cuts, distinguishability is governed by boundary tube algebras within a symmetry-constrained measurement resource theory. The physically admissible instruments are characterized by complete positivity, entanglement-cut locality, boundary-module covariance, and sequential stability. The resulting optimal measurement structure is uniquely fixed by the center of the boundary tube algebra, $\mathcal{A}_{\mathrm{phys}} = Z\!\left(\mathrm{Tube}_{\mathcal{C}}(\mathcal{M}_A)\right)$, whose primitive idempotents define tube-sector probabilities that refine fidelity-based and symmetry-resolved descriptions. The associated tube positive-operator-valued measures (POVM) are extremal and yield optimal one-shot hypothesis-testing distinguishability under symmetry constraints. The construction is universal across fusion categories and independent of microscopic realization.

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23.
Nature Medicine 2026-06-09

Adjuvanted inactivated rabies virus-vectored Lassa virus vaccine in healthy adults: a phase 1 trial

作者:
Justin R. Ortiz↗

Lassa fever causes substantial morbidity and mortality in West Africa, and no licensed vaccine is available. We evaluated LASSARAB, an inactivated rabies virus-vectored Lassa virus (Josiah strain) glycoprotein complex vaccine. We conducted a randomized, controlled, dose-escalation phase 1 trial. Participants (total n = 54) received two intramuscular doses of LASSARAB containing 700 (n = 15), 1,400 (n = 15) or 2,800 (n = 14) relative units of antigen formulated with the TLR-4 agonist 3D-6-acyl PHAD-SE adjuvant, or licensed rabies vaccine control (n = 10), administered 28 days apart. This protocol-defined interim analysis reports the primary safety evaluation and secondary immunogenicity assessments through day 61. There were no prespecified hypotheses or formal power calculations. All primary safety end points demonstrated an acceptable safety profile. After dose 1, local solicited adverse events occurred in 86.7–100.0% of LASSARAB groups and 80% of controls; systemic events in 33.3–71.4% and 60.0% of controls. After dose 2, local solicited adverse events occurred in 66.7–86.7% of LASSARAB groups and 55.6% of controls; systemic events in 53.3–71.4% of LASSARAB groups and 55.6% of controls. Events were predominantly mild and self-limited. Unsolicited adverse events occurred in 28.6–60.0% of LASSARAB groups and 20.0% of controls. No serious adverse event, immune-mediated condition or sensorineural hearing loss occurred. Safety laboratory abnormalities occurred in 13.3–66.7% of LASSARAB groups and 30.0% of controls (14 mild, 6 moderate and none severe). After two doses, Lassa virus GPC IgG ELISA seroconversion (≥fourfold rise) was achieved in 100.0% (44 of 44) of LASSARAB recipients and 0.0% (0 of 10) of controls. Rabies glycoprotein IgG ELISA seroconversion (≥fourfold rise) and neutralizing antibody by rapid fluorescent focus inhibition test (RFFIT) seroprotection (≥0.5 IU ml−1) were also 100% across all groups, including controls. LASSARAB + 3D-6-acyl phosphorylated hexaacyl disaccharide (PHAD)-SE demonstrated a favorable safety profile and immunogenicity against Lassa and rabies viruses. The per-protocol final study report will include safety and durability through day 394. ClinicalTrials.gov identifier NCT06546709 . An interim report of a first-in-human phase 1 trial found an adjuvanted, combination inactivated rabies-vectored, Lassa fever vaccine (LASSARAB + 3D-6-acyl PHAD-SE) to be safe and induced immunogenicity to both Lassa and rabies viruses in healthy participants.

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24.
arXiv (CS.LG) 2026-06-11

Capacity-Constrained Online Convex Optimization with Delayed Feedback

作者:
Alexander Ryabchenko↗Idan Attias↗Daniel M. Roy↗

arXiv:2606.11711v1 Announce Type: new Abstract: Online learning with delayed feedback typically assumes that the learner can track all pending rounds until their feedback arrives. In practice, tracking resources are finite, and feedback from untracked rounds is permanently lost. In this paper, we study delayed online convex optimization (OCO) under a hard capacity constraint, where at most $C$ pending rounds can be tracked at any time. To model delay information, we introduce a semi-clairvoyant model that refines the clairvoyant assumption from prior work: rather than requiring delays to be known at prediction time, the learner observes delay expirations online, consistent with the classical unconstrained delayed setting. Our approach proceeds via a reduction to a novel ``delayed and weighted'' OCO problem, using a scheduler that randomizes tracking decisions and importance-weights the resulting observations. For this base problem, we propose and analyze Delayed-Weighted FTRL and its bandit analogue, establishing regret bounds that explicitly characterize the interaction between time-varying weights and delayed feedback. Combining these base learners with our schedulers yields the first regret guarantees for capacity-constrained OCO under convex and strongly convex losses, for both first-order and bandit feedback. For first-order feedback, capacity $C = \Omega(\log T)$ suffices to recover standard delayed OCO rates up to logarithmic factors. For bandit feedback, the regret rates are modulated by powers of $(1 + \sigma_{max}/C)$, where $\sigma_{max}$ is the maximum number of pending observations at any time. This allows the regret bound to degrade gracefully when $C < \sigma_{max}$, while remaining sublinear.

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

Simplicity Suffices for Parameter Noise Injection in Stochastic Gradient Descent

作者:
Benjamin Leblanc↗Louis-Jacob Lebel↗Teddy Kana↗Richard Kamel↗

arXiv:2606.12054v1 Announce Type: new Abstract: Injecting noise into the optimization process is a well-established technique for improving the training and generalization of deep neural networks. Yet, despite the breadth of existing approaches, it remains unclear which design choices truly matter in practice. In this work, we investigate parameter noise injection for stochastic gradient descent, focusing on two key questions: how to efficiently pair each training example with its own perturbation in mini-batch training, and whether sophisticated noise parameterizations or multi-sample gradient averaging yield meaningful gains over simpler alternatives. To address the first question, we leverage a distributional identity for linear layers that allows per-example noise injection without breaking batched computation. To address the second, we systematically compare several diagonal Gaussian parameterizations against an isotropic baseline across varying noise levels on CIFAR100. Our results consistently show that simple, lightweight strategies, isotropic noise with a single perturbed forward pass per update step, recover most of the benefit of more complex schemes. These findings suggest that simplicity suffices for parameter noise injection, and that practitioners need not resort to elaborate perturbation designs to reap the optimization and generalization benefits of noisy SGD.

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