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01.
arXiv (CS.CL) 2026-06-16

Spokes: Optimizing for Diverse Pretraining Data Selection

Diversity plays a critical role in data selection, improving performance under fixed data budgets by reducing redundancy and repetition. However, optimizing for diversity is inherently challenging, as it is a set-level property that depends on interactions between data points rather than individual examples. As a result, existing approaches typically rely on proxies or approximations, which often fail to ensure sufficiently diverse subsets. In this work, we directly optimize diversity by introducing a probabilistic diversification framework based on the G-Vendi score, optimized via exponentiated gradient descent. Our method produces subsets that are substantially more diverse than those obtained via random sampling, achieving a +489 increase in G-Vendi score on a 500k-sample subset. We evaluate our approach on FineWeb and DCLM, where it consistently outperforms existing methods. Notably, SPOKES (diversity-only) improves average downstream performance by +0.4 and +0.5 points over random sampling on DCLM and FineWeb, respectively. More importantly, jointly optimizing for both quality and diversity yields the strongest results: SPOKES achieves gains of +1.5 and +1.4 points on DCLM and FineWeb, outperforming all baselines, including semantic deduplication and quality filtering.

02.
arXiv (CS.CL) 2026-06-18

ScholaWrite: A Dataset of End-to-End Scholarly Writing Process

Writing is a cognitively demanding activity that requires constant decision-making, heavy reliance on working memory, and frequent shifts between tasks of different goals. To build writing assistants that truly align with writers' cognition, we must capture and decode the complete thought process behind how writers transform ideas into final texts. We present ScholaWrite, the first dataset of end-to-end scholarly writing, tracing the multi-month journey from initial drafts to final manuscripts. We contribute three key advances: (1) a Chrome extension that unobtrusively records keystrokes on Overleaf, enabling the collection of realistic, in-situ writing data; (2) a novel corpus of full scholarly manuscripts, enriched with fine-grained annotations of cognitive writing intentions. The dataset includes \LaTeX-based edits from five computer science preprints, capturing nearly 62K text changes over four months; and (3) analyses and insights into the micro-dynamics of scholarly writing, highlighting gaps between human writing processes and the current capabilities of large language models (LLMs) in providing meaningful assistance. ScholaWrite underscores the value of capturing end-to-end writing data to develop future writing assistants that support, not replace, the cognitive work of scientists.

03.
bioRxiv (Bioinfo) 2026-06-12

CAREPath: Semantic Context-Aware Reasoning Paths with Mechanism-Augmented Embeddings for Drug Repurposing

Biomedical knowledge graphs (BKGs) that include drugs, genes, and diseases support drug repurposing by connecting drugs to diseases through gene-mediated multi-hop paths, thereby enabling mechanism-of-action reasoning. However, deeper traversal does not necessarily improve mechanistic reasoning: long paths grow combinatorially and frequently pass through hub genes, producing irrelevant gene regulatory signals, whereas overly constrained or sparse paths may miss broader biological context. We propose CAREPath, a KG-LLM framework inspired by depth-first search (DFS)-like and breadth-first search (BFS)-like reasoning to balance mechanistic specificity, scalability, and context recovery. The DFS-like module constrains traversal to short disease-gene-drug paths, converts each path into a structured prompt, and encodes it with a biomedical language model to generate semantic path embeddings. Complementarily, the BFS-like module constructs entity-level mechanism-context embeddings from one-hop gene neighborhoods and enriches them through similarity-guided augmentation using pharmacologically related drugs and gene-signature-similar diseases. Across five biomedical KGs, CAREPath achieves the best overall AUPRC among 18 baselines, improving performance by up to 3.8%. Additional analyses show that semantic short-path encoding contributes most to performance, while mechanism-context augmentation improves robustness under sparse evidence and strengthens Gene Ontology functional agreement. Case studies and recently FDAapproved indications further demonstrate its practical relevance, positioning CAREPath as an interpretable framework for scalable and mechanism-aware drug repurposing. Source code is available at https://github.com/hamppy-song/CAREPath.

04.
arXiv (CS.AI) 2026-06-17

Membership Inference Attacks against Large Audio Language Models

arXiv:2603.28378v2 Announce Type: replace-cross Abstract: We present the first systematic Membership Inference Attack (MIA) evaluation of LALMs. Using Multi-modal Blind Baselines based on textual, spectral and prosodic features, we demonstrate that common audio datasets exhibit near-perfect train/test separability (AUC ~ 1.0) even without model inference, thus MIA may primarily detect distribution shift. We therefore introduce a blind-baseline protocol to control for this confound. Under this protocol, we identify that the distribution-matched datasets enable reliable MIA evaluation without distribution-shift artifacts. We benchmark multiple MIA methods and conduct modality disentanglement experiments on these datasets. The results reveal that LALM memorization is cross-modal, arising only from binding a speaker's vocal identity with its text. These findings establish a principled standard for auditing LALMs beyond spurious correlations. Our codebase is available at https://github.com/snooow1029/ALM_MIA.

05.
arXiv (CS.AI) 2026-06-19

Stabilizing the Q-Gradient Field for Policy Smoothness in Actor-Critic Methods

arXiv:2601.22970v2 Announce Type: replace-cross Abstract: Policies learned via continuous actor-critic methods often exhibit erratic, high-frequency oscillations, making them unsuitable for physical deployment. Current approaches attempt to enforce smoothness by directly regularizing the policy's output. We argue that this approach treats the symptom rather than the cause. In this work, we theoretically establish that policy non-smoothness is fundamentally governed by the differential geometry of the critic. By applying implicit differentiation to the actor-critic objective, we prove that the sensitivity of the optimal policy is bounded by the ratio of the Q-function's mixed-partial derivative (noise sensitivity) to its action-space curvature (signal distinctness). To empirically validate this theoretical insight, we introduce PAVE (Policy-Aware Value-field Equalization), a critic-centric regularization framework that treats the critic as a scalar field and stabilizes its induced action-gradient field. PAVE rectifies the learning signal by minimizing the Q-gradient volatility while preserving local curvature. Experimental results demonstrate that PAVE achieves smoothness comparable to policy-side smoothness regularization methods, while maintaining competitive task performance, without modifying the actor.

06.
medRxiv (Medicine) 2026-06-15

Natural Language Processing Based Solution for Labeling Brain Metastasis Identified in Radiology Reports

Abstract Purpose: Brain metastases (BM) far exceed primary CNS tumours and constitute the majority workload for neuro-oncology care providers. Currently, the cancer registries only capture synchronous BMs, which is only a small proportion of all BMs. We aim to develop and validate a natural language processing (NLP) algorithm that identifies brain metastases in radiology reports, enabling scalable surveillance of asynchronous BMs. Methods: Using population-based cancer registry data in Alberta, Canada, we identified a cancer cohort diagnosed between 2012–2019 with follow-up to 2022. All brain/head radiology reports at and post-cancer diagnosis were identified. Reports were sampled through a multi-phase approach and manually labeled for BM presence. We trained two Bio_ClinicalBERT models on the "Findings" and "Impressions" sections, respectively, and took the maximum predicted probability as the report-level prediction. Internal and external validation used reports from the Canadian provinces of Alberta, Ontario, and British Columbia. Results: The models were trained on 1,879 samples. For internal validation, 1,833 reports from 357 patients were tested. At a probability threshold of 0.4, the model achieved a sensitivity of 0.888 and precision of 0.499. The ensemble substantially outperformed single-section models, which achieved sensitivities of only 67.8% (Findings) and 74.2% (Impressions). On external validation, sensitivity was 0.918 in Ontario and 0.726 in British Columbia, demonstrating robustness across diverse data distributions. Conclusions: An NLP-based pipeline processing both Findings and Impressions sections has been developed and validated in three Canadian provinces. It meets cancer registry operational requirements and to be implemented into the surveillance workflow in Alberta and British Columbia, providing a foundation for population-level BM surveillance.

07.
arXiv (CS.AI) 2026-06-18

Dynamic In-Group Persona Generation for Enhancing Human-AI Rapport

arXiv:2606.18256v1 Announce Type: cross Abstract: LLM-based chatbots are increasingly applied in interpersonal domains such as counseling and peer support, where establishing human-AI rapport is crucial yet remains challenging. In this work, we introduce a novel approach for conditioning LLMs with in-group personas, which (i) first identifies a user's primary concern and brief personal context (e.g., a computer science undergraduate worried about future career prospects), and (ii) generates a synthetic in-group persona that shares a similar primary concern while differing in background and narrative details, such as age or profession (e.g., a junior researcher at an AI startup). Furthermore, we conduct a human-subject study to systematically evaluate the effectiveness of in-group persona agents in enhancing human-AI rapport. We compare our approach against two baseline conditions: a conventional agent without persona conditioning and an agent exhibiting minimal self-disclosure (e.g., "I've felt that too"). Results from post-task questionnaires assessing rapport and user experience indicate that the in-group persona agent significantly improves perceived rapport and personal relevance compared to the baselines, and also yields more positive user experience-most notably higher engagement.

08.
arXiv (quant-ph) 2026-06-19

Many-body chirality of topological stabilizer states

arXiv:2606.20472v1 Announce Type: new Abstract: A defining feature of chirality is the distinction between a system and its mirror image. Despite extensive experimental observations of chiral phases and theoretical advances, a quantum-information theoretic characterization of chirality based solely on the entanglement structure of many-body quantum states remains elusive. Here, we introduce the notion of many-body chirality by formulating it as an obstruction to transforming a quantum state into its complex conjugate through finite-depth local operations. We rigorously establish many-body chirality for stabilizer realizations of $\mathbb{Z}_d^{(k)}$ anyon theories, proving that complex conjugation can be implemented by local quantum channels if and only if the underlying anyon data are mirror invariant. This reveals forms of chirality that evade conventional diagnostics, including examples with vanishing modular commutator, vanishing chiral central charge, and commuting-projector realizations. We further show that this obstruction is intrinsically four-partite, while invisible to tripartite entanglement structure. Finally, we prove that $\mathbb{Z}_d^{(k)}$ states with $d>2$ possess intrinsic many-body imaginarity: their complex phase structure cannot be removed by finite-depth local unitaries. Remarkably, this includes states that are not many-body chiral.

09.
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

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

AI4SLT: Empirical Processes in Lean 4 for Formal Statistical Learning Theory

We present the first comprehensive Lean 4 formalization of statistical learning theory (SLT) grounded in empirical process theory. Our en-to-end formal infrastructure implement the missing contents in latest Lean library, including a complete development of Gaussian Lipschitz concentration, Dudley's entropy integral theorem for sub-Gaussian processes, and an application to least-squares (sparse) regression with a sharp rate. The project was carried out using a human-AI collaborative workflow, in which humans design proof strategies and AI agents execute tactical proof construction, leading to the human-verified Lean 4 toolbox for SLT. Beyond implementation, the formalization process exposes and resolves implicit assumptions and missing details in standard SLT textbooks, enforcing a granular, line-by-line understanding of the theory. This work establishes a reusable formal foundation and opens the door for future developments in machine learning theory. The code is provided in https://github.com/YuanheZ/lean-stat-learning-theory.

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

UR-BERT: Scaling Text Encoders for Massively Multilingual TTS Through Universal Romanization and Speech Token Prediction

We propose UR-BERT, a Romanized transcription-based text-to-speech (TTS) encoder for massively multilingual TTS systems. Conventional grapheme-to-phoneme (G2P)-based approaches are limited to around 100 languages due to the availability of reliable G2P resources. In contrast, UR-BERT scales to 495 languages by unifying diverse writing systems into a shared Romanization representation. To further enhance phonetic fidelity and text-speech alignment, we introduce a speech token prediction objective during training, which encourages the encoder to learn speech-aware phonetic representations in a data-efficient manner. Experiments show that TTS systems built on UR-BERT consistently outperform recent text encoder baselines across a wide range of languages and resource conditions, and demonstrate strong generalization to unseen languages.

12.
arXiv (quant-ph) 2026-06-11

Locally Acting Grover Mixers for Constraint-Preserving QAOA

arXiv:2606.11530v1 Announce Type: new Abstract: The Grover mixer quantum alternating operator ansatz (GM-QAOA) employs the Grover mixer to confine the quantum evolution to the feasible subspace defined by the problem. Its mixing unitary, however, requires a global multi-controlled phase-shift gate acting on all qubits, resulting in substantial circuit overhead on near-term quantum devices. In this work, we propose locally acting Grover mixers tailored to initial states that admit a product structure over disjoint qubit subsystems, which may be obtained by encoding only a subset of problem constraints into the initial state preparation. The proposed method preserves the search space defined by the initial state while significantly lowering implementation cost, as the global multi-controlled phase-shift gate is replaced with local operations on disjoint subsystems. Numerical simulations on the exact-cover problem and the traveling salesman problem (TSP) demonstrate that the proposed method achieves convergence behavior comparable to that of the original GM-QAOA, while using shallower circuits with fewer gates. We further compare two constraint encoding strategies for the TSP, encoding only a subset of constraints versus all constraints into the initial state preparation, and show that the former combined with the proposed mixer yields markedly more compact circuits at the point where comparable solution quality is achieved.

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

RaBiT: Residual-Aware Binarization Training for Accurate and Efficient LLMs

arXiv:2602.05367v3 Announce Type: replace Abstract: Efficient deployment of large language models (LLMs) requires extreme quantization, forcing a critical trade-off between low-bit efficiency and performance. Residual binarization enables hardware-friendly, matmul-free inference by stacking binary ($\pm$1) layers, but is plagued by pathological feature co-adaptation. We identify a key failure mode, which we term inter-path adaptation: during quantization-aware training (QAT), parallel residual binary paths learn redundant features, degrading the error-compensation structure and limiting the expressive capacity of the model. While prior work relies on heuristic workarounds (e.g., path freezing) that constrain the solution space, we propose RaBiT, a novel quantization framework that resolves co-adaptation by algorithmically enforcing a residual hierarchy. Its core mechanism sequentially derives each binary path from a single shared full-precision weight, which ensures that every path corrects the error of the preceding one. This process is stabilized by a robust initialization that prioritizes functional preservation over mere weight approximation. RaBiT redefines the 2-bit accuracy-efficiency frontier: it achieves state-of-the-art performance, rivals even hardware-intensive Vector Quantization (VQ) methods, and delivers a $4.49\times$ inference speed-up over full-precision models on an RTX 4090. Code is available at https://github.com/SamsungLabs/RaBiT.

14.
arXiv (CS.CL) 2026-06-15

Learning to Hear Hesitation: Continual Learning for Disfluency-Aware ASR

Despite advances in large-scale Automatic Speech Recognition (ASR), disfluent speech remains challenging, as state-of-the-art systems are often optimized to omit disfluencies, leading to information loss and hallucinations. Prior work has focused on verbatim transcription and the integration of disfluency markers, but adapting models on limited datasets can lead to catastrophic forgetting of general-domain knowledge. We address this gap by leveraging continual learning (CL) with explicit disfluency tokens. We first introduce these tokens into a pretrained ASR model to establish stable token mechanisms, and then continue training on additional datasets with varying disfluency distributions. Through a detailed analysis of model dynamics during training, we identify a trade-off between marker learning and ASR performance, and a consistent cross-attention head mechanism shared across CL methods.

15.
medRxiv (Medicine) 2026-06-16

Higher Population Coverage with Typhoid Conjugate Vaccine is Needed to Induce Herd Protection: Evidence from a Cluster-Randomized Trial in Urban Bangladesh

Introduction: A cluster randomized trial (CRT) in Bangladesh found that Vi-tetanus toxoid (Vi-TT) vaccine conferred 85% protection to vaccinees at 18 months of follow-up; however, it failed to confer significant herd protection to non-vaccinees. Methods: In the CRT, children aged 9 months to

16.
medRxiv (Medicine) 2026-06-15

Quality Improvement Based Implementation and Evaluation of a Decision Aid for Patients with Nephrolithiasis

Introduction Patients with nephrolithiasis face challenges in making a high-quality, preference sensitive decision. Our prior work established feasibility and patient acceptance of a software-based decision aid (DA). The objectives for this study were to identify implementation strategies for the DA in routine care and determine whether DA implementation enhances decisional quality for patients. Methods New nephrolithiasis patients were recruited from the institution Medical Center from June 2018 to April 2024 to receive a software-based pre-visit DA that measured care preferences and used decision analysis to rank treatments. The RE-AIM framework and Plan-Do-Study-Act (PDSA) cycles were used to improve implementation outcomes. Patients completed survey instruments evaluating decisional conflict, shared decision-making, care satisfaction, and treatment choice following their provider visit. These metrics were compared in the DA cohort (n=81) to those in a usual care cohort (n=78) with Wilcoxon rank-sum and Chi-square (or Fishers exact) tests. Results Implementation data revealed sustained reach and progressive improvement in fidelity. The DA cohort reported higher decisional quality relative to controls (p=0.003) and reported greater support/advice to make a choice (p=0.005). The DA cohort more often discussed options with their doctor (87.5% vs 69.2%, p=0.005) and were more likely to be promoters of their provider (p

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

Advancing DialNav through Automatic Embodied Dialog Augmentation

arXiv:2606.19948v1 Announce Type: new Abstract: For embodied agents capable of physical interaction, the capability to create and understand dialog is crucial to ensure both safety and effectiveness. While DialNav[han2025dialnav] provides a framework for holistic evaluation of the dialog–execution loop in photorealistic indoor navigation, its performance remains limited by a critical scarcity of training data (2K episodes). To address this, we propose an automatic generation pipeline, and construct the RAINbow dataset, a large-scale training dataset with 238K episodes for DialNav. Our pipeline converts existing VLN datasets into multi-turn dialog and creates cost-efficient and high-quality dataset. Then, we introduce two additional complementary advances to unlock the data's full potential: (1) Dual-Strategy Training, a navigation training scheme to align the navigation training with the dynamic dialog-navigation loop, and (2) a localization model that leverages VLN knowledge. By combining these complementary solutions, our model substantially outperforms the baseline in success rate on both Val Seen (58.24, +89\%) and Val Unseen (29.05, +100\%) splits, establishing a new state of the art.

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

Understanding Latent Diffusability via Fisher Geometry

arXiv:2604.02751v2 Announce Type: replace Abstract: Diffusion models often degrade in latent spaces, yet the formal causes remain poorly understood. We quantify latent-space diffusability via the rate of change of the Minimum Mean Squared Error (MMSE) along the diffusion trajectory. Our framework decomposes this MMSE rate into contributions from Fisher Information (FI) and Fisher Information Rate (FIR). We demonstrate that while global isometry ensures FI alignment, FIR is governed by the interplay between encoder and data geometries. Our analysis decouples diffusion degradation into four penalties: dimensional compression, tangential distortion, high-frequency encoder curvature, and intrinsic data curvature. We derive theoretical conditions for FIR preservation to ensure stable diffusability. Experiments across diverse autoencoding architectures demonstrate the implications of our theoretical bounds. We establish FI and FIR as a comprehensive analytical framework for understanding latent diffusability.

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

ForecastBench-Sim: A Simulated-World Forecasting Benchmark

Forecasting benchmarks for general-purpose AI systems usually inherit the constraints of the real world: outcomes resolve slowly, tail events are rare, and counterfactual questions are difficult to score. We introduce ForecastBench-Sim, a simulated-world forecasting benchmark built on game rollouts from Freeciv, a turn-based strategy game modelled on the Civilization series. Forecasters receive a fixed world report (a structured snapshot of the current game state) and answer questions about hidden future states; the benchmark then continues the simulation and scores forecasts. Because the world is simulated, the same setup can generate continuous or binary forecasting questions at arbitrary time horizons, paired intervention worlds for conditional or causal questions, and resolved examples of rare or disruptive outcomes. We describe the benchmark pipeline, question families, scoring protocol, and release artifacts, and report validation slices from model evaluations and an anonymized human pilot. ForecastBench-Sim is intended to complement real-world forecasting benchmarks by providing controlled, immediately resolvable tasks for studying probabilistic reasoning under dynamic world states.

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

Moving Out: Physically-grounded Human-AI Collaboration

arXiv:2507.18623v4 Announce Type: replace-cross Abstract: The ability to adapt to physical actions and constraints in an environment is crucial for embodied agents (e.g., robots) to effectively collaborate with humans. Such physically grounded human-AI collaboration must account for the increased complexity of the continuous state-action space and constrained dynamics caused by physical constraints. However, most existing collaboration benchmarks are discrete or do not consider physical attributes and constraints. To address this, we introduce Moving Out, a human-AI collaboration benchmark that resembles a wide range of collaboration modes affected by physical attributes and constraints, such as moving heavy items together and coordinating actions to move an item around a corner. Moving Out consists of two challenges and human-human interaction data to comprehensively evaluate models' abilities to adapt to diverse human behaviors and unseen physical attributes. To give embodied agents the capability to collaborate with humans under physical attributes and constraints, we propose a novel method, BASS (Behavior Augmentation, Simulation, and Selection), to enhance the diversity of agents and their understanding of the outcome of actions. We systematically compare BASS and state-of-the-art models in AI-AI and human-AI experiments, showing that BASS can effectively collaborate with both unseen AI and humans. The project page is available at https://live-robotics-uva.github.io/movingout_ai/.

21.
arXiv (CS.AI) 2026-06-12

ReSET: Accurate Latency-Critical NVFP4 Reasoning via Step-Aware Temperature Scaling

arXiv:2606.13233v1 Announce Type: cross Abstract: Large reasoning models (LRMs) improve complex problem-solving by generating long intermediate reasoning traces, but this substantially increases inference costs. NVFP4 inference offers a promising approach to reduce both computational and memory costs through hardware-supported low-precision execution. However, directly applying NVFP4 to LRMs introduces two practical limitations: reasoning accuracy degrades under quantization, and existing NVFP4 kernels do not fully realize latency benefits in small-batch autoregressive decoding. In this work, we analyze the effect of NVFP4 quantization on token-level uncertainty during reasoning. We show that quantization increases incorrect sampling at low-entropy symbolic tokens, while causing over-concentration on a small set of tokens in high-uncertainty reasoning steps. Based on this observation, we propose ReSET, a reasoning-step entropy-based temperature-scaling method that estimates step-level uncertainty online and adapts the decoding temperature using both token-level and step-level entropy signals. To address the latency gap, we further design a CUDA-core small-$M$ NVFP4 kernel for latency-critical autoregressive decoding. Across reasoning benchmarks and model scales, ReSET improves NVFP4 reasoning accuracy by up to $\sim\!$2 points over the NVFP4 baseline. Our CUDA-core small-$M$ kernel further improves latency-critical decoding, delivering up to $2.5\!\times$ kernel-level speedup over NVFP4 vLLM and approximately $2\!\times$ end-to-end decoding speedup over BF16. Code is available at https://github.com/aiha-lab/ReSET.

22.
medRxiv (Medicine) 2026-06-15

The clinical utility of functional testing in fibroblasts to diagnose primary mitochondrial disease

Genome sequencing of the heterogeneous primary mitochondrial disorders (PMD) frequently reveals variants of uncertain significance that require functional tests for diagnosis, and does not identify variants in all patients. We analyzed mitochondrial enzyme assays, blue native polyacrylamide gel electrophoresis (BN-PAGE) with in-gel activity staining, complex I assembly blot, and select protein abundances in fibroblasts of a case series of 204 PMD patients divided into functional classes, in comparison to 51 controls and 53 differential diagnostic conditions. Overall, sensitivity and specificity for respiratory chain enzyme assays were 46% and 93% respectively, for BN-PAGE 40% and 98%, for complex I assembly assay 49% and 99%. The overall sensitivity of all tests was 76%, specificity 93%, with positive predictive value 96% and negative predictive value 67%. Categories with high sensitivity were isolated complex deficiencies, nuclear DNA-encoded mitochondrial protein synthesis defects, co-factor defects, and mitochondrial amino-acyl-tRNA synthetase conditions when aided by protein abundance. Mitochondrial DNA mutations and maintenance disorders showed poor sensitivities. Secondary dysfunctions were rare. A complete battery of functional tests showed strong diagnostic clinical utility in fibroblasts.

23.
arXiv (CS.LG) 2026-06-11

Mahalanobis-Guided Latent OOD Detection for Hybrid ES-DRL Control in Time-Varying Systems

arXiv:2606.11474v1 Announce Type: new Abstract: In this paper, we study Mahalanobis-guided latent out-of-distribution (OOD) detection for test-time RL controller switching in nonlinear time-varying systems. RL controllers can quickly control high-dimensional systems within the training distribution, but their performance can degrade when time-varying dynamics produce unseen observations. We consider a combined ES–DRL controller, where RL provides fast in-distribution actions and bounded extremum seeking (ES) provides robust model-independent control under OOD operation. The key challenge is deciding when to switch. We train a variational autoencoder (VAE) on in-distribution beam-profile observations and use Mahalanobis distance in the VAE latent space to detect OOD beam profiles at test time. This OOD decision sets a binary switch that selects either the RL controller or the ES controller. We evaluate the approach in safety-critical particle accelerator control. In this setting, spatial magnet motion creates OOD beam profiles that were not seen during RL training. Visualization of the VAE latent space shows that the proposed method identifies this OOD scenario and provides an interpretable signal for switching between RL and ES in the combined controller.

24.
Nature (Science) 2026-06-10

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

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.

25.
arXiv (quant-ph) 2026-06-19

Mitigating Trotter Errors via Post-Processed Symmetry Restoration

arXiv:2606.20242v1 Announce Type: new Abstract: Quantum simulation is a powerful tool for exploring complex quantum many-body systems such as condensed matter physics and gauge theories. Trotterization, which approximates the ideal time evolution operator by decomposing it into a sequence of local gate operations, is one of the most widely used quantum simulation algorithms. However, such Trotterized implementations generally fail to preserve the symmetries of the target Hamiltonian during compilation. As a result, they can drive quantum states out of symmetrically allowed subspaces, leading to unphysical dynamics and symmetry-violating algorithmic errors. In this work, we propose a symmetry-based Trotter error mitigation protocol using classical post-processing. By applying symmetry transformations to the initial state or interleaving them between discrete Trotter layers, and then averaging an ensemble of the resulting measurement outcomes via classical post-processing, our method systematically projects out the symmetry-violating components of the Trotter error while leaving the ideal dynamics unchanged. Importantly, this framework naturally accommodates non-local spatial symmetries and anti-unitary operations such as time reversal, which are difficult or impossible to implement directly with hardware-native quantum gates. We benchmark our protocol on the one-dimensional XY model and the one-dimensional Schwinger model. In the XY model, enforcing reflection symmetry suppresses the leading-order Trotter error, whereas in the Schwinger model, interleaving gauge transformations between Trotter layers enables gauge-twirling effectively to reduce unphysical violations of local Gauss's law. These results demonstrate that symmetry-based post-processing provides a depth-preserving route to substantially improving the fidelity of Trotterized quantum simulations on near-term devices.