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

Teaching Values to Machines: Simulating Human-Like Behavior in LLMs

Large Language Models (LLMs) demonstrate a remarkable capacity to adopt different personas and roles; however, it remains unclear whether they can manifest behavior that adheres to a coherent, human-like value structure. In this work, we draw on established psychological value theory to induce human-like values in LLMs and assess their alignment with patterns observed in human studies. Using validated psychological questionnaires, we conduct large-scale experiments – over 5 million questions – to evaluate value structures and value-behavior relationships in leading LLMs and compare them to humans. Our findings reveal strong agreement between value-prompted LLMs and humans across both dimensions. Moreover, incorporating human value distributions enhances population-level simulations with value-induced LLMs. These findings highlight the potential of value-induced LLMs as effective, psychologically grounded tools for simulating human behavior.

02.
arXiv (CS.AI) 2026-06-15

AudioDER: A Deduplication-Enhanced Reasoning Dataset for Post-Training Large Audio-Language Models

arXiv:2606.14591v1 Announce Type: cross Abstract: Large Audio-Language Models (LALMs) have shown strong performance on a wide range of audio understanding tasks, yet they still struggle with complex audio reasoning. A practical way to improve such capabilities is post-training, whose effectiveness critically depends on the quality and diversity of training data. However, existing audio-language datasets often contain substantial redundancy, where many samples are highly similar in acoustic content and thus provide overlapping supervisory signals. Such redundancy not only increases annotation cost, but also limits corpus diversity and reduces the effectiveness of post-training. To address this issue, we propose a redundancy-aware data construction pipeline for building reasoning-oriented supervision for LALMs. Specifically, we first perform acoustic similarity-based deduplication across raw audio datasets to improve corpus diversity. We then integrate existing audio captions and question-answer pairs into a unified multiple-choice format. Based on these unified annotations, we leverage Qwen3-30B to generate chain-of-thought (CoT) rationales for reasoning-oriented supervision. Based on this pipeline, we construct AudioDER, a reasoning-oriented post-training dataset containing approximately 191k samples spanning sound, speech, and music. Each sample consists of an audio clip, a multiple-choice question, four answer candidates, an audio caption, and a CoT rationale. Extensive experiments show that post-training on AudioDER consistently improves the performance of Qwen2-Audio-7B-Instruct on multiple audio reasoning benchmarks, including MMAU-mini, MMSU, and MMAR. We hope AudioDER can serve as a valuable resource for advancing audio reasoning research and the development of more capable LALMs.

03.
arXiv (CS.CV) 2026-06-19

CrossFlow: One-Step Generation Across Latent and Pixel Spaces

Most diffusion and flow-matching generators define the prior, probability path, and prediction target in the same representation space. Latent diffusion improves efficiency by moving this path into an autoencoder latent space, but the final sample is still produced by a separately trained decoder. This separation creates a mismatch: the generator is optimized for latent-space prediction, while final quality depends on how the decoder handles generated latents that may differ from clean encoder outputs. We introduce CrossFlow, a cross-space flow formulation that maps noisy latent inputs directly to pixel-space images. The key technical step is a velocity-free one-step objective: the latent trajectory defines the training path, but the supervised prediction is an image rather than a latent displacement. This lets one model act both as a one-step latent-to-pixel generator and as a decoder replacement for latent diffusion pipelines. On class-conditional ImageNet-1k at $256\times256$, CrossFlow-XL achieves 1.62 FID with one function evaluation. Ablations show that the latent encoder and pixel-space perceptual and adversarial losses are important for fidelity. These results indicate that cross-space flow objectives can combine the efficiency of latent representations with direct pixel-space supervision, without requiring a separate decoder at inference.

04.
Nature Medicine 2026-06-11

Clinical Profile and Genomic Characterization of the 2026 Bundibugyo Virus Index Case in Uganda

Bundibugyo virus disease (BVD) remains a high-consequence threat in Eastern and Central Africa, where cross-border mobility, nonspecific early symptoms, and delayed recognition can obscure transmission. In this case report, we describe Uganda’s 2026 BVD index case: a male patient who traveled from the Democratic Republic of the Congo to Uganda and was admitted to a private hospital in Kampala on 11 May 2026 after more than two weeks of vomiting and diarrhea, with epigastric pain, weakness, and hiccups. He deteriorated rapidly, developing acute kidney injury, pulmonary edema, hepatic dysfunction, hypoxemia, delirium, atrial flutter, possible disseminated intravascular coagulation, and multiorgan failure, and died on 14 May. A posthumous EDTA whole-blood specimen tested at the Central Emergency Response and Surveillance Laboratory was positive for orthoebolavirus RNA and confirmed as Bundibugyo virus (BDBV) by RT-qPCR. Sequencing achieved 99% genome coverage at ≥100× depth. The 2026 BDBV genome formed a distinct lineage approximately equidistant from the 2007–2008 Butalya and 2012 Isiro variants, differing by 216–227 nucleotides (~1.2% sequence divergence). Here, we demonstrate the value of fatality surveillance, private-sector surveillance, diagnostic optimization through national specimen referral, and rapid molecular-genomic diagnostics for early detection, transmission chain interruption, and public health response coordination.

05.
arXiv (CS.CL) 2026-06-25

Efficient and Trainable Language Model Test-Time Scaling via Local Branch Routing

Test-time scaling improves language-model reasoning, but existing approaches often face a difficult trade-off: long chain-of-thought sampling remains single-threaded, while sentence- or solution-level search can be computationally expensive and hard to train end-to-end. We introduce Local Branch Routing (LBR), a token-level test-time scaling framework that expands a small local lookahead tree, forwards all sampled branches through the language model, and uses a lightweight router to select the depth-1 subtree to commit. By routing over the hidden states of candidate local futures, LBR allows each token decision to use evidence beyond the root next-token distribution while avoiding full solution-level search. The resulting prune-shift-grow decoding process preserves discrete branch identities and defines a tractable tree-trajectory likelihood: newly grown nodes are counted when first sampled, and router decisions are assigned explicit probabilities. This enables end-to-end reinforcement learning with verifiable rewards, jointly optimizing the base model and router under the same likelihood-ratio principle as discrete-token RLVR. On synthetic hierarchical-planning tasks, LBR shows that post-candidate hidden states provide useful routing evidence. On mathematical reasoning benchmarks, LBR improves both Pass@1 and Pass@32 over discrete chain-of-thought, vanilla discrete-token RLVR, and RL-compatible soft-token branching baselines. These results suggest that lightweight local branching offers an efficient, trainable, and discrete form of language-model test-time scaling.

06.
bioRxiv (Bioinfo) 2026-06-16

Super Learner Ensemble Modeling of CPTAC Proteomic Data for Survival Prediction in Head and Neck Squamous Cell Carcinoma

Survival analysis in head and neck squamous cell carcinoma (HNSCC) is traditionally performed using Cox proportional hazards models, alongside some exploration into black-box machine learning methods. The Super Learner (SL) algorithm addresses this model selection dilemma by combining diverse candidate algorithms into a weighted ensemble to perform comparably to the best candidate method. This study evaluates the performance of SL in HNSCC. Proteomic features as well as clinical covariates from 96 CPTAC HNSCC samples were modeled with three candidate algorithms (Cox LASSO, Cox Ridge, and Random Survival Forest) as well as the ensemble SL method. Models were optimized via Uno's time-dependent Concordance Index (C-index) and tested at 1- and 3-year time horizons using 2000 bootstrap resamples. The Cox Ridge regression model achieved the highest predictive accuracy among the four total methods. However, the SL demonstrated stable performance over both time horizons (1-year C-index: 0.985; 3-year C-index: 0.960). Variable importance analysis of the Cox Ridge model successfully identified malignant proteins (ATR, MAML1, MIEN1) alongside novel potential prognostic indicators (ZNF800, KERA). This analysis emphasizes the statistical necessity for larger cohorts for ensemble learning, while providing a benchmark of proteomic indicators in HNSCC.

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

EmoMind: Decoding Affective Captions from Human Brain fMRI

Decoding visual experience from brain activity has advanced substantially, but current brain-to-text systems largely recover semantic content while discarding affect. Additionally, language models can generate emotional text when prompted with categorical labels, but such labels collapse rich inter-subject variability into coarse discrete bins. We present EmoMind, the first end-to-end pipeline for decoding affective captions directly from fMRI signals. EmoMind first retrieves a semantically grounded neutral scene description from brain-decoded visual features, then rewrites it using a continuous 34-dimensional emotion vector decoded from the same fMRI recording. To control the balance between content preservation and affective expression, we train the rewriter with classifier-free guidance against an identity-preserving null branch, enabling smooth interpolation between semantic fidelity and affective expressivity. We evaluate affective caption generation with a three-axis validation framework spanning subject-specificity, structural geometry, and causal control. We further augment this framework with a synthetic-brain substitution test that probes robustness to the measurement apparatus, and we benchmark each axis against GPT-4 prompted with brain-decoded top-5 emotion labels as a strong discrete baseline. Across two independent emotion fMRI datasets, EmoMind significantly outperforms label-prompted GPT-4 on all three axes, with the largest gains on metrics that require person-specific affective structure rather than population-level emotion aggregation. These results establish continuous brain-decoded affect as a viable control signal for individualized affective caption generation and open new directions for studying individual affective brain organisation.

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

Spatially Masked Regression Reveals Local and Distributed Predictability in Electrophysiological Recordings

arXiv:2606.11415v1 Announce Type: cross Abstract: Neural recordings are often interpreted as local measurements, yet the signal at any one sensor can also reflect structured activity distributed across the broader network. This raises a basic question: to what extent does an electrode's signal reflect local versus distributed information in the underlying system? More specifically, how much of an electrode's activity is carried by its immediate neighborhood, and how much is embedded more broadly across the array? We address this with a Spatially Masked Regression (SMR) framework that reconstructs each electrode's timeseries from the remaining electrodes while excluding a configurable neighborhood around the target. By progressively increasing this mask, spatial locality becomes an experimental control for quantifying how much predictive information survives after nearby channels are withheld. We apply SMR to intracranial EEG with heterogeneous electrode coverage and to scalp EEG with standardized montages over sensorimotor cortex. Using distance correlation between original and reconstructed signals, we find strong within-subject reconstruction in both modalities, substantial residual predictability even when local neighbors are excluded, and markedly stronger cross-subject transfer in EEG than in iEEG. Masking shows that nearby electrodes contribute strongly to reconstruction but do not account for all of it, indicating that individual channels reflect both local redundancy and broader distributed structure. Surrogates that preserve selected marginal or spectral properties while disrupting phase structure or temporal ordering substantially reduce performance, supporting the conclusion that SMR depends on structured temporal and cross-channel organization rather than on marginal statistics alone. These results position SMR as an interpretable framework for quantifying the balance between local and distributed information in recordings.

09.
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.

10.
arXiv (math.PR) 2026-06-24

Random sequential nearest-neighbor coloring on trees

arXiv:2606.24793v1 Announce Type: new Abstract: We study a nearest-neighbor coloring process in which vertices are revealed in random order and inherit the color of the closest vertex revealed before them. This model is a discrete analogue of coloring processes previously studied by Preater (2009) and Aldous (2018) in Euclidean spaces. We focus here on regular trees and analyze the associated genealogy of color inheritance. In contrast with the Euclidean case, the genealogical graph on an infinite regular tree is not connected: it has infinitely many infinite one-ended components, each with a distinct asymptotic direction, while every vertex has only finitely many descendants. We also describe how this structure is modified in the presence of finitely many initial seeds. Finally, we study local limits of the coloring on finite regular trees as their height tends to infinity, for two natural seed configurations: two fixed seeds, and one blue seed at the root with red seeds at the leaves.

11.
bioRxiv (Bioinfo) 2026-06-11

Integrating Spatially Adjusted Protein Summaries for Survival Prediction in Spatial Proteomics

Recent advances in spatial proteomics, particularly imaging mass cytometry, enable the measurement of protein expression at the single-cell level while preserving a spatial context. Conventional survival analyses, however, typically rely on patient-level averages of protein intensities and therefore overlook spatial heterogeneity and tissue architecture. To address this limitation, we introduce a framework that incorporates spatial information into survival modeling by generating spatially adjusted protein summaries (SAPS). In this approach, cell-level protein intensities within each patient are modeled using spatial spline regression to capture spatial trends. From these models, we extract two complementary features: a spatially adjusted mean expression and a residual variance that reflects cell-to-cell variability unexplained by spatial effects. These summaries are then incorporated into Cox proportional hazards models in combination with clinical covariates. In simulation studies, our proposed framework achieved improved predictive performance compared to other alternative methods. The application of the method to breast cancer imaging mass cytometry data indicate that spatially adjusted summaries may enhance survival prediction and reveal biologically interpretable spatial protein patterns, suggesting high translational potential. This methodology offers an efficient means of translating complex spatial proteomics data into patient-level features, providing both improved survival prediction and new insights into the role of spatial heterogeneity in cancer outcomes.

12.
medRxiv (Medicine) 2026-06-10

Impact of Early Treatment on Symptom Improvement and Procedural Events among Men with BPH and Bothersome Lower Urinary Tract Symptoms: A Contemporary Analysis of the American Urological Association Quality (AQUA) Registry

PURPOSE: As the armamentarium of BPH therapies continues to expand, it remains imperative to maximize patient satisfaction and minimize decisional regret. We sought to determine the impact of time from BPH diagnosis to index treatment on symptom improvement and subsequent procedural events. MATERIALS AND METHODS: We queried the American Urological Association Quality Registry for men [&ge;] 40 years old with BPH, available IPSS data, and no receipt of prior BPH treatment. Index treatment included medication, surgery, or minimally invasive surgical therapy (MIST). Outcomes included IPSS over 3 years of follow-up, change in percentage of mild lower urinary tract symptoms (LUTS) by 3 months, and time to procedural event. Patients were stratified by time from index diagnosis to treatment by 3 years. Outcomes were compared across time-to-treatment cohorts with appropriate statistical tests with p < 0.05 as significant. RESULTS: 43,919 patients met criteria with 19,642 pursuing treatments. Patients pursued treatment at comparably lower baseline IPSS compared to prior prospective series. Patients undergoing surgery and MIST had significantly higher baseline IPSS, while medical comorbidities were significantly more common among men initiating pharmacotherapy. Early surgery and MIST were associated with significant improvement in IPSS within 6-12 months and an increase in mild LUTS by 3 months. All forms of early treatment were associated with delayed time to procedural events, including catheterization and fulguration. CONCLUSIONS: Early procedural intervention for BPH is associated with early symptom improvement and delayed time to procedural events among real-world, contemporary practice.

13.
Nature (Science) 2026-06-24

Long-sought chemical inhibitors of β-arrestin proteins

作者: 未知作者

Proteins called β-arrestins regulate signalling through members of the G protein-coupled receptor (GPCR) superfamily. Small molecules that bind directly to the β-arrestins and inhibit their activities are the first chemical tools to probe their biology, opening avenues for transducer-targeted, pathway-specific GPCR therapeutics. Three small molecules disrupt the engagement of β-arrestins with G-protein-coupled receptor proteins.

14.
arXiv (CS.LG) 2026-06-16

TriAdReview: Triangular Adversarial Review Architecture for Multi-Model Technical Document Generation

arXiv:2606.15074v1 Announce Type: new Abstract: Large language models (LLMs) are increasingly used for technical document generation, yet single-model outputs often suffer from over-engineering, security blind spots, and incomplete coverage. We propose TriAdReview, a triangular adversarial review architecture that employs two independent reviewer models (engineering and boundary perspectives) and a triangular judging mechanism to iteratively improve a generator model's output. We evaluate TriAdReview across five benchmark tasks - architecture design, code generation, proposal review, security audit, and requirements analysis - using three configurations: single model (baseline), dual model (single review), and triple model (full system). Results across 75 experiments (n=5 per cell) show that the triple model configuration achieves a 10.1% overall improvement over the single model baseline (26.2 vs. 23.8 out of 50; p

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

ShapeBench: A Scalable Benchmark and Diagnostic Suite for Standardized Evaluation in Aerodynamic Shape Optimization

arXiv:2605.20763v2 Announce Type: replace Abstract: Rapid progress in aerodynamic shape optimization (ASO) has outpaced currently-available standardized evaluation frameworks. Fair comparison requires a unified benchmark spanning diverse shape classes, objective formulations, and matched-budget state-of-the-art baselines. We introduce ShapeBench, an open-source ASO benchmark with a unified API spanning 103 tasks across eight shape categories and multiple optimization regimes. Each ShapeBench task includes a validated surrogate for fast search; when feasible, a high-fidelity Computational Fluid Dynamics (CFD) pipeline for final verification is available, enabling systematic fidelity-gap analysis. ShapeBench provides a reproducible protocol with well-configured baselines to compare fairly using a consistent budget metric, allowing for comparison among both classical and LLM-driven methods, including general-purpose optimizers and a new domain-specialized evolutionary LLM baseline, ShapeEvolve. Results on ShapeBench demonstrate substantial variance in optimizer rankings across shape categories and problem formulations, with mean pairwise Spearman $\rho = 0.013$, so single-task conclusions do not reliably generalize across problem classes. The benchmark is also far from saturation; classical methods are rarely applicable across all shape categories and tasks, further highlighting the need for more general-purpose approaches.

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

Benchmarking Local LLMs for Natural-Language-to-SQL Querying in Biopharmaceutical Manufacturing: An Empirical Benchmark on Consumer-Grade Hardware

Biopharmaceutical manufacturing organizations operate under regulatory frameworks such as FDA guidance, EU Good Manufacturing Practice (GMP), and the EU AI Act, which can restrict the use of cloud-based artificial intelligence systems. Locally deployed large language models (LLMs) offer a privacy-preserving alternative, but their suitability for pharmaceutical manufacturing tasks remains underexplored. This study evaluates four open-source LLMs (Qwen 2.5 Coder 7B, Llama 3.1 8B, Mistral 7B, and Meditron 7B) deployed locally via Ollama for natural-language-to-SQL generation over a pharmaceutical manufacturing database. A FastAPI-based evaluation platform, PharmaBatchDB AI, was developed using a synthetic Microsoft SQL Server database containing approximately 63,000 records across Batch, Manufacturing Execution System (MES), and Clean-In-Place (CIP) modules. Models were benchmarked on 60 domain-specific natural-language questions using metrics including SQL extraction rate, SQL compliance, factual consistency, ROUGE-L, hallucination rate, throughput, and latency. Qwen 2.5 Coder 7B, Llama 3.1 8B, and Mistral 7B generated SQL for all evaluation tasks, while Meditron 7B failed on nearly all tasks due to context-window limitations and poor SQL generation capability. Llama 3.1 8B achieved the highest SQL compliance, whereas Qwen 2.5 Coder 7B achieved the strongest overall text similarity and factual consistency. Performance differences between the two leading models were not statistically significant. The results show that code-tuned general-purpose LLMs outperform a domain-specific biomedical model on structured query generation for pharmaceutical manufacturing data. Although fully local, GxP-aligned NLQ systems are feasible on consumer hardware, current performance levels still require human oversight and downstream validation for regulated use.

17.
arXiv (quant-ph) 2026-06-25

Arbitrarily Loss-Tolerant Quantum Position Verification in a Single Execution

arXiv:2606.25037v1 Announce Type: new Abstract: Quantum position verification (QPV) seeks to certify the spatial location of an untrusted prover, but is challenged fundamentally by entanglement-based attacks and experimentally by photon loss. Both issues were addressed separately in different works and were simultaneously resolved for sequentially repeated protocols in Phys.\ Rev.\ Lett.\ 135,~260801 via a commitment-based modification that renders security independent of transmission losses. However, single-execution protocols are preferable in practice, and the original techniques do not extend to the parallel setting due to their reliance on sequential structure. We overcome this by utilizing different techniques based on no-signalling correlations, lifting the commitment modification to the parallel regime while preserving the security guarantees of the underlying QPV protocol. Applying this to a BB84-based QPV protocol suitable for near-term implementation and secure against bounded-entanglement adversaries, we prove that fixing a threshold~$k$ on the number of successfully committed qubits yields an adversarial acceptance probability that decays exponentially in~$k$. The resulting protocol maintains robustness to noise levels of up to~$3.7\%$ and remains secure under arbitrarily slow quantum communication, as does the original protocol. This yields the first fully loss-tolerant single-shot QPV protocol secure against entangled attackers, making QPV feasible over arbitrary distances. Finally, we refine the sequential analysis and obtain improved quantitative parameters for experimental implementations.

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

OrthoTrack: Continuous 6-DoF UAV Trajectory Estimation Anchored in Public Orthophotos

Continuous 6-DoF pose estimation is essential for autonomous UAV operations. Yet, existing visual odometry and SLAM methods accumulate drift and yield only relative, up-to-scale trajectories. Single-frame geo-localization, in turn, discards temporal continuity and remains too slow for real-time use. We present OrthoTrack, a training-free system that estimates continuous 6-DoF UAV trajectories using only publicly available orthophotos and surface models as a map prior. OrthoTrack matches keyframes against the orthophoto and lifts correspondences to metric 3D via the surface model. It then propagates these map-anchored correspondences to intermediate frames with optical flow, producing absolute, metrically scaled poses at every frame without GPS or post-hoc alignment. We also introduce the MovingDrone Dataset, a large-scale benchmark pairing photorealistic UAV sequences with dense 6-DoF ground truth and co-registered multi-modal geodata including multi-temporal orthophotos. On MovingDrone and real-world benchmarks, OrthoTrack runs in real time on a single GPU. It outperforms all baselines by a large margin, even those receiving oracle scale and alignment. By relying on publicly available geodata, OrthoTrack enables deployment to new regions without site-specific adaptation.

19.
arXiv (CS.AI) 2026-06-15

STaR-DRO: Stateful Tsallis Reweighting for Group-Robust Structured Prediction

arXiv:2604.09737v2 Announce Type: replace-cross Abstract: Structured prediction with large language models requires outputs that are label-accurate, ontology-constrained, structurally valid, and evidence-grounded under label imbalance and heterogeneous group difficulty. We present a unified framework for ontology-constrained generation. First, we introduce a modular prompt-engineering architecture combining XML-style structure, expert disambiguation rules, chain-of-thought reasoning, metadata-aware decision logic, schema contracts, and a self-validation gate. It targets recurrent in-context failures, including format drift, label ambiguity, evidence hallucination, and metadata-conditioned confusion. Second, we propose STaR-DRO, combining Tsallis mirror ascent, sparse entmax-style primal mapback, EMA-smoothed group-loss tracking, rescaled ascent signals, and bounded excess-only multipliers. Unlike conventional DRO, which relies on dense Shannon-entropy exponentiated-gradient updates, can introduce high-variance stochastic reweighting, assigns positive adversarial mass to groups that are not persistently hard, and incurs costs through simplex competition, STaR-DRO upweights only persistently hard groups without suppressing easier ones. We evaluate the framework on EPPC Miner, a clinically grounded high-stakes structured-prediction task requiring hierarchical label prediction and evidence-span extraction from patient-provider secure messages. Across 1B-70B Llama models, prompt engineering improves zero-shot extraction, yielding an average label F1 gain of +14.46 and a Span F1 gain of +17.40. Building on supervised fine-tuning, STaR-DRO further improves accuracy and robustness, increasing average label F1 by +1.08 and +2.20 while reducing mean groupwise validation cross-entropy by 21.3% and 14.8% relative to SFT and standard DRO, respectively. These results advance reliable automated communication mining for patient-centered clinical care analysis.

20.
PLOS Computational Biology 2026-06-12

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

作者:

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

21.
arXiv (CS.LG) 2026-06-17

Variational autoencoders with latent high-dimensional steady geometric flows for dynamics

arXiv:2410.10137v5 Announce Type: replace Abstract: We develop Riemannian approaches to variational autoencoders (VAEs) for PDE-type ambient data with regularizing geometric latent dynamics, which we refer to as VAE-DLM, or VAEs with dynamical latent manifolds. We redevelop the VAE framework such that manifold geometries, subject to our geometric flow, embedded in Euclidean space are learned in the intermediary latent space developed by encoders and decoders. By tailoring the geometric flow in which the latent space evolves, we induce latent geometric properties of our choosing, which are reflected in empirical performance. We reformulate the traditional evidence lower bound (ELBO) loss with a considerate choice of prior. We develop a linear geometric flow with a steady-state regularizing term. This flow requires only automatic differentiation of one time derivative, and can be solved in moderately high dimensions in a physics-informed approach, allowing more expressive latent representations. We discuss how this flow can be formulated as a gradient flow, and maintains entropy away from metric singularity. This, along with an eigenvalue penalization condition, helps ensure the manifold is sufficiently large in measure, nondegenerate, and a canonical geometry, which contribute to a robust representation. Our methods focus on the modified multi-layer perceptron architecture with tanh activations for the manifold encoder-decoder. We demonstrate, on our datasets of interest, our methods perform at least as well as the traditional VAE, and oftentimes better. Our methods can outperform this and a VAE endowed with our proposed architecture, frequently reducing out-of-distribution (OOD) error between 15% to 35% on select datasets. We highlight our method on ambient PDEs whose solutions maintain minimal variation in late times. We provide empirical justification towards how we can improve robust learning for external dynamics with VAEs.

22.
arXiv (CS.CL) 2026-06-19

SAGE-OPD: Selective Agent-Guided Intervention for Multi-Turn On-Policy Distillation

On-policy distillation (OPD) improves student models by training them on trajectories induced by their own policy, making it a promising approach for mitigating exposure bias in agent training. However, most OPD studies focus on single-turn settings, while realistic LLM agents interact with environments over multiple turns. In this regime, early errors can alter future observations and compound across the trajectory, and standard dense token-level OPD becomes brittle, as it may over-penalize semantically valid alternatives, reinforce local degeneracies such as repeated actions, and propagate unreliable teacher supervision on off-distribution histories. We propose SAGE-OPD, a verifier-free selective intervention framework specifically designed for multi-turn OPD. Instead of applying teacher supervision uniformly across all turns, SAGE-OPD first observes environment feedback and uses teacher judgment to decide whether each student response should be skipped or intervened on. To further address compounding errors, SAGE-OPD weights token-level distillation by teacher confidence, reducing the influence of uncertain teacher distributions on corrupted or ambiguous histories. Finally, SAGE-OPD applies loss normalization to preserve the overall loss scale of standard OPD while retaining selective turn-level weighting. Experiments on agent tasks show that SAGE-OPD consistently improves over baselines, achieving up to a 13.3% relative improvement in ALFWorld unseen success rate over standard OPD. Ablation studies further demonstrate that turn-level intervention, teacher confidence weighting, and loss normalization provide complementary benefits. Our results suggest that effective multi-turn OPD should remain on-policy, but teacher supervision should be selectively allocated to turns where intervention is necessary and reliable.

23.
arXiv (CS.CL) 2026-06-12

If LLMs Have Human-Like Attributes, Then So Does Age of Empires II

Much research has been carried out on large language models (LLMs) and LLM-powered agentic workflows. However, many works within the field state emergence of, ascribe to, or assume, generalised anthropomorphic attributes to them (e.g., morality or understanding of natural language). Our goal is not to argue in favour or against the existence of these attributes, but to point out that these conclusions could be incorrect. For this we build and train a simple neural network on the videogame Age of Empires II, and note that any entity in a sufficiently-powerful substrate, such as LEGO or the Greater Boston Area, could also present such attributes. Hence, the purported anthropomorphic attributes of LLMs are empirically non-unique: although some properties (e.g., responses to prompts) could remain invariant, others, such as the interpretation of their perceived behaviour, might change with the substrate. Thus, any empirically-grounded discussion on these attributes requires explicit measurement criteria; otherwise the interpretation is left to the representation. We then show that assuming that these attributes exist or not in a system, independent of the substrate and in a generalised way, leads to either circular or uninformative conclusions. This is regardless of the experimenter's viewpoint on the subject, or whether the outcome shows existence or non-existence. Finally we propose a 'null' assumption, where one assumes LLM non-uniqueness instead of assuming anthropomorphic attributes to set up an experiment, along with examples of it. We also discuss potential objections to our work, briefly survey the field, and prove that Age of Empires II is functionally- and Turing-complete.

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

Pretraining A Large Language Model using Distributed GPUs: A Memory-Efficient Decentralized Paradigm

Pretraining large language models (LLMs) typically requires centralized clusters with thousands of high-memory GPUs (e.g., H100/A100). Recent decentralized training methods reduce communication overhead by employing federated optimization; however, they still need to train the entire model on each node, remaining constrained by GPU memory limitations. In this work, we propose SParse Expert Synchronization (SPES), a memory-efficient decentralized framework for pretraining mixture-of-experts (MoE) LLMs. SPES trains only a subset of experts per node, substantially lowering the memory footprint. Each node updates its local experts and periodically synchronizes with other nodes, eliminating full-parameter transmission while ensuring efficient knowledge sharing. To mitigate limited per-expert data utilization under sparse expert updates, we introduce an expert-merging warm-up strategy, where experts exchange knowledge early in training, to rapidly establish foundational capabilities. With SPES, we train a 2B-parameter MoE LLM using 16 standalone 48GB GPUs over internet connections, which achieves competitive performance with centrally trained LLMs under similar computational budgets. We further demonstrate scalability by training a 7B model from scratch and a 9B model upcycled from a dense checkpoint, both of which match prior centralized baselines. Our code is available at https://github.com/zjr2000/SPES.

25.
arXiv (CS.AI) 2026-06-15

FAConformer: Frequency-Aware Convolutional Transformer for Auditory Attention Decoding

arXiv:2606.14120v1 Announce Type: cross Abstract: Auditory attention decoding (AAD) aims to infer the attended speaker from neural responses in multi-speaker acoustic environments and is a key problem for neuro-steered hearing systems. Although recent studies have achieved encouraging progress, existing AAD models still do not fully exploit frequency domain electroencephalography (EEG) information. In particular, most approaches introduce multi-band information through handcrafted feature extraction or direct cross-band feature concatenation, which mainly exploit frequency information at a shallow level and may overlook band-specific patterns and cross-band interactions. To address these limitations, this paper proposes FAConformer, a frequency-aware CNN-Transformer framework for AAD that explicitly integrates band-specific encoding and adaptive cross-band interaction. Specifically, FAConformer first decomposes EEG signals into multiple frequency bands and assigns each band to an independent CNN-Transformer encoder for band-specific modeling. The resulting band-wise features are then adaptively fused by a carefully designed frequency-aware attention (FAA) module that models cross-band dependencies by treating band-wise features as tokens. Further, band-wise auxiliary supervision (BAS) is introduced to prevent weakly contributing branches from being under-optimized during joint training. In this way, FAConformer performs frequency-aware modeling that more effectively exploits frequency domain information. Extensive experiments on two public AAD datasets with three decision-window lengths demonstrated that FAConformer consistently outperformed 12 competitive baselines, surpassing the current state-of-the-art model by 4.9%. Further analyses of band importance, ablation, and parameter sensitivity verify the effectiveness, robustness, and interpretability of the proposed framework. Code is available at https://github.com/wzwvv/FAConformer.