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01.
arXiv (CS.CL) 2026-06-12

IVIE: A Neuro-symbolic Approach to Incremental and Validated Generation of Interactive Fiction Worlds

Computational creativity in Interactive Fiction faces a fundamental tension: Large Language Models (LLM) may produce creative narratives but struggle with world coherence, while symbolic systems ensure consistency but lack creative flexibility. We present IVIE (Incremental & Validated Interactive Experiences), a neuro-symbolic approach to generating complete and playable interactive fiction worlds from scratch. Building upon PAYADOR's neuro-symbolic framework, IVIE implements a four-stage incremental generation pipeline that delegates creative decisions–setting and character creation, puzzle design–to LLMs while grounding the world state through symbolic validation. The system generates worlds with interconnected locations, functional items, non-player characters, and coherent puzzles, all structured around a central goal-oriented architecture. Human evaluation shows the approach generates immersive, thematically coherent worlds with high player engagement. Results seem to indicate that the neuro-symbolic approach successfully balances flexibility with narrative coherence: symbolic validation grounds LLM generation without eliminating generative freedom. However, challenges remain: LLM inconsistencies occasionally bypass puzzle constraints, and objective validation gaps allow some structurally impossible goals. We identify key design considerations for future neurosymbolic interactive storytelling systems, particularly regarding LLM capabilities and their limitations.

02.
arXiv (CS.LG) 2026-06-11

A Multi-Modal Sensor Fusion Instrument for Measuring Regional Human Mobility: The Distributed Human Data Engine (DHDE)

arXiv:2603.21639v2 Announce Type: replace-cross Abstract: Accurately estimating human mobility in peripheral regional economies presents a fundamental measurement challenge: physical ground-truth sensors are sparse, behavioral intent signals are heterogeneous, and environmental friction introduces systematic bias into demand inference. We introduce the Distributed Human Data Engine (DHDE), a multi-modal sensor fusion architecture that addresses this challenge by integrating physical instrumentation (Edge-AI cameras), digital intent signals (route search impression metrics), behavioral records (90,350 spending records, 97,719 standardized survey responses), and meteorological data across four geographically distributed nodes in Fukui, Japan. The primary measurement-science contribution is the design, deployment, and cross-node validation of the DHDE as a sparse-sensor compensation instrument: a heterogeneous sensor fusion architecture that anchors non-stationary digital intent signals to concurrent physical ground-truth counts, correcting for systematic bias introduced by meteorological planning friction. The instrument is implemented as an ensemble inference pipeline (Random Forest and Ordinary Least Squares with Newey-West robust inference), calibrated across 397 daily observations and validated by chronological holdout replication across four geographically distinct node types. The primary OLS specification achieved an in-sample explanatory power of R2 = 0.810 and a chronological out-of-sample predictive performance of R2 = 0.683. Results identify an Under-Vibrancy Paradox where macro-regional visitor satisfaction correlates positively with crowd density (Spearman rank correlation rs = +0.150, p = 0.002). We estimate an annual proxy gap of 865,917 intent-implied visits, corresponding to JPY 11.96 billion (USD 72.6 million) in foregone revenue.

03.
PLOS Computational Biology 2026-06-05

StPedf: Cell trajectory inference of spatial transcriptomics via spatial proximity embedding and spatial density-adaptive fusion

Authors:

by Yuan Zhang, Ziyan Sun, Zhixin Shi, Mengdi Nan, Yuhan Fu, Qing Ren, Jie Gao Spatial transcriptomics is transforming our multidimensional understanding of cellular spatial organization and its functional mechanisms in processes such as development and disease by systematically resolving the spatial heterogeneity of gene expression within tissues. To delve deeper into the dynamic processes underlying spatial expression patterns, spatial trajectory inference integrates genetic and spatial information to reconstruct the spatial developmental trajectories of cells within tissues. This approach reveals the patterns of differentiation and dynamic changes as cellular states evolve continuously along spatial axes. However, existing methods often struggle to uniformly model the complex, nonlinear interactions between high-dimensional gene expression and spatial coordinates. Here, we introduce StPedf, whose core lies in employing a neural network with a masking mechanism to capture complex nonlinear interactions between high-dimensional genes and spatial positions. It further leverages spatial proximity information as a guiding cue, dynamically and adaptively adjusting the embedding of gene and spatial information and the weighting of spatial proximity information based on spatial density. This enables trajectory inference guided by spatial information. This enables optimal transport to derive intercellular transition matrices, reconstruct cellular differentiation trajectories, and construct pseudo-spatiotemporal maps. StPedf demonstrates superior performance over existing methods on five structurally distinct simulated datasets. Using StPedf, we successfully mapped distinct lineages in the spatial trajectories of telencephalon regeneration in the Ambystoma mexicanum, multiple malignant lineages expanding within primary tumors, and developmental spatial trajectories and pseudo-spatiotemporal maps in human dorsolateral prefrontal cortex (DLPFC). StPedf significantly enhances the accuracy and interpretability of spatial trajectory inference, providing critical technical support for revealing the dynamic patterns of cellular fate transitions within tissue microenvironments.

04.
arXiv (CS.CV) 2026-06-19

SSD: Spatially Speculative Decoding Accelerates Autoregressive Image Generation

Autoregressive models excel in visual generation by treating images as 1D sequences of discrete tokens, mirroring language modeling. However, this flattening discards the intrinsic 2D spatial locality of visual signals, creating severe computational bottlenecks during inference. We introduce Spatially Speculative Decoding (SSD), a framework that aligns the predictive objective with the natural geometry of images. Rather than predicting only the immediate next token in a 1D sequence, our model simultaneously predicts the adjacent horizontal token and the token directly below it. By capitalizing on this 2D spatial correlation, spatially speculative decoding overcomes the memory wall in visual inference. Our approach accelerates autoregressive image generation by up to 13.3x while maintaining high fidelity on DPG-Bench and GenEval. Our results suggest that respecting the underlying geometry of vision unlocks massive computational efficiencies, paving the way for real-time, high-resolution autoregressive generative models.

05.
bioRxiv (Bioinfo) 2026-06-15

RepGene: Toward a Unified Gene Representation Space Robust to Missing Biological Views

Genes can be described through multiple heterogeneous biological views, including genomic sequence, transcript sequence, protein sequence, textual knowledge, and single-cell expression context, yet existing gene embeddings remain largely modality-specific and difficult to compare or reuse when many views are unavailable. We study a narrower but practically important question: whether pretrained embeddings from these distinct sources can be organized into a shared gene representation interface that remains usable under severe missing-modality conditions. To investigate this question, we introduce RepGene, a lightweight single-branch framework that combines modality adapters, a shared encoder, presence-aware fusion, and self-supervised cross-view objectives to map five biological views into one latent space. Our goal is not to claim a new multimodal learning principle or to establish superiority over all simpler fusion strategies, but to provide an initial technical instantiation for testing whether such a shared interface is feasible in a fixed-feature setting. Under a two-stage protocol in which RepGene is trained self-supervised on frozen upstream embeddings and evaluated by downstream linear probing, we find preliminary evidence that the learned representation is broadly competitive in the full-modality setting and remains informative when only partial modality subsets are observed at inference time. The strongest signal in our study is robustness under missing views: average performance changes are often limited when one modality is removed, and even single-view inference remains non-trivial in the evaluated benchmark regime.These results do not resolve unified biological representation learning, and they should be interpreted in light of incomplete simple-fusion baselines, limited architectural ablation, benchmark dependence, and possible upstream feature exposure. We therefore position RepGene as a feasibility study and a starting point for stronger comparisons, broader benchmarks, and leakage-aware validation.

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

ReMoT: Reinforcement Learning with Motion Contrast Triplets

We present ReMoT, a unified training paradigm to systematically address the fundamental shortcomings of VLMs in spatio-temporal consistency – a critical failure point in navigation, robotics, and autonomous driving. ReMoT integrates two core components: (1) A rule-based automatic framework that generates ReMoT-16K, a large-scale (16.5K triplets) motion-contrast dataset derived from video meta-annotations, surpassing costly manual or model-based generation. (2) Group Relative Policy Optimization, which we empirically validate yields optimal performance and data efficiency for learning this contrastive reasoning, far exceeding standard Supervised Fine-Tuning. We also construct the first benchmark for fine-grained motion contrast triplets to measure a VLM's discrimination of subtle motion attributes (e.g., opposing directions). The resulting model achieves state-of-the-art performance on our new benchmark and multiple standard VLM benchmarks, culminating in a remarkable 25.1% performance leap on spatio-temporal reasoning tasks.

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

Traditional machine learning vs. deep learning from dynamic graph representations of proteins' 3D folds in the task of protein structure classification

arXiv:2605.29228v2 Announce Type: replace Abstract: Protein structure classification (PSC) uses supervised learning to predict a protein's CATH/SCOP(e) class from the protein's sequence or 3D structural feature(s). We already modeled 3D structures as (static) protein structure networks (PSNs), demonstrating the competitiveness of PSN-based features to sequence or direct (i.e. non-network) 3D structural features in the PSC task. More recently, we demonstrated the power of features extracted from dynamic PSNs over features extracted from static PSNs (and thus by transitivity over sequence and direct 3D structural features) in the same task. That dynamic PSN approach used traditional machine learning (ML), combining manual (pre-engineered) features with an off-the-shelf classifier. Here, we evaluate whether automatic deep learning (DL) from the dynamic PSNs yields improvements. Our evaluation on 72 datasets spanning ~44,000 CATH- or SCOPe-labeled dynamic PSNs reveals that in terms of PSC accuracy, traditional ML and DL are (close to) tied for a large majority of the datasets, while DL is on average 10+ times slower. We are the first to evaluate traditional ML vs. DL in the dynamic PSN-based PSC task.

08.
arXiv (quant-ph) 2026-06-15

Nonadiabatic Self-Healing of Trotter Errors in Digitized Counterdiabatic Dynamics

arXiv:2512.22636v2 Announce Type: replace Abstract: Trotter errors in digitized quantum dynamics arise from approximating time-ordered evolution under noncommuting Hamiltonian terms with a product formula. In the adiabatic regime, such errors are known to exhibit long-time self-healing [Phys. Rev. Lett. 131, 060602 (2023)], where discretization effects are effectively suppressed. Here we show that self-healing persists at finite evolution times once nonadiabatic errors induced by finite-speed ramps are compensated. Using counterdiabatic driving to cancel diabatic transitions and isolate discretization effects, we study both noninteracting and interacting spin models and characterize the finite-time scaling with the Trotter steps and the total evolution time. In the instantaneous eigenbasis of the driven Hamiltonian, the leading digital error maps to an effective harmonic perturbation whose dominant Fourier component yields an analytic upper bound on the finite-time Trotter error and reveals the phase-cancellation mechanism underlying self-healing. Our results establish finite-time self-healing as a generic feature of digitized counterdiabatic protocols, clarify its mechanism beyond the long-time adiabatic limit, and provide practical guidance for high-fidelity state preparation on gate-based quantum processors.

09.
arXiv (quant-ph) 2026-06-12

Entanglement Detection by Approximate Entanglement Witnesses

arXiv:2402.14755v2 Announce Type: replace Abstract: The problem of determining whether a given quantum state is separable is known to be computationally difficult. We develop an approach to this problem based on approximations of convex polytopes in high dimensions. By showing that a convex polytope constructed from a finite number of hyperplanes approximates the Euclidean ball arbitrarily well in high dimensions, we find evidence that a finite set of approximate entanglement witnesses is potentially sufficient to determine the entanglement of a state with high probability.

10.
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.

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

AI systems out-persuade expert humans

arXiv:2606.16475v1 Announce Type: cross Abstract: Many societal decisions are settled by contests of persuasion. Conversational AI is a powerful new entrant in these contests, but whether it can out-persuade skilled and highly incentivized humans has remained unclear. Here, in a series of four preregistered experiments (n = 18,978 conversations from 6,923 people), we pitted AI systems against a range of human persuaders, including laypeople, winners of a separately preregistered four-round online persuasion tournament, professional canvassers, and world championship debaters. We found that AI systems were reliably more persuasive than expert humans, even when expert humans chose their issues, researched in advance, underwent hours of live, structured practice, and were incentivized with {\pounds}1,000 cash bonuses. In a follow-up study, AI's advantage persisted after experts received a coaching tool that let them practice against the AI that beat them, review their performance history, and see what AI would have said at key moments. We found converging evidence that AI's advantage stemmed from rapidly deploying larger quantities of information: after coaching, expert humans could tie an AI constrained to respond at human speeds and with human-length messages. In a final study, we show that AI's advantage extends to consequential real-world behavior: AI was nearly 3x more effective than professional canvassers from a UK fundraising firm at raising real-money donations to Save the Children. Together, these results establish that frontier AI systems out-persuade expert humans in conversation, with significant implications for political communication.

12.
arXiv (CS.LG) 2026-06-17

Eigen-Spike Emergence and Quadratic Equivalents for Conjugate Kernels on Nonlinearly Separable Data

arXiv:2605.29669v2 Announce Type: replace-cross Abstract: Recent work in random matrix theory (RMT) has developed the notion of deterministic equivalents: typically linear surrogate models that approximate the spectral behavior of large nonlinear random matrices, such as nonlinear feature maps in neural networks (NNs). Such equivalents make theoretical predictions tractable by reducing a complex model to a simpler one with properties that fall under the umbrella of classical RMT tools. However, this leaves open the question of whether this idealized linear equivalence remains meaningful for classification of high-dimensional nonlinearly separable data. Motivated by this, we consider the conjugate kernel (CK), which is the nonlinear feature map of a one-layer feedforward NN, under a canonical nonlinearly separable dataset for the XOR problem; and we use the study of informative outlier eigenvalues in the CK and whether their corresponding eigenvectors asymptotically align with XOR labels as a proxy for nonlinear learnability. We develop a robust quadratic equivalent of the CK matrix that enables a precise analysis of emergent informative spikes, as one modifies various knobs common in ML practice: sample complexity, signal-to-noise ratio (SNR), nonlinear activation choice, and pretrained features. We identify regimes in which these knobs move the CK beyond the linear equivalent and produce BBP-type transitions to label-aligned outlier eigenspaces. Our analysis helps bring deterministic-equivalence tools from RMT to bear on problems of practical relevance in ML.

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

A theory of learning data statistics in diffusion models, from easy to hard

arXiv:2603.12901v2 Announce Type: replace-cross Abstract: While diffusion models have emerged as a powerful class of generative models, their learning dynamics remain poorly understood. We address this issue first by empirically showing that standard diffusion models trained on natural images exhibit a distributional simplicity bias, learning simple, pair-wise input statistics before specializing to higher-order correlations. We reproduce this behaviour in simple denoisers trained on a minimal data model, the mixed cumulant model, where we precisely control both pair-wise and higher-order correlations of the inputs. We identify a scalar invariant of the model that governs the sample complexity of learning pair-wise and higher-order correlations that we call the diffusion information exponent, in analogy to related invariants in different learning paradigms. Using this invariant, we prove that the denoiser learns simple, pair-wise statistics of the inputs at linear sample complexity, while more complex higher-order statistics, such as the fourth cumulant, require at least cubic sample complexity. We also prove that the sample complexity of learning the fourth cumulant is linear if pair-wise and higher-order statistics share a correlated latent structure. Our work describes a key mechanism for how diffusion models can learn distributions of increasing complexity.

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

Efficient Reinforcement Learning by Guiding World Models with Non-Curated Data

arXiv:2502.19544v3 Announce Type: replace Abstract: Leveraging offline data is a promising way to improve the sample efficiency of online reinforcement learning (RL). This paper expands the pool of usable data for offline-to-online RL by leveraging abundant non-curated data that is reward-free, of mixed quality, and collected across multiple embodiments. Although learning a world model appears promising for utilizing such data, we find that naive fine-tuning fails to accelerate RL training on many tasks. Through careful investigation, we attribute this failure to the distributional shift between offline and online data during fine-tuning. To address this issue and effectively use the offline data, we propose two techniques: i) experience rehearsal and ii) execution guidance. With these modifications, the non-curated offline data substantially improves RL's sample efficiency. Under limited sample budgets, our method achieves nearly twice the aggregate score of learning-from-scratch baselines across 72 visuomotor tasks spanning 6 embodiments. On challenging tasks such as locomotion and robotic manipulation, it outperforms prior methods that utilize offline data by a decent margin.

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

The Benchmark Illusion: Pruned LLMs Can Pass Multiple Choice but Fail to Answer

Compressing large language models reduces memory use and inference cost, but it can also create failures that standard benchmarks miss. A pruned model may still perform well on multiple-choice evaluations, yet fail to answer the same question in open generation. We ask what pruning changes: does it erase the correct answer, or does it make the answer harder to produce as the top output? We study this question with multilingual question answering, tracking the same questions before and after pruning. We find a benchmark illusion. Under high-sparsity pruning, especially Wanda, models often fail in greedy open generation while still selecting the correct answer under multiple-choice scoring. In these recognition-only errors, the answer is usually not gone, but demoted: it often reappears with beam search, sampling, or one in-context example. Overall, multiple-choice benchmarks can overstate the usability of compressed LLMs, creating an evaluation blind spot. Compressed models should be tested on what they can produce, not only on what they can recognize.

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

STREAM: Multi-Tier LLM Inference Middleware with Dual-Channel HPC Token Streaming

arXiv:2606.13968v1 Announce Type: cross Abstract: Researchers and practitioners working with large language models face a fragmented landscape: local models are free and private but hardware limits the model size and context windows a researcher can use; institutional HPC centers offer powerful GPU resources at no marginal cost and keep data within institutional boundaries, but operate behind firewalls and are designed for batch jobs rather than interactive use; commercial cloud APIs provide frontier-model quality on demand but impose significant cost and data retention policies unsuitable for sensitive research data. No existing system unifies all three. STREAM (Smart Tiered Routing Engine for AI Models) addresses this gap with four contributions: (1) a three-tier routing architecture combining local, HPC, and cloud inference with a local LLM-based complexity judge; (2) a dual-channel HPC streaming architecture that separates the Globus Compute control plane (authentication and job dispatch) from a WebSocket relay data plane (token delivery), enabling sub-second TTFT (0.54 s median, 21.1x over batch mode's 11.40 s) through institutional firewalls without VPN or firewall rule changes, with end-to-end AES-256-GCM encryption ensuring the relay operator cannot read token payloads; (3) tier-aware context summarization that prevents long conversations from forcing simple queries onto expensive tiers; and (4) an HPC-as-API proxy mode that exposes HPC inference as an OpenAI-compatible endpoint callable from any standard client with no HPC expertise, a deployment pattern made practical only by the sub-second TTFT of contribution (2). Llama 3.2 3B achieves 85.1% free-tier retention on a 1,200-query benchmark spanning ten domains. Measured TTFT: 0.26 s local, 0.54 s HPC (relay), 1.68 s cloud.

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

MedLatentDx: Latent Multi-Agent Communication for Cross-Hospital Rare-Disease Diagnosis

Rare diseases affect over $300$ million patients across more than $7{,}000$ conditions, yet no single hospital encounters enough cases of any one condition for reliable diagnosis. Cross-hospital collaboration could help by allowing a diagnosing institution to use distributed, case-specific diagnostic evidence, but privacy regulations restrict the transmission of identifiable clinical text across institutional boundaries. This setting raises two challenges: existing medical agent systems often rely on textual evidence exchange, while raw latent states such as hidden states and KV caches may still reveal prompt-derived clinical content. We introduce MedLatentDx, a latent multi-agent communication framework in which hospital agents keep private clinical records and retrieved cases local, and send compact latent KV blocks to a host agent for rare-disease diagnosis. MedLatentDx supports two deployment settings: same-backbone hospital agents use latent KV distillation, while hospitals with different LLM backbones use cross-family latent alignment. On CrossRare-Bench, a self-built large-scale rare-disease benchmark with hospital-level partitions, MedLatentDx improves cross-hospital diagnostic performance while reducing reconstructable clinical content relative to raw-latent communication baselines.

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

UniIntervene: Agentic Intervention for Efficient Real-World Reinforcement Learning

arXiv:2606.12372v1 Announce Type: cross Abstract: Human-in-the-loop reinforcement learning (HiL-RL) has emerged as an effective paradigm for real-world robotic manipulation, enabling online policy improvement with human guidance. However, current HiL-RL frameworks remain intervention-intensive, relying on frequent human corrections to redirect the policy out of unproductive exploration, which incurs high labor cost and limits real-world scalability. To address this, we propose UniIntervene, an agentic intervention model that detects unproductive exploration and autonomously recovers the policy toward high-value states, taking over the bulk of interventions from human operators. Specifically, UniIntervene first performs future-conditioned action-value estimation, predicting the latent consequence of the current action and evaluating its induced value, which provides a more stable progress signal. Building on this, a temporal value-risk critic aggregates recent value dynamics and triggers intervention when the estimated value exhibits sustained stagnation or degradation. When intervention is required, UniIntervene retrieves a high-value recovery target from a memory of past intervention episodes and produces executable corrective actions through a goal-conditioned recovery policy. In this way, UniIntervene turns intervention from passive human correction into a value-aware recovery process for efficient real-world RL. Extensive experiments on diverse real-world manipulation tasks demonstrate that UniIntervene improves the average success rate by 8.6% while reducing human interventions by 57% relative to state-of-the-art HiL-RL baselines.

19.
bioRxiv (Bioinfo) 2026-06-11

Pillbox: A Leakage-Aware Foundation-Model Predictor and Lineage-Ceiling Diagnostic for Cancer Drug Response

We present Pillbox, a predictor whose pipeline is audited against the six Asiaee leakage modes with the one residual pathway shown by per-fold ablation to be non-load-bearing on hard splits. Our model combines CpGPT methylation embeddings, CLAMP drug embeddings, and per-fold-fit gene-expression principal components which are fused by Feature-wise Linear Modulation (FiLM)-conditioned graph attention on the STRING v12 protein-protein interaction graph. Then we alpha-ensemble the model against a histogram-based gradient boosting regressor baseline. On GDSC GSE68379 (987 cell lines, 375 drugs) across seeds 42, 7, and 123, the ensemble reaches test R-Squared of 0.78, 0.77, and 0.76 on random, histology-blind, and site-blind splits respectively, with cell-aware lifts above the drug-mean floor of +0.054, +0.060, and +0.037. As a quantitative diagnostic for feature-stack saturation we propose the cross-architecture residual correlation, calibrated against a same-architecture-different-initialization control. On histology-blind splits the cross-architecture value of 0.939 falls short of the same-architecture ceiling of 0.974 by approximately 0.03 in residual correlation, a gap we interpret as the headroom available to architecture choice on top of the current foundation-model representation and consistent with the long-established observation that tissue lineage dominates cell-line drug response. We integrated curated mutation, methylation, and drug-target-expression channels, but these do not improve prediction once foundation-model embeddings are in place. Cross-screen validation against PRISM matches the GDSC-to-PRISM measurement reproducibility ceiling within 0.01 Spearman.

20.
arXiv (CS.LG) 2026-06-18

Not Just How Much, But Where: Decomposing Epistemic Uncertainty into Per-Class Contributions

arXiv:2602.21160v3 Announce Type: replace-cross Abstract: In safety-critical classification, the cost of failure is often asymmetric, yet Bayesian deep learning summarises epistemic uncertainty with a single scalar, mutual information (MI), that cannot distinguish whether a model's ignorance involves a benign or safety-critical class. We decompose MI into a per-class vector $C_k(x)=\sigma_k^{2}/(2\mu_k)$, with $\mu_k{=}\mathbb{E}[p_k]$ and $\sigma_k^2{=}\mathrm{Var}[p_k]$ across posterior samples. The decomposition follows from a second-order Taylor expansion of the entropy; the $1/\mu_k$ weighting corrects boundary suppression and makes $C_k$ comparable across rare and common classes. By construction $\sum_k C_k \approx \mathrm{MI}$, and a companion skewness diagnostic flags inputs where the approximation degrades. After characterising the axiomatic properties of $C_k$, we validate it on three tasks: (i) selective prediction for diabetic retinopathy, where critical-class $C_k$ reduces selective risk by 34.7\% over MI and 56.2\% over variance baselines; (ii) out-of-distribution detection on clinical and image benchmarks, where $\sum_k C_k$ achieves the highest AUROC and the per-class view exposes asymmetric shifts invisible to MI; and (iii) a controlled label-noise study in which $\sum_k C_k$ shows less sensitivity to injected aleatoric noise than MI under end-to-end Bayesian training, while both metrics degrade under transfer learning. Across all tasks, the quality of the posterior approximation shapes uncertainty at least as strongly as the choice of metric, suggesting that how uncertainty is propagated through the network matters as much as how it is measured.

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

SymQNet: Amortized Acquisition for Low-Latency Adaptive Hamiltonian Learning

arXiv:2606.12808v1 Announce Type: cross Abstract: Adaptive Hamiltonian learning is central to calibrating and characterizing quantum devices. In an adaptive controller, choosing the next experiment is itself a computation. Bayesian design rules are recomputed after every posterior update, and that step can take seconds. Across hundreds of shots, those seconds become a significant wall-clock cost for adaptivity. We introduce SymQNet, an amortized reinforcement-learning approach for low-latency adaptive Hamiltonian learning. SymQNet learns a posterior-conditioned acquisition policy offline, then uses a fast policy forward pass online while retaining Bayesian posterior feedback. On transverse-field Ising benchmarks, SymQNet substantially reduces acquisition latency relative to bounded Fisher-information search and bounded two-step Bayesian active learning by disagreement (BALD). At five qubits, it reduces acquisition-only decision latency by $47.1\times$ and $72.6\times$ relative to these online baselines; at twelve qubits, full simulated steps take $1.02$ s for SymQNet versus $13.27$ s for bounded two-step BALD. Overall, we show that learned acquisition can make adaptive Hamiltonian learning practical for repeated low-latency workloads.

22.
medRxiv (Medicine) 2026-06-15

Population-scale genomics reveals divergent pathogenicity of variant classes across paralogous collagen IV genes

Monoallelic pathogenic or likely pathogenic variants in COL4A3 and COL4A4 occur in approximately 1 in 106 individuals, yet whether these paralogous genes confer equivalent pathogenicity for the same variant classes has not been tested at population scale. Using whole-genome sequencing data from the UK Biobank (UKB; n = 500,000), with replication in the All of Us Research Program (n = 414,000), we performed per-variant association testing, gene-based collapsing analyses and phenome-wide association studies (PheWAS) across haematuria, proteinuria and chronic kidney disease. We identified 64 COL4A3 and 92 COL4A4 rare variants significantly associated with haematuria or proteinuria, generating a quantitative allelic series for clinical variant interpretation. Glycine substitutions within collagenous domains conferred similar risks in both genes. In contrast, truncating and non-collagenous domain (NC1) missense variants were strongly associated with haematuria and proteinuria in COL4A4 carriers but showed substantially attenuated or absent associations in COL4A3 carriers despite comparable carrier frequencies and predicted pathogenicity scores. These findings were independently replicated in All of Us. Genome-wide association analysis identified the COL4A3/COL4A4 locus as the dominant genetic determinant of haematuria, with the signal attributable to the aggregate effects of rare coding variants and no evidence of independent common variant or trans-acting modifier effects. These findings demonstrate substantial gene-specific differences in tolerance to truncating and NC1 variants between COL4A3 and COL4A4, challenging assumptions of equivalent pathogenicity across paralogous collagen IV genes. Gene identity and not variant class alone, should inform risk stratification, variant interpretation and genetic counselling in individuals carrying collagen IV risk genotypes.

23.
arXiv (CS.LG) 2026-06-18

ActiTect: A Generalizable Machine Learning Pipeline for REM Sleep Behavior Disorder Screening through Standardized Actigraphy

arXiv:2511.05221v3 Announce Type: replace Abstract: Isolated rapid eye movement sleep behavior disorder (iRBD) is a major prodromal marker of $\alpha$-synucleinopathies, often preceding the clinical onset of Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. While wrist-worn actimeters hold significant potential for detecting RBD in large-scale screening efforts by capturing abnormal nocturnal movements, they become inoperable without a reliable and efficient analysis pipeline. This study presents ActiTect, a fully automated, open-source machine learning tool to identify RBD from actigraphy recordings. To ensure generalizability across heterogeneous acquisition settings, our pipeline includes robust preprocessing and automated sleep-wake detection to harmonize multi-device data and extract physiologically interpretable motion features characterizing activity patterns. Model development was conducted on a cohort of 78 individuals, yielding strong discrimination under nested cross-validation (AUROC = 0.95). Generalization was confirmed on a blinded local test set (n = 31, AUROC = 0.86) and on two independent external cohorts (n = 113, AUROC = 0.84; n = 57, AUROC = 0.94). To assess real-world robustness, leave-one-dataset-out cross-validation across the internal and external cohorts demonstrated consistent performance (AUROC range = 0.84-0.89). A complementary stability analysis showed that key predictive features remained reproducible across datasets, supporting the final pooled multi-center model as a robust pre-trained resource for broader deployment. By being open-source and easy to use, our tool promotes widespread adoption and facilitates independent validation and collaborative improvements, thereby advancing the field toward a unified and generalizable RBD detection model using wearable devices.

24.
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.

25.
arXiv (math.PR) 2026-06-15

Trivariate Hypergeometric Series Formulas for Pure Partition Functions of Multiple $3$-SLE$_\kappa$

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arXiv:2606.14038v1 Announce Type: new Abstract: Pure partition functions of multiple SLE are characterized by null-state partial differential equations, Möbius covariance, and boundary asymptotics. After quotienting by Möbius covariance, the case of three curves is the first genuinely multivariable one: the moduli space has three independent variables, naturally represented by the three unoriented cross-ratios of the three pairs of links. We solve this Möbius-normalized three-variable problem for the two basic link-pattern types of multiple \(3\)-SLE\(_\kappa\), namely the rainbow and neighbor patterns. Writing \(\beta=4/\kappa\), we construct explicit trivariate hypergeometric-series normal forms and identify them with the corresponding pure partition functions for all \(\beta>1/2\) in the rainbow case and all \(\beta\ge2/3\) in the neighbor case. Equivalently, these ranges are \(\kappa\in(0,8)\) and \(\kappa\in(0,6]\), respectively. The proof is analytic. The null-state PDEs and Möbius covariance yield recursion relations for the trivariate coefficient arrays. In the rainbow case, coefficient estimates give convergence and boundary regularity on the closed cube. In the neighbor case, Pfaff systems continue the local power series to a neighborhood of \([0,1)^3\), while side-face equations, regular normal estimates, and corner propagation give continuity on \([0,1]^3\) for \(\beta\ge2/3\). The endpoint \(\beta=2/3\), corresponding to \(\kappa=6\), requires a logarithmic normal term. The two-dimensional boundary degenerations are classical Appell \(F_1\) and Horn \(G_2\) functions. The probabilistic identification uses SLE martingale arguments and Itô calculus, together with positivity and boundary regularity. We also discuss boundary degenerations, including heuristic connections with boundary Green's functions.