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

A Decision-Theoretic View of Test-Time Training: When, How Far, and Which Directions to Adapt

arXiv:2606.15569v1 Announce Type: new Abstract: Test-time training (TTT) adapts a pretrained model to each prompt via parameter updates, improving accuracy under pretraining-to-test distribution shifts. Yet, its performance often suffers from instability and sensitivity to hyperparameters such as update steps and subspace. We explain this behavior through a decision-theoretic lens, treating TTT as implicit Bayesian inference in the kernel regime. Under a Gaussian process benchmark, we show that TTT reduces prediction error when updates are spectrally matched to the prompt's signal-to-noise ratio and aligned with query-relevant eigen-directions. This perspective underpins the following results: (1) we show when fixed update steps and subspaces fail under distribution shifts, motivating adaptive strategies; (2) we prove that selecting update steps via prompt evidence admits a PAC-Bayes guarantee against overfitting; and (3) we characterize the Bayes-optimal update subspace under a linear-Gaussian correction model, yielding a scoring rule for selecting Transformer blocks and heads. Our theory helps explain the empirical instability of TTT, taking a step toward principled guidance for when, how far, and which directions to adapt.

02.
arXiv (CS.CL) 2026-06-12

Influcoder: Distilling Decoders' Gradient Influence Rankings into an Encoder for Data Attribution

With the growth of LLMs' (Large Language Models) capabilities, there has been an increasing push to curate high quality datasets by filtering samples in the training data. In general, Data Attribution (DA) methods aim to estimate how individual samples in a training dataset can precondition a model to generate certain outputs. As an example, one might be interested in which samples in the data could be the source of toxic behavior after training the LLM. Many methods quantify this conditioning through the paradigm of influence functions. While methods of this family are effective in its function, they lack the necessary processing speed and storage compactness to be practically implemented on large datasets. We propose a method, Influcoder, as a quick and cost-effective approach to influence-based Data Attribution at scale.

03.
arXiv (CS.AI) 2026-06-15

A Two-Stage Statistical Framework for Evaluating Associative Interference in Large Language Models

arXiv:2606.14117v1 Announce Type: cross Abstract: Large language models (LLMs) are increasingly evaluated for bias using adaptations of human psychological paradigms, yet methodological limitations-particularly the conflation of refusal behavior with task performance-have hindered clear interpretation. Here, we adapt the Implicit Association Test (IAT) to a controlled, forced-choice framework and introduce a two-stage modeling approach that separates response compliance from task-consistent classification. Across three contemporary LLMs (Claude Sonnet-4, Gemini 2.5 Pro, and GPT-5), we evaluate associative interference, defined as reduced task-consistency in incongruent relative to congruent conditions. While compliance with the structured response format was uniformly high, interference effects varied substantially across models and domains. Claude Sonnet-4 exhibited strong interference in the Gender–Career domain (DeltaP = 0.086, 95% CrI [0.026, 0.173]) and smaller but credible effects in Gender–Science. Gemini 2.5 Pro showed attenuated interference, and GPT-5 exhibited minimal or no detectable interference across domains. These findings demonstrate that IAT-style associative asymmetries are not a universal property of LLMs, but instead depend on model-specific characteristics. By isolating interference from compliance and modeling item-level variability, this study provides a principled framework for evaluating structured response patterns in LLMs. The results highlight the importance of model-specific assessment and suggest that associative interference can be substantially mitigated in modern systems.

04.
arXiv (CS.LG) 2026-06-25

Multi-Stream Temporal Fusion for Financial Fraud Detection

arXiv:2606.25007v1 Announce Type: new Abstract: Financial fraud detection in digital banking requires reasoning over multiple heterogeneous event streams – transactions, login sessions, risk signals – that individually appear benign but collectively reveal fraudulent patterns. We propose the Multi-Stream Fraud Transformer (MSFT), a unified architecture that encodes each event stream with independent Transformer encoders and fuses their representations through configurable mechanisms. We conduct a systematic ablation study comparing five fusion strategies: concatenation, gated fusion, time-aware positional encoding, cross-stream attention, and a full combination. On a large-scale dataset (10M users, 1.5% fraud rate) with 85M parameter models, we demonstrate that (1) sequence models significantly outperform gradient-boosted trees operating on aggregated features (0.74 vs. 0.99 AUROC), (2) per-stream encoding is essential – a single-stream Transformer baseline with matched parameter budget reaches only 0.82 AUROC, an 18-point gap that confirms the multi-stream inductive bias is necessary, (3) time-aware positional encoding achieves the highest discrimination (0.9961 AUROC), (4) gated fusion yields the best precision (0.989) suitable for production deployment, and (5) the risk event stream provides the strongest individual signal contribution. We further validate on proprietary production data from a digital banking platform, showing over 22% relative AUROC improvement over the XGBoost baseline.

05.
medRxiv (Medicine) 2026-06-15

Association of Genetic Liability to Psychiatric Disorders with Peripheral Metabolic Dysregulation

Importance: Individuals with psychiatric disorders face elevated cardiometabolic risk which is linked to increased mortality. The extent to which this reflects shared pathogenesis or the downstream effects of illness and treatment remains poorly understood. Objective: To characterize the direct pleiotropic effects of psychiatric genetic liability on circulating metabolites and aggregate cardiometabolic risk, independent of psychiatric diagnosis and psychotropic medication use. Design: Cohort study. Setting: Mass General Brigham Biobank (MGBB). Participants: MGBB participants with metabolomic profiling, genomic data, and linked electronic health records. Exposures: Genetic liability to nine psychiatric disorders quantified using polygenic risk scores (PRS): attention deficit/hyperactivity disorder (ADHD), anorexia nervosa (ANO), anxiety disorder (ANX), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), PTSD, schizophrenia (SCZ), and substance use disorder (SUD). Main Outcomes and Measures: 249 circulating metabolites and four metabolomic risk scores (MRS) for type 2 diabetes, myocardial infarction, ischemic stroke, and vascular dementia. PRS-metabolite associations were estimated using nested models adjusting for lifetime psychiatric diagnosis and psychotropic medication use. Results: Across 25,290 participants, we identified 604 significant PRS-metabolite associations (Bonferroni p< 1.36 x 10-4), of which 89% persisted after adjustment for lifetime diagnosis and medication use, suggesting that the direct genetic effects on metabolism are largely independent of illness or treatment. PRS for MDD, PTSD, and ADHD showed the most extensive dysregulation, with a transdiagnostic pattern of elevated lipids and systemic inflammation, specifically triglycerides ({beta} = 0.04 to 0.05, all p< 4.4 x10-13) and glycoprotein acetyls ({beta} = 0.05, all p< 2.2 x10-16). Notably, PRS for SCZ and BD showed minimal metabolite dysregulation despite having the strongest association with their target diagnoses. PRS for MDD, PTSD, ADHD, and SUD were associated with increased MRS across cardiometabolic conditions ({beta} = 0.03 to 0.08, all p< 2.1 x10-4). Sensitivity analyses controlling for BMI or excluding participants without any psychiatric history (N: 21,305 and 11,150, respectively) showed a similar pattern. Conclusions and Relevance: Psychiatric genetic liability is associated with systemic metabolic dysregulation independent of illness onset or treatment, supporting a partially pleiotropic basis for psychiatric-cardiometabolic comorbidity.

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

Not All Skills Help: Measuring and Repairing Agent Knowledge

LLM agents can improve without weight updates by accumulating natural-language skills from experience, but current systems entrust every decision about which skills to keep and how to apply them to LLM judgment alone. We argue that this conflates two distinct roles: generating a skill from experience is a creative act that judgment handles well, while deciding whether that skill actually helps requires empirical evidence across many tasks. Measuring per-skill causal contributions via randomized masking, we find that skill libraries exhibit pervasive causal heterogeneity: individual skills routinely help on some task types while hurting on others, yet their opposing effects cancel in aggregate, making them invisible to global curation methods. We propose ASSAY, a framework that separates generation from curation: it computes a per-skill causal attribution on a small development set, restructures the library offline, and suppresses skills with negative predicted effect for each test task. Across seven base models spanning four providers and two benchmarks (AppWorld and tau-bench), ASSAY consistently improves over prior skill-curation approaches. On AppWorld's hardest split, DeepSeek-V3 achieves 69.3% task-goal completion (47.4% relative improvement), a new state of the art among all published methods including weight-tuned approaches. On tau-bench retail, GPT-4.1 improves by 8.7% relative, advancing past o4-mini, o1, and GPT-4.5 on the public leaderboard without any weight modification. Ablation traces the dominant gain to per-task masking, confirming that the bottleneck is matching skills to tasks at inference time, not removing bad skills globally. Code is available at https://github.com/aiming-lab/assay.

07.
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.

08.
arXiv (CS.CL) 2026-06-16

Revisiting the Systematicity in Negation in the Era of In-Context Learning

Understanding the meaning of negated sentences remains one of the challenges for language models, even in the era of large language models (LLMs). We analyze systematicity regarding LLM understanding of negation from two perspectives: behavioral systematicity and representational systematicity. For behavioral systematicity, we confirm that through demonstrations and in-context learning, LLMs can recognize negation expressions and scope within sentences to some extent, but they fail to achieve perfect performance. In particular, the difficulty of the negation scope recognition for models varies depending on the output format. For representational systematicity, we analyze the extent to which function vectors can be robustly constructed from in-context examples for tasks that are essential to understanding negation. The experiments suggest that while function vectors can be composed for negation cue extraction tasks, extracting function vectors for recognizing scope is more challenging.

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

Split-Evolution Quantum Phase Estimation for Particle-Conserving Hamiltonians

arXiv:2604.14921v2 Announce Type: replace Abstract: We present a hardware demonstration and resource analysis of split-evolution quantum phase estimation (SE-QPE) on a Quantinuum System Model H2 quantum computer. SE-QPE is a modification to canonical QPE for particle-conserving Hamiltonians in which controlled time evolution is replaced by CSWAP-based interference between a target register and a reference register. For factorizations of time evolution with a shared eigenbasis, SE-QPE preserves the phase-register outcome distribution of canonical QPE and, unlike with compute–uncompute substitutions, it remains compatible with non-exact eigenstates. The substitution removes controlled-simulation overhead and enables parallel evolution on two registers, reducing the depth of each phase-kickback block. Resource analysis for Trotterized double-factorized chemistry Hamiltonians shows that the substitution becomes increasingly favorable at higher phase powers and combining QPE and SE-QPE implementations can be a useful option. Over a range of FeMoco active spaces, SE-QPE reduces time evolution resources, with asymptotic reductions of about 33% in CX count, 25% in $T$ count, and an asymptotic depth ratio of $3/N$ for CX layers. On Quantinuum H2-2, a four-qubit model ethylene demonstration with explicit inverse QFT and repeated phase-kickback steps up to 8 phase bits yields distinct energies and shows the auxiliary registers provide useful error detection filters.

10.
arXiv (quant-ph) 2026-06-25

Hodge Spectral Surrogates for Topology-Constrained Optimization

arXiv:2606.25194v1 Announce Type: cross Abstract: Topological information is widely used in data analysis, network design, and machine learning, and topological constraints naturally arise when optimizing or generating objects with prescribed homological structure. However, directly controlling Betti numbers and persistent homology is difficult because they are discrete and combinatorial. We propose a differentiable framework for topology-constrained optimization based on Hodge-spectral relaxations of homological constraints and low-pass spectral filters. From soft graphs and soft clique complexes, we construct Hodge-Laplacian-type spectral relaxations that unify graph clique complexes and Vietoris–Rips filtrations of point clouds. In the hard limit, the penalty-regularized ambient operator recovers the ordinary Hodge Laplacian on the active subcomplex, while in the soft regime it serves as a differentiable low-frequency spectral surrogate. Homological information is represented by zero and near-zero modes, and differentiable topological objectives are defined using heat filters, resolvent filters, and polynomial Laplacian moments. For point clouds, we show that the proposed Hodge spectral-filter losses yield more spatially distributed gradients, smoother scale-normalized behavior under persistence-pairing changes, and geometry-aware update directions than persistent-homology-based losses. For graph clique complexes, Laplacian moments control normalized first-Betti-type quantities and can be combined with ordinary graph-feature objectives. We also discuss connections to trace-based normalized Betti-number estimation, polynomial spectral methods, and possible quantum trace estimation.

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

Koshur Diacritizer: A Byte-Level Sequence-to-Sequence Model for Kashmiri Diacritic Restoration

Kashmiri, an Indo-Aryan language written in a modified Perso-Arabic script, frequently omits diacritic marks in digital text, creating ambiguity and challenging downstream NLP applications. We present Koshur Diacritizer, a ByT5-small byte-level sequence-to-sequence model for restoring diacritics in Kashmiri text. To support this task, we release a publicly available dataset of 23.7k aligned undiacritized diacritized Kashmiri sentence pairs. The proposed framework combines script-aware normalization, alignment validation, and skeleton-preserving inference to ensure reliable restoration while maintaining the original base-letter sequence. Experimental results on a held-out test set achieve a DERm of 0.2012 and a WER of 0.2159. Additionally, evaluation by a native Kashmiri linguistic expert yields a mean accuracy of 77.5%. The dataset, model, and source code are publicly released to provide a reproducible baseline for Kashmiri diacritic restoration and future low-resource language research.

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

SHIFT: Semantic Harmonization via Index-side Feature Transformation for Multilingual Information Retrieval

arXiv:2606.18801v1 Announce Type: cross Abstract: With the rapid expansion of massive multilingual corpora, Multilingual Information Retrieval (MLIR) has emerged as a critical technology for global information access. MLIR enables users to retrieve semantically relevant documents from multilingual text collections using a single-language query. However, recent multilingual dense retrieval models often exhibit a strong preference for documents in the same language as the query. This leads to severe language bias, where top-ranked results are dominated by documents of specific languages, even when documents in other languages contain more semantically relevant information. To address this issue, we propose SHIFT, a training-free method applicable in the indexing stage. Specifically, SHIFT utilizes parallel translation pairs to estimate a relative language vector for each target language with respect to a source language. Subsequently, SHIFT corrects the language-specific offset by subtracting this relative language vector from document embeddings during indexing. Our comprehensive evaluation across four MLIR benchmarks and diverse dense retrieval models confirms that SHIFT can effectively mitigate language bias and enhance MLIR performance.

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

LLM Jaggedness Unlocks Scientific Creativity

arXiv:2605.10574v3 Announce Type: replace Abstract: As artificial intelligence advances, models are not improving uniformly. Instead, progress unfolds in a jagged fashion, with capabilities growing unevenly across tasks, domains, and model scales. In this work, we examine this dynamic jaggedness through the lens of scientific idea generation. We introduce SciAidanBench, a benchmark of open-ended scientific questions designed to measure the scientific creativity of large language models (LLMs). Given a scientific question, models are asked to generate as many unique and coherent ideas as possible, with the total number of valid responses serving as a proxy for creative potential. Evaluating 19 base models across 8 providers (30 total variants including reasoning versions), we find that jaggedness manifests both across models and within models. First, in a cross-task comparison between general and scientific creativity, improvements in general creativity do not translate uniformly to scientific creativity, revealing divergent capability profiles across models. Second, at the prompt level, stronger models do not improve uniformly; instead, they exhibit high variability, with bursts of creativity on some questions and limited performance on others. Third, at the domain level, individual models display uneven strengths across scientific subfields, reflecting fragmented internal capability profiles. Finally, we show that this jaggedness can be harnessed. We explore mechanisms of inference-time compute, knowledge pooling, and brainstorming to combine models effectively and construct meta-model ensembles that outperform any single model. Our results position jaggedness not as a limitation, but as a resource, a structural feature of AI progress that, when understood and leveraged, can amplify LLM-driven scientific creativity.

14.
arXiv (CS.CL) 2026-06-19

Reliability without Validity: A Systematic, Large-Scale Evaluation of LLM-as-a-Judge Models Across Agreement, Consistency, and Bias

LLM-as-a-Judge has become the dominant evaluation paradigm for language models, but judge validation in practice relies on exact-match agreement, a metric that does not correct for chance and systematically overstates discriminative ability. We present the largest systematic evaluation of LLM-as-a-Judge to date: 21 judges from nine providers across MT-Bench, JudgeBench, and RewardBench, evaluated under three protocols (agreement, consistency, bias audit) over 118 runs and approximately 541,000 individual judgments. Four findings emerge, consistent across the full cohort, including the April 2026 frontier: kappa deflation between exact match and Cohen's kappa is universal (33–41 pp on MT-Bench), judge rankings shift by up to 14 positions across benchmarks, high test–retest reliability (>0.95) coexists with severe position bias (>0.10) in two production-deployed judges (instantiating a consistency–bias paradox), and verbosity bias is small (

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

SIMMER: Benchmarking Latent Failures in LLM Executable Planning with a World Model

Large language models (LLMs) are increasingly deployed as planners for autonomous agents in household environments. While existing benchmarks evaluate whether LLM-generated plans execute successfully, they overlook a critical type of failure: latent failures. Unlike immediate failures that trigger instant feedback at execution time and enable timely correction, latent failures do not immediately halt plan execution but silently compromise goal achievement. In severe cases, they cause irreversible harm. To address this gap, we introduce SIMMER, a benchmark for evaluating latent failures in LLM planning through a human-curated symbolic world model grounded in the kitchen domain. SIMMER defines a world model comprising 77 actions, 262 unique objects, and approximately 46,800 possible interactions that are semantically realistic, derived from real-world cooking scripts. It then leverages a state machine executor that validates plans against the world model and detects immediate precondition violations, latent hazards, and irreversible failures. Experiments across six LLMs show that even frontier models achieve at most 17% error-free plans. Moreover, up to 56% of plans contain latent failures, the majority of which lead to irreversible consequences. We further demonstrate that explicit state reasoning via counterfactual foresight simulation can reduce latent failures by up to 72% and irreversible cases by up to 75%, suggesting a promising direction for more robust LLM planners.

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

XPR: An Extensible Cross-Platform Point-Based Differentiable Renderer

Point-based differentiable rendering underpins modern 3D reconstruction, novel-view synthesis, and learning-based graphics pipelines, but developing new rendering methods often requires extensive low-level implementation, hardware-specific kernels, and manually written backward passes. This limits rapid prototyping, reproducibility, exploration, and deployment, especially across diverse hardware platforms. This paper presents XPR, an extensible cross-platform framework for point-based differentiable rendering. XPR introduces a high-level programming interface that separates method-specific logic from the shared rendering pipeline, allowing users to implement new methods in a few lines of code. Its pipeline decomposes rendering into modular, statically shaped parallel operations that can be lowered by a cross-platform compiler to GPUs, TPUs, CPUs, and other ML accelerators. We demonstrate implementations of 3DGS, 3DGUT, and LinPrim, with only a few 100s lines of Python code, each of which can be compiled to a range of hardware platforms with the XLA compiler. These results show that XPR enables fast experimentation and portable execution for emerging point-based differentiable rendering systems.

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

Unsupervised Causal Abstractions Discovery

arXiv:2606.19594v1 Announce Type: new Abstract: Causal abstractions formalize when a high-level structural causal model (SCM) captures the interventional behavior of a lower-level SCM. Existing applications of this notion largely follow a hypothesis-testing paradigm: an expert proposes a candidate high-level model and then evaluates if the low-level system implements it. We study the complementary problem of learning a high-level model directly from low-level measurements. Our contributions leverage hypotheses from low-rank causal discovery, and can be summarized as follows: (1) we show that observations generated by a low-rank graph induce latents that form a causal abstraction, (2) we provide identifiability results about these latents, and (3) we propose a practical objective to learn this high-level SCM.

18.
arXiv (CS.AI) 2026-06-24

Inclusive Interactive Collisions for Multi-View Consistent Compositional 3D Generation

arXiv:2606.24206v1 Announce Type: cross Abstract: Recent breakthroughs in 3D generation have advanced notably with the development of text-to-image diffusion model. However, existing methods remain two practical challenges: (1) They primarily generate single 3D object, but struggle to generate multi-object compositional 3D assets due to the lack of the modeling for Gaussian primitives in reasonable interactions. (2) They often suffer from cross-view inconsistency during 3D optimization, as Score Distillation Sampling inherently performs on each single view, inevitably resulting in cross-view hallucinations. To solve above issues, we propose I2C-3D, a novel optimization-based method to generate multi-view consistent compositional 3D assets with reasonable interactions. Specifically, we propose an Inclusive Interactive Collisions strategy to guide Gaussian primitives appearing in reasonable interaction regions naturally, thereby ensuring objects in the compositional scene interact in a physically plausible and visually coherent way. Additionally, to enhance multi-view consistency, Multi-View Adaptive Score Distillation Sampling is devised to distill multi-view consistency prior and layout prior from pre-trained diffusion model by modulating attention map of instance token and spatial token across viewpoints. Benefiting from above elaborate designs, I2C-3D not only generates high-fidelity multi-view consistent compositional 3D assets but also supports 3D editing flexibly, facilitating complex scene generation. Extensive experiments demonstrate our I2C-3D outperforms existing methods in generation quality and multi-view consistency.

19.
Nature Medicine 2026-06-17

Why large-scale randomized trials of live-attenuated shingles vaccination for dementia prevention are urgently needed

In my view, we have never had as robust a body of evidence from observational data on an intervention for dementia as we do for live-attenuated shingles vaccination. Both a recent US National Institutes of Health expert workshop and an international expert consensus on Alzheimer’s disease drug repurposing identified large-scale randomized trials of shingles vaccination for dementia prevention as the crucial next step for the field.

20.
arXiv (CS.LG) 2026-06-24

Density-Informed Pseudo-Counts for Calibrated Evidential Deep Learning

arXiv:2602.01477v2 Announce Type: replace-cross Abstract: Evidential Deep Learning (EDL) is a popular framework for uncertainty-aware classification that models predictive uncertainty via Dirichlet distributions parameterized by neural networks. Despite its popularity, its theoretical foundations and behavior under distributional shift remain poorly understood. In this work, we provide a principled statistical interpretation by proving that EDL training corresponds to amortized variational inference in a hierarchical Bayesian model with a tempered pseudo-likelihood. This perspective reveals a major drawback: standard EDL conflates epistemic and aleatoric uncertainty, leading to systematic overconfidence on out-of-distribution (OOD) inputs. To address this, we introduce Density-Informed Pseudo-count EDL (DIP-EDL), a new parametrization that decouples class prediction from the magnitude of uncertainty by separately estimating the conditional label distribution and the marginal covariate density. This separation preserves evidence in high-density regions while shrinking predictions toward a uniform prior for OOD data. Theoretically, we prove that DIP-EDL achieves asymptotic concentration. Empirically, we show that our method enhances interpretability and improves robustness and uncertainty calibration under distributional shift.

21.
arXiv (math.PR) 2026-06-25

Breuer-Major Theorems for Hilbert Space-Valued Random Variables

arXiv:2405.11452v2 Announce Type: replace Abstract: Let $\{X_k\}_{k\in\mathbb{Z}}$ be a stationary Gaussian process with values in a separable Hilbert space $\mathcal{H}_1$, and let $G:\mathcal{H}_1\to\mathcal{H}_2$ be a measurable map into another separable Hilbert space $\mathcal{H}_2$. We derive a central limit theorem for the centered normalized partial sums of the Hilbert space-valued subordinated process $\{G[X_k]\}_{k\in\mathbb{Z}}$. Our result holds under either of two sets of sufficient conditions, formulated in terms of the transformation $G$ and the temporal and cross-sectional dependence structure of $\{X_k\}_{k\in\mathbb Z}$. These conditions coincide in finite dimensions but lead to genuinely different phenomena in the infinite-dimensional setting. The proof relies on the recently developed Fourth Moment Theorem on Hilbert spaces, leveraging tools from the infinite-dimensional Malliavin-Stein framework. We also provide continuous-time and quantitative versions of the central limit theorem. In a series of examples, we recover and strengthen limit theorems for a wide array of statistics relevant in functional data analysis, and present, as an application of our result, a novel limit theorem in the framework of neural operators.

22.
Nature Medicine 2026-06-10

Dual-target gene therapy in Parkinson’s disease: a multicenter phase 1 trial

Authors:

Restoring striatal dopamine synthesis is a promising gene therapy strategy for Parkinson’s disease. Previous adeno-associated virus-mediated aromatic L-amino acid decarboxylase (AADC) monotherapies remain dependent on exogenous levodopa, whereas multigene delivery is constrained by strict adeno-associated virus packaging limits. A ‘dual approach’ targeting the two rate-limiting enzymes, tyrosine hydroxylase (TH) and AADC, offers the potential for autonomous dopamine synthesis. We report the 12-month primary safety and tolerability outcomes of a multicenter, open-label, dose-escalation, phase 1 trial evaluating BBM-P002, a new adeno-associated virus vector—AAVT42—codelivering constitutively active TH and AADC. Ten participants with moderate-to-advanced Parkinson’s disease were enrolled and received bilateral intraputaminal infusions across doses of 4.0 × 1011 vg (Cohort 1; n = 1), 6.0 × 1011 vg (Cohort 2; n = 2), 1.0 × 1012 vg (Cohort 3; n = 2) and 1.2 × 1012 vg (Cohort 4; n = 5). The trial achieved its primary outcome, as BBM-P002 demonstrated a favorable safety and tolerability profile within 12 months post-treatment. No dose-limiting toxicities or drug-related serious adverse events occurred. A total of 23 adverse events were reported, all judged unrelated to BBM-P002 and primarily mild and transient. Systemic toxicity and clinically meaningful immunogenicity were absent. In conclusion, intraputaminal delivery of BBM-P002 was safe and well tolerated in this phase 1 trial, supporting continued clinical development. ClinicalTrials.gov registration: NCT05822739 . Phase 1 results reveal that BBM-P002, a dual-target gene therapy co-delivering TH and DDC, is safe and well tolerated in Parkinson’s disease, with 12-month motor improvements signaling therapeutic potential.

23.
arXiv (CS.LG) 2026-06-15

FreshRetailNet-LT: A Stockout-Annotated Censored Demand Dataset for Latent Demand Recovery and Forecasting in Fresh Retail

arXiv:2505.16319v4 Announce Type: replace Abstract: Accurate demand estimation is critical for the retail business in guiding the inventory and pricing policies of perishable products. However, it faces fundamental challenges from censored sales data during stockouts, where unobserved demand creates systemic policy biases. Existing datasets lack the temporal resolution and annotations needed to address this censoring effect. To fill this gap, we present FreshRetailNet-50K, the first large-scale benchmark for censored demand estimation. It comprises 50,000 store-product time series of detailed hourly sales data from 898 stores in 18 major cities, encompassing 863 perishable SKUs meticulously annotated for stockout events. The hourly stock status records unique to this dataset, combined with rich contextual covariates, including promotional discounts, precipitation, and temporal features, enable innovative research beyond existing solutions. We demonstrate one such use case of two-stage demand modeling: first, we reconstruct the latent demand during stockouts using precise hourly annotations. We then leverage the recovered demand to train robust demand forecasting models in the second stage. Experimental results show that this approach achieves a 2.73% improvement in prediction accuracy while reducing the systematic demand underestimation from 7.37% to near-zero bias. With unprecedented temporal granularity and comprehensive real-world information, FreshRetailNet-50K opens new research directions in demand imputation, perishable inventory optimization, and causal retail analytics. The unique annotation quality and scale of the dataset address long-standing limitations in retail AI, providing immediate solutions and a platform for future methodological innovation. The data (https://huggingface.co/datasets/Dingdong-Inc/FreshRetailNet-50K) and code (https://github.com/Dingdong-Inc/frn-50k-baseline}) are openly released.

24.
bioRxiv (Bioinfo) 2026-06-24

RNabel-A Standalone Software Tool for Annotating Tandem Mass Spectra of Modified Ribonucleic Acids

Ribonucleic acid (RNA) modifications, with over 170 identified types, play diverse roles in cellular processes. The past decade has witnessed surging demand for accurate identification and localization of RNA modifications in both endogenous and synthetic therapeutic RNAs. With accurate spectral annotation for RNA, tandem mass spectrometry (MS/MS) can meet this demand. Here we present RNabel, a user-friendly software tool for in-depth annotation of MS/MS spectra of RNA oligonucleotides. RNabel considers a full set of backbone-cleavage ions (a, b, c, d, a-B, w, x, y, z) in which the ribonucleotide unit could be A, U, C, G, Y (pseudouridine), or I (Inosine). Additionally, RNabel considers 196 modifications on the base, the phosphoribose linkage, the 5' or the 3' terminus, or detachment of a sub-nucleotide fragment as a neutral or charged group. Users can create new components if needed, including ribonucleotides, modifications, neutral or charged groups that could detach from a ribonucleotide. RNabel efficiently processes large datasets in four acceptable formats including .mgf, .raw, .txt from msConvert, and RNabel batch files. Multiple statistical metrics are provided for quality assessment of spectral annotation. To accelerate RNA modification analysis, RNabel is made freely available for Mac and Windows users at https://github.com/songge1111/RNabel/releases.

25.
arXiv (math.PR) 2026-06-24

On the stability of rarefaction for stochastic viscous conservation law

arXiv:2606.24167v1 Announce Type: new Abstract: We study the asymptotic stability of rarefaction waves for one-dimensional stochastic viscous conservation laws driven by nonlinear conservative noise. In a critical scaling where stochastic energy injection and viscous dissipation compete at comparable magnitudes, standard kinetic and viscosity frameworks encounter obstructions due to regularity gaps and non-integrable profiles. To address this, we introduce a stochastic area inequality controlling accumulated energy fluctuations, a local $L^1$ contraction principle via stochastic Kru\v{z}kov doubling-of-variables that yields pathwise uniqueness without global integrability, and a modified Galerkin scheme preserving the $H^2$ energy structure. Assuming local $H^2$ regularity, we prove almost sure algebraic convergence to the rarefaction wave. For sufficiently small initial perturbations, we establish global well-posedness and sharp decay estimates in expectation. The smallness condition identifies a regime where viscous dissipation dominates stochastic injection, reflecting a structural stability threshold rather than a technical artifact. Our approach extends the analytical framework for conservative SPDEs with rough fluxes.