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01.
medRxiv (Medicine) 2026-06-22

Midlife Measures of General Cognitive Performance in the National Longitudinal Study of Adolescent to Adult Health (Add Health)

Objective: The Add Health Cognitive Assessment, Physical, and Sensory Function Protocol (Add CAPS) was developed to assess cognitive, physical, and sensory function in early midlife in a nationally representative sample in the United States. Using Add CAPS, we developed two general cognitive performance measures. Methods: The sample included 2,525 participants from Add Health Wave VI who completed an in- home assessment of cognitive performance. Confirmatory factor analysis (CFA) was used to derive two general cognitive performance (GCP) scores: (1) a five-domain score based on originally designed cognitive domains (Add CAPS GCP), and (2) a modified score aligned with the Harmonized Cognitive Assessment Protocol (HCAP) framework (Add CAPS GCP-H). We evaluated model fit using Root Mean Square Error of Approximation (RMSEA), Standardized Root Mean Square Residual (SRMR), and Comparative Fit Index (CFI) and tested factor scores for criterion validity. Results: Both models showed good fit (Add CAPS GCP: RMSEA = 0.025, SRMR = 0.031, CFI = 0.968; Add CAPS GCP-H: RMSEA = 0.027, SRMR = 0.033, CFI = 0.962), indicating that they adequately represent the underlying GCP construct. Discussion: The Add CAPS cognitive battery captures a robust, hierarchical structure of GCP across alternative domain specifications. The derived factor scores provide a valuable method for characterizing a person's cognitive baseline during midlife. Importantly, the Add CAPS GCP-H enhances comparability with the HCAP network, supporting cross-cohort analyses of cognitive aging.

02.
bioRxiv (Bioinfo) 2026-06-11

OMIO: A policy-driven Python library for reproducible microscopy image I/O

Modern fluorescence and multiphoton microscopy workflows operate within a heterogeneous ecosystem of file formats, partially overlapping metadata standards, and reader-specific conventions. In practice, this frequently leads to silent axis misinterpretations, loss or corruption of physical voxel size information, and laboratory-specific glue code that is fragile, poorly documented, and difficult to reproduce. OMIO, short for Open Microscopy Image I/O, addresses these issues by providing a lightweight, policy-driven image I/O layer for Python that enforces a canonical, OME-compatible data representation at the API boundary. The central contribution of OMIO is the explicit separation of low-level format access from semantic normalization. Existing reader libraries are used as interchangeable backends for extracting pixel data and available metadata, while OMIO enforces axis conventions, metadata interpretation, and fallback decisions in a centralized and auditable policy layer. This design allows heterogeneous microscopy inputs to be converted into a stable representation without propagating backend-specific assumptions into downstream analysis code. The core design principles of OMIO include canonical axis semantics (TZCYX), robust metadata normalization with explicit and auditable fallbacks, memory-aware operation via optional Zarr-based backends, and workflow-level semantics that extend beyond individual files to folder stacks and BIDS-like project structures. This architecture allows OMIO to orchestrate existing reader libraries into a coherent and reproducible I/O pipeline without replacing or duplicating their functionality. OMIO is implemented as an open-source and community-oriented system in which support for additional file formats and metadata conventions can be added incrementally through modular reader backends. By encouraging the contribution of example datasets, backend extensions, and feature requests, OMIO is designed to evolve alongside emerging acquisition systems while preserving strict semantic guarantees at the interface level. The resulting standardized OME-TIFF outputs are immediately suitable for downstream quantitative analysis and interactive inspection in scientific Python workflows, including workflows based on ImageJ and Napari.

03.
arXiv (math.PR) 2026-06-11

Heat kernel estimates for Markov processes with blowing-up jump kernels

arXiv:2512.24807v2 Announce Type: replace Abstract: In this paper, we establish sharp two-sided heat kernel estimates for a large class of purely discontinuous symmetric Markov processes on closed subsets $F$ of $\mathbb{R}^d$, whose jump kernels blow up on a Borel subset $\Sigma$ of $F$. We assume that $F\setminus \Sigma$ is a $\kappa$-fat set and is dense in $F$. To the best of our knowledge, this is the first work establishing sharp heat kernel estimates for jump processes whose jump kernels blow up on part of the state space. The jump kernels under consideration take the form $J(x,y)=|x-y|^{-d-\alpha}{\mathcal B}(x,y)$, where $\alpha\in (0,2)$ and the function ${\mathcal B}(x,y)$ blows up at a subset $\Sigma$ of $F$. A fundamental obstacle is that the tails of the jump measures are not uniformly bounded, and hence standard techniques in heat kernel analysis do not provide a priori off-diagonal estimates. To overcome this difficulty, we develop a new approach based on weighted integral estimates for the heat kernel that are sensitive to both the blow-up behavior of the jump kernel and the geometry of $F\setminus \Sigma$. Examples of processes falling within our general framework include traces of isotropic $\alpha$-stable processes in $C^{1,\rm Dini}$ sets, processes in Lipschitz sets arising in connection with the nonlocal Neumann problem, and a large class of resurrected self-similar processes in the closed upper half-space.

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

LLMs Infer Cultural Context but Fail to Apply It When Responding

Recent work has shown that LLMs overrepresent dominant cultures, particularly Western ones, while marginalizing others. We investigate whether this affects models' ability to generate culturally adapted responses by evaluating their use of local measurement units based on the user's perceived cultural background. We introduce Cultural and Pragmatic Response Inference (CAPRI), a dataset of conversations with varying levels of cultural cues. Experiments with state-of-the-art LLMs show that models can infer cultural background and recall relevant conventions, but often fail to utilize the information to adapt their answers to the relevant cultural conventions, unless explicitly prompted to perform the tasks sequentially. We further evaluate adaptation to the interpretation of time and quantity expressions, two subjective language grounding dimensions that are affected by culture. We find that models increasingly adapt their answers as cultural cues accumulate, but their priors are not culture-neutral, sometimes aligning with the model's country of origin. Overall, CAPRI provides a resource for future research aimed at narrowing the gap between cultural knowledge and culturally adaptive language generation.

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

Advances in Scientific Machine Learning for Coupled Fluid Flow and Transport

arXiv:2606.19562v1 Announce Type: new Abstract: This chapter reviews recent advances in Scientific Machine Learning (SciML) for modeling coupled fluid flow and transport phenomena governed by the incompressible Navier-Stokes and scalar transport equations. Such systems, found in applications like turbidity currents and thermal convection, feature strong nonlinear coupling and multiscale behavior that make high-fidelity simulations computationally expensive. To address this, the chapter surveys state-of-the-art SciML methods for building efficient surrogate models, including linear reduced-order techniques based on Singular Value Decomposition (such as Dynamic Mode Decomposition) and nonlinear neural network approaches like Physics-Informed Neural Networks (PINNs) and $\beta$-Variational Autoencoders ($\beta$-VAEs). It first covers the authors' work combining these models with High Performance Computing strategies, including Adaptive Mesh Refinement/Coarsening (AMR/C) and scientific floating-point data compression. It then presents two new contributions: surrogate modeling of turbidity currents via PINNs, and the extraction of disentangled nonlinear modes from thermal flows using $\beta$-VAEs. Governing equations and representative benchmarks, including lock-exchange flows and Rayleigh-Bénard convection, illustrate these methodologies. The chapter is intentionally long, covering both the mathematical and physical foundations of coupled fluid flow and the computational aspects of state-of-the-art modeling. Overall, it demonstrates how SciML enables fast, accurate approximations of complex coupled systems within the specific data regimes and modeling assumptions considered, while substantially reducing computational cost relative to full-order simulations. Broader capabilities such as real-time prediction and uncertainty quantification remain active research directions whose feasibility depends strongly on the problem at hand.

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

VeriGraph: Towards Verifiable Data-Analytic Agents

LLM-based agents have demonstrated strong capabilities in data-intensive analytical tasks, yet their outputs are rarely verifiable: a reliance on linear text trajectories makes their reasoning difficult to audit. In particular, deterministic computations over raw data and semantic deductions over natural-language claims are often entangled in an unstructured stream, leaving numerical conclusions hard to reproduce and qualitative judgments hard to inspect. To address this, we propose VeriGraph, a traceable neuro-symbolic reasoning framework that enables agents to construct an explicit heterogeneous evidence directed acyclic graph (DAG) during execution. VeriGraph introduces three evidence-expansion primitives, namely computational, grounding, and derivational expansion, to connect raw data, interpreter variables, computed results, and natural-language claims in a unified graph. Under this formulation, structural traceability is reduced to graph reachability from raw data sources to terminal claims, while semantic support is measured by claim-level evidence evaluation. To improve graph construction, we further design a graph-based policy optimization strategy with a composite reward that jointly supervises answer correctness, computational integrity, and derivational coherence. Experiments on four benchmarks show that VeriGraph-8B achieves the highest overall score among all baselines. More importantly, VeriGraph produces auditable evidence graphs with substantially stronger claim grounding, achieving a 87.61\% Grounding Rate under our claim-level evidence support evaluation. These results suggest that explicit evidence-graph construction is a promising path toward verifiable data-analytic agents. Our code is available at https://github.com/ignorejjj/VeriGraph.

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

Decoupled Latent Optimization of Diffusion Models for Full Waveform Inversion

arXiv:2606.14139v1 Announce Type: new Abstract: Full waveform inversion (FWI) recovers subsurface velocity from seismic recordings by solving a severely ill-posed, nonconvex PDE-constrained optimization. Classical regularizers stabilize the inversion but fail to reproduce realistic geological structures; recent diffusion-prior methods improve realism at the cost of a fragile trade-off between data fidelity and prior consistency. We propose Decoupled Latent Optimization (DLO), which relaxes the standard latent-optimization formulation into a quadratic-penalty objective over an auxiliary physical variable and a latent variable. The data-fidelity gradient acts in physical space, the diffusion sampler contributes only through a decoded prior sample, and the standard smoothed-velocity initialization of classical FWI is preserved. On the OpenFWI benchmark, DLO outperforms classical regularizers and existing diffusion-based methods under clean, noisy, and missing-trace acquisitions. The prior, trained on 70*70 OpenFWI models, transfers directly to the Marmousi and Overthrust benchmarks, where DLO recovers intricate fault structures and remains robust to initialization smoothing and measurement noise.

08.
arXiv (CS.CL) 2026-06-18

Dual Dimensionality for Local and Global Attention

Decoder-only Transformers compute attention over the KV cache of preceding tokens. Keys (and Values) are typically represented with the same dimensionality, regardless of its distance from the prediction target. In natural language, however, the next word is most strongly influenced by the immediately preceding tokens. We hypothesize that local and distant tokens impose asymmetric demands on representational capacity: local tokens are more critical for predicting immediate outputs and thus require richer representations, whereas distant tokens primarily serve as long-range memory, for which lower-dimensional representations may suffice. We formalize this idea as Distance-Adaptive Representation (DAR), implemented in a controlled setting that preserves full-dimensional representations within a local context window while assigning reduced-dimensional representations (e.g. 1/4 of the original dimensionality) to tokens beyond that window. Across multiple pretraining scales (70M to 410M parameters), as well as continued supervised fine-tuning on a 1B-scale model, this approach closely matches the performance of full-dimensional baselines. In contrast, uniformly reducing dimensionality across all token positions leads to worse performance. These results challenge the common assumption that key and value dimensionality should be uniform across token positions. Our findings suggest a new direction for designing attention architectures that adaptively allocate representational capacity across sequences, enabling further reductions in KV cache during inference.

09.
arXiv (math.PR) 2026-06-16

Mean-field BSDEs with non-Lipschitz coefficients and double mean reflections

arXiv:2510.11228v2 Announce Type: replace Abstract: The present paper is devoted to the study of mean-field backward stochastic differential equations (MFBSDEs) with double mean reflections whose generators are not Lipschitz continuous. With the help of the Skorokhod problem and some a priori estimates for MFBSDEs, we establish the existence and uniqueness results for doubly mean reflected MFBSDEs.

10.
arXiv (quant-ph) 2026-06-16

Linear algebra at exponential scale via tensor network dimension reduction

arXiv:2606.15350v1 Announce Type: cross Abstract: Many problems in modern scientific computing are challenging because of a curse of dimension, where their mathematical formulation involves objects whose dimension is exponential in the nominal "size" of the problem. Tensor networks can provide a compact representation for exponentially large vectors and matrices that arise in applications, but these representations do not always lead to reliable algorithms. This paper develops and analyzes techniques for randomized dimension reduction of tensor network data. These techniques support a suite of efficient algorithms for provably solving exponential-scale linear algebra problems, including trace estimation and eigenvalue approximation. The paper includes several stylized illustrations from quantum many-body physics with ambient dimension up to $2^{200}$.

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

Biarchetype analysis for univariate functional data. An application to macroeconomic financial time series

arXiv:2606.15881v1 Announce Type: cross Abstract: We introduce biarchetype analysis for the first time in the context of univariate functional data. This unsupervised methodology extends archetype analysis by simultaneously identifying archetypal structures across both the cases (countries, in our application) and the temporal argument. Both cases and time points are expressed as mixtures of biarchetypes, yielding a concise and highly interpretable representation of complex functional observations. Although biarchetype analysis is not intended as a clustering technique, it offers superior interpretability compared with biclustering approaches, as it is based on extreme, representative patterns rather than average centroids, thereby enhancing human comprehension. We apply the proposed method to 10-year government bond yields of European countries over the period 2001-2025. The results identify three distinct time regimes (the pre-crisis period, the euro-area sovereign debt crisis, and the post-crisis period), and reveal Germany, Greece, and Hungary as country archetypes.

12.
medRxiv (Medicine) 2026-06-22

Efficacy and safety of semaglutide for obesity and hyperphagia in adults with Prader-Willi syndrome

Context: Prader-Willi syndrome is a genetic neurodevelopmental disorder characterized by hyperphagia and early-onset obesity from hypothalamic dysfunction with endocrinopathies and learning disability. Management is challenging with strict control of the food environment needed. While newer glucagon-like peptide-1 receptor agonists, such as semaglutide, have efficacy in non-PWS obesity, there have been limited case reports in PWS. Objective/Design/Setting: Retrospective records review of 12 adults with PWS and overweight/obesity treated with semaglutide at a UK academic hospital centre specialist clinic. Patients: mean +/- SD age 28.3 +/- 10.1 years, 83% female, BMI 46.6 +/- 8.2kg/m2, 75% type 2 diabetes mellitus. Intervention: Median follow-up 17.2 months (range 8.7-36.1) with median semaglutide dose 2.4mg once weekly (1.0-2.4). Results: Although there was no significant weight loss on semaglutide, there was stabilisation of the weight gain prior to treatment over previous 12.4 months (7.6-23.0) (post -3.1 +/- 9.9% vs. pre +5.7 +/- 5.6%: d -0.72, P=0.037). There was a significant decrease in hyperphagia on semaglutide from hyperphagia questionnaire for clinical trials (n=11, -7.3 +/- 6.1 (max 36), d -1.19, P=0.003), having been stable before treatment. HbA1c improved in those with elevated baseline levels (n=6, -4.2 +/- 4.9%, d -0.74, P=0.13). Mild gastrointestinal side effects were seen in 25% but did not lead to discontinuation. Conclusions: In adults with PWS, semaglutide produced weight maintenance, reduced hyperphagia, and improved glycaemic control, with good tolerability. Larger placebo-controlled trials are needed to confirm these findings in adults and adolescents with PWS, especially in those without T2DM, where efficacy may be greater.

13.
arXiv (CS.CL) 2026-06-12

SkillCAT: Contrastive Assessment and Topology-Aware Skill Self-Evolution for LLM Agents

Skill self-evolution methods for LLM agents aim to turn execution trajectories into reusable skill documents, but current pipelines typically learn from one trajectory per task, merge candidate skill patches before checking them, and load the full skill corpus before inference. We propose SkillCAT, a training-free framework that separates this process into three stages. Contrastive Causal Extraction (CCE) samples multiple trajectories for each task and compares same-task success/failure pairs to identify evidence that explains outcome differences. Assessment-Augmented Evolution (AAE) replays each candidate patch on source-task clones and keeps only patches that improve or preserve task outcomes before hierarchical skill patch merging. Topology-Aware Task Execution (TTE) compiles the evolved skills into a routable sub-skill topology, so inference loads only the capability nodes relevant to the task. We evaluate SkillCAT on common agent benchmarks, including SpreadsheetBench, WikiTableQuestions, and DocVQA, and further test cross-model and out-of-distribution generalization. Across these settings, SkillCAT raises the average score over baselines by up to 40.40%, demonstrating reliable skill evolution without model training.

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

MeshPad: Interactive Sketch-Conditioned Artist-Reminiscent Mesh Generation and Editing

We introduce MeshPad, a generative approach that creates 3D meshes from sketch inputs. Building on recent advances in artist-reminiscent triangle mesh generation, our approach addresses the need for interactive mesh creation. To this end, we focus on enabling consistent edits by decomposing editing into 'deletion' of regions of a mesh, followed by 'addition' of new mesh geometry. Both operations are invoked by simple user edits of a sketch image, facilitating an iterative content creation process and enabling the construction of complex 3D meshes. Our approach is based on a triangle sequence-based mesh representation, exploiting a large Transformer model for mesh triangle addition and deletion. In order to perform edits interactively, we introduce a vertex-aligned speculative prediction strategy on top of our additive mesh generator. This speculator predicts multiple output tokens corresponding to a vertex, thus significantly reducing the computational cost of inference and accelerating the editing process, making it possible to execute each editing step in only a few seconds. Comprehensive experiments demonstrate that MeshPad outperforms state-of-the-art sketch-conditioned mesh generation methods, achieving more than 22% mesh quality improvement in Chamfer distance, and being preferred by 90% of participants in perceptual evaluations.

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

SP-GCRL: Influence Maximization on Incomplete Social Graphs

arXiv:2605.12513v2 Announce Type: replace-cross Abstract: Influence maximization (IM) in real platforms is challenged by incomplete, noisy social graphs and non-stationary diffusion dynamics. We propose SP-GCRL, a social-propagation-aware graph contrastive reinforcement learning framework that learns end-to-end seed selection under partial observability.We first introduce a social-propagation-aware nonlinear diffusion function to model reinforcement/diminishing effects and probability drift under repeated exposure; we then construct dual structural views and perform contrastive learning to obtain node representations robust to missing edges and weak ties, while replacing expensive strategy metrics with a GAT-based regression surrogate to improve efficiency and scalability; finally, we use DDQN to learn an end-to-end seed selection policy on top of these representations. Experiments on multiple real-world networks show that SP-GCRL achieves significant gains over heuristic and learning-based baselines across budgets and topologies, while maintaining strong large-scale scalability.

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

Retell, Reward, Repeat: Reinforcement Learning for Narrative Theory-Informed Story Retelling

Counterfactual story retelling exposes LLM shortcomings in constrained narrative solution spaces where they can no longer rely on recalling memorised training data. Ground-truth-based post-training, such as SFT, fails to teach LLMs how to generate logical and rational narrative events. In this paper, we introduce Retell, Reward, Repeat (RRR), an RL-based pipeline synthesising Structuralist Narratology with scalar narrativity to teach storytelling structure. We extend the TimeTravel dataset with human-annotated stages of narrative equilibrium to evaluate reward models. By using d-RLAIF, RRR derives training signals from the narrativity of textual features without the need for reference outputs. Evaluations demonstrate that RRR-trained LLMs outperform few-shot and SFT baselines in logic, rationality, and completeness, with output quality additionally validated by blind human preference. Relying on a small, query-only dataset, RRR provides a linguistically grounded, cost-effective post-training mechanism for storytelling–a domain currently lacking effective post-training methods. RRR highlights the continued relevance of integrating established linguistic theories into contemporary NLP.

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

OCOO-T : A Simple and Scalable Virtual Cell Model for Transcriptional Perturbation Response Prediction

arXiv:2606.12838v1 Announce Type: cross Abstract: Predicting single-cell transcriptional responses to genetic, chemical and cytokine perturbations is a fundamental challenge in computational biology and AI Virtual Cell (AIVC) modeling, with direct implications for drug discovery and the elucidation of gene regulatory networks. Existing approaches often rely on auxiliary cell-state encoders, hierarchical variational autoencoders, dedicated Transformer encoder-decoder modules, or gene-interaction priors to compress high-dimensional expression profiles into latent representations. While effective, these designs increase architectural complexity and may limit scalability and generalizability. This paper introduces OCOO-T, a minimalist flow-matching-based AIVC model for transcriptional perturbation response prediction. OCOO-T utilizes a vanilla Transformer stack that operates directly on continuous gene expression profiles and formulates perturbation response prediction as a continuous-time denoising process. Perturbation embeddings, dosage information, and cell-line/cell-type specificity are integrated through adaptive layer normalization and in-context tokens. Comprehensive evaluations on Tahoe100M, Replogle, and PBMC benchmarks demonstrate that OCOO-T achieves state-of-the-art performance across diverse perturbations and cell types while effectively scaling to long transcriptional profiles through patching and depatching of cellular contexts. By leveraging the simplicity of Transformer-based denoising for single-cell omics, OCOO-T provides an effective and scalable framework for in-silico cellular simulation.

18.
arXiv (quant-ph) 2026-06-16

Intermodal entanglement in a quantum optical model of HHG due to the back-action on the driving field

arXiv:2603.01315v2 Announce Type: replace Abstract: Preparation of nonclassical light with special quantum properties is essential for quantum technologies. High-harmonic generation (HHG) is a process which not only enables the creation of attosecond pulses but also has the potential to generate light with intricate quantum properties. In a recent experiment [1], nonclassical inter-harmonic correlations have been measured from a HHG source. In this work, we theoretically investigate entanglement between different harmonics within an effective quantum optical model. This model implements a signifcant degree of simplifcation regarding the processes within the target material, treating the material through susceptibilities, as it is usual in quantum optics. Such an approach yields a general description of HHG, permitting the implications that can be derived within it to hold broadly. We find that entanglement is produced as a result of the often neglected back-action. We can qualitatively reproduce experimentally measured nonclassicalities, which suggests that intermodal entanglement can, to an extent, be considered a universal phenomenon associated with HHG, rather than a result of using specific material targets.

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

Gated QKAN-FWP: Scalable Quantum-inspired Sequence Learning

arXiv:2605.06734v2 Announce Type: replace-cross Abstract: Fast Weight Programmers (FWPs) encode temporal dependencies through dynamically updated parameters rather than recurrent hidden states. Quantum FWPs (QFWPs) extend this idea with variational quantum circuits (VQCs), but existing implementations rely on multi-qubit architectures that are difficult to scale on noisy intermediate-scale quantum (NISQ) devices and expensive to simulate classically. We propose gated QKAN-FWP, a fast-weight framework that integrates FWP with Quantum-inspired Kolmogorov-Arnold Network (QKAN) using single-qubit data re-uploading circuits as learnable nonlinear activation, known as DatA Re-Uploading ActivatioN (DARUAN). We further introduce a scalar-gated fast-weight update rule that stabilizes parameter evolution, supported by a theoretical analysis of its adaptive memory kernel, geometric boundedness, and parallelizable gradient paths. We evaluate the framework across time-series benchmarks, MiniGrid reinforcement learning, and highlight real-world solar cycle forecasting as our main practical result. In the long-horizon setting with 528-month input window and 132-month forecast horizon, our 12.5k-parameter model achieves lower scaled Mean Square Error (MSE), peak amplitude error, and peak timing error than a suite of classical recurrent baselines with up to 13x more parameters, including Long Short-Term Memory (LSTM) networks (25.9k-89.1k parameters), WaveNet-LSTM (167k), Vanilla recurrent neural network (11.5k), and a Modified Echo State Network (132k). To validate NISQ compatibility, we further deploy the trained fast programmer on IonQ and IBM Quantum processors, recovering forecasting accuracy within 0.1% relative MSE of the noiseless simulator at 1024 shots. These results position gated QKAN-FWP as a scalable, parameter-efficient, and NISQ-compatible approach to quantum-inspired sequence modeling.

20.
Nature (Science) 2026-06-17

Spatial distribution of the proteome in the human body and in cancers

Authors:

A detailed, spatially resolved quantitative map of the human proteome is essential for a deeper understanding of human biology and disease1–4. Here we present a comprehensive human proteomic landscape, generated by profiling more than 13,000 proteins across 2,856 samples using data-independent acquisition mass spectrometry. The dataset spans 58 major tissue types, 251 specific tissue subtypes and 25 distinct carcinomas. This resource enables the depiction of spatially resolved proteome trajectories across tissue types and physiological states, including fetal, tumour, adjacent non-tumour and healthy adult tissue, thereby providing insight into both developmental processes and oncogenic progression. Furthermore, quantitative proteomics comparisons across diverse tissue types and states facilitate the indication of organ-specific toxicity, the identification of repurposable anticancer drug candidates and the prioritization of therapeutic targets for cancers. This study establishes a quantitative resource for navigating the proteome in the human body and in common cancers. A spatially resolved map of the human proteome across a variety of healthy tissues and cancers provides wide-ranging insights in developmental biology and oncology, and could aid the identification of therapeutic targets and development of treatments for cancer.

21.
PLOS Computational Biology 2026-06-12

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

Authors:

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.

22.
arXiv (CS.CL) 2026-06-24

Function-Vector Heads Are Two Populations: Writers and Cancellers in In-Context Learning

Authors:

Function-vector (FV) heads are identified by the magnitude of their causal contribution to in-context rule tasks, and the resulting top set is treated as a single functional class. We show this hides a sign structure. Under a sign-preserving criterion (refined direct logit attribution, validated head by head with path patching) the FV population splits into two opposing groups: writers push the rule-correct logit up, cancellers push it down, and ablating both together moves the readout less than the sum of the two. The split is causal and reproducible. It holds in all but two of the fifteen (model, task) cells we test, spanning three architectures and six Pythia scales, and a sign-shuffle null rejects the single-class account in all but one of the six main cells. It is also invisible to magnitude-only ranking, which surfaces whichever group locally dominates and misses the other, so any function vector or ablation built that way silently averages a promoting and a suppressing mechanism. Cancellers are not attention sinks, induction heads, or copy-suppression heads, and their causal effect is larger than that of magnitude-matched non-FV controls. Zero-ablating them recovers $+0.13$ to $+0.29$ nats on the correct label in every main cell, and shifts accuracy by $+2$ to $+7$ pp in the same direction.

23.
arXiv (CS.CL) 2026-06-16

Vocabulary Dropout for Curriculum Diversity in LLM Co-Evolution

Co-evolutionary self-play, where one language model generates problems and another solves them, promises autonomous curriculum learning without human supervision. In practice, the proposer quickly converges to a narrow distribution of problems that satisfy the reward function. This diversity collapse renders the curriculum uninformative for the solver, stalling the co-evolutionary loop. We introduce vocabulary dropout, a random mask applied to the proposer's output logits during both policy training and curriculum generation, as a lightweight mechanism to sustain diversity. The mask is hard and non-stationary, preventing the proposer from locking into fixed token sequences. Training Qwen3-4B and Qwen3-8B on mathematical reasoning via R-Zero, we find that vocabulary dropout sustains proposer diversity across lexical, semantic, and functional metrics throughout training. It also yields solver improvements averaging +4.4 points at 8B, with the largest gains on competition-level benchmarks. Our findings suggest that explicit action-space constraints, analogous to the structural role that game rules play in classical self-play, can help sustain productive co-evolution in language. Vocabulary dropout is one simple instantiation of this principle.

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

OpenThoughts-Agent: Data Recipes for Agentic Models

arXiv:2606.24855v1 Announce Type: new Abstract: Agentic language models dramatically expand the applications of AI yet little is publicly known about how to curate training data for broadly capable agents. Existing open efforts such as SWE-Smith, SERA, and Nemotron-Terminal typically target a single benchmark, leaving open the question of how to train models that generalize across diverse agentic tasks. The OpenThoughts-Agent (OT-Agent) project addresses this gap with a fully open data curation pipeline for training agentic models. We conduct more than 100 controlled ablation experiments to systematically investigate each stage of the pipeline, yielding insights on the importance of task sources and diversity. We then assemble a training set of 100K examples from our pipeline and fine-tune Qwen3-32B on this dataset, which yields an average accuracy of 44.8% across seven agentic benchmarks and a 3.9 percentage point improvement over the strongest existing open data agentic model (Nemotron-Terminal-32B, 40.9%). Moreover, our training data exhibits strong scaling properties, outperforming alternative open datasets at every training set size in compute-controlled comparisons. We publicly release our training sets, data pipeline, experimental data, and models at openthoughts.ai to support future open research on agentic model training.

25.
arXiv (CS.LG) 2026-06-16

Empirical Study of Pop and Jazz Mix Ratios for Genre-Adaptive Chord Generation

Authors:

arXiv:2605.04998v2 Announce Type: replace-cross Abstract: This revision updates a pop-to-jazz chord-generation rehearsal study. Best-epoch metrics still show that modest pop rehearsal preserves pop accuracy while improving jazz prediction, but v2 corrects released-checkpoint selection: the released F1 equals Phase 0, F2 had a transcription error, and ft-pop80-v2 restores a hash-distinct jazz-adapted F1 across 3 seeds.