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01.
arXiv (CS.CV) 2026-06-18

MUFASA: A Multi-Layer Framework for Slot Attention

Unsupervised object-centric learning (OCL) decomposes visual scenes into distinct entities. Slot attention is a popular approach that represents individual objects as latent vectors, called slots. Current methods obtain these slot representations solely from the last layer of a pre-trained vision transformer (ViT), ignoring valuable, semantically rich information encoded across the other layers. To better utilize this latent semantic information, we introduce MUFASA, a lightweight plug-and-play framework for slot-attention-based approaches to unsupervised object segmentation. Our model computes slot attention across multiple feature layers of the ViT encoder, fully leveraging their semantic richness. We propose a fusion strategy to aggregate slots obtained on multiple layers into a unified object-centric representation. Integrating MUFASA into existing OCL methods improves their segmentation results across multiple datasets, setting a new state of the art while simultaneously improving training convergence with only minor inference overhead.

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

Creating and Evaluating K-12 GenAI Assessment Graders Through Context Engineering

arXiv:2606.12422v1 Announce Type: cross Abstract: The integration of large language models (LLMs) into educational assessment represents a transformative shift in classroom grading practices. While automated scoring systems and machine learning techniques have existed for decades, generative AI (GenAI) now enables educators to implement standards-based grading (SBG) with unprecedented efficiency and scale. This paper examines the theoretical foundations and evaluates an LLM grader that uses commercially available foundation models with context and prompt engineering to score student work against a rubric. Drawing on an empirical interrater agreement study using Massachusetts Comprehensive Assessment System (MCAS) data, we observed the Quadratic Weighted Kappa (QWK) and Proportional Reduction in Mean-Squared Error (PRMSE) across mathematics, science, and ELA, using Claude Sonnet 4, Haiku 4.5, GPT-5, and GPT-5 Mini. The results demonstrate that LLM graders, especially when based on foundational models with more parameters, achieve substantial agreement with human raters in mathematics and science assessments, while the performances vary in ELA, suggesting generic foundation models can be effective at scoring in given contexts. Additional analysis of teacher and student feedback reveals strong acceptance of AI-generated narrative feedback but skepticism toward numerical scores, suggesting that LLMs function most effectively as formative tools rather than summative evaluators. Our findings indicate that thoughtfully designed hybrid models that combine AI efficiency with teacher judgment can reduce workload, enhance feedback quality, and support equitable assessment practices without displacing professional expertise.

03.
arXiv (CS.AI) 2026-06-12

Interaction-Centered Intelligence: Toward an Interaction-Based Theory of Human-AI Co-Creation

arXiv:2606.00807v2 Announce Type: replace Abstract: Traditional artificial intelligence has largely conceptualized intelligence as isolated computation occurring within bounded agents. Across classical AI, machine learning, and many generative systems, the dominant unit of analysis remains the individual model or autonomous system evaluated through outputs, benchmarks, prediction accuracy, or optimization performance. While these approaches have produced major advances, they often under-theorize the role of interaction in the emergence of intelligence, creativity, meaning, and adaptive behavior. This paper proposes interaction as the primary unit of analysis for co-creative AI and interaction-centered intelligence more broadly. Drawing from distributed cognition, embodied cognition, enaction, participatory sense-making, human-computer interaction, and computational creativity, the paper traces a historical progression toward increasingly relational accounts of intelligence. Building upon prior work in Creative Sense-Making, quantified co-creation, and co-creative systems such as the Drawing Apprentice and AI Drawing Partner, it argues that intelligence emerges through evolving interaction dynamics among agents, environments, and socio-technical systems rather than solely through internal computation. The paper introduces Interaction-Centered Intelligence as a framework for understanding human-AI co-creation, collaborative emergence, adaptive participation, and interactional dynamics. Rather than evaluating intelligence solely through generated outputs, the framework emphasizes interaction trajectories, coordination patterns, participatory engagement, adaptive regulation, and interactional drift unfolding through time. Implications for explainable co-creative AI, hybrid intelligence, enactive AI, and future human-AI systems are discussed.

04.
arXiv (quant-ph) 2026-06-16

Classical Explanations in (and of) General Probabilistic Theories

arXiv:2603.05627v2 Announce Type: replace Abstract: We introduce a notion of the ``explanation" of one (generalized) probabilistic model by another as particular kind of span in the category $\Prob$ of probabilistic models and morphisms. We show that explanations compose under a standard pullback construction (notwithstanding that $\Prob$ does not support arbitrary pullbacks). We then show that every locally-finite probabilistic model has a canonical, sharp classical explanation. The construction is functorial, so every locally-finite probabilistic theory has a canonical, sharp classical (though of course, usually non-local) representation.

05.
medRxiv (Medicine) 2026-06-22

Level of Physical Activity and ApoE Status - Effects on Alzheimer's Disease and on Mortality

Background: Alzheimer's disease and related dementias (ADRD) affect over 7.2 million Americans aged 65 and older, with the APOE-4 allele representing the strongest known genetic risk factor. Physical activity (PA) has been associated with reduced dementia risk, but its interaction with APOE genotype remains poorly characterized in large, genomically informed cohorts. Methods: We conducted a retrospective cohort analysis using linked genomic, survey, and longitudinal electronic health record data from the VA Million Veteran Program (MVP). Veterans aged

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

A Unified Framework for Efficient Remote Sensing Visual Question Answering: Adapting Dual, Hybrid, and Encoder-Decoder Architectures

Visual Question Answering (VQA) in the Remote Sensing (RS) domain presents unique challenges due to the high resolution, multi scale object distribution, and semantic complexity of aerial imagery. While general domain Foundation Models have achieved remarkable success, their direct application to RSVQA is hindered by massive domain shifts and the computationally prohibitive nature of full fine tuning. This study presents a comparative analysis of RS Adapter, a Parameter Efficient Fine Tuning (PEFT) strategy, applied across three distinct Vision Language Model (VLM) architectures: the Dual Encoder CLIP, the Encoder Decoder BLIP, and the Hybrid FLAVA. We introduce a unified architectural surgery pipeline that injects lightweight bottleneck adapters into the attention and MLP layers of frozen backbones, enabling rapid adaptation with less than 5 percent of trainable parameters. Experimental results on the high resolution RSVQA x dataset demonstrate that while all adapted models achieve convergence, the Hybrid FLAVA architecture offers a superior balance of multimodal reasoning and retrieval capabilities compared to its unimodal counterparts. Our findings establish a new baseline for resource efficient VQA in disaster assessment and urban monitoring.

07.
medRxiv (Medicine) 2026-06-16

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

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

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

Heteroskedastic Signals in Budgeted LLM Verification: Structural Heterogeneity Limits Optimization Gains

Authors:

arXiv:2606.15841v1 Announce Type: new Abstract: Large language model (LLM) systems increasingly use uncertainty signals to allocate limited computation across verification, test-time scaling, tool execution, and other selective-compute decisions. Such policies rely on a global signal comparability assumption: equal scores should carry comparable decision value across inputs. Using budgeted verification as a controlled diagnostic setting, we identify a failure mode of this assumption: uncertainty quality is heteroskedastic across cost strata, with some regions exhibiting near-random discriminability despite concentrating many errors. Under an explicit local model, we characterize the resulting distortion of global allocation and show that its upper bound scales with cross-stratum signal-quality dispersion. We separate weak signals, optimization instability, and structural heterogeneity through a controlled intervention hierarchy: Threshold, MP-Adapt, MP-Strat, and a deliberately simple cost-stratified thresholding intervention (CST). Across MBPP and MATH using Qwen3-8B, LLaMA3-8B, and GPT-4o-mini, global online adaptation yields inconsistent gains over static thresholding; MP-Strat partially recovers performance, while CST improves hit rate by up to 17 percentage points in strongly heterogeneous settings without gradient updates. These results identify structural heterogeneity, rather than optimizer weakness alone, as the primary bottleneck in the observed settings. More broadly, misaligned feedback structure cannot always be repaired by stronger optimization.

09.
arXiv (CS.LG) 2026-06-12

Interpretable Factor Decomposition for Decision Intelligence in Large-Scale Financial Markets: Evidence from China's A-Share Market

arXiv:2606.12843v1 Announce Type: new Abstract: We present an interpretable machine learning pipeline to decompose Cross-Sectional Equity Return Predictability into auditable factor contribution. We apply an XGBoost model with TreeSHAP attribution and conduct stress testing on 3632 Chinese A-share stocks from 2009 until 2019. Using 60-month, rolling windows over 55 months of out-of-sample data, XGBoost obtains a mean AUC of 0.547 and +2.38%/month (Newey-West t = 5.94; Annualized Sharpe 2.23) long-short spread for the top vs bottom quintiles. This alpha is persistent after adjusting for the Carhart four-factor model (+2.31%/month; t = 7.48). SHAP Decomposition indicates that behavioral signals (turnover and momentum) account for 58.2% of predictive attribution compared to 10.7% for valuation ratios, on average, across 55 industry groups. Ablation analysis serves to cross-validate this ranking and provides evidence that SHAP and ablation diverge in a manner that highlights feature substitutability structure that is largely invisible to either method used in isolation.

10.
arXiv (CS.LG) 2026-06-17

On Surjectivity of Neural Networks: Can you elicit any behavior from your model?

arXiv:2508.19445v3 Announce Type: replace Abstract: Given a trained neural network, can any specified output be generated by some input? Equivalently, does the network correspond to a function that is surjective? In generative models, surjectivity implies that any output, including harmful or undesirable content, can in principle be generated by the networks, raising concerns about model safety and jailbreak vulnerabilities. In this paper, we prove that many fundamental building blocks of modern neural architectures, such as networks with pre-layer normalization and linear-attention modules, are almost always surjective. As corollaries, widely used generative frameworks, including GPT-style transformers and diffusion models with deterministic ODE solvers, admit inverse mappings for arbitrary outputs. By studying surjectivity of these modern and commonly used neural architectures, we contribute a formalism that sheds light on their unavoidable vulnerability to a broad class of adversarial attacks.

11.
arXiv (CS.AI) 2026-06-15

TRACE: Trajectory-Routed Causal Memory for Delayed-Evidence Visuomotor Imitation

arXiv:2606.14551v1 Announce Type: cross Abstract: Robots under autonomous operation may require decisions based on evidence that is no longer visible. We study delayed-evidence tasks, where an early cue disappears before a later decision point, so visually similar observations can require different actions. In these settings, the current observation is not a sufficient state for control. We introduce TRAjectory-routed Causal Evidence (TRACE), a memory framework for visuomotor imitation policies. TRACE stores task-relevant visual and robot-state evidence, such as object identity, target choice, or route-dependent state, in a fixed-size latent memory that remains bounded over long episodes. Instead of indexing memory by raw time or manually provided task labels, TRACE uses path signatures: compact, order-sensitive features of the executed robot-state trajectory. These signatures do not store the visual cue itself; rather, they provide trajectory-conditioned keys for writing and retrieving the evidence stored when the cue was visible. When the robot later reaches an ambiguous observation, the policy conditions on TRACE memory to recover the missing context and choose the correct branch. TRACE attaches through lightweight adapters to policies, without changing the policy backbone, action head, or imitation objective. Across real-world long-horizon manipulation tasks with visually ambiguous branch points, TRACE improves branch selection and task success over alternative baselines, including short-history and recurrent memory. Project page: https://jeong-zju.github.io/trace

12.
arXiv (CS.LG) 2026-06-16

Multi-Agent Framework for Audit Risk Assessment with Explicit Uncertainty and Evidence Conflict Modeling

arXiv:2606.15640v1 Announce Type: new Abstract: Audit risk assessment increasingly benefits from combining heterogeneous evidence sources, yet existing approaches typically produce point predictions without quantifying how well different evidence streams agree. We propose UMAR (Uncertainty-Aware Multi-Agent Risk Assessment), a framework that employs three specialized agents: an MD&A Text Agent, a Financial Ratio Agent, and a CAM Agent, each producing independent risk scores with calibrated uncertainty estimates. An Uncertainty Aggregator based on Dempster-Shafer evidence theory fuses these scores while explicitly measuring inter-agent conflict. We evaluate UMAR on a U.S. dataset of 3,200 firm-year observations from SEC 10-K filings (2019-2023), with financial restatement as the target label. Experimental results show that UMAR achieves an AUROC of 0.782 and a PR-AUC of 0.341, outperforming logistic regression, XGBoost, FinBERT, and single-agent and dual-agent LLM baselines. UMAR attains the lowest expected calibration error (ECE = 0.052) among all methods and identifies evidence-conflict patterns that correlate with actual restatement risk, offering auditors potentially actionable and interpretable risk signals.

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

Bootstrapped Monitoring: Leveraging Transparent Reasoning to Oversee Stronger AI Agents

arXiv:2606.11998v1 Announce Type: new Abstract: Trusted monitoring is a cornerstone of AI control. However, as frontier models grow more capable, the increasing capabilities gap between trusted and untrusted models may render trusted models unreliable monitors. We introduce bootstrapped monitoring, a protocol that addresses this by inserting a stronger, intermediate untrusted model with transparent chain-of-thought reasoning into the oversight chain. The untrusted monitor ($U_m$) evaluates the agent's actions, while a weaker trusted model ($T$) oversees $U_m$'s reasoning to detect collusion. We evaluate bootstrapped monitoring on multi-turn software engineering tasks (BashArena) across multiple agents and monitors. Bootstrapped monitoring substantially improves catch rates over trusted-only monitoring, even when the untrusted monitor actively colludes with the agent, provided we have access to its raw chain-of-thought. Our results suggest that bootstrapped monitoring can extend the useful lifetime of trusted models in control as AI capabilities advance.

14.
arXiv (CS.CV) 2026-06-17

High-Fidelity 3D Geometric Reconstruction of Pelvic Organs from MRI: A Hybrid Deep Learning and Iterative Optimization Approach

Patient-specific 3D reconstruction of pelvic organ geometry from MRI is important for pelvic floor modeling and downstream patient-specific analysis. However, while previous studies have focused primarily on either image segmentation or downstream use of 3D models, the reconstruction of high-fidelity, high-quality geometries remains labor-intensive and poorly standardized. The study introduced a hybrid deformable shape modeling framework that integrates deep learning prediction with iterative optimization for the reconstruction of the bladder, uterus, and rectum. The framework consists of three core components: a geometry-aware multi-level deep learning architecture that preserves topological consistency of pelvic organs; a two-stage amortized optimization training strategy that balances global shape capture and local surface refinement; and a holistic synergy mechanism–where iterative optimization provides supervision for deep learning during the training phase, and during inference, deep learning rapidly predicts the global organ morphology, followed by iterative optimization to refine local surfaces and mesh quality. This framework demonstrated marked superiority in geometric fidelity than current mainstream deep learning-based organ reconstruction models. For individual anatomical structures, the reconstructed 3D geometries for the bladder, rectum, and uterus achieved significantly lower Chamfer Distance values and higher Dice Similarity Coefficient scores. In addition, while maintaining high computational efficiency, the proposed architecture yielded superior overall volumetric mesh quality. At the patient level, the framework achieved higher mean values for the 10 worst elements for both minSICN and minSIGE compared to traditional geometric post-processing algorithms.

15.
arXiv (CS.AI) 2026-06-24

THEIA: Learning Complete Kleene Three-Valued Logic in a Pure-Neural Modular Architecture

arXiv:2604.11284v5 Announce Type: replace-cross Abstract: We present THEIA, a 2.75M-parameter modular neural architecture that learns the complete Kleene three-valued logic (K3) truth table from task data without external symbolic inference or hand-encoded K3 gate primitives. Across 5 seeds it passes all 39 K3 rules at >99% per-rule accuracy. K3 learnability is not the central finding: Transformer baselines also pass all 39 rules, and flat MLPs match THEIA on Phase-1 accuracy within 0.04pp. The contributions are two properties of the learned system. (1) Uncertainty-verdict asymmetric propagation. THEIA preserves Has-Unknown at every upstream boundary (80.0/91.1/90.8/99.7% across Arith/Order/Set/Logic vs. ~52% majority) while final-verdict decodability stays at or below a 73.4% U-vs-non-U oracle reference under linear and nonlinear probes. Activation patching on non-absorbent T->U cases flips 4,898/4,898 OR and 4,719/4,719 AND pairs across 5 seeds, ruling out residual shortcuts. (2) Reliability spectrum under discretized end-to-end training, on tasks decomposable along the engine boundaries. A mod-3 sequential composition task generalizes from 5- to 500-step evaluation at 99.96+-0.04% (5 seeds). Under identical Gumbel-softmax training, flat MLPs collapse to chance by 50 steps; a 2x2 ResMLP grid reaches >=99% on only 3/20 (config, seed) trials; a pre-LN Transformer reaches 99.24+-0.34%. Straight-through discretization prevents 0.999^500 compounding; the architectural separator is sustaining Phase-1 accuracy under Phase-3 training, where flat MLPs fail. Auxiliary: under per-architecture development defaults (not optimizer-controlled), THEIA reaches 12/12 Kleene coverage 6.5x faster than a parameter-comparable 8L Transformer; this narrows to ~3.6x with Transformer-standard tuning and 4.93x with the same recipe on both. Ratios are config-specific, not asymptotic.

16.
PLOS Computational Biology 2026-06-02

Data-driven model reveals increased stability of CAG-expanded <i>huntingtin</i> RNA due to MID1 binding

Authors:

by Yuhong Liu, Annika Reisbitzer, Domagoj Dorešić, Jan Hasenauer, Sybille Krauß, Tatjana Tchumatchenko RNA-binding proteins (RBP) are important regulators of RNA metabolism. In neurodegenerative disorders such as Huntington’s Disease (HD), disrupted RBP-RNA interactions contribute to neuronal dysfunction. One such RBP, Midline 1 (MID1), has been shown to aberrantly associate with mutant huntingtin (Htt) RNA, enhancing its translation, yet the mechanism driving this effect remains unknown. Here, we develop a computational model to understand the role of MID1. Based on previously published data, our model predicts that MID1 increases the stability of the Htt RNA. We experimentally validate this prediction, showing that overexpression of MID1 significantly prolongs the half-life of mutant Htt RNA. Furthermore, we evaluate model refinements, including clustering of MID1-bound RNA, which allow capturing all key observations in the data. Together, we provide a data-driven framework that underlines the importance of RBP-RNA interaction in post-transcriptional regulation. This framework also shows how individual molecular reactions jointly determine RNA stability and protein levels in HD.

17.
arXiv (CS.CL) 2026-06-16

GePBench: Evaluating Fundamental Geometric Perception for Multimodal Large Language Models

Geometric shapes play important roles in both physical world and human cognition. While multimodal large language models (MLLMs) have made significant advancements in visual understanding, their abilities to recognize geometric shapes and their spatial relationships, which we term geometric perception, are not explicitly and systematically explored. To address this gap, we introduce GePBench, a novel benchmark specifically designed to assess the geometric perception capabilities of MLLMs. Our extensive evaluations reveal that even the current state-of-the-art MLLMs exhibit significant deficiencies in geometric perception tasks. Furthermore, we show that models trained with GePBench data demonstrate considerable improvements on a wide range of downstream tasks, highlighting the critical role of geometric perception in enabling advanced multimodal applications. Our code and datasets are available at \href{https://github.com/Changhao-Xiang/GePBench}{https://github.com/Changhao-Xiang/GePBench}.

18.
bioRxiv (Bioinfo) 2026-06-11

A multi-agent system for spine MRI report generation from multi-sequence imaging

Spinal pathology is a leading cause of pain and disability worldwide. Spine magnetic resonance imaging (MRI) is central to clinical evaluation, yet its interpretation remains complex and time-consuming, requiring integration of information across multiple imaging sequences and anatomical regions. Despite recent advances in automated MRI analysis, effectively combining multi-sequence data while preserving sequence-specific diagnostic information remains an open challenge. Here we present SpineAgent, a multi-agent framework for spine MRI report generation built upon a multi-sequence foundation model trained on routine clinical data from 32,047 patients and 453,683 MRI series, comprising a total of 13,441,191 MRI slices. To accommodate diverse modalities of sequences, we first pre-train two DINOv3-based encoders separately on T1- and T2-weighted sequences. We then introduce a continual training strategy that learns a synthesizer to embed images of other sequences using the T1 and T2 encoders, producing patient-level embedding that integrates various signals across MRI sequences. Using these embeddings, SpineAgent achieves state-of-the-art performance, with mean 10.8% AUROC improvement across 17 spinal condition-prediction tasks compared to the best competing method, and demonstrates strong generalizability under cross-manufacturer and cross-cohort evaluation. Beyond classification, SpineAgent enables pathology localization by identifying findings-relevant slices and segmenting pathological regions. It also supports multimodal image-report retrieval, providing a solid foundation for scalable and explainable MRI report generation. We further integrate these validated capabilities of SpineAgent into 37 specialized agents for condition diagnosis, pathological-region localization, and clinically-similar-cases retrieval. Finally, we incorporate their outputs as structured tokens within a Medical Report Agent trained end-to-end for report generation. Through both automated metrics and expert evaluation by five radiologists, SpineAgent achieves leading performance in spine MRI report generation. Together, SpineAgent introduces a continual training approach for multi-sequence spine MRI understanding. By decomposing report generation into clinically grounded subtasks addressed by specialized agents, the SpineAgent framework enables accurate, interpretable and generalizable spine MRI reporting across diverse imaging sequences and anatomical regions.

19.
arXiv (CS.AI) 2026-06-24

Difference-Making without Making a Difference

arXiv:2606.24832v1 Announce Type: new Abstract: Over a series of seven papers, Andreas & Günther have introduced seven definitions of actual causation and have classified them as belonging to three different, competing, types of accounts: factual difference-making, counterfactual difference-making, and regularity-based. I show that their most recent - factual difference-making - definition instantiates all three types, thereby proving that these are distinctions without a difference. I further compare their novel account to the other six accounts on several crucial examples, revealing that this undermines all seven of their accounts.

20.
arXiv (CS.AI) 2026-06-19

Cross-Dataset, Age, and Gender Generalization: A Comprehensive Analysis of Fine-Tuning Strategies for Low-Resource Children's ASR

arXiv:2606.19791v1 Announce Type: cross Abstract: The challenge associated with recognizing dysarthric speech primarily arises from pronounced acoustic variability attributed to impaired articulatory precision. Past research has demonstrated improved recognition through the use of hybrid DNN/HMM sequence discriminative training. This paper presents a comprehensive investigation of various combinations of acoustic features tailored to different Acoustic Models, offering suitable feature selections for each. The incorporation of Pitch features notably improved recognition performance, especially for sentence recognition tasks involving dysarthric speech. Through a systematic examination of the TORGO database, we have demonstrated the potential to enhance the performance of the state-of-the-art Factorized Time Delay Neural Network (F-TDNN) model for recognizing dysarthric speech. Our methods, implemented with the F-TDNN model, resulted in a 4.65\% relative improvement in isolated word recognition and a 4.63\% relative improvement in sentence recognition for dysarthric speech, compared to previous research. This improvement effectively compensates for speech variability, attributable to our deliberate selection of the number of overlapping frames between consecutive training example chunks.

21.
arXiv (CS.LG) 2026-06-24

Target-Aware Linear Regression Under Distribution Shift

arXiv:2606.22775v2 Announce Type: replace-cross Abstract: Distribution shift between training and deployment is a pervasive challenge for modern AI systems. In many cases, the target marginals of covariates and response are known or specified through population-level observations, boundary conditions, properties of simulator configurations, or alignment-time distributional constraints. Such knowledge may provide valuable side information for regression estimation. We study this problem in the multivariate linear regression setting with a stable conditional mean $E[Y\mid X]$ across source and target, and identify the hybrid-loss estimator, which jointly incorporates both target marginals, as a benchmark target-aware estimator. Its direct computation, however, requires solving a coupled nonlinear optimization that is expensive at scale. Our main contribution is to develop and evaluate two computationally tractable alternatives: a constrained moment-matching estimator and a two-stage estimator that augments ordinary least squares with a calibration step. For all three estimators, we derive and compare closed-form asymptotic mean squared errors, yielding conditions under which the tractable alternatives match or closely approximate the hybrid benchmark, and regimes in which they do not. Monte Carlo experiments across three controlled shift regimes validate the theoretical results, investigate the accuracy-runtime tradeoffs among the three estimators, and translate into guidance on estimator choice. In particular, the two-stage estimator nearly matches the hybrid benchmark in the high signal-to-noise regime at essentially no additional cost, providing theoretical grounding for empirical observations in nonlinear settings.

22.
Nature (Science) 2026-06-10

SIRT7 regulates dosage compensation and safeguards the female X&#xa0;chromosome

Sirtuins are deacetylases implicated in stress responses and longevity in mammals1,2. Although their differential impact on disease for the two sexes has been noted3–7, the underlying reasons are unclear. Here, using Sirt7 as a model in mice, we examine the mechanisms leading to sex differences and find that Sirt7−/− female mice have decreased fitness throughout their lifespan. Notably, SIRT7 preferentially localizes to the sex chromosomes. In female&nbsp;individuals, SIRT7 loss affects X-chromosome inactivation, the first arm of dosage compensation that equalizes X-linked gene expression between males and females8–10. Xist is overexpressed and gene silencing becomes more efficient. However,&nbsp;SIRT7 loss has greatest impact on the active X (Xa) chromosome. The Xa chromosome becomes hyperacetylated at Lys36 of histone H3, structurally disorganized, prone to DNA damage and overexpressed. Increased Xa-chromosome expression leads to genome imbalance and augmented X-chromosome upregulation—the second arm of dosage compensation that balances X-chromosome versus autosomal gene expression. These data reveal an essential crosstalk between sirtuins and the sex chromosomes, with SIRT7 safeguarding X-chromosome integrity and dosage balance with autosomes. We propose that the sex bias in SIRT7 biology can be explained in part by unequal effects on the sex chromosomes. SIRT7 safeguards X-chromosome integrity and dosage balance with autosomes.

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

Iterative Tool Usage Exploration for Multimodal Agents via Step-wise Preference Tuning

Multimodal agents, which integrate a controller e.g., a vision language model) with external tools, have demonstrated remarkable capabilities in tackling complex multimodal tasks. Existing approaches for training these agents, both supervised fine-tuning and reinforcement learning, depend on extensive human-annotated task-answer pairs and tool trajectories. However, for complex multimodal tasks, such annotations are prohibitively expensive or impractical to obtain. In this paper, we propose an iterative tool usage exploration method for multimodal agents without any pre-collected data, namely SPORT, via step-wise preference optimization to refine the trajectories of tool usage. Our method enables multimodal agents to autonomously discover effective tool usage strategies through self-exploration and optimization, eliminating the bottleneck of human annotation. SPORT has four iterative components: task synthesis, step sampling, step verification, and preference tuning. We first synthesize multimodal tasks using language models. Then, we introduce a novel trajectory exploration scheme, where step sampling and step verification are executed alternately to solve synthesized tasks. In step sampling, the agent tries different tools and obtains corresponding results. In step verification, we employ a verifier to provide AI feedback to construct step-wise preference data. The data is subsequently used to update the controller for tool usage through preference tuning, producing a SPORT agent. By interacting with real environments, the SPORT agent gradually evolves into a more refined and capable system. Evaluation in the GTA and GAIA benchmarks shows that the SPORT agent achieves 6.41% and 3.64% improvements, underscoring the generalization and effectiveness introduced by our method. The project page is https://SPORT-Agents.github.io.

24.
Nature (Science) 2026-06-17

These ‘master’ proteins protect us from deadly mutations — and could inspire new drugs

Authors:

Biology has clever ways to mask the effects of potentially harmful gene mutations. Scientists are investigating how this ‘buffering’ works — and how to exploit it. Biology has clever ways to mask the effects of potentially harmful gene mutations. Scientists are investigating how this ‘buffering’ works — and how to exploit it.