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01.
arXiv (math.PR) 2026-06-15

Scaling limits of multitype Bienaymé trees

arXiv:2507.23241v2 Announce Type: replace Abstract: We consider critical multitype Bienaymé trees that are either irreducible or possess a critical irreducible component with attached subcritical components. These trees are studied under two distinct conditioning frameworks: first, conditioning on the value of a linear combination of the numbers of vertices of given types; and second, conditioning on the precise number of vertices belonging to a selected subset of types. We prove that, under a finite exponential moment condition, the scaling limit as the tree size tends to infinity is given by the Brownian Continuum Random Tree. Additionally, we establish strong nonasymptotic tail bounds for the height of such trees. Our main tools include a flattening operation applied to multitype trees and sharp estimates regarding the structure of monotype trees with a given sequence of degrees.

02.
arXiv (quant-ph) 2026-06-15

Fourier analysis of quantum neural network with non-linear data embedding

arXiv:2606.14206v1 Announce Type: new Abstract: Fourier analysis has become a crucial tool for understanding the expressivity of Variational Quantum Circuit (VQC) models, as well as an important indicator of barren plateaus (BP). While existing literature has only studied angle-embedded VQCs in a noiseless environment, here we develop the Fourier analysis of VQCs with non-linear data embedding, with particular focus on amplitude embedding, which provides a naturally compact encoding scheme. We first investigate a subtle difference in the domain of input features within amplitude embedding that leads to a distinct expressivity of the zero-frequency Fourier coefficient. By assuming that the ensemble of unitaries generated from the parameter space forms at least a 2-design with respect to the unitary group, we derive, via Weingarten calculus, that the mean of the Fourier coefficients is concentrated at zero, and the variance scales at an exponentially decaying order with respect to the multi-dimensional frequency magnitude. When a noise channel with unitary Kraus operators and probabilities $\{p_k\}$ is taken into account, the variance is further suppressed by a factor $\left(\sum_k p_k^2\right)^{Q}

03.
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.

04.
arXiv (CS.CL) 2026-06-16

Emergent retokenization symmetry in large language models: phenomenology and applications

Tokenization introduces representational redundancy: under a fixed token vocabulary, every byte string admits many valid token encodings, or segmentations, that decode to the same surface string. However, given a prompt, most language model tokenizers break this representational symmetry by returning a canonical segmentation. Training only on canonical segmentations should influence inference behavior, and there is little reason to expect models to respect segmentation symmetry on downstream tasks. We find that this symmetry partially emerges during training. Here, we probe this emergent symmetry through experiments testing token compositional understanding, representation diversity, and task focused benchmark performance. We primarily use retokenization – replacing a prompt's canonical tokenization with an alternative segmentation while preserving its bytes exactly. Relative to other prompt perturbations, retokenization is unusually clean because it isolates segmentation effects without changing syntax, semantics or surface form. We use retokenization to study sensitivity and robustness to semantically identical input representations across pretraining and post-training. Moreover, this partial retokenization symmetry suggests a distinct inference-time sampling axis. While temperature sampling generates diverse outputs from the model using its next-token probability distribution, retokenization generates diversity from the model's internal computations through semantically equivalent input representations. We find that while this retokenization sampling strategy can hurt performance on easy problems, it can also recover solutions that conventional sampling does not find. Overall, our work presents retokenization as a simple yet powerful probe of large language models, shedding light on compositional understanding and prompt sensitivity, and offering a novel sampling strategy.

05.
arXiv (CS.CL) 2026-06-15

The Coin Flip Judge? Reliability and Bias in LLM-as-a-Judge Evaluation

Authors:

LLM-as-a-Judge is now widely used to rank model outputs, train reward models, and populate public leaderboards, but its run-to-run reliability remains under-characterized. We study repeated identical evaluations on 29 tasks spanning 10 categories using two OpenAI judge models (GPT-4o-mini and GPT-4.1-mini), with 50 pairwise trials and 50 pointwise trials per question, supplemented by temperature and prompt-sensitivity ablations. Across judges, pairwise preferences flip on average 13.6% of the time, with 28% of questions exceeding a 20% flip rate and one question reaching 56%. GPT-4o-mini also exhibits a significant first-position bias (72% A-majority, p = 0.024). At the same time, mean pointwise score gaps are small (0.19–0.36 on a 10-point scale) and not statistically significant in aggregate, producing a pairwise–pointwise gap: judges frequently choose a winner even when their own scalar scores provide little evidence of a meaningful quality difference. Beyond within-judge instability, cross-judge agreement is only 76% ($\kappa = 0.51$), semantically equivalent prompt templates change majority outcomes in 25% of tested cases, and deterministic decoding reduces but does not eliminate inconsistency. A reliability curve analysis shows that, in our dataset, 11 repeated trials are needed for a majority vote to recover the 50-trial reference verdict with 95% probability on average, rising to 15 for high-variance questions. These findings suggest that single-trial LLM judging is often too noisy for high-stakes evaluation, and that multi-trial aggregation, position randomization, and explicit uncertainty reporting should be standard practice. Because both judges are from a single provider, cross-provider replication remains an important next step.

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

Simulation-Based Multi-Fillet Evaluation of Woody Breast Poultry Fillets

Woody breast (WB) is a myopathy in modern broiler chickens that causes the breast muscle to become unusually stiff and fibrous, leading to decreased meat quality and significant economic losses. State-of-the-art automated WB detection relies on a side-view imaging system to analyze the bending behavior of a single fillet as it falls off a conveyor belt. While highly accurate, this approach is constrained by its single-fillet field of view, creating throughput bottlenecks on commercial processing lines. In this paper, we address this limitation via a novel multi-fillet detection architecture utilizing a top-down camera configuration. To validate our approach, we first develop a high-fidelity digital twin of an industrial conveyor system. Next, we synthesize a diverse dataset of 3D fillet meshes and model their viscoelastic bending dynamics using a physics-based simulation engine. Lastly, a continuous 2D shape deformation score is extracted from the top-down perspective as the simulated fillets traverse the roller precipice. Experimental results demonstrate that the top-down shape score effectively captures the contour changes of the fillets as it bends, providing a robust and scalable alternative to a side-view imaging system for simultaneous multi-fillet WB evaluation.

07.
arXiv (quant-ph) 2026-06-11

A Cryogenic Uniaxial Strain Cell for Quantum Devices

arXiv:2606.11485v1 Announce Type: new Abstract: Mechanical strain is a powerful resource for tuning quantum systems, but existing piezoelectric strain cells are generally optimized for fragile, high-aspect-ratio single crystals rather than the thick, square-profile chips typical of semiconductor quantum devices. Furthermore, adapting these cells for qubits requires accommodating dense RF and DC wiring while maintaining strict electrical isolation from high-voltage piezo actuators. Here, we present a piezoelectric uniaxial strain cell designed to homogeneously strain thick, square-profile substrates. We introduce a highly symmetric dual-chip loading configuration that effectively suppresses flexural deformation and shear stress. The cell integrates a high-density RF/DC interposer to support standard wire bonding and encloses the actuators in a grounded Faraday cage to prevent unwanted Stark shifts in the device layer. Finite element simulations confirm that combining stiff actuators with this symmetric mounting drastically improves strain homogeneity. Finally, we validate the apparatus experimentally by applying uniaxial strain to a 200 $\mu$m thick silicon die. Surface strain measurements demonstrate an applied strain of 215 $\mu\epsilon$ for 200 V applied piezo bias.

08.
arXiv (CS.LG) 2026-06-19

DF-ExpEnse: Diffusion Filtered Exploration for Sample Efficient Finetuning

arXiv:2606.19656v1 Announce Type: cross Abstract: A natural recipe for intelligent robotic decision-making is initializing from pretrained generative control policies, which have summarized offline experience, and adapting them to self-collected online experience. We present DF-ExpEnse, an exploration technique that improves the quality of online experience collection, thus increasing finetuning sample-efficiency. DF-ExpEnse leverages the multimodal modeling capabilities of the generative control policy to create an expressive and tractably evaluatable candidate set. It then utilizes an ensemble of critics to identify the action that best balances quality with high exploration interest. In fleet settings, DF-ExpEnse further enables cross-agent communication to facilitate collaborative exploration as a group. DF-ExpEnse can be seamlessly integrated with existing strategies that finetune pretrained generative control policies via reinforcement learning. We experimentally validate consistent sample-efficiency benefits through DF-ExpEnse across a variety of manipulation and locomotion tasks, compared to default finetuning and alternative action selection schemes. Project can be found at https://df-expense.github.io.

09.
arXiv (CS.LG) 2026-06-16

Analytic Torsion and Spectral Gap Capture Persistent-Laplacian Performance

arXiv:2606.16990v1 Announce Type: new Abstract: While persistent Laplacians (PL) offer a richer geometric representation of data than persistent homology, utilizing their full eigenspectrum for learning tasks is often hampered by high dimensionality and the ``varying length'' problem across different filtration scales. We propose a compact spectral representation that distills the persistent Laplacian into three mathematically grounded invariants: Betti numbers, the spectral gap, and analytic torsion. Across benchmark datasets including MNIST, QM-3D, and SKEMPI WT, we demonstrate that this reduced feature space captures the essential predictive signal of the full spectrum, and in some cases outperforms it, while significantly reducing computational overhead and preventing the noise introduced by higher-frequency eigenvalues. Our results suggest that these invariants provide a principled, fixed-length interface between spectral geometry and topological learning.

10.
arXiv (quant-ph) 2026-06-19

Arrival times of an atomic Bose-Einstein condensate

arXiv:2606.20281v1 Announce Type: cross Abstract: The times of flight of an atomic Bose-Einstein condensate are theoretically investigated in the experimentally unexplored regime corresponding to detection close to the trap of the condensate. In this regime, there is no consensus on how to calculate the distribution of times of arrival onto the detector. For non-interacting particles, distinct theoretical predictions have been made in the past. This work analyses how these predictions are modified for an interacting Bose-Einstein condensate. For this purpose, a time-dependent Gross-Pitaevskii equation is solved analytically and numerically.

11.
arXiv (CS.CV) 2026-06-17

FUSER: Feed-Forward MUltiview 3D Registration Transformer and SE(3)$^N$ Diffusion Refinement

Registration of multiview point clouds conventionally relies on extensive pairwise matching to build a pose graph for global synchronization, which is computationally expensive and inherently ill-posed without holistic geometric constraints. This paper proposes FUSER, the first feed-forward multiview registration transformer that jointly processes all scans in a unified, compact latent space to directly predict global poses without any pairwise estimation. To maintain tractability, FUSER encodes each scan into low-resolution superpoint features via a sparse 3D CNN that preserves absolute translation cues, and performs efficient intra- and inter-scan reasoning through a Geometric Alternating Attention module. Particularly, we transfer 2D attention priors from off-the-shelf foundation models to enhance 3D feature interaction and geometric consistency. Building upon FUSER, we further introduce FUSER-DF, an SE(3)$^N$ diffusion refinement framework to correct FUSER's estimates via denoising in the joint SE(3)$^N$ space. FUSER acts as a surrogate multiview registration model to construct the denoiser, and a prior-conditioned SE(3)$^N$ variational lower bound is derived for denoising supervision. Extensive experiments on 3DMatch, ScanNet and ArkitScenes demonstrate that our approach achieves the superior registration accuracy and outstanding computational efficiency.

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

Artemis: Anatomy-Resolved inTervention for Eliminating Multimodal NeuroImage confounderS

arXiv:2606.18287v1 Announce Type: new Abstract: Multimodal neuroimaging, integrating functional connectivity from fMRI and structural connectivity from DTI, enables non-invasive analysis of brain networks using graph neural networks. However, demographic factors such as age and sex systematically confound the relationship between brain connectivity and clinical outcomes, causing GNNs to exploit spurious shortcuts rather than learning causally invariant representations. While recent causal GNN methods introduce causality at the graph-modeling level, their causal mechanisms remain domain-agnostic without accounting for the real-world confounders inherent in clinical neuroimaging data. Moreover, brain networks are constructed from atlas-based parcellations where each region exhibits distinct sensitivity to demographic factors, necessitating region-aware adjustment. We propose Artemis, a region-level causal framework that bridges this gap with causal intervention at each brain region independently by learning region-specific confounder representations with lightweight parameters. Our adjustment comprehensively utilized the multimodal functional and structural features for graph reasoning as a plug-in module compatible with arbitrary GNN backbones. Experiments on three benchmarks, ADNI for disease diagnosis, OASIS for dementia staging, and HCP for sex classification, demonstrate consistent improvements over representative GNN-based baselines. Multiple supporting experiments further demonstrate statistical significance and neuroscientific interpretability.

13.
arXiv (math.PR) 2026-06-17

Cutoff for asymmetric shelf shuffle

arXiv:2606.18039v1 Announce Type: new Abstract: A mechanical shuffler consists of $m$ shelves. A deck of $n$ cards, arranged in increasing order, is dealt from the bottom sequentially. Each card is assigned a shelf uniformly at random and placed on the top (bottom) of the existing pile with probability $p$ ($1-p$) independently. We refer to this as asymmetric shelf-shuffle. We find the law $\nu_{n, m}^{(p)}$ of the permutation induced by the asymmetric shelf-shuffle and show that the pair consisting of the number of descents and the number of valleys is a sufficient statistic. This generalizes a result of Diaconis, Fulman, and Holmes (Ann. Appl. Prob., 2013) corresponding to the case $p=1/2$. For $p=1/2$, Chen and Ottolini (ECP, 2025) established the cutoff in the total variation distance near $\lfloor n^{5/4}\rfloor$. We establish the cutoff for the asymmetric shelf shuffle. Let $\nu_n$ be the uniform measure on the set of all permutations $S_n$ of $\{1, \ldots, n\}$. For a fixed $p\neq 1/2$ and $c>0$, we show that \[\operatorname{TV}\left(\nu_{n, \lfloor cn^{3/2}\rfloor }^{(p)}, \nu_n\right)=1-2\Phi\left(-\frac{|2p-1|}{4\sqrt{3}c}\right)+O_{c, p}(n^{-1/2})\;.\] We also establish the cutoff in the separation distance near $m\approx n^{2}$ and in the relative entropy near $m=n^{3/2}$. In both cases, we also obtain the cutoff profile explicitly.

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

Optimizing Health Coverage in Ethiopia: A Learning-augmented Approach and Persistent Proportionality Under an Online Budget

arXiv:2509.00135v2 Announce Type: replace Abstract: As part of nationwide efforts aligned with the United Nations' Sustainable Development Goal 3 on Universal Health Coverage, Ethiopia's Ministry of Health is strengthening health posts to expand access to essential healthcare services. However, only a fraction of this health system strengthening effort can be implemented each year due to limited budgets and other competing priorities, thus the need for an optimization framework to guide prioritization across the regions of Ethiopia. In this paper, we develop a tool, Health Access Resource Planner (HARP), based on a principled decision-support optimization framework for sequential facility planning that aims to maximize population coverage under budget uncertainty while satisfying region-specific proportionality targets at every time step. We then propose two algorithms: (i) a learning-augmented approach that improves upon expert recommendations at any single-step; and (ii) a greedy algorithm for multi-step planning, both with strong worst-case approximation estimation. In collaboration with the Ethiopian Public Health Institute and Ministry of Health, we demonstrated the empirical efficacy of our method on three regions across various planning scenarios.

15.
arXiv (math.PR) 2026-06-16

Hua-Chen New Theory of Economic Optimization

arXiv:2504.19134v4 Announce Type: replace-cross Abstract: Between 1957-1985, Chinese mathematician Loo-Keng Hua pioneered economic optimization theory through three key contributions: establishing economic stability's fundamental theorem, proving the uniqueness of equilibrium solutions in economic systems, and developing a consumption-integrated model 50 days before his death. Since 1988, Mu-Fa Chen has been working on Hua's theory. He introduced stochastics, namely Markov chains, to economic optimization theory. He updated and developed Hua's model and came up with a new model (Chen's model) which has become the starting point of a new economic optimization theory. Chen's theory can be applied to economic stability test, bankruptcy prediction, product ranking and classification, economic prediction and adjustment, economic structure optimization. Chen's theory can also provide efficient algorithms that are programmable and intelligent. {Stochastics} is the cornerstone of Chen's theory. There is no overlap between Chen's theory, and the existing mathematical economy theory and the economics developments that were awarded Nobel Prizes in Economics between 1969 and 2024. The distinguished features of Chen's theory from the existing theories are quantitative, calculable, predictable, optimizable, programmable and can be intelligent. This survey provides a theoretical overview of the newly published monograph [5rw24]. Specifically, the invariant of the economic structure matrix, also known as the Chen's invariant, was first published in this survey.

16.
medRxiv (Medicine) 2026-06-22

Starting, stopping and restarting. Patterns of Methylphenidate Use over 14 years in a large public health system

Background Persistence with stimulant medication is poor in children and adolescents with ADHD, and the evidence base is derived predominantly from high-income countries. We describe methylphenidate utilisation patterns and predictors of 12-month retention across 14 years in a large South African public health service. Methods Retrospective cohort study using routine pharmacy data from the Western Cape provincial health service (2011-2024). Children aged 5-18 at first prescription were included. Treatment episodes were defined as continuous prescription sequences with no gap exceeding 90 days and classified as initiations or restarts. Logistic regression modelled 12-month retention against early visit frequency and formulation type as pre-specified exposures. Findings 421,925 prescription events for 23,243 children across 115 facilities generated 65,885 treatment episodes. Median age at first prescription was 10 years (IQR 8-12); 77.6% were male. Kaplan-Meier 12-month survival was 28.2% for initiations and 15.4% for restarts, substantially below high-income country comparators. A quarter of all initiating prescriptions were not followed by a subsequent dispensing event; nearly 40% of patients had three or more treatment episodes. Early visit frequency was the strongest predictor of 12-month retention (high vs low: OR 2.85, 95% CI 2.65-3.06). The sustained-release formulation effect was present but attenuated on multivariable adjustment. Treatment re-initiations showed a marked seasonal pattern consistent with the South African school calendar. Interpretation Twelve-month retention was markedly lower than high-income country rates. Against a backdrop of high attrition, both early visit frequency and sustained-release formulation access predicted persistence; clinical engagement and reducing structural barriers to access are modifiable factors in this setting. Funding None.

17.
arXiv (CS.AI) 2026-06-11

Libra: Efficient Resource Management for Agentic RL Post-Training

arXiv:2606.03077v2 Announce Type: replace-cross Abstract: Reinforcement learning (RL) has emerged as a standard post-training paradigm for shaping large language models (LLMs) into capable agents. In agentic RL, the rollout stage generates trajectories while invoking tools, producing long-tailed and non-stationary workloads that expose two fundamental challenges in resource management. First, due to the long-tail distribution, a small fraction of trajectories dominates rollout makespan. Second, rollout and training are subject to cross-stage imbalance, as they exhibit strong asymmetry in compute patterns, memory demands, and sensitivity to sequence length. Compounding this asymmetry, the sequence length distribution drifts continuously as the policy evolves, rendering any static resource split progressively suboptimal. We present Libra, a resource management system to address both challenges via two core mechanisms. The first is a global resource planner that jointly optimizes GPU allocation across rollout and training clusters. It leverages an elastic hybrid pool to enable lightweight, non-blocking worker reallocation between stages. The second is a causality-driven multi-level feedback queue (C-MLFQ) scheduler, which routes requests to heterogeneous rollout buckets based on causal signals derived from tool-return outcomes, rather than relying on fragile length predictions. Evaluated on 48 A800 GPUs, Libra achieves up to 3.0x higher throughput and converges up to 2.5x faster in reward compared to the baselines.

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

How Useful is Causal Invariance for Domain Adaptation in Finite-Sample Settings?

arXiv:2606.12680v1 Announce Type: new Abstract: Machine learning models often degrade when they are deployed on a target distribution that differs from the source distributions they were trained on. Recent work in causality-based domain generalization has shown how shared causal structure between domains can induce invariant predictors, e.g., models on a subset of features which have stable risk across structured domain shifts. However, the extent to which such population-level causal invariances can lead to gains in finite-sample settings remains underexplored. In particular, in practice we often have access to a few labeled target samples, a setting called supervised domain adaptation (sDA). In this paper, we explore when (full or partial) causal knowledge can provably improve supervised domain adaptation. As a first step, we study linear regression, where full or partial causal knowledge specifies a collection of invariant or possibly invariant feature subsets, each yielding a source-trained candidate predictor. We derive matching upper and lower bounds showing that finite-sample gains are governed by the target-risk margins separating the candidates, together with the finite-source estimation error. When these margins are sufficiently large relative to $n_Q$, an adaptive aggregation procedure can match the best candidate predictor while avoiding negative transfer relative to target-only learning. On the other hand, when the margins are too small, no algorithm can reliably exploit the candidate collection to obtain faster finite-sample rates. We further connect these margins to structural shift magnitude in linear SCMs and validate the theory on real-world causal benchmarks.

19.
arXiv (CS.AI) 2026-06-18

RTSGameBench: An RTS Benchmark for Strategic Reasoning by Vision-Language Models

arXiv:2606.18950v1 Announce Type: new Abstract: Modern Vision-Language Models (VLMs) often struggle with strategic reasoning, i.e., anticipating and influencing other agents' actions, under uncertainty in competitive and cooperative settings. Real-time strategy (RTS) games can be a natural testbed for diagnosing this limitation, as they demand coordination with allies, adaptation to opponents' strategy, and long-horizon planning under partial observability. However, existing RTS benchmarks offer limited evaluation scope, lack systematic competency diagnosis, and remain fixed in the pre-designed scenario coverage. To address these limitations, we present RTSGameBench, which is built on Beyond All Reason, a large-scale RTS game with an expanded battlefield that demands broader strategy diversity than the existing testbeds. The proposed benchmark provides evaluations through diverse gameplay across various matchup structures, diagnostic assessment via mini-games, each targeting an individual strategic competency, and extensible coverage via a self-evolving generation framework that converts free-form queries into new mini-games, improving over successive cycles. Additionally, for VLMs to operate in large-scale RTS games, we provide RTSGameAgent that manages units by an FSM with agentic memory. We empirically validate that multiple state-of-the-art VLMs do not perform well when matchups demand tighter coordination, multiagent coordination and when task scale increases.

20.
arXiv (CS.AI) 2026-06-16

StarOR: Synergizing Tree Search and Test-Time Reinforcement Learning for Optimization Modeling

arXiv:2606.15197v1 Announce Type: cross Abstract: Optimization modeling is inherently hierarchical, requiring a precise sequence of symbolic commitments. Traditional learning-based automated optimization modeling methods improve modeling policies through large-scale annotated or curated training data, but are costly to adapt to new problem distributions. Meanwhile, one-shot generation remains brittle in hierarchical modeling, where early symbolic errors can propagate into invalid formulations. Test-time scaling offers a promising alternative by enabling structural exploration with additional instance-level computation; however, existing search-based methods typically rely on a fixed policy, causing repeated rollouts to inherit similar modeling biases and providing limited credit assignment for intermediate decisions. To address these limitations, we propose StarOR, a synergistic search-and-adaptation framework that couples MCTS with Test-Time Reinforcement Learning for optimization modeling. StarOR decomposes the modeling process into four stages and updates a transient LoRA adapter via GRPO at each non-terminal node. By using MCTS-generated siblings as local comparison sets, StarOR transforms search-time exploration into instance-specific policy refinement. Moreover, an unsupervised multi-faceted reward system provides fine-grained feedback for intermediate formulation decisions without ground-truth labels. Experiments across five optimization benchmarks show that StarOR achieves state-of-the-art performance even with a 4B backbone, outperforming existing methods and the frontier LLMs.

21.
Nature (Science) 2026-06-17

Towards autonomous medical artificial intelligence agents

Authors:

Large language models (LLMs) show great potential for clinical decision-making, yet most applications remain narrow, task-specific chat tools rather than systems integrated into clinical workflows1,2. However, building physician copilots will require models that operate within the electronic health record (EHR), with governed access to patient data and the ability to initiate permitted EHR actions within defined safety constraints. Yet it remains unproven whether such a system can manage patient cases with physician-level performance. Here we show that MIRA (Medical Intelligence for Reasoning and Action), an autonomous artificial intelligence agent operating in a sandboxed EHR environment, can navigate a large clinical action space to obtain patient histories; order and interpret laboratory, imaging and microbiology tests; generate differential diagnoses; and formulate treatment plans such as prescribing medications, scheduling surgical procedures and planning admissions. In simulations on real patient cases spanning multiple diagnoses, MIRA outperformed physicians in diagnostic accuracy and made guideline-concordant, medication-safe and appropriate admission decisions. Compared with previous LLM applications that addressed isolated subtasks or provided free-text advice, these results suggest that an EHR-integrated artificial intelligence agent can turn clinical intent into structured, actionable EHR operations, possibly making it a more effective decision-support partner for physicians. Further work is needed to establish generalization, safety and governance through prospective, real-world studies. A large language model artificial intelligence agent operating in a sandboxed electronic health record system can autonomously take patient histories, order tests, interpret findings, diagnose conditions and propose treatments, outperforming experienced clinicians while adhering to safety standards and clinical guidelines.

22.
arXiv (CS.LG) 2026-06-15

Muon$^p$: Muon with Fractional Spectral Powers

arXiv:2606.13867v1 Announce Type: new Abstract: Muon is an increasingly widely used optimizer that replaces a gradient $G=USV^\top$ with its polar factor $UV^\top$, thereby flattening the singular spectrum. However, full flattening discards singular-value information that may matter for adaptation. We introduce Muon$^p$, a Muon-style optimizer that instead uses fractional spectral-power updates $US^pV^\top$ for rational $p\in(0,1)$, interpolating between Muon and gradient descent. To make it practical, we prove that fractional spectral powers cannot be computed by any fixed univariate polynomial iteration, and furthermore derive low-degree odd bivariate recurrences that approximate $US^pV^\top$ using only matrix multiplications, preserving Muon's matrix-multiplication-only structure and compute complexity. We show that Muon$^p$ maximizes the linear improvement in loss under the Schatten $q$-norm for $q=1+\frac{1}{p}$. Empirically, Muon$^p$ is especially effective for finetuning: on billion-scale models, Muon$^p$ improves validation perplexity and downstream task performance. We further analyze when Muon$^p$ is less suitable, through the lens of spectral geometry. Our results reveal important insights on when preserving the singular spectrum can bring significant gains, and introduce a principled way to achieve them.

23.
arXiv (CS.LG) 2026-06-19

BLISS: A Lightweight Bilevel Influence Scoring Method for Data Selection in Language Model Pretraining

arXiv:2510.06048v5 Announce Type: replace Abstract: Effective data selection is essential for pretraining large language models (LLMs), enhancing efficiency and improving generalization to downstream tasks. However, existing approaches often require leveraging external pretrained models, making it difficult to disentangle the effects of data selection from those of the external pretrained models. In addition, they often overlook the long-term impact of selected data if the model is trained to convergence, primarily due to the prohibitive cost of full-scale LLM pretraining. In this paper, we introduce BLISS (BileveL Influence Scoring method for data Selection): a lightweight data selection method that operates entirely from scratch, without relying on any external pretrained oracle models, while explicitly accounting for the long-term impact of selected data. BLISS leverages a small proxy model as a surrogate for the LLM and employs a score model to estimate the long-term influence of training samples if the proxy model is trained to convergence. We formulate data selection as a bilevel optimization problem, where the upper-level objective optimizes the score model to assign importance weights to training samples, ensuring that minimizing the lower-level objective (i.e., training the proxy model over the weighted training loss until convergence) leads to best validation performance. Once optimized, the trained score model predicts influence scores for the dataset, enabling efficient selection of high-quality samples for LLM pretraining. We validate BLISS by pretraining 410M/1B/2.8B Pythia and LLaMA-0.5B models on selected subsets of the C4 dataset. Notably, under the 1B model setting, BLISS achieves $1.7\times$ speedup in reaching the same performance as the state-of-the-art method, demonstrating superior performance across multiple downstream tasks.

24.
Nature (Science) 2026-06-17

The ancestors of eukaryotic cells contained a mix of genes from various microbes

Authors: Unknown Author

Reconstruction of the ancestral gene repertoire of eukaryotic cells reveals traces of a series of close, long-term interactions with diverse microorganisms, and a role of viruses in gene exchange. The findings challenge the view that eukaryotic cells evolved from a simple merger of just two organisms. A series of gene-transfer events might have taken place in complex microbial communities.

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

Curvature-Informed Potential Energy Surface for Protein-Ligand Binding Affinity Prediction

arXiv:2606.14217v1 Announce Type: new Abstract: Accurate prediction of protein-ligand binding affinity is essential for structure-based drug discovery. Recent geometric deep learning methods have achieved promising performance by representing protein-ligand complexes as three-dimensional graphs. However, most existing approaches mainly rely on static interaction geometry from a single bound conformation, while neglecting molecular flexibility and binding-induced conformational changes. To address this limitation, we propose a curvature-informed potential energy surface (CPES) graph neural network for protein-ligand binding affinity prediction, which incorporates physics-informed curvature representations to model conformational flexibility. CPES first derives curvature spectral descriptors from the Hessian of the potential energy surface evaluated at equilibrium configurations, whose eigenvalues define the local principal curvatures of the potential energy surface. It then uses spectral cross-attention to compare the unbound ligand and protein with the bound complex, thereby capturing binding-induced changes in conformational dynamics. In parallel, hierarchical protein-ligand interaction representations are learned from static structural features through geometry-aware message passing, soft clustering, and bidirectional cross-attention. Finally, CPES fuses the curvature-informed dynamic representations with static interaction representations for affinity regression. Extensive evaluations on multiple benchmark datasets demonstrate that CPES achieves improved predictive performance and offers physical interpretability.