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01.
medRxiv (Medicine) 2026-06-22

Paired plasma and EV-enriched plasma proteomics reveal nonredundant sepsis-associated host-response signatures in critical illness

Background: Plasma proteomics may identify host-response signatures in sepsis, but it is unclear whether extracellular vesicle (EV)-enriched plasma provides distinct or redundant information compared with plasma. We compared paired plasma and EV-enriched plasma proteomes in critically ill patients with sepsis and critically ill non-sepsis controls (CINS). Methods: In this prospective observational study, paired plasma and EV-enriched plasma samples were analyzed from 56 critically ill adults, including 40 patients with sepsis and 16 CINS patients. Protein abundance was quantified using liquid chromatography-tandem mass spectrometry. Analyses compared proteomic depth, protein overlap, global concordance between compartments, and differential protein abundance between CINS and sepsis. Exploratory Gene Ontology enrichment was performed as a supplementary analysis. Results: EV-enriched plasma expanded proteomic detection, identifying 2,476 filtered proteins compared with 506 in plasma. Only 386 proteins were detected in both compartments, while 2,090 were unique to EV-enriched plasma and 120 were unique to plasma. Among shared proteins, plasma and EV-enriched plasma showed modest global concordance across critically ill patients (Spearman coeff = 0.322, p = 9.19 x 10^-11), with similar findings in sepsis alone. Differential abundance analysis identified 11 sepsis-associated proteins in plasma and 22 in EV-enriched plasma. Only SAA1, SAA2, and IGFBP6 were significant in both compartments. Exploratory pathway analysis supported acute-phase and inflammatory enrichment in plasma sepsis-associated proteins, while EV-enriched signals were directionally plausible but did not meet prespecified FDR thresholds. Conclusion: Plasma and EV-enriched plasma proteomics capture related but nonredundant sepsis-associated host-response information in critically ill patients.

02.
PLOS Computational Biology 2026-06-02

A comparative study of simulation-based inference methods for epidemic models with identifiability considerations

作者:

by Geunsoo Jang, K. Selçuk Candan, Gerardo Chowell Epidemic models play a critical role in understanding transmission dynamics, generating forecasts, and informing public health interventions when they are properly calibrated to epidemiological data. Traditional Bayesian inference methods rely on the likelihood function to update prior knowledge using observed data. However, for realistic epidemic models, likelihood functions are often analytically intractable or computationally prohibitive, which can limit the applicability of these methods. Simulation-based inference provides a promising alternative by approximating posterior distributions through forward simulations rather than an explicit likelihood evaluation. In this study, we present a systematic comparison of four approaches: Approximate Bayesian Computation (ABC), Neural Posterior Estimation (NPE), a neural method with temporal embedding, and Preconditioned Neural Posterior Estimation (PNPE), which integrates elements of both classical and neural techniques. These methods are evaluated across epidemic models of increasing complexity under fixed simulation budgets and varying levels of observational noise, with explicit attention to both structural and practical identifiability. Our results show that neural methods generally improve posterior fidelity and predictive accuracy compared with ABC under constrained simulation budgets. PNPE achieved strong performance in several simulation settings, whereas temporal embeddings improved inference in models with complex epidemic dynamics by capturing sequential dependencies. These gains come with important trade-offs: PNPE required substantially greater computational resources and, unlike fully amortized NPE-based methods, may require reconditioning for each new observation. In contrast, ABC remained computationally efficient and provided reasonable, though often more conservative, posterior estimates. Overall, our findings highlight trade-offs among computational efficiency, posterior accuracy, uncertainty calibration, and inference reusability, suggesting that method selection should depend on model complexity, data quality, identifiability, and available computational resources.

03.
arXiv (CS.AI) 2026-06-16

BRIDGE: Biological Evidence Refinement and Heterogeneous Dynamic Gating for Gene Regulatory Networks

arXiv:2606.14734v1 Announce Type: cross Abstract: Motivation: Gene regulatory network inference from single-cell RNA sequencing (scRNA-seq) data is important for uncovering cell-state-specific transcriptional programs. However, scRNA-seq measurements are sparse and noisy, and experimentally validated TF-target interactions remain limited, making reliable inference challenging. Although graph neural networks have advanced GRN prediction, existing methods often rely on biologically unconstrained graph augmentation, such as random edge perturbation, and insufficiently control information transfer between genes and cells. These limitations may distort regulatory structures and weaken robustness under noisy and weakly supervised settings. Results: To address these issues, we propose an innovative framework named Biological Evidence Refinement and Heterogeneous Dynamic Gating for Gene Regulatory Networks (BRIDGE). BRIDGE extracts gene and cell representations from the expression matrix and its matrix dual, and performs contrastive learning in the gene space and cell space between self and neighbors across the co-expression-refined regulatory view and the original graph. It then applies heterogeneous gated encoding to adaptively regulate information transfer between genes and cells, enabling robust transcription factor-to-target gene prediction. Experiments on benchmark datasets spanning three network types and seven cell types show that BRIDGE achieves state-of-the-art AUROC and AUPRC in most settings. In particular, on Specific networks, BRIDGE improves average AUPRC by 5% over the second-best baseline, GCLink. In cross-cell-type few-shot transfer, BRIDGE consistently outperforms GCLink and GENELink across all six target cell types. A case study on hESC further supports the biological relevance of the predictions, with 9 of the top 10 and 46 of the top 100 novel TF-target interactions validated by ChIPBase.

04.
arXiv (CS.CL) 2026-06-15

Harsher on Male? Evaluating LLMs on Gender-Asymmetric Moral Framing Across Diverse Conflict Scenarios

Existing studies on gender bias in LLMs have largely focused on stereotypes, occupational associations, or explicit harmful outputs. In this work, we ask whether LLMs apply consistent response standards to the same negative behavior under matched male-actor and female-actor conditions. We introduce GAMA-Bench, a gender-mirrored benchmark of 1,298 scenarios covering intimate relationship and public social conflicts. It constructs gender-neutral misconduct templates through controlled grids and cross-model review, then compiles them into paired first-person prompts with matched actor-gender and role-reference variations. We further design a structured response-framing protocol to measure how models allocate punishment, empathy, escalation, instruction, and blame. Experiments on 10 representative LLMs reveal a consistent male-disadvantaging asymmetry: male actors receive more punitive, escalatory, and blame-centered framing, whereas female actors receive more therapeutic and empathy-oriented framing for the same misconduct. Further analyses show that this pattern persists across model families, scenario tracks, model scale, and explicit thinking-style reasoning. The official code is available at https://github.com/xufeiqiong/GAMA-Bench.

05.
arXiv (CS.CL) 2026-06-12

PiDA: Phonetically-Informed Data Augmentation for Robust Vietnamese Speech Translation

Cascaded speech translation (ST) systems suffer from error propagation when Automatic Speech Recognition (ASR) outputs incorrect transcripts. We present the first systematic categorization of ASR errors for Vietnamese ST, classifying substitution errors by phonetic cause and quantifying their impact on downstream Neural Machine Translation (NMT) performance using Linear Mixed-Effects Modelling. We confirm that most ASR substitution errors arise from phonetic confusions rather than random noise, and that these phonetic errors significantly degrade ST quality. Motivated by this finding, we propose Phonetically-Informed Data Augmentation (PiDA), which generates ASR-like corruptions by substituting words with phonetically similar alternatives using phonetic word embeddings. Fine-tuning on a PiDA-augmented version of FLEURS Vietnamese-English improves translation of erroneous ASR outputs (up to +2.04 BLEU over standard fine-tuning) while also slightly improving clean-text performance.

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

Navigating Distribution Shifts in Medical Image Analysis: A Survey

Medical Image Analysis (MedIA) has become indispensable in modern healthcare, enhancing clinical diagnostics and personalized treatment. Despite the remarkable advancements supported by deep learning (DL) technologies, their practical deployment faces challenges posed by distribution shifts, where models trained on specific datasets underperform on others from varying hospitals, or patient populations. To address this issue, researchers have been actively developing strategies to increase the adaptability of DL models, enabling their effective use in unfamiliar environments. This paper systematically reviews approaches that apply DL techniques to MedIA systems affected by distribution shifts. Rather than organizing existing methods by technical characteristics, we explicitly bridge real-world clinical constraints – such as limited data accessibility, strict privacy requirements, and heterogeneous collaboration protocols – with the technical paradigms able to address them. By establishing this connection between operational constraints and methodological evolution, we categorize existing works into Joint Training, Federated Learning, Fine-tuning, and Domain Generalization, each aligned with specific healthcare scenarios. Beyond this taxonomy, our empirical analysis suggests that, as domain information becomes progressively less accessible across these paradigms, performance improvements become increasingly constrained, and further uncovers a gradual shift in methodological focus from explicit distribution alignment toward uncertainty-aware modeling, ultimately pointing to the need for more deployability-aware design in real-world MedIA.

07.
arXiv (CS.LG) 2026-06-19

Judging to Improve: A De-biased VLM-as-3D-Judge Protocol for Single-Image 3D Generation

arXiv:2606.20364v1 Announce Type: new Abstract: A companion study established a de-biased, cross-model VLM-as-3D-judge that reliably ranks single-image-to-3D mesh quality where cheap geometry and CLIP proxies fall short. This paper asks: can that judge's preferences specialize a strong open generator, TRELLIS, on one asset class (furniture), cheaply and without human labels? Taking the judge from ranking to optimization is where the work lives. Pushing a VLM judge into the training and evaluation loop exposes failure modes ranking never triggered, so our contribution is an optimization-grade hardening of the judge: a training judge (Qwen2.5-VL-7B) held distinct from an evaluation judge (InternVL3-8B) to break circularity; position-bias correction; and fixes for three failure modes (image overload, geometry-hiding splat renders, and reference-free judging that rewards clean-but-wrong outputs), with calibration evidence (clear-gap win-rate 0.83-1.0; base-vs-base ~0.5). Using this protocol as an independent evaluator, and working only from public models and data with lightweight parameter-efficient adaptation, we find our methods match the strong base rather than exceed it. Independent base samples carry essentially no learnable preference (0.94 order-flip rate), so signal must be engineered by quality-contrastive construction. Across six adaptation methods, two input regimes, and a severity sweep, the most targeted - conditioner repair under severe degradation - reaches parity (0.50) with the base, while no method clears the >=65% win-rate target. The result is mechanistic: clean inputs saturate the judge, flow-DIT fine-tuning washes out through the sampler, and conditioning repair is the locus that moves geometry. Win-rates are directional at n=8 objects. Matching a strong public-data base with cheap adaptation is itself informative: exceeding it needs more than lightweight PEFT on public data, and the judge protocol is reusable.

08.
arXiv (CS.AI) 2026-06-11

ProGRank: Probe-Gradient Reranking to Defend Dense-Retriever RAG from Corpus Poisoning

arXiv:2603.22934v3 Announce Type: replace Abstract: Retrieval-Augmented Generation (RAG) improves large language model applications by grounding generation in retrieved evidence, but also introduces corpus poisoning as a new attack surface. In this setting, an adversary injects or edits passages so that they enter the Top-$K$ results for target queries and influence downstream generation. Existing defences often rely on content filtering, auxiliary models, or generator-side reasoning, which complicates deployment. We propose ProGRank, a post hoc, training-free retriever-side defence for dense-retriever RAG. ProGRank stress-tests each query–passage pair under mild randomized perturbations, extracts probe gradients from a small fixed parameter subset, and derives two instability signals: representational consistency and dispersion risk. It then combines these signals with a score gate for reranking. ProGRank preserves the original passage content, requires no retraining, and supports a surrogate-based variant when the deployed retriever is unavailable. Experiments across datasets, retrievers, attacks, and retrieval-stage and end-to-end settings show that ProGRank improves robustness and maintains a favorable robustness–utility trade-off, including under adaptive evasive attacks.

09.
arXiv (CS.AI) 2026-06-19

A Systematic Evaluation of Black-Box Uncertainty Estimation Methods for Large Language Models

arXiv:2606.19868v1 Announce Type: new Abstract: Although large language models (LLMs) have shown strong capabilities across a wide range of tasks, their outputs often remain unreliable and may contain hallucinations, making uncertainty estimation (UE) essential for building trustworthy LLMs. In practice, many mainstream LLMs are only accessible through restricted APIs, where internal signals such as logits and hidden states are unavailable, making black-box UE especially important. However, existing work on black-box UE for LLMs remains fragmented in methodology and lacks a unified empirical comparison. To address this gap, we present a systematic review of black-box UE methods and organize them into five categories: verbalization-based, sampling-based, explanation-based, multi-agent, and hybrid methods. We further build a unified evaluation framework and benchmark 24 representative methods across 4 models and 4 dataset settings. Our results show that no single method consistently dominates across all settings. Nevertheless, methods that reason over and compare candidates in the answer space are generally effective, and hybrid methods that combine multiple uncertainty signals perform well under most conditions. By releasing the benchmark data and a unified evaluation framework, we aim to facilitate reproducible comparisons and support future research, while our empirical findings provide practical guidance for developing future black-box UE methods for LLMs.

10.
arXiv (CS.LG) 2026-06-16

An Exploratory Study of Blood Glucose Estimation from Photoplethysmography Signals using Machine Learning

arXiv:2606.15927v1 Announce Type: new Abstract: Diabetes and extreme blood sugar levels are some of the major health problems faced by humans today across the world. While Continuous Glucose Monitoring (CGM) has emerged as an effective technology for management of diabetes as well as for monitoring blood sugar levels, this technology has traditionally been invasive (that is, requiring the piercing of the skin) and carries the risk of irritation, induration, etc. This highlights the need for accurate and non-invasive CGM methods that can be deployed at scale. With the emergence of various sensing technologies and their integration in wearables like the smart-watch, we now have the capability to continuously monitor body signals like the Photoplethysmogram (PPG) in a non-invasive manner. Having the ability to continuously monitor blood glucose through CGMs and continuously monitor PPG signals through a smart-watch offers an opportunity to get dense data on these two, opening the possibility of building machine learning and deep learning based models to estimate blood glucose level from PPG signals. In this work, we first present a paired dataset comprising continuous PPG signals from a smartwatch along with glucose values recorded using a CGM device. We also present the results of some preliminary experimental explorations performed on our dataset. These preliminary results suggest that some predictive signals may exist, though more exploration is needed with more data from a larger number of individuals. The dataset can be accessed at https://zenodo.org/records/20577959

11.
arXiv (CS.AI) 2026-06-19

Mitigating Simplicity Bias in OOD Detection through Object Co-occurrence Analysis

arXiv:2605.07821v2 Announce Type: replace-cross Abstract: Out-of-distribution (OOD) detection is crucial for ensuring the reliability of deep learning models. Existing methods mostly focus on regular entangled representations to discriminate in-distribution (ID) and OOD data, neglecting the rich contextual information within images. This issue is particularly challenging for detecting near-OOD, as models with simplicity bias struggle to learn discriminative features in disentangled representations. The human visual system can use the co-occurrence of objects in the natural environment to facilitate scene understanding. Inspired by this, we propose an Object-Centric OOD detection framework that learns to capture Object CO-occurrence (OCO) patterns within images. The proposed method introduces a new OOD detection paradigm that understands object co-occurrence within an image by predicting disentangled representations for the test sample, then adaptively divides patterns into three scenarios based on object co-occurrence patterns observed in ID training data, and finally performs OOD detection in a divide-and-conquer manner. By doing so, OCO can distinguish near-OOD by considering the semantic contextual relationships present in their images, avoiding the tendency to focus solely on simple, easily learnable regions. We evaluate OCO through experiments across challenging and full-spectrum OOD settings, demonstrating competitive results and confirming its ability to address both semantic and covariate shifts. Code is released at https://github.com/Michael-McQueen/OCO.

12.
arXiv (CS.AI) 2026-06-19

Latent Confounded Causal Discovery via Lie Bracket Geometry

arXiv:2606.19610v1 Announce Type: cross Abstract: Recent work on Kan-Do-Calculus (KDC) has established that the boundary between passive observation and active intervention in causal inference is a category-theoretic bi-adjunction, with interventions modeled by left Kan extensions and conditioning by right Kan extensions. This paper introduces two causal discovery algorithms under latent confounding, building on the information-geometric and categorical consequences of KDC. In smooth statistical settings, Radon-Nikodym derivatives between observational and interventional measures induce local causal vector fields; failures of these fields to close under Lie brackets become computable Frobenius residuals, which we interpret as witnesses of failed visible integrability and possible latent or unmodeled structure. Our first algorithm, BRIDGE (Bracket Residuals for Interventional Discovery and Geometric Estimation), combines an interventional density or Radon-Nikodym-ratio engine with a geometric screen that proposes a high-recall family of admissible arrows, identifies non-closing visible pairs as latent-obstruction candidates, and passes the reduced family to downstream score-based or differentiable discovery routines. The second algorithmic contribution, Spectral Kan-Do Flow Matching (SKFM), learns amortized intervention fields and factors latent curvature spectrally, exposing the direct Lie-space endpoint toward which BRIDGE points. A detailed set of experiments show that both algorithms are capable of discovering causal models with latent confounders while collapsing the super-exponential space of possible DAGs by many orders of magnitude. This paper introduces a new paradigm in causal discovery, where latent structure is inferred directly from the geometry of intervention-induced flows.

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

M*: A Modular, Extensible, Serving System for Multimodal Models

arXiv:2606.12688v1 Announce Type: cross Abstract: We are entering a new era of composite model architectures that integrate diverse components such as vision encoders, language backbones, diffusion and flow heads, audio codecs, action generators, and world-model predictors. Such architectures underpin a broad class of multimodal models, including unified multimodal models, omni models, speech-language models, vision-language-action policies, and world models. However, existing model serving frameworks were built on narrow assumptions about model structure, making them ill-suited to accommodate this new architectural diversity. Here we present M*, a universal serving system for efficient serving of composite AI models. M* represents models as dataflow graphs, processing requests spanning diverse modalities and tasks as traversals over these graphs. The core insight is a modular abstraction that supports arbitrary composition of model components, flexible placement onto a physical cluster, and model-agnostic optimizations within a distributed runtime. We call this abstraction the Walk Graph and show how it can concisely capture composite models from a broad range of families. We instantiate M* on representative models and find that it achieves, on average, 20% lower end-to-end latency than vLLM-Omni for text-to-image workloads on BAGEL, while delivering up to 2.9x lower real-time factor and 2.7x higher throughput for text-to-speech workloads on Qwen3-Omni. M* also outperforms the V-JEPA 2-AC rollout baseline for robotic planning by up to 12.5x. Thus, our work paves the road towards more efficient serving of complex models with minimal developer effort.

14.
bioRxiv (Bioinfo) 2026-06-17

Correcting spatial transcriptomics data affected by a prevalent transcript leakage problem across platforms, species, and tissues

Spatial transcriptomics has been widely applied to study the spatial distribution of cell types, cell states, and specific gene expression in tissue samples. However, we show that there is a prevalent transcript leakage problem in spatial transcriptomics data, where transcripts expressed by a cell diffuse to its neighborhood and are recurrently detected in the nearby cells. By analyzing published data sets, we show that this problem is general across data produced from different tissues and different species using different imaging-based and sequencing-based spatial transcriptomics platforms. It affects both upstream tasks such as expression quantification as well as downstream tasks such as cell-type annotation and detection of spatially-dependent gene expression. To tackle the transcript leakage problem, we propose a reference-free Bayesian model-based method, DeLeakage, which cleans up the data much more effectively than existing denoising methods. DeLeakage also improves cell-type annotation and avoids false detection of spatially dependent expression.

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

Decision-Aware Memory Cards: Counterfactual-Inspired Context Selection and Compression for Tool-Using LLM Agents

arXiv:2606.08151v2 Announce Type: replace Abstract: Modern large language model (LLM) agents do not simply need longer contexts; they need decision-relevant evidence at the moment of action. We study decision-aware context selection: ranking retrieved files, tests, traces, rules, and memories by their expected effect on an agent's next action rather than by semantic similarity alone. We present the Counterfactual-Inspired Context Layer (CICL), which builds an instance context graph, estimates decision-oriented utility for candidate units, and compresses selected evidence into typed memory cards. The same schema can be instantiated with hosted LLM judges, local surrogates, or lightweight rankers, making the selection protocol auditable across model choices. On 50 SWE-bench Verified file-retrieval instances, Qwen3.6-Plus reranking of BM25 top-50 candidates improves hit@1 from 0.58 to 0.78 and MRR@10 from 0.634 to 0.790, with all 2,500 judgments parseable. Controlled diagnostics show that CICL identifies action-critical evidence: removing the top-utility semantic unit reduces F1 from 0.245 to 0.000. In selected-then-compressed mode, memory cards save 44.93 tokens per query while preserving selected evidence. CICL provides a practical layer for measuring, ranking, and compressing decision-critical context for tool-using agents. Code is available at https://github.com/stephen-guan-researcher/CICL.

17.
arXiv (CS.LG) 2026-06-18

How Does the ReLU Activation Affect the Implicit Bias of Gradient Descent on High-dimensional Neural Network Regression?

arXiv:2603.04895v2 Announce Type: replace-cross Abstract: Overparameterized ML models, including neural networks, typically induce underdetermined training objectives with multiple global minima. The implicit bias refers to the limiting global minimum that is attained by a common optimization algorithm, such as gradient descent (GD). In this paper, we characterize the implicit bias of GD for training a shallow ReLU model with the squared loss on high-dimensional random features. Prior work (Vardi and Shamir, 2021) showed that the implicit bias does not exist in the worst-case, or corresponds exactly to the minimum-$\ell_2$-norm interpolating solution under exactly orthogonal data (Boursier et al., 2022). Our work interpolates between these two extremes and shows that, for sufficiently high-dimensional random data, the implicit bias approximates the minimum-$\ell_2$-norm solution with high probability with a gap on the order $\Theta(\sqrt{n/||\lambda||_1})$, where $n$ is the number of training examples and $\lambda$ denotes the spectrum of the data covariance matrix. Our results are obtained through a novel primal-dual analysis that carefully tracks the evolution of predictions, data-span coefficients, as well as their interactions, and show that the ReLU activation pattern quickly stabilizes with high probability over random data.

18.
bioRxiv (Bioinfo) 2026-06-16

Better data, better trees: GenBank-GISAID deduplication and source-specific artifact masking in viral genomics

GenBank and GISAID are the primary repositories for viral genomic data, but integrating records across them remains a challenge. The same sequence could be made available in both databases without any cross-reference linking the two entries. Consequently, there is no systematic way to identify this redundancy, which compromises the compilation of representative, non-redundant large-scale datasets. In parallel, the growth of viral genomic data has increased the risk of systematic technical artifacts introduced during sequencing or assembly. These artifacts can inflate substitution rate estimates and degrade temporal signal, biasing evolutionary rate estimates. To address both challenges, here we present a formal, reproducible workflow integrating two newly developed complementary tools: G2G matcher for cross-repository harmonization and Lab-Specific Bias FILTer (LSBFILT) for masking of laboratory-specific artifacts. Using the Eastern/Central/South African (ECSA) chikungunya virus lineage as a proof-of-concept, we demonstrate that our integrated workflow restores temporal signal and provides a robust, curated dataset for downstream phylodynamic analyses. Critically, restricting masking of homoplastic sites to specific sequences reduces the substitution rate estimate from an inflated 8.517 x 10e-4; to 5.078 x 10e-4; substitutions/site/year and increases the coefficient of determination (R2) of the root-to-tip regression analysis from 0.353 to 0.677. By enabling systematic cross-repository harmonization and source-specific artifact masking, we provide the molecular epidemiological community with scalable tools to reconcile fragmented genomic data and reduce technical biases, fostering more accurate and reproducible phylogenetic analysis. G2G matcher is available at https://github.com/andrezaleite/G2G-Matcher, and LSBFILT at https://github.com/khourious/LSBFILT.

19.
arXiv (CS.CV) 2026-06-12

Mana: Dexterous Manipulation of Articulated Tools

Articulated tool manipulation remains a major challenge in dexterous robotics due to the need to coordinate internal degrees of freedom and contact-rich interactions. While prior work has largely focused on rigid objects, articulated tool use remains underexplored because of its physical complexity and the difficulty of learning functional grasping and manipulation policies. We present Mana (Manipulation Animator), a general sim-to-real framework that reinterprets dexterous manipulation as an animation problem. Inspired by computer animation, Mana employs a coarse-to-fine pipeline that transforms procedurally-generated grasp keyframes into manipulation trajectories through motion planning and reinforcement learning. The data generation process is largely automatic, requiring only a few mouse clicks to specify functional affordances (

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

Brownian Kernel Ladders

arXiv:2606.15812v1 Announce Type: new Abstract: Constructing mathematically tractable function spaces that capture hierarchical compositional representations remains a central challenge in statistical learning theory. We introduce Brownian kernel ladders (BKLs), a recursively defined hierarchy of integral reproducing kernel Hilbert spaces generated through Brownian-kernel integral constructions. Starting from linear functionals, each layer is obtained by integrating Brownian kernels over probability measures supported on subsets of the previous layer, yielding a recursive function-space model in which depth is encoded directly through the hierarchy. Based on this framework, we define canonical BKL spaces together with an associated complexity functional. We establish several analytical and statistical properties of these spaces. In particular, we show that BKL spaces form quasi-Banach spaces, satisfy depth-dependent Hölder regularity estimates, and exhibit strict monotonicity with respect to depth. We further prove existence results for regularized empirical risk minimization and derive Gaussian complexity bounds that remain uniformly controlled with respect to both the ambient dimension and the hierarchy depth. A key ingredient of the analysis is a combinatorial proof technique based on recursive subset decompositions and Brownian-kernel threshold representations. These estimates yield excess-risk guarantees of near-parametric order for regularized empirical risk minimization over BKL spaces. Our results provide a mathematically tractable hierarchical function-space framework for studying compositional representations in deep learning.

21.
Nature (Science) 2026-06-09

Don’t compete, collaborate: why collective funding applications are the future

Scientists with disparate expertise writing grants together can identify knowledge gaps and drive progress — but systems must change to incentivize them. Scientists with disparate expertise writing grants together can identify knowledge gaps and drive progress — but systems must change to incentivize them.

22.
bioRxiv (Bioinfo) 2026-06-18

Metrics for Evaluating Biological AI Model Predictive Accuracy at the Data-Substrate Level

作者:

Reports in the biological literature disagree on whether a given model can predict a biological outcome from a given data sample — one study finding a model capable, another, on the same kind of data, finding it is not. This is particularly a challenge in relation to LLMs–where the models are large and opaque, with weights and training data inaccessible.textbf{ }Such disagreements cannot be settled by directly inspecting the model. To address this challenge, we considertextbf{ }an alternative approach: assessing whether the data sample is adequate to support the prediction asserted. For a given dataset, its substrate — the underlying structure of the data — determines what any model can recover, independent of architecture or capacity. At the same time, predicting the present state of a biological process and predicting the direction of its future change are different tasks; the second is supportable among AI models only where the data encode direction as determinable from the state — a property we call encoding — and is unsupportable where the same observed state precedes change in opposite directions — a property we call non-identifiability, in the informational rather than the statistical sense. We introduce two generic metrics, Predictive Blindness Risk (PBR) and Prediction Indeterminacy Measure (PIM), that evaluate a data substrate for predictive accuracy directly — without access to model weights, architecture, or training data — and locate the regions of a data substrate where a predictive claim can be supported and where it cannot. Using human biological subjects, we employ the Yale Brain Metastases Longitudinal Data (1,430 human subjects; 11,892 MRI studies; four sequences) and show that direction of change was non-identifiable across regions encompassing the majority of transitions; a nonlinear AI model gained essentially nothing over majority-direction prediction there while recovering direction near-perfectly where the state encoded it; and model accuracy tracked data-substrate resolvability continuously (Spearman {rho} = -0.95 to -1.00). The metrics adjudicate, before any model is trusted and from the data alone, where claims of predictive accuracy — of state, or of the law of change — can be supported.

23.
arXiv (math.PR) 2026-06-16

Flowing to Normality and the Fate of the Single Ring Theorem

arXiv:2606.15791v1 Announce Type: cross Abstract: Random non-hermitian matrix ensembles with double-sided rotation invariance obey, in the limit of large matrix size, the Single Ring Theorem, which states that the support of the mean eigenvalue distribution in the complex plane is either a disk or an annulus. In contrast, rotational-invariant random normal matrix ensembles can have mean eigenvalue densities supported over any number of concentric annuli in the complex plane. In this paper we introduce and investigate, both analytically and numerically, a non-hermitian matrix model which flows from a generic matrix distribution obeying the Single Ring Theorem to a distribution of normal matrices by tuning a parameter which penalizes non-normality. We observe numerically breakdown of the Single Ring Theorem as the model flows towards normality, and determine the critical value of the parameter at which the transition occurs. We also study in detail the behavior of the singular values of these matrices under the flow. These singular values form a Fermi gas confined to the positive half-line. In particular, we find that at small values of the flow parameter, the interparticle spacings in the gas exhibit Wigner-Dyson repulsion, whereas for asymptotically large values of the flow parameter, at the normal matrix endpoint of the flow, the spacing statistics is Poissonian. The flow interpolates continuously between these two types of statistics. However, this change in statistics is not related directly to breaking of the Single Ring Theorem, which occurs very early-on along the flow, in the regime of Wigner-Dyson statistics. Finally, we introduce a certain ensemble of random permutations associated with the gas, and make a conjecture on how to use it in order to reconstruct approximately the average density of complex eigenvalues from that of the singular values in the large-$N$ limit.

24.
arXiv (CS.CL) 2026-06-16

LiFT: Local Search via Linear Programming for Overfitting-Controlled Transformers

This paper proposes a Linear Programming (LP)-based local search framework for fine-tuning pretrained transformer models with explicit control against overfitting. The approach formulates transformer fine-tuning as a bilevel optimization-based regularization problem, in which model parameters and regularization hyperparameters are jointly updated. Information collected during initial warm-up iterations, including validation gradients and training Hessian information, is used to construct a local descent direction by solving an LP that minimizes a scaled directional derivative while preserving training optimality. This validation-aware descent direction enables focused local updates of both parameters and regularization hyperparameters, reducing overfitting without requiring repeated full retraining cycles. The resulting method, termed Linear Programming-based Fine-Tuning (LiFT) for transformers, differs from conventional fine-tuning by systematically identifying task-specific updates rather than relying on heuristic or grid-based hyperparameter selection. Experiments on GPT-2 Small fine-tuned on WikiText-2 demonstrate that LiFT enables effective adaptation through selective tuning of transformer blocks and regularization parameters, yielding consistent improvements in test perplexity across multiple layer configurations and regularization settings, with particularly pronounced gains in overfitting-prone scenarios. Beyond empirical performance, LiFT establishes a principled connection between transformer fine-tuning, bilevel optimization, local search, and regularization theory.

25.
arXiv (quant-ph) 2026-06-15

Sensitivity of polaron-molecule observables to MDR/GUP-like ultraviolet deformations at low energies via quantum computing

arXiv:2606.14479v1 Announce Type: new Abstract: We show that impurity many-body observables can display enhanced sensitivity to ultraviolet deformations of generalized-uncertainty-principle and modified-dispersion-relation type at accessible energy scales. Using a deformed polaron-molecule Hamiltonian constructed to preserve the infrared sector, we quantify the impact of such deformations on spectral and Ramsey observables and implement the corresponding dynamics in a controlled quantum computing setting. We identify regimes near the polaron-molecule crossover where small ultraviolet deformations are strongly amplified, leading to experimentally resolvable changes in quasiparticle properties and spectral response. Our results establish a concrete sensitivity-based route to low-energy quantum-gravity phenomenology in a well-defined many-body platform and delimit the validity of the effective description. Furthermore, we report experimental validation on the QRed superconducting quantum processor (BSC-CNS).