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01.
Nature (Science) 2026-06-17

A 98-qubit trapped-ion quantum computer with all-to-all connectivity

Quantum computers require both high-fidelity operations and large qubit numbers to surpass classical capabilities1. Trapped-ion platforms have demonstrated the highest gate fidelities of any modality2–6 but scaling to larger qubit numbers while preserving performance has remained a central challenge. We report on Quantinuum Helios, a 98-qubit trapped-ion quantum processor based on the quantum charge-coupled device (QCCD) architecture7. Helios features 137Ba+ hyperfine qubits8,9, all-to-all connectivity enabled by a rotatable ion storage ring connecting two quantum operation regions by a junction10,11, speed improvements from parallelized operations12 and a new software stack with real-time compilation of dynamic programs13. Averaged over all operational zones in the system, we achieve average infidelities of 2.5(1) × 10−5 for single-qubit (1Q) gates, 7.9(2) × 10−4 for two-qubit (2Q) gates and 3.3(5) × 10−4 for state preparation and measurement (SPAM), none of which are fundamentally limited and probably able to be improved. These component infidelities are predictive of system-level performance in both random Clifford circuits and random circuit sampling (RCS), the latter demonstrating that Helios operates well beyond the reach of classical simulation and establishes a new frontier of fidelity and complexity for quantum computers14. A new quantum computer, Quantinuum Helios, which is a 98-qubit trapped-ion quantum processor built on the QCCD architecture, demonstrates performance well beyond classical capabilities and provides a path for scaling up quantum computing.

02.
arXiv (CS.LG) 2026-06-16

MolE-RAG: Molecular Structure-Enhanced Retrieval-Augmented Generation for Chemistry

arXiv:2606.05693v2 Announce Type: replace Abstract: Large language models (LLMs) have shown promise for molecular property prediction, but their ability to reason over chemical structures remains limited, as molecular representations such as SMILES differ substantially from the natural language on which LLMs are primarily trained. To bridge this semantic and chemical knowledge gap, we propose MolE-RAG, a training-free, molecule-centric retrieval-augmented generation framework for LLM-based molecular property prediction. MolE-RAG augments each prediction with three complementary sources of inference-time context: retrieved chemistry literature, molecule-specific information including compound synonyms, identifiers, functional group annotations, and physicochemical descriptors, and structurally similar molecules retrieved from the training set. We evaluate MolE-RAG across nine molecular property prediction tasks using proprietary, chemistry-specialized, and open-source LLMs. Across general-purpose LLMs, MolE-RAG improves ROC-AUC by up to 28 percentage points on classification tasks and reduces regression RMSE by up to 67% relative to a SMILES-only baseline. We further find that the utility of each context source varies across models and tasks, with different models benefiting most from textual retrieval, molecular context, or structural retrieval. These results suggest that molecule-centric retrieval can improve LLM-based molecular property prediction without model fine-tuning while providing a flexible framework for integrating heterogeneous chemical knowledge at inference time.

03.
arXiv (CS.AI) 2026-06-11

SPEA2$^+$: Improved Density Estimation in SPEA2 with Provable Runtime Guarantees

arXiv:2606.12382v1 Announce Type: cross Abstract: The Strength Pareto Evolutionary Algorithm 2 (SPEA2) is a popular and prominent evolutionary algorithm for solving multi-objective optimisation problems. Despite its popularity, theoretical analyses of SPEA2 have only appeared recently. Moreover, these analyses focus exclusively on how SPEA2 handles non-dominated solutions and disregard the algorithmic components responsible for handling dominated solutions. We conduct a first runtime analysis of SPEA2 for which these components are analysed. We prove that, unlike other prominent algorithms, including NSGA-II, NSGA-III and SMS-EMOA under the same setting of constant population size and duplicate elimination, SPEA2 is unable to cover the Pareto front of the OneTrapZeroTrap benchmark efficiently. Our results indicate that using k-th nearest-neighbour distance in the fitness assignment provides an insufficient signal to maintain diversity among dominated individuals. To address this issue, we propose an improved variant, SPEA2$^+$, that considers all pairwise distances. The new algorithm achieves the same performance guarantees as the other prominent algorithms on OneTrapZeroTrap, while matching the performance of the original SPEA2 on simpler problems. Experimental results complement our theoretical findings.

04.
arXiv (CS.AI) 2026-06-11

TAHOE: Text-to-SQL with Automated Hint Optimization from Experience

arXiv:2606.12387v1 Announce Type: cross Abstract: Large Language Models (LLMs) have democratized database access through Text-to-SQL, but moving from prototypes to production remains difficult. Real deployments must handle strict SQL dialects, massive schemas, and evolving user preferences, while supervised fine-tuning is costly and rigid and agentic test-time scaling is expensive. We present Tahoe, a system that treats prompt optimization as a dynamic data management problem. Tahoe uses an error-driven hint learning pipeline across Development and Deployment to consolidate debugging traces into a structured Hint Bank. Compiler feedback is distilled into reusable Syntax Hints for dialect-specific rules, while execution and user feedback are converted into Semantic Hints for schema- and user-specific logic. Tahoe further introduces a Strategy Layer that models conflicting user intents as competing strategies under shared natural-language triggers, with recency signals and post-learning attribution statistics that summarize empirical success, harm, inertness, and support. At inference time, Tahoe retrieves relevant hints and guides the LLM through Logic Planning followed by SQL Synthesis. We implement and evaluate the development-phase workflow, leaving deployment-time human-feedback updates for future work. On Spider 2.0-Snow, Tahoe substantially improves Text-to-SQL without updating model parameters. On 113 supervised Spider 2.0-Snow-0212 examples using GPT-5.5, Tahoe raises pass rate from 61.95 percent to 79.42 percent and pass-at-4 from 72.57 percent to 87.61 percent, achieves 100 percent Snowflake syntax pass rate, and reduces average compiler-feedback critic rounds from 2.79 to 0.12 per sampled candidate. The same Hint Bank also transfers to weaker backbones, including a 19.7 percentage-point pass-rate gain on Doubao-2.0-lite.

05.
arXiv (CS.CV) 2026-06-16

DenseControl: Instance-Level Controllable Synthesis of Dense Crowd Image

In this paper, we introduce DenseControl, a novel pipeline for generating dense crowd images. Specifically, DenseControl meticulously positions and sizes each generated instance to align precisely with the predefined coordinates and scales. Based on this, we further allow for control over the background, style, and attributes of instances. The motivation behind DenseControl stems from the observation of two main challenges in synthesizing crowd images: controlling signal embedding and maintaining topological integrity when imparting instance scale guidance. To address these, we first introduce the Isolated Object Embedding (IOE) map, a novel representation that facilitates spatial location control while mitigating the difficulties associated with learning projections for model. Secondly, we propose an Implicit Scale Embedding (ISE) strategy that seamlessly integrates with the IOE map to encode precise scale information. To further enhance the efficacy of combining ISE with the IOE map, we incorporate a Position Shortcut mechanism that enhances cross-attention to alleviate projection challenges. We evaluate DenseControl through two lenses: synthesis quality and applicability in latent applications. Experiments across different control conditions demonstrate DenseControl achieves state-of-the-art results in dense crowd image synthesis. Furthermore, we showcase applications in augmenting crowd analysis under data scarcity, transfer learning, and weather generalization scenes, to highlight the practical utility of DenseControl. The codebase will be released.

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

Large Deviations for the Nonlinear Schrödinger Equation with Randomized Quasi-Periodic Initial Data in Higher Dimensions: Subcritical Case

arXiv:2604.17253v2 Announce Type: replace Abstract: We study the cubic weakly nonlinear Schrödinger equation with randomized spatially quasi-periodic initial data in higher dimensions. Under a polynomial decay assumption in Fourier space, we establish a Large Deviations Principle for rogue waves in the so-called subcritical time regime. The proof proceeds in two main steps. We first characterize the distribution of the linear solution and establish the corresponding linear large deviations principle. The lower bound is obtained via pointwise estimates, while the upper bound follows from a combination of truncation and probabilistic arguments. {The method used in this step appears to be new; compare with [GGKS23].} We then perform a detailed combinatorial analysis of the Picard iteration, deriving an effective bound for the Duhamel term and thereby establishing the nonlinear large deviations principle.

07.
arXiv (CS.LG) 2026-06-17

Finite-Time Queue Peak Laws in Stochastic Networks: Logarithmic Scaling After Geometric Thresholds

arXiv:2606.18218v1 Announce Type: cross Abstract: We study finite-horizon queue peaks in generalized switches, a standard stochastic-network model in which many queues share constrained service resources. Arrivals may be dependent, time-varying, and adapted to the past; the standing load condition is uniform interior slack, meaning the conditional mean arrival vector stays in a fixed contraction of the capacity region. We show that this slack reshapes the finite-time peak law for drift-minimizing scheduling policies such as MaxWeight. The square-root envelope that is sharp without slack persists only up to a geometry-dependent threshold; beyond that threshold, the running maximum grows only logarithmically with the horizon, both with high probability and in expectation. The mechanism is self-normalization: in the current queue direction, the projected fluctuation scale is normalized by the stabilizing drift scale. This removes capacity geometry from the logarithmic coefficient, while geometry remains in the threshold. Matching lower bounds show that both the logarithmic term and a geometric threshold are unavoidable. When finite-time state-space collapse is available, the threshold can be sharpened using local bottleneck geometry. For generalized input-queued switches, we obtain finite-time peak bounds with tight logarithmic coefficients. Simulations illustrate the two-phase envelope, local geometric refinements, and variance-sensitive improvements predicted by the theory.

08.
arXiv (CS.CV) 2026-06-12

An Extensible and Lightweight Unified Architecture for Demosaicing Pixel-bin Image Sensors

Pixel-bin image sensors are becoming the default choice for smartphone cameras due to their resolution vs light-gathering trade-off. However, their larger inter-color separation compared to the Bayer color filter array (CFA) makes them challenging to demosaic. Furthermore, existing deep learning-based demosaicing methods are CFA-specific, requiring multiple individual models that take up precious onboard resources and demand larger development and maintenance efforts. In this work, we propose a modular unified architecture for demosaicing various pixel-bin sensors that provides higher image quality while being extensible and lightweight. Additionally, to enable plug-and-play operation, we introduce a learning-free CFA-identification module to detect the CFA type of raw data accurately.

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

SENTINEL: Failure-Driven Reinforcement Learning for Training Tool-Using Language Model Agents

Language model agents are increasingly effective in solving realistic tasks through multi-turn tool use. However, training reliable tool-using agents remains challenging in practice. While reinforcement learning provides an on-policy paradigm for improving agents from their own environment interactions, its effectiveness depends heavily on the training task distribution. When tasks are fixed before training, the task distribution can become increasingly mismatched with the policy's evolving capabilities, causing many rollouts to be spent on uninformative tasks. We propose SENTINEL, a failure-driven reinforcement learning framework that turns the Solver's rollout failures into targeted training tasks. SENTINEL follows a Controller–Proposer–Solver loop: the Controller analyzes failed trajectories and summarizes recurring error patterns, the Proposer generates executable tasks that stress these weaknesses, and the Solver is trained on the targeted tasks. On Tau2-Bench Retail with Qwen3-4B-Thinking-2507, SENTINEL improves Pass\^{}1 from 66.4 to 74.9 and outperforms RL on general synthetic tasks across Pass\^{}k metrics. These results demonstrate that model failures provide an effective and scalable source of targeted training signal for improving tool-using language model agents.

10.
arXiv (quant-ph) 2026-06-17

Many-body spectral transitions through the lens of the variable-range SYK2 model

arXiv:2412.14280v2 Announce Type: replace-cross Abstract: The Sachdev-Ye-Kitaev (SYK) model is a cornerstone in the study of quantum chaos and holographic quantum matter. Real-world implementations, however, deviate from the idealized all-to-all connectivity, raising questions about the robustness of its chaotic properties. In this work, we investigate a quadratic SYK model with distance-dependent interactions governed by a power-law decay. By analytically and numerically studying the spectral form factor (SFF), we uncover how transitions present in the single-particle limit carry over to the many-body system. Non-trivial cancellations in the one-loop contributions lead to a robustness of the SFF under a considerable reduction of the interaction range. Further suppression leads to a breakdown of perturbation theory around the infinite-range path-integral saddle and the appearance of new spectral regimes, marked by a higher dip and the emergence of a secondary plateau. Our results highlight the interplay between single-particle criticality and many-body dynamics, offering new insights into the quantum chaos-to-localization transition and its reflection in spectral statistics.

11.
arXiv (quant-ph) 2026-06-16

TENSO: Software Package for Numerically Exact Open Quantum Dynamics Based on Efficient Tree Tensor Network Decomposition of the Hierarchical Equations of Motion

arXiv:2603.17711v2 Announce Type: replace-cross Abstract: TENSO is a versatile and powerful open-source software package for numerically exact simulations of the dynamics of quantum systems immersed in structured thermal environments. It is based on a tree tensor network decomposition of the hierarchical equations of motion (HEOM) that efficiently curbs its curse of dimensionality with bath complexity. As such, TENSO enables exact non-Markovian open quantum dynamics simulations even with complex environments typical of chemistry and quantum information science. TENSO allows for time-dependent drive in the system, and for non-commuting fluctuations. More generally, TENSO efficiently propagates the dynamics for any method with a generator of the dynamics that can be expressed in a sum-of-products form, including the HEOM and multi-layer multiconfigurational time-dependent Hartree methods. TENSO enables simulations using tensor trees and trains of arbitrary order, and implements three propagation strategies for the coupled master equations; two fixed-rank methods that require a constant memory footprint during the dynamics and one adaptive rank method with a variable memory footprint controlled by the target level of computational error. In contrast to the accompanying theory and algorithmic paper [J. Chem. Phys. 163, 104109 (2025)] the focus here is on the practical usage and applications of TENSO with underlying theoretical concepts introduced only as needed.

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

Mordal: Automated Pretrained Model Selection for Vision Language Models

Incorporating multiple modalities into large language models (LLMs) is a powerful way to enhance their understanding of non-textual data, enabling them to perform multimodal tasks. Vision language models (VLMs) form the fastest growing category of multimodal models because of their many practical use cases, including in healthcare, robotics, and accessibility. Unfortunately, even though different VLMs in the literature demonstrate impressive visual capabilities in different benchmarks, they are handcrafted by human experts; there is no automated framework to create task-specific multimodal models. We introduce Mordal, an automated multimodal model search framework that efficiently finds the best VLM for a user-defined task without manual intervention. Mordal achieves this both by reducing the number of candidates to consider during the search process and by minimizing the time required to evaluate each remaining candidate. Our evaluation shows that Mordal can find the best VLM for a given problem using $8.9\times$–$11.6\times$ lower GPU hours than grid search. We have also discovered that Mordal achieves about 69\% higher weighted Kendall's $\tau$ on average than the state-of-the-art model selection method across diverse tasks.

13.
arXiv (quant-ph) 2026-06-12

Approximability limits for bounded-degree max-LINSAT and implications for decoded quantum interferometry

arXiv:2606.13570v1 Announce Type: new Abstract: For general max-k-XORSAT with $k \geq 3$, no polynomial-time algorithm can do substantially better than random guessing on worst-case instances unless $\mathsf{P} = \mathsf{NP}$: approximating beyond the random-assignment value of $1/2$ is $\mathsf{NP}$-hard. The picture changes when each variable appears in at most $D$ constraints. In that bounded-degree setting, polynomial-time algorithms can provably beat the random baseline by an additive amount of order $1/\sqrt{D}$. For Boolean instances, this scaling is known to be optimal: the matching hardness result is due to Trevisan, while the corresponding algorithmic guarantee was established by Barak et al. Whether the same holds over general finite fields, and what it implies for quantum algorithms, has not been established. We make this connection explicit and extend the hardness to max-E$k$-LINSAT$(q,r)$ with bounded degree $D$ and over arbitrary finite fields $\mathbb{F}_q$, proving that it is $\mathsf{NP}$-hard to exceed $r/q + \mathcal{O}_{q,r}(1/\sqrt{D})$. These results provide the complexity-theoretic benchmark for the bounded-degree instances targeted by decoded quantum interferometry (DQI), QAOA, and classical heuristics. Any quantum advantage on bounded-degree instances is therefore confined to the constant prefactor. We further show that in the context of DQI and on $(k,D)$-regular instances, this prefactor is sensitive to the nature of the decoder: DQI with classical decoders faces an information-theoretic $1/\sqrt{D \log D}$ barrier that prevents it from matching the hardness scaling, while DQI with quantum decoders is compatible with the $1/\sqrt{D}$ scaling – identifying quantum decoding as the key ingredient for matching the complexity-theoretic scaling with DQI.

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

KVEraser: Learning to Steer KV Cache for Efficient Localized Context Erasing

Post-hoc context erasing over the KV cache is challenging because a local edit has a global consequence: once a span has been processed, its influence propagates into the cached states of all subsequent tokens. This issue arises naturally in long-context LLM applications, where stale retrieved facts, incorrect tool observations, retracted user preferences, or harmful prompt injections may be identified only after prefill. Exact erasing must then recompute all tokens after the deleted span, making its computational cost depend on suffix length rather than erased-span length. We introduce KVEraser, a learned KV-cache editing method for efficient localized context erasing. Given a processed context and a span to remove, KVEraser replaces only the KV states of the erased interval with learned steering states while reusing the remaining cache unchanged. To learn a transferable erasing mechanism, we build a two-stage training pipeline: generic span-neighbor pre-training teaches the eraser to suppress the influence of the erased span, while task-specific fine-tuning adapts this capability to downstream scenarios. Experiments show that KVEraser nearly matches full recomputation in post-erasure performance on in-domain tasks across 1K–32K context lengths, while its latency increases by only 24% compared with a 17.6x increase for full recomputation. KVEraser also generalizes to unseen long-document QA tasks with harmful factual distractors, achieving the best performance among approximate baselines with a 3–4x speedup over full recomputation.

15.
arXiv (CS.CL) 2026-06-12

ArogyaSutra: A Multi-Agent Framework for Multimodal Medical Reasoning in Indic Languages

Multimodal Large Language Models (MLLMs) have shown promising reasoning capabilities in general domains, yet their performance remains limited in specialized settings such as healthcare, especially in multilingual and low-resource scenarios. This gap is critical in regions like rural India, where patients often express complex medical queries in native Indic languages and rely on multimodal inputs such as medical images. Existing English-centric MLLMs struggle to support such use cases, limiting equitable access to AI-driven healthcare assistance. To address this challenge, we introduce ArogyaBodha, a large-scale multilingual multimodal medical question-answer dataset constructed from eight heterogeneous sources, covering 31 body systems, six imaging modalities, and 21 clinical domains across English and seven major Indian languages. We further propose ArogyaSutra, an actor-critic-based multi-agent framework that integrates tool grounding with dual-memory mechanisms for step-wise, reasoning-aware decision making, and uses stored actor-critic simulation trajectories for distillation. Experiments show that our dataset and framework improve multilingual medical reasoning accuracy across all Indic languages, with ablations validating the contribution of each component. The source code and dataset are available at: https://iitp-cse.github.io/ ArogyaSutra/

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

Two-Layer Linear Auto-Regressive Models Estimate Latent States

arXiv:2606.12691v1 Announce Type: cross Abstract: Auto-regressive models have emerged as powerful tools for sequential data, from language to video. Understanding how and why these models learn latent representations remains an open theoretical question. In this work, we demonstrate that when trained by empirical risk minimization on data from partially observed linear dynamical systems, two-layer linear auto-regressive models naturally learn to approximate Kalman filtering. In particular, we show that the learned hidden representation coincides, up to a similarity transformation, with the state estimates produced by the optimal (Kalman) filter, even though the model has no explicit knowledge of the underlying dynamics or state. The result follows from three main insights. First, we establish that the Kalman filter is well approximated by an auto-regressive model with bounded truncation error. Second, we show that despite non-convexity, the two-layer optimization landscape is benign, i.e., all stationary points are either strict saddles or global minima. Finally, as our main contributions, we provide finite-sample guarantees on prediction error, parameter estimation error, and latent state recovery. Numerical simulations support the theoretical results and demonstrate that the latent representations of auto-regressive models recover state estimates.

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

SING: Synthetic Intention Graph for Scalable Active Tool Discovery in LLM Agents

Large language model (LLM) agents increasingly rely on agent harnesses that manage context, tools, and multi-turn execution, making tools a central interface for acting in realistic digital environments. As harness-connected tool ecosystems expand to hundreds or thousands of APIs, services, and task-specific skills, exhaustive tool schema injection becomes costly and imposes a closed-world assumption that limits agents to a predefined static inventory. Retrieval-augmented tool selection offers a natural alternative, but existing one-shot retrieval methods often fail to align isolated tool descriptions with the agent's true task intention, especially in long-horizon tasks where required capabilities emerge through decomposition, observations, and newly induced subgoals. We propose SING, an intention-aware active tool discovery framework that builds an intention-tool graph linking user intentions, tool capabilities, and tool collaboration patterns, and dynamically retrieves tools according to evolving task states. Using a unified corpus of 7,471 tools, we evaluate SING on three real-world tool-use benchmarks. SING improves Global Recall@5 by up to 59.8% and downstream success rate by up to 28.9% over baselines, while reducing full-corpus tool-schema exposure by 99.8%, demonstrating that intention-aware graph structure enables more accurate and context-efficient tool discovery in large-scale agentic ecosystems.

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

Gaussian superpositions for bosonic encodings

arXiv:2603.15258v2 Announce Type: replace Abstract: Non-Gaussian bosonic states are ubiquitous in interacting light–matter systems, many-body platforms, and relativistic quantum field settings, but their quantitative characterization is hindered by the infinite-dimensional Hilbert space and by the poor scalability of Fock-space truncation methods. We introduce an exact finite-manifold encoding for states supported on a finite span of Gaussian branches, enabling the use of standard finite-dimensional quantum-information tools directly on an effective density matrix whose entries are determined by Gaussian overlaps. As demonstrations, we obtain closed-form and numerically stable evaluations of entropies and relative-entropy non-Gaussianity, and derive an analytic expression for the bipartite entanglement negativity of arbitrary multimode two-branch Gaussian superpositions, including a minimal which-branch dephasing model. Our framework provides a practical bridge between experimentally accessible continuous-variable resources (e.g., cat-like and measurement-conditioned states) and discrete-variable information measures, with immediate applications to benchmarking non-Gaussian resources in several quantum technology platforms.

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

Meta-classification of one-class classification models using ranking correlation and nearest neighbor

arXiv:2606.17858v1 Announce Type: new Abstract: Machine Learning (ML) techniques have been applied to various problems. However, applying ML to ML models is an unexplored direction. For this purpose, this paper considers a meta-classification of one-class classification (OCC) models, because all ML models could be approximated as OCC models. The proposal represents OCC models as normality rankings and classifies them using nearest-neighbor and ranking-correlation metrics. The experiment classifies OCC models, where classes correspond to training datasets, algorithms, and hyperparameters. The proposal achieves high accuracy when class labels are datasets. Moreover, it can classify algorithms when the training datasets contain the same class. In addition, the discussion highlights that the classification of OCC models is essentially the classification of datasets that treats multiple samples as a single input. The experiment demonstrates the classification of datasets using sleeping records. The proposed method can provide a unified solution for classifying OCC models, datasets, and rankings. Source code is uploaded to the public repository https://github.com/ToshiHayashi/ClassOCC.

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

Contrastive-Difference CKA Reveals Concept-Specific Structural Alignment Across Language Model Architectures

作者:

Do different LLM architectures encode high-level concepts in structurally compatible ways? We systematically characterize a geometric-functional universality dissociation: across multiple concept domains and architectural families, moderate geometric convergence coexists with near-perfect functional transfer. Using contrastive-difference CKA (CKA_Delta), a training-free diagnostic that computes kernel alignment on per-sample contrastive differences, we isolate concept-specific convergence from generic similarity – achieving significant discrimination where standard CKA cannot. The dissociation replicates across all six concept domains we test (five with p =70B models. We position CKA_Delta as a practical regime classifier and architectural outlier detector (Gemma: d = 1.08, AUC = 0.79) rather than an absolute transfer-accuracy predictor, providing a training-free diagnostic for cross-architecture concept monitoring.

21.
arXiv (CS.LG) 2026-06-18

Measurement noise limits the advantage of nonlinear models over linear models in biomedical prediction

arXiv:2606.18420v1 Announce Type: new Abstract: On biomedical tabular data, flexible models such as deep networks, gradient-boosted trees, and kernel methods are repeatedly matched or beaten by linear and logistic regression given the same features. The usual reaction is to treat this as a model-side shortfall, to be fixed with more data, a better architecture, or tuning, on the assumption that the nonlinear structure is there and the model has failed to capture it. We argue that these fixes cannot help when the binding limit is the measurement rather than the model, as it frequently is in biomedicine. Additive noise blurs the population-optimal predictor, and because blurring removes a function's fine, rapidly varying detail before its broad shape, it erases nonlinear structure faster than linear structure. A degree-$k$ interaction is attenuated by the $k$-th power of feature reliability, while the linear part is attenuated only once. At the reliabilities typical of biomedical measurement, the nonlinear advantage can vanish even when the underlying biology is strongly nonlinear, and what the noise removes cannot be recovered by a larger cohort or a more flexible model, only by better measurement. The nonlinearity is hidden, not absent, and a tie between linear and flexible models is not by itself a verdict on the biology. These pieces are classical, drawn from measurement-error statistics, psychometrics, and Gaussian analysis, and we assemble them into an exact excess-risk identity. Measurement reliability is one of three conditions, alongside sample size and feature representation, that must align for a flexible model to help, and together they leave only a narrow window that most biomedical tasks fall outside. Across 140 UK Biobank tasks, the gap between flexible and linear models, where it exists, carries the predicted noise signature, and the three conditions can be separated by intervention but not by a benchmark alone.

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

Safety-Contract Graph Multi-Agent Reinforcement Learning for Autonomous Network Security Response

arXiv:2606.13832v1 Announce Type: cross Abstract: Autonomous network-security response systems promise to reduce Security Operations Centre (SOC) reaction latency, but reward-only multi-agent reinforcement learning (MARL) can improve security reward while remaining non-deployable. We present a safety-contract graph MARL framework and instantiate it as ACD$^3$-GAT (Adaptive Constrained Counterfactual Decisioning with a Graph Attention Network encoder), an architecture that separates simulator observations from reusable operational budgets, constrained optimization, graph state encoding, and counterfactual action screening. We evaluate the method in CAGE Challenge 4, where agents operate under budgets for Mean Time to Recover (MTTR), false-positive response, and firewall change-management disruption. Across the benchmark, every unconstrained method violates the SOC downtime budget in 100% of evaluated episodes, with mean downtime proxy costs of 311-430 against a budget of 50. This complements prior CAGE Challenge 4 findings by showing that reward-only learning lacks operational discipline. Constrained MAPPO-GAT (C-MAPPO-GAT) isolates Lagrangian operational-cost control and budget-aware screening, while ACD$^3$-GAT adds budget context, CVaR tail-risk estimation, opponent-belief state, and Graph Counterfactual Risk Propagation (G-CRP). The replicated comparison includes three 200-episode seeds for IPPO, MAPPO-GAT, C-MAPPO-GAT, and ACD$^3$-GAT. C-MAPPO-GAT reduces downtime violation from 100% to 0.3% and mean downtime cost from 355.4 to 15.5 relative to MAPPO-GAT. ACD$^3$-GAT reduces mean downtime cost to 48.2 with a 13.8% violation rate, placing it on the safety-contract frontier rather than at the most conservative compliance point. Topology-seed and coupled adaptive Red-process stress tests preserve this contrast and show lower worst adaptive degradation for safety-constrained policies than reward-only MAPPO-GAT.

23.
bioRxiv (Bioinfo) 2026-06-21

OracleScreen-LILRB4: Machine Learning-Guided Discovery of Myeloid Immune Checkpoint Binders Validated in Patient-Derived Cells

The identification of small molecule modulators of immune checkpoint proteins remains a significant challenge in drug discovery due to the flat, featureless nature of protein-protein interaction interfaces and the characteristically low hit rates observed in conventional high-throughput screening campaigns. Here we report OracleScreen-LILRB4, an ensemble machine learning framework trained on quantitative biophysical screening data from two structurally diverse compound libraries (19,800 compounds total) screened against the myeloid immune checkpoint leukocyte immunoglobulin-like receptor B4 (LILRB4/ILT3). By formulating binding prediction as a regression task targeting continuous {Delta}Fnorm values rather than binary hit classifications, OracleScreen-LILRB4 achieved a mean Spearman R of 0.61 and ROC-AUC of 0.86 under scaffold-aware cross-validation. Prospective virtual screening of a 45,760-member compound library and experimental validation of the top 200 predictions yielded a 28.5% hit rate, representing a 15.0-fold enrichment over baseline, with 16 compounds demonstrating nanomolar-affinity LILRB4 (ILT3) engagement. Lead compounds ORS-22 and ORS-14 restored anti-tumor immune activity across patient-derived colorectal cancer and acute myeloid leukemia co-culture systems, reversing SCG2-mediated immunosuppression and recovering cytotoxic T-cell function. These findings establish OracleScreen-LILRB4 as an effective computational framework for accelerating small molecule discovery against non-enzymatic immune checkpoint targets.

24.
medRxiv (Medicine) 2026-06-18

Rare Coding Variants Reveal Distinct Genetic Architectures Across Multidimensional Sleep Phenotypes

Sleep and circadian traits have been widely studied using common variants, but the contribution of rare coding variation remains unclear. We analyzed rare coding variants in 397,065 whole-exome sequenced UK Biobank participants across 36 sleep phenotypes from self-report, diagnoses, sleep medication use and accelerometry, and meta-analyzed results with 171,536 whole-genome sequenced All of Us participants of diverse ancestries, with replication in the Mass General Brigham Biobank (N = 31,275). We identified 260 genes associated with sleep phenotypes, including novel associations with sleep medication use in 29 genes and 24 out of 29 have not previously been reported with any sleep phenotypes. We observed modest but significant rare variant heritability and strong genetic correlations between sleep medication use, insomnia and fatigue. Temporal gene expression trajectory analyses indicate that genes associated with self-reported sleep traits show constant high prenatal expression, whereas genes linked to sleep medication phenotypes exhibit peak expression in the late prenatal period. These findings highlight distinct biological mechanisms captured by different measurement sources of sleep phenotypes and reveal rare-variant-informed targets for therapeutic discovery.

25.
arXiv (CS.CL) 2026-06-11

A PubMed-Scale Dataset of Structured Biomedical Abstracts

Structured abstracts are important for biomedical literature processing, by facilitating information retrieval, text mining, and knowledge synthesis. However, a vast portion of abstracts indexed in PubMed remain unstructured, presenting a significant bottleneck for downstream text-processing workflows and applications. To resolve this limitation, we introduce Structured PubMed, a comprehensive corpus of section-labeled biomedical abstracts compiled from the complete PubMed database, encompassing over 23.2 million research-article records. The corpus is divided into two distinct subsets: a collection of 5.9 million author-structured abstracts parsed from official XML files, and an automatically labeled collection of 17.2 million originally unstructured abstracts structured via a verbatim-extraction Large Language Model pipeline. Every record is harmonized under a unified five-section schema and mapped to its original PubMed identifier, publication type, and publication date. This dataset can be utilized to train sentence-classification models, benchmark text-segmentation architectures, and perform large-scale, section-specific information extraction at an unprecedented PubMed-wide scale.