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01.
arXiv (CS.AI) 2026-06-16

When Do We Need LLMs? A Diagnostic for Language-Driven Bandits

arXiv:2604.05859v2 Announce Type: replace Abstract: We study Contextual Multi-Armed Bandits (CMABs) for non-episodic decision-making problems where the context includes both textual and numerical information (e.g., recommendation systems, dynamic portfolio adjustments, offer selection; all frequent problems in finance). While Large Language Models (LLMs) are increasingly applied to these settings, utilizing LLMs for reasoning at every decision step is computationally expensive, and uncertainty estimates are difficult to obtain. To address this, we introduce LLMP-UCB, a bandit algorithm that derives uncertainty estimates from LLMs via repeated inference. However, our experiments demonstrate that lightweight numerical bandits operating on text embeddings (dense or Matryoshka) match or exceed the accuracy of LLM-based solutions at a fraction of their cost. We further show that embedding dimensionality is a practical lever on the exploration-exploitation balance, enabling cost-performance tradeoffs without prompt complexity. Finally, to guide practitioners, we propose a geometric diagnostic based on the arms' embeddings to decide when to use LLM-driven reasoning versus a lightweight numerical bandit. Our results provide a principled deployment framework for cost-effective, uncertainty-aware decision systems with broad applicability across AI use cases.

02.
arXiv (CS.LG) 2026-06-17

Physics-Constrained Neural Networks for Improved Short-Term Weather Forecasting: A Case Study over the South Pacific

arXiv:2606.17659v1 Announce Type: new Abstract: This study introduces enhancements to physics-constrained neural networks (PCNNs) that improve the accuracy and stability of hybrid short-term weather forecasting models. Building on the WeatherGFT architecture, three innovations are proposed. First, an upgraded numerical solver, combining a fifth-order weighted essentially non-oscillatory scheme (WENO-5), a beta-plane approximation, and subgrid-scale viscosity, permits a fourfold increase in the integration time step to 1200 s while reducing the daily mean squared error by up to 26%. Second, a unified autoregressive hybrid block replaces the original chain of 24 specialised modules, eliminating overfitting to specific lead times. Third, the physical core is integrated with two state-of-the-art neural backbones, resulting in PI-PredFormer and PI-IAM4VP. Evaluation on the WeatherBench South Pacific subset from 2000 to 2004 shows that these hybrids reduce root mean squared error at 1-12 h lead times by 8-22% compared to purely neural counterparts, while better preserving physical consistency. These results demonstrate that incremental refinement of hybrid components offers a practical route toward more accurate and efficient short-range weather forecasting.

03.
arXiv (CS.CL) 2026-06-15

AgentSpec: Understanding Embodied Agent Scaffolds Through Controlled Composition

LLM agents are increasingly built not as single model calls, but as scaffolded systems that combine reasoning, memory, reflection, action execution, and learning. While such scaffolds often improve performance, they are often embedded in tightly coupled pipelines, making it difficult to isolate component contributions, compare alternative designs, or understand how module interactions shape agent behavior. We introduce AgentSpec, a modular specification framework that represents embodied agents as typed compositions of reusable policy components with standardized interfaces. AgentSpec standardizes the interfaces among perception, memory, reasoning, reflection, action, and optional learning, enabling components to be swapped and recombined under controlled conditions. We instantiate this framework across DeliveryBench, ALFRED, MiniGrid, and RoboTHOR, and analyze reasoning, memory, reflection, and reinforcement-learning modules across model backbones. Our results show that agent performance is governed by scaffold compatibility and interaction effects rather than isolated module strength. In particular, structured multi-granularity memory improves long-horizon state tracking, reasoning and memory interact non-uniformly across environments, reflection trades off correction and cost, and RL-trained policies compose best when optimized with deployment-time scaffold structure. AgentSpec provides a controlled foundation for studying, comparing, and designing composable LLM agents. Our code, baselines and interactive playground are publicly available at https://agentspec-embodied.github.io.

04.
arXiv (CS.LG) 2026-06-19

VIMPO: Value-Implicit Policy Optimization for LLMs

arXiv:2606.20008v1 Announce Type: new Abstract: Reinforcement learning with verifiable rewards has become a central tool for improving the reasoning ability of large language models, but current methods face a trade-off between simplicity and credit assignment. Group-relative methods such as GRPO avoid training a critic, but typically assign a trajectory-level advantage to every token. Actor-critic methods provide denser learning signals, but require a learned value function with its own training instability. We introduce VIMPO, a critic-free policy optimization method that derives a policy-implied value function from the optimality conditions of KL-regularized reinforcement learning. For autoregressive generation, the resulting value recurrence can be written in terms of policy-reference log-ratios and anchored by the terminal condition that no future reward remains at the end of a trajectory. This gives a simple value loss that incorporates outcome-level verifiable rewards without training a critic. The same derivation also yields a critic-free actor advantage, allowing VIMPO to separate reward incorporation through the value loss from policy improvement through a PPO-style actor update. On mathematical RLVR benchmarks, VIMPO improves over GRPO across MATH-500, AIME 2024, AIME 2025, and OlympiadBench, with especially larger gains on competition-style evaluations. Under noisy rewards, VIMPO retains a consistent advantage over GRPO, suggesting that policy-implied value optimization can provide finer credit assignment while preserving the practical simplicity of critic-free training.

05.
medRxiv (Medicine) 2026-06-16

Upper airway disease in primary ciliary dyskinesia: Clinical management and factors influencing decision-making, a multicentre analysis

Background Upper airway disease is common in primary ciliary dyskinesia (PCD), but management evidence is limited. We aimed to describe management practices and identify factors influencing management decisions. Methods Using data from the Ear-Nose-Throat (ENT) Prospective International Cohort of patients with PCD (EPIC-PCD) and an ENT-specialist survey across participating centres, we described management practices recorded at routine follow-up. We assessed clinical factors associated with practices via mixed-effects logistic regression models. In a subgroup of patients, we assessed factors associated with initiation or discontinuation of practices. Results We included 579 patients: median age 15 years, 46% female. Nasal rinsing (54%) and nasal corticosteroids (22%) were most frequently prescribed. Among 466 patients with available data, 47 had grommets (10%) and 42 hearing aids (9%). Nasal corticosteroids and rinsing were more frequently prescribed in patients with polyps (odds ratio [OR] 3.74, 95% confidence interval [CI] 1.80-7.76; OR 3.39, 95% CI 1.37-8.37) or turbinate hypertrophy (OR 1.89, 95% CI 1.03-3.47; OR 2.89, 95% CI 1.55-5.38), and upper airway nebulisation in patients with frequent nasal symptoms (OR 2.86, 95% CI 1.11-7.39). Management practices differed between centres, as seen also by the specialists survey responses. In 177 patients with multiple visits, initiation of nasal rinsing was associated with frequent nasal symptoms (OR 3.18, 95% CI 1.24-8.18) and turbinate hypertrophy (OR 3.21, 95% CI 1.20-8.59). Conclusion Upper airway disease management in PCD varies and is partly guided by symptom burden and clinical findings. This variation across centres highlights the need for care standardisation and PCD-specific management guidelines.

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

Improving low-resource ASR using bilingual fine-tuning with language identification: a cross-linguistic evaluation

This study explores how bilingual fine-tuning affects automatic speech recognition (ASR) in low-resource languages. We evaluate this method across nine linguistically and geographically diverse language pairs, covering a range of language families and writing systems. To distinguish the two languages, during training, we pre-pend each input text with a language identification token. At inference, the model jointly predicts both the language and transcription from the speech input alone. As texts for which the language is incorrectly determined show low ASR performance, we also conduct a follow-up experiment in which the language identification token is provided both during training and inference. Our results show that bilingual fine-tuning can be beneficial when language identification accuracy is high, and that in cases where language identification performance is low, including the language identification token at inference helps to improve ASR performance.

07.
arXiv (quant-ph) 2026-06-17

A Quantum Approach to Stochastic Optimization in Insurance Underwriting

arXiv:2605.01169v2 Announce Type: replace Abstract: The presence of stochastic elements in combinatorial optimization problems makes them particularly challenging, as such problems quickly become intractable for classical computers even at relatively small sizes. In this work, we propose a novel quantum-classical hybrid scheme for solving a class of stochastic optimization problems known as chance-constrained knapsack problems, in which item weights follow probability distributions and constraints may be violated within a specified risk tolerance. Our method employs knapsack-specific QAOA-based circuits to generate samples which, when combined with a new self-consistent classical recovery scheme introduced in this work, produce high-quality solutions. Experiments carried out on IBM Heron processors, using circuits with depths up to 177 and comprising 3443 gates acting on as many as 150 qubits, yield solutions that indicate performance comparable to classical optimization schemes. The proposed quantum-classical scheme paves the way to tackling such problems, with the potential to outperform approaches that rely solely on classical computation.

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

Computational Safety for Generative AI: A Hypothesis Testing Perspective

Authors:

arXiv:2502.12445v2 Announce Type: replace Abstract: AI safety is a rapidly growing area of research that seeks to prevent the harm and misuse of frontier AI technology, particularly with respect to generative AI (GenAI) tools that are capable of creating realistic and high-quality content through text prompts. Examples of such tools include large language models (LLMs) and text-to-image (T2I) diffusion models. As the performance of various leading GenAI models approaches saturation due to similar training data sources and neural network architecture designs, the development of reliable safety guardrails has become a key differentiator for responsibility and sustainability. This paper presents a formalization of the concept of computational safety, which is a mathematical framework that enables the quantitative assessment, formulation, and study of safety challenges in GenAI through the lens of signal processing theory and methods. In particular, we explore two exemplary categories of computational safety challenges in GenAI that can be formulated as hypothesis testing problems. For the safety of model input, we show how sensitivity analysis and loss landscape analysis can be used to detect malicious prompts with jailbreak attempts. For the safety of model output, we elucidate how statistical signal processing can be used to detect AI-generated content. Finally, we discuss key open research challenges, opportunities, and the essential role of signal processing in computational AI safety.

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

Optical Implementation of Equilibrium Propagation Using Spatial Photonic Ising Machines

arXiv:2606.13454v1 Announce Type: cross Abstract: Equilibrium Propagation offers a compelling alternative to traditional machine learning for training energy-based networks. Here we demonstrate a hybrid optical-digital implementation of EP using a Spatial Photonic Ising Machine (SPIM). The SPIM exploits the gauge transformation method to optically encode both continuous neuron states and rank-1 binary trainable patterns as phase modulations via a spatial light modulator, with inference realized using a finite difference scheme. The experimental system is evaluated on the Wine classification dataset. The potential of this approach, including the use of continuous couplings and structured coupling matrices, is evaluated numerically on the more complex MNIST dataset. Our work provides a concrete pathway toward energy-efficient physical implementations of Equilibrium Propagation.

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

Towards Unified Song Generation and Singing Voice Conversion with Accompaniment Co-Generation

arXiv:2606.07015v2 Announce Type: replace-cross Abstract: While song generation and singing voice conversion (SVC) have evolved significantly, they have long been developed isolated: the former lacks zero-shot speaker cloning, while the latter overlooks vocal-accompaniment synergy. To bridge this gap, we propose UniSinger, the first end-to-end framework unifying speaker cloning song generation and accompaniment co-generation SVC. Building on the multimodal diffusion transformer, we construct a unified speaker embedding space transferring speaker representation from SVC to song generation, endowing fine-grained cross-task timbre control. To mitigate multi-task optimization conflicts, we design a curriculum learning strategy using task-specific modality masking to guide the model to gradually master the generative mechanisms among semantic content, vocal timbre, and accompaniment. Experiments show state-of-the-art performance on both tasks and realizes complementary benefits, offering new possibilities for intelligent music production.

11.
Nature (Science) 2026-06-10

A first-in-class pulsatile FXR agonist for bile-acid-related liver diseases

Authors:

Nuclear receptors are central regulators of metabolism1, yet therapeutic strategies that enforce continuous receptor activation frequently lead to reduced efficacy and unacceptable toxicity. Here we report a first-principles drug design strategy that aligns pharmacokinetics with physiological signalling cycles. We developed linafexor, a potent non-bile-acid agonist of the farnesoid X receptor (FXR)2; it is engineered for rapid systemic clearance, which enables pulsatile receptor activation that mirrors endogenous bile acid dynamics3–5. Linafexor has robust efficacy across multiple preclinical models of metabolic dysfunction-associated steatohepatitis6, liver fibrosis7, primary biliary cholangitis and primary sclerosing cholangitis8,9. Transcriptomic analyses reveal that, unlike long-acting FXR agonists10,11, linafexor preserves cyclic FXR signalling, avoids receptor downregulation and prevents broad transcriptional dysregulation. Direct manipulation of delivery patterns demonstrates that sustained FXR activation—independent of compound identity—induces severe toxicity, establishing activation duration as a determinant of therapeutic index. In phase 1 clinical studies (ClinicalTrials.gov; NCT05082779), linafexor administered once daily produces transient FXR pathway engagement, marked by (1) induction of FGF1912–14, a key endocrine mediator of bile acid feedback regulation; and (2) suppression of C415, an intermediate reflecting hepatic bile acid synthesis, with no treatment-related adverse events. Together, these findings identify pulsatile FXR activation as a mechanistically grounded and clinically translatable strategy, and establish linafexor as a first-in-class therapeutic for bile acid–related liver diseases. Linafexor is a rapidly cleared FXR agonist designed to mimic natural bile acid signalling, achieving transient receptor activation with strong efficacy and reduced toxicity in preclinical and early clinical studies.

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

Through the PRISM: Preference Representation in Intermediate States of Video Diffusion Models

Evaluating video generation with clean, pixel-based reward models disconnects evaluation from the noisy diffusion process and incurs massive VAE decoding costs. In this paper, we challenge this paradigm by asking a fundamental question: Can a powerful video generator inherently discriminate preferences directly from noisy latents? To answer this, we introduce PRISM (Preference Representation in Intermediate States of Diffusion Models). PRISM employs a lightweight Query-based Aggregation head with a frozen video diffusion backbone to decode preference signals from noisy latents. Surprisingly, PRISM not only achieves SOTA preference accuracy but also unlocks strong noise-robustness, which enables early-stage Best-of-$N$ sampling. This allows for filtering suboptimal candidates at the very beginning of denoising, drastically reducing computation while boosting video quality. We also reveal a strong positive correlation between a backbone's generative performance and its inherent evaluative power, enabling self-improving video backbones.

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

CP4SBI: Local Conformal Calibration of Credible Sets in Simulation-Based Inference

arXiv:2508.17077v3 Announce Type: replace-cross Abstract: Current experimental scientists have been increasingly relying on simulation-based inference (SBI) to invert complex non-linear models with intractable likelihoods. However, posterior approximations obtained with SBI are often miscalibrated, causing credible regions to undercover true parameters. We develop $\texttt{CP4SBI}$, a model-agnostic conformal calibration framework that constructs credible sets with local Bayesian coverage. Our two proposed variants, namely local calibration via regression trees and CDF-based calibration, enable finite-sample local coverage guarantees for any scoring function, including HPD, symmetric, and quantile-based regions. Experiments on widely used SBI benchmarks demonstrate that our approach improves the quality of uncertainty quantification for neural posterior estimators using both normalizing flows and score-diffusion modeling.

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

Predicting gestational age at birth in the context of preterm birth from multi-modal fetal MRI

arXiv:2606.20172v1 Announce Type: new Abstract: Preterm birth is associated with significant mortality and a risk for lifelong morbidity. The complex multifactorial aetiology hampers accurate prediction and thus optimal care. A pipeline consisting of bespoke machine learning methods for data imputation, feature selection, and regression models to predict gestational age (GA) at birth was developed and evaluated from comprehensive multi-modal morphological and functional fetal MRI data from 333 control cases and 93 preterm birth cases. The GA at birth predictions were classified into term and preterm categories and their accuracy, sensitivity, and specificity were reported. An ablation study was performed to further validate the design of the pipeline. Performance was evaluated using stratified 10-fold cross-validation. The pipeline achieves an R2 score of 0.13 and a mean absolute error of 2.74 weeks. It also achieves a 0.77 accuracy, 0.59 sensitivity, and 0.82 specificity across folds. The predominant features selected by the pipeline include cervical length and statistics derived from placental T2* values. The confluence of fast, motion-robust and multi-modal fetal MRI techniques and machine learning prediction allowed the prediction of the gestation at birth. This information is essential for any pregnancy. To the best of our knowledge, preterm birth had only been addressed as a classification problem in the literature. Therefore, this work provides a proof of concept. Future work will increase the cohort size to allow for finer stratification within the preterm birth cohort. Our code is available at https://github.com/dfajardorojas/ml-for-preterm-birth-.

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

Spectral Analysis of Molecular Features: When Richer Features Do Not Guarantee Better Generalization

arXiv:2510.14217v2 Announce Type: replace Abstract: The spectral properties of feature embeddings offer critical insights into model generalization and representation quality. While deep learning models are widely used for molecular property prediction, kernel methods remain competitive in low-data regimes, yet their spectral behavior is largely unexplored. We present the first comprehensive spectral analysis of kernel ridge regression across diverse representations-including molecular fingerprints (ECFP), pretrained transformers, graph neural networks, and 3D descriptors-evaluated on QM9 and 3 MoleculeNet benchmarks. Surprisingly, richer spectral features do not consistently yield better generalization performance, contradicting common representation heuristics used in self-supervised learning (SSL). Across 4 spectral metrics, only ECFP-based kernels show a strictly positive correlation with performance. Transformer and global 3D representations exhibit mixed behavior, whereas local 3D representations show consistently negative correlations. Truncation analysis further emphasizes this disparity: for local 3D representations on thermodynamic targets, fewer than 2\% of eigenvalues (and occasionally as few as 0.02\%) are needed to recover 95\% of performance, whereas ECFP and transformer kernels require significantly more. By demonstrating a strong dependence on both task and representation, our results challenge the heuristic that richer spectra inherently improve generalization, providing new guidance for evaluating representations in SSL and in label-limited scientific tasks.

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

Deep Doubly Debiased Longitudinal Effect Estimation with ICE G-Computation

arXiv:2602.12379v2 Announce Type: replace Abstract: Estimating longitudinal treatment effects is essential for sequential decision-making but is challenging due to treatment-confounder feedback. While Iterative Conditional Expectation (ICE) G-computation offers a principled approach, its recursive structure suffers from error propagation, corrupting the learned outcome regression models. We propose D3-Net, a framework that mitigates error propagation in ICE training and then applies a robust final correction. First, to interrupt error propagation during learning, we train the ICE sequence using Sequential Doubly Robust (SDR) pseudo-outcomes, which provide bias-corrected targets for each regression. Second, we employ a multi-task transformer with a covariate simulator head for auxiliary supervision, regularizing representation learning, and a target network to stabilize training dynamics. For the final estimate, we discard the SDR correction and instead use the uncorrected nuisance models to perform Longitudinal Targeted Minimum Loss-Based Estimation (LTMLE) on the original outcomes. This second-stage, targeted debiasing ensures robustness and optimal finite-sample properties. Comprehensive experiments demonstrate that our model, D3-Net, robustly reduces bias and variance across different horizons, counterfactuals, and time-varying confoundings, compared to existing state-of-the-art ICE-based estimators.

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

Speeding up the annotation process in semantic segmentation industrial applications

arXiv:2606.19934v1 Announce Type: cross Abstract: Current machine learning models commonly require large and well-annotated datasets. However, the annotation process often becomes a bottleneck, with increased complexity leading to higher chances of human errors. Within this context, our goal in this paper is to leverage unsupervised algorithms to improve data annotation efficiency for complex semantic segmentation problems in industrial materials science. Previous research has quantified labeling time and others explored unsupervised methods. However, to the best of our knowledge, this is the first study to quantify how much unsupervised algorithms accelerate the labeling process. We aim to validate the extent to which this laborious process can be accelerated, focusing on semantic segmentation tasks that involve annotating each pixel of high-resolution images, such as the microstructure characterization challenge in materials science. Specifically, we demonstrate that by using unsupervised computer vision algorithms, the time required for the labeling process can be reduced from 170 hours to 37 hours, achieving an approximate reduction of 78\%. The dataset we work with includes large images of dimensions 1280x959 and 960x703, which further increases the complexity of the annotation task. Despite these challenges, we create and share the largest public steel microstructure segmentation dataset to date, available under MIT License with permanent DOI, contributing a fully annotated, high-resolution dataset to the field. Additionally, this is the first work to compare the labeling time from scratch (a common approach in previous studies) to the labeling time when using these unsupervised algorithms as a pre-annotation step. Furthermore, we provide a Deep Learning model trained on this dataset, validated by field experts, and deployed in an industrial setting, serving as an initial benchmark for this public dataset.

18.
arXiv (quant-ph) 2026-06-12

Supersymmetry of dissipative Bose-Fermi systems with application to Jaynes-Cummings and Dicke models

arXiv:2606.12682v1 Announce Type: new Abstract: We demonstrate how supersymmetries of Hamiltonians for coupled Bose-Fermi systems can be used to place the Hamiltonians of the Jaynes-Cummings model and Dicke model under the rotating wave approximation in matrix form and provide explicit analytic solutions for their eigenvalues. We then use this supersymmetry to place the Liouvillians of the associated Markovian open systems in matrix form and provide explicit solutions for their eigenvalues. These results are a consequence of the fact that the Hamiltonian of the Jaynes-Cummings model commutes with the linear Casimir invariant of the superalgebra $u(1|1)$ and that the Hamiltonian of the Dicke model commutes both with the linear invariant of $\sum_{i} u_{i}(1|1)$ and with the invariant of an additional $su(2)$ algebra. Our methods apply to various coupled Bose-Fermi systems with $u(1|1)$ and more generally with $u(n|m)$ dynamical superalgebras, and may provide efficient tools for studying more complicated examples.

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

The Market in the Model: Latent Diffusion as Neural Economy

Valuable critique of generative image models within visual culture and the humanities has emphasized the role of datasets in shaping the images they produce. Yet, close studies of the ideological positions embedded into the mechanism of the models have been neglected, leaving them imagined as "black boxes." In a bid to expand, rather than replace, dataset critique, this paper examines the mechanisms of the latent diffusion model in terms of the problems they were brought in to solve on behalf of computer vision engineers, and the decisions each component was tasked with automating. I interpret that ensemble through the histories of its parts and the theory of vision the system inscribes into every generated image. Drawing on Impett and Offert's notion of neural exchange value, I offer this analysis to argue that the model operates as a neural economy: a contained symbolic system that abstracts social communication into commensurable vectors as it transfers the social sphere into parcels for sale. Tracing the training and generation pipelines component by component reveals what each operation displaces, and how it further entrenches the logics of platform and attention economies over social communication. The paper warns that any critique fixated exclusively on copyright and commodity defenses risks reaffirming the very fetishism the model produces, and argues instead for centering social exchange.

20.
arXiv (CS.AI) 2026-06-17

The Stanford EDGAR Filings Dataset: Reconstructing U.S. Corporate and Financial Disclosures into Layout-Faithful and Token-Efficient Pretraining Data

arXiv:2606.18192v1 Announce Type: new Abstract: As high-quality public web corpora become increasingly exhausted, clean long-context documents have become a scarce and expensive source of training data for large language models (LLMs). Existing long-context corpora are often proprietary and costly to acquire, synthetically generated, or concentrated in narrow domains such as programming. We introduce the Stanford EDGAR Filings Dataset (SEFD), an open reconstruction of SEC filings into layout-faithful MultiMarkdown for financial language modeling and evaluation. SEFD makes audited financial statements, risk disclosures, ownership reports, accounting notes, and market-moving event filings usable as long-context pretraining data and as a basis for financial reasoning, forecasting, compliance, and document understanding. The resulting corpus is token-efficient, model-ready, and has less than 0.1% overlap with Common Crawl-derived corpora. We release SEFD-v1, a 152B-token initial public snapshot, and provide corpus-level analyses of a larger 18.5M-filing archive estimated at 550B tokens. We further introduce two SEFD-derived benchmarks: EDGAR-Forecast, which evaluates filing-grounded numerical forecasting after model knowledge cutoffs, and EDGAR-OCR, which evaluates transcription of complex financial tables.

21.
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.

22.
arXiv (CS.CL) 2026-06-19

Beyond Global Replanning: Hierarchical Recovery for Cross-Device Agent Systems

Real-world computer-use tasks often span multiple applications and devices, requiring agents to coordinate heterogeneous environments under dynamic runtime failures. Existing multi-device agent systems support task decomposition and cross-device assignment, but recovery remains largely coarse-grained: when execution fails, they typically retry the same strategy, reassign the subtask, or revise the global plan, without systematically modeling the device-local strategy space. This limits their ability to distinguish failures that can be repaired within the current device from those that require cross-device replanning. We propose H-RePlan, a hierarchical replanning framework for multi-device agents with unified API–CLI–GUI execution. H-RePlan equips each device with interchangeable execution strategies and separates device-local strategy recovery from orchestrator-level global replanning through a compact cross-layer failure abstraction. To evaluate this capability, we introduce HeraBench, a fault-injected benchmark that constructs cross-device workflows over Linux and Android devices and injects strategy- and device-level failures. Experiments show that H-RePlan substantially outperforms single-strategy and coarse-grained multi-device baselines, achieving higher completion, instruction adherence, and perfect-pass rates while reducing the token cost required for reliable end-to-end success. These results demonstrate that scope-aware hierarchical recovery is essential for robust multi-device agent execution.

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

Viral Proteins Reveal Geometry of Protein Language Models

arXiv:2606.12609v1 Announce Type: new Abstract: Protein language models are trained on highly imbalanced datasets, raising the question of how they represent underrepresented biological sequences. Using viral proteins as a case study across ESM model families, we identify a dominant nativeness axis in embedding space, aligned with masked reconstruction perplexity, that orders sequences from well-modeled cellular proteins through viral proteins to shuffled and random sequences. Scaling contracts this axis unevenly across viral families. Despite this, protein language model embeddings retain viral-specific signal: viral proteins remain linearly separable beyond zero-shot perplexity and shallow sequence features. Together, these results suggest that pLM representations are structured by a general notion of nativeness while preserving information specific to distinct biological groups.

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

Quantized Evolution Strategies: High-precision Fine-tuning of Quantized LLMs at Low-precision Cost

arXiv:2602.03120v2 Announce Type: replace-cross Abstract: Post-Training Quantization (PTQ) is essential for deploying Large Language Models (LLMs) on memory-constrained devices, yet it renders models static and difficult to fine-tune. Standard fine-tuning paradigms, including Reinforcement Learning (RL), fundamentally rely on backpropagation and continuous weights to compute gradients. Thus they cannot be used on quantized models, where the parameter space is discrete and non-differentiable. While Evolution Strategies (ES) offer a backpropagation-free alternative, optimization of the quantized parameters can still fail due to vanishing or inaccurate gradient estimation. This paper introduces Quantized Evolution Strategies (QES), an optimization paradigm that performs full-parameter fine-tuning directly in the quantized space. QES is based on two innovations: (1) it integrates accumulated error feedback to preserve high-precision weight updating signals, and (2) it utilizes a stateless seed replay to reduce memory usage to low-precision inference levels. QES significantly outperforms the state-of-the-art zeroth-order fine-tuning methods on a variety of tasks, making direct fine-tuning for quantized models possible. It therefore opens up the possibility for scaling up LLMs entirely in the quantized space. The source code is available at https://github.com/dibbla/Quantized-Evolution-Strategies .

25.
arXiv (CS.LG) 2026-06-19

Adaptive Distance-Aware Trunk Deep Operator Learning for Long-Span Roadway Bridges

arXiv:2606.20015v1 Announce Type: new Abstract: Long-span roadway bridges exhibit highly localized structural responses under vehicular loading, making repeated FE analysis computationally expensive for applications such as influence surface generation and structural digital twins. Existing SciML approaches struggle to accurately capture these localized responses. To address this challenge, this study proposes an adaptive-trunk DeepONet for localized structural response prediction in large-scale bridge systems. The framework dynamically constructs a load-dependent learning domain using a KNN strategy, allowing the network to focus on structural influence zones. The trunk network is further enhanced using distance-aware features that encode the geometric relationship between the load and structural nodes. A physics-based full-field reconstruction is incorporated through a stiffness-informed Schur complement formulation, enabling predictions at adaptive nodes to be extended to the entire structural domain. To enable scalable training, response data are generated using a reduced-order equivalent shell model that preserves the dominant global behavior while significantly reducing computational cost. The proposed framework is validated on both a benchmark bridge model and the real-world Mussafah Bridge. Results show that the method achieves FEM-level accuracy with relative errors below 5%, while reducing the total response evaluation time (including full-field reconstruction) by approximately 60x; excluding the post-processing reconstruction step, the AD-DeepONet inference is up to four orders of magnitude faster than FEM. In addition, the framework enables rapid generation of full-field responses, influence lines, and influence surfaces under arbitrary vehicular loading configurations, demonstrating strong potential for large-scale bridge analysis and digital twin applications.