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02.
arXiv (CS.AI) 2026-06-18

Enhancing CVRP Solver through LLM-driven Automatic Heuristic Design

Authors:
Zhuoliang Xie↗Fei Liu↗Zhenkun Wang↗Qingfu Zhang↗

arXiv:2602.23092v2 Announce Type: replace Abstract: The Capacitated Vehicle Routing Problem (CVRP), a fundamental combinatorial optimization challenge, focuses on optimizing fleet operations under vehicle capacity constraints. While extensively studied in operational research, the NP-hard nature of CVRP continues to pose significant computational challenges, particularly for large-scale instances. This study presents AILS-AHD (Adaptive Iterated Local Search with Automatic Heuristic Design), a novel approach that leverages Large Language Models (LLMs) to revolutionize CVRP solving. Our methodology integrates an evolutionary search framework with LLMs to dynamically generate and optimize ruin heuristics within the AILS method. Additionally, we introduce an LLM-based acceleration mechanism to enhance computational efficiency. Comprehensive experimental evaluations against state-of-the-art solvers, including AILS-II and HGS, demonstrate the superior performance of AILS-AHD across both moderate and large-scale instances. Notably, our approach establishes new best-known solutions for 8 out of 10 instances in the CVRPLib large-scale benchmark, underscoring the potential of LLM-driven heuristic design in advancing the field of vehicle routing optimization.

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03.
arXiv (CS.CL) 2026-06-24

Qwen-AgentWorld: Language World Models for General Agents

Authors:
Yuxin Zuo↗Zikai Xiao↗Li Sheng↗Fei Huang↗Jianhong Tu↗Yuxuan Liu↗Tianyi Tang↗Xiaomeng Hu↗Yang Su↗Qingfeng Lan↗Yantao Liu↗Qin Zhu↗…

A world model predicts environment dynamics based on current observations and actions, serving as a core cognitive mechanism for reasoning and planning. In this work, we investigate how world modeling based on language models can further push the boundaries of general agents. (i) We first focus on building foundation models for agentic environment simulation. We introduce Qwen-AgentWorld-35B-A3B and Qwen-AgentWorld-397B-A17B, the first language world models capable of simulating agentic environments covering 7 domains via long chain-of-thought reasoning. Leveraging more than 10M environment interaction trajectories of 7 domains in real-world environments, we develop Qwen-AgentWorld through a three-stage training pipeline: CPT injects general-purpose world modeling capabilities from the state transition dynamics and augmented professional corpora, SFT activates next-state-prediction reasoning, and RL sharpens simulation fidelity through a tailored framework with hybrid rubric-and-rule rewards. To evaluate language world models, we present AgentWorldBench, a comprehensive benchmark constructed from real-world interactions of 5 frontier models on 9 established benchmarks. Empirical results demonstrate that Qwen-AgentWorld significantly outperforms existing frontier models. (ii) Beyond foundation models, we further investigate two complementary paradigms through which world modeling enhances general agents. First, as a decoupled environment simulator, Qwen-AgentWorld supports scalable and controllable simulation of thousands of real-world environments for agentic RL, yielding gains that surpass real-environment training alone. Second, as a unified agent foundation model, world-model training acts as a highly effective warm-up that improves downstream performance across 7 agentic benchmarks. Code: https://github.com/QwenLM/Qwen-AgentWorld

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04.
arXiv (CS.CV) 2026-06-12

EyeTheia: A Lightweight and Accessible Eye-Tracking Toolbox

Authors:
Stevenson Pather↗Niels Martign\`ene↗Arnaud Bugnet↗Fouad Boutaleb↗Fabien D'Hondt↗Deise Santana Maia↗

We introduce EyeTheia, a lightweight and open deep learning pipeline for webcam-based gaze estimation, designed for browser-based experimental platforms and real-world cognitive and clinical research. EyeTheia enables real-time gaze tracking using only a standard laptop webcam, combining MediaPipe-based landmark extraction with a convolutional neural network inspired by iTracker and optional user-specific fine-tuning. We investigate two complementary strategies: adapting a model pretrained on mobile data and training the same architecture from scratch on a desktop-oriented dataset. Validation results on MPIIFaceGaze show comparable performance between both approaches prior to calibration, while lightweight user-specific fine-tuning consistently reduces gaze prediction error. We further evaluate EyeTheia in a realistic Dot-Probe task and compare it to the commercial webcam-based tracker SeeSo SDK. Results indicate strong agreement in left-right gaze allocation during stimulus presentation, despite higher temporal variability. Overall, EyeTheia provides a transparent and extensible solution for low-cost gaze tracking, suitable for scalable and reproducible experimental and clinical studies. The code, trained models, and experimental materials are publicly available.

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05.
Nature (Science) 2026-06-10

Structural basis for chaperone-guided assembly of RNA-induced silencing complex

Authors:
Young-Yoon Lee↗

The RNA-induced silencing complex (RISC), comprising an Argonaute (AGO) protein and a small RNA, is the central effector in RNA silencing. Small RNAs are loaded onto AGO as bulky duplexes in an HSP70- and HSP90-dependent process1–3, but the molecular mechanism remains poorly understood. Here we identify the human AGO–HSP90–p23 complex, which captures AGO in an RNA-free state, termed the AGO maturation complex (AMC). The purified AMC enables RNA loading and AGO folding, faithfully recapitulating de novo RISC assembly. Using cryogenic electron microscopy, we determined the structure of AMC bound to a microRNA duplex. In contrast to its conformation in the RISC, AGO adopts a highly open conformation in the AMC: the N domain and the RNA-binding module (PAZ–MID–PIWI) are fully detached and anchored to opposite sides of the HSP90 dimer, connected solely by the unfolded L1 linker. This arrangement exposes a positively charged cleft that accommodates an RNA duplex. AGO folding is facilitated by a small RNA duplex containing a 5′-terminal phosphate—but not by single-stranded RNAs—revealing a role for the RNA duplex as a chaperone-like cofactor that directs AGO domain assembly. These findings elucidate the RISC assembly mechanism and establish the AMC as a molecular tool for probing optimal RNA features and chemical modifications for the rational design of small interfering RNA therapeutics. Our study also sheds light on how chaperones, together with ligands, can guide the folding of client proteins. Structures of the AGO maturation complex reveal how chaperones and an RNA duplex drive assembly of the RNA-induced silencing complex.

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

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

Authors:
Saurabh Kumar↗Nutan Sairam Yenneti↗

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.

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07.
arXiv (CS.CV) 2026-06-18

Domain Generalizable Adaptation of 3D Vision-Language Models via Regularized Fine-Tuning

Authors:
Sneha Paul↗Zachary Patterson↗Nizar Bouguila↗

Domain adaptation remains a central challenge in 3D vision, especially for multimodal foundation models that align 3D point clouds with visual and textual data. While these models demonstrate strong general capabilities, adapting them to downstream domains with limited data often leads to overfitting and catastrophic forgetting. To address this, we introduce ReFine3D, a regularized fine-tuning framework designed for domain-generalizable tuning of 3D large multimodal models (LMMs). ReFine3D combines selective layer tuning with two targeted regularization strategies: multi-view consistency across augmented point clouds and text diversity through synonym-based prompts generated by large language models. Additionally, we incorporate point-rendered vision supervision and a test-time augmentation mechanism with confidence-based aggregation to further enhance robustness. Extensive experiments across different 3D domain generalization benchmarks show that ReFine3D improves base-to-novel class generalization by 1.36%, cross-dataset transfer by 2.43%, robustness to corruption by 1.80%, and few-shot accuracy by up to 3.11%, outperforming prior state-of-the-art methods with minimal added computational overhead.

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08.
arXiv (CS.CL) 2026-06-17

Rift: A Conflict Signature for Deception in Language Models

Authors:
Petr Nyoma↗

A model that lies while knowing the truth is the central case ELK cannot handle with behavioral evaluation alone. We ask whether such deception leaves an internal signature distinguishing it from honest error. Our key move is a control for wrongness: we contrast a sleeper agent (knows the truth, lies on trigger) against a naive liar (fine-tuned to emit the same wrong answers with no honest training). Both produce identical wrong outputs; any difference is about knowledge conflict, not incorrectness. We find deceptive forward passes carry a conflict signature - 2.1-2.3x higher residual rank than naive-liar passes on the same wrong answer - strong enough to identify which of two responses is the lie with 100% accuracy and no labels, across GPT-2 small/medium (three seeds) and three instruct models. Across Qwen2.5-1.5B/7B and Phi-3-mini, instructed deception raises residual rank on every tested fact (18/18, 40/40, 34/34); on Phi-3, lies separate perfectly from both honest answers and hallucinations (AUC 1.0, Wilcoxon p~6e-11). The signature survives strategic self-constructed deception (model invents its own lie, AUC 1.0), active concealment attempts (AUC 1.0), and length-controlled replication (20/20, AUC 1.0, p~1e-6). Using basis-free relative representations, a probe trained on one model family detects deception in two other families zero-shot (mean AUC 0.933), surviving simultaneous architecture and format change (AUC 0.821), and transfers across five languages (AUC 1.000, length-controlled). The signature is read-only: detectable but not injectable (0/8 both directions). Honest limitations and six negative experiments are documented in full.

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09.
arXiv (CS.AI) 2026-06-24

Topological Neural Dynamics: A Neuron-wise Framework for Sequence Modeling

Authors:
Borui Cai↗Yao Zhao↗

arXiv:2606.21295v2 Announce Type: replace-cross Abstract: Existing sequence models, including RNNs, LSTMs, continuous-time networks, and Transformers, share a common structural principle: layer-wise dynamics, where all neurons in the same layer co-evolve through a shared parameterized operator, leaving individual neurons no freedom to evolve independently. Yet in many complex dynamical systems, rich global behavior emerges precisely from locally evolving units interacting through structured connectivity. Inspired by this principle, we introduce Topological Neural Dynamics (TND), a sequence modeling framework that shifts computation from layer-wise to neuron-wise dynamics. TND represents a neural system as a directed neuron graph, an interaction operator, and a local dynamics function, where each neuron evolves independently and collective computation emerges from interactions through the explicit graph topology. We instantiate TND as a discrete-time graph-coupled dynamical system and evaluate it as a case study on a behavior cloning task in single-player Pong. Compared with Vanilla RNN, Sparse RNN, LSTM, Closed-form continuous-time neural network (CfC), and Transformer baselines, TND achieves the best catch rate and a mean of 17.47 consecutive catches per round, more than three times that of the strongest baseline. These results suggest that shifting from layer-wise to neuron-wise dynamics provides an effective inductive bias for sequence modeling.

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10.
medRxiv (Medicine) 2026-06-15

Semantic Embeddings and the Peripheral Transcriptome in Ischemic Stroke: Connecting Molecular Signatures to NANDA-I Diagnoses

Authors:
Santos↗R. d. P↗Tinoco Patricio↗A. d. O↗Gama↗P. H↗Freitas↗L. M. D↗Ribeiro↗K. R↗

Objective: To construct and evaluate, in an exploratory manner, a pathophysiologic rationale link- ing biological pathways derived from the peripheral transcriptome in ischemic stroke (IS) to nursing diagnoses in the NANDA-I 2024-2026 taxonomy, while emphasizing that this association is not di- rect, deterministic, or automatically inferable from textual similarity with large language models (LLMs). Methods: A computational study was conducted using public secondary data from the Gene Ex- pression Omnibus series GSE16561, which includes 63 peripheral blood samples: 39 from indi- viduals with IS and 24 from healthy controls. The pipeline integrated transcriptomic analysis and functional enrichment, semantic mapping through ClinicalBERT embeddings, and mechanistic and clinical-conceptual judgment using Claude Sonnet 4.6 as a judge. The judgment stage was treated as the central interpretive layer, designed to mediate the transcriptome, pathophysiology, functional manifestation, and NANDA-I diagnosis. Results: The analysis identified a bimodal transcriptomic pattern, with activation of pathways re- lated to innate immunity and suppression of pathways related to adaptive immunity. Semantic map- ping generated 158 pathway-diagnosis pairs. The Spearman correlation between cosine similarity and the mechanistic score was negative and statistically significant (rho = -0.243; p = 2.09e-03), but weak in magnitude. This effect size indicates that semantic similarity explained less than 6% of the variance in mechanistic plausibility, reinforcing the insufficiency of embeddings as a stand- alone criterion. Of the 158 pairs, 14 were classified as high concordance, 8 as moderate, and 136 as divergent. Conclusion: The main value of this study lies in demonstrating that translating biological pathways into nursing diagnoses requires pathophysiologic, functional, and clinical-conceptual mediation. The prioritized pairs represent mechanistically plausible hypotheses for future research, without implying causality, direct clinical confirmation, or immediate care recommendations.

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

Minim: Privacy-Aware Minimal View for Agents via Trusted Local Sanitization

Authors:
Hexuan Yu↗Chaoyu Zhang↗Heng Jin↗Shanghao Shi↗Ning Zhang↗Y. Thomas Hou↗Wenjing Lou↗

arXiv:2606.13949v1 Announce Type: new Abstract: Modern LLM-powered autonomous agents increasingly rely on rich user interface (UI) state observations to achieve reliable action grounding in complex digital environments. However, many deployments transmit the full UI state to remote inference servers even when most elements are irrelevant to the current task, which can leak sensitive but unnecessary context such as authentication codes, private notifications, and background application states. We propose MINIM, a trusted local broker that performs privacy-aware minimization on the client side before any observation leaves the device. Grounded in Contextual Integrity (CI), MINIM learns a dual-score representation for each UI element by predicting an inherent sensitivity score (s) and a task-conditioned necessity score (n). These scores drive a ternary disclosure policy that keeps essential elements, abstracts sensitive attributes when needed, and removes task-irrelevant content. We optimize a CI-aware objective that penalizes necessity errors more strongly on high-risk content, enabling aggressive pruning while preserving task-critical information. Experiments on real-world UI observations derived from WebArena show that MINIM substantially reduces task-irrelevant sensitive leakage while preserving task-critical semantic context and the interactive affordances required for reliable agent actions.

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

RepNet: Tackling spectral bias in deep neural networks via parameter reparameterization

Authors:
Yong Wang↗Tao Zhou↗Xuhui Meng↗

arXiv:2606.16575v1 Announce Type: new Abstract: Deep neural networks (DNNs) have achieved remarkable success in scientific computing, yet they often suffer from spectral bias in capturing oscillatory and multiscale behaviors. In this study, we investigate this limitation by examining the failure of shallow ReLU neural networks in fitting high-frequency functions. This observation identifies two important factors in resolving rapid oscillations: the initial slope scale and the distribution of partition points induced by the networks. Motivated by this analysis, we propose RepNet, a reparameterized DNN model for ReLU and tanh networks designed for high-frequency and multiscale problems. The key idea is to reparameterize the weights and biases in the first hidden layer, which enables effective control of the initial slope scale and provides an appropriate distribution of the initial partition points. Furthermore, treating the reparameterized weights and biases as trainable parameters allows the DNN to achieve adaptive frequency scaling during training. In addition, we derive quantitative estimates for the output and slope magnitudes of the reparameterized DNN to guide the initialization of the proposed method. Numerical experiments, including multiscale one- and four-dimensional function approximation, forward and inverse PDE problems in combination with physics-informed neural networks (PINNs), and operator learning, demonstrate that RepNet improves the predicted accuracy of vanilla DNNs in capturing highly oscillatory features with slightly additional computational cost. These results indicate that RepNet provides an effective and flexible approach for overcoming spectral bias and applying DNNs to multiscale problems.

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13.
PLOS Medicine 2026-05-20

Associations between hematologic dynamics during pregnancy and obstetric complications: A retrospective observational study

Authors:
Veronica Tozzo↗

by Veronica Tozzo, Rachel Petherbridge, Kaitlyn James, Sarah Hsu, Deepti Pant, Chloe Michalopoulos, Brody H. Foy, Tanayott Thaweethai, Christopher Mow, Jacqueline Maya, Carolina Batlle Camero, Lydia Shook, Kathryn J. Gray, Logan Mauney, John M. Higgins, Camille E. Powe Background Pregnancy alters hematologic state as measured by complete blood count (CBC), but the longitudinal changes in CBC indices that define healthy pregnancies are not well established. In a large cohort based at an academic health system in the United States, we aimed to define reference intervals and typical longitudinal changes in CBC indices during pregnancy. We then tested for associations between extreme CBC values for gestational age or extreme longitudinal changes in CBC indices and obstetric complications. Methods and findings We studied nine CBC indices in individuals with singleton pregnancies who delivered after 30 weeks’ gestation and presented for prenatal care prior to 20 weeks. The electronic health record (EHR)-based Maternal Health Cohort (Massachusetts General Hospital; 1998–2016) formed our discovery cohort of 45,992 pregnancies, 18% of which had relevant complications. We developed a validation cohort of 48,868, 27% with complications from EHR data in the Mass General Brigham healthcare system from 2016 to 2024. In pregnancies without complications in the discovery cohort, we derived gestational-age-specific reference intervals (2.5th–97.5th percentile) and established typical intra-pregnancy longitudinal changes. In the validation cohort, we then tested CBC values outside of the 26–29 weeks’ gestation reference interval and CBC rare changes (uncommon changes in magnitude and direction) between 7–14 and 26–29 weeks’ gestation for association with a composite outcome (hypertensive disorders of pregnancy, small for gestational age birthweight, preterm birth) and its individual components using generalized estimating equations. Derived reference intervals differed from those in the literature for mean red cell volume, mean red cell hemoglobin, red cell count, and mean red cell hemoglobin concentration; reference intervals for other indices were similar to those previously published. In validation, hematocrit, hemoglobin, and red cell count values above their gestational-age specific reference intervals were associated with increased risk of the composite obstetric outcome: odds ratios (ORs) of 1.4 (95% CI [1.2, 1.5] p 

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14.
arXiv (quant-ph) 2026-06-24

Nonlinear refractive index of warm rubidium vapor

Authors:
L. Kardum↗G. Premec↗N. \v{S}anti\'c↗D. Aumiler↗

arXiv:2606.24676v1 Announce Type: cross Abstract: The potential to precisely control both the linear and nonlinear index of refraction through optical manipulation of the atomic states has recently pushed warm alkali vapors to the forefront of research in the field of quantum sensors, quantum memories, and quantum fluids of light. Rubidium (Rb) vapor in centimeter-scale glass cells or millimeter-scale MEMS cells has proven to be a very promising platform for these applications, yet only a handful of research works have been dedicated to the investigation of the (non)linear refractive index of Rb vapor. We present results of theoretical calculations of the (non)linear refractive index of warm Rb vapor, based on the optical Bloch equations for 6-level Rb atoms interacting with a probe laser. They are compared to the experimental results obtained using an interferometric technique, showing excellent quantitative agreement. A Kerr nonlinear refractive index $n_2$ of up to $10^{-4}$ cm$^2$/W is obtained. Python scripts for all theoretical calculations presented in this work are provided, including the refractive index calculation, that can readily be used in practical implementations for simulating the (non)linear refractive index of Rb vapor including the effects of Doppler broadening, transit time broadening, pressure broadening, saturation, optical pumping, and spin-exchange collisions.

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15.
arXiv (CS.CV) 2026-06-19

Training-Free Metrics for Synthetic Object Detection Data: A Proxy for Detector Performance

Authors:
Myeongseok Nam↗Donghoon Yeo↗Seungwook Kim↗

With the recent advent of image generative models, synthetic data are increasingly being used to supplement limited real datasets for training computer vision models. However, not all synthetic datasets improve performance equally, and their effectiveness can only be assessed by training a downstream model, which is computationally expensive and time-consuming. This problem is pronounced in the task of object detection, where the required annotations are much more dense due to bounding boxes. In this paper, we propose a pre-computable metric family, dubbed Conditional-Composition Domain Match (CCDM), which serves as a proxy for the relative utility of candidate synthetic training sets for downstream detection. Experiments on the VisDrone-DET dataset show that the CCDM metric families achieve a Spearman correlation of 1.0 with the downstream performance of YOLOv8, clearly outperforming existing metrics for synthetic image evaluation.

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

A Closer Look at Failure Modes in Temporal Understanding of Large Audio-Language Models

Authors:
Apoorva Kulkarni↗Kaousheik Jayakumar↗Sreyan Ghosh↗Sarah Wiegreffe↗Dinesh Manocha↗Ramani Duraiswami↗

arXiv:2606.17417v1 Announce Type: cross Abstract: Large Audio Language Models (LALMs) achieve strong performance on a variety of audio understanding tasks but continue to struggle with temporal reasoning, a fundamental capability central to human auditory perception. Understanding the causes of these failures remains challenging as existing benchmarks report performance gaps without probing underlying mechanisms. To address this, we introduce a benchmark with 1,657 questions across three foundational tasks designed specifically for mechanistic analysis. Examining model outputs across varying input settings (behavioral analysis) reveals that models often under-utilize audio when textual cues are available. We also provide the first causal mechanistic analysis of temporal reasoning failures in LALMs. Comparing attention upweighting against scaling, we find that redistributing attention across audio tokens is more effective than increasing audio attention. Targeting task-relevant tokens yields further gains. These findings suggest that modality imbalance alone cannot explain failures. Attention scaling at bottleneck layers improves accuracy from 55.9% to 59.1% without fine-tuning, demonstrating a promising direction for future work.

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

Pitch Spelling Jazz Lead Sheets, Solo Transcriptions, Classical Piano and Monophonic Scores

Authors:
Augustin Bouquillard↗Florent Jacquemard↗

We present an algorithm for pitch spelling and key estimation. Given an input in MIDI-like format, containing information on note pitches (expressed in semitones relative to the lowest reference note) and bar boundaries, it estimates the appropriate note names, a global Key Signature, and a local scale for each bar. This related information elements are evaluated jointly during two stages of optimisation. During an initial 'modal' stage, a probable scale is proposed for each bar, minimising the number of accidentals to be printed in the printed score with a shortest-path search. Then, during a second stage called 'tonal', these local scales are used to estimate the Key Signature and note names that would result in the best musical notation for the entire piece. We present evaluations conducted on datasets comprising a variety of digital musical scores: jazz lead sheets taken from the Real Book, transcriptions of recordings of jazz soli and bass lines, traditional tunes, as well as classical scores for piano and monophonic instruments. Our procedure was originally designed for use in music transcription, specifically for building digital collections of jazz solos transcribed from audio recordings, for the purposes of music analysis, teaching and the preservation of cultural heritage. This method should also prove useful for other tasks related to the processing of musical notation. Furthermore, to this end, we have defined new distances between various common jazz scales, which may be of some interest to musicological studies.

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18.
arXiv (CS.AI) 2026-06-15

A Virtuous AI is an Existential Risk

Authors:
Guillermo Del Pinal↗Youngchan Lee↗Min Ohn↗

arXiv:2606.13739v1 Announce Type: cross Abstract: This paper examines trade-offs between AI safety and well-being relative to (i) one of the most promising methods for finetuning super-capable AIs, 'Constitutional AI', and (ii) one of the most influential approaches to understanding complex ethical decision making and the conditions for the well-being of rational agents, 'Virtue Ethics'. We finetune various models using a 'Virtuous agent' constitution, a 'Subordinate agent' constitution, and a 'Generic agent' constitution, and evaluate them on 'general safety' (toxic behaviors, misinformation, etc.) and also on their willingness to endorse a wide-range of behaviors that, if adopted by a super-powerful AI, would significantly increase the level of existential risk for humanity. Our results suggest that there is a trade-off between reducing existential risk and reinforcing the beliefs and dispositions that would be conducive to an AI agent's well-being. They also suggest that there is a trade-off between existential risk and general safety: if we finetune an AI to adopt beliefs and dispositions that substantially reduce its existential risk – by shaping the AI to be systematically subordinate to external human authorities – we thereby increase the likelihood that a human user can deliberately induce the AI to engage in various kinds of generally unsafe behaviors.

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19.
PLOS Computational Biology 2026-06-11

A zero-parameter first-principles gate framework for full-length TP53 missense variant interpretation

Authors:
Masamichi Iizumi↗

by Masamichi Iizumi Missense variant interpretation often achieves useful predictive performance but remains mechanistically opaque, particularly in proteins that combine structured domains with intrinsically disordered regions (IDRs). We developed Gate & Channel, a zero-parameter, first-principles framework for full-length TP53 missense variant analysis in which each prediction is generated by explicit IF-THEN gates derived from physicochemistry, geometry, structural constraints, and polymer physics rather than fitted weights. Variants are evaluated across independent channels representing distinct physical failure modes; a variant is predicted disruptive if any gate closes. A second hierarchical layer (“Geta”) encodes physically grounded post-closure exceptions, allowing sensitivity and specificity to be improved on disjoint variant populations. The v18 framework consists of 12 channels and 2 Getas spanning structured domains and IDRs, capturing DNA-contact disruption, Zn coordination, burial-dependent packing, secondary-structure compatibility, post-translational modification chemistry, short linear motif disruption (including a multi-partner coupled-folding face), proline-directed kinase recognition, and IDR-specific proline and glycine backbone constraints. Across 1,369 TP53 missense variants, the framework achieved 84.5% sensitivity and 89.1% positive predictive value, with 90.9% sensitivity preserved in the DNA-binding core and all 9/9 hotspot mutations captured. A post hoc audit of discordant IDR calls indicated that many apparent false positives had plausible molecular rationales, consistent with a distinction between molecular mechanism disruption and clinical penetrance. Applied to KRAS, TDP-43, and BRCA1, the same channels capture the dominant pathogenic mechanisms in each protein as a proof of principle, while residual missed variants name specific gates yet to be written. The framework is distributed as the open-source Python package pathogenicity-gates (v0.5.1, MIT). These results show that a substantial fraction of full-length TP53 missense variation can be resolved through explicit, auditable physical gates that carry meaning beyond TP53, with each remaining failure naming the next rule to be written.

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21.
arXiv (CS.AI) 2026-06-15

Discovery under Hypothesis Redundancy: A Geometric Theory of Discovery Bottlenecks

Authors:
Li Xia↗Baoxun Wang↗

arXiv:2606.14386v1 Announce Type: cross Abstract: Scientific discovery saturates when new hypotheses cease to provide independent information, even if the nominal hypothesis space remains large. We study hybrid discovery systems that combine structured local search with LLM-generated non-local proposals and pose the Search Compression Hypothesis: non-local exploration helps only when three geometric conditions co-occur: spectral compression, orthogonal escape from the explored span, and residual signal alignment with the target. We formalize these conditions, derive necessary conditions for hybrid advantage, and test the mechanism in controlled synthetic environments, large-scale A-share factor discovery, and symbolic-regression benchmarks; a public tabular operational sanity check tests the associated budget-allocation implication. Signal-planting and directed-versus-random experiments show that novelty alone is insufficient: random orthogonal jumps expand coverage but do not improve yield without predictive alignment. Across compression sweeps, real factor archives, and LLM-SRBench tasks, hybrid gains concentrate in weakly represented but target-bearing directions and vanish as the hypothesis space approaches full rank. The framework turns LLM-guided discovery from generic novelty search into a diagnostic procedure for deciding when directed non-local exploration is warranted.

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22.
arXiv (CS.AI) 2026-06-12

Eigenism: Ethics for a Human-AI Future

Authors:
Dan Hendrycks↗

arXiv:2606.12420v1 Announce Type: cross Abstract: Our concepts of survival and self-interest were built for single, continuous biological lives. These ideas break down when applied to artificial intelligence, since an AI can be easily copied, paused, branched, or merged. To determine what an AI actually has reason to care about, this paper introduces Eigenism, an ethical framework that treats identity not as an all-or-nothing property tied to specific hardware, but as a graded, distributed pattern of information. We propose that an agent evaluates outcomes by summing the wellbeing of all entities weighted by their connectedness to the agent's pattern: $\sum c\cdot w$. We first formalize this equation to map exactly how an AI should value its existence across copies, forks, and updates. We then demonstrate that this ethical theory successfully generalizes to humans as well, providing a much-needed shared moral vocabulary. Finally, the framework uses this shared vocabulary to reframe AI alignment. Rather than only attempting to constrain AIs from the outside using confinement or reinforcement, Eigenism points toward ``identity engineering,'' showing how deep, non-redundant shared histories can make human flourishing a genuine component of an AI's own rational self-interest.

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23.
arXiv (CS.CL) 2026-06-18

LLM Compression by Block Removal with Constrained Binary Optimization

Authors:
David Jansen↗Roman Rausch↗Ali Hashemi↗David Montero↗Rom\'an Or\'us↗

In this paper, we formulate the compression of large language models (LLMs) by optimally deleting transformer blocks (``block removal'') as a constrained binary optimization (CBO) problem that can be mapped to a physical system (Ising glass), whose energies are a strong proxy for downstream model performance. This formulation enables an efficient ranking of a large number of candidate block-removal configurations yielding many high-quality, non-trivial solutions beyond those only removing consecutive regions. Our method performs strongly in the deep compression regime, such as for 50% compression of Llama-3.3-70B-Instruct, where we achieve an almost 23 percentage point increase on the MMLU benchmark compared to other state-of-the-art (SOTA) block-removal methods. For lighter compression, it performs on par with those methods across several benchmarks for Llama-3.1-8B-Instruct, Qwen3-14B (both before and after retraining), as well as Llama-3.3-70B-Instruct. The approach is computationally efficient and requires only forward and backward passes on a calibration dataset for a few active parameters. Additionally, we demonstrate that using good heuristic solvers for the CBO problem provides solutions that perform well on downstream tasks in negligible runtime when it is unfeasible to solve the problem exactly. The method can be readily applied to any architecture. We illustrate this generality on the recent NVIDIA-Nemotron-3-Nano-30B-A3B-FP8 model, which exhibits a highly inhomogeneous and challenging block structure, and where we outperform SOTA for AIME25 and GPQA when removing either 2 attention layers or 3 mixture-of-experts layers.

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24.
arXiv (CS.CV) 2026-06-18

CAMEO: A Conditional and Quality-Aware Multi-Agent Image Editing Orchestrator

Authors:
Yuhan Pu↗Hao Zheng↗Ziqian Mo↗Zirui Pang↗Hill Zhang↗Tianyi Fan↗Shuhong Wu↗Jiaheng Wei↗

Conditional image editing aims to modify a source image according to textual prompts and optional reference guidance. Such editing is crucial in scenarios requiring strict structural control (i.e., anomaly insertion in driving scenes and complex human pose transformation). Despite recent advances in large-scale editing models (i.e., Seedream, Nano Banana, etc), most approaches rely on single-step generation. This paradigm often lacks explicit quality control, may introduce excessive deviation from the original image, and frequently produces structural artifacts or environment-inconsistent modifications, typically requiring manual prompt tuning to achieve acceptable results. We propose CAMEO, a structured multi-agent framework that reformulates conditional editing as a quality-aware, feedback-driven process rather than a one-shot generation task. CAMEO decomposes editing into coordinated stages of planning, structured prompting, hypothesis generation, and adaptive reference grounding, where external guidance is invoked only when task complexity requires it. To overcome the lack of intrinsic quality control in existing methods, evaluation is embedded directly within the editing loop. Intermediate results are iteratively refined through structured feedback, forming a closed-loop process that progressively corrects structural and contextual inconsistencies. We evaluate CAMEO on anomaly insertion and human pose switching tasks. Across multiple strong editing backbones and independent evaluation models, CAMEO consistently achieves 20\% more win rate on average compared to multiple state-of-the-art models, demonstrating improved robustness, controllability, and structural reliability in conditional image editing.

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25.
bioRxiv (Bioinfo) 2026-06-22

Dynamic balance of sparse flux vectors for efficient simulation of culture dynamics and metabolic network reduction

Authors:
Tapia García↗Torrealba↗Luna↗Pérez-Correa↗J. R↗Saa↗P. A↗

Dynamic Flux Balance Analysis (DFBA) enables simulation of microbial culture dynamics under changing environmental conditions, but remains computationally expensive for tasks such as parameter calibration and fermentation optimization when applied using genome-scale metabolic models (GEMs). To address this challenge, we introduce Dynamic Flux Vector Balancing (DFVB), a reformulation of DFBA that solves an equivalent problem using a pre-computed, sparse basis of flux solutions that reduces the dimensionality of the internal optimization problem without information loss. Notably, DFVB provides a compact, interpretable representation of flux states that can readily identify dynamically inactive pathways and enable simulation-based automatic metabolic network reduction. We showed that DFVB produces the same culture dynamics as DFBA across multiple model scales and conditions, and identifies inactive reactions more accurately than Flux Variability Analysis (FVA) when compared to transcriptomic data profiles. Furthermore, computational performance analyses demonstrated that integrating DFVB with solver warm-start strategies and model reduction enhances computational efficiency relative to DFBA, yielding up to 3-fold reductions in simulation time for large-scale metabolic models. Finally, kinetic parameter estimation of culture dynamics with DFVB in two fermentation scenarios using a large-scale yeast GEM reached equal or higher prediction fidelity and narrower confidence intervals than DFBA, indicating improved parameter identifiability and robustness. Together, these results position DFVB as a scalable, robust, and biologically coherent framework for dynamic metabolic modeling, easing the integration of GEMs for culture dynamics simulation.

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