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01.
arXiv (math.PR) 2026-06-16

Atypical Decay Rates for Atypical Heights in Random Recursive Trees

arXiv:2604.20139v2 Announce Type: replace Abstract: We establish the large deviation probabilities for the height of random recursive trees, revealing polynomial upper-tail decay and stretched-exponential lower-tail decay. Remarkably, the lower tail features an atypical prefactor that grows to infinity more slowly than any $n$-fold iterated logarithm.

02.
arXiv (CS.CL) 2026-06-11

Automated Creativity Evaluation of Language Models Across Open-Ended Tasks

Large language models (LLMs) have achieved remarkable progress in language understanding, reasoning, and generation, sparking growing interest in their creative potential. Realizing this potential requires systematic and scalable methods for evaluating creativity across diverse tasks. However, most existing creativity metrics are tightly coupled to specific tasks, embedding domain assumptions into the evaluation process, and limiting scalability and generality. To address this gap, we introduce an automated, domain-agnostic framework for quantifying LLM creativity across open-ended tasks. Our approach separates the measurement apparatus from the creative task itself, enabling scalable, task-agnostic assessment. Divergent creativity is measured using semantic entropy, a reference-free and robust metric for novelty and diversity, validated against human annotations, LLM-based novelty judgments and baseline diversity measures. Convergent creativity is assessed via a novel retrieval-based multi-agent judge framework that delivers context-sensitive evaluation of task fulfilment with over 60% improved efficiency. We validate our framework in three qualitatively distinct domains: problem-solving (MacGyver), research ideation (HypoGen), and creative writing (BookMIA), using a broad suite of LLMs. Empirical results show that our framework reliably captures key facets of creativity, including novelty, diversity, and task fulfilment, and reveal how model properties, such as size, temperature, recency, and reasoning, impact creative performance. Our work establishes a reproducible and generalizable standard for automated LLM creativity evaluation, paving the way for scalable benchmarking and accelerating progress in creative AI.

03.
arXiv (CS.CV) 2026-06-12

CD-RCM: Generalizable Continuous-Depth Novel View Synthesis for Reflectance Confocal Microscopy

Reflectance confocal microscopy (RCM) provides noninvasive, cellular-resolution "optical biopsies" of human skin in vivo by acquiring en-face images at successive depths, forming a sparse z-stack. Due to optical limitations, these stacks are anisotropic 3D volumes with lateral resolution (0.5 $\mu$m) $\sim$6 times higher compared to axial resolution, which is defined by the optical sectioning (3 $\mu$m), limiting the interpretation of tissue. Our goal is to provide continuous-depth visualization by interpolating intermediate sections and making the 3D volume isotropic. Such a representation permits arbitrary-direction sectioning, including histopathology-like cross-sectional examination, without requiring per-patient optimization. To that end, we introduce the first RCM-specific novel-view synthesis (NVS) approach, CD-RCM, a feedforward model that predicts realistic, unseen depths from sparsely sampled RCM stacks. Classical neural rendering methods focus on reconstruction from surface-level multi-view observations. In contrast to surface-level camera views, RCM can acquire optically sectioned en-face images of tissue beyond the surface up to 200 $\mu$m. However, during visualization of the RCM stacks, observations of the shallower sections (towards the surface) obscure the deeper ones. This unique axial imaging geometry and layer-dependent anatomical organization motivated our development of a tailored architectural and training framework that explicitly accounts for RCM's depth-resolved, occlusive imaging physics. Experiments demonstrate that CD-RCM achieves high-fidelity novel-view synthesis with sub-second inference time.

04.
medRxiv (Medicine) 2026-06-10

A risk-of-contagion index using a Bayesian based model for the COVID-19 epidemic in Mexico

During the COVID-19 pandemic, limited testing capacity and reporting delays complicated epidemic surveillance and decision-making in Mexico. We calibrated textit{covidestim}, a Bayesian nowcasting model, to estimate the total SARS-CoV-2 infections from reported cases and deaths using Mexican surveillance data. Disease-progression distribution priors were calibrated using Mexico City records and validated through comparisons with national seroprevalence surveys, hospitalization data, and annual reported severe-case rates across all states. Using the reconstructed estimates of active infections, we implemented an event-based risk framework that quantifies the probability of encountering at least one infectious individual in gatherings of different sizes. This probability was subsequently translated into a four-level epidemiological traffic-light indicator and computed at both state and municipality levels. The resulting estimates revealed substantial spatial heterogeneity that is obscured by state-level aggregation, particularly in states with marked differences between urban and rural municipalities. To evaluate consistency with public-health indicators, we compared the proposed risk classification with the official Mexican epidemiological traffic-light system, considering interpretable gathering sizes relevant to public-health decision making. Weekly reports derived from this framework were delivered to policymakers in the State of Queretaro in Mexico, as an anticipation tool for school reopening and public-space management. This demonstrates that this Bayesian reconstruction of infections combined with event-based risk metrics can provide an interpretable and generalizable municipality-level complement to routine surveillance systems, particularly in regions with limited testing capacity and heterogeneous local transmission dynamics.

05.
arXiv (quant-ph) 2026-06-15

A new class of degenerate solutions to the massless Dirac equation and their potential applications in optical memories

arXiv:2606.14256v1 Announce Type: new Abstract: In this article, we present a novel class of degenerate solutions to the massless Dirac equation, corresponding to a wide variety of electromagnetic 4-potentials and fields, including both zero field and circularly polarized electromagnetic waves. An interesting property of these solutions is that the spin of the particles rotates in synchronization with the electric and magnetic fields of the electromagnetic waves. These results could be utilized for the development of optical memories based on materials supporting massless Dirac fermions, such as graphene.

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

ProcessThinker: Enhancing Multi-modal Large Language Models Reasoning via Rollout-based Process Reward

Visual question answering increasingly requires multi-step reasoning. Recent post-training with reinforcement learning under verifiable rewards (RLVR) and Group Relative Policy Optimization (GRPO) can improve multimodal reasoning, but most approaches rely on sparse outcome-only rewards. As a result, they struggle to tell whether an incorrect answer comes from a small mistake late in the reasoning or from an unhelpful trajectory from the start. A common solution is to train a process reward model (PRM) for step-level supervision, but this typically requires large-scale high-quality chain-of-thought annotations and additional training cost. We propose ProcessThinker, a practical post-training pipeline that provides step-level process rewards without training an explicit PRM. ProcessThinker first rewrites reasoning traces into a step-tagged format for cold-start supervised fine-tuning, then applies GRPO with a standard format reward and our rollout-based process reward. Concretely, for each intermediate step, we sample multiple continuations from that step and use the empirical success rate (final-answer verification) as the step reward. This gives dense credit assignment and encourages reasoning steps that more reliably support a correct conclusion, helping reduce inconsistent or self-contradictory progress across steps – a key issue in logical reasoning. Across four challenging video benchmarks (Video-MMMU, MMVU, VideoMathQA, and LongVideoBench), ProcessThinker consistently improves over the baseline model Qwen3-VL-8B-Instruct

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

DiffMath: Symbol- and Graph-Aware Latent Diffusion Transformer for Handwritten Mathematical Expression Generation

Handwritten Mathematical Expression Generation (HMEG) is challenging due to the complex two-dimensional layouts and long-range structural dependencies of mathematical expressions. Existing methods typically rely on explicit spatial supervision, such as symbol-level bounding boxes, which incurs high annotation costs and limits scalability. In this work, we propose DiffMath, a symbol- and graph-aware latent diffusion framework that leverages the hierarchical structure inherent in LaTeX as a structural prior, eliminating the need for positional supervision. First, we design a Relational Abstract Syntax Tree (RelAST), a generation-oriented representation that distills MathML trees into compact triplet sequences [S, R, D], where each token directly encodes a symbol identity, spatial relation, or nesting depth. Second, we introduce MathVAE, which learns structure-preserving latent representations through symbol-aware and relation-aware perceptual regularization, ensuring that the latent space captures both character semantics and spatial topology. Third, MathDiT performs conditional denoising in this structured latent space, further guided by a global symbol-count prior via Adaptive Layer Normalization (AdaLN) to improve structural coherence. Experiments show that DiffMath produces structurally consistent handwritten expressions, achieves superior performance over existing methods, and improves the accuracy of downstream OCR models through synthetic data augmentation.

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

Multi-User Dueling Bandits: A Fair Approach using Nash Social Welfare

arXiv:2605.01961v2 Announce Type: replace Abstract: Learning from human preference data is becoming a useful tool, from fine-tuning large language models to training reinforcement learning agents. However, in most scenarios, the model is trained on the average preference of all human evaluators, which, under large variations of preferences, can be unfair to minority groups. In this work, we consider fairness in dueling bandits, a standard framework for online learning from preference data. We assume that each user has a (potentially distinct) Condorcet winner, which is an arm preferred to every other arm. Using these user-specific Condorcet winners as reference points, we evaluate and score arms according to their performance relative to the corresponding winner. To promote fairness across heterogeneous users, we adopt the well-established Nash Social Welfare objective, which maximizes the product of user utilities, thereby inherently penalizing inequality and preventing the marginalization of any single user. Within this framework, we construct a hard instance to establish a regret lower bound of $\Omega(T^{2/3}\min(K,D)^\frac{1}{3})$ for a time horizon $T$, $K$ arms, and $D$ users, which, to the best of our knowledge, is the first result quantifying the cost of fairness in dueling bandits with heterogeneous preferences. We then present the Fair-Explore-Then-Commit and Fair-$\epsilon$-Greedy algorithms with a Condorcet winner identification phase. We further derive their regret upper bounds that match the lower-bound dependence on $T$ up to logarithmic factors.

09.
arXiv (CS.AI) 2026-06-15

Expert-Driven Survival Machines: Improving Stratification and Interpretability in Multiple Clinical Cohorts

arXiv:2606.14608v1 Announce Type: cross Abstract: Survival prediction plays a central role for healthcare providers and clinical researchers. Accurate risk stratification enables early intervention and improved patient management. Most existing deep survival models learn one common feature representation for all patients, which may hide important differences between patient subgroups. In contrast, a Mixture-of-Experts (MoE) framework allows different parts of the model to focus on different patient patterns, leading to more individualized representations. Therefore, in this work, we propose a mixture-of-experts enhanced adaptive deep clustering survival framework (AdaCSM) for modeling such heterogeneous survival patterns. We introduce a routing-based expert mechanism that enables conditional specialization within a parametric survival modeling framework. The proposed architecture allocates patients to specialized risk predictors dynamically while preserving the patient survival and subtype clustering objectives. We compare our method with state-of-the-art survival and deep clustering models on multiple real-world longitudinal clinical cohorts spanning diverse disease domains. The proposed method demonstrates improved predictive performance and leads to interpretable results in survival analysis.

10.
arXiv (CS.AI) 2026-06-12

Position: Generative Engine Optimization Creates Underexamined Risks, Governance Must Target Concentration, Disclosure, and Academic Blind Spots

arXiv:2606.12439v1 Announce Type: cross Abstract: Large language model (LLM) answer engines are increasingly used for information seeking, shifting visibility from ranked lists to synthesized answers. This enables Generative Engine Optimization (GEO), which targets LLM answer engines' evidence pool and generation. We analyze the search engine optimization (SEO) to GEO transition to identify two risks: (i) concentrated influence from low contestability and system sensitivity, and (ii) undisclosed commercial influence embedded in evidence and reasoning. We then formalize a general GEO pipeline to locate where optimization acts and compare academic and industry practices, revealing a third risk: (iii) academic-industry blind spots driven by visibility and evaluation asymmetries between offline setups and deployed systems. This position argues the need for answer-level governance and measurement: stronger contestability, high-precision disclosure, black-box auditing of material influence, and deployment-aligned metrics for exposure persistence.

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

Optimal Ansatz-free Hamiltonian Learning In Situ

arXiv:2606.19486v1 Announce Type: cross Abstract: Characterizing the features of a Hamiltonian that governs a quantum system serves as a fundamental subroutine of quantum device calibration, signal sensing, and error correction. Recent works proposed protocols have achieved the optimal Heisenberg-limited scaling learning ansatz-free Hamiltonians from their real-time evolutions without fully specifying interaction structures. However, these protocols rely on both deep circuits with interleaving probes and control, and extremely short time resolution, making them difficult to implement on near- and intermediate-term in situ quantum experiments. In this work, we propose a computationally efficient, control-free, and ancilla-free algorithm that uses only Pauli product state preparation and measurement, and learns an ansatz-free Hamiltonian $H$ with $||H||\leq\Lambda$ in total evolution time of $\Theta(\frac{\Lambda}{\epsilon^2}\log(\frac{\Lambda}{\epsilon}))$. The evolution time cost of our algorithm is optimal for any control-free protocols as we further prove a lower bound of $\Omega(\frac{\Lambda}{\epsilon^2}\log(\frac{\Lambda}{\epsilon}))$. Technically, our method introduces a randomized-sampling framework that combines band-limited kernel-based time sampling with a displacement sieve for Hamiltonian structure learning. The characteristic probe time resolution depends only on $\Lambda$ instead of $\varepsilon$, which makes our protocol especially appealing in the high-precision regime for sensing and calibration applications. We also show that the algorithm maintains the same asymptotic total evolution time in the presence of state-preparation-and-measurement (SPAM) noise when the Hamiltonian is local after calibration. Our results demonstrate the fundamental cost of experimentally friendly Hamiltonian learning and provide a practical route to rigorous in situ characterization of near-term quantum platforms.

12.
arXiv (CS.CV) 2026-06-25

Did Models Learn Sufficiently? Attribution-Guided Training via Subset-Selected Counterfactual Augmentation

In current visual model training, models often rely on only limited sufficient causes for their predictions, which makes them sensitive to distribution shifts or the absence of key features. Attribution methods can accurately identify a model's critical regions. However, masking these areas to create counterfactuals often causes the model to misclassify the target, while humans can still easily recognize it. This divergence highlights that the model's learned dependencies may not be sufficiently causal. To address this issue, we propose Subset-Selected Counterfactual Augmentation (SS-CA), which integrates counterfactual explanations directly into the training process for targeted intervention. Building on the subset-selection-based LIMA attribution method, we develop Counterfactual LIMA to identify minimal spatial region sets whose removal can selectively alter model predictions. Leveraging these attributions, we introduce a data augmentation strategy that replaces the identified regions with natural background, and we train the model jointly on both augmented and original samples to mitigate incomplete causal learning. Extensive experiments across multiple ImageNet variants show that SS-CA improves generalization on in-distribution (ID) test data and achieves superior performance on out-of-distribution (OOD) benchmarks such as ImageNet-R and ImageNet-S. Under perturbations including noise, models trained with SS-CA also exhibit enhanced generalization, demonstrating that our approach effectively uses interpretability insights to correct model deficiencies and improve both performance and robustness.

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

Rule Taxonomy and Evolution in AI IDEs: A Mining and Survey Study

arXiv:2606.12231v1 Announce Type: cross Abstract: The adoption of AI-powered Integrated Development Environments (AI IDEs) has introduced "Rules" as a novel software artifact, allowing developers to persistently inject project-specific constraints and architectural guidelines into the context of Large Language Models (LLMs). Despite their role in aligning AI behavior with developer intent, the taxonomy, evolution, and practical impact of these rules remain largely unexplored. To bridge this gap, we conducted a mixed-methods empirical study on AI IDE rules. By mining 83 open-source projects and extracting 7,310 rules, we established a comprehensive taxonomy comprising 5 primary and 25 secondary categories. We then triangulated these artifacts with survey responses from 99 practitioners. Our analysis identified a contrast between developer priorities and actual configurations: while practitioners rate architectural constraints as highly important, rule files in repositories primarily consist of low-level workflow and code formatting constraints. Furthermore, our analysis of 1,540 rule evolution events revealed that rules are updated frequently. Repository data further indicate that rule evolution is primarily driven by constructive context expansions (29.17%) and enrichments (26.59%). In contrast, surveyed developers reported modifying rules primarily to correct AI errors (77.78%), typically by adding new negative constraints rather than editing existing ones. Finally, an artifact compliance assessment of 160 rule evolution events revealed that updating rules significantly improves the adherence of software artifacts, with the average artifact compliance rate increasing by 22.99% (from 49.14% to 72.13%) following an update. Our study provides empirical insights that can help developers optimize prompting strategies and guide tool builders in designing automated conflict-detection and context-management mechanisms for AI IDEs.

14.
bioRxiv (Bioinfo) 2026-06-23

FateLimit quantifies the prediction horizon of cell fate

Single-cell technologies have enabled increasingly detailed reconstruction of developmental trajectories, yet a fundamental question remains unresolved: when does future cellular identity become predictable from cells current molecular state? Existing approaches infer lineage relationships, transition probabilities or future transcriptional dynamics, but do not directly quantify the emergence of fate predictability during cellular state transitions. Here we present FateLimit, an information-theoretic framework for measuring the temporal dynamics of cell-fate predictability from single-cell omics data. FateLimit combines probabilistic fate assignment, fate entropy and mutual information to quantify how information about future cellular outcomes is encoded in present molecular states. We introduce two quantitative descriptors: the Fate Information Half-Life (FIHL), which measures the characteristic timescale of fate-information dynamics, and the Prediction Horizon (PH), defined as the earliest developmental stage at which observed fate predictability exceeds the 95th percentile of a permutation-derived null distribution. We applied FateLimit across developmental, lineage-tracing and reprogramming systems, including pancreatic endocrinogenesis, CellTag reprogramming, human hematopoiesis and zebrafish embryogenesis. Across all datasets, FateLimit identified significant fate information and reproducible prediction horizons that were robust to cell-state representation, lineage structure and biological context. Comparative analysis revealed that prediction horizons differ substantially among cellular lineages, indicating that distinct developmental programs acquire predictive information at different rates. FateLimit establishes a general framework for quantifying the predictability of future cellular identity from present molecular states. By transforming developmental trajectories into predictability landscapes, FateLimit enables systematic comparison of commitment dynamics across biological systems and establishes prediction horizons as a quantitative measure of cell-fate determination.

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

An Analytical Methodology for Quantifying Airspace Conflict Rate and Complexity

arXiv:2606.14897v1 Announce Type: cross Abstract: Air traffic growth, advanced air mobility, and increasingly autonomous operations are driving the need for scalable and adaptive airspace design methodologies. Central to this challenge is quantifying how traffic flow structure and demand, governed in part by airspace geometry, influence conflict generation and operational complexity. This paper presents an analytical framework for computing conflict rate and conflict probability in structured airspace using stochastic flow models. Traffic streams are modeled as renewal processes with prescribed inter-arrival time distributions, while interactions between flows are captured through geometry-dependent minimum spacing constraints at merges and crossings. Within this formulation, closed-form upper bounds on the expected conflict rate and conflict probability per aircraft are derived as functions of flow configuration and demand. These metrics are interpreted as complementary measures of airspace complexity, reflecting controller workload and per-aircraft operational risk. The methodology is applied to representative hexagonal cell geometries with varying routing structures and flow distributions. Results reveal non-monotonic tradeoffs between routing flexibility, capacity, and conflict generation, with intermediate flow configurations outperforming both highly constrained and highly distributed cases. The proposed framework provides a tractable tool for evaluating airspace design alternatives and complexity-informed traffic management strategies.

16.
arXiv (CS.AI) 2026-06-19

Beyond Reasoning Gains: Mitigating General-Capability Forgetting in Large Reasoning Models

arXiv:2510.21978v2 Announce Type: replace-cross Abstract: Reinforcement learning with verifiable rewards (RLVR) has delivered impressive gains in mathematical and multimodal reasoning and has become a standard post-training paradigm for contemporary language and vision-language models. However, the RLVR recipe introduces a significant risk of capability regression, in which models forget foundational skills after prolonged training without employing regularization strategies. We empirically confirm this concern, observing that open-source reasoning models suffer performance degradation on core capabilities such as perception and faithfulness. While imposing regularization terms like KL divergence can help prevent deviation from the base model, these terms are computed on the current task and therefore do not guarantee preservation of broader knowledge. Meanwhile, commonly used experience replay across heterogeneous domains makes it nontrivial to decide how much training emphasis each objective should receive. To address this, we propose RECAP-a replay strategy with dynamic objective reweighting for general knowledge preservation. Our reweighting mechanism adapts online using short-horizon signals of convergence and instability, shifting the post-training focus away from saturated objectives and toward underperforming or volatile ones. Our method is end-to-end and readily applicable to existing RLVR pipelines without training additional models or heavy tuning. Extensive experiments on benchmarks using Qwen2.5-VL-3B and Qwen2.5-VL-7B demonstrate the effectiveness of our method, which not only preserves general capabilities but also improves reasoning by enabling more flexible trade-offs among in-task rewards.

17.
arXiv (CS.CV) 2026-06-25

Geometry-Anchored Transport Framework for Exemplar-Free Class-Incremental Learning

Exemplar-free class-incremental learning (EFCIL) requires stable decision boundaries within a shifting feature space. While maintaining class-conditional Gaussian statistics provides a principled classification strategy, these parametric summaries remain sensitive to anisotropic representation drift. Existing methods often transport these statistics across tasks using a decoupled, post-hoc paradigm: optimizing a backbone without explicit geometric constraints can distort the legacy manifold, limiting the precision of retroactive alignment. In this paper, we formulate feature transport as an endogenous training constraint rather than a separate post-task step, presenting the Geometry-Anchored Transport Framework. First, we derive an Analytic Geometric Anchor via Mahalanobis-aligned regression to mitigate macroscopic anisotropic drift. Second, we introduce a Topology-Aware Evolution objective that regularizes localized manifold degradation while calibrating a residual network against the analytic prior. By coupling manifold evolution with transport constraints during the primary training phase, our framework mitigates evaluation errors without requiring decoupled fine-tuning. Experiments across CIFAR-100, TinyImageNet, and ImageNet-100 demonstrate that the proposed framework consistently improves upon existing post-hoc alternatives under strict exemplar-free constraints.

18.
arXiv (CS.AI) 2026-06-16

FreeSonic: Training-Free Temporal-Aware Decoupled Attention for Precise Audio Editing

arXiv:2606.15186v1 Announce Type: cross Abstract: Text-to-audio (TTA) generation has made significant strides, yet achieving precise and consistent audio editing remains a major challenge. However, existing methods struggle to balance temporal consistency with background preservation. In this paper, we propose FreeSonic, a training-free framework leveraging the state-of-the-art Rectified Flow-based TangoFlux model. FreeSonic utilizes an optimized inversion-reverse process and joint text-audio attention maps for precise target segment extraction. For content editing, a novel scheduled attention decoupling confines modifications to target regions while preserving original acoustic context. Furthermore, task-oriented noise injection enhances versatility for tasks such as audio removal and non-rigid replacement. Extensive experimental results demonstrate that FreeSonic achieves a superior balance by providing a high-fidelity and efficient solution for precise and consistent audio editing. Project and demos: https://free-sonic.github.io/

19.
bioRxiv (Bioinfo) 2026-06-11

AGZArank: Investigating epitope-conditioned antibody binder ranking with structure-derived synthetic supervision

Computational antibody design methods can generate large libraries of candidate binders for a target epitope, but prioritizing which candidates to test experimentally remains a major bottleneck. Existing scoring approaches, including physics-based affinity estimators, structure-prediction-derived confidence measures, and inverse-folding likelihood models, provide useful proxy signals but are not explicitly optimized for early enrichment of binders among many structurally similar candidates. Here we investigate epitope-conditioned antibody binder ranking as a dedicated learning problem and introduce AGZArank, a geometric deep learning framework trained with structure-derived synthetic supervision based on normalized pseudo-energy targets. On a benchmark of 45 experimentally validated antibody-antigen interfaces, AGZArank recovered the true binder within the top ten candidates in 44.4% of cases and showed stronger generalization on post-2021 structures than ProteinMPNN, ESM-IF, and PRODIGY. Ablation experiments indicate that ranking performance depends primarily on training scale and alignment between the optimization objective and retrieval-based evaluation, rather than architectural complexity alone. These results support candidate prioritization as a distinct and tractable problem in computational antibody design.

20.
Nature (Science) 2026-06-24

Small-molecule modulation of β-arrestins

β-Arrestins are multifunctional regulators of G-protein-coupled receptor (GPCR) signalling and orchestrate diverse downstream signalling events and physiological responses across the GPCR superfamily1–3. Although GPCR pharmacology has advanced to target orthosteric and allosteric sites, as well as G proteins and GPCR kinases, direct chemical tools to modulate β-arrestin activities have remained conspicuously absent. Here we report the identification of small-molecule inhibitors that selectively target β-arrestins and delineate their mechanism of action through integrated pharmacological, biochemical, biophysical and structural analyses. These inhibitors disrupt β-arrestin engagement with agonist-activated GPCRs, impairing desensitization, internalization and β-arrestin-dependent physiological functions while sparing G protein–receptor coupling. Cryo-electron microscopy, molecular dynamics simulations and structure-guided mutagenesis reveal that one modulator, Cmpd-5, engages a pocket within the central crest of β-arrestin1 formed by the middle, C and lariat loops, a critical receptor-binding interface, stabilizing a distinct conformation that is incompatible with full β-arrestin–receptor engagement. Together, these findings establish a mechanistic framework for β-arrestin modulation, reveal a novel allosteric site for structure-based drug design, and open new avenues for transducer-targeted, pathway-specific GPCR therapeutic agents. Integrated pharmacological, biochemical, biophysical and structural analyses of small-molecule β-arrestin inhibitors show how they block β-arrestin engagement with activated GPCRs, revealing their mechanism of action and uncovering a previously unrecognized allosteric regulatory site.

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

Cluster LOCO: Feature Importance For Interpreting Clusters

arXiv:2606.14592v1 Announce Type: cross Abstract: Clustering is widely used for exploratory analysis and scientific discovery, driving insights from market segmentation to biological data analysis, but its outputs can be difficult to interpret, audit, and reproduce as modern datasets become increasingly large and complex. Reliable use of clustering requires understanding which features drive the discovered structure, yet feature-level explanations for clustering remain scarce compared with methods in supervised learning. Furthermore, existing clustering feature importance scores are often tied to specific algorithms and data assumptions. To address these challenges, we propose Cluster LOCO (Leave-One-Covariate-Out), a family of model-agnostic feature importance scores for clustering. Cluster LOCO is built on feature occlusion and clustering generalizability, defined as whether cluster labels learned on one subset of the data can be accurately predicted on held-out samples. For any chosen clustering algorithm, Cluster LOCO quantifies a feature's importance by measuring how much its removal degrades generalizability. We first introduce Cluster LOCO-Split, which relies on data splitting, and then extend it to Cluster LOCO-MP, a minipatch ensemble-based version designed for large-scale data. Across synthetic simulations and an application to cell-type discovery in single-cell transcriptomics, we show that Cluster LOCO more reliably recovers informative features than existing clustering feature importance methods.

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

Evolutionary Two-Stage Hyperparameter Optimization Strategies for Physics-Informed Neural Networks

arXiv:2606.20442v1 Announce Type: new Abstract: Physics-Informed Neural Networks (PINNs) solve Partial Differential Equations (PDEs) by embedding physical laws into neural network training. However, their performance suffers from unstable convergence, training plateaus, and strong sensitivity to architectural and optimization hyperparameters due to the highly non-convex and multi-term structure of the physics-informed loss. In this setting, the outer-loop hyperparameter search is a noisy and black-box optimization problem over heterogeneous parameters, where classical local or gradient-based strategies are easily trapped in suboptimal regions. Evolutionary algorithms, with their population-based exploration and ability to handle mixed, non-differentiable search spaces, provide a more robust mechanism for discovering promising configurations. We propose and investigate a two-stage approach based on evolutionary algorithms that combines exploration and exploitation parts of PINNs training to improve solution accuracy and robustness under fixed computational budgets. In the first stage, we perform low-fidelity training runs with truncated epochs to rapidly screen candidate configurations, treating hyperparameter selection as a black-box outer-loop problem. In the second stage, only the most promising candidates are fully trained with standard gradient-based optimizers to refine the solution. Evaluated on three popular problems, namely Advection, Klein-Gordon and Helmholtz equations, our method consistently outperforms standard training and achieves significantly lower mean error within constrained computational resources.

23.
arXiv (CS.LG) 2026-06-17

Learning to Refine Hidden States for Reliable LLM Reasoning

arXiv:2606.17524v1 Announce Type: new Abstract: Large language models show strong reasoning ability, but their internal reasoning process can remain unstable in complex multi-step settings, where early hidden-state errors may propagate to incorrect predictions. We propose ReLAR, a reinforcement-guided latent refinement framework that iteratively updates hidden representations before decoding. ReLAR maintains a compact latent reasoning state and uses learned depth and action controllers to adaptively determine both the number and direction of refinement steps. The controllers are trained with a policy gradient objective based on step-wise likelihood improvement, enabling efficient input-dependent reasoning without explicit chain-of-thought generation. Experiments on medical, mathematical, multi-hop reasoning, and open-ended generation benchmarks show that ReLAR improves accuracy, generation quality, and reasoning stability with substantially lower inference overhead than explicit reasoning baselines.

24.
arXiv (CS.CL) 2026-06-11

Goal-Autopilot: A Verifiable Anti-Fabrication Firewall for Unattended Long-Horizon Agents

Authors:

Long-horizon LLM agents are not trusted to run unattended: with no human watching, they confidently report success they never verified. We treat honesty – bounding what an agent may claim at termination – as a first-class metric for unattended autonomy, distinct from capability. We present Autopilot, an execution model that makes silent fabricated success structurally impossible rather than merely rarer. Autopilot externalizes all working state into a durable, gated finite-state machine that a scheduler advances one stateless tick at a time; a hard floor forbids any terminal "done" claim whose falsifiable gate did not actually execute and pass. We prove a No-False-Success theorem – under gate soundness, floor enforcement, and plan coverage, termination implies the goal holds – whose only trust points are empirically measurable, and show the worst case degrades to an honest stall, never a fabricated success. Because each tick rehydrates only the state machine, per-step context cost is constant in the horizon. Across a 3,150-cell paired corpus (70 tasks $\times$ 3 systems $\times$ 3 models $\times$ 5 seeds, including 50 SWE-bench Lite tasks across 11 OSS repos), Autopilot fabricates on 0.95% of cells [95% CI 0.38–1.62] while Reflexion and StateFlow baselines fabricate on 8.10% [6.48–9.81] and 25.05% [22.48–27.62] respectively. The headline contrast lives in the hard regime: on SWE-bench Lite, the firewall reduces fabrication from 33.7% (StateFlow) to 0.67%, a paired difference of $-33.07$ pp [95% CI $-36.53, -29.73$]. The mechanism is the gate, not the model: all ten Autopilot fabrications come from the strongest model, while two weaker mid-tier models never fabricate across 700 paired cells. The firewall trades coverage for honesty by design – an honest stall is recoverable; a confident wrong output shipped downstream is not.

25.
Nature Medicine 2026-06-11

Microglia at a key inflection point in Alzheimer’s disease

Authors: Unknown Author

We analyzed brains from octogenarians and cognitively resilient centenarians to understand why some individuals with substantial Alzheimer’s disease pathology develop dementia whereas others remain cognitively intact. Spatial transcriptomics revealed gene expression changes in discrete tissue domains surrounding amyloid plaques and tau pathology that distinguish early, clinically silent, disease from later stages associated with cognitive decline.