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01.
arXiv (CS.LG) 2026-06-15

PostDeg: Placement Beats Parameterization in LayerNorm GNNs

arXiv:2606.14022v1 Announce Type: new Abstract: LayerNorm-based GNNs routinely erase the topology signals (degree, centrality, $k$-core) that node-selection policies should depend on, but the literature has not located where in the residual block the erasure happens. We answer that question: a positive per-node scalar inserted before LayerNorm is divided out up to a stabilizer term, while the same scalar inserted after LayerNorm reaches the score head as representation magnitude. The surviving slot is the post-LayerNorm position. We instantiate it with PostDeg, a parameter-free post-LayerNorm inverse-degree scale, and pre-register four falsifiers (graphwise scalars, extra LayerNorm, expressive same-slot capacity, backbone-agnostic source) that would reject the rule. PostDeg gains $+3.5\%/+2.5\%/+5.6\%$ over the LN backbone on influence maximization, network dismantling, and maximum independent set, with $10/10$ paired-seed wins per task; none of the four falsifiers fires. The takeaway is that placement, not parameterization, carries the gain – a small invariance check that generalizes to any positive topology scalar in any normalized residual stack.

02.
medRxiv (Medicine) 2026-06-22

A Controlled Human Malaria Infection model for relapsing Plasmodium vivax

Background Plasmodium vivax malaria relapses are a major source of morbidity and onward transmission of infection. The underlying mechanisms are poorly understood and current therapies sub-optimal. We examined the safety and feasibility of a controlled human malaria infection (CHMI) model for relapsing P. vivax. Methods We conducted an open-label, proof-of-concept, CHMI study of relapsing P. vivax. Healthy, malaria-naive, Duffy-positive adults aged 18-45 years with extensive CYP2D6 metaboliser phenotype and normal blood glucose-6-phosphate dehydrogenase (G6PD) levels were recruited in Oxford, UK. Mosquito-bite CHMI was performed in Nijmegen, The Netherlands, using Anopheles stephensi mosquitoes infected with PvW1, a clonal isolate of P. vivax from Thailand. All follow-up visits were conducted in Oxford, UK. Primary P. vivax infections (qPCR > 500 genome copies/mL) were treated with artemether-lumefantrine (80mg/480mg at 8, 24, 36, 48 and 60 hours). From Day 28 following CHMI, participants attended a fortnightly clinic for clinical review and qPCR blood sampling, with additional assessments performed for any reported symptoms. P. vivax relapse infections (qPCR > 500 genome copies/mL) were treated with artemether-lumefantrine as per primary infection. Definitive anti-malarial treatment with atovaquone-proguanil (1000mg/400mg once daily for three days) and primaquine (0{middle dot}5 mg/kg/day for 14 days) was administered six months following CHMI, regardless of parasitaemia or symptoms. The primary objective was to assess the safety, feasibility and frequency of relapsing P. vivax after CHMI. Remote follow-up (5 years) is ongoing. The study is registered with ISRCTN registry (ISRCTN48625883). Findings 20 participants were screened for eligibility from 21 January 2025. Five participants (median age 22 years) underwent CHMI (five infected mosquitoes per participant) on 15 April 2025. All participants developed primary P. vivax infection and experienced at least one relapse infection. Two participants experienced a second relapse. Overall incidence rate was 3{middle dot}6 relapse infections per person-year. Solicited adverse events were mild or moderate and there were no serious adverse events. Definitive anti-malarial treatment was administered to all participants. One participant experienced primaquine-induced methaemoglobinaemia, resolving with early discontinuation of treatment (total dose 5{middle dot}3 mg/kg). To date, more than six months after primaquine treatment, no further relapses have been recorded. Interpretation CHMI of relapsing P. vivax is safe and feasible, allowing exploration of the mechanisms underlying relapse infections and providing a platform for future anti-relapse efficacy studies. Funding European Union Horizon Europe programme and UK Research and Innovation (UKRI) via OptiVivax consortium; UK National Institute for Health and Care Research Biomedical Research Centre: Oxford; and UK Medical Research Council.

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

CausalDrive: Real-time Causal World Models for Autonomous Driving

World models have emerged as a promising paradigm for scaling autonomous driving (AD) data, yet existing video generative models fall short as interactive simulators. Layout-conditioned renderers rely on "oracle" future trajectories of all background agents, rendering them strictly non-reactive. Conversely, pure action-conditioned predictors lack semantic control over complex interactions and suffer from prohibitive diffusion latencies, hindering closed-loop policy learning. To bridge this gap, we present CausalDrive, a controllable, real-time foundation driving world renderer. CausalDrive operates solely on the initial front-view frame, the ego-vehicle's trajectory, and a macroscopic text prompt. By excluding future NPC layouts, we compel the model to intrinsically predict causal interactions, enabling text-driven control over Driving Sociology, allowing users to dynamically orchestrate diverse counterfactual reactions to identical ego-actions. To overcome the efficiency bottleneck and address the covariate shift in autoregressive generation, we propose a novel Context-Forced DMD architecture. This combines continuous flow-matching with a self-correcting distillation objective, achieving interactive speeds of 12 FPS. This breakthrough transforms the passive video generator into a playable neural simulator. We demonstrate its versatility across three downstream applications: (1) generative closed-loop evaluation with significantly mitigated collision artifacts, (2) large-scale Reinforcement Learning (RL) post-training driven by a Video2Reward module, and (3) real-time human-in-the-loop simulation. Extensive experiments validate that policies trained within CausalDrive's reactive scenarios exhibit superior interaction capabilities in the real world.

04.
arXiv (CS.AI) 2026-06-16

AgenticRec: A Recommendation-Oriented Agentic Framework with Progressive Tool-Integrated Reasoning Optimization

arXiv:2603.21613v2 Announce Type: replace-cross Abstract: Recommender agents built on Large Language Models offer a promising paradigm for personalized recommendation. However, existing agents typically suffer from a misalignment between their tool-integrated reasoning trajectories and recommendation feedback, limiting their ability to distinguish fine-grained user preferences. To address these challenges, we propose AgenticRec, an agentic recommendation framework that formulates recommendation as a tool-integrated reasoning process over a recommendation-oriented tool suite. Built upon this framework, we further develop a dedicated two-stage training paradigm tailored for recommender agents. In the first stage, we introduce Recommendation-Oriented Trajectory Activation, optimize the agentic recommendation ability under implicit feedback. In the second stage, Progressive Preference Refinement further refines the agent through bidirectional preference reasoning over self-bootstrapped hard pairs, progressively sharpening preference boundaries. Theoretical analysis and extensive experiments demonstrate the effectiveness of AgenticRec. Our code is available at https://anonymous.4open.science/r/AgenticRec-FB16.

05.
arXiv (CS.AI) 2026-06-18

Guava: An Effective and Universal Harness for Embodied Manipulation

arXiv:2606.18363v1 Announce Type: cross Abstract: Language models trained on large-scale vision-language data have demonstrated strong potential for embodied agents. Harnessing models through embodied tools use offers a promising alternative to end-to-end vision-language-action systems by combining high-level reasoning with external modules for perception, planning, and control. However, it remains unclear what makes an effective harness for embodied manipulation, and to what extent such a harness can unlock embodied capabilities in a wide range of reasoning models. In this work, we present Guava, a harness framework for embodied tool use developed through systematic exploration of the design space of agent workflows, action spaces, and observation spaces. Our study identifies three key ingredients for effective embodied agents: iterative perception-reasoning-action loops, semantic action abstractions, and multimodal observations. To understand whether these design principles are universal even to small models, we develop an end-to-end training pipeline that distills embodied manipulation capabilities into a 4B open-source model using fewer than 2K trajectories collected entirely in simulation. Experimental results in both simulation and real-world environments show performance comparable to frontier proprietary models while exhibiting strong generalization to unseen objects, novel instructions, and long-horizon tasks. Results suggest that a well-designed harness can serve as a scalable, model-agnostic interface for embodied manipulation, enabling strong emergent embodied capabilities in compact open-source models with minimal training data.

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

From Bounding Boxes to Visual Reasoning: An On-Policy Data Annotation Tool for Vision-Language Models

Vision-language models (VLMs) are rapidly advancing toward sophisticated grounded structured visual reasoning. Training models for such advanced capabilities demands a new genre of data that seamlessly unifies spatial coordinates, open-vocabulary descriptions, structured attributes, and topological relationships into a singular representation. However, existing data annotation tools fundamentally fail to meet these intricate demands, suffering from three systematic bottlenecks: limited expressiveness, severe annotation-training decoupling, and poor data reusability. To bridge this infrastructure gap, we introduce an open-source annotation tool, ScreenAnnotator. First, we define a unified annotation atom schema that binds spatial, semantic, and structural primitives into a single unit. Second, we implement an on-policy annotation loop embedded with a Bayesian Annotation Verifier (BAV). Finally, we design a template-driven multi-task data synthesis process dynamically transforms static atoms into diverse multi-dimensional reasoning tasks, eliminating redundant re-annotation. The on-policy loop drives the annotation accept rate to nearly 100% on flowcharts and 77% on GUI screenshots, while steadily reducing per-image annotation time as labeled data accumulate. In the flowchart scenario, fine-tuning a VLM yields 76.1% average accuracy, which is a 35.1% point absolute gain. Our code is available at: https://github.com/WnQinm/Annotator.

07.
arXiv (quant-ph) 2026-06-12

Asymmetric quantum steering harvested near a Lorentz-violating BTZ black hole

arXiv:2606.12766v1 Announce Type: cross Abstract: We investigate the harvesting of quantum steering and its directional asymmetry between two Unruh-DeWitt detectors in a Lorentz-violating BTZ black hole spacetime. Since the detectors are located at different radial positions outside the black hole, they experience inequivalent local environments induced by gravitational redshift, causing Alice to undergo stronger effective thermal noise than Bob. Remarkably, we uncover a counterintuitive phenomenon in which the detector subjected to a higher effective temperature exhibits stronger steerability than the other one, revealing a nontrivial inversion of thermal intuition in curved spacetime. Furthermore, quantum steering survives only within a finite window of detector energy gaps and reaches its maximum within an optimal regime. We find that Lorentz violation suppresses steering most strongly near this optimal energy gap, indicating an enhanced sensitivity of maximal correlation extraction to symmetry breaking effects. Our results demonstrate that Lorentz violation acts as a geometric constraint on the quantum information capacity of spacetime, simultaneously restricting both the strength and the directionality of quantum correlations.

08.
medRxiv (Medicine) 2026-06-15

Diabetes and the Life-Course: Evidence from Panel Data and Electronic Health Records

Incidence of type 2 diabetes is increasing at ages when education, work, family, and financial transitions are taking place, yet we lack robust evidence of whether earlier treatment changes life-course outcomes and over which time span this takes place. This paper uses the medical cutoff for diabetes diagnosis (HbA1c of 6.5 percent) as a natural experiment to study the effects of diabetes treatment using electronic health records (EHR) and panel data. This paper has three main findings. First, using EHR data, we find that there is a sharp increase in the probability of both diagnosis of diabetes and prescription when the HbA1c equals 6.5 percent. Second, we find that treating diabetes reduces HbA1c levels, weight, BMI, and blood pressure and increases the amount of care received, proxied by the number of HbA1c tests. Both the diagnosis and a prescription are independently able to produce positive changes in metabolic health, although a prescription is more effective in this regard. Third, we conclude that treating diabetes does not have a significant effect on life-course outcomes for a cohort of young Americans aged 24-32, although it does result in a reduction in HbA1c levels that are seen even eight years after the intervention. Taken together, these findings suggest that receiving a diagnosis and prescription are both effective treatments for diabetes, but they do not translate to significant alterations in the lives of young adults in the medium-term.

09.
arXiv (CS.AI) 2026-06-11

T2S: A Rehearsal-Based Approach for Extraction-Resistant Model Watermarking

arXiv:2606.11698v1 Announce Type: cross Abstract: Model watermarking safeguards AI model intellectual property by embedding distinctive knowledge that induces unique behavioral signatures. The primary technical challenge lies in ensuring watermark robustness against various post-processing attacks on the watermarked model. Model extraction attacks emerge as the most severe threat, where adversaries exploit prediction outputs to train surrogate models that illegally replicate the original model's functionality. In this work, we propose a rehearsal-based watermark embedding framework to enhance the robustness of model watermarks against model extraction attacks. By simulating the extraction process, our method leverages the loss of a simulated stolen model on a trigger set as a training signal to fine-tune the watermark knowledge within the target model. This fine-tuning step encourages the watermark to be embedded in a way that boosts transferability, thereby increasing its chances of persisting and remaining detectable in stolen models. Comprehensive experiments conducted under diverse settings demonstrate that the proposed method significantly improves the robustness of model watermarks against both model extraction and subsequent watermark removal attacks.

10.
arXiv (CS.CV) 2026-06-17

High-Fidelity 3D Geometric Reconstruction of Pelvic Organs from MRI: A Hybrid Deep Learning and Iterative Optimization Approach

Patient-specific 3D reconstruction of pelvic organ geometry from MRI is important for pelvic floor modeling and downstream patient-specific analysis. However, while previous studies have focused primarily on either image segmentation or downstream use of 3D models, the reconstruction of high-fidelity, high-quality geometries remains labor-intensive and poorly standardized. The study introduced a hybrid deformable shape modeling framework that integrates deep learning prediction with iterative optimization for the reconstruction of the bladder, uterus, and rectum. The framework consists of three core components: a geometry-aware multi-level deep learning architecture that preserves topological consistency of pelvic organs; a two-stage amortized optimization training strategy that balances global shape capture and local surface refinement; and a holistic synergy mechanism–where iterative optimization provides supervision for deep learning during the training phase, and during inference, deep learning rapidly predicts the global organ morphology, followed by iterative optimization to refine local surfaces and mesh quality. This framework demonstrated marked superiority in geometric fidelity than current mainstream deep learning-based organ reconstruction models. For individual anatomical structures, the reconstructed 3D geometries for the bladder, rectum, and uterus achieved significantly lower Chamfer Distance values and higher Dice Similarity Coefficient scores. In addition, while maintaining high computational efficiency, the proposed architecture yielded superior overall volumetric mesh quality. At the patient level, the framework achieved higher mean values for the 10 worst elements for both minSICN and minSIGE compared to traditional geometric post-processing algorithms.

11.
arXiv (CS.CL) 2026-06-16

It's About Time: Temporal References in Emergent Communication

Emergent communication enables agents to develop bespoke languages that improve communication efficiency. Despite the known importance of temporal structure in natural language, there is no existing evidence of temporal references in emergent communication. This paper addresses this gap, by exploring how agents communicate about temporal relationships. We analyse three potential factors for the emergence of temporal references: environmental, external, and architectural. Our experiments demonstrate that altering the loss function is insufficient for temporal references to emerge; rather, architectural changes are necessary. A minimal change in agent architecture, using a different batching method, allows the emergence of temporal references. This modified design is compared with the standard architecture in a temporal referential games environment, which emphasises temporal relationships. The analysis shows that over 95% of the agents with the modified batching method develop temporal references, without changes to their loss function. We consider temporal referencing necessary for future improvements to the agents' communication efficiency, enabling future agents to use a closer to optimal coding as compared to purely compositional languages. These insights provide the basis for incorporation of temporal references into other emergent communication settings, and investigation of other aspects of language.

12.
arXiv (CS.CL) 2026-06-18

Possible or Definite? A Benchmark for Evaluating Diagnostic Uncertainty Preservation in Clinical Text

Large language models (LLMs) are increasingly used for clinical text tasks such as summarization and revision. While most studies evaluate the fluency and coherence of LLM-generated text, whether LLMs correctly preserve diagnostic uncertainty remains underexplored. In clinical practice, phrases such as ``possible pneumonia'' communicate the strength of available evidence and directly guide decisions about follow-up testing and treatment. Altering these uncertainty expressions can change the clinical meaning entirely. In this paper, we systematically evaluated this problem in two steps. First, we constructed a benchmark of 1,200 clinical documents with 9,184 uncertainty annotations across five levels. Second, we evaluated three LLMs on this benchmark. Our results show that (1) LLMs preserve the original uncertainty cues poorly, often less than half the time; (2) LLMs struggle with nuanced distinctions between adjacent levels. This work reveals a failure mode not captured by standard evaluation metrics and provides implications for the safe deployment of LLMs in clinical workflows.

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

CRAG: Can 3D Generative Models Help 3D Assembly?

Most existing 3D assembly methods treat the problem as pure pose estimation, rearranging observed parts via rigid transformations. In contrast, human assembly naturally couples structural reasoning with holistic shape inference. Inspired by this intuition, we reformulate 3D assembly as a joint problem of assembly and generation. We show that these two processes are mutually reinforcing: assembly provides part-level structural priors for generation, while generation injects holistic shape context that resolves ambiguities in assembly. Unlike prior methods that cannot synthesize missing geometry, we propose CRAG, which simultaneously generates plausible complete shapes and predicts poses for input parts. Extensive experiments demonstrate state-of-the-art performance across in-the-wild objects with diverse geometries, varying part counts, and missing pieces. Project Page: https://ai4ce.github.io/CRAG/

14.
medRxiv (Medicine) 2026-06-18

Plasma proteomics reveals clinical and mechanistic heterogeneity among individuals who develop coronary artery disease

BACKGROUND: Individuals who develop coronary artery disease (CAD) are clinically and mechanistically heterogeneous, and understanding this variation is crucial for precise risk stratification and tailored interventions. However, the molecular mechanisms that connect these two kinds of heterogeneity remain unclear, limiting progress toward biologically grounded risk stratification and targeted interventions. Here, we investigated the heterogeneity of individuals who develop CAD by leveraging plasma proteomic signatures, placed individuals along continuous metabolic gradients and revealed the molecular programs underlying these patterns, thereby linking mechanistic variation to clinical heterogeneity. METHODS AND RESULTS: From 42,803 UK Biobank participants, including 3,713 individuals who developed CAD within 10 years (incident CAD), we first identified a 320-protein panel from 2,923 baseline proteins that improved prediction of incident CAD beyond clinical risk scores. Using reverse graph embedding, we reduced the proteomic data to two dimensions and mapped each incident case onto the resulting two-dimensional latent proteomic space. These proteomic dimensions show significant associations with cardiometabolic and kidney-related clinical markers. The patterns were replicated in the EPIC-Norfolk study. Phenome-wide Cox regression analyses further linked these proteomic dimensions to 10-year incidence rates for various diseases, including type 2 diabetes, obesity, and chronic kidney disease (CKD). Furthermore, adding the proteomic dimensions to clinical variable-based Cox regression model improved prediction of 10-year incidence of CKD and other diseases, demonstrating the value of proteomic dimensions beyond conventional clinical risk factors. Moreover, individuals with prevalent CAD (diagnosed before proteomic sampling) exhibited high, metabolically adverse dimension values, indicating that these axes capture cumulative metabolic burden. Pathway enrichment analyses implicated altered extracellular matrix organization and immune programs among the proteins contributing to the proteomic dimensions. CONCLUSIONS: Our findings demonstrate that plasma proteomic signatures can dissect the heterogeneity of individuals who develop CAD in continuous phenotypic gradients, improve prediction of CAD and comorbidities, and map underlying biological mechanisms.

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

An Angular-Temporal Interaction Network for Light Field Object Tracking in Low-Light Scenes

High-quality 4D light field representation with efficient angular feature modeling is crucial for scene perception, as it can provide discriminative spatial-angular cues to identify moving targets. However, recent developments still struggle to deliver reliable angular modeling in the temporal domain, particularly in complex low-light scenes. In this paper, we propose a novel light field epipolar-plane structure image (ESI) representation that explicitly defines the geometric structure within the light field. By capitalizing on the abrupt changes in the angles of light rays within the epipolar plane, this representation can enhance visual expression in low-light scenes and reduce redundancy in high-dimensional light fields. We further propose an angular-temporal interaction network (ATINet) for light field object tracking that learns angular-aware representations from the geometric structural cues and angular-temporal interaction cues of light fields. Furthermore, ATINet can also be optimized in a self-supervised manner to enhance the geometric feature interaction across the temporal domain. Finally, we introduce a large-scale light field low-light dataset for object tracking. Extensive experimentation demonstrates that ATINet achieves state-of-the-art performance in single object tracking. Furthermore, we extend the proposed method to multiple object tracking, which also shows the effectiveness of high-quality light field angular-temporal modeling.

16.
medRxiv (Medicine) 2026-06-11

Ferritin across long-term conditions in England: cross-sectional primary care study

Background Iron deficiency (ID) is a readily treatable condition once identified. Ferritin is the primary diagnostic marker, but cut-offs vary and inflammation complicates interpretation in patients with long-term conditions (LTCs). Aim To describe ferritin distribution and the prevalence of threshold-defined low ferritin in adults with and without LTCs in primary care. Design and setting Cross-sectional observational study using routinely collected electronic health records from a national primary care database in England (1st January 2015 to 31st December 2021). Method Adults with >1 ferritin test in Clinical Practice Research Datalink (CPRD) Aurum were included. LTCs were identified using validated primary-care code lists. Outcomes included ferritin distribution and threshold-defined ID prevalence using World Health Organization (WHO) (

17.
medRxiv (Medicine) 2026-06-12

Genetic basis of dynamic brain states reveals cellular and disease associations

Dynamic resting-state fMRI captures the time-varying patterns of brain activity that are obscured by static approaches. Hidden Markov Models (HMMs) characterise these dynamics as recurring whole-brain states and quantify their fractional occupancy (FO), the proportion of time spent in each state, yet the biological basis of inter-individual variation in FO remains unclear. Using data from 52,335 White UK Biobank participants, with replication in East and South Asian subsamples, this study examined the heritability, cellular and neurotransmitter basis of brain states, and their links with complex phenotypes. FO was significantly heritable and enriched for neuronal populations, particularly glutamatergic and GABAergic signalling. Analyses identified shared and state-specific loci and revealed genetic correlations, colocalisation, and potential causal relationships between FO and several phenotypes, including educational attainment, sleep duration, and disease risk. These findings establish dynamic brain states as biologically grounded intermediate phenotypes, linking genetic variation to neural dynamics, diseases and traits.

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

Orbital-optimized spin-adapted multistate contracted VQE for excited states and properties on quantum hardware

arXiv:2606.15489v1 Announce Type: new Abstract: We introduce the orbital-optimized multistate contracted variational quantum eigensolver (oo-MC-VQE) method with spin-adapted operators for the computation of ground and excited states, as well as state-specific and transition properties. The use of spin-adapted operators ensures that the spin symmetry of the reference states is conserved throughout the VQE optimization. In multistate variational approaches, achieving a balanced description of an increasing number of electronic states places growing demands on the expressibility of the underlying ansatz, thereby introducing a fundamental trade-off between accuracy and circuit complexity. We consider the effects of this trade-off explicitly and find that the number of circuit parameters required to obtain accurate results is reported to scale approximately linearly in the number of states. We further present an explicit quantum-circuit implementation of the oo-MC-VQE method and demonstrate its integration with quantum error mitigation techniques. Finally, we execute the method on real quantum devices to compute absorption spectra for two benchmark molecular systems.

19.
arXiv (quant-ph) 2026-06-11

On-Chip Quantum Randomness Amplification

arXiv:2606.12173v1 Announce Type: new Abstract: Randomness amplification, the task of extracting uniform private bits from biased seeds that may be partly known by a malicious third party, is of central importance in cryptography. The highest security in this task is provided by a class of quantum protocols known as device-independent, which however are challenging to integrate into scalable devices. Semi-device-independent (SDI) protocols are a promising alternative that guarantees security under few natural assumptions, such as bounds on the amount of energy used by the devices. Here, we provide the first demonstration of SDI randomness amplification on an integrated silicon photonic chip, achieving a throughput rate of 20 Mbps suitable for practical applications. This rate is achieved through a novel technique for SDI entropy certification, which delivers strictly tighter von Neumann entropy bounds compared to existing methods and remains valid even if the preparation and measurement devices share quantum correlations. Overall, the methods developed in this work enable the integration of SDI technology into portable telecom devices, opening up a new generation of quantum cryptographic hardware.

20.
arXiv (CS.CL) 2026-06-11

Steering the Noise: Turning Random Perturbations into Effective Descent for Memory-Efficient LLM Fine-Tuning

Fine-tuning large language models (LLMs) achieves strong performance but is often limited by the memory overhead of backpropagation. Zeroth-order (ZO) optimization avoids this overhead by estimating gradients through forward passes alone, yet it typically converges slowly because random Gaussian perturbations yield high-variance gradient estimates in high-dimensional parameter spaces. In this paper, we propose a plug-and-play framework that turns random perturbations into more effective descent directions. The key idea is to draw a small pool of candidate perturbations, evaluate their loss values, and then select or combine those that are best aligned with the optimization objective. We develop two instantiations of this idea: MeZO-GV, which forms a guiding vector from the contrast between low-loss and high-loss perturbation groups, and MeZO-Greedy, which keeps the single best perturbation within a fixed evaluation budget. We theoretically show that both strategies yield a larger per-step reduction in the objective than standard ZO estimation, leading to improved convergence rates. Experiments on LLMs of different scales and architectures confirm that the proposed methods integrate naturally with existing ZO optimizers and consistently improve convergence speed and task accuracy. On OPT-13B, our approach outperforms all ZO baselines across 11 benchmarks and exceeds gradient-based methods on 9 of them, while retaining the memory efficiency of forward-only optimization.

21.
arXiv (CS.LG) 2026-06-11

My Chemical Harness: Evolutionary Molecular Design over Synthetic Pathways with Large Language Model Agents

arXiv:2606.11256v1 Announce Type: cross Abstract: Designing molecules with target properties is most useful when candidate structures are accompanied by feasible synthetic routes. We introduce My Chemical Harness, a route-native evolutionary framework for goal-directed molecular design in which the search population consists of executable synthetic pathways rather than isolated molecular graphs. Each route is built from purchasable building blocks and reaction templates, executed by deterministic chemistry tools, and scored through task-specific molecular oracles. Large language models (LLMs) are used only as strategy controllers that select high-level preferences over route length, move type, reaction families, motifs, and exploration pressure, while local code performs route construction, validation, deduplication, scoring, selection, and memory updates. This separation lets the LLM guide exploration without allowing it to introduce hallucinated products or unsupported reaction steps. On a soluble epoxide hydrolase proxy task, our LLM agent improves over single pass LLM and deterministic controllers, reaching state-of-the-art performance across the sEH score, synthetic accessibility score, and AiZynthFinder success rate metrics. These results suggest that constrained LLM agents can play a significant role in molecular discovery without requiring training, fine-tuning, or dedicated generative models.

22.
arXiv (math.PR) 2026-06-18

A Unified Approach to Beta Moments, Combinatorial Identities, and Random Walks

arXiv:2605.05420v2 Announce Type: replace Abstract: The study of random walks has increasingly been popular across diverse disciplines such as statistics, mathematics, quantum physics, where they are used to model paths consisting of successive random steps in a mathematical space. A fundamental quantity of interest is the probability that a simple symmetric random walk returns to the origin after 2n steps. In this paper, we develop a unified probabilistic approach that connects the return probabilities in arbitrary dimensions with moment representations. Using this framework, we provide probabilistic proofs of several combinatorial identities involving beta and gamma functions, and derive new combinatorial identities in general dimensions.

23.
Nature (Science) 2026-06-10

Mitochondria tethered to the nucleus secure its energy supply

Direct interactions between the cell’s powerhouses and nuclear pores might channel energy straight into the nucleus, fuelling cell division and differentiation. Direct interactions between the cell’s powerhouses and nuclear pores might channel energy straight into the nucleus, fuelling cell division and differentiation.

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

Descriptive versus Regulatory Uncertainty in Bounded Predictive Systems

arXiv:2605.18909v2 Announce Type: replace Abstract: Any system that models the world under finite representational capacity must compress; any compression entails a prior; and the prior is the system's bias. What has not been established is whether uncertainty participates in the dynamics governing future behavior, or merely describes the output distribution without consequence. We introduce a structural distinction between descriptive uncertainty, which does not recursively modulate the system's policy, and regulatory uncertainty, which directly enters the optimization landscape and drives persistent adaptive restructuring. We prove formally that current transformer architectures are confined to descriptive uncertainty at inference. We ground this in thermodynamics via Landauer's principle: for uncertainty to be regulatory, epistemic error must cost real energy; in a decoupled system, hallucinations and correct derivations dissipate identical energy. We test this empirically across three locally-deployed language models (3B, 8B, 70B parameters). Token-level Shannon entropy is statistically invariant across tasks spanning pattern retrieval, causal operator application, and out-of-distribution causal generalization in all three models (all pairwise p >= 0.568; within-model ranges 0.011-0.028 nats), while task accuracy varies substantially across the same conditions (0%-100%). Entropy and accuracy are orthogonal. The decoupling is scale-invariant: larger models achieve higher accuracy but identical entropy flatness. This structural incapacity is not resolvable by additional parameters or training data. Genuine epistemic grounding requires physical coupling between thermodynamic substrate state and information processing cost.

25.
arXiv (quant-ph) 2026-06-11

A Geometric Family of Correlations Containing the Quantum Singlet

arXiv:2606.12045v1 Announce Type: new Abstract: We introduce a geometrically constrained hidden-variable framework that generates a family of correlations parametrized by a boundary function, within which the quantum singlet correlation appears as a particular member. Exact expressions for the correlation function are derived. Several structural results are established, including admissibility conditions, symmetry properties, a universal stationary point of the associated CHSH function, and an exact relation between the CHSH value at $\nu=\pi/4$ and a geometric contrast measure defined on the underlying hidden-variable distributions. Rather than treating the quantum singlet correlation as an isolated target to be reproduced, the present framework places it within a broader geometric structure of correlations. These results suggest the existence of a nontrivial geometric structure underlying the family of correlations and motivate the search for a principle capable of selecting the quantum singlet solution from within that family.