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01.
arXiv (CS.AI) 2026-06-11

LSTM-Based Detection of Structural Breaks in Property Insurance Loss Reserving: A Climate-Informed Approach

arXiv:2606.11463v1 Announce Type: cross Abstract: Accurate loss reserving is foundational to insurer solvency, yet accelerating climate driven catastrophes systematically violate the stability assumptions on which traditional actuarial methods depend. This white paper presents a research program testing whether Long Short Term Memory (LSTM) neural networks can detect and adapt to these structural breaks faster and more accurately than Chain Ladder, Bornhuetter Ferguson, and Cape Cod methods. Using 15 plus years of regulatory development triangle data from Florida and Louisiana, enriched with NOAA hurricane intensity indices and sea surface temperatures, we hypothesize a targeted improvement of 15, 20% in reserve accuracy for catastrophe exposed years, a threshold grounded both in the prior neural network reserving literature and in the formal convergence results developed here. Beyond empirical validation, we develop a theoretical framework grounding LSTM structural break detection in probabilistic terms, providing formal performance guarantees that compensate for the limited number of catastrophe events in the test period. We document the research design, methodology, expected contributions, and a candid assessment of limitations.

02.
Nature Medicine 2026-06-10

Dual-target gene therapy in Parkinson’s disease: a multicenter phase 1 trial

Authors:

Restoring striatal dopamine synthesis is a promising gene therapy strategy for Parkinson’s disease. Previous adeno-associated virus-mediated aromatic L-amino acid decarboxylase (AADC) monotherapies remain dependent on exogenous levodopa, whereas multigene delivery is constrained by strict adeno-associated virus packaging limits. A ‘dual approach’ targeting the two rate-limiting enzymes, tyrosine hydroxylase (TH) and AADC, offers the potential for autonomous dopamine synthesis. We report the 12-month primary safety and tolerability outcomes of a multicenter, open-label, dose-escalation, phase 1 trial evaluating BBM-P002, a new adeno-associated virus vector—AAVT42—codelivering constitutively active TH and AADC. Ten participants with moderate-to-advanced Parkinson’s disease were enrolled and received bilateral intraputaminal infusions across doses of 4.0 × 1011 vg (Cohort 1; n = 1), 6.0 × 1011 vg (Cohort 2; n = 2), 1.0 × 1012 vg (Cohort 3; n = 2) and 1.2 × 1012 vg (Cohort 4; n = 5). The trial achieved its primary outcome, as BBM-P002 demonstrated a favorable safety and tolerability profile within 12 months post-treatment. No dose-limiting toxicities or drug-related serious adverse events occurred. A total of 23 adverse events were reported, all judged unrelated to BBM-P002 and primarily mild and transient. Systemic toxicity and clinically meaningful immunogenicity were absent. In conclusion, intraputaminal delivery of BBM-P002 was safe and well tolerated in this phase 1 trial, supporting continued clinical development. ClinicalTrials.gov registration: NCT05822739 . Phase 1 results reveal that BBM-P002, a dual-target gene therapy co-delivering TH and DDC, is safe and well tolerated in Parkinson’s disease, with 12-month motor improvements signaling therapeutic potential.

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

Encoder Winners Do Not Reliably Transfer Across VLA Backbone Scale: A Frozen-Backbone Grafting Diagnostic

Vision-language-action (VLA) policies typically inherit their vision encoder from upstream VLM releases, but it is unclear whether an encoder choice validated on a small VLA transfers to a larger backbone. We introduce a frozen-backbone grafting diagnostic: the vision tower of a released VLA is replaced by a candidate encoder under a fixed protocol (adaptive average pooling, LayerNorm, and a single trainable linear projector), with the language model and action expert frozen. Across four encoders, two LIBERO suites, two backbones (SmolVLA-450M and $\pi_{0.5}$-3.3B), and two-to-three seeds per cell (40 main grafting runs plus native, LoRA, pooling, and zero-/shuffled-image controls, all scored by offline action MSE), the small-backbone winner does not reliably select the large-backbone top tier: SigLIP is best on SmolVLA across both suites, while on $\pi_{0.5}$ DINOv2-small leads the spatial suite and the object suite is a seed-sensitive near-tie band; three of the four backbone-suite comparisons (and 11 of 12 seed-level cells) support backbone-dependent rankings. The grafting wrapper is itself non-neutral with opposite sign across backbones (+45-56% MSE on the SmolVLA native tower, -50-52% on $\pi_{0.5}$), so all conclusions are conditional on the fixed grafting protocol. We position frozen grafting as a cheap target-backbone diagnostic to run before committing to an encoder at scale, not as a closed-loop deployment claim.

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

Sovereign Assurance Boundary: Certificate-Bound Admission for Agentic Infrastructure

arXiv:2606.11632v1 Announce Type: cross Abstract: Agentic infrastructure introduces a critical control-plane authorization problem: non-deterministic reasoning systems can propose high-stakes mutations to production resources, yet existing security mechanisms – such as identity and access management (IAM), policy engines, consensus protocols, and audit logs – either enforce static, context-unaware permissions or merely record actions post-execution. This paper introduces the Sovereign Assurance Boundary (SAB), a certificate-bound runtime admission layer for autonomous execution authority. SAB intercepts agent proposals at an assurance airlock, compiles them into typed execution contracts $C$, and binds these contracts to cryptographic evidence digests $H(E)$ and policy versions. The contracts are then routed through consequence-aware certification paths. Upon successful admission, the system emits a signed Sovereign Assurance Certificate ($\Omega$) that is strictly scoped to a specific execution identity, revocation epoch, and validity window. Finally, a sovereign execution broker verifies $\Omega$ and performs fresh pre-execution revocation and drift checks before invoking infrastructure APIs. We detail the airlock-broker architecture, formalize its admission and revocation invariants, and report preliminary feasibility measurements from a Go prototype evaluated over 2,500 admission attempts. Ultimately, this broker-enforced model prevents autonomous reasoning from directly mutating state, transforming delegated execution authority into a cryptographically verifiable, evidence-bound, revocable, and replayable runtime artifact.

05.
medRxiv (Medicine) 2026-06-16

A Poisson Process Life Expectancy framework for optimising patient lifetime during chemotherapy

Cancer therapy balances between two competing objectives - treatment efficacy against the tumour and the risk of treatment related severe adverse events, including patient death. Most existing optimal control theory (OCT) formulations rely on optimising heuristic cost functionals that lack direct clinical interpretability. In clinical practice treatment efficacy and patient tolerability are primarily assessed through survival metrics and adverse event rates. Here we introduce the Continuous Lifetime Payoff (CLP), a novel OCT objective functional that directly links treatment decisions to patient survival. It explicitly incorporates tumour dynamics, tumour eradication, and patient mortality from tumour progression, drug-related toxicity and age. We fit age-related mortality from life tables and infer parameters from simulated survival data. The CLP provides a clinically grounded framework for optimising chemotherapy regimens.

06.
medRxiv (Medicine) 2026-06-15

Wellbeing After Stroke-2 (WAterS-2): a feasibility study with process evaluation exploring inclusive, accessible, online psychological support after stroke

Objectives: Explore feasibility and acceptability of upskilling a workforce to deliver a co-developed intervention, based on Acceptance and Commitment Therapy (ACT), to support psychological adjustment post-stroke targeting underserved groups. Design: Multi-site, single-arm feasibility study with embedded mixed-methods process evaluation (ISRCTN17628580). Setting: Four NHS community stroke services across England. Participants: 1. Stroke survivors [≥]18 years of age, [≥]4 months post-stroke, reporting psychological difficulties adjusting to stroke, able to consent and access remote group sessions in English; 2. Group facilitators from NHS stroke services, not ACT specialists. Intervention: WAterS-2: an eight-session, remotely-delivered ACT-informed group intervention. Outcome measures: Recruitment, fidelity, safety, acceptability and perceived value were assessed using fidelity checklists, post-intervention surveys and semi-structured interviews with stroke survivors and facilitators. Clinical outcomes including mood (HADS), wellbeing (ONS4), psychological flexibility (AAQ-ABI), measured post-group and three-months later. Results: Nineteen stroke survivors recruited (mean 9.6 months post-stroke; n=5 (26%) minoritised ethnicities; n=10 (52%) with aphasia). Thirteen facilitators - including two peer support workers - delivered the intervention with fidelity following structured training across four services. Drop-out was low (2/19; 11%); with 15 (79%) attending [≥]5/8 sessions. Remote data collection was feasible (79% follow-up completion), with no adverse events recorded. Acceptability was high: survivors valued peer connection, grounding and mindfulness practices. ACT metaphors were helpful for some but challenging for others, including some with aphasia. Online delivery was suitable but limited informal connection. Facilitators reported increased capability, incorporating ACT skills into routine care. NHS workforce pressures and geographically-constrained referral pathways limited recruitment reach. Conclusions: WAterS-2 is feasible, safe, acceptable and inclusive. A mixed workforce, including NHS peer support workers, can be upskilled to deliver with fidelity. Inclusion of underserved groups is achievable but requires active strategies beyond standard NHS referral routes. Findings inform a provisional logic model and a future pragmatic trial.

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

SPARX: Secure and Privacy-Aware Approximate CNN Acceleration with Edge RISC-V SoC

Edge-AI systems increasingly require real-time CNN inference under strict energy, performance, security, and privacy constraints. Approximate computing improves hardware efficiency by exploiting the error resilience of neural network workloads; however, most approximate CNN accelerators do not jointly consider secure, privacy-aware edge deployment. This paper presents SPARX, a Secure and Privacy-Aware Approximate CNN Acceleration framework integrated within a heterogeneous RV32IMC RISC-V System-on-Chip (SoC). SPARX combines a custom RISC-V instruction extension, an approximate logarithmic CNN acceleration unit, a lightweight differential-noise-based privacy engine, and a challenge-response authentication mechanism. To guide arithmetic selection, an approximation-aware decision framework is introduced that uses the Approximation Severity Index (ASI), Approximation Efficiency (AE), Quality of Approximation (QoA), Approximation Figure-of-Merit (AFOM), and Hardware Acceleration Efficiency (HAE). Evaluation across 11 state-of-the-art approximate MAC architectures identifies the Iterative Logarithmic Multiplier (ILM) as the most suitable design, achieving 51.7% area reduction, 81.5% power reduction, and 2.13x throughput improvement compared with an accurate radix-4 Booth MAC, while only reducing ResNet-20/CIFAR-10 accuracy by 2.82 percentage points. FPGA implementation on a Xilinx VC707 platform achieves 58.4 GOPS/W energy efficiency at 250 MHz, while 28-nm CMOS physical implementation validates ASIC feasibility

08.
medRxiv (Medicine) 2026-06-15

Genome-wide colocalization of body fat distribution GWAS and subcutaneous adipose eQTLs identifies SNX10, DGKQ, and CBX3 as candidate causal genes for cardiometabolic disease

Authors:

Background: Genome-wide association studies (GWAS) have identified hundreds of loci associated with body fat distribution, yet the causal genes and regulatory mechanisms through which these variants exert their effects remain largely unknown. Expression quantitative trait locus (eQTL) colocalization provides a powerful framework for identifying genes whose expression is genetically coregulated with complex traits. Methods: We performed a genome-wide colocalization analysis integrating waist-hip ratio adjusted for body mass index (WHRadjBMI) GWAS summary statistics from 694,649 individuals (Pulit et al., 2019) with subcutaneous adipose tissue eQTLs from the Genotype-Tissue Expression (GTEx) Project v8 (N = 581 donors). GWAS coordinates were lifted from GRCh37 to GRCh38 to enable direct alignment with GTEx data. We incorporated CAVIAR fine-mapping results to overcome the limitation of FDR-significant eQTL filtering. Colocalization was assessed using the approximate Bayes factor framework (coloc.abf) across 335 independent genome-wide significant loci. Results: Of 2,897 locus-gene pairs tested, 489 (16.9%) showed strong colocalization (PP.H4 > 0.8) and 618 (21.3%) showed moderate evidence (PP.H4 > 0.5). The strongest colocalization was observed for SNX10 (sorting nexin 10; PP.H4 = 1.000), a recently characterized regulator of adipocyte differentiation and female-specific diet-induced obesity. Other top hits included DGKQ (diacylglycerol kinase theta; PP.H4 = 0.9999999), an emerging pharmacological target for insulin resistance, and CBX3 (chromobox 3; PP.H4 = 0.9999974), an epigenetic regulator linked to cardiovascular disease. Established adiposity genes including GRB14 (PP.H4 = 0.681) and KLF14 (PP.H4 = 0.590) were recovered, validating our approach. Several loci exhibited extensive allelic heterogeneity, with 50 genes colocalizing at a single chromosome 3 locus. Conclusions: Our analysis provides a comprehensive map of adipose tissue gene regulatory mechanisms underlying genetic risk for body fat distribution. The identification of SNX10, DGKQ, and CBX3 as high-confidence candidate causal genes advances the translation of GWAS associations into mechanistic understanding and therapeutic targets for obesity-related cardiometabolic disease.

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

Physics-informed generative AI for semiconductor manufacturing: Enforcing hard physical constraints in generative models by construction

arXiv:2606.11247v1 Announce Type: cross Abstract: Generative models are increasingly used to propose designs, data, and control actions for physical systems, yet many such systems are governed by hard physical constraints rather than by perceptual plausibility. Semiconductor manufacturing provides a demanding test case: generated masks, layouts, synthetic defect data, and process recipes must obey lithography, transport, reaction, and device-physics constraints, because physically invalid samples are not merely low quality but unusable. This Perspective argues that semiconductor manufacturing exposes a broader computational-science challenge, namely that generative AI for constrained physical domains must be physics-informed by construction, not corrected only through post-hoc filtering. We survey the emerging architectural toolkit, including physics-informed diffusion, PDE-constrained variational models, neural-operator priors, and conservation-law-respecting generative networks, and show how it connects to differentiable lithography, TCAD, process simulation, and autonomous experimentation. We identify four integration patterns between generative models and physics-based simulators, and we propose a research agenda centered on physics-fidelity benchmarks, differentiable simulator infrastructure, and multimodal foundation models for physical design and manufacturing. The central claim is analytical rather than rhetorical: where physical validity is the binding criterion of success, architectures that enforce it by construction should be expected to outperform those that filter for it after the fact, and the fab is the setting where this distinction is sharpest.

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

Belief-Space Control for Personalized Cancer Treatment via Active Inference

arXiv:2606.10376v2 Announce Type: replace Abstract: Cancer treatment is at the core a sequential decision-making problem with partial observability, latent patient heterogeneity, and explicit constraints on the budget for medical measurements. Unlike standard Reinforcement Learning (RL) approaches that control state trajectories, cancer treatments permanently modify patients' transition dynamics, changing how states evolve over time. We model cancer treatment as a belief-space planning problem using active inference, deriving an expected free-energy objective that unifies goal-directed control and information acquisition under measurement budgets without. We implement this framework using real clinical cancer data from the AACR Project GENIE Biopharma Collaborative dataset. Results on clinical data demonstrate a simultaneous patient categorization and high treatment efficacy, under real measurement and treatment constraints.

11.
arXiv (CS.LG) 2026-06-18

OpenAnt: LLM-Powered Vulnerability Discovery Through Code Decomposition, Adversarial Verification, and Dynamic Testing

arXiv:2606.19149v1 Announce Type: cross Abstract: Automated vulnerability discovery in large codebases remains challenging: traditional static analysis produces high false-positive rates, while dynamic approaches such as fuzzing require substantial infrastructure and often target narrow classes of bugs. Recent advances in large language models (LLMs) enable semantic reasoning about program behavior, but applying LLMs to repository-scale security analysis introduces challenges related to context management, cost, and verification. We present OpenAnt, an open-source vulnerability discovery system that integrates static program analysis with LLM-based reasoning in a multi-stage pipeline. OpenAnt introduces three key techniques. First, codebases are decomposed into self-contained analysis units filtered by reachability from external entry points, reducing the analysis surface by up to 97% while preserving attack-relevant code. Second, candidate vulnerabilities undergo adversarial verification through constrained attacker simulation, where the model evaluates exploitability under realistic attacker capabilities. Third, findings are validated through dynamic verification, in which exploit environments are generated automatically, executed in sandboxed containers, and discarded after use. Evaluation on widely used open-source projects including OpenSSL, WordPress, and Flowise shows that this architecture can identify previously unknown vulnerabilities while maintaining manageable analysis cost and substantially reducing false positives. Our results suggest that closed-loop vulnerability discovery pipelines, combining semantic reasoning with exploit validation, provide a practical path toward scalable automated security analysis. OpenAnt is released as open source under the Apache 2.0 license at https://github.com/knostic/OpenAnt.

12.
arXiv (CS.CV) 2026-06-24

Does it matter which Gaussians you pick in 4D Gaussian streaming?

Anchor-driven 4D Gaussian streaming methods such as Instant Gaussian Stream (IGS) update a dynamic scene each frame from a compact set of Gaussian anchors, chosen by default with Farthest Point Sampling (FPS) at a fixed budget of $8{,}192$. Because these anchors act as control points that drive the whole scene through linear blend skinning, the rule used to choose them ought to affect reconstruction quality. We test this by holding the IGS pipeline fixed and changing only the sampler, comparing FPS, random, uniform, an opacity-scale heuristic, and a learned policy across budgets and refinement settings on N3DV and MeetingRoom. At deployment budgets the sampler has no measurable effect: a cheap random or uniform sampler at $4{,}096$ anchors matches FPS@8192 within measurement error, the default budget is over-provisioned, and the result holds on a second backbone (3DGStream). The learned policy is mixed rather than consistently better: it can improve the N3DV validation set at tight budgets, but does not give a stable cross-dataset rule, and selection is never the bottleneck because refinement dominates runtime. We will release our full sweep and evaluation protocol as a sampler benchmark.

13.
arXiv (CS.AI) 2026-06-17

ANEForge: Python for direct computation on the Apple Neural Engine

arXiv:2606.17090v1 Announce Type: cross Abstract: ANEForge is a Python package that programs the Apple Neural Engine (ANE), the fixed-function neural accelerator on every recent Apple device, directly and without CoreML. In production the engine is reachable only through CoreML, which treats it as a scheduling option: no configuration requires the ANE, and a model can silently run on the CPU or GPU instead. ANEForge compiles a lazy tensor graph, built from 58 fused operators and 19 native bridge operators, into a single ANE program. The program is dispatched through the same ANE daemon and kernel-driver stack as Apple's internal framework. Beyond inference, the package reaches the engine's native fused attention, streams int8, int4, and sparse weights, keeps decoder and optimizer state resident across steps, and runs the forward pass, backward pass, and optimizer update of training on the engine. A small fused program completes a call in about 90us, near the engine's 70us per-program dispatch floor, and a pretrained ResNet-18 forward runs end-to-end in 0.33ms. ResNet-18, a sentence encoder, and a Vision Transformer run end-to-end against framework references, and a Stable Diffusion U-Net validates its forward pass. ANEForge targets Apple Silicon under macOS 14 and later. Each release is verified against a recorded macOS and ANE-compiler version.

14.
arXiv (quant-ph) 2026-06-16

Temporal modulation as a resource: enhanced frequency estimation in continuous variable systems

arXiv:2606.15108v1 Announce Type: new Abstract: Frequency estimation, a cornerstone of quantum metrology, has been significantly enhanced by advanced quantum sensing strategies. However, most protocols rely either on static or time-independent encoding mechanisms, inherently limiting their achievable precision scaling, or on control strategies requiring changing the Hamiltonian and/or implementing feedback mechanisms. To overcome this, we investigate a simpler dynamical encoding protocol where the quantum oscillator is driven by a general continuous temporal frequency modulation $\Omega(t) = \omega_0 f(t)$. We analytically demonstrate that for a given modulation profile $f(t)$ and its corresponding time-integral $F(t)$, the quantum Fisher information (QFI) scales as $\mathcal{O}(F(t)^2)$. This enhancement stems from the fact that temporal encoding fundamentally alters the mechanism of dynamical phase accumulation. Crucially, when evaluated under the energy and evolution-time constraints, this framework reveals a genuine precision enhancement over the conventional time-independent baseline. By analyzing explicit polynomial and exponential modulations, we establish that arbitrary precision scaling can be deterministically engineered, with ultimate bounds that are asymptotically saturable via optimal homodyne detection. Our framework provides a universal paradigm for exploiting time-dependent quantum control in next-generation sensors.

15.
medRxiv (Medicine) 2026-06-22

Clinical-grade Cuffless Blood Pressure Monitoring via Deep-tissue Diffuse Speckle Pulsatile Flowmetry

Blood pressure (BP) is a vital sign which is measured to diagnose and manage hypertension. However, current methods to measure BP use inflatable cuffs which cause discomfort and limit the frequency at which measurements can be made, or intra-arterial catheters which are invasive and pose infection risks. Here, we propose and evaluate the use of Diffuse Speckle Pulsatile Flowmetry (DSPF) as a cuffless BP measurement method to address these limitations. DSPF is a laser speckle-based technique which simultaneously records blood flow rate and blood volume (i.e. photoplethysmography or PPG) signals from relatively deep vascular tissue. Using information from these signals, we studied DSPFs effectiveness in measuring systolic BP (SBP) and diastolic BP (DBP) through an outpatient study in which 133 patients were recruited, and in measuring beat-to-beat BP waveforms through an inpatient study in which two patients were recruited. In the outpatient study, the DSPF method was able to achieve mean absolute errors (MAEs) of 4.17 mmHg and 2.42 mmHg for SBP and DBP respectively compared to conventional cuff-based methods. It was also able to fulfil the requirements of the AAMI/ESH/ISO 81060-2:2018 standard for BP measurement devices and attain an "A" grade according to the British Hypertension Society grading scheme. For the inpatient study, it produced BP waveforms which had MAEs of 2.35 mmHg and 3.06 mmHg compared to arterial-line measurements for the two patients, respectively. Compared to PPG which has been studied more extensively as a cuffless BP measurement method, we found through ablation studies that DSPF was able to reach significantly lower MAEs and hence better accuracies. DSPF augments the performance of PPG-only methods by leveraging additional information from the blood flow rate signal, and we therefore find it to be a superior cuffless BP measurement method which can potentially be used in outpatient, inpatient, and remote settings.

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

Human-on-the-Loop Orchestration for AI-Assisted Legal Discovery

arXiv:2606.19812v1 Announce Type: new Abstract: Autonomous Large Language Model (LLM) agents are increasingly deployed in electronic discovery (e-discovery), where compounding errors across multi-step reasoning chains can constitute legal malpractice. Unlike single-turn retrieval, agentic workflows operating over privileged document corpora exhibit a class of failure we term "trajectory collapse": an early misclassification silently propagates, rendering an entire privilege review invalid. This paper makes three contributions. First, we propose a structured taxonomy of agentic failures in legal information retrieval, organized by functional stage. Second, we introduce a four-layer verification architecture – spanning planning, reasoning, execution, and uncertainty quantification – designed to intercept these failures before they compound. Third, we present a preliminary simulation study on a synthetic e-discovery corpus that demonstrates how mandatory Human-on-the-Loop (HOTL) escalation thresholds reduce privilege-waiver risk relative to fully autonomous baselines. Our results suggest that calibrated uncertainty thresholds can reduce privilege-waiver risk by up to 61% versus fully autonomous deployment, while routing fewer than one quarter of documents to attorney review.

17.
arXiv (math.PR) 2026-06-24

Conditionally Poissonian random digraphs

arXiv:1705.03801v2 Announce Type: replace Abstract: We define a Poissonian model of directed random graphs which generalises the undirected Poissonian random graph process introduced by Norros and Reittu in Adv. Appl. Probab. 38 (2006), 59–75. Its loopless simple projection is a rank-one independent-arc inhomogeneous digraph of the type studied by Cao and Olvera-Cravioto, Random Struct. Alg. 56 (2020), 722–774. For the Poissonian multigraph itself, we discuss the relation to Norros-Reittu graphs, characterise limiting degree distributions, and record explicit exploration estimates. In particular, we give fixed-depth directed local weak limits, stopped branching-process couplings with weight-mass collision budgets, a comparison with the simple projection, and a rare-event concentration criterion. These estimates are intended as graph-side structural inputs for later dynamics on the graph.

18.
arXiv (math.PR) 2026-06-25

Face volume densities of positive-intensity and ideal Poisson–Voronoi tessellations in hyperbolic spaces

arXiv:2606.26049v1 Announce Type: new Abstract: We determine analytically for all $k\in\{0,1,\ldots,d-1\}$ the $k$-volume densities of a Poisson–Voronoi tessellation of intensity $\lambda>0$ in the $d$-dimensional hyperbolic space of constant curvature $-1$. This largely extends previous results of Isokawa in dimensions two and three. As applications, we provide closed form expressions for all face volume densities and all typical face volumes of the ideal Poisson–Voronoi tessellation (IPVT), which is the low-intensity limit as $\lambda\downarrow0$ of the hyperbolic Poisson–Voronoi tessellation. As a main tool we develop a new Blaschke–Petkantschin–type formula in hyperbolic space.

19.
medRxiv (Medicine) 2026-06-15

Two Blood-based Endotypes Reveal Divergent Clinical Outcomes of Fibrotic Hypersensitivity Pneumonitis

Rationale: Fibrotic hypersensitivity pneumonitis (fHP) is an antigen-driven, life-threatening interstitial lung disease characterized by heterogeneous radiologic features, clinical outcomes, and treatment responses. Objectives: To identify blood-based fHP endotypes that inform mechanism, prognosis and therapeutic response. Methods: We performed integrative analyses of multi-compartment transcriptomic data derived from whole blood, peripheral blood mononuclear cells, bronchoalveolar lavage, and surgical lung biopsies, alongside circulating plasma proteomics. Multiple clustering algorithms were cross-compared to ensure robustness and reproducibility of endotypes identification. Immune cell composition was inferred using bulk RNA-seq deconvolution and annotated with BAL single-cell RNA-seq. Pathway activities were characterized using Gene Set Enrichment Analysis. Transplant-free survival (TFS) was evaluated for endotype and corticosteroid exposure by Kaplan-Meier methods, with hazard ratios analyzed using multivariable Cox proportional hazards models. Results: Two molecular endotypes, lymphocytic-associated (L-fHP) and non-lymphocytic-associated (N-fHP), were identified and validated. L-fHP showed enrichment of adaptive immune signaling and lymphocyte predominance, whereas N-fHP demonstrated myeloid-cell activation with neutrophil and macrophage predominance. Corticosteroid exposure was associated with worse TFS in L-fHP but not in N-fHP after adjusting for age, sex, and baseline pulmonary function. Compared to L-fHP, N-fHP had poorer baseline pulmonary function, faster 12-month FVC decline, and shorter TFS. N-fHP also exhibited elevated neutrophil-associated markers, including matrix metalloproteinase-9, across paired transcriptomic and proteomic datasets, supporting a neutrophil-driven, cross-compartment disease process. Conclusion: Multi-omic, multi-compartment analysis identifies two reproducible fHP endotypes with distinct clinical outcomes and corticosteroid responses, supporting a precision medicine approach beyond current clinical and radiologic classification.

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

SEAGym: An Evaluation Environment for Self-Evolving LLM Agents

arXiv:2606.17546v1 Announce Type: new Abstract: Self-evolving LLM-based agents improve mainly by changing their agent harness: the structured execution layer around a base model, including prompts, memory, tools, middleware, runtime state, and the model-tool interaction loop. Existing evaluations often reduce this process to isolated task scores or a single sequential curve, obscuring whether an update produces reusable improvement, overfits recent tasks, increases cost, or harms older behavior. We introduce SEAGym, an evaluation environment for measuring agent harness updates across training, validation, test, replay, and cost records. SEAGym turns Harbor-compatible benchmarks into dynamic self-evolution task sources with train batches, frozen update-validation, held-out ID and OOD transfer views, replay diagnostics, and saved snapshot and metric records. Instantiating SEAGym on Terminal-Bench 2.0 and HLE, we compare ACE, TF-GRPO, and AHE under a shared epoch/batch protocol. The results show that these evaluation views provide complementary signals about the evolution process: frequent updates may fail to improve held-out performance, useful intermediate snapshots may collapse later, and source diversity and model backend can affect harness reliability.

21.
arXiv (math.PR) 2026-06-18

Extrema of microscopically slowed-down Gaussian fields

Authors:

arXiv:2606.19207v1 Announce Type: new Abstract: We introduce a family of Gaussian fields whose covariance structure exhibits an inhomogeneous, microscopic slowdown and it interpolates between a $\log$ profile (for a certain interpolation parameter $\alpha=0$) and a $\log\log$ profile (when the interpolation parameter is $\alpha=1/2$). We consider both one dimensional such objects (which we call {\it Branching Brownian Motions in a cooling environment}) as well as higher dimensional, spatial fields. We identify the correct centering of the maximum at time $T$ and prove tightness of the recentered maximum. While the exponent in the first-order growth varies linearly with $\alpha$, giving a leading order of $T^{1-\alpha}$, the second-order correction exhibits a phase transition at $\alpha=1/3$.

22.
bioRxiv (Bioinfo) 2026-06-18

Structure-Based Immunoinformatics Design of a CTB-Adjuvanted Multi-Epitope Mucosal Vaccine Against Helicobacter pylori

Background: Helicobacter pylori coloniz the gastric mucosa of nearly half of the global population and is classified as a Group I carcinogen by the World Health Organization due to its strong association with gastric cancer. The growing prevalence of antibiotic-resistant H. pylori strains significantly compromises current therapeutic strategies, emphasizing the urgent need for effective prophylactic approaches. Research design and methods; In this study, a novel multi-epitope vaccine was designed targeting H. pylori, incorporating epitopes from four key virulence proteins: BabB, SabB, SabA, and VacA. Using an immunoinformatics-guided structural vaccinology approach, B- and T-cell epitopes were predicted, prioritized based on immunogenicity, conservation, population coverage, and non-homology to human proteins, and assembled into the final vaccine construct. To enhance immunogenicity and specifically stimulate mucosal immune responses, the cholera toxin B subunit (CTB) was fused at the N-terminal via an EAAAK linker, a novel application in H. pylori multi-epitope vaccines. The PADRE universal epitope and additional linkers were incorporated to optimize epitope presentation and helper T-cell activation. Results: Comprehensive evaluations of physicochemical, antigenic, allergenic, and toxic properties were conducted, followed by secondary and tertiary structure modeling, refinement, and validation. Conformational B-cell epitopes were mapped, and molecular docking, binding affinity analysis, energy minimization, and molecular dynamics simulations confirmed structural stability and receptor interactions. Codon optimization and in silico cloning predicted efficient expression in Escherichia coli, while immune simulations suggested robust humoral and cellular responses. Conclusions: This study presents a promising multi-epitope vaccine candidate against H. pylori, offering a rational framework for future experimental validation and potential clinical application.

23.
medRxiv (Medicine) 2026-06-17

MedAgent: A Retrieval-Augmented Clinical Decision Support Agent with Verifiable Evidence Grounding for Evidence-Based Medicine

Evidence-based medicine demands clinical answers that are not only fluent and medically plausible, but also anchored in traceable evidence, tailored to patient-specific clinical questions, sensitive to the hierarchy of evidence, and respectful of clinical safety boundaries. While general-purpose large language models (LLMs) exhibit strong medical language generation ability, they tend to lean on parametric memory, underuse retrieved evidence, hallucinate citations, conflate evidence levels, and draw conclusions that are not fully supported by the underlying literature. Such limitations pose particular risks in clinical decision support, where answer reliability, evidence traceability, and reasoning consistency are paramount. To address these issues, we present MedAgent, an evidence-based medical agent trained through an end-to-end pipeline that integrates supervised fine-tuning (SFT) cold start, reward modeling, and Group Relative Policy Optimization (GRPO). The agent is designed to execute a structured workflow encompassing clinical question understanding, PICO extraction, evidence retrieval, evidence stratification, citation-grounded answer generation, and quality evaluation. Specifically, a Qwen2.5-14B-Instruct backbone is first cold-started on 200 human-verified agent trajectories, equipping it with tool invocation, PICO parsing, structured response generation, and citation faithfulness. Next, a Qwen2.5-7B reward model is trained on 2{,}099 pairwise preference samples to provide semantic-level quality signals for evidence-based responses. Finally, GRPO reinforcement learning is conducted in a retrieval-augmented agent environment, where every rollout involves real evidence retrieval and is scored jointly by rule-based rewards and reward-model signals. To avoid over-reliance on training rewards, we further construct an independent evidence-based medical evaluation benchmark, MedTrustBench, which contains 200 clinical questions spanning 10 specialties and four difficulty levels. Each question is annotated with standardized PICO elements and rubric-based scoring criteria. The benchmark includes 1{,}187 rubrics across seven dimensions: question relevance, evidence hierarchy, evidence quality and timeliness, evidence-answer consistency, completeness and depth, logical rigor, and medical terminology. Under an identical RAG pipeline, retrieval tool, retrieval configuration, and evaluation protocol, MedAgentv17 attains 78.6 points, outperforming GPT-4.1 (75.3) and approaching GPT-5.4 (80.3). These results show that a 14B domain-aligned model can surpass strong general-purpose baselines on specialized evidence-based medical reasoning, while delivering practical advantages in cost, privacy, controllability, and hospital-oriented private deployment. The model and associated datasets are publicly released at https://www.modelscope.cn/profile/InfoxmedModel

24.
arXiv (CS.CL) 2026-06-19

Granularity-Regulated Adaptive Computational Efficiency for Optimal Verification in Test-Time Scaling

Test-time scaling (TTS) has emerged as a powerful paradigm for improving the reasoning performance of large language models (LLMs) by investing additional compute at inference time. A central component of TTS is the verifier, which selects or scores candidate solutions to guide the search process. While prior work has explored the benefit of verification, a fundamental question remains underexplored: what is the optimal granularity of verification under a given compute budget? Coarse-grained outcome reward models (ORMs) and fine-grained process reward models (PRMs) represent two extremes, yet neither alone achieves compute-optimality across all regimes. In this paper, we establish a unified theoretical framework, called GRACE (\underline{G}ranularity-\underline{R}egulated \underline{A}daptive \underline{C}omputational \underline{E}fficiency), that characterizes the optimal verification granularity as an explicit function of problem difficulty, verifier accuracy, and compute budget. We prove that there exists a phase transition: fine-grained verification dominates when either the compute budget is large or the problem is hard, whereas coarse-grained verification is preferred in the low-budget, easy-problem regime. Our theory unifies Best-of-$N$, beam search, and step-level MCTS within a single Pareto-optimality framework, and motivates an adaptive granularity strategy that provably achieves the compute-performance Pareto frontier. Empirical results on MATH-500, GSM8K, and AIME benchmarks corroborate all four theoretical claims, with our adaptive strategy outperforming fixed-granularity baselines by up to 3.1\% accuracy at matched compute.

25.
arXiv (math.PR) 2026-06-12

Stochastic dominations for FK percolation and sharp thinning thresholds for the Ising energy field

arXiv:2606.13648v1 Announce Type: new Abstract: At first glance, one would imagine that the energy field of the Ising model, the set of edges whose endpoints share the same spin, is stochastically monotone as a function of the coupling constants. However, this is not generally the case. In this paper, we introduce two weaker notions of stochastic domination that make this result true: $p$–weak and $p$–weak$^\dagger$ domination. Both of these notions depend on a parameter $p$ and we find the optimal values $p$ and $p^\dagger$ so that these dominations hold. One of the key ingredient to obtain some of the results is a new stochastic domination relating FK percolations with different parameters $q,\tilde{q}\geq 1$ that is of independent interest.