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01.
arXiv (math.PR) 2026-06-11

On Skorokhod Problems for Reflected and Singular Stochastic Heat Equations

arXiv:2606.11951v1 Announce Type: new Abstract: We prove a Skorokhod decomposition for the Markov processes $X^a$ and $X$ associated to the gradient Dirichlet forms with respect to the measures $\rho^a\mu^{\beta}$ and $\rho\mu^{\beta}$, respectively. Here, $\mu^{\beta}$ is the law of the standard Brownian bridge $\beta$, while $\rho^a$ and $\rho$ denote densities which are given by $\rho^a(z) := \mathbf{1}_{[0,\infty)}(\bar{z}_a)$ and $\rho(z) := \int_0^1 \mathbf{1}_{[0,\infty)}(\bar{z}_x) \, dx$, respectively, for all $z\in L^2(0,1)$ which have a (unique) continuous representative $\bar{z}$ which vanishes at zero and one. To this end, we derive infinite-dimensional integration by parts formulas (IbPFs) w.r.t. $\rho^a\mu^{\beta}$ and $\rho\mu^{\beta}$, which contain Hida distributions alongside the usual drift terms. We represent these Hida distributions by integration w.r.t. vector measures of bounded variation. The vector measures in question are constructed via an approximation argument, making use of a generalization of Prokhorov's theorem for vector measures. We further prove that, almost surely, the sample paths of $X^a$ and $X$ take values in the equivalence class of continuous functions vanishing at zero and one for all and $dt$-almost all times, respectively. The main motivation for studying $\rho^a\mu^{\beta}$ and $\rho\mu^{\beta}$ lies in the fact that the distributional terms in their IbPFs are simplifications of the distributional term in the IbPF w.r.t. the law of the reflected Brownian bridge on the unit interval $\mu^{|\beta|}$. Representing the latter by integration w.r.t. a vector measure of bounded variation is still an open problem.

02.
arXiv (CS.AI) 2026-06-16

Heteroskedastic Signals in Budgeted LLM Verification: Structural Heterogeneity Limits Optimization Gains

作者:

arXiv:2606.15841v1 Announce Type: new Abstract: Large language model (LLM) systems increasingly use uncertainty signals to allocate limited computation across verification, test-time scaling, tool execution, and other selective-compute decisions. Such policies rely on a global signal comparability assumption: equal scores should carry comparable decision value across inputs. Using budgeted verification as a controlled diagnostic setting, we identify a failure mode of this assumption: uncertainty quality is heteroskedastic across cost strata, with some regions exhibiting near-random discriminability despite concentrating many errors. Under an explicit local model, we characterize the resulting distortion of global allocation and show that its upper bound scales with cross-stratum signal-quality dispersion. We separate weak signals, optimization instability, and structural heterogeneity through a controlled intervention hierarchy: Threshold, MP-Adapt, MP-Strat, and a deliberately simple cost-stratified thresholding intervention (CST). Across MBPP and MATH using Qwen3-8B, LLaMA3-8B, and GPT-4o-mini, global online adaptation yields inconsistent gains over static thresholding; MP-Strat partially recovers performance, while CST improves hit rate by up to 17 percentage points in strongly heterogeneous settings without gradient updates. These results identify structural heterogeneity, rather than optimizer weakness alone, as the primary bottleneck in the observed settings. More broadly, misaligned feedback structure cannot always be repaired by stronger optimization.

03.
arXiv (CS.LG) 2026-06-17

ResAware: Cross-Environment Website Fingerprinting via Resource-Privileged Distillation

arXiv:2606.17462v1 Announce Type: new Abstract: While Website Fingerprinting (WF) attacks achieve high accuracy in controlled laboratory settings, they often degrade substantially in real-world environments due to spatio-temporal drift, browser heterogeneity, proxy obfuscation and etc. This limitation stems from their sole reliance on low-level traffic features that are noisy and highly sensitive to environmental perturbations. To address this problem, we propose ResAware, a cross-environment resource-aware distillation framework under a training-rich/inference-poor asymmetric setting. Specifically, ResAware trains a teacher model on resource-level features, and then distills the resulting privileged knowledge into a student model through heterogeneous knowledge distillation. At deployment time, the student model performs inference using only encrypted traffic, incurring zero additional cost. We evaluate ResAware on a large-scale dataset collected over five months from six globally distributed vantage points, comprising more than $160{,}000$ paired samples. The results show that ResAware significantly enhances the cross-environment robustness of diverse WF baselines. Under a 150-day temporal drift, for example, ResAware improves the F1-score of Var-CNN from $72.77\%$ to $81.49\%$ and the open-world $TPR@1\%FPR$ from $22.40\%$ to $27.20\%$. Our results demonstrate that resource-level supervision improves WF robustness without expanding online observation capabilities.

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

Robust Transformer-Based One-Step Stock Index Forecasting via Shifted Data Augmentation

arXiv:2606.15701v1 Announce Type: new Abstract: Transformers have shown remarkable success in sequence modeling, yet their direct application to financial time series remains challenging due to noisy signals, short-memory dynamics, and distributional shifts. This paper proposes a modified Transformer architecture for one-step stock index forecasting, combined with advanced learning-rate scheduling and a novel Shifted Data Augmentation (SDA) technique. We evaluate the proposed framework on two benchmark stock index datasets, VN30 and S&P 500. Experimental results demonstrate that cosine annealing with warmup consistently improves forecasting accuracy over the generalized inverse-power scheduler. Furthermore, SDA substantially reduces forecasting errors and run-to-run variability while improving robustness to hyperparameter selection. The combination of cosine annealing scheduling and SDA achieved the best performance on both datasets, indicating that data augmentation can play a more important role than increasing model complexity in Transformer-based financial forecasting. These findings provide a practical and computationally efficient approach for robust stock index forecasting in noisy financial environments.

05.
bioRxiv (Bioinfo) 2026-06-21

Machine learning evaluation of gene expression-based ALS subtypes across brain and blood tissues

The clinical and molecular heterogeneity observed in amyotrophic lateral sclerosis (ALS) presents a challenge for diagnosis, prognosis, and treatment. RNA sequencing of post-mortem brain samples from ALS patients has identified several subtypes with distinct molecular signatures. We sought to evaluate these subtypes across diverse tissues and datasets and assess the feasibility of supervised machine learning models for sample classification. Unsupervised clustering and pathway analysis were performed to confirm the presence of ALS subtypes in motor cortex samples. Three machine learning strategies were then used to create models based on post-mortem motor cortex expression data of 112 people with ALS from the London Neurodegenerative Diseases Brain Bank. These models were subsequently improved through feature selection and evaluated in independent cohorts from motor cortex (n = 257, NYGC ALS Consortium) and blood (n = 96, Macquarie University Neurodegenerative Disease Biobank) samples. Multi-class linear discriminant analysis (LDA) models were then used for subtype classification. Clustering of ALS post-mortem motor cortex samples confirmed the presence of three subtypes: neuroinflammation (ALS-Neu), extracellular matrix organisation and muscle contraction (ALS-OxA), and synaptic and neuropeptide signalling (ALS-SNs). Among all machine learning strategies, random forests produced the most accurate and stable models for binary classification (~93% accuracy across the three subtypes). After feature selection, random forest models were able to classify samples from an independent post-mortem motor cortex cohort in their respective subtypes (AUC of ~0.98 across the three subtypes). When these models were evaluated in blood using LDA, we found consistent clustering patterns, with samples aligning in the same subtype regions of the post-mortem motor cortex samples, with ALS-SNs being the subtype in which samples were classified with the highest confidence (LDA class probability ~86%). Moreover, classification for this subtype improved when blood samples were collected closer to death. Our findings support the presence of three gene expression-based ALS subtypes in motor cortex samples and the utility of machine learning strategies for subtype classification. We also observed that the subtypes identified in the brain partially match those in the blood, with samples from the late stages of the disease more likely to be correctly predicted into the ALS-SNs cluster. This suggests a longitudinal effect in subtype identification that requires further investigation.

06.
bioRxiv (Bioinfo) 2026-06-11

PhyloZoo: a unified framework for phylogenetic network analysis in Python

作者:

Reticulate evolutionary processes (events in which lineages merge, such as hybridization, recombination, and horizontal gene transfer) are widespread across nature but cannot be represented by phylogenetic trees alone. Phylogenetic networks have therefore become an important modelling tool, yet existing software is typically tied to specific inference paradigms and provides limited support for working with multiple network representations in a unified and programmable environment. PhyloZoo is an open-source Python framework that lowers the barrier to developing practical, easy-to-use software for phylogenetic network analysis. It provides data structures and algorithms covering the main representations used in the field, together with dedicated visualization tools and robust I/O for all major phylogenetic file formats. A particular emphasis lies on semi-directed phylogenetic networks, which explicitly represent root uncertainty and have so far received limited support in existing software. By offering a shared foundation for developing interoperable tools and a combinatorial layer that supports computational proofs and theoretical exploration, PhyloZoo enables reproducible workflows for applied, methodological, and theoretical studies of reticulate evolution. Availability and implementation: PhyloZoo is implemented in Python and installable from PyPI, with source code, documentation, and examples available at https://github.com/nholtgrefe/phylozoo.

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

PiDR: Physics-Informed Inertial Dead Reckoning for Autonomous Platforms

arXiv:2601.03040v2 Announce Type: replace-cross Abstract: A fundamental requirement for full autonomy is the ability to sustain accurate navigation in the absence of external data, such as GNSS signals or visual information. In these challenging environments, the platform must rely exclusively on inertial sensors, leading to pure inertial navigation. However, the inherent noise and other error terms of the inertial sensors in such real-world scenarios will cause the navigation solution to drift over time. Although conventional deep-learning models have emerged as a possible approach to inertial navigation, they are inherently black-box in nature. Furthermore, they struggle to learn effectively with limited supervised sensor data and often fail to preserve physical principles. To address these limitations, we propose PiDR, a physics-informed inertial dead-reckoning framework for autonomous platforms in situations of pure inertial navigation. PiDR offers transparency by explicitly integrating inertial navigation principles into the network training process through the physics-informed residual component. PiDR plays a crucial role in mitigating abrupt trajectory deviations even under limited or sparse supervision. We evaluated PiDR on real-world datasets collected by a mobile robot and an autonomous underwater vehicle. We obtained more than 29% positioning improvement in both datasets, demonstrating the ability of PiDR to generalize different platforms operating in various environments and dynamics. Thus, PiDR offers a robust, lightweight, yet effective architecture and can be deployed on resource-constrained platforms, enabling real-time pure inertial navigation in adverse scenarios.

08.
arXiv (CS.AI) 2026-06-18

A CEFR-Inspired Classification Framework with Fuzzy C-Means To Automate Assessment of Programming Skills in Scratch

arXiv:2604.00730v2 Announce Type: replace-cross Abstract: Context: Schools, training platforms, and technology firms increasingly need to assess programming proficiency at scale with transparent, reproducible methods that support personalized learning pathways. Objective: This study introduces a pedagogical framework for Scratch project assessment, aligned with the Common European Framework of Reference (CEFR), providing universal competency levels for students and teachers alongside actionable insights for curriculum design. Method: We apply Fuzzy C-Means clustering to 2008246 Scratch projects evaluated via Dr.Scratch, implementing an ordinal criterion to map clusters to CEFR levels (A1-C2), and introducing enhanced classification metrics that identify transitional learners, enable continuous progress tracking, and quantify classification certainty to balance automated feedback with instructor review. Impact: The framework enables diagnosis of systemic curriculum gaps-notably a "B2 bottleneck" where only 13.3% of learners reside due to the cognitive load of integrating Logic Synchronization, and Data Representation–while providing certainty–based triggers for human intervention.

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

Geometry of Reason: Spectral Signatures of Valid Mathematical Reasoning

Verifying whether a language model is genuinely reasoning or pattern-matching remains an open problem: learned verifiers are expensive, and output-based heuristics are brittle. We show that valid mathematical reasoning induces a measurable, training-free spectral signature in transformer attention. By treating each attention matrix as a weighted token graph, we extract four diagnostics: Fiedler value, High-Frequency Energy Ratio (HFER), spectral entropy, and smoothness, that require no learned parameters. Experiments across seven models from four architectural families yield effect sizes up to Cohen's $d = 3.30$ ($p < 10^{-116}$), enabling $85$–$96\%$ single-threshold classification accuracy. Two findings sharpen the interpretation. First, Platonic validity: the spectral signal tracks logical coherence rather than compiler acceptance, proofs rejected for timeouts or missing imports are correctly classified as valid, a distinction confirmed by a manual audit ($\kappa = 0.82$, $n = 51$). Second, architectural determinism: Sliding Window Attention shifts the discriminative feature from HFER to smoothness ($d = 2.09$, $p < 10^{-48}$), showing that attention design governs which spectral channel encodes reasoning quality. Causal ablation confirms the signature traces induction-head circuits. The method generalises to informal chain-of-thought ($d = 0.78$, $p < 10^{-3}$), and in proof search, HFER reranking improves Best-of-16 Pass@1 by $+4.4$–$6.6$\%, matching $98\%$ of the AUC of fully supervised probes with zero labels. Spectral graph analysis is a principled, architecture-aware primitive for reasoning verification.

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

Smarter Saboteurs, Better Fixers: Scaling & Security in Linear Multi-Agent Workflows

arXiv:2606.12709v1 Announce Type: cross Abstract: As LLM-based multi-agent systems (MAS) are deployed in the wild, the resilience of their collaboration structures against adversarial compromise becomes a critical safety concern. Attackers may leverage prompt-injection or jailbreaking to sabotage individual agents within MAS workflows, but the interaction between model scaling and system-level resilience remains poorly understood. This paper investigates how model scale affects the security of linear multi-agent workflows. Our experiments across scales of two open-weight model families on the HumanEval benchmark reveal a compliance-correction symmetry: larger models are far more likely to faithfully execute malicious instructions, with the control-to-malicious performance drop reaching 53.7pp at 27B in uncorrected pipelines. However, appending a lightweight terminal Fixer stage collapses this to 0.6pp and restores statistical parity with control-level performance, demonstrating that strictly linear collaboration structures can be viable and resilient to adversaries at this scale, and suggesting that the brittleness previously attributed to linear topology may stem from a lack of correction.

11.
arXiv (CS.CL) 2026-06-12

Low-Latency Real-Time Audio Game Commentary System via LLM-Based Parallel Text Generation

We present a low-latency real-time audio game commentary system that generates spoken commentary directly from live gameplay video. In this end-to-end setting, a key bottleneck is accumulated waiting time; conventional pipelines capture frames, generate text, and synthesize speech sequentially for each utterance, and do not request the next generation until speech playback has completed. This strict sequentiality causes long and unnatural silence between utterances. To address this latency bottleneck, our system runs text generation in parallel with speech playback and buffers multiple candidate utterances ahead of time, enabling immediate synthesis at playback boundaries. Experiments on fast-paced game videos show that our parallel design reduces the mean inter-utterance silence from 9.6 seconds to 0.3 seconds compared to sequential baselines. It also improves similarity to professional speaking–silence timing patterns by over 40 %, and a user study with 120 experienced game players confirms significantly improved perceived speaking rhythm. Our demo video is available at: https://youtu.be/pmrRUlvav8M.

12.
arXiv (CS.AI) 2026-06-17

EvolveNav: Proactive Preflection and Self-Evolving Memory for Zero-Shot Object Goal Navigation

arXiv:2606.18235v1 Announce Type: new Abstract: Zero-Shot Object-Goal Navigation (ZS-OGN) requires embodied agents to explore and locate target objects without any prior training. To this end, recent methods leverage foundation models. But they typically rely on static priors and lack adaptation, which leads to repeated errors and costly trial and error. In this paper, we propose a self-evolving ZS-OGN framework that enables continuous test-time improvement. Specifically, we build an agentic rule memory by extracting actionable knowledge from past trajectories. Then, we propose a retrieval strategy based on upper confidence bound, selecting effective rules by balancing semantic relevance and historical success. In addition, we introduce a memory-guided preflection module that forecasts potential outcomes before action, reducing inefficient exploration. Extensive experiments show that our method outperforms existing zero-shot baselines, achieving a 10.1\% improvement in success rate with fewer unnecessary steps.

13.
arXiv (CS.CV) 2026-06-16

Structural Energy Guidance for View-Consistent Text-to-3D Generation

Text-to-3D generation based on diffusion models often suffers from the Janus problem, leading to inconsistent geometry across viewpoints. This work identifies viewpoint bias in 2D diffusion priors as the main cause and proposes Structural Energy-Guided Sampling (SEGS), a training-free and plug-and-play framework to improve multi-view consistency. SEGS constructs a structural energy in the PCA subspace of U-Net features and injects its gradient into the denoising process. It can be easily integrated into SDS/VSD pipelines without retraining. Experiments show that SEGS reduces the Janus Rate by about 10% on average and improves View-CS scores across multiple baselines, including DreamFusion, Magic3D, and LucidDreamer. This method effectively alleviates viewpoint artifacts while preserving appearance fidelity, providing a flexible solution for high-quality text-to-3D content generation.

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

BioMamba: Domain-Adaptive Biomedical Language Models

Background. Biomedical language models should improve performance on biomedical text while retaining general-language-modeling fluency. For Mamba-based models, this trade-off has not been systematically studied across biomedical literature and clinical text. Methods. We developed BioMamba, a family of biomedical Mamba2 models at five scales obtained by continued pretraining of released public Mamba2 checkpoints on a balanced 80%/10%/10% mixture of PubMed abstracts, the Colossal Clean Crawled Corpus (C4), and Wikipedia. The contribution is the adaptation recipe and the accompanying open-weight checkpoints. Results. Across five scales, BioMamba consistently lowered PubMed perplexity, improved Wikipedia-style held-out perplexity by 1.46-4.72 PPL, and left C4 perplexity essentially unchanged. On six out-of-domain multiple-choice benchmarks, BioMamba stayed within +/-3 percentage points of Mamba2 with no systematic regression. After supervised fine-tuning, BioMamba+SFT matched or exceeded Mamba2+SFT on MIMIC-IV note completion and discharge summary generation at every evaluated scale, and improved PubMedQA at every scale. The strongest model (BioMamba-2.7B) reached a PubMed perplexity of 5.28 and accuracies of 90.24% and 73.00% on BioASQ and PubMedQA, respectively. Conclusions. A balanced domain-adaptive continued pretraining recipe strengthens Mamba2 language models on biomedical literature and clinical text while preserving general-language-modeling fluency.

16.
medRxiv (Medicine) 2026-06-11

Vascular Phenotyping in Parkinson's Disease: Diabetes Mellitus Operationalizes a Microvascular Metabolic Syndrome Cluster Across PPMI Diagnostic Cohorts

Background: Diabetes mellitus elevates Parkinson's disease (PD) risk, via hypothesized cerebrovascular mediation. Whether the diabetes/prediabetes vascular-risk phenotype concentrates in cardiometabolic risk or macrovascular events across prodromal and clinically diagnosed PD remains unresolved. Objectives: To quantify the vascular-risk burden associated with diabetes/prediabetes across the PPMI diagnostic cohorts to test whether this association differs by cohort. Methods: Cross-sectional analysis of 413 PPMI participants (76 healthy controls, 145 prodromal PD, 192 clinically diagnosed PD) examined diabetes/prediabetes (n = 73) and seven vascular risk factors. The Vascular Burden Score (0 to 7) was a priori partitioned into microvascular and macrovascular sub-scores. Modified Poisson regression estimated adjusted prevalence ratios (aPR), adjusted for age, sex, and body mass index. A cohort-by-diabetes interaction tested cross-cohort consistency. Sensitivity analyses incorporated nigral diffusion tensor imaging (PD-risk biomarker) and FreeSurfer white matter hypointensity volume (cerebrovascular marker). Results: Diabetes/prediabetes elevated Vascular Burden Score ({beta} = 0.53, 95% CI 0.29 to 0.77, p < 0.001) versus non-diabetic participants, with a non-significant cohort-by-diabetes interaction (F = 0.29, p = 0.747). Three microvascular factors survived false discovery rate correction: obesity (aPR 2.28), hypertension (aPR 1.60), and hyperlipidemia (aPR 1.45). Macrovascular events showed no diabetic amplification ({beta} = -0.06, p = 0.25). In the imaging-phenotyped subset, Vascular Burden Score components contributed classifier variance distinct from nigral microstructure. Conclusions: Diabetes/prediabetes operationalize a microvascular cluster stable across prodromal and idiopathic PD. Cardiometabolic phenotyping may complement established PD-risk biomarkers (dopamine transporter SPECT, nigral diffusion), pending longitudinal validation linking vascular phenotype to dopaminergic markers.

17.
arXiv (math.PR) 2026-06-19

Maximal rigidity of random measure and uniqueness pairs: stealthy processes, quasicrystals and periodicity

arXiv:2512.10686v2 Announce Type: replace Abstract: This article investigates the phenomenon of maximal rigidity in spatial processes, where perfect interpolation of the process is possible from partial information, specifically, from its restriction to a strict subdomain, often resulting in a trivial tail $\sigma$algebra. A classical example known since the 1930's is that a time series is fully determined by its values on the negative integers if its spectrum has a gap, or at least a sufficiently deep zero. We extend such results to higher dimensions and continuous settings by establishing a connection with the concept of uniqueness pairs, rooted in the uncertainty principle of harmonic analysis. We present several other manifestations of this principle, unify and strengthen seemingly unrelated results across different models: quasicrystals and stealthy processes are shown to be maximally rigid on cones, and discrete integer-valued processes are necessarily periodic when they have a simply connected spectrum. Finally, we identify a surprising class of continuous fields with seemingly standard behavior, such as linear variance and finite dependency range, that undergo a phase transition: they are perfectly interpolable on B(0, $\rho$) for $\rho$ ___ 2 $\pi$ but exhibit no rigidity for $\rho$ > 2.

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

Skill-MAS: Evolving Meta-Skill for Automatic Multi-Agent Systems

arXiv:2606.18837v1 Announce Type: cross Abstract: Large Language Model (LLM)-based automatic Multi-Agent Systems (MAS) generation has become a crucial frontier for tackling complex tasks. However, existing methods face a dilemma between model capability and experience retention. Inference-time MAS leverages frozen frontier LLMs but repeats identical searches without learning from past experience. Conversely, Training-time MAS internalizes experience via gradient updates but is constrained by the low capability ceiling of smaller models, and is hard to scale to large frontier LLMs. To bridge this gap, we propose Skill-MAS, a novel third path that decouples experience retention from parametric updates by conceptualizing the high-level orchestration capability as an evolvable Meta-Skill. Skill-MAS refines this architectural knowledge through a closed optimization loop: (1) Multi-Trajectory Rollout samples a behavioral distribution for each task under the current Meta-Skill; and (2) Selective Reflection adaptively selects priority tasks and applies hierarchical contrastive analysis to distill systemic experience into generalizable, strategy-level principles. Extensive experiments across four complex benchmarks and four distinct LLMs demonstrate that Skill-MAS not only achieves remarkable performance gains but also maintains a favorable cost-performance trade-off. Further analysis reveals that the evolved Meta-Skills are highly robust and exhibit strong transferability across unseen tasks and different LLMs.

19.
medRxiv (Medicine) 2026-06-17

Macrophage-targeted glucocorticoid prodrug resolves acute inflammation while preserving HPA axis function: mechanistic, preclinical, and Phase II/III clinical evidence

Glucocorticoids (GCs) remain the fastest-acting anti-inflammatory agents but are constrained by systemic exposure that suppresses the hypothalamic pituitary adrenal (HPA) axis, silences adaptive immunity, and drives chronic toxicities. Chronic inflammatory diseases are sustained by long-lived CD206+ macrophages containing immune-resistant pathogenic material not cleared physiologically. We developed 101-PGC-005 ('005), a macrophage-targeted type 1a dexamethasone prodrug engineered for low-affinity, recycling-compatible uptake via CD206, with intracellular release triggered by acidic endosomes. We evaluated '005 in mechanistic assays, pathogen-diverse preclinical models, three human pharmacokinetic (PK) studies, and an adaptive-design randomized Phase II/III trial in 309 hospitalized patients with moderate COVID-19. In two completed Phase I human studies, a first-in-human dose-escalation and repeated-dose study and a dedicated single/multiple-dose PK and safety study; '005 circulated as intact prodrug with rapid systemic clearance (Tmax ~0.5 h; terminal half-life ~1.9 h), with no measurable free dexamethasone after single dosing and only low, clinically non-significant free dexamethasone after repeated dosing, and intact prodrug recovered unchanged in urine. Morning cortisol and ACTH were preserved after 30 mg once daily for three consecutive days (1.5 times the intended therapeutic dose). A cerebrospinal fluid PK study is evaluating central-compartment penetration. In the Phase II/III trial, powered for non-inferiority, conducted across six sites in India under GCP with Ministry of Health approval and independent DSMB oversight; '005 (20 mg IV daily for 3 days) was superior to dexamethasone (6 mg IV daily for 3 -10 days) on the primary endpoint of time to > a 2-point improvement on the WHO ordinal scale (HR 2.31; 95% CI 1.83-2.93; p < 0.0001; median 3 vs. 4 days). '005 was also superior on viral clearance (HR 1.47; 95% CI 1.17-1.84; p = 0.0001), hospital discharge rate, SpO2; recovery, and fever resolution. Zero patients in the '005 arm received investigator-initiated corticosteroid supplementation despite protocol allowance. All 309 randomized patients completed the study (ITT = per-protocol). Safety profiles were equivalent (TEAEs 54.8% vs 54.5%; p = 0.958), with no Grade 3+ events, SAEs, deaths, or discontinuations in either arm. Mechanistically, '005 delivered dual benefit: acute debulking of inflammatory macrophages and selective depletion of chronically activated pathology-sustaining macrophages, while preserving CXCL10 antiviral signaling and physiologic HPA control. Critically, HPA preservation is not merely a safety feature, it is a core efficacy mechanism: by clearing the pathogenic macrophage burden that was overriding HPA regulation, '005 restores the conditions for endogenous cortisol to resume its pulsatile, demand-responsive anti-inflammatory role across all GR-expressing cells, lymphocytes, endothelial cells, neurons, and newly differentiated macrophages, that '005 itself cannot reach. These findings support regulatory-grade evidence for macrophage-targeted corticosteroid therapy and provide the foundation for further development across acute inflammatory indications (sepsis, viral pneumonia, cytokine-release syndromes) and chronic macrophage-driven diseases (atherosclerosis, metabolic steatohepatitis, neurodegeneration, tumor-associated macrophages).

20.
arXiv (quant-ph) 2026-06-17

Quantum statistical enhancement of collective behaviour in a bosonic active Ising model

arXiv:2606.18091v1 Announce Type: new Abstract: Collective behaviour such as flocking (the collective motion of a spontaneously formed group along a common direction) or aster formation (the binding of opposing flocks, inhibiting each others motion) are intriguing emergent phenomena in active systems with local alignment rules. Until recently, their occurrence was mainly studied for classical systems, a prime example being the active Ising model (AIM), which translates the main ingredients of flocking and aster formation (i.e., alignment and self-propulsion) to a lattice framework. Here we introduce and study a one-dimensional (1D) quantum lattice variant of the AIM, based on ideal bosons with a spin degree of freedom. We find that both the collective behaviours of the 1D classical model, flocking and aster formation, are markedly enhanced by the bosonic quantum statistics. This contrasts with a recent quantum generalization of the AIM based onto hard-core bosons [Khasseh et al., Phys. Rev. Lett. 135, 248302 (2025)], where flocking, but neither its quantum-statistical stabilization nor aster states were observed as a consequence of interactions. Moreover, we investigate the competition of this quantum statistical stabilization of collective phases with their suppression by the quantum fluctuations induced by a transverse external magnetic field.

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

CountZES: Counting via Zero-Shot Exemplar Selection

Object counting in complex scenes is particularly challenging in the zero-shot (ZS) setting, where instances of unseen categories are counted using only a class name. Existing ZS counting methods that infer exemplars from text often rely on off-the-shelf open-vocabulary detectors (OVDs), which in dense scenes suffer from semantic noise, appearance variability, and multi-instance proposals. Alternatively, random image-patch sampling is employed, which fails to accurately delineate object instances. Since counting is sensitive to exemplar quality, such selection strategies often yield poorly representative exemplars, leading to inaccurate count estimation. To address these issues, we propose CountZES, an inference-only approach for object counting via ZS exemplar selection. CountZES discovers diverse exemplars through three synergistic stages: Detection-Anchored Exemplar (DAE), Density-Guided Exemplar (DGE), and Feature-Consensus Exemplar (FCE). DAE refines OVD detections to isolate precise single-instance exemplars. DGE introduces a density-driven, self-supervised paradigm to identify statistically consistent and semantically compact exemplars, while FCE reinforces visual coherence through feature-space clustering. Together, these stages yield a complementary exemplar set that balances textual grounding, count consistency, and feature representativeness. Experiments on diverse datasets demonstrate CountZES superior performance among ZOC methods while generalizing effectively across domains.

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

Insulin4RL: Real-Time Insulin Management in the Intensive Care Unit for Offline Reinforcement Learning

arXiv:2606.19481v1 Announce Type: new Abstract: Offline reinforcement learning (ORL) offers the potential to improve the quality of clinical decision-making using historical electronic health record (EHR) data. Current training and evaluative practices in this field rely heavily on EHR datasets that have been temporally discretised into fixed, regular time intervals. Discretisation creates fictional representations of complex clinical scenarios and compromises the generalisability of retrospective model evaluations. In this paper, we introduce Insulin4RL, a healthcare ORL dataset featuring naturally irregular inputs and actions from real clinical trajectories. Derived from MIMIC-IV, Insulin4RL comprises over 375,000 labelled decisions across 12,209 patients requiring insulin infusion titration in the Intensive Care Unit. The dataset can thus be used for research into ORL model performance under realistic clinical sampling assumptions. We provide a description of the dataset's structure and characteristics, baseline performance metrics using model-free offline reinforcement learning, and a standardised evaluation protocol using fitted Q-evaluation. We conclude with suggested areas for future research that could be addressed using this resource.

23.
arXiv (quant-ph) 2026-06-11

Isotropic random walks and Brownian diffusion on complex projective space

arXiv:2606.11438v1 Announce Type: new Abstract: We show that isotropic random walks on the complex projective space provide a canonical and analytically tractable stochastic-geometric framework for the exploration of quantum-state space. The approach combines harmonic analysis on compact rank-one symmetric spaces with stochastic pure-state evolution and yields explicit analytical expressions for transition kernels, fidelity statistics, and geometric observables associated with the Fubini–Study metric. In particular, the framework provides a solvable reference model for isotropic depolarization and Haar equilibration, reproducing Haar-random fidelity statistics and the invariant measure on projective Hilbert space without specifying a microscopic Lindblad generator. In the short-time regime, the stochastic evolution converges to Brownian diffusion generated by the Fubini–Study Laplace–Beltrami operator, while the long-time limit exhibits concentration-of-measure behaviour characteristic of high-dimensional random quantum states. We further derive analytical and asymptotic results for the first-passage-time problem, including closed-form expressions in the Brownian limit for the mean first passage time and the long-time tail of the first-passage-time distribution. For high-fidelity target states, the mean first passage time exhibits a strong dimension-dependent divergence originating from the concentration properties of the Fubini–Study geometry.

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

MiniPIC: Flexible Position-Independent Caching in <100LOC

Retrieval-augmented and agentic workloads repeatedly prefill recurring predictable structured inputs (which we call "spans") such as documents and code files. Yet, prefix caching in engines such as vLLM cannot reuse their KV entries unless they share identical prefixes with another request, while Position-Independent Caching (PIC) implementations within production-grade inference servers typically either require substantial server code changes or keep KV state outside the server, incurring host-to-device transfer overhead. We present Minimalistic PIC (MiniPIC): a minimal, flexible and fast vLLM design built from two ingredients: positional-encoding-free KV cache and user-controlled cache-reuse primitives. MiniPIC stores unrotated K vectors in the KV cache, applies RoPE to K tiles inside attention using per-request logical positions, and exposes three user-facing and token-level primitives: block-aligned padding, span separator (SSep), and prompt depend (PDep), that modify hashing behavior and effective block-level causal attention structure. With fewer than 100 lines of core-engine changes plus a custom attention backend, these primitives are sufficient to realize multiple PIC methods, including Block-Attention, EPIC, and Prompt Cache, within the same running vLLM instance, while natively integrating with KV cache CPU offload implementations. On 2WikiMultihopQA, MiniPIC with interleaved scheduling improves prefill throughput by 49% over baseline vLLM, reduces cached-span time-to-first-token by up to two orders of magnitude, preserves the linear prefill scaling of uncached spans, and incurs only 5.7% worst-case overhead.

25.
arXiv (quant-ph) 2026-06-15

Emission of time-ordered photon pairs from a coherently-driven Kerr microcavity

arXiv:2601.06468v2 Announce Type: replace-cross Abstract: Weakly-interacting many-body systems possess remarkable quantum properties that are essential components of quantum technologies, and constitute a topic of fundamental interest. Here we show that in a solid-state nonlinear microcavity embedding discrete modes of exciton-dressed photons, we can isolate a single eigenmode of quantum fluctuations from the much brighter coherent fraction of the field. In this regime, we perform frequency- and time-resolved correlations measurements between photons on the red and blue side of the fluctuations spectrum. When the average number of fluctuation quanta is smaller than one, we observe the formation of large pairwise time-ordered correlations: red photon first and blue photon second. We show that this peculiar time-ordering correlation emerges spontaneously from the interplay between frequency-resolved detection, and the non-trivial internal quantum structure of the elementary fluctuations.