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01.
arXiv (CS.AI) 2026-06-12

Cluster Aggregated GAN (CAG): A Cluster-Based Hybrid Model for Appliance Pattern Generation

arXiv:2512.22287v3 Announce Type: replace-cross Abstract: Synthetic appliance data are essential for developing non-intrusive load monitoring algorithms and enabling privacy preserving energy research, yet the scarcity of labeled datasets remains a significant barrier. Recent GAN-based methods have demonstrated the feasibility of synthesizing load patterns, but most existing approaches treat all devices uniformly within a single model, neglecting the behavioral differences between intermittent and continuous appliances and resulting in unstable training and limited output fidelity. To address these limitations, we propose the Cluster Aggregated GAN framework, a hybrid generative approach that routes each appliance to a specialized branch based on its behavioral characteristics. For intermittent appliances, a clustering module groups similar activation patterns and allocates dedicated generators for each cluster, ensuring that both common and rare operational modes receive adequate modeling capacity. Continuous appliances follow a separate branch that employs an LSTM-based generator to capture gradual temporal evolution while maintaining training stability through sequence compression. Extensive experiments on the UVIC smart plug dataset demonstrate that the proposed framework consistently outperforms baseline methods across metrics measuring realism, diversity, and training stability, and that integrating clustering as an active generative component substantially improves both interpretability and scalability. These findings establish the proposed framework as an effective approach for synthetic load generation in non-intrusive load monitoring research.

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

ActiTect: A Generalizable Machine Learning Pipeline for REM Sleep Behavior Disorder Screening through Standardized Actigraphy

arXiv:2511.05221v3 Announce Type: replace Abstract: Isolated rapid eye movement sleep behavior disorder (iRBD) is a major prodromal marker of $\alpha$-synucleinopathies, often preceding the clinical onset of Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. While wrist-worn actimeters hold significant potential for detecting RBD in large-scale screening efforts by capturing abnormal nocturnal movements, they become inoperable without a reliable and efficient analysis pipeline. This study presents ActiTect, a fully automated, open-source machine learning tool to identify RBD from actigraphy recordings. To ensure generalizability across heterogeneous acquisition settings, our pipeline includes robust preprocessing and automated sleep-wake detection to harmonize multi-device data and extract physiologically interpretable motion features characterizing activity patterns. Model development was conducted on a cohort of 78 individuals, yielding strong discrimination under nested cross-validation (AUROC = 0.95). Generalization was confirmed on a blinded local test set (n = 31, AUROC = 0.86) and on two independent external cohorts (n = 113, AUROC = 0.84; n = 57, AUROC = 0.94). To assess real-world robustness, leave-one-dataset-out cross-validation across the internal and external cohorts demonstrated consistent performance (AUROC range = 0.84-0.89). A complementary stability analysis showed that key predictive features remained reproducible across datasets, supporting the final pooled multi-center model as a robust pre-trained resource for broader deployment. By being open-source and easy to use, our tool promotes widespread adoption and facilitates independent validation and collaborative improvements, thereby advancing the field toward a unified and generalizable RBD detection model using wearable devices.

03.
arXiv (quant-ph) 2026-06-24

Active interference suppression in frequency-division-multiplexed quantum gates via off-resonant microwave tones

arXiv:2601.14547v3 Announce Type: replace Abstract: The increasing number of control lines connecting quantum processors to external electronics constitutes a major bottleneck in the realization of large-scale quantum computers. Frequency-division multiplexing is expected to enable control of multiple qubits through a single microwave cable; however, interference from off-resonant microwave tones hinders precise qubit control. Here, we propose an active interference suppression method for frequency-division-multiplexed simultaneous gates on microwave-controlled qubits. We demonstrate that the deliberate incorporation of off-resonant microwave tones improves single-qubit gate fidelity. In particular, the gate infidelity scales inversely with the square of the number of microwave tones when off-resonant orthogonal or quasi-orthogonal tones are incorporated. Furthermore, we show that fast oscillations, neglected under the rotating wave approximation, degrade the gate fidelity, and that this degradation can be mitigated through optimized frequency allocation. The proposed approach is simple and effective for improving the performance of frequency-division-multiplexed quantum gates.

04.
arXiv (CS.CV) 2026-06-15

A Unified Theory of Sinusoidal Activation Families for Implicit Neural Representations

Implicit Neural Representations (INRs) model continuous signals with compact neural networks and have become a standard tool in vision, graphics, and signal processing. A central challenge is accurately capturing fine detail without heavy hand-crafted encodings or brittle training heuristics. Across the literature, periodic activations have emerged as a compelling remedy: from SIREN, which uses a single sinusoid with a fixed global frequency, to more recent architectures employing multiple sinusoids and, in some cases, trainable frequencies and phases. We study this family of sinusoidal activations and develop a principled theoretical and practical framework for trainable sinusoidal activations in INRs. Concretely, we instantiate this framework with Sinusoidal Trainable Activation Functions (STAF), a Fourier-like activation whose amplitudes, frequencies, and phases are learned. Our analysis (i) establishes a Kronecker-equivalence construction that expresses trainable sinusoidal activations with standard sine networks and quantifies expressive growth, (ii) characterizes how the Neural Tangent Kernel (NTK) spectrum changes under trainable sinusoidal parameterization, and (iii) provides an initialization that yields standard normal post-activations without asymptotic central limit theorem (CLT) arguments. Empirically, on images, audio, shapes, inverse problems (super-resolution, denoising) and NeRF, STAF is competitive and often stronger on distortion-oriented reconstruction metrics such as PSNR/SSIM across the evaluated INR tasks, with favorable parameter efficiency under layer-wise sharing. While periodic activations can alleviate practical manifestations of spectral bias, our results indicate they do not eliminate it; instead, trainable sinusoids can improve the observed capacity-optimization trade-off in the evaluated settings.

05.
arXiv (CS.LG) 2026-06-11

Modelling magnetic material properties with uncertainty-aware neural networks

arXiv:2606.11870v1 Announce Type: cross Abstract: Machine learning is increasingly applied to accelerate the discovery of novel materials by exploring large compositional and structural design spaces. Yet, the scarcity of high-quality data and the frequent need for out-of-distribution prediction introduce substantial uncertainty, making the assessment of model reliability essential. In this work, we investigate uncertainty quantification as a means to evaluate model confidence in the context of permanent magnet research. In a first study, we benchmark classical and modern machine learning models for predicting intrinsic magnetic properties, focusing on the quality of their uncertainty estimates. We apply Gaussian negative log-likelihood loss and dropout-based Bayesian approximation as practical strategies for estimating predictive uncertainty. In a second study, we transfer these architectural features for uncertainty estimation to a more complex task: predicting coercivity from microstructural information using a graph neural network. Together, these studies demonstrate that uncertainty quantification not only enhances the trustworthiness of predictions but is also transferable across different modeling tasks.

06.
medRxiv (Medicine) 2026-06-15

Modelling the public-health impact of indoor air quality interventions on respiratory virus transmission

Respiratory virus transmission occurs in indoor settings where ventilation, occupancy, and dwell time determine exposure levels. Improving indoor air quality (IAQ) therefore could help reduce disease burden associated with respiratory viruses, yet its population-level impact remains poorly quantified. Here, we develop an individual-based transmission modelling framework that links within-location airborne dynamics to individual infection risk and population-level spread, whilst explicitly incorporating heterogeneity in ventilation and baseline indoor air quality across locations. We use this modelling approach to evaluate IAQ-improving interventions (air-quality interventions or AQIs), using hypothetical endemic and pandemic pathogen archetypes with properties similar to SARS-CoV-2 and influenza, and evaluate how effects on key epidemiological metrics (such as annualized incidence and epidemic final size) depend on AQI coverage, efficacy and allocation strategy. At 20% AQI intervention coverage and 80% efficacy, annualized incidence was reduced by approximately 7.2% for an endemic 'SARS-CoV-2-like' respiratory virus, and 17.0% for an endemic 'influenza-like' virus; at 60% coverage (80% efficacy) the reductions were 26.3% and 56.4%, respectively. Targeting AQI installation to the highest-risk locations outperformed random allocation: for SARS-CoV-2-like transmission, 20% coverage at 80% efficacy cut absolute incidence by 10.8% when targeted versus 7.2% when random; for influenza-like transmission, this comparison was 28.9% versus 17.0%. In epidemic scenarios, random installation at 40% coverage and 60% efficacy reduced final size by 23.7% (influenza-like) versus 6.3% (SARS-CoV-2-like). These results support treating clean indoor air as core public-health infrastructure and prioritising risk-based deployment of IAQ-improving interventions to maximise population-level benefit within budgetary and operational constraints.

07.
arXiv (quant-ph) 2026-06-19

Resolving problems with the continuum limit in coherent-state path integrals

arXiv:2602.02466v2 Announce Type: replace Abstract: The paper solves the problem of continuum limit in bosonic thermal coherent-state path integrals. For this purpose, exact discrete versions of the path integral are constructed for three different orderings of the Hamiltonian: normal, anti-normal and symmetric (Weyl order). Subsequently, their different continuum versions are checked on the harmonic oscillator, to choose the symmetric ordering as a possibly correct choice for all polynomial Hamiltonians. Spotted mathematical subtleties in the simple case serve as a clue to the general solution. Finally, a general justification for the symmetric order is provided by deriving the continuum path integral starting from the exact discrete case using a renormalization procedure in the imaginary time frequency domain. While the role of Weyl order has already been found, the paper provides the missing proof of its suitability for every polynomial Hamiltonian and simplifies the previously established construction by referring only to creation and annihilation operators (without position and momentum operators).

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

From Tokens to Policy: Causal and Interpretable Heterogeneous Treatment Effects Identification

arXiv:2606.17010v1 Announce Type: new Abstract: Heterogeneous Treatment Effect (HTE) identification is crucial to explain the impact of an intervention and optimize our policies accordingly. Existing approaches trade expressivity for interpretability, but, if some active heterogeneity drivers are unmeasured, methods at both ends of this spectrum allow for spurious HTE characterization with no causal reading. In this work, we focus on controlled experiments and argue that an oracle HTE causal characterization via the latent interactors is now within reach, thanks to (i) more extensive pre-treatment measurements, i.e., multi-modal and multi-view, and (ii) scalable representations with minimal human supervision. We then re-frame HTE identification as a Markov-blanket discovery problem on a sufficient and aligned pre-treatment representation, and introduce Neural EXposure Interaction Search (NEXIS), an iterative procedure with provable and empirically validated consistent selection. We deploy NEXIS on two anti-poverty programs in Africa, augmenting each with satellite imagery capturing previously unmeasured environmental effect modifiers, leading to novel, interpretable and prescriptive guidelines to optimize the programs' next iterations.

09.
arXiv (quant-ph) 2026-06-16

Finite-Element Matrix Product States for Continuum Models in One Dimension

arXiv:2606.14873v1 Announce Type: new Abstract: We present a matrix product state framework for simulating one-dimensional quantum many-body systems in the continuum using non-orthogonal single-particle basis sets. By mapping the physical problem to an auxiliary computational space, we show that the resulting many-body overlap operator can be efficiently encoded as a matrix product operator for sufficiently localized orbitals, thereby generalizing a construction that first appeared in [arXiv:2405.10285]. This construction recasts the variational ground-state search into a generalized eigenvalue problem, which can be solved using a generalized density matrix renormalization group algorithm. As a primary application, we employ a first-order finite-element expansion to study the ground state properties of the Lieb-Liniger gas in the presence of inhomogeneities. This approach also provides a natural setting for exactly refining the lattice, thereby enabling multigrid optimization strategies for matrix product states.

10.
arXiv (CS.AI) 2026-06-24

Cryptographic certificates of validity for trustworthy AI

arXiv:2606.23768v1 Announce Type: cross Abstract: We propose cryptographic certificates of validity for agentic AI systems. The core idea is to formally specify a correctness or policy condition as a logical predicate, compile this predicate to a witness-checking problem over polynomial constraints, and use a succinct cryptographic proof system (and optionally zero-knowledge) to certify that the condition holds. This offers a middle ground between formal verification of source code, and cryptographic authentication. An agent's action can be accompanied by an independently checkable proof that it satisfies an agreed formal policy, without requiring the verifier to trust the agent or to re-execute computation. We outline the approach at a high level, give the core mathematical translation, relate the proposal to proof-carrying code, zkVMs, formal methods, and agent governance, and note the specification, auditing, and deployment questions that a full implementation must answer.

11.
arXiv (CS.CV) 2026-06-17

Million-scale multimodal pollen microscopy with expert-guided foundation models

Automated pollen identification from microscopy remains a bottleneck in aerobiology, palaeoecology and biodiversity monitoring, because scalable systems must generalise across specimen preparation, scanner settings and geographic origins while retaining palynological interpretability. To address this gap, we present a million-scale multimodal pollen microscopy resource, Pollen AI Atlas, assembled from pure-species whole-slide bright-field images spanning four geographic origins, four scanner settings and 46 taxon labels across 31 botanical families. Seeded by one manually selected exemplar per source slide, token-level mining and filtering produced 1,511,390 released grain detections with 99.6\% proposal precision in expert-curated test regions. Each detection was paired with machine-generated grain-level morphological captions from five open-weight vision-language models, guided by expert-verified palynological anchors, yielding structured descriptions of aperture systems, wall ornamentation, shape and size. Among the evaluated models, Gemma4 provided the most controlled primary caption set, combining tight length control, no leakage and the strongest text-retrieval performance. Baseline benchmarks with frozen visual features reached 88.16\% top-1 accuracy, while cross-regional retrieval showed that caption-derived text embeddings remained robust when image similarity degraded (mAP@20 0.811 versus 0.262). Released data, annotations, captions, splits, code, and weights provide a benchmark for pollen recognition, cross-regional domain adaptation and domain-specific multimodal microscopy learning.

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

Cross-Lingual Exploration for Parametric Knowledge

Parametric knowledge in Large Language Models is not equally accessible across languages. As a result, standard inference techniques often struggle to surface localized facts, leading to failures in cross-lingual knowledge transfer and consistency. In this work, we investigate techniques for accessing hidden factual knowledge by exploring cross-lingual prompting strategies. We identify four inherent dimensions of cross-lingual exploration that directly govern parametric knowledge retrieval and evaluate them on multilingual factual benchmarks covering 17 typologically diverse languages. Our results demonstrate that cross-lingual exploration significantly improves knowledge transfer and factual recall, representing a more efficient compute Pareto frontier than native-language scaling. Furthermore, we observe corresponding improvements in cross-lingual consistency, exceeding what can be explained by accuracy gains alone. Overall, our work establishes multilingual prompt exploration as a highly effective inference-time strategy for unlocking latent parametric knowledge.

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

From Compression to Deployment: Real-Time and Energy-Efficient FastGRNN on Ultra-Constrained Microcontrollers

arXiv:2606.17249v1 Announce Type: cross Abstract: The dominant trajectory of modern machine learning has been to scale up: larger models, larger accelerators, larger memory budgets. Yet a multi-year global semiconductor supply constraint and the growing energy and carbon cost of always-online inference expose the fragility of this trajectory and motivate the opposite direction: refactoring AI and ML algorithms to fit the small, ubiquitous microcontrollers already in mass production in wearables, sensors, and edge appliances. We present an end-to-end open-source reproduction of FastGRNN, a compact gated recurrent cell, deployed on two bare-metal targets: the 8-bit Arduino (ATmega328P) and the 16-bit MSP430 (no hardware multiplier; 16 KB Flash; 512 B SRAM). Our compression pipeline combines low-rank weight factorization, iterative hard-thresholding sparsity, and per-tensor Q15 post-training quantization with explicit activation calibration. The deployed model occupies 566 bytes of weights and achieves macro F1 = 0.918 (seed 0; five-seed Q15 mean 0.853+-0.107) on the HAPT test set. It matches a PyTorch reference at 100% prediction agreement across 3,399 test windows (MCU seed 0; 99.91-100% C-equivalent across five seeds). Both platforms sustain real-time 50 Hz streaming inference (9.21 ms per sample on Arduino; 13 ms on MSP430), where a 256-entry sigmoid/tanh look-up table delivers a 30.5x speedup on the multiplier-less MSP430. Four contributions extend the original FastGRNN paper: (i) cross-platform bit-equivalent deterministic inference; (ii) characterization of recurrent warm-up latency (median 74 samples, 1.48 s; worst-case 125 samples, 2.50 s over 100 test windows); (iii) a deployable look-up-table recipe for multiplier-less embedded targets; and (iv) hardware energy characterization showing 17.7 mW active inference power,

14.
arXiv (CS.LG) 2026-06-16

Semi-Supervised Speech Confidence Detection using Pseudo-Labelling and Whisper Embeddings

arXiv:2606.16505v1 Announce Type: cross Abstract: Understanding speaker confidence is crucial in educational settings, as it can enhance personalised feedback and improve learning outcomes. This study introduces a novel framework for detecting speaker confidence by integrating human-engineered features with embeddings from the Whisper encoder. To address data limitations, a pseudo-labelling technique is employed to expand the labelled dataset, allowing the model to learn from both human-annotated and model-generated labels. The framework combines traditional speech features including pitch, volume, rate of speech, and the presence of disfluencies and stress, with Whisper embeddings, and uses a co-attention mechanism to fuse these representations and achieve an overall accuracy of 75%. This study contributes to advancing speech analysis, enabling applications that support personalised learning and speaking skill development.

15.
arXiv (CS.LG) 2026-06-16

TS-ICL: A Flexible Time-Indexed Foundation Model for Time Series via In-Context Learning

arXiv:2606.05878v2 Announce Type: replace Abstract: Foundation models mark a profound paradigm shift in time series modeling, with task-specific models being superseded by general-purpose zero-shot models. Yet, current approaches primarily focus on forecasting, while real-world time series are often irregularly and partially observed, requiring models that can jointly forecast, impute missing values, and handle degraded sampling conditions. To address these challenges, we introduce TS-ICL, a novel probabilistic In-Context Learning encoder–regressor Transformer that unifies forecasting and imputation. TS-ICL formulates time series tasks as timestamp-aligned regression and naturally incorporates covariates by training on synthetic dependency structures generated from a novel causal data prior. Empirically, TS-ICL achieves a new state-of-the-art in imputation, while remaining competitive with leading forecasting foundation models across both univariate and covariate-aware benchmarks. It shows particularly strong performance in forecasting with partially observed look-back windows.

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

Alternating Direction Method of Multipliers for Nonlinear Matrix Decompositions

arXiv:2512.17473v3 Announce Type: replace-cross Abstract: We present an algorithm based on the alternating direction method of multipliers (ADMM) for solving nonlinear matrix decompositions (NMD). Given an input matrix $X \in \mathbb{R}^{m \times n}$ and a factorization rank $r \ll \min(m, n)$, NMD seeks matrices $W \in \mathbb{R}^{m \times r}$ and $H \in \mathbb{R}^{r \times n}$ such that $X \approx f(WH)$, where $f$ is an element-wise nonlinear function. We evaluate our method on several representative nonlinear models: the rectified linear unit activation $f(x) = \max(0, x)$, suitable for nonnegative sparse data approximation, the component-wise square $f(x) = x^2$, applicable to probabilistic circuit representation, and the MinMax transform $f(x) = \min(b, \max(a, x))$, relevant for recommender systems. The proposed framework flexibly supports diverse loss functions, including least squares, $\ell_1$ norm, and the Kullback-Leibler divergence, and can be readily extended to other nonlinearities and metrics. We illustrate the applicability, efficiency, and adaptability of the approach on real-world datasets, highlighting its potential for a broad range of applications.

17.
Nature (Science) 2026-06-08

Targeting Cancer-Specific Mutations with RNA-Triggered Chromatin Shredding

Authors:

Genetic mutations that drive cancer often occur in tumor suppressor proteins, including the p53 transcription factor which is altered in ~40-50% of cases1,2. However, current therapies fail to target most such mutations because the mutant proteins typically lack defined drug-binding pockets, and restoring the endogenous function has proven challenging. Here, we programmed CRISPR-Cas12a2, an RNA-guided nuclease with trans-nucleolytic cleavage activities3,4, to selectively kill cancer cells by targeting cancer-specific transcripts. This approach limits cell growth by inducing trans shredding of chromatin, triggering DNA damage responses and cell death. Unlike existing methods, RNA-guided Cas12a2 senses cellular RNA signatures, enabling precise targeting of undruggable mutations. Transcript-activated chromatin shredding provides a new approach to precision disease treatments for undruggable targets.

18.
medRxiv (Medicine) 2026-06-18

Biomedical Capacity, Governance, and Health Security: A Dominican Republic Research Analysis of Stakeholder Perspectives

The COVID-19 pandemic exposed critical vulnerabilities in globally concentrated biomedical supply chains and accelerated interest in nearshoring and hemispheric health-security strategies. The Dominican Republic, already the third-largest medical device exporter in Latin America, occupies a strategically significant but institutionally constrained position within this realignment. This study evaluates stakeholder perceptions of the principal opportunities and barriers affecting biomedical ecosystem development in the Dominican Republic, with particular attention to governance, workforce capacity, and value-chain upgrading pathways. Methods. A concurrent mixed-methods design was employed, integrating a cross-sectional electronic survey of 142 purposively sampled domain experts (administered September-December 2025) with a qualitative executive consultation with senior government and industry leaders. Survey analyses combined descriptive statistics, one-sample t-tests against the scale neutral midpoint, chi-square goodness-of-fit tests, Friedman non-parametric ranking, Spearman rank correlations, and exploratory linear and logistic multivariable regression. Qualitative responses were analyzed using a framework approach grounded in the Triple Helix model of innovation systems. Results. Perceived government support was significantly below neutral (mean = 2.67, SD = 1.12; p = 0.034). Workforce shortages (83.3%) and weak academia-industry collaboration (71.4%) were the most frequently endorsed barriers ({chi}2(5) = 18.7, p = 0.002). Regulatory modernization (88.1%) and workforce development (85.7%) ranked as the highest-priority policy levers (Friedman p = 0.005). Clinical trials and contract research organization services were the dominant sub-sector priority (76.2%, binomial p < 0.001). In multivariable analysis, perceived government support, talent availability, and confidence in IP protection jointly explained 46% of the variance in sector competitiveness (R2 = 0.46, p < 0.001). Strong majority support existed for a formal public-private biomedical coordination authority (73.8%, p < 0.001).Conclusion. Institutional credibility and advanced human capital–rather than geography or market access–are the perceived binding constraints on the Dominican Republics biomedical trajectory. Regulatory modernization, targeted workforce investment, and the establishment of a national biomedical coordination authority represent the highest-leverage interventions for positioning the country as a hemispheric hub for biomedical manufacturing, clinical research, and health security.

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

Dialogue to Discovery: Attribute-Aware Preference Elicitation for Conversational Product Search Assistants

Conversational product search assistants offer a more expressive, natural, and interactive alternative to traditional keyword-based product search. With limited screen space, showing only a few items increases the need for precise preference elicitation, which can prolong conversations, leading to user frustration and session abandonment. Conversely, rushing to recommend items without a clear understanding of preferences risks poor matches and a degraded user experience. We present Dialogue to Discovery (D2D), an attribute-oriented preference elicitation framework that dynamically exploits the structure of product attributes to efficiently steer conversations toward the user's desired item. D2D adaptively prioritizes the most informative queries and strategically times product recommendations, reducing premature or off-target suggestions that harm engagement. To evaluate D2D, we curate three datasets from the Amazon Reviews corpus. In simulated conversations modelled using a multi-factor utilitarian patience framework, D2D achieves a 22.2-29.9% improvement in target-finding accuracy, 6.6-16.1% reduction in abandonment, and 27.5% shorter average conversations over the state-of-the-art baselines. A complementary user study further confirms significant gains in both user satisfaction and perceived efficiency.

20.
arXiv (CS.CL) 2026-06-16

REFLEX: Reflective Evolution from LLM Experience

Authors:

Large multimodal language models (LLMs) have emerged as powerful tools for guiding evolutionary search toward interpretable programmatic policies. However, existing frameworks rely on a monolithic model call to simultaneously interpret visual behavioral evidence and synthesize corrective code. This diagnosis-repair entanglement creates an opaque feedback loop, obscuring the rationale behind mutations and preventing the retention of algorithmic insights across independent runs. To achieve auditable and efficient policy search, we argue that visual diagnosis must be structurally decoupled from code generation. We present REFLEX, a train-free evolutionary framework that operationalizes this decoupling. In REFLEX, a vision-enabled Critic first distills task-specific behavioral evidence into structured, auditable diagnoses. Subsequently, a text-optimized Actor synthesizes child policies using these diagnoses alongside a persistent, self-evolving Skill Memory of reusable code snippets. This architecture not only provides transparent mutation traces but also enables cross-run programmatic knowledge transfer. Extensive evaluations across control benchmarks (Lunar Lander, Acrobot, Pendulum) and a 36-dimensional antenna array synthesis task demonstrate exceptional sample efficiency. Notably, REFLEX solves Acrobot and Pendulum in under 10 LLM calls and reaches a best Normalized Weighted Score of 1.092 on Lunar Lander, achieving highly competitive final performance while significantly accelerating the early-stage discovery of transparent policies.

21.
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).

22.
arXiv (quant-ph) 2026-06-16

Theory of the correlated quantum Zeno effect in a monitored qubit dimer

arXiv:2503.22846v2 Announce Type: replace Abstract: We theoretically investigate the stochastic dynamics of two qubits subject to one- and two-site correlated continuous weak measurements. When measurements dominate over the local unitary evolution, the system's dynamics is constrained and part of the physical Hilbert space becomes inaccessible: a typical signature of the Quantum Zeno (QZ) effect. In this work, we show how the competition between these two measurement processes give rise to two distinct QZ regimes, we dubbed standard and correlated, characterised by a different topology of the allowed region of the physical Hilbert space being a simply and non-simply connected domain, respectively. We develop a theory based on a stochastic Gutzwiller ansatz for the wavefunction that is able to capture the structure of the phase diagram. Finally we show how the two QZ regimes are intimately connected to the topology of the flow of the underlying non-Hermitian Hamiltonian governing the no-click evolution.

23.
arXiv (CS.CL) 2026-06-24

AI-PAVE-Br: Leveraging Large Language Models for Enhanced Product Attribute Value Extraction through a Golden Set Approach

The explosive growth and complexity of product data within the dynamic Brazilian e-commerce landscape demand robust and specialized methods for structured information extraction. Traditional approaches to Product Attribute Value Extraction (PAVE) often struggle with the linguistic nuances and sheer diversity of product descriptions in Portuguese. To address this critical gap, this paper introduces two major contributions. First, we present AI-PAVEBr, a specialized system engineered with Large Language Models (LLMs) to perform high-accuracy PAVE specifically for Brazilian e-commerce catalogs. Second, to facilitate reproducible research and provide a definitive benchmark, we introduce and share the Golden Set, a new, meticulously curated, and manually annotated dataset for PAVE in Portuguese. We detail the creation process and structure (Entity, Category, Subcategories) of this high-quality reference set. Our experiments conclusively show that AI-PAVE-Br, leveraging targeted prompt engineering, dramatically outperforms conventional Named Entity Recognition (NER) baselines. This work not only delivers a superior, scalable solution for a major non-English market but also enriches the NLP community with a valuable, publicly available resource for future PAVE research.

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

Hey Chat, Can You Teach Me? Structuring Socratic Dialogue for Human Learning in the Wild

Large language models are now widely used for everyday learning, but the underlying interactions are typically unstructured chats rather than following a curriculum. Unlike formal online learning systems, these interactions carry no prior record of the student, so any estimate of what the student already knows must be inferred from the dialogue itself. We show that this gap is not closed by scaling models alone. Frontier and education-tuned LLMs perform poorly when asked to tutor a student over an extended session, because doing so requires three things at once. The tutor must sequence a curriculum, conduct Socratic dialogue, and infer the student's knowledge state from that dialogue. We propose separating these responsibilities. Given a student query, our system constructs a prerequisite knowledge graph in which subtopics are nodes and dependencies are edges, and frames tutoring as deciding which node to teach next and how many dialogue turns to spend on it before moving on. A lightweight PPO policy handles this sequencing decision, while an LLM conducts the Socratic exchange at the chosen node and returns a signal of student progress. Across held-out STEM and non-STEM topics, our PPO-paired tutor outperforms heuristic baselines, frontier general-purpose models, and a model specialised for Socratic dialogue: on both the rate at which students reach full curriculum mastery and the number of turns required. Explicit curriculum structure delivers gains that scaling the underlying model does not.

25.
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.