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01.
Science (Express) 2026-05-21

DNA polymerization activates RNA cleavage of a reverse transcriptase–like antiviral enzyme | Science

作者: 未知作者

Defense-associated reverse transcriptases (DRTs) transcribe noncoding RNAs (ncRNAs) for antiviral defense, but the mechanisms of ncRNA-independent DRTs remain unclear. In this work, we show that a single DRT4 mediates RNA-targeting antiphage defense by integrating DNA polymerase, exonuclease, and RNA endonuclease activities. First, through an equilibrium between its DNA polymerase and exonuclease activities, DRT4 senses phage infection, as elevated dNTP levels shift the equilibrium toward polymerase activity, thereby promoting protein-primed single-stranded DNA (ssDNA) synthesis. Second, ssDNA of sufficient length, phage DNA-binding proteins, and deoxyguanosine triphosphate collectively activate an unusual RNA endonuclease activity of DRT4, excising 3′–guanosine monophosphate from both phage and host RNA to terminate infection. These findings reveal a distinctive immune strategy combining nucleic acid synthesis and degradation, expanding the functional landscape of DRTs for new DNA- and RNA-processing technologies.

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

Imbalanced Semi-Supervised Learning via Label Refinement and Threshold Adjustment

arXiv:2407.05370v3 Announce Type: replace Abstract: Semi-supervised learning (SSL) algorithms often struggle to perform well when trained on imbalanced data. In such scenarios, the generated pseudo-labels tend to exhibit a bias toward the majority class, and models relying on these pseudo-labels can further amplify this bias. Existing imbalanced SSL algorithms explore pseudo-labeling strategies based on either pseudo-label refinement (PLR) or threshold adjustment (THA), aiming to mitigate the bias through heuristic-driven designs. However, through a careful statistical analysis, we find that existing strategies are suboptimal: most PLR algorithms are either overly empirical or rely on the unrealistic assumption that models remain well-calibrated throughout training, while most THA algorithms depend on flawed metrics for pseudo-label selection. To address these shortcomings, we first derive the theoretically optimal form of pseudo-labels under class imbalance. This foundation leads to our key contribution: SEmi-supervised learning with pseudo-label optimization based on VALidation data (SEVAL), a unified framework that learns both PLR and THA parameters from a class-balanced subset of training data. By jointly optimizing these components, SEVAL adapts to specific task requirements while ensuring per-class pseudo-label reliability. Our experiments demonstrate that SEVAL outperforms state-of-the-art SSL methods, producing more accurate and effective pseudo-labels across various imbalanced SSL scenarios while remaining compatible with diverse SSL algorithms. The code is publicly available (https://github.com/ZerojumpLine/SEVAL).

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

Towards Physically Realizable Adversarial Attenuation Patch against SAR Object Detection

Deep neural networks have demonstrated excellent performance in SAR target detection tasks but remain susceptible to adversarial attacks. Existing SAR-specific attack methods can effectively deceive detectors; however, they often introduce noticeable perturbations and are largely confined to digital domain, neglecting physical implementation constrains for attacking SAR systems. In this paper, a novel Adversarial Attenuation Patch (AAP) method is proposed that employs energy-constrained optimization strategy coupled with an attenuation-based deployment framework to achieve a seamless balance between attack effectiveness and stealthiness. More importantly, AAP exhibits strong potential for physical realization by aligning with signal-level electronic jamming mechanisms. Experimental results show that AAP effectively degrades detection performance while preserving high imperceptibility, and shows favorable transferability across different models. This study provides a physical grounded perspective for adversarial attacks on SAR target detection systems and facilitates the design of more covert and practically deployable attack strategies. The source code is made available at https://github.com/boremycin/SAAP.

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

LLMpedia: A Transparent Framework to Materialize an LLM's Encyclopedic Knowledge at Scale

Benchmarks like MMLU suggest flagship language models approach factuality saturation above 90\%. LLMpedia shows this picture is incomplete. We materialize ${\sim}$1.3M encyclopedia articles entirely from parametric memory across three model families, then audit every claim against Wikipedia and curated web evidence. For \texttt{gpt-5-mini}, the verifiable true rate is 68.4\% on Wikipedia-covered subjects - more than 21\,pp below MMLU - and the gap is driven by unverifiability (30.5\%), not refutation (1.2\%). Beyond Wikipedia, frontier articles audited against curated web evidence reach 57.6\%; Wikipedia covers only 56.7\% of model-surfaced subjects, and three model families overlap in just 7.3\% of subject choices. In a retrieval-trap benchmark inspired by prior analysis of Grokipedia, LLMpedia is more factual at roughly half the textual similarity to Wikipedia. Every prompt, article, and verdict is released. Data, code, interface: https://llmpedia.net.

05.
arXiv (CS.CV) 2026-06-17

SCC-Loc: A Unified Semantic Cascade Consensus Framework for UAV Thermal Geo-Localization

Cross-modal Thermal Geo-localization (TG) provides a robust, all-weather solution for Unmanned Aerial Vehicles (UAVs) in Global Navigation Satellite System (GNSS)-denied environments. However, profound thermal-visible modality gaps introduce severe feature ambiguity, systematically corrupting conventional coarse-to-fine registration. To dismantle this bottleneck, we propose SCC-Loc, a unified Semantic-Cascade-Consensus localization framework. By sharing a single DINOv2 backbone across global retrieval and MINIMA$_{RoMa}$ matching, it minimizes memory footprint and achieves zero-shot, highly accurate absolute position estimation. Specifically, we tackle modality ambiguity by introducing three cohesive components. First, we design the Semantic-Guided Viewport Alignment (SGVA) module to adaptively optimize satellite crop regions, effectively correcting initial spatial deviations. Second, we develop the Cascaded Spatial-Adaptive Texture-Structure Filtering (C-SATSF) mechanism to explicitly enforce geometric consistency, thereby eradicating dense cross-modal outliers. Finally, we propose the Consensus-Driven Reliability-Aware Position Selection (CD-RAPS) strategy to derive the optimal solution through a synergy of physically constrained pose optimization. To address data scarcity, we construct Thermal-UAV, a comprehensive dataset providing 11,890 diverse thermal queries referenced against a large-scale satellite ortho-photo and corresponding spatially aligned Digital Surface Model (DSM). Extensive experiments demonstrate that SCC-Loc establishes a new state-of-the-art, suppressing the mean localization error to 9.37 m and providing a 7.6-fold accuracy improvement within a strict 5-m threshold over the strongest baseline. Code and dataset are available at https://github.com/FloralHercules/SCC-Loc.

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

Subliminal Learning Is Steering Vector Distillation

arXiv:2606.00995v3 Announce Type: replace Abstract: Subliminal learning refers to a student language model acquiring a teacher's traits (e.g. a system-prompted preference for owls) when fine-tuned on the teacher's outputs, despite the outputs being semantically unrelated to those traits. It remains poorly understood how data without semantic meaning can transfer specific semantic traits. In this work, we show that subliminal learning is mediated by a single steering vector, i.e. a vector added to the model's activations. Across two open-source models, we find that the teacher's system prompt is well approximated by a steering vector, and that the student's behavior is driven by learning an aligned vector over fine-tuning. System prompts that are not well approximated by steering vectors are not subliminally learned. This is a special case of steering vector distillation, in which a student trained on the outputs of a steered teacher learns to imitate that steering. We demonstrate steering vector distillation on a range of semantic and random vectors. Adding a semantic vector to a model's activations can have both model-independent and model-specific (i.e. non-semantic) effects on its behavior, so generated data that is non-semantic can transmit a vector with semantic effects, enabling subliminal learning. This also explains why subliminal learning does not transfer between models. We find that adaptive optimizers are necessary for subliminal learning in language models: activation gradients on steered data carry a small but consistent component along the steering direction, and non-adaptive optimizers impede this by allowing outlier gradients to dominate.

07.
arXiv (CS.LG) 2026-06-17

A 3D Isovist World Model – Revealing a City's Unseen Geometry and Its Emergent Cross-City Signature

arXiv:2606.03609v3 Announce Type: replace-cross Abstract: Embodied agents that navigate cities rely on world models that predict how their surroundings will change as they move. But for navigation, what matters is not what the buildings look like; it is where the agent can go. Most world models nonetheless predict appearance, learning how a scene looks rather than the space an agent can move through. Those that do target geometry, such as bird's-eye-view occupancy grids, flatten the three-dimensional environment onto a ground plane, discarding the above-ground and multi-level structure that shapes real navigation. What is missing is a predictive target that captures the navigable geometry an agent actually traverses, without photometric entanglement and without collapsing the third dimension. Our key idea is to model the open volume between buildings, the negative space, encoded as a 3D isovist: a spherical visibility-depth map recording the distance to the nearest surface in every direction. We introduce an embodied world model that predicts the next isovist from a short history of past isovists and a movement action. The prediction is formulated as a depth residual so the decoder inherits sharp building edges, trained with self-rollout scheduled sampling to keep corrupted context on the geometry manifold, and equipped with a persistent latent bird's-eye-view spatial map for cross-path consistency. Our central finding is emergent and unexpected: a single city-blind model trained on Manhattan and Paris develops a cross-city spatial signature, with city identity linearly decodable from its temporal latents far above single-frame baselines, so the signature lives in the learned dynamics rather than in appearance. The representation is lightweight, interpretable, and reproducible, offering a geometric substrate for spatial reasoning in embodied AI, robotics, and urban analysis, released with an open dataset and pipeline.

08.
medRxiv (Medicine) 2026-06-10

"We don't complain; it's just part of being a woman": frequency, knowledge, and sociocultural beliefs about dysmenorrhoea in a South African university cohort

Introduction Dysmenorrhoea is highly prevalent globally and interferes with engagement in education, work, social participation, and quality of life. Although evidence suggests that sociocultural beliefs influence how menstrual pain is understood and managed, relatively little research has explored dysmenorrhoea-related knowledge and beliefs within South Africa. This study aimed to (1) determine the frequency of dysmenorrhoea, (2) assess dysmenorrhoea-related knowledge and compare knowledge between menstruating and non-menstruating individuals, and (3) explore commonly held generational, cultural, and religious beliefs related to dysmenorrhoea in a South African university cohort. Methods We analysed data collected as part of a cross-sectional survey conducted among staff and students at a South African university. Participants completed demographic questions, items assessing dysmenorrhoea-related knowledge, and an adapted Working Ability, Location, Intensity, Days of Pain, Dysmenorrhoea (WaLIDD) questionnaire. Participants were also invited to provide free-text responses describing generational, cultural, and religious beliefs about dysmenorrhoea. Quantitative data were analysed descriptively and compared between menstruating and non-menstruating participants. Free-text responses were analysed using reflexive thematic analysis. Results A total of 863 participants completed the survey, including 578 current or past menstruators. The frequency (95%CI) of dysmenorrhoea was 75.4% (71.7-78.9). Most participants were classified as having moderate (53%) or severe (31%) dysmenorrhoea on the WaLIDD scale. Awareness of dysmenorrhoea was higher among participants who had menstruated than among those who had never menstruated (80.4% vs 55.3%, p

09.
arXiv (CS.CL) 2026-06-19

Apparent Psychological Profiles of Large Language Models are Largely a Measurement Artifact

Psychological instruments designed for humans are increasingly used to assign large language models (LLMs) stable psychological profiles that affect their usability, safety assessment, and use as proxies for human participants in research. Using a formal psychometric framework, we show that these profiles are largely a measurement artifact. Administering a battery of personality and risk-preference instruments spanning self-reports and behavioral tasks to 56 instruction-tuned LLMs alongside large human reference samples, we report four findings. First, differences between models are driven not by the traits an instrument targets but by a directional response bias, a tendency to respond toward one end of the scale, or one labeled option, regardless of item content; a variance decomposition attributes 81-90% of between-model variation to this bias, against 9-16% in humans. Second, the bias declines with model capability but is not eliminated by it. Third, because bias rather than trait drives responding, an instrument's apparent reliability is almost entirely predicted by its response orthogonality, a term we coin for the proportion of items for which trait and bias point in opposite directions. Fourth, the profile a model appears to have shifts with the items used and can be manufactured through item selection. These results demonstrate that the apparent psychological profiles of LLMs are artifacts of the instrument used to measure them, not properties of the models themselves. As instruments borrowed from human psychology are rarely fully orthogonal and may inherently lack validity for LLMs, we call for dedicated assessments centered on response orthogonality.

10.
arXiv (CS.AI) 2026-06-16

AI-Driven Test Case Generation from Natural Language Requirements: A Survey of Techniques and Research Gaps

arXiv:2606.06563v2 Announce Type: replace-cross Abstract: Software testing is critical for verifying that systems meet specified requirements, yet remains among the most time-consuming and expensive activities in development. Requirements-based test generation allows test cases to be derived early from requirements artifacts, but generating them directly from natural language is challenging due to inherent ambiguity and imprecision. Recent advances in AI, natural language processing (NLP), and large language models (LLMs) have made automating this pipeline increasingly feasible, while introducing new risks including hallucination, reduced traceability, and inconsistent evaluation. This survey addresses four research questions: what AI and NLP techniques have been proposed for generating test cases from natural language requirements; what tools and frameworks support these approaches; how generated test cases are evaluated; and what research gaps remain. Following Kitchenham and Charters' systematic review guidelines, we searched major scholarly databases spanning 2000-2025 and, after applying strict inclusion criteria, identified 21 primary studies. The literature is organized into three evolutionary eras, revealing that no existing approach simultaneously satisfies six key quality dimensions: automation, ambiguity handling, domain applicability, traceability, evaluation thoroughness, and hallucination control. The survey makes three main contributions: a three-era evolutionary synthesis of AI-based test generation; a six-criteria gap analysis showing no current approach fully addresses all quality dimensions; and four actionable research guidelines targeting hallucination, traceability, complexity sensitivity, and compliance.

11.
arXiv (math.PR) 2026-06-12

Symmetric Cooperative Motion in Higher Dimensions

arXiv:2606.13459v1 Announce Type: new Abstract: We prove a distributional convergence result for a multidimensional version of symmetric cooperative motion which was introduced and studied in one dimension in [HRW, SCM1]. Our approach relies on framing the associated recursive distributional equation as a discretization of the porous medium equation. A major challenge is to analyze the behaviour of finite difference schemes which approximate weak solutions of the porous medium equation with unbounded initial data. In overcoming this difficulty, we perform a detailed analysis of the probability mass function of symmetric cooperative motion, in which we introduce several new comparison arguments for the discrete process. Consequently, along the way, we establish a novel multidimensional convergence result for a finite difference scheme approximating the ZKB/Barenblatt solution of the porous medium equation, which is of independent interest.

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

Skill-Augmented AI Agents for Medical Research Analysis: An Exploratory Multi-Model Human Evaluation in an NSCLC Transcriptomic Biomarker Task

arXiv:2606.11830v1 Announce Type: new Abstract: Background. Large language models and AI agents are increasingly used to support biomedical research, but native model outputs may omit key analytical steps, misuse methods, or overstate conclusions. We evaluated whether autonomous access to a medical research skill package was associated with higher-quality AI-generated transcriptomic research-analysis outputs compared with native AI without skills. Methods. We conducted an exploratory multi-model human evaluation using a non-small cell lung cancer immunotherapy biomarker task. Six model backbones were tested. The evaluation included 21 anonymized outputs: 9 native-AI outputs and 12 skill-augmented outputs generated through an AI agent implementation represented by OpenClaw. Four non-expert biomedical reviewers and two blinded experts evaluated each output, with two ratings from each reviewer type. The primary outcome was expert-rated overall quality. Results. Skill-augmented outputs showed directionally higher expert overall quality than native-AI outputs (mean 5.50 vs 5.11; difference=0.39; bootstrap 95\% CI, -0.04 to 0.90; Welch p=0.156). Non-expert reviewer quality showed the same direction (mean 4.72 vs 4.47; difference=0.26; bootstrap 95\% CI, -0.25 to 0.80; Welch p=0.373). Expert agreement was limited (single-rating ICC=-0.15), and model-specific effects were descriptive and heterogeneous. Conclusions. Autonomous skill access showed a directional quality signal in this exploratory sample, but the signal was smaller than expert-rating noise and should not be interpreted as confirmatory evidence. The findings primarily motivate larger evaluations of skill-augmented AI agents with stronger reliability controls, platform replication, and biological-validity assessment.

13.
arXiv (CS.CV) 2026-06-15

Scratched Lenses, Shifted Depth: Passive Camera-Side Optical Attacks

Physical adversarial attacks on vision systems are typically studied through scene manipulation, such as adversarial patches or projections, where the adversary controls what the camera observes. Camera-side attacks using stickers or auxiliary optics have also been explored, but they treat attacks as image-space perturbations from designed patterns. This misses how physical imperfections interact with scene-dependent lighting and optics. We identify a threat: passive lens-side damage that is persistent yet trigger-conditioned, producing optical artifacts that bias geometric inference under particular visual conditions. We instantiate this threat through Scratch-induced Lens Adversarial Streak Hijacking SLASH, a physical-world attack caused by small scratches on a camera lens or protective cover. Scratches interact with bright light sources and specular reflections to create structured streak artifacts that distort depth cues. Since the perturbation is fixed in the optical path but triggered by the scene, it is both persistent and selective. We formulate the attack in optical space, model the scratch pattern as a trigger-conditioned optical channel, and optimize one fixed configuration across diverse viewing conditions. We evaluate SLASH on monocular depth estimation and monocular 3D object detection in digital and real-world settings. Under the fixed-scratch constraint, directional depth shifts reach up to 32% relative error for monocular depth estimation, with consistent effects on monocular 3D object detection. Physical experiments confirm transfer to real camera recordings, inducing depth shifts above the model's natural prediction baseline. These findings reveal an attack surface where benign-looking hardware imperfections act as latent, scene-triggered adversarial mechanisms, challenging assumptions about physical robustness and motivating defenses for secure vision systems.

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

Local-GS: Accelerating 3D Gaussian Splatting via Tile-Local Warp Coherence

3D Gaussian Splatting (3DGS) has significantly advanced real-time novel view synthesis by representing scenes as dense collections of anisotropic 3D Gaussian primitives. However, the irregular spatial distribution of Gaussians often leads to poor GPU utilization, as warp divergence and redundant computation degrade rendering performance. To address this, we present Local-GS, a warp-coherent rendering paradigm that, organizes Gaussian primitives with respect to SIMT (Single Instruction, Multiple Threads) execution boundaries rather than scene geometry. Specifically, we propose three warp-coherent stages: a hoisting stage that precomputes shared parameters at tile level, a culling stage that discards warps with no contribution, and a blending stage that replaces per-pixel branching with a uniform instruction stream. Across extensive benchmarks on multiple datasets, Local-GS improves efficiency without compromising quality. As a plug-and-play optimization, it provides additional performance gains to all tested baselines, culminating in a $7.76\times$ speedup on Deep Blending scenes.

15.
arXiv (quant-ph) 2026-06-17

Cavity method for permutation models on Cayley trees

arXiv:2606.17751v1 Announce Type: new Abstract: Motivated by permutation statistical models arising in random tensor networks, we study permutation models on a Cayley tree whose variables take values in the symmetric group $\Sn$. The pair interaction is assumed to depend only on the cycle type of the relative permutation. Then the Boltzmann weight is written as a class function on $\Sn$. This property diagonalizes the edge convolution operator in irreducible representation sectors. As a result, the linear stability of the uniform paramagnetic cavity solution is controlled by the character eigenvalue ratios. For cycle-factorized weights, these eigenvalues can be expressed as specializations of Schur functions. We derive the instability criteria and also verify their validity by comparison with direct numerical iterations of the cavity equation.

17.
arXiv (CS.LG) 2026-06-18

Decomposing Prediction Mechanisms for In-Context Recall

arXiv:2507.01414v2 Announce Type: replace Abstract: We introduce a new family of toy problems that combine features of linear-regression-style continuous in-context learning (ICL) with discrete associative recall. We pretrain transformer models on sample traces from this toy, specifically symbolically-labeled interleaved state observations from randomly drawn linear deterministic dynamical systems. We study if the transformer models can recall the state of a sequence previously seen in its context when prompted to do so with the corresponding in-context label. Taking a closer look at this task, it becomes clear that the model must perform two functions: (1) identify which system's state should be recalled and apply that system to its last seen state, and (2) continuing to apply the correct system to predict the subsequent states. Training dynamics reveal that the first capability emerges well into a model's training. Surprisingly, the second capability, of continuing the prediction of a resumed sequence, develops much earlier. Via out-of-distribution experiments, and a mechanistic analysis on model weights via edge pruning, we find that next-token prediction for this toy problem involves at least two separate mechanisms. One mechanism uses the discrete symbolic labels to do the associative recall required to predict the start of a resumption of a previously seen sequence. The second mechanism, which is largely agnostic to the discrete symbolic labels, performs a "Bayesian-style" prediction based on the previous token and the context. These two mechanisms have different learning dynamics. To confirm that this multi-mechanism (manifesting as separate phase transitions) phenomenon is not just an artifact of our toy setting, we used OLMo training checkpoints on an ICL translation task to see a similar phenomenon: a decisive gap in the emergence of first-task-token performance vs second-task-token performance.

18.
arXiv (quant-ph) 2026-06-11

Fabricating fiber cavity mirror substrates compatible with high coupling efficiency

arXiv:2606.12168v1 Announce Type: cross Abstract: Fiber optical cavities offer small mode volumes and correspondingly strong light-matter interactions in an open Fabry-Perot geometry. However, existing fabrication techniques do not reliably produce substrates with surface profiles amenable to high mode matching between the cavity mode and fiber core, thereby limiting the achievable collection efficiency. Here we present a technique to fabricate fiber mirror substrates while using $in situ$ reflectometry to constrain the achievable mode matching prior to coating. By measuring the back-reflection from freshly cleaved fiber tips, we pre-select 138 fibers compatible with 96.5-99.5% mode matching, and after a single CO$_2$ laser ablation pulse, these fibers remained compatible with 95.3-99.2\%. This simple technique provides rapid feedback during each stage of substrate fabrication, greatly enhancing the yield of viable fiber mirror substrates prior to (expensive) coating runs.

19.
arXiv (CS.LG) 2026-06-17

BioArtlas: Computational Clustering of Multi-Dimensional Complexity in Bioart

arXiv:2511.19162v3 Announce Type: replace-cross Abstract: Bioart brings living material into artistic practice, where a single work can be at once an aesthetic object, a scientific instrument, and an ethical provocation. Traditional categories sort such works along one axis at a time, which flattens the very hybridity that defines the field and leaves curators no way to compare works across many dimensions together. I introduce BioArtlas, a computational atlas that represents each bioartwork along many curated dimensions at once and organizes the field by conceptual similarity rather than by medium or chronology. My method embeds the keywords of all 81 works on each of thirteen interpretive axes, groups related concepts into a shared codebook that tames inconsistent terminology, and then searches systematically for a clustering that is both statistically clean and interpretable. Among the methods that place every work on the map, agglomerative clustering separates the field far more cleanly than the usual k-means baseline (silhouette 0.664 versus 0.483), whereas density-based methods reach higher scores only by discarding most of the corpus as noise. By separating rigorous analysis from public storytelling, BioArtlas turns the tangled complexity of bioart into a navigable landscape, openly available as an interactive interface (https://www.bioartlas.com) and dataset (https://github.com/joonhyungbae/BioArtlas).

20.
arXiv (CS.LG) 2026-06-15

Curvature-Guided Geometric Representation for Protein-Ligand Binding Affinity Prediction

arXiv:2606.14159v1 Announce Type: new Abstract: Protein-ligand binding affinity (PLA) prediction is critical in drug discovery. Despite the notable advancements in machine learning-based approaches, existing methods struggle to jointly characterize local geometric organization and globally coordinated cross-molecular interactions, limiting their ability to model complex binding mechanisms. Here, we propose RicciBind, a geometric representation framework that integrates curvature-guided hierarchical structure learning with optimal transport (OT)-based cross-domain alignment to model molecular interactions. Specifically, RicciBind leverages Ricci curvature to capture local interaction tightness within molecular structures, enhancing structural awareness and organizing atomic interactions into curvature-aware hierarchical representations. An OT-based cluster matching mechanism then aligns protein and ligand clusters across heterogeneous domains under geometric constraints, enabling globally consistent correspondences and revealing higher-order interaction patterns beyond local neighborhoods. By coupling curvature-guided structure encoding with OT-driven cross-domain alignment, RicciBind effectively models complex interaction semantics and substantially improves both the accuracy and interpretability of binding affinity prediction. Extensive experiments demonstrate that RicciBind achieved superior predictive performance and generalization across PLA benchmarks and virtual screening tasks. Ablation studies further confirmed the essential role of Ricci curvature in enhancing molecular interaction representations.

21.
bioRxiv (Bioinfo) 2026-06-22

HTS-Oracle X: AI-Guided Prospective Discovery of Small Molecule Immune Checkpoint Binders

Targeting immune checkpoint protein-protein interactions (PPIs) using small molecules remains limited by the shallow, featureless binding surfaces of co-stimulatory and co-inhibitory receptors and the characteristically low hit rates of conventional high-throughput screening against these interfaces. Here we report HTS-Oracle X, a multimodal deep learning platform that integrates bidirectional cross-attention fusion of ChemBERTa SMILES embeddings with extended RDKit descriptors, trains on continuous biophysical binding signals rather than binary labels, and employs Monte Carlo Dropout uncertainty quantification for uncertainty-adjusted compound selection. Trained on 45,760 Dianthus TRIC-screened compounds per target under scaffold-aware cross-validation, HTS-Oracle X was applied prospectively to a 100,160-compound Enamine library against CD28, TIM-3, and VISTA. From 150 model-selected compounds, 45 dose-response confirmed binders were identified (30.0% overall hit rate), yielding enrichment factors of 234-408x over experimentally established random prospective baselines and 16 sub-micromolar hits. The top hits, HX-CD28-1 (KD = 233 nM), HX-TIM3-1 (KD = 249 nM), and HX-VISTA-1 (KD = 345 nM), demonstrated on-target functional activity in immune cell and tumor co-culture assays. HTS-Oracle X represents a scalable AI-guided framework for small molecule discovery against non-enzymatic immune checkpoint targets.

22.
PLOS Medicine 2026-05-22

Differences in tuberculosis prevalence by sex in low- and middle-income countries over 1993–2025: A systematic review and meta-analysis

by Nicole A. Swartwood, Nanki Singh, Seyed Alireza Mortazavi, Melike Hazal Can, Hening Cui, Do Kyung Ryuk, Peter MacPherson, Katherine C. Horton, Nicolas A. Menzies Background Global and national initiatives to combat tuberculosis (TB) have expanded over recent years. Despite this, the TB burden remains high in some population groups, with men recognized as having elevated TB risks. Summary measures of sex differences in TB prevalence were last estimated in 2016. Since then, many additional prevalence surveys have been conducted, including in the highest TB burden countries. We conducted a systematic review of sex-stratified TB prevalence survey data published over 1993–2025, to provide updated estimates of male-to-female (M:F) TB prevalence ratios and determine whether sex-related disparities in TB burden have closed over time. Methods and findings We identified surveys reporting community-representative, sex-stratified estimates of pulmonary TB prevalence in low- and middle-income countries (LMICs), including surveys from an earlier review (covering January 1993–March 2016) and a new systematic review (covering 1st December 2015–13th October 2025). This review was prospectively registered with PROSPERO (CRD42024503853) and included searches of PubMed, Embase, Global Health, the Cochrane Library, Africa Index Medicus, LILACS, and SciELO. We extracted data on bacteriologically confirmed and smear-positive TB prevalence among adults (aged ≥ 15 years), stratified by sex. Risk of bias was evaluated using eight criteria specific to prevalence surveys. We fit multi-level Bayesian regression models with study- and country-level random effects to estimate the M:F ratio of TB prevalence (male prevalence divided by female prevalence), overall and for key subgroups. In meta-regression analyses, we estimated how prevalence ratios varied over time and according to known TB risk factors and TB case definitions.We identified 10,124 publications and extracted data from 100 eligible studies representing 102 unique prevalence surveys and 4,658,310 participants (45.6% male) in 33 LMICs. TB prevalence was higher in men than women in 90/102 of the included surveys, with a pooled M:F prevalence ratio of 2.02 (95% credible interval (CrI): 1.71, 2.34) for bacteriologically confirmed TB and 2.38 (95% CrI: 1.91, 2.90) for smear-positive TB. Time trend analyses showed a 2.0% (95% CrI: −0.2, 4.5%) average annual change in the M:F ratio of bacteriologically confirmed TB over the study period. The M:F prevalence ratio was estimated to be higher for countries with greater excess HIV prevalence among men, and countries with greater gender equity (as measured by the United Nation’s Gender Development Index). The estimated M:F prevalence ratio was also higher for surveys that did not restrict testing to individuals reporting TB symptoms. Study limitations include heterogeneity in survey methods and definitions, as well as limited data from the Americas, Eastern Mediterranean, and Europe WHO world regions and post-COVID-19 period. Conclusions Men in LMICs consistently experience TB at a higher prevalence than women. Time trend estimates are uncertain, but consistent with widening sex differences in TB prevalence over the last three decades, despite efforts to address the risk factors underlying this excess TB burden.

24.
arXiv (quant-ph) 2026-06-17

Entanglement transition in unitary system-bath dynamics

arXiv:2512.06081v3 Announce Type: replace Abstract: The evolution of a system coupled to baths is commonly described by a master equation that, in the long-time limit, yields a steady-state density matrix. However, when the same evolution is unraveled into quantum trajectories, it is possible to observe a transition in the scaling of entanglement within the system as the system-bath coupling increases - a phenomenon that is invisible in the trajectory-averaged reduced density matrix of the system. Here, we go beyond the paradigm of trajectories from master equations and explore whether a qualitatively analogous entanglement-scaling transition emerges in a single unitary evolution of the combined system-bath setup, without monitoring the dynamics of the system. We investigate the scaling of entanglement in a unitary quantum setup composed of a two-dimensional lattice of free fermions, where each site is coupled to a fermionic bath. As the system-bath coupling increases, the logarithmic fermionic negativity reveals an entanglement transition from logarithmic-law to area-law scaling. This occurs while the system's steady-state properties are trivial, highlighting that the signatures of these different scalings are within the bath-bath correlations. Evidence of the transition is also found in the mutual information and the correlations of the full system-bath setup, suggesting that the entanglement transition is underpinned by a change in the spatial structure of quantum information.

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

L-Proto: Language-Aware Episodic Prototypical Training for Multilingual Speaker Verification

arXiv:2606.17416v1 Announce Type: cross Abstract: Multilingual speaker verification remains challenging because language-dependent acoustic variability causes speaker identity to become entangled with linguistic characteristics, degrading generalization across languages. In multilingual training, embeddings often encode language cues with speaker identity, causing speakers to form language-specific clusters. We propose L-Proto, a language-aware episodic prototypical training strategy that constructs language-consistent episodes. By sampling speakers from a single language per episode, L-Proto reduces language-driven variation during training and encourages embeddings to focus more directly on speaker identity. Experiments on the TidyVoice Challenge benchmark demonstrate consistent performance improvements over conventional fine-tuning and random episodic sampling across multiple backbone architectures.