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01.
Nature (Science) 2026-06-08

Targeting Cancer-Specific Mutations with RNA-Triggered Chromatin Shredding

作者:

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.

02.
arXiv (CS.LG) 2026-06-12

Attacking the First-Principle: A Black-Box, Query-Free Targeted Mimicry Attack on Binary Function Classifiers

arXiv:2605.18231v2 Announce Type: replace Abstract: Binary function classifiers play a crucial role in maintaining the security and integrity of software systems by detecting malicious code and unauthorized modifications. However, machine learning-based classifiers are vulnerable to adversarial attacks that can evade detection. In this study, we present Kelpie, a novel framework for executing mimicry attacks, a stronger type of targeted evasion attacks, on binary function classifiers in a black-box, zero-query setting. Unlike previous approaches that rely on querying the target classifier to refine untargeted evasion attacks, Kelpie leverages code transformations that preserve the functionality of malicious payloads while causing them to be misclassified as we want. Through extensive experimentation, we demonstrate that Kelpie can successfully execute mimicry attacks against six state-of-the-art binary function classifiers representing different model architectures without requiring direct interaction with them. We further validate our approach with a practical demonstration, involving a keylogger and a wiper concealed within benign-looking functions embedded in an application. This work, to our best knowledge, is the first to demonstrate such a mimicry attack in a black-box, zero-query context, raising important questions about the reliability and security of existing machine learning-based binary function classifiers.

03.
arXiv (quant-ph) 2026-06-19

Quantifying Imaginarity in Neutrino Systems

arXiv:2412.01871v2 Announce Type: replace-cross Abstract: It is a fundamental question why quantum mechanics employs complex numbers rather than solely real numbers. In this work, we conduct the first analysis of imaginarity quantification in neutrino flavor and spin-flavor oscillations. As quantum systems in coherent superposition, neutrinos are ideal candidates for quantifying imaginarity within the resource theoretic framework, using measures such as the $\ell_1$-norm and the relative entropy of imaginarity. We show that in the case of two-flavor mixing, these measures of imaginarity are nonzero. The measures of imaginarity reach their extreme values when the probabilistic features of quantum theory are fully maximized, i.e., both the transitional and survival probabilities are approximately equal. Our study reveals that the imaginarity, as a resource, can be harnessed not solely from the presence of a complex phase in the mixing matrix but also from the intrinsic quantum dynamics of time evolution itself. We further extend our analysis to explore the dynamics of three-flavor neutrino mixing, incorporating the effects of a nonzero $CP$ phase.

04.
arXiv (CS.AI) 2026-06-17

SkillChain-Gym: A Benchmark for Reskilling-Aware Production-Inventory Control under Disruptions

arXiv:2606.17266v1 Announce Type: new Abstract: Production planning increasingly has to treat workforce capability as a decision variable: certifications lapse when skills are not maintained, new products require skills the current workforce does not hold, and reskilling competes for the same worker hours needed for production. Existing operations benchmarks usually treat labor as exogenous, while workforce-planning models with skills and learning are rarely released as reusable testbeds. We introduce SkillChain-Gym, a benchmark specification for reskilling-aware production-inventory control: a single-site environment with stylized worker skill-state dynamics, hard threshold certification, forgetting, and capacity-consuming training actions constrained by the same per-worker time budget as production. The benchmark includes seed-controlled disruption scenarios, three feasibility modes with projection diagnostics, deterministic replay, and metrics covering operations, resilience, capability growth, and training-access distribution. We evaluate production-only, reactive adaptive, water-filling adaptive, and static-insurance policies with budget variants over 60-shift horizons with paired statistical tests. The results are regime-dependent rather than a ranking. Training-capable policies dominate the production-only baseline, and maintenance training is necessary under forgetting even without disruptions. Among training-capable classes, adaptive training helps when bottlenecks are visible in the forecast, while a lean static cross-training plan, a deliberately favorable comparator whose structure encodes relevant skill contingencies, acts as strong insurance under surprise shocks and absenteeism. Capacity slack and the forgetting rate govern the boundary between these regimes. No policy class dominates across regimes, motivating forecast-driven controllers that decide when to buy skill insurance and when to react.

05.
arXiv (CS.CL) 2026-06-12

GENEB: Why Genomic Models Are Hard to Compare

Progress in genomic foundation models is difficult to assess due to fragmented benchmarks, incompatible evaluation protocols, and task-specific reporting. As a result, claims of superiority or generality across models are often not directly comparable. We introduce GENEB, a large-scale diagnostic benchmark that evaluates frozen representations from 40 genomic foundation models across 100 tasks spanning 13 functional categories under a unified probing-based protocol, including few-shot regimes. GENEB enables controlled comparison across model scale, architecture, tokenization, and pretraining data while explicitly exposing task-level trade-offs. Our analysis shows that aggregate leaderboards are unstable: model rankings vary sharply across task categories, scale provides only modest and inconsistent gains, and architectural and pretraining alignment frequently outweigh parameter count. These results highlight limitations of current evaluation practices and position GENEB as a reference framework for principled comparison and category-aware model selection in genomic machine learning.

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

R1-SyntheticVL: Is Synthetic Data from Generative Models Ready for Multimodal Large Language Model?

In this work, we aim to develop effective data synthesis techniques that autonomously synthesize multimodal training data for enhancing MLLMs in solving complex real-world tasks. To this end, we propose Collective Adversarial Data Synthesis (CADS), a novel and general approach to synthesize high-quality, diverse and challenging multimodal data for MLLMs. The core idea of CADS is to leverage collective intelligence to ensure high-quality and diverse generation, while exploring adversarial learning to synthesize challenging samples for effectively driving model improvement. Specifically, CADS operates with two cyclic phases, i.e., Collective Adversarial Data Generation (CAD-Generate) and Collective Adversarial Data Judgment (CAD-Judge). CAD-Generate leverages collective knowledge to jointly generate new and diverse multimodal data, while CAD-Judge collaboratively assesses the quality of synthesized data. In addition, CADS introduces an Adversarial Context Optimization mechanism to optimize the generation context to encourage challenging and high-value data generation. With CADS, we construct MMSynthetic-20K and train our model R1-SyntheticVL, which demonstrates superior performance on various benchmarks.

07.
arXiv (CS.CV) 2026-06-11

TRON: Tracing Rays to Orchestrate a Neural Renderer for 3D Gaussian Reconstructions

We introduce TRON, a rendering framework that combines 3D Gaussian ray tracing with neural rendering to enable realistic and controllable rendering of real-world 3D scenes under novel lighting, dynamic object motion, object insertion, and material editing. Prior approaches that rely solely on physically based rendering (PBR) of Gaussian representations struggle to achieve realistic relighting due to imperfections in reconstructed geometry, material estimates, and light transport estimation. At the same time, neural rendering methods often lack an explicit scene representation, limiting their ability to support interactive editing with fine-grained manipulation. TRON bridges these two paradigms. We use intrinsic decomposition priors from a learned inverse rendering model to regularize the material properties of a Gaussian field, and repurpose a ray tracer to provide radiometric guidance rather than final pixels. By treating this output as a structured 3D scaffold, we empower a lightweight neural renderer to bridge the domain gap between shading-model constrained estimates and photorealistic output. Our key insight is that the combination of explicit 3D knowledge with robust material priors provides speed and controllability, while neural rendering enables the synthesis of photorealistic images. To support real-world scenarios, we train our neural renderer with a multi-stage strategy consisting of large-scale pretraining and targeted fine-tuning on a newly constructed dataset of 2.1M rendered synthetic and real-world frames from 3D reconstructions. TRON outperforms Gaussian-based relighting methods in realism, and prior neural renderers in editability and speed. To the best of our knowledge, TRON is the first method to enable practical interactive applications in captured 3D environments, offering realistic appearance under dynamic geometric, lighting and material conditions.

08.
arXiv (CS.CV) 2026-06-15

Rethinking Global Average Pooling: Your Classifier Is Secretly a Multi-Instance Learner

作者:

Modern image classifiers widely adopt global average pooling (GAP) followed by a linear classification head. This linearity ensures that the image-level logits equal the average of logits obtained by applying the classification head pointwise to the feature grid prior to GAP. Consequently, standard classifiers may inherently retain spatial class evidence that remains recoverable even when the image-level prediction is incorrect. This structure naturally suggests a multiple-instance learning (MIL) interpretation, where an image is viewed as a bag of spatial instances. Within this formulation, we demonstrate that standard classifiers trained with a single label per image can still learn the intended classification task in multi-object scenes. We further exploit this property to decompose image-level logits into a prediction grid, providing a post-hoc diagnostic to extract spatial class evidence that GAP otherwise obscures. Our systematic evaluation reveals that off-the-shelf models consistently recover the ground-truth class within foreground regions. The MIL interpretation further suggests that common classifier failures reflect known limitations of mean aggregation.

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

Sign-Language Datasets at Scale: A Comprehensive Survey on Resources, Benchmarks, and Annotation Standards

Sign languages are expressive visual languages used by Deaf and Hard-of-Hearing (DHH) communities. Despite substantial progress in sign-language recognition, translation, and production, advances remain constrained by fragmented datasets, inconsistent annotations, and limited linguistic coverage. Existing benchmarks often fail to reflect real-world communication needs, and systematic analyses of these limitations remain limited. In this survey, we present a comprehensive index of sign-language datasets, covering 120 resources across 35 sign languages. We analyze key challenges such as modality imbalance, annotation granularity, and signer bias, and outline considerations for future dataset design. We also introduce a 24-field Sign-Language Datasheet and release a public GitHub repository (https://github.com/Ginqwerty/Open-Sign-Language) to support standardized documentation and reproducible evaluation. Overall, our work provides a unified and practical foundation for developing inclusive, robust, and scalable sign-language technologies in real-world applications.

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

Beyond Classification: A Cough Regression Benchmark for Respiratory Acoustic Foundation Models

arXiv:2606.15436v1 Announce Type: cross Abstract: Respiratory acoustic foundation models (FMs) excel at cough classification, yet their ability to predict continuous health quantities from cough audio remains largely unexplored, despite the clinical value of passive age, BMI, and disease probability estimation in settings where physical measurements are unavailable. We introduce the multi-model, multi-target cough regression benchmark evaluating five FMs (OPERA-CT, OPERA-CE, OPERA-GT, HeAR, M2D+Resp) across six targets on three datasets under subject-disjoint protocols, comparing linear, MLP-small, and full MLP regression heads. MLP-small beats the mean-predictor baseline on all tasks and linear probing in 23 of 30 model x task cases, with full MLP overfitting on small clinical data but recovering on larger sets, revealing a dataset size x head-capacity trade-off. HeAR leads within-dataset age regression on Coswara (9.12 yr MAE); its CIDRZ result is excluded from headline claims owing to possible HeAR-CIDRZ pretraining overlap. OPERA-GT is favored over OPERA-CT on age in all three datasets, with the CIDRZ margin within seed variance, extending a generative-pretraining advantage from breath to cough. HeAR and M2D+Resp reach near-full performance at N = 50 samples while OPERA models require N = 400. Cross-dataset transfer is strongly asymmetric as large diverse data generalises to small clinical populations (CoughVID to CIDRZ: -0.17 yr) but not vice versa (CIDRZ to Coswara: +2.43 yr, +26.6%).

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

RAMAC: Multimodal Risk-Aware Offline Reinforcement Learning and the Role of Behavior Regularization

arXiv:2510.02695v3 Announce Type: replace-cross Abstract: In safety-critical domains where online data collection is infeasible, offline reinforcement learning (RL) is attractive only if policies achieve high returns without catastrophic lower-tail risk. Prior work on risk-averse offline RL achieves safety at the cost of either (i) value/model-based pessimism or (ii) restricted policy classes that limit expressiveness, whereas diffusion/flow-based expressive generative policies have largely been used in risk-neutral settings. We introduce Risk-Aware Multimodal Actor-Critic (RAMAC), a simple, modular, model-free framework that couples an expressive generative actor (e.g., diffusion/flow) with a distributional critic and optimizes a composite objective that combines Conditional Value-at-Risk (CVaR) with behavioral cloning (BC), enabling risk-sensitive learning in complex multimodal scenarios. Since out-of-distribution (OOD) actions are a major driver of catastrophic failures in offline RL, we further provide an objective-level analysis showing that controlling behavior divergence via BC suppresses OOD actions and stabilizes CVaR. Instantiating RAMAC with a diffusion actor, we illustrate these insights on a 2-D risky bandit and evaluate on Stochastic-D4RL, observing consistent gains in $\mathrm{CVaR}_{0.1}$ while maintaining strong returns. The code and experimental results are available on the \href{https://kaifukazawa.github.io/ramac-project/} {project website}

12.
arXiv (CS.CL) 2026-06-16

Do Safety Monitors Stay Reliable After an Update? Benchmarking and Predicting Activation-Monitor Staleness

作者:

Activation monitors-lightweight probes trained on a language model's internal representations-are an increasingly common layer in deployment safety stacks. Deployed models however are rarely static: they are quantized, fine-tuned, adapted with LoRA, or served with merged adapters while the monitor remains frozen. We present the first systematic test of whether this implicit contract holds: whether activation monitors trained on a base model remain reliable after these routine model updates. Across multiple safety-relevant monitors, model depths, update families, and open-weight models, we find a sharp split: quantization-style updates largely preserve frozen probe performance, while fine-tuning-style updates frequently make probes stale. Fragility is highly monitor-dependent, with privacy/PII probes most affected and refusal-compliance probes comparatively stable, showing that retraining a behavior need not stale its corresponding monitor. QLoRA is especially damaging despite NF4 quantization alone being relatively benign, suggesting that quantization becomes riskier when combined with adaptation. We further show that degradation is predictable from pre-deployment features, enabling revalidation budgets to be triaged toward the monitors most likely to fail. These results suggest that fine-tuning should trigger activation-monitor revalidation by default, while prediction can help prioritize which monitors to check first.

13.
arXiv (quant-ph) 2026-06-17

Quantum conditional entropies from convex trace functionals

arXiv:2410.21976v4 Announce Type: replace Abstract: We study geometric properties of trace functionals that generalize those in [Zhang, Adv. Math. 365:107053 (2020)], arising from a novel family of conditional entropies with applications in quantum information. Building on new convexity results for these functionals, we establish data-processing inequalities and additivity properties for our entropies, demonstrating their operational significance. We further prove completeness under duality, chain rules, and various monotonicity properties for this family. Our proofs draw on tools from complex interpolation theory, multivariate Araki–Lieb and Lieb–Thirring inequalities, variational characterizations of trace functionals, and spectral pinching techniques.

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

XMedFusion: A Knowledge-Guided Multimodal Perception and Reasoning Framework for Autonomous Medical Systems

Autonomous medical and robotic systems increasingly rely on intelligent perception and reasoning capabilities to interpret visual data and support clinical decision making. Radiology report generation represents a critical component of such automated diagnostic workflows, yet existing end-to-end multimodal models often suffer from weak visual grounding, resulting in unreliable interpretations and omission of subtle clinical findings. This paper presents XMedFusion, a modular AI framework designed as an intelligent perception and reasoning module for autonomous medical systems. The proposed framework decomposes visual information into coordinated functional components that emulate expert-driven analysis, including a visual perception agent that extracts image-grounded evidence, a knowledge graph construction agent that structures clinically relevant findings, and a retrieval-guided drafting process that ensures a consistent reporting structure. A synthesis agent iteratively integrates visual and structured evidence through reasoning-driven verification to produce reliable and interpretable diagnostic outputs. Experimental evaluation on a public chest radiograph dataset demonstrates significant improvements over baseline vision-language models, achieving gains from 0.0493 to 0.3359 in BLEU-1, 0.0863 to 0.2440 in ROUGE-L, and 0.0829 to 0.1708 in METEOR, along with substantial improvements in semantic evaluation metrics such as Consistency (2.38 to 7.80) and Accuracy (2.34 to 6.93). The results highlight the effectiveness of structured multi-agent perception and reasoning for enhancing robustness, transparency, and automation in intelligent medical imaging systems, enabling integration into autonomous healthcare and robotic diagnostic workflows.

15.
arXiv (CS.AI) 2026-06-12

Arbor: Tree Search as a Cognition Layer for Autonomous Agents

arXiv:2606.12563v1 Announce Type: new Abstract: Arbor is a multi-agent framework that introduces structured tree search as a cognition layer for autonomous agents operating in large, stateful action spaces. Prior autonomous optimization systems operate on isolated targets with stateless evaluation. Arbor instead maintains an explicit search tree of scored hypotheses that serves as the shared working memory across agents, evolving with every measurement, treating failures as diagnostic signal that reshapes subsequent exploration, and expanding as prior successes shift the bottleneck distribution. We validate Arbor on full-stack LLM inference optimization, a domain where achieving peak performance has historically required coordinated effort from engineering teams across the application, framework, compiler, kernel, and hardware stack. Arbor pairs an Orchestrator agent, which drives optimization by delegating to Domain Specialists across the inference stack, with a Critic agent that safeguards stability through root-cause analysis, introspection, and measurement validation – a checks-and-balances architecture where neither agent can unilaterally drive the system. Agent capabilities are decomposed into hard skills (domain expertise) and soft skills (coordination protocols that determine how contributions compose), enabling fully autonomous multi-day campaigns. Arbor achieves up to 193% inference throughput-latency Pareto improvement over vendor-optimized baselines, while a single agent without the harness plateaus at +33% throughput improvement and crashes irrecoverably within hours. Arbor generalizes to multiple generations of hardware platform, and run-to-run variance is within 2 percentage points demonstrating that the method is hardware-agnostic and reproducible.

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

Measuring Curriculum Alignment across Topical Coverage, Competency, and Cognitive Depth: A Longitudinal Framework Applied to CS2013 and CS2023

arXiv:2606.19469v1 Announce Type: new Abstract: Undergraduate computer science is governed by international curricular guidelines revised about once a decade, yet programs lack a reliable, reproducible way to measure how completely they cover the current guidelines and how that coverage shifts when the guidelines are restructured. We address this with a human-in-the-loop pipeline that measures a program's coverage of an external body of knowledge, applied longitudinally to one accredited BSc in Computer Science against Computer Science Curricula 2013 (CS2013) and 2023 (CS2023). The pipeline represents the program and each guideline as structured corpora, generates candidate course-to-knowledge-unit matches by semantic retrieval, and confirms them through human judgment under an explicit coverage definition. Of seven benchmarked retrievers, a reciprocal-rank-fusion ensemble was strongest, and a reputed long-context model underperformed a small sentence model, so retriever choice must be measured. Both maps were validated by an independent second rater (Cohen's kappa 0.64 for CS2023, 0.69 for CS2013). The program covers 49.7% of CS2023 and 50.9% of CS2013 knowledge units, near-constant across a decade. Extending the same retrieve-then-confirm design to competency articulation and cognitive depth shows that the program articulates the competency for ~88% of covered units under each guideline, yet delivers it at the recommended depth for 76% of present units under CS2023 against 95% under CS2013, a gap reflecting the newer guideline's raised expectations, not the program. The longitudinal comparison separates persistent structural gaps (parallel and distributed computing, foundations of programming languages, systems fundamentals), uncovered against both guidelines and ABET, from differences that reflect the standard's evolution. The instrument is reusable and available from the authors on request.

17.
arXiv (CS.AI) 2026-06-16

An affordable hardware-aware neural architecture search for deploying convolutional neural networks on ultra-low-power computing platforms

arXiv:2606.16290v1 Announce Type: cross Abstract: Hardware-aware neural architecture search (HW-NAS) allows the integration of Convolutional Neural Networks (CNNs) in microcontrollers devices by automatically designing neural architectures that can fit prearranged hardware constraints. However, state-of-the-art HW-NAS target high-performance microcontrollers, whose power consumption does not meet sensing nodes requirements. This work presents a HW-NAS generating tiny CNNs that can run on ultra-low-power microcontrollers, featuring a lightweight search procedure enabling its execution even on embedded devices. Empirical results on three well-known benchmarks for tiny computer vision proved that the proposed HW-NAS was able to generate tiny CNNs while preserving state-of-the-art classification accuracy.

18.
arXiv (CS.CV) 2026-06-16

MolSight: Molecular Property Prediction with Images

Every molecule ever synthesised can be drawn as a 2D skeletal diagram, yet in modern property prediction this universally available representation has received less focus in favour of molecular graphs, 3D conformers, or billion-parameter language models, each imposing its own computational and data-engineering overhead. We present $MolSight$, the first systematic large-scale study of vision-based Molecular Property Prediction (MPP). Using 10 vision architectures, 7 pre-training strategies, and $2\,M$ molecule images, we evaluate performance across 10 downstream tasks spanning physical-property regression, drug-discovery classification, and quantum-chemistry prediction. To account for the wide variation in structural complexity across pre-training molecules, we further propose a $chemistry-informed curriculum$: five structural complexity descriptors partition the corpus into five tiers of increasing chemical difficulty, consistently outperforming non-curriculum baselines. We show that a single rendered bond-line image, processed by a vision encoder, is sufficient for competitive molecular property prediction, i.e. $chemical insight from sight alone$. The best curriculum-trained configuration achieves the top result on $5 of 10$ benchmarks and top two on $all 10$, at $$80$\times$ lower$$ FLOPs than the nearest multi-modal competitor.

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

Your Mouse and Eyes Secretly Leak Your Preference: LLM Alignment using Implicit Feedback from Users

To align a Large Language Model (LLM), most existing methods collect explicit human feedback and train a reward model to predict the human preference based on the response text. These existing methods have two key limitations. First, the users rarely provide explicit feedback for LLM responses, which makes the high-quality preference annotation expensive to collect. Second, the methods do not leverage implicit human feedback, which has proven vital to the economic moats of Internet giants. To quantify the value of implicit feedback, we build a new dataset called IFLLM, which collects 1336 multi-turn questions from the 59 Mechanical Turk workers, their mouse trajectories, and eye gazing points to the LLMs' responses from their webcams. IFLLM shows that the users have very diverse types of gazing behavior and mouse trajectories. Our reward model based on the implicit user feedback boosts the accuracy of the text-based reward model from 55% to 64% and nearly triples the relative response quality improvements after applying the DPO to eight LLMs, demonstrating the value of implicit feedback in the wild. Our data collection website, dataset, and codes can be found at https://github.com/themehulpatwari/llm-implicit-feedback/.

20.
arXiv (quant-ph) 2026-06-11

Quantum ergodicity and semiclassical measures: mathematical results

arXiv:2606.12098v1 Announce Type: new Abstract: In this chapter we review some results describing the high-frequency eigenmodes of the Laplacian on compact manifolds, or Euclidean domains, for which the geodesic flow is chaotic. We focus on the macroscopic distribution of these eigenmodes, which is described by the concept of semiclassical measure. The main result on the question is the Quantum Ergodicity theorem, originally due to Schnirelman. We provide the detailed proof of this theorem, including the adjustments necessary to treat the case of manifolds with boundary. We also discuss the Quantum Unique Ergodicity conjecture, and some progress towards this conjecture for strongly chaotic (Anosov) systems. In particular, we describe the constraints on admissible semiclassical measures, in terms of their Kolmogorov-Sinai entropy, as well as more recent delocalization results.

21.
bioRxiv (Bioinfo) 2026-06-18

Predicting optimal growth temperatures of bacteria using learned structural information from a single protein

Temperature is a fundamental determinant of bacterial physiology and ecology. Optimal growth temperature (OGT) is highly variable across species, contributing to differences in where and when species are most likely to thrive. Although the OGTs for most bacteria remain unknown, the increasing availability of genomes from uncultivated and cultivated taxa has made it advantageous to build genomic, cultivation-independent models to infer OGT. However, pre-existing genomic models often lack the generalizability and mechanistic grounding required for robust inferences of OGT. We propose a novel framework for predicting bacterial OGT which uses learned protein structural signatures of thermal adaptation. We hypothesize that biophysical tradeoffs which dictate enzymatic functions across variable temperatures provide a more robust empirical basis for OGT prediction than broad genomic features. Our OGT-predicting model, ROSEATE, is based on a single gene, adenylate kinase (ADK), that encodes for a ubiquitous enzyme essential for energy homeostasis. ROSEATE uses high-dimensional latent space encoding via MSA Transformer, a protein language model which embeds ADKs in a manner which preserves biophysical information about embedded proteins. We show that the accuracy of the ROSEATE model is on par with other genome-based models, has a high degree of phylogenetic generalizability, and the ESM embeddings effectively capture key temperature-adaptive enzyme characteristics derived from AlphaFold structures. Because ROSEATE is based on analyses of a single ubiquitous protein, it can be used with metagenomic data to infer the community-level variation in bacterial OGTs. We demonstrate this feature of ROSEATE by reconstructing ADK sequences from over 500 environmental and host-associated metagenomes, successfully distinguishing community-wide thermal preferences across diverse habitats, from polar oceans to mammalian guts. By transitioning from genomic proxies to informationally dense protein structural features, this work provides an efficient, interpretable tool for predicting bacterial OGTs across taxa and whole communities.

22.
Science (Express) 2026-04-16

Protein-templated synthesis of dinucleotide repeat DNA by an antiphage reverse transcriptase | Science

作者: 未知作者

Defense-associated reverse transcriptases (DRTs) are widespread bacterial anti-phage systems that use unconventional mechanisms of polynucleotide synthesis. We show that DRT3, which comprises two distinct RTs (Drt3a and Drt3b) and a noncoding RNA (ncRNA), synthesizes alternating poly(GT/AC) double-stranded DNA. Cryo–electron microscopy structures at 2.6 Å resolution reveal a D3-symmetric 6:6:6 complex of Drt3a, Drt3b, and ncRNA. Drt3a produces the poly(GT) strand using a conserved ACACAC template within the ncRNA. Notably, Drt3b synthesizes a complementary, protein-primed poly(AC) strand in the complete absence of a nucleic acid template, using conserved active site residues specific to Drt3b to enforce precise base alternation. These findings expand the functional landscape of nucleic acid polymerases, revealing a protein-templated mechanism for sequence-specific DNA synthesis.

23.
arXiv (CS.LG) 2026-06-18

Identifying Structural Biases from Causal Mechanism Shifts

arXiv:2606.18834v1 Announce Type: new Abstract: Causal discovery methods commonly assume that all data is independently and identically distributed (i.i.d.) and that there are no unmeasured variables affecting the system. In practice, these assumptions are often violated, leading to inaccurate inference. In this paper, we study how to identify hidden confounding and selection biases from causal mechanism shifts. In particular, we show that structural biases lead to dependent mechanism shifts. That is, by considering for which variables the mechanisms change given data from different environments, we can tell which variables are unbiased, which are subject to hidden confounding, and which are undergoing selection bias. We formalize this into an empirically testable criterion based on mutual information, and show under which conditions it identifies structural biases. To tell which nodes are subject to what kind of bias, we introduce the StruBI algorithm. Experiments on synthetic and real-world data show that StruBI works well in practice, accurately recovering affected variable sets and types of biases, outperforming the state-of-the-art by a wide margin.

24.
arXiv (math.PR) 2026-06-11

Multiple Poisson-Dirichlet diffusions on generalized Kingman simplices

arXiv:2602.20266v2 Announce Type: replace Abstract: We construct a new class of infinite-dimensional diffusions with values in a generalized Kingman simplex with finitely many marks. The model describes the temporal evolution of the relative frequencies of infinitely many types that are labeled by a finite number $H$ of marks, but unlabeled within each mark. We first establish a blockwise skew-product representation for a finite-type Wright-Fisher diffusion, extending the aggregation-renormalization self-similarity property of Dirichlet laws. The decomposition separates an $H$-dimensional Wright-Fisher diffusion governing the evolving random mark masses, from $H$ Wright-Fisher diffusions, each run on its own random clock, which describe the evolution of the relative frequencies within each mark. After ranking the within-mark frequencies in decreasing order, we identify the distributional limit as the number of types per mark tends to infinity and we derive an explicit form of its infinitesimal generator on a suitable domain. The limiting diffusion admits the multiple Poisson-Dirichlet distribution as a stationary distribution; it recovers the infinitely-many-neutral-alleles diffusion when all types share the same mark and yields a diffusion on the Thoma simplex when there are two marks.

25.
arXiv (CS.CL) 2026-06-16

A Systematic Evaluation of Large Language Models for PTSD Severity Estimation: The Role of Contextual Knowledge and Modeling Strategies

Large language models (LLMs) are increasingly being used in a zero-shot (generative) fashion to assess mental health conditions, yet we have limited knowledge on what factors affect their accuracy. In this study, we use a clinical dataset of natural language narratives and self-reported PTSD severity scores from 1,437 individuals to comprehensively evaluate the performance of 11 state-of-the-art LLMs. To understand the factors affecting model's assessment accuracy, we systematically varied (i) contextual knowledge prompted to the models like subscale definitions, distribution summary, and interview questions, and (ii) modeling strategies including zero-shot vs few shot, amount of reasoning effort, model sizes, structured subscales vs direct scalar prediction, output rescaling and nine ensemble methods. Our findings indicate that (a) LLMs are most accurate when provided with detailed construct definitions and context of the narrative, even exceeding human raters agreement with self-reported scores; (b) increased reasoning effort leads to better estimation accuracy; (c) performance of open-weight models (Llama, DeepSeek) plateaus beyond 70B parameters while closed-weight (gpt-o3-mini, gpt-5) alternatives improve with newer generations; and (d) best performance is achieved when ensembling a supervised model with the zero-shot LLMs. Beyond agreement with self-reports, LLMs' estimates discriminated PTSD severity from depression, anxiety, and alcohol use, and prospectively predicted future mental healthcare expenditure. Together, these results suggest that contextual knowledge and modeling strategies meaningfully affect accuracy and clinical utility of LLM-based assessments of PTSD severity.