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01.
arXiv (math.PR) 2026-06-16

A small noise approximation for Muller's Ratchet

arXiv:2606.15842v1 Announce Type: new Abstract: We consider an infinite system of SDEs with Fleming-Viot noise indexed by $k=0,1,2,\dots$, whose parameters $\alpha,\lambda$, and $\nu$ are the (deleterious) selection coefficient, the (uni-directional) mutation rate, and a quantity which determines the size of the system's fluctuations. The SDE's unique weak solution $X(t) = (X_k(t))_{k=0,1,2,...}$ models what is known in population genetics as Muller's ratchet. Here, $X_k(t)$ stands for the frequency of individuals carrying $k$ deleterious mutations. Since the mutation process is uni-directional, $t\mapsto \inf\{k: X_k(t)> 0\}$ is non-decreasing for almost every path of $X$, and we refer to an increase as a click of Muller's ratchet. A long standing question concerns the clicking rate of Muller's ratchet. Using Duhamel's principle for semigroups, we give a partial answer by approximating $E(\sum_{k=1}^\infty kX_k(t) )$ and $E\big(X_0(t)\big)$ up to $O(1/\nu^2)$ for fixed $\alpha$, $\lambda$ and $t>0$. Our results suggest that $\psi:=\nu \alpha e^{-\lambda/\alpha}$ is a crucial quantity also when the mutation/selection ratio $\theta = \lambda/\alpha$ is moderately large: for large $\nu \alpha$, clicking of the ratchet on the time scale $\frac 1\alpha \log \theta$ becomes rare as soon as $\psi$ becomes large.

02.
bioRxiv (Bioinfo) 2026-06-12

DNA Compression with Genomic Language Models: Tokenization, Benchmarking, and an Information-Content Map

Lossless compression and probabilistic sequence modeling are two faces of the same coin: a model that assigns high probability to a sequence can encode it in few bits via arithmetic coding. We exploit this duality to evaluate genomic language models as compressors of DNA, using compression primarily as an objective probe of generative sequence modeling rather than as a deployable storage system. We release DNAGPT2, a family of ten GPT-2-small models pretrained for one epoch on a single A40 using the DNABERT2 multi-species corpus that differ only in byte-pair encoding vocabulary size. Coupled with arithmetic coding, the best model reaches 1.47 bits per base (bpb) on the T2T human genome, fourth in the Cobilab compression benchmark and ahead of every general-purpose compressor. Our results suggest that NLP-style tokenization choices may be suboptimal for DNA: a 32-token BPE vocabulary compresses better than larger vocabularies. We also find that, in this benchmark, published long-context genomic LMs underperform a much shorter-context BPE GPT-2; we discuss in Section 5 that this is not a controlled context-length ablation, since the compared models also differ in architecture, training data, parameter count, and tokenization. Finally, we compute a per-nucleotide information-content map of the human genome and show that exons, introns, intergenic regions, and Alu repeats have statistically distinct information profiles.

03.
arXiv (CS.AI) 2026-06-16

Phishing Email Detection Using Large Language Models

arXiv:2512.10104v2 Announce Type: cross Abstract: Email phishing is one of the most prevalent and globally consequential vectors of cyber intrusion. As systems increasingly deploy Large Language Models (LLMs) applications, these systems face evolving phishing email threats that exploit their fundamental architectures. Current LLMs require substantial hardening before deployment in email security systems, particularly against coordinated multi-vector attacks that exploit architectural vulnerabilities. This paper proposes LLMPEA, an LLM-based framework to detect phishing email attacks across multiple attack vectors, including prompt injection, text refinement, and multilingual attacks. We evaluate three frontier LLMs (e.g., GPT-4o, Claude Sonnet 4, and Grok-3) and comprehensive prompting design to assess their feasibility, robustness, and limitations against phishing email attacks. Our empirical analysis reveals that LLMs can detect the phishing email over 90% accuracy while we also highlight that LLM-based phishing email detection systems could be exploited by adversarial attack, prompt injection, and multilingual attacks. Our findings provide critical insights for LLM-based phishing detection in real-world settings where attackers exploit multiple vulnerabilities in combination.

04.
bioRxiv (Bioinfo) 2026-06-18

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

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

05.
arXiv (CS.AI) 2026-06-16

Overcoming the Impedance Mismatch: A Theoretical Roadmap for Fusing Foundation Models and Knowledge Graphs

arXiv:2606.15656v1 Announce Type: new Abstract: Modern artificial intelligence remains fundamentally divided between the continuous, probabilistic spaces of Foundation Models and the discrete, deterministic structures of Knowledge Graphs. While Retrieval-Augmented Generation (RAG) attempts to connect them by serializing graph data into text, we argue this lexical bridging is merely a superficial patch. In this paper, we formalize the underlying structural and geometric friction as the Impedance Mismatch. By categorizing current neuro-symbolic integration strategies into a three-tiered hierarchy, we demonstrate that neither surface-level prompt injection nor continuous representation alignment can preserve the strict logical motifs required for reliable multi-hop reasoning. We define the specific mathematical limits, such as the Lexical Bottleneck and Topological Collapse, that show current architectures will eventually hallucinate or conflate semantic nodes. To achieve true semantic fusion, we propose a rigorous theoretical roadmap. We advocate for natively internalizing discrete symbolic structures through Structured Residual Streams, utilizing Vector Symbolic Architectures for latent sub-graph injection, and performing model updates via Orthogonal Subspace Editing. This actionable framework paves the way for models that seamlessly fuse the precision of symbolic logic with the expressivity of parametric memory.

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

Sustainable Face Recognition on Low-Power Devices with VQ-VAE Embeddings

Face recognition has become a cornerstone of modern AI applications, yet conventional approaches often rely on computationally intensive models deployed in cloud environments, leading to increased network traffic, high energy consumption, and a heavy carbon footprint. This work introduces a sustainable, edge-deployable face recognition framework based on Vector-Quantized Variational Autoencoders (VQ-VAE), which generates compact and semantically rich latent representations of facial images. By leveraging the compression capacity and reconstruction quality of VQ-VAE embeddings on the edge and combining them with the power of pre-trained face embeddings in a knowledge distillation setup, our system achieves comparable accuracy to state-of-the-art face embedding models while significantly reducing memory and computation requirements on the edge, making it suitable for low-power edge devices. The integration of VQ-VAE compression minimizes network overhead while keeping the matching accuracy high by retaining only the most informative facial features in the latent space. As a result, the reconstructed images preserve the key identity characteristics, improving the robustness and overall performance of the face embeddings.

07.
arXiv (CS.LG) 2026-06-12

Machine Learning-based Two-Stage Graph Sparsification for the Travelling Salesman Problem

arXiv:2604.20236v2 Announce Type: replace Abstract: High-performance TSP solvers such as Lin-Kernighan-Helsgaun (LKH) search within a candidate graph – a small subset of edges pre-selected for the solver – rather than over the complete graph. The two leading sparsification heuristics, $\alpha$-Nearest and POPMUSIC, each fall short of the density-coverage balance: $\alpha$-Nearest is dense with stable recall, while POPMUSIC is sparser but its recall degrades with scale. Their union closes the recall gap while remaining far below the complete graph in density, leaving room for further reduction. Existing learning-based sparsifiers score edges on the complete graph, an approach that is expensive and largely limited to Euclidean instances. We propose a two-stage method that inverts this logic. Stage~1 takes the union of $\alpha$-Nearest and POPMUSIC, achieving near-perfect recall at ${\sim}6N$ edges. Crucially, the union annotates each edge with its source provenance – whether it was endorsed by $\alpha$-Nearest, POPMUSIC, or both. Stage~2 trains a lightweight classifier on these annotated edges and prunes the lowest-scoring ones. Because dual-source edges are almost always optimal, the learning problem reduces to filtering the single-source subset – a substantially easier task than classifying all $O(N^2)$ edges from scratch. Across four distance types, five spatial distributions, and problem sizes from 50 to 500, the pipeline reduces candidate-graph density by $37$-$47\%$ while retaining ${\geq}99.69\%$ of optimal-tour edges, and matches or exceeds the coverage of recent Euclidean-only neural sparsifiers at lower density at TSP500.

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

LabOSBench: Benchmarking Computer Use Agents for Scientific Instrument Control

arXiv:2606.16802v1 Announce Type: new Abstract: Current computer-use benchmarks primarily focus on software operation tasks in virtualized systems, whereas scientific instrumentation scenarios require coordinated control over complex interfaces, and feedback-driven parameter adjustment. However, directly evaluating agents on physical high-precision instruments is impractical due to high cost, safety risks, limited accessibility, and difficulty in ensuring reproducible evaluation. This motivates the need for a simulated yet realistic testbed that preserves the operational challenges of scientific instruments while enabling scalable and safe benchmarking. To this end, we introduce LabOSBench, a challenging benchmark for multimodal GUI agents built on a suite of web-based scientific-instrument simulators. Operating directly via a browser, LabOSBench avoids resource-heavy OS virtualization while supporting flexible task configuration and execution-based evaluation. Specifically, LabOSBench constructs 96 subtasks across eight instrument simulators, covering workflows from sample loading, alignment, parameter tuning, and data acquisition to result inspection. We evaluate general-purpose vision-language models, specialized GUI agent models, and advanced agentic frameworks at both subtask and end-to-end levels. Our experiments reveal that while existing agents can complete many structured GUI subtasks, they still struggle with feedback-driven operations and long-horizon workflow execution. Overall, LabOSBench provides a reproducible, low-cost testbed for advancing computer-using agents toward scientific-instrument control.

09.
arXiv (CS.CV) 2026-06-16

Sex-based Network-Specific Differences in Connectomes: A Krakencoder-Based Analysis

This study examines how deficiencies in one brain connectome modality propagate to the other, using the Krakencoder as a simulation framework. Structural and functional connectomes from 702 healthy participants in the Human Connectome Project were analyzed, with the impact of each of the Yeo-7 functional networks assessed separately. Seven scenarios were considered, each involving the removal of a single network while the remaining networks were preserved. The resulting perturbations in cross-modal predictions were quantified using three complementary metrics: KL divergence on eigenvalue spectra, Frobenius norm, and Wasserstein distance. In addition, the persistence of sex-specific information within the predicted connectomes was evaluated. Across all metrics and both prediction directions, the Default Mode Network produced the largest perturbations, whereas the Somatomotor network yielded the smallest. Sex differences in network-level perturbation signatures were subtle, with the best result being an accuracy of 66.09% from connectomes predicted under network-removal conditions. In contrast, connectomes predicted from intact inputs achieved substantially higher sex classification accuracy, reaching up to 84.76%. These findings confirm that full predicted connectomes retain considerably more sex-discriminative information than perturbation-derived signatures alone.

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

Fine-tuning LLMs for Passive Depression Severity Estimation from AI Mental Health Dialogue

Depression is the leading cause of disability worldwide, and early detection of symptom change is essential for timely intervention. Validated instruments such as the Patient Health Questionnaire-9 (PHQ-9) support symptom monitoring at scale, but real-world completion rates are low, introducing response bias and systematic missingness. Passive approaches that infer severity from routinely generated data could close this gap. We address this by predicting PHQ-9 total scores directly from transcripts of conversations between users and an AI mental health application, requiring only conversation text and no additional clinical data. We fine-tune a Qwen3.5-27B backbone with a regression head, augment 3,111 ground-truth labels with pseudolabels generated by a reasoning model (Claude Opus) and iteratively trained intermediate models, for a combined dataset of 6,283 users. On a held-out test set of 842 users, our best model achieves MAE = 2.6, RMSE = 4.0, Pearson r = 0.80, and AUC = 0.91 at the PHQ-9 >= 10 clinical threshold. We also find AUC > 0.87 at every severity threshold from PHQ-9 >= 3 to PHQ-9 >= 24, demonstrating that the model captures depression severity across the full clinical spectrum. This work opens the door to passive, continuous symptom monitoring in AI mental health platforms, without requiring users to complete self-report measures.

11.
arXiv (CS.AI) 2026-06-16

TrustedARI: Towards Trust-Native Agentic Routing Infrastructure for Agentic AI

arXiv:2606.15822v1 Announce Type: new Abstract: AI agents increasingly access external models, tools, and services through Agentic Routing Infrastructure (ARI) to manage the overhead of heterogeneous interfaces and fragmented subscriptions. Yet, the architecture of ARI introduces fundamental trust risks: it obtains plaintext access to agent queries and service responses, while leaving agents unable to verify that their queries are routed to intended service providers or that requests and responses remain untampered. To address this problem, we present TrustedARI, the first trust-native agentic routing infrastructure for agentic AI. Architecturally, TrustedARI is built upon three core innovations: (i) an ARI-adapted three-party TLS handshake that enables the agent and ARI to jointly authenticate the service provider through role-specific distribution of TLS key materials; (ii) a privacy-preserving query-construction protocol that allows the agent and ARI to collaboratively construct well-formed queries without exposing their respective private inputs; and (iii) a verifiable billing protocol that supports fair usage-based settlement while preserving the integrity and confidentiality of service responses. We implemented and extensively evaluated a prototype of TrustedARI to validate its performance. Experiments confirm that TrustedARI is highly efficient: our ARI-adapted handshake protocol reduces communication overhead by 39.34% compared to the existing three-party TLS handshake. Furthermore, the privacy-preserving query-construction protocol imposes negligible overhead-averaging 0.19 seconds in computation time and 0.58 MB in communication costs-while the verifiable billing protocol speeds up proof generation by 28.20x. Crucially, TrustedARI is readily deployable without any modification to the service providers.

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

Let LLMs Judge Each Other: Multi-Agent Peer-Reviewed Reasoning for Medical Question Answering

Objective: To enhance the accuracy, interpretability, and robustness of large language models (LLMs) in medical question answering (MedQA). Method: We designed a multi-agent peer-reviewed reasoning method in which multiple LLM agents independently generate chain-of-thought reasoning with candidate answers, then act as peer reviewers to evaluate each other's reasoning for factual correctness and logical soundness. The highest-rated reasoning chain is selected to produce the final answer. Experiments were conducted with five state-of-the-art LLMs (Llama-3.1-8B, Qwen2.5-7B, Phi-4, DeepSeek-LLM-7B, GPT-oss-20B) on three benchmark datasets: HeadQA, MedQA-USMLE, and PubMedQA. Performance was compared against single-model chain-of-thought reasoning and chain-of-thought-based majority voting. Results: Peer-reviewed reasoning consistently outperformed both baselines. The best model combination achieved an average accuracy of 0.820 across datasets, exceeding the strongest single model (0.777) and majority voting ensembles (up to 0.789). The method also scaled effectively with more participating models, while peer assessments reliably distinguished high- from low-quality reasoning chains. Conclusion: The proposed multi-agent peer-reviewed reasoning method enables LLMs to act as both solvers and evaluators, yielding superior performance in MedQA. By emphasizing reasoning quality rather than answer agreement alone, this approach improves accuracy, interpretability, and robustness, offering a promising direction for trustworthy biomedical AI systems.

13.
arXiv (quant-ph) 2026-06-16

Light-induced nonadiabatic dissipative quantum dynamics of the Na2 molecule

arXiv:2606.15292v1 Announce Type: new Abstract: Strong light-matter coupling between molecules and optical or plasmonic cavity modes has emerged as a promising platform for advancing photonics, materials science, and chemistry. However, optical cavities and plasmonic resonators in particular are inherently lossy systems characterized by finite photon lifetimes. Accurate theoretical descriptions of molecular dynamics under strong coupling therefore require a proper treatment of cavity losses. In this work, we compare three theoretical approaches for modeling dissipative molecule-cavity dynamics within a realistic parameter regime: the Lindblad master equation, the stochastic Schrödinger equation, and the non-Hermitian Schrödinger equation. As an example, we consider the two lowest energy state of Na2 molecule coupled to a cavity mode and analyze the time evolution of the excited-state population and the mean photon number. Our results demonstrate that the stochastic Schrödinger equation provides an accurate and computationally efficient alternative to the Lindblad master equation, while the non-Hermitian Schrödinger approach is found to be applicable only within a limited range of conditions. Furthermore, we show that inclusion of molecular rotation leads to rotational-vibrational-photonic coupling and gives rise to pronounced nonadiabatic dynamics through light-induced conical intersections. These findings highlight the importance of both dissipation and rotational degrees of freedom for a realistic description of molecular dynamics in strongly coupled molecule-cavity systems.

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

Contrastive-Difference CKA Reveals Concept-Specific Structural Alignment Across Language Model Architectures

作者:

Do different LLM architectures encode high-level concepts in structurally compatible ways? We systematically characterize a geometric-functional universality dissociation: across multiple concept domains and architectural families, moderate geometric convergence coexists with near-perfect functional transfer. Using contrastive-difference CKA (CKA_Delta), a training-free diagnostic that computes kernel alignment on per-sample contrastive differences, we isolate concept-specific convergence from generic similarity – achieving significant discrimination where standard CKA cannot. The dissociation replicates across all six concept domains we test (five with p =70B models. We position CKA_Delta as a practical regime classifier and architectural outlier detector (Gemma: d = 1.08, AUC = 0.79) rather than an absolute transfer-accuracy predictor, providing a training-free diagnostic for cross-architecture concept monitoring.

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

Analytic Torsion and Spectral Gap Capture Persistent-Laplacian Performance

arXiv:2606.16990v1 Announce Type: new Abstract: While persistent Laplacians (PL) offer a richer geometric representation of data than persistent homology, utilizing their full eigenspectrum for learning tasks is often hampered by high dimensionality and the ``varying length'' problem across different filtration scales. We propose a compact spectral representation that distills the persistent Laplacian into three mathematically grounded invariants: Betti numbers, the spectral gap, and analytic torsion. Across benchmark datasets including MNIST, QM-3D, and SKEMPI WT, we demonstrate that this reduced feature space captures the essential predictive signal of the full spectrum, and in some cases outperforms it, while significantly reducing computational overhead and preventing the noise introduced by higher-frequency eigenvalues. Our results suggest that these invariants provide a principled, fixed-length interface between spectral geometry and topological learning.

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

Uncertainty Quality of VGGT: An Analysis on the DTU Benchmark Dataset

Visual Geometry Grounded Transformer (VGGT) has already attracted a great deal of attention in a short period of time, not least due to the Best Paper Award at CVPR-2025. Similar to DUSt3R and MASt3R, VGGT aims to bring about a paradigm shift by replacing established methods like bundle adjustment and feature matching with a simple, unified, feed-forward neural network that predicts camera poses, depth maps, and dense 3D structure directly from multiple images of a scene in a few seconds. A key aspect is its ability to process an arbitrary number of views consistently in a single forward pass without any post-processing or iterative optimization. For photogrammetry, this opens new possibilities for real-time, scalable, and accessible 3D reconstruction. In this context, not only high reconstruction accuracy but also high-quality uncertainty estimates are crucial, as they foster trust and enable robust quality assurance. This paper therefore investigates the quality of VGGT's uncertainty predictions. The analysis identifies an effective confidence threshold for filtering VGGT's raw output and demonstrates that enhancing uncertainty quality holds strong potential for improving the accuracy of its 3D reconstructions.

17.
arXiv (CS.AI) 2026-06-15

DiffusionBlocks: Block-wise Neural Network Training via Diffusion Interpretation

arXiv:2506.14202v4 Announce Type: replace-cross Abstract: End-to-end backpropagation requires storing activations throughout all layers, creating memory bottlenecks that limit model scalability. Existing block-wise training methods offer means to alleviate this problem, but they rely on ad-hoc local objectives and remain largely unexplored beyond classification tasks. We propose $DiffusionBlocks$, a principled framework for transforming transformer-based networks into genuinely independent trainable blocks that maintain competitive performance with end-to-end training. Our key insight leverages the fact that residual connections naturally correspond to updates in a dynamical system. With minimal modifications to this system, we can convert the updates to those of a denoising process, where each block can be learned independently by leveraging the score matching objective. This independence enables training with gradients for only one block at a time, thereby reducing memory requirements in proportion to the number of blocks. Our experiments on a range of transformer architectures (vision, diffusion, autoregressive, recurrent-depth, and masked diffusion) demonstrate that DiffusionBlocks training matches the performance of end-to-end training while enabling scalable block-wise training on practical tasks beyond small-scale classification. DiffusionBlocks provides a theoretically grounded approach that successfully scales to modern generative tasks across diverse architectures. Code is available at https://github.com/SakanaAI/DiffusionBlocks .

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

Relational Structural Causal Models

arXiv:2606.14892v1 Announce Type: new Abstract: An artificial intelligence must have a model of its environment that is causal, supporting reasoning about interventions and counterfactuals, and also combinatorial, supporting generalization to unseen combinations of objects. In this work, we formally study when and how such a model can be learned. We develop relational structural causal models, extending structural causal models (Pearl 2009) to settings where objects and their relations vary. First, we show how answers to not only causal but also observational queries about unseen combinations of objects can not be identified without further assumptions. To enable such identification–including in the presence of unobserved confounding–we define relational causal graphs and derive symbolic identification criteria. Finally, we propose relational neural causal models, a provably correct approach that outperforms non-relational baselines on simulated traffic scenes with varying cars, signals, and pedestrians.

19.
medRxiv (Medicine) 2026-06-18

Hospital staff views on the visibility, role and impact of Acute Learning Disability Liaison Services in Wales: a service evaluation

People with a learning disability experience marked health inequalities. In Wales, Acute Learning Disability Liaison Services (ALDLS) are delivered by specialised learning disability services, and all roles within them are undertaken by Learning Disability Liaison Nurses (LDLN). These services aim to enable access to, and delivery of, secondary care by supporting reasonable adjustments, facilitating communication, and coordinating care for people with learning disability during hospital encounters. However, independent evidence of the impact of ALDLS on patient care remains limited. This evaluation tries to address this evidence gap by examining hospital staff perceptions of the visibility, role, and impact of ALDLS across Welsh Health Boards, with the aim of informing service design and development and improving secondary care access and care for people with learning disability. The service evaluation used a qualitative approach involving interviews and a focus group with hospital staff across the seven Welsh Health Boards who had experience working with or interacting with ALDLS staff to care for patients with learning disability. Findings cover six key areas including i) visibility and delivery of ALDLS, ii) Barriers and challenges to effective ALDLS delivery, iii) Enablers of effective ALDLS delivery, iv) Positive impacts for patients with learning disability, v) Negative impacts and unintended consequences when the service is absent or limited, and vi) Participants recommendations for future improvements of ALDLS. To synthesise the findings, we developed an overview diagram, which illustrates how ALDLS may influence care quality in acute hospitals. The overview places the liaison service at the centre, showing how organisational enablers and barriers shape its delivery, and how its core functions support improvements in safety, timeliness, effectiveness, efficiency, equity, and patient-centred care. From the findings we have identified recommendations for practice and policy. These include that ALDLS should be recognised as a core, safety-critical component of acute hospital care for people with a learning disability, rather than an optional add-on. In practice, services should be more visibly embedded within routine pathways, with consistent site-based presence, clear referral criteria, early identification through electronic flagging and notification systems, and routine involvement in multidisciplinary planning for complex admissions and procedures. At policy level, ALDLS provision should be recognised within equality and patient safety frameworks as an essential service requiring sustained investment, national minimum configuration standards, adequate staffing, and better-integrated digital systems to support continuity, equitable access, and person-centred care.

20.
Nature Biotechnology 2026-06-05

Multiplexed, precise genome engineering in monocots with twin prime editing systems

作者:

Simultaneously introducing diverse genomic edits remains a challenge in crop genome engineering. Here we describe a twin prime editing-based knockout (TKO) system that installs stop codon clusters (SCCs) for precise translational termination with minimal in-frame mutations. TKO achieves knockout efficiencies of up to 70.5%, 58.6% and 75.1% in rice, maize and wheat protoplasts, respectively, and produces heritable knockout alleles in 96.8% of regenerated rice plants. In hexaploid wheat, TKO outperforms Cas9 4.2-fold in generating triple-homolog knockouts, largely by reducing in-frame mutations. Orthogonal TKO editors with sequence-divergent SCCs enable simultaneous knockout of up to ten genes without cross-interference. Integration of TKO with conventional prime editing establishes TRIM1 (TKO editor-enabled gene rupture and development of integrated multitype genome modification system) for simultaneous knockout and precise editing, achieving a 22.8% coediting of four genes in rice. TRIM2 extends this capacity to kilobase-scale modifications through a prime editor–recombinase system, enabling a 4.9-kb insertion (1.2% efficiency) and gene knockout (up to 79.8%) in protoplasts. Plant genome editing is multiplexed with twin prime editing.

21.
arXiv (CS.AI) 2026-06-17

Statistical Foundations of LLM-based A/B Testing: A Surrogacy Framework for Human Causal Inference

arXiv:2606.17165v1 Announce Type: cross Abstract: Organizations and researchers show increasing interest in using large language models (LLMs) in place of human participants in A/B tests, in the hope of experimenting faster and at lower cost. We study when a treatment effect estimated on LLM outcomes recovers the effect that would have been measured on the human population of interest. Distributional equivalence between LLM and human outcomes would make any standard estimator valid but is unrealistic. We therefore develop a statistical framework that adapts surrogate endpoint theory to LLMs. The framework shows that calibrating LLM outcomes to human outcomes identifies the average treatment effect under surrogacy and comparability conditions that are jointly weaker than distributional equivalence. When these conditions fail, the effect of interest is only partially identified, and we provide diagnostics that can falsify surrogacy on historical experiments together with a bound on the worst-case bias from limited overlap. We further show that the stochasticity inherent to LLMs introduces both bias and variance, but using an average of multiple draws as the surrogate mitigates both. We illustrate the methods and theory in simulations and an application to A/B tests on Upworthy headlines. A central takeaway from our work is that the validity of LLM outcomes as surrogates can only be falsified for past treatments and never verified for new ones, so human experiments remain indispensable for novel interventions. We discuss the role of LLM choice, prompting, and temperature as design variables, and how to size human experiments for validation.

22.
arXiv (CS.CV) 2026-06-18

SMART: A Flexible, Interpretable, and Scalable Spatio-temporal Brain Atlas from High-Resolution Imaging Data

We introduce SMART, a framework for learning a flexible, interpretable, and scalable spatio-temporal brain atlas from longitudinal high-resolution 3D medical images. Existing approaches to spatio-temporal atlas construction rely on black-box generative models that lack flexibility, limit interpretability, and struggle to scale to high-dimensional data. SMART addresses these challenges by learning a continuous disease-time atlas that decouples global group-wise disease dynamics from their patient-specific anatomical manifestation. Guided by anatomically inspired priors, SMART models interpretable global trajectories of regional progression along a shared disease timeline through region-specific differential equations. Global trajectories are further personalized to individual anatomies via dense diffeomorphic displacements parameterized by a flexible and scalable multi-scale Neural Cellular Automata. Evaluated on five longitudinal MRI datasets in Alzheimer's disease (ADNI-1/GO/2, OASIS-3, AIBL; > 1,300 subjects), SMART produces anatomically meaningful predictions of disease progression and achieves state-of-the-art forecasting accuracy and improved temporal consistency over adversarial and diffusion baselines. Our approach establishes a new paradigm for flexible, interpretable, and scalable modeling of spatio-temporal change in high-dimensional medical image time-series.

23.
Nature (Science) 2026-06-10

Diverse binding poses of agonistic neurotoxins on human Na<sub>v</sub>1.6

作者:

Voltage-gated sodium (Nav) channels are key targets of various venomous toxins. Deciphering the binding poses and mechanisms of action of representative toxins will help to dissect the functional mechanism of the channels and facilitate therapeutic development targeting Nav channels1,2. Here we present cryo-electron microscopy&nbsp;(cryo-EM) structures of distinct binding poses of three agonistic peptide toxins on the human Nav1.6–β1 channel complex. The globular β-scorpion toxin Cn2 nestles between the extracellular segment of voltage-sensing domain (VSD)&nbsp;in the second repeat of the Nav1.6 core α-unit (VSDII) and the pore extracellular loops in the third repeat of the Nav1.6 core α-unit (ECLIII), where it is stabilized by interactions with both protein regions and the branched N1372-glycan. Cone&nbsp;snail ι-conotoxin RXIA adopts an elongated conformation, spanning VSDI and VSDIV to wrap around the shoulder of the pore domain (PD). The bullet&nbsp;ant-derived toxin δ-paraponeritoxin-Pc1a exists as a transmembrane helix that stands between VSDII and PDIII. Our findings, corroborated by functional characterizations, illustrate the diversity in peptide toxin binding poses and mechanisms of action, link stabilization of the up state of VSDI or VSDII to channel activation, and provide clues to the rational design of selective Nav channel modulators. Structures of the distinct binding poses of three agonistic peptide toxins—bullet-ant-derived toxin δ-paraponeritoxin-Pc1a, cone&nbsp;snail ι-conotoxin RXIA and the globular β-scorpion toxin Cn2—on the human Nav1.6–β1 channel complex illustrate a diversity in binding poses and mechanisms of action.

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

Continual Quadruped Robots Coordination via Semantic Skill Discovery

arXiv:2606.08102v2 Announce Type: replace-cross Abstract: Multi-quadruped coordination has attracted increasing attention due to its enhanced payload capacity, broader contact coverage, and improved adaptability to challenging tasks. Existing methods for multi-quadruped manipulation typically focus on predefined or closed task families, often relying on multi-agent reinforcement learning (MARL) to train task-specific coordination policies. However, such methods struggle in open-ended continual learning settings, where tasks arrive sequentially and robots are expected to acquire new coordination skills while reusing previously learned ones without catastrophic forgetting. To address this challenge, we propose Conquer, a semantic skill-library framework that formulates continual multi-quadruped coordination as a retrieve-adapt-update process. First, to accommodate varying team sizes across tasks, we design a team-structured Self-Allies-Goal (SAG) backbone that supports variable-cardinality robot teams by explicitly modeling each robot's own state, teammate context, and task goal. For each incoming task, Conquer constructs a task-level semantic descriptor from pre-execution information and retrieves a relevant skill from the library for adaptation. After successful execution, Conquer updates the skill library by extracting trajectory-level semantic descriptors and organizing them according to semantic distance, thereby enabling continual skill accumulation and cross-task knowledge transfer. Simulation experiments show that Conquer achieves a final average success rate of 95.6%, demonstrating strong forward transfer and negligible catastrophic forgetting. Real-world rollouts on Unitree Go2 teams further validate the deployment feasibility of Conquer for practical multi-quadruped coordination. Simulation and real-robot demonstration videos are available at: https://conquer-project.pages.dev/.

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arXiv (CS.AI) 2026-06-18

Clin-JEPA: A Multi-Phase Co-Training Framework for Joint-Embedding Predictive Pretraining on EHR Patient Trajectories

arXiv:2605.10840v3 Announce Type: replace-cross Abstract: We present Clin-JEPA, a multi-phase co-training framework for joint-embedding predictive (JEPA) pretraining on EHR patient trajectories. JEPA architectures have enabled latent-space planning in robotics and high-quality representation learning in vision, but extending the paradigm to EHR data – to obtain a single backbone that simultaneously forecasts patient trajectories and serves diverse downstream risk-prediction tasks without per-task fine-tuning – remains an open challenge. Existing JEPA frameworks either discard the predictor after pretraining (I-JEPA, V-JEPA) or train it on a frozen pretrained encoder (V-JEPA 2-AC), leaving the encoder unaware of the rollout signal that the retained predictor must use at inference; co-training the encoder and predictor under a shared JEPA prediction objective would supply this grounding, but naïve co-training is unstable, with representation collapse and online/target drift causing autoregressive rollout to diverge. Clin-JEPA's five-phase pretraining curriculum – predictor warmup, joint refinement, EMA target alignment, hard sync, and predictor finalization – addresses each failure mode by phase, stably co-training a Qwen3-8B-based encoder and a 92M-parameter latent trajectory predictor. On MIMIC-IV ICU data, three independent evaluations support the framework: (1) latent $\ell_1$ rollout drift uniquely converges ($-$15.7%) over 48-hour horizons while baselines and ablations diverge (+3% to +4951%); (2) the encoder learns a clinically discriminative latent geometry (deteriorating-patient cohorts displace 4.83$\times$ further than stable patients in latent space, vs $\leq$2.62$\times$ for baseline encoders); (3) a single backbone outperforms strong tabular and sequence baselines on multi-task downstream evaluation. Clin-JEPA achieves mean AUROC 0.851 on ICareFM EEP and 0.883 on 8 binary risk tasks (+0.038 and +0.041 vs baseline average).