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01.
arXiv (CS.AI) 2026-06-11

GPO: Learning from Critical Steps to Improve LLM Reasoning

arXiv:2509.16456v3 Announce Type: replace Abstract: Large language models (LLMs) are increasingly used in various domains, showing impressive potential on different tasks. Recently, reasoning LLMs have been proposed to improve the reasoning or thinking capabilities of LLMs to solve complex problems. Despite the promising results of reasoning LLMs, enhancing the multi-step reasoning capabilities of LLMs still remains a significant challenge. While existing optimization methods have advanced the LLM reasoning capabilities, they often treat reasoning trajectories as a whole, without considering the underlying critical steps within the trajectory. In this paper, we introduce Guided Pivotal Optimization (GPO), a novel fine-tuning strategy that dives into the reasoning process to enable more effective improvements. GPO first identifies the `critical step' within a reasoning trajectory - a point that the model must carefully proceed to succeed at the problem. We locate the critical step by estimating the advantage function. GPO then resets the policy to the critical step, samples the new rollout and prioritizes the learning process on those rollouts. This focus allows the model to learn more effectively from pivotal moments within the reasoning process to improve the reasoning performance. We demonstrate that GPO is a general strategy that can be integrated with various optimization methods to improve reasoning performance. Besides theoretical analysis, our experiments across challenging reasoning benchmarks show that GPO can consistently and significantly enhance the performance of existing optimization methods, showcasing its effectiveness and generalizability in improving LLM reasoning by concentrating on pivotal moments within the generation process.

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

Ultrafast On-chip Online Learning via Spline Locality in Kolmogorov-Arnold Networks

arXiv:2602.02056v3 Announce Type: replace-cross Abstract: Ultrafast online learning is essential for high-frequency systems, such as controls for quantum computing and nuclear fusion, where adaptation must occur on sub-microsecond timescales. Meeting these requirements demands low-latency, fixed-precision computation under strict memory constraints, a regime in which conventional Multi-Layer Perceptrons (MLPs) are both inefficient and numerically unstable. We identify key properties of Kolmogorov-Arnold Networks (KANs) that align with these constraints. Specifically, we show that: (i) KAN updates exploiting B-spline locality are sparse, enabling superior on-chip resource scaling, and (ii) KANs are inherently robust to fixed-point quantization. By implementing fixed-point online training on Field-Programmable Gate Arrays (FPGAs), a representative platform for on-chip computation, we demonstrate that KAN-based online learners are significantly more efficient and expressive than MLPs across a range of low-latency and resource-constrained tasks. To our knowledge, this work is the first to demonstrate model-free online learning at sub-microsecond latencies.

03.
arXiv (quant-ph) 2026-06-11

TensorKit.jl: A Julia package for large-scale tensor computations, with a hint of category theory

arXiv:2508.10076v2 Announce Type: replace-cross Abstract: TensorKit$.$jl is a Julia-based software package for tensor computations, especially focusing on tensors with internal symmetries. This paper introduces the design philosophy, core functionalities, and distinctive features, including how to handle abelian, non-abelian, and anyonic symmetries through the ``TensorMap'' type. We highlight the software's flexibility, performance, and its capability to extend to new tensor types and symmetries, illustrating its practical applications through select case studies.

04.
arXiv (CS.AI) 2026-06-12

From Verdict to Process: Agentic Reinforcement Learning for Multi-Stage Fact Verification

arXiv:2606.13262v1 Announce Type: new Abstract: Recent approaches combining Large Language Models (LLMs) with retrieval-augmented reasoning have shown promise for automated fact verification. To process complex claims, these verification pipelines typically execute multi-stage workflows that coordinate tightly coupled modules, including claim decomposition, evidence gathering, and verdict prediction. However, existing methods optimize individual stages in isolation or rely on fixed heuristics, which limits adaptive coordination among stages and can lead to suboptimal outcomes. In this work, we propose ProFact, an agentic reinforcement learning framework for end-to-end optimization of multi-stage fact verification trajectories. ProFact trains a unified policy to coordinate claim decomposition, evidence seeking, answer generation, and verdict prediction. To address the sparse and delayed supervision provided by final veracity labels, ProFact introduces process-aware rewards that provide stage-level learning signals throughout the verification process. Empirical evaluation shows that ProFact consistently outperforms strong baselines in both verification performance and inference efficiency. These results highlight the effectiveness of process-aware trajectory optimization for multi-stage fact verification.

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

HairPort: In-context 3D-aware Hair Import and Transfer for Images

Transferring hairstyles between images is an important but challenging task in computer graphics, computer vision, and visual effects. It enables users to explore new looks without physically altering their hair, with applications in virtual try-on systems, augmented reality, and entertainment. Most prior works operate best under small pose gaps, and they fall short under large viewpoint and scale differences, where missing hair content must be synthesized rather than transferred. We propose HairPort, a 3D-aware hairstyle transfer framework that attempts to solve these issues by explicitly separating hair removal from transfer and enforcing geometric consistency before synthesis. We introduce a Bald Converter, which produces realistic bald versions of faces through LoRA-based in-context adaptation of FLUX.1 Kontext. To train our Bald Converter, we introduce a new dataset, Baldy, containing 6,000 paired bald and original images across diverse identities and conditions. We also use a 3D-Aware Transfer Pipeline that reconstructs and re-renders the reference hairstyle from the target viewpoint before compositing it onto the source image. Being 3D aware, our method supports large pose and scale discrepancies between the source and target. Finally, a conditional flow-matching generator synthesizes the transferred result from the bald source and geometry-aligned reference guidance. Together, our method enables accurate, pose-consistent, and identity-preserving hairstyle transfer, outperforming existing methods both qualitatively and quantitatively.

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

MacrOData: New Benchmarks of Thousands of Datasets for Tabular Outlier Detection

arXiv:2602.09329v3 Announce Type: replace Abstract: Quality benchmarks are essential for fairly and accurately tracking scientific progress and enabling practitioners to make informed methodological choices. Outlier detection (OD) on tabular data underpins numerous real-world applications, yet existing OD benchmarks remain limited. The prominent OD benchmark AdBench is the de facto standard in the literature, yet comprises only 57 datasets. In addition to other shortcomings discussed in this work, its small scale severely restricts diversity and statistical power. We introduce MacrOData, a large-scale benchmark suite for tabular OD comprising three carefully curated components: OddBench, with 790 datasets containing real-world semantic anomalies; OvrBench, with 856 datasets featuring real-world statistical outliers; and SynBench, with 800 synthetically generated datasets spanning diverse data priors and outlier archetypes. Owing to its scale and diversity, MacrOData enables comprehensive and statistically robust evaluation of tabular OD methods. Our benchmarks further satisfy several key desiderata: We provide standardized train/test splits for all datasets, public/private benchmark partitions with held-out test labels for the latter reserved toward an online leaderboard, and annotate our datasets with semantic metadata. We conduct extensive experiments across all benchmarks, evaluating a broad range of OD methods comprising classical, deep, and foundation models, over diverse hyperparameter configurations. We report detailed empirical findings, practical guidelines, as well as individual performances as references for future research. All benchmarks containing 2,446 datasets combined are open-sourced, along with a publicly accessible leaderboard hosted at https://huggingface.co/MacrOData-CMU.

07.
arXiv (quant-ph) 2026-06-11

Polarization-Resolved Photon Statistics of Cavity Quantum Materials

arXiv:2606.11550v1 Announce Type: cross Abstract: By forming hybrid light-matter states, optical cavities offer a route for engineering material properties, however, unambiguously probing the effects of light-matter coupling remains difficult. Here, we show that the polarization-resolved statistics of photons transmitted through a cavity, measurable via $g^{(2)}$, provide one such diagnostic. By relating $g^{(2)}$ to matter correlation functions such as the Raman structure factor, we link photon bunching and antibunching to material properties. By applying this method to the stripy-to-antiferromagnetic transition in the Kitaev-Heisenberg spin model, we find that polarization-dependent patterns of bunching and antibunching encode the magnetic point-group symmetries of each phase and characterize the behavior at the phase boundary. Finally, we predict measuring $g^{(2)}$ for output photon pairs polarized orthogonal to the input field will isolate higher-order light-matter scattering processes that probe higher-order material correlations.

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

Automated 3D Kinematic Monitoring for Circadian Activity and Anomaly Detection in Juvenile Fish

Precision aquaculture faces a "phenotyping bottleneck" in tracking high-resolution behavioral traits, as conventional methods cannot quantify instantaneous three-dimensional (3D) physical exertion. To address this, we present a high-throughput 3D behavioral phenotyping framework integrating deep learning object detection with binocular stereo vision for real-time monitoring of juvenile tilapia in high-density environments. The system automates non-contact body length estimation and reconstructs 3D swimming trajectories from absolute spatial coordinates. By eliminating 2D perspective distortions, this approach precisely quantifies 3D velocity and acceleration, marking the first estimation of true physical swimming speeds in free-roaming juveniles. Results show the framework successfully establishes circadian locomotor baselines, serving as an early warning system for physiological stress and providing an objective metric for fish vitality.

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

Intelligent Skin Cancer Detection Using a Multispectral Metasurface and a Hybrid

Skin cancer is among the most prevalent malignancies worldwiAdbe satnradcitts early detection is essential for improving patient survival and reducing treatment costs Conventional dermoscopic and visual imaging techniques are primarily limited to the visible spectrum and often fail to capture subtle spectral signatures associated with early stage malignancies This study proposes an innovative framework that integrates a multispectral metasurface for imaging with a hybrid deep learning architecture based on Convolutional Neural Networks and Vision Transformers The designed metasurface enables noninvasive acquisition of rich spectral information highly sensitive to tissue alterations while the hybrid CNN ViT model simultaneously extracts local and global features to robustly classify skin lesions Simulation-based evaluations demonstrate that the proposed method achieves approximately 98 accuracy 95 percentages sensitivity and 99 perentage specificity surpassing conventional RGB-based and single-architecture approaches Qualitative analyses using attention maps reveal that the model focuses on clinically relevant lesion regions improving interpretability Overall the results indicate that combining metasurface based multispectral imaging with hybrid deep learning can introduce a new generation of diagnostic tools in dermatology and pave the way for portable fast and highly accurate clinical systems

10.
arXiv (CS.LG) 2026-06-11

Mechanisms of Introspective Awareness

arXiv:2603.21396v5 Announce Type: replace Abstract: Recent work has shown that LLMs can sometimes detect when steering vectors are injected into their residual stream and identify the injected concept – a phenomenon termed "introspective awareness." We investigate the mechanisms underlying this capability in open-weights models. First, we find that it is behaviorally robust: models detect injected steering vectors at moderate rates with 0% false positives across diverse prompts and dialogue formats. Notably, this capability emerges specifically from post-training; we show that preference optimization algorithms like DPO can elicit it, but standard supervised finetuning does not. We provide evidence that detection cannot be explained by simple linear association between certain steering vectors and directions promoting affirmative responses. We trace the detection mechanism to a two-stage circuit in which "evidence carrier" features in early post-injection layers detect perturbations monotonically along diverse directions, suppressing downstream "gate" features that implement a default negative response. This circuit is absent in base models and robust to refusal ablation. Identification of injected concepts relies on largely distinct later-layer mechanisms that only weakly overlap with those involved in detection. Finally, we show that introspective capability is substantially underelicited: ablating refusal directions improves detection by +53%, and a trained bias vector improves it by +75% on held-out concepts, both without meaningfully increasing false positives. Our results suggest that this introspective awareness of injected concepts is robust and mechanistically nontrivial, and could be substantially amplified in future models. Code: https://github.com/safety-research/introspection-mechanisms.

11.
arXiv (CS.AI) 2026-06-18

Better Adherence, Richer Context: A Field Evaluation of LLM-Powered Conversational Voice Diaries for Sleep

arXiv:2606.18596v1 Announce Type: cross Abstract: Sleep diaries are central to behavioral sleep medicine and cognitive behavioral therapy for insomnia, yet daily completion is difficult to sustain, and static forms often provide limited context for interpreting night-to-night sleep variation. We designed an LLM-powered conversational voice diary that delivers clinically grounded morning and evening sleep diary questions through proactive smart-speaker prompts, structured conversational intake, and adaptive follow-up dialogue. We evaluated the system in a four-week between-subjects field study with 30 university students, comparing it with a text-based mobile diary using matched diary items, reporting windows, and reminder intervals. Compared with the text-based diary, the conversational voice diary showed higher adherence and elicited more detailed contextual self-report about routines, stressors, environmental conditions, and other sleep-related factors. Participants also described the voice diary as easier to integrate into daily routines, despite longer perceived completion time. However, voice-based conversational intake produced lower completeness for some structured diary fields, revealing a trade-off between expressive richness and structured precision. These findings show both the promise and the challenge of using LLM-powered conversational voice assistants for longitudinal health self-report.

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

Benchmarking AI Agents for Addressing Scientific Challenges Across Scales

arXiv:2606.12736v1 Announce Type: new Abstract: AI agents are increasingly being developed to accelerate scientific discovery, yet their practical capabilities in real research settings remain poorly understood. Existing benchmarks for AI agents rarely capture the complexity, heterogeneity, and extended reasoning required by scientific work, whereas benchmarks for scientific tasks often reduce research to static, direct problems and provide limited support for interactive evaluation. Here, we introduce SciAgentArena, a systematic benchmark for evaluating AI agents in real-world scientific research scenarios drawn from emerging needs across multiple domains. SciAgentArena comprises approximately 200 tasks with stepwise verification and an interactive, agent-agnostic environment for assessing diverse AI agents. Using this benchmark, we find that current agents can contribute effectively to well-specified data-analysis workflows, particularly when the task structure and evaluation criteria are clear. However, their performance remains uneven across scientific contexts: agents struggle to generate genuinely novel insights, sustain self-directed exploration, and formulate robust solutions for open-ended research questions. We further characterize common failure modes across agents and identify opportunities for improving their reliability, autonomy, and scientific reasoning. Together, SciAgentArena provides a practical framework for measuring progress in AI agents for science and for guiding the design of future agents capable of addressing complex scientific challenges. Full codes, tasks, and datasets can be accessed via this link: https://sciagentarena.github.io/.

13.
medRxiv (Medicine) 2026-06-16

Re-evaluating the Cross-Sectional Prevalence of Severe Age-Related Hearing Loss Using Extreme Value Statistics

作者:

Standard demographic models of age-related hearing loss (presbycusis) predominantly utilize symmetric functions, such as log-normal distributions for age-binned thresholds and 4-parameter logistic curves for prevalence estimates. While these models capture early-to-moderate degradation effectively, they structurally struggle to characterize the heavy tails associated with severe clinical impairment. In this study, we present a statistical critique using a secondary analysis of the historical Medical Research Council (MRC) National Study of Hearing (1980-1986) dataset. By applying Generalized Extreme Value (GEV) distribution theory, we demonstrate that as severity increases, the underlying statistical geometry of hearing loss shifts. The asymmetric, heavy-tailed GEV distribution provides a parsimonious description of severe impairment, requiring fewer parameters than standard symmetric models. However, we explicitly acknowledge that utilizing static population data to infer progression introduces an ecological fallacy. Furthermore, the dataset's historical nature embeds unquantified generational cohort effects. We conclude that while extreme value statistics offer a compelling mathematical framework for modeling the variance of severe presbycusis, true longitudinal datasets are required to isolate physiological degradation from historical cohort variance.

14.
arXiv (CS.LG) 2026-06-18

Unraveling the Mechanism of Drug Binding to SARS-CoV-2 RNA Pseudoknot with Thermodynamics-Driven Machine Learning

arXiv:2604.14906v3 Announce Type: replace-cross Abstract: The pseudoknot secondary structure in SARS-CoV-2 RNA is essential for regulating protein synthesis through $-$1 programmed ribosomal frameshifting ($-1$ PRF), a mechanism that allows the virus to generate both structural and non-structural proteins from overlapping reading frames. This pseudoknot exhibits both threaded and unthreaded long-lived topologies. The influence of ligand binding on its folding is a process critical for the development of $-$1 PRF small-molecule inhibitors. Understanding this process through unbiased molecular dynamics (MD) simulations can be facilitated by introducing collective variables (CVs) that capture the corresponding slowest dynamical modes. Here, we use spectral map (SM), a thermodynamics-driven machine learning technique, to learn such CVs directly from all-atom MD trajectories of the SARS-CoV-2 RNA pseudoknot in complex with the $-$1 PRF inhibitor merafloxacin and its two structural analogs in neutral and ionized forms. Free-energy landscapes (FELs) derived from the learned CVs indicate that ligand-induced destabilization is topology-selective. In the threaded pseudoknot, the inhibitors destabilize the S2 stem, while in the unthreaded pseudoknot, destabilization occurs in the S1 and S3 stems. Furthermore, the extent to which each ligand reshapes the FEL matches experimentally reported antiviral potency, whereas the protonation state qualitatively alters dynamics within the same RNA topology. Overall, our results show how pseudoknot topology, ligand type, and protonation state collectively influence the slow conformational dynamics of viral RNA and establish physiological protonation as a critical factor for modeling RNA-targeted drug action.

15.
arXiv (math.PR) 2026-06-12

Branching-selection particle systems and inverse first passage problems

作者:

arXiv:2606.13487v1 Announce Type: new Abstract: A generalised inverse first passage problem asks whether, given a probability measure $p$ on $[0,\infty]$, one can find a boundary $b:[0,\infty]\to \mathbb{R}$ such that the stopping time:\[\tau:=\inf\left\{t:\Lambda\int_0^t \omega(W_s-b(s))ds \geq U\right\}\] has distribution $p$, where $U\sim Exp(1)$, $\Lambda\in(0,\infty)$ and $\omega$ is a monotonic decreasing function. We construct a branching-selection particle system whose hydrodynamic limit is governed by a free boundary problem and connect this to the generalised inverse first passage problem. In the $N$-particle system, particles move as independent Brownian motions, branch at a prescribed rate, and are removed at a rate proportional to their location relative to a position $b^N(t)$ which is a function of the empirical distribution. We identify the limit of $b^N$ as the solution of the inverse first passage problem.

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

RAGPPI: RAG Benchmark for Protein-Protein Interactions in Drug Discovery

Retrieving the biological impacts of protein-protein interactions (PPIs) is essential for target identification (Target ID) in drug development. Given the vast number of proteins involved, this process remains time-consuming and challenging. Large Language Models (LLMs) and Retrieval-Augmented Generation (RAG) frameworks have supported Target ID; however, no benchmark currently exists for identifying the biological impacts of PPIs. To bridge this gap, we introduce the RAG Benchmark for PPIs (RAGPPI), a factual question-answer benchmark of 4,420 question-answer pairs that focus on the potential biological impacts of PPIs. Through interviews with experts, we identified criteria for a benchmark dataset, such as a type of QA and source. We built a gold-standard dataset (500 QA pairs) through expert-driven data annotation. We developed an ensemble auto-evaluation LLM that incorporates expert labeling characteristics, average fact-abstract similarity (F1), and low-similarity fact counts (F2), enabling the construction of a silver-standard dataset (3,720 QA pairs). We are committed to maintaining RAGPPI as a resource to support the research community in advancing RAG systems for drug discovery QA solutions.

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

DYNA-PRUNER: Input-Adaptive Data-Model Co-Pruning for Efficient and Scalable Spatio-Temporal Media Prediction

Spatio-temporal prediction supports radar/satellite nowcasting and city-scale traffic monitoring, but modern models are often too expensive for real-time deployment. This stems from a mismatch between dense computation and strong input-dependent redundancy (e.g., calm seas or clear skies). To enable automated, resource-aware architecture optimization in scalable media analysis, we propose Dyna-Pruner, an end-to-end framework for input-dependent co-pruning of data and model structure. A shared-importance synchronization mechanism generates coupled masks that prune redundant regions and their corresponding computational units (e.g., convolutional filters), yielding per-sample sparse sub-networks at inference time. Experiments on WeatherBench, SEVIR, and TaxiBJ show seamless integration with CNN, RNN, and Transformer backbones, reducing FLOPs by up to $70\%$ and achieving a $2.5\times$ speedup on NVIDIA Jetson AGX Orin with negligible accuracy loss ($

18.
PLOS Computational Biology 2026-06-16

Evolution and the ultimatum game: An agent-based model with interbirth intervals and population structure

by Jeffrey C. Schank, Matt L. Miller The ultimatum game (UG) is widely used to study mutually beneficial exchanges, fairness, and prosocial behavior across different societies. However, human behavior in UG experiments does not align with the game-theoretical prediction that proposers should offer the least positive amount and responders should accept such offers. Instead, proposers make generous offers that are greater than the minimum responders are willing to accept, resulting in generous offers with wide offer-acceptance gaps. Numerous evolutionary models of the UG have been created and studied to explain human behavior, particularly generous offers made in UG experiments. These models have recently faced criticism for lacking biological realism and not adequately explaining the data. Here, we present an agent-based model inspired by our hunter-gatherer ancestors and with a biologically more realistic selection process. We assume that (1) agents exist in group-structured and group-clustered populations, where reproduction (2) depends on resource accumulation, but (3) is limited by interbirth intervals. We ran simulations to assess whether this biologically more realistic model evolves patterns of behavior consistent with patterns in the data from meta-analyses of human behavior in the UG. For the proposed model, we show that generous offers robustly evolve, as well as the difficult-to-explain offer-acceptance gaps, only in group-structured populations with interbirth intervals. We demonstrate that these results are robust and may help explain variation in data across societies. We discuss how interbirth intervals interact with group structure to modulate offer and rejection costs, favoring the evolution of generous offers, offer-acceptance gaps, and other patterns in the data on human behavior in the UG. We also discuss why weak selection and/or high mutation rate models cannot explain all the patterns in UG experimental data. We discuss biological realism and conclude that group structure and interbirth intervals may be essential for explaining prosocial behavior across societies.

19.
arXiv (CS.CV) 2026-06-11

Task-Aware Structured Memory for Dynamic Multi-modal In-Context Learning

Multi-modal large language models (MLLMs) depend on in-context learning (ICL) for rapid task adaptation, but their scalability is severely limited by finite context windows and the growing cost of key-value (KV) caches in long multi-modal sequences. Existing memory compression approaches typically rely on rigid token removal or sample-dependent importance estimation, which introduces bias, disrupts semantic structure, particularly for visual representations, and yields static memories that cannot adapt to new queries. We introduce TASM (Task-Aware Structured Memory), a training-free framework that addresses these limitations through task-aware, structure-preserving, and dynamically accessible memory construction. TASM employs task-vector guided compression to replace sample-specific signals with a task-level direction that captures shared relevance across demonstrations. To preserve the underlying manifold, it applies semantics-aware token merging via bipartite graph matching, aggregating tokens without destructive pruning. Finally, TASM structures memory into a hierarchy comprising a compact Core Memory and a Latent Bank, facilitating query-adaptive dynamic retrieval. Evaluations confirm TASM maintains high performance under heavy compression, effectively balancing efficiency with adaptability.

20.
bioRxiv (Bioinfo) 2026-06-18

Deciphering shared and divergent tissue architectures from cross-species spatial transcriptomics

作者:

The integration of spatial transcriptomics (ST) data across species is essential for cross-species and translational studies, but remains challenging due to molecular divergence and anatomical differences between organisms. We present STACAME, a graph attention autoencoder-based framework to decipher shared and divergent tissue architectures from cross-species ST data by explicitly modeling both orthologous and species-specific genes. STACAME aligns ST slices in a spatially aware manner, identifies homologous and species-specific domains, and enables a suite of downstream comparative analyses. We demonstrate its utility by integrating ST datasets from diverse tissues, including hippocampus, isocortex, embryo, breast, liver, and cerebellum, across multiple species such as human, macaque, marmoset, mouse, and zebrafish. STACAME supports cross-species spatial domain alignment, the detection of shared and divergent spatially variable genes, development alignment and comparison, and the 3D integration of tissue architecture. This flexible approach facilitates the translation of findings from model organisms to humans, providing a unified computational platform for cross-species spatial transcriptomics.

21.
Nature Biotechnology 2026-06-23

Efficient generation of epitope-targeted antibodies with Germinal

Obtaining antibodies to specific protein targets is a widely important yet experimentally laborious process. Meanwhile, computational methods for antibody design have been limited by low success rates that require resource-intensive screening. Here we introduce Germinal, a broadly enabling generative pipeline that designs antibodies against specific epitopes with nanomolar binding affinities while requiring only low-n experimental testing. Our method co-optimizes antibody structure and sequence by integrating a structure predictor with an antibody-specific protein language model to perform de novo design of functional complementarity-determining regions onto a user-specified structural framework. When tested against four diverse protein targets, Germinal designed functional antibodies across all targets and binder formats, testing only 43–101 designs for each antigen. Validated designs also exhibited robust expression in mammalian cells and high sequence and structural novelty. We provide open-source code and full computational and experimental protocols to facilitate wide adoption. Germinal achieves epitope-targeted, de novo complementarity-determining region design with high experimental success rates.

22.
Science (Express) 2026-04-23

Structural N- and O-glycans revealed by high-resolution cryo-EM analysis of tubular mastigonemes | Science

作者: 未知作者

The chemical complexity and non-templated biosynthesis of glycans have posed significant challenges for establishing sequence-structure relationships. Here we report cryo-EM structures of tubular mastigonemes from a golden alga species, Ochromonas danica , in which a large number of N- and O-glycans are resolved at 1.8-2.2 Å resolution. Beyond high-mannose and complex N-glycans, we identify a non-canonical N-glycan on the Ala- Asn -Asp (A N D) motif. The surface spikes comprise dense O-glycans coating PSXX tetrapeptide repeats, with two glycans linked on trihydroxylated proline and one on serine per repeat. In addition to various types of sugars and their covalent modifiers, water molecules (>10% of resolved volume) and cations are clearly resolved and mediate the structural assembly. Our study establishes a framework for investigating glycan folding in high-order biological assemblies.

23.
arXiv (CS.CV) 2026-06-17

Partial Ring Scan: Revisiting Scan Order in Vision State Space Models

State Space Models (SSMs) have emerged as efficient alternatives to attention for vision tasks, offering lineartime sequence processing with competitive accuracy. Vision SSMs, however, require serializing 2D images into 1D token sequences along a predefined scan order, a factor often overlooked. We show that scan order critically affects performance by altering spatial adjacency, fracturing object continuity, and amplifying degradation under geometric transformations such as rotation. We present Partial RIng Scan Mamba (PRISMamba), a rotation-robust traversal that partitions an image into concentric rings, performs order-agnostic aggregation within each ring, and propagates context across rings through a set of short radial SSMs. Efficiency is further improved via partial channel filtering, which routes only the most informative channels through the recurrent ring pathway while keeping the rest on a lightweight residual branch. On ImageNet-1K, PRISMamba achieves 84.5% Top-1 with 3.9G FLOPs and 3,054 img/s on A100, outperforming VMamba in both accuracy and throughput while requiring fewer FLOPs. It also maintains performance under rotation, whereas fixed-path scans drop by 1~2%. These results highlight scan-order design, together with channel filtering, as a crucial, underexplored factor for accuracy, efficiency, and rotation robustness in Vision SSMs. Code will be released upon acceptance.

25.
medRxiv (Medicine) 2026-06-22

Evidence-guided AI regularization for suicidal ideation prediction in pediatric bipolar disorder

Background: Suicide prediction models in psychiatry often rely on purely data-driven feature selection, which can produce unstable and clinically opaque predictor sets in modest-sized samples. We developed Evidence-Based AI LASSO (EBAL), an evidence-guided regularization framework that incorporates curated clinical evidence into feature-specific penalty factors for interpretable prediction. Methods: Baseline data from 136 youth with confirmed bipolar spectrum disorder in the Greater Houston Area Bipolar Registry were analyzed using 20 candidate clinical predictors. Forty higher-level evidence documents on suicidality and related predictor domains were curated through a structured evidence synthesis workflow and indexed as an auditable evidence corpus. An open-weight large language model assigned feature-specific penalty factors using a prespecified scoring rubric, and these penalties were used to fit a weighted LASSO model. EBAL was compared with a standard evidence-agnostic LASSO using nested leave-one-out cross-validation. Results: For suicidal ideation, EBAL achieved an AUROC of 0.768, balanced accuracy of 0.757, sensitivity of 0.758, and specificity of 0.757. The standard LASSO achieved an AUROC of 0.760 and balanced accuracy of 0.715. EBAL improved balanced accuracy (+0.042, p=0.010) and Matthews correlation coefficient (+0.079, p=0.010), while retaining fewer stable predictors than standard LASSO (11/20 vs 18/20). The strongest positive predictors were current depressed mood, duration of mood disorder illness, and comorbid generalized anxiety disorder. For suicidal behavior, both models performed near chance and retained all candidate predictors. Limitations: The study was cross-sectional, single-site, and modest in sample size, with no external validation cohort. Conclusions: EBAL produced a sparser and more clinically coherent model for suicidal ideation in pediatric bipolar disorder, but did not improve prediction of suicidal behavior. These findings support evidence-guided regularization as a transparent strategy for aligning psychiatric prediction models with prior clinical knowledge while preserving interpretability.