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

On Regret Bounds of Thompson Sampling for Bayesian Optimization

arXiv:2603.09276v2 Announce Type: replace-cross Abstract: We study a widely used Bayesian optimization method, Gaussian process Thompson sampling (GP-TS), under the assumption that the objective function is a sample path from a GP. Compared with the GP upper confidence bound (GP-UCB) with established high-probability and expected regret bounds, most analyses of GP-TS have been limited to expected regret. Moreover, whether the recent analyses of GP-UCB for the lenient regret and the improved cumulative regret upper bound can be applied to GP-TS remains unclear. To fill these gaps, this paper shows several regret bounds: (i) a regret lower bound for GP-TS, which implies that GP-TS suffers from a polynomial dependence on $1/\delta$ with probability $\delta$, (ii) an upper bound of the second moment of cumulative regret, which directly suggests an improved regret upper bound on $\delta$, (iii) expected lenient regret upper bounds, and (iv) an improved cumulative regret upper bound on the time horizon $T$. Along the way, we provide several useful lemmas, including a relaxation of the necessary condition from recent analysis to obtain improved regret upper bounds on $T$.

02.
bioRxiv (Bioinfo) 2026-06-22

EMAlign: accurate alignment of cryo-EM maps through main-chain probability using deep learning

Accurate alignment of cryo-EM density maps is essential for comparing conformational states, searching map libraries, and guiding atomic model building, but remains challenging for noisy experimental maps and partially overlapping structures. Existing alignment methods are often based on raw maps, which may result in reduced accuracy due to the density noise, or require manual intervention for local alignment, which suffers from limited general applicability. Addressing the limitations, we present EMAlign, an automatic global and local cryo-EM map alignment with predicted main-chain probability using deep learning. First, EMAlign predicts main-chain prob ability maps from raw cryo-EM density maps using a BiMCUNet network. Then, a fast Fourier transform (FFT)-based search strategy is used to globally search the accurate alignment between cryo-EM maps based on predicted main-chain probability maps. As such, the main-chain prob ability map overcomes the noisy raw map problem, and the FFT-based exhaustive global search ensures the general applicability of alignment. EMAlign is evaluated on 64 global map pairs, 195 local map pairs, and 60 structure-to-map pairs at 3-10 [A] resolution and compared with gmfit, fitmap, VESPER, and CryoAlign. It is shown that EMAlign outperforms the other methods in both global and local alignment, achieving mean RMSDs of 1.03 [A] (global), 2.56 [A] (local), and 0.82 [A] (structure-to-map), with success rates of 100.0%, 100.0%, and 98.3% under the criterion of RMSD < 10 [A]. The EMAlign package is freely available at https://github.com/huang-laboratory/EMAlign/.

03.
arXiv (CS.LG) 2026-06-17

Damage Adaptation in Seconds for Architected Materials

arXiv:2606.17394v1 Announce Type: cross Abstract: Adaptation to damages and in-situ physical repairs is essential for long-term robot autonomy, yet challenging outside of narrowly defined and well-anticipated bounds. In this work we proprioceptively adapt to catastrophic damage in soft-actuated systems in under one minute. Architected materials are well equipped for adaptation: actuator failure occurs gradually rather than acutely, and damage can be described in a low-dimensional, discrete coordinate space. Surprisingly, latent damage representations plus a simple yet robust ensemble method is sufficient for adapting to unseen damage in real-time. Moreover, we identify conditions under which exponential sample complexity collapses to linear sample complexity for learned representations of architected materials, a concrete advantage over rigid components or continuum soft mechanisms. We demonstrate LEAP, our method for adaptive proprioception, via a tracing task for a 6DoF soft wrist based on Handed Shearing Auxetic (HSA) actuators. Our algorithm is able to adapt to cuts, burns, and actuator repairs, enabling simulation-free real-time adaptation that is critical for realizing the promise of soft robots outside the lab. Videos and more information are available at https://murpheylab.github.io/leap.

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

Enhancing LLM Safety Through a Theoretical Minimax Game Lens

The rapid advancement of large language models (LLMs) necessitates effective mechanisms to ensure their responsible deployment by accurately distinguishing unsafe content from benign content. While substantial safety datasets are available in English, multilingual safety modeling remains underexplored due to limited open-source safety datasets in other languages. Even within English datasets, safe yet sensitive corner-case content is scarce, leading to shortcut learning by models and non-trivial false-positive rates. To mitigate these issues, we introduce a novel minimax reinforcement learning (RL) framework wherein a data generator and a classifier model co-evolve, facilitating the production of high-quality synthetic multilingual safety data. We theoretically formalize this interaction as a minimax game and rigorously demonstrate convergence to a Nash equilibrium. Empirical evaluations confirm that our synthetic data generation method significantly enhances the classifier model performance, enabling a substantially smaller model to surpass the state-of-the-art by nearly 10% on English benchmarks while achieving 4.5x faster inference speed. These results establish a scalable and efficient methodology for synthetic data generation, advancing the development of safer and more robust multilingual LLM deployments.

06.
medRxiv (Medicine) 2026-06-22

Biopsychosocial determinants of HPV vaccine perception in university students of both sexes in Cucuta, Colombia, 2024: a cross-sectional study

Colombia has been internationally recognised as a paradigmatic case of vaccine confidence crisis since the 2014 Carmen de Bolivar event, and national HPV vaccination coverage remains far below the World Health Organization 2030 target. Most published evidence focuses on female adolescents and on cervical cancer; the perception of the HPV vaccine in university-age populations of both sexes–and across the broader spectrum of HPV-attributable disease–remains comparatively understudied. We aimed to describe the influence of biopsychosocial determinants on HPV vaccine perception among university students of both sexes in Cucuta, Norte de Santander, Colombia. We conducted a cross-sectional study with a mixed quantitative-qualitative approach in 2024 among four universities (Universidad de Santander, Universidad Francisco de Paula Santander, Universidad de Pamplona and Universidad Libre; combined enrolment 21,033 students). Using convenience sampling stratified by institution, 750 actively enrolled undergraduate students of both sexes (18-60 years) completed a structured online questionnaire adapted from previously validated instruments. The instrument captured sociodemographic information, HPV knowledge and HPV vaccine perception. Data were analysed using Students t-test, one-way analysis of variance, Tukey post-hoc tests, effect sizes and 95% confidence intervals, with a 0.05 significance threshold. Of 750 respondents, 54.2% were women, 61.3% were under 20 years of age, and 75.1% attended public universities. HPV knowledge was high in 39.2%, intermediate in 42.4% and low in 18.4%; women and students aged 26 years or older displayed higher knowledge. Although 91.2% had heard of HPV and 82.5% knew that both sexes could acquire it, recognition of clinical manifestations and complications was uneven: cervical cancer 51.7%, penile cancer 30.5%, vaginal warts 45.9% and warts in the penis, larynx, anus or rectum 34.0%. Vaccine-specific knowledge was low in 77.1%, with men disproportionately represented (85.9% versus 69.5% in women). Overall positive perception of HPV vaccination was 66.6%, slightly higher in women (68.8%) than men (63.9%), in students aged 26 years or older (70.1%) and in students from private universities (68.1% versus 65.9%). Inferential analysis identified sex (Cohens d = -0.357), type of university (d = 0.189) and HPV knowledge (partial eta-squared = 0.096) as the only significant determinants. Age, socioeconomic stratum, age at sexual debut and vaccine-specific knowledge did not reach meaningful significance. HPV vaccine perception was predominantly positive but conditioned by three biopsychosocial determinants, with HPV knowledge as the primary driver. The persistent gender gap reflects historical anchoring of HPV messaging in cervical disease and female-targeted campaigns. Public-health strategies should adopt comprehensive, gender-inclusive educational interventions that explicitly visibilise non-cervical HPV-related cancers and address both sexes from a common evidence base.

07.
arXiv (CS.AI) 2026-06-18

Deep Learning-Driven Inverse Design of Doherty Power Amplifiers Using Pixelated Combiners and Dual-State Impedance Synthesis

arXiv:2606.18395v1 Announce Type: cross Abstract: The output combiner of a Doherty power amplifier (PA) integrates load modulation, impedance matching, and phase compensation within a single network, making its design and synthesis highly challenging. In this paper, we propose a three-port Doherty combiner design methodology that combines deep convolutional neural networks (CNNs), pixelated layout representations, and genetic algorithms (GA) with dual-state impedance synthesis to address both peak and back-off power conditions. As a proof of concept, two GaN HEMT Doherty PA prototypes incorporating three-port pixelated combiners are designed and fabricated. Both prototypes achieve a measured saturated output power exceeding 44.2 dBm with peak drain efficiency above 71.2% within 2.6-2.8 GHz. Furthermore, a drain efficiency as high as 64% is measured at the 6-dB back-off level. After applying digital predistortion, each prototype achieves an adjacent channel leakage ratio (ACLR) better than -51.3 dBc.

08.
arXiv (quant-ph) 2026-06-19

Universality in Ionic Three-body Systems Near an Ion-atom Feshbach Resonance

arXiv:2511.00325v3 Announce Type: replace-cross Abstract: We calculate bound and scattering properties of a system of two neutral atoms and an ion near an atom-ion Feshbach resonance. Our results indicate that long-range atom-ion interactions lead to significant deviations from universal behavior derived from contact or van der Waals potentials. We find that ionic systems display an overall suppression of inelastic transitions leading to recombination rates and lifetimes of Efimov state orders of magnitude smaller with respect to those for neutral atoms. We further characterize the dense spectra of triatomic molecular ions with extended lifetimes. Our results provide a deeper insight on the universality and structure of three-body ionic systems and establishing them as a promising platform for exploring novel few- and many-body phenomena with long-range interactions.

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

Steady-Forcing: Balancing Spatial Persistence and Motion Continuity in Long-Horizon Nature Video Diffusion

Autoregressive video diffusion models enable streaming generation but often degrade over long rollouts: static scene layouts drift, while mechanisms that improve spatial stability tend to suppress motion, causing natural flows such as water, fire, or smoke to stagnate. We study this stability-motion trade-off in fixed-camera long-horizon nature video generation, where the two failure modes can be more clearly separated than in moving-camera settings. We propose Steady-Forcing, a memory and training framework combining a persistent visual anchor (V-Sink), an exponential moving-average motion memory (EMA-Sink), block-relative temporal encoding, periodic cache purification, and distillation from a Wan2.1-14B teacher with motion-rewarded priors under task-focused configurations. Together, these components are designed to preserve background identity while sustaining visually plausible fluid dynamics over multi-minute autoregressive rollouts. Evaluations across seven baselines show that Steady-Forcing improves long horizon background consistency and imaging quality, while a blind user study indicates stronger perceived stability and motion continuity. The benchmark evaluation further suggest that generic VBench aggregate scores under-penalize fixed-camera artifacts as well as rewarding drift-induced optical flow as Dynamic Degree while not directly penalizing texture hardening or flow stagnation - motivating future task-specific benchmarks for static-camera nature-flow evaluation. Project page: https://minar09.github.io/steadyforcing/

10.
arXiv (CS.CL) 2026-06-12

PersonaDrive: Human-Style Retrieval-Augmented VLA Agents for Closed-Loop Driving Simulation

Closed-loop driving simulators typically populate their environments with non-ego traffic agents that behave largely the same way, produced either by rule-based traffic managers or by learned models trained toward a single behavioral mode. Recent work introduces style variation through post-hoc labels on observational data or LLM-inferred reward weights, but these signals act as proxies for what a style should reward rather than demonstrations of humans explicitly asked to drive in that style. We introduce PersonaDrive, a pipeline that conditions a vision-language-action (VLA) driving agent on retrieved demonstrations from a style-instructed human driving dataset, in which participants drive CARLA leaderboard routes under aggressive, neutral, and conservative instructions on a driver-in-the-loop rig. The pipeline has three stages: (i) offline triplet mining over per-style human driving data using a combined image-text similarity score; (ii) training a lightweight retrieval head that fuses frozen visual features with a small control encoder over per-style databases; and (iii) fine-tuning a single VLA backbone to treat retrieved context points as in-context behavioral demonstrations during waypoint prediction. At inference, the same backbone is conditioned on any style by swapping which per-style database the retrieval head queries, so selecting a style requires no per-style retraining while enabling human-style, style-diverse non-ego agents for closed-loop simulation. On Bench2Drive, PersonaDrive (no style) improves the driving score by 4.6% over SimLingo and 2.5% over HiP-AD, and under style conditioning attains the highest driving score in every style within a roughly 2% band (its weakest style surpassing the strongest baseline, DMW, by 5.4%), while average speed and acceleration rise by 18% and 25% from the conservative to the aggressive instruction.

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

Federated Foundation Language Model Post-Training Should Focus on Open-Source Models

arXiv:2505.23593v4 Announce Type: replace Abstract: Post-training of foundation language models has emerged as a promising research domain in federated learning (FL) with the goal to enable privacy-preserving model improvements and adaptations to user's downstream tasks. Recent advances in this area adopt centralized post-training approaches that build upon black-box foundation language models where there is no access to model weights and architecture details. Although the use of black-box models has been successful in centralized post-training, their blind replication in FL raises several concerns. Our opinion is that using black-box models in FL contradicts the core principles of federation such as data privacy and autonomy. In this paper, we critically analyze the usage of black-box models in federated post-training, and provide a detailed account of various aspects of openness and their implications for FL.

12.
medRxiv (Medicine) 2026-06-10

Gendered pathways to adolescent mental health: An empirical assessment of a new conceptual framework

Introduction Gender norms and roles are important determinants of physical and mental health in the key period of adolescence. Yet, the gendered pathways to mental health in adolescents are not fully understood. Using a conceptual framework for global adolescent mental health that we developed based on a Delphi process, we empirically investigated the associations between six gender-related constructs and adolescent mental health. Methods We used cross-sectional Gender and Adolescence: Global Evidence (GAGE) data from Ethiopia (2020) to explore the associations between sex, gender norms, psychological competencies, gender attitudes, gender roles, with the latter two also serving as mediators, and psychological distress (GHQ-12), using Structural Equation Modelling (SEM). Results The SEM model contained measurements from 1,584 adolescents, including 843 girls and 741 boys, with a median age of 13 years. Out of 14 pathways tested, we found statistically significant associations between psychological competencies and psychological distress; sex and gender attitudes; and between gender norms and psychological competencies, gender attitudes, and gender roles. Hence, the gender-related constructs were mostly associated with each other, rather than with psychological distress. Conclusion The gender-related constructs are strongly interrelated, thereby attenuating their individual effects on psychological distress. The interplay of gender-related constructs should be considered when developing interventions to promote mental health in adolescents.

13.
arXiv (CS.LG) 2026-06-16

Information Leakage Detection through Approximate Bayes-optimal Prediction

arXiv:2401.14283v4 Announce Type: replace-cross Abstract: In today's data-driven world, the proliferation of publicly available information raises security concerns due to the information leakage (IL) problem. IL involves unintentionally exposing sensitive information to unauthorized parties via observable system information. Conventional statistical approaches rely on estimating mutual information (MI) between observable and secret information for detecting ILs, face challenges of the curse of dimensionality, convergence, computational complexity, and MI misestimation. Though effective, emerging supervised machine learning based approaches to detect ILs are limited to binary system sensitive information and lack a comprehensive framework. To address these limitations, we establish a theoretical framework using statistical learning theory and information theory to quantify and detect IL accurately. Using automated machine learning, we demonstrate that MI can be accurately estimated by approximating the typically unknown Bayes predictor's log-loss and accuracy. Based on this, we show how MI can effectively be estimated to detect ILs. Our method performs superior to state-of-the-art baselines in an empirical study considering synthetic and real-world OpenSSL TLS server datasets.

14.
arXiv (CS.AI) 2026-06-19

Beyond Static Endpoints: Tool Programs as an Interface for Flexible Agentic Web Services

arXiv:2606.19992v1 Announce Type: cross Abstract: In the agentic web era, LLM-based agents increasingly invoke web services as tools, yet most interfaces remain static endpoints that poorly express long-horizon workflows with loops, conditionals, joins, and retries. We present ToolPro, which represents an agent's tool intent as an executable tool program that compactly encodes multi-step service interactions with explicit effect types. ToolPro combines constraint-guided program construction, effect-aware replay for exactly-once state-modifying calls, and a profile-driven policy that decides when program execution outperforms stepwise calling. We instantiate ToolPro over MCP-style services with WebAssembly sandboxing and evaluate it on diverse workflows of real-world applications. ToolPro reduces end-to-end latency by up to 53.4\% and client-side traffic by up to 96.1\%, with larger gains under higher network latency and workflow complexity.

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

Optimal Hidden-Target Learning for Online Inventory Optimization on General Convex Sets

arXiv:2606.14679v1 Announce Type: new Abstract: Online inventory optimization (OIO) is online convex optimization with physical memory: inventory carryover makes the feasible action set depend on the past. A natural principle, used in stochastic inventory learning and recently in OIO under a single linear capacity constraint, is to maintain a hidden target chosen by an online learner and implement its projection onto the currently feasible order-up-to set. We prove that this simple principle is optimal for OIO on arbitrary bounded convex capacity sets. With online gradient descent as the base learner, the method improves the best known regret guarantee for OIO on general convex sets from inverse to inverse-square-root dependence on the common-demand probability, and we prove a matching lower bound. The same principle gives the first polylogarithmic regret guarantee for strongly convex losses and the first dynamic regret guarantee adapting to Euclidean path variation on general convex capacity sets. The analysis introduces a norm alignment principle: the right state variable is the distance from the hidden target to the feasible set, measured in the same norm as the projection. Under norm alignment, this distance evolves pathwise as a scalar queue, with target movement as arrival and common demand as service. This reduction to one-dimensional queue control resolves the state dependence and extends the guarantees to general convex capacity sets, beyond the reach of prior productwise approaches. Experiments on synthetic and real-world inventory data corroborate the theory.

16.
bioRxiv (Bioinfo) 2026-06-20

The recount3 Python package for programmatic access to uniformly processed RNA-seq data

The recount3 online resource provides tens of thousands of uniformly processed RNA-seq samples across human and mouse from major sequencing repositories like the Sequence Read Archive. While access to these datasets has traditionally been centered in the R/Bioconductor ecosystem, the growing prominence of Python in bioinformatics and machine learning necessitates native, efficient tooling for Python users. Therefore, we present the recount3 Python package with robust application programming interface (API) and command-line interface (CLI) for discovering, downloading, and materializing recount3 resources. The software orchestrates uniform resource locator (URL) resolution, persistent on-disk caching, and the automatic parsing of data into analysis-ready data structures, including Pandas DataFrames and BiocPy RangedSummarizedExperiment objects. The recount3 Python package drastically lowers the barrier to entry for large-scale utilization of RNA-seq data in Python-based computational pipelines, bridging the gap between massive public transcriptomic data and modern machine learning ecosystems.

17.
medRxiv (Medicine) 2026-06-23

Intrapartum Oxytocin and Maternal Outcomes Following Vaginal and Unscheduled Cesarean Delivery

Objective To examine whether intrapartum synthetic oxytocin exposure for labor induction or augmentation is associated with breastfeeding and postpartum depressive and traumatic stress symptoms. Methods We studied 1,296 postpartum women who delivered at a single tertiary care center, with assessments from the third trimester through approximately two months postpartum. Intrapartum oxytocin exposure was obtained from electronic medical records. Outcomes included exclusive breastfeeding, postpartum depression, and childbirth-related traumatic stress. Analyses were stratified by delivery mode and adjusted for key maternal and obstetric covariates. Results Overall, 63.3% of participants received intrapartum oxytocin. Among participants with vaginal delivery, oxytocin exposure was associated with lower exclusive breastfeeding at two months after adjustment (58.2% vs 70.3%; adjusted RR 0.86, 95% CI 0.76- 0.97; p = 0.02), but not with postpartum mental health outcomes. Among participants with unscheduled cesarean delivery, oxytocin exposure was independently associated with higher immediate postpartum depressive symptoms (F = 4.97, p = 0.03), acute childbirth-related stress (F = 4.56, p = 0.03), and two-month childbirth-related posttraumatic stress symptoms (F = 4.30, p = 0.04), but not two-month depressive symptoms. Conclusion Intrapartum oxytocin exposure was associated with lower exclusive breastfeeding after vaginal delivery and modestly higher childbirth-related distress after unscheduled cesarean delivery. These findings suggest that oxytocin exposure may mark or contribute to postpartum vulnerability in specific delivery contexts.

18.
arXiv (CS.AI) 2026-06-19

One Probe Won't Catch Them All: Towards Targeted Deception Detection

arXiv:2602.01425v2 Announce Type: replace Abstract: Linear probes are a promising approach for monitoring AI systems for deceptive behaviour. Previous work has shown that a linear classifier trained on a contrastive instruction pair and a simple dataset can achieve good performance. However, these probes exhibit notable failures even in straightforward scenarios, including spurious correlations and false positives on non-deceptive responses. In this paper, we demonstrate that deception detection is inherently heterogeneous: while a single universal probe achieves modest improvements (+0.032 AUC), post-hoc oracle analysis reveals substantially higher potential (+0.108 AUC) when probes are matched to specific deception types, and synthetic validation experiments suggest this ceiling is achievable a priori when the deception type is known in advance. Our findings reveal that instruction pairs capture deceptive intent rather than content-specific patterns, explaining why prompt choice dominates probe performance (70.6% of variance). Given this heterogeneity, we conclude that organizations should define their specific threat models and deploy appropriately matched probes rather than seeking a universal deception detector.

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

LSTM based IoT Device Identification

arXiv:2304.13905v2 Announce Type: replace-cross Abstract: While the use of the Internet of Things is becoming more and more popular, many security vulnerabilities are emerging with the large number of devices being introduced to the market. In this environment, IoT device identification methods provide a preventive security measure as an important factor in identifying these devices and detecting the vulnerabilities they suffer from. In this study, we present an end-to-end machine learning pipeline that identifies IoT devices in the Aalto university dataset (IoT devices captures) using Long Short-Term Memory (LSTM) networks. Raw network packet captures (PCAP) are processed into 25 engineered features, which are then arranged as sliding-window time-series sequences. We systematically evaluate sequence lengths from 2 to 20, reporting that performance improves approximately linearly up to length 6 and thereafter in a wave-like pattern, reaching its peak at length 18. On the final held-out test set with the optimal configuration, the model achieves an accuracy of 79.85% and a macro-averaged F1-score of 75.70% across 27 device classes.

20.
arXiv (CS.CV) 2026-06-11

How Seemingly Inconsequential Design Choices Dictate Performance of LLMs in Pathology

General-purpose large language models (LLMs) are routinely used as baselines when evaluating specialized pathology models on whole-slide images (WSIs). Because WSIs exceed contemporary model context limits, LLM baselines routinely use small, high-magnification patches processed independently via majority voting, without systematic evaluation of seemingly inconsequential design choices such as patch size, patch count, and magnification. Generalist LLMs have consistently underperformed specialized systems, reinforcing the perception that domain-specific training or architectural adaptation is necessary for pathology tasks involving WSIs. Here, we conduct a systematic factorial analysis of four input design factors: inference mode, patch size, magnification, and patch count. We demonstrate that prior studies have overstated the gap between specialized models and general-purpose LLMs by choosing non-optimized input configurations. On the MultiPathQA benchmark, switching to a single balanced configuration (large patches at lower magnification, processed jointly) raises GPT-5 from 15.1% to 39.5% on cancer-type classification (TCGA) and from 38.1% to 62.9% on organ classification (GTEx). Per-task optimization yields further gains up to 43.9% (TCGA) and 71.6% (GTEx). The same configuration generalizes to two other models and to a fully held-out CPTAC cohort, where it improves Gemini 3 Flash by 23.4 percentage points without any task-specific tuning.

21.
arXiv (CS.CV) 2026-06-18

Simple Domain Generalization Methods are Strong Baselines for Open Domain Generalization

In real-world applications, a machine learning model is required to handle an open-set recognition (OSR), where unknown classes appear during the inference, in addition to a domain shift, where the data distribution differs between the training and inference phases. Domain generalization (DG) aims to handle the domain shift situation where the target domain of the inference phase is inaccessible during the model training. Open domain generalization (ODG) considers DG and OSR. Domain-augmented meta-learning (DAML) is a method targeting ODG; however, it has a complicated learning process. By contrast, although various DG methods have been proposed, they have not been evaluated in ODG situations. In this study, we comprehensively evaluate the existing DG methods in ODG and show that the two simple DG methods, CORrelation ALignment (CORAL) and maximum mean discrepancy (MMD), are competitive with DAML in several cases. In addition, we propose simple extensions of CORAL and MMD by introducing the techniques used in DAML, such as ensemble learning and Dirichlet mixup data augmentation. The experimental evaluation demonstrates that the extended CORAL and MMD can perform comparably to DAML with lower computational costs. This suggests that the simple DG methods and their simple extensions are strong baselines for ODG.

22.
bioRxiv (Bioinfo) 2026-06-19

Geometric Deep Learning Reveals Ligandable and Cryptic RNA Binding Small Molecule Pockets (SMARTPocket)

RNAs are important therapeutic targets, however identifying ligandable small-molecule binding pockets remains a major barrier to RNA-targeted drug discovery. Here, SMARTPocket, an atomic-level geometric deep learning framework for predicting RNA-small molecule binding pockets directly from three-dimensional structure is introduced. SMARTPocket represents RNA as full-atom point clouds and uses transfer learning from more than 110,000 protein binding interface structures to overcome the limited number of experimentally elucidated RNA-ligand complexes. Across four established single-chain benchmarks and three broader curated benchmarks, SMARTPocket consistently outperforms existing RNA pocket predictors and general biomolecular modeling approaches. The model generalizes to apo RNA structures when conformational changes are modest, identifies cryptic ligandable pockets, and recapitulates experimentally validated binding sites in the SARS-CoV-2 frameshifting element and an RNA aptamer evolved to bind small molecules. SMARTPocket-guided docking further improves near-native RNA-ligand pose recovery and computational efficiency compared with blind docking. These results establish SMARTPocket as a generalizable framework for structure-based identification of ligandable RNA pockets and for accelerating discovery of RNA-targeted small molecules.

23.
Nature (Science) 2026-06-22

C-glycoside synthesis via radical cross-coupling of glycohydrazides

作者:

Carbohydrates are among the most abundant and structurally diverse biomolecules in nature, playing central roles in energy storage, molecular recognition, and cell signaling. Within this domain, C-glycosides1-3, in which the oxygen atom of the glycosidic bond in O-glycosides is replaced by carbon, have emerged as valuable motifs in medicinal chemistry due to their resistance to enzymatic hydrolysis2,4. Of particular importance are C-aryl glycosides, exemplified by the SGLT2 inhibitors dapagliflozin, canagliflozin, and empagliflozin, which are frontline therapies for type 2 diabetes5-7. However, scalable syntheses of C-aryl glycosides have traditionally relied on protected sugar derivatives, lengthy sequences, or conventional cross-couplings that often suffer from poor selectivity, limited scope, and extensive protecting-group manipulation6. Herein, we report a practical approach to C-aryl glycosides using glycosyl sulfonyl hydrazides as redox-neutral radical precursors for cross-coupling. Prepared directly from unprotected native sugars, these reagents generate glycosyl radicals under mild conditions and enable efficient access to diverse C-aryl glycosides, including all approved SGLT2 inhibitors, natural products such as salmochelins and neopetrosins, and medicinally relevant probes. Beyond anomeric functionalization, this platform enables C–C bond formation at multiple positions on carbohydrate scaffolds and supports stereoretentive radical coupling that can override inherent stereochemical biases, expanding practical access to carbohydrate-derived therapeutics and chemical tools.

24.
arXiv (CS.LG) 2026-06-16

Bayesian Tensor Decomposition with Diffusion Model Prior

arXiv:2606.03212v2 Announce Type: replace Abstract: Low-rank tensor decomposition (TD) is usually effective on clean, fully observed data, but it often degrades under severe missingness or noise. Low-rankness is itself a useful but limited structural prior, and additional handcrafted priors (e.g., sparsity or smoothness) still fall short of capturing the rich statistics of real-world data. To compensate for this weak inductive bias under heavy corruption, one would like to inject a learned, data-driven prior; however, the state-of-the-art diffusion models are not readily compatible with current TD and tractable posterior inference. To address these challenges, we introduce DiffBCP, a hybrid-prior Bayesian CP decomposition framework that couples a cumulative shrinkage process prior over the CP factors for automatic rank selection with an off-the-shelf pre-trained diffusion model as an implicit data prior on the reconstructed tensor. To make posterior inference tractable despite the coupling among the likelihood, low-rank constraint, and diffusion prior, we develop a split Gibbs sampler: CP factors admit conjugate updates, while the diffusion block is sampled via low-rank-guided denoising. A noise-adaptive coupling schedule further reduces sensitivity to hand-tuned annealing. Experiments on image inpainting and denoising, including high-resolution out-of-distribution images, show consistent gains over Bayesian, nonlinear, and plug-and-play TD baselines.

25.
arXiv (CS.CV) 2026-06-19

SAFE-Cascade: Cost-Adaptive Vision-Language Routing for Chart Question Answering

Vision-language models (VLMs) are powerful for chart question answering, but invoking a VLM for every query can be unnecessarily expensive when many questions are answerable from OCR text and lightweight language reasoning. We demonstrate SAFE-Cascade, an interactive system for cost-adaptive chart question answering. Given a chart image and a natural-language question, SAFE-Cascade first extracts chart text with OCR, obtains a provisional answer from a text-only language model, and then uses a learned router to decide whether to accept the text answer or escalate to a VLM. The demo exposes this decision process to users: OCR evidence, text-only answer, routing probability, escalation decision, final answer, estimated cost, and estimated latency are shown side by side. SAFE-Cascade is designed as a transparent interface for understanding when visual grounding is actually needed. Users can upload or select charts, ask questions, inspect the evidence used by each pathway, compare text-only and VLM answers, and adjust the escalation threshold to explore the accuracy-cost frontier. The system is implemented with Azure Document Intelligence for OCR, gpt-5-mini as the text-only model, gemini-2.5-flash-image as the VLM, and a Random Forest router trained on inference-time features. On a held-out ChartQA test split of 375 examples from a 2,500-example experiment, SAFE-Cascade achieves 69.1% unified accuracy with 73.1% VLM invocation, compared with 67.7% accuracy and 100% VLM invocation for the full-VLM baseline. The observed +1.4 percentage-point difference is statistically uncertain, so we interpret SAFE-Cascade as matching full-VLM performance while reducing VLM calls by 26.9% and estimated cost by 9.3%. The demonstration shows how selective modality routing can make multimodal knowledge systems more transparent, tunable, and cost-aware.