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01.
arXiv (CS.AI) 2026-06-17

S4oP: Operator-level Pruning of Structured State Space Models for Resource-Constrained Devices

arXiv:2606.18096v1 Announce Type: cross Abstract: Structured State Space Models (SSMs), including the S4 and S4D architectures, have recently emerged as powerful alternatives to attention-based models for capturing long-range dependencies in sequential data. Despite their strong empirical performance, deploying these models in time- and resource-constrained settings remains challenging due to their computational and memory demands. In this paper, we propose a novel incremental, operator-level pruning approach for S4- and S4D-based models that significantly reduces inference cost while preserving predictive performance. To the best of our knowledge, this is the first work to systematically investigate structured operator pruning for SSMs. Our method progressively prunes model operators by interleaving structured masking with fine-tuning, while jointly monitoring accuracy and inference latency. We implement this approach within a unified training and evaluation framework that enables systematic exploration of efficiency-accuracy trade-offs. Experiments across multiple benchmark datasets show that pruning up to 70% of the model operators preserves the performance of the original models in most cases, while substantially reducing inference latency. These results demonstrate that structured operator pruning is an effective and previously unexplored strategy for improving the efficiency of SSMs and facilitate their deployment in practical, resource-constrained scenarios.

02.
arXiv (CS.LG) 2026-06-24

Which Spaces can be Embedded in $L_p$-type Reproducing Kernel Banach Space? A Characterization via Metric Entropy

arXiv:2410.11116v4 Announce Type: replace-cross Abstract: In this paper, we establish a novel connection between the metric entropy growth and the embeddability of function spaces into reproducing kernel Hilbert/Banach spaces. Metric entropy characterizes the information complexity of function spaces and has implications for their approximability and learnability. Classical results show that embedding a function space into a reproducing kernel Hilbert space (RKHS) implies a bound on its metric entropy growth. Surprisingly, we prove a converse: a bound on the metric entropy growth of a function space allows its embedding to a $L_p-$type Reproducing Kernel Banach Space (RKBS). This shows that the ${L}_p-$type RKBS provides a broad modeling framework for learnable function classes with controlled metric entropies. Our results shed new light on the power and limitations of kernel methods for learning complex function spaces.

03.
bioRxiv (Bioinfo) 2026-06-16

Better data, better trees: GenBank-GISAID deduplication and source-specific artifact masking in viral genomics

GenBank and GISAID are the primary repositories for viral genomic data, but integrating records across them remains a challenge. The same sequence could be made available in both databases without any cross-reference linking the two entries. Consequently, there is no systematic way to identify this redundancy, which compromises the compilation of representative, non-redundant large-scale datasets. In parallel, the growth of viral genomic data has increased the risk of systematic technical artifacts introduced during sequencing or assembly. These artifacts can inflate substitution rate estimates and degrade temporal signal, biasing evolutionary rate estimates. To address both challenges, here we present a formal, reproducible workflow integrating two newly developed complementary tools: G2G matcher for cross-repository harmonization and Lab-Specific Bias FILTer (LSBFILT) for masking of laboratory-specific artifacts. Using the Eastern/Central/South African (ECSA) chikungunya virus lineage as a proof-of-concept, we demonstrate that our integrated workflow restores temporal signal and provides a robust, curated dataset for downstream phylodynamic analyses. Critically, restricting masking of homoplastic sites to specific sequences reduces the substitution rate estimate from an inflated 8.517 x 10e-4; to 5.078 x 10e-4; substitutions/site/year and increases the coefficient of determination (R2) of the root-to-tip regression analysis from 0.353 to 0.677. By enabling systematic cross-repository harmonization and source-specific artifact masking, we provide the molecular epidemiological community with scalable tools to reconcile fragmented genomic data and reduce technical biases, fostering more accurate and reproducible phylogenetic analysis. G2G matcher is available at https://github.com/andrezaleite/G2G-Matcher, and LSBFILT at https://github.com/khourious/LSBFILT.

04.
medRxiv (Medicine) 2026-06-23

Multidimensional motivation in aging: a person-centred framework spanning goal-directed behaviour, social reward and pleasure

Motivational changes are determinants of healthy aging, social engagement, and functional independence, and may signal early neurodegenerative risk. Existing assessment approaches in aging typically treat motivation as a unitary construct. Here, we introduce MotDem, an age-appropriate measure of motivation co-designed with people living with dementia, carers, and clinicians. Across a broad adult lifespan sample (18-80 years), MotDem revealed a robust three-domain motivational architecture encompassing goal-directed behaviour, social reward, and pleasure, with a fourth satiety factor retained as exploratory. This structure was replicated in an independent older cohort (45-80 years) from a different national context. MotDem showed strong convergence with established measures of apathy and anhedonia, alongside more modest associations with depressive symptomatology. Together, these findings show that motivational aging is multifaceted and poorly captured by traditional unitary assessment. MotDem provides a multidimensional framework for measuring distinct motivational drivers of heterogeneous aging trajectories, with implications for resilience, wellbeing, and neurodegenerative risk.

05.
arXiv (CS.CV) 2026-06-25

Neural Network Quantization by Learning Low-Loss Subspaces

Neural network quantization aims to find a discrete representation of parameters that preserves the performance of a full-precision (FP) model as faithfully as possible. Enforcing discrete constraints perturbs parameters away from a well-optimized minimum, generally resulting in performance degradation. Recent studies indicate that low-loss FP solutions are not isolated, but instead belong to connected low-loss subspaces of the loss landscape, where the loss maintains nearly the same minimum value. Models sampled from these subspaces are diverse and retain high accuracy. This raises the question: can a quantized model be constructed to lie within a low-loss subspace of the FP model, thereby automatically preserving performance? We address this question by learning quantization-aware linear paths in weight space optimized to minimize loss. We demonstrate that the midpoint of the resulting subspace is, by design, quantization-friendly and that its direct quantization yields performance comparable to that of quantization-aware training. The proposed procedure offers a novel perspective on weight quantization and, in contrast to conventional methods, neither relies on the straight-through estimator nor involves explicit discretization during training.

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

PepALD: Macrocyclic Peptide Generation via Autoregressive Latent Diffusion

arXiv:2606.14510v1 Announce Type: new Abstract: Macrocyclic peptides are promising therapeutic candidates for intracellular targets, but their design requires simultaneous control over non-natural monomer chemistry, ring topology, membrane permeability, and target binding. Existing SMILES- or HELM-string generative models either operate in long atom-level sequence spaces or treat monomers as symbolic tokens with limited chemical grounding. We introduce PepALD, an Autoregressive Latent Diffusion (ALD) foundation model for de novo macrocyclic peptide generation. The model represents HELM monomers with structured chemical embeddings, generates each residue through context-conditioned diffusion in chemically informed latent space, predicts R-group-aware ring closures during autoregressive generation, and aligns the denoiser to affinity rewards using winner-protected diffusion-adapted preference optimization. In silico experiments demonstrate PepALD's generation quality and reward-optimization performance against representative peptide generation baselines.

07.
arXiv (CS.CV) 2026-06-25

Efficient Cross-Scale Invertible Hiding Network with Spatial-Frequency Collaboration and Non-Invertible Mechanism

Image hiding aims to conceal image-level messages within cover images at the same resolution. Invertible neural networks (INN)-based image hiding has emerged as an important branch. It treats concealing and revealing as a pair of inverse problems on image domain transformation and uses INN's forward and backward processes to address them. Due to architectural constraints, existing INN-based methods suffer from single-scale and single-domain feature extraction and limited nonlinear representation capability, resulting in inferior image quality. To mitigate these limitations, we propose an efficient cross-scale invertible hiding network with the spatial-frequency collaboration and the non-invertible mechanism, termed CrosInv. CrosInv exploits cross-scale and spatial-frequency collaborative features while enhancing nonlinear representation. Specifically, we introduce a cross-scale invertible module that bijectively maps inputs to cross-scale representations. To effectively integrate spatial and frequency information, the cross-scale invertible module employs pixel shuffle, Haar wavelet transformation, and their inverse operations for scale transformation. Furthermore, a non-invertible cross dense module is integrated to enhance the nonlinearity. Comprehensive experiments verify the effectiveness and superiority of the proposed CrosInv.

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

Toward Vibe Medicine: A Self-Evolving Multi-Agent Framework for Clinical Decision Support

arXiv:2606.15504v1 Announce Type: new Abstract: In recent years, the advances of large language models and autonomous agents have revolutionized the healthcare field, facilitating diagnosis and improving treatment results. However, most existing AI systems rely on pre-trained knowledge and predefined pipelines, which struggle to learn dynamically from the interactive chat session history that contains patient outcomes and past failures. To address this limitation, we propose VIBEMed, a multi-agent framework with a built-in self-evolution mechanism and architecture-level safety sandbox for robust clinical decision support. The system integrates three specialized agents, including a Clinical Diagnostic Agent (CDA) for hypothesis generation, a Therapeutic Execution Agent (TEA) for treatment planning, and a Clinical Evolution Manager Agent (CEMA) that distills longitudinal clinical feedback into reusable knowledge, transforming multimodal patient information into personalized medical decisions. Through self-evolution mechanism, the framework enables iterative updates across memory, model behavior, and decision strategies, allowing the system to improve over time. Experimental results show that VIBEMed demonstrates superior performance through its evolving mechanism in complex clinical cases, particularly in tasks that require integrated decision-making and longitudinal planning. The framework also supports reliable end-to-end decisions in challenging scenarios such as oncology treatment planning, highlighting its feasibility in real-world clinical contexts. Overall, VIBEMed provides a practical path beyond static AI systems toward adaptive, experience-driven clinical decision support, demonstrating the value of combining multi-agent collaboration with continuous evolution for advancing precision medicine.

09.
arXiv (CS.AI) 2026-06-18

Benchmarking Action Spaces in Reinforcement Learning for Vision-based Robotic Manipulation

arXiv:2606.18594v1 Announce Type: cross Abstract: In real-world reinforcement learning (RL), the choice of action space can play a key role in shaping motion smoothness, safety, and overall task performance. In this study, we evaluate pose increment, pose velocity, joint position increment, and joint velocity across two vision-based manipulation tasks: object picking and pushing. We train policies in simulation and deploy them to the real world using sim-to-real transfer. We find that action-space representation indeed significantly affects sim-to-real performance. In particular, we find that the joint velocity action space is best for the vision-based picking and pushing tasks in terms of smoothness and final task performance. We also provide practical guidance for RL practitioners in choosing action spaces for both simulation and real-world experiments.

10.
medRxiv (Medicine) 2026-06-15

Fanconi Anemia as a Window into Premalignant Field Cancerization of the Oral Mucosa

Head and neck squamous cell carcinoma (HNSCC) evolves through stepwise clonal expansion within genetically altered mucosa fields, yet actionable biomarkers remain undefined. Leveraging Fanconi anemia (FA), a cancer predisposition syndrome with extreme HNSCC risk due to defective DNA interstrand crosslink repair, we profiled premalignant changes in the oral cavity using noninvasive brush biopsies. Consistent with our prior demonstration of genomic instability in FA-associated SCCs, we detected pathogenic TP53 variants in 26% and copy number alterations in 60.5% in clinically normal-appearing oral mucosa of individuals with FA. These subclinical clonal expansions define candidate biomarkers of early clonal evolution amenable to serial sampling for risk stratification and prevention studies. Since FA-associated SCCs share genomic features with sporadic HNSCC, these findings may extend to the broader population. We also identify somatic reversion of a pathogenic FANCB variant, providing evidence of genomic self-correction and suggesting a potential avenue for gene-based cancer prevention in FA.

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

XFlow: An Executable Protocol Programming System for Reliable Multi-Agent Workflows

arXiv:2606.14790v1 Announce Type: cross Abstract: LLM-based multi-agent systems increasingly coordinate planning, reasoning, tool use, and human interaction, yet their reliability remains limited. A central source of this limitation is the underspecified prompt–harness boundary. Current systems lack a principled way to decide which workflow commitments should remain in prompts and which should become harness structure. We present XFlow, an executable protocol programming system for reliable multi-agent workflows, and XPF (XFlow Protocol Format), its domain-specific protocol programming language. XFlow occupies a middle position between prompt-only orchestration and markup-like workflow descriptions. XPF remains readable as a literate protocol, but it is compiled and executed as a program. Its design keeps informal semantic work inside actors while moving selected commitments into harness structure that can be checked, preserved, and enforced. At runtime, XFlow stages uncertainty through lifecycle-governed symbols, which are typed state cells with validation and commit states. Actor outputs are mediated before they become shared state, instead of spreading through prompts, transcripts, or implicit memory. Our experiments cover Constrained Interaction, Long-Context Reasoning, and Agentic Software Engineering. They show that XFlow improves reliability by making constraints, evidence handling, and process requirements explicit and enforceable.

12.
arXiv (CS.LG) 2026-06-17

Conformalized Quantum DeepONet Ensembles for Scalable Operator Learning with Distribution-Free Uncertainty

arXiv:2605.00330v2 Announce Type: replace Abstract: Operator learning enables fast surrogate modeling of high-dimensional dynamical systems, but existing approaches face two fundamental limitations: quadratic inference complexity and unreliable uncertainty quantification in safety-critical settings. We propose Conformalized Quantum DeepONet Ensembles, a framework that addresses both challenges simultaneously. By leveraging Quantum Orthogonal Neural Networks (QOrthoNNs), we reduce operator inference complexity from O(n^2) to O(n), enabling scalable evaluation over fine discretizations. To provide rigorous uncertainty quantification, we combine ensemble-based epistemic modeling with adaptive conformal prediction, yielding distribution-free coverage guarantees. A key challenge in ensembling is that naive parallelism scales hardware resources linearly with the number of models. We resolve this by using Superposed Parameterized Quantum Circuits (SPQCs), which compress multiple ensemble members into a single circuit and enable simultaneous multi-model execution. Experiments on synthetic partial differential equations and real-world power system dynamics demonstrate that our approach achieves accurate predictions while maintaining calibrated uncertainty under realistic quantum noise. These results establish a practical pathway toward scalable, uncertainty-aware operator learning in quantum machine learning.

13.
PLOS Computational Biology 2026-06-22

Heterogeneous suppressive effect of <i>Wolbachia</i> incompatible insect technique coupled with sterile insect technique across time and historical <i>Ae. aegypti</i> abundance - using distributional synthetic controls

作者:

by Yichen Zhai, Chia-Chen Chang, Zhiyong Xi, Cheong Huat Tan, Lee Ching Ng, Jue Tao Lim Background Biological control tools such as Wolbachia incompatible-insect technique, are a promising class of interventions to modify and suppress Aedes aegypti mosquitoes to reduce risk of Aedes-borne diseases. Due to the spatial nature of the intervention, intervention effects can be spatio-temporally heterogeneous. Yet, most evaluations of field-based technologies rely on average treatment effects, which preclude characterization and understanding of treatment effect heterogeneities and the factors influencing it. Methods Here, we developed a causal inference framework using distributional synthetic controls to explicitly account for spatio-temporal trap-level mosquito abundance data to ascertain the entomological efficacy of Wolbachia in suppressing Ae. aegypti abundance. This method is able to construct counterfactual distributions of intervened areas, provide detailed comparisons to actual distributions and quantify treatment effects of the intervention on mosquito abundance over different quantiles. By employing our framework to trap-level mosquito abundance data from 57,990 unique mosquito traps routinely maintained and measured twice a week, and a large-scale field trial of Wolbachia incompatible-insect technique coupled with sterile insect technique (IIT-SIT) in Singapore, we (1) quantified heterogeneous treatment effects for IIT-SIT across the time-since-intervention, over the traps’ historical mosquito abundance, over calendar time, (2) quantified whether elimination of wild-type Aedes aegypti was possible in intervention locations and (3) addressed if suppressive effects in spillover locations adjacent to directly intervened locations were heterogeneous. Results IIT-SIT interventions led to a strong suppressive effect on adult Aedes aegypti abundance. From the onset of intervention in directly treated locations, sector-specific intervention effectiveness (IE) ranged from 24.04% in the earliest treatment period, and reached 86.08% in the latest treatment period. Raw reductions in aegypti abundance were also found to increase over time as sectors were intervened over longer time periods. In spillover sectors, IE was lower in magnitude and more variable, but average IE reached a maximum of 78.08% in 2-years post-treatment. Wolbachia interventions also led to an increase in the percentage of traps recording no mosquitoes from 6.8% at the start of intervention to 33.01% 124-weeks post-intervention. We found that IE was higher in sectors with lower historical mosquito abundance. However, IE converged across sectors with different historical mosquito abundance as intervention time increased. Conclusion This study revealed spatial heterogeneities in suppressing wild-type female Ae. aegypti by IIT-SIT and provided strong evidence that IIT-SIT can drastically suppress wild-type Ae. aegypti populations despite heterogeneous treatment effects over time.

14.
arXiv (CS.CL) 2026-06-25

How Large Language Models Source Brand Reputation Across Languages and Markets

When a large language model (LLM) answers a question about a company, it grounds the answer in retrieved web sources, and those sources decide what the model says. Most analysis of AI brand visibility looks at the answer text. This study looks one step earlier, at the citations. We merge three Rankfor.AI datasets covering 128 brands across 12 home markets and 13 languages, and analyse 167,551 URL-grounded citations (189,974 total attribution rows). We classify each citation by domain and source type and measure where AI gets its brand information, by language and by market. Four patterns hold. First, AI grounds brand answers overwhelmingly in third-party sources: 85.7% of citations point to sites the brand does not own, against 14.3% owned. Second, the source base is concentrated and long-tailed: 80% of citations come from about 18% of domains, fitting a Zipf law (alpha = 0.86, R^2 = 0.983). Third, one reference site dominates almost everywhere: Wikipedia is the most-cited domain in 11 of 12 languages, the exception being Lithuanian, where the business daily vz.lt edges it (4.38%). Fourth, the source mix is market-specific at the margin: for 46 Polish national brands the most-cited domain is YouTube, and four HR and careers portals supply 637 citations against 297 for Polish Wikipedia, about twice as many.

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

When Smaller Wins: Dual-Stage Distillation and Pareto-Guided Compression of Liquid Neural Networks for Edge Battery Prognostics

arXiv:2601.06227v3 Announce Type: replace-cross Abstract: Battery management systems increasingly require accurate battery health prognostics under strict on-device constraints. This paper presents DLNet, a practical framework with dual-stage distillation of liquid neural networks that turns a high-capacity model into compact and edge-deployable models for battery health prediction. DLNet first applies Euler discretization to reformulate liquid dynamics for embedded compatibility. It then performs dual-stage knowledge distillation to transfer the teacher model's temporal behavior and recover it after further compression. Pareto-guided selection under joint error-cost objectives retains student models that balance accuracy and efficiency. We evaluate DLNet on a widely used dataset and validate real-device feasibility on an Arduino Nano 33 BLE Sense using int8 deployment. The final deployed student achieves a low error of 0.0066 when predicting battery health over the next 100 cycles, which is 15.4% lower than the teacher model. It reduces the model size from 616 kB to 94 kB with 84.7% reduction and takes 21 ms per inference on the device. These results support a practical smaller wins observation that a small model can match or exceed a large teacher for edge-based prognostics with proper supervision and selection. Beyond batteries, the DLNet framework can extend to other industrial analytics tasks with strict hardware constraints.

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

Prompt Perturbation for Reliable LLM Evaluation over Comparison Graphs

Evaluating large language models (LLMs) is important for understanding their capabilities, comparing competing systems, and supporting the deployment of reliable models in practice. For open-ended tasks, pairwise evaluation has become a popular paradigm, in which two responses to the same prompt are compared and the resulting judgments are aggregated into an overall ranking. A central challenge of this paradigm is intransitivity: the induced comparison outcomes may fail to support any coherent global ranking. For example, one may observe cyclic preferences such as $A \succ B \succ C \succ A$, or inconsistencies involving ties such as $A \equiv B\equiv C\neq A$. Such contradictions make the resulting leaderboard unstable and challenging to interpret. In this paper, we propose a prompt perturbation framework for improving the consistency of pairwise LLM evaluation. Our approach generates perturbed variants of each prompt, uses the resulting comparison graphs to identify and filter out structurally inconsistent comparison patterns, and then applies standard ranking methods to the filtered comparisons. A key feature of the proposed framework is that graph-level structural consistency is incorporated explicitly into the evaluation pipeline before ranking aggregation. This provides a simple and principled way to reduce cyclic inconsistencies and improve the reliability of LLM rankings.

17.
PLOS Computational Biology 2026-06-02

Assessing the importance of sex and disease-specific anatomy in electrophysiology and mechanical simulations with a newly developed public virtual cohort of four-chamber heart models

by José Alonso Solís-Lemus, Rosie K. Barrows, Cristobal Rodero, Marina Strocchi, Natalie Montarello, Nishant Lahoti, Cesare Corrado, Abdul Qayyum, Shahrokh Rahmani, Caroline Roney, Gernot Plank, Christoph Augustin, Hao Xu, Alistair Young, Pras Pathmanathan, Ronak Rajani, Steven A. Niederer This work presents a study on how differences in cardiac anatomy attributed to sex and disease can influence cardiac electrophysiology and mechanics using a virtual cohort of four-chamber heart models. Patient anatomy varies across sex and disease. However, capturing this variation in in-silico studies remains poorly accounted for, with studies often using either single representative cases or imbalanced virtual cohorts. Whole-heart electromechanics models incorporate the patient’s anatomy, electrophysiology and mechanics across different scales, from molecular, tissue and whole-heart and circulatory system levels. However, cardiac models are typically built from one or a small number of anatomies, with sex rarely reported and the effects of anatomical variability, which include those due to sex or disease, largely unexplored. This limits clinical translation and reduces regulatory credibility. We developed fifty patient-specific anatomical models of 25 male and 25 female hearts in heart failure and control cases. We ran benchmark passive inflation and paced activation simulations with consistent parameters and boundary conditions across cases to isolate the impact of anatomical variations with sex and disease. Heart failure models exhibited increased chamber volumes, larger volume changes during inflation, and delayed activation times relative to controls. These trends were consistent across sexes, although right ventricular activation showed a significant sex-based difference. Variations in anatomy with sex and disease have a significant impact on cardiac simulations, which support the inclusion of multiple heart anatomical models in in-silico trials. The resulting virtual cohort captures key anatomical variability and is publicly available, along with the underlying code (see Data Availability statement).

18.
medRxiv (Medicine) 2026-06-24

IgG2 Galactosylation is related to higher antibody dependent enhancement for dengue in cross-reactive antibodies from Sars-CoV-2

Cross-reactive antibodies against dengue virus are known to cause antibody-dependent enhancement (ADE) of infection or disease severity under specific conditions. In our previous study, we showed that primary immunization with the COVID-19 vaccine induces induces cross-reactive IgG causing ADE against dengue. In the present study, we investigated the influence of IgG Fc-glycosylation (analyzed by LC-MS/MS) on ADE mediated by cross-reactive IgG against dengue from IgG against SARS-CoV-2. We found a clear correlation between anti-DENV2 E IgG2 galactosylation and the ADE capacity of cross-reactive IgG against dengue in individuals vaccinated against COVID-19. IgG2 sialylation increased over time; however, it was not correlated with ADE capacity. This phenomenon was restricted to IgG2, whereas anti-DENV2 E IgG1 Fc-glycosylation remained stable after COVID-19 vaccination.

19.
PLOS Computational Biology 2026-06-05

StPedf: Cell trajectory inference of spatial transcriptomics via spatial proximity embedding and spatial density-adaptive fusion

作者:

by Yuan Zhang, Ziyan Sun, Zhixin Shi, Mengdi Nan, Yuhan Fu, Qing Ren, Jie Gao Spatial transcriptomics is transforming our multidimensional understanding of cellular spatial organization and its functional mechanisms in processes such as development and disease by systematically resolving the spatial heterogeneity of gene expression within tissues. To delve deeper into the dynamic processes underlying spatial expression patterns, spatial trajectory inference integrates genetic and spatial information to reconstruct the spatial developmental trajectories of cells within tissues. This approach reveals the patterns of differentiation and dynamic changes as cellular states evolve continuously along spatial axes. However, existing methods often struggle to uniformly model the complex, nonlinear interactions between high-dimensional gene expression and spatial coordinates. Here, we introduce StPedf, whose core lies in employing a neural network with a masking mechanism to capture complex nonlinear interactions between high-dimensional genes and spatial positions. It further leverages spatial proximity information as a guiding cue, dynamically and adaptively adjusting the embedding of gene and spatial information and the weighting of spatial proximity information based on spatial density. This enables trajectory inference guided by spatial information. This enables optimal transport to derive intercellular transition matrices, reconstruct cellular differentiation trajectories, and construct pseudo-spatiotemporal maps. StPedf demonstrates superior performance over existing methods on five structurally distinct simulated datasets. Using StPedf, we successfully mapped distinct lineages in the spatial trajectories of telencephalon regeneration in the Ambystoma mexicanum, multiple malignant lineages expanding within primary tumors, and developmental spatial trajectories and pseudo-spatiotemporal maps in human dorsolateral prefrontal cortex (DLPFC). StPedf significantly enhances the accuracy and interpretability of spatial trajectory inference, providing critical technical support for revealing the dynamic patterns of cellular fate transitions within tissue microenvironments.

20.
arXiv (CS.AI) 2026-06-17

EAGG: Embodiment-Aligned Grasp Generation via Geometry-Aware Graph Conditioning

arXiv:2606.18092v1 Announce Type: cross Abstract: Cross-end-effector grasp generation seeks a unified model that generalizes across objects and across embodiments ranging from parallel grippers to dexterous end effectors. Existing grasp generators are typically designed for a fixed embodiment or encode embodiment identity with a static descriptor, which weakens transfer when topology, actuation coupling, and contact geometry differ substantially. We present EAGG, an embodiment-aligned grasp generator that represents each embodiment with a topology-aware end-effector graph and an embodiment-specific low-dimensional end-effector control space. A frozen end-effector-cognition backbone converts the current articulated state into geometry-aware tokens that act as a reusable morphology prior, and iterative geometry injection refreshes these tokens throughout sampling so that conditioning remains synchronized with the evolving end-effector geometry. On the MultiGripperGrasp benchmark, EAGG reaches 56.17% average success across six training end effectors, remaining within 1.10 percentage points of specialized training while preserving transfer to finetuning and zero-shot end effectors. Iterative geometry injection further reduces the pooled median contact distance from 0.239 cm to 0.189 cm. These results show that cross-end-effector grasp generation is strengthened by aligning embodiment structure inside a shared generator rather than suppressing embodiment differences. Code is available at https://github.com/wanhaoniu/EAGG.

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

Be Your Own Teacher: Steering Protein Language Models via Unsupervised Reward Optimization

arXiv:2606.18961v1 Announce Type: new Abstract: Protein language models (PLMs) have emerged as powerful tools for controllable biomolecular design, yet their post-training adaptation typically relies on costly wet-lab validation or curated preference datasets. To overcome this supervision bottleneck, we introduce unsupervised reward optimization of PLMs, a comprehensive framework for steerable protein generation without ground-truth labels. Our key insight is that task-agnostic rewards, which combine intrinsic model uncertainty with extrinsic semantic consistency informed by protein representation models, exhibit strong correlation with controllability measures across base models and temperature regimes. Building upon this discovery, we propose two offline algorithms: Soft Reward Optimization (SRO) and Binarized Reward Optimization (BRO), which effectively maximize the classical RLHF objective induced by these proxy rewards. Extensive experiments on compositional out-of-distribution prompts demonstrate that both methods significantly outperform competitive baselines (DPO, KTO), while approaching oracle performance across multiple sampling temperatures, model scales and protein families. Moreover, PLMs fine-tuned with unsupervised rewards can achieve consistently higher coverage compared to their base model in pass@k evaluations. By enabling self-improvement of PLMs through their own generated experience, our framework provides a scalable pathway toward controllable biomolecular design in settings where labeled preferences or experimental feedback are scarce or unavailable.

22.
arXiv (CS.AI) 2026-06-17

Model Validation of Agentic AI Systems: A POMDP-Based Framework for Belief-State, Forecast, and Policy Validation

arXiv:2606.17383v1 Announce Type: cross Abstract: Agentic artificial intelligence systems introduce a new class of model risk. Unlike traditional predictive models, autonomous agents continuously acquire information, form beliefs regarding latent states of the environment, generate forecasts, select actions, and adapt their behavior over time. Existing validation methodologies focus primarily on predictive accuracy and therefore provide limited insight into the quality of the underlying decision process. This paper proposes a model validation framework for agentic AI based on Partially Observable Markov Decision Processes (POMDPs). The framework decomposes autonomous decision making into information, beliefs, forecasts, actions, and utility, allowing each component to be validated independently. Large language models (LLMs) are formalized as approximate Bayesian filtering operators, and a model-risk taxonomy is developed encompassing state-space, filtering, forecast, policy, utility-specification, and parameter risks. The model risk validation methodology is demonstrated through a portfolio-management case study in which an agent infers latent market regimes from market and macroeconomic information, generates belief-conditioned forecasts, and constructs portfolios using a Black–Litterman framework. Empirical validation combines performance analysis, belief calibration diagnostics, coverage tests, ablation studies, and parameter-sensitivity analysis. The results indicate that latent-state inference contributes independently to decision quality and that the principal conclusions remain robust across a broad range of parameter values. The principal contribution of the paper is a practical framework for extending established model risk management concepts to autonomous AI systems and providing a rigorous foundation for their validation, governance, and monitoring.

23.
PLOS Computational Biology 2026-06-17

Machine learning-driven identification of virulence determinants in <i>Borrelia burgdorferi</i> associated with human dissemination

by Hoa Thanh Nguyen, Catherine A. Brissette Lyme disease, the most common tick-borne infectious disease in the United States, presents with highly variable clinical outcomes, ranging from localized erythema migrans to severe disseminated complications affecting the heart, joints, and nervous system. The bacterial determinants underlying this phenotypic variation remain largely unknown, limiting our ability to predict disease progression and optimize treatment strategies. Here, we applied machine learning (ML) approaches to identify specific amino acid residues within surface-exposed virulence factors that predict human dissemination phenotypes. Utilizing the published whole genome sequences from 299 clinical Borrelia burgdorferi isolates collected from the United States and Slovenia over a 30-year period (1992–2021), we extracted and characterized translated amino acid sequences (variants) of seven known virulence factors (BB_0406, BBK32, DbpA, OspA, OspC, P66, and RevA). Protein variants were classified based on their association with disseminated versus localized infections using clinical metadata. Cramér’s V analysis revealed possible strong associations between dissemination phenotypes and five adhesins: BBK32, DbpA, OspC, P66, and RevA. We developed ML models using five algorithms with multiple feature selection strategies, achieving robust predictive performance for DbpA, OspC, and RevA variants (all performance metrics > 0.7). Feature importance analysis identified 57, 29, and 42 key predictive residues for DbpA, OspC, and RevA, respectively. Notably, B-cell epitope prediction revealed significant enrichment of ML-identified residues within predicted epitope regions for OspC (11 overlapping residues, OR = 3.57, p = 0.006) and RevA (12 overlapping residues, OR = 2.37, p = 0.048), suggesting these residues may influence immune recognition and bacterial persistence. This study establishes the first computational framework linking Borrelia protein sequence variants to clinical dissemination phenotypes, providing molecular insights into Lyme disease pathogenesis that may inform the development of improved diagnostics and therapeutic targets.

24.
medRxiv (Medicine) 2026-06-24

Using outlier detection methods to incorporate highly heterogeneous infection rates into compartment models

Superspreading events (SSEs) produce extreme, rare bursts of disease transmission that standard compartment models, which assume population homogeneity, fail to capture. This inability to model heterogeneity in transmission rates can result in biased estimates of transmissivity. To address this limitation, we present a modular framework that treats SSEs as statistical outliers in case count time series and incorporates them into SIR-type models via pulse terms that transfer SSE cases directly from susceptible to infected compartments. This separation isolates anomalous SSE-driven transmission from background spread, which reduces bias when estimating mean transmission rates. We validate the approach on synthetic data generated by a stochastic model with embedded SSEs, demonstrating accurate recovery of the true non-SSE transmission parameter. We then apply the method to COVID-19 outbreaks in Hong Kong and the German district of Gutersloh, showing improved model fits and more robust estimates of background transmissivity both for a period with constant transmission and for a period with temporally structured NPI-driven heterogeneities. The framework's interchangeable outlier-detection, compartment, and SSE modules make it adaptable to diverse diseases and data contexts.

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

SSIL: Self-Supervised Imitation Learning for End-to-End Driving

arXiv:2308.14329v4 Announce Type: replace-cross Abstract: In autonomous driving, the end-to-end (E2E) driving approach that predicts vehicle control signals directly from sensor data is rapidly gaining attention. To learn a safe E2E driving system, one needs an extensive amount of driving data and human intervention. Vehicle control data is constructed by many hours of human driving, and it is challenging to construct large vehicle control datasets. Often, publicly available driving datasets are collected with limited driving scenes, and collecting vehicle control data is only available by vehicle manufacturers. To address these challenges, this paper proposes the first self-supervised learning framework, Self-Supervised Imitation Learning (SSIL), for E2E driving. The proposed SSIL framework can learn vision-based E2E driving networks without using driving command data or a pre-trained model. To construct pseudo steering angle data, proposed SSIL predicts a pseudo target from the vehicle's poses at the current and previous time points that are estimated with light detection and ranging sensors. In addition, we propose a new cross-attention-based conditioning approach (CACA) for a vision encoder in E2E driving, where a high-level instruction serves as the conditioning signal for visual information. Our numerical experiments with three different benchmark datasets demonstrate that the proposed SSIL framework achieves very comparable E2E driving accuracy with the supervised learning counterpart. Furthermore, the proposed pseudo-label predictor outperformed an existing one using proportional integral derivative controller, and proposed CACA achieved superior performance over existing conditioning approaches.