As shown in Figure 13, we applied higher noise settings (SNR 0.005, 0.001) to the

Single particle cryo-electron microscopy (cryo-EM) is a widely used imaging technique for visualizing biomolecular complexes at near-atomic resolution.

Protein structure prediction models are now capable of generating accurate 3D structural hypotheses from sequence alone. However, they routinely fail to capture the conformational diversity of dynamic biomolecular complexes, often requiring heuristic MSA subsampling approaches for generating alternative states. In parallel, cryo-electron microscopy (cryo-EM) has emerged as a powerful tool for imaging near-native structural heterogeneity, but is challenged by arduous pipelines to transform raw experimental data into atomic models. Here, we bridge the gap between these modalities, combining cryo-EM density maps with the rich sequence and biophysical priors learned by protein structure prediction models. Our method, CryoBoltz, guides the sampling trajectory of a pretrained biomolecular structure prediction model using both global and local structural constraints derived from density maps, driving predictions towards conformational states consistent with the experimental data. We demonstrate that this flexible yet powerful inference-time approach allows us to build atomic models into heterogeneous cryo-EM maps across a variety of dynamic biomolecular systems including transporters and antibodies. Code is available at https://github.com/ml-struct-bio/cryoboltz .

As shown in Figure 13, we applied higher noise settings (SNR 0.005, 0.001) to the

Single particle cryo-electron microscopy (cryo-EM) is a widely used imaging technique for visualizing biomolecular complexes at near-atomic resolution.

Autonomous vehicles (AV) look set to become common on our roads within the next few years. However, to achieve the final breakthrough, not only functional progress is required, but also satisfactory safety assurance must be provided. Among those, a question demanding special attention is the need to assess and quantify the overall safety of an AV. Such an assessment must consider on the one hand the imperfections of the AV functionality and on the other hand its interaction with the environment. In a previous paper we presented a model-based approach to AV safety assessment in which we use a probabilistic model to describe road hazards together with the impact on AV safety of imperfect behavior of AV functions, such as safety monitors and perception systems. With this model, we are able to quantify the likelihood of the occurrence of a fatal accident, for a single operating condition. In this paper, we extend the approach and show how the model can deal explicitly with a set of different operating conditions defined in a given ODD.

Cryo-electron microscopy (cryo-EM) is a powerful technique for determining high-resolution 3D biomolecular structures from imaging data. As this technique can capture dynamic biomolecular complexes, 3D reconstruction methods are increasingly being developed to resolve this intrinsic structural heterogeneity. However, the absence of standardized benchmarks with ground truth structures and validation metrics limits the advancement of the field. Here, we propose CryoBench, a suite of datasets, metrics, and performance benchmarks for heterogeneous reconstruction in cryo-EM. We propose five datasets representing different sources of heterogeneity and degrees of difficulty. These include conformational heterogeneity generated from simple motions and random configurations of antibody complexes and from tens of thousands of structures sampled from a molecular dynamics simulation. We also design datasets containing compositional heterogeneity from mixtures of ribosome assembly states and 100 common complexes present in cells. We then perform a comprehensive analysis of state-of-the-art heterogeneous reconstruction tools including neural and non-neural methods and their sensitivity to noise, and propose new metrics for quantitative comparison of methods. We hope that this benchmark will be a foundational resource for analyzing existing methods and new algorithmic development in both the cryo-EM and machine learning communities.

As solar power continues to grow and replace traditional energy sources, the need for reliable forecasting models becomes increasingly important to ensure the stability and efficiency of the grid. However, the management of these models still needs to be improved, and new tools and technologies are required to handle the deployment and control of solar facilities. This work introduces a novel framework named Cloud-based Analysis and Integration for Data Efficiency (CAIDE), designed for real-time monitoring, management, and forecasting of solar irradiance sensor farms. CAIDE is designed to manage multiple sensor farms simultaneously while improving predictive models in real-time using well-grounded Modeling and Simulation (M&S) methodologies. The framework leverages Model Based Systems Engineering (MBSE) and an Internet of Things (IoT) infrastructure to support the deployment and analysis of solar plants in dynamic environments. The system can adapt and re-train the model when given incorrect results, ensuring that forecasts remain accurate and up-to-date. Furthermore, CAIDE can be executed in sequential, parallel, and distributed architectures, assuring scalability. The effectiveness of CAIDE is demonstrated in a complex scenario composed of several solar irradiance sensor farms connected to a centralized management system. Our results show that CAIDE is scalable and effective in managing and forecasting solar power production while improving the accuracy of predictive models in real time. The framework has important implications for the deployment of solar plants and the future of renewable energy sources.

The single-particle cryo-EM field faces the persistent challenge of preferred orientation, lacking general computational solutions. We introduce cryoPROS, an AI-based approach designed to address the above issue. By generating the auxiliary particles with a conditional deep generative model, cryoPROS addresses the intrinsic bias in orientation estimation for the observed particles. We effectively employed cryoPROS in the cryo-EM single particle analysis of the hemagglutinin trimer, showing the ability to restore the near-atomic resolution structure on non-tilt data. Moreover, the enhanced version named cryoPROS-MP significantly improves the resolution of the membrane protein NaX using the no-tilted data that contains the effects of micelles. Compared to the classical approaches, cryoPROS does not need special experimental or image acquisition techniques, providing a purely computational yet effective solution for the preferred orientation problem. Finally, we conduct extensive experiments that establish the low risk of model bias and the high robustness of cryoPROS.

Emergent behavior is a key feature defining a system under study as a complex system. Simulation has been recognized as the only way to deal with the study of the emergency of properties (at a macroscopic level) among groups of system components (at a microscopic level), for the manifestations of emergent structures cannot be deduced from analysing components in isolation. A systems-oriented generalisation must consider the presence of feedback loops (micro components react to macro properties), interaction among components of different classes (modular composition) and layered interaction of subsystems operating at different spatio-temporal scales (hierarchical organisation). In this work we introduce Emergent Behavior-DEVS (EB-DEVS) a Modeling and Simulation (M&S) formalism that permits reasoning about complex systems where emergent behavior is placed at the forefront of the analysis activity. EB-DEVS builds on the DEVS formalism, adding upward/downward communication channels to well-established capabilities for modular and hierarchical M&S of heterogeneous multi-formalism systems. EB-DEVS takes a minimalist stance on expressiveness, introducing a small set of extensions on Classic DEVS that can cope with emergent behavior, and making both formalisms interoperable (the modeler decides which subsystems deserve to be expressed via micro-macro dynamics). We present three case studies: flocks of birds with learning, population epidemics with vaccination and sub-cellular dynamics with homeostasis, through which we showcase how EB-DEVS performs by placing emergent properties at the center of the M&S process.