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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds the receptor angiotensin converting enzyme 2 (ACE2) and drives virus-host membrane fusion through refolding of its S2 domain. Whereas the S1 domain contains high sequence variability, the S2 domain is conserved and is a promising pan-betacoronavirus vaccine target. We applied cryo–electron tomography to capture intermediates of S2 refolding and understand inhibition by antibodies to the S2 stem-helix. Subtomogram averaging revealed ACE2 dimers cross-linking spikes before transitioning into S2 intermediates, which were captured at various stages of refolding. Pan-betacoronavirus neutralizing antibodies targeting the S2 stem-helix bound to and inhibited refolding of spike prehairpin intermediates. Combined with molecular dynamics simulations, these structures elucidate the process of SARS-CoV-2 entry and reveal how pan-betacoronavirus S2-targeting antibodies neutralize infectivity by arresting prehairpin intermediates. 

We propose a data-driven learning framework for the analytic continuation problem in numerical quantum many-body physics. Designing an accurate and efficient framework for the analytic continuation of imaginary time using computational data is a grand challenge that has hindered meaningful links with experimental data. The standard Maximum Entropy (MaxEnt)-based method is limited by the quality of the computational data and the availability of prior information. Also, the MaxEnt is not able to solve the inversion problem under high level of noise in the data. Here we introduce a novel learning model for the analytic continuation problem using a Adams-Bashforth residual neural network (AB-ResNet). The advantage of this deep learning network is that it is model independent and, therefore, does not require prior information concerning the quantity of interest given by the spectral function. More importantly, the ResNet-based model achieves higher accuracy than MaxEnt for data with higher level of noise. Finally, numerical examples show that the developed AB-ResNet is able to recover the spectral function with accuracy comparable to MaxEnt where the noise level is relatively small.

 

Reduced order models (ROMs) are computational models whose dimension is significantly lower than those obtained through classical numerical discretizations (e.g., finite element, finite difference, finite volume, or spectral methods). Thus, ROMs have been used to accelerate numerical simulations of many query problems, e.g., uncertainty quantification, control, and shape optimization. Projection-based ROMs have been particularly successful in the numerical simulation of fluid flows. In this brief survey, we summarize some recent ROM developments for the quasi-geostrophic equations (QGE) (also known as the barotropic vorticity equations), which are a simplified model for geophysical flows in which rotation plays a central role, such as wind-driven ocean circulation in mid-latitude ocean basins. Since the QGE represent a practical compromise between efficient numerical simulations of ocean flows and accurate representations of large scale ocean dynamics, these equations have often been used in the testing of new numerical methods for ocean flows. ROMs have also been tested on the QGE for various settings in order to understand their potential in efficient numerical simulations of ocean flows. In this paper, we survey the ROMs developed for the QGE in order to understand their potential in efficient numerical simulations of more complex ocean flows: We explain how classical numerical methods for the QGE are used to generate the ROM basis functions, we outline the main steps in the construction of projection-based ROMs (with a particular focus on the under-resolved regime, when the closure problem needs to be addressed), we illustrate the ROMs in the numerical simulation of the QGE for various settings, and we present several potential future research avenues in the ROM exploration of the QGE and more complex models of geophysical flows. 

There are two main strategies for improving the projection-based reduced order model (ROM) accuracy—(i) improving the ROM, that is, adding new terms to the standard ROM; and (ii) improving the ROM basis, that is, constructing ROM bases that yield more accurate ROMs. In this paper, we use the latter. We propose two new Lagrangian inner products that we use together with Eulerian and Lagrangian data to construct two new Lagrangian ROMs, which we denote α-ROM and λ-ROM. We show that both Lagrangian ROMs are more accurate than the standard Eulerian ROMs, that is, ROMs that use standard Eulerian inner product and data to construct the ROM basis. Specifically, for the quasi-geostrophic equations, we show that the new Lagrangian ROMs are more accurate than the standard Eulerian ROMs in approximating not only Lagrangian fields (e.g., the finite time Lyapunov exponent (FTLE)), but also Eulerian fields (e.g., the streamfunction). In particular, the α-ROM can be orders of magnitude more accurate than the standard Eulerian ROMs. We emphasize that the new Lagrangian ROMs do not employ any closure modeling to model the effect of discarded modes (which is standard procedure for low-dimensional ROMs of complex nonlinear systems). Thus, the dramatic increase in the new Lagrangian ROMs’ accuracy is entirely due to the novel Lagrangian inner products used to build the Lagrangian ROM basis. 

Developing accurate, efficient, and robust closure models is essential in the construction of reduced order models (ROMs) for realistic nonlinear systems, which generally require drastic ROM mode truncations. We propose a deep residual neural network (ResNet) closure learning framework for ROMs of nonlinear systems. The novel ResNet-ROM framework consists of two steps: (i) In the first step, we use ROM projection to filter the given nonlinear system and construct a spatially filtered ROM. This filtered ROM is low-dimensional, but is not closed. (ii) In the second step, we use ResNet to close the filtered ROM, i.e., to model the interaction between the resolved and unresolved ROM modes. We emphasize that in the new ResNet-ROM framework, data is used only to complement classical physical modeling (i.e., only in the closure modeling component), not to completely replace it. We also note that the new ResNet-ROM is built on general ideas of spatial filtering and deep learning and is independent of (restrictive) phenomenological arguments, e.g., of eddy viscosity type. The numerical experiments for the 1D Burgers equation show that the ResNet-ROM is significantly more accurate than the standard projection ROM. The new ResNet-ROM is also more accurate and significantly more efficient than other modern ROM closure models. 

In this paper, we introduce the evolve-then-filter (EF) regularization method for reduced order modeling of convection-dominated stochastic systems. The standard Galerkin projection reduced order model (G-ROM) yield numerical oscillations in a convection-dominated regime. The evolve-then-filter reduced order model (EF-ROM) aims at the numerical stabilization of the standard G-ROM, which uses explicit ROM spatial filter to regularize various terms in the reduced order model (ROM). Our numerical results are based on a stochastic Burgers equation with linear multiplicative noise. The numerical result shows that the EF-ROM is significantly better than G-ROM.