13 research outputs found

    Anelastic sensitivity kernels with parsimonious storage for adjoint tomography and full waveform inversion

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    We introduce a technique to compute exact anelastic sensitivity kernels in the time domain using parsimonious disk storage. The method is based on a reordering of the time loop of time-domain forward/adjoint wave propagation solvers combined with the use of a memory buffer. It avoids instabilities that occur when time-reversing dissipative wave propagation simulations. The total number of required time steps is unchanged compared to usual acoustic or elastic approaches. The cost is reduced by a factor of 4/3 compared to the case in which anelasticity is partially accounted for by accommodating the effects of physical dispersion. We validate our technique by performing a test in which we compare the KαK_\alpha sensitivity kernel to the exact kernel obtained by saving the entire forward calculation. This benchmark confirms that our approach is also exact. We illustrate the importance of including full attenuation in the calculation of sensitivity kernels by showing significant differences with physical-dispersion-only kernels

    Spike residue 403 affects binding of coronavirus spikes to human ACE2

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    The bat sarbecovirus RaTG13 is a close relative of SARS-CoV-2, the cause of the COVID-19 pandemic. However, this bat virus was most likely unable to directly infect humans since its Spike (S) protein does not interact efficiently with the human ACE2 receptor. Here, we show that a single T403R mutation increases binding of RaTG13 S to human ACE2 and allows VSV pseudoparticle infection of human lung cells and intestinal organoids. Conversely, mutation of R403T in the SARS-CoV-2 S reduces pseudoparticle infection and viral replication. The T403R RaTG13 S is neutralized by sera from individuals vaccinated against COVID-19 indicating that vaccination might protect against future zoonoses. Our data suggest that a positively charged amino acid at position 403 in the S protein is critical for efficient utilization of human ACE2 by S proteins of bat coronaviruses. This finding could help to better predict the zoonotic potential of animal coronaviruses

    On‐the‐fly full Hessian Kernel calculations based upon seismic‐wave simulations

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    Full waveform inversion or adjoint tomography has routinely been performed to image the internal structure of the Earth at high resolution. This is typically done using the Fréchet kernels and the approximate Hessian or the approximate inverse Hessian because of the high‐computational cost of computing and storing the full Hessian. Alternatively, the full Hessian kernels can be used to improve inversion resolutions and convergence rates, as well as possibly to mitigate interparameter trade‐offs. The storage requirements of the full Hessian kernel calculations can be reduced by compression methods, but often at a price of accuracy depending on the compression factor. Here, we present open‐source codes to compute both Fréchet and full Hessian kernels on the fly in the computer random access memory (RAM) through simultaneously solving four wave equations, which we call Quad Spectral‐Element Method (QuadSEM). By recomputing two forward fields at the same time that two adjoint fields are calculated during the adjoint simulation, QuadSEM constructs the full Hessian kernels using the exact forward and adjoint fields. In addition, we also implement an alternative approach based on the classical wavefield storage method (WSM), which stores forward wavefields every kth (k≥1) timestep during the forward simulation and reads required fields back into memory during the adjoint simulation for kernel construction. Both Fréchet and full Hessian kernels can be computed simultaneously through the QuadSEM or the WSM code, only doubling the computational cost compared with the computation of Fréchet kernels alone. Compared with WSM, QuadSEM can reduce the disk space and input/output cost by three orders of magnitude in the presented examples that use 15,000 timesteps. Numerical examples are presented to demonstrate the functionality of the methods, and the computer codes are provided with this contribution

    Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination Boosts Neutralizing Activity Against Seasonal Human Coronaviruses

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    Background: Most of the millions of people that are vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), have previously been infected by related circulating human coronaviruses (hCoVs) causing common colds and will experience further encounters with these viruses in the future. Whether COVID-19 vaccinations impact neutralization of seasonal coronaviruses is largely unknown. Methods: We analyzed the capacity of sera derived from 24 individuals before and after heterologous ChAdOx1 nCoV-19 BNT162b2 prime-boost vaccination to neutralize genuine OC43, NL63, and 229E hCoVs, as well as viral pseudoparticles carrying the SARS-CoV-1, SARS-CoV-2, Middle East Respiratory Syndrome (MERS)-CoV, and hCoV-OC43, hCoV-NL63, and hCoV-229E spike proteins. Genuine hCoVs or spike containing pseudovirions were incubated with different concentrations of sera and neutralization efficiencies were determined by measuring viral RNA yields, intracellular viral nucleocapsid expression, or reporter gene expression in Huh-7 cells. Results: All individuals showed strong preexisting immunity against hCoV-OC43. Neutralization of hCoV-NL63 was more variable and all sera showed only modest inhibitory activity against genuine hCoV-229E. SARS-CoV-2 vaccination resulted in efficient cross-neutralization of SARS-CoV-1 but not of MERS-CoV. On average, vaccination significantly increased the neutralizing activity against genuine hCoV-OC43, hCoV-NL63, and hCoV-229E. Conclusions: Heterologous COVID-19 vaccination may confer some cross-protection against endemic seasonal coronaviruses

    Spike residue 403 affects binding of coronavirus spikes to human ACE2

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    Abstract The bat sarbecovirus RaTG13 is a close relative of SARS-CoV-2, the cause of the COVID-19 pandemic. However, this bat virus was most likely unable to directly infect humans since its Spike (S) protein does not interact efficiently with the human ACE2 receptor. Here, we show that a single T403R mutation increases binding of RaTG13 S to human ACE2 and allows VSV pseudoparticle infection of human lung cells and intestinal organoids. Conversely, mutation of R403T in the SARS-CoV-2 S reduces pseudoparticle infection and viral replication. The T403R RaTG13 S is neutralized by sera from individuals vaccinated against COVID-19 indicating that vaccination might protect against future zoonoses. Our data suggest that a positively charged amino acid at position 403 in the S protein is critical for efficient utilization of human ACE2 by S proteins of bat coronaviruses. This finding could help to better predict the zoonotic potential of animal coronaviruses.Deutsche Forschungsgemeinschaft https://doi.org/10.13039/501100001659Bundesministerium für Bildung und Forschung https://doi.org/10.13039/50110000234

    Cube2sph : a toolkit enabling flexible and accurate continental-scale seismic wave simulations using the SPECFEM3D_Cartesian package

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    To enable flexible and accurate seismic wave simulations at continental scales (10°−60°) based on the spectral-element method using the open-source SPECFEM3D_Cartesian package, we develop a toolkit, Cube2sph, that allows the generation of customized spherical meshes that account for the Earth's curvature. This toolkit enables the usage of the perfectly matched layer (PML) absorbing boundary condition even when the artificial boundaries do not align with the coordinate axes. A series of numerical experiments are presented to validate the effectiveness of this toolkit. From these numerical experiments, we conclude that (1) continental-scale seismic wave simulations, especially surface wave simulations, can be more efficiently performed without the loss of accuracy by truncating the mesh at an appropriate depth, (2) curvilinear-grid PML can be used to effectively suppress artificial reflections for seismic wave simulations at continental scales, and (3) the Earth's spherical geometry needs to be accurately meshed in order to obtain accurate simulation results for study regions larger than 8°.</p

    Endogenous IFITMs boost SARS-coronavirus 1 and 2 replication whereas overexpression inhibits infection by relocalizing ACE2

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    Summary: Opposing effects of interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) on SARS-CoV-2 infection have been reported. The reasons for this are unclear and the role of IFITMs in infection of other human coronaviruses (hCoVs) remains poorly understood. Here, we demonstrate that endogenous expression of IFITM2 and/or IFITM3 is critical for efficient replication of SARS-CoV-1, SARS-CoV-2 and hCoV-OC43 but has little effect on MERS-, NL63-and 229E-hCoVs. In contrast, overexpression of IFITMs inhibits all these hCoVs, and the corresponding spike-containing pseudo-particles, except OC43, which is enhanced by IFITM3. We further demonstrate that overexpression of IFITMs impairs cell surface expression of ACE2 representing the entry receptor of SARS-CoVs and hCoV-NL63 but not hCoV-OC43. Our results explain the inhibitory effects of artificial IFITM overexpression on ACE2-tropic SARS-CoVs and show that three hCoVs, including major causative agents of severe respiratory disease, hijack IFITMs for efficient infection of human cells

    SPECFEM/specfem2d: SPECFEM2D v8.0.0

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    &lt;p&gt;New in SPECFEM2D 8.0.0:&lt;/p&gt; &lt;ul&gt; &lt;li&gt;GPU support&lt;/li&gt; &lt;li&gt;axisymmetric 2.5D simulations&lt;/li&gt; &lt;li&gt;various code improvements&lt;/li&gt; &lt;/ul&gt; &lt;p&gt;&lt;em&gt;many thanks for all your contributions to this version&lt;/em&gt;: Etienne Bachmann, Alexis Bottero, Bryant Chow, Paul Cristini, Rene Gassmoeller, Michael Gineste, Felix Halpaap, Dimitri Komatitsch, Matthieu Lefebvre, Qiancheng Liu, Qinya Liu, Zhaolun Liu, David Luet, Ryan Modrak, Christina Morency, Daniel Peter, Eric Rosenkrantz, Herurisa Rusmanugroho, Elliott Sales de Andrade, Eduardo Valero Cano, Zhinan Xie, Zhendong Zhang&lt;/p&gt

    SPECFEM/specfem2d: SPECFEM2D v8.1.0

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    &lt;p&gt;New in SPECFEM2D v8.1.0:&lt;/p&gt; &lt;ul&gt; &lt;li&gt;adds support for Q values in tomographic models&lt;/li&gt; &lt;li&gt;updates GPU support, OpenMP and test workflows&lt;/li&gt; &lt;li&gt;various code updates and improvements (noise simulations)&lt;/li&gt; &lt;/ul&gt; &lt;p&gt;&lt;em&gt;with many thanks for your contributions to this version&lt;/em&gt;: Hom Nath Gharti, Daniel Peter, Eduardo Valero Cano&lt;/p&gt
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