Browsing by Author "Zhang, Yufei"

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    Carrier-Domain Method for high-resolution computation of time-periodic long-wake flows
    (Springer Nature, 2023) Liu, Yang; Takizawa, Kenji; Tezduyar, Tayfun E.; Kuraishi, Takashi; Zhang, Yufei
    We are introducing the Carrier-Domain Method (CDM) for high-resolution computation of time-periodic long-wake flows, with cost-effectives that makes the computations practical. The CDM is closely related to the Multidomain Method, which was introduced 24 years ago, originally intended also for cost-effective computation of long-wake flows and later extended in scope to cover additional classes of flow problems. In the CDM, the computational domain moves in the free-stream direction, with a velocity that preserves the outflow nature of the downstream computational boundary. As the computational domain is moving, the velocity at the inflow plane is extracted from the velocity computed earlier when the plane’s current position was covered by the moving domain. The inflow data needed at an instant is extracted from one or more instants going back in time as many periods. Computing the long-wake flow with a high-resolution moving mesh that has a reasonable length would certainly be far more cost-effective than computing it with a fixed mesh that covers the entire length of the wake. We are also introducing a CDM version where the computational domain moves in a discrete fashion rather than a continuous fashion. To demonstrate how the CDM works, we compute, with the version where the computational domain moves in a continuous fashion, the 2D flow past a circular cylinder at Reynolds number 100. At this Reynolds number, the flow has an easily discernible vortex shedding frequency and widely published lift and drag coefficients and Strouhal number. The wake flow is computed up to 350 diameters downstream of the cylinder, far enough to see the secondary vortex street. The computations are performed with the Space–Time Variational Multiscale method and isogeometric discretization; the basis functions are quadratic NURBS in space and linear in time. The results show the power of the CDM in high-resolution computation of time-periodic long-wake flows.
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    Q493K and Q498H substitutions in Spike promote adaptation of SARS-CoV-2 in mice
    (Elsevier, 2021) Huang, Kun; Zhang, Yufei; Hui, Xianfeng; Zhao, Ya; Gong, Wenxiao; Wang, Ting; Zhang, Shaoran; Yang, Yong; Deng, Fei; Zhang, Qiang; Chen, Xi; Yang, Ying; Sun, Xiaomei; Chen, Huanchun; Tao, Yizhi Jane; Zou, Zhong; Jin, Meilin
    Background: An ideal animal model to study SARS-coronavirus 2 (SARS-CoV-2) pathogenesis and evaluate therapies and vaccines should reproduce SARS-CoV-2 infection and recapitulate lung disease like those seen in humans. The angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS-CoV-2, but mice are resistant to the infection because their ACE2 is incompatible with the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein . Methods: SARS-CoV-2 was passaged in BALB/c mice to obtain mouse-adapted virus strain. Complete genome deep sequencing of different generations of viruses was performed to characterize the dynamics of the adaptive mutations in SARS-CoV-2. Indirect immunofluorescence analysis and Biolayer interferometry experiments determined the binding affinity of mouse-adapted SARS-CoV-2 WBP-1 RBD to mouse ACE2 and human ACE2. Finally, we tested whether TLR7/8 agonist Resiquimod (R848) could also inhibit the replication of WBP-1 in the mouse model. Findings: The mouse-adapted strain WBP-1 showed increased infectivity in BALB/c mice and led to severe interstitial pneumonia. We characterized the dynamics of the adaptive mutations in SARS-CoV-2 and demonstrated that Q493K and Q498H in RBD significantly increased its binding affinity towards mouse ACE2. Additionally, the study tentatively found that the TLR7/8 agonist Resiquimod was able to protect mice against WBP-1 challenge. Therefore, this mouse-adapted strain is a useful tool to investigate COVID-19 and develop new therapies. Interpretation: We found for the first time that the Q493K and Q498H mutations in the RBD of WBP-1 enhanced its interactive affinities with mACE2. The mouse-adapted SARS-CoV-2 provides a valuable tool for the evaluation of novel antiviral and vaccine strategies. This study also tentatively verified the antiviral activity of TLR7/8 agonist Resiquimod against SARS-CoV-2 in vitro and in vivo. Funding: This research was funded by the National Key Research and Development Program of China (2020YFC0845600) and Emergency Science and Technology Project of Hubei Province (2020FCA046) and Robert A. Welch Foundation (C-1565).