Respiratory syncytial virus(RSV) continues to pose serious threats to pediatric populations due to the lack of a vaccine and effective antiviral drugs. RSV fusion(F) glycoprotein mediates viral-host membrane fusion an...Respiratory syncytial virus(RSV) continues to pose serious threats to pediatric populations due to the lack of a vaccine and effective antiviral drugs. RSV fusion(F) glycoprotein mediates viral-host membrane fusion and is a key target for neutralizing antibodies. We generated 23 full-human monoclonal antibodies(hm Abs) against prefusion F protein(pre-F) from a healthy adult with natural RSV infection by single B cell cloning technique. A highly potent RSV-neutralizing hm Ab, named as 25-20, is selected, which targets a new site Φ-specific epitope. Site-directed mutagenesis and structural modelling analysis demonstrated that 25-20 mainly targets a highly conserved hydrophobic region located at the a4 helix and a1 helix of pre-F, indicating a site of vulnerability for drug and vaccine design. It is worth noting that 25-20 uses an unreported inferred germline(i GL) that binds very poorly to pre-F, thus high levels of somatic mutations are needed to gain high binding affinity with pre-F. Our observation helps to understand the evolution of RSV antibody during natural infection. Furthermore, by in silico prediction and experimental verification, we optimized 25-20 with KD values as low as picomolar range. Therefore, the optimized 25-20 represents an excellent candidate for passive protection against RSV infection.展开更多
A modified flux-coupling type superconducting fault current limiter(SFCL)is proposed here for suppressing fault currents.The modified SFCL consists of a coupling transformer,an yttrium barium copper oxide(YBCO)pancake...A modified flux-coupling type superconducting fault current limiter(SFCL)is proposed here for suppressing fault currents.The modified SFCL consists of a coupling transformer,an yttrium barium copper oxide(YBCO)pancake coil,and a controlled switch.By flexibly adjusting the controlled switch’s contact states based on the system operational conditions,the coupling transformer’s primary inductance as well as the YBCO coil’s normal-state resistance are incorporated into the main system for current limitation.Because the modified SFCL has the advantages of resistive and inductive SFCLs,it may improve the power system’s transient behavior.Hence,the SFCL’s effect on the transient stability of a multi-machine power system was also theoretically investigated.Further,simulations were conducted for accessing the SFCL’s performance characteristics under different fault conditions.The results show that using the proposed SFCL can effectively restrain the increased fault current and improve the bus voltage sag;meanwhile,the imitated multi-machine system’s power-angle oscillation can be obviously reduced.展开更多
基金supported by the Ministry of Science and Technology of China(2018YFA0507402)the National Natural Science Foundation of China(32270991,82041015,31630024,81761128009,32100123,32100751,81991492 and 82041039)。
文摘Respiratory syncytial virus(RSV) continues to pose serious threats to pediatric populations due to the lack of a vaccine and effective antiviral drugs. RSV fusion(F) glycoprotein mediates viral-host membrane fusion and is a key target for neutralizing antibodies. We generated 23 full-human monoclonal antibodies(hm Abs) against prefusion F protein(pre-F) from a healthy adult with natural RSV infection by single B cell cloning technique. A highly potent RSV-neutralizing hm Ab, named as 25-20, is selected, which targets a new site Φ-specific epitope. Site-directed mutagenesis and structural modelling analysis demonstrated that 25-20 mainly targets a highly conserved hydrophobic region located at the a4 helix and a1 helix of pre-F, indicating a site of vulnerability for drug and vaccine design. It is worth noting that 25-20 uses an unreported inferred germline(i GL) that binds very poorly to pre-F, thus high levels of somatic mutations are needed to gain high binding affinity with pre-F. Our observation helps to understand the evolution of RSV antibody during natural infection. Furthermore, by in silico prediction and experimental verification, we optimized 25-20 with KD values as low as picomolar range. Therefore, the optimized 25-20 represents an excellent candidate for passive protection against RSV infection.
基金Supported by the Fujian Young and Middle-Aged Teachers’Science and Technology Research Project(JAT201101).
文摘A modified flux-coupling type superconducting fault current limiter(SFCL)is proposed here for suppressing fault currents.The modified SFCL consists of a coupling transformer,an yttrium barium copper oxide(YBCO)pancake coil,and a controlled switch.By flexibly adjusting the controlled switch’s contact states based on the system operational conditions,the coupling transformer’s primary inductance as well as the YBCO coil’s normal-state resistance are incorporated into the main system for current limitation.Because the modified SFCL has the advantages of resistive and inductive SFCLs,it may improve the power system’s transient behavior.Hence,the SFCL’s effect on the transient stability of a multi-machine power system was also theoretically investigated.Further,simulations were conducted for accessing the SFCL’s performance characteristics under different fault conditions.The results show that using the proposed SFCL can effectively restrain the increased fault current and improve the bus voltage sag;meanwhile,the imitated multi-machine system’s power-angle oscillation can be obviously reduced.
