近年来世界VLBI(Very Large Baseline Interferometry)终端技术发展迅速,主流的记录终端已发展到Mark5B记录系统,Mark5C也正在研制和测试阶段。为了适应未来高速率、海量数据以及数字基带转换器观测的要求,需要将现有的Mark5A升级到Mar...近年来世界VLBI(Very Large Baseline Interferometry)终端技术发展迅速,主流的记录终端已发展到Mark5B记录系统,Mark5C也正在研制和测试阶段。为了适应未来高速率、海量数据以及数字基带转换器观测的要求,需要将现有的Mark5A升级到Mark5B或Mark5B+,相应地需要将Mark4格式器升级为Mark5B采样器。主要描述了相关设备的原理以及Mark4格式器升级的步骤。展开更多
Gliomas are the most common primary intracranial neoplasms among all brain malignancies,and the microtubule affinity regulating kinases(MARKs)have become potential drug targets for glioma.Here,we report a novel dual s...Gliomas are the most common primary intracranial neoplasms among all brain malignancies,and the microtubule affinity regulating kinases(MARKs)have become potential drug targets for glioma.Here,we report a novel dual small-molecule inhibitor of MARK3 and MARK4,designated as PCC0208017.In vitro,PCC0208017 strongly inhibited kinase activity against MARK3 and MARK4,and strongly reduced proliferation in three glioma cell lines.This compound attenuated glioma cell migration,glioma cell invasion,and angiogenesis.Molecular mechanism studies revealed that PCC0208017 decreased the phosphorylation of Tau,disrupted microtubule dynamics,and induced a G2/M phase cell cycle arrest.In an in vivo glioma model,PCC0208017 showed robust anti-tumor activity,blood-brain barrier permeability,and a good oral pharmacokinetic profile.Molecular docking studies showed that PCC0208017 exhibited high binding affinity to MARK3 and MARK4.Taken together,our study describes for the first time that PCC0208017,a novel MARK3/MARK4 inhibitor,might be a promising lead compound for treatment of glioma.展开更多
文摘近年来世界VLBI(Very Large Baseline Interferometry)终端技术发展迅速,主流的记录终端已发展到Mark5B记录系统,Mark5C也正在研制和测试阶段。为了适应未来高速率、海量数据以及数字基带转换器观测的要求,需要将现有的Mark5A升级到Mark5B或Mark5B+,相应地需要将Mark4格式器升级为Mark5B采样器。主要描述了相关设备的原理以及Mark4格式器升级的步骤。
基金partially supported by National Science Foundation of China(NSFC,81728020)Key Research Project of Shandong Province(2017GSF18177,China)+3 种基金Natural Science Foundation of Shandong Province(ZR2018LH025,China)The Science and Technology Support Program for Youth Innovation in Universities of Shandong(2019KJM009)Key Research Project of Yantai(2019XDHZ102,China)Taishan Scholar Project.
文摘Gliomas are the most common primary intracranial neoplasms among all brain malignancies,and the microtubule affinity regulating kinases(MARKs)have become potential drug targets for glioma.Here,we report a novel dual small-molecule inhibitor of MARK3 and MARK4,designated as PCC0208017.In vitro,PCC0208017 strongly inhibited kinase activity against MARK3 and MARK4,and strongly reduced proliferation in three glioma cell lines.This compound attenuated glioma cell migration,glioma cell invasion,and angiogenesis.Molecular mechanism studies revealed that PCC0208017 decreased the phosphorylation of Tau,disrupted microtubule dynamics,and induced a G2/M phase cell cycle arrest.In an in vivo glioma model,PCC0208017 showed robust anti-tumor activity,blood-brain barrier permeability,and a good oral pharmacokinetic profile.Molecular docking studies showed that PCC0208017 exhibited high binding affinity to MARK3 and MARK4.Taken together,our study describes for the first time that PCC0208017,a novel MARK3/MARK4 inhibitor,might be a promising lead compound for treatment of glioma.
