Background:Integrins facilitate binding to the extracellular matrix and other cells.Their subunit β2 is exclusively expressed by leukocytes,binds to the intercellular cell adhesion molecule 1(ICAM-1),and is pivotal f...Background:Integrins facilitate binding to the extracellular matrix and other cells.Their subunit β2 is exclusively expressed by leukocytes,binds to the intercellular cell adhesion molecule 1(ICAM-1),and is pivotal for their recruitment to sites of inflammation such as the atherosclerotic plaque.Methods:To investigate β2-integrin-mediated adhesiveness,a well-established assay for human whole blood was adapted for the analysis of murine T cell subsets.Changes in avidity and affinity were assessed by incubation of murine complexes ICAM-1 in murine whole blood and consecutive stimulation with PMA and Mg^(2+)/EGTA.Underlying signaling pathways in β2-integrin-mediated adhesiveness upon chemokine stimulation with CCL-19 were identified by incubation with reducing substances,and a Ca^(2+)chelator and ROS and Ca^(2+)measurements were carried out.Results:Incubation of murine whole blood with PMA leads to 30-fold and Mg^(2+)/EGTA to 65-fold increase in β2-integrin-mediated adhesiveness of T cells.Specificity of the assay was proven by preincubation of a blocking antibody,leading to a 60%reduction in adhesion capacity.ROS species and Ca^(2+)are crucial for chemokine-mediated β2-integrin activation.In vivo relevance was proven by induction of T cell adhesiveness in whole blood of mice upon myocardial infarction.Conclusions:Our assay allows specific quantification of β2-integrin-mediated affinity and avidity of T cells in whole blood samples.In congruence to human adhesion,these mechanisms are ROS and Ca^(2+)dependent and significantly elevated after myocardial infarction.Our refined and robust assay may be of particular use in phenotyping involved mechanisms in T cell activation in atherosclerotic cardiovascular disease.展开更多
基于有限元法对比十字形调谐质量阻尼器(cross-type tuned mass damper,CTMD)、X形调谐质量阻尼器(X-type tuned mass damper,XTMD)及旋风形调谐质量阻尼器(tourbillion-type tuned mass damper,TTMD)在钢框架结构中的减震性能。建立钢...基于有限元法对比十字形调谐质量阻尼器(cross-type tuned mass damper,CTMD)、X形调谐质量阻尼器(X-type tuned mass damper,XTMD)及旋风形调谐质量阻尼器(tourbillion-type tuned mass damper,TTMD)在钢框架结构中的减震性能。建立钢框架结构模型,结合3种调谐质量阻尼器(tuned mass damper,TMD)构造形式,评估其在地震作用下的位移、加速度及弹簧出力特性。结果表明:3种TMD均能有效降低结构动力响应,其中TTMD综合性能最优,其Y向加速度减震率达97.09%,X向加速度减震率为72.4%,弹簧双向均衡出力对称性最优。展开更多
Toroidal torques,generated by the resonant magnetic perturbation(RMP)and acting on the plasma column,are numerically systematically investigated for an ITER baseline scenario.The neoclassical toroidal viscosity(NTV),i...Toroidal torques,generated by the resonant magnetic perturbation(RMP)and acting on the plasma column,are numerically systematically investigated for an ITER baseline scenario.The neoclassical toroidal viscosity(NTV),in particular the resonant portion,is found to provide the dominant contribution to the total toroidal torque under the slow plasma flow regime in ITER.While the electromagnetic torque always opposes the plasma flow,the toroidal torque associated with the Reynolds stress enhances the plasma flow independent of the flow direction.A peculiar double-peak structure for the net NTV torque is robustly computed for ITER,as the toroidal rotation frequency is scanned near the zero value.This structure is found to be ultimately due to a non-monotonic behavior of the wave-particle resonance integral(over the particle pitch angle)in the superbanana plateau NTV regime in ITER.These findings are qualitatively insensitive to variations of a range of factors including the wall resistivity,the plasma pedestal flow and the assumed frequency of the rotating RMP field.展开更多
Cholangiocarcinoma(CCA)is a rare type of cancer which arises from the bile duct epithelium and carries a poor prognosis.One of the main risk factors in the Western world is primary sclerosing cholangitis.Surgical rese...Cholangiocarcinoma(CCA)is a rare type of cancer which arises from the bile duct epithelium and carries a poor prognosis.One of the main risk factors in the Western world is primary sclerosing cholangitis.Surgical resection has traditionally been the only curative treatment but can only be offered to patients with early disease,excluding those with locally advanced disease.Despite initial poor outcomes,liver transplantation(LT)has evolved as a viable treatment for a select group of patients with CCAs that are deemed unresectable.This review aims to explore the evolution of the role of LT in patients with CCA.展开更多
基金DZHK(German Centre for Cardiovascular Research)。
文摘Background:Integrins facilitate binding to the extracellular matrix and other cells.Their subunit β2 is exclusively expressed by leukocytes,binds to the intercellular cell adhesion molecule 1(ICAM-1),and is pivotal for their recruitment to sites of inflammation such as the atherosclerotic plaque.Methods:To investigate β2-integrin-mediated adhesiveness,a well-established assay for human whole blood was adapted for the analysis of murine T cell subsets.Changes in avidity and affinity were assessed by incubation of murine complexes ICAM-1 in murine whole blood and consecutive stimulation with PMA and Mg^(2+)/EGTA.Underlying signaling pathways in β2-integrin-mediated adhesiveness upon chemokine stimulation with CCL-19 were identified by incubation with reducing substances,and a Ca^(2+)chelator and ROS and Ca^(2+)measurements were carried out.Results:Incubation of murine whole blood with PMA leads to 30-fold and Mg^(2+)/EGTA to 65-fold increase in β2-integrin-mediated adhesiveness of T cells.Specificity of the assay was proven by preincubation of a blocking antibody,leading to a 60%reduction in adhesion capacity.ROS species and Ca^(2+)are crucial for chemokine-mediated β2-integrin activation.In vivo relevance was proven by induction of T cell adhesiveness in whole blood of mice upon myocardial infarction.Conclusions:Our assay allows specific quantification of β2-integrin-mediated affinity and avidity of T cells in whole blood samples.In congruence to human adhesion,these mechanisms are ROS and Ca^(2+)dependent and significantly elevated after myocardial infarction.Our refined and robust assay may be of particular use in phenotyping involved mechanisms in T cell activation in atherosclerotic cardiovascular disease.
文摘基于有限元法对比十字形调谐质量阻尼器(cross-type tuned mass damper,CTMD)、X形调谐质量阻尼器(X-type tuned mass damper,XTMD)及旋风形调谐质量阻尼器(tourbillion-type tuned mass damper,TTMD)在钢框架结构中的减震性能。建立钢框架结构模型,结合3种调谐质量阻尼器(tuned mass damper,TMD)构造形式,评估其在地震作用下的位移、加速度及弹簧出力特性。结果表明:3种TMD均能有效降低结构动力响应,其中TTMD综合性能最优,其Y向加速度减震率达97.09%,X向加速度减震率为72.4%,弹簧双向均衡出力对称性最优。
基金funded by National Natural Science Foundation of China(NSFC)(Nos.12075053,11505021 and 11975068)by National Key R&D Program of China(No.2022YFE 03060002)+1 种基金by Fundamental Research Funds for the Central Universities(No.2232024G-10)supported by the U.S.DoE Office of Science(No.DE-FG02–95ER54309)。
文摘Toroidal torques,generated by the resonant magnetic perturbation(RMP)and acting on the plasma column,are numerically systematically investigated for an ITER baseline scenario.The neoclassical toroidal viscosity(NTV),in particular the resonant portion,is found to provide the dominant contribution to the total toroidal torque under the slow plasma flow regime in ITER.While the electromagnetic torque always opposes the plasma flow,the toroidal torque associated with the Reynolds stress enhances the plasma flow independent of the flow direction.A peculiar double-peak structure for the net NTV torque is robustly computed for ITER,as the toroidal rotation frequency is scanned near the zero value.This structure is found to be ultimately due to a non-monotonic behavior of the wave-particle resonance integral(over the particle pitch angle)in the superbanana plateau NTV regime in ITER.These findings are qualitatively insensitive to variations of a range of factors including the wall resistivity,the plasma pedestal flow and the assumed frequency of the rotating RMP field.
文摘Cholangiocarcinoma(CCA)is a rare type of cancer which arises from the bile duct epithelium and carries a poor prognosis.One of the main risk factors in the Western world is primary sclerosing cholangitis.Surgical resection has traditionally been the only curative treatment but can only be offered to patients with early disease,excluding those with locally advanced disease.Despite initial poor outcomes,liver transplantation(LT)has evolved as a viable treatment for a select group of patients with CCAs that are deemed unresectable.This review aims to explore the evolution of the role of LT in patients with CCA.
