Objective To study the role of sirtuin 1 (SIRT1) in Fas ligand (FasL) expression regulation during vascular lesion formation and to elucidate the potential mechanisms. Methods SIRT1 and FasL protein levels were d...Objective To study the role of sirtuin 1 (SIRT1) in Fas ligand (FasL) expression regulation during vascular lesion formation and to elucidate the potential mechanisms. Methods SIRT1 and FasL protein levels were detected by Western blotting in either mouse arteries extract or the whole rat aortic vascular smooth muscle cell (VSMC) lysate. Smooth muscle cell (SMC)-specific human SIRT1 transgenic (Tg) C57BL/6 mice and their littermate wild-type (WT) controls underwent complete carotid artery ligation (ligation groups) or the ligation-excluded operation (sham groups). The carotid arteries were collected 1 day after operation. Reverse transcription-polymerase chain reaction was performed to detect the mRNA levels of SIRT1 and FasL. Luciferase reporter assays were performed to detect the effect of WT-SIRT1, a dominant-negative form of SIRT1 (SIRT1H363Y), and GATA-6 on the promoter activity of FasL. Flow cytometry assay was applied to measure the hypodiploid DNA content of VSMC so as to monitor cellular apoptosis. Results SIRTI was expressed in both rat aortic VSMCs and mouse arteries. Forced SIRT1 expression increased FasL expression both in injured mouse carotid arteries 1 day after ligation (P〈0.001) and VSMCs treated with serum (P〈0.05 at the transcriptional level, P〈0.001 at the protein level). No notable apoptosis was observed. Furthermore, transcription factor GATA-6 increased the promoter activity of FasL (P〈0.001). The induction of FasL promoter activity by GATA-6 was enhanced by WT-SIRT1 (P〈0.001), while SIRT1H363Y significantly relieved the enhancing effect of WT-SIRT1 on GATA-6 (P〈0.001). Conclusions Overexpression of SIRT1 up-regulates FasL expression in both flow-restricted mouse carotid arteries and serum-stimulated VSMCs. The transcription factor GATA-6 participates in the transcriptional regulation of FasL expression by SIRT 1.展开更多
To address the problem of maneuvering target tracking, where the target trajectory has prolonged smooth regions and abrupt maneuvering regions, a modified variable rate particle filter (MVRPF) is proposed. First, a ...To address the problem of maneuvering target tracking, where the target trajectory has prolonged smooth regions and abrupt maneuvering regions, a modified variable rate particle filter (MVRPF) is proposed. First, a Cartesian-coordinate based variable rate model is presented. Compared with conventional variable rate models, the proposed model does not need any prior knowledge of target mass or external forces. Consequently, it is more convenient in practical tracking applications. Second, a maneuvering detection strategy is adopted to adaptively adjust the parameters in MVRPF, which helps allocate more state points at high maneuver regions and fewer at smooth regions. Third, in the presence of small measurement errors, the unscented particle filter, which is embedded in MVRPF, can move more particles into regions of high likelihood and hence can improve the tracking performance. Simulation results illustrate the effectiveness of the proposed method.展开更多
基金Supported by the National Natural Science Foundation of China(81102444)Special Fund of the National Laboratory of China(2060204)
文摘Objective To study the role of sirtuin 1 (SIRT1) in Fas ligand (FasL) expression regulation during vascular lesion formation and to elucidate the potential mechanisms. Methods SIRT1 and FasL protein levels were detected by Western blotting in either mouse arteries extract or the whole rat aortic vascular smooth muscle cell (VSMC) lysate. Smooth muscle cell (SMC)-specific human SIRT1 transgenic (Tg) C57BL/6 mice and their littermate wild-type (WT) controls underwent complete carotid artery ligation (ligation groups) or the ligation-excluded operation (sham groups). The carotid arteries were collected 1 day after operation. Reverse transcription-polymerase chain reaction was performed to detect the mRNA levels of SIRT1 and FasL. Luciferase reporter assays were performed to detect the effect of WT-SIRT1, a dominant-negative form of SIRT1 (SIRT1H363Y), and GATA-6 on the promoter activity of FasL. Flow cytometry assay was applied to measure the hypodiploid DNA content of VSMC so as to monitor cellular apoptosis. Results SIRTI was expressed in both rat aortic VSMCs and mouse arteries. Forced SIRT1 expression increased FasL expression both in injured mouse carotid arteries 1 day after ligation (P〈0.001) and VSMCs treated with serum (P〈0.05 at the transcriptional level, P〈0.001 at the protein level). No notable apoptosis was observed. Furthermore, transcription factor GATA-6 increased the promoter activity of FasL (P〈0.001). The induction of FasL promoter activity by GATA-6 was enhanced by WT-SIRT1 (P〈0.001), while SIRT1H363Y significantly relieved the enhancing effect of WT-SIRT1 on GATA-6 (P〈0.001). Conclusions Overexpression of SIRT1 up-regulates FasL expression in both flow-restricted mouse carotid arteries and serum-stimulated VSMCs. The transcription factor GATA-6 participates in the transcriptional regulation of FasL expression by SIRT 1.
基金Project supported by the National Natural Science Foundation of China(No.61174024)
文摘To address the problem of maneuvering target tracking, where the target trajectory has prolonged smooth regions and abrupt maneuvering regions, a modified variable rate particle filter (MVRPF) is proposed. First, a Cartesian-coordinate based variable rate model is presented. Compared with conventional variable rate models, the proposed model does not need any prior knowledge of target mass or external forces. Consequently, it is more convenient in practical tracking applications. Second, a maneuvering detection strategy is adopted to adaptively adjust the parameters in MVRPF, which helps allocate more state points at high maneuver regions and fewer at smooth regions. Third, in the presence of small measurement errors, the unscented particle filter, which is embedded in MVRPF, can move more particles into regions of high likelihood and hence can improve the tracking performance. Simulation results illustrate the effectiveness of the proposed method.