目的下调胶质瘤细胞系中CWF19L1(CWF19 like cell cycle control factor 1)的表达,探究胶质瘤细胞的增殖能力、迁移能力及侵袭能力的变化,为胶质瘤治疗研发新的治疗靶点。方法生物信息学分析肿瘤与正常组织中CWF19L1表达差异,验证胶质...目的下调胶质瘤细胞系中CWF19L1(CWF19 like cell cycle control factor 1)的表达,探究胶质瘤细胞的增殖能力、迁移能力及侵袭能力的变化,为胶质瘤治疗研发新的治疗靶点。方法生物信息学分析肿瘤与正常组织中CWF19L1表达差异,验证胶质瘤细胞中CWF19L1蛋白质的基础表达量,构建敲低慢病毒转染胶质瘤细胞,下调胶质瘤细胞中CWF19L1蛋白质表达。使用该稳转细胞系进行细胞周期、细胞增殖、细胞迁移和Transwell实验,以验证CWF19L1敲低对胶质瘤细胞功能的影响。结果生物信息分析表明肿瘤细胞中CWF19L1基因表达上调,蛋白质印迹法(WB)证明在U251胶质瘤细胞系中CWF19L1蛋白质表达量最高。敲低U251胶质瘤细胞中CWF19L1表达后,细胞周期实验示处于S/G2期的细胞比例上调(42.22%比33.00%P<0.05),CCK-8实验结果表明细胞数量明显上调(P<0.001),划痕实验显示划痕宽度明显缩短(P<0.001),迁移和侵袭实验证明穿过小室的细胞数量明显增多(P<0.001)。结论CWF19L1能够通过抑制细胞周期G1/S期转化,对胶质瘤细胞的增殖、迁移与侵袭能力产生抑制。展开更多
岩体的峰后强度对大型地下洞室群围岩开挖变形稳定具有较大影响。针对此问题,采用基于损伤的黏聚力弱化-摩擦角强化(cohesion weakening and friction strengthening, CWFS)模型并以动态链接库(dynamic link library, DLL)的形式植入FLA...岩体的峰后强度对大型地下洞室群围岩开挖变形稳定具有较大影响。针对此问题,采用基于损伤的黏聚力弱化-摩擦角强化(cohesion weakening and friction strengthening, CWFS)模型并以动态链接库(dynamic link library, DLL)的形式植入FLAC~(3D)程序中,针对依托工程的大型地下洞室群围岩开挖稳定性,开展考虑围岩开挖损伤和不考虑损伤的开挖全过程模拟。通过分析围岩的变形、应力、塑性区与损伤区的规律及其与现场监测数据的对比,研究开挖损伤对围岩稳定性的影响。结果表明:考虑围岩开挖损伤相对于不考虑损伤时,围岩应力释放程度较高,不利于地下洞室群的稳定;围岩塑性区和变形在主厂房顶拱与边墙等区域增加至1.5~2.0倍。CWFS模型能有效反映围岩塑性屈服的诱因,即损伤系数在0.5~1.0范围内为开挖卸荷导致的屈服,损伤系数在0~0.5范围内为开挖损伤导致的屈服;采用该模型得到的围岩开挖变形在量值上与采用多点位移计得到的现场监测值相近,变化趋势基本相同,不考虑围岩开挖损伤时得到分析结果相对于实际工程偏危险。展开更多
An augmented methodology is developed to estimate the reliability of deep excavations along spatially variable massive rock masses using the cohesion weakening friction strengthening(CWFS)model.Sensitive parameters of...An augmented methodology is developed to estimate the reliability of deep excavations along spatially variable massive rock masses using the cohesion weakening friction strengthening(CWFS)model.Sensitive parameters of the CWFS model were initially identified using Sobol’s global sensitivity analysis based on their influence on the displacements and excavation damage zone around excavations.The probability of failure was estimated by performing Mont–Carlo Simulations on random finite difference models of excavations generated via MATLAB-FLAC2D coupling,considering the spatial variation of these sensitive parameters.Spatial variation was modeled by generating anisotropic random fields of sensitive CWFS parameters via the recently developed Fourier series method and updated correlations suggested by Walton(2019).The proposed methodology was demonstrated for a proposed deep nuclear waste repository to be located in Canada.Results from the developed methodology were systematically compared with those of traditional reliability(ignoring spatial variation)and deterministic methods(ignoring uncertainty).Although the developed methodology was computationally complex,it was judged to be the most realistic due to the realistic consideration of heterogeneous distributions of rock properties.Traditional methodologies underestimate/overestimate the excavation performance due to negligence of uncertainty and spatial variability.Finally,a parametric analysis was performed using developed methodology by varying the initial friction angle,scale of fluctuations(SOFs)and dilation angle.The effect of initial friction angle was observed to be more pronounced on the probability of failures as compared to SOFs and dilation angle.Similar observations were made related to the excavation damage zone(EDZ)development quantified using yield area ratio.展开更多
文摘目的下调胶质瘤细胞系中CWF19L1(CWF19 like cell cycle control factor 1)的表达,探究胶质瘤细胞的增殖能力、迁移能力及侵袭能力的变化,为胶质瘤治疗研发新的治疗靶点。方法生物信息学分析肿瘤与正常组织中CWF19L1表达差异,验证胶质瘤细胞中CWF19L1蛋白质的基础表达量,构建敲低慢病毒转染胶质瘤细胞,下调胶质瘤细胞中CWF19L1蛋白质表达。使用该稳转细胞系进行细胞周期、细胞增殖、细胞迁移和Transwell实验,以验证CWF19L1敲低对胶质瘤细胞功能的影响。结果生物信息分析表明肿瘤细胞中CWF19L1基因表达上调,蛋白质印迹法(WB)证明在U251胶质瘤细胞系中CWF19L1蛋白质表达量最高。敲低U251胶质瘤细胞中CWF19L1表达后,细胞周期实验示处于S/G2期的细胞比例上调(42.22%比33.00%P<0.05),CCK-8实验结果表明细胞数量明显上调(P<0.001),划痕实验显示划痕宽度明显缩短(P<0.001),迁移和侵袭实验证明穿过小室的细胞数量明显增多(P<0.001)。结论CWF19L1能够通过抑制细胞周期G1/S期转化,对胶质瘤细胞的增殖、迁移与侵袭能力产生抑制。
文摘岩体的峰后强度对大型地下洞室群围岩开挖变形稳定具有较大影响。针对此问题,采用基于损伤的黏聚力弱化-摩擦角强化(cohesion weakening and friction strengthening, CWFS)模型并以动态链接库(dynamic link library, DLL)的形式植入FLAC~(3D)程序中,针对依托工程的大型地下洞室群围岩开挖稳定性,开展考虑围岩开挖损伤和不考虑损伤的开挖全过程模拟。通过分析围岩的变形、应力、塑性区与损伤区的规律及其与现场监测数据的对比,研究开挖损伤对围岩稳定性的影响。结果表明:考虑围岩开挖损伤相对于不考虑损伤时,围岩应力释放程度较高,不利于地下洞室群的稳定;围岩塑性区和变形在主厂房顶拱与边墙等区域增加至1.5~2.0倍。CWFS模型能有效反映围岩塑性屈服的诱因,即损伤系数在0.5~1.0范围内为开挖卸荷导致的屈服,损伤系数在0~0.5范围内为开挖损伤导致的屈服;采用该模型得到的围岩开挖变形在量值上与采用多点位移计得到的现场监测值相近,变化趋势基本相同,不考虑围岩开挖损伤时得到分析结果相对于实际工程偏危险。
基金supported by the Initiation Research Grant from Indian Institute of Technology Kanpur,India.
文摘An augmented methodology is developed to estimate the reliability of deep excavations along spatially variable massive rock masses using the cohesion weakening friction strengthening(CWFS)model.Sensitive parameters of the CWFS model were initially identified using Sobol’s global sensitivity analysis based on their influence on the displacements and excavation damage zone around excavations.The probability of failure was estimated by performing Mont–Carlo Simulations on random finite difference models of excavations generated via MATLAB-FLAC2D coupling,considering the spatial variation of these sensitive parameters.Spatial variation was modeled by generating anisotropic random fields of sensitive CWFS parameters via the recently developed Fourier series method and updated correlations suggested by Walton(2019).The proposed methodology was demonstrated for a proposed deep nuclear waste repository to be located in Canada.Results from the developed methodology were systematically compared with those of traditional reliability(ignoring spatial variation)and deterministic methods(ignoring uncertainty).Although the developed methodology was computationally complex,it was judged to be the most realistic due to the realistic consideration of heterogeneous distributions of rock properties.Traditional methodologies underestimate/overestimate the excavation performance due to negligence of uncertainty and spatial variability.Finally,a parametric analysis was performed using developed methodology by varying the initial friction angle,scale of fluctuations(SOFs)and dilation angle.The effect of initial friction angle was observed to be more pronounced on the probability of failures as compared to SOFs and dilation angle.Similar observations were made related to the excavation damage zone(EDZ)development quantified using yield area ratio.
