背景与目的:可变剪接在细胞增殖、生长、凋亡及分化等复杂的蛋白质功能调控中发挥着至关重要的作用,能参与包括肿瘤在内的多种疾病的发生、发展过程,目前大多数可变剪接调控因子的功能及其作用机制尚不清楚。本研究旨在探讨KH型剪接调...背景与目的:可变剪接在细胞增殖、生长、凋亡及分化等复杂的蛋白质功能调控中发挥着至关重要的作用,能参与包括肿瘤在内的多种疾病的发生、发展过程,目前大多数可变剪接调控因子的功能及其作用机制尚不清楚。本研究旨在探讨KH型剪接调控蛋白(KH-type splicing regulatory protein,KHSRP)在肺腺癌中的差异剪接靶基因及靶基因的表达与患者预后及免疫细胞功能的相关性。方法:通过高通量可变剪接测序,筛选KHSRP下游差异剪接靶基因。通过肿瘤免疫评估资源(Tumor IMmune Estimation Resource,TIMER)和阿拉巴马大学伯明翰分校癌症数据分析门户(the University of Alabama at Birmingham cancer data analysis portal,ULCAN)分析KHSRP下游差异剪接靶基因在肺腺癌中的表达。通过Kaplan数据库分析KHSRP下游差异剪接靶基因的表达与患者预后的相关性。通过TIMER免疫模块分析KHSRP下游差异剪接靶基因与免疫细胞功能的相关性。结果:NUMB、ADD3及LIMCH1为KHSRP的下游关键可变剪接靶基因。NUMB、ADD3及LIMCH1在肺腺癌肿瘤组织中均呈低表达,其低表达者预后不良。NUMB、ADD3及LIMCH1与免疫细胞功能呈正相关。结论:在肺腺癌中,NUMB、ADD3及LIMCH1为KHSRP的差异剪接靶基因,且NUMB、ADD3及LIMCH1低表达会导致预后不良,并且与免疫细胞功能呈正相关。展开更多
目的探讨蛋白酶体抑制剂(EPO)诱导前列腺癌DU145细胞凋亡机制是否与内质网应激(Er-stress)有关。方法用不同浓度的EPO处理DU145细胞,MTS检测细胞生长情况;流式细胞仪检测细胞凋亡率;实时定量聚合酶链反应(Real-time PCR)检测Er-stress...目的探讨蛋白酶体抑制剂(EPO)诱导前列腺癌DU145细胞凋亡机制是否与内质网应激(Er-stress)有关。方法用不同浓度的EPO处理DU145细胞,MTS检测细胞生长情况;流式细胞仪检测细胞凋亡率;实时定量聚合酶链反应(Real-time PCR)检测Er-stress相关分子同源蛋白质(CHOP)、葡萄糖调节蛋白78(GRP78)、X盒结合蛋白1(XBP-1)、剪接型X盒结合蛋白1信使核糖核酸(XBP-1s m RNA);Western blot检测CHOP和GRP78的表达。结果 EPO抑制DU145细胞生长,并且呈现浓度梯度依赖性,处理组细胞凋亡率高于未处理组,高剂量组凋亡率高于低剂量组。EPO处理后,CHOP、剪接型X盒结合蛋白1(XBP-1s)、GRP78 m RNA明显升高,72 h最明显。低剂量组与高剂量组48 h CHOP和XBP-1s的表达比较差异均有统计学意义,两组48和72 h GRP78比较差异均有统计学意义。EPO处理后,XBP-1和XBP-1s基因转录水平升高,而XBP-1s随处理时间增长基因转录水平变化不明显。EPO处理后,CHOP和GRP78不断增加,72 h两种蛋白质均达到最高值,并且低剂量组与高剂量组在72 h比较差异有统计学意义。结论 EPO能抑制DU145细胞生长,诱导凋亡,其机制可能与激活Er-stress,诱发内质网的相关分子CHOP、XBP-1s、XBP-1、GRP78的表达有关。展开更多
The mechanical behaviors of the interface between coarse-grained soil and concrete were investigated by simple shear tests under condition of mixed soil slurry (bentonite mixed with cement grout).For comparison,the in...The mechanical behaviors of the interface between coarse-grained soil and concrete were investigated by simple shear tests under condition of mixed soil slurry (bentonite mixed with cement grout).For comparison,the interfaces both without slurry and with bentonite slurry were analyzed.The experimental results show that different slurries exert much influence on the strength and deformation of soil/structure interface.Under mixed soil slurry,strain softening and shear dilatation are observed,while shear dilatation appears under the small normal stress of the interface without slurry,and shear contraction is significant under the condition of the bentonite slurry.The thickness of the interface was determined by analyzing the disturbed height of the sample with both simple shear test and particle flow code (PFC).An elasto-plastic constitutive model incorporating strain softening and dilatancy for thin layer element of interface was formulated in the framework of generalized potential theory.The relation curves of shear stress and shear strain,as well as the relation curves of normal strain and shear strain,were fitted by a piecewise function composed by hyperbolic functions and resembling normal functions.The entire model parameters can be identified by tests.The new model is verified by comparing the measured data of indoor cut-off wall model tests with the predictions from finite element method (FEM).The FEM results indicate that the stress of wall calculated by using Goodman element is too large,and the maximum deviation between the test data and prediction is about 45%.While the prediction from the proposed model is close to the measured data,and the error is generally less than 10%.展开更多
A filter cake is often formed between soil and concrete during casting concrete in the ground,such as constructions of diaphragm walls and bored piles.The present study aims to investigate the effect of the filter cak...A filter cake is often formed between soil and concrete during casting concrete in the ground,such as constructions of diaphragm walls and bored piles.The present study aims to investigate the effect of the filter cake on the shear behavior of the sand-concrete pile interface.A series of sand-concrete interface direct shear tests were performed with a large-direct shear apparatus while considering different roughness(I=0,10,20 and 30 mm)and filter cake thickness(Δh=0,5 and 10 mm).For a smooth interface without a filter cake,the shear stress-horizontal displacement curves showed a“softening”response.The peak shear strength and friction angle decreased exponentially with increasing theΔh.Whereas,for a rough interface withΔh=5 or 10 mm,the shear stress-horizontal displacement curves presented a“hardening”response.The peak strength,as well as friction angle,decreased linearly with increasing theΔh.Moreover,a critical roughness I_(cr)of 10 mm was observed in the tests without a filter cake.The interface shear strength initially increased with increasing I but gradually decreased when the I exceeded I_(cr).In addition,the filter cake could reduce the roughness sensitivity on shear strength.展开更多
Cold-formed steel structures are steel structure products constructed from sheets or coils using cold rolling, press brake or bending brake method. These structures are extensively employed in building construction in...Cold-formed steel structures are steel structure products constructed from sheets or coils using cold rolling, press brake or bending brake method. These structures are extensively employed in building construction industry due to their light mass, ductility by economic cold forming operations, favorable strength-to-mass ratio and other factors. The utilization of cold formed steel sections with concrete as composite can hugely reduce the construction cost. However, the use of cold formed steel members in composite concrete beams has been very limited. A comprehensive review of developments in composite beam with cold formed steel sections was introduced. It was revealed that employing cold-formed steel channel section to replace reinforcement bars in conventional reinforced concrete beam results in a significant cost reduction without reducing strength capacity. The use of composite beam consisting of cold-formed steel open or close box and filled concrete could also reduce construction cost. Lighter composite girder for bridges with cold-formed steel of U section was introduced. Moreover, types of shear connectors to provide composite action between cold-formed steel beam and concrete slab were presented. However, further studies to investigate the effects of metal decking on the behavior of composite beam with cold-formed steel section and introduction of ductile shear connectors were recommended.展开更多
文摘背景与目的:可变剪接在细胞增殖、生长、凋亡及分化等复杂的蛋白质功能调控中发挥着至关重要的作用,能参与包括肿瘤在内的多种疾病的发生、发展过程,目前大多数可变剪接调控因子的功能及其作用机制尚不清楚。本研究旨在探讨KH型剪接调控蛋白(KH-type splicing regulatory protein,KHSRP)在肺腺癌中的差异剪接靶基因及靶基因的表达与患者预后及免疫细胞功能的相关性。方法:通过高通量可变剪接测序,筛选KHSRP下游差异剪接靶基因。通过肿瘤免疫评估资源(Tumor IMmune Estimation Resource,TIMER)和阿拉巴马大学伯明翰分校癌症数据分析门户(the University of Alabama at Birmingham cancer data analysis portal,ULCAN)分析KHSRP下游差异剪接靶基因在肺腺癌中的表达。通过Kaplan数据库分析KHSRP下游差异剪接靶基因的表达与患者预后的相关性。通过TIMER免疫模块分析KHSRP下游差异剪接靶基因与免疫细胞功能的相关性。结果:NUMB、ADD3及LIMCH1为KHSRP的下游关键可变剪接靶基因。NUMB、ADD3及LIMCH1在肺腺癌肿瘤组织中均呈低表达,其低表达者预后不良。NUMB、ADD3及LIMCH1与免疫细胞功能呈正相关。结论:在肺腺癌中,NUMB、ADD3及LIMCH1为KHSRP的差异剪接靶基因,且NUMB、ADD3及LIMCH1低表达会导致预后不良,并且与免疫细胞功能呈正相关。
文摘目的探讨蛋白酶体抑制剂(EPO)诱导前列腺癌DU145细胞凋亡机制是否与内质网应激(Er-stress)有关。方法用不同浓度的EPO处理DU145细胞,MTS检测细胞生长情况;流式细胞仪检测细胞凋亡率;实时定量聚合酶链反应(Real-time PCR)检测Er-stress相关分子同源蛋白质(CHOP)、葡萄糖调节蛋白78(GRP78)、X盒结合蛋白1(XBP-1)、剪接型X盒结合蛋白1信使核糖核酸(XBP-1s m RNA);Western blot检测CHOP和GRP78的表达。结果 EPO抑制DU145细胞生长,并且呈现浓度梯度依赖性,处理组细胞凋亡率高于未处理组,高剂量组凋亡率高于低剂量组。EPO处理后,CHOP、剪接型X盒结合蛋白1(XBP-1s)、GRP78 m RNA明显升高,72 h最明显。低剂量组与高剂量组48 h CHOP和XBP-1s的表达比较差异均有统计学意义,两组48和72 h GRP78比较差异均有统计学意义。EPO处理后,XBP-1和XBP-1s基因转录水平升高,而XBP-1s随处理时间增长基因转录水平变化不明显。EPO处理后,CHOP和GRP78不断增加,72 h两种蛋白质均达到最高值,并且低剂量组与高剂量组在72 h比较差异有统计学意义。结论 EPO能抑制DU145细胞生长,诱导凋亡,其机制可能与激活Er-stress,诱发内质网的相关分子CHOP、XBP-1s、XBP-1、GRP78的表达有关。
基金Project(20110094110002) supported by the Specialized Research Fund for the Doctoral Program of Higher Education of ChinaProject(200801014) supported by the Ministry of Water Resources of ChinaProject(50825901) supported by the National Natural Science Foundation of China
文摘The mechanical behaviors of the interface between coarse-grained soil and concrete were investigated by simple shear tests under condition of mixed soil slurry (bentonite mixed with cement grout).For comparison,the interfaces both without slurry and with bentonite slurry were analyzed.The experimental results show that different slurries exert much influence on the strength and deformation of soil/structure interface.Under mixed soil slurry,strain softening and shear dilatation are observed,while shear dilatation appears under the small normal stress of the interface without slurry,and shear contraction is significant under the condition of the bentonite slurry.The thickness of the interface was determined by analyzing the disturbed height of the sample with both simple shear test and particle flow code (PFC).An elasto-plastic constitutive model incorporating strain softening and dilatancy for thin layer element of interface was formulated in the framework of generalized potential theory.The relation curves of shear stress and shear strain,as well as the relation curves of normal strain and shear strain,were fitted by a piecewise function composed by hyperbolic functions and resembling normal functions.The entire model parameters can be identified by tests.The new model is verified by comparing the measured data of indoor cut-off wall model tests with the predictions from finite element method (FEM).The FEM results indicate that the stress of wall calculated by using Goodman element is too large,and the maximum deviation between the test data and prediction is about 45%.While the prediction from the proposed model is close to the measured data,and the error is generally less than 10%.
基金Projects(51978672,51878671)supported by the National Natural Science Foundation of ChinaProject(2017zzts159)supported by the Graduate Innovation Program of Central South University,China+1 种基金Project(HNTY2021K09)supported by the Open Research Project of the Hunan Tieyuan Civil Engineering Testing Co.Ltd.,China。
文摘A filter cake is often formed between soil and concrete during casting concrete in the ground,such as constructions of diaphragm walls and bored piles.The present study aims to investigate the effect of the filter cake on the shear behavior of the sand-concrete pile interface.A series of sand-concrete interface direct shear tests were performed with a large-direct shear apparatus while considering different roughness(I=0,10,20 and 30 mm)and filter cake thickness(Δh=0,5 and 10 mm).For a smooth interface without a filter cake,the shear stress-horizontal displacement curves showed a“softening”response.The peak shear strength and friction angle decreased exponentially with increasing theΔh.Whereas,for a rough interface withΔh=5 or 10 mm,the shear stress-horizontal displacement curves presented a“hardening”response.The peak strength,as well as friction angle,decreased linearly with increasing theΔh.Moreover,a critical roughness I_(cr)of 10 mm was observed in the tests without a filter cake.The interface shear strength initially increased with increasing I but gradually decreased when the I exceeded I_(cr).In addition,the filter cake could reduce the roughness sensitivity on shear strength.
文摘Cold-formed steel structures are steel structure products constructed from sheets or coils using cold rolling, press brake or bending brake method. These structures are extensively employed in building construction industry due to their light mass, ductility by economic cold forming operations, favorable strength-to-mass ratio and other factors. The utilization of cold formed steel sections with concrete as composite can hugely reduce the construction cost. However, the use of cold formed steel members in composite concrete beams has been very limited. A comprehensive review of developments in composite beam with cold formed steel sections was introduced. It was revealed that employing cold-formed steel channel section to replace reinforcement bars in conventional reinforced concrete beam results in a significant cost reduction without reducing strength capacity. The use of composite beam consisting of cold-formed steel open or close box and filled concrete could also reduce construction cost. Lighter composite girder for bridges with cold-formed steel of U section was introduced. Moreover, types of shear connectors to provide composite action between cold-formed steel beam and concrete slab were presented. However, further studies to investigate the effects of metal decking on the behavior of composite beam with cold-formed steel section and introduction of ductile shear connectors were recommended.
