背景:近年研究表明哺乳动物雷帕霉素靶蛋白/核糖体40S小亚基S6蛋白激酶(mammalian target of rapamycin/P70S6K,mTOR/P70S6K)信号通路在某些肿瘤形成过程中具有一定作用。病理性瘢痕特别是瘢痕疙瘩具有某些肿瘤的性质,因此该信号通路在...背景:近年研究表明哺乳动物雷帕霉素靶蛋白/核糖体40S小亚基S6蛋白激酶(mammalian target of rapamycin/P70S6K,mTOR/P70S6K)信号通路在某些肿瘤形成过程中具有一定作用。病理性瘢痕特别是瘢痕疙瘩具有某些肿瘤的性质,因此该信号通路在病理性瘢痕形成中可能具有重要作用。目的:观察mTOR/P70S6K信号通路在病理性瘢痕中的的作用。方法:采用免疫组织化学SP法检测磷酸化mTOR/P70S6K(p-mTOR和p-P70S6K)在瘢痕疙瘩、增生性瘢痕、非病理性瘢痕及正常皮肤组织中的表达水平。实验所取瘢痕组织来自临床上诊断明确的瘢痕患者。结果:瘢痕疙瘩和增生性瘢痕组织中p-mTOR和p-P70S6K阳性表达率高于非病理性瘢痕及正常皮肤组(P<0.05)。p-mTOR和p-P70S6K表达呈正相关(r=0.482,P<0.05)。结果提示mTOR/P70S6K信号通路的激活参与了病理性瘢痕的形成过程,且mTOR和P70S6K之间具有协同作用。展开更多
Creep testing was conducted on K40S alloy. The detailed creep deformation and fracture mechanisms under constant load were studied. The results show that the stress exponent ranges between 7 and 14.4 at elevated tempe...Creep testing was conducted on K40S alloy. The detailed creep deformation and fracture mechanisms under constant load were studied. The results show that the stress exponent ranges between 7 and 14.4 at elevated temperature 973~1173 K, and that the activation energy is approximately 449.1 kJ/mol. During creep, the grain boundary sliding cut off primary carbides at the boundary, generating the 'O' model cracks. The creep failure mode of K40S alloy is transgranular ductile and cracks originate at the primary carbides. A long carbide and matrix interface is often a preferential path for crack propagation. The creep mechanism is discussed in light of the creep microstructure, the stress exponent and the activation energy.展开更多
Generation of three dimensional structures of macromolecules using in silico structural modeling technologies such as homology and de novo modeling has improved dramatically and increased the speed by which tertiary s...Generation of three dimensional structures of macromolecules using in silico structural modeling technologies such as homology and de novo modeling has improved dramatically and increased the speed by which tertiary structures of organisms can be generated. This is especially the case if a homologous crystal structure is already available. High-resolution structures can be rapidly created using only their sequence information as input, a process that has the potential to increase the speed of scientific discovery. In this study, homology modeling and structure prediction tools such as RNA123 and SWISS–MODEL were used to generate the 40 S ribosomal subunit from Plasmodium falciparum. This structure was modeled using the published crystal structure from Tetrahymena thermophila, a homologous eukaryote. In the absence of the Plasmodium falciparum 40 S ribosomal crystal structure, the model accurately depicts a global topology, secondary and tertiary connections, and gives an overall root mean square deviation(RMSD) value of 3.9 ? relative to the template's crystal structure. Deviations are somewhat larger in areas with no homology between the templates. These results demonstrate that this approach has the power to identify motifs of interest in RNA and identify potential drug targets for macromolecules whose crystal structures are unknown. The results also show the utility of RNA homology modeling software for structure determination and lay the groundwork for applying thisapproach to larger and more complex eukaryotic ribosomes and other RNA-protein complexes. Structures generated from this study can be used in in silico screening experiments and lead to the determination of structures for targets/hit complexes.展开更多
文摘背景:近年研究表明哺乳动物雷帕霉素靶蛋白/核糖体40S小亚基S6蛋白激酶(mammalian target of rapamycin/P70S6K,mTOR/P70S6K)信号通路在某些肿瘤形成过程中具有一定作用。病理性瘢痕特别是瘢痕疙瘩具有某些肿瘤的性质,因此该信号通路在病理性瘢痕形成中可能具有重要作用。目的:观察mTOR/P70S6K信号通路在病理性瘢痕中的的作用。方法:采用免疫组织化学SP法检测磷酸化mTOR/P70S6K(p-mTOR和p-P70S6K)在瘢痕疙瘩、增生性瘢痕、非病理性瘢痕及正常皮肤组织中的表达水平。实验所取瘢痕组织来自临床上诊断明确的瘢痕患者。结果:瘢痕疙瘩和增生性瘢痕组织中p-mTOR和p-P70S6K阳性表达率高于非病理性瘢痕及正常皮肤组(P<0.05)。p-mTOR和p-P70S6K表达呈正相关(r=0.482,P<0.05)。结果提示mTOR/P70S6K信号通路的激活参与了病理性瘢痕的形成过程,且mTOR和P70S6K之间具有协同作用。
文摘Creep testing was conducted on K40S alloy. The detailed creep deformation and fracture mechanisms under constant load were studied. The results show that the stress exponent ranges between 7 and 14.4 at elevated temperature 973~1173 K, and that the activation energy is approximately 449.1 kJ/mol. During creep, the grain boundary sliding cut off primary carbides at the boundary, generating the 'O' model cracks. The creep failure mode of K40S alloy is transgranular ductile and cracks originate at the primary carbides. A long carbide and matrix interface is often a preferential path for crack propagation. The creep mechanism is discussed in light of the creep microstructure, the stress exponent and the activation energy.
基金supported by European Union Grant Contract No. 018834Development of New Drugs for the Treatment of Malaria “ANTIMAL, ISP-KEN-02 PROJECT: Drug Discovery from Kenya's Biodiversity and the Chinese Government for travel fellowships to the Institute of Materia Medica Symposium on Drug Discovery of Infectious Diseas,May 2015
文摘Generation of three dimensional structures of macromolecules using in silico structural modeling technologies such as homology and de novo modeling has improved dramatically and increased the speed by which tertiary structures of organisms can be generated. This is especially the case if a homologous crystal structure is already available. High-resolution structures can be rapidly created using only their sequence information as input, a process that has the potential to increase the speed of scientific discovery. In this study, homology modeling and structure prediction tools such as RNA123 and SWISS–MODEL were used to generate the 40 S ribosomal subunit from Plasmodium falciparum. This structure was modeled using the published crystal structure from Tetrahymena thermophila, a homologous eukaryote. In the absence of the Plasmodium falciparum 40 S ribosomal crystal structure, the model accurately depicts a global topology, secondary and tertiary connections, and gives an overall root mean square deviation(RMSD) value of 3.9 ? relative to the template's crystal structure. Deviations are somewhat larger in areas with no homology between the templates. These results demonstrate that this approach has the power to identify motifs of interest in RNA and identify potential drug targets for macromolecules whose crystal structures are unknown. The results also show the utility of RNA homology modeling software for structure determination and lay the groundwork for applying thisapproach to larger and more complex eukaryotic ribosomes and other RNA-protein complexes. Structures generated from this study can be used in in silico screening experiments and lead to the determination of structures for targets/hit complexes.
