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1.
增加了屏蔽层的防辐射驾驶舱较之原来驾驶舱增重了5.5 t,有必要对其支座的强度进行分析与校核.本文应用ANSYS Workbench对防辐射挖掘机驾驶舱支座进行有限元分析,得到其应变和应力分布情况;采取支撑板和回转平台底板加厚等措施对驾驶舱支座进行结构优化.最后对挖掘机回转平台进行模态分析,得出回转平台前十阶的固有频率和振型.模态分析为支撑座的强度设计,减少驾驶舱的振动提供了理论依据.  相似文献   
2.
Ubiquitination, the covalent attachment of ubiquitin to a target protein, regulates most cellular processes and is involved in several neurological disorders. In particular, Angelman syndrome and one of the most common genomic forms of autism, dup15q, are caused respectively by lack of or excess of UBE3A, a ubiquitin E3 ligase. Its Drosophila orthologue, Ube3a, is also active during brain development. We have now devised a protocol to screen for substrates of this particular ubiquitin ligase. In a neuronal cell system, we find direct ubiquitination by Ube3a of three proteasome-related proteins Rpn10, Uch-L5, and CG8209, as well as of the ribosomal protein Rps10b. Only one of these, Rpn10, is targeted for degradation upon ubiquitination by Ube3a, indicating that degradation might not be the only effect of Ube3a on its substrates. Furthermore, we report the genetic interaction in vivo between Ube3a and the C-terminal part of Rpn10. Overexpression of these proteins leads to an enhanced accumulation of ubiquitinated proteins, further supporting the biochemical evidence of interaction obtained in neuronal cells.  相似文献   
3.
Opisthorchis viverrini-related cholangiocarcinoma (CCA), a fatal bile duct cancer, is a major public health concern in areas endemic for this parasite. We report here whole-exome sequencing of eight O. viverrini-related tumors and matched normal tissue. We identified and validated 206 somatic mutations in 187 genes using Sanger sequencing and selected 15 genes for mutation prevalence screening in an additional 46 individuals with CCA (cases). In addition to the known cancer-related genes TP53 (mutated in 44.4% of cases), KRAS (16.7%) and SMAD4 (16.7%), we identified somatic mutations in 10 newly implicated genes in 14.8-3.7% of cases. These included inactivating mutations in MLL3 (in 14.8% of cases), ROBO2 (9.3%), RNF43 (9.3%) and PEG3 (5.6%), and activating mutations in the GNAS oncogene (9.3%). These genes have functions that can be broadly grouped into three biological classes: (i) deactivation of histone modifiers, (ii) activation of G protein signaling and (iii) loss of genome stability. This study provides insight into the mutational landscape contributing to O. viverrini-related CCA.  相似文献   
4.
Human non-small cell lung cancers (NSCLCs) with activating mutations in EGFR frequently respond to treatment with EGFR-targeted tyrosine kinase inhibitors (TKIs), such as erlotinib, but responses are not durable, as tumors acquire resistance. Secondary mutations in EGFR (such as T790M) or upregulation of the MET kinase are found in over 50% of resistant tumors. Here, we report increased activation of AXL and evidence for epithelial-to-mesenchymal transition (EMT) in multiple in vitro and in vivo EGFR-mutant lung cancer models with acquired resistance to erlotinib in the absence of the EGFR p.Thr790Met alteration or MET activation. Genetic or pharmacological inhibition of AXL restored sensitivity to erlotinib in these tumor models. Increased expression of AXL and, in some cases, of its ligand GAS6 was found in EGFR-mutant lung cancers obtained from individuals with acquired resistance to TKIs. These data identify AXL as a promising therapeutic target whose inhibition could prevent or overcome acquired resistance to EGFR TKIs in individuals with EGFR-mutant lung cancer.  相似文献   
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Mapping units were developed based on landform, soils, and plant communities for the 40,000 ha of salt desert vegetation located below the maximum level of pluvial Lake Gilbert in Grass Valley, Nevada. Lake plain, beach, and bar features of the pluvial lake provide the dominant landforms. Fine textured lake sediments have produced salt- and Na-affected soils. The distribution and structure of plant communities are related to depth of the groundwater table, fluctuations in this depth, and the salt content of the groundwater. Wind and water erosion combine to continually evolve new environments for colonization by plants in this ecosystem.    相似文献   
7.
Long-term potentiation (LTP) defines persistent increases in neurotransmission strength at synapses that are triggered by specific patterns of neuronal activity. LTP, the most widely accepted molecular model for learning, is best characterised at glutamatergic synapses on dendritic spines. In this context, LTP involves increases in dendritic spine size and the insertion of glutamate receptors into the post-synaptic spine membrane, which together boost post-synaptic responsiveness to neurotransmitters. In dendrites, the material required for LTP is sourced from an organelle termed the endosomal-recycling compartment (ERC), which is localised to the base of dendritic spines. When LTP is induced, material derived from the recycling compartment, which contains α-amino-3-hydroxy-5-methyl-4-isoxazole propionate-type glutamate receptors (AMPARs), is mobilised into dendritic spines feeding the increased need for receptors and membrane at the spine neck and head. In this review, we discuss the importance of endosomal-recycling and the role of key proteins which control these processes in the context of LTP.  相似文献   
8.
Representation assumes that those who govern have knowledge of those for whom they govern. It is easy to presume knowledge of the “other”, but as we know this can be based in prejudice, cultural difference, or simply misinformation or simplification. Usually our explorations of this process have focused on populations identified as disadvantaged, disempowered or somehow “non-privileged”. However, the research process outlined here has revealed previously unexplored diversity within a population commonly described as privileged suggesting that good governance requires alertness to presuming to know both the unprivileged and the privileged. The research approach outlined in this paper has used a blend of historical reappraisal and qualitative techniques focusing on a population who have been conceptualized as doubly privileged. This population focus is that of older British; post World War II male migrants in South Australia. These people have been conceptualized as privileged because they are male, and they were part of the preferred ethnic group that Australian politicians and policy makers favoured post WW2. However, review of the historical data and qualitative interviews with some of these men show that the accepted narrative of a homogenous pre-WW2 British origin population is over simplistic. The historical research suggests that the presumption that post WW2 British migrant men were coming into an homogenous, privileging environment in migrating to SA is both ahistorical and crude. Furthermore the belief that post WW2 British migrant men were ethnically homogenous is undermined by the qualitative research, that reveals that their presumed homogeneity is much more fluid and nuanced than dominant conceptualisations have allowed. The impact of core ethnicities that continue to exist and compete in Britain, the social class focus and economic commodification of migrants in the machinations of powerful players in the state of South Australia all confound homogenizing, simplistic knowing of British migrant men in this state. Generically these findings caution social researchers with regard to presuming to know so called “privileged” populations as well as presumed non-privileged groups.  相似文献   
9.
二氧化碳减量技术包括捕获、封存及再利用技术,是目前国际上亟待发展的减量技术的研究状况.阐述了近年来台湾致力于研发各项减量技术的研究状况,希望通过能源计划将针对化学吸收法、物理吸附法、超重力旋转填充床技术、化学循环程序、CO2转化技术等对台湾未来CO2减量提出一整合性技术.除了基础减量技术的研发之外,国科会通过能源计划整合产学研各界资源,共同开发CO2补获及再利用技术,并建立示范工厂,成为台湾CO2减量的重点技术平台.  相似文献   
10.
Interleukin (IL)-33 is a recently described pro-inflammatory cytokine. Here we demonstrate IL-33 as a regulator of functional osteoclasts (OCs) from human CD14+ monocytes. IL-33 stimulates formation of tartrate-resistant acid phosphatase (TRAP)+ multinuclear OCs from monocytes. This action was suppressed by anti-ST2 antibody, suggesting that IL-33 acts through its receptor ST2, but not by the receptor activator of NF-κB ligand (RANKL) decoy, osteoprotegerin, or anti-RANKL antibody. IL-33 stimulated activating phosphorylations of signaling molecules in monocytes that are critical for OC development. These included Syk, phospholipase Cγ2, Gab2, MAP kinases, TAK-1, and NF-κB. IL-33 also enhanced expression of OC differentiation factors including TNF-α receptor-associated factor 6 (TRAF6), nuclear factor of activated T cells cytoplasmic 1, c-Fos, c-Src, cathepsin K, and calcitonin receptor. IL-33 eventually induced bone resorption. This study suggests that the osteoclastogenic property of IL-33 is mediated through TRAF6 as well as the immunoreceptor tyrosine-based activation motif-dependent Syk/PLCγ pathway in human CD14+ monocytes.  相似文献   
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