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The metalloprotease ADAM17 is a key regulator of the TNFα, IL-6R and EGFR signaling pathways. The maturation and function of ADAM17 is controlled by the seven-membrane-spanning proteins iRhoms1 and 2. The functional properties of the ADAM17/iRhom1 and ADAM17/iRhom2 complexes differ, in that stimulated shedding of most ADAM17 substrates tested to date can be supported by iRhom2, whereas iRhom1 can only support stimulated shedding of very few ADAM17 substrates, such as TGFα. The first transmembrane domain (TMD1) of iRhom2 and the sole TMD of ADAM17 are important for the stimulated shedding of ADAM17 substrates by iRhom2. However, little is currently known about how the iRhoms interact with different substrates to control their stimulated shedding by ADAM17. To provide new insights into this topic, we tested how various chimeras between iRhom1 and iRhom2 affect the stimulated processing of the EGFR-ligands TGFα (iRhom1- or 2-dependent) and EREG (iRhom2-selective) by ADAM17. This uncovered an important role for the TMD7 of the iRhoms in determining their substrate selectivity. Computational methods utilized to characterize the iRhom1/2/substrate interactions suggest that the substrate selectivity is determined, at least in part, by a distinct accessibility of the substrate cleavage site to stimulated ADAM17. These studies not only provide new insights into why the substrate selectivity of stimulated iRhom2/ADAM17 differs from that of iRhom1/ADAM17, but also suggest new approaches for targeting the release of specific ADAM17 substrates.  相似文献   
955.
Huang  Yao  Tang  Yong  Yuan  Wei  Fang  GuoYun  Yang  Yang  Zhang  XiaoQing  Wu  YaoPeng  Yuan  YuHang  Wang  Chun  Li  JinGuang 《中国科学:技术科学(英文版)》2021,64(5):919-956
Electric vehicles(EVs) are globally undergoing rapid developments, and have great potentials to replace the traditional vehicles based on fossil fuels. Power-type lithium-ion batteries(LIBs) have been widely used for EVs, owing to high power densities,good charge/discharge stability, and long cycle life. The driving ranges and acceleration performances are gaining increasing concerns from customers, which depend highly on the power level of LIBs. With the increase in power outputs, rising heat generation significantly affects the battery performances, and in particular operation safety. Meanwhile, the cold-start performance is still an intractable problem under extreme conditions. These challenges put forward higher requirements for a dedicated battery thermal management system(BTMS). Compared to traditional BTMSs in EVs, the heat pipe-based BTMS has great application prospects owing to its compact structure, flexibility, low cost, and especially high thermal conductivity. Encompassing this topic, this review first introduces heat generation phenomena and temperature characteristics of LIBs. Multiple abuse conditions and thermal runaway issues are described afterward. Typical cooling and preheating methods for designing a BTMS are also discussed. More emphasis on this review is put on the use of various heat pipes for BTMSs to enhance the thermal performances of LIBs. For lack of wide application in actual EVs, more efforts should be made to extend the use of heat pipes for constructing an energy-efficient, cost-effective, and reliable BTMS to improve the performances and safety of EVs.  相似文献   
956.
针对光伏并网变流器故障预测问题,提出了基于鲁棒最小二乘-支持向量回归(RLS-SVR)的早期故障预测方法.从系统层面分析了光伏并网变流器脆弱元件退化互相耦合机理及对系统状态特征和早期故障特征选取的影响,进而提出了以特征相对变化量表征变流器状态的电路故障预测方法.为了减小工作条件对特征退化预测的影响,方法首先采用RLS-...  相似文献   
957.
吉林省白山市大横路铜钴矿的工艺矿物学特征   总被引:1,自引:1,他引:0  
于宏东  汤集刚 《矿冶》2006,15(3):90-94
在我国,大横路铜钴矿床是迄今为止发现的唯一的大型独立钴矿床。为开发利用,对它进行了系统的工艺矿物学研究,并评估了影响回收指标的矿物学因素。该工作在国内尚属首次。所获结果不仅对选冶工艺研究有指导意义,而且也丰富了矿区矿物学资料。  相似文献   
958.
针对铝电解槽针振信息元诊断手段的不足,提出基于小波-神经网络技术的铝电解槽针振信息元分析与诊断的新方法。获取5种针振信息元的特征波谱作为神经网络的训练样本,建立神经网络诊断系统。分析了系统软硬件结构及其特点,并在350kA预焙铝电解槽上进行实验和仿真。实验证明该系统有很高的精度,且具有很好的应用价值。  相似文献   
959.
惯性圆锥破碎机运动学和动力学分析   总被引:4,自引:1,他引:3  
唐威 《矿冶》1996,5(3):72-80
惯性圆锥破碎机是具有独特原理和结构的高效超细粉碎设备。本文通过对惯性圆锥破碎机破碎机理的研究,对该破碎机的运动学和动力学作了较全面的分析,建立了惯性圆锥破碎机的运动学模型,推导出惯性圆锥破碎机的运动学和动力学公式,得出破碎力计算公式,并运用运动学和动力学分析了惯性圆锥破碎机的工作特点。  相似文献   
960.
Salmonella enterica, serovar Gallinarum, biovar Pullorum, is an avian-specific pathogen which has caused considerable economic losses to the poultry industry worldwide. Two-component systems (TCSs) play an essential role in obtaining nutrients, detecting the presence of neighboring bacteria and regulating the expression of virulence factors. The genome analysis of S. Pullorum strain S06004 suggesting the carriage of 22 pairs of TCSs, which belong to five families named CitB, OmpR, NarL, Chemotaxis and LuxR. In the CitB family, three pairs of TCSs, namely CitA-CitB, DcuS-DcuR and DpiB-DpiA, remain unaddressed in S. Pullorum. To systematically investigate the function of the CitB family in S. Pullorum, four mutants, ΔcitAB (abbreviated as Δcit), ΔdcuSRdcu), ΔdpiBAdpi) and ΔcitABΔdcuSRΔdpiBA (Δ3), were made using the CRISPR/Cas9 system. The results demonstrated that the CitB family did not affect the growth of bacteria, the results of biochemical tests, invasion and proliferation in chicken macrophage HD-11 cells and the expression of fimbrial protein. But the mutants showed thicker biofilm formation, higher resistance to antimicrobial agents, enhanced tolerance to inhibition by egg albumen and increased virulence in chicken embryos. Moreover, the deletion of Dpi TCS was detrimental to survival after exposure to hyperosmotic and oxidative environments, as well as the long-term colonization of the small intestine of chickens. Collectively, we provided new knowledge regarding the possible role of the CitB family involved in the pathogenic processes of S. Pullorum.  相似文献   
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