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11.
Dr. Alejandra A. Carriles Alberto Mills Dr. María-José Muñoz-Alonso Dr. Dolores Gutiérrez Dr. Juan M. Domínguez Prof. Dr. Juan A. Hermoso Prof. Dr. Federico Gago 《Chembiochem : a European journal of chemical biology》2021,22(2):374-391
Spontaneous mutations in the EEF1A2 gene cause epilepsy and severe neurological disabilities in children. The crystal structure of eEF1A2 protein purified from rabbit skeletal muscle reveals a post-translationally modified dimer that provides information about the sites of interaction with numerous binding partners, including itself, and maps these mutations onto the dimer and tetramer interfaces. The spatial locations of the side chain carboxylates of Glu301 and Glu374, to which phosphatidylethanolamine is uniquely attached via an amide bond, define the anchoring points of eEF1A2 to cellular membranes and interorganellar membrane contact sites. Additional bioinformatic and molecular modeling results provide novel structural insight into the demonstrated binding of eEF1A2 to SH3 domains, the common MAPK docking groove, filamentous actin, and phosphatidylinositol-4 kinase IIIβ. In this new light, the role of eEF1A2 as an ancient, multifaceted, and articulated G protein at the crossroads of autophagy, oncogenesis and viral replication appears very distant from the “canonical” one of delivering aminoacyl-tRNAs to the ribosome that has dominated the scene and much of the thinking for many decades. 相似文献
12.
Among various carbon materials, diamond stands out due to excellent physical and chemical properties. In this work, we designed Dia@SiO2@Ag composites combining diamond micropowder and Ag nanoparticles by a simple chemical method and obtained stable substrate for surface enhanced Raman scattering (SERS) owing to its high surface-to-volume ratio, low density, as well as close bond between diamond and Ag. As-prepared Dia@SiO2@Ag presented high activity to detect crystal violet and rhodamine 6G molecules, which was demonstrated by significantly enhanced SERS spectra and high enhancement factor values (108-109). Moreover, Dia@SiO2@Ag also showed desired sensitivity, which was investigated by detection limit. Therefore, our study provided more theoretical support and broadened the functional applications of diamond, particularly in Raman detection. 相似文献
13.
社会经济的快速发展促进了科学技术水平的显著提升,社会生产生活各个领域当中对计算机网络的应用程度不断提升,当前,网络已经成为了人们日常生活与工作的重要组成部分。为此,加强对网络安全等因素影响研究就显得格外重要。网络环境关系着用户的使用质量,更加影响人们的工作效率,加强对网络安全技术的研究时解决相关问题的核心内容。本文针对网络安全威胁因素以及常见的网络安全技术进行了简要分析。 相似文献
14.
Filippo Lococo Massimiliano Paci Cristian Rapicetta Teresa Rossi Valentina Sancisi Luca Braglia Silvio Cavuto Alessandra Bisagni Italia Bongarzone Douglas M. Noonan Adriana Albini Sally Maramotti 《International journal of molecular sciences》2015,16(8):19612-19630
Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered. This study investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and also characterizes the biological function of sEGFR to clarify the molecular mechanisms involved in the course of action of this protein. Plasma sEGFR levels from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy subjects were analyzed by using an enzyme-linked immunosorbent assay. The biological function of sEGFR was analyzed in vitro using NSCLC cell lines, investigating effects on cell proliferation and migration. We found that plasma sEGFR was significantly decreased in the NSCLC patient group as compared to the control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002). Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell signaling and holoreceptor internalization. These data show that sEGFR is a potential circulating biomarker with a physiological protective role, providing a first approach to the functional role of the soluble isoform of EGFR. However, the impact of these data on daily clinical practice needs to be further investigated in larger prospective studies. 相似文献
15.
竖向循环荷载作用下桩土界面的作用机理是研究桩土摩擦疲劳的关键。针对循环荷载作用下桩-粉土界面的剪切性能,使用改进的剪切试验装置在恒刚度条件下进行循环剪切试验,研究循环次数、累积位移和法向刚度对其摩擦疲劳性能、循环后单调剪切性能的影响。试验结果表明,粉土在循环剪切过程中,法向应力和剪应力在初始10个循环内随循环数增加快速衰减,随着循环进行,逐渐趋于稳定;单次循环内在剪切位移方向变化时,土体呈现表现出剪缩-剪胀-剪缩交替现象,总体变形呈现剪缩的趋势;循环荷载作用下,粉土界面的法向应力和剪应力随法向刚度增大衰减速率增大,达到稳定的累积循环位移越小;粉土循环后的单调剪切、法向应力恢复的单调剪切的剪应力比小于首次单调剪切试验值,且法向应力恢复的循环后剪切试验的剪胀程度较小,表明循环剪切过程中界面处粉土颗粒棱角破碎,颗粒变得光滑。在对试验数据分析的基础上,提出了与累积位移、法向刚度和初始应力相关的无量纲累积位移,建立了法向应力和界面摩擦角随累积位移的衰减方程。 相似文献
16.
F. Schröder R. M. Ward A. R. Walpole R. P. Turner M. M. Attallah J.-C. Gebelin 《Materials Science & Technology》2015,31(3):372-384
Linear friction welding of the Ti6Al4V alloy is studied. A new definition of the energy input rate is proposed, based on an integration over time of the in-plane force and velocity; a strong correlation with the upset rate is then found. The effective friction coefficient is estimated to be 0·5±0·1 for varying frequencies and amplitudes, with only a weak dependence on the processing conditions displayed. A model is proposed that accounts for both the conditioning and equilibrium stages of the process, which is shown to be in good agreement with the experimental data. The model is used to study the mechanism by which the flash is formed. A criterion is proposed by which the rippled nature of its morphology can be predicted. 相似文献
17.
湿式摩擦副滑摩过程温度场与应力场相互耦合作用,温度场分布受到多种因素影响,其中压力、旋转速度、润滑流量作为湿式摩擦副工作参数对其温度场的影响尤为显著。在理论分析基础上,采用有限元数值模拟分析与实验研究相结合的方法,对摩擦界面温度场时空分布特性进行研究,同时研究界面温度场在摩擦副工作压力、相对转速和润滑流量作用下的变化规律。研究表明:在对偶钢片和摩擦片近外径侧更易出现高温和应力集中区,且对偶钢片相对于摩擦片更易出现温度和应力分布不均匀情况;温度场中高温集中区与应力场中应力集中区相对应,最大温度随着压力增加、相对转速增大、润滑流量减少而显著上升,该结果得到试验结果的验证。 相似文献
18.
Konstantin V. Dergilev Evgeny K. Shevchenko Zoya I. Tsokolaeva Irina B. Beloglazova Ekaterina S. Zubkova Maria A. Boldyreva Mikhail Yu. Menshikov Elizaveta I. Ratner Dmitry Penkov Yelena V. Parfyonova 《International journal of molecular sciences》2020,21(24)
Cell therapy of the post-infarcted myocardium is still far from clinical use. Poor survival of transplanted cells, insufficient regeneration, and replacement of the damaged tissue limit the potential of currently available cell-based techniques. In this study, we generated a multilayered construct from adipose-derived mesenchymal stromal cells (MSCs) modified to secrete stem cell factor, SCF. In a rat model of myocardium infarction, we show that transplantation of SCF producing cell sheet induced activation of the epicardium and promoted the accumulation of c-kit positive cells in ischemic muscle. Morphometry showed the reduction of infarct size (16%) and a left ventricle expansion index (0.12) in the treatment group compared to controls (24–28%; 0.17–0.32). The ratio of viable myocardium was more than 1.5-fold higher, reaching 49% compared to the control (28%) or unmodified cell sheet group (30%). Finally, by day 30 after myocardium infarction, SCF-producing cell sheet transplantation increased left ventricle ejection fraction from 37% in the control sham-operated group to 53%. Our results suggest that, combining the genetic modification of MSCs and their assembly into a multilayered construct, we can provide prolonged pleiotropic effects to the damaged heart, induce endogenous regenerative processes, and improve cardiac function. 相似文献
19.
In order to improve the process effectiveness and joint quality, ultrasonic vibrations were integrated with friction stir lap welding. Effect of ultrasonic exertion on the process and joint quality of AA 6061-T6 were investigated. Upon ultrasonic exertion, joints owned larger effective lap width, shorter hooks and improved strength. Weld fracture mode changed from a ductile–brittle mixed mode to a more ductile mode while the fracture path shifted from lap interface to beyond the stir zone. Material flow and interface defects were characterised using lap welded dissimilar aluminium alloy joints. Ultrasonic vibration improved the material flow and reduced the interfacial defects. Variations in failure load of joints were found in accordance with the variations in material flow and interfacial defects. 相似文献
20.
《Planning》2019,(4)
目的探讨腹腔手术后重症患者心肌损伤的发生情况及可能的危险因素。方法回顾性分析北京大学人民医院2017年1月至2019年1月腹腔手术后重症患者的一般临床资料及心肌损伤情况,收集并观察基础病史、术中(手术时间、是否急诊手术、术中出血>800 ml和术中低血压等)及术后指标(改良氧合指数、血乳酸、急性肾损伤和术后24 h内使用升压药情况等)。根据术后是否发生心肌损伤,将患者分为心肌损伤组和非心肌损伤组,采用Logistic回归分析腹腔手术后重症患者心肌损伤的危险因素。结果在纳入的803例腹腔手术后重症患者中,心肌损伤发生率为17. 2%(138/803),而急性心肌梗死发生率仅为0. 9%(7/803)。单因素分析显示,慢性肾功能不全病史、手术时间、急诊手术、术中低血压、术后24 h内使用升压药、高APACHEⅡ评分及术后即刻急性肾损伤与术后重症患者心肌损伤相关(P<0. 05)。多因素回归分析显示,急诊手术(OR=3. 14,95%CI:1. 76~5. 60,P<0. 001)、术后24 h内使用升压药(OR=2. 26,95%CI:1. 23~4. 15,P=0. 008)、APACHEⅡ评分(OR=1. 05,95%CI:1. 01~1. 09,P=0. 008)和术后急性肾损伤(OR=3. 18,95%CI:1. 78~5. 69,P <0. 001)与腹腔手术后重症患者发生心肌损伤独立相关。结论重症患者腹腔手术后心肌损伤发生率高,急诊手术、术后24 h内使用升压药、高APACHEⅡ评分和术后急性肾损伤是导致腹腔手术后重症患者发生心肌损伤的独立危险因素。 相似文献