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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   
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Cancer remains an intractable medical problem. Rapid diagnosis and identification of cancer are critical to differentiate it from nonmalignant diseases. High-throughput biofluid metabolic analysis has potential for cancer diagnosis. Nevertheless, the present metabolite analysis method does not meet the demand for high-throughput screening of diseases. Herein, a high-throughput, cost-effective, and noninvasive urine metabolic profiling method based on TiO2/MXene-assisted laser desorption/ionization mass spectrometry (LDI-MS) is presented for the efficient screening of bladder cancer (BC) and nonmalignant urinary disease. Combined with machine learning, TiO2/MXene-assisted LDI-MS enables high diagnostic accuracy (96.8%) for the classification of patient groups (including 47 BC and 46 ureteral calculus (UC) patients) from healthy controls (113 cases). In addition, BC patients can also be identified from noncancerous UC individuals with an accuracy of 88.3% in the independent test cohort. Furthermore, metabolite variations between BC and UC individuals are investigated based on relative quantification, and related pathways are also discussed. These results suggest that this method, based on urine metabolic patterns, provides a potential tool for rapidly distinguishing urinary diseases and it may pave the way for precision medicine.  相似文献   
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在进行能量色散X射线荧光光谱(EDXRF)解谱时,如果给定样品的元素构成,采用纯元素谱图剥离的方式会更加合理,但由于每个元素的谱线都不止一条,如果仅仅针对主线对齐做剥离,会导致结果的严重失真,同时剥离次序对解谱结果有较大影响。介绍了一种最优化算法与纯元素谱剥离相结合的EDXRF解谱方法,该方法以多个纯元素谱的强度大小和峰位漂移道数作为变量构建残差方程,并用最优化计算的方法去调整,直至残差达到极小。实验采用强度顺序剥离、能量顺序剥离和最优化算法拟合3种方法分别对谱线重叠较为严重的La-Ce-Pr-Nd混合液样品的L系谱线进行了解析,结果表明最优化计算方法拟合的谱图与原始谱的残差 (1415.0)比另两种方法(166094.0和3192.7)大幅度缩小,拟合谱与原始谱更为吻合,并且方法在实现时对初值不敏感,解谱精度也不依赖于剥离次序。  相似文献   
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In this paper, a novel approach was presented to vibration analysis and identification of breathing cracks in Timoshenko beam under single or multiple moving mass. Dynamic strain energies (DSEs) and translational accelerations in beam structures under moving mass were used as forward problem and application of an emergent learning algorithm called the online sequential extreme learning machine algorithm as inverse problem to predict crack depths and locations. To demonstrate the potential of the proposed vibration analysis over existing ones, two validation studies have been done. To evaluate the proposed method to identify breathing cracks, two examples, namely, clamped–clamped beam and two span continuous beams have been studied. Also, the effect of the discrepancy in stiffness between the finite-element model and the actual tested dynamic system has been investigated. Another examination has been performed in which moving mass with different speeds are utilized. Also, the effect of multi mass passing through the beam has been studied. The obtained results indicated that the proposed method could identify the breathing cracks existence and severity in the beam under moving mass using DSE and accelerations, which may be noisy or noise free.  相似文献   
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For decades now, Douglas Crimp’s landmark 1980 essay ‘The Photographic Activity of Postmodernism’ has shaped our understanding of modernism’s aftermath, at least as it unfolded in North America and Western Europe. Less remembered, however, is the degree to which the procedures of disjunction, copying, appropriation, and outright theft that he highlighted were epitomised not just by contemporary photography, but by photomontage in particular. This article recovers the debates that led critics such as Crimp, Abigail Solomon-Godeau, Christopher Phillips, Benjamin Buchloh and others to turn to photomontage as one of their principal objects of concern in what became known as the postmodern critique of photography. Why was montage tasked to perform this critical function, particularly by people around the journal October who had not otherwise devoted the balance of their writing to photography’s history? The article suggests that these men and women, along with the contemporary artists they foregrounded, manifested what Mary Anne Doane has called a ‘desire for signification’, a reaction in the late 1970s against the mute theatricality of minimalist and conceptual art. Photomontage reintroduced representation to contemporary art and to the canon of art history. But unlike the reemerging illusionism in painting that also manifested this desire, montage guarded against an uncomplicated realism by highlighting and critiquing operations of representation in a manner that painting no longer could.  相似文献   
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