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91.
ULK1 (unc-51 like autophagy activating kinase 1), a mammalian serine/threonine kinase, is a key component of
autophagy initiation complex and helps to induce all types of autophagy. Canonical autophagy is a process in which,
through the interactions of a series of autophagy-related proteins, damaged organelles or misfolded proteins are
engulfed by autophagosomes and then merged with lysosomes to be degraded. Thus, canonical autophagy is an
important constituent part of the cellular “quality control.” Besides, accumulating evidence indicates that ULK1 exerts
autophagy-independent effects in a cell-specific manner. For example, ULK1 facilitates neurite elongation through the
regulation of endoplasmic reticulum (ER)–Golgi trafficking in neurons, stimulates phosphopentose pathway to help
NADPH (nicotinamide adenine dinucleotide phosphate hydrogen) production, and acts as a duplex regulator in type
I IFN (type I interferon) induced innate immune response. Considering the importance and diversity of ULK1 in
various biological processes, this review aims to present a comprehensive overview of autophagy and non-autophagy
related functions of ULK1 in a variety of human physiological, pathological, and disease processes. 相似文献
92.
新汶矿业集团经过探索和实践,研究运用了差异互补式全掩护支护技术、掩护支架自牵引联动装置工艺、矿车运输、滑移运输多用轨道、自动找正装车平台、液控调整装置等新技术、新工艺,做到了液压支架综合流程快速回撤,实现了高效化、连贯化安全回撤,取得了良好的经济效益。 相似文献
93.
94.
Dr. Yahu A. Liu Dr. Qihui Jin Qiang Ding Dr. Xueshi Hao Tingting Mo Shanshan Yan Dr. Yefen Zou Dr. Zhihong Huang Xiaoyue Zhang Wenqi Gao Dr. Tom Y.-H. Wu Chun Li Dr. Badry Bursalaya Dr. Michael Di Donato Dr. You-Qing Zhang Lisa Deaton Dr. Weijun Shen Dr. Brandon Taylor Anwesh Kamireddy Dr. George Harb Dr. Jing Li Dr. Yong Jia Dr. Andrew M. Schumacher Dr. Bryan Laffitte Dr. Richard Glynne Dr. Shifeng Pan Dr. Peter McNamara Dr. Valentina Molteni Dr. Jon Loren 《ChemMedChem》2020,15(16):1562-1570
Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation. 相似文献
95.
豫西熊耳山雷门沟钼矿床位于东秦岭多金属成矿带东段,是已探明的超大型斑岩型钼矿,前人研究程度高、地质成果丰硕,但对矿床开采技术条件方面研究较少。本次通过地质调查工程、水文地质试验等方法,从水文地质角度,对雷门沟钼矿床水文地质条件进行研究,填补了该方面的空白,丰富了研究成果;采用水文地质比拟法预测未来矿坑最大排水量2613 m3/d,经实践检验结果较为可靠;总结的采坑排水量预测方法、含水层特点、矿床充水因素以及防治水措施,以期对该区域水文地质工作具有参考价值。 相似文献
96.
作为畜禽屠宰的副产物,动物骨因其丰富的蛋白质和广阔的深加工利用的发展前景而成为当今环境、农业和能源等领域的研究热点.受自身骨骼结构和综合利用技术的制约,骨骼的深加工利用率不足2%,造成了严重的资源浪费与环境污染.蛋白水解作为蛋白质资源深加工领域最有效的技术手段,可实现大宗蛋白质资源的高效回收利用;而蛋白水解物优异的溶解性、可降解性、生物相容性和独特的生物功能活性使其具有开发高值材料的潜力.随着石化资源的短缺和人们健康环保意识的增强,人们对环保型可再生型新材料的需求逐渐迫切,而畜禽骨蛋白质材料的开发利用紧密结合国家新型战略产业——生物制造业,将促进农副产品加工业的持续健康发展.针对畜禽骨蛋白质材料化开发利用的发展历程及当前的研究热点,本文阐述了絮凝剂、粘结剂、可降解塑料、表面活性剂、医用材料等近年来研究较广的畜禽骨蛋白质材料化利用途径,并总结了各种利用途径的应用效果和局限性;同时,总结分析了现今利用蛋白水解物开发新型材料的相关理论及研究成果,为开发畜禽骨蛋白质材料提供了理论支持;最后,基于目前生物基材料的发展趋势及畜禽骨深加工技术的难点问题,客观展望了畜禽骨蛋白质材料的制备及应用发展方向. 相似文献
97.
We propose an analytical model to evaluate the lightpath blocking performance for a single ROADM node with intra-node add/drop contention,in which the number of lightpaths that can be added/dropped with the same wavelength is limited by the add/drop contention factor.Different models of traffic load per nodal degree are considered to validate the effectiveness of the analytical model.The simulation results show that the proposed analytical model is effective in predicting the performance for different values of add/drop contention factor C and for variable offered loads at the node.The add/drop contention factor shows an important impact on the lightpath blocking performance and properly raising the contention factor can significantly improve the lightpath blocking performance.When the add/drop contention factor C exceeds a certain level,the performance of a ROADM with intra-node contention is close to that of a contentionless ROADM. 相似文献
98.
ZHAO Pengfei TIAN Yuming LIU Aiping KONG Xiangchen CHAI Yuesheng LI Zhangang BAI Pinbo 《中国耐火材料》2015,(2):36-41
Based on the needs of the market,a new 52 MPa medium-density and high-strength ceramic proppant was prepared by adopting third grade bauxite and clay as raw materials and using the solid phase sintering method,and the effect of the firing temperature on the microstructure,phase composition and mechanical properties of the ceramic proppant was studied. The broken resistance mechanism of this ceramic proppant was also discussed. The results show that the main phases of the prepared ceramic proppant are mullite and corundum; the broken rates are 3. 92% and 7. 21% under 52 MPa and69 MPa,respectively. 相似文献
99.
This paper discusses the compressive performance of perforated brick masonry after fire exposure. Compressive strength tests of the mortar, clay perforated brick, and perforated brick masonry specimens were performed in accordance with ISO834 fire tests of different durations. The temperature distribution of the masonry materials and specimens was simulated using the finite element software ABAQUS, with the thermal parameters of masonry materials recommended by European standard Eurocode 6 and related literature. The compressive strength reduction factors of mortar and clay perforated brick exposed to different fire durations were calculated via the layered method suggested by European standard Eurocode 1. In addition, the compressive strength reduction factors after cooldown were obtained from the experimental data of the masonry materials, and by considering further reductions in the compressive strength after cooling from high temperatures. Experimental data of the masonry specimens were compared with the numerical results obtained using the reduction factors proposed in this work. The comparison revealed an overall acceptable approximation. Thus, the method presented in this paper can be used to evaluate the residual capacity of masonry structures after fire. 相似文献
100.
In this work,the ionospheric variability is analyzed by applying the wavelet decomposition technique to the noontime fo F2,F10.7,interplanetary magnetic field(IMF)Bz,Ap,and lower thermospheric temperature at pressure of 10?4 h Pa in 2002.Results show that the variance of periodic oscillations in the ionosphere is largest in the 2–4-day period and declines with the increase of the period.The maximum variance of the periodic oscillations in solar irradiation is in the 16–32-day period.For geomagnetic activities,most of the variance is about equally distributed on intervals of periods shorter than 32 days.Variance distributions of IMF Bz and lower thermospheric temperature are similar to those of the ionosphere.They show the maximum in the 2–4-day period and decline with the increase of the period.By analyzing the distributions of the variances,the potential connections between the ionosphere and the external sources are discussed. 相似文献