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Cell surface and secreted proteins provide essential functions for multicellular life. They enter the endoplasmic reticulum (ER) lumen co-translationally, where they mature and fold into their complex three-dimensional structures. The ER is populated with a host of molecular chaperones, associated co-factors, and enzymes that assist and stabilize folded states. Together, they ensure that nascent proteins mature properly or, if this process fails, target them for degradation. BiP, the ER HSP70 chaperone, interacts with unfolded client proteins in a nucleotide-dependent manner, which is tightly regulated by eight DnaJ-type proteins and two nucleotide exchange factors (NEFs), SIL1 and GRP170. Loss of SIL1′s function is the leading cause of Marinesco-Sjögren syndrome (MSS), an autosomal recessive, multisystem disorder. The development of animal models has provided insights into SIL1′s functions and MSS-associated pathologies. This review provides an in-depth update on the current understanding of the molecular mechanisms underlying SIL1′s NEF activity and its role in maintaining ER homeostasis and normal physiology. A precise understanding of the underlying molecular mechanisms associated with the loss of SIL1 may allow for the development of new pharmacological approaches to treat MSS. 相似文献
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Atsuki Yamaguchi Kazuki Fukui Yuki Fujiwara Shingo Tamaki Sachie Kusaka Fuminobu Sato 《Journal of Nuclear Science and Technology》2021,58(1):80-86
ABSTRACT It is important to perform neutron transport simulations with accurate nuclear data in the neutronics design of a fusion reactor. However, absolute values of large-angle scattering cross sections vary among nuclear data libraries even for well-examined nuclide of iron. Benchmark experiments focusing on large-angle scattering cross sections were thus performed to confirm the correctness of nuclear data libraries. The series benchmark experiments were performed at a DT neutron source facility, OKTAVIAN of Osaka University, Japan, by the unique experimental system established by the authors’ group, which can extract only the contribution of large-angle scattering reactions. This system consists of two shadow bars, target plate (iron), and neutron detector (niobium). Two types of shadow bars were used and four irradiations were conducted for one experiment, so that contribution of room-return neutrons was effectively removed and only large-angle scattering neutrons were extracted from the measured four Nb reaction rates. The obtained experimental results were compared with calculations for five nuclear data libraries including JENDL-4.0, JEFF.-3.3, FENDL-3.1, ENDF/B- VII, and recently released ENDF/B-VIII. It was found from the comparison that ENDF/B-VIII showed the best result, though ENDF/B-VII showed overestimation and others are in large underestimation at 14 MeV. 相似文献
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Seyed M. N. GHOREISHI Mahdi FAKOOR Ahmad AZIZI 《Frontiers of Structural and Civil Engineering》2021,15(3):623
In this study, gradual and sudden reduction methods were combined to simulate a progressive failure in notched composite plates using a macro mechanics approach. Using the presented method, a progressive failure is simulated based on a linear softening law prior to a catastrophic failure, and thereafter, sudden reduction methods are employed for modeling a progressive failure. This combination method significantly reduces the computational cost and is also capable of simultaneously predicting the first and last ply failures (LPFs) in composite plates. The proposed method is intended to predict the first ply failure (FPF), LPF, and dominant failure modes of carbon/epoxy and glass/epoxy notched composite plates. In addition, the effects of mechanical properties and different stacking sequences on the propagation of damage in notched composite plates were studied. The results of the presented method were compared with experimental data previously reported in the literature. By comparing the numerical and experimental data, it is revealed that the proposed method can accurately simulate the failure propagation in notched composite plates at a low computational cost. 相似文献
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宰前倒挂因能有效提高屠宰效率成为肉鸭宰杀前必经的一个工艺过程,但倒挂往往会加剧肉鸭的应激程度,影响其血液品质,已成为工厂生产中亟待解决的问题。因此,本实验旨在借助血液学与凝血相关指标探究宰前倒挂应激对鸭血凝胶特性的影响。在屠宰前,将40 只樱桃谷鸭随机分为2 个处理组:对照组和宰前倒挂组(宰前倒挂2.5 min),屠宰后采集血样并制备血凝块,随后分析血液指标(应激指标、血液学指标、凝血指标)以及鸭血凝胶特性。结果表明,宰前倒挂组鸭血中皮质酮激素及促肾上腺皮质激素的水平均高于对照组,说明实验所建立宰前倒挂模型成立。倒挂应激后,红细胞计数、血小板计数、血红蛋白质量浓度增加,红细胞比容、平均红细胞体积及平均血小板体积增大;凝血酶原的水平极显著上升(P<0.01),组织因子的水平显著上升(P<0.05)。宰前倒挂最终导致鸭血凝胶化加快,鸭血凝胶体系中水分迁移速率增大,结合水与自由水比例减少,不易流动水比例增大,质构特性和保水性变差。研究揭示了宰前倒挂应激通过影响鸭血的血液学指标和凝血系统从而改变其凝胶行为及凝胶特性,可为工厂改善应激对鸭血凝胶品质的影响提供理论依据。 相似文献
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