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31.
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
32.
Abulyazied Dalia E. Alturki Asma M. Youness Rasha A. Abomostafa H. M. 《Journal of Inorganic and Organometallic Polymers and Materials》2021,31(10):4077-4092
Journal of Inorganic and Organometallic Polymers and Materials - In this work, a borosilicate glass sample (5SiO2–45B2O3–20Na2O–25CaO–5Ag2O) was added to nano-sized... 相似文献
33.
Automation and Remote Control - We consider multicriteria minimax optimization problems with criteria in the form of the maxima of functionals given by the induced norms of linear operators taking... 相似文献
34.
Viktoria M. S. Kjær Loukas Ieremias Dr. Viktorija Daugvilaite Dr. Michael Lückmann Prof. Thomas M. Frimurer Prof. Trond Ulven Prof. Mette M. Rosenkilde Dr. Jon Våbenø 《ChemMedChem》2021,16(17):2623-2627
The G protein-coupled receptor GPR183/EBI2, which is activated by oxysterols, is a therapeutic target for inflammatory and metabolic diseases where both antagonists and agonists are of potential interest. Using the piperazine diamide core of the known GPR183 antagonist (E)-3-(4-bromophenyl)-1-(4-(4-methoxybenzoyl)piperazin-1-yl)prop-2-en-1-one (NIBR189) as starting point, we identified and sourced 79 structurally related compounds that were commercially available. In vitro screening of this compound collection using a Ca2+ mobilization assay resulted in the identification of 10 compounds with agonist properties. To enable establishment of initial structure-activity relationship trends, these were supplemented with five in-house compounds, two of which were also shown to be GPR183 agonists. Taken together, our findings suggest that the agonist activity of this compound series is dictated by the substitution pattern of one of the two distal phenyl rings, which functions as a molecular efficacy-switch. 相似文献
35.
Claudia Paredes Francisco J. Martínez-Vázquez Hamada Elsayed Paolo Colombo Antonia Pajares Pedro Miranda 《Journal of the European Ceramic Society》2021,41(1):892-900
Bioactive ceramic scaffolds for bone regeneration consisting of a three-dimensional mesh of interpenetrating struts with square section were fabricated via Digital Light Processing (DLP). The ability of the technique to manufacture 3D porous structures from β-tricalcium phosphate (β-TCP) powders with different dimensions of struts and pores was evaluated, identifying the possibilities and limitations of the manufacturing process. Small pore sizes were found to seriously complicate the elimination of excess slurry from the scaffold’s innermost pores. The effect of the strut/pore size on the mechanical performance of the scaffolds under compressive stresses was also evaluated, but no significant influence was found. Under compressive stresses, the structures resulted weaker when tested perpendicularly to the printing plane due to interlayer shear failure. Interlayer superficial grooves are proposed as potential failure-controlling defects, which could also explain the lack of a Weibull size effect on the mechanical strength of the fabricated DLP scaffolds. 相似文献
36.
William M. Pitts Martin Werrel Marco Fernandez Mary A. Long Evan A. Eisenberg James Filliben Cory D. Runyon 《火与材料》2021,45(1):127-154
Fire spread and growth on real‐scale four cushion mock‐ups of residential upholstered furniture (RUF) were investigated with the goal of identifying whether changes in five classes of materials (barrier, flexible polyurethane foam, polyester fiber wrap, upholstery fabric, and sewing thread), referred to as factors, resulted in statistically significant changes in burning behavior. A fractional factorial experimental design plus practical considerations yielded a test matrix with 20 material combinations. Experiments were repeated a minimum of two times. Measurements included fire spread rates derived from video recordings and heat release rates (HRRs). A total of 13 experimental parameters (3 based on the videos and 10 on the HRR results), referred to as responses, characterized the measurements. Statistical analyses based on Main Effects Plots (main effects) and Block Plots (main effects and factor interactions) were used. The results showed that three of the factors resulted in statistically significant effects on varying numbers of the 13 responses. The Barrier and Fabric factors had the strongest main effects with roughly comparable magnitudes. Foam was statistically significant for fewer of the responses and its overall strength was weaker than for Barrier and Fabric. No statistically significant main effects were identified for Wrap or Thread. Multiple two‐term interactions between factors were identified as being statistically significant. The Barrier*Fabric interaction resulted in the highest number of and strongest statistically significant effects. The existence of two‐term interactions means that it will be necessary to consider their effects in approaches designed to predict the burning behavior of RUF. 相似文献
37.
Olga Yu Kurapova Sergey M. Shugurov Evgenia A. Vasil'eva Daniil A. Savelev Vladimir G. Konakov Sergey I. Lopatin 《Ceramics International》2021,47(8):11072-11079
Ceria-based solid solutions are important materials for high- and medium-temperature electrochemical applications. However, the stabilities of both binary and ternary ceria-based solid solutions are insufficient at elevated temperatures, which limits their application as solid electrolytes or SOFC cathodes. Data on the high-temperature stability of ceria-based ceramics are unavailable in the literature. In the present study, we report a thermodynamic stability investigation of Y2O3-CeO2 and Y2O3-ZrO2-CeO2 solid solutions. The thermal prehistories of binary and ternary systems were investigated using STA, XRD, and ESCA techniques. The vaporization processes were investigated in the temperature range of 1577–2227°С via the Knudsen effusion mass spectrometry technique. Using data on the component activity in solid-phase thermodynamic properties of Y2O3-CeO2 solid solutions, which is represented as the Gibbs energy, the excess Gibbs energy was calculated as a function of the ceria mol. %. It was shown that the reduction of Ce4+ to Ce3+ in Y2O3-CeO2 and Y2O3-ZrO2-CeO2 solid solutions corresponds to less-negative Gibbs energy compared to ZrO2-CeO2 solid solutions. 相似文献
38.
Mobile Networks and Applications - Blockchain applications have continuously improved ever since its first debut on cryptocurrency. From then on, its uses have branched out from the financial... 相似文献
39.
Fabiana D'Isanto Federico Smeacetto Hans-Peter Martin Richard Sedlák Maksym Lisnichuk Andreas Chrysanthou Milena Salvo 《Ceramics International》2021,47(14):19774-19783
A silica-based glass-ceramic, with Y2Ti2O7 as the major crystalline phase, is designed, characterised and tested as an oxidation-protective coating for a titanium suboxide (TiOx) thermoelectric material at temperatures of up to 600 °C. The optimised sinter-crystallisation treatment temperatures are found to be 1300 °C and 855 °C for a duration of 30 min, and this treatment leads to a glass-ceramic with cubic Y2Ti2O7 and CaAl2Si2O8 as crystalline phases. An increase of ~270 °C in the dilatometric softening temperature is observed after devitrification of the parent glass, thus further extending its working temperature range.Excellent adhesion of the glass-ceramic coating to the thermoelectric material is maintained after exposure to a temperature of 600 °C for 120 h under oxidising conditions, thus confirming the effectiveness of the T1 glass-ceramic in protecting the TiOx material. 相似文献
40.
Journal of Signal Processing Systems - Convolutional Neural Networks (CNNs) have improved several computer vision applications, like object detection and classification, when compared to other... 相似文献