To simulate ballast performance accurately and efficiently,the input in discrete element models should be carefully selected,including the contact model and applied particle shape.To study the effects of the contact m...To simulate ballast performance accurately and efficiently,the input in discrete element models should be carefully selected,including the contact model and applied particle shape.To study the effects of the contact model and applied particle shape on the ballast performance(shear strength and deformation),the direct shear test(DST)model and the large-scale process simulation test(LPST)model were developed on the basis of two types of contact models,namely the rolling resistance linear(RRL)model and the linear contact(LC)model.Particle shapes are differentiated by clumps.A clump is a sphere assembly for one ballast particle.The results show that compared with the typical LC model,the RRL method is more efficient and realistic to predict shear strength results of ballast assemblies in DSTs.In addition,the RRL contact model can also provide accurate vertical and lateral ballast deformation under the cyclic loading in LPSTs.展开更多
Glycosphingolipid (GSL) metabolism is involved in various physiological processes, including all major cell signaling pathways, and its dysregulation is linked to some diseases. The four-phosphate adaptor protein FAPP...Glycosphingolipid (GSL) metabolism is involved in various physiological processes, including all major cell signaling pathways, and its dysregulation is linked to some diseases. The four-phosphate adaptor protein FAPP2-mediated glucosylceramide (GlcCer) transport for complex GSL synthesis has been studied extensively. However, the molecular machinery of FAPP2 as a GlcCer-transferring protein remains poorly defined. Here, we identify a Golgi-resident protein, acyl-coenzyme A binding domain containing 3 (ACBD3), as an interacting partner of FAPP2. We find that ACBD3 knockdown leads to dramatic Golgi fragmentation, which subsequently causes FAPP2 dispersal throughout the cytoplasm and a decreased localization at trans-Golgi network. The further quantitative Upidomic analysis indicates that ACBD3 knockdown triggers abnormal sphingolipid metabolism. Interestingly, the expression of siRNA-resistant full-length ACBD3 can rescue these defects caused by ACBD3 knockdown. These data reveal critical roles for ACBD3 in maintaining the integrity of Golgi morphology and cellular sphingolipid homeostasis and establish the importance of the integrated Golgi complex for the transfer of GlcCer and complex GSL synthesis.展开更多
基金by the China Scholarship Council and the Natural Science Foundation of China(Grant No.51578469)We also would like to acknowledge the support of the Chinese Program of Introducing Talents of Discipline to Universities(111 Project,Grant No.B16041)。
文摘To simulate ballast performance accurately and efficiently,the input in discrete element models should be carefully selected,including the contact model and applied particle shape.To study the effects of the contact model and applied particle shape on the ballast performance(shear strength and deformation),the direct shear test(DST)model and the large-scale process simulation test(LPST)model were developed on the basis of two types of contact models,namely the rolling resistance linear(RRL)model and the linear contact(LC)model.Particle shapes are differentiated by clumps.A clump is a sphere assembly for one ballast particle.The results show that compared with the typical LC model,the RRL method is more efficient and realistic to predict shear strength results of ballast assemblies in DSTs.In addition,the RRL contact model can also provide accurate vertical and lateral ballast deformation under the cyclic loading in LPSTs.
基金the National Natural Science Foundation of China (31271517 and 31271518)State Key Laboratory of Molecular Developmental Biology+1 种基金ZHYX (2017zhyx29) of Scientific Research Foundation of the Institute for Translational Medicine of Anhui ProvinceBSKY (XJ201123) of Anhui Medical University.
文摘Glycosphingolipid (GSL) metabolism is involved in various physiological processes, including all major cell signaling pathways, and its dysregulation is linked to some diseases. The four-phosphate adaptor protein FAPP2-mediated glucosylceramide (GlcCer) transport for complex GSL synthesis has been studied extensively. However, the molecular machinery of FAPP2 as a GlcCer-transferring protein remains poorly defined. Here, we identify a Golgi-resident protein, acyl-coenzyme A binding domain containing 3 (ACBD3), as an interacting partner of FAPP2. We find that ACBD3 knockdown leads to dramatic Golgi fragmentation, which subsequently causes FAPP2 dispersal throughout the cytoplasm and a decreased localization at trans-Golgi network. The further quantitative Upidomic analysis indicates that ACBD3 knockdown triggers abnormal sphingolipid metabolism. Interestingly, the expression of siRNA-resistant full-length ACBD3 can rescue these defects caused by ACBD3 knockdown. These data reveal critical roles for ACBD3 in maintaining the integrity of Golgi morphology and cellular sphingolipid homeostasis and establish the importance of the integrated Golgi complex for the transfer of GlcCer and complex GSL synthesis.
