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Objective Based on the virtual simulation fatigue test technology, fatigue life analysis and reliability evaluation of the bogie arm positioning node of a certain type of vehicle are carried out to improve the vehicle stability and guarantee the train operation safety. Method ABAQUS software is used to establish a finite element model of the arm positioning node and obtain the stress and strain data. FE-SAFE software is used to set the fatigue parameters of rubber material, simulate and analyze its fatigue life. Graph test method is used to test the distribution hypothesis of pseudo-failure fatigue life and to select the optimal life distribution. The relation between the life distribution parameters and the stress level is used to fit a proper functional relation and evaluate the reliability of the arm positioning node fatigue life under normal stress level. Result & Conclusion Under normal stress level, only the rubber bushing in arm positioning node will have fatigue damage. The bottom end of the rubber bushing is the area with the lowest pseudo-failure fatigue life value, and is also the area where the damage occurs first. On-site test and fatigue simulation results verify the accuracy of the finite element model of arm positioning node. The optimal normal life distribution is determined. Under normal stress level, the number of fatigue life cycles is about 210,000 when the reliability of the arm positioning node is 0.9.

Abstract Background The filamentous fungus Ashbya gossypii grows into a multicellular mycelium that is distinct from the unicellular morphology of its closely related yeast species. It has been proposed that genes important for cell cycle regulation play central roles for such phenotypic differences. Because A. gossypii shares an almost identical set of cell cycle genes with the typical yeast Saccharomyces cerevisiae, the differences might occur at the level of orthologous gene regulation. Codon usage patterns were compared to identify orthologous genes with different gene regulation between A. gossypii and nine closely related yeast species. Results Here we identified 3,151 orthologous genes between A. gossypii and nine yeast species. Two groups of genes with significant differences in codon usage (gene translation efficiency) were identified between A. gossypii and yeasts. 333 genes (Group I) and 552 genes (Group II) have significantly higher translation efficiency in A. gossypii and yeasts, respectively. Functional enrichment and pathway analysis show that Group I genes are significantly enriched with cell cycle functions whereas Group II genes are biased toward metabolic functions. Conclusion Because translation efficiency of a gene is closely related to its functional importance, the observed functional distributions of orthologous genes with different translation efficiency might account for phenotypic differentiation between A. gossypii and yeast species. The results shed light on the mechanisms for pseudohyphal growth in pathogenic yeast species.

Modern humans have experienced explosive population growth in the past thousand years. We hypothesized that recent human populations have inhabited environments with relaxation of selective constraints, possibly due to the more abundant food supply after the Last Glacial Maximum. The ratio of nonsynonymous to synonymous mutations (N/S ratio) is a useful and common statistic for measuring selective constraints. In this study, we reconstructed a high-resolution phylogenetic tree using a total of 26,419 East Eurasian mitochondrial DNA genomes, which were further classified into expansion and nonexpansion groups on the basis of the frequencies of their founder lineages. We observed a much higher N/S ratio in the expansion group, especially for nonsynonymous mutations with moderately deleterious effects, indicating a weaker effect of purifying selection in the expanded clades. However, this observation on N/S ratio was unlikely in computer simulations where all individuals were under the same selective constraints. Thus, we argue that the expanded populations were subjected to weaker selective constraints than the nonexpanded populations were. The mildly deleterious mutations were retained during population expansion, which could have a profound impact on present-day disease patterns. [ABSTRACT FROM AUTHOR]

A universal platform is developed for dropletizing single cell plate‐based multiomic assays, consisting of three main pillars: a miniaturized open Heterogeneous Hydrogel reactor (abbreviated HetHydrogel) for multi‐step biochemistry, its tunable permeability that allows Tn5 tagmentation, and single cell droplet barcoding. Through optimizing the HetHydrogel manufacturing procedure, the chemical composition, and cell permeation conditions, simultaneous high‐throughput mitochondrial DNA genotyping and chromatin profiling at the single‐cell level are demonstrated using a mixed‐species experiment. This platform offers a powerful way to investigate the genotype‐phenotype relationships of various mtDNA mutations in biological processes. The HetHydrogel platform is believed to have the potential to democratize droplet technologies, upgrading a whole range of plate‐based single cell assays to high throughput format. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) predominantly affects the brain, causing a mixed movement disorder, cognitive decline and behavioural abnormalities. It also causes a peripheral phenotype involving skeletal muscle. Mitochondrial dysfunction has been reported in tissues of HD models, including skeletal muscle, and lymphoblast and fibroblast cultures from patients with HD. Mutant huntingtin protein (mutHTT) expression can impair mitochondrial quality control and accelerate mitochondrial ageing. Here, we obtained fresh human skeletal muscle, a post-mitotic tissue expressing the mutated HTT allele at physiological levels since birth, and primary cell lines from HTT CAG repeat expansion mutation carriers and matched healthy volunteers to examine whether such a mitochondrial phenotype exists in human HD. Using ultra-deep mitochondrial DNA (mtDNA) sequencing, we showed an accumulation of mtDNA mutations affecting oxidative phosphorylation. Tissue proteomics indicated impairments in mtDNA maintenance with increased mitochondrial biogenesis of less efficient oxidative phosphorylation (lower complex I and IV activity). In full-length mutHTT expressing primary human cell lines, fission-inducing mitochondrial stress resulted in normal mitophagy. In contrast, expression of high levels of N-terminal mutHTT fragments promoted mitochondrial fission and resulted in slower, less dynamic mitophagy. Expression of high levels of mutHTT fragments due to somatic nuclear HTT CAG instability can thus affect mitochondrial network dynamics and mitophagy, leading to pathogenic mtDNA mutations. We show that life-long expression of mutant HTT causes a mitochondrial phenotype indicative of mtDNA instability in fresh post-mitotic human skeletal muscle. Thus, genomic instability may not be limited to nuclear DNA, where it results in somatic expansion of the HTT CAG repeat length in particularly vulnerable cells such as striatal neurons. In addition to efforts targeting the causative mutation, promoting mitochondrial health may be a complementary strategy in treating diseases with DNA instability such as HD. [ABSTRACT FROM AUTHOR]