To address a recent challenge related to broken spikes in premium elastic fastening systems that have led to at least ten derailments and require manual walking inspections as well as build upon mechanistic-empirical (M-E) design principles for future fastening system component design, this paper quantifies the vertical, lateral, and longitudinal fastening system loads under revenue service traffic in a curve that has regularly experienced spike fastener fatigue failures. Previous data has indicated that the high rail of Track 3 experienced the most failures at this location. The data from this investigation sheds light into why failures are more predominant at this location than others and how the vertical, lateral, and longitudinal loads cannot be considered independently. Specifically, while the magnitude of the applied loading was the lowest on the high rail of Track 3, the threshold for failure was also the lowest given the operations at this location led to unloading of the high rail, thus indirectly highlighting the importance of friction within a fastening system. The data also show the high rail of Track 3 was subjected to the highest L/V load ratios and was an outlier in the typical lateral load reversals applied likely leading to spike stress reversals and thus a shorter fatigue life. Finally, based upon the data, it is recommended that to mitigate spike failures, as well as similar fastener challenges in other track types (e.g. rail seat deterioration, etc.) railroads should ensure trains operate close to the balance speed and use fastening system that transfer loads through friction. This study also provides novel data for M-E design of fastening systems.
Progressive Supranuclear Palsy (PSP) is a neurodegenerative tauopathy and, to date, the pathophysiological mechanisms in PSP that lead to Tau hyperphosphorylation and neurodegeneration are not clear. The development of a model using neural cell lines derived from patients has the potential to identify molecules and possible biomarkers. We developed a model of induced pluripotent stem cells iPSC-derived astrocytes to investigate the pathophysiology of PSP, particularly early events that might contribute to Tau hyperphosphorylation, applying an omics approach to detect differentially expressed genes, metabolites, and proteins, including those from the secretome. Skin fibroblasts from PSP patients and controls were reprogrammed to iPSCs, which were further differentiated into neuroprogenitor cells and astrocytes. In the 5th passage, astrocytes were harvested for total ribonucleic acid sequencing. Intracellular and secreted proteins were processed for proteomics experiments. Metabolomics profiling was obtained from supernatants only. We identified hundreds of differentially expressed genes in PSP. The main networks were related to cell cycle activation. Several proteins were found exclusively secreted by the PSP group. The cellular processes related to the cell cycle and mitotic proteins, chaperonins of the TriC/CCT pathway, and redox signaling are enriched in the secretome of the PSP group. Moreover, we found spatial segregation by PCA in the metabolomics data, indicating distinct sets of metabolites between PSP and control groups. Our iPSC-derived astrocyte model can provide distinct molecular signatures for PSP patients and it is useful to elucidate the initial stages of PSP pathogenesis.
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