Ubiquitous expression of amyotrophic lateral sclerosis (ALS)-causing mutations in superoxide dismutase 1 (SOD1) provokes noncell autonomous paralytic disease. By combining ribosome affinity purification and high-throughput sequencing, a cascade of mutant SOD1-dependent, cell type-specific changes are now identified. Initial mutant-dependent damage is restricted to motor neurons and includes synapse and metabolic abnormalities, endoplasmic reticulum (ER) stress, and selective activation of the PRKR-like ER kinase (PERK) arm of the unfolded protein response. PERK activation correlates with what we identify as a naturally low level of ER chaperones in motor neurons. Early changes in astrocytes occur in genes that are involved in inflammation and metabolism and are targets of the peroxisome proliferator-activated receptor and liver X receptor transcription factors. Dysregulation of myelination and lipid signaling pathways and activation of ETS transcription factors occur in oligodendrocytes only after disease initiation. Thus, pathogenesis involves a temporal cascade of cell type-selective damage initiating in motor neurons, with subsequent damage within glia driving disease propagation.
After collisions at sea, situation evaluation and analysis are very important to follow-up rescue operations. At present, there are few ways give weights in the current situational safety evaluation methods after collisions of marine ships. Most safety evaluation models ignore the blurred boundaries of evaluation grades. To solve these issues, this paper identifies the safety evaluation indicator system and evaluation standards, and establishes an after-collisions safety evaluation model of maritime ships based on the extension cloud theory. This model combines the extension cloud model, the analytic hierarchy process, the entropy weight method, and game theory. Using this model, the situation safety of two collisions was evaluated. The evaluation results reflect the effectiveness of the model. In order to ensure the safety of the lives and property of marine personnel, suggestions have been made to strengthen crew training, improve ship’s self-rescue ability at sea, and establish a complete marine emergency response rescue system.
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