A statistically-designed test matrix has been developed to govern test conditions for measurement of the fracture toughness properties of A285 carbon steel. The effects of several variables on ductile tearing were investigated. The results of initial J-Integral testing are presented along with preliminary observations and data analysis. These results will contribute to a database of J-resistance (J-R) curves, which will be used for flaw stability analyses in waste storage tanks constructed in the 1950s at the Savannah River Site (SRS). J-Integral toughness tests were conducted to evaluate fracture behavior as functions of composition and orientation around the minimum operating temperature of waste storage tanks at SRS (294 K). The selected ranges of composition and grain size were based on available heats of new and vintage material from archival site sources. The specimen dimensions were designed to represent the thickness of tank wall regions in the structure and to a width that ensured back end constraint after crack extension up to several millimeters. The loading rate was held constant at 8.2 × 10-3 (MPa-√m)/s.
Rationale for the studyCardiomyopathy is an increasingly recognised presentation of mitochondrial disease in infancy. This may be an isolated finding or part of a wider multisystem disease presentation. Isolated deficiency of respiratory chain complex I is the most commonly identified biochemical defect in paediatric mitochondrial disease. Here we used a candidate gene and homozygosity mapping approach to identify the causative gene defect in two children with complex I deficiency and cardiomyopathy.MethodologyComplex I assembly was investigated in a cohort of children with isolated complex I deficiency using Blue Native polyacrylamide gel electrophoresis (BN-PAGE). An integrative genomics approach, combining homozygosity mapping and candidate gene and bioinformatics analyses, was used to search for the presumed nuclear gene defect in these patients.ResultsBN-PAGE analysis provided evidence of defective assembly of the complex I holoenzyme in several patients. Two patients were shown to have cardiomyopathy caused by mutations in two different complex I assembly factor genes. The mutations segregated with disease in each family and were absent in >200 control alleles. Western blot analysis demonstrated reduced steady-state level of the mutated proteins, and lentiviral rescue was used to confirm the genetic defect in one case.ConclusionsMitochondrial complex I deficiency is an important cause of infantile-onset cardiomyopathy. This disorder is extremely genetically heterogeneous, but identification of the precise genetic defect is important, since this will inform treatment options, provide more accurate information regarding recurrence risks, and allow prevention of further cases by prenatal or preimplantation genetic diagnosis.
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