Accumulating evidence shows that the severity and rapidity of onset of diabetic retinopathy are influenced by genetic factors. Expression of the nitric oxide synthases is altered in the retinal vasculature in the early stages of diabetic retinopathy. We analyzed the allele distribution of a polymorphic pentanucleotide repeat within the 5' upstream promoter region of the NOS2A gene in samples of diabetic patients. In diabetic patients from Northern Ireland, the 14-repeat allele of the NOS2A marker was significantly associated with the absence of diabetic retinopathy. Carriers of this repeat had 0.21-fold the relative risk of developing diabetic retinopathy than noncarriers of this allele. They also had significantly fewer renal and cardiovascular complications. The ability of differing numbers of (CCTTT)(n) pentanucleotide repeats to induce transcription of the NOS2A gene was analyzed using a luciferase reporter gene assay in transfected colonic carcinoma cells. Interleukin 1beta (IL-1beta) induction was most effective in constructs carrying the 14-repeat allele. When cells were incubated in 25 mM glucose to mimic the diabetic state, IL-1beta induction was inhibited in all cases, but to a significantly lesser extent with the 14-repeat allele. These unique properties of the 14-repeat allele may confer selective advantages in diabetic individuals, which may delay or prevent microvascular complications of diabetes.
This paper attempts to rationalise, and assess, the existing design requirement for the sizing of the outer plating of a ship superstructure against an external air blast. First, a review of the current design guideline, specifically on how the blast load parameters were specified by the Rules and Regulations of Lloyd's Register and the assumptions behind the use of the scantling equation, is provided by way of a design case study. Next, a non-linear SDOF model that incorporates a new plastic membrane phase is developed in this paper, together with three-dimensional FE simulations, to model the large inelastic deformation of the platings. The required plate thickness needed to resist a specified load intensity is then compared for the three different methods, viz. Lloyd's Register design rule, SDOF and FE. As expected, it will be shown that existing design guideline achieves the purpose of maintaining water or gas-tight integrity of a plating; however, there exists significant unnecessary redundancies (or over-design) with implications on light-weighting. Additionally, the results will be summarised in the form of a failure map that will be useful to designers. KEYWORDS navy ship superstructure outer plating; external blast; rules and regulations; single degree of freedom (SDOF); finite elements modelling (FE)
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