Increased concentrations of the oxidative DNA adduct 7, 8-dihydro-8-oxo-2-deoxyguanosine in the germ-line of men with type 1 diabetes

The effects of diabetes mellitus on male reproductive health have not been clearly defined. A previous publication from this group reported significantly higher levels of nuclear DNA fragmentation and mitochondrial DNA deletions in spermatozoa from men with type 1 diabetes. This study compared semen profiles, sperm DNA fragmentation and levels of oxidative DNA modification in spermatozoa of diabetic and non-diabetic men. Semen samples from 12 non-diabetic, fertile men and 11 type 1 diabetics were obtained and subjected to conventional light microscopic semen analysis. Nuclear DNA fragmentation was assessed using an alkaline Comet assay and concentrations of 7,8-dihydro-8-oxo-2-deoxyguanosine (8-OHdG), an oxidative adduct of the purine guanosine, were assessed by high-performance liquid chromatography. Conventional semen profiles were similar in both groups, whilst spermatozoa from type 1 diabetics showed significantly higher levels of DNA fragmentation (44% versus 27%; P < 0.05) and concentrations of 8-OHdG (3.6 versus 2.0 molecules of 8-OHdG per 105 molecules of deoxyguanosine; P < 0.05). Furthermore, a positive correlation was observed between DNA fragmentation and concentrations of 8-OHdG per 105 molecules of deoxyguanosine (rs = 0.7, P < 0.05). The genomic damage evident in spermatozoa of type 1 diabetics may have important implications for their fertility and the outcome of pregnancies fathered by these individuals.

A generic tool for cost estimating in aircraft design

A methodology to estimate the cost implications of design decisions by integrating cost as a design parameter at an early design stage is presented. The model is developed on a hierarchical basis, the manufacturing cost of aircraft fuselage panels being analysed in this paper. The manufacturing cost modelling is original and relies on a genetic-causal method where the drivers of each element of cost are identified relative to the process capability. The cost model is then extended to life cycle costing by computing the Direct Operating Cost as a function of acquisition cost and fuel burn, and coupled with a semi-empirical numerical analysis using Engineering Sciences Data Unit reference data to model the structural integrity of the fuselage shell with regard to material failure and various modes of buckling. The main finding of the paper is that the traditional minimum weight condition is a dated and sub-optimal approach to airframe structural design.