An Incremental Language Conversion Method to Convert C++ into Ada95

This thesis develops a methodology to incrementally convert a legacy object oriented C++ application into Ada95. Using the experience of converting a graphic application, called Remote Debriefing Tool (RDT), in the Graphics Lab of the Air Force Institute of Technology (AFIT), this effort defined a process to convert a C++ application into Ada95. The methodology consists of five phases: (1) reorganizing the software application, (2) breaking mutual dependencies, (3) creating package specifications to interface the existing C++ classes, (4) converting C++ code into Ada programs, and (5) embellishing. This methodology used the GNAT\u27s C++ low level interface capabilities to support the incremental conversion. The goal of this methodology is not only to correctly convert C++ code into Ada95, but also to take advantage of Ada\u27s features which support good software engineering principles

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Advanced glycation end-products induce skeletal muscle atrophy and dysfunction in diabetic mice via a RAGE-mediated, AMPK-down-regulated, Akt pathway

Diabetic myopathy, a less studied complication of diabetes, exhibits the clinical observations characterized by a less muscle mass, muscle weakness and a reduced physical functional capacity. Accumulation of advanced glycation end-products (AGEs), known to play a role in diabetic complications, has been identified in ageing human skeletal muscles. However, the role of AGEs in diabetic myopathy remains unclear. Here, we investigated the effects of AGEs on myogenic differentiation and muscle atrophy in vivo and in vitro. We also evaluated the therapeutic potential of alagebrium chloride (Ala-Cl), an inhibitor of AGEs. Muscle fibre atrophy and immunoreactivity for AGEs, Atrogin-1 (a muscle atrophy marker) and phosphorylated AMP-activated protein kinase (AMPK) expressions were markedly increased in human skeletal muscles from patients with diabetes as compared with control subjects. Moreover, in diabetic mice we found increased blood AGEs, less muscle mass, lower muscular endurance, atrophic muscle size and poor regenerative capacity, and increased levels of muscle AGE and receptor for AGE (RAGE), Atrogin-1 and phosphorylated AMPK, which could be significantly ameliorated by Ala-Cl. Furthermore, in vitro, AGEs (in a dose-dependent manner) reduced myotube diameters (myotube atrophy) and induced Atrogin-1 protein expression in myotubes differentiated from both mouse myoblasts and primary human skeletal muscle-derived progenitor cells. AGEs exerted a negative regulation of myogenesis of mouse and human myoblasts. Ala-Cl significantly inhibited the effects of AGEs on myotube atrophy and myogenesis. We further demonstrated that AGEs induced muscle atrophy/myogenesis impairment via a RAGE-mediated AMPK-down-regulation of the Akt signalling pathway. Our findings support that AGEs play an important role in diabetic myopathy, and that an inhibitor of AGEs may offer a therapeutic strategy for managing the dysfunction of muscle due to diabetes or ageing

Targeting of pro-apoptotic TLR adaptor SARM to mitochondria: Definition of the critical region and residues in the signal sequence

10.1042/BJ20111653Biochemical Journal4422263-271BIJO

Hepatitis B Virus transmission and hepatocarcinogenesis: a 9 year retropective cohort of 13676 relatives with hepatocellular carcinoma

Background/Aims Familial clustering of hepatitis B virus (HBV) infection is related to perinatal transmission, and is the main cause of familial-type hepatocellular carcinoma (HCC). The route of HBV transmission differs between the children and siblings of patients with HCC. This study examined the differences in HBV carrier rates and HCC-related mortality between two generations in HCC families.Methods From 1992 to 1997, relatives of individuals with HCC were screened prospectively with ultrasonography, alpha-fetoprotein, liver biochemistry tests and viral markers. Total HCC-related deaths during a 9-year period were compared between the generations of index patients and their children.Results The study included a total of 13 676 relatives in two generations. More HCC-related deaths occurred in the index patient generation than in the child generation. Furthermore, children of female index patients had higher rates of liver cancer related mortality than children of male index patients. The same was true when the analysis was limited to male HBV carriers. The prevalence of HBsAg in the offspring of HBsAg positive mothers was 66% in the child generation and 72% in the index patient generation. These high prevalences indicated high maternal HBV replication status.Conclusions Perinatal transmission and maternal viral load are important risk factors in hepatocarcinogenesis.<br /