Genetic analysis of coronary artery disease single nucleotide polymorphisms in diabetic nephropathy

Background. Diabetic nephropathy is a leading cause of end-stage renal disease. Premature mortality is common in patients with nephropathy, largely due to cardiovascular disease. Genetic variants implicated in macrovascular disease are therefore excellent candidates to assess for association with diabetic nephropathy. Recent genome-wide association studies have identified a total of 15 single-nucleotide polymorphisms (SNPs) that are reproducibly associated with cardiovascular disease.

Methods. We initially assessed these SNPs for association in UK type 1 diabetic patients with (cases; n = 597) and without (controls; n = 502) nephropathy using iPLEXTM and TaqMan® assays. Replication studies were performed with DNA genotyped in a total of 2668 individuals from the British Isles.

Results. One SNP (rs4420638) on chromosome 19q13 was found to be significantly associated with diabetic nephropathy before (P = 0.0002) and after correction for multiple testing (Pcorrected = 0.002). We replicated this finding in a phenotypically similar case–control collection comprising 709 individuals with type 1 diabetes (P = 0.002; combined P < 0.00001; OR = 1.54, 95% CI: 1.29–1.84).

Conclusions. Our case–control data suggest that rs4420638, or a functional SNP in linkage disequilibrium with this SNP, may be associated with diabetic nephropathy.

Effect of wall thickness on the ferroelastic domain size of BaTiO3

Extremely regular self-organized patterns of 90^o ferroelastic domains have been reported in freestanding single crystal thin films of ferroelectric BaTiO₃. Lukyanchuk et al. [Phys Rev B 79, 144111 (2009)] have recently shown that the domain size as a function of thickness for such free standing films can be well described assuming that the domains are due to stress caused by a surface tension layer that does not undergo the paraelectric–ferroelectric transition. From the starting point of Lukyanchuk’s model, it is shown here that the ‘‘universal’’relationship between domain size and domain wall thickness previously observed in ferroelectrics, ferromagnets and multiferroics is also valid for ferroelastic domains.Further analysis of experimental data also shows that the domain wall thickness can vary considerably (an order of magnitude) from sample to sample even for the same material (BaTiO₃), in spite of which the domain size scaling model is still valid, provided that the correct,sample dependent, domain wall thickness is used.

The Role of Process Parameters in Determining Wall Thickness Distribution in Plug-Assisted Thermoforming

This article describes the results of a comprehensive investigation to determine the link between process parameters and observed wall thickness output for the plug-assisted thermoforming process. The overall objective of the work was to systematically investigate the process parameters that may be adjusted during production to control the wall thickness distribution of parts manufactured by plug-assisted thermoforming. The parameters investigated were the sheet temperature, plug temperature, plug speed, plug displacement, plug shape, and air pressure. As well as quantifying the effects of each parameter on the wall thickness distribution, a further aim of the work was to improve the understanding of the physical mechanisms of deformation of the sheet during the different stages of the process. The process parameters shown to have the greatest effect on experimentally determined wall thickness distribution were the plug displacement, sheet temperature, plug temperature, and plug shape. It is proposed that during the plug-assisted thermoforming of polystyrene the temperature dependent friction between the plug and sheet surface was the most important factor in determining product wall thickness distribution, whereas heat transfer was shown to play a less important role. POLYM. ENG. SCI., 2010. © 2010 Society of Plastics Engineers

The structure of helokinestatin-5 and its biosynthetic precursor from Gila monster (Heloderma suspectum) venom: Evidence for helokinestatin antagonism of bradykinin-induced relaxation of rat tail artery smooth muscle

Here we report the primary structure of a novel peptide, named helokinestatin-5 (VPPPLQMPLIPR), from the venom of the Gila monster (Heloderma suspectum). Helokinestatin-5 differs in structure from helokinestatin-3 by deletion of a single prolyl residue in the N-terminally located polyproline region. Two different biosynthetic precursors were consistently cloned from a venom-derived cDNA library. The first encoded helokinestatins 1–4 and a single copy of C-type natriuretic peptide, as previously described, whereas the second was virtually identical, lacking only a single prolyl codon as found in the mature attenuated helokinestatin-5 peptide. Helokinestatins 1–3 and 5 were synthesized by solid-phase fmoc chemistry and each synthetic replicate was found to antagonize the relaxation effect induced by bradykinin on rat tail artery smooth muscle. Helokinestatins thus represent a novel family of vasoactive peptides from the venom of helodermatid lizards