Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q

The epilepsies are a group of disorders characterised by recurrent seizures caused by episodes of abnormal neuronal hyperexcitability involving the brain. Up to 60 million people are affected worldwide and genetic factors may contribute to the aetiology in up to 40% of patients. The most common human genetic epilepsies display a complex pattern of inheritance. These are categorised as idiopathic in the absence of detectable structural or metabolic abnormalities. Juvenile myoclonic epilepsy (JME) is a distinctive and common variety of familial idiopathic generalised epilepsy (IGE) with a prevalence of 0.5-1.0 per 1000 and a ratio of sibling risk to population prevalence (lambda(s)) of 42. The molecular genetic basis of these familial idiopathic epilepsies is entirely unknown, but a mutation in the gene CHRNA4, encoding the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (nAChR), was recently identified in a rare Mendelian variety of idiopathic epilepsy. Chromosomal regions harbouring genes for nAChR subunits were therefore tested for linkage to the JME trait in 34 pedigrees. Significant evidence for linkage with heterogeneity was found to polymorphic loci encompassing the region in which the gene encoding the alpha7 subunit of nAChR (CHRNA7) maps on chromosome 15q14 (HLOD = 4.4 at alpha = 0.65; Z(all) = 2.94, P = 0.0005). This major locus contributes to genetic susceptibility to JME in a majority of the families studied.     

Corrosion morphologies on magnesium alloy AZ 91

Initiation and early propagation of pitting and filiform corrosion on bare alloy AZ91 (9% Al, 1% Zn) are investigated by natural immersion corrosion tests, electrochemical measurements and microanalytical studies. Initiation sites are few. Corrosion spreads from these sites first in the form of filiform corrosion for a limited period of time and pitting which later develops into a cellular type of etching. The important factors affecting filiform corrosion are temperature, material structure and degree of polarization at the anodic sites. Filiform attack on AZ91, unlike the classical mechanisms of filiform corrosion on coated metals, is driven by hydrogen evolution reaction on the cathodic sites of the surface, occurs under significant anodic control, propagates at a high, constant speed independent of degree of polarization along preferential paths determined by compositional and crystallographic factors, and is a temporary phenomenon under open circuit conditions. Pitting corrosion is more predominant with decreasing anodic polarization.     

Kinetics of vinyl chloride and vinyl acetate emulsion polymerization

The kinetics of vinyl chloride and vinyl acetate emulsion polymerization are reexamined. The validity of Ugelstad's model for systems with high desorption rate is confirmed by simulating conversion histories for both systems at different initiator concentrations and particle numbers. On the basis of the model, it is shown that at ordinary initiation rates, termination reactions are unimportant with respect to molecular weight development in both systems, and as a consequence, molecular weight development is independent of number and size distribution of polymer particles and of initiator and emulsifier level. Based on this conclusion, it is shown that in accordance with experimental facts, the molecular weight distribution obtained in vinyl chloride emulsion polymerization is the most probable distribution, and it is concluded that the number of long-chain branch points per repetition unit is less than 2 × 10^?4 at high conversions. In vinyl acetate emulsion polymerization, an almost logarithmic normal distribution is obtained. The distribution is strongly broadened by branching reactions with the number of long-chain branch points increasing rapidly with monomer conversion. The increase of M_n with increasing conversion is due to terminal double-bond polymerization, while the increase in M_w is due mainly to transfer to polymer.     

Pseudo-T2 mapping for normalization of T2-weighted prostate MRI

Magnetic Resonance Materials in Physics, Biology and Medicine - Signal intensity normalization is necessary to reduce heterogeneity in T2-weighted (T2W) magnetic resonance imaging (MRI) for...     

Surface tension measurements of Al-Ni based alloys from ground-based and parabolic flight experiments: Results from the thermolab project

Surface tension measurements of different alloys of the Al-Ni system, performed both under reduced gravity conditions in parabolic flights and on ground by conventional techniques, are presented. The alloys compositions were selected on the basis of the intrinsic compound forming tendency with the aim to allow a sensitive test of model predictions.     

Production and Characterization of Peptide Antibodies to the C-Terminal of Frameshifted Calreticulin Associated with Myeloproliferative Diseases

Myeloproliferative Neoplasms (MPNs) constitute a group of rare blood cancers that are characterized by mutations in bone marrow stem cells leading to the overproduction of erythrocytes, leukocytes, and thrombocytes. Mutations in calreticulin (CRT) genes may initiate MPNs, causing a novel variable polybasic stretch terminating in a common C-terminal sequence in the frameshifted CRT (CRTfs) proteins. Peptide antibodies to the mutated C-terminal are important reagents for research in the molecular mechanisms of MPNs and for the development of new diagnostic assays and therapies. In this study, eight peptide antibodies targeting the C-terminal of CRTfs were produced and characterised by modified enzyme-linked immunosorbent assays using resin-bound peptides. The antibodies reacted to two epitopes: CREACLQGWTE for SSI-HYB 385-01, 385-02, 385-03, 385-04, 385-07, 385-08, and 385-09 and CLQGWT for SSI-HYB 385-06. For the majority of antibodies, the residues Cys¹, Trp⁹, and Glu¹¹ were essential for reactivity. SSI-HYB 385-06, with the highest affinity, recognised recombinant CRTfs produced in yeast and the MARIMO cell line expressing CRTfs when examined in Western immunoblotting. Moreover, SSI-HYB 385-06 occasionally reacted to CRTfs from MPN patients when analysed by flow cytometry. The characterized antibodies may be used to understand the role of CRTfs in the pathogenesis of MPNs and to design and develop new diagnostic assays and therapeutic targets.     

Characterization of Ceramic Foam Filters Used for Liquid Metal Filtration

In the current study, the morphology including tortuosity, and the permeability of 50-mm thick commercially available 30, 40, 50, and 80 pores per inch (PPI) alumina ceramic foam filters (CFFs) have been investigated. Measurements have been taken of cell (pore), window, and strut sizes, porosity, tortuosity, and liquid permeability. Water velocities from ~0.015 to 0.77 m/s have been used to derive both first-order (Darcy) and second-order (Non-Darcy) terms for being used with the Forchheimer equation. Measurements were made using 49-mm “straight through” and 101-mm diameter “expanding flow field” designs. Results from the two designs are compared with calculations made using COMSOL 4.2a^® 2D axial symmetric finite element modeling (FEM), as a function of velocity and filter PPI. Permeability results are correlated using directly measurable parameters and compared with the previously published results. Development of improved wall sealing (49 mm) and elimination of wall effects (101 mm) have led to a high level of agreement between experimental, analytic, and FEM methods (±0 to 7 pct on predicted pressure drop) for both types of experiments. Tortuosity has been determined by two inductive methods, one using cold-solidified samples at 60 kHz and the other using liquid metal at 50 Hz, giving comparable results.