Clinical chemistry of common apolipoprotein E isoforms

Apolipoprotein E plays a central role in clearance of lipoprotein remnants by serving as a ligand for low-density lipoprotein and apolipoprotein E receptors. Three common alleles (apolipoprotein E(2), E(3) and E(4)) give rise to six phenotypes. Apolipoprotein E(3) is the ancestral form. Common apolipoprotein E isoforms derive from nucleotide substitutions in codons 112 and 158. Resulting cysteine-arginine substitutions cause differences in: affinities for low-density lipoprotein and apolipoprotein E receptors, low-density lipoprotein receptor activities, distribution of apolipoprotein E among lipoproteins, low-density lipoprotein formation rate, and cholesterol absorption. Accompanying changes in triglycerides, cholesterol and low-density lipoprotein may promote atherosclerosis development. Over 90% of patients with familial dysbetalipoproteinaemia have apolipoprotein E(2)/E(2). Apolipoprotein E(4) may promote atherosclerosis by its low-density lipoprotein raising effect. Establishment of apolipoprotein E isoforms may be important for patients with diabetes mellitus and several non-atherosclerotic diseases. Apolipoprotein E phenotyping exploits differences in isoelectric points. Isoelectric focusing uses gels that contain pH 4-7 ampholytes and urea. Serum is directly applied, or prepurified by delipidation, lipoprotein precipitation or dialysation. Isoelectric focusing is followed by immunofixation/protein staining. Another approach is electro- or diffusion blotting, followed by protein staining or immunological detection with anti-apolipoprotein E antibodies and an enzyme-conjugated second antibody. Apolipoprotein E genotyping demonstrates underlying point mutations. Analyses of polymerase chain reaction products are done by allele-specific oligonucleotide probes, restriction fragment length polymorphism, single-stranded conformational polymorphism, the primer-guided nucleotide incorporation assay, or denaturating gradient gel electrophoresis. Detection with primers that either or not initiate amplification is performed with the amplification refractory mutation system. Disparities between phenotyping and genotyping may derive from isoelectric focusing methods that do not adequately separate apolipoprotein E posttranslational variants, storage artifacts or faint isoelectric focusing bands.     

Interaction of triton X-100 on silica: A relationship between surface characteristics and adsorption isotherms

Adsorption of Triton X-100 on various silica substrates has been investigated. A number of solids, including a natural quartz, this quartz washed with HCl acid and subsequently heated at 1273 K; two aerosils and one Kieselgel silicas were studied. These solids exhibit surface areas in the range of 5 to 430 m² g^?1. All the Triton adsorption isotherms display an S-shape at the adsorption temperatures studied (298 and 308 K). It has been found that the pretreatments of natural quartz (by water washing, impurities removed by acid and/or high temperature calcination) affect considerably the amounts of TX-100 adsorbed. Measurements of surface composition have been made by X-ray photoelectron spectroscopy (XPS) with particular emphasis on the presence of impurities and on the number of OH groups at the surface of the samples. The nature of the surface hydroxyl has also been studied by infrared spectroscopy. Furthermore, the specific number of hydroxyl groups on the surface of the silica samples has been determined by thermogravimetric analysis. Finally an attempt to correlate solid surface characteristics with adsorption isotherms has been developed.     

EEG spectral abnormalities and psychosis as predictors of cognitive and functional decline in probable Alzheimer's disease

We examined whether either psychotic features (e.g., delusions and hallucinations) or EEG abnormalities are associated with more rapid progression of Alzheimer's disease (AD). AD patients with psychosis have exhibited more EEG abnormalities than those without psychosis, and both abnormal EEG and psychosis have been noted to be predictors of functional and cognitive decline in AD. Ninety-five probable AD patients participating in a longitudinal study of dementia had an EEG and a semistructured psychiatric interview at baseline. Using EEG spectral analysis, we classified records as normal/abnormal based on the parasagittal mean frequency. Patients with abnormal EEGs were more functionally (e.g., Blessed Rating Scale for activities of daily living) and cognitively (e.g., Mini-Mental State) impaired than patients with normal EEG. AD patients with psychosis were only more functionally impaired than patients without psychosis. A two-factor analysis showed no interaction between abnormal EEG and psychosis. In addition, using a Cox proportional hazard model adjusted for age and education, the presence of an abnormal EEG or psychotic symptom at study entry was associated with higher risk of reaching severe cognitive and functional impairment during follow-up. Neither abnormal EEG nor the presence of psychosis predicted death. These results indicate that both abnormal EEG and psychosis are independent predictors of disease progression but not of physical survival.     

The ultradian clocks of eukaryotic microbes: timekeeping devices displaying a homeostasis of the period

Ultra-high-sensitivity, biopolymer sequencing is a goal in many fields of molecular biology, and collisionally activated decomposition electrospray mass spectrometry (CAD ES MS/MS) using a triple quadrupole mass spectrometer has become a method of choice for work in the high- to mid-femtomole range. However, when the detection of ions becomes statistical, as it may in that range, the mass assignment of fragment ions is inaccurate and either sequencing becomes impossible or ambiguities result due, for example, to the closeness in amino acid residue masses (I/L, N or K/Q, E). Some ambiguities may be resolved by synthesizing possible sequences, but this is unsatisfactory. In considering the limitations of triple quadrupole MS/MS with respect to scanning ion detection, resolution, transmission, and mass accuracy, we reasoned that a novel geometry quadrupole orthogonal acceleration time-of-flight (Q-TOF) instrument would have special merit for ultra-high-sensitivity MS/MS sequencing, and suggested its construction for this purpose some three years ago. A prototype Q-TOF has now been built by Micromass [Morris et al. (1996), Rapid Commun. Mass Spectrom. 10, 889-896], and in the first research on the instrument, including MHC antigen and filarial nematode glycoprotein studies, we demonstrate low-femtomole- and attomole-range sequencing with mass accuracy of better than 0.1 Da throughout the daughter-ion spectrum, thus removing sequencing ambiguities in some of the most challenging work demanding the highest sensitivity.     

Epilepsy, retarded growth and onchocerciasis, in two areas of different endemicity of onchocerciasis in Burundi

A high prevalence of epilepsy (up to 1.3%) was observed in an area hyperendemic for onchocerciasis in the province of Bururi, Burundi. Following this observation, epileptics and controls were examined in 2 communes (administrative units) with different endemicity for onchocerciasis. Altogether, onchocerciasis was more frequent in epileptics (81.8%) than in controls from the same households (68.3%; P < 0.05). This difference was more marked in the hyperendemic area. Other possible causes of epilepsy, including cysticercosis, were infrequent (18 possible cases among 110 epileptics). During this survey, 9 epileptics with growth retardation were seen. They showed most characteristics of Nakalanga syndrome, which was described from Uganda. All 9 such cases were suffering from onchocerciasis. These findings give more evidence of a possible association between onchocerciasis and epilepsy, and between onchocerciasis and Nakalanga syndrome.     

Magnet Safety Assessment for ITER

The ITER magnet system consists of structurally linked sets of toroidal (TF) and poloidal (PF) field coils, central solenoid (CS), and various support structures. The coils are superconducting, force flow Helium cooled with a Kapton-Glass-Epoxy multilayer insulation system. The stored magnetic energy is about 100GJ in the TF system and 20GJ in the PF-CS. Coils and structure are maintained at 4 K by enclosing them in a vacuum cryostat. The cryostat, comprising an outer envelope to the magnets, forms most of the second radioactivity confinement barrier. The inner primary barrier is formed by the vacuum vessel, its ports and their extensions. To keep the machine size within acceptable bounds, it is essential that the magnets are in close proximity to both of the nuclear confinement barriers. The objective of the magnet design is that, although local damage to one of the barriers may occur in very exceptional circumstances, large scale magnet structural or thermal failure leading to simultaneous breaching of both barriers is not credible. Magnet accidents fall into three categories: thermal (which includes arcing arising from insulation failure and local overheating due to discharge failure in the event of a superconductor quench), structural (which includes component mechanical failure arising from material inadequacies, design errors and exceptional force patterns arising from coil shorts or control failures), and fluid (Helium release due to cooling line failure). After a preliminary survey to select initial faults conceivable within the present design, these faults are systematically analyzed to provide an assessment of the damage potential. The results of this damage assessment together with an assessment of the reliability of the monitoring and protective systems, shows that the magnets can operate with the required safety condition.     

Design and performance evaluation of a banyan network basedinterconnection structure for ATM switches

This paper presents a new self-routing packet network called the plane interconnected parallel network (PIPN). In the proposed design, the traffic arriving at the network is shaped and routed through two banyan network based interconnected planes. The interconnections between the planes distribute the incoming load more homogeneously over the network. The throughput of the network under uniform and heterogeneous traffic requirements is studied analytically and by simulation. The results are compared with the results of the baseline network and another banyan network based parallel interconnection network. It is shown that, for the proposed design, a higher degree of heterogeneity results in better performance     

Densification involved in the UV-based photosensitivity of silicaglasses and optical fibers

A comprehensive survey of photosensitivity in silica glasses and optical fiber is reviewed. Recent work on understanding the mechanisms contributing to germanium or aluminum doped fiber photosensitivity is discussed within the framework of photoelastic densification models