Solid-state NMR studies of the prion protein H1 fragment

Conformational changes in the prion protein (PrP) seem to be responsible for prion diseases. We have used conformation-dependent chemical-shift measurements and rotational-resonance distance measurements to analyze the conformation of solid-state peptides lacking long-range order, corresponding to a region of PrP designated H1. This region is predicted to undergo a transformation of secondary structure in generating the infectious form of the protein. Solid-state NMR spectra of specifically 13C-enriched samples of H1, residues 109-122 (MKHMAGAAAAGAVV) of Syrian hamster PrP, have been acquired under cross-polarization and magic-angle spinning conditions. Samples lyophilized from 50% acetonitrile/50% water show chemical shifts characteristic of a beta-sheet conformation in the region corresponding to residues 112-121, whereas samples lyophilized from hexafluoroisopropanol display shifts indicative of alpha-helical secondary structure in the region corresponding to residues 113-117. Complete conversion to the helical conformation was not observed and conversion from alpha-helix back to beta-sheet, as inferred from the solid-state NMR spectra, occurred when samples were exposed to water. Rotational-resonance experiments were performed on seven doubly 13C-labeled H1 samples dried from water. Measured distances suggest that the peptide is in an extended, possibly beta-strand, conformation. These results are consistent with the experimental observation that PrP can exist in different conformational states and with structural predictions based on biological data and theoretical modeling that suggest that H1 may play a key role in the conformational transition involved in the development of prion diseases.     

Gender differences in altruistic reputation: Are they artifactual?

Tested the notion that observed sex differences in children's altruistic reputations that favor girls are due to sex-biased items found in commonly used peer-assessment measures. A gender-fair assessment of altruistic reputation was attempted by including items that were empirically derived examples of masculine, feminine, and gender-neutral prosocial behaviors. These items were based on prosocial incidents reported by 65 5th graders. 123 additional 5th graders were asked to respond to the new items by nominating 2 classmates most likely to engage in prosocial behavior or by indicating which sex was most likely to perform the behaviors. Results show that, overall, females were judged to be more altruistic than males. However, endorsement differed across item content: Males were selected more often for masculine items and females more often for feminine and sex-neutral items. In general, males endorsed males for helpful behaviors and females endorsed females. The gender-rating form of the test produced responses more closely related to the empirically based item-gender-content classes than did the peer-nomination form. (18 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A General-Purpose Multi-Microprocessor Raster Graphics Display System with Anti-Aliasing

The raster graphics display system described represents a general purpose mini-computer, specially for CAD applications. The system is based on a hierarchical asynchronous multiple microprocessor system. In practice this mini-computer is extendable up to 15–20 workstations. On the workstations, different graphical and non-graphical devices can be connected. The most interesting workstation is a raster graphics display device which was developed specially for the computer system described. This raster graphics display device contains a processor for the application program, two dedicated processors and two separate identical frame buffers, each of them containing one whole set of image data. Applying algorithms for anti-aliasing, virtual pixel dislocation (intensity dislocation) and multi-pixel-overlappings with hidden line (surface) elimination the image readability and quality can be increased considerably. In particular the paper deals with an anti-aliasing algorithm with a real-time hardware realization.     

Wasserstoffinduzierte Spannungsrißkorrosion an unverzinkten und verzinkten Baustählen

Hydrogen induced stress corrosion cracking of non galvanized and galvanized construction steels The processes of atmospheric corrosion and corrosion in collected water which may lead to hydrogen induced stress corrosion cracking of high-strength reinforcing steels in casing tubes before injection with concrete are discussed. Hydrogen uptake during corrosion occurs in weakly acid solutions as well as in neutral or alkaline aqueous solutions. The hydrogen uptake by proton discharge in acid solutions decreases with increasing pH of the electrolyte. Hydrogen can also be absorbed in neutral to weakly alkaline solutions if steels are plastically deformed and water reacts with the fresh iron surface. In alkaline solutions, hydrogen uptake is possible if, at the generally passivated steel surface, localized corrosion (pitting or crevice corrosion), local galvanic cells and a sufficient decrease in the pH of the pit electrolyte occurs. In the case of galvanized steels with damaged zinc layers, hydrogen uptake may result from the cathodic polarization of the free steel surface by zinc dissolution. The absorbed hydrogen interacts with the microstructure of the steels and weakens the bonds between the iron atoms. The influence of the microstructure of high-strength steels on the fracture behaviour is discussed on the basic of the so-called decohesion theory.     

Proton spectroscopy in myotonic dystrophy: correlations with CTG repeats

We have previously reported inhibition of cell-free activation of the neutrophil superoxide-generating NADPH oxidase by a soluble cationic protein of neutrophil granules and by low concentrations of human defensin. Subcellular fractionation carried out in the current study indicated that the inhibitory substance was derived from azurophilic granules, was released into the medium on cell stimulation, and was resistant to phenylmethylsulfonyl fluoride (PMSF). Phorbol ester was the most effective stimulus for the release of the blocking activity. The possibility was raised that granule protein(s) act in vivo as negative modulators of superoxide production. Gel filtration of granule extract revealed a markedly retarded protein peak exhibiting oxidase-blocking activity and containing lysozyme as the main protein. Because lysozyme did not exert inhibitory effects on oxidase activation, association of the inhibitory protein with lysozyme was assumed. Indeed a column of immobilized lysozyme retained a fraction of the granule extract's oxidase-blocking activity. Elution with a low-pH buffer recovered a component capable of inhibition of the NADPH oxidase in stimulated neutrophils and in the cell-free system. The main 29-kDa protein band in the eluted fraction was identified as proteinase 3, a serine protease of azurophilic granules. Enzymatically active as well as PMSF-blocked conventionally purified proteinase 3 interfered with phorbol myristate acetate-induced superoxide release. These findings support the hypothesis that exocytosed granule constituents may prevent excessive activation of the NADPH oxidase.     

Pantoprazole does not interact with the pharmacokinetics of carbamazepine

OBJECTIVE: Pantoprazole is a H+/K+-ATPase inhibitor with a minimized potential of interaction with the cytochrome P450 system. Imidazole derivatives such as cimetidine and omeprazole have been shown to markedly interact with carbamazepine, a major anticonvulsant with a narrow therapeutic range. Therefore, the influence of steady-state pantoprazole on the pharmacokinetics of carbamazepine was investigated. SUBJECTS AND METHODS: N = 20 healthy volunteers (12 male/8 female) completed a double-blind, placebo-controlled, randomized crossover study. During the test period they received 40 mg pantoprazole p.o. once daily for 11 days and concomitantly a single oral dose of 400 mg carbamazepine on day 5. In the reference period placebo was administered instead of pantoprazole. RESULTS: Serum concentrations of carbamazepine and its active metabolite carbamazepine-10,11-epoxide were measured until day 11. Geometric means of AUC (extent characteristic) and Cmax/AUC (rate characteristic) of carbamazepine were 292 and 287 mgxh/l, and 0.0150 and 0.0144 l/h (reference and test), respectively. Point estimates and 90% confidence intervals of the ratios were 0.98 (0.95, 1.01) for AUC, and 0.96 (0.92, 1.00) for Cmax/AUC, respectively. Since the 90% confidence intervals of the primary characteristics, AUC and Cmax/AUC were entirely within the predefined equivalence range of 0.80 - 1.25, lack of interaction of pantoprazole with the pharmacokinetics of carbamazepine was demonstrated. Equivalence was also demonstrated for carbamazepine-10,11-epoxide using the characteristics AUC and Cmax. CONCLUSION: No dose adjustment of carbamazepine is therefore required during concomitant treatment with pantoprazole.     

G 2 interpolation and blending on surfaces

We introduce a method for curvature-continuous (G ²) interpolation of an arbitrary sequence of points on a surface (implicit or parametric) with prescribed tangent and geodesic curvature at every point. The method can also be used forG ² blending of curves on surfaces. The interpolation/blending curve is the intersection curve of the given surface with a functional spline (implicit) surface. For the construction of blending curves, we derive the necessary formulas for the curvature of the surfaces. The intermediate results areG ² interpolation/blending methods in IR².