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.     

Through the looking glass darkly? When self-doubts turn into relationship insecurities.

The authors argue that individuals regulate perceptions of their relationships in a self-protective way, finding virtue in their partners only when they feel confident that their partners also see virtues in them. In 4 experiments, the authors posed an acute threat to low and high self-esteem individuals' feelings of self-worth (e.g., guilt about a transgression, fears of being inconsiderate or intellectually inept). They then collected measures of confidence in the partner's positive regard and acceptance (i.e., reflected appraisals) and perceptions of the partner. The results revealed that low self-esteem individuals reacted to self-doubt with heightened doubts about their partners' regard, which then tarnished impressions of their partners. In contrast, high self-esteem individuals reacted to self-doubts by becoming more convinced of their partners' continued acceptance, using their relationships as a resource for self-affirmation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modeling of rumen water kinetics and effects of rumen pH changes

Mechanistic elements for determining water kinetics and effects of pH on VFA production and cellulose hydrolysis were incorporated into a model of rumen digestion and metabolism. Elements necessary for water kinetics were estimates of salivary flow during eating, resting, and ruminating, time course and amount of drinking water, osmotic flux across the rumen wall based on changes in rumen fluid osmolality, and liquid turnover rate. Osmotic flux equations predicted a significant net absorption of water from rumens of dairy cattle. Water kinetic equations predicted experimental changes in rumen volume during twice daily feeding, and produced marker dilution data qualitatively resembling published data. Increased marker dilution during feeding was due to increased rumen volume. An empirical equation predicting rumen pH from VFA concentration was validated against literature data. Changes in molar percentages of acetate and propionate as pH declined below 6.2 were produced by decreasing cellulose hydrolysis and fermentation and by altering stoichiometric coefficients for fermentation of soluble sugars and starch. Insufficient data prevented an adequate challenge of equations predicting decreases in cellulose hydrolysis and changes in stoichiometric coefficients as pH decreased.     

Neck masses: diagnosis & treatment. (The occult primary tumor)

Solid dispersions of naltrexone in natural glycerides were used to form injectable implants which continuously release narcotic antagonists in vivo. The dispersions were formed and tested either as small cylindrical pellets, e.g. l x 3.0 mm in size, or as particles with diameters in size ranges between 125-250 mu, that are suspended in an aqueous methyl cellulose solution. Both types of implants delivered naltrexone to mice at rates that were effective in blocking the antiociceptive action of morphine for at least one month. The rate of naltrexone release was controlled by altering its concentration in the dispersion and by varying the glyceride composition. Degradation and absorption of the implants were found to depend on their composition, dimensions and location in the body. No appreciable tissue incompatibility was seen in mice, rats, rabbits, monkeys and swine, even when long-lasting preparations were removed a year after treatment.     

Parasitic noise on the output of a CW YAG:Nd+3laser

An experimental investigation was conducted to reduce the parasitic noise appearing on the output of a 6-W CW YAG:Nd⁺³laser. Initially, low-frequency fluctuations as high as 30 percent and relaxation oscillation bursts exceeding 80 percent of the CW power level were present. Low-frequency modulation was reduced by the addition of an active feedback loop to control lamp current. Relaxation oscillations were determined to be influenced by laser rod cooling, pump-lamp aging, vibration, and intracavity optical interface quality. At the conclusion of the program, low-power fluctuations and relaxation oscillation excursions did not exceed 2 percent.