On the nucleation and growth of amyloid beta-protein fibrils: detection of nuclei and quantitation of rate constants.

We have studied the fibrillogenesis of synthetic amyloid beta-protein-(1-40) fragment (A beta) in 0.1 M HCl. At low pH, A beta formed fibrils at a rate amenable to detailed monitoring by quasi-elastic light-scattering spectroscopy. Examination of the fibrils with circular dichroism spectroscopy and electron microscopy showed them to be highly similar to those found in amyloid plaques. We determined the hydrodynamic radii of A beta aggregates during the entire process of fibril nucleation and growth. Above an A beta concentration of approximately 0.1 mM, the initial rate of elongation and the final size of fibrils were independent of A beta concentration. Below an A beta concentration of 0.1 mM, the initial elongation rate was proportional to the peptide concentration, and the resulting fibrils were significantly longer than those formed at higher concentration. We also found that the surfactant n-dodecylhexaoxyethylene glycol monoether (C12E6) slowed nucleation and elongation of fibrils in a concentration-dependent manner. Our observations are consistent with a model of A beta fibrillogenesis that includes the following key steps: (i) peptide micelles form above a certain critical A beta concentration, (ii) fibrils nucleate within these micelles or on heterogeneous nuclei (seeds), and (iii) fibrils grow by irreversible binding of monomers to fibril ends. Interpretation of our data enabled us to determine the sizes of fibril nuclei and A beta micelles and the rates of fibril nucleation (from micelles) and fibril elongation. Our approach provides a powerful means for the quantitative assay of A beta fibrillogenesis.

Optimization of rates of protein folding: the nucleation-condensation mechanism and its implications.

Small, single-module proteins that fold in a single cooperative step may be paradigms for understanding early events in protein-folding pathways generally. Recent experimental studies of the 64-residue chymotrypsin inhibitor 2 (CI2) support a nucleation mechanism for folding, as do some computer stimulations. CI2 has a nucleation site that develops only in the transition state for folding. The nucleus is composed of a set of adjacent residues (an alpha-helix), stabilized by long-range interactions that are formed as the rest of the protein collapses around it. A simple analysis of the optimization of the rate of protein folding predicts that rates are highest when the denatured state has little residual structure under physiological conditions and no intermediates accumulate. This implies that any potential nucleation site that is composed mainly of adjacent residues should be just weakly populated in the denatured state and become structured only in a high-energy intermediate or transition state when it is stabilized by interactions elsewhere in the protein. Hierarchical mechanisms of folding in which stable elements of structure accrete are unfavorable. The nucleation-condensation mechanism of CI2 fulfills the criteria for fast folding. On the other hand, stable intermediates do form in the folding of more complex proteins, and this may be an unavoidable consequence of increasing size and nucleation at more than one site.

Boiling water reactor technology status of the art report / [edited by C. Victor Pearson].

"Reactor technology."

Every-day cookery for every family : containing nearly 1,000 receipts adapted to moderate incomes and comprising the best and most economical methods of roasting, boiling, broiling, and stewing all kinds of meats, fish, poultry, game and vegetables : simple inexpensive instructions for making pies, puddings, tarts and all other pastry : how to pickle and preserve fruits and vegetables : suitable cookery for invalids and children : food in season and how to choose it : the best ways to make domestic wines and syrups : and ample receipts for bread, cake, soups, gravies, sauces, desserts, jellies, brandied fruits, soaps, perfumes, etc., etc. : and ample directions for carving /

"Domestic wines and liquors": p. 226-236.

Basic experimental studies on boiling fluid flow and heat transfer at elevated pressures for month of ...

"Monthly progress report".

Boiling Nuclear Superheater (BONUS) Power Station : final summary design report /

"May 1, 1962."

Boiling water reactors : an annotated bibliography of selected literature /

"June 1959."

Boiling Nuclear Superheater (BONUS) project : interim report /

"PWRA-GNEC Report No. 1."

Boiling Nuclear Superheater (BONUS) Power Station : supplementary study: extrapolation to large central station intergral nuclear superheat plant /

"January 28, 1960."

Boiling Nuclear Superheater (BONUS) Power Station : final hazards summary report /

"Prepared under contract with the United States Atomic Energy Commission, GNEC/AEC contract AT-(40-I)-2674 and PRWRA/AEC contract AT-(40-I)-2672."