A model is proposed to account for the observation that the denaturation of small proteins apparently occurs in two kinetic phases. It is suggested that only one of these phases--the fast one--is actually an unfolding process. The slow phase is assumed to arise from the cis-trans isomerism of proline residues in the denaturated protein. From model compound data, it is shown that the expected rate for isomerism is in satisfactory agreement with the rates actually observed for protein folding. It is also shown that a simple model of protein unfolding based on the isomerism concept is very successful in accounting for many known experimental characteristics of the kinetics and thermodynamic of protein denaturation. Thus, the model is able to predict that two kinetic phases will be seen in the transition region while none are seen in the base-line regions, that both the fast and slow refolding phases lead to the native protein as the product, that the fast phase becomes the only observable phase for jumps ending far in the denatured base-line region, that most or all small proteins show a limiting low-temperature activation energy of ca. 20,000 cal, and that the relaxtion time for the slow phase seen in cytochrome c denaturation is much shorter than for all other small proteins. By utilizing "double-jump" experiments, it is shown directly that the slow phase is not part of the unfolding process but that it corresponds to a transition among two or more denatured forms which have identical spectroscopic (286.5 nm) properties. Thus, the slow relaxation is "invisible" except in the transition region where it couples to the fast unfolding equilibrium. Finally, since the present model assumes that only one of the major kinetic phases seen in denaturation reactions is concerned with the denaturation process per se, it is in agreement with numerous thermodynamic studies which show consistency with the two-state model for unfolding.
Preparation of bispecific antibodies by the chemical reassociation of monovalent fragments derived from monoclonal mouse immunoglobulin G1 is inefficient because of side reactions during reoxidation of the multiple disulfide bonds linking the heavy chains. These side reactions can be avoided by using specific dithiol complexing agents such as arsenite and effecting disulfide formation with a thiol activating agent such as 5,5'-dithiobis(2-nitrobenzoic acid). In this way bispecific antibodies were obtained in high yield and free of monospecific contaminants from monoclonal mouse immunoglobulin G1 fragments. The bispecific antibodies were used as agents for the selective immobilization of enzymes.
BiochemistryUnfolding and refolding occur much faster for a proline-free protein than for most proline-containing proteins ( Communicated by Walter Kauzmann, June 27,1977 ABSTRACT The kinetics for unfolding and refolding of a parvalbumin (band 5) have been examined as a function of pH near the transition region, using stopped-flow techniques. This protein is rather unusual in that it has no proline residues, and therefore serves as a good example to test the hypothesis that the rate-limiting step seen in denaturation reactions is due to the cis-trans isomerization of proline peptide bonds in the denatured state.The kinetics for parvalbumin unfolding and refolding are complex, with the data being resolvable into two fast phases at
This mapping between ICD and AIS provides a comprehensive, expert-designed solution for analysts to bridge the data gap between the injury descriptions provided in hospital codes (ICD-9-CM, ICD-10-CM) and injury severity codes (AIS08). By applying consistent rules from both the ICD and AIS taxonomies, the expert panel created these definitive maps, which are the only ones endorsed by the Association for the Advancement of Automotive Medicine (AAAM). Initial validation upheld the quality of these maps for the estimation of AIS severity, but future work should include verification of these maps for MAIS and ISS estimations with large data sets. These ICD-AIS maps will support data analysis from databases with injury information classified in these 2 different systems and open new doors for the investigation of injury from traumatic events using large injury data sets.
This paper considers the meaning of consent for nursing. Consent had traditionally been looked at in relation to the medical profession. The paper argues for patient advocacy and discusses issues of competency and advocacy and implications for practice. The paper then goes on to critique the process of concept analysis and suggests ways of proceeding with this vital development for nursing.
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