Comparison of the acetylation of procainamide and sulfadimidine in man

The acetylation of procainamide and sulfadimidine has been measured simultaneously in plasma and urine in 20 healthy human volunteers by a specific G.L.C. method, after single and multiple oral dral doses of procainamide retard tablets. A distinct bimodality (9 rapid and 11 slow acetylators) was apparent from the concentrations of procainamide and N-acetylprocainamide both in urine and plasma, which was in complete agreement with data about sulfadimidine acetylation. The influence of acetylator phenotype on the relative concentrations of procainamide and N-acetylprocainamide in plasma as cn 5 additional healthy subjects after a single oral dose of procainamide. The present results show that acetylator phenotype can now be determined using procainamide as the test substance, and for this purpose multiple doses offer hardly any advantage over a single dose of the drug. However, because the separation between rapid and slow acetylators is less pronounced for procainamide than for sulfadimidine, precise criteria must be established for the conditions of the test, and the influence of diseases, such as renal insufficiency, should be taken into consideration.     

Unfolding dynamics of proteins under applied force

Understanding the mechanisms of protein folding is a major challenge that is being addressed effectively by collaboration between researchers in the physical and life sciences. Recently, it has become possible to mechanically unfold proteins by pulling on their two termini using local force probes such as the atomic force microscope. Here, we present data from experiments in which synthetic protein polymers designed to mimic naturally occurring polyproteins have been mechanically unfolded. For many years protein folding dynamics have been studied using chemical denaturation, and we therefore firstly discuss our mechanical unfolding data in the context of such experiments and show that the two unfolding mechanisms are not the same, at least for the proteins studied here. We also report unexpected observations that indicate a history effect in the observed unfolding forces of polymeric proteins and explain this in terms of the changing number of domains remaining to unfold and the increasing compliance of the lengthening unstructured polypeptide chain produced each time a domain unfolds.     

Context-aware agents for user-oriented web services discovery and execution

Service-oriented computing (SOC) suggests that the Internet will be an open repository of many modular capabilities realized as web services. Organizations may be able to leverage this SOC paradigm if their employees are able to ubiquitously incorporate such capabilities and their resulting information into their daily practices. It is impractical to assume that human users will be able to manually search vast distributed repositories at real-time. This paper presents an architecture, Software Agent-Based Groupware using E-services (SAGE), that incorporates the use of intelligent agents to integrate human users with web services. SAGE provides background search and discovery approaches, thus enabling human users to exploit service-based capabilities that were previously too time-consuming to locate and integrate. We present a multi-agent system where each agent learns the rule-based preferences of a human user with regards to their current operational “context” and manages the incorporation of relevant web services. Recommended by: Djamal Benslimane and Zakaria Maamar