An Improved Surrogate Constraints Method for Separable Nonlinear Integer Programming

An improved surrogate constraints method for solving separable nonlinear integer programming problems with multiple constraints is presented. The surrogate constraints method is very effective in solving problems with multiple constraints. The method solves a succession of surrogate constraints problems having a single constraint instead of the original multiple constraint problem. A surrogate problem with an optimal multiplier vector solves the original problem exactly if there is no duality gap. However, the surrogate constraints method often has a duality gap, that is it fails to find an exact solution to the original problem. The modification proposed closes the surrogate duality gap. The modification solves a succession of target problems that enumerates all solutions hitting a particular target. The target problems are produced by using an optimal surrogate multiplier vector. The computational results show that the modification is very effective at closing the surrogate gap of multiple constraint problems

Coronary artery spasm—Clinical features, diagnosis, pathogenesis, and treatment

SummaryCoronary (artery) spasm plays an important role in the pathogenesis of ischemic heart disease, including stable angina, unstable angina, myocardial infarction, and sudden death. The prevalence of coronary spasm differs among populations, is higher in Japan and Korea than in the Western countries probably due to genetic as well as environmental factors. Coronary spasm occurs most often from midnight to early morning and is usually not induced by exercise in the daytime. The attacks of coronary spasm are associated with either ST segment elevation or depression, or negative U wave on ECG. Patients with multi-vessel coronary spasm may suffer from lethal arrhythmia, including advanced AV block, ventricular tachycardia or fibrillation, or even sudden death, and they are often resistant to conventional medical therapy including Ca-channel blockers (CCBs). Endothelial nitric oxide (NO) activity is reduced and markers of oxidative stress are elevated in patients with coronary spasm. Thrombogenesis is enhanced and plasma levels of hsCRP and P-selection are elevated in patients with coronary spasm. Thus, patients with coronary spasm have endothelial dysfunction and are suffering from a low-grade chronic inflammation. Polymorphisms of endothelial NO synthase, smoking, and low-grade inflammation are the most important risk factors for coronary spasm. Coronary spasm is a hyper-contraction of coronary smooth muscle triggered by an increase of intracellular Ca2+ in the presence of an increased Ca2+ sensitivity. It has been shown that RhoA/ROCK pathway is involved in Ca2+ sensitivity and that the reduced endothelial NO activity results in increased Ca2+ sensitivity through enhanced RhoA/ROCK pathway. Accordingly, it is possible that in addition to CCBs, RhoA/ROCK pathway blockers may prove to be useful for the treatment of coronary spasm