Side chain-positioning as an integer programming problem

Abstract. An important aspect of homology modeling and protein design algorithms is the correct positioning of protein side chains on a fixed backbone. Homology modeling methods are necessary to complement large scale structural genomics projects. Recently it has been shown that in automatic protein design it is of the uttermost importance to find the global solution to the side chain positioning problem [1]. If a suboptimal solution is found the difference in free energy between different sequences will be smaller than the error of the side chain positioning. Several different algorithms have been developed to solve this problem. The most successful methods use a discrete representation of the conformational space. Today, the best methods to solve this problem, are based on the dead end elimination theorem. Here we introduce an alternative method. The problem is formulated as a linear integer program. This programming problem can then be solved by efficient polynomial time methods, using linear programming relaxation. If the solution to the relaxed problem is integral it corresponds to the global minimum energy conformation (GMEC). In our experimental results, the solution to the relaxed problem has always been integral.

The Gastro-Esophageal Malignancies in Northern Iran research project: Impact on the health research and health care systems in Iran

Background: The Gastro-Esophageal Malignancies in Northern Iran (GEMINI) research project is an example of recent progress in health research in Iran. The original aim of this project was to identify etiologic factors and prevention measures for upper gastrointestinal cancers in Northern provinces of Iran, but its achievements have gone much beyond this initial goal. Methods: GEMINI consists of several projects including cancer registries, pilot studies, case-control studies, and the Golestan Cohort Study. GEMINI has been conducted through extensive collaborations between the Digestive Disease Research Center of Tehran University of Medical Sciences with other domestic and international health organizations. The achievements of GEMINI include producing new knowledge, introducing new research methods, developing and expanding health research and health care infrastructures, investing in human resources, and increasing the awareness and knowledge of policy makers and officials at all levels about the importance of chronic diseases in Iran's health priorities. Conclusions: The success of GEMINI reveals the feasibility of large-scale health research studies in developing countries and serves as a successful model not only for health research in Iran, but also for similar research studies in other developing nations

A prospective study of tea drinking temperature and risk of esophageal squamous cell carcinoma

Previous studies have reported an association between hot tea drinking and risk of esophageal cancer, but no study has examined this association using prospectively and objectively measured tea drinking temperature. We examined the association of tea drinking temperature, measured both objectively and subjectively at study baseline, with future risk of esophageal squamous cell carcinoma (ESCC) in a prospective study. We measured tea drinking temperature using validated methods and collected data on several other tea drinking habits and potential confounders of interest at baseline in the Golestan Cohort Study, a population-based prospective study of 50,045 individuals aged 40-75�years, established in 2004-2008 in northeastern Iran. Study participants were followed-up for a median duration of 10.1 years (505,865 person-years). During 2004-2017, 317 new cases of ESCC were identified. The objectively measured tea temperature (HR 1.41, 95 CI 1.10-1.81; for �60°C vs. <60°C), reported preference for very hot tea drinking (HR 2.41, 95 CI 1.27-4.56; for "very hot" vs. "cold/lukewarm"), and reported shorter time from pouring tea to drinking (HR 1.51, 95 CI 1.01-2.26; for <2 vs. �6 min) were all associated with ESCC risk. In analysis of the combined effects of measured temperature and amount, compared to those who drank less than 700�ml of tea/day at <60°C, drinking 700�mL/day or more at a higher-temperature (�60°C) was consistently associated with an about 90 increase in ESCC risk. Our results substantially strengthen the existing evidence supporting an association between hot beverage drinking and ESCC. © 2019 UICC