ConfGen: a conformational search method for efficient generation of bioactive conformers.

We describe the methodology, parametrization, and application of a conformational search method, called ConfGen, designed to efficiently generate bioactive conformers. We define efficiency as the ability to generate a bioactive conformation within a small total number of conformations using a reasonable amount of computer time. The method combines physics-based force field calculations with empirically derived heuristics designed to achieve efficient searching and prioritization of the ligand's conformational space. While many parameter settings are supported, four modes spanning a range of speed and quality trades-offs are defined and characterized. The validation set used to test the method is composed of ligands from 667 crystal structures covering a broad array of target and ligand classes. With the fastest mode, ConfGen uses an average of 0.5 s per ligand and generates only 14.3 conformers per ligand, at least one of which lies within 2.0 A root-mean-squared deviation of the crystal structure for 96% of the ligands. The most computationally intensive mode raises this recovery rate to 99%, while taking 8 s per ligand. Combining multiple search modes to "fill-in" holes in the conformation space or energy minimizing using an all-atom force field each lead to improvements in the recovery rates at higher resolutions. Overall, ConfGen is at least as good as competing programs at high resolution and demonstrates higher efficiency at resolutions sufficient for many downstream applications, such as pharmacophore modeling.

Non-edible plant oils as new sources for biodiesel production.

Due to the concern on the availability of recoverable fossil fuel reserves and the environmental problems caused by the use those fossil fuels, considerable attention has been given to biodiesel production as an alternative to petrodiesel. However, as the biodiesel is produced from vegetable oils and animal fats, there are concerns that biodiesel feedstock may compete with food supply in the long-term. Hence, the recent focus is to find oil bearing plants that produce non-edible oils as the feedstock for biodiesel production. In this paper, two plant species, soapnut (Sapindus mukorossi) and jatropha (jatropha curcas, L.) are discussed as newer sources of oil for biodiesel production. Experimental analysis showed that both oils have great potential to be used as feedstock for biodiesel production. Fatty acid methyl ester (FAME) from cold pressed soapnut seed oil was envisaged as biodiesel source for the first time. Soapnut oil was found to have average of 9.1% free FA, 84.43% triglycerides, 4.88% sterol and 1.59% others. Jatropha oil contains approximately 14% free FA, approximately 5% higher than soapnut oil. Soapnut oil biodiesel contains approximately 85% unsaturated FA while jatropha oil biodiesel was found to have approximately 80% unsaturated FA. Oleic acid was found to be the dominant FA in both soapnut and jatropha biodiesel. Over 97% conversion to FAME was achieved for both soapnut and jatropha oil.

Injury prevention training: a cluster randomised controlled trial assessing its effect on the knowledge, attitudes, and practices of midwives and health visitors.

OBJECTIVE: To evaluate the effectiveness of injury prevention training. DESIGN: Cluster randomised controlled trial. SETTING: Primary care facilities in the East Midlands area of the United Kingdom. SUBJECTS: Midwives and health visitors. INTERVENTION: Evidence based training session on the risks associated with baby walkers. MAIN OUTCOME MEASURES: The primary outcome measures were knowledge of baby walker use and walker related injury, attitudes towards walkers and towards walker education, and practices relating to walker health education. RESULTS: Trained midwives and health visitors had greater knowledge of the risks associated with baby walkers than untrained midwives and health visitors (difference between the means 0.22; 95% confidence interval (CI) 0.12 to 0.33). Trained health visitors had more negative attitudes to baby walkers (difference between the means 0.35; 95% CI 0.10 to 0.59) and more positive attitudes towards baby walker health education (difference between the means 0.31; 95% CI 0.00 to 0.62) than untrained health visitors. Midwives who had been trained were more likely to discuss baby walkers in the antenatal period than those who were not trained (odds ratio 9.92; 95% CI 2.02 to 48.83). CONCLUSIONS: Injury prevention training was associated with increased knowledge, more negative attitudes towards walkers, and more positive attitudes towards walker education. Trained midwives were more likely to give advice antenatally. Training did not impact on other practices. Larger trials are required to assess the impact of training on parental safety behaviours, the adoption of safety practices, and injury reduction.

Fish oil produces an atherogenic lipid profile in hypertensive men.

The effects of fish oil supplements on plasma and platelet membrane lipids, lipoproteins, sex steroid hormones, glucose, insulin, platelet aggregation, and blood pressure in normal subjects (n = 13) and patients with essential hypertension (n = 13) were studied in this randomized, double-blind, placebo-controlled, two-way crossover study. Treatments consisted of 30 days of 5 g of n-3 fatty acids (ten 1-g capsules of fish oil daily) or placebo capsules (ten wheat germ oil capsules daily) with a one-month washout in between each crossover. Serum lipids and lipoproteins were measured before dosing and every two weeks during the study. Sex steroid hormones, glucose, insulin, and fatty acid composition in platelet membrane phospholipids were measured before dosing and at the end of each crossover. During treatment with fish oil, only the hypertensive had increases in total cholesterol (8%, p less than 0.026), LDL cholesterol (19%, p less than 0.006) and apolipoprotein B (18%, p less than 0.026). Serum androgens (total and free testosterone) were 30% lower in hypertensives than normotensives before any dosing, but were unchanged with placebo or fish oil capsules in either group. Plasma glucose, insulin, platelet aggregation, and the incorporation of n-3 fatty acids into platelet membrane phospholipid subfractions were similar in both normotensive and hypertensive men. Blood pressure was not affected by fish oil treatment in either group of men. These results provide evidence that fish oil may adversely affect serum lipids to yield an atherogenic lipid profile in hypertensive men.