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31.
Robotic synthesis is making possible the synthesis of large, systematically designed sets of compounds. We analyze a 512-compound set that is a 2(9) full factorial experimental design using a recursive partitioning algorithm, FIRM, and a high-dimension visualization tool, TempleMVV. These techniques are used to quickly and easily identify the main trends in the data set and also identify unusual observations. We show that analytical and visualization methods can be used synergistically to analyze a large, complex, high-dimensional data set. We also show that a fractional factorial design of 128 compounds would give essentially the same information. 相似文献
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T Peelen M van Vliet A Petrij-Bosch R Mieremet C Szabo AM van den Ouweland F Hogervorst R Brohet MJ Ligtenberg E Teugels R van der Luijt AH van der Hout JJ Gille G Pals I Jedema R Olmer I van Leeuwen B Newman M Plandsoen M van der Est G Brink S Hageman PJ Arts MM Bakker P Devilee 《Canadian Metallurgical Quarterly》1997,60(5):1041-1049
We have identified 79 mutations in BRCA1 in a set of 643 Dutch and 23 Belgian hereditary breast and ovarian cancer families collected either for research or for clinical diagnostic purposes. Twenty-eight distinct mutations have been observed, 18 of them not previously reported and 12 of them occurring more than once. Most conspicuously, a 2804delAA mutation has been found 19 times and has never been reported outside the Netherlands. A common haplotype spanning > or = 375 kb could be identified for each of the nine examined recurrent mutations, indicating the presence of multiple BRCA1 founder mutations in the Dutch population. The 2804delAA mutation has been estimated to have originated approximately 32 generations ago. No specific breast or ovarian cancer phenotype could be assigned to any of the common mutations, and the ovarian cancer incidence among 18 families with the 2804delAA mutation was heterogeneous. 相似文献
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V Kamath CN Jones JC Yip BB Varasteh AH Cincotta GM Reaven YD Chen 《Canadian Metallurgical Quarterly》1997,20(11):1697-1701
OBJECTIVE: To assess the effect on various aspects of carbohydrate and lipid metabolism of administering a quick-release formulation of bromocriptine (Ergoset) to obese, nondiabetic, hyperinsulinemic women. RESEARCH DESIGN AND METHODS: Hourly concentrations of prolactin, glucose, insulin, free fatty acid (FFA), and triglyceride were measured for 24 h before and after approximately 8 weeks of treatment with Ergoset. In addition, fasting lipid and lipoprotein concentrations and the steady-state plasma glucose (SSPG) concentration in response to a continuous infusion of somatostatin, insulin, and glucose were determined before and after Ergoset administration. RESULTS: Circulating prolactin concentrations were dramatically decreased (P < 0.001) following treatment, associated with a significant fall (P < 0.05) in 24-h-long plasma glucose, FFA, and triglyceride concentrations. Neither circulating plasma insulin concentrations nor the ability of insulin to mediate glucose disposal changed with treatment. Finally, fasting total cholesterol fell (P < 0.05) and the ratio of total to HDL cholesterol decreased (P = 0.06) in association with Ergoset treatment. CONCLUSIONS: The fact that significant metabolic improvement was seen in the obese nondiabetic hyperinsulinemic women studied suggests that Ergoset could be of therapeutic benefit in clinical conditions of hyperglycemia and/or dyslipidemia. 相似文献
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Amplification of a 340 bp sequence of the 38 kDa protein gene of Mycobacterium tuberculosis by the polymerase chain reaction has been developed. The sensitivity of this PCR was shown to be 10 fg both by agarose gel electrophoresis and Southern blot hybridisation being equivalent to 2-3 organisms and highly specific to M. tuberculosis and excluding even M. tuberculosis H37Ra and Mycobacterium bovis BCG. Sputum samples from patients with pulmonary tuberculosis gave a positivity rate of 45%. PCR was also performed using pt8 and pt9 primers which amplified a 541 bp sequence of IS6110. 41% of the above samples gave positive amplification. Three samples that were positive for 38 kDa sequence were negative for IS6110. 相似文献
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We have investigated the effects of the neutral endopeptidase inhibitor, SCH 42354, on the vasoreactivity of atrial natriuretic peptide (ANP) in rat isolated pulmonary resistance vessels (PRV) and isolated perfused lungs (IPL). PRV (n = 37) were mounted onto the jaws of a myograph and precontracted with PGF2alpha (100 mu M). Concentration-responses to ANP (0.17 to 340 nM) were determined before and after the addition of SCH 42354 (10, 30 and 100 nM). Each concentration of SCH 42354 caused a significant increase in potency (- log EC50) of ANP in isolated PRV. Lungs from normoxic rats (n = 13) were isolated and perfused with whole blood. An increase in pulmonary artery pressure was achieved by ventilating with an hypoxic gas mixture and concentration-responses obtained by incremental additions of ANP (40 nM to 12 mu M), before and after the addition of SCH 42354 (100 nM). SCH 42354 significantly increased the potency (- log EC50) of ANP in the rat IPL. ANP is partly metabolized by NEP. That an inhibitor of NEP increased the potency of ANP in isolated pulmonary vessels, and in isolated perfused whole lungs, suggested that SCH 42354 may be having a local action within the pulmonary vasculature. 相似文献
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Recovery of residual oil using the alkali/surfactant/polymer process: effect of alkali concentration
An experimental study was conducted to examine the effectiveness of sodium carbonate in alkali, surfactant and polymer combined slugs in recovering waterflood residual oil. The effects of sodium carbonate concentration on the slug viscosity, interfacial tension, and phase behavior were first examined. Core flood experiments were conducted with unfired linear Berea sandstone cores. The incremental oil recovery, oil cut, residual resistance factor, and chemical propagation were measured for each flood.A significant oil bank was formed for all combined slugs having sodium carbonate concentration ≥1 wt%. The incremental oil recovery, oil cut and the injectivity of the combined slugs greatly improved as sodium carbonate concentration was increased. The effect of sodium carbonate concentration on chemical propagation was dramatic for the synthetic surfactant; a slight delay in surfactant breakthrough and a much slower rate of surfactant propagation were observed at high sodium carbonate concentrations.The results obtained in the present study indicate that the residual oil was recovered by two mechanisms: low interfacial tension and wettability reversal. The former mechanism is dominant at sodium carbonate concentrations ≤1 wt%, whereas the latter plays an important role only at high sodium carbonate concentrations. 相似文献
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