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  • 1
    Keywords: LOCI ; GENOME-WIDE ASSOCIATION ; MISSING HERITABILITY
    Abstract: Objectives: We aimed at extending the Natural and Orthogonal Interaction (NOIA) framework, developed for modeling gene-gene interactions in the analysis of quantitative traits, to allow for reduced genetic models, dichotomous traits, and gene-environment interactions. We evaluate the performance of the NOIA statistical models using simulated data and lung cancer data. Methods: The NOIA statistical models are developed for additive, dominant, and recessive genetic models as well as for a binary environmental exposure. Using the Kronecker product rule, a NOIA statistical model is built to model gene-environment interactions. By treating the genotypic values as the logarithm of odds, the NOIA statistical models are extended to the analysis of case-control data. Results: Our simulations showed that power for testing associations while allowing for interaction using the NOIA statistical model is much higher than using functional models for most of the scenarios we simulated. When applied to lung cancer data, much smaller p values were obtained using the NOIA statistical model for either the main effects or the SNP-smoking interactions for some of the SNPs tested. Conclusion: The NOIA statistical models are usually more powerful than the functional models in detecting main effects and interaction effects for both quantitative traits and binary traits.
    Type of Publication: Journal article published
    PubMed ID: 22889990
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  • 2
    ISSN: 0992-7689
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract Based on the linearized theory of atmospheric gravity waves (AGW) and considering the effects of temperature perturbation on the chemical rate coefficients, the formulae of coupling relations between nj/nj and T′/T driven by AGW (nj and T denote the background quantities) are described, the coupling phases and amplitudes of minor constituents O3, NO, H, OH, and O are analyzed in detail for the mesopause (86 km) and just upside of the O layer (100 km) at daytime. A general principle is outlined: the coupling phases are strongly dependent on density scale heights and perturbation scales, while the amplitudes are little affected by these two factors. A criterion to distinguish the coupling behavior is given: when the minor constituent number density scale height Hj satisfies 1-〈Gamma〉Hm/Hj〉0 (Hm denotes the scale height of the major constituent), the dynamical perturbation process always keeps the nj/nj in phase with T’/T, i.e. keeps the nj/nj in antiphase with that of the major constituent. The results obtained indicate that both the temperature dependence of reaction rate coefficients and the profile slopes of the O distribution may have a major influence on the behavior of the coupling relations.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. In the chronic, awake, instrumented sheep model NG-nitro-L-arginine (NOLA) an inhibitor of nitric oxide synthesis, injected at a dose of 40 mg/kg, produced a significant increase in systolic blood pressure (from 110±6 to 145±8 mmHg after 5 min) which persisted for at least 1 h but returned to baseline after 24 h.2. When NOLA was repeated 1 and 4 days after the first injection, the blood pressure response was significantly attenuated, and at 1 day was no greater than the response to an equivalent volume of saline. The blood pressure response returned to the initial response with an 8 day interval between injections.3. There was no significant blood pressure response to 100 mL of saline before the NOLA injection; however, 1 and 4 days after NOLA there was a significant rise in blood pressure.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The acid inhibitory effect of lansoprazole depends on the S-mephenytoin 4′-hydroxylase (CYP2C19) genotype status. The effect of famotidine is independent of this genotype.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To investigate the acid inhibitory effects of lansoprazole vs. famotidine during the daytime and night-time with reference to different CYP2C19 genotypes.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:Fifteen healthy volunteers were given 20 mg famotidine twice a day or 30 mg lansoprazole once a day for 8 days. On post-dose day 8, 24-h intragastric pH monitoring was performed.〈section xml:id="abs1-4"〉〈title type="main"〉Results:During the daytime, the intragastric pH with lansoprazole was significantly higher than that with famotidine in the heterozygous extensive metabolizer group, whereas no significant difference was observed in the homozygous extensive metabolizer group. During the night-time, the intragastric pH with famotidine was quite similar to that with lansoprazole in the heterozygous extensive metabolizer and poor metabolizer groups. However, during the night-time, the intragastric pH with famotidine was significantly higher than that with lansoprazole in the homozygous extensive metabolizer group.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:An insufficient acid inhibition by lansoprazole during the night-time in the homozygous extensive metabolizer group could be compensated for by famotidine. CYP2C19 genotype testing appears to be useful for predicting the optimal acid inhibitory drug treatment collated with circadian intragastric pH change.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Omeprazole is mainly metabolized in the liver by CYP2C19, a genetically determined enzyme, whereas rabeprazole is mainly reduced non-enzymatically and partially metabolized by CYP2C19. The therapeutic effects of rabeprazole are therefore assumed to be less affected by an individual’s CYP2C19 status.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To investigate the acid inhibitory effects and plasma levels of omeprazole and rabeprazole with reference to different CYP2C19 genotypes.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:Fifteen healthy volunteers took a daily dose of 20 mg of omeprazole or rabeprazole for 8 days. On post-dose days 1 and 8, 24-h profiles of intragastric pH were recorded and plasma concentrations of omeprazole, rabeprazole and their metabolites were determined.〈section xml:id="abs1-4"〉〈title type="main"〉Results:After single and repeated doses of omeprazole, the intragastric pH values and plasma concentrations of omeprazole and its metabolites were significantly dependent on the CYP2C19 genotype. Significant differences in the same kinetic and dynamic parameters were also observed after single doses of rabeprazole. Although the plasma levels of rabeprazole differed among the different CYP2C19 genotype groups after repeated doses, no significant differences in intragastric pH values were observed.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:The acid inhibitory effects of omeprazole and rabeprazole are significantly dependent on the CYP2C19 genotype status, as well as on their intrinsic pharmacokinetic and pharmacodynamic characteristics and dosing schemes.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Marie Unna hereditary hypotrichosis (MUHH) is a rare autosomal dominant disorder with progressive hair loss starting in early childhood and aggravating at puberty. Several studies have mapped the MUHH gene to chromosome 8p21. Here we report a Chinese MUHH family with variable phenotypes. All affected individuals have anomalies affecting both hair density and hair shafts. Major clinical characteristics, disease history and histological examination support the diagnosis of MUHH, but the features of scarring in this kindred are modest and none of the patients have vertex hair loss, which is in contrast with typical MUHH. We now report genotyping and linkage analysis using 11 polymorphic microsatellite markers spanning the MUHH locus at 8p. Two-point linkage analysis using these markers revealed significant exclusion of this locus (log of the odds scores 〈 − 2) at θ = 0 indicating that there is a range of clinical presentations in MUHH, and that more than one genetic locus is responsible for the disorder.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 372 (1994), S. 346-348 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Investigations of gas-metal clusters demonstrate that their reactivities depend strongly on their structures. Reactions of D2 with Fe, Ni, Pd and Pt clusters show striking patterns of both reaction rates and coverage of clusters with D ligands depending on the metal, and the charge and number of ...
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1588-2837
    Keywords: CuCl/MCM-41 ; nitrogen monoxide ; selective catalytic reduction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Selective catalytic reduction of nitrogen monoxide with propene over two kinds of CuCl/MCM-41 catalysts prepared by a dispersion method has been studied. It was found that CuCl/AlMCM-41 exhibits substantially higher activity over CuCl/SiMCM-41. Characterization of these samples by H2-TPR, IR and XRD showed that the active copper species were mainly related to Cu2+ and Cu+ ions in CuCl/AlMCM-41 catalyst.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Macromolecules 28 (1995), S. 1654-1660 
    ISSN: 1520-5835
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: To investigate the effects of Helicobacter pylori infection and eradication on nutrition.〈section xml:id="abs1-2"〉〈title type="main"〉Methods:The body weight, height, blood pressure, gastric juice pH and fasting serum levels of glucose, total protein, albumin, total cholesterol and triglyceride were measured in H. pylori-positive and H. pylori-negative subjects, and the effect of eradication of H. pylori on these parameters was determined. The development of gastro-oesophageal reflux disease after treatment was also examined. Eight patients underwent a pancreatic function test before and after H. pylori eradication therapy.〈section xml:id="abs1-3"〉〈title type="main"〉Results:The incidence of hypoproteinaemia in H. pylori-positive subjects was significantly higher than that in H. pylori-negative subjects. After eradication of H. pylori, the gastric juice pH values were significantly decreased, and the body weight and serum levels of total cholesterol, total protein and albumin were significantly increased. The incidence of hyperlipidaemia significantly increased and that of hypoproteinaemia significantly decreased in the group with eradication. Pancreatic function improved significantly after eradication of H. pylori. No significant changes in these parameters were observed in the group without eradication. Obese patients had a higher risk of the development of gastro-oesophageal reflux disease after eradication of H. pylori infection.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions:The eradication of H. pylori appears to improve some nutritional parameters.
    Type of Medium: Electronic Resource
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