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Träfflista för sökning "WFRF:(Townsend Paul A.) "

Sökning: WFRF:(Townsend Paul A.)

  • Resultat 11-18 av 18
  • Föregående 1[2]
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11.
  • Matejcic, Marco, et al. (författare)
  • Germline variation at 8q24 and prostate cancer risk in men of European ancestry
  • 2018
  • Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 x 10(-15)), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95% CI = 3.62-4.40) greater risk compared to the population average. These 12 variants account for similar to 25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification.
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12.
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13.
  • Wu, Lang, et al. (författare)
  • Identification of Novel Susceptibility Loci and Genes for Prostate Cancer Risk : A Transcriptome-Wide Association Study in over 140,000 European Descendants
  • 2019
  • Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 79:13, s. 3192-3204
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association study-identified prostate cancer risk variants explain only a relatively small fraction of its familial relative risk, and the genes responsible for many of these identified associations remain unknown. To discover novel prostate cancer genetic loci and possible causal genes at previously identified risk loci, we performed a transcriptome-wide association study in 79,194 cases and 61,112 controls of European ancestry. Using data from the Genotype-Tissue Expression Project, we established genetic models to predict gene expression across the transcriptome for both prostate models and cross-tissue models and evaluated model performance using two independent datasets. We identified significant associations for 137 genes at P < 2.61 x 10(-6), a Bonferroni-corrected threshold, including nine genes that remained significant at P < 2.61 x 10(-6) after adjusting for all known prostate cancer risk variants in nearby regions. Of the 128 remaining associated genes, 94 have not yet been reported as potential target genes at known loci. We silenced 14 genes and many showed a consistent effect on viability and colony-forming efficiency in three cell lines. Our study provides substantial new information to advance our understanding of prostate cancer genetics and biology. Significance: This study identifies novel prostate cancer genetic loci and possible causal genes, advancing our understanding of the molecular mechanisms that drive prostate cancer.
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15.
  • Dickinson, Paul A, et al. (författare)
  • Clinical relevance of dissolution testing in quality by design
  • 2008
  • Ingår i: AAPS Journal. - 1550-7416 .- 1550-7416. ; 10:2, s. 380-390
  • Forskningsöversikt (refereegranskat)abstract
    • Quality by design (QbD) has recently been introduced in pharmaceutical product development in a regulatory context and the process of implementing such concepts in the drug approval process is presently on-going. This has the potential to allow for a more flexible regulatory approach based on understanding and optimisation of how design of a product and its manufacturing process may affect product quality. Thus, adding restrictions to manufacturing beyond what can be motivated by clinical quality brings no benefits but only additional costs. This leads to a challenge for biopharmaceutical scientists to link clinical product performance to critical manufacturing attributes. In vitro dissolution testing is clearly a key tool for this purpose and the present bioequivalence guidelines and biopharmaceutical classification system (BCS) provides a platform for regulatory applications of in vitro dissolution as a marker for consistency in clinical outcomes. However, the application of these concepts might need to be further developed in the context of QbD to take advantage of the higher level of understanding that is implied and displayed in regulatory documentation utilising QbD concepts. Aspects that should be considered include identification of rate limiting steps in the absorption process that can be linked to pharmacokinetic variables and used for prediction of bioavailability variables, in vivo relevance of in vitro dissolution test conditions and performance/interpretation of specific bioavailability studies on critical formulation/process variables. This article will give some examples and suggestions how clinical relevance of dissolution testing can be achieved in the context of QbD derived from a specific case study for a BCS II compound.
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16.
  • Lynch, S.A., et al. (författare)
  • Toward silicon-based lasers for terahertz sources
  • 2006
  • Ingår i: IEEE Journal of Selected Topics in Quantum Electronics. - 1077-260X .- 1558-4542. ; 12:6, s. 1570-1577
  • Tidskriftsartikel (refereegranskat)abstract
    • Producing an electrically pumped silicon-based laser at terahertz frequencies is gaining increased attention these days. This paper reviews the recent advances in the search for a silicon-based terahertz laser. Topics covered include resonant tunneling in p-type Si/SiGe, terahertz intersubband electroluminescence from quantum cascade structures, intersubband lifetime measurements in Si/SiGe quantum wells, enhanced optical guiding using buried suicide layers, and the potential for exploiting common impurity dopants in silicon such as boron and phosphorus to realize a terahertz laser. © 2006 IEEE.
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17.
  • Zhao, Ming, et al. (författare)
  • Low-temperature molecular beam epitaxy growth of Si/SiGe THz quantum cascade structures on virtual substrates
  • 2006
  • Ingår i: Thin Solid Films. - 0040-6090. ; 508:1-2, s. 24-28
  • Tidskriftsartikel (refereegranskat)abstract
    • Si/SiGe quantum cascade structures containing superlattice up to 100 periods have been grown on SiGe virtual substrates by using solid-source molecular beam epitaxy at low temperature. The surface morphology and structural properties of the grown samples were characterized using various experimental techniques. It has been concluded that the structures were completely symmetrically strained with high crystalline quality, precise layer parameters, and excellent reproducibility. Electroluminescence was observed with peaked intensity at 3 THz at both 4 and 40 K, which agrees very well with expected interwell intersubband transition according to the design.
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18.
  • Zhao, Ming, et al. (författare)
  • Molecular beam epitaxy growth of Si/SiGe bound-to-continuum quantum cascade structures for THz emission
  • 2008
  • Ingår i: Thin Solid Films. - 0040-6090 .- 1879-2731. ; 517:1, s. 34-37
  • Tidskriftsartikel (refereegranskat)abstract
    • A Si/SiGe bound-to-continuum quantum cascade design for THz emission was grown using solid-source molecular beam epitaxy on Si0.8Ge0.2 virtual substrates. The growth parameters were carefully studied and several samples with different boron doping concentrations were grown at optimized conditions. Extensive material characterizations revealed a high crystalline quality of the grown structures with an excellent growth control. Layer undulations resulting from a nonuniform strain field, introduced by high doping concentration, were observed. The device characterizations suggested that a modification on the design was needed in order to enhance the THz emission.
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  • Resultat 11-18 av 18
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