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排序方式: 共有351条查询结果,搜索用时 11 毫秒
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Mark S. Tichenor John M. Keith William M. Jones Joan M. Pierce Jeff Merit Natalie Hawryluk Mark Seierstad James A. Palmer Michael Webb Mark J. Karbarz Sandy J. Wilson Michelle L. Wennerholm Filip Woestenborghs Dominiek Beerens Lin Luo Sean M. Brown Marlies De Boeck Sandra R. Chaplan J. Guy Breitenbucher 《Bioorganic & medicinal chemistry letters》2012,22(24):7357-7362
The structure–activity relationships for a series of heteroaryl urea inhibitors of fatty acid amide hydrolase (FAAH) are described. Members of this class of inhibitors have been shown to inactivate FAAH by covalent modification of an active site serine with subsequent release of an aromatic amine from the urea electrophile. Systematic Ames II testing guided the optimization of urea substituents by defining the structure–mutagenicity relationships for the released aromatic amine metabolites. Potent FAAH inhibitors were identified having heteroaryl amine leaving groups that were non-mutagenic in the Ames II assay. 相似文献
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The phenology and pollination ecology of three native fig species were studied in southeastern Brazil. Populations displayed continual syconia production, with one species showing intra-tree flowering asynchrony. Pollination of the fig flowers was necessary for the development of the syconia; lack of pollination induced abortion of syconia. All three species follow the general pattern of pollination known for figs, but the behavior of the pollinator wasps, Pegoscapus spp., differed in some aspects from those of other neotropical and paleotropical fig wasps, mainly with respect to pollen loading and unloading during pollination. The longevity of Pegoscapus wasps outside the syconium was about two days. 相似文献
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Chronic respiratory infections are a major cause of morbidity and mortality, most particularly in Cystic Fibrosis (CF) patients. The recent finding that gastro-esophageal reflux (GER) frequently occurs in CF patients led us to investigate the impact of bile on the behaviour of Pseudomonas aeruginosa and other CF-associated respiratory pathogens. Bile increased biofilm formation, Type Six Secretion, and quorum sensing in P. aeruginosa, all of which are associated with the switch from acute to persistent infection. Furthermore, bile negatively influenced Type Three Secretion and swarming motility in P. aeruginosa, phenotypes associated with acute infection. Bile also modulated biofilm formation in a range of other CF-associated respiratory pathogens, including Burkholderia cepacia and Staphylococcus aureus. Therefore, our results suggest that GER-derived bile may be a host determinant contributing to chronic respiratory infection. 相似文献
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Wendy W. J. de Leng Christa G. Gadellaa-van Hooijdonk Fran?oise A. S. Barendregt-Smouter Marco J. Koudijs Ies Nijman John W. J. Hinrichs Edwin Cuppen Stef van Lieshout Robert D. Loberg Maja de Jonge Emile E. Voest Roel A. de Weger Neeltje Steeghs Marlies H. G. Langenberg Stefan Sleijfer Stefan M. Willems Martijn P. Lolkema 《PloS one》2016,11(2)
Background
Targeted Next Generation Sequencing (NGS) offers a way to implement testing of multiple genetic aberrations in diagnostic pathology practice, which is necessary for personalized cancer treatment. However, no standards regarding input material have been defined. This study therefore aimed to determine the effect of the type of input material (e.g. formalin fixed paraffin embedded (FFPE) versus fresh frozen (FF) tissue) on NGS derived results. Moreover, this study aimed to explore a standardized analysis pipeline to support consistent clinical decision-making.Method
We used the Ion Torrent PGM sequencing platform in combination with the Ion AmpliSeq Cancer Hotspot Panel v2 to sequence frequently mutated regions in 50 cancer related genes, and validated the NGS detected variants in 250 FFPE samples using standard diagnostic assays. Next, 386 tumour samples were sequenced to explore the effect of input material on variant detection variables. For variant calling, Ion Torrent analysis software was supplemented with additional variant annotation and filtering.Results
Both FFPE and FF tissue could be sequenced reliably with a sensitivity of 99.1%. Validation showed a 98.5% concordance between NGS and conventional sequencing techniques, where NGS provided both the advantage of low input DNA concentration and the detection of low-frequency variants. The reliability of mutation analysis could be further improved with manual inspection of sequence data.Conclusion
Targeted NGS can be reliably implemented in cancer diagnostics using both FFPE and FF tissue when using appropriate analysis settings, even with low input DNA. 相似文献9.
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