1000 resultados para Stephenson, Robert, 1803-1859.


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Background Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer. Methods We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS).We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived agespecific absolute risks of developing prostate cancer by PRS stratum and family history. Results The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2-5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). Conclusions Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. Impact:We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs.

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Catalytic antibodies have shown great promise for catalyzing a tremendously diverse set of natural and unnatural chemical transformations. However, few catalytic antibodies have efficiencies that approach those of natural enzymes. In principle, random mutagenesis procedures such as phage display could be used to improve the catalytic activities of existing antibodies; however, these studies have been hampered by difficulties in the recombinant expression of antibodies. Here, we have grafted the antigen binding loops from a murine-derived catalytic antibody, 17E8, onto a human antibody framework in an effort to overcome difficulties associated with recombinant expression and phage display of this antibody. “Humanized” 17E8 retained similar catalytic and hapten binding properties as the murine antibody while levels of functional Fab displayed on phage were 200-fold higher than for a murine variable region/human constant region chimeric Fab. This construct was used to prepare combinatorial libraries. Affinity panning of these resulted in the selection of variants with 2- to 8-fold improvements in binding affinity for a phosphonate transition-state analog. Surprisingly, none of the affinity-matured variants was more catalytically active than the parent antibody and some were significantly less active. By contrast, a weaker binding variant was identified with 2-fold greater catalytic activity and incorporation of a single substitution (Tyr-100aH → Asn) from this variant into the parent antibody led to a 5-fold increase in catalytic efficiency. Thus, phage display methods can be readily used to optimize binding of catalytic antibodies to transition-state analogs, and when used in conjunction with limited screening for catalysis can identify variants with higher catalytic efficiencies.

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Mode of access: Internet.

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Imprint varies : vols. 1-25: as above; vols. 26-29, 32-35, 43-45, 47-50: Philadelphia, Samuel F. Bradford for John Laval.

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Title from caption.

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With this is bound: Foster, B. F. Prospectus of the Commercial Academy, no. 183 Broadway, N. Y., conducted by B. F. Foster ... New York, 1837.

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v. 1-2. The Iliad of Homer, tr. by Alexander Pope.--v. 3. The Odyssey of Homer, tr. by Alexander Pope.--v. 4-5. The comedies of Aristophanes; by T. Mitchell.--v. 5. The comedies of Aristophanes; Select comedies of Terence, tr. by George Coleman, The satires of Perseus, tr. into English verse by William Gifford.--v. 6-7. The vision of Dante Alighieri, tr. by H.F. Cary.--v. 8. The Lusiad; tr. fr. Camoens by W.J. Mickle.--v. 9-10. Tasso's Jerusalem delivered; tr. by J.H. Hunt.--v. 11. Selections from the tragedies of Aeschylus, Sophocles & Euripides.

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Goldsmiths'-Kress no. 32168.29.

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Bibliographical references included in "Primechanīi︠a︡".