116 research outputs found

    The Grizzly, November 2, 1984

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    Limerick, Part 3, the Controversy: No Simple Solution in Sight • Students Harassed in Two Incidents • Majority of Students Choose Reagan • Editorial: Some Illuminating Self-abuse en Route to an Endorsement • Letter to the Editor • Election \u2784 • 3000 Alumni Return for Homecoming • News of Yesteryear: Coeds to Hold Dormitory Dawn Patrols • UC Student Attends London\u27s Richmond College • Faculty Symposium Here Tomorrow • proTheatre Presents A Thurber Carnival • Shorts: E.T. Forum; PMA Offers Free Admission; H & PE Offers New Course • Career Planning and Placement Offers Services • Debaters Shine • Bears Upset National Power • Soccer Team to Visit China • Diaphragms Stop Delta Pi in Football • Soccer Wins Two, Record at 14-3 • Swimmers Look Strong • Magic Show Tonight • O\u27Chi\u27s Fiftiethhttps://digitalcommons.ursinus.edu/grizzlynews/1126/thumbnail.jp

    Submicron Structures Technology and Research

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    Contains table of contents for Part I, table of contents for Section 1 and reports on thirteen research projects.Joint Services Electronics Program Contract DAAL03-89-C-0001National Science Foundation Grant ECS 87-09806Semiconductor Research Corporation Contract 87-SP-080Hampshire Instruments CorporationNational Science Foundation Grant ECS-85-03443U.S. Air Force - Office of Scientific Research Grant AFOSR-88-0304U.S. Air Force - Office of Scientific Research Grant AFOSR-85-0154X-Opt., IncorporatedNational Aeronautics and Space Administration Contract NAS8-36748AT&T Bell Laboratorie

    Genetic variants of CYP3A5, CYP2D6, SULT1A1, UGT2B15 and tamoxifen response in postmenopausal patients with breast cancer

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    INTRODUCTION: Tamoxifen therapy reduces the risk of recurrence and prolongs the survival of oestrogen-receptor-positive patients with breast cancer. Even if most patients benefit from tamoxifen, many breast tumours either fail to respond or become resistant. Because tamoxifen is extensively metabolised by polymorphic enzymes, one proposed mechanism underlying the resistance is altered metabolism. In the present study we investigated the prognostic and/or predictive value of functional polymorphisms in cytochrome P450 3A5 CYP3A5 (*3), CYP2D6 (*4), sulphotransferase 1A1 (SULT1A1; *2) and UDP-glucuronosyltransferase 2B15 (UGT2B15; *2) in tamoxifen-treated patients with breast cancer. METHODS: In all, 677 tamoxifen-treated postmenopausal patients with breast cancer, of whom 238 were randomised to either 2 or 5 years of tamoxifen, were genotyped by using PCR with restriction fragment length polymorphism or PCR with denaturing high-performance liquid chromatography. RESULTS: The prognostic evaluation performed in the total population revealed a significantly better disease-free survival in patients homozygous for CYP2D6*4. For CYP3A5, SULT1A1 and UGT2B15 no prognostic significance was observed. In the randomised group we found that for CYP3A5, homozygous carriers of the *3 allele tended to have an increased risk of recurrence when treated for 2 years with tamoxifen, although this was not statistically significant (hazard ratio (HR) = 2.84, 95% confidence interval (CI) = 0.68 to 11.99, P = 0.15). In the group randomised to 5 years' tamoxifen the survival pattern shifted towards a significantly improved recurrence-free survival (RFS) among CYP3A5*3-homozygous patients (HR = 0.20, 95% CI = 0.07 to 0.55, P = 0.002). No reliable differences could be seen between treatment duration and the genotypes of CYP2D6, SULT1A1 or UGT2B15. The significantly improved RFS with prolonged tamoxifen treatment in CYP3A5*3 homozygotes was also seen in a multivariate Cox model (HR = 0.13, CI = 0.02 to 0.86, P = 0.03), whereas no differences could be seen for CYP2D6, SULT1A1 and UGT2B15. CONCLUSION: The metabolism of tamoxifen is complex and the mechanisms responsible for the resistance are unlikely to be explained by a single polymorphism; instead it is a combination of several mechanisms. However, the present data suggest that genetic variation in CYP3A5 may predict response to tamoxifen therapy

    Submicron Structures Technology and Research

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    Contains table of contents for Part I, table of contents for Section 1 and reports on fourteen research projects.Joint Services Electronics Program (Contract DAAL03-86-K-0002)Joint Services Electronics Program (Contract DAAL03-89-C-0001)National Science Foundation (Grant ECS-87-09806)Semiconductor Research Corporation (Contract 87-SP-080)Hampshire Instruments CorporationNational Science Foundation (Grant ECS-85-03443)U.S. Air Force - Office of Scientific Research (Grant AFOSR-88-0304)National Science Foundation (Grant ECS-85-06565)X-Opt., IncorporatedU.S. Air Force - Office of Scientific Research (Grant AFOSR-85-0154)National Aeronautics and Space Administration (Grant NGL22-009-683)KMS Fusion, Incorporate

    The utility and predictive value of combinations of low penetrance genes for screening and risk prediction of colorectal cancer

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    Despite the fact that colorectal cancer (CRC) is a highly treatable form of cancer if detected early, a very low proportion of the eligible population undergoes screening for this form of cancer. Integrating a genomic screening profile as a component of existing screening programs for CRC could potentially improve the effectiveness of population screening by allowing the assignment of individuals to different types and intensities of screening and also by potentially increasing the uptake of existing screening programs. We evaluated the utility and predictive value of genomic profiling as applied to CRC, and as a potential component of a population-based cancer screening program. We generated simulated data representing a typical North American population including a variety of genetic profiles, with a range of relative risks and prevalences for individual risk genes. We then used these data to estimate parameters characterizing the predictive value of a logistic regression model built on genetic markers for CRC. Meta-analyses of genetic associations with CRC were used in building science to inform the simulation work, and to select genetic variants to include in logistic regression model-building using data from the ARCTIC study in Ontario, which included 1,200 CRC cases and a similar number of cancer-free population-based controls. Our simulations demonstrate that for reasonable assumptions involving modest relative risks for individual genetic variants, that substantial predictive power can be achieved when risk variants are common (e.g., prevalence > 20%) and data for enough risk variants are available (e.g., ~140–160). Pilot work in population data shows modest, but statistically significant predictive utility for a small collection of risk variants, smaller in effect than age and gender alone in predicting an individual’s CRC risk. Further genotyping and many more samples will be required, and indeed the discovery of many more risk loci associated with CRC before the question of the potential utility of germline genomic profiling can be definitively answered

    Submicron and Nanometer Structures Technology and Research

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    Contains reports on sixteen research projects and a list of publications.Joint Services Electronics Program Contract DAAL03-89-C-0001Joint Services Electronics Program Contract DAAL03-92-C-0001National Science Foundation Grant ECS 90-16437Semiconductor Research Corporation Contract 90-SP-080U.S. Navy - Naval Research Laboratory Contract N00014-90-K-2018IBM CorporationU.S. Air Force - Office of Scientific Research Grant F49620-92-J-0064National Science Foundation Grant DMR 87-19217National Science Foundation Grant DMR 90-22933National Aeronautics and Space Administration Contract NAS8-36748National Aeronautics and Space Administration Grant NAGW-2003National Science Foundation Grant DMR 90-01698Spire Corporatio

    Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis

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    Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis

    New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.

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    Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism
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