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The Nurses' Health Study (NHS), Nurses' Health Study II (NHSII), Health Professionals Follow Up Study (HPFS) and the Physicians Health Study (PHS) have collected detailed longitudinal data on multiple exposures and traits for approximately 310,000 study participants over the last 35 years. Over 160,000 study participants across the cohorts have donated a DNA sample and to date, 20,691 subjects have been genotyped as part of genome-wide association studies (GWAS) of twelve primary outcomes. However, these studies utilized six different GWAS arrays making it difficult to conduct analyses of secondary phenotypes or share controls across studies. To allow for secondary analyses of these data, we have created three new datasets merged by platform family and performed imputation using a common reference panel, the 1,000 Genomes Phase I release. Here, we describe the methodology behind the data merging and imputation and present imputation quality statistics and association results from two GWAS of secondary phenotypes (body mass index (BMI) and venous thromboembolism (VTE)). We observed the strongest BMI association for the FTO SNP rs55872725 (β = 0.45, p = 3.48x10-22), and using a significance level of p = 0.05, we replicated 19 out of 32 known BMI SNPs. For VTE, we observed the strongest association for the rs2040445 SNP (OR = 2.17, 95% CI: 1.79-2.63, p = 2.70x10-15), located downstream of F5 and also observed significant associations for the known ABO and F11 regions. This pooled resource can be used to maximize power in GWAS of phenotypes collected across the cohorts and for studying gene-environment interactions as well as rare phenotypes and genotypes.
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ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnzyme-catalyzed organic synthesis: NAD(P)H cofactor regeneration by using glucose-6-phosphate and the glucose-5-phosphate dehydrogenase from Leuconostoc mesenteroidesChi-Huey Wong and George M. WhitesidesCite this: J. Am. Chem. Soc. 1981, 103, 16, 4890–4899Publication Date (Print):August 1, 1981Publication History Published online1 May 2002Published inissue 1 August 1981https://pubs.acs.org/doi/10.1021/ja00406a037https://doi.org/10.1021/ja00406a037research-articleACS PublicationsRequest reuse permissionsArticle Views1482Altmetric-Citations223LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
This paper is concerned with some aspects of nonuniform stressing above a deep creeping portion of a fault zone prior to a large crust‐breaking earthquake. The model that we use involves a slipping crack, representing the deeper, more stably sliding portions of the fault zone, which penetrates upward from depth and is blocked in the lower region of the seismogenic zone. When conditions are uniform along strike, the upward penetration at the crack front is by mode III in strike‐slip fault zones but by mode II in thrust or normal fault zones. Two major results are reported. First, we analyze approximately, via a linear perturbation formulation, how a tectonic crack front encounters and ultimately shears through arrays of localized “asperities” that are distributed parallel to the crack front and have a toughness which is greater than that of adjoining segments of the fault zone. Using a fast Fourier transform based numerical procedure to simulate crack penetration into asperities, we find a notable difference between mode II and mode III crack fronts in that the former penetrates approximately twice as far between the asperities as the latter under the same loading level. This is interesting because observations of slip distribution in large earthquakes suggest that there is a significant aseismic component to the total slip budget in subduction zone earthquakes, which in contrast does not seem to be present in strike‐slip zone earthquakes, and also that the surface slip distribution in continental dip‐slip faulting is typically much more irregular than for strike‐slip faulting. In a simulation involving multiple rows of periodic asperities we note that the more deeply penetrating mode II crack front contacts more asperities simultaneously while breaking them at different load levels compared to the less flexible mode III crack front, which simply breaks one row of asperities and jumps (unstably) to the next. The second major result concerns whether a straight crack front in the lithosphere along a strike‐slip fault zone is configurationally stable, that is, whether the crack front will tend to remain straight as the crack penetrates upward from depth. It is found that for infinitesimal perturbations of the straight front beyond a critical wavelength, of the order of the crustal lithosphere thickness, the stress intensity factor is higher at the most advanced portions of the crack front rather than at the least advanced; the opposite is true at shorter wavelengths. When resistance to crack growth is essentially uniform over the fault plane, this means that the straight crack front is configurationally unstable at long wavelengths. The issue of configurational stability is related to the concept of fault segmentation, which is based on the observation that fault zones, particularly long ones, do not rupture along their entire length during a single earthquake. Effect of a vertical gradient of fracture resistance is discussed in the appendix, where it is shown that a significant upward gradient of resistance to crack growth may completely stabilize the straight crack configuration.
Three low-permeability cut-off walls were required for seepage control along the upstream toe of two new dams as part of the Lac des IIes (LDI) water management facility works. The LDI palladium mine is located 135 km North of Thunder Bay, ON, Canada. Jet grouting was used to create the low permeability cut-off walls by installing overlapping soil-cement columns. Jet grout columns were constructed using the double-fluid process. A comprehensive quality control program was implemented to ensure that specified geometric properties and performance requirements of the cut-off wall were achieved. An acoustic column inspector (ACI) tool was used to verify the diameters of the pre-production test columns. All jet grout locations were pre-drilled to prevent difficulties resulting from geological conditions and to ensure adequate penetration into bedrock. A three-dimensional profile of each jet grout column installed was generated and updated daily based on the results of pre-drill hole alignment measurements completed at every hole. In-situ permeability testing was also conducted during the pre-production test program and during the installation of the production columns. Permeability testing was performed in-situ and on cast cylinders of soil-cement samples. The low permeability cut-off walls were successfully installed and satisfied the specified performance criteria. Jet grouting was performed between the months of February and May under challenging winter conditions. This paper focusses on the quality management program (QMP) that was implemented to successfully complete this project.
Although evidences indicate that C-reactive protein (CRP) levels are independent predictors of type 2 diabetes (DM), some studies either did not support this association or examine it extensively throughout the stages of glucose tolerance.In a cross-sectional population-based survey, we investigated the relation between CRP and the risk of newly diagnosed impaired glucose tolerance (IGT), and DM among Japanese-Brazilians (374 men and 464 women).In agegender-adjusted analyses, the risks of IGT and type 2 diabetes were significantly higher in the highest CRP tertile as compared with participants with a normal glucose tolerance status (P for trend = 0.0001 in both conditions).After further adjustments for confounding factors, including waist circumference, only the odds of having IGT in the highest CRP tertile was still significant (odds ratio 1.87 [95% CI 1.04-3.37).Our results suggest that low-grade inflammation increases the risk of IGT in Japanese-Brazilians but that some of the risk is confounded by abdominal adiposity.
Buckling load of cylindrical shell with asymmetric and axisymmetric imperfections and calculation of upper bound to buckling load for shell with axisymmetric imperfections
Self-assembled monolayers (SAMs) are part of a class of organized molccular assemblies (OMAs) that represent a major new theme in condensed-matter science. The character- istics of SAMs and a summary of research recommendations are first presented in an executive summary. After introducing the definitions and characteristics of OMAs in which Langmuir-Blodgett (LB) films are compared with SAMs, the opportunities for scientific study. technological applications of SAMs. and limitations to transf-erring scientific understandin-e into technology are discussed. The discussion of SAMs includes the scientific opportunities in condensed-matter science. heteroepitaxy. and nanostructurest the technolo-sical applications in fuel cells. photoelectrochemistry. polymer/ metal (oxirle) interfaces, and thin-film. multilayer. solar collectors; and the lirnitations of stability. monolayer-substrate interactions. and mechanical stability for the transf'er of science into technology. Afier providing an overview and discussing potential payoffs from research, the needs and opportu- nities are summarized fbr tribology. fuel cells, photovoltaic cells, electrochromic windows. surface contamination, selectivity, and lbulin-e in membrane separations. biosurfaces. sensors. and corrosion.
Purpose There is little prior study of major dietary patterns and breast cancer survival. Methods Patients included 2,619 Nurses' Health Study participants who were diagnosed with invasive breast cancer between 1982 and 1998 and completed a dietary questionnaire more than 1 year after diagnosis. Participants were followed through 2002 (median = 9 years). During follow-up, 414 patients died of any cause, 242 patients died of breast cancer, and 172 patients died from causes other than breast cancer. Women with in situ or metastatic disease at diagnosis were excluded. We used Cox proportional hazards models to evaluate prospective associations of prudent and Western dietary patterns assessed both before and after diagnosis with time to event after diagnosis. Results In multivariate-adjusted analyses assessed after diagnosis, the Western and prudent dietary patterns were unrelated to all-cause or breast cancer mortality. However, compared with women with the lowest intake of the prudent dietary pattern, the relative risks (and 95% CIs) of death from causes other than breast cancer were 0.85 (95% CI, 0.53 to 1.35), 0.74 (95% CI, 0.45 to 1.21), 0.70 (95% CI, 0.42 to 1.17), and 0.54 (95% CI, 0.31 to 0.95; P = .03, from lowest to highest quintile of intake). In contrast, the Western dietary pattern was positively associated with this outcome (P = .04). Results for the assessment of dietary patterns before diagnosis were similar, except the prudent dietary pattern was unrelated to mortality. Conclusion A higher intake of the prudent pattern and a lower intake of the Western pattern may protect against mortality from causes unrelated to breast cancer.