21 research outputs found

    Automatic classification and chemical structure-activity correlation.

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    Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

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    Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction

    New genetic loci link adipose and insulin biology to body fat distribution.

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    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

    The James Webb Space Telescope Mission

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    Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least 4m4m. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the 6.5m6.5m James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

    Joe Orton and Shakespeare: collage, class and queerness

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    This essay considers Joe Orton's relationship to Shakespeare through the library book covers that he redesigned with his partner Kenneth Halliwell and through his plays. It proposes that Orton and Halliwell's neglected Shakespeare dust jackets are as subversive as the better-known covers of the popular and middlebrow library books they reworked. Their collages ironise or queer Shakespeare's themes and contest critical authority. By focusing specifically on Arden editions, Orton and Halliwell resist the gentrification of Shakespeare engendered by elitist academic discourse and bourgeois spaces such as the public library and the theatre. The same irreverent attitude to Shakespeare is evident in Orton's plays. Although he admired, identified with and drew inspiration from his predecessor, Orton recycles Shakespeare's plots, lines and motifs to transform their class politics and to amplify their sexual dissidence. Overall, this essay contends that by reshaping Shakespeare from a working class, queer perspective Orton resists the Bard's growing function as an emblem of social distinction in mid-century Britain

    ‘Lives of living death’: The reproductive lives of slave women in the cane world of Louisiana

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    This paper examines the seasonality of childbirth among slave women and addresses the relationship between seasonal workloads, nutrition, and pregnancy on large sugar plantations in nineteenth-century Louisiana. Unlike the rest of the American South, where the slave population grew, bondspeople in southern Louisiana experienced natural population decrease. This derived in part from imbalanced sex ratios, but as this article shows, conceptions peaked during the annual harvest season but fell away at other times due to nutritional stress, overwork, heat, and exhaustion. By combining plantation sources with contemporary scholarship on reproductive physiology, the article places Louisiana's reproductive history in contest and establishes the limits sugar production imposed on the slave women's capacity for childbirth

    Rodent Allergen in Los Angeles Inner City Homes of Children with Asthma

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    Recent studies have examined the presence of mouse allergen in inner city children with asthma. Researchers have found high levels of rodent allergen in homes sampled in the northeast and midwest United States, but there has been considerable variation between cities, and there have been few studies conducted in western states. We evaluated the frequency of rodent sightings and detectable mouse allergen and the housing conditions associated with these outcomes in inner city homes in Los Angeles. Two hundred and two families of school children, ages 6–16 living in inner city neighborhoods, participated in the study. Families were predominantly Latino (94%), and Spanish speaking (92%). At study entry, parents completed a home assessment questionnaire, and staff conducted a home evaluation and collected kitchen dust, which was analyzed for the presence of mouse allergen. Fifty-one percent of homes had detectable allergen in kitchen dust. All 33 families who reported the presence of rodents had detectable allergen in the home and were also more likely to have increased levels of allergen compared to those who did not report rodents. Unwashed dishes or food crumbs, lack of a working vacuum, and a caretaker report of a smoker in the home were all significantly associated with a greater risk of rodent sightings or detectable allergen (P < 0.05). Detached homes were significantly more likely to have detectable allergen. The prevalence of allergen is common enough that it may have public health implications for asthmatic children, and detectable allergen was not routinely identified based on rodent sightings. Many of the predictors of rodent allergen are amenable to low-cost interventions that can be integrated with other measures to reduce exposure to indoor allergens
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