554 research outputs found

    A Smarter Way to Make Early and Mid-Career Decisions

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    Libraries set themselves apart as safe spaces for people of all ages to learn, explore, and share new ideas. That being said, how comfortable are you talking to your colleagues about making a career move? Do you have reliable information to help you make decisions

    Twitter Marketing Research

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    Research Objective: • To examine the relationship between usage rates for individuals ages 46 and up, versus other similar social media platforms. • Are adults aged 46+ using Facebook at a disproportionate rate to Twitter? • What atmosphere/content is the 46+ age demographic seeking when surfing social media? • What can Twitter marketing do to improve brand image among older potential users

    Mining microbial genomes for new natural products and biosynthetic pathways

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    Analyses of microbial genome sequences have revealed numerous examples of ‘cryptic’ or ‘orphan’ biosynthetic gene clusters, with the potential to direct the production of novel, structurally complex natural products. This article summarizes the various methods that have been developed for discovering the products of cryptic biosynthetic gene clusters in microbes and gives an account of my group's discovery of the products of two such gene clusters in the model actinomycete Streptomyces coelicolor M145. These discoveries hint at new mechanisms, roles and specificities for natural product biosynthetic enzymes. Our efforts to elucidate these are described. The identification of new secondary metabolites of S. coelicolor raises the question: what is their biological function? Progress towards answering this question is also summarized

    Planning for the Strategic Redevelopment of Downtown Detroit

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    Executive Summary Since its founding in 1701, Downtown Detroit has evolved from a major shipping port and industrial mega-power, to a place of racial unrest and economic troubles, to its present incarnation as a gritty city looking for a comeback. At this point, the main question for the downtown area concerns how to revitalize this once glorious city into a major hub of entertainment, retail, office and residential for residents and visitors alike. Our goal for the city was to create an oasis of walkable urbanity that would be a destination place for visitors and a safe, clean and attractive city for residents. This study begins with a summary of Detroit’s history. In our historical review, we concentrated on information that pertained to the downtown’s layout and character and could help inform future redevelopment. Additionally, an inventory of the historic buildings, public spaces, and known sites of environmental concern was conducted to get an accurate snapshot of some of the key features of the study area. Working closely with the Brookings Institution Metropolitan Policy Program Urban Markets Initiative and the Social Compact, we conducted an in-depth market analysis. The market analysis included a review and revision of the widely available demographic information. Using alternative data sources to the census, we found that the current downtown population is higher than previously thought and the earning potential, aggregate income, and disposable income are all higher than previously anticipated.Master of ScienceSchool of Natural Resources & EnvironmentA. Alfred Taubman College of Architecture and Urban PlanningStephen M. Ross School of BusinessUniversity of Michiganhttps://deepblue.lib.umich.edu/bitstream/2027.42/48791/4/Strategic Redevelopment of Dtwn Detroit Jan 07.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/48791/6/downtown_detroit.mp4Description of Strategic Redevelopment of Dtwn Detroit Jan 07.pdf : OpusDescription of downtown_detroit.mp4 : Video: Downtown Detroit, Oct. 24, 200

    The Impact of the C-Terminal Domain on the Interaction of Human DNA Topoisomerase II α and β with DNA

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    <b>Background</b> Type II DNA topoisomerases are essential, ubiquitous enzymes that act to relieve topological problems arising in DNA from normal cellular activity. Their mechanism of action involves the ATP-dependent transport of one DNA duplex through a transient break in a second DNA duplex; metal ions are essential for strand passage. Humans have two isoforms, topoisomerase IIα and topoisomerase IIβ, that have distinct roles in the cell. The C-terminal domain has been linked to isoform specific differences in activity and DNA interaction. <b>Methodology/Principal Findings</b> We have investigated the role of the C-terminal domain in the binding of human topoisomerase IIα and topoisomerase IIβ to DNA in fluorescence anisotropy assays using full length and C-terminally truncated enzymes. We find that the C-terminal domain of topoisomerase IIβ but not topoisomerase IIα affects the binding of the enzyme to the DNA. The presence of metal ions has no effect on DNA binding. Additionally, we have examined strand passage of the full length and truncated enzymes in the presence of a number of supporting metal ions and find that there is no difference in relative decatenation between isoforms. We find that calcium and manganese, in addition to magnesium, can support strand passage by the human topoisomerase II enzymes. <b>Conclusions/Significance</b> The C-terminal domain of topoisomerase IIβ, but not that of topoisomerase IIα, alters the enzyme's KD for DNA binding. This is consistent with previous data and may be related to the differential modes of action of the two isoforms in vivo. We also show strand passage with different supporting metal ions for human topoisomerase IIα or topoisomerase IIβ, either full length or C-terminally truncated. They all show the same preferences, whereby Mg > Ca > Mn

    Pulmonary Arterial Hypertension: A Current Perspective on Established and Emerging Molecular Genetic Defects.

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    Pulmonary arterial hypertension (PAH) is an often fatal disorder resulting from several causes including heterogeneous genetic defects. While mutations in the bone morphogenetic protein receptor type II (BMPR2) gene are the single most common causal factor for hereditary cases, pathogenic mutations have been observed in approximately 25% of idiopathic PAH patients without a prior family history of disease. Additional defects of the transforming growth factor beta pathway have been implicated in disease pathogenesis. Specifically, studies have confirmed activin A receptor type II-like 1 (ACVRL1), endoglin (ENG), and members of the SMAD family as contributing to PAH both with and without associated clinical phenotypes. Most recently, next-generation sequencing has identified novel, rare genetic variation implicated in the PAH disease spectrum. Of importance, several identified genetic factors converge on related pathways and provide significant insight into the development, maintenance, and pathogenetic transformation of the pulmonary vascular bed. Together, these analyses represent the largest comprehensive compilation of BMPR2 and associated genetic risk factors for PAH, comprising known and novel variation. Additionally, with the inclusion of an allelic series of locus-specific variation in BMPR2, these data provide a key resource in data interpretation and development of contemporary therapeutic and diagnostic tools
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