224 research outputs found

    The voice of song : a prosodic and phonological approach to William Blake

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    Thesis (M.A.) -- University of Adelaide, Dept. of English, 198

    Egocentric

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    Adobe

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    Women, child-free and single

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    The Spice Apple

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    The Night Wind

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    Otto\u27s Soldier

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    Knitting

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    Eviction Prevention Programming (EPP): Best Practices Review Feb 2015

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    There is no question that eviction is bad news for renters. Forced moves put individuals and families at risk in so many ways: They have a more difficult time being accepted as tenants elsewhere; they frequently are disconnected from social-support networks, health care providers, employment and schools; and the stress takes a psychological toll of its own.For property owners and managers, turnover means additional expense for legal procedures, recruitment of new tenants and apartment make-ready. But in the nonprofit, mission-oriented world, it's not just about money; it's also about addressing the underlying challenges that drive nonpayment of rent to begin with. The question is what (resident) services are most successful as well as cost efficient. This is the issue this study set out to explore

    The serotonin transporter promotes a pathological estrogen metabolic pathway in pulmonary hypertension via cytochrome P450 1B1 pulmonary circulation

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    Pulmonary arterial hypertension (PAH) is a devastating vasculopathy that predominates in women and has been associated with dysregulated estrogen and serotonin signaling. Overexpression of the serotonin transporter (SERT+) in mice results in an estrogen-dependent development of pulmonary hypertension (PH). Estrogen metabolism by cytochrome P450 1B1 (CYP1B1) contributes to the pathogenesis of PAH, and serotonin can increase CYP1B1 expression in human pulmonary arterial smooth muscle cells (hPASMCs). We hypothesized that an increase in intracellular serotonin via increased SERT expression may dysregulate estrogen metabolism via CYP1B1 to facilitate PAH. Consistent with this hypothesis, we found elevated lung CYP1B1 protein expression in female SERT+ mice accompanied by PH, which was attenuated by the CYP1B1 inhibitor 2,3',4,5'-tetramethoxystilbene (TMS). Lungs from female SERT+ mice demonstrated an increase in oxidative stress that was marked by the expression of 8-hydroxyguanosine; however, this was unaffected by CYP1B1 inhibition. SERT expression was increased in monocrotaline-induced PH in female rats; however, TMS did not reverse PH in monocrotaline-treated rats but prolonged survival. Stimulation of hPASMCs with the CYP1B1 metabolite 16α-hydroxyestrone increased cellular proliferation, which was attenuated by an inhibitor (MPP) of estrogen receptor alpha (ERα) and a specific ERα antibody. Thus, increased intracellular serotonin caused by increased SERT expression may contribute to PAH pathobiology by dysregulation of estrogen metabolic pathways via increased CYP1B1 activity. This promotes PASMC proliferation by the formation of pathogenic metabolites of estrogen that mediate their effects via ERα. Our studies indicate that targeting this pathway in PAH may provide a promising antiproliferative therapeutic strategy
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