1,261 research outputs found

    Flame temperatures in an internal combustion engine measured by spectral line reversal

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    Reinforced concrete settling basin

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    Includes 6 folded architectural drawings.Last 12 leaves are blank."A thesis for the degree of Bachelor of Science in Civil Engineering."Manuscript copy.The basin is designed for the City of St. Joseph, Missouri, to partly relieve the present basin, which has become inadequate for the present needs of the city. The capacity of the basin is 5,000,000 gallons, which is one fourth more than the old basin. The system or method used is known as the "Continuous Flow" type of settling basin.Digitized at the University of Missouri--Columbia MU Libraries Digitization Lab in 2011

    Efficiency in public management

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    In a word my conclusion is this: that more than any private business or undertaking, the public office is in need of agencies which may develop complete, accurate, and prompt information about the business in hand; that efficient administration depends on the erection of well-equipped conning towers; that without instruments of precision, not only is the officer handicapped, but the public is without the means of making government responsible; between the government and the people is an impassable gulf and an impenetrable darkness, which produce discontent and suspicion, on the one hand, and deprive the officer of his support necessary to the success of a constructive program on the other

    Synthetic dibenzofurans structurally related to known analgesics

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    A Role for Histone Modification in the Mechanism of Action of Antidepressant and Stimulant Drugs: a Dissertation

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    Depression and stimulant drug addiction each result in massive losses of health, productivity and human lives every year. Despite decades of research, current treatment regimes for depression are ineffective in approximately half of all patients. Therapy available to stimulant drug addicts is largely ineffective and moreover, dedicated treatments for drug dependence (including abuse of cocaine) are non-existent. Thus, there is a pressing need to further understanding of the molecular mechanisms underlying these disorders in order to develop novel, targeted therapeutic strategies. Chromatin remodeling, including changes in histone acetylation, has been proposed to play a role in both the etiology and treatment of depression and stimulant abuse. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate numerous cellular processes, including transcription, cell cycle progression and differentiation. Moreover, histone acetylation has been shown to regulate hippocampal neurogenesis, a cellular response associated with the pathogenesis and treatment of depression and stimulant abuse (Hsieh et al., 2004, Yamaguchi et al., 2004, Fischer et al., 2007). Ultimately, such basic cellular processes impact higher order function, namely cognition and emotion. Indeed, recent studies suggest that HDAC activity in selected forebrain regions, including ventral striatum and hippocampus, modulate stimulant- and antidepressantinduced behavior (Kumar et al., 2005, Tsankova et al., 2006a, Fischer et al., 2007). These reports highlight an association between chromatin remodeling and diverse behavioral changes, including changes induced by the pleiotropic HDAC inhibitor, sodium butyrate (SB), (Kumar et al., 2005, Tsankova et al., 2006a, Fischer et al., 2007). However, behavioral, brain-metabolic and molecular effects of SB treatment in the context of rodent models of depression, dopaminergic sensitization and repeated cocaine administration remained unclear. The work described in this thesis illustrates the potential for chromatin modifying drugs in mechanisms underlying the experimental pharmacology of depression and stimulant addiction. Specifically, the data presented here support the view that treatment with the short chain fatty acid, sodium butyrate enhances: (1) antidepressant-like behavioral effects of the selective serotonin reuptake inhibitor (SSRI), fluoxetine (2) locomotor sensitization induced by repeated administration of the dopamine D1/D5 receptor agonist SKF82958; and(3) brain metabolic activation upon repeated cocaine administration as evidenced by fMRI in awake rats. Furthermore, this report provides evidence that these treatment paradigms will result in chromatin modification changes associated with active transcription, in addition to increased mRNA levels of plasticity-associated genes, including brain-derived neurotrophic factor (BDNF) at key brain regions implicated in the pathogenesis of depression and stimulant addiction. To date, little is known regarding the underlying mechanisms of action mediating the enhancing effects of sodium butyrate on the various antidepressant- and stimulantrelated paradigms. Our findings underscore the potential of chromatin-modifying drugs to profoundly affect the behavioral response of an animal to antidepressant and stimulant drugs and warrants consideration in the context of developing novel therapeutic strategies
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