1,604 research outputs found

    University of Northern Colorado: Collaborate. Standardize. Grow

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    Chapter 38 in the book Hidden Architectures of Information Literacy Programs: Structures, Practices, and Contexts edited by Carolyn Caffrey Gardner, Elizabeth Galoozis, and Rebecca Halpern. The chapter provides an overview of University Libraries Information Literacy and Undergraduate Support department and discussed the importance of standardizing one-shot curriculum in order to grow a robust information literacy program

    A Typical Large Area Farm in the Murrumbidgee Irrigation Area, N.S.W., Australia

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    EXPLORING T. BRUCEI HEXOKINASE BIOLOGY: LOCALIZATION AND INHIBITION STUDIES

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    Trypanosoma brucei, the causative agent of the disease African sleeping sickness in humans and nagana in animals, is a scourge of sub-Saharan Africa. There is a desperate need for more efficacious therapies for the disease; here we describe research validating T. brucei hexokinase 1 (TbHK1) as a drug therapeutic target for T. brucei infection and the identification and characterization of novel inhibitors of the enzyme by both low throughput and high throughput means. Additionally this thesis introduces efforts at characterizing a second T. brucei hexokinase, focusing mostly on cell biology and the determination of localization. The small molecule quercetin (QCN) was tested and found to inhibit recombinant TbHK1 and spectroscopic study revealed that quercetin binds to TbHK1 proximal to the active site. Genetic experiments revealed that QCN may be cytotoxic to parasites as a result of TbHK inhibition. QCN localized to punctate bodies and the flagellum of T. brucei (consistent with the localization of TbHKs) and over expression of TbHK1 was partially protective. In order to identify additional TbHK1 inhibitors, high through-put screening (HTS) techniques were implemented. HTS of \u3e220,000 compounds yielded 239 primary inhibitors of TbHK1. Of the 239 hits, 15 were confirmed in validation assays as TbHK1 inhibitors; these compounds had a spectrum of activity against trypanosomes, suggesting possible therapeutic leads. In order to initiate characterization of the unknown function of TbHK2, localization studies of TbHK2 were performed. Immunofluorescence assays were employed and TbHK2 was found to localize to the parasite\u27s flagellum, a novel finding that suggests that glycolysis in the parasite may not be limited to glycosomes, organelles related to peroxisomes that heretofore were considered the cellular compartments of glycolysis. Immunofluorescence signal was not exclusive to the flagellum but was observed in the cytosol and glycosomes. To understand the mode of localization, the TbHK sequences were aligned with known and predicted flagellum proteins and a conserved flagellum localization peptide signal was identified in the C-termini of TbHK1 and TbHK2. The peptide signal (RAVLAK) was further explored as a flagellum targeting sequence using fusions to a reporter. These experiments, along with expression and localization of HA-tagged TbHK2 revealed that TbHK2 associates with the flagellum and basal body. This unusual localization suggested that TbHK2 may act as an environmental glucose sensor or perhaps in energy production for the active flagellum. The appendix is comprised of three chapters. The first appendix section is a published paper that focuses on AMP dependent protein kinase from T. brucei. I contributed microscopic expertise (and intellectual input) and am an author on this work. The second appendix section is a summary of research performed to characterize a library of lonidamine analogs against TbHK1 and trypanosomes. And lastly, the third appendix section is the developed assay for testing the viability of T. brucei cells and adaptation for high throughput screening

    An Environmental Toxic Model of Parkinson\u27s Disease: The Fruit Fly

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    Parkinson’s disease (PD) is the second most common neurodegenerative disorder with no known specific cause; although genetic risk factors and/or environmental exposure are thought to be involved. The etiology of PD is currently unknown, although the combination of non-genetic components such as environmental exposures, the accumulation of exposure, and gene-environment interactions are thought to play a major role. However, despite this knowledge it is important to develop better models that parallel PD pathophysiology to further understand the mechanisms underlying dopaminergic neuron (DaN) damage. The use of mammalian models to study the degenerative processes in PD has been the most common approach. However, Drosophila melanogaster use has proven to be important to identify the physiological role of PD associated genes, and to identify pathological mechanisms of environmental toxins associated with sporadic PD. The synthetic drug MPTP (1-methyl- 4-phenyl-1,2,3,4-tetrahydropyridine) has been extensively used to generate animal models of PD. MPTP is the most used toxin model with highly reproducible effects in mice and non-human primates, and its use is a requirement for the development of new therapeutic approaches. However, MPTP neurotoxicity has not been reported in D. melanogaster. Results from the studies presented in this thesis show that Drosophila exposure to MPTP may be a useful model of PD, as evidenced by: loss of brain DA, reduction in tyrosine-hydroxylase positive neurons and inhibition of mitochondrial complex I. Thus, taken together this recapitulates the mammalian mode

    Alien Registration- Smith, Lyda (Houlton, Aroostook County)

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    https://digitalmaine.com/alien_docs/34855/thumbnail.jp

    Importancia relativa de la auditoria Norma Internacional de Auditoria - 320

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    La importancia relativa de la auditoria habla de la responsabilidad que tiene el auditor en la planeación y realización de una auditoria a los estados financieros, el auditor debe considerar la importancia relativa tanto en el momento de la elaboración como en el de la presentación de los estados financieros, para esto debe aplicar su juicio profesional.This rule speaks of the responsibility of the auditor in planning and preforming an audit of financial statements, the auditor should consider the relative importance both at the time of the elaboration and presentation of the financial statements for this should apply their professional judgment.Pregrad

    Messianism in the novels of Romulo Gallegos /

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    SYNTHESIS OF N\u3csub\u3eB\u3c/sub\u3e-ARYL-ASPARTAMIDES, N\u3csub\u3ea\u3c/sub\u3e-ARYLAMIDE-ASPARTATES, AND HYDROXY-L-PROLINE DERIVATIVES AS INHIBITORS OF AMINO ACID TRANSPORT FOR EVALUATING THE GLUTAMINE / GLUTAMATE CYCLE

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    The glutamate / glutamine cycle is most traditionally described as the recycling of L-glutamate and L-glutamine via a concerted effort by a variety of cell membrane spanning amino acid transporters and amino acid converting enzymes, glutaminase and glutamine synthetase. This work details the design and synthesis of amino acid analogs, based off of an L-aspartate or L-proline scaffold, to be evaluated as inhibitors of the amino acid transporters ASCT (subtypes 1 & 2) and the excitatory amino acid transporters EAATs (subtypes 1-3), both involved in the glutamate / glutamine cycle. Furthermore, we have identified a number of potent substrate and nonsubstrate inhibitors of the ASCT and EAAT transporters by electrophysiological and radiolabeled uptake screening. Computational modeling of the synthesized analogs docked into a homology structure suggests a conformational bias that is indeed supported by the pharmacologic activity of our lead compounds. These novel pharmacologic leads will be applied in the design and synthesis of a new generation of inhibitors with greater potency and selectivity towards these transporters of interest

    Una alternativa para el desarrollo del mercadeo en Colombia

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    El presente trabajo busca de una manera constructiva desarrollar el concepto de consumo y sus manifestaciones en la contemporaneidad desde una perspectiva crítica, destacando el análisis de lo que se ha considerado es el consumismo desde la posmodernidad. Todo lo anterior con el objeto de desarrollar un análisis sistemático e integral para su aplicación en la investigación del consumidor y en las estrategias de mercadeo aplicables a los problemas reales y a las necesidades particulares del mercado colombiano y mas ampliamente del latinoamericano. La propuesta incluye también el tener en cuenta herramientas cualitativas (como la etnografía), tomadas de diversas disciplinas tanto de las ciencias económicas como de las ciencias humanas que tendrán en cuenta nuevas variables y nos dirán nuevas cosas acerca del consumidorThe presente paperwork looks for a constructive way to develope the concept of consume and its manifestations in contemporaneity from a critic perspective, remarking the analisys of what has been considered the consumerism fenomena from posmodernity. All this with the porpuse to develop a systematic and integral analysis for its application in the researching of the consumer and the marketing strategies applicables to real problems and to the particular needs of the colombian market and in a wider way to the latinamerican one. This offer inclues also the having in focus of some cualitative tools (like etnography), took from the various disciplines of the economics sciences and human sciences that will have on mind new variables and will tell us more new stuffs about the consume
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