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Title: [FeFe]-hydrogenase substrate transport mechanisms and investigation of algal hydrogen metabolism
Creator: Cornish, Adam
Date: 2012
Collection: Electronic Theses & Dissertations
Description: The global population has recently exceeded 7 billion people and the demand for energy continues to expand as the number of industrialized countries grows. Currently, the energy economy is dominated by the utilization of polluting and non-renewable fossil fuels. Both the collection and use of petroleum-based fuels is destructive to the environment and is not sustainable over a long time-scale, which justifies the investigation into the development of renewable, alternative fuels. Of the...
Show moreThe global population has recently exceeded 7 billion people and the demand for energy continues to expand as the number of industrialized countries grows. Currently, the energy economy is dominated by the utilization of polluting and non-renewable fossil fuels. Both the collection and use of petroleum-based fuels is destructive to the environment and is not sustainable over a long time-scale, which justifies the investigation into the development of renewable, alternative fuels. Of the various fuels that have been proposed, molecular hydrogen (H₂) in particular holds great promise as a clean-burning fuel capable of supplementing the current energy economy, especially as the combustion of H₂ generates only water vapor as by-product. H₂ can be generated via a number of chemical processes, but current H₂ technologies either require fossil fuels as inputs or are energy-inefficient. The biological production of H₂, however, has garnered a great deal of interest because microorganisms are able to drive H₂ synthesis using energy derived from both light and dark fermentative metabolisms. This manner of production does not depend on mining non-renewable resources and microbes can be cultured at the industrial scale without competing with arable land needed for agriculture. H₂ evolution in these microorganisms is dependent on nitrogenases and/or hydrogenases, enzymes which utilize unique metal centers for catalysis. Hydrogenases have been of particular interest for industrial-scale H₂ production because these enzymes are found in a diverse array of organisms and require only protons and electrons as substrates. In particular, [FeFe]-hydrogenases have very high turnover numbers and catalysis can be coupled to photosynthesis. Unfortunately, these enzymes are inactivated by molecular oxygen (O₂), and a number of studies have therefore attempted to engineer O₂-tolerant hydrogenases. However, engineering enzymes to introduce optimal qualities has been impeded by an incomplete understanding of the overall reaction mechanism. Substrate (protons, electrons, and ₂) transport is essential to hydrogenase activity, yet relatively little information is available regarding the intraprotein transport of substrate in [FeFe]-hydrogenase. I focused my investigation on identifying and testing pathways important for substrate transport between the enzyme surface and the active site in the Clostridium pasteurianum [FeFe]-hydrogenase. I have elucidated a key pathway for proton transport and confirmed that two iron-sulfur clusters are essential in an electron transfer relay, contributing to the overall characterization of [FeFe]-hydrogenase activity. Green algae utilize [FeFe]-hydrogenases to catalyze H₂ production using reducing equivalents derived from photosynthesis and these enzymes are an integral component of anaerobic metabolism in these microalgae. I explored the H₂ production capabilities of a multicellular green alga, Volvox carteri, and characterized two hydrogenases likely responsible for this activity. In addition, a unique hydrogenase gene cluster discovered within the Volvox carteri genome provided interesting hints into the origin of [FeFe]-hydrogenase in green algae.
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Title: [Delta]2079-tetrahydrocannabinol-mediated suppression of the Interferon-alpha (IFNalpha) response by plasmacytoid dendritic cells and IFNalpha-mediated activation of T cells in healthy and human immunodeficiency virus (HIV) infected human subjects
Creator: Henriquez, Joseph Edgar
Date: 2018
Collection: Electronic Theses & Dissertations
Description: Δ9-tetrahydrocannabinol (THC) is the primary psychoactive cannabinoid congener in Cannabis sativa and is a well characterized modulator of immune activation. In murine models, treatment with THC can exacerbate viral and bacterial infection, in part, by suppression of the inflammatory cytokine response. One of the key classes of cytokines suppressed by THC is type I interferons (IFN), a group of cytokines consisting of IFNα and IFNβ. The primary source of IFNα during acute antiviral immune...
Show moreΔ9-tetrahydrocannabinol (THC) is the primary psychoactive cannabinoid congener in Cannabis sativa and is a well characterized modulator of immune activation. In murine models, treatment with THC can exacerbate viral and bacterial infection, in part, by suppression of the inflammatory cytokine response. One of the key classes of cytokines suppressed by THC is type I interferons (IFN), a group of cytokines consisting of IFNα and IFNβ. The primary source of IFNα during acute antiviral immune responses is the Plasmacytoid Dendritic Cell (pDC), which can secrete 1000-fold more IFNα than other circulating peripheral blood mononuclear cells (PBMC). Paradoxically, patients infected with human immunodeficiency virus (HIV), a chronic viral infection that causes immunodeficiency via infection and depletion of CD4+ T cells, have fewer circulating pDC with a reduced capacity to secrete IFNα. Furthermore, circulating pDC number has been correlated with CD4+ T cell number and treatment with IFNα can reduce HIV-mediated CD4+ T cell depletion. Conversely, hyperactivation of pDC is associated with T cell exhaustion and is implicated in HIV-associated neurocognitive disorders (HAND). Interestingly, many HIV patients utilize medicinal cannabinoids to combat the effects of chronic HIV infection. The focus of this project was to determine if IFNα-mediated stimulation of T-cells can be suppressed by THC by testing the following hypothesis: THC will suppress TLR-9-dependent activation of pDC, subsequent efficacy of pDC-mediated T cell activation, and CD8+ T cell-mediated activation of astrocytes. These studies revealed that CpG-ODN-induced IFNα secretion and expression of CD83, a costimulatory molecule, by pDC is suppressed by THC in a concentration dependent manner. Furthermore, key intracellular signaling events required for inflammatory cytokine secretion by pDC were suppressed by treatment with THC and CBR2-specific agonists in pDC from healthy donors. Additionally, pDC from HIV+ donors were more sensitive to THC-mediated suppression than pDC from healthy donors. Treatment with THC also inhibited IFNα-mediated activation of CD4+ and CD8+ T cells from healthy and HIV+ donors. Specifically, treatment with THC diminished IFNα-induced IL-7R expression, cognate signaling, and subsequent proliferation. Interestingly, and in contrast to the results in pDC, T cells from HIV+ donors were less sensitive to the suppressive effects of THC. Finally, stimulation by CD3/CD28/IFNα induced the secretion of IFNγ and TNFα by CD8+ T cells from healthy donors. Further, IFNγ and TNFα induced secretion of inflammatory cytokines by U251 astrocytes. Coculture of CD8+ T cells with U251 astrocytes and direct stimulation of U251 astrocytes with recombinant TNFα and IFNγ revealed that treatment with THC reduced both the activation and secretion of cytokines from CD8+ T cells and the subsequent cytokine-mediated stimulation of the U251 astrocytes. Collectively, these studies have provided evidence for the use of cannabinoids in ablating the type of neuroimmune interactions which can lead to HAND by demonstrating that THC can suppress the activation of pDC, and subsequent activation of T cells and astrocytes.
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Title: [Delta]2079-tetrahydrocannabinol suppresses human monocyte activation and monocyte-mediated astrocyte inflammation : implications for HIV-associated neuroinflammation
Creator: Rizzo, Michael Denton
Date: 2019
Collection: Electronic Theses & Dissertations
Description: A hallmark of human immunodeficiency virus (HIV) infection is chronic immune activation and is believed to be one of the major contributors to neuroinflammation and HIV-associated neurocognitive disorder (HAND). Circulating activated monocytes, including those that are CD16⁺, have been implicated in HIV-associated neuroinflammation. These activated monocytes become infected with HIV in the periphery, cross the blood-brain barrier (BBB) and release inflammatory factors, HIV virions and viral...
Show moreA hallmark of human immunodeficiency virus (HIV) infection is chronic immune activation and is believed to be one of the major contributors to neuroinflammation and HIV-associated neurocognitive disorder (HAND). Circulating activated monocytes, including those that are CD16⁺, have been implicated in HIV-associated neuroinflammation. These activated monocytes become infected with HIV in the periphery, cross the blood-brain barrier (BBB) and release inflammatory factors, HIV virions and viral proteins. These factors lead to HIV infection and activation of brain-resident cells, including microglia and astrocytes, driving a pro-inflammatory environment in the brain. Ultimately, these processes contribute to neuronal dysfunction and death, ultimately resulting in cognitive decline in up to 50% of the HIV-infected population. Cannabis is widely used by the HIV-infected population at an estimated prevalence of 23-56% in the United States. [Delta]2079-Tetrahydrocannabinol (THC) and cannabidiol (CBD), two major constituents of cannabis, are known to have immune suppressive and anti-inflammatory properties. The overall objective of this project was to determine whether the cannabinoids, THC and CBD, could suppress monocyte activation and monocyte-mediated astrocyte inflammation, which are key processes implicated in chronic neuroinflammation and HAND. Herein, it is shown that HIV-infected donors using cannabis displayed a lower level of circulating activated (CD16⁺) monocytes and plasma IP-10 compared to non-using HIV-infected donors. Furthermore, in vitro studies revealed that THC but not CBD suppressed monocyte expression of CD16 and secretion of IP-10, suggesting that THC is the major cannabinoid in cannabis promoting the anti-inflammatory effects. To determine whether activated monocytes could promote inflammatory functions of brain-resident glial cells, we developed a human co-culture system utilizing primary monocytes and cell-line/primary fetal astrocytes with viral-related stimulators (IFNa a0333nd a TLR7 agonist - R837). Monocytes, together with IFNa a0333nd/or R837, promoted astrocyte secretion of MCP-1, IL-6 and IP-10. Furthermore, monocyte-derived IL-1v0333 was critical for astrocyte secretion of pro-inflammatory factors, as neutralization of IL-1v0333 strongly hampered the astrocyte response, while direct addition of recombinant IL-1v0333 to astrocyte monocultures mimicked the actions of monocytes. In vitro THC treatment of the R837-stimulated co-culture resulted in decreased astrocyte production of MCP-1 and IL-6, while CBD increased IL-6 production and had no effect on MCP-1 production. With the use of separate monocyte and astrocyte monocultures, THC and CBD were shown to directly target both cell types. Interestingly, THC and CBD were both shown to decrease the percent of astrocytes producing IL-6 and MCP-1, which for THC, is concordant with the co-culture observation. However, the CBD-mediated decrease in IL-6 and MCP-1 production in the astrocyte monoculture differed from the observations in the CBD-treated co-culture. Our findings were explained when THC and CBD were shown to suppress and augment monocyte production of IL-1v0333, respectively. Furthermore, the CBD-mediated augmentation of monocyte-derived IL-1v0333 was able to override the direct CBD suppression on the astrocytes. Collectively, THC but not CBD, impairs monocyte activation and monocyte-driven astrocyte inflammatory responses. In the context of HAND, cannabis use, in particular THC, may decelerate monocyte processes that are implicated in neuroinflammation and cognitive dysfunction.
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Title: Zymogen granule membrane phosphorylation and glycoprotein topology in the exocrine pancreas
Creator: Lewis, Douglas S.
Date: 1977
Collection: Electronic Theses & Dissertations

Title: Zygosporogenesis in Zygorhynchus heterogamus, and zygosporogenesis and sporangiosporogenesis in Mycotypha africana
Creator: Edelmann, Richard Edward
Date: 1994
Collection: Electronic Theses & Dissertations

Title: Zwitterionic excited states of the delta-manifold of quadruply bonded metal dimers
Creator: Engebretson, Daniel Scott
Date: 1998
Collection: Electronic Theses & Dissertations

Title: Zinc-phosphorus interactions in Phaseolus vulgaris
Creator: Lessman, Gary Max
Date: 1967
Collection: Electronic Theses & Dissertations

Title: Zinc levels in soils as related to zinc uptake and yield of Phaseolus vulgaris
Creator: Melton, James Ray
Date: 1968
Collection: Electronic Theses & Dissertations

Title: Zinc availability from soil applied zinc sulfate and zinc EDTA
Creator: Judy, W. H. (William H.,)
Date: 1967
Collection: Electronic Theses & Dissertations

Title: Zeeman background correction with an electrothermal graphite braid atomizer
Creator: Gano, James T.
Date: 1981
Collection: Electronic Theses & Dissertations

Title: Zebra mussels (Dreissena polymorpha) in a Great Lakes coastal marsh : population dynamics and effects on the invertebrates
Creator: Brady, Valerie J.
Date: 1996
Collection: Electronic Theses & Dissertations

Title: Zapotec use of e-commerce : the portrait of Teotitlán Del Valle, Mexico
Creator: Rivers, Deanna Sue
Date: 2005
Collection: Electronic Theses & Dissertations

Title: ZZ 2p-actions on the 2-dimensional and the solid Klein bottles
Creator: Abudiak, Fawaz Mohammad
Date: 1984
Collection: Electronic Theses & Dissertations

Title: ZIKA VIRUS-INDUCED PREGNANCY LOSS : LESSONS FROM THE MOUSE EMBRYO
Creator: Watts, Jennifer Leticia
Date: 2021
Collection: Electronic Theses & Dissertations
Description: Adults contracting Zika virus (ZIKV) exhibit mild cold-like symptoms, whereas newborn babiesexhibit fetal defects ranging from mild growth retardation to miscarriage. Aside from transmission via mosquito, ZIKV is also sexually transmitted, which introduces the possibility that ZIKV infection could occur shortly after conception. However, the mechanisms underlying ZIKV-induced birth defects in early development are not understood. I hypothesize that sexually transmitted ZIKA virus infects...
Show moreAdults contracting Zika virus (ZIKV) exhibit mild cold-like symptoms, whereas newborn babiesexhibit fetal defects ranging from mild growth retardation to miscarriage. Aside from transmission via mosquito, ZIKV is also sexually transmitted, which introduces the possibility that ZIKV infection could occur shortly after conception. However, the mechanisms underlying ZIKV-induced birth defects in early development are not understood. I hypothesize that sexually transmitted ZIKA virus infects embryos around the time of conception, leading to the most severe congenital defects. Consistent with this hypothesis, I have discovered that candidate proviral factors are present in mouse embryo-derived stem cell lines and preimplantation development. However, embryo-derived stem cell lines exhibited low viral infection and replication. Nevertheless, Puerto Rican (ZIKVPR) and the Ugandan (ZIKVUG) strains of ZIKV caused two-cell embryos to undergo developmental arrest. Moreover, infected blastocyst exhibited reduced SOX2 expression, an epiblast cell marker, CDX2 a trophectoderm cell marker, and SOX17, a primitive endoderm marker. Therefore, my results suggest that preimplantation ZIKV infection causes embryonic demise or embryonic cell fate defects depending on the time of infection. My studies are significant to human health because they will further our knowledge of viral infection in early pregnancy and the outcomes.
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Title: Z-source inverter design, analysis, and its application in fuel cell vehicles
Creator: Shen, Miaosen
Date: 2006
Collection: Electronic Theses & Dissertations

Title: Z-source inverter based powerconditioning systems for PV power generation
Creator: Huang, Yi
Date: 2009
Collection: Electronic Theses & Dissertations

Title: Ytterbium based alloys for space-based thermoelectric cooling applications
Creator: Lehr, Gloria Jeannine
Date: 2014
Collection: Electronic Theses & Dissertations
Description: Solid-state thermoelectric devices are of great interest for researchers in many fields due to their potential to increase the efficiency of electrical power generation as well as provide localized heating or cooling in inconvenient environments. Improving the thermoelectric properties of the materials used in these devices is critical to improve their efficiencies and thus feasibility for niche applications. Unfortunately, several of the underlying materials properties are inversely...
Show moreSolid-state thermoelectric devices are of great interest for researchers in many fields due to their potential to increase the efficiency of electrical power generation as well as provide localized heating or cooling in inconvenient environments. Improving the thermoelectric properties of the materials used in these devices is critical to improve their efficiencies and thus feasibility for niche applications. Unfortunately, several of the underlying materials properties are inversely correlated making the thermoelectric figure of merit difficult to improve. In addition, the performance of traditional semiconducting materials is degraded as the operating temperature is decreased. Thus, a unique approach must be taken to achieve larger thermoelectric figures of merit at low temperatures. The research presented here investigates the use of intermediate valence Yb-based compounds for Peltier cooling in the cryogenic regime. These Yb-based intermediate valence compounds demonstrate large Seebeck coefficients at low temperatures, which is essential to a large figure of merit. The Seebeck coefficient is related to the fluctuating Yb valence, a relationship that is investigated in several compounds and utilized to maximize the thermoelectric figure of merit. Solid solutions are synthesized in order to reduce the lattice thermal conductivity as well as alter the size of the unit cell. Changes in the unit cell volume may contribute to a change in the average Yb valence, and thus be utilized to tune the magnitude and peak temperature of the Seebeck coefficient. By reducing the lattice thermal conductivity and optimizing the Seebeck coefficient, enhancements in the thermoelectric figure of merit can be achieved.
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