Matching Items (26)
Description
This study aims to unearth monological and monocultural discourses buried under the power of the dominant biomedical model governing the HIV/AIDS debate. The study responds to an apparent consensus, rooted in Western biomedicine and its "standardizations of knowledge," in the production of the current HIV/AIDS discourse, especially in Sub-Saharan Africa. As a result, biomedicine has become the dominant actor (in) writing and rewriting discourse for the masses while marginalizing other forms of medical knowledge. Specifically, in its development, the Western biomedical model has arguably isolated the disease from its human host and the social experiences that facilitate the disease's transmission, placing it in the realm of laboratories and scientific experts and giving full ownership to Western medical discourse. Coupled with Western assumptions about African culture that reproduce a one-sided discourse informing the social construction of HIV/AIDS in Africa, this Western monopoly thus constrained the extent and efficacy of international prevention efforts. In this context, the goal for this study is not to demonize the West and biomedicine in general. Rather, this study seeks an alternative and less monolithic understanding currently absent in scientific discourses of HIV/AIDS that frequently elevates Western biomedicine over indigenous medicine; the Western expert over the local. The study takes into account the local voices of Sub-Saharan Africa and how the system has affected them, this study utilizes a Foucauldian approach to analyze discourse as a way to explore how certain ways of knowledge are formed in relation to power. This study also examines how certain knowlege is maintaned and reinforced within specific discourses.
ContributorsAbdalla, Mohamed (Author) / Jacobs, Bertram (Thesis advisor) / Robert, Jason (Committee member) / Klimek, Barbara (Committee member) / Arizona State University (Publisher)
Created2014
Description
Natural hydrogenases catalyze the reduction of protons to molecular hydrogen reversibly under mild conditions; these enzymes have an unusual active site architecture, in which a diiron site is connected to a cubane type [4Fe-4S] cluster. Due to the relevance of this reaction to energy production, and in particular to sustainable fuel production, there have been substantial amount of research focused on developing biomimetic organometallic models. However, most of these organometallic complexes cannot revisit the structural and functional fine-tuning provided by the protein matrix as seen in the natural enzyme. The goal of this thesis is to build a protein based functional mimic of [Fe-Fe] hydrogenases. I used a 'retrosynthetic' approach that separates out two functional aspects of the natural enzyme. First, I built an artificial electron transfer domain by engineering two [4Fe-4S] cluster binding sites into an existing protein, DSD, which is a de novo designed domain swapped dimer. The resulting protein, DSD-bis[4Fe-4S], contains two clusters at a distance of 36 Å . I then varied distance between two clusters using vertical translation along the axis of the coiled coil; the resulting protein demonstrates efficient electron transfer to/from redox sites. Second, I built simple, functional artificial hydrogenases by using an artificial amino acid comprising a 1,3 dithiol moiety to anchor a biomimetic [Fe-Fe] active site within the protein scaffold Correct incorporation of the cluster into a model helical peptide was verified by UV-Vis, FTIR, ESI-MS and CD spectroscopy. This synthetic strategy is extended to the de novo design of more complex protein architectures, four-helix bundles that host the di-iron cluster within the hydrophobic core. In a separate approach, I developed a generalizable strategy to introduce organometallic catalytic sites into a protein scaffold. I introduced a biomimetic organometallic complex for proton reduction by covalent conjugation to biotin. The streptavidin-bound complex is significantly more efficient in photocatalytic hydrogen production than the catalyst alone. With these artificial proteins, it will be possible to explore the effect of second sphere interactions on the activity of the diiron center, and to include in the design properties such as compatibility with conductive materials and electrodes.
ContributorsRoy, Anindya (Author) / Ghirlanda, Giovanna (Thesis advisor) / Yan, Hao (Committee member) / Gust, Devens (Committee member) / Arizona State University (Publisher)
Created2014
Description
Regional differences of inventive activity and economic growth are important in economic geography. These differences are generally explained by the theory of localized knowledge spillovers, which argues that geographical proximity among economic actors fosters invention and innovation. However, knowledge production involves an increasing number of actors connecting to non-local partners. The space of knowledge flows is not tightly bounded in a given territory, but functions as a network-based system where knowledge flows circulate around alignments of actors in different and distant places. The purpose of this dissertation is to understand the dynamics of network aspects of knowledge flows in American biotechnology. The first research task assesses both spatial and network-based dependencies of biotechnology co-invention across 150 large U.S. metropolitan areas over four decades (1979, 1989, 1999, and 2009). An integrated methodology including both spatial and social network analyses are explicitly applied and compared. Results show that the network-based proximity better defines the U.S. biotechnology co-invention urban system in recent years. Co-patenting relationships of major biotechnology centers has demonstrated national and regional association since the 1990s. Associations retain features of spatial proximity especially in some Midwestern and Northeastern cities, but these are no longer the strongest features affecting co-inventive links. The second research task examines how biotechnology knowledge flows circulate over space by focusing on the structural properties of intermetropolitan co-invention networks. All analyses in this task are conducted using social network analysis. Evidence shows that the architecture of the U.S. co-invention networks reveals a trend toward more organized structures and less fragmentation over the four years of analysis. Metropolitan areas are increasingly interconnected into a large web of networked environment. Knowledge flows are less likely to be controlled by a small number of intermediaries. San Francisco, New York, Boston, and San Diego monopolize the central positions of the intermetropolitan co-invention network as major American biotechnology concentrations. The overall network-based system comes close to a relational core/periphery structure where core metropolitan areas are strongly connected to one another and to some peripheral areas. Peripheral metropolitan areas are loosely connected or even disconnected with each other. This dissertation provides empirical evidence to support the argument that technological collaboration reveals a network-based system associated with different or even distant geographical places, which is somewhat different from the conventional theory of localized knowledge spillovers that once dominated understanding of the role of geography in technological advance.
ContributorsLee, Der-Shiuan (Author) / Ó Huallacháin, Breandán (Thesis advisor) / Anselin, Luc (Committee member) / Kuby, Michael (Committee member) / Lobo, Jose (Committee member) / Arizona State University (Publisher)
Created2011
Description
Variants of human butyrylcholinesterase (BChE) have been designed to have high cocaine hydrolytic activity. These variants have potential pharmacological applications toward treating cocaine overdose and addiction. These enzymes must be stable in the human body over fairly long periods of time in order to be effective at treating cocaine addiction. Recombinantly expressed BChE, however, tends to be in monomer or dimer oligomeric forms, which are far less stable than the tetramer form of the enzyme. When BChE is transiently expressed in Nicotiana benthamiana, it is produced mainly as monomers and dimers. However, when the protein is expressed through stable transformation, it produces much greater proportions of tetramers. Tetramerization of WT human plasma derived BChE is facilitated by the binding of a proline rich peptide. In this thesis, I investigated if a putative plant-derived analog of the mammalian proline-rich attachment domain caused stably expressed cocaine hydrolase variants of human BChE to undergo tetramerization. I also examined if co-expression of peptides with known proline-rich attachment domains further shifted the monomer-tetramer ratio toward the tetramer.
ContributorsKendle, Robert Player (Author) / Mor, Tsafrir (Thesis director) / Mason, Hugh (Committee member) / Larrimore, Kathy (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Electrical stimulation has previously been effective in neural cells activation within retinas affected by degenerative retinal disease. However current technology has at most allowed blind individuals to perceive light without significant resolution, as implants are limited by the spatial constraints of the eye. Photoreactive nanoparticles may provide a solution to this issue, as their small size would allow for the incorporation of higher numbers of stimulatory elements, thus increasing visual resolution. Semiconductive nanocrystal quantum dots (QDs) and gold nanoparticles (AuNPs) both exhibit photoreactive properties which may result in sufficient electrical stimulation to activate neural cells in the retina. This study investigated the electrochemistry and photoreactivity of QDs and AuNPs encapsulated within the hydrophobic region of small unilamellar lipid vesicles (SUVs) to evaluate their potential for application in retinal stimulation. Absorbance of the constructs was evaluated on the day of fabrication and 24 hours later to determine the ability of the particles to react to light while encapsulated, as well as to evaluate stability of the construct over time. Electrical impedance spectroscopy (EIS) was conducted at both time points to determine the electrochemical character of the bilayer and further evaluate construct stability. Although quantum dots may increase the stability of the bilayer over time and improve its capacitative properties, lipid encapsulation appears to obscure the photoreactive properties of the quantum dots. In the case of gold nanoparticles, the construct is initially stabilized but deteriorates more quickly than those SUVs containing quantum dots, as evidenced by an increase in substrate diffusion. Additionally, although these constructs are more photoreactive than those containing QDs, the increase in absorbance is observed primarily in a range below that of the visible spectrum, a feature which is of limited use for the proposed application. Further studies should investigate alternative methods of nanoparticle capping to improve stability and absorbance in this system.
ContributorsReidell, Olivia Rose (Author) / La Belle, Jeffrey T (Thesis director) / Coursen, Jerry (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Influenza is a deadly disease for which effective vaccines are sorely lacking. This is largely due to the phenomena of antigenic shift and drift in the influenza virus's surface proteins, hemagglutinin (HA) and neuraminidase (NA). The ectodomain of the matrix 2 protein (M2e) of influenza A, however, has demonstrated high levels of conservation. On its own it is poorly immunogenic and offers little protection against influenza infections, but by combining it with a potent adjuvant, this limitation may be overcome. Recombinant immune complexes, or antigens fused to antibodies that have been engineered to form incredibly immunogenic complexes with one another, were previously shown to be useful, immunogenic platforms for the presentation of various antigens and could provide the boost in immunogenicity that M2e needs to become a powerful universal influenza A vaccine. In this thesis, genetic constructs containing geminiviral replication proteins and coding for a consensus sequence of dimeric M2e fused to antibodies featuring complimentary epitopes and epitope tags were generated and used to transform Agrobacterium tumefaciens. The transformed bacteria was then used to cause Nicotiana benthamiana to transiently express M2e-RICs at very high levels, with enough RICs being gathered to evaluate their potency in future mouse trials. Future directions and areas for further research are discussed.
ContributorsFavre, Brandon Chetan (Author) / Mason, Hugh (Thesis director) / Mor, Tsafrir (Committee member) / Diamos, Andrew (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Photosynthesis is the process by which plants, algae, and bacteria use light energy to synthesize organic compounds to use as energy. Among these organisms are a kind of purple photosynthetic bacteria called Rhodobacter sphaeroides, a non-sulfur purple bacteria that grows aerobically in the dark by respiration. There have been many contributions throughout the history of this group of bacteria. Rhodobacter sphaeroides is metabolically very diverse as it has many different ways to obtain energy--aerobic respiration and anoxygenic photosynthesis being just a couple of the ways to do so. This project is part of a larger ongoing project to study different mutant strains of Rhodobacter and the different ways in which carries out electron transfer/photosynthesis. This thesis focused on the improvements made to protocol (standard procedure of site directed mutagenesis) through a more efficient technique known as infusion.
ContributorsNucuta, Diana Ileana (Author) / Woodbury, Neal (Thesis director) / Lin, Su (Committee member) / Loskutov, Andrey (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
Fermentative bioproduction is an efficient production avenue for many small organic acids with less greenhouse gas emissions than petrochemical conversion. Export of these organic acids from the cell is proposed to be mediated by networks of transmembrane transport proteins. However characterization of full transporter networks or the substrate promiscuity of individual transporters is often incomplete. Here, we used a cheminformatic approach to predict previously unknown native activity of E. coli transporters based on substrate promiscuity. Experimental validation in characterized several major putative malate exporters, whereas others were characterized as weak putative lactate exporters. The lactate export network remains incompletely characterized and might be mediated by a large, evolved network of promiscuous transporters.
ContributorsSchneider, Aidan (Author) / Wang, Xuan (Thesis director) / Varman, Arul (Committee member) / Nielsen, David (Committee member) / Department of Finance (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
Machine learning for analytics has exponentially increased in the past few years due to its ability to identify hidden insights in data. It also has a plethora of applications in healthcare ranging from improving image recognition in CT scans to extracting semantic meaning from thousands of medical form PDFs. Currently in the BioElectrical Systems and Technology Lab, there is a biosensor in development that retrieves and analyzes data manually. In a proof of concept, this project uses the neural network architecture to automatically parse and classify a cardiac disease data set as well as explore health related factors impacting cardiac disease in patients of all ages.
ContributorsMurella, Akhila Sainagaki (Author) / Blain-Christen, Jennifer (Thesis director) / Meuth, Ryan (Committee member) / Computer Science and Engineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / School of the Arts, Media and Engineering (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Plasmid DNA (pDNA) purification has been extensively investigated for various biological and biochemical applications such as transfection, polymerase chain reaction and DNA therapeutics. In the previous paper, we have described the synthesis, characterization and evaluation of microbeads (“Amikabeads”) derived from aminoglycoside amikacin for pDNA binding via anion-exchange chromatography. Here, we investigated the pDNA binding performance of conjugating Amikabeads with two highly specific DNA binding ligands via minor groove hydrophobic interaction. The pDNA maximum binding capacity of doxorubicin drug-conjugated Amikabeads (“doxo-beads”) was found out to be 429 μg pDNA/ mg of doxo-beads with a Langmuir constant of 8.21*10-4 L/mg, whereas the binding performance of berenil drug-conjugated "mikabeads (“berenil-beads”) was 142 μg pDNA/mg of berenil-beads with a adsorption constant of 4.71*10-5 L/mg. In addition, the desorption percentage of doxo-beads and berenil-beads was obtained as 52% and 41%, respectively. Our results indicate that by conjugating with highly specific DNA binding ligands, Amikabeads-drug complex enhances the pDNA binding performance and contains a promising potential for future applications in biotechnology field.
ContributorsLin, Nan (Author) / Rege, Kaushal (Thesis director) / Grandhi, Taraka Sai Pavan (Committee member) / Chemical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05