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Fluoroquinolone antibiotics have been known to cause severe, multisystem adverse side effects, termed fluoroquinolone toxicity (FQT). This toxicity syndrome can present with adverse effects that vary from individual to individual, including effects on the musculoskeletal and nervous systems, among others. The mechanism behind FQT in mammals is not known, although various possibilities have been investigated. Among the hypothesized FQT mechanisms, those that could potentially explain multisystem toxicity include off-target mammalian topoisomerase interactions, increased production of reactive oxygen species, oxidative stress, and oxidative damage, as well as metal chelating properties of FQs. This review presents relevant information on fluoroquinolone antibiotics and FQT and explores the mechanisms that have been proposed. A fluoroquinolone-induced increase in reactive oxygen species and subsequent oxidative stress and damage presents the strongest evidence to explain this multisystem toxicity syndrome. Understanding the mechanism of FQT in mammals is important to aid in the prevention and treatment of this condition.
ContributorsHall, Brooke Ashlyn (Author) / Redding, Kevin (Thesis director) / Wideman, Jeremy (Committee member) / Borges, Chad (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
The contemporary architectural pedagogy is far removed from its ancestry: the classical Beaux-Arts and polytechnic schools of the 19th century and the Bauhaus and Vkhutemas models of the modern period. Today, the "digital" has invaded the academy and shapes pedagogical practices, epistemologies, and ontologies within it, and this invasion is reflected in teaching practices, principles, and tools. Much of this digital integration goes unremarked and may not even be explicitly taught. In this qualitative research project, interviews with 18 leading architecture lecturers, professors, and deans from programs across the United States were conducted. These interviews focused on advanced practices of digital architecture, such as the use of digital tools, and how these practices are viewed. These interviews yielded a wealth of information about the uses (and abuses) of advanced digital technologies within the architectural academy, and the results were analyzed using the methods of phenomenology and grounded theory. Most schools use digital technologies to some extent, although this extent varies greatly. While some schools have abandoned hand-drawing and other hand-based craft almost entirely, others have retained traditional techniques and use digital technologies sparingly. Reasons for using digital design processes include industry pressure as well as the increased ability to solve problems and the speed with which they could be solved. Despite the prevalence of digital design, most programs did not teach related design software explicitly, if at all, instead requiring students (especially graduate students) to learn to use them outside the design studio. Some of the problems with digital design identified in the interviews include social problems such as alienation as well as issues like understanding scale and embodiment of skill.
ContributorsAlqabandy, Hamad (Author) / Brandt, Beverly (Thesis advisor) / Mesch, Claudia (Committee member) / Newton, David (Committee member) / Arizona State University (Publisher)
Created2012
Description
In the middle of the 20th century, juried annuals of Native American painting in art museums were unique opportunities because of their select focus on two-dimensional art as opposed to "craft" objects and their inclusion of artists from across the United States. Their first fifteen years were critical for patronage and widespread acceptance of modern easel painting. Held at the Philbrook Art Center in Tulsa (1946-1979), the Denver Art Museum (1951-1954), and the Museum of New Mexico Art Gallery in Santa Fe (1956-1965), they were significant not only for the accolades and prestige they garnered for award winners, but also for setting standards of quality and style at the time. During the early years of the annuals, the art was changing, some moving away from conventional forms derived from the early art training of the 1920s and 30s in the Southwest and Oklahoma, and incorporating modern themes and styles acquired through expanded opportunities for travel and education. The competitions reinforced and reflected a variety of attitudes about contemporary art which ranged from preserving the authenticity of the traditional style to encouraging experimentation. Ultimately becoming sites of conflict, the museums that hosted annuals contested the directions in which artists were working. Exhibition catalogs, archived documents, and newspaper and magazine articles about the annuals provide details on the exhibits and the changes that occurred over time. The museums' guidelines and motivations, and the statistics on the award winners reveal attitudes toward the art. The institutions' reactions in the face of controversy and their adjustments to the annuals' guidelines impart the compromises each made as they adapted to new trends that occurred in Native American painting over a fifteen year period. This thesis compares the approaches of three museums to their juried annuals and establishes the existence of a variety of attitudes on contemporary Native American painting from 1946-1960. Through this collection of institutional views, the competitions maintained a patronage base for traditional style painting while providing opportunities for experimentation, paving the way for the great variety and artistic progress of Native American painting today.
ContributorsPeters, Stephanie (Author) / Duncan, Kate (Thesis advisor) / Fahlman, Betsy (Thesis advisor) / Mesch, Claudia (Committee member) / Arizona State University (Publisher)
Created2012
Description
Cancer claims hundreds of thousands of lives every year in US alone. Finding ways for early detection of cancer onset is crucial for better management and treatment of cancer. Thus, biomarkers especially protein biomarkers, being the functional units which reflect dynamic physiological changes, need to be discovered. Though important, there are only a few approved protein cancer biomarkers till date. To accelerate this process, fast, comprehensive and affordable assays are required which can be applied to large population studies. For this, these assays should be able to comprehensively characterize and explore the molecular diversity of nominally "single" proteins across populations. This information is usually unavailable with commonly used immunoassays such as ELISA (enzyme linked immunosorbent assay) which either ignore protein microheterogeneity, or are confounded by it. To this end, mass spectrometric immuno assays (MSIA) for three different human plasma proteins have been developed. These proteins viz. IGF-1, hemopexin and tetranectin have been found in reported literature to show correlations with many diseases along with several carcinomas. Developed assays were used to extract entire proteins from plasma samples and subsequently analyzed on mass spectrometric platforms. Matrix assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) mass spectrometric techniques where used due to their availability and suitability for the analysis. This resulted in visibility of different structural forms of these proteins showing their structural micro-heterogeneity which is invisible to commonly used immunoassays. These assays are fast, comprehensive and can be applied in large sample studies to analyze proteins for biomarker discovery.
ContributorsRai, Samita (Author) / Nelson, Randall (Thesis advisor) / Hayes, Mark (Thesis advisor) / Borges, Chad (Committee member) / Ros, Alexandra (Committee member) / Arizona State University (Publisher)
Created2012
Description
Bacteria play a vital role in the world ecosystem, more importantly human health and disease. The capability to differentiate and identify these microorganisms serves as an important research objective. In past years, separations-based approaches have served as a way to observe and identify bacteria based on their characteristics. Gradient insulator dielectrophoresis (g-iDEP) provides benefits in identifying serotypes of a single species with precise separation. Separation of Staphylococcus epidermidis in a single g-iDEP microchannel is conducted exploiting their electrophoretic and electrokinetic properties. The cells were captured and concentrated at gates with interacting forces within the microchannel to clearly distinguish between the two strains. These results provide support for g-iDEP serving as a separating method and, furthermore, future clinical applications.
ContributorsDavis, Paige Elizabeth (Author) / Hayes, Mark (Thesis director) / Borges, Chad (Committee member) / Jones, Paul (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor)
Created2015-05
Description
Background: High risk types of human papillomavirus (HPV) are known to cause cancer, including cervical (99%) and oropharyngeal cancer (70%). HPV type 16 is the most common subtype. Three antigens that are critical for integration or tumor progression are E2, E6 and E7. In this study, we developed a systematic approach to identify naturally-processed HPV16-derived HLA class I epitopes for immunotherapy development. Methods: K562 cells, which lack HLA expression, were transduced with each HPV16 antigen using lentivirus and supertransfected with HLA-A2 by nucleofection. Stable cell lines expressing each antigen were selected for and maintained throughout the investigation. In order to establish a Gateway-compatible vector for robust transient gene expression, a Gateway recombination expression cloning cassette was inserted into the commercial Lonza pMAX GFP backbone, which has been experimentally shown to display high transfection expression efficiency. GFP was cloned into the vector and plain K562 cells were transfected with the plasmid by nucleofection. Results: Expression of K562-A2 was tested at various time points by flow cytometry and A2 expression was confirmed. Protein expression was shown for the transduced K562 E7 by Western blot analysis. High transfection efficiency of the pMAX_GFP_Dest vector (up to 97% GFP+ cells) was obtained 48 hours post transfection, comparable to the commercial GFP-plasmid. Conclusion: We have established a rapid system for target viral antigen co-expression with single HLA molecules for analysis of antigen presentation. Using HPV as a model system, our goal is to identify specific antigenic peptide sequences to develop immunotherapeutic treatments for HPV-associated cancers.
ContributorsVarda, Bianca Marie (Author) / Anderson, Karen (Thesis director) / Borges, Chad (Committee member) / Krishna, Sri (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Protein AMPylation is a recently discovered and relatively unstudied post-translational modification (PTM). AMPylation has previously been shown to play an important role in metabolic regulation and host pathogenesis in bacteria, but the recent identification of potential AMPylators across many species in every domain of life has supported the possibility that AMPylation could be a more fundamental and physiologically significant regulatory PTM. For the first time, we characterized the auto-AMPylation capability of the human protein SOS1 through in vitro AMPylation experiments using full-length protein and whole-domain truncation mutants. We found that SOS1 can become AMPylated at a tyrosine residue possibly within the Cdc25 domain of the protein, the Dbl homology domain is vital for efficient auto-AMPylation activity, and the C-terminal proline-rich domain exhibits a complex regulatory function. The proline-rich domain alone also appears to be capable of catalyzing a separate, unidentified covalent self-modification using a fluorescent ATP analogue. Finally, SOS1 was shown to be capable of catalyzing the AMPylation of two endogenous human protein substrates: a ubiquitous, unidentified protein of ~49kDa and another breast-cancer specific, unidentified protein of ~28kDa.
ContributorsOber-Reynolds, Benjamin John (Author) / LaBaer, Joshua (Thesis director) / Borges, Chad (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
In this thesis, glycan nodes, the basic subunits of complex biological sugars, were studied to determine the reproducibility of gas chromatography-mass spectrometry (GC/MS) based methylation analysis of whole blood plasma by normalization using an internal standard of heavy permethylated glycans. Glycans are complex biological sugars that have a variety of applications in the human body and will display aberrant compositions when produced by cancerous cells. Thus an assay to determine their composition can be used as a diagnostic tool. It was shown that the assay may have potential use, but needs further refinement to become an improvement over current methods by analyzing the results of ratio-determination and replicate experiments.
ContributorsMiyasaki, Tyler Takeo (Author) / Borges, Chad (Thesis director) / Van Horn, Wade (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Chemical Engineering Program (Contributor)
Created2015-05
Description
Western diets, high in dietary fat and red meat, are associated with hyperglycemia and weight gain, symptoms that promote insulin resistance and diabetes. Previous studies have shown that elevated glucose promotes glycation of circulating proteins such as albumin, which is thought to lead to hyperglycemia complications. It was hypothesized that diets with no meat consumption (pesco-vegetarian and lacto-vegetarian) would reduce protein glycation, in comparison to a diet with meat. Forty six healthy adult omnivorous subjects were randomized into one of three groups and instructed to either consume red meat (i.e. meat) or poultry twice per day (control), eliminate meat and increase fish consumption (pesco-vegetarian), or adopt a vegetarian diet devoid of fish, meat or poultry (lacto-vegetarian) for four weeks. Fasting plasma samples were collected from participants at baseline and after 4 weeks of the dietary intervention. Plasma glucose concentrations were measured using a commercially available kit. Percent glycated albumin was measured on a separate aliquot of plasma by mass spectrometry. Plasma glucose concentrations were significantly increased following 4-weeks of pesco-vegetarian diet (P=0.002, paired t-test). Neither the lacto-vegetarian (P=0.898) or the control diet (P=0.233) affected plasma glucose concentrations. Despite the significant increase in plasma glucose following a pesco-vegetarian diet, no change in percent glycated albumin was observed (P>0.50, ANOVA). These findings may indicate a protective effect of the pesco-vegetarian diet on protein glycation in the presence of elevated plasma glucose and suggest the need for additional studies to examine the link between increased fish consumption and glucose regulation.
ContributorsRaad, Noor (Author) / Sweazea, Karen (Thesis director, Committee member) / Borges, Chad (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
This project is a critical look at Chicano artist Vincent Valdez's 2002-2004 series Stations. The theoretical framework for this work is the concept of cultural citizenship, which refers to a variety of ways in which marginalized groups of people create, fight for, and retain space, identity, and rights within American society through acts of daily life. This research considers how the ten large-scale charcoal drawings that comprise Stations contribute to the construction and representation of distinct and unique Latino spaces and identities. Valdez establishes space in the sense of belonging and community engagement that his work allows. Within this context, thoughtful attention is paid to the cultural meaning of the artist's subject choices of boxing and religion. This research considers the significance of these subject choices and how the connections between the two create unique spaces of shared experience and consciousness for a viewer of the work. However, the parallels that Valdez draws between the Christ figure and his boxer also allow for a careful examination of the representations and contradictions of contemporary constructions of masculinity that are present in the series. Within this project, the work of Gloria Anzaldúa is critical in understanding and discussing the fluid nature of Chicano identity. This study also considers how in the tradition of Chicana writers, Valdez expresses and affirms identity through autobiographical methods. Further, the artist's use of charcoal to create these large scale drawings is considered for its narrative qualities. This study concludes that Valdez's series Stations is an act of cultural citizenship.
ContributorsStemm Patel, Shannon (Author) / Malagamba-Ansótegui, Amelia (Thesis advisor) / Mesch, Claudia (Committee member) / Sweeney, Gray (Committee member) / Arizona State University (Publisher)
Created2010