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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 gameplay experience can be understood as an interaction between player and game design characteristics. A greater understanding of these characteristics can be gained through empirical means. Subsequently, an enhanced knowledge of these characteristics should enable the creation of games that effectively generate desirable experiences for players. The purpose of this study was to investigate the relationships between gameplay enjoyment and the individual characteristics of gaming goal orientations, game usage, and gender. A total of 301 participants were surveyed and the data were analyzed using Structural Equation Modeling (SEM). This led to an expanded Gameplay Enjoyment Model (GEM) with 41 game features, an overarching Enjoyment factor, and 9 specific components, including Challenge, Companionship, Discovery, Fantasy, Fidelity, Identity, Multiplayer, Recognition, and Strategy. Furthermore, the 3x2 educational goal orientation framework was successfully applied to a gaming context. The resulting 3x2 Gaming Goal Orientations (GGO) model consists of 18 statements that describe players' motivations for gaming, which are distributed across the six dimensions of Task-Approach, Task-Avoidance, Self-Approach, Self-Avoidance, Other-Approach, and Other-Avoidance. Lastly, players' individual characteristics were used to predict gameplay enjoyment, which resulted in the formation of the GEM-Individual Characteristics (GEM-IC) model. In GEM-IC, the six GGO dimensions were the strongest predictors. Meanwhile, game usage variables like multiplayer, genre, and platform preference, were minimal to moderate predictors. Although commonly appearing in games research, gender and game time commitment variables failed to predict enjoyment. The results of this study enable important work to be conducted involving game experiences and player characteristics. After several empirical iterations, GEM is considered suitable to employ as a research and design tool. In addition, GGO should be useful to researchers interested in how player motivations relate to gameplay experiences. Moreover, GEM-IC points to several variables that may prove useful in future research. Accordingly, it is posited that researchers will derive more meaningful insights on games and players by investigating detailed, context-specific characteristics as compared to general, demographic ones. Ultimately, it is believed that GEM, GGO, and GEM-IC will be useful tools for researchers and designers who seek to create effective gameplay experiences that meet the needs of players.
ContributorsQuick, John (Author) / Atkinson, Robert (Thesis advisor) / McNamara, Danielle (Committee member) / Nelson, Brian (Committee member) / Savenye, Wilhelmina (Committee member) / Arizona State University (Publisher)
Created2013
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
Do good readers embody more or less? The current investigation examined embodiment effects as a function of individual reading skill in the context of two cognitive theories of reading comprehension. The Construction-Integration model predicts that sensorimotor activity during reading will correlate negatively with reading skill, because good readers focus on relations among abstract ideas derived from the text. Supposedly those abstract ideas have little or no sensorimotor content, hence any sensorimotor activity while reading is wasted effort. In contrast, the simulation theory predicts that sensorimotor activity will correlate positively with reading skill, because good readers create a simulation of what is happening within the text to comprehend it. The simulation is based in neural and bodily systems of action, perception, and emotion. These opposing predictions were tested using the reading-by-rotation paradigm to measure embodiment effects. Those effects were then correlated with reading skill measured using the Gates-McGinite standardized reading test. Analyses revealed an unexpected interaction between condition and congruency, and a negative relationship between embodiment and reading skill. Several caveats to the results are discussed.
ContributorsRakestraw, Hannah Marie (Author) / Glenberg, Arthur (Thesis director) / McNamara, Danielle (Committee member) / Van Gelderen, Elly (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / School of Film, Dance and Theatre (Contributor) / Department of English (Contributor)
Created2013-12
Description
The influence that agent-student interaction has on learning can have significant outcomes in an ITS. Agent-human relationships within ITSs possess elements modeled by teacher-student relationships in the classroom. As a result, student perceptions of pedagogical agents can affect learning outcomes. An efficient environment can depend upon the intention for which the virtual agent is designed. As researchers gain more knowledge on the effect that characteristics outside of language have on learning, agent pedagogies can begin to be developed and perfected. In this research, we investigate the role that the pedagogical agent's gender has in the learning process. Specifically, we examine whether gender of agent interacts with gender of student to influence variables related to affect and motivation in ITSs
ContributorsStone, Melissa Linn (Author) / McNamara, Danielle (Thesis director) / Snow, Erica (Committee member) / Barrett, The Honors College (Contributor) / School of Film, Dance and Theatre (Contributor) / Department of Psychology (Contributor)
Created2014-05
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