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Description
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
In an effort to begin validating the large number of discovered candidate biomarkers, proteomics is beginning to shift from shotgun proteomic experiments towards targeted proteomic approaches that provide solutions to automation and economic concerns. Such approaches to validate biomarkers necessitate the mass spectrometric analysis of hundreds to thousands of human samples. As this takes place, a serendipitous opportunity has become evident. By the virtue that as one narrows the focus towards "single" protein targets (instead of entire proteomes) using pan-antibody-based enrichment techniques, a discovery science has emerged, so to speak. This is due to the largely unknown context in which "single" proteins exist in blood (i.e. polymorphisms, transcript variants, and posttranslational modifications) and hence, targeted proteomics has applications for established biomarkers. Furthermore, besides protein heterogeneity accounting for interferences with conventional immunometric platforms, it is becoming evident that this formerly hidden dimension of structural information also contains rich-pathobiological information. Consequently, targeted proteomics studies that aim to ascertain a protein's genuine presentation within disease- stratified populations and serve as a stepping-stone within a biomarker translational pipeline are of clinical interest. Roughly 128 million Americans are pre-diabetic, diabetic, and/or have kidney disease and public and private spending for treating these diseases is in the hundreds of billions of dollars. In an effort to create new solutions for the early detection and management of these conditions, described herein is the design, development, and translation of mass spectrometric immunoassays targeted towards diabetes and kidney disease. Population proteomics experiments were performed for the following clinically relevant proteins: insulin, C-peptide, RANTES, and parathyroid hormone. At least thirty-eight protein isoforms were detected. Besides the numerous disease correlations confronted within the disease-stratified cohorts, certain isoforms also appeared to be causally related to the underlying pathophysiology and/or have therapeutic implications. Technical advancements include multiplexed isoform quantification as well a "dual- extraction" methodology for eliminating non-specific proteins while simultaneously validating isoforms. Industrial efforts towards widespread clinical adoption are also described. Consequently, this work lays a foundation for the translation of mass spectrometric immunoassays into the clinical arena and simultaneously presents the most recent advancements concerning the mass spectrometric immunoassay approach.
ContributorsOran, Paul (Author) / Nelson, Randall (Thesis advisor) / Hayes, Mark (Thesis advisor) / Ros, Alexandra (Committee member) / Williams, Peter (Committee member) / Arizona State University (Publisher)
Created2011
Description
This project uses the tintype process to create contemporary portraits. The tintype is a nineteenth century photographic process that creates a direct positive on a sheet of metal. The images were created using the same process from the 1800s, as well as a more contemporary method. The natural imperfections caused by both processes were used to help examine the intimacy and emotion present in the portraits.
ContributorsRichey, Jordyn Elizabeth (Author) / Danh, Binh (Thesis director) / Schneider, Betsy (Committee member) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / School of Art (Contributor)
Created2014-05
Description
Signal processing techniques have been used extensively in many engineering problems and in recent years its application has extended to non-traditional research fields such as biological systems. Many of these applications require extraction of a signal or parameter of interest from degraded measurements. One such application is mass spectrometry immunoassay (MSIA) which has been one of the primary methods of biomarker discovery techniques. MSIA analyzes protein molecules as potential biomarkers using time of flight mass spectrometry (TOF-MS). Peak detection in TOF-MS is important for biomarker analysis and many other MS related application. Though many peak detection algorithms exist, most of them are based on heuristics models. One of the ways of detecting signal peaks is by deploying stochastic models of the signal and noise observations. Likelihood ratio test (LRT) detector, based on the Neyman-Pearson (NP) lemma, is an uniformly most powerful test to decision making in the form of a hypothesis test. The primary goal of this dissertation is to develop signal and noise models for the electrospray ionization (ESI) TOF-MS data. A new method is proposed for developing the signal model by employing first principles calculations based on device physics and molecular properties. The noise model is developed by analyzing MS data from careful experiments in the ESI mass spectrometer. A non-flat baseline in MS data is common. The reasons behind the formation of this baseline has not been fully comprehended. A new signal model explaining the presence of baseline is proposed, though detailed experiments are needed to further substantiate the model assumptions. Signal detection schemes based on these signal and noise models are proposed. A maximum likelihood (ML) method is introduced for estimating the signal peak amplitudes. The performance of the detection methods and ML estimation are evaluated with Monte Carlo simulation which shows promising results. An application of these methods is proposed for fractional abundance calculation for biomarker analysis, which is mathematically robust and fundamentally different than the current algorithms. Biomarker panels for type 2 diabetes and cardiovascular disease are analyzed using existing MS analysis algorithms. Finally, a support vector machine based multi-classification algorithm is developed for evaluating the biomarkers' effectiveness in discriminating type 2 diabetes and cardiovascular diseases and is shown to perform better than a linear discriminant analysis based classifier.
ContributorsBuddi, Sai (Author) / Taylor, Thomas (Thesis advisor) / Cochran, Douglas (Thesis advisor) / Nelson, Randall (Committee member) / Duman, Tolga (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
Since the early 1990's, researchers have been looking at intersections between education and music. After a highly popular study correlating listening to Mozart to temporary increases in spatial reasoning, many other researchers tried to find a link between different musical genres and learning outcomes. Using three musical treatments (Pop, classical, silence), this study had subjects (N=34) complete a reading-based task whereupon they were tested on their comprehension. Using a suite of sensors, data was collected to analyze the participants' emotions and affect while they read from an educational psychology textbook. The present study has two major focuses: They detail whether (1) changes in musical condition affect learning outcomes and (2) whether changes in musical condition affect emotional outcomes. The popular conception that listening to classical music makes you smarter was proven false long ago, but there may actually be some merit to using music to assist one in studying. While there were no significant changes in test scores depending on musical condition; frustration levels were significantly lower for those who listened to classical instead of pop music.
ContributorsPaley, Benjamin Henry (Author) / Atkinson, Robert (Thesis director) / Feisst, Sabine (Committee member) / Barrett, The Honors College (Contributor) / School of Music (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor)
Created2015-05
Description
This thesis was an analysis of items in the Late Adolescent Home Observation for Measure of the Environment (LA HOME) after the first wave of N = 138 interviews. The purpose of this project was to learn how to utilize a statistical software such as SPSS to analyze items and interpret results. Frequency analysis, inter-rater reliability (IRR), correlation analysis, internal consistency using Cronbach's alpha, and feedback from research assistants were considered when deciding which items should be eliminated from the measure. After running these analyses, ten items were suggested for deletion including: clean, adolescent's room allows for privacy, reference materials, news, family encourages adolescent to think independently, community service, parent knows where adolescent spends time, weekly household responsibilities, school/career planning, and dentist. Future interviews generating a larger sample size as well as discussions and subsequent revisions to the manual will clarify additional items that may be eliminated from the final version of the instrument.
ContributorsMiller, Ava Kathryn (Author) / Bradley, Robert (Thesis director) / Spinrad, Tracy (Committee member) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor)
Created2015-05
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
In the United States, many new cases of type I diabetes appear among youth. Upon diagnosis, many patients experience psychosocial issues in addition to physical issues, including depression, anxiety, and poor self-esteem. Diabetes educators have found that it is important to form interpersonal connections and trust with their adolescent patients. One tool that may be particularly useful for diabetes educators to implement is art therapy, which combines creativity and problem solving in a practical manner. Art therapy may be particularly helpful for individuals with type 1 diabetes because of the great cognitive and emotional changes, which occur during adolescence. In order for caretakers and educators to implement tenants of art therapy, it is helpful to have a medium, such as an art journal, which provides a foundation on which to process the emotions and thoughts the adolescent is experiencing as they process diabetes and their feelings throughout diagnosis. Keywords: art therapy, type I diabetes
ContributorsFowle, Mikaelah Jenee (Author) / Bodman, Denise (Thesis director) / Rogers, Jennifer (Committee member) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor)
Created2015-05
Description
In the mid-1970s, social scientists began observing marital dyad conversations in laboratory settings with the hope of determining which observable features best discriminate couples who report being either satisfied or unsatisfied with their relationship. These studies continued until about a decade ago when, in addition to increasing laboratory costs slowing the pace of new data collection, researchers realized that distressed couples were easier to quantitatively describe than nondistressed couples. Specifically, distressed couples exhibit rigid patterns of negativity whereas couples who report being maritally satisfied show minimal rigidity in the opposite direction \u2014 positivity. This was, and is, a theoretical dilemma: how can clinicians understand and eventually modify distressed relationships when the behavior of satisfied couples are less patterned, less predictable and more diverse? A recent study by Griffin and Li (2015), using contemporary machine learning techniques, reanalyzed existing marital interaction data and found that, contrary to expectation and existing theory, nondistressed couples should be further subdivided into two groups \u2014 those who are predictably positive or neutral and those who interact using diverse and varying levels of positive and negative behaviors. The latter group is the focus of this thesis. Using these recent findings as discussion points, I review how the unexpected behaviors in this novel group can maintain and possibly perpetuate marital satisfaction.
ContributorsAbdul-Quadir, Hasana (Author) / Griffin, William A. (Thesis director) / Li, Xun (Committee member) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / School of International Letters and Cultures (Contributor) / Hugh Downs School of Human Communication (Contributor)
Created2015-05