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- Creators: Ira A. Fulton Schools of Engineering
- Resource Type: Text
- Status: Published
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
Over the past century in the southwestern United States human actions have altered hydrological processes that shape riparian ecosystems. One change, release of treated wastewater into waterways, has created perennial base flows and increased nutrient availability in ephemeral or intermittent channels. While there are benefits to utilizing treated wastewater for environmental flows, there are numerous unresolved ecohydrological issues regarding the efficacy of effluent to sustain groundwater-dependent riparian ecosystems. This research examined how nutrient-rich effluent, released into waterways with varying depths to groundwater, influences riparian plant community development. Statewide analysis of spatial and temporal patterns of effluent generation and release revealed that hydrogeomorphic setting significantly influences downstream riparian response. Approximately 70% of effluent released is into deep groundwater systems, which produced the lowest riparian development. A greenhouse study assessed how varying concentrations of nitrogen and phosphorus, emulating levels in effluent, influenced plant community response. With increasing nitrogen concentrations, vegetation emerging from riparian seed banks had greater biomass, reduced species richness, and greater abundance of nitrophilic species. The effluent-dominated Santa Cruz River in southern Arizona, with a shallow groundwater upper reach and deep groundwater lower reach, served as a study river while the San Pedro River provided a control. Analysis revealed that woody species richness and composition were similar between the two systems. Hydric pioneers (Populus fremontii, Salix gooddingii) were dominant at perennial sites on both rivers. Nitrophilic species (Conium maculatum, Polygonum lapathifolium) dominated herbaceous plant communities and plant heights were greatest in effluent-dominated reaches. Riparian vegetation declined with increasing downstream distance in the upper Santa Cruz, while patterns in the lower Santa Cruz were confounded by additional downstream agricultural input and a channelized floodplain. There were distinct longitudinal and lateral shifts toward more xeric species with increasing downstream distance and increasing lateral distance from the low-flow channel. Patterns in the upper and lower Santa Cruz reaches indicate that water availability drives riparian vegetation outcomes below treatment facilities. Ultimately, this research informs decision processes and increases adaptive capacity for water resources policy and management through the integration of ecological data in decision frameworks regarding the release of effluent for environmental flows.
ContributorsWhite, Margaret Susan (Author) / Stromberg, Juliet C. (Thesis advisor) / Fisher, Stuart G. (Committee member) / White, Dave (Committee member) / Holway, James (Committee member) / Wu, Jianguo (Committee member) / Arizona State University (Publisher)
Created2011
Description
Driven by concern over environmental, economic and social problems, small, place based communities are engaging in processes of transition to become more sustainable. These communities may be viewed as innovative front runners of a transition to a more sustainable society in general, each one, an experiment in social transformation. These experiments present learning opportunities to build robust theories of community transition and to create specific, actionable knowledge to improve, replicate, and accelerate transitions in real communities. Yet to date, there is very little empirical research into the community transition phenomenon. This thesis empirically develops an analytical framework and method for the purpose of researching community transition processes, the ultimate goal of which is to arrive at a practice of evidence based transitions. A multiple case study approach was used to investigate three community transitions while simultaneously developing the framework and method in an iterative fashion. The case studies selected were Ashton Hayes, a small English village, BedZED, an urban housing complex in London, and Forres, a small Scottish town. Each community was visited and data collected by interview and document analysis. The research design brings together elements of process tracing, transformative planning and governance, sustainability assessment, transition path analysis and transition management within a multiple case study envelope. While some preliminary insights are gained into community transitions based on the three cases the main contribution of this thesis is in the creation of the research framework and method. The general framework and method developed has potential for standardizing and synthesizing research of community transition processes leading to both theoretical and practical knowledge that allows sustainability transition to be approached with confidence and not just hope.
ContributorsForrest, Nigel (Author) / Wiek, Arnim (Thesis advisor) / Golub, Aaron (Thesis advisor) / Redman, Charles (Committee member) / White, Dave (Committee member) / Arizona State University (Publisher)
Created2011
Description
The sacred San Francisco Peaks in northern Arizona have been at the center of a series of land development controversies since the 1800s. Most recently, a controversy arose over a proposal by the ski area on the Peaks to use 100% reclaimed water to make artificial snow. The current state of the San Francisco Peaks controversy would benefit from a decision-making process that holds sustainability policy at its core. The first step towards a new sustainability-focused deliberative process regarding a complex issue like the San Francisco Peaks controversy requires understanding the issue's origins and the perspectives of the people involved in the issue. My thesis provides an historical analysis of the controversy and examines some of the laws and participatory mechanisms that have shaped the decision-making procedures and power structures from the 19th century to the early 21st century.
ContributorsMahoney, Maren (Author) / Hirt, Paul W. (Thesis advisor) / Tsosie, Rebecca (Committee member) / White, Dave (Committee member) / Arizona State University (Publisher)
Created2011
Description
Despite similar climate, ecosystem, and population size, the cities of Hermosillo, Mexico and Mesa, USA manage their water very differently. Mesa has a stable and resilient system organized around state and federal regulations. Hermosillo, after rapidly industrializing, has not been able to cope with climate change and long-term drought conditions. Water distribution statistics, stakeholders, policy structure, and government organization were combined in an organizational framework to compare the practices of the two cities. These inputs were weighed against the outcomes and the sustainability of each system. While Mesa is part of a massive metropolitan area, Hermosillo is still developing into a metropolitan center and does not have access to the same infrastructure and resources. In Hermosillo local needs are frequently discounted in favor of broad political goals.
ContributorsMoe, Rud Lamb (Author) / Chhetri, Netra (Thesis director) / White, Dave (Committee member) / Robles-Morua, Agustin (Committee member) / Barrett, The Honors College (Contributor) / School of Earth and Space Exploration (Contributor) / School of Sustainability (Contributor) / School of Geographical Sciences and Urban Planning (Contributor)
Created2013-05
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
The storm events of summer 2014 proved to be some of the highest on record for Maricopa County. Flash flooding has been an ongoing issue within Arizona during the monsoon season due to the remnants of hurricanes that result in short, high intensity storms. The proximity of these intense storm events and their corresponding flooding structures is imperative in reducing the impact of these events on the community. The analysis of the maximum precipitation events for Tempe, Scottsdale, Phoenix, Mesa, Chandler, Goodyear, Peoria, Avondale and Glendale during the summer of 2014 proved that there were many events that had a calculated recurrence of 100 years or greater. The storm event with the most precipitation events with a recurrence of 100 years or greater was September 8, 2014. This storm event also produced a streamflow response that had the highest recorded streamflow at gages near the events with a 100 year recurrence. These intervals represent a larger amount of rain during a precipitation event and this correlation suggests that short burst of extreme weather was not a trend in this data. Rather, high storm events occurred over the span of 24 hours. The most frequent response of the stream gage to this rain event was a streamflow event that has a recurrence of 2-5 years. This suggests that the channels and flooding structures used to contain the rain events were effective in reducing the amount of water and therefore effectively managing the flooding response. An analysis of newspaper commentary and an interview with a representative from the Flood Control District of Maricopa County (FCDMC) indicated that there is a disconnect between public perception and the structure of FCDMC. Through this analysis a better understanding of the FCDMC as well as the impact of severe storm events in Maricopa County was found.
ContributorsBrancati, Olivia Anne (Author) / Vivoni, Enrique (Thesis director) / White, Dave (Committee member) / Civil, Environmental and Sustainable Engineering Programs (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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