Matching Items (183)
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
Nucleosomes are the basic repetitive unit of eukaryotic chromatin and are responsible for packing DNA inside the nucleus of the cell. They consist of a complex of eight histone proteins (two copies of four proteins H2A, H2B, H3 and H4) around which 147 base pairs of DNA are wrapped in ~1.67 superhelical turns. Although the nucleosomes are stable protein-DNA complexes, they undergo spontaneous conformational changes that occur in an asynchronous fashion. This conformational dynamics, defined by the "site-exposure" model, involves the DNA unwrapping from the protein core and exposing itself transiently before wrapping back. Physiologically, this allows regulatory proteins to bind to their target DNA sites during cellular processes like replication, DNA repair and transcription. Traditional biochemical assays have stablished the equilibrium constants for the accessibility to various sites along the length of the nucleosomal DNA, from its end to the middle of the dyad axis. Using fluorescence correlation spectroscopy (FCS), we have established the position dependent rewrapping rates for nucleosomes. We have also used Monte Carlo simulation methods to analyze the applicability of FRET fluctuation spectroscopy towards conformational dynamics, specifically motivated by nucleosome dynamics. Another important conformational change that is involved in cellular processes is the disassembly of nucleosome into its constituent particles. The exact pathway adopted by nucleosomes is still not clear. We used dual color fluorescence correlation spectroscopy to study the intermediates during nucleosome disassembly induced by changing ionic strength. Studying the nature of nucleosome conformational change and the kinetics is very important in understanding gene expression. The results from this thesis give a quantitative description to the basic unit of the chromatin.
ContributorsGurunathan, Kaushik (Author) / Levitus, Marcia (Thesis advisor) / Lindsay, Stuart (Committee member) / Woodbury, Neal (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2011
Description
Healthy mitochondria are essential for cell survival. Described herein is the synthesis of a family of novel aminoquinone antioxidants designed to alleviate oxidative stress and prevent the impairment of cellular function. In addition, a library of bleomycin disaccharide analogues has also been synthesized to better probe the tumor targeting properties of bleomycin. The first study involves the synthesis of a benzoquinone natural product and analogues that closely resemble the redox core of the natural product geldanamycin. The synthesized 5-amino-3-tridecyl-1,4-benzoquinone antioxidants were tested for their ability to protect Friedreich's ataxia (FRDA) lymphocytes from induced oxidative stress. Some of the analogues synthesized conferred cytoprotection in a dose-dependent manner in FRDA lymphocytes at micromolar concentrations. The biological assays suggest that the modification of the 2-hydroxyl and N-(3-carboxypropyl) groups in the natural product can improve its antioxidant activity and significantly enhance its ability to protect mitochondrial function under conditions of oxidative stress. The second project focused on the synthesis of a library of bleomycin disaccharide-dye conjugates and monitored their cellular uptake by fluorescence microscopy. The studies reveal that the position of the carbamoyl group plays an important role in modulating the cellular uptake of the disaccharide. It also led to the discovery of novel disaccharides with improved tumor selectivity.
ContributorsMathilakathu Madathil, Manikandadas (Author) / Hecht, Sidney M. (Thesis advisor) / Rose, Seth (Committee member) / Woodbury, Neal (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
It has been well established that mitochondria play a critical role in the pathology of Friedreich's Ataxia. This disease is believed to be caused by a deficiency of frataxin, which research suggests is responsible for iron sulfur cluster assembly. This incomplete assembly of iron sulfur clusters is believed to be linked with dysfunctional complexes in the mitochondrial respiratory chain, increased oxidative stress, and potential cell death. Increased understanding of the pathophysiology of this disease has enabled the development of various therapeutic strategies aimed at restoring mitochondrial respiration. This thesis contains an analysis of the biological activity of several classes of antioxidants against oxidative stress induced by diethyl maleate in Friedreich's Ataxia lymphocytes and CEM leukemia cells. Analogues of vitamin E α-tocopherol have been shown to protect cells under oxidative stress. However, these same analogues show various levels of inhibition towards the electron transport chain complex I. Bicyclic pyridinols containing a ten carbon substituent provided favorable cytoprotection. N-hydroxy-4-pyridone compounds were observed to provide little protection. Similarly, analogues of CoQ10 in the form of pyridinol and pyrimidinol compounds also preserved cell viability at low concentrations.
ContributorsJaruvangsanti, Jennifer (Author) / Hecht, Sidney (Thesis advisor) / Woodbury, Neal (Committee member) / Skibo, Edward (Committee member) / Arizona State University (Publisher)
Created2012
Description
The field of biomedical research relies on the knowledge of binding interactions between various proteins of interest to create novel molecular targets for therapeutic purposes. While many of these interactions remain a mystery, knowledge of these properties and interactions could have significant medical applications in terms of understanding cell signaling and immunological defenses. Furthermore, there is evidence that machine learning and peptide microarrays can be used to make reliable predictions of where proteins could interact with each other without the definitive knowledge of the interactions. In this case, a neural network was used to predict the unknown binding interactions of TNFR2 onto LT-ɑ and TRAF2, and PD-L1 onto CD80, based off of the binding data from a sampling of protein-peptide interactions on a microarray. The accuracy and reliability of these predictions would rely on future research to confirm the interactions of these proteins, but the knowledge from these methods and predictions could have a future impact with regards to rational and structure-based drug design.
ContributorsPoweleit, Andrew Michael (Author) / Woodbury, Neal (Thesis director) / Diehnelt, Chris (Committee member) / Chiu, Po-Lin (Committee member) / School of Molecular Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Some of the most talented, innovative, and experimental artists are students, but they are often discouraged by the price of higher education and lack of scholarship or funding opportunities. Additionally, the art industry has become stagnant. Traditional brick-and-mortar galleries are not willing to represent young, unknown artists. Their overhead is simply too high for risky choices.
The Student Art Project is art patronage for the 21st century—a curated online gallery featuring exceptional student artists. The Student Art Project is a highly curated experience for buyers. Only five artists are featured each month. Buyers are not bombarded with thousands of different products and separate artists “shops”. They can read artists bios and find art they connect with.
Student artists apply through an online form. Once accepted to the program, artists receive a $200 materials stipend to create an exclusive collection of 5-10 pieces. Original artwork and limited edition prints are sold through our website. These collections can potentially fund an entire year of college tuition, a life-changing amount for many students.
Brick-and-mortar galleries typically take 40-60% of the retail price of artwork. The Student Art Project will only take 30%, which we will use to reinvest in future artists. Other art websites, like Etsy, require the artists to ship, invoice, and communicate with customers. For students, this means less time spent in the classroom and less time developing their craft. The Student Art Project handles all business functions for our artists, allowing them to concentrate on what really matters, their education.
The Student Art Project is art patronage for the 21st century—a curated online gallery featuring exceptional student artists. The Student Art Project is a highly curated experience for buyers. Only five artists are featured each month. Buyers are not bombarded with thousands of different products and separate artists “shops”. They can read artists bios and find art they connect with.
Student artists apply through an online form. Once accepted to the program, artists receive a $200 materials stipend to create an exclusive collection of 5-10 pieces. Original artwork and limited edition prints are sold through our website. These collections can potentially fund an entire year of college tuition, a life-changing amount for many students.
Brick-and-mortar galleries typically take 40-60% of the retail price of artwork. The Student Art Project will only take 30%, which we will use to reinvest in future artists. Other art websites, like Etsy, require the artists to ship, invoice, and communicate with customers. For students, this means less time spent in the classroom and less time developing their craft. The Student Art Project handles all business functions for our artists, allowing them to concentrate on what really matters, their education.
ContributorsDangler, Rebecca Leigh (Author) / Trujillo, Rhett (Thesis director) / Coleman, Sean (Committee member) / Barrett, The Honors College (Contributor) / Herberger Institute for Design and the Arts (Contributor) / Department of Management (Contributor)
Created2015-05
Description
Drought is one of the most pressing issues affecting the future of the standard of living here in Phoenix. With the threat of water rationing and steep price hikes looming on the horizon for water customers in California, the desert southwest, and in drought-stricken communities worldwide, industrial designers are in a prime position to help improve the experience of water conservation so that consumers are willing to start taking conscious steps toward rethinking their relationship with water usage.
In a research group, several designers sought to understand the depth and complexity of this highly politicized issue by interviewing a wide variety of stakeholders, including sustainability experts, landscapers, water company executives, small business owners, reservoir forest rangers, and many more. Data synthesis led to the conclusion that residential water use is a lifestyle issue, and the only real way to conserve involves a significant shift in the collective idea of an “ideal” home—lawns, pools, and overwatered landscaping contribute to 70% of all water use by residences in the Phoenix area. The only real way to conserve involves increasing population density and creating communal green spaces.
DR. DISH is a dishwashing device that is meant to fit into the high-density living spaces that are rapidly being built in the face of the massive exodus of people into the world’s cities. To help busy apartment and condominium dwellers conserve water and time, DR. DISH converts a standard kitchen sink into a small dishwasher, which uses significantly less water than hand-washing dishes or rinsing dishes before putting them into a conventional dishwasher. Using advanced filtration technology and a powerful rinse cycle, a load dishes can be cleaned with about 2 gallons of water. Fully automating the dishwashing process also saves the user time and minimizes unpleasant contact with food residue and grease.
This device is meant to have a significant impact upon the water use of households that do not have a dishwasher, or simply do not use their dishwasher. With a low target price point and myriad convenient features, DR. DISH is a high-tech solution that promises water savings at a time when every effort toward conservation is absolutely critical. As we move toward a new era in determining water rights and imposing mandatory restrictions upon each and every person living in affected areas, creating conservation solutions that will be relevant for the lifestyles of the future is especially important, and the agility of designers in coming up with products that quickly cut consumer water consumption will be a key factor in determining whether humanity will be able to adapt to a new era in our relationship with natural resources.
In a research group, several designers sought to understand the depth and complexity of this highly politicized issue by interviewing a wide variety of stakeholders, including sustainability experts, landscapers, water company executives, small business owners, reservoir forest rangers, and many more. Data synthesis led to the conclusion that residential water use is a lifestyle issue, and the only real way to conserve involves a significant shift in the collective idea of an “ideal” home—lawns, pools, and overwatered landscaping contribute to 70% of all water use by residences in the Phoenix area. The only real way to conserve involves increasing population density and creating communal green spaces.
DR. DISH is a dishwashing device that is meant to fit into the high-density living spaces that are rapidly being built in the face of the massive exodus of people into the world’s cities. To help busy apartment and condominium dwellers conserve water and time, DR. DISH converts a standard kitchen sink into a small dishwasher, which uses significantly less water than hand-washing dishes or rinsing dishes before putting them into a conventional dishwasher. Using advanced filtration technology and a powerful rinse cycle, a load dishes can be cleaned with about 2 gallons of water. Fully automating the dishwashing process also saves the user time and minimizes unpleasant contact with food residue and grease.
This device is meant to have a significant impact upon the water use of households that do not have a dishwasher, or simply do not use their dishwasher. With a low target price point and myriad convenient features, DR. DISH is a high-tech solution that promises water savings at a time when every effort toward conservation is absolutely critical. As we move toward a new era in determining water rights and imposing mandatory restrictions upon each and every person living in affected areas, creating conservation solutions that will be relevant for the lifestyles of the future is especially important, and the agility of designers in coming up with products that quickly cut consumer water consumption will be a key factor in determining whether humanity will be able to adapt to a new era in our relationship with natural resources.
ContributorsMarcinkowski, Margaret Nicole (Author) / Shin, Dosun (Thesis director) / McDermott, Lauren (Committee member) / Barrett, The Honors College (Contributor) / The Design School (Contributor) / Herberger Institute for Design and the Arts (Contributor)
Created2015-05
Description
Students across the United States lack the necessary skills to be successful college students in Science, Technology and Math (STEM) majors and as a result post-secondary institutions are developing summer bridge programs to aid in their transition. As they develop these programs, effective theory and approach are critical to developing successful programs. Though there are a multitude of theories on successful student development, a focus on self-efficacy is critical. Summer Bridge programs across the country as well as the Bio Bridge summer program at Arizona State University were studied alone and through the lens of Cognitive Self-Efficacy Theory as mentioned in Albert Bandura's "Perceived Self-Efficacy in Cognitive Development and Functioning." Cognitive Self-Efficacy Theory provides a framework for self-efficacy development in academic settings. An analysis of fifteen bridge programs found that a large majority focused on developing academic capabilities and often overlooked development of community and social efficacy. An even larger number failed to focus on personal psychology in managing self-debilitating thought patterns based on published goals. Further, Arizona State University's Bio Bridge program could not be considered successful at developing cognitive self-efficacy or increasing retention as data was inconclusive. However, Bio Bridge was tremendously successful at developing social efficacy and community among participants and faculty. Further research and better evaluative techniques need to be developed to understand the program's effectiveness in cognitive self-efficacy development and retention.
ContributorsTummala, Sailesh Vardhan (Author) / Orchinik, Miles (Thesis director) / Brownell, Sara (Committee member) / Shortlidge, Erin (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Fire Shelter Foam Assist is meant as a firefighter's last effort of survival when a wildfire threatens their position. When deployed, it will cover the firefighter as the fire blows over. By reducing the time of deployment and simplifying the process, firefighters will have more time to ensure the area around them is cleared. The Fire Shelter Foam Assist has features that allow it to auto deploy around the firefighter through the use of fire foam retardant. The fire foam retardant inflates the shelter as well as provides an extra layer of protection against the wildfire.
ContributorsSmith, Tori Elizabeth (Author) / Shin, Dosun (Thesis director) / McDermott, Lauren (Committee member) / Barrett, The Honors College (Contributor) / Herberger Institute for Design and the Arts (Contributor) / The Design School (Contributor)
Created2015-05