Matching Items (237)
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
Over the last two decades programs and mandates to encourage and foster sustainable urban development have arisen throughout the world, as cities have emerged as key opportunity sites for sustainable development due to the compactness and localization of services and resources. In order to recognize this potential, scholars and practitioners have turned to the practice of visioning as a way to motivate actions and decision making toward a sustainable future. A "vision" is defined as desirable state in the future and scholars believe that the creation of a shared, motivational vision is the best starting point to catalyze positive and sustainable change. However, recent studies on city visions indicate that they do not offer substantive sustainability content, and methods or processes to evaluate the sustainability content of the resulting vision (sustainability appraisal or assessment) are often absent from the visioning process. Thus, this paper explores methods for sustainability appraisal and their potential contributions to (and in) visioning. The goal is to uncover the elements of a robust sustainability appraisal and integrate them into the visioning process. I propose an integrated sustainability appraisal procedure based on sustainability criteria, indicators, and targets as part of a visioning methodology that was developed by a team of researchers at Arizona State University (ASU) of which I was a part. I demonstrate the applicability of the appraisal method in a case study of visioning in Phoenix, Arizona. The proposed method allows for early and frequent consideration and evaluation of sustainability objectives for urban development throughout the visioning process and will result in more sustainability-oriented visions. Further, it can allow for better measurement and monitoring of progress towards sustainability goals, which can make the goals more tangible and lead to more accountability for making progress towards the development of more sustainable cities in the future.
ContributorsMinowitz, Amy (Author) / Wiek, Arnim (Thesis advisor) / Golub, Aaron (Committee member) / Pfeiffer, Deirdre (Committee member) / Arizona State University (Publisher)
Created2013
Description
Contemporary urban food security in the US is influenced by complex, multidimensional, and multi-scale factors. However, most assessment methods and intervention efforts in food security research are: 1) narrowly focused on environmental factors (i.e. the presence or absence of quality food outlets), 2) divorced from the human dimension and, 3) ultimately disempower communities to affect change at the local level. New approaches are needed to capture the lived experiences and unique perspectives of people potentially most vulnerable to food insecurity, while also empowering people to become change agents in their lives and in the wider community. This thesis argues that sustainability problem solving frameworks such as transformational sustainability research (TSR), and community-based participatory research (CBPR) provide promising bases from which to address these deficiencies. Through interactive workshops with youth in Canyon Corridor, a neighborhood in Phoenix, Arizona, I demonstrate the potential of concept mapping, sketch mapping, and intervention mapping methods that prioritize participation and co-production of knowledge to: 1) better understand the contextual, community-identified factors that contribute to food security or food insecurity, 2) identify and adapt interventions for the local context and, 3) promote community agency and action. Workshop outcomes suggest the relevance of these frameworks and methods, and the potential for more people- and place-based approaches to food security research.
ContributorsTalbot, Kathleen (Author) / Eakin, Hallie (Thesis advisor) / Wiek, Arnim (Committee member) / Szkupinski-Quiroga, Seline (Committee member) / Arizona State University (Publisher)
Created2012
Description
Growing concerns over climate change and the lack of a federal climate policy have prompted many sub-national organizations to undertake greenhouse gas (GHG) mitigation actions on their own. However, the interventions associated with these efforts are typically selected in a top-down and ad hoc manner, and have not created the desired GHG emissions reductions. Accordingly, new approaches are needed to identify, select, develop, and coordinate effective climate change mitigation interventions in local and regional contexts. This thesis develops a process to create a governance system for negotiating local and regional climate interventions. The process consists of four phases: 1) mapping the overall transition, 2) reconstructing the current intervention selection system, 3) assessing the system against principles identified in the literature, and 4) creating an improved system based on the assessment. This process gives users a detailed understanding of how the overall transition has progressed, how and why interventions are currently selected, what changes are needed to improve the selection system, and how to re-structure the system to create more desirable outcomes. The process results in an improved system that relies on participation, coordination, and accountability to proactively select evidence-based interventions that incorporate the interests of stakeholders and achieve system-level goals. The process was applied to climate change mitigation efforts underway in Sonoma County, California to explore the implications of real-world application, and demonstrate its utility for current climate change mitigation efforts. Note that results and analysis from interviews with Sonoma County climate actors are included as a supplementary file.
ContributorsCulotta, Daniel Scott (Author) / Wiek, Arnim (Thesis advisor) / Basile, George (Committee member) / Shrestha, Milan (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
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
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
Lung cancer is the leading cause of cancer-related deaths in the US. Low-dose computed tomography (LDCT) scans are speculated to reduce lung cancer mortality. However LDCT scans impose multiple risks including false-negative results, false- positive results, overdiagnosis, and cancer due to repeated exposure to radiation. Immunosignaturing is a new method proposed to screen and detect lung cancer, eliminating the risks associated with LDCT scans. Known and blinded primary blood sera from participants with lung cancer and no cancer were run on peptide microarrays and analyzed. Immunosignatures for each known sample collectively indicated 120 peptides unique to lung cancer and non-cancer participants. These 120 peptides were used to determine the status of the blinded samples. Verification of the results from Vanderbilt is pending.
ContributorsNguyen, Geneva Trieu (Author) / Woodbury, Neal (Thesis director) / Zhao, Zhan-Gong (Committee member) / Stafford, Phillip (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Department of Psychology (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