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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
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
I travelled and worked in international fisheries policy for 7 months in preparation for this thesis. During this time I completed one internship in Rome, Italy with the Food and Agriculture Organization of the United Nations (UNFAO) and another internship on the island of Pohnpei with the Secretariat of the Western and Central Pacific Fisheries Commission (WCPFC). From these experiences, I selected the subject of this thesis. My thesis analyzes the management system for South Pacific albacore tuna, the source stock for brands like "Chicken of the Sea" and "Starkist". South Pacific albacore tuna pass through international waters and the waters of several Pacific Island countries and territories, necessitating States to cooperate and coordinate to sustain the future viability of the stock. A case study for transboundary natural resource management, I discuss the institutional complexity that arises from managing such a resource. I use common-pool resource (CPR) theory to describe this complexity, which frames natural resource management as a collective-action problem among resource users. I first conceptualize the management system as having multiple institutional scales and multiple levels of organization. Then, employing Ostrom's 8 design principles for successful CPR management, I conduct a multi-institution analysis of the international, regional, and subregional institutions that participate in the management system. Finally, I also conduct a cross-institution analysis by examining the interactions between these institutions. I find that significant space for theoretical development exists in CPR theory for understanding complex management systems for transboundary natural resources. Furthermore, I find that interactions between institutions create linkages that could be retooled to improve the performance of the South Pacific albacore tuna management system.
ContributorsAbolhassani, Angela Maryam (Author) / Abbott, Kenneth (Thesis director) / Schoon, Michael (Committee member) / Barrett, The Honors College (Contributor) / School of Politics and Global Studies (Contributor) / School of Life Sciences (Contributor) / Department of English (Contributor)
Created2015-05
Description
This paper explores two areas of study: Colony Collapse Disorder and urban apiculture--the practice of keeping bees in urban areas. Additionally, this paper discusses the ways in which Colony Collapse Disorder has encouraged an increase in urban beekeeping, and the possible role of urban apiculture as a means of combatting the negative effects of Colony Collapse Disorder. The symptoms, history, and possible causes of Colony Collapse Disorder are presented, as well as the important role that honey bees play in human agriculture. Following the discussion of Colony Collapse Disorder is a description of my urban beekeeping apprenticeship at Desert Marigold School where I kept bees, researched various hives, attended a beekeeping workshop in Tucson, and eventually built a hive and established a colony with my mentor. This paper includes a guide to beekeeping basics, as well as a guide to starting a hive based upon the lessons learned during my apprenticeship.
ContributorsRomero, Madelyn Rattan (Author) / Schoon, Michael (Thesis director) / Silcox, Holly (Committee member) / Barrett, The Honors College (Contributor) / School of Sustainability (Contributor) / School of Geographical Sciences and Urban Planning (Contributor)
Created2015-05
Description
South Mountain is the largest municipal park in the nation. It is a bundled amenity, providing a series of linked services to the surrounding communities. A dataset of 19,209 homes in 155 neighborhoods within three miles of the park was utilized in order to complete a hedonic estimation for two nearby urban villages, Ahwatukee Foothills and South Mountain Village. Measures of access include proximity to the park, trailhead access, and adjacency to the park. Two regressions were estimated, the first including lot characteristics and subdivision fixed effects and the second using the coefficients for each subdivision as the dependent variable. These estimates describe how the location of a house in a subdivision contributes to its conditional mean price. As a result they offer a direct basis for capturing amenities measured at the neighborhood scale on home values. Park proximity, trailhead access and adjacency were found to significantly influence the price of homes at the 5% confidence level in Ahwatukee, but not in South Mountain Village. The results of this study can be applied to issues of environmental justice and park access in determining which areas and attributes of the park are associated with a high premium. Though South Mountain was preserved some time ago, development and future preservation in the City of Phoenix can be informed by such studies.
ContributorsRamakrishna, Saritha Kambhampati (Author) / Abbott, Joshua (Thesis director) / Smith, V. Kerry (Committee member) / Schoon, Michael (Committee member) / Barrett, The Honors College (Contributor) / School of Sustainability (Contributor) / Economics Program in CLAS (Contributor) / Department of English (Contributor)
Created2015-05
Hiking and Hegemony: Destabilizing the nature/culture and gender binaries through outdoor recreation
Description
This paper explores the contested relationships between nature, culture, and gender. In order to analyze these relationships, we look specifically at outdoor recreation. Furthermore, we employ poststructuralist feminist theory in order to produce three frameworks; the first of which is titled Mother Nature’s Promiscuous Past. Rooted in Old World and colonial values, this framework illustrates the flawed feminization of nature by masculinity, and its subsequent extortion of anything related to femininity — including women and nature itself. This belief barred women from nature, resulting in a lack of access for women to outdoor recreation.
Our second framework, titled The Pleasurable Potential of Outdoor Recreation, cites second-wave feminism as a catalyst for women’s participation in wilderness exploration and outdoor recreation. The work of radical feminists and the women’s liberation movement in 1960s and 1970s empowered women at home, in the workplace, and eventually, in the outdoors; women reclaimed their wilderness, yet they continued to employ Framework One’s feminization of nature. Ecofeminsim brought together nature and women, seeking to bring justice to two groups wronged by the same entity: masculinity. In this context, outdoor recreation is empowering for women.
Despite the potential of Framework Two to reinscribe and better the experiences of women in outdoor recreation, we argue that both Frameworks One and Two perpetuate the gender binary and the nature/culture binary, because they are based upon the notion that women are in fact fundamentally different and separate from men, the notion that nature is an entity separate from culture, or human society, as well as the notion that nature is in fact a feminine entity.
Our third framework, Deer Pay No Mind to Your Genitals, engages poststructuralism, asserting that outdoor recreation and activities that occur in nature can serve to destabilize and deconstruct notions of the gender binary. However, we argue that care must be exercised during this process as not to perpetuate the problematic nature/culture binary, a phenomenon that is unproductive in terms of both sustainability and gender liberation. Outdoor recreation has been used by many as a tool to deconstruct numerous societal constraints, including the gender binary; this, however, continues to attribute escapist and isolationist qualities toward nature, and therefore perpetuating the nature/culture divide. Ultimately, we argue outdoor recreation can and should be used as a tool deconstruct the gender binary, however needs to account for the fact that if nature is helping to construct elements of culture, then the two cannot be separate.
Our second framework, titled The Pleasurable Potential of Outdoor Recreation, cites second-wave feminism as a catalyst for women’s participation in wilderness exploration and outdoor recreation. The work of radical feminists and the women’s liberation movement in 1960s and 1970s empowered women at home, in the workplace, and eventually, in the outdoors; women reclaimed their wilderness, yet they continued to employ Framework One’s feminization of nature. Ecofeminsim brought together nature and women, seeking to bring justice to two groups wronged by the same entity: masculinity. In this context, outdoor recreation is empowering for women.
Despite the potential of Framework Two to reinscribe and better the experiences of women in outdoor recreation, we argue that both Frameworks One and Two perpetuate the gender binary and the nature/culture binary, because they are based upon the notion that women are in fact fundamentally different and separate from men, the notion that nature is an entity separate from culture, or human society, as well as the notion that nature is in fact a feminine entity.
Our third framework, Deer Pay No Mind to Your Genitals, engages poststructuralism, asserting that outdoor recreation and activities that occur in nature can serve to destabilize and deconstruct notions of the gender binary. However, we argue that care must be exercised during this process as not to perpetuate the problematic nature/culture binary, a phenomenon that is unproductive in terms of both sustainability and gender liberation. Outdoor recreation has been used by many as a tool to deconstruct numerous societal constraints, including the gender binary; this, however, continues to attribute escapist and isolationist qualities toward nature, and therefore perpetuating the nature/culture divide. Ultimately, we argue outdoor recreation can and should be used as a tool deconstruct the gender binary, however needs to account for the fact that if nature is helping to construct elements of culture, then the two cannot be separate.
ContributorsPolick-Kirkpatrick, Kaelyn (Co-author) / Downing, Haley Marie (Co-author) / Dove-Viebahn, Aviva (Thesis director) / Schoon, Michael (Committee member) / School of Sustainability (Contributor) / School of Social Transformation (Contributor) / Economics Program in CLAS (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
DescriptionA small-scale aquaponic system was created to demonstrate the sustainable properties of the system as well as the effectiveness of raising fish and plants symbiotically.
ContributorsSerna, Desiree Marie (Author) / Schoon, Michael (Thesis director) / Peterson, Greg (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
The following Student Sustainability Consultant's Portfolio was created with the intention of being duplicated and utilized by Arizona State University (ASU) students to build their own Portfolio and to help prepare them for success after graduation. Student Consultants in GreenLight Solutions (GLS) are in a unique position to prepare themselves to create value for organizations while in school, and then continue to after graduation. When I enrolled in the School of Sustainability as an undergraduate transfer student I heard some constructive criticism from graduates of the school. Those students shared that while they had attained a great theoretical understanding of the science of sustainability, they lacked the ability to apply their knowledge in a practical way. They were struggling with finding work in their field because they could not communicate to employers how their knowledge was useful. They did not know how to apply their sustainability knowledge to create value for an organization. I did not want to have that same problem when I graduated. Enter GreenLight Solutions.
ContributorsKeleher, Kevin Robert (Author) / Schoon, Michael (Thesis director) / Basile, George (Committee member) / Buch, Rajesh (Committee member) / Barrett, The Honors College (Contributor) / School of Sustainability (Contributor) / Department of Supply Chain Management (Contributor)
Created2013-12
Description
My project is an examination of the process ASU Tempe campus took to institute an organics collection program. Working from a sustainability science perspective I demonstrate the structural and logistical barriers faced during program creation and expansion. My examination lead to the creation of a manual designed as a tool for other organizations in which I document ASU's process and provide information on key steps and procedures necessary to implement a unique organics collection program.
ContributorsSchumacher, Katherine Marie (Author) / Schoon, Michael (Thesis director) / Brundiers, Katja (Committee member) / Levine, Alana (Committee member) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / School of Sustainability (Contributor)
Created2013-05