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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
Meteorology is an uncommon term rarely resonating through elementary classrooms. However, it is a concept found in both fourth and sixth grade Arizona science standards. As issues involving the environment are becoming more pertinent, it is important to study and understand atmospheric processes along with fulfilling the standards for each grade level. This thesis project teaches the practical skills of weather map reading and weather forecasting through the creation and execution of an after school lesson with the aide of seven teen assistants.
ContributorsChoulet, Shayna (Author) / Walters, Debra (Thesis director) / Oliver, Jill (Committee member) / Balling, Robert (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2012-12
Description
Plants are essential to human life. They release oxygen into the atmosphere for us to breathe. They also provide shelter, medicine, clothing, tools, and food. For many people, the food that is on their tables and in their supermarkets isn't given much thought. Where did it come from? What part of the plant is it? How does it relate to others in the plant kingdom? How do other cultures use this plant? The most many of us know about them is that they are at the supermarket when we need them for dinner (Nabhan, 2009) (Vileisis, 2008).
ContributorsBarron, Kara (Author) / Landrum, Leslie (Thesis director) / Swanson, Tod (Committee member) / Pigg, Kathleen (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2012-12
DescriptionBased on previous research and findings it is proven that a non-profit class to create awareness will be beneficial in the prevention of eating disorders. This analysis will provide significant research to defend the proposed class.
ContributorsAllen, Brittany (Author) / Chung, Deborah (Author) / Fey, Richard (Thesis director) / Peck, Sidnee (Committee member) / Mazurkiewicz, Milena (Committee member) / Barrett, The Honors College (Contributor) / W. P. Carey School of Business (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2012-12
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
Through this creative project, I executed a Distracted Driving Awareness Campaign at Arizona State University to raise awareness about the dangers of distracted driving, specifically texting while driving. As an Undergraduate Student Government Senator, my priority is the safety and success of students, both in and out of the classroom. By partnering with State Farm and AT&T, we were able to raise awareness about the dangers of distracted driving and collected over 200 pledges from students to never text and drive.
ContributorsHibbs, Jordan Ashley (Author) / Miller, Clark (Thesis director) / Parmentier, Mary Jane (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Politics and Global Studies (Contributor) / Department of Psychology (Contributor) / Graduate College (Contributor)
Created2014-05
Description
Background: Latinos represent 40.8% of the population in Phoenix (U.S. Census Bureau Population Division, 2010). South Phoenix, also known as the South Mountain Village, defined in geographical terms as area zip codes 85040 and 85042; is a predominantly Latino community comprised of mixed citizenship status households. During the 2010 United States Census 60.3% of the population in South Phoenix identified as Latino, 25.75% of the total population was foreign born. Of the foreign born population, 88.95% were of Latin American origin (United States Census Bureau, 2007-2011 American Community Survey). Understanding how Latino immigrants perceive differences in health between their communities in country of origin and communities in the United States is largely unknown. Irrespective of political positions, understanding how Latino immigrants perceive personal health and the health of their communities is of interest to inform public policy and implement needed interventions in the
public health sphere.
Methods: Semi-structured interviews were collected from 55 adults from the South Phoenix community between November 2009 and September 2010. Interviews were digitally recorded with participant permission and transcribed. Of those collected, 48 transcribed interviews were analyzed using a codebook designed by the researcher. Percent agreement evaluated inter-rater reliability.Results: Latino immigrants in South Phoenix largely agree that health quality is heavily dependent on personal responsibility and not an intrinsic attribute of a given place. Emotional contentedness and distress, both factors of mental health, are impacted by cross-cultural differences between Latino and U.S. culture systems.
Conclusions: As people’s personal perceptions of differences in health are complex concepts influenced by personal backgrounds, culture, and beliefs, attempting to demark a side of the border as ‘healthier’ than the other using personal perceptions is overly simplified and misses central concepts. Instead, exploration of individual variables impacting health allowed this study to gain a more nuanced understanding in how people determine quality of both personal and environmental health. While Latino migrants in South Phoenix largely agree that health is based on personal responsibility and choices, many nonetheless experience higher levels of contentedness and emotional health in their country of origin.
public health sphere.
Methods: Semi-structured interviews were collected from 55 adults from the South Phoenix community between November 2009 and September 2010. Interviews were digitally recorded with participant permission and transcribed. Of those collected, 48 transcribed interviews were analyzed using a codebook designed by the researcher. Percent agreement evaluated inter-rater reliability.Results: Latino immigrants in South Phoenix largely agree that health quality is heavily dependent on personal responsibility and not an intrinsic attribute of a given place. Emotional contentedness and distress, both factors of mental health, are impacted by cross-cultural differences between Latino and U.S. culture systems.
Conclusions: As people’s personal perceptions of differences in health are complex concepts influenced by personal backgrounds, culture, and beliefs, attempting to demark a side of the border as ‘healthier’ than the other using personal perceptions is overly simplified and misses central concepts. Instead, exploration of individual variables impacting health allowed this study to gain a more nuanced understanding in how people determine quality of both personal and environmental health. While Latino migrants in South Phoenix largely agree that health is based on personal responsibility and choices, many nonetheless experience higher levels of contentedness and emotional health in their country of origin.
ContributorsGray, Laurel (Author) / Wutich, Amber (Thesis director) / Quiroga, S. Seline (Committee member) / Nelson, Margaret (Committee member) / Slade, B. Alexandra (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2013-05
Description
Identifying disease biomarkers may aid in the early detection of breast cancer and improve patient outcomes. Recent evidence suggests that tumors are immunogenic and therefore patients may launch an autoantibody response to tumor associated antigens. Single-chain variable fragments of autoantibodies derived from regional lymph node B cells of breast cancer patients were used to discover these tumor associated biomarkers on protein microarrays. Six candidate biomarkers were discovered from 22 heavy chain-only variable region antibody fragments screened. Validation tests are necessary to confirm the tumorgenicity of these antigens. However, the use of single-chain variable autoantibody fragments presents a novel platform for diagnostics and cancer therapeutics.
ContributorsSharman, M. Camila (Author) / Magee, Dewey (Mitch) (Thesis director) / Wallstrom, Garrick (Committee member) / Petritis, Brianne (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor) / Virginia G. Piper Center for Personalized Diagnostics (Contributor) / Biodesign Institute (Contributor)
Created2012-12
Description
In September 1974, a guerrilla organization called the Montoneros captured Juan and Jorge Born, two Argentinean heirs to a massive food processing conglomerate, and held them for ransom. After months of negotiations between this radical political group and the brothers' family, the Montoneros received $61.5 million dollars for the brothers' re- lease. Other kidnappings followed, netting the revolutionaries close to $100 million dol- lars. Although their tactics initially brought them recognition, they also unleashed a vio- lent response. Through a military coup, General Jorge Videla assumed power and used counterinsurgency tactics against the radical left wing of the Peronist party members. The coming years of military repression put an end to the revolutionary efforts of the Mon- toneros and gave the military leaders a reputation of violators of human rights. Even the Argentine people called the repression the "Dirty War," and investigations estimate that 30,000 people, the Montoneros among them, disappeared.
ContributorsScarvie, Matthew (Author) / Stoner, Kathryn (Thesis director) / Hinojosa, Magda (Committee member) / Mitchell, Michael (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2012-12