Matching Items (343)
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
The purpose of this study is to first investigate the role of political socialization on young men and women and what motivates them to become politically active and make the ultimate decision to run for elected office. These effects include parental attitudes, exposure to political shows and news sources, participation in voluntary organizations, and overall community involvement. After understanding these direct and indirect effects of political socialization, I can attempt to explain the causes for the gender gap in political ambition \u2014 meaning that significantly more men are running for elected office compared to women.
ContributorsOsgood, Shannon Marie (Author) / Woodall, Gina (Thesis director) / Herrera, Richard (Committee member) / Barrett, The Honors College (Contributor) / College of Public Service and Community Solutions (Contributor) / School of Public Affairs (Contributor) / School of Politics and Global Studies (Contributor)
Created2015-05
Description
The Undoing Project is an ongoing educational feminist YouTube channel that serves as an introduction to feminism and feminist theory. The objective for this project is to present feminist theory and feminist ideology in an accessible and entertaining way. Through this project I sought to accomplish three goals: to challenge the negative image of feminism, bridge the gap between the language of academia and the public, and to acknowledge and unlearn ingrained prejudices. The videos focus on theory, history, legislation, current events, and pop culture. The initial project consists of ten videos addressing the feminist wave models, a brief history of the feminist movement, and discussions of concepts like hegemony, intersectionality, masculinity, femininity, and race.
ContributorsBuchholtz, Kaylee Marie (Author) / Brian, Jennifer (Thesis director) / Grzanka, Patrick (Committee member) / Brouwer, Dan (Committee member) / Barrett, The Honors College (Contributor) / College of Public Service and Community Solutions (Contributor) / School of Social Transformation (Contributor) / Department of English (Contributor)
Created2015-05
Description
Introduction/Purpose: the purpose of this study was to explore the perception of care after stillbirth and the use of physical activity and/or mindful approaches (e.g., yoga) to cope with grief in women of racial/ethnic minority who have experienced stillbirth.
Methods: This was an exploratory qualitative research study. Participants were African American, Hispanic, Asian, and American Indian women, between the ages of 26 and 38, who have experienced stillbirth within the past 3 years. Participants completed a 20-30 minute phone interview.
Results: Fourteen women participated in the study (M age = 31.02 ± 5.97 years; M time since stillbirth = 1.47 ± 0.94 years). Women’s perceptions about physical activity and mindfulness to cope with grief were coded into the following major themes: perception of health care after stillbirth (satisfaction with the level of care provided), recommendations about inter-conception health care from physician (relating to mental, emotional, and physical health), grief (comfort with communicating with the physician), coping mechanisms, perception of the relationship between physical activity and mood, barriers to participating in physical activity (social and behavioral), pre-pregnancy physical activity, and perception of mindful approach (e.g., yoga) as a coping mechanism.
Conclusion: This was the first study to explore perceptions of health care and the use of physical activity and/or mindful approaches (e.g., yoga) to cope with grief after stillbirth in women of racial/ethnic minority. Findings from this study may help inform health care professionals alter their care practices and introduce physical activity and mindfulness based approaches as coping mechanisms to mothers of stillborn babies.
Methods: This was an exploratory qualitative research study. Participants were African American, Hispanic, Asian, and American Indian women, between the ages of 26 and 38, who have experienced stillbirth within the past 3 years. Participants completed a 20-30 minute phone interview.
Results: Fourteen women participated in the study (M age = 31.02 ± 5.97 years; M time since stillbirth = 1.47 ± 0.94 years). Women’s perceptions about physical activity and mindfulness to cope with grief were coded into the following major themes: perception of health care after stillbirth (satisfaction with the level of care provided), recommendations about inter-conception health care from physician (relating to mental, emotional, and physical health), grief (comfort with communicating with the physician), coping mechanisms, perception of the relationship between physical activity and mood, barriers to participating in physical activity (social and behavioral), pre-pregnancy physical activity, and perception of mindful approach (e.g., yoga) as a coping mechanism.
Conclusion: This was the first study to explore perceptions of health care and the use of physical activity and/or mindful approaches (e.g., yoga) to cope with grief after stillbirth in women of racial/ethnic minority. Findings from this study may help inform health care professionals alter their care practices and introduce physical activity and mindfulness based approaches as coping mechanisms to mothers of stillborn babies.
ContributorsArvayo, Jordan Michelle (Author) / Huberty, Jennifer (Thesis director) / Hoffner, Kristin (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2015-05
Description
This study examined the effect of an 8-week exercise intervention on functional exercise capacity in adolescents with Down syndrome (DS). Forty participants were randomly assigned to one of three groups: assisted cycling (ACT) (n = 17) where participants experienced at least a 35% increase in their voluntary cycling speed through the use of a motor, voluntary cycling (VC) (n = 15) where participants cycled at a self-selected cadence, and no cycling (NC) (n = 8) where participants did not participate in any cycling intervention. In each cycling intervention, each participant completed three, 30 minute cycling sessions per week for a total of eight weeks. The Six-Minute Walk Test (6MWT) was administered prior to and after the 8-week intervention in pre-test and post-test assessment sessions, respectively. Our hypothesis was somewhat supported in that functional exercise capacity improved after ACT as measured by an increase in total number of laps walked, total distance walked, and average walking speed during the 6MWT, when compared to VC or NC.
ContributorsCook, Megan Rey (Author) / Ringenbach, Shannon (Thesis director) / Huberty, Jennifer (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2015-05
Description
Previous research has found improvements in motor and cognitive measures following Assisted Cycle Therapy (AC) in adolescence with Down syndrome (DS). Our study investigated whether we would find improvements in older adults with DS on measures of leisure physical activity (GLTEQ) and sleep, which are early indicators of Alzheimer's disease (AD) in persons with Down syndrome. This study consisted of eight participants with Down syndrome between 31 and 51 years old that cycled for 30 minutes 3 x/week for eight weeks either at their voluntary cycling rate (VC) or approximately 35% faster with the help of a mechanical motor (AC). We predicted that, based on pilot data (Gomez, 2015), GLTEQ would either maintain or improve after AC, but would decrease after VC and would stay the same after NC. We predicted that the sleep score may improve after both VC or AC or it may improve more after VC than AC based on pilot data related to leisure activity. Our results were consistent with our prediction that GLTEQ will either maintain or improve after AC but will decrease after VC. Our results were not consistent with our prediction that sleep may improve after both VC or AC or it may improve more after VC than AC, possibly because we did not pre-screen for sleep disorders. Future research should focus on recruiting more participants and using both objective and subjective measures of sleep and physical activity to improve the efficacy of the study.
ContributorsParker, Lucas Maury (Author) / Ringenbach, Shannon (Thesis director) / Buman, Matthew (Committee member) / Holzapfel, Simon (Committee member) / School of Social and Behavioral Sciences (Contributor) / School of Nutrition and Health Promotion (Contributor) / College of Public Service and Community Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Objective: Fewer than 50% of female college freshmen meet physical activity (PA) guidelines. Innovative approaches that help college women increase their PA are warranted. The study purpose was to pilot test a magazine-based discussion group for improving PA, self-worth, and nutrition behaviors in freshmen college females. Method: Thirty-seven women (18-20 years) were randomized to intervention (n=17) and control (n=20) groups. The intervention group participated in an 8-week magazine-based discussion group adapted from a previously tested social cognitive theory based intervention, Fit Minded. Excerpts from a popular women's health magazine were discussed during weekly meetings incorporating PA, self-worth and nutrition education. The control group did not attend meetings, but received the magazines. Outcomes and feasibility measures included: self-reported PA, general self-worth, knowledge self-worth, self-efficacy, social support, and daily fruits, vegetables, junk food, sugar-sweetened beverage consumption. Results: Twelve participants from the intervention group attended more than 75% of meetings. A time effect was observed for PA (p=0.001) and family social support (p=0.002). Time x group effects were observed for PA (p=0.001), general self-worth (p=0.04), knowledge self-worth (p=0.03), and daily sugar-sweetened beverage consumption (p=0.03), with the intervention group reporting greater increases in PA, general self-worth and knowledge self-worth and greater decreases in daily sugar-sweetened beverage consumption. Although not significant, the intervention group demonstrated positive trends in self-efficacy, friend social support and fruit and veggie consumption as compared to the control group. Conclusion: A magazine-based discussion group may provide a promising platform to improve PA, self-worth and nutrition behaviors in female college freshmen.
ContributorsPellitteri, Katelyn (Author) / Huberty, Jennifer (Thesis director) / Bruening, Meg (Committee member) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / School of Social Transformation (Contributor) / Sandra Day O'Connor College of Law (Contributor)
Created2014-05
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