Matching Items (28)
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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

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
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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

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
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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

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
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Description
The creative project, The Tiniest Tumbleweed, produces a piece of children's literature in the form of a fully illustrated e-book that can serve as a model for parents, caretakers, and teachers to bring awareness to the importance of imparting positive self-efficacy concepts to young children. The project uses the work

The creative project, The Tiniest Tumbleweed, produces a piece of children's literature in the form of a fully illustrated e-book that can serve as a model for parents, caretakers, and teachers to bring awareness to the importance of imparting positive self-efficacy concepts to young children. The project uses the work of acclaimed psychologist Albert Bandura in the field of self-efficacy as the theoretical foundation of the story. The theme is clearly stated as striving to be all YOU can be and that achieving one's personal best, "is just fine, just fine indeed." By creating a children's picture book, two things are accomplished; first, children hear an endearing story of a tumbleweed and a sparrow that use principles of positive self-efficacy to overcome adversities in their lives. Second, those who teach children have a tool to use to deliver the message over and over again. The Tiniest Tumbleweed also presents a link to science with photographs of the growth patterns of tumbleweeds and house sparrows in their natural environment.
ContributorsPeach, Kathy (Co-author) / Yost, Ashley (Co-author) / Oakes, Wendy (Thesis director) / Ralston, Laurie (Committee member) / Harris, Pamela (Committee member) / Barrett, The Honors College (Contributor) / Mary Lou Fulton Teachers College (Contributor) / Division of Teacher Preparation (Contributor)
Created2013-05
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Description
Background
In the weeks following the first imported case of Ebola in the U. S. on September 29, 2014, coverage of the very limited outbreak dominated the news media, in a manner quite disproportionate to the actual threat to national public health; by the end of October, 2014, there were only

Background
In the weeks following the first imported case of Ebola in the U. S. on September 29, 2014, coverage of the very limited outbreak dominated the news media, in a manner quite disproportionate to the actual threat to national public health; by the end of October, 2014, there were only four laboratory confirmed cases of Ebola in the entire nation. Public interest in these events was high, as reflected in the millions of Ebola-related Internet searches and tweets performed in the month following the first confirmed case. Use of trending Internet searches and tweets has been proposed in the past for real-time prediction of outbreaks (a field referred to as “digital epidemiology”), but accounting for the biases of public panic has been problematic. In the case of the limited U. S. Ebola outbreak, we know that the Ebola-related searches and tweets originating the U. S. during the outbreak were due only to public interest or panic, providing an unprecedented means to determine how these dynamics affect such data, and how news media may be driving these trends.
Methodology
We examine daily Ebola-related Internet search and Twitter data in the U. S. during the six week period ending Oct 31, 2014. TV news coverage data were obtained from the daily number of Ebola-related news videos appearing on two major news networks. We fit the parameters of a mathematical contagion model to the data to determine if the news coverage was a significant factor in the temporal patterns in Ebola-related Internet and Twitter data.
Conclusions
We find significant evidence of contagion, with each Ebola-related news video inspiring tens of thousands of Ebola-related tweets and Internet searches. Between 65% to 76% of the variance in all samples is described by the news media contagion model.
Created2015-06-11
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Description

This paper presents a Bayesian framework for evaluative classification. Current education policy debates center on arguments about whether and how to use student test score data in school and personnel evaluation. Proponents of such use argue that refusing to use data violates both the public’s need to hold schools accountable

This paper presents a Bayesian framework for evaluative classification. Current education policy debates center on arguments about whether and how to use student test score data in school and personnel evaluation. Proponents of such use argue that refusing to use data violates both the public’s need to hold schools accountable when they use taxpayer dollars and students’ right to educational opportunities. Opponents of formulaic use of test-score data argue that most standardized test data is susceptible to fatal technical flaws, is a partial picture of student achievement, and leads to behavior that corrupts the measures.

A Bayesian perspective on summative ordinal classification is a possible framework for combining quantitative outcome data for students with the qualitative types of evaluation that critics of high-stakes testing advocate. This paper describes the key characteristics of a Bayesian perspective on classification, describes a method to translate a naïve Bayesian classifier into a point-based system for evaluation, and draws conclusions from the comparison on the construction of algorithmic (including point-based) systems that could capture the political and practical benefits of a Bayesian approach. The most important practical conclusion is that point-based systems with fixed components and weights cannot capture the dynamic and political benefits of a reciprocal relationship between professional judgment and quantitative student outcome data.

ContributorsDorn, Sherman (Author) / Mary Lou Fulton Teachers College (Contributor)
Created2009
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Description

The spread of academic testing for accountability purposes in multiple countries has obscured at least two historical purposes of academic testing: community ritual and management of the social structure. Testing for accountability is very different from the purpose of academic challenges one can identify in community “examinations” in 19th century

The spread of academic testing for accountability purposes in multiple countries has obscured at least two historical purposes of academic testing: community ritual and management of the social structure. Testing for accountability is very different from the purpose of academic challenges one can identify in community “examinations” in 19th century North America, or exams’ controlling access to the civil service in Imperial China. Rather than testing for ritual or access to mobility, the modern uses of testing are much closer to the state-building project of a tax census, such as the Domesday Book of medieval Britain after the Norman Invasion, the social engineering projects described in James Scott's Seeing like a State (1998), or the “mapping the world” project that David Nye described in America as Second Creation (2004). This paper will explore both the instrumental and cultural differences among testing as ritual, testing as mobility control, and testing as state-building.

ContributorsDorn, Sherman (Author) / Mary Lou Fulton Teachers College (Contributor)
Created2014-12-08
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This is a brief text intended for use in undergraduate school-and-society classes. Your class may also be titled “Social foundations of education.” “Social foundations of education” is an interdisciplinary field that includes both humanities and social-science perspectives on schooling. It thus includes study of the philosophy and history of education

This is a brief text intended for use in undergraduate school-and-society classes. Your class may also be titled “Social foundations of education.” “Social foundations of education” is an interdisciplinary field that includes both humanities and social-science perspectives on schooling. It thus includes study of the philosophy and history of education as well as sociological, economic, anthropological, and political perspectives on schooling.

The core of most social foundations classes lies in the relationship between formal schooling and broader society. This emphasis means that while some parts of psychology may be related to the core issues of social foundations classes—primarily social psychology—the questions that are asked within a social-foundations class are different from the questions raised in child development, educational psychology, and most teaching-methods classes. For example, after finishing the first chapter of this text, you should be able to answer the question, “Why does the federal government pay public schools to feed poor students at breakfast and lunch?” Though there is some psychology research tying nutrition to behavior and learning, the policy is based on much broader expectations of schools. In this case, “Children learn better if they are well-fed” both is based on research and also is an incomplete answer.

ContributorsDorn, Sherman (Author) / Mary Lou Fulton Teachers College (Contributor)
Created2013
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The current debate over graduate rate calculations and results has glossed over the relationship between student migration and the accuracy of various graduation rates proposed over the past five years. Three general grade-based graduation rates have been proposed recently, and each has a parallel version that includes an adjustment for

The current debate over graduate rate calculations and results has glossed over the relationship between student migration and the accuracy of various graduation rates proposed over the past five years. Three general grade-based graduation rates have been proposed recently, and each has a parallel version that includes an adjustment for migration, whether international, internal to the U.S., or between different school sectors. All of the adjustment factors have a similar form, allowing simulation of estimates from real data, assuming different unmeasured net migration rates. In addition, a new age-based graduation rate, based on mathematical demography, allows the simulation of estimates on a parallel basis using data from Virginia's public schools.

Both the direct analysis and simulation demonstrate that graduation rates can only be useful with accurate information about student migration. A discussion of Florida's experiences with longitudinal cohort graduation rates highlights some of the difficulties with the current status of the oldest state databases and the need for both technical confidence and definitional clarity. Meeting the No Child Left Behind mandates for school-level graduation rates requires confirmation of transfers and an audit of any state system for accuracy, and basing graduation rates on age would be a significant improvement over rates calculated using grade-based data.

ContributorsDorn, Sherman (Author) / Mary Lou Fulton Teachers College (Contributor)
Created2009