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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
Description

This thesis will assess the relationship between race and perceptions of incarceration through responses gathered from interviews administered to men incarcerated at the Arizona State Prison Complex in Florence, Arizona. The interviews were conducted by incarcerated men through a Participatory Action Research (PAR) project to enhance the prison environment. Critically,

This thesis will assess the relationship between race and perceptions of incarceration through responses gathered from interviews administered to men incarcerated at the Arizona State Prison Complex in Florence, Arizona. The interviews were conducted by incarcerated men through a Participatory Action Research (PAR) project to enhance the prison environment. Critically, men who were interviewed answered the question “What would you do if you were the Director of the Department of Corrections?” The purpose of this thesis is twofold. First, what are the major themes provided to this question? Second, did these themes differ depending on the race or ethnicity of the respondent? The results from this survey can provide a more informed future for corrections that acknowledges the unique criminal justice system experiences held by members of different racial and ethnic groups.

ContributorsQuintero, Karen Rotna (Author) / Wright, Kevin (Thesis director) / Young, Jacob (Committee member) / School of Social and Behavioral Sciences (Contributor) / School of International Letters and Cultures (Contributor) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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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
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

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
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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
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

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
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Description

This study was conducted to determine the difference in compressive strength between decayed and healthy teeth. The teeth were subjected to a compressive force to simulate the process of mastication. This was done to show that healthy teeth would be better at handling these compressive forces since they have more

This study was conducted to determine the difference in compressive strength between decayed and healthy teeth. The teeth were subjected to a compressive force to simulate the process of mastication. This was done to show that healthy teeth would be better at handling these compressive forces since they have more enamel. 26 teeth samples were collected (19 molars, 4 canines, and 3 premolars) evenly distributed between healthy and decayed. The samples were dimensionally analyzed using electronic calipers and then categorized as either decayed or healthy. The samples were then placed in a nut bolt with epoxy so that the samples could be compressed. Each sample was recorded on video while they were being exposed to the compressive force. This was done to observe how the samples were coming in contact with the Shimadzu compression machine. The amount of force that was required for the samples to exhibit the first point of breakage was recorded by the machine in pounds of force. Various analyses were conducted to determine relationships between several variables. The results showed that as the total and occlusal surface area increased, so did the amount of force the samples could absorb before breakage. As the machine came in contact with more cusps among the molar samples, those samples were able to absorb a larger compressive force. The average force that the decayed and healthy molar samples endured before breakage was roughly even, with the decayed samples average being slightly greater.

ContributorsHenscheid, Keaton J (Author) / Quaranta, Kimberly (Thesis director) / Peoples, Samuel (Committee member) / College of Health Solutions (Contributor) / Dean, W.P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

This study examines the effectiveness of two modes of exercise on inhibitory control in adults with Down Syndrome (DS). Thirteen participants attended four sessions: a baseline assessment, an Assisted Cycling Therapy (ACT) session, a Resistance Training (RT) session, and a session of No Training (NT). In the baseline assessment, 1-repetition

This study examines the effectiveness of two modes of exercise on inhibitory control in adults with Down Syndrome (DS). Thirteen participants attended four sessions: a baseline assessment, an Assisted Cycling Therapy (ACT) session, a Resistance Training (RT) session, and a session of No Training (NT). In the baseline assessment, 1-repetition max (1RM) measurements and voluntary pedal rate measurements were taken. In the resistance training session, the leg press, chest press, seated row, leg curl, shoulder press, and latissimus pulldown were performed. In the cycling intervention, the participant completed 30 minutes of cycling. The Erikson Flanker task was administered prior to each session (i.e., pretest) and after the intervention (i.e., post-test). The results were somewhat consistent with the hypothesis that inhibition time improved more following RT and ACT than NT. there was also a significant difference between ACT and NT. Additionally, it was hypothesized that all measures would improve following each acute exercise intervention, but the most significant improvements were seen following ACT. In conclusion, an acute session of ACT demonstrated a significant trend towards improvements in inhibitory control in adults with DS which we interpreted using a model of neural changes.

ContributorsHayes, Claire (Author) / Ringenbach, Shannon (Thesis director) / Arnold, Nate (Committee member) / Rand, Miya (Committee member) / Edson College of Nursing and Health Innovation (Contributor) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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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

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
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Description

The various health benefits of vinegar ingestion have been studied extensively in the<br/>literature. Moreover, emerging research suggests vinegar may also have an effect on mental<br/>health. Beneficial effects of certain diets on mood have been reported, however, the mechanisms<br/>are unknown. The current study aimed to determine if vinegar ingestion positively affects

The various health benefits of vinegar ingestion have been studied extensively in the<br/>literature. Moreover, emerging research suggests vinegar may also have an effect on mental<br/>health. Beneficial effects of certain diets on mood have been reported, however, the mechanisms<br/>are unknown. The current study aimed to determine if vinegar ingestion positively affects mood<br/>state in healthy young adults. This was a randomized, single blinded controlled trial consisting of<br/>25 subjects. Participants were randomly assigned to either the vinegar group (consumed 2<br/>tablespoons of liquid vinegar diluted in one cup water twice daily with meals) or the control<br/>group (consumed one vinegar pill daily with a meal), and the intervention lasted 4 weeks.<br/>Subjects completed mood questionnaires pre- and post-intervention. Results showed a significant<br/>improvement in CES-D and POMS-Depression scores for the vinegar group compared to the<br/>control. This study suggests that vinegar ingestion may improve depressive symptoms in healthy<br/>young adults.

ContributorsWilliams, Susanna (Author) / Johnston, Carol (Thesis director) / Whisner, Corrie (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05