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- Creators: Novak, Gail (Pianist)
- Status: Published
ContributorsKierum, Caitlin (Contributor) / Novak, Gail (Pianist) (Performer) / Liang, Jack (Performer) / ASU Library. Music Library (Publisher)
Created2018-04-11
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
ContributorsLougheed, Julia (Performer) / Novak, Gail (Pianist) (Performer) / Bayer, Elizabeth Kennedy (Performer) / Clifton-Armenta, Tyler (Performer) / Park, Julie (Performer) / Javier de Alba, Francisco (Performer) / Vientos Dulces (Performer) / ASU Library. Music Library (Publisher)
Created2018-04-07
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
ContributorsCoffey, Brennan (Performer) / Novak, Gail (Pianist) (Performer) / ASU Library. Music Library (Publisher)
Created2021-04-26
ContributorsHolly, Sean (Performer) / Wright, Aaron (Performer) / Novak, Gail (Pianist) (Performer) / ASU Library. Music Library (Publisher)
Created2021-04-29
ContributorsBreeden, Katherine (Performer) / German, Lindsey (Performer) / Novak, Gail (Pianist) (Performer) / ASU Library. Music Library (Publisher)
Created2018-04-13
Description
ABSTRACT Many musicians, both amateur and professional alike, are continuously seeking to expand and explore their performance literature and repertory. Introducing new works into the standard repertory is an exciting endeavor for any active musician. Establishing connections, commissioning new works, and collaborating on performances can all work together toward the acceptance and success of a composer's music within an instrument community. For the flute, one such composer is Daniel Dorff (b. 1956). Dorff, a Philadelphia-based composer, has written for symphony orchestra, clarinet, contrabassoon, and others; however, his award-winning works for flute and piccolo are earning him much recognition. He has written works for such illustrious flutists as Mimi Stillman, Walfrid Kujala, and Gary Schocker; his flute works have been recorded by Laurel Zucker, Pamela Youngblood and Lois Bliss Herbine; and his pieces have been performed and premiered at each of the National Flute Association Conventions from 2004 to 2009. Despite this success, little has been written about Dorff's life, compositional style, and contributions to the flute repertory. In order to further promote the flute works of Daniel Dorff, the primary focus of this study is the creation of a compact disc recording of Dorff's most prominent works for flute: April Whirlwind, 9 Walks Down 7th Avenue, both for flute and piano, and Nocturne Caprice for solo flute. In support of this recording, the study also provides biographical information regarding Daniel Dorff, discusses his compositional methods and ideology, and presents background information, description, and performance notes for each piece. Interviews with Daniel Dorff regarding biographical and compositional details serve as the primary source for this document. Suggestions for the performance of the three flute works were gathered through interviews with prominent flutists who have studied and performed Dorff's pieces. Additional performance suggestions for Nocturne Caprice were gathered through a coaching session between the author and the composer. This project is meant to promote the flute works of Daniel Dorff and to help establish their role in the standard flute repertory.
ContributorsRich, Angela Marie (Contributor) / Novak, Gail (Pianist) (Performer) / Buck, Elizabeth Y (Thesis advisor) / Hill, Gary W. (Committee member) / Holbrook, Amy (Committee member) / Schuring, Martin (Committee member) / Arizona State University (Publisher)
Created2010
Description
The development of stab-resistant Kevlar armor has been an ongoing field of research
since the late 1990s, with the ultimate goal of improving the multi-threat capabilities of
traditional soft-body armor while significantly improving its protective efficiency - the amount
of layers of armor material required to defeat threats. To create a novel, superior materials
system to reinforce Kevlar armor for the Norica Capstone project, this thesis set out to
synthesize, recover, and characterize zinc oxide nanowire colloids.
The materials synthesized were successfully utilized in the wider Capstone effort to
dramatically enhance the protective abilities of Kevlar, while the data obtained on the 14
hydrothermal synthesis attempts and numerous challenges at recovery provided critical
information on the synthesis parameters involved in the reliable, scalable mass production of the
nanomaterial additive. Additionally, recovery was unconventionally facilitated in the absence of
a vacuum filtration apparatus with nanoscale filters by intentionally inducing electrostatic
agglomeration of the nanowires during standard gravity filtration. The subsequent application of
these nanowires constituted a pioneering use in the production of nanowire-reinforced
STF-based Kevlar coatings, and support the future development and, ultimately, the
commercialization of lighter and more-protective soft armor systems.
since the late 1990s, with the ultimate goal of improving the multi-threat capabilities of
traditional soft-body armor while significantly improving its protective efficiency - the amount
of layers of armor material required to defeat threats. To create a novel, superior materials
system to reinforce Kevlar armor for the Norica Capstone project, this thesis set out to
synthesize, recover, and characterize zinc oxide nanowire colloids.
The materials synthesized were successfully utilized in the wider Capstone effort to
dramatically enhance the protective abilities of Kevlar, while the data obtained on the 14
hydrothermal synthesis attempts and numerous challenges at recovery provided critical
information on the synthesis parameters involved in the reliable, scalable mass production of the
nanomaterial additive. Additionally, recovery was unconventionally facilitated in the absence of
a vacuum filtration apparatus with nanoscale filters by intentionally inducing electrostatic
agglomeration of the nanowires during standard gravity filtration. The subsequent application of
these nanowires constituted a pioneering use in the production of nanowire-reinforced
STF-based Kevlar coatings, and support the future development and, ultimately, the
commercialization of lighter and more-protective soft armor systems.
ContributorsDurso, Michael Nathan (Author) / Tongay, Sefaattin (Thesis director) / Zhuang, Houlong (Committee member) / Materials Science and Engineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05