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Description
Sparsity has become an important modeling tool in areas such as genetics, signal and audio processing, medical image processing, etc. Via the penalization of l-1 norm based regularization, the structured sparse learning algorithms can produce highly accurate models while imposing various predefined structures on the data, such as feature groups

Sparsity has become an important modeling tool in areas such as genetics, signal and audio processing, medical image processing, etc. Via the penalization of l-1 norm based regularization, the structured sparse learning algorithms can produce highly accurate models while imposing various predefined structures on the data, such as feature groups or graphs. In this thesis, I first propose to solve a sparse learning model with a general group structure, where the predefined groups may overlap with each other. Then, I present three real world applications which can benefit from the group structured sparse learning technique. In the first application, I study the Alzheimer's Disease diagnosis problem using multi-modality neuroimaging data. In this dataset, not every subject has all data sources available, exhibiting an unique and challenging block-wise missing pattern. In the second application, I study the automatic annotation and retrieval of fruit-fly gene expression pattern images. Combined with the spatial information, sparse learning techniques can be used to construct effective representation of the expression images. In the third application, I present a new computational approach to annotate developmental stage for Drosophila embryos in the gene expression images. In addition, it provides a stage score that enables one to more finely annotate each embryo so that they are divided into early and late periods of development within standard stage demarcations. Stage scores help us to illuminate global gene activities and changes much better, and more refined stage annotations improve our ability to better interpret results when expression pattern matches are discovered between genes.
ContributorsYuan, Lei (Author) / Ye, Jieping (Thesis advisor) / Wang, Yalin (Committee member) / Xue, Guoliang (Committee member) / Kumar, Sudhir (Committee member) / Arizona State University (Publisher)
Created2013
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Description
In order to cope with the decreasing availability of symphony jobs and collegiate faculty positions, many musicians are starting to pursue less traditional career paths. Also, to combat declining audiences, musicians are exploring ways to cultivate new and enthusiastic listeners through relevant and engaging performances. Due to these challenges, many

In order to cope with the decreasing availability of symphony jobs and collegiate faculty positions, many musicians are starting to pursue less traditional career paths. Also, to combat declining audiences, musicians are exploring ways to cultivate new and enthusiastic listeners through relevant and engaging performances. Due to these challenges, many community-based chamber music ensembles have been formed throughout the United States. These groups not only focus on performing classical music, but serve the needs of their communities as well. The problem, however, is that many musicians have not learned the business skills necessary to create these career opportunities. In this document I discuss the steps ensembles must take to develop sustainable careers. I first analyze how groups build a strong foundation through getting to know their communities and creating core values. I then discuss branding and marketing so ensembles can develop a public image and learn how to publicize themselves. This is followed by an investigation of how ensembles make and organize their money. I then examine the ways groups ensure long-lasting relationships with their communities and within the ensemble. I end by presenting three case studies of professional ensembles to show how groups create and maintain successful careers. Ensembles must develop entrepreneurship skills in addition to cultivating their artistry. These business concepts are crucial to the longevity of chamber groups. Through interviews of successful ensemble members and my own personal experiences in the Tetra String Quartet, I provide a guide for musicians to use when creating a community-based ensemble.
ContributorsDalbey, Jenna (Author) / Landschoot, Thomas (Thesis advisor) / McLin, Katherine (Committee member) / Ryan, Russell (Committee member) / Solis, Theodore (Committee member) / Spring, Robert (Committee member) / Arizona State University (Publisher)
Created2013
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Description
This thesis research focuses on developing a single-cell gene expression analysis method for marine diatom Thalassiosira pseudonana and constructing a chip level tool to realize the single cell RT-qPCR analysis. This chip will serve as a conceptual foundation for future deployable ocean monitoring systems. T. pseudonana, which is a common

This thesis research focuses on developing a single-cell gene expression analysis method for marine diatom Thalassiosira pseudonana and constructing a chip level tool to realize the single cell RT-qPCR analysis. This chip will serve as a conceptual foundation for future deployable ocean monitoring systems. T. pseudonana, which is a common surface water microorganism, was detected in the deep ocean as confirmed by phylogenetic and microbial community functional studies. Six-fold copy number differences between 23S rRNA and 23S rDNA were observed by RT-qPCR, demonstrating the moderate functional activity of detected photosynthetic microbes in the deep ocean including T. pseudonana. Because of the ubiquity of T. pseudonana, it is a good candidate for an early warning system for ocean environmental perturbation monitoring. This early warning system will depend on identifying outlier gene expression at the single-cell level. An early warning system based on single-cell analysis is expected to detect environmental perturbations earlier than population level analysis which can only be observed after a whole community has reacted. Preliminary work using tube-based, two-step RT-qPCR revealed for the first time, gene expression heterogeneity of T. pseudonana under different nutrient conditions. Heterogeneity was revealed by different gene expression activity for individual cells under the same conditions. This single cell analysis showed a skewed, lognormal distribution and helped to find outlier cells. The results indicate that the geometric average becomes more important and representative of the whole population than the arithmetic average. This is in contrast with population level analysis which is limited to arithmetic averages only and highlights the value of single cell analysis. In order to develop a deployable sensor in the ocean, a chip level device was constructed. The chip contains surface-adhering droplets, defined by hydrophilic patterning, that serve as real-time PCR reaction chambers when they are immersed in oil. The chip had demonstrated sensitivities at the single cell level for both DNA and RNA. The successful rate of these chip-based reactions was around 85%. The sensitivity of the chip was equivalent to published microfluidic devices with complicated designs and protocols, but the production process of the chip was simple and the materials were all easily accessible in conventional environmental and/or biology laboratories. On-chip tests provided heterogeneity information about the whole population and were validated by comparing with conventional tube based methods and by p-values analysis. The power of chip-based single-cell analyses were mainly between 65-90% which were acceptable and can be further increased by higher throughput devices. With this chip and single-cell analysis approaches, a new paradigm for robust early warning systems of ocean environmental perturbation is possible.
ContributorsShi, Xu (Author) / Meldrum, Deirdre R. (Thesis advisor) / Zhang, Weiwen (Committee member) / Chao, Shih-hui (Committee member) / Westerhoff, Paul (Committee member) / Arizona State University (Publisher)
Created2013
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Description
American Primitive is a composition written for wind ensemble with an instrumentation of flute, oboe, clarinet, bass clarinet, alto, tenor, and baritone saxophones, trumpet, horn, trombone, euphonium, tuba, piano, and percussion. The piece is approximately twelve minutes in duration and was written September - December 2013. American Primitive is absolute

American Primitive is a composition written for wind ensemble with an instrumentation of flute, oboe, clarinet, bass clarinet, alto, tenor, and baritone saxophones, trumpet, horn, trombone, euphonium, tuba, piano, and percussion. The piece is approximately twelve minutes in duration and was written September - December 2013. American Primitive is absolute music (i.e. it does not follow a specific narrative) comprising blocks of distinct, contrasting gestures which bookend a central region of delicate textural layering and minimal gestural contrast. Though three gestures (a descending interval followed by a smaller ascending interval, a dynamic swell, and a chordal "chop") were consciously employed throughout, it is the first gesture of the three that creates a sense of unification and overall coherence to the work. Additionally, the work challenges listeners' expectations of traditional wind ensemble music by featuring the trumpet as a quasi-soloist whose material is predominately inspired by transcriptions of jazz solos. This jazz-inspired material is at times mimicked and further developed by the ensemble, also often in a soloistic manner while the trumpet maintains its role throughout. This interplay of dialogue between the "soloists" and the "ensemble" further skews listeners' conceptions of traditional wind ensemble music by featuring almost every instrument in the ensemble. Though the term "American Primitive" is usually associated with the "naïve art" movement, it bears no association to the music presented in this work. Instead, the term refers to the author's own compositional attitudes, education, and aesthetic interests.
ContributorsJandreau, Joshua (Composer) / Rockmaker, Jody D (Thesis advisor) / Rogers, Rodney I (Committee member) / Demars, James R (Committee member) / Arizona State University (Publisher)
Created2014
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Description
This project is a practical annotated bibliography of original works for oboe trio with the specific instrumentation of two oboes and English horn. Presenting descriptions of 116 readily available oboe trios, this project is intended to promote awareness, accessibility, and performance of compositions within this genre.

The annotated bibliography focuses

This project is a practical annotated bibliography of original works for oboe trio with the specific instrumentation of two oboes and English horn. Presenting descriptions of 116 readily available oboe trios, this project is intended to promote awareness, accessibility, and performance of compositions within this genre.

The annotated bibliography focuses exclusively on original, published works for two oboes and English horn. Unpublished works, arrangements, works that are out of print and not available through interlibrary loan, or works that feature slightly altered instrumentation are not included.

Entries in this annotated bibliography are listed alphabetically by the last name of the composer. Each entry includes the dates of the composer and a brief biography, followed by the title of the work, composition date, commission, and dedication of the piece. Also included are the names of publishers, the length of the entire piece in minutes and seconds, and an incipit of the first one to eight measures for each movement of the work.

In addition to providing a comprehensive and detailed bibliography of oboe trios, this document traces the history of the oboe trio and includes biographical sketches of each composer cited, allowing readers to place the genre of oboe trios and each individual composition into its historical context. Four appendices at the end include a list of trios arranged alphabetically by composer's last name, chronologically by the date of composition, and by country of origin and a list of publications of Ludwig van Beethoven's oboe trios from the 1940s and earlier.
ContributorsSassaman, Melissa Ann (Author) / Schuring, Martin (Thesis advisor) / Buck, Elizabeth (Committee member) / Holbrook, Amy (Committee member) / Hill, Gary (Committee member) / Arizona State University (Publisher)
Created2014
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Description
Given the process of tumorigenesis, biological signaling pathways have become of interest in the field of oncology. Many of the regulatory mechanisms that are altered in cancer are directly related to signal transduction and cellular communication. Thus, identifying signaling pathways that have become deregulated may provide useful information

Given the process of tumorigenesis, biological signaling pathways have become of interest in the field of oncology. Many of the regulatory mechanisms that are altered in cancer are directly related to signal transduction and cellular communication. Thus, identifying signaling pathways that have become deregulated may provide useful information to better understanding altered regulatory mechanisms within cancer. Many methods that have been created to measure the distinct activity of signaling pathways have relied strictly upon transcription profiles. With advancements in comparative genomic hybridization techniques, copy number data has become extremely useful in providing valuable information pertaining to the genomic landscape of cancer. The purpose of this thesis is to develop a methodology that incorporates both gene expression and copy number data to identify signaling pathways that have become deregulated in cancer. The central idea is that copy number data may significantly assist in identifying signaling pathway deregulation by justifying the aberrant activity being measured in gene expression profiles. This method was then applied to four different subtypes of breast cancer resulting in the identification of signaling pathways associated with distinct functionalities for each of the breast cancer subtypes.
ContributorsTrevino, Robert (Author) / Kim, Seungchan (Thesis advisor) / Ringner, Markus (Committee member) / Liu, Huan (Committee member) / Arizona State University (Publisher)
Created2011
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Description
Plants are a promising upcoming platform for production of vaccine components and other desirable pharmaceutical proteins that can only, at present, be made in living systems. The unique soil microbe Agrobacterium tumefaciens can transfer DNA to plants very efficiently, essentially turning plants into factories capable of producing virtually any gene.

Plants are a promising upcoming platform for production of vaccine components and other desirable pharmaceutical proteins that can only, at present, be made in living systems. The unique soil microbe Agrobacterium tumefaciens can transfer DNA to plants very efficiently, essentially turning plants into factories capable of producing virtually any gene. While genetically modified bacteria have historically been used for producing useful biopharmaceuticals like human insulin, plants can assemble much more complicated proteins, like human antibodies, that bacterial systems cannot. As plants do not harbor human pathogens, they are also safer alternatives than animal cell cultures. Additionally, plants can be grown very cheaply, in massive quantities.

In my research, I have studied the genetic mechanisms that underlie gene expression, in order to improve plant-based biopharmaceutical production. To do this, inspiration was drawn from naturally-occurring gene regulatory mechanisms, especially those from plant viruses, which have evolved mechanisms to co-opt the plant cellular machinery to produce high levels of viral proteins. By testing, modifying, and combining genetic elements from diverse sources, an optimized expression system has been developed that allows very rapid production of vaccine components, monoclonal antibodies, and other biopharmaceuticals. To improve target gene expression while maintaining the health and function of the plants, I identified, studied, and modified 5’ untranslated regions, combined gene terminators, and a nuclear matrix attachment region. The replication mechanisms of a plant geminivirus were also studied, which lead to additional strategies to produce more toxic biopharmaceutical proteins. Finally, the mechanisms employed by a geminivirus to spread between cells were investigated. It was demonstrated that these movement mechanisms can be functionally transplanted into a separate genus of geminivirus, allowing modified virus-based gene expression vectors to be spread between neighboring plant cells. Additionally, my work helps shed light on the basic genetic mechanisms employed by all living organisms to control gene expression.
ContributorsDiamos, Andy (Author) / Mason, Hugh S (Thesis advisor) / Mor, Tsafrir (Committee member) / Hogue, Brenda (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2017
Description
Circular RNAs (circRNAs) are a class of endogenous, non-coding RNAs that are formed when exons back-splice to each other and represent a new area of transcriptomics research. Numerous RNA sequencing (RNAseq) studies since 2012 have revealed that circRNAs are pervasively expressed in eukaryotes, especially in the mammalian brain. While their

Circular RNAs (circRNAs) are a class of endogenous, non-coding RNAs that are formed when exons back-splice to each other and represent a new area of transcriptomics research. Numerous RNA sequencing (RNAseq) studies since 2012 have revealed that circRNAs are pervasively expressed in eukaryotes, especially in the mammalian brain. While their functional role and impact remains to be clarified, circRNAs have been found to regulate micro-RNAs (miRNAs) as well as parental gene transcription and may thus have key roles in transcriptional regulation. Although circRNAs have continued to gain attention, our understanding of their expression in a cell-, tissue- , and brain region-specific context remains limited. Further, computational algorithms produce varied results in terms of what circRNAs are detected. This thesis aims to advance current knowledge of circRNA expression in a region specific context focusing on the human brain, as well as address computational challenges.

The overarching goal of my research unfolds over three aims: (i) evaluating circRNAs and their predicted impact on transcriptional regulatory networks in cell-specific RNAseq data; (ii) developing a novel solution for de novo detection of full length circRNAs as well as in silico validation of selected circRNA junctions using assembly; and (iii) application of these assembly based detection and validation workflows, and integrating existing tools, to systematically identify and characterize circRNAs in functionally distinct human brain regions. To this end, I have developed novel bioinformatics workflows that are applicable to non-polyA selected RNAseq datasets and can be used to characterize circRNA expression across various sample types and diseases. Further, I establish a reference dataset of circRNA expression profiles and regulatory networks in a brain region-specific manner. This resource along with existing databases such as circBase will be invaluable in advancing circRNA research as well as improving our understanding of their role in transcriptional regulation and various neurological conditions.
ContributorsSekar, Shobana (Author) / Liang, Winnie S (Thesis advisor) / Dinu, Valentin (Thesis advisor) / Craig, David (Committee member) / Liu, Li (Committee member) / Arizona State University (Publisher)
Created2018
ContributorsPagano, Caio, 1940- (Performer) / Mechetti, Fabio (Conductor) / Buck, Elizabeth (Performer) / Schuring, Martin (Performer) / Spring, Robert (Performer) / Rodrigues, Christiano (Performer) / Landschoot, Thomas (Performer) / Rotaru, Catalin (Performer) / Avanti Festival Orchestra (Performer) / ASU Library. Music Library (Publisher)
Created2018-03-02
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Description
Parkinson’s disease (PD) is a progressive neurodegenerative disorder, diagnosed late in

the disease by a series of motor deficits that manifest over years or decades. It is characterized by degeneration of mid-brain dopaminergic neurons with a high prevalence of dementia associated with the spread of pathology to cortical regions. Patients exhibiting

Parkinson’s disease (PD) is a progressive neurodegenerative disorder, diagnosed late in

the disease by a series of motor deficits that manifest over years or decades. It is characterized by degeneration of mid-brain dopaminergic neurons with a high prevalence of dementia associated with the spread of pathology to cortical regions. Patients exhibiting symptoms have already undergone significant neuronal loss without chance for recovery. Analysis of disease specific changes in gene expression directly from human patients can uncover invaluable clues about a still unknown etiology, the potential of which grows exponentially as additional gene regulatory measures are questioned. Epigenetic mechanisms are emerging as important components of neurodegeneration, including PD; the extent to which methylation changes correlate with disease progression has not yet been reported. This collection of work aims to define multiple layers of PD that will work toward developing biomarkers that not only could improve diagnostic accuracy, but also push the boundaries of the disease detection timeline. I examined changes in gene expression, alternative splicing of those gene products, and the regulatory mechanism of DNA methylation in the Parkinson’s disease system, as well as the pathologically related Alzheimer’s disease (AD). I first used RNA sequencing (RNAseq) to evaluate differential gene expression and alternative splicing in the posterior cingulate cortex of patients with PD and PD with dementia (PDD). Next, I performed a longitudinal genome-wide methylation study surveying ~850K CpG methylation sites in whole blood from 189 PD patients and 191 control individuals obtained at both a baseline and at a follow-up visit after 2 years. I also considered how symptom management medications could affect the regulatory mechanism of DNA methylation. In the last chapter of this work, I intersected RNAseq and DNA methylation array datasets from whole blood patient samples for integrated differential analyses of both PD and AD. Changes in gene expression and DNA methylation reveal clear patterns of pathway dysregulation that can be seen across brain and blood, from one study to the next. I present a thorough survey of molecular changes occurring within the idiopathic Parkinson’s disease patient and propose candidate targets for potential molecular biomarkers.
ContributorsHenderson, Adrienne Rose (Author) / Huentelman, Matthew J (Thesis advisor) / Newbern, Jason (Thesis advisor) / Dunckley, Travis L (Committee member) / Jensen, Kendall (Committee member) / Wilson, Melissa (Committee member) / Arizona State University (Publisher)
Created2019