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Description
Following a traumatic brain injury (TBI) 5-50% of patients will develop post traumatic epilepsy (PTE). Pediatric patients are most susceptible with the highest incidence of PTE. Currently, we cannot prevent the development of PTE and knowledge of basic mechanisms are unknown. This has led to several shortcomings to the treatment of PTE, one of which is the use of anticonvulsant medication to the population of TBI patients that are not likely to develop PTE. The complication of identifying the two populations has been hindered by the ability to find a marker to the pathogenesis of PTE. The central hypothesis of this dissertation is that following TBI, the cortex undergoes distinct cellular and synaptic reorganization that facilitates cortical excitability and promotes seizure development. Chapter 2 of this dissertation details excitatory and inhibitory changes in the rat cortex after severe TBI. This dissertation aims to identify cortical changes to a single cell level after severe TBI using whole cell patch clamp and electroencephalogram electrophysiology. The work of this dissertation concluded that excitatory and inhibitory synaptic activity in cortical controlled impact (CCI) animals showed the development of distinct burst discharges that were not present in control animals. The results suggest that CCI induces early "silent" seizures that are detectable on EEG and correlate with changes to the synaptic excitability in the cortex. The synaptic changes and development of burst discharges may play an important role in synchronizing the network and promoting the development of PTE.
ContributorsNichols, Joshua (Author) / Anderson, Trent (Thesis advisor) / Neisewander, Janet (Thesis advisor) / Newbern, Jason (Committee member) / Arizona State University (Publisher)
Created2014
Description
The ability to detect and appropriately respond to chemical stimuli is important for many organisms, ranging from bacteria to multicellular animals. Responses to these stimuli can be plastic over multiple time scales. In the short-term, the synaptic strengths of neurons embedded in neural circuits can be modified and result in various forms of learning. In the long-term, the overall developmental trajectory of the olfactory network can be altered and synaptic strengths can be modified on a broad scale as a direct result of long-term (chronic) stimulus experience. Over evolutionary time the olfactory system can impose selection pressures that affect the odorants used in communication networks. On short time scales, I measured the effects of repeated alarm pheromone exposure on the colony-level defense behaviors in a social bee. I found that the responses to the alarm pheromone were plastic. This suggests that there may be mechanisms that affect individual plasticity to pheromones and regulate how these individuals act in groups to coordinate nest defense. On longer time scales, I measured the behavioral and neural affects of bees given a single chronic odor experience versus bees that had a natural, more diverse olfactory experience. The central brains of bees with a deprived odor experience responded more similarly to odorants in imaging studies, and did not develop a fully mature olfactory network. Additionally, these immature networks showed behavioral deficits when recalling odor mixture components. Over evolutionary time, signals need to engage the attention of and be easily recognized by bees. I measured responses of bees to a floral mixture and its constituent monomolecular components. I found that natural floral mixtures engage the orientation of bees’ antennae more strongly than single-component odorants and also provide more consistent central brain responses between stimulations. Together, these studies highlight the importance of olfactory experience on different scales and how the nervous system might impose pressures to select the stimuli used as signals in communication networks.
ContributorsJernigan, Christopher (Author) / Smith, Brian H. (Thesis advisor) / Newbern, Jason (Committee member) / Harrisoin, Jon (Committee member) / Rutowski, Ronald (Committee member) / Pratt, Stephen (Committee member) / Arizona State University (Publisher)
Created2018
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 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.
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
Description
Multicellular organisms use precise gene regulation, executed throughout development, to build and sustain various cell and tissue types. Post-transcriptional gene regulation is essential for metazoan development and acts on mRNA to determine its localization, stability, and translation. MicroRNAs (miRNAs) and RNA binding proteins (RBPs) are the principal effectors of post-transcriptional gene regulation and act by targeting the 3'untranslated regions (3'UTRs) of mRNA. MiRNAs are small non-coding RNAs that have the potential to regulate hundreds to thousands of genes and are dysregulated in many prevalent human diseases such as diabetes, Alzheimer's disease, Duchenne muscular dystrophy, and cancer. However, the precise contribution of miRNAs to the pathology of these diseases is not known.
MiRNA-based gene regulation occurs in a tissue-specific manner and is implemented by an interplay of poorly understood and complex mechanisms, which control both the presence of the miRNAs and their targets. As a consequence, the precise contributions of miRNAs to gene regulation are not well known. The research presented in this thesis systematically explores the targets and effects of miRNA-based gene regulation in cell lines and tissues.
I hypothesize that miRNAs have distinct tissue-specific roles that contribute to the gene expression differences seen across tissues. To address this hypothesis and expand our understanding of miRNA-based gene regulation, 1) I developed the human 3'UTRome v1, a resource for studying post-transcriptional gene regulation. Using this resource, I explored the targets of two cancer-associated miRNAs miR-221 and let-7c. I identified novel targets of both these miRNAs, which present potential mechanisms by which they contribute to cancer. 2) Identified in vivo, tissue-specific targets in the intestine and body muscle of the model organism Caenorhabditis elegans. The results from this study revealed that miRNAs regulate tissue homeostasis, and that alternative polyadenylation and miRNA expression patterns modulate miRNA targeting at the tissue-specific level. 3) Explored the functional relevance of miRNA targeting to tissue-specific gene expression, where I found that miRNAs contribute to the biogenesis of mRNAs, through alternative splicing, by regulating tissue-specific expression of splicing factors. These results expand our understanding of the mechanisms that guide miRNA targeting and its effects on tissue-specific gene expression.
MiRNA-based gene regulation occurs in a tissue-specific manner and is implemented by an interplay of poorly understood and complex mechanisms, which control both the presence of the miRNAs and their targets. As a consequence, the precise contributions of miRNAs to gene regulation are not well known. The research presented in this thesis systematically explores the targets and effects of miRNA-based gene regulation in cell lines and tissues.
I hypothesize that miRNAs have distinct tissue-specific roles that contribute to the gene expression differences seen across tissues. To address this hypothesis and expand our understanding of miRNA-based gene regulation, 1) I developed the human 3'UTRome v1, a resource for studying post-transcriptional gene regulation. Using this resource, I explored the targets of two cancer-associated miRNAs miR-221 and let-7c. I identified novel targets of both these miRNAs, which present potential mechanisms by which they contribute to cancer. 2) Identified in vivo, tissue-specific targets in the intestine and body muscle of the model organism Caenorhabditis elegans. The results from this study revealed that miRNAs regulate tissue homeostasis, and that alternative polyadenylation and miRNA expression patterns modulate miRNA targeting at the tissue-specific level. 3) Explored the functional relevance of miRNA targeting to tissue-specific gene expression, where I found that miRNAs contribute to the biogenesis of mRNAs, through alternative splicing, by regulating tissue-specific expression of splicing factors. These results expand our understanding of the mechanisms that guide miRNA targeting and its effects on tissue-specific gene expression.
ContributorsKotagama, Kasuen Indrajith Bandara (Author) / Mangone, Marco (Thesis advisor) / LaBaer, Joshua (Committee member) / Newbern, Jason (Committee member) / Rawls, Alan (Committee member) / Arizona State University (Publisher)
Created2019
Description
The advertising agency, in its variety of forms, is one of the most powerful forces in the modern world. Its products are seen globally through various multimedia outlets and they strongly impact culture and economy. Since its conception in 1843 by Volney Palmer, the advertising agency has evolved into the recognizable—and unrecognizable—firms scattered around the world today. In the United States alone, there are roughly 13.4 thousand agencies, many of which also have branches in other countries. The evolution of the modern advertising agency coincided with, and even preceded, some of the major inflection points in history. Understanding how and why changes in advertising agencies affected these inflection points provides a glimpse of understanding into the relationship between advertising, business, and societal values.
In the pages ahead we will explore the future of the advertising industry. We will analyze our research to uncover the underlying trends pointing towards what is to come and work to apply those explanations to our understanding of advertising in the future.
In the pages ahead we will explore the future of the advertising industry. We will analyze our research to uncover the underlying trends pointing towards what is to come and work to apply those explanations to our understanding of advertising in the future.
ContributorsHarris, Chase (Co-author) / Potthoff, Zachary (Co-author) / Gray, Nancy (Thesis director) / Samper, Adriana (Committee member) / Department of Information Systems (Contributor) / Department of Marketing (Contributor) / Herberger Institute for Design and the Arts (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The inherent risk in testing drugs has been hotly debated since the government first started regulating the drug industry in the early 1900s. Who can assume the risks associated with trying new pharmaceuticals is unclear when looked at through society's lens. In the mid twentieth century, the US Food and Drug Administration (FDA) published several guidance documents encouraging researchers to exclude women from early clinical drug research. The motivation to publish those documents and the subsequent guidance documents in which the FDA and other regulatory offices established their standpoints on women in drug research may have been connected to current events at the time. The problem of whether women should be involved in drug research is a question of who can assume risk and who is responsible for disseminating what specific kinds of information. The problem tends to be framed as one that juxtaposes the health of women and fetuses and sets their health as in opposition. That opposition, coupled with the inherent uncertainty in testing drugs, provides for a complex set of issues surrounding consent and access to information.
ContributorsMeek, Caroline Jane (Author) / Maienschein, Jane (Thesis director) / Brian, Jennifer (Committee member) / School of Life Sciences (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Few studies have examined the correlations between individual characteristics and other popular forms of social media other than Facebook. This study explored the ways emerging adults use Instagram and Snapchat and examined the relationships between social media and individual characteristics. A sample of 393 participants were recruited from a large university in the Southwestern United States. The participants completed an online questionnaire that included a newly developed social media measure along with established measures that examined the individual characteristics of social comparison orientation, self-esteem, loneliness, contingent self-worth, narcissism, and life satisfaction. In the present study, more participants reported having an active Instagram account than an active Facebook or Snapchat account. Additionally, a higher number of participants also reported preferring Instagram and Snapchat compared to Facebook. Significant correlations were found between various individual characteristics and three aspects of social media use: overall time spent on social media, whether the individual felt that their time spent on social media was meaningful, and how the individual felt emotionally after comparing themselves to others' photos and posts. Potential explanations and implications of the results are discussed.
ContributorsArndorfer, Sydney (Author) / Field, Ryan (Thesis director) / Sechler, Casey (Committee member) / School of Community Resources and Development (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The town of Guadalupe, Arizona has a long history of divided residents and high poverty rates. The high levels of poverty in the town can be attributed to numerous factors, most notably high rates of drug abuse, low high school graduation rates, and teen pregnancy. The town has named one of its most pressing issues of today to be youth disengagement. There are currently a handful of residents and community members passionate about finding a solution to this issue. After working with Guadalupe's Ending Hunger Task Force and resident youth, I set out to create a program design for a Guadalupe Youth Council. This council will contribute to combating youth disengagement. The program design will assist the task force in creating a standing youth council and deciding on the structure and role the council has in the town. I will offer learning outcomes and suggestions to the Task Force, youth council staff, and the youth of the youth council. This study contains an analysis of relevant literature, youth focus group results and data, and how the information gathered has contributed to the design of the youth council. The results of this study contain recommendations about four themes within the program design of a youth council: size, recruitment, activities and engagement, and adult support. The results also explore how the youth council will impact the power, policy, and behavior of Guadalupe youth.
ContributorsBalderas, Erica Theresa (Author) / Wang, Lili (Thesis director) / Avalos, Francisco (Committee member) / School of Community Resources and Development (Contributor) / Department of Information Systems (Contributor) / W.P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
This thesis project was conducted to create a practical tool to help micro and small local food enterprises identify potential strategies and sources of finance. Currently, many of these enterprises are unable to obtain the financial capital needed to start-up or maintain operations.
Sources and strategies of finance studied and ultimately included in the tool were Loans, Equity, Membership, Crowdfunding, and Grants. The tool designed was a matrix that takes into account various criteria of the business (e.g. business lifecycle, organizational structure, business performance) and generates a financial plan based on these criteria and how they align with the selected business strategies. After strategies are found, stakeholders can search through an institutional database created in conjunction with the matrix tool to find possible institutional providers of financing that relate to the strategy or strategies found.
The tool has shown promise in identifying sources of finance for micro and small local food enterprises in practical use with hypothetical business cases, however further practical use is necessary to provide further input and revise the tool as needed. Ultimately, the tool will likely become fully user-friendly and stakeholders will not need the assistance of another expert helping them to use it. Finally, despite the promise of the tool itself, the fundamental and underlying problem that many of these businesses face (lack of infrastructure and knowledge) still exists, and while this tool can also help capacity-building efforts towards both those seeking and those providing finance, an institutional attitude adjustment towards social and alternative enterprises is necessary in order to further simplify the process of obtaining finance.
Sources and strategies of finance studied and ultimately included in the tool were Loans, Equity, Membership, Crowdfunding, and Grants. The tool designed was a matrix that takes into account various criteria of the business (e.g. business lifecycle, organizational structure, business performance) and generates a financial plan based on these criteria and how they align with the selected business strategies. After strategies are found, stakeholders can search through an institutional database created in conjunction with the matrix tool to find possible institutional providers of financing that relate to the strategy or strategies found.
The tool has shown promise in identifying sources of finance for micro and small local food enterprises in practical use with hypothetical business cases, however further practical use is necessary to provide further input and revise the tool as needed. Ultimately, the tool will likely become fully user-friendly and stakeholders will not need the assistance of another expert helping them to use it. Finally, despite the promise of the tool itself, the fundamental and underlying problem that many of these businesses face (lack of infrastructure and knowledge) still exists, and while this tool can also help capacity-building efforts towards both those seeking and those providing finance, an institutional attitude adjustment towards social and alternative enterprises is necessary in order to further simplify the process of obtaining finance.
ContributorsDwyer, Robert Francis (Author) / Wiek, Arnim (Thesis director) / Forrest, Nigel (Committee member) / Department of Finance (Contributor) / Department of Information Systems (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
RecyclePlus is an iOS mobile application that allows users to be knowledgeable in the realms of sustainability. It gives encourages users to be environmental responsible by providing them access to recycling information. In particular, it allows users to search up certain materials and learn about its recyclability and how to properly dispose of the material. Some searches will show locations of facilities near users that collect certain materials and dispose of the materials properly. This is a full stack software project that explores open source software and APIs, UI/UX design, and iOS development.
ContributorsTran, Nikki (Author) / Ganesh, Tirupalavanam (Thesis director) / Meuth, Ryan (Committee member) / Watts College of Public Service & Community Solut (Contributor) / Department of Information Systems (Contributor) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05