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Description
A coincidence reporter construct, consisting of the p21-promoter and two luciferase genes (Firefly and Renilla), was constructed for the screening of drugs that might inhibit Olig2's tumorigenic role in glioblastoma. The reporter construct was tested using an Olig2 inhibitor, HSP990, as well as short hairpin RNA targeting Olig2. Further confirmatory

A coincidence reporter construct, consisting of the p21-promoter and two luciferase genes (Firefly and Renilla), was constructed for the screening of drugs that might inhibit Olig2's tumorigenic role in glioblastoma. The reporter construct was tested using an Olig2 inhibitor, HSP990, as well as short hairpin RNA targeting Olig2. Further confirmatory analysis is needed before the reporter cell line is ready for high-throughput screening at the NIH and lead compound selection.
ContributorsCusimano, Joseph Michael (Author) / LaBaer, Joshua (Thesis director) / Mangone, Marco (Committee member) / Mehta, Shwetal (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2014-05
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Description
The pathogenesis of type 1 diabetes (T1D) is still not fully understood in the scientific community. Evidence has shown that viral infections are one of the important environmental factors associated with the disease development. Seven of the top T1D related viruses were selected to study the prevalence of viral humoral

The pathogenesis of type 1 diabetes (T1D) is still not fully understood in the scientific community. Evidence has shown that viral infections are one of the important environmental factors associated with the disease development. Seven of the top T1D related viruses were selected to study the prevalence of viral humoral response in T1D patients using our innovative protein array platform called Nucleic Acid Programmable Protein Array (NAPPA). In this study, each viral gene was individually captured using various PCR based techniques, cloned into a protein expression vector, and assembled as the first version of T1D viral protein array. Humoral responses of IgG, IgA, and IgM were examined. Although each class of immunoglobulin generated a wide-range of reactivity, responses to various viral proteins from different proteins were observed. In summary, we captured most of the T1D related viral genes, established viral protein expression on the protein array, and displayed the serum response on the viral protein array. The successful progress will help to fulfill the long term goal of testing the viral infection hypothesis in T1D development.
ContributorsDavis, Amy Darlene (Author) / LaBaer, Joshua (Thesis director) / Qiu, Ji (Committee member) / Desi, Paul (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2013-05
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Description
Childhood obesity is a growing public health concern in the United States. For several years, many interventions have been established to reduce the prevalence of childhood obesity. However, these interventions have not adequately utilized existing models of behavior change, and as a result, have been unsuccessful in increasing levels of

Childhood obesity is a growing public health concern in the United States. For several years, many interventions have been established to reduce the prevalence of childhood obesity. However, these interventions have not adequately utilized existing models of behavior change, and as a result, have been unsuccessful in increasing levels of physical activity and healthy dietary intake. One such model of change, the Transtheoretical Model, views behavior change as occurring through a series of stages with progression through the stages being facilitated by cognitive and behavioral processes. Within these processes the constructs of consciousness-raising, helping relationships, and self-efficacy have been shown to be most influential in changing behaviors. Thus, the objective of this paper is to evaluate the effectiveness of such constructs and establish a multi-faceted approach to combat this epidemic.
ContributorsWang, Janice (Author) / Broman, Tannah (Thesis director) / Hoffner, Kristin (Committee member) / Baldwin, Marjorie (Committee member) / Barrett, The Honors College (Contributor) / College of Health Solutions (Contributor)
Created2012-12
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Description
Children's wellbeing has been of utmost concern to society, and recently this topic has taken a particular focus in both health and achievement. As the focus shifts towards promoting a healthier and more academically successful youth, the relationship between the two warrants investigation. Specifically, the relationship between physical fitness and

Children's wellbeing has been of utmost concern to society, and recently this topic has taken a particular focus in both health and achievement. As the focus shifts towards promoting a healthier and more academically successful youth, the relationship between the two warrants investigation. Specifically, the relationship between physical fitness and academic performance (i.e. grades) in 4th grade students was assessed. A cross-sectional design was used to assess physical fitness of children (M=9.39 years) by means of the FITNESSGRAM assessment tool. Third-quarter grades were used to measure academic performance. Relationships between the variables were determined through bivariate plots, Pearson product moment correlation analysis, independent t-tests, and a three-step regression analysis. The results show a significant relationship between students' aerobic fitness and academic performance. Furthermore, the findings of this study suggest incremental validity between aerobic fitness and academic performance, thus implying predictive value associated with increased physical fitness and academic achievement.
ContributorsMoore, Shannon (Author) / Kulinna, Pamela (Thesis director) / Hoffner, Kristin (Committee member) / Stylianou, Michalis (Committee member) / Barrett, The Honors College (Contributor) / College of Health Solutions (Contributor)
Created2012-12
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Description
Protein AMPylation is a recently discovered and relatively unstudied post-translational modification (PTM). AMPylation has previously been shown to play an important role in metabolic regulation and host pathogenesis in bacteria, but the recent identification of potential AMPylators across many species in every domain of life has supported the possibility that

Protein AMPylation is a recently discovered and relatively unstudied post-translational modification (PTM). AMPylation has previously been shown to play an important role in metabolic regulation and host pathogenesis in bacteria, but the recent identification of potential AMPylators across many species in every domain of life has supported the possibility that AMPylation could be a more fundamental and physiologically significant regulatory PTM. For the first time, we characterized the auto-AMPylation capability of the human protein SOS1 through in vitro AMPylation experiments using full-length protein and whole-domain truncation mutants. We found that SOS1 can become AMPylated at a tyrosine residue possibly within the Cdc25 domain of the protein, the Dbl homology domain is vital for efficient auto-AMPylation activity, and the C-terminal proline-rich domain exhibits a complex regulatory function. The proline-rich domain alone also appears to be capable of catalyzing a separate, unidentified covalent self-modification using a fluorescent ATP analogue. Finally, SOS1 was shown to be capable of catalyzing the AMPylation of two endogenous human protein substrates: a ubiquitous, unidentified protein of ~49kDa and another breast-cancer specific, unidentified protein of ~28kDa.
ContributorsOber-Reynolds, Benjamin John (Author) / LaBaer, Joshua (Thesis director) / Borges, Chad (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2014-05
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Description
AMPylation is a post-translation modification that has an important role in the survival of many bacterial pathogens by affecting the host cell's molecular signaling. In the course of studying this intercellular manipulation, there has only been modest progression in the identification of the enzymes with AMPylation capabilities (AMPylators) and their

AMPylation is a post-translation modification that has an important role in the survival of many bacterial pathogens by affecting the host cell's molecular signaling. In the course of studying this intercellular manipulation, there has only been modest progression in the identification of the enzymes with AMPylation capabilities (AMPylators) and their respective targets. The reason for these minimal developments is the inability to analyze a large subset of these proteins. Therefore, to increase the efficiency of the identification and characterization of the proteins, Yu et al developed a high-throughput non-radioactive discovery platform using Human Nucleic Acid Programmable Protein Arrays (NAPPA) and a validation platform using bead-based assays. The large-scale unbiased screening of potential substrates for two bacterial AMPylators containing Fic domain, VopS and IbpAFic2, had been performed and dozens of novel substrates were identified and confirmed. With the efficiency of this method, the platform was extended to the identification of novel substrates for a Legionella virulence factor, SidM, containing a different adenylyl transferase domain. The screening was performed using NAPPA arrays comprising of 10,000 human proteins, the active AMPylator SidM, and its inactive D110/112A mutant as a negative control. Many potential substrates of SidM were found, including Rab GTPases and non-GTPase proteins. Several of which have been confirmed with the bead-based AMPylation assays.
ContributorsGraves, Morgan C. (Author) / LaBaer, Joshua (Thesis director) / Qiu, Ji (Committee member) / Yu, Xiaobo (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2013-05
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Description
The purpose of this project was to identify proteins associated with the migration and invasion of non-transformed MCF10A mammary epithelial cells with ectopically expressed missense mutations in p53. Because of the prevalence of TP53 missense mutations in basal-like and triple-negative breast cancer tumors, understanding the effect of TP53 mutations on

The purpose of this project was to identify proteins associated with the migration and invasion of non-transformed MCF10A mammary epithelial cells with ectopically expressed missense mutations in p53. Because of the prevalence of TP53 missense mutations in basal-like and triple-negative breast cancer tumors, understanding the effect of TP53 mutations on the phenotypic expression of human mammary epithelial cells may offer new therapeutic targets for those currently lacking in treatment options. As such, MCF10A mammary epithelial cells ectopically overexpressing structural mutations (G245S, H179R, R175H, Y163C, Y220C, and Y234C) and DNA-binding mutations (R248Q, R248W, R273C, and R273H) in the DNA-binding domain were selected for use in this project. Overexpression of p53 in the mutant cell lines was confirmed by western blot and q-PCR analysis targeting the V5 epitope tag present in the pLenti4 vector used to transduce TP53 into the mutant cell lines. Characterization of the invasion and migration phenotypes resulting from the overexpression of p53 in the mutant cell lines was achieved using transwell invasion and migration assays with Boyden chambers. Statistical analysis showed that three cell lines—DNA-contact mutants R248W and R273C and structural mutant Y220C—were consistently more migratory and invasive and demonstrated a relationship between the migration and invasion properties of the mutant cell lines. Two families of proteins were then explored: those involved in the Epithelial-Mesenchymal Transition (EMT) and matrix metalloproteinases (MMPs). Results of q-PCR and immunofluorescence analysis of epithelial marker E-cadherin and mesenchymal proteins Slug and Vimentin did not show a clear relationship between mRNA and protein expression levels with the migration and invasiveness phenotypes observed in the transwell studies. Results of western blotting, q-PCR, and zymography of MMP-2 and MMP-9 also did not show any consistent results indicating a definite relationship between MMPs and the overall invasiveness of the cells. Finally, two drugs were tested as possible treatments inhibiting invasiveness: ebselen and SBI-183. These drugs were tested on only the most invasive of the MCF10A p53 mutant cell lines (R248W, R273C, and Y220C). Results of invasion assay following 30 μM treatment with ebselen and SBI-183 showed that ebselen does not inhibit invasiveness; SBI-183, however, did inhibit invasiveness in all three cell lines tested. As such, SBI-183 will be an important compound to study in the future as a treatment that could potentially serve to benefit triple-negative or basal-like breast cancer patients who currently lack therapeutic treatment options.
ContributorsZhang, Kathie Q (Author) / LaBaer, Joshua (Thesis director) / Anderson, Karen (Committee member) / Gonzalez, Laura (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2015-05
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Description

It is well known that the lack of care coordination in the healthcare system causes numerous problems including cost inefficiency and inconsistent care, specifically for complex pediatric and adult patients. Many pediatric patients have complex medical and social service needs which can be expensive for both the patient’s parents and

It is well known that the lack of care coordination in the healthcare system causes numerous problems including cost inefficiency and inconsistent care, specifically for complex pediatric and adult patients. Many pediatric patients have complex medical and social service needs which can be expensive for both the patient’s parents and the general healthcare system. Therefore, it is difficult for the healthcare system to deliver the highest quality care possible, due to the number of appointments that have to be scheduled (with some being out of state), the large volume of physical health records, and overall lack of time parents have to coordinate this care while also caring for themselves and other family members. It is integral to find a more efficient way to coordinate care for these patients, in order to improve overall care, cost efficiency, and outcomes. <br/>A number of stakeholders in Arizona came together to work on this problem over several years. They were funded through a PCORI Eugene Washington Engagement grant to investigators at ASU. This project, Take Action for Arizona's Children through Care Coordination: A Bridge to Action was developed in order to further develop a research agenda and build the network (PCOR). Regional conferences were conducted in Flagstaff, Yuma, Phoenix, and Tucson, as well as a final capstone conference held in Phoenix. At these conferences, frustrations, suggestions, and opinions regarding Children with Special Health Care Needs (CSHCN) and navigating the healthcare system were shared and testimonials were transcribed.<br/>This study focused on the capstone conference. The study design was a strategic design workshop; results of the design analysis were analyzed qualitatively using descriptive content analysis. Themes described parent’s common experiences navigating the system, impacts resulting from such experiences, and desires for the care coordination system. Quotes were then grouped into major themes and subthemes for the capstone conference. After these themes were determined, the overarching goals of stakeholders could be assessed, and implementation projects could be described.

ContributorsBrennan, Bayley (Author) / Doebbeling, Bradley (Thesis director) / Lamb, Gerri (Committee member) / College of Health Solutions (Contributor, Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

This thesis discusses why there is so much employee turnover in the Sports Programs department, which is a working department of the Sun Devil Fitness Complex on Arizona State’s Tempe Campus. The analysis discusses the problems that have been noticed from personal experience, and the problems that have been

This thesis discusses why there is so much employee turnover in the Sports Programs department, which is a working department of the Sun Devil Fitness Complex on Arizona State’s Tempe Campus. The analysis discusses the problems that have been noticed from personal experience, and the problems that have been explained by employees that left about why they decided to leave. The analysis is done based on the concepts of the four frames, based on research documented by Bolman and Deal in their book. There is an overview of all of the departments and specifically the Sports Programs department, and a deep dive into what that department does. There is a discussion of what problems may be present, and some solutions such as debriefings, trainings, and more objective evaluations that can be implemented into the department to try to fix the problems that have been noticed.

ContributorsRoegge, Kylie Anne (Author) / deLusé, Stephanie (Thesis director) / Cobb, Ethan (Committee member) / School of International Letters and Cultures (Contributor) / College of Health Solutions (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

This project explorers the potential reasons for the discrepancies between state responses to the COVID-19 pandemic, with a particular focus on the possibility of a correlation between political ideology and a state’s nonpharmacological intervention policy timing. In addition to outlining the current literature on the preferences of conservative and liberal

This project explorers the potential reasons for the discrepancies between state responses to the COVID-19 pandemic, with a particular focus on the possibility of a correlation between political ideology and a state’s nonpharmacological intervention policy timing. In addition to outlining the current literature on the preferences of conservative and liberal ideology, examples of both past and present scientific based pandemic responses are described as well. Given the current understanding of the social and economic dimension of conservative and liberal political ideology, it was hypothesized that there may be a positive correlation between conservative ideology and premature action by a state. Data was collected on the current ideological landscape and the daily COVID-19 cases numbers of each state in addition to tracking each state’s policy changes. Two correlation tests were performed to find that there was no significant positive or negative correlation between the two variables.

ContributorsArlak, Alexis Taylor (Author) / Green, Ellen (Thesis director) / Biviji, Rizwana (Committee member) / Historical, Philosophical & Religious Studies (Contributor) / College of Health Solutions (Contributor) / Historical, Philosophical & Religious Studies, Sch (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05