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Many factors are at play within the genome of an organism, contributing to much of the diversity and variation across the tree of life. While the genome is generally encoded by four nucleotides, A, C, T, and G, this code can be expanded. One particular mechanism that we examine in this thesis is modification of bases—more specifically, methylation of Adenine (m6A) within the GATC motif of Escherichia coli. These methylated adenines are especially important in a process called methyl-directed mismatch repair (MMR), a pathway responsible for repairing errors in the DNA sequence produced by replication. In this pathway, methylated adenines identify the parent strand and direct the repair proteins to correct the erroneous base in the daughter strand. While the primary role of methylated adenines at GATC sites is to direct the MMR pathway, this methylation has also been found to affect other processes, such as gene expression, the activity of transposable elements, and the timing of DNA replication. However, in the absence of MMR, the ability of these other processes to maintain adenine methylation and its targets is unknown.
To determine if the disruption of the MMR pathway results in the reduced conservation of methylated adenines as well as an increased tolerance for mutations that result in the loss or gain of new GATC sites, we surveyed individual clones isolated from experimentally evolving wild-type and MMR-deficient (mutL- ;conferring an 150x increase in mutation rate) populations of E. coli with whole-genome sequencing. Initial analysis revealed a lack of mutations affecting methylation sites (GATC tetranucleotides) in wild-type clones. However, the inherent low mutation rates conferred by the wild-type background render this result inconclusive, due to a lack of statistical power, and reveal a need for a more direct measure of changes in methylation status. Thus as a first step to comparative methylomics, we benchmarked four different methylation-calling pipelines on three biological replicates of the wildtype progenitor strain for our evolved populations.
While it is understood that these methylated sites play a role in the MMR pathway, it is not fully understood the full extent of their effect on the genome. Thus the goal of this thesis was to better understand the forces which maintain the genome, specifically concerning m6A within the GATC motif.
To determine if the disruption of the MMR pathway results in the reduced conservation of methylated adenines as well as an increased tolerance for mutations that result in the loss or gain of new GATC sites, we surveyed individual clones isolated from experimentally evolving wild-type and MMR-deficient (mutL- ;conferring an 150x increase in mutation rate) populations of E. coli with whole-genome sequencing. Initial analysis revealed a lack of mutations affecting methylation sites (GATC tetranucleotides) in wild-type clones. However, the inherent low mutation rates conferred by the wild-type background render this result inconclusive, due to a lack of statistical power, and reveal a need for a more direct measure of changes in methylation status. Thus as a first step to comparative methylomics, we benchmarked four different methylation-calling pipelines on three biological replicates of the wildtype progenitor strain for our evolved populations.
While it is understood that these methylated sites play a role in the MMR pathway, it is not fully understood the full extent of their effect on the genome. Thus the goal of this thesis was to better understand the forces which maintain the genome, specifically concerning m6A within the GATC motif.
ContributorsBoyer, Gwyneth (Author) / Lynch, Michael (Thesis director) / Behringer, Megan (Committee member) / Geiler-Samerotte, Kerry (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
The passage of 2007's Legal Arizona Workers Act, which required all new hires to be tested for legal employment status through the federal E-Verify database, drastically changed the employment prospects for undocumented workers in the state. Using data from the 2007-2010 American Community Survey, this paper seeks to identify the impact of this law on the labor force in Arizona, specifically regarding undocumented workers and less educated native workers. Overall, the data shows that the wage bias against undocumented immigrants doubled in the four years studied, and the wages of native workers without a high school degree saw a temporary, positive increase compared to comparable workers in other states. The law did not have an effect on the wages of native workers with a high school degree.
ContributorsSantiago, Maria Christina (Author) / Pereira, Claudiney (Thesis director) / Mendez, Jose (Committee member) / School of International Letters and Cultures (Contributor) / Department of Economics (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
This paper is intended to identify a correlation between the winning percentage of sports teams in the four major professional sports leagues in the United States and the GDP per capita of their respective cities. We initially compiled fifteen years of franchise performance along with economic data from the Federal Reserve Bank of St. Louis to analyze this relationship. After converting the data into a language recognized by Stata, the regression tool we used, we ran multiple regressions to find relevant correlations based off of our inputs. This paper will show the value of the economic impact of strong or weak performance throughout various economic cycles through data analysis and conclusions drawn from the results of the regression analysis.
ContributorsAndl, Tyler (Co-author) / Shirk, Brandon (Co-author) / Goegan, Brian (Thesis director) / Eaton, John (Committee member) / School of Accountancy (Contributor) / Department of Finance (Contributor) / Department of Supply Chain Management (Contributor) / Department of Information Systems (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
Description
Breast cancer is the leading cause of cancer-related deaths of women in the united states. Traditionally, Breast cancer is predominantly treated by a combination of surgery, chemotherapy, and radiation therapy. However, due to the significant negative side effects associated with these traditional treatments, there has been substantial efforts to develop alternative therapies to treat cancer. One such alternative therapy is a peptide-based therapeutic cancer vaccine. Therapeutic cancer vaccines enhance an individual's immune response to a specific tumor. They are capable of doing this through artificial activation of tumor specific CTLs (Cytotoxic T Lymphocytes). However, in order to artificially activate tumor specific CTLs, a patient must be treated with immunogenic epitopes derived from their specific cancer type. We have identified that the tumor associated antigen, TPD52, is an ideal target for a therapeutic cancer vaccine. This designation was due to the overexpression of TPD52 in a variety of different cancer types. In order to start the development of a therapeutic cancer vaccine for TPD52-related cancers, we have devised a two-step strategy. First, we plan to create a list of potential TPD52 epitopes by using epitope binding and processing prediction tools. Second, we plan to attempt to experimentally identify MHC class I TPD52 epitopes in vitro. We identified 942 potential 9 and 10 amino acid epitopes for the HLAs A1, A2, A3, A11, A24, B07, B27, B35, B44. These epitopes were predicted by using a combination of 3 binding prediction tools and 2 processing prediction tools. From these 942 potential epitopes, we selected the top 50 epitopes ranked by a combination of binding and processing scores. Due to the promiscuity of some predicted epitopes for multiple HLAs, we ordered 38 synthetic epitopes from the list of the top 50 epitope. We also performed a frequency analysis of the TPD52 protein sequence and identified 3 high volume regions of high epitope production. After the epitope predictions were completed, we proceeded to attempt to experimentally detected presented TPD52 epitopes. First, we successful transduced parental K562 cells with TPD52. After transduction, we started the optimization process for the immunoprecipitation protocol. The optimization of the immunoprecipitation protocol proved to be more difficult than originally believed and was the main reason that we were unable to progress past the transduction of the parental cells. However, we believe that we have identified the issues and will be able to complete the experiment in the coming months.
ContributorsWilson, Eric Andrew (Author) / Anderson, Karen (Thesis director) / Borges, Chad (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
The January 12, 2010 Haiti earthquake, which hit Port-au-Prince in the late afternoon, was the cause of over 220,000 deaths and $8 billion in damages \u2014 roughly 120% of national GDP at the time. A Mw 7.5 earthquake struck rural Guatemala in the early morning in 1976 and caused 23,000-25,000 deaths, three times as many injuries, and roughly $1.1 billion in damages, which accounted for approximately 30% of Guatemala's GDP. The earthquake which hit just outside of Christchurch, New Zealand early in the morning on September 4, 2010 had a magnitude of 7.1 and caused just two injuries, no deaths, and roughly 7.2 billion USD in damages (5% of GDP). These three earthquakes, all with magnitudes over 7 on the Richter scale, caused extremely varied amounts of economic damage for these three countries. This thesis aims to identify a possible explanation as to why this was the case and suggest ways in which to improve disaster risk management going forward.
ContributorsHeuermann, Jamie Lynne (Author) / Schoellman, Todd (Thesis director) / Mendez, Jose (Committee member) / Department of Supply Chain Management (Contributor) / Department of Economics (Contributor) / W. P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
The ability to draft and develop productive Major League players is vital to the success of any MLB organization. A core of cost-controlled, productive players is as important as ever with free agent salaries continuing to rise dramatically. In a sport where mere percentage points separate winners from losers at the end of a long season, any slight advantage in identifying talent is valuable. This study examines the 2004-2008 MLB Amateur Drafts in order to analyze whether certain types of prospects are more valuable selections than others. If organizations can better identify which draft prospects will more likely contribute at the Major League level in the future, they can more optimally spend their allotted signing bonus pool in order to acquire as much potential production as possible through the draft. Based on the data examined, during these five drafts high school prospects provided higher value than college prospects. While college players reached the Majors at a higher rate, high school players produced greater value in their first six seasons of service time. In the all-important first round of the draft, where signing bonuses are at their largest, college players proved the more valuable selection. When players were separated by position, position players held greater expected value than pitchers, with corner infielders leading the way as the position group with the highest expected value. College players were found to provide better value than high school players at defensively demanding positions such as catcher and middle infield, while high school players were more valuable among outfielders and pitchers.
ContributorsGildea, Adam Joseph (Author) / Eaton, John (Thesis director) / McIntosh, Daniel (Committee member) / Department of Economics (Contributor) / W. P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
The following paper consists of a review of sovereign debt sustainability economics and IMF debt sustainability frameworks, as well as a historical case study of Greece and a variable suggestion for the IMF to improve baseline assumptions. The purpose of this paper is to review the current methodology of perceiving debt and improve upon it in the face of an increasingly indebted global economy. Thus, this paper suggests the IMF adopt the variable calculated in Reinhart and Rogoff (2009) as a new benchmark for determining debt sustainability of market access countries. Through an exploration of the most recent Greek crisis, as well as modern Greek financial and political history, the author of this paper contends the IMF should reduce the broadness of the MAC DSA, as it will make for better debt sustainability projections and assumptions in implementing debt program policy.
ContributorsJennings, Zane Phillips (Author) / Mendez, Jose (Thesis director) / Roberts, Nancy (Committee member) / Economics Program in CLAS (Contributor) / School of Politics and Global Studies (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Alternative currencies have a long and varied history, in which Bitcoin is the latest chapter. The pseudonymous Satoshi Nakamoto created Bitcoin as an implementation of the concept of a cryptocurrency, or a decentralized currency based on the principles of cryptography. Since its creation in 2008, Bitcoin has had a fairly tumultuous existence that limited its adoption. Wide price fluctuations occurred as the appeal of free money by running a piece of computer software drove people to purchase expensive hardware, and high-profile scandals cast Bitcoin as an unstable currency well-suited primarily for purchasing illicit materials. Consumer confidence in the currency was extremely low, and businesses were extremely hesitant to accept a currency that could easily lose half (or more) of its value overnight. However, recent years have seen the currency begin to stabilize as businesses and mainstream investors have begun to accept and support it. Alternative cryptocurrencies, titled "altcoins," have also been created to fill market niches that Bitcoin was not addressing. Governmental intervention, a concern of many following the currency, has been surprisingly restrained and has actually contributed to its stability. The future of Bitcoin looks very bright as it carries the dream of the alternative currency forward into the 21st century.
ContributorsReardon, Brett (Co-author) / Burke, Ryan (Co-author) / Happel, Stephen (Thesis director) / Boyes, William (Committee member) / School of Politics and Global Studies (Contributor) / Department of Information Systems (Contributor) / Department of Finance (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Background: Noninvasive MRI methods that can accurately detect subtle brain changes are highly desirable when studying disease-modifying interventions. Texture analysis is a novel imaging technique which utilizes the extraction of a large number of image features with high specificity and predictive power. In this investigation, we use texture analysis to assess and classify age-related changes in the right and left hippocampal regions, the areas known to show some of the earliest change in Alzheimer's disease (AD). Apolipoprotein E (APOE)'s e4 allele confers an increased risk for AD, so studying differences in APOE e4 carriers may help to ascertain subtle brain changes before there has been an obvious change in behavior. We examined texture analysis measures that predict age-related changes, which reflect atrophy in a group of cognitively normal individuals. We hypothesized that the APOE e4 carriers would exhibit significant age-related differences in texture features compared to non-carriers, so that the predictive texture features hold promise for early assessment of AD. Methods: 120 normal adults between the ages of 32 and 90 were recruited for this neuroimaging study from a larger parent study at Mayo Clinic Arizona studying longitudinal cognitive functioning (Caselli et al., 2009). As part of the parent study, the participants were genotyped for APOE genetic polymorphisms and received comprehensive cognitive testing every two years, on average. Neuroimaging was done at Barrow Neurological Institute and a 3D T1-weighted magnetic resonance image was obtained during scanning that allowed for subsequent texture analysis processing. Voxel-based features of the appearance, structure, and arrangement of these regions of interest were extracted utilizing the Mayo Clinic Python Texture Analysis Pipeline (pyTAP). Algorithms applied in feature extraction included Grey-Level Co-Occurrence Matrix (GLCM), Gabor Filter Banks (GFB), Local Binary Patterns (LBP), Discrete Orthogonal Stockwell Transform (DOST), and Laplacian-of-Gaussian Histograms (LoGH). Principal component (PC) analysis was used to reduce the dimensionality of the algorithmically selected features to 13 PCs. A stepwise forward regression model was used to determine the effect of APOE status (APOE e4 carriers vs. noncarriers), and the texture feature principal components on age (as a continuous variable). After identification of 5 significant predictors of age in the model, the individual feature coefficients of those principal components were examined to determine which features contributed most significantly to the prediction of an aging brain. Results: 70 texture features were extracted for the two regions of interest in each participant's scan. The texture features were coded as 70 initial components andwere rotated to generate 13 principal components (PC) that contributed 75% of the variance in the dataset by scree plot analysis. The forward stepwise regression model used in this exploratory study significantly predicted age, accounting for approximately 40% of the variance in the data. The regression model revealed 5 significant regressors (2 right PC's, APOE status, and 2 left PC by APOE interactions). Finally, the specific texture features that contributed to each significant PCs were identified. Conclusion: Analysis of image texture features resulted in a statistical model that was able to detect subtle changes in brain integrity associated with age in a group of participants who are cognitively normal, but have an increased risk of developing AD based on the presence of the APOE e4 phenotype. This is an important finding, given that detecting subtle changes in regions vulnerable to the effects of AD in patients could allow certain texture features to serve as noninvasive, sensitive biomarkers predictive of AD. Even with only a small number of patients, the ability for us to determine sensitive imaging biomarkers could facilitate great improvement in speed of detection and effectiveness of AD interventions..
ContributorsSilva, Annelise Michelle (Author) / Baxter, Leslie (Thesis director) / McBeath, Michael (Committee member) / Presson, Clark (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Mammary gland development in humans during puberty involves the enlargement of breast tissue, but this is not true in non-human primates. To identify potential causes of this difference, I examined variation in substitution rates across genes related to mammary development. Genes undergoing purifying selection show slower-than-average substitution rates, while genes undergoing positive selection show faster rates. These may be related to the difference between humans and other primates. Three genes were found to be accelerated were FOXF1, IGFBP5, and ATP2B2, but only the latter one was found in humans and it seems unlikely that it would be related to the differences between mammary gland development at puberty between humans and non-human primates.
ContributorsArroyo, Diana (Author) / Cartwright, Reed (Thesis director) / Wilson Sayres, Melissa (Committee member) / Schwartz, Rachel (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05