Matching Items (190)
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Description
Cell fate is a complex and dynamic process with many genetic components. It has often been likened to “multistable” mathematical systems because of the numerous possible “stable” states, or cell types, that cells may end up in. Due to its complexity, understanding the process of cell fate and

Cell fate is a complex and dynamic process with many genetic components. It has often been likened to “multistable” mathematical systems because of the numerous possible “stable” states, or cell types, that cells may end up in. Due to its complexity, understanding the process of cell fate and differentiation has proven challenging. A better understanding of cell differentiation has applications in regenerative stem cell therapies, disease pathologies, and gene regulatory networks.
A variety of different genes have been associated with cell fate. For example, the Nanog/Oct-4/Sox2 network forms the core interaction of a gene network that maintains stem cell pluripotency, and Oct-4 and Sox2 also play a role in the tissue types that stem cells eventually differentiate into. Using the CRISPR/cas9 based homology independent targeted integration (HITI) method developed by Suzuki et al., we can integrate fluorescent tags behind genes with reasonable efficiency via the non-homologous end joining (NHEJ) DNA repair pathway. With human embryonic kidney (HEK) 293T cells, which can be transfected with high efficiencies, we aim to create a three-parameter reporter cell line with fluorescent tags for three different genes related to cell fate. This cell line would provide several advantages for the study of cell fate, including the ability to quantitatively measure cell state, observe expression heterogeneity among a population of genetically identical cells, and easily monitor fluctuations in expression patterns.
The project is partially complete at this time. This report discusses progress thus far, as well as the challenges faced and the future steps for completing the reporter line.
ContributorsLoveday, Tristan Andre (Author) / Wang, Xiao (Thesis director) / Brafman, David (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative brain disease that results from repetitive brain trauma causing brain structure, personality, behavioral, and cognitive changes. CTE is currently undiagnosable and untreatable in living patients. This thesis investigates research surrounding CTE and presents a comparative discussion of the advantages and disadvantages of current

Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative brain disease that results from repetitive brain trauma causing brain structure, personality, behavioral, and cognitive changes. CTE is currently undiagnosable and untreatable in living patients. This thesis investigates research surrounding CTE and presents a comparative discussion of the advantages and disadvantages of current diagnostic methods used for other neurodegenerative diseases that may be useful for the diagnosis of CTE.
ContributorsBlair, Sierra (Co-author) / Blair, Taylor (Co-author) / Brafman, David (Thesis director) / Stabenfeldt, Sarah (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
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Description
Cardiovascular disease attributed to about 800,000 deaths per year and is the leading cause of all-cause mortality in the U.S. Previous studies indicate that reducing sedentary time or increasing physical activity (PA) can independently reduce cardiometabolic risk (CMR). Further, studies have shown that higher levels of moderate-to-vigorous PA can attenuate

Cardiovascular disease attributed to about 800,000 deaths per year and is the leading cause of all-cause mortality in the U.S. Previous studies indicate that reducing sedentary time or increasing physical activity (PA) can independently reduce cardiometabolic risk (CMR). Further, studies have shown that higher levels of moderate-to-vigorous PA can attenuate the negative effects of sedentary behavior on CMR.
In this study, we evaluated the association between sedentary time, light-intensity PA (LPA), and moderate-vigorous PA (MVPA) and CMR biomarkers (high density lipoprotein level, low density lipoprotein level, triglycerides, fasting glucose, total cholesterol, blood pressure, and body mass index). Additionally, we examined if the detrimental association between sedentary time and CMR biomarkers is partially or fully attenuated by MVPA. Baseline objective physical activity and cardiometabolic risk data from a two-arm-cluster randomized trial (Stand&Move@work) were used in this study. Multilevel models clustered by worksite evaluated the fixed effects and interaction between MVPA and sedentary time on CMR. Data from 630 sedentary working adults (from 24 worksites) were included in the analysis. The sample was mainly middle aged (44.6±11.2) females (74%) with race distributions as follows; 70.5% white, 13.8% hispanic, 4.1% black, 5.1% asian, and 2.1% other. Our study showed detrimental trends consistent with previous studies between sedentary behavior and cardiometabolic outcomes including HDL, LDL, and total cholesterol. MVPA demonstrated beneficial associations with lipoproteins including HDL, LDL, total cholesterol, and triglycerides. We observed that high levels of MVPA may be able to partially attenuate the negative effects of highly sedentary behavior on fasting glucose, total cholesterol, and LDL levels. Overall, sedentary behavior indicated deleterious associations with cardiometabolic outcomes. Future directions for this study could examine a more at-risk population or a highly active population for further assessment of CMR biomarkers and the effects of behavior.
ContributorsMeyer, Emily Camille (Author) / Buman, Matthew (Thesis director) / Toledo, Meynard (Committee member) / Pereira, Mark (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
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Description
While type 2 diabetes (T2D) rates have soared, the number of Americans classified as ‘prediabetic’ has also increased. Despite this, current preventative approaches are costly and often not without undue side-effects. Instead, behavioral lifestyle approaches hold promise in reducing conversion rates of T2D as the latest treatment option that could

While type 2 diabetes (T2D) rates have soared, the number of Americans classified as ‘prediabetic’ has also increased. Despite this, current preventative approaches are costly and often not without undue side-effects. Instead, behavioral lifestyle approaches hold promise in reducing conversion rates of T2D as the latest treatment option that could mitigate and transform disease management. However, present interventions do not possess the scope necessary for implementation in a realistic, scalable way that can target the large at-risk population.
The application (app) “BeWell24” mitigates this diabetes risk through targeting sleep, physical activity, sedentary behavior, and diet, and is being delivered through mHealth technology to attenuate the higher-risk of the prediabetic Veteran population. In order for full scale dissemination, this thesis examines a provider perspective of the ‘Post-intervention interview guide’, performed with a Phoenix Veterans Affairs Health Care System (PVAHCS) provider. It then suggests revisions to the interview guide based on the provider’s interview and existing literature. This thesis also emphasizes the rationale behind these proposed changes to be organized in line with the iPARIHS framework (integrated Promoting Action on Research Implementation in Health Services).
Overall, the provider responded positively to BeWell24 and the ‘Post-intervention interview guide’, with constructive suggestions for each question in the interview guide. The main theme of the provider’s answers and comments were to prioritize efficiency and preserve standard clinical flow. A revised interview guide is provided, which prospectively presents as a more brief and focused interview organized by the iPARIHS framework. This revised interview guide could aid in the clarity of provider responses, specifically for the prospective interviews of the ongoing larger BeWell24 study and future studies.
ContributorsWojtas, Abby Ann (Author) / Buman, Matthew (Thesis director) / Larouche, Miranda (Committee member) / Epstein, Dana (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
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Description
The importance of second language learning in today’s ever-increasing globalized world is becoming ever more paramount. Despite seeming trends which indicate aversion to globalization, the international phenomenon which describes the connection made between peoples and cultures, will only increase its influence in coming years. With the advances globalization has made,

The importance of second language learning in today’s ever-increasing globalized world is becoming ever more paramount. Despite seeming trends which indicate aversion to globalization, the international phenomenon which describes the connection made between peoples and cultures, will only increase its influence in coming years. With the advances globalization has made, it is becoming more important to learn and study foreign languages in order to keep abreast of this trend and not be left behind by globalization. Why electronic translation is not so viable in the long run (at least currently) is that culture and syntax are not things which can be simply ascertained via mediums such as application use. Due to the fact that advanced language proficiency is considered to be an integral piece towards stronger sentiments of “integration” (i.e. Syrian refugees integrating into EU and US) it is of more importance that increasing second language proficiency receives the adequate study and implementation to reflect a more cohesive globalized world. Accompanying this necessity is the simple fact that adult second language learners often struggle to overcome difficulty to the challenging yet rewarding task of learning and eventually mastering a second language.

To truly understand the difficulty some adult second language learners have with learning a second language it can be helpful to compare second language acquisition to how one naturally, and seemingly effortlessly in many cases, acquires their native language. How can a comparative analysis of how native speakers and adult second language learners each learn their first and second language respectively be successfully converted to a specific means of assisting adult second language learners achieve the highest level of possible fluency? In order to more accurately propose a viable solution to the overarching question, the following three questions have been proposed as a means to springboard into better understanding the nature of the main topic.
The points to consider while analyzing the main question throughout this analysis are as follows: How would it be best for an adult second language learner to achieve the same level off proficiency as a native speaker of a given language whom has been exposed to all of its intricacies since birth? At what point exactly is someone considered to have the same level of proficiency which a native speaker of a given language would have and how does that differ from being a heritage speaker? With the final supporting question being: What type of learning would be best suited in helping a heritage speaker (someone who learns a language in the home by virtue of their heritage) or adult second language learner to become highly proficient in a second language?
In order to propose a wide variety of integration between these questions with the conjoined purpose of answering the inquiry of this thesis, many different sources supporting each of the above questions will contain certain overlap, providing a clear basis for constructing a tri-fold argument in answering the thesis question as acutely as possible. In regards to the first question, the question of “proficiency” will be a subsection committed to understanding the nature of how language proficiency works and at what point (if ever) one can ever be considered “highly proficient” in a second language.

All three exploratory questions are compatible with a theory known as Critical Period Theory, a theory in linguistics proposed by Montreal neurologist Wilder Penfield, which states, “There is a critical age, before puberty, that one must learn language. If one has not learned to speak before puberty it is much more difficult, and sometimes impossible, to learn language and speak in a meaningful way.” The overlap which this method binds to Universal Grammar is a rather close-knit relationship. Research composed by certain linguists suggest that “children are born with a certain universal grammar wired into their brains.” This will be compared and cross-examined to a higher degree in a later section of the paper.

The importance of Universal Grammar in relation to Critical Period Theory cannot be overstated.  Universal Grammar in relation to the second language Critical Period Theory will help explain at which point, someone is considered to be a “native speaker” of a given language. The third question posed of how would it be best for heritage and second language learners to increase their proficiency in a second language really touches on both of these theories in regards to at which age someone is exposed to a specific language in addition to how Universal Grammar affects the development of second language acquisition. In the realm of perpetually working towards mitigating an answer to this analysis’s thesis, the connecting thread or “roter Faden”, as it is said in German, will be the integrative domain the above questions will have on arriving to a clearer understanding of the nature of how a comparative analysis of second language learners and mother-tongue speakers can expedite the language learning process of second language learners, using techniques of native speakers which they inherently pick-up.
Created2018-12
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Description
Mobile health or "mHealth" defines a broad spectrum of medical or public health practice supported by mobile devices. The patient's perception of mobile health applications is the key point in confronting whether or not patients will utilize the tools at their disposal As such, the primary aim of this study

Mobile health or "mHealth" defines a broad spectrum of medical or public health practice supported by mobile devices. The patient's perception of mobile health applications is the key point in confronting whether or not patients will utilize the tools at their disposal As such, the primary aim of this study was to examine participant feedback through quantitative and qualitative measures using the Therapy Evaluation Questionnaire and a patient interview, respectively, to further understand the patient rated acceptability of using BeWell24 and SleepWell24 for improving health outcomes. For BeWell24, it was hypothesized that patients who received the Multicomponent version would report higher acceptability scores than those randomized to the Health Education version. Furthermore, in regard to SleepWell24, it was hypothesized that the SleepWell24 patient would provide positive feedback and suggestions regarding their own experience with the SleepWell24 app. Data from this thesis was pulled from two ongoing randomized controlled trials currently being conducted at the Phoenix Veteran Affairs Health Care Service (PVACHS) and Mayo Clinic hospitals. Means, standard deviations, frequencies, and percentages were commuted to summarize demographics and TEQ scores. In addition, key concepts from a qualitative interview with a SleepWell24 participant were derived. The results showed a greater acceptability of the multicomponent versions of BeWell24 and SleepWell24 but a lower TEQ score of perceived usability. mHealth implementations pose a potential to become an important part of the health sector for establishing innovative approaches to delivering care, and while benefits have been highly praised, it is clear that the perceptions of mHealth must be positive if the technology is to transcend into a practical clinical setting.
ContributorsJimenez, Asael (Author) / Buman, Matthew (Thesis director) / Epstein, Dana (Committee member) / School of Nutrition and Health Promotion (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
Alzheimer’s Disease (AD) affects over 5 million individuals in the U.S. and has a direct cost estimated in excess of $200 billion per year. Broadly speaking, there are two forms of AD—early-onset, familial AD (FAD) and late-onset-sporadic AD (SAD). Animal models of AD, which rely on the overexpression of FAD-related

Alzheimer’s Disease (AD) affects over 5 million individuals in the U.S. and has a direct cost estimated in excess of $200 billion per year. Broadly speaking, there are two forms of AD—early-onset, familial AD (FAD) and late-onset-sporadic AD (SAD). Animal models of AD, which rely on the overexpression of FAD-related mutations, have provided important insights into the disease. However, these models do not display important disease-related pathologies and have been limited in their ability to model the complex genetics associated with SAD.

Advances in cellular reprogramming, have enabled the generation of in vitro disease models that can be used to dissect disease mechanisms and evaluate potential therapeutics. To that end, efforts by many groups, including the Brafman laboratory, to generated patient-specific hiPSCs have demonstrated the promise of studying AD in a simplified and accessible system. However, neurons generated from these hiPSCs have shown some, but not all, of the early molecular and cellular hallmarks associated with the disease. Additionally, phenotypes and pathological hallmarks associated with later stages of the human disease have not been observed with current hiPSC-based systems. Further, disease relevant phenotypes in neurons generated from SAD hiPSCs have been highly variable or largely absent. Finally, the reprogramming process erases phenotypes associated with cellular aging and, as a result, iPSC-derived neurons more closely resemble fetal brain rather than adult brain.

It is well-established that in vivo cells reside within a complex 3-D microenvironment that plays a significant role in regulating cell behavior. Signaling and other cellular functions, such as gene expression and differentiation potential, differ in 3-D cultures compared with 2-D substrates. Nonetheless, previous studies using AD hiPSCs have relied on 2-D neuronal culture models that do not reflect the 3-D complexity of native brain tissue, and therefore, are unable to replicate all aspects of AD pathogenesis. Further, the reprogramming process erases cellular aging phenotypes. To address these limitations, this project aimed to develop bioengineering methods for the generation of 3-D organoid-based cultures that mimic in vivo cortical tissue, and to generate an inducible gene repression system to recapitulate cellular aging hallmarks.
ContributorsBounds, Lexi Rose (Author) / Brafman, David (Thesis director) / Wang, Xiao (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
This study examined the type and frequency of questions asked by attorneys in cases of children alleging sexual abuse. Of interest was whether child age would affect the questions asked. The participants included 25 child witnesses testifying in criminal trials in Maricopa County over a recent ten-year period. Children were

This study examined the type and frequency of questions asked by attorneys in cases of children alleging sexual abuse. Of interest was whether child age would affect the questions asked. The participants included 25 child witnesses testifying in criminal trials in Maricopa County over a recent ten-year period. Children were placed into two groups: younger (five to seven-year-olds) and older (eight to nine-year-olds). Every question asked, and answer provided, during children's testimony, was systematically and reliably coded for the content of the interaction. Attorneys exhibited developmental sensitivity, varying the amount of question they asked across content areas by the age of the child. In addition, attorneys varied in what they asked about: the prosecution focused more on the plausibility of abuse, whereas the defense focused more on how others may have suggestively influenced the child's report. Both attorneys were equally concerned about the consistency of narratives. The findings from the present study have direct policy implications for how attorneys structure their arguments, both in an attempt to establish, and question, children's credibility in these important cases. Keywords: children, age, suggestibility, consistency, inconsistency, plausibility
ContributorsHogan, Caitlyn Rose (Author) / Stolzenberg, Stacia (Thesis director) / Fradella, Hank (Committee member) / College of Public Service and Community Solutions (Contributor) / School of Criminology and Criminal Justice (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
Throughout history, terrorism has had major effects on tourists and tourism destinations that are targeted. When terrorists execute an attack in order to communicate a message, resulting impacts go far beyond lives lost. Included in these impacts is the fear that terror attacks leave on tourists, sometimes creating such an

Throughout history, terrorism has had major effects on tourists and tourism destinations that are targeted. When terrorists execute an attack in order to communicate a message, resulting impacts go far beyond lives lost. Included in these impacts is the fear that terror attacks leave on tourists, sometimes creating such an impression that tourists change travel plans as a result. Although there are many studies on destination image, risk perception, and decision-making, very few focus specifically on the millennial generation. Because millennials are changing the travel and tourism scene - as they now make up the largest percentage of the population \u2014 it is important for stakeholders in the tourism industry and DMOs to understand this shift and the implications that come with these changes. This study provides a qualitative analysis of millennials' views, attitudes, and beliefs regarding terror impacted tourist destinations. Specifically, it will explore how millennials develop their destination images, if millennials view international travel to be risky, and if millennials are willing to travel to terror impacted tourist destinations. Using focus group methodology, this study gathered data from students from a number of disciplines, genders, and travel experience, in order to understand the themes listed above. Analysis of the findings and implications for officials and DMOs follow, as well as a conclusion including limitations and recommendations for future studies.
Created2017-05
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Description
Genetic manipulation of human cell lines has widespread applications in biomedical research ranging from disease modeling to therapeutic development. Human cells are generally difficult to genetically engineer, but exogenous nucleic acids can be expressed by viral, chemical, or nonchemical means. Chemical transfections are simpler in practice than both viral and

Genetic manipulation of human cell lines has widespread applications in biomedical research ranging from disease modeling to therapeutic development. Human cells are generally difficult to genetically engineer, but exogenous nucleic acids can be expressed by viral, chemical, or nonchemical means. Chemical transfections are simpler in practice than both viral and nonchemical delivery of genetic material, but often suffer from cytotoxicity and low efficiency. Novel aminoglycoside antibiotic-derived lipopolymers have been synthesized to mediate transgene delivery to human cells. These polymers are comprised of either paromomycin or apramycin crosslinked with glycerol diglycidylether and derivatized with stearoyl chloride in varying molar ratios. In this work, three previously identified target lipopolymers were screened against a library of human embryonic and induced pluripotent stem cell lines. Cells were transfected with a plasmid encoding green fluorescent protein (GFP) and expression was quantified with flow cytometry 48 hours after transfection. Transfection efficiency was evaluated between three distinct lipopolymers and four lipopolymer:DNA mass ratios. GFP expression was compared to that of cells transfected with commercially available chemical gene delivery reagent controls\u2014JetPEI, Lipofectamine, and Fugene\u2014at their recommended reagent:DNA ratios. Improved transgene expression in stem cell lines allows for improved research methods. Human stem cell-derived neurons that have been genetically manipulated to express phenotypic characteristics of aging can be utilized to model neurodegenerative diseases, elucidating information about these diseases that would be inaccessible in unmanipulated tissue.
ContributorsMehta, Frea (Author) / Brafman, David (Thesis director) / Rege, Kaushal (Committee member) / Chemical Engineering Program (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05