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Cancer claims hundreds of thousands of lives every year in US alone. Finding ways for early detection of cancer onset is crucial for better management and treatment of cancer. Thus, biomarkers especially protein biomarkers, being the functional units which reflect dynamic physiological changes, need to be discovered. Though important, there

Cancer claims hundreds of thousands of lives every year in US alone. Finding ways for early detection of cancer onset is crucial for better management and treatment of cancer. Thus, biomarkers especially protein biomarkers, being the functional units which reflect dynamic physiological changes, need to be discovered. Though important, there are only a few approved protein cancer biomarkers till date. To accelerate this process, fast, comprehensive and affordable assays are required which can be applied to large population studies. For this, these assays should be able to comprehensively characterize and explore the molecular diversity of nominally "single" proteins across populations. This information is usually unavailable with commonly used immunoassays such as ELISA (enzyme linked immunosorbent assay) which either ignore protein microheterogeneity, or are confounded by it. To this end, mass spectrometric immuno assays (MSIA) for three different human plasma proteins have been developed. These proteins viz. IGF-1, hemopexin and tetranectin have been found in reported literature to show correlations with many diseases along with several carcinomas. Developed assays were used to extract entire proteins from plasma samples and subsequently analyzed on mass spectrometric platforms. Matrix assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) mass spectrometric techniques where used due to their availability and suitability for the analysis. This resulted in visibility of different structural forms of these proteins showing their structural micro-heterogeneity which is invisible to commonly used immunoassays. These assays are fast, comprehensive and can be applied in large sample studies to analyze proteins for biomarker discovery.
ContributorsRai, Samita (Author) / Nelson, Randall (Thesis advisor) / Hayes, Mark (Thesis advisor) / Borges, Chad (Committee member) / Ros, Alexandra (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Cancer is a heterogeneous disease with discrete oncogenic mechanisms. P53 mutation is the most common oncogenic mutation in many cancers including breast cancer. This dissertation focuses on fundamental genetic alterations enforced by p53 mutation as an indirect target. p53 mutation upregulates the mevalonate pathway genes altering cholesterol biosynthesis and prenylation.

Cancer is a heterogeneous disease with discrete oncogenic mechanisms. P53 mutation is the most common oncogenic mutation in many cancers including breast cancer. This dissertation focuses on fundamental genetic alterations enforced by p53 mutation as an indirect target. p53 mutation upregulates the mevalonate pathway genes altering cholesterol biosynthesis and prenylation. Prenylation, a lipid modification, is required for small GTPases signaling cascades. Project 1 demonstrates that prenylation inhibition can specifically target cells harboring p53 mutation resulting in reduced tumor proliferation and migration. Mutating p53 is associated with Ras and RhoA activation and statin prevents this activity by inhibiting prenylation. Ras-related pathway genes were selected from the transcriptomic analysis for evaluating correlation to statin sensitivity. A gene signature of seventeen genes and TP53 genotype (referred to as MPR signature) is generated to predict response to statins. MPR signature is validated through two datasets of drug screening in cell lines. As advancements in targeted gene modification are rising, the CRISPR-Cas9 technology has emerged as a new cancer therapeutic strategy. One of the important risk factors in gene therapy is the immune recognition of the exogenous therapeutic tool, resulting in obstruction of treatment and possibly serious health consequences. Project 2 describes a method development that can potentially improve the safety and efficacy of gene-targeting proteins. A cohort of 155 healthy individuals was screened for pre-existing B cell and T cell immune response to the S. pyogenes Cas9 protein. We detected antibodies against Cas9 in more than 10% of the healthy population and identified two immunodominant T cell epitopes of this protein. A de-immunized Cas9 that maintains the wild-type functionality was engineered by mutating the identified T cell epitopes. The gene signature and method described here have the potential to improve strategies for genome-driven tumor targeting.
ContributorsRoshdi Ferdosi, Shayesteh (Author) / Anderson, Karen S (Thesis advisor) / LaBaer, Joshua (Thesis advisor) / Woodbury, Neel (Committee member) / Borges, Chad (Committee member) / Arizona State University (Publisher)
Created2017
Description
The saxophone is privileged to have a wide variety of repertoire from contemporary composers. Due to its invention in the later half of the nineteenth century, it has no repertoire written by baroque composers, including Johann Sebastian Bach. There are several published arrangements of Bach’s three solo violin partitas including

The saxophone is privileged to have a wide variety of repertoire from contemporary composers. Due to its invention in the later half of the nineteenth century, it has no repertoire written by baroque composers, including Johann Sebastian Bach. There are several published arrangements of Bach’s three solo violin partitas including that of Ronald Caravan and Raaf Hekkema. These collections either do not present every movement of each of these three partitas, or they do not present them in their original keys. An advantage to arranging these works in their original keys is that saxophonists have the opportunity to learn more about the works by playing along with recordings of great violinists such as Itzhak Perlman and Hilary Hahn, something that would be very difficult to do if they were not in the original keys. In Ronald Caravan’s Bach for Solo Saxophone, Caravan includes a collection of many unaccompanied works by Bach for saxophone but does not include all of the movements from the three partitas and they are not in the original keys that Bach wrote for. In Raaf Hekkema’s Bach for Saxophone, Hekkema arranges the entirety of the three partitas, however they are not set in the original keys that Bach wrote for. In addition to these points, those collections do not provide information of the life of J.S. Bach, baroque performance practice, mechanics of the baroque violin, baroque dances, and advice on going about the mechanics of these pieces from a saxophonist’s perspective. This information is very useful to a young saxophonist who is trying to fully understand and perform Bach’s three solo violin partitas.
ContributorsSalazar, Nathan John (Author) / Creviston, Christopher (Thesis director) / Saucier, Catherine (Committee member) / School of Music (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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Description
Due to artificial selection, dogs have high levels of phenotypic diversity, yet, there appears to be low genetic diversity within individual breeds. Through their domestication from wolves, dogs have gone through a series of population bottlenecks, which has resulted in a reduction in genetic diversity, with a large amount of

Due to artificial selection, dogs have high levels of phenotypic diversity, yet, there appears to be low genetic diversity within individual breeds. Through their domestication from wolves, dogs have gone through a series of population bottlenecks, which has resulted in a reduction in genetic diversity, with a large amount of linkage disequilibrium and the persistence of deleterious mutations. This has led to an increased susceptibility to a multitude of diseases, including cancer. To study the effects of artificial selection and life history characteristics on the risk of cancer mortality, we collected cancer mortality data from four studies as well as the percent of heterozygosity, body size, lifespan and breed group for 201 dog breeds. We also collected specific types of cancer breeds were susceptible to and compared the dog cancer mortality patterns to the patterns observed in other mammals. We found a relationship between cancer mortality rate and heterozygosity, body size, lifespan as well as breed group. Higher levels of heterozygosity were also associated with longer lifespan. These results indicate larger breeds, such as Irish Water Spaniels, Flat-coated Retrievers and Bernese Mountain Dogs, are more susceptible to cancer, with lower heterozygosity and lifespan. These breeds are also more susceptible to sarcomas, as opposed to carcinomas in smaller breeds, such as Miniature Pinschers, Chihuahuas, and Pekingese. Other mammals show that larger and long-lived animals have decreased cancer mortality, however, within dog breeds, the opposite relationship is observed. These relationships could be due to the trade-off between cellular maintenance and growing fast and large, with higher expression of growth factors, such as IGF-1. This study further demonstrates the relationships between cancer mortality, heterozygosity, and life history traits and exhibits dogs as an important model organism for understanding the relationship between genetics and health.
ContributorsBalsley, Cassandra Sierra (Author) / Maley, Carlo (Thesis director) / Wynne, Clive (Committee member) / Tollis, Marc (Committee member) / School of Life Sciences (Contributor) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
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Description
This creative project explores the concept of how music is like a language and how, as a teacher, I plan to enforce this concept through my teaching. The aim of this project is to highlight the importance of completing research and acquiring knowledge of aspects, such as the composer's life,

This creative project explores the concept of how music is like a language and how, as a teacher, I plan to enforce this concept through my teaching. The aim of this project is to highlight the importance of completing research and acquiring knowledge of aspects, such as the composer's life, historical background and literary references, when learning a piece of music. Through this project, I address connections between the brain and music pertaining to memorization, the components of language, the similarities between language and music, the role of the teacher and the development of a "toolbox" of knowledge for studying a piece of music. I present my own research on Schumann's Novelette Op. 21, No. 8 in f-sharp minor as well as my own experiences of learning the piece to demonstrate an example of the process and discoveries I hope my students will make in their own studies of repertoire.
ContributorsLee, Kara Jia-Shan (Author) / Pagano, Caio (Thesis director) / Creviston, Hannah (Committee member) / Division of Teacher Preparation (Contributor) / School of Music (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
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Description
The SolarSPELL is an offline, ruggedized, digital library, created by Dr. Laura Hosman for the U.S. Peace Corps. It has thousands of pieces of educational content that can be accessed through a self-contained Wi-Fi hotspot on the device itself. Currently, there are more than 200 deployed in several Pacific Island

The SolarSPELL is an offline, ruggedized, digital library, created by Dr. Laura Hosman for the U.S. Peace Corps. It has thousands of pieces of educational content that can be accessed through a self-contained Wi-Fi hotspot on the device itself. Currently, there are more than 200 deployed in several Pacific Island nations. After visiting one of these nations, Tonga, in December of 2016, I learned that almost all of the Peace Corps volunteers stationed around the Pacific Islands suffered from a lack of resources due to a variety of reasons. While the SolarSPELL helps to remedy that, the device is lacking classroom activities and resources for creative work and educational drama. Furthermore, for many students in these environments, schools are for learning information and producing high scores on exams, not for learning about creative strengths and identity. After researching curriculum development and the use of drama in an educational setting, I compiled over 50 pieces of content to include on the SolarSPELL involving art, drama, music, movement, and most importantly, imagination. These resources will allow Peace Corps volunteers to explore additional ways to teach English in their schools, while also creating a classroom environment that allows for creative expression. All the content is compiled into one folder as "Teaching Resources", and is then broken down into seven sub- categories. In the first sub-category, Art Projects, there is a collection of several hands-on projects, many of which involve recyclable or readily available materials. These projects will allow for a greater understanding of conservation and "green" living, concepts that are crucial to the stability of these island nations. The next 5 categories are Drama Readings, Music, Movement, and Video, Group Exercises, Creative Writing, and Worksheets. The second sub- category is a collection of beginner-level "Reader's Theater" scripts. The third sub-category involves music and video to engage students in movement activities. The fourth sub-category is a compilation of group games and activities to help students express themselves and learn social skills. The fifth sub-category includes a collection of activities such as fill-in-the-blank story worksheets and journal prompts which will aid in creative thinking and the practice of the English language. The sixth sub-category involves a collection of worksheets that mainly focus on self-reflection and identity. The seventh and final sub-category, Content Guide and Information, works to explain the benefits of using of drama and creative play in the classroom, as well as strategies teachers can implement in order to further engage their students in dramatic learning and play. Overall, these pieces of content are meant to be used as resources for the Peace Corps volunteers in order to provide alternative ways to practice reading, writing, and speaking the English language, a critical part of education in the Pacific Islands.
ContributorsTaylor, Amanda Nicole (Author) / Hosman, Laura (Thesis director) / McAvoy, Mary (Committee member) / School of Film, Dance and Theatre (Contributor) / Division of Teacher Preparation (Contributor) / Barrett, The Honors College (Contributor) / School for the Future of Innovation in Society (Contributor)
Created2017-12
Description
This creative project thesis involves electronic music composition and production, and it uses some elements of algorithmic music composition (through recurrent neural networks). Algorithmic composition techniques are used here as a tool in composing the pieces, but are not the main focus. Thematically, this project explores the analogy between artificial

This creative project thesis involves electronic music composition and production, and it uses some elements of algorithmic music composition (through recurrent neural networks). Algorithmic composition techniques are used here as a tool in composing the pieces, but are not the main focus. Thematically, this project explores the analogy between artificial neural networks and neural activity in the brain. This project consists of three short pieces, each exploring these concept in different ways.
ContributorsKarpur, Ajay (Author) / Suzuki, Kotoka (Thesis director) / Ingalls, Todd (Committee member) / Electrical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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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 develo

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
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Description
Musical interpretation is challenging when one's goal is to evoke an emotional response from an audience. In order to develop a well-informed interpretation of Mozart's Fantasia in D minor K. 397, a study was conducted on the historical background of the piece and various performances by well-regarded performers. Fantasias are

Musical interpretation is challenging when one's goal is to evoke an emotional response from an audience. In order to develop a well-informed interpretation of Mozart's Fantasia in D minor K. 397, a study was conducted on the historical background of the piece and various performances by well-regarded performers. Fantasias are written works, but improvisatory by nature. Mozart's fantasias were influenced by C. P. E. Bach's, which included sudden changes in emotion. An Emil Gilels performance provided a classically trained approach, while Mitsuko Uchida's performance provided an emotional approach. Colin Tilney and John Irving performances elucidated the sound of the instruments that Mozart would have been composing with. Altogether, the research culminated in an interpretation of the D minor Fantasia that endeavored to capture the essence of fantasy, improvisation and emotion.
ContributorsMo, Gina Nan (Author) / Emmery, Laura (Thesis director) / Creviston, Hannah (Committee member) / Department of Psychology (Contributor) / School of International Letters and Cultures (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
This purpose of this thesis study was to examine variables of the "War on Cancer" frame, loss-gain prime, and patient gender on treatment decision for advanced cancer patients. A total of 291 participants (141 females) participated in an online survey experiment and were randomly assigned to one of eight possible

This purpose of this thesis study was to examine variables of the "War on Cancer" frame, loss-gain prime, and patient gender on treatment decision for advanced cancer patients. A total of 291 participants (141 females) participated in an online survey experiment and were randomly assigned to one of eight possible conditions, each of which were comprised of a combination of one of two levels for three total independent variables: war frame ("War on Cancer" frame or neutral frame), loss-gain prime (loss prime or gain prime), and patient gender (female or male). Each of the three variables were operationalized to determine whether or not the exposure to the war on cancer paradigm, loss-frame language, or male patient gender would increase the likelihood of a participant choosing a more aggressive cancer treatment. Participants read a patient scenario and were asked to respond to questions related to motivating factors. Participants were then asked to report preference for one of two treatment decisions. Participants were then asked to provide brief demographic information in addition to responding to questions about military history, war attitudes, and cancer history. The aforementioned manipulations sought to determine whether exposure to various factors would make a substantive difference in final treatment decision. Contrary to the predicted results, participants in the war frame condition (M = 3.85, SD = 1.48) were more likely to choose the pursuit of palliative care (as opposed to aggressive treatment) than participants in the neutral frame condition (M = 3.54, SD = 1.23). Ultimately, these significant findings suggest that there is practical information to be gained from treatment presentation manipulations. By arming healthcare providers with a more pointed understanding of the nuances of treatment presentation, we can hope to empower patients, their loved ones, and healthcare providers entrenched in the world of cancer treatment.
ContributorsKnowles, Madelyn Ann (Author) / Kwan, Virginia S. Y. (Thesis director) / Presson, Clark (Committee member) / Salamone, Damien (Committee member) / Department of Psychology (Contributor) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05