Matching Items (181)
Description
Horizon is a young adult dystopian fiction piece that addresses issues of gender and LGBTQIA+ identity. In the story, the world has been divided into two separate societies: earth, inhabited by females, and a platform in the sky, inhabited by males. This physical division is the result of a war between the two groups. Ever since this war, there has been limited communication between the two societies, and the members of each society have animosity for those who are of a different sex or gender. The plot follows two main characters, Andrea and Susumu, as they come to understand the corruption of their societies and attempt to cross the gender divide. They are joined on their journey by other characters of varied gender and LGBTQIA+ identities, each of them unable to fit into their society's parameters of appropriate gendered behavior. This creative project looks critically at the ways in which members of different genders can become alienated from each other through societal pressure. It also analyzes how LGBTQIA+ identity may factor into the gendering of an individual, explores how people can be ostracized because of their identity, and critiques the gender binary. The second component of this creative project is a detailed reflection on the creative writing process. It outlines the steps of creating Horizon, from brainstorming through writing and editing. An explanation of the purpose the project and a discussion of writing challenges and future goals is included. The reflection also puts Horizon in context with other LGBTQIA+ media and dystopian novels and explains some of the most crucial decisions that were made in the creation of this story.
ContributorsPerry, Samantha Lynn (Author) / Himberg, Julia (Thesis director) / Dove-Viebahn, Aviva (Committee member) / Hugh Downs School of Human Communication (Contributor) / College of Public Service and Community Solutions (Contributor) / Department of English (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Arizona and Florida are unique venues are they are the only two locations in the world to host the preseason leagues known as Spring Training for all thirty Major League Baseball teams. With fan bases willing to travel and spend disposable income to follow their favorite teams and/or escape the cold spells of their home state, the sports and tourism industries in Arizona and Florida have been able to captivate a status as top spring destinations. This study takes a focus on the economic impact that Spring Training in March has on the state of Arizona; specifically the Phoenix Metropolitan area. Consumer research is presented and a SWOT analysis is generated to further assess the condition of the Cactus League and Arizona as a host state. An economic impact study driven by the Strengths, Weaknesses, Opportunities & Threats (SWOT) analysis method is the primary focuses of research due to the sum and quality of usable data that can be organized using the SWOT structure. The scope of this research aims to support the argument that Spring Training impacts the host city in which it resides in. In conjunction with the SWOT analysis, third parties will be able to get a sense of the overall effectiveness and impact of Cactus League Spring Training in the Valley of the Sun. Integration of findings from a Tampa Bay sight visit will also be assessed to determine the health of the competition. This study will take an interdisciplinary approach as it views the topics at hand from the lenses of the consumer, baseball professional, and investor.
ContributorsOlden, Kyle (Co-author) / Farmer, James (Co-author) / Eaton, John (Thesis director) / Mokwa, Michael (Committee member) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / College of Public Service and Community Solutions (Contributor) / Department of Information Systems (Contributor) / Department of Economics (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Almost every form of cancer deregulates the expression and activity of anabolic glycosyltransferase (GT) enzymes, which incorporate particular monosaccharides in a donor acceptor as well as linkage- and anomer-specific manner to assemble complex and diverse glycans that significantly affect numerous cellular events, including tumorigenesis and metastasis. Because glycosylation is not template-driven, GT deregulation yields heterogeneous arrays of aberrant intact glycan products, some in undetectable quantities in clinical bio-fluids (e.g., blood plasma). Numerous glycan features (e.g., 6 sialylation, β-1,6-branching, and core fucosylation) stem from approximately 25 glycan “nodes:” unique linkage specific monosaccharides at particular glycan branch points that collectively confer distinguishing features upon glycan products. For each node, changes in normalized abundance (Figure 1) may serve as nearly 1:1 surrogate measure of activity for culpable GTs and may correlate with particular stages of carcinogenesis. Complementary to traditional top down glycomics, the novel bottom-up technique applied herein condenses each glycan node and feature into a single analytical signal, quantified by two GC-MS instruments: GCT (time-of-flight analyzer) and GCMSD (transmission quadrupole analyzers). Bottom-up analysis of stage 3 and 4 breast cancer cases revealed better overall precision for GCMSD yet comparable clinical performance of both GC MS instruments and identified two downregulated glycan nodes as excellent breast cancer biomarker candidates: t-Gal and 4,6-GlcNAc (ROC AUC ≈ 0.80, p < 0.05). Resulting from the activity of multiple GTs, t-Gal had the highest ROC AUC (0.88) and lowest ROC p‑value (0.001) among all analyzed nodes. Representing core-fucosylation, glycan node 4,6-GlcNAc is a nearly 1:1 molecular surrogate for the activity of α-(1,6)-fucosyltransferase—a potential target for cancer therapy. To validate these results, future projects can analyze larger sample sets, find correlations between breast cancer stage and changes in t-Gal and 4,6-GlcNAc levels, gauge the specificity of these nodes for breast cancer and their potential role in other cancer types, and develop clinical tests for reliable breast cancer diagnosis and treatment monitoring based on t-Gal and 4,6-GlcNAc.
ContributorsZaare, Sahba (Author) / Borges, Chad (Thesis director) / LaBaer, Joshua (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
This study investigates how the patient-provider relationship between lesbian, gay, and bisexual women and their healthcare providers influences their access to, utilization of, and experiences within healthcare environments. Nineteen participants, ages 18 to 34, were recruited using convenience and snowball sampling. Interviews were conducted inquiring about their health history and their experiences within the healthcare system in the context of their sexual orientation. The data collected from these interviews was used to create an analysis of the healthcare experiences of those who identify as queer. Although the original intention of the project was to chronicle the experiences of LGB women specifically, there were four non-binary gender respondents who contributed interviews. In an effort to not privilege any orientation over another, the respondents were collectively referred to as queer, given the inclusive and an encompassing nature of the term. The general conclusion of this study is that respondents most often experienced heterosexism rather than outright homophobia when accessing healthcare. If heterosexism was present within the healthcare setting, it made respondents feel uncomfortable with their providers and less likely to inform them of their sexuality even if it was medically relevant to their health outcomes. Gender, race, and,socioeconomic differences also had an effect on the patient-provider relationship. Non-binary respondents acknowledged the need for inclusion of more gender options outside of male or female on the reporting forms often seen in medical offices. By doing so, medical professionals are acknowledging their awareness and knowledge of people outside of the binary gender system, thus improving the experience of these patients. While race and socioeconomic status were less relevant to the context of this study, it was found that these factors have an affect on the patient-provider relationship. There are many suggestions for providers to improve the experiences of queer patients within the healthcare setting. This includes nonverbal indications of acknowledgement and acceptance, such as signs in the office that indicate it to be a queer friendly space. This will help in eliminating the fear and miscommunication that can often happen when a queer patient sees a practitioner for the first time. In addition, better education on medically relevant topics to queer patients, is necessary in order to eliminate disparities in health outcomes. This is particularly evident in trans health, where specialized education is necessary in order to decrease poor health outcomes in trans patients. Future directions of this study necessitate a closer look on how race and socioeconomic status have an effect on a queer patient's relationship with their provider.
ContributorsRajan, Sindhu (Co-author) / Bradley, Arianna (Co-author) / Larson, Michelle (Co-author) / Alvarado, Aimee (Co-author) / Ingram-Waters, Mary (Thesis director) / Arnold, Michelle (Committee member) / School of Molecular Sciences (Contributor) / School of Social Transformation (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / College of Public Service and Community Solutions (Contributor) / School of Human Evolution and Social Change (Contributor) / School of Historical, Philosophical and Religious Studies (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Netflix has positioned itself at the forefront of the future of television with its original programming, which has been rolled out in greater and more frequent amounts just in the last couple of years. The streaming service has already experimented with creativity in ways most other shows and creators haven't, playing with the pacing of overall seasons as well as the length of episodes. So, too, Netflix has been at the forefront of increasing visibility for minority characters on television. Many of its shows incorporate racially diverse casts and depict lots of LGBTQ characters, a refreshingly realistic view of the world that many of its viewers have always lived in but haven't yet witnessed on television. Visibility and representation are critical concepts for analyzing minority characters on television. It is important for diverse characters to be seen, first and foremost, but also to be seen in positive or at least realistic lights. Care must be taken to avoid fulfilling stereotypes or tropes, and attention must be paid to what has happened to other characters who have come before. However, many of Netflix's portrayals of these characters, particularly bisexual characters, leave much to be desired. With the original dramas House of Cards, Hemlock Grove, Orange is the New Black, and Sense8, all of which include characters who identify as or behave bisexually, Netflix has been reluctant to use the specific word bisexual to describe characters, and many don't even identify their sexuality with a synonym for the term. Many of the bisexual characters that I identified died or were killed on the shows, and nearly all of them fulfilled stereotypes or tropes in some way. There were multiple scenes of threesomes or other distinctly kinky sexual encounters, which served to exoticize bisexuality and distance it from the more normatively viewed identities of heterosexuality and homosexuality. Ultimately, while Netflix's original programming has offered increased visibility to bisexual characters, it has yet to reflect the real community it seeks to portray. In particular, Netflix's refusal to label characters as bisexual is frustrating and limiting. It can be argued that this is a progressive move toward more ideas of sexual fluidity and a post-modern lack of sexual labels, but there are not enough depictions of identified bisexual characters on television yet for this to make sense. Until bisexual characters and their identities are not invisibilized or stigmatized, more work has to be done to ensure that bisexual people are represented fairly and accurately on television and in all media.
ContributorsKoerth, Kimberly Marie (Author) / Himberg, Julia (Thesis director) / Sturges, Robert (Committee member) / Department of English (Contributor) / College of Public Service and Community Solutions (Contributor) / Walter Cronkite School of Journalism and Mass Communication (Contributor) / School of Social Transformation (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Disturbances in the protein interactome often play a large role in cancer progression. Investigation of protein-protein interactions (PPI) can increase our understanding of cancer pathways and will disclose unknown targets involved in cancer disease biology. Although numerous methods are available to study protein interactions, most platforms suffer from drawbacks including high false positive rates, low throughput, and lack of quantification. Moreover, most methods are not compatible for use in a clinical setting. To address these limitations, we have developed a multiplexed, in-solution protein microarray (MISPA) platform with broad applications in proteomics. MISPA can be used to quantitatively profile PPIs and as a robust technology for early detection of cancers. This method utilizes unique DNA barcoding of individual proteins coupled with next generation sequencing to quantitatively assess interactions via barcode enrichment. We have tested the feasibility of this technology in the detection of patient immune responses to oropharyngeal carcinomas and in the discovery of novel PPIs in the B-cell receptor (BCR) pathway. To achieve this goal, 96 human papillomavirus (HPV) antigen genes were cloned into pJFT7-cHalo (99% success) and pJFT7-n3xFlag-Halo (100% success) expression vectors. These libraries were expressed via a cell-free in vitro transcription-translation system with 93% and 96% success, respectively. A small-scale study of patient serum interactions with barcoded HPV16 antigens was performed and a HPV proteome-wide study will follow using additional patient samples. In addition, 15 query proteins were cloned into pJFT7_nGST expression vectors, expressed, and purified with 93% success to probe a library of 100 BCR pathway proteins and detect novel PPIs.
ContributorsRinaldi, Capria Lakshmi (Author) / LaBaer, Joshua (Thesis director) / Mangone, Marco (Committee member) / Borges, Chad (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Dyslexia is a learning disability that negatively affects reading, writing, and spelling development at the word level in 5%-9% of children. The phenotype is variable and complex, involving several potential cognitive and physical concomitants such as sensory dysregulation and immunodeficiencies. The biological pathogenesis is not well-understood. Toward a better understanding of the biological drivers of dyslexia, we conducted the first joint exome and metabolome investigation in a pilot sample of 30 participants with dyslexia and 13 controls. In the metabolite analysis, eight metabolites of interest emerged (pyridoxine, kynurenic acid, citraconic acid, phosphocreatine, hippuric acid, xylitol, 2-deoxyuridine, and acetylcysteine). A metabolite-metabolite interaction analysis identified Krebs cycle intermediates that may be implicated in the development of dyslexia. Gene ontology analysis based on exome variants resulted in several pathways of interest, including the sensory perception of smell (olfactory) and immune system-related responses. In the joint exome and metabolite analysis, the olfactory transduction pathway emerged as the primary pathway of interest. Although the olfactory transduction and Krebs cycle pathways have not previously been described in the dyslexia literature, these pathways have been implicated in other neurodevelopmental disorders including autism spectrum disorder and obsessive-compulsive disorder, suggesting the possibility of these pathways playing a role in dyslexia as well. Immune system response pathways, on the other hand, have been implicated in both dyslexia and other neurodevelopmental disorders.
ContributorsNandakumar, Rohit (Author) / Dinu, Valentin (Thesis director) / Peter, Beate (Committee member) / Barrett, The Honors College (Contributor) / College of Health Solutions (Contributor)
Created2022-05
Description
The TP53 tumor suppressor gene is the most frequently mutated gene in human cancers. In the highly aggressive triple negative breast cancer (TNBC), TP53 is mutated in 80% of cases. TNBC lacks viable drug targets, resulting in a low prognosis (12.2% 5 year survivability rate). As such, the discovery of druggable targets in TNBC would be beneficial. Mutated p53 protein typically occurs as a missense mutation and often endows cancer cells with gain of function (GOF) properties by dysregulating metabolic pathways. One of these frequently dysregulated pathways is the Hippo/Yes-associated protein-1 (YAP1)/WW Domain Containing Transcription Regulator 1 (TAZ) tumor suppressor pathway. This study therefore analyzed the involvement of the Hippo/YAP1/TAZ pathway in p53-mediated breast cancer cell invasion. From an RNA-seq screen in MCF10A cell lines harboring different TP53 missense mutations, each with a differing invasive phenotype, components of the Hippo pathway were found to correlate with cell invasion. To this end, the active and inactive forms of YAP1 and TAZ were studied. Phosphorylated (inactive) YAP1 and TAZ are retained in the cytoplasm and eventually degraded. Unphosphorylated (active) YAP1 and TAZ translocate to the nucleus to activate TEAD-family transcription factors, inducing cell survival and proliferation genes leading to increased cell invasion. Using quantitative western blot analysis, it was found that inactive TAZ expression was lower in the most invasive cell lines and higher in the least invasive cell lines (p = 0.003). Moreover, the ratio of inactive TAZ protein to total TAZ protein was also shown to be predominantly lower in the invasive cell lines compared to the non-invasive lines (p = 0.04). Finally, active TAZ expression was primarily higher in p53-mutant invasive cell lines and lower in non-invasive p53 mutant cells. Additionally, although YAP1 and TAZ are thought to be functionally redundant, the pattern seen in TAZ was not seen in the YAP1 protein. Taken together, the results demonstrated here suggest that TAZ holds a more dominant role in governing TNBC cell invasion compared to YAP1 and further highlights TAZ as a potential therapeutic target in TNBC.
ContributorsGrief, Dustin (Author) / LaBaer, Joshua (Thesis advisor) / Anderson, Karen (Committee member) / Nikkhah, Mehdi (Committee member) / Arizona State University (Publisher)
Created2022
Description
Glioblastoma (GBM), the most common and aggressive primary brain tumor affecting adults, is characterized by an aberrant yet druggable epigenetic landscape. The Histone Deacetylases (HDACs), a major family of epigenetic regulators, favor transcriptional repression by mediating chromatin compaction and are frequently overexpressed in human cancers, including GBM. Hence, over the last decade there has been considerable interest in using HDAC inhibitors (HDACi) for the treatment of malignant primary brain tumors. However, to date most HDACi tested in clinical trials have failed to provide significant therapeutic benefit to patients with GBM. This is because current HDACi have poor or unknown pharmacokinetic profiles, lack selectivity towards the different HDAC isoforms, and have narrow therapeutic windows. Isoform selectivity for HDACi is important given that broad inhibition of all HDACs results in widespread toxicity across different organs. Moreover, the functional roles of individual HDAC isoforms in GBM are still not well understood. Here, I demonstrate that HDAC1 expression increases with brain tumor grade and is correlated with decreased survival in GBM. I find that HDAC1 is the essential HDAC isoform in glioma stem cells and its loss is not compensated for by its paralogue HDAC2 or other members of the HDAC family. Loss of HDAC1 alone has profound effects on the glioma stem cell phenotype in a p53-dependent manner and leads to significant suppression of tumor growth in vivo. While no HDAC isoform-selective inhibitors are currently available, the second-generation HDACi quisinostat harbors high specificity for HDAC1. I show that quisinostat exhibits potent growth inhibition in multiple patient-derived glioma stem cells. Using a pharmacokinetics- and pharmacodynamics-driven approach, I demonstrate that quisinostat is a brain-penetrant molecule that reduces tumor burden in flank and orthotopic models of GBM and significantly extends survival both alone and in combination with radiotherapy. The work presented in this thesis thereby unveils the non-redundant functions of HDAC1 in therapy- resistant glioma stem cells and identifies a brain-penetrant HDACi with higher selectivity towards HDAC1 as a potent radiosensitizer in preclinical models of GBM. Together, these results provide a rationale for developing quisinostat as a potential adjuvant therapy for the treatment of GBM.
ContributorsLo Cascio, Costanza (Author) / LaBaer, Joshua (Thesis advisor) / Mehta, Shwetal (Committee member) / Mirzadeh, Zaman (Committee member) / Mangone, Marco (Committee member) / Paek, Andrew (Committee member) / Arizona State University (Publisher)
Created2022
Description
High throughput transcriptome data analysis like Single-cell Ribonucleic Acid sequencing (scRNA-seq) and Circular Ribonucleic Acid (circRNA) data have made significant breakthroughs, especially in cancer genomics. Analysis of transcriptome time series data is core in identifying time point(s) where drastic changes in gene transcription are associated with homeostatic to non-homeostatic cellular transition (tipping points). In Chapter 2 of this dissertation, I present a novel cell-type specific and co-expression-based tipping point detection method to identify target gene (TG) versus transcription factor (TF) pairs whose differential co-expression across time points drive biological changes in different cell types and the time point when these changes are observed. This method was applied to scRNA-seq data sets from a SARS-CoV-2 study (18 time points), a human cerebellum development study (9 time points), and a lung injury study (18 time points). Similarly, leveraging transcriptome data across treatment time points, I developed methodologies to identify treatment-induced and cell-type specific differentially co-expressed pairs (DCEPs). In part one of Chapter 3, I presented a pipeline that used a series of statistical tests to detect DCEPs. This method was applied to scRNA-seq data of patients with non-small cell lung cancer (NSCLC) sequenced across cancer treatment times. However, this pipeline does not account for correlations among multiple single cells from the same sample and correlations among multiple samples from the same patient. In Part 2 of Chapter 3, I presented a solution to this problem using a mixed-effect model. In Chapter 4, I present a summary of my work that focused on the cross-species analysis of circRNA transcriptome time series data. I compared circRNA profiles in neonatal pig and mouse hearts, identified orthologous circRNAs, and discussed regulation mechanisms of cardiomyocyte proliferation and myocardial regeneration conserved between mouse and pig at different time points.
ContributorsNyarige, Verah Mocheche (Author) / Liu, Li (Thesis advisor) / Wang, Junwen (Thesis advisor) / Dinu, Valentin (Committee member) / Arizona State University (Publisher)
Created2022