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- All Subjects: Biology
- Creators: School of Life Sciences
- Creators: Sweazea, Karen
- Creators: Kuang, Yang
- Resource Type: Text
Description
Efforts to treat prostate cancer have seen an uptick, as the world’s most commoncancer in men continues to have increasing global incidence. Clinically, metastatic
prostate cancer is most commonly treated with hormonal therapy. The idea behind
hormonal therapy is to reduce androgen production, which prostate cancer cells
require for growth. Recently, the exploration of the synergistic effects of the drugs
used in hormonal therapy has begun. The aim was to build off of these recent
advancements and further refine the synergistic drug model. The advancements I
implement come by addressing biological shortcomings and improving the model’s
internal mechanistic structure. The drug families being modeled, anti-androgens,
and gonadotropin-releasing hormone analogs, interact with androgen production in a
way that is not completely understood in the scientific community. Thus the models
representing the drugs show progress through their ability to capture their effect
on serum androgen. Prostate-specific antigen is the primary biomarker for prostate
cancer and is generally how population models on the subject are validated. Fitting
the model to clinical data and comparing it to other clinical models through the
ability to fit and forecast prostate-specific antigen and serum androgen is how this
improved model achieves validation. The improved model results further suggest that
the drugs’ dynamics should be considered in adaptive therapy for prostate cancer.
prostate cancer is most commonly treated with hormonal therapy. The idea behind
hormonal therapy is to reduce androgen production, which prostate cancer cells
require for growth. Recently, the exploration of the synergistic effects of the drugs
used in hormonal therapy has begun. The aim was to build off of these recent
advancements and further refine the synergistic drug model. The advancements I
implement come by addressing biological shortcomings and improving the model’s
internal mechanistic structure. The drug families being modeled, anti-androgens,
and gonadotropin-releasing hormone analogs, interact with androgen production in a
way that is not completely understood in the scientific community. Thus the models
representing the drugs show progress through their ability to capture their effect
on serum androgen. Prostate-specific antigen is the primary biomarker for prostate
cancer and is generally how population models on the subject are validated. Fitting
the model to clinical data and comparing it to other clinical models through the
ability to fit and forecast prostate-specific antigen and serum androgen is how this
improved model achieves validation. The improved model results further suggest that
the drugs’ dynamics should be considered in adaptive therapy for prostate cancer.
ContributorsReckell, Trevor (Author) / Kostelich, Eric (Thesis advisor) / Kuang, Yang (Committee member) / Mahalov, Alex (Committee member) / Arizona State University (Publisher)
Created2020
Description
Lipolysis or hydrolysis of triglyceride (TG) stored within intracellular lipid droplets (LD), is vital to maintaining metabolic homeostasis in mammals. Regulation of lipolysis and subsequent utilization of liberated fatty acids impacts cellular and organismal functions including body fat accumulation and thermogenesis. Adipose triglyceride lipase (ATGL) is the intracellular rate-limiting enzyme responsible for catalyzing hydrolysis of TG to diacylglycerol (DAG), the initial step of the lipolytic reaction. G0/G1 switch gene-2 (G0S2) and hypoxia-inducible gene-2 (HIG2) are selective inhibitors of ATGL. G0S2 facilitates accumulation of TG in the liver and adipose tissue, while HIG2 functions under hypoxic conditions. Sequence analysis and mutagenesis were used to confirm the presence of conserved domains between these proteins, and that these domains are required for efficient binding and inhibition of ATGL. Further analysis revealed a Positive sequence (Pos-Seq)-LD binding motif in G0S2 but not HIG2. The Pos-Seq mediated ATGL-independent localization to LD and was required for achieving maximal inhibition of ATGL activity by G0S2. Identification and mutational analysis of this motif revealed distinct mechanisms for HIG2 and G0S2 LD association. In addition to molecular characterization of known protein inhibitors of lipolysis, an intracellular member of the apolipoprotein L (ApoL) family, ApoL6, was also identified as a LD and mitochondria associated protein expressed in adipose tissue. Brown adipose tissue uses fatty acids as fuel for increasing its energy output as heat during acute responses to cold exposure. A Comprehensive Lab Animal Monitoring System was used to compare heat production at room temperature (RT) and 4oC in transgenic animals overexpressing ApoL6 in brown adipose tissue. Overexpression of ApoL6 delayed utilization of long-chain fatty acids (LCFAs) as a fuel source while promoting an enhanced thermogenic response during initial cold exposure. ApoL6 mediated inhibition of LCFA utilization results from binding of ApoL6 to Mitochondrial Trifunctional Protein (MTP/TFP), which catalyzes mitochondrial β-oxidation. Indirect calorimetry and fasting acute cold exposure experiments suggest the augmented thermogenic profile of ApoL6 transgenic animals is a result of enhanced utilization of medium-chain fatty acids (MCFAs), glucose, and amino acids as fuel sources. Cumulatively these results indicate multiple mechanisms for regulation lipolysis and fatty acid utilization.
ContributorsCampbell, Latoya E (Author) / Lake, Douglas (Thesis advisor) / Liu, Jun (Committee member) / Folmes, Clifford (Committee member) / Sweazea, Karen (Committee member) / Baluch, Debra (Committee member) / Arizona State University (Publisher)
Created2021
Description
The desire to start a family is something millions of people around the globe strive to achieve. However, many factors such as the societal changes in family planning due to increasing maternal age, use of birth control, and ever-changing lifestyles have increased the number of infertility cases seen in the United States each year. Infertility can manifest as a prolonged inability to conceive, or inability to carry a pregnancy full-term. Modern advancements in the field of reproductive medicine have begun to promote the use of Assisted Reproductive Technologies (ART) to circumvent reduced fertility in both men and women. Implementation of techniques such as In Vitro Fertilization, Intracytoplasmic Sperm Injection, and Pre-Implantation Genetic Testing have allowed many couples to conceive. There is continual effort being made towards developing more effective and personalized fertility treatments. This often begins in the form of animal research—a fundamental step in biomedical research. This dissertation examines infertility as a medical condition through the characterization of normal reproductive anatomy and physiology in the introductory overview of reproduction. Specific pathologies of male and female-factor infertility are described, which necessitates the use of ARTs. The various forms of ARTs currently utilized in a clinical setting are addressed including history, preparations, and protocols for each technology. To promote continual advancement of the field, both animal studies and human trials provide fundamental stepping-stones towards the execution of new techniques and protocols. Examples of research conducted for the betterment of human reproductive medicine are explored, including an animal study conducted in mice exploring the role of tyramine in ovulation. With the development and implementation of new technologies and protocols in the field, this also unearths ethical dilemmas that further complicate the addition of new technologies in the field. Combining an extensive review in assisted reproduction, research and clinical fieldwork, this study investigates the history and development of novel research conducted in reproductive medicine and explores the broader implications of new technologies in the field.
ContributorsPeck, Shelbi Marie (Author) / Baluch, Debra P (Thesis advisor) / Maienschein, Jane (Thesis advisor) / Sweazea, Karen (Committee member) / Ellison, Karin (Committee member) / Arizona State University (Publisher)
Created2021
Description
Cooperative cellular phenotypes are universal across multicellular life. Division of labor, regulated proliferation, and controlled cell death are essential in the maintenance of a multicellular body. Breakdowns in these cooperative phenotypes are foundational in understanding the initiation and progression of neoplastic diseases, such as cancer. Cooperative cellular phenotypes are straightforward to characterize in extant species but the selective pressures that drove their emergence at the transition(s) to multicellularity have yet to be fully characterized. Here we seek to understand how a dynamic environment shaped the emergence of two mechanisms of regulated cell survival: apoptosis and senescence. We developed an agent-based model to test the time to extinction or stability in each of these phenotypes across three levels of stochastic environments.
ContributorsDanesh, Dafna (Author) / Maley, Carlo (Thesis director) / Aktipis, Athena (Committee member) / Compton, Zachary (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2021-12
Description
Early detection of disease is essential for alleviating disease burden, increasing success rate and decreasing mortality rate especially for cancer. To improve disease diagnostics, many candidate biomarkers have been suggested using molecular biology or image analysis techniques over the past decade. The receiver operating characteristics (ROC) curve is a standard technique to evaluate a diagnostic accuracy of biomarkers, but it has some limitations especially for heterogeneous diseases. As an alternative of the ROC curve analysis, we suggest a jittered dot plot (JDP) and JDP-based evaluation measures, above mean difference (AMD) and averaged above mean difference (AAMD). We demonstrate how JDP and AMD or AAMD together better evaluate biomarkers than the standard ROC curve. We analyze real and heterogeneous basal-like breast cancer data.
ContributorsBrister, Danielle (Author) / Chung, Yunro (Thesis director) / Park, Jin (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / School of Molecular Sciences (Contributor) / School of International Letters and Cultures (Contributor) / School of Human Evolution & Social Change (Contributor)
Created2021-12
Description
Art is an inherent concept instilled in human nature, which utilizes the abilities of the creative mind to invent. Art has served many purposes in the history of mankind, including, but not limited to story telling, entertainment, decoration, exploration, propaganda, education, and therapy. The primary aim of this creative project was to explore the importance of the art, as a creative process, as a way to supplement academic endeavors. The idea derived from an observation made by myself that contemporary regard for art has been on a decline, which made me question if I also value art as much as I think I do, having done art in the past and recently added a studio art minor. I thought of ways to again incorporate art and the creative process into my life. I asked myself the question: can the creative process be used as a supplement to schoolwork in order to relieve stress? To explore this, an experiment was designed, which entailed my creation of drawings twice a week, accompanied by journal documentation for a full semester of college. Afterwards, analyses were done between the documented journal entries and the artworks to see if any relationships were apparent between various aspects of my life at the times of the drawings and the drawings themselves. Further research was also conducted in related areas of study and documented in written format, which cited and analyzed numerous journal articles, artworks, artists, and research papers. This included art therapy, art education, and the relationships between art and science. Results from the experiment indicated that art as a creative process allowed for the relief of stress by cleansing my mind from any concern or interferences, therefore offering myself a complete break and relaxation, effectively refreshing my mind and allowing me to resume schoolwork or other tasks more mentally taxing. In addition, the research also showed that art therapy could effectively utilize this palliative effect of art making to ease the problems of people in distress. The findings also concluded that art and science go hand in hand, which explains a lot of the similarities in methodologies utilized by scientists and artists. In conclusion, art is a paramount part of mankind in exercising the creative mind and is ubiquitous; we should learn to actively embrace it to enrich our lives.
ContributorsSun, Sean Yu-Hsiang (Author) / Dove-Viebahn, Aviva (Thesis director) / Chandler, Douglas (Committee member) / School of Art (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
The overturning of Roe v. Wade in June of 2022 has left a lasting mark on the United
States as it entered a Post Roe era that has dramatically changed the course of reproductive
freedom, leaving much uncertainty throughout the country. With termination laws now at the
discretion of the states rather than the federal government, the fate of access to pregnancy
termination for medical indications is at stake. One area in healthcare where the overturning of
Roe v. Wade is expected to demonstrate a significant impact is within prenatal care for
individuals and couples at an increased risk of having a child affected by a genetic condition.
This study aims to understand the impact the Post Roe Era has had on the conversations
prenatal genetic counselors have with their patients considering termination in the southwest
of the United States across the states of California, Arizona, Nevada, and New Mexico. The
complexities of prenatal genetic counselors’ experiences with Roe v. Wade will be described by
analyzing survey responses and informational interviews with practicing genetic counselors.
When Roe v. Wade was overturned, it changed how prenatal genetic counselors care for their
patients. The types of discussions providers have surrounding pregnancy termination now vary
widely across the fifty states.
ContributorsCasey, Allison (Author) / Hunt Brendish, Katherine (Thesis director) / Haskin, Jennifer (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / School of Life Sciences (Contributor)
Created2024-05