ASU Electronic Theses and Dissertations
This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.
In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.
Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.
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Biological and immunological characterization of plant-produced HIV-1 Gag/dgp41 virus-like particles
Description
Anti-retroviral drugs and AIDS prevention programs have helped to decrease the rate of new HIV-1 infections in some communities, however, a prophylactic vaccine is still needed to control the epidemic world-wide. Despite over two decades of research, a vaccine against HIV-1 remains elusive, although recent clinical trials have shown promising results. Recent successes have focused on highly conserved, mucosally-targeted antigens within HIV-1 such as the membrane proximal external region (MPER) of the envelope protein, gp41. MPER has been shown to play critical roles in the viral mucosal transmission, though this peptide is not immunogenic on its own. Gag is a structural protein configuring the enveloped virus particles, and has been suggested to constitute a target of the cellular immunity potentially controlling the viral load. It was hypothesized that HIV-1 enveloped virus-like particles (VLPs) consisting of Gag and a deconstructed form of gp41 comprising the MPER, transmembrane, and cytoplasmic domains (dgp41) could be expressed in plants. Plant-optimized HIV-1 genes were constructed and expressed in Nicotiana benthamiana by stable transformation, or transiently using a tobacco mosaic virus-based expression system or a combination of both. Results of biophysical, biochemical and electron microscopy characterization demonstrated that plant cells could support not only the formation of HIV-1 Gag VLPs, but also the accumulation of VLPs that incorporated dgp41. These particles were purified and utilized in mice immunization experiments. Prime-boost strategies combining systemic and mucosal priming with systemic boosting using two different vaccine candidates (VLPs and CTB-MPR - a fusion of MPER and the B-subunit of cholera toxin) were administered to BALB/c mice. Serum antibody responses against both the Gag and gp41 antigens could be elicited in mice systemically primed with VLPs and these responses could be recalled following systemic boosting with VLPs. In addition, mucosal priming with VLPs allowed for a robust boosting response against Gag and gp41 when boosted with either candidate. Functional assays of these antibodies are in progress to test the antibodies' effectiveness in neutralizing and preventing mucosal transmission of HIV-1. This immunogenicity of plant-based Gag/dgp41 VLPs represents an important milestone on the road towards a broadly-efficacious and inexpensive subunit vaccine against HIV-1.
ContributorsKessans, Sarah (Author) / Mor, Tsafrir S (Thesis advisor) / Matoba, Nobuyuki (Committee member) / Mason, Hugh (Committee member) / Hogue, Brenda (Committee member) / Fromme, Petra (Committee member) / Arizona State University (Publisher)
Created2011
Description
A dental exam in twenty-first century America generally includes the taking of radiographs, which are x-ray images of the mouth. These images allow dentists to see structures below the gum line and within the teeth. Having a patient's radiographs on file has become a dental standard of care in many states, but x-rays were only discovered a little over 100 years ago. This research analyzes how and why the x-ray image has become a ubiquitous tool in the dental field. Primary literature written by dentists and scientists of the time shows that the x-ray was established in dentistry by the 1950s. Therefore, this thesis tracks the changes in x-ray technological developments, the spread of information and related safety concerns between 1890 and 1955. X-ray technology went from being an accidental discovery to a device commonly purchased by dentists. X-ray information started out in the form of the anecdotes of individuals and led to the formation of large professional groups. Safety concerns of only a few people later became an important facet of new devices. These three major shifts are described by looking at those who prompted the changes; they fall into the categories of people, technological artifacts and institutions. The x-ray became integrated into dentistry as a product of the work of people such as C. Edmund Kells, a proponent of dental x-rays, technological improvements including faster film speed, and the influence of institutions such as Victor X-Ray Company and the American Dental Association. These changes that resulted established a strong foundation of x-ray technology in dentistry. From there, the dental x-ray developed to its modern form.
ContributorsMartinez, Britta (Author) / Ellison, Karin (Thesis advisor) / Maienschein, Jane (Thesis advisor) / Hurlbut, Ben (Committee member) / Arizona State University (Publisher)
Created2013
Description
Adoptive transfer of T cells engineered to express synthetic antigen-specific T cell receptors (TCRs) has provocative therapeutic applications for treating cancer. However, expressing these synthetic TCRs in a CD4+ T cell line is a challenge. The CD4+ Jurkat T cell line expresses endogenous TCRs that compete for space, accessory proteins, and proliferative signaling, and there is the potential for mixed dimer formation between the α and β chains of the endogenous receptor and that of the synthetic cancer-specific TCRs. To prevent hybridization between the receptors and to ensure the binding affinity measured with flow cytometry analysis is between the tetramer and the TCR construct, a CRISPR-Cas9 gene editing pipeline was developed. The guide RNAs (gRNAs) within the complex were designed to target the constant region of the α and β chains, as they are conserved between TCR clonotypes. To minimize further interference and confer cytotoxic capabilities, gRNAs were designed to target the CD4 coreceptor, and the CD8 coreceptor was delivered in a mammalian expression vector. Further, Golden Gate cloning methods were validated in integrating the gRNAs into a CRISPR-compatible mammalian expression vector. These constructs were transfected via electroporation into CD4+ Jurkat T cells to create a CD8+ knockout TCR Jurkat cell line for broadly applicable uses in T cell immunotherapies.
ContributorsHirneise, Gabrielle Rachel (Author) / Anderson, Karen (Thesis advisor) / Mason, Hugh (Committee member) / Lake, Douglas (Committee member) / Arizona State University (Publisher)
Created2020
Description
In the US, menstrual education, which provides key information about menstrual hygiene and health to both young girls and boys, historically lacks biologically accurate information about the menstrual cycle and perpetuates harmful perceptions about female reproductive health. When people are unable to differentiate between normal and abnormal menstrual bleeding, based on a lack of quality menstrual education, common gynecological conditions often remain underreported. This raises a question as to how girls’ menstrual education experiences influence the ways in which they perceive normal menstrual bleeding and seek treatment for common abnormalities, such as heavy, painful, or irregular menstrual bleeding. A mixed methods approach allowed evaluation of girls’ abilities to recognize abnormal menstrual bleeding. A literature review established relevant historical and social context on the prevalence and quality of menstrual education in the US. Then, five focus groups, each including five to eight college-aged women, totaling thirty-three participants, allowed for macro-level analysis of current challenges and gaps in knowledge related to menstruation. To better examine the relationship between menstrual education and reproductive health outcomes, twelve semi-structured, one-on-one interviews allowed micro-level analysis. Those interviews consisted of women diagnosed with endometriosis and polycystic ovary syndrome, common gynecological conditions that include abnormal menstrual bleeding. Developing a codebook of definitions and exemplars of significant text segments and applying it to the collected data revealed several themes. For example, mothers, friends, teachers, the Internet, and social media are among the most common sources of information about menstrual hygiene and health. Yet, women reported that those sources of information often echoed stigmatized ideas about menstruation, eliciting feelings of shame and fear. That poor quality of information was instrumental to women’s abilities to detect and report abnormal menstrual bleeding. Women desire and need biologically accurate information about reproductive health, including menstruation and ovulation, fertility, and methods of birth control as treatments for abnormal menstrual bleeding. Unfortunately, menstrual education often leaves girls ill-equipped to identify and seek treatment for common gynecological conditions. Those findings may influence current menstrual education, incorporating biological information and actively dismissing common misconceptions about menstruation that influence stigma.
ContributorsSantora, Emily Katherine (Author) / Maienschein, Jane (Thesis advisor) / Ellison, Karin (Committee member) / Hurlbut, Ben (Committee member) / Arizona State University (Publisher)
Created2021