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Description
Infections caused by the Hepatitis C Virus (HCV) are very common worldwide, affecting up to 3% of the population. Chronic infection of HCV may develop into liver cirrhosis and liver cancer which is among the top five of the most common cancers. Therefore, vaccines against HCV are under intense study in order to prevent HCV from harming people's health. The envelope protein 2 (E2) of HCV is thought to be a promising vaccine candidate because it can directly bind to a human cell receptor and plays a role in viral entry. However, the E2 protein production in cells is inefficient due to its complicated matured structure. Folding of E2 in the endoplasmic reticulum (ER) is often error-prone, resulting in production of aggregates and misfolded proteins. These incorrect forms of E2 are not functional because they are not able to bind to human cells and stimulate antibody response to inhibit this binding. This study is aimed to overcome the difficulties of HCV E2 production in plant system. Protein folding in the ER requires great assistance from molecular chaperones. Thus, in this study, two molecular chaperones in the ER, calreticulin and calnexin, were transiently overexpressed in plant leaves in order to facilitate E2 folding and production. Both of them showed benefits in increasing the yield of E2 and improving the quality of E2. In addition, poorly folded E2 accumulated in the ER may cause stress in the ER and trigger transcriptional activation of ER molecular chaperones. Therefore, a transcription factor involved in this pathway, named bZIP60, was also overexpressed in plant leaves, aiming at up-regulating a major family of molecular chaperones called BiP to assist protein folding. However, our results showed that BiP mRNA levels were not up-regulated by bZIP60, but they increased in response to E2 expression. The Western blot analysis also showed that overexpression of bZIP60 had a small effect on promoting E2 folding. Overall, this study suggested that increasing the level of specific ER molecular chaperones was an effective way to promote HCV E2 protein production and maturation.
ContributorsHong, Fan (Author) / Mason, Hugh (Thesis advisor) / Gaxiola, Roberto (Committee member) / Chang, Yung (Committee member) / Chen, Qiang (Committee member) / Arizona State University (Publisher)
Created2011
Description
In an effort to address the lack of literature in on-campus active travel, this study aims to investigate the following primary questions:<br/>• What are the modes that students use to travel on campus?<br/>• What are the motivations that underlie the mode choice of students on campus?<br/>My first stage of research involved a series of qualitative investigations. I held one-on-one virtual interviews with students in which I asked them questions about the mode they use and why they feel that their chosen mode works best for them. These interviews served two functions. First, they provided me with insight into the various motivations underlying student mode choice. Second, they provided me with an indication of what explanatory variables should be included in a model of mode choice on campus.<br/>The first half of the research project informed a quantitative survey that was released via the Honors Digest to attract student respondents. Data was gathered on travel behavior as well as relevant explanatory variables.<br/>My analysis involved developing a logit model to predict student mode choice on campus and presenting the model estimation in conjunction with a discussion of student travel motivations based on the qualitative interviews. I use this information to make a recommendation on how campus infrastructure could be modified to better support the needs of the student population.
ContributorsMirtich, Laura Christine (Author) / Salon, Deborah (Thesis director) / Fang, Kevin (Committee member) / School of Public Affairs (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Defines the concept of the arcology as conceived by architect Paolo Soleri. Arcology combines "architecture" and "ecology" and explores a visionary notion of a self-contained urban community that has agricultural, commercial, and residential facilities under one roof. Two real-world examples of these projects are explored: Arcosanti, AZ and Masdar City, Abu Dhabi, UAE. Key aspects of the arcology that could be applied to an existing urban fabric are identified, such as urban design fostering social interaction, reduction of automobile dependency, and a development pattern that combats sprawl. Through interviews with local representatives, a holistic approach to applying arcology concepts to the Phoenix Metro Area is devised.
ContributorsSpencer, Sarah Anne (Author) / Manuel-Navarrete, David (Thesis director) / Salon, Deborah (Committee member) / Barrett, The Honors College (Contributor) / School of Geographical Sciences and Urban Planning (Contributor) / School of Sustainability (Contributor)
Created2015-05
Description
Pathogenic Gram-negative bacteria employ a variety of molecular mechanisms to combat host defenses. Two-component regulatory systems (TCR systems) are the most ubiquitous signal transduction systems which regulate many genes required for virulence and survival of bacteria. In this study, I analyzed different TCR systems in two clinically-relevant Gram-negative bacteria, i.e., oral pathogen Porphyromonas gingivalis and enterobacterial Escherichia coli. P. gingivalis is a major causative agent of periodontal disease as well as systemic illnesses, like cardiovascular disease. A microarray study found that the putative PorY-PorX TCR system controls the secretion and maturation of virulence factors, as well as loci involved in the PorSS secretion system, which secretes proteinases, i.e., gingipains, responsible for periodontal disease. Proteomic analysis (SILAC) was used to improve the microarray data, reverse-transcription PCR to verify the proteomic data, and primer extension assay to determine the promoter regions of specific PorX regulated loci. I was able to characterize multiple genetic loci regulated by this TCR system, many of which play an essential role in hemagglutination and host-cell adhesion, and likely contribute to virulence in this bacterium. Enteric Gram-negative bacteria must withstand many host defenses such as digestive enzymes, low pH, and antimicrobial peptides (AMPs). The CpxR-CpxA TCR system of E. coli has been extensively characterized and shown to be required for protection against AMPs. Most recently, this TCR system has been shown to up-regulate the rfe-rff operon which encodes genes involved in the production of enterobacterial common antigen (ECA), and confers protection against a variety of AMPs. In this study, I utilized primer extension and DNase I footprinting to determine how CpxR regulates the ECA operon. My findings suggest that CpxR modulates transcription by directly binding to the rfe promoter. Multiple genetic and biochemical approaches were used to demonstrate that specific TCR systems contribute to regulation of virulence factors and resistance to host defenses in P. gingivalis and E. coli, respectively. Understanding these genetic circuits provides insight into strategies for pathogenesis and resistance to host defenses in Gram negative bacterial pathogens. Finally, these data provide compelling potential molecular targets for therapeutics to treat P. gingivalis and E. coli infections.
ContributorsLeonetti, Cori (Author) / Shi, Yixin (Thesis advisor) / Stout, Valerie (Committee member) / Nickerson, Cheryl (Committee member) / Sandrin, Todd (Committee member) / Arizona State University (Publisher)
Created2013
Description
The study of bacterial resistance to antimicrobial peptides (AMPs) is a significant area of interest as these peptides have the potential to be developed into alternative drug therapies to combat microbial pathogens. AMPs represent a class of host-mediated factors that function to prevent microbial infection of their host and serve as a first line of defense. To date, over 1,000 AMPs of various natures have been predicted or experimentally characterized. Their potent bactericidal activities and broad-based target repertoire make them a promising next-generation pharmaceutical therapy to combat bacterial pathogens. It is important to understand the molecular mechanisms, both genetic and physiological, that bacteria employ to circumvent the bactericidal activities of AMPs. These understandings will allow researchers to overcome challenges posed with the development of new drug therapies; as well as identify, at a fundamental level, how bacteria are able to adapt and survive within varied host environments. Here, results are presented from the first reported large scale, systematic screen in which the Keio collection of ~4,000 Escherichia coli deletion mutants were challenged against physiologically significant AMPs to identify genes required for resistance. Less than 3% of the total number of genes on the E. coli chromosome was determined to contribute to bacterial resistance to at least one AMP analyzed in the screen. Further, the screen implicated a single cellular component (enterobacterial common antigen, ECA) and a single transporter system (twin-arginine transporter, Tat) as being required for resistance to each AMP class. Using antimicrobial resistance as a tool to identify novel genetic mechanisms, subsequent analyses were able to identify a two-component system, CpxR/CpxA, as a global regulator in bacterial resistance to AMPs. Multiple previously characterized CpxR/A members, as well as members found in this study, were identified in the screen. Notably, CpxR/A was found to transcriptionally regulate the gene cluster responsible for the biosynthesis of the ECA. Thus, a novel genetic mechanism was uncovered that directly correlates with a physiologically significant cellular component that appears to globally contribute to bacterial resistance to AMPs.
ContributorsWeatherspoon-Griffin, Natasha (Author) / Shi, Yixin (Thesis advisor) / Clark-Curtiss, Josephine (Committee member) / Misra, Rajeev (Committee member) / Nickerson, Cheryl (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2013
Description
The contemporary architectural pedagogy is far removed from its ancestry: the classical Beaux-Arts and polytechnic schools of the 19th century and the Bauhaus and Vkhutemas models of the modern period. Today, the "digital" has invaded the academy and shapes pedagogical practices, epistemologies, and ontologies within it, and this invasion is reflected in teaching practices, principles, and tools. Much of this digital integration goes unremarked and may not even be explicitly taught. In this qualitative research project, interviews with 18 leading architecture lecturers, professors, and deans from programs across the United States were conducted. These interviews focused on advanced practices of digital architecture, such as the use of digital tools, and how these practices are viewed. These interviews yielded a wealth of information about the uses (and abuses) of advanced digital technologies within the architectural academy, and the results were analyzed using the methods of phenomenology and grounded theory. Most schools use digital technologies to some extent, although this extent varies greatly. While some schools have abandoned hand-drawing and other hand-based craft almost entirely, others have retained traditional techniques and use digital technologies sparingly. Reasons for using digital design processes include industry pressure as well as the increased ability to solve problems and the speed with which they could be solved. Despite the prevalence of digital design, most programs did not teach related design software explicitly, if at all, instead requiring students (especially graduate students) to learn to use them outside the design studio. Some of the problems with digital design identified in the interviews include social problems such as alienation as well as issues like understanding scale and embodiment of skill.
ContributorsAlqabandy, Hamad (Author) / Brandt, Beverly (Thesis advisor) / Mesch, Claudia (Committee member) / Newton, David (Committee member) / Arizona State University (Publisher)
Created2012
Description
In the middle of the 20th century, juried annuals of Native American painting in art museums were unique opportunities because of their select focus on two-dimensional art as opposed to "craft" objects and their inclusion of artists from across the United States. Their first fifteen years were critical for patronage and widespread acceptance of modern easel painting. Held at the Philbrook Art Center in Tulsa (1946-1979), the Denver Art Museum (1951-1954), and the Museum of New Mexico Art Gallery in Santa Fe (1956-1965), they were significant not only for the accolades and prestige they garnered for award winners, but also for setting standards of quality and style at the time. During the early years of the annuals, the art was changing, some moving away from conventional forms derived from the early art training of the 1920s and 30s in the Southwest and Oklahoma, and incorporating modern themes and styles acquired through expanded opportunities for travel and education. The competitions reinforced and reflected a variety of attitudes about contemporary art which ranged from preserving the authenticity of the traditional style to encouraging experimentation. Ultimately becoming sites of conflict, the museums that hosted annuals contested the directions in which artists were working. Exhibition catalogs, archived documents, and newspaper and magazine articles about the annuals provide details on the exhibits and the changes that occurred over time. The museums' guidelines and motivations, and the statistics on the award winners reveal attitudes toward the art. The institutions' reactions in the face of controversy and their adjustments to the annuals' guidelines impart the compromises each made as they adapted to new trends that occurred in Native American painting over a fifteen year period. This thesis compares the approaches of three museums to their juried annuals and establishes the existence of a variety of attitudes on contemporary Native American painting from 1946-1960. Through this collection of institutional views, the competitions maintained a patronage base for traditional style painting while providing opportunities for experimentation, paving the way for the great variety and artistic progress of Native American painting today.
ContributorsPeters, Stephanie (Author) / Duncan, Kate (Thesis advisor) / Fahlman, Betsy (Thesis advisor) / Mesch, Claudia (Committee member) / Arizona State University (Publisher)
Created2012
Description
Hepatitis C virus (HCV) is a globally prevalent infection which is a main contributor to the global burden of liver disease. Due to its ability to establish a chronic infection, and the lack of usefulness of traditional neutralizing antibody vaccine design in producing a protective immune response, a preventative vaccine has been notoriously difficult to produce. To overcome this, a vaccine using non-structural protein 3 (NS3) as a target to elicit a T cell specific immune response is thought to be a possible strategy for eliciting a protective immune response against hepatitis C infection. In this paper, a recombinant strain of measles virus (MV) that expresses HCV NS3 protein was analyzed. The replication fitness of this recombinant virus also indicates that this construct replicates at a higher rate than parental measles strain. It is also demonstrated through western blot analysis of protein expression and immunofluorescence that this recombinant virus expresses both the inserted HCV NS3 protein, as well as native measles proteins.
ContributorsWoell, Dana Marie (Author) / Reyes del Valle, Jorge (Thesis director) / Nickerson, Cheryl (Committee member) / Julik, Emily (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Human Evolution and Social Change (Contributor)
Created2015-05
Description
Is it possible to treat the mouth as a natural environment, and determine new methods to keep the microbiome in check? The need for biodiversity in health may suggest that every species carries out a specific function that is required to maintain equilibrium and homeostasis within the oral cavity. Furthermore, the relationship between the microbiome and its host is mutually beneficial because the host is providing microbes with an environment in which they can flourish and, in turn, keep their host healthy. Reviewing examples of larger scale environmental shifts could provide a window by which scientists can make hypotheses. Certain medications and healthcare treatments have been proven to cause xerostomia. This disorder is characterized by a dry mouth, and known to be associated with a change in the composition, and reduction, of saliva. Two case studies performed by Bardow et al, and Leal et al, tested and studied the relationships of certain medications and confirmed their side effects on the salivary glands [2,3]. Their results confirmed a relationship between specific medicines, and the correlating complaints of xerostomia. In addition, Vissink et al conducted case studies that helped to further identify how radiotherapy causes hyposalivation of the salivary glands [4]. Specifically patients that have been diagnosed with oral cancer, and are treated by radiotherapy, have been diagnosed with xerostomia. As stated prior, studies have shown that patients having an ecologically balanced and diverse microbiome tend to have healthier mouths. The oral cavity is like any biome, consisting of commensalism within itself and mutualism with its host. Due to the decreased salivary output, caused by xerostomia, increased parasitic bacteria build up within the oral cavity thus causing dental disease. Every human body contains a personalized microbiome that is essential to maintaining health but capable of eliciting disease. The Human Oral Microbiomics Database (HOMD) is a set of reference 16S rRNA gene sequences. These are then used to define individual human oral taxa. By conducting metagenomic experiments at the molecular and cellular level, scientists can identify and label micro species that inhabit the mouth during parasitic outbreaks or a shifting of the microbiome. Because the HOMD is incomplete, so is our ability to cure, or prevent, oral disease. The purpose of the thesis is to research what is known about xerostomia and its effects on the complex microbiome of the oral cavity. It is important that researchers determine whether this particular perspective is worth considering. In addition, the goal is to create novel experiments for treatment and prevention of dental diseases.
ContributorsHalcomb, Michael Jordan (Author) / Chen, Qiang (Thesis director) / Steele, Kelly (Committee member) / Barrett, The Honors College (Contributor) / College of Letters and Sciences (Contributor)
Created2015-05
Description
Clean water for drinking, food preparation, and bathing is essential for astronaut health and safety during long duration habitation of the International Space Station (ISS), including future missions to Mars. Despite stringent water treatment and recycling efforts on the ISS, it is impossible to completely prevent microbial contamination of onboard water supplies. In this work, we used a spaceflight analogue culture system to better understand how the microgravity environment can influence the pathogenesis-related characteristics of Burkholderia cepacia complex (Bcc), an opportunistic pathogen previously recovered from the ISS water system. The results of the present study suggest that there may be important differences in how this pathogen can respond and adapt to spaceflight and other low fluid shear environments encountered during their natural life cycles. Future studies are aimed at understanding the underlying mechanisms responsible for these phenotypes.
ContributorsKang, Bianca Younseon (Author) / Nickerson, Cheryl (Thesis director) / Barrila, Jennifer (Committee member) / Ott, Mark (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05