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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
Diseases have been part of human life for generations and evolve within the population, sometimes dying out while other times becoming endemic or the cause of recurrent outbreaks. The long term influence of a disease stems from different dynamics within or between pathogen-host, that have been analyzed and studied by many researchers using mathematical models. Co-infection with different pathogens is common, yet little is known about how infection with one pathogen affects the host's immunological response to another. Moreover, no work has been found in the literature that considers the variability of the host immune health or that examines a disease at the population level and its corresponding interconnectedness with the host immune system. Knowing that the spread of the disease in the population starts at the individual level, this thesis explores how variability in immune system response within an endemic environment affects an individual's vulnerability, and how prone it is to co-infections. Immunology-based models of Malaria and Tuberculosis (TB) are constructed by extending and modifying existing mathematical models in the literature. The two are then combined to give a single nine-variable model of co-infection with Malaria and TB. Because these models are difficult to gain any insight analytically due to the large number of parameters, a phenomenological model of co-infection is proposed with subsystems corresponding to the individual immunology-based model of a single infection. Within this phenomenological model, the variability of the host immune health is also incorporated through three different pathogen response curves using nonlinear bounded Michaelis-Menten functions that describe the level or state of immune system (healthy, moderate and severely compromised). The immunology-based models of Malaria and TB give numerical results that agree with the biological observations. The Malaria--TB co-infection model gives reasonable results and these suggest that the order in which the two diseases are introduced have an impact on the behavior of both. The subsystems of the phenomenological models that correspond to a single infection (either of Malaria or TB) mimic much of the observed behavior of the immunology-based counterpart and can demonstrate different behavior depending on the chosen pathogen response curve. In addition, varying some of the parameters and initial conditions in the phenomenological model yields a range of topologically different mathematical behaviors, which suggests that this behavior may be able to be observed in the immunology-based models as well. The phenomenological models clearly replicate the qualitative behavior of primary and secondary infection as well as co-infection. The mathematical solutions of the models correspond to the fundamental states described by immunologists: virgin state, immune state and tolerance state. The phenomenological model of co-infection also demonstrates a range of parameter values and initial conditions in which the introduction of a second disease causes both diseases to grow without bound even though those same parameters and initial conditions did not yield unbounded growth in the corresponding subsystems. This results applies to all three states of the host immune system. In terms of the immunology-based system, this would suggest the following: there may be parameter values and initial conditions in which a person can clear Malaria or TB (separately) from their system but in which the presence of both can result in the person dying of one of the diseases. Finally, this thesis studies links between epidemiology (population level) and immunology in an effort to assess the impact of pathogen's spread within the population on the immune response of individuals. Models of Malaria and TB are proposed that incorporate the immune system of the host into a mathematical model of an epidemic at the population level.
ContributorsSoho, Edmé L (Author) / Wirkus, Stephen (Thesis advisor) / Castillo-Chavez, Carlos (Thesis advisor) / Chowell-Puente, Gerardo (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
Solution methods for certain linear and nonlinear evolution equations are presented in this dissertation. Emphasis is placed mainly on the analytical treatment of nonautonomous differential equations, which are challenging to solve despite the existent numerical and symbolic computational software programs available. Ideas from the transformation theory are adopted allowing one to solve the problems under consideration from a non-traditional perspective. First, the Cauchy initial value problem is considered for a class of nonautonomous and inhomogeneous linear diffusion-type equation on the entire real line. Explicit transformations are used to reduce the equations under study to their corresponding standard forms emphasizing on natural relations with certain Riccati(and/or Ermakov)-type systems. These relations give solvability results for the Cauchy problem of the parabolic equation considered. The superposition principle allows to solve formally this problem from an unconventional point of view. An eigenfunction expansion approach is also considered for this general evolution equation. Examples considered to corroborate the efficacy of the proposed solution methods include the Fokker-Planck equation, the Black-Scholes model and the one-factor Gaussian Hull-White model. The results obtained in the first part are used to solve the Cauchy initial value problem for certain inhomogeneous Burgers-type equation. The connection between linear (the Diffusion-type) and nonlinear (Burgers-type) parabolic equations is stress in order to establish a strong commutative relation. Traveling wave solutions of a nonautonomous Burgers equation are also investigated. Finally, it is constructed explicitly the minimum-uncertainty squeezed states for quantum harmonic oscillators. They are derived by the action of corresponding maximal kinematical invariance group on the standard ground state solution. It is shown that the product of the variances attains the required minimum value only at the instances that one variance is a minimum and the other is a maximum, when the squeezing of one of the variances occurs. Such explicit construction is possible due to the relation between the diffusion-type equation studied in the first part and the time-dependent Schrodinger equation. A modication of the radiation field operators for squeezed photons in a perfect cavity is also suggested with the help of a nonstandard solution of Heisenberg's equation of motion.
ContributorsVega-Guzmán, José Manuel, 1982- (Author) / Sulov, Sergei K (Thesis advisor) / Castillo-Chavez, Carlos (Thesis advisor) / Platte, Rodrigo (Committee member) / Chowell-Puente, Gerardo (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
Mortality of 1918 influenza virus was high, partly due to bacteria coinfections. We characterize pandemic mortality in Arizona, which had high prevalence of tuberculosis. We applied regressions to over 35,000 data points to estimate the basic reproduction number and excess mortality. Age-specific mortality curves show elevated mortality for all age groups, especially the young, and senior sparing effects. The low value for reproduction number indicates that transmissibility was moderately low.
ContributorsJenner, Melinda Eva (Author) / Chowell-Puente, Gerardo (Thesis director) / Kostelich, Eric (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Background: While research has quantified the mortality burden of the 1957 H2N2 influenza pandemic in the United States, little is known about how the virus spread locally in Arizona, an area where the dry climate was promoted as reducing respiratory illness transmission yet tuberculosis prevalence was high.
Methods: Using archival death certificates from 1954 to 1961, this study quantified the age-specific seasonal patterns, excess-mortality rates, and transmissibility patterns of the 1957 pandemic in Maricopa County, Arizona. By applying cyclical Serfling linear regression models to weekly mortality rates, the excess-mortality rates due to respiratory and all-causes were estimated for each age group during the pandemic period. The reproduction number was quantified from weekly data using a simple growth rate method and generation intervals of 3 and 4 days. Local newspaper articles from The Arizona Republic were analyzed from 1957-1958.
Results: Excess-mortality rates varied between waves, age groups, and causes of death, but overall remained low. From October 1959-June 1960, the most severe wave of the pandemic, the absolute excess-mortality rate based on respiratory deaths per 10,000 population was 17.85 in the elderly (≥65 years). All other age groups had extremely low excess-mortality and the typical U-shaped age-pattern was absent. However, relative risk was greatest (3.61) among children and young adolescents (5-14 years) from October 1957-March 1958, based on incidence rates of respiratory deaths. Transmissibility was greatest during the same 1957-1958 period, when the mean reproduction number was 1.08-1.11, assuming 3 or 4 day generation intervals and exponential or fixed distributions.
Conclusions: Maricopa County largely avoided pandemic influenza from 1957-1961. Understanding this historical pandemic and the absence of high excess-mortality rates and transmissibility in Maricopa County may help public health officials prepare for and mitigate future outbreaks of influenza.
Methods: Using archival death certificates from 1954 to 1961, this study quantified the age-specific seasonal patterns, excess-mortality rates, and transmissibility patterns of the 1957 pandemic in Maricopa County, Arizona. By applying cyclical Serfling linear regression models to weekly mortality rates, the excess-mortality rates due to respiratory and all-causes were estimated for each age group during the pandemic period. The reproduction number was quantified from weekly data using a simple growth rate method and generation intervals of 3 and 4 days. Local newspaper articles from The Arizona Republic were analyzed from 1957-1958.
Results: Excess-mortality rates varied between waves, age groups, and causes of death, but overall remained low. From October 1959-June 1960, the most severe wave of the pandemic, the absolute excess-mortality rate based on respiratory deaths per 10,000 population was 17.85 in the elderly (≥65 years). All other age groups had extremely low excess-mortality and the typical U-shaped age-pattern was absent. However, relative risk was greatest (3.61) among children and young adolescents (5-14 years) from October 1957-March 1958, based on incidence rates of respiratory deaths. Transmissibility was greatest during the same 1957-1958 period, when the mean reproduction number was 1.08-1.11, assuming 3 or 4 day generation intervals and exponential or fixed distributions.
Conclusions: Maricopa County largely avoided pandemic influenza from 1957-1961. Understanding this historical pandemic and the absence of high excess-mortality rates and transmissibility in Maricopa County may help public health officials prepare for and mitigate future outbreaks of influenza.
ContributorsCobos, April J (Author) / Jehn, Megan (Thesis director) / Chowell-Puente, Gerardo (Committee member) / Barrett, The Honors College (Contributor) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (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