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Description
The concept of vaccination dates back further than Edward Jenner's first vaccine using cowpox pustules to confer immunity against smallpox in 1796. Nevertheless, it was Jenner's success that gave vaccines their name and made vaccinia virus (VACV) of particular interest. More than 200 years later there is still the need to understand vaccination from vaccine design to prediction of vaccine efficacy using mathematical models. Post-exposure vaccination with VACV has been suggested to be effective if administered within four days of smallpox exposure although this has not been definitively studied in humans. The first and second chapters analyze post-exposure prophylaxis of VACV in an animal model using v50ΔB13RMγ, a recombinant VACV expressing murine interferon gamma (IFN-γ) also known as type II IFN. While untreated animals infected with wild type VACV die by 10 days post-infection (dpi), animals treated with v50ΔB13RMγ 1 dpi had decreased morbidity and 100% survival. Despite these differences, the viral load was similar in both groups suggesting that v50ΔB13RMγ acts as an immunoregulator rather than as an antiviral. One of the main characteristics of VACV is its resistance to type I IFN, an effect primarily mediated by the E3L protein, which has a Z-DNA binding domain and a double-stranded RNA (dsRNA) binding domain. In the third chapter a VACV that independently expresses both domains of E3L was engineered and compared to wild type in cells in culture. The dual expression virus was unable to replicate in the JC murine cell line where both domains are needed together for replication. Moreover, phosphorylation of the dsRNA dependent protein kinase (PKR) was observed at late times post-infection which indicates that both domains need to be linked together in order to block the IFN response. Because smallpox has already been eradicated, the utility of mathematical modeling as a tool for predicting disease spread and vaccine efficacy was explored in the last chapter using dengue as a disease model. Current modeling approaches were reviewed and the 2000-2001 dengue outbreak in a Peruvian region was analyzed. This last section highlights the importance of interdisciplinary collaboration and how it benefits research on infectious diseases.
ContributorsHolechek, Susan A (Author) / Jacobs, Bertram L (Thesis advisor) / Castillo-Chavez, Carlos (Committee member) / Frasch, Wayne (Committee member) / Hogue, Brenda (Committee member) / Stout, Valerie (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
This study contributes to the ongoing discussion of Mathematical Knowledge for Teaching (MKT). It investigates the case of Rico, a high school mathematics teacher who had become known to his colleagues and his students as a superbly effective mathematics teacher. His students not only developed excellent mathematical skills, they also developed deep understanding of the mathematics they learned. Moreover, Rico redesigned his curricula and instruction completely so that they provided a means of support for his students to learn mathematics the way he intended. The purpose of this study was to understand the sources of Rico's effectiveness. The data for this study was generated in three phases. Phase I included videos of Rico's lessons during one semester of an Algebra II course, post-lesson reflections, and Rico's self-constructed instructional materials. An analysis of Phase I data led to Phase II, which consisted of eight extensive stimulated-reflection interviews with Rico. Phase III consisted of a conceptual analysis of the prior phases with the aim of creating models of Rico's mathematical conceptions, his conceptions of his students' mathematical understandings, and his images of instruction and instructional design. Findings revealed that Rico had developed profound personal understandings, grounded in quantitative reasoning, of the mathematics that he taught, and profound pedagogical understandings that supported these very same ways of thinking in his students. Rico's redesign was driven by three factors: (1) the particular way in which Rico himself understood the mathematics he taught, (2) his reflective awareness of those ways of thinking, and (3) his ability to envision what students might learn from different instructional approaches. Rico always considered what someone might already need to understand in order to understand "this" in the way he was thinking of it, and how understanding "this" might help students understand related ideas or methods. Rico's continual reflection on the mathematics he knew so as to make it more coherent, and his continual orientation to imagining how these meanings might work for students' learning, made Rico's mathematics become a mathematics of students--impacting how he assessed his practice and engaging him in a continual process of developing MKT.
ContributorsLage Ramírez, Ana Elisa (Author) / Thompson, Patrick W. (Thesis advisor) / Carlson, Marilyn P. (Committee member) / Castillo-Chavez, Carlos (Committee member) / Saldanha, Luis (Committee member) / Middleton, James A. (Committee member) / Arizona State University (Publisher)
Created2011
Description
Olfaction is an important sensory modality for behavior since odors inform animals of the presence of food, potential mates, and predators. The fruit fly, Drosophila melanogaster, is a favorable model organism for the investigation of the biophysical mechanisms that contribute to olfaction because its olfactory system is anatomically similar to but simpler than that of vertebrates. In the Drosophila olfactory system, sensory transduction takes place in olfactory receptor neurons housed in the antennae and maxillary palps on the front of the head. The first stage of olfactory processing resides in the antennal lobe, where the structural unit is the glomerulus. There are at least three classes of neurons in the antennal lobe - excitatory projection neurons, excitatory local neurons, and inhibitory local neurons. The arborizations of the local neurons are confined to the antennal lobe, and output from the antennal lobe is carried by projection neurons to higher regions of the brain. Different views exist of how circuits of the Drosophila antennal lobe translate input from the olfactory receptor neurons into projection neuron output. We construct a conductance based neuronal network model of the Drosophila antennal lobe with the aim of understanding possible mechanisms within the antennal lobe that account for the variety of projection neuron activity observed in experimental data. We explore possible outputs obtained from olfactory receptor neuron input that mimic experimental recordings under different connectivity paradigms. First, we develop realistic minimal cell models for the excitatory local neurons, inhibitory local neurons, and projections neurons based on experimental data for Drosophila channel kinetics, and explore the firing characteristics and mathematical structure of these models. We then investigate possible interglomerular and intraglomerular connectivity patterns in the Drosophila antennal lobe, where olfactory receptor neuron input to the antennal lobe is modeled with Poisson spike trains, and synaptic connections within the antennal lobe are mediated by chemical synapses and gap junctions as described in the Drosophila antennal lobe literature. Our simulation results show that inhibitory local neurons spread inhibition among all glomeruli, where projection neuron responses are decreased relatively uniformly for connections of synaptic strengths that are homogeneous. Also, in the case of homogeneous excitatory synaptic connections, the excitatory local neuron network facilitates odor detection in the presence of weak stimuli. Excitatory local neurons can spread excitation from projection neurons that receive more input from olfactory receptor neurons to projection neurons that receive less input from olfactory receptor neurons. For the parameter values for the network models associated with these results, eLNs decrease the ability of the network to discriminate among single odors.
ContributorsLuli, Dori (Author) / Crook, Sharon (Thesis advisor) / Baer, Steven (Committee member) / Castillo-Chavez, Carlos (Committee member) / Smith, Brian (Committee member) / Arizona State University (Publisher)
Created2013
Description
Research shows that the subject of mathematics, although revered, remains a source of trepidation for many individuals, as they find it difficult to form a connection between the work they do on paper and their work's practical applications. This research study describes the impact of teaching a challenging introductive applied mathematics course on high school students' skills and attitudes towards mathematics in a college Summer Program. In the analysis of my research data, I identified several emerging changes in skills and attitudes towards mathematics, skills that high-school students needed or developed when taking the mathematical modeling course. Results indicated that the applied mathematics course had a positive impact on several students' attitudes, in general, such as, self-confidence, meanings of what mathematics is, and their perceptions of what solutions are. It also had a positive impact on several skills, such as translating real-life situations to mathematics via flow diagrams, translating the models' solutions back from mathematics to the real world, and interpreting graphs. Students showed positive results when the context of their problems was applied or graphical, and fewer improvement on problems that were not. Research also indicated some negatives outcomes, a decrease in confidence for certain students, and persistent negative ways of thinking about graphs. Based on these findings, I make recommendations for teaching similar mathematical modeling at the pre-university level, to encourage the development of young students through educational, research and similar mentorship activities, to increase their inspiration and interest in mathematics, and possibly consider a variety of sciences, technology, engineering and mathematics-related (STEM) fields and careers.
Contributorsagoune, linda (Author) / Castillo-Chavez, Carlos (Thesis advisor) / Castillo-Garsow, Carlos W (Thesis advisor) / Mubayi, Anuj (Committee member) / Arizona State University (Publisher)
Created2020
Description
The Mathematical and Theoretical Biology Institute (MTBI) is a summer research program for undergraduate students, largely from underrepresented minority groups. Founded in 1996, it serves as a 'life-long' mentorship program, providing continuous support for its students and alumni. This study investigates how MTBI supports student development in applied mathematical research. This includes identifying of motivational factors to pursue and develop capacity to complete higher education.
The theoretical lens of developmental psychologists Lev Vygotsky (1978, 1987) and Lois Holzman (2010) that sees learning and development as a social process is used. From this view student development in MTBI is attributed to the collaborative and creative way students co-create the process of becoming scientists. This results in building a continuing network of academic and professional relationships among peers and mentors, in which around three quarters of MTBI PhD graduates come from underrepresented groups.
The extent to which MTBI creates a Vygotskian learning environment is explored from the perspectives of participants who earned doctoral degrees. Previously hypothesized factors (Castillo-Garsow, Castillo-Chavez and Woodley, 2013) that affect participants’ educational and professional development are expanded on.
Factors identified by participants are a passion for the mathematical sciences; desire to grow; enriching collaborative and peer-like interactions; and discovering career options. The self-recognition that they had the ability to be successful, key element of the Vygotskian-Holzman theoretical framework, was a commonly identified theme for their educational development and professional growth.
Participants characterize the collaborative and creative aspects of MTBI. They reported that collaborative dynamics with peers were strengthened as they co-created a learning environment that facilitated and accelerated their understanding of the mathematics needed to address their research. The dynamics of collaboration allowed them to complete complex homework assignments, and helped them formulate and complete their projects. Participants identified the creative environments of their research projects as where creativity emerged in the dynamics of the program.
These data-driven findings characterize for the first time a summer program in the mathematical sciences as a Vygotskian-Holzman environment, that is, a `place’ where participants are seen as capable applied mathematicians, where the dynamics of collaboration and creativity are fundamental components.
The theoretical lens of developmental psychologists Lev Vygotsky (1978, 1987) and Lois Holzman (2010) that sees learning and development as a social process is used. From this view student development in MTBI is attributed to the collaborative and creative way students co-create the process of becoming scientists. This results in building a continuing network of academic and professional relationships among peers and mentors, in which around three quarters of MTBI PhD graduates come from underrepresented groups.
The extent to which MTBI creates a Vygotskian learning environment is explored from the perspectives of participants who earned doctoral degrees. Previously hypothesized factors (Castillo-Garsow, Castillo-Chavez and Woodley, 2013) that affect participants’ educational and professional development are expanded on.
Factors identified by participants are a passion for the mathematical sciences; desire to grow; enriching collaborative and peer-like interactions; and discovering career options. The self-recognition that they had the ability to be successful, key element of the Vygotskian-Holzman theoretical framework, was a commonly identified theme for their educational development and professional growth.
Participants characterize the collaborative and creative aspects of MTBI. They reported that collaborative dynamics with peers were strengthened as they co-created a learning environment that facilitated and accelerated their understanding of the mathematics needed to address their research. The dynamics of collaboration allowed them to complete complex homework assignments, and helped them formulate and complete their projects. Participants identified the creative environments of their research projects as where creativity emerged in the dynamics of the program.
These data-driven findings characterize for the first time a summer program in the mathematical sciences as a Vygotskian-Holzman environment, that is, a `place’ where participants are seen as capable applied mathematicians, where the dynamics of collaboration and creativity are fundamental components.
ContributorsEvangelista, Arlene Morales (Author) / Castillo-Chavez, Carlos (Thesis advisor) / Holmes, Raquell M. (Committee member) / Mubayi, Anuj (Committee member) / Arizona State University (Publisher)
Created2015