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Infectious diseases are a leading cause of death worldwide. With the development of drugs, vaccines and antibiotics, it was believed that for the first time in human history diseases would no longer be a major cause of mortality. Newly emerging diseases, re-emerging diseases and the emergence of microorganisms resistant to

Infectious diseases are a leading cause of death worldwide. With the development of drugs, vaccines and antibiotics, it was believed that for the first time in human history diseases would no longer be a major cause of mortality. Newly emerging diseases, re-emerging diseases and the emergence of microorganisms resistant to existing treatment have forced us to re-evaluate our optimistic perspective. In this study, a simple mathematical framework for super-infection is considered in order to explore the transmission dynamics of drug-resistance. Through its theoretical analysis, we identify the conditions necessary for the coexistence between sensitive strains and drug-resistant strains. Farther, in order to investigate the effectiveness of control measures, the model is extended so as to include vaccination and treatment. The impact that these preventive and control measures may have on its disease dynamics is evaluated. Theoretical results being confirmed via numerical simulations. Our theoretical results on two-strain drug-resistance models are applied in the context of Malaria, antimalarial drugs, and the administration of a possible partially effective vaccine. The objective is to develop a monitoring epidemiological framework that help evaluate the impact of antimalarial drugs and partially-effective vaccine in reducing the disease burden at the population level. Optimal control theory is applied in the context of this framework in order to assess the impact of time dependent cost-effective treatment efforts. It is shown that cost-effective combinations of treatment efforts depend on the population size, cost of implementing treatment controls, and the parameters of the model. We use these results to identify optimal control strategies for several scenarios.
ContributorsUrdapilleta, Alicia (Author) / Castillo-Chavez, Carlos (Thesis advisor) / Wang, Xiaohong (Thesis advisor) / Wirkus, Stephen (Committee member) / Camacho, Erika (Committee member) / Arizona State University (Publisher)
Created2011
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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

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
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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

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
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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

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
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Description

The Electoral College, the current electoral system in the U.S., operates on a Winner-Take-All or First Past the Post (FPTP) principle, where the candidate with the most votes wins. Despite the Electoral College being the current system, it is problematic. According to Lani Guinier in Tyranny of the Majority, “the

The Electoral College, the current electoral system in the U.S., operates on a Winner-Take-All or First Past the Post (FPTP) principle, where the candidate with the most votes wins. Despite the Electoral College being the current system, it is problematic. According to Lani Guinier in Tyranny of the Majority, “the winner-take-all principle invariably wastes some votes” (121). This means that the majority group gets all of the power in an election while the votes of the minority groups are completely wasted and hold little to no significance. Additionally, FPTP systems reinforce a two-party system in which neither candidate could satisfy the majority of the electorate’s needs and issues, yet forces them to choose between the two dominant parties. Moreover, voting for a third party candidate only hurts the voter since it takes votes away from the party they might otherwise support and gives the victory to the party they prefer the least, ensuring that the two party system is inescapable. Therefore, a winner-take-all system does not provide the electorate with fair or proportional representation and creates voter disenfranchisement: it offers them very few choices that appeal to their needs and forces them to choose a candidate they dislike. There are, however, alternative voting systems that remedy these issues, such as a Ranked voting system, in which voters can rank their candidate choices in the order they prefer them, or a Proportional voting system, in which a political party acquires a number of seats based on the proportion of votes they receive from the voter base. Given these alternatives, we will implement a software simulation of one of these systems to demonstrate how they work in contrast to FPTP systems, and therefore provide evidence of how these alternative systems could work in practice and in place of the current electoral system.

ContributorsSummers, Jack Gillespie (Co-author) / Martin, Autumn (Co-author) / Burger, Kevin (Thesis director) / Voorhees, Matthew (Committee member) / Computer Science and Engineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

System and software verification is a vital component in the development and reliability of cyber-physical systems - especially in critical domains where the margin of error is minimal. In the case of autonomous driving systems (ADS), the vision perception subsystem is a necessity to ensure correct maneuvering of the environment

System and software verification is a vital component in the development and reliability of cyber-physical systems - especially in critical domains where the margin of error is minimal. In the case of autonomous driving systems (ADS), the vision perception subsystem is a necessity to ensure correct maneuvering of the environment and identification of objects. The challenge posed in perception systems involves verifying the accuracy and rigidity of detections. The use of Spatio-Temporal Perception Logic (STPL) enables the user to express requirements for the perception system to verify, validate, and ensure its behavior; however, a drawback to STPL involves its accessibility. It is limited to individuals with an expert or higher-level knowledge of temporal and spatial logics, and the formal-written requirements become quite verbose with more restrictions imposed. In this thesis, I propose a domain-specific language (DSL) catered to Spatio-Temporal Perception Logic to enable non-expert users the ability to capture requirements for perception subsystems while reducing the necessity to have an experienced background in said logic. The domain-specific language for the Spatio-Temporal Perception Logic is built upon the formal language with two abstractions. The main abstraction captures simple programming statements that are translated to a lower-level STPL expression accepted by the testing monitor. The STPL DSL provides a seamless interface to writing formal expressions while maintaining the power and expressiveness of STPL. These translated equivalent expressions are capable of directing a standard for perception systems to ensure the safety and reduce the risks involved in ill-formed detections.

ContributorsAnderson, Jacob (Author) / Fainekos, Georgios (Thesis director) / Yezhou, Yang (Committee member) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description

The market for searching for food online is exploding. According to one expert at Google, “there are over 1 billion restaurant searches on Google every month” (Kelso, 2020). To capture this market and ride the general digital trend of internet personalization (as evidenced by Google search results, ads, YouTube and

The market for searching for food online is exploding. According to one expert at Google, “there are over 1 billion restaurant searches on Google every month” (Kelso, 2020). To capture this market and ride the general digital trend of internet personalization (as evidenced by Google search results, ads, YouTube and social media algorithms, etc), we created Munch to be an algorithm meant to help people find food they’ll love. <br/><br/>Munch offers the ability to search for food by restaurant or even as specific as a menu item (ex: search for the best Pad Thai). The best part? It is customized to your preferences based on a quiz you take when you open the app and from that point continuously learns from your behavior.<br/><br/>This thesis documents the journey of the team who founded Munch, what progress we made and the reasoning behind our decisions, where this idea fits in a competitive marketplace, how much it could be worth, branding, and our recommendations for a successful app in the future.

ContributorsInocencio, Phillippe Adriane (Co-author) / Rajan, Megha (Co-author) / Krug, Hayden (Co-author) / Byrne, Jared (Thesis director) / Sebold, Brent (Committee member) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

CubeSats can encounter a myriad of difficulties in space like cosmic rays, temperature<br/>issues, and loss of control. By creating better, more reliable software, these problems can be<br/>mitigated and increase the chance of success for the mission. This research sets out to answer the<br/>question: how do we create reliable flight software

CubeSats can encounter a myriad of difficulties in space like cosmic rays, temperature<br/>issues, and loss of control. By creating better, more reliable software, these problems can be<br/>mitigated and increase the chance of success for the mission. This research sets out to answer the<br/>question: how do we create reliable flight software for CubeSats? by providing a concentrated<br/>list of the best flight software development practices. The CubeSat used in this research is the<br/>Deployable Optical Receiver Aperture (DORA) CubeSat, which is a 3U CubeSat that seeks to<br/>demonstrate optical communication data rates of 1 Gbps over long distances. We present an<br/>analysis over many of the flight software development practices currently in use in the industry,<br/>from industry leads NASA, and identify three key flight software development areas of focus:<br/>memory, concurrency, and error handling. Within each of these areas, the best practices were<br/>defined for how to approach the area. These practices were also developed using experience<br/>from the creation of flight software for the DORA CubeSat in order to drive the design and<br/>testing of the system. We analyze DORA’s effectiveness in the three areas of focus, as well as<br/>discuss how following the best practices identified helped to create a more reliable flight<br/>software system for the DORA CubeSat.

ContributorsHoffmann, Zachary Christian (Author) / Chavez-Echeagaray, Maria Elena (Thesis director) / Jacobs, Daniel (Committee member) / Computer Science and Engineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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"No civil discourse, no cooperation; misinformation, mistruth." These were the words of former Facebook Vice President Chamath Palihapitiya who publicly expressed his regret in a 2017 interview over his role in co-creating Facebook. Palihapitiya shared that social media is ripping apart the social fabric of society and he also sounded

"No civil discourse, no cooperation; misinformation, mistruth." These were the words of former Facebook Vice President Chamath Palihapitiya who publicly expressed his regret in a 2017 interview over his role in co-creating Facebook. Palihapitiya shared that social media is ripping apart the social fabric of society and he also sounded the alarm regarding social media’s unavoidable global impact. He is only one of social media’s countless critics. The more disturbing issue resides in the empirical evidence supporting such notions. At least 95% of adolescents own a smartphone and spend an average time of two to four hours a day on social media. Moreover, 91% of 16-24-year-olds use social media, yet youth rate Instagram, Facebook, and Twitter as the worst social media platforms. However, the social, clinical, and neurodevelopment ramifications of using social media regularly are only beginning to emerge in research. Early research findings show that social media platforms trigger anxiety, depression, low self-esteem, and other negative mental health effects. These negative mental health symptoms are commonly reported by individuals from of 18-25-years old, a unique period of human development known as emerging adulthood. Although emerging adulthood is characterized by identity exploration, unbounded optimism, and freedom from most responsibilities, it also serves as a high-risk period for the onset of most psychological disorders. Despite social media’s adverse impacts, it retains its utility as it facilitates identity exploration and virtual socialization for emerging adults. Investigating the “user-centered” design and neuroscience underlying social media platforms can help reveal, and potentially mitigate, the onset of negative mental health consequences among emerging adults. Effectively deconstructing the Facebook, Twitter, and Instagram (i.e., hereafter referred to as “The Big Three”) will require an extensive analysis into common features across platforms. A few examples of these design features include: like and reaction counters, perpetual news feeds, and omnipresent banners and notifications surrounding the user’s viewport. Such social media features are inherently designed to stimulate specific neurotransmitters and hormones such as dopamine, serotonin, and cortisol. Identifying such predacious social media features that unknowingly manipulate and highjack emerging adults’ brain chemistry will serve as a first step in mitigating the negative mental health effects of today’s social media platforms. A second concrete step will involve altering or eliminating said features by creating a social media platform that supports and even enhances mental well-being.

ContributorsGupta, Anay (Author) / Flores, Valerie (Thesis director) / Carrasquilla, Christina (Committee member) / Barnett, Jessica (Committee member) / The Sidney Poitier New American Film School (Contributor) / Computer Science and Engineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

Over the years, advances in research have continued to decrease the size of computers from the size of<br/>a room to a small device that could fit in one’s palm. However, if an application does not require extensive<br/>computation power nor accessories such as a screen, the corresponding machine could be microscopic,<br/>only

Over the years, advances in research have continued to decrease the size of computers from the size of<br/>a room to a small device that could fit in one’s palm. However, if an application does not require extensive<br/>computation power nor accessories such as a screen, the corresponding machine could be microscopic,<br/>only a few nanometers big. Researchers at MIT have successfully created Syncells, which are micro-<br/>scale robots with limited computation power and memory that can communicate locally to achieve<br/>complex collective tasks. In order to control these Syncells for a desired outcome, they must each run a<br/>simple distributed algorithm. As they are only capable of local communication, Syncells cannot receive<br/>commands from a control center, so their algorithms cannot be centralized. In this work, we created a<br/>distributed algorithm that each Syncell can execute so that the system of Syncells is able to find and<br/>converge to a specific target within the environment. The most direct applications of this problem are in<br/>medicine. Such a system could be used as a safer alternative to invasive surgery or could be used to treat<br/>internal bleeding or tumors. We tested and analyzed our algorithm through simulation and visualization<br/>in Python. Overall, our algorithm successfully caused the system of particles to converge on a specific<br/>target present within the environment.

ContributorsMartin, Rebecca Clare (Author) / Richa, Andréa (Thesis director) / Lee, Heewook (Committee member) / Computer Science and Engineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05