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Description
Dengue virus infects millions of people every year. Yet there is still no vaccine available to prevent it. Here we use a neutralizing epitope determinant on the dengue envelope (E) protein as an immunogen to be vectored by a measles virus (MV) vaccine. However the domain III (DIII) of the

Dengue virus infects millions of people every year. Yet there is still no vaccine available to prevent it. Here we use a neutralizing epitope determinant on the dengue envelope (E) protein as an immunogen to be vectored by a measles virus (MV) vaccine. However the domain III (DIII) of the dengue 2 E protein is too small to be immunogenic by itself. In order for it to be displayed on a larger particle, it was inserted into the amino terminus of small hepatitis B surface antigen (HBsAg, S) coding sequence. To generate the recombinant MV vector and verify the efficiency of this concept, a reverse genetics system was used where the MV vectors express one or two additional transcription units to direct the assembly of hybrid HBsAg particles. Two types of recombinant measles virus were produced: pB(+)MVvac2(DIII-S,S)P and pB(+)MVvac2(DIII-S)N. Virus recovered from pB(+)MVvac2(DIII-S,S)P was viable. An ELISA assay was performed to demonstrate the expression and secretion of HBsAg. Supernatant from MVvac2(DIII-S,S)P infected cells confirmed that hybrid HBsAg-domain III particles with a density similar to traditional HBsAg particles were released. Characteristics of the subviral particle have been analyzed for the successful incorporation of domain III. The replication fitness of the recombinant MV was evaluated using multi-step growth kinetics and showed reduced replication fitness when compared to the parental strain MVvac2. This demonstrates that viral replication is hindered by the addition of the two inserts into MV genome. Further analysis of MVvac2(DIII-S)N is needed to justify immune response studies in a small animal model using both of the generated recombinant vectors.
ContributorsHarahap, Indira Saridewi (Author) / Reyes del Valle, Jorge (Thesis director) / Hogue, Brenda (Committee member) / Misra, Rajeev (Committee member) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor)
Created2014-05
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Description
The HIV-1 pandemic continues to cause millions of new infections and AIDS-related deaths each year, and a majority of these occur in regions of the world with limited access to antiretroviral therapy. Therefore, an HIV-1 vaccine is still desperately needed. The most successful HIV-1 clinical trial to date used a

The HIV-1 pandemic continues to cause millions of new infections and AIDS-related deaths each year, and a majority of these occur in regions of the world with limited access to antiretroviral therapy. Therefore, an HIV-1 vaccine is still desperately needed. The most successful HIV-1 clinical trial to date used a non-replicating canarypox viral vector and protein boosting, yet its modest efficacy left room for improvement. Efforts to derive novel vectors which can be both safe and immunogenic, have spawned a new era of live, viral vectors. One such vaccinia virus vector, NYVAC-KC, was specifically designed to replicate in humans and had several immune modulators deleted to improve immunogenicity and reduce pathogenicity. Two NYVAC-KC vectors were generated: one expressing the Gag capsid, and one with deconstructed-gp41 (dgp41), which contains an important neutralizing antibody target, the membrane proximal external region (MPER). These vectors were combined with HIV-1 Gag/dgp41 virus-like particles (VLPs) produced in the tobacco-relative Nicotiana benthamiana. Different plant expression vectors were compared in an effort to improve yield. A Geminivirus-based vector was shown to increase the amount of MPER present in VLPs, thus potentially enhancing immunogenicity. Furthermore, these VLPs were shown to interact with the innate immune system through Toll-like receptor (TLR) signaling, which activated antigen presenting cells to induce a Th2-biased response in a TLR-dependent manner. Furthermore, expression of Gag and dgp41 in NYVAC-KC vectors resulted in activation of antiviral signaling pathways reliant on TBK1/IRF3, which necessitated the use of higher doses in mice to match the immunogenicity of wild-type viral vectors. VLPs and NYVAC-KC vectors were tested in mice, ultimately showing that the best antibody and Gag-specific T cell responses were generated when both components were administered simultaneously. Thus, plant-produced VLPs and poxvirus vectors represent a highly immunogenic HIV-1 vaccine candidate that warrants further study.
ContributorsMeador, Lydia Rebecca (Author) / Mor, Tsafrir S (Thesis advisor) / Jacobs, Bertram L (Thesis advisor) / Blattman, Joseph N (Committee member) / Mason, Hugh S (Committee member) / Arizona State University (Publisher)
Created2016
Description

Most asteroids originated in larger parent bodies that underwent accretion and heating during the first few million years of the solar system. We investigated the parent body of S-type asteroid 25143 Itokawa by developing a computational model which can approximate the thermal evolution of an early solar system body. We

Most asteroids originated in larger parent bodies that underwent accretion and heating during the first few million years of the solar system. We investigated the parent body of S-type asteroid 25143 Itokawa by developing a computational model which can approximate the thermal evolution of an early solar system body. We compared known constraints on Itokawa’s thermal history to simulations of its parent body and constrained its time of formation to between 1.6 and 2.5 million years after the beginning of the solar system, though certain details could allow for even earlier or later formation. These results stress the importance of precise data required of the material properties of asteroids and meteorites to place better constraints on the histories of their parent bodies. Additional mathematical and computational details are discussed, and the full code and data is made available online.

ContributorsHallstrom, Jonas (Author) / Bose, Maitrayee (Thesis director) / Beckstein, Oliver (Committee member) / Barrett, The Honors College (Contributor) / Department of Physics (Contributor) / Materials Science and Engineering Program (Contributor)
Created2023-05
Description

This creative project develops an environment in which three species inhabit a shared land and models the movement of the creatures to determine the survival rates over time in specific conditions. The three species modelled include a predator and a prey species with movement capabilities as well as a stagnant

This creative project develops an environment in which three species inhabit a shared land and models the movement of the creatures to determine the survival rates over time in specific conditions. The three species modelled include a predator and a prey species with movement capabilities as well as a stagnant fruit species. There are a variety of configurable variables that can be used to modify and control the simulation to observe how the resulting population charts change. The big difference between this project and a normal approach to simulating a predation relationship is that actual creatures themselves are being created and their movement is simulated in this virtual environment which then leads to population counts, rather than integrating differential equations relating the population sizes of both species and purely tracking the populations but not the creatures themselves. Because of this difference, my simulation is not meant to handle all the complexities of life that come in the real-world but instead is intended as a simplified approach to simulating creatures' lives with the purpose of conveying the idea of a real predation relationship. Thus, the main objective of my simulation is to produce data representative of real-world predator-prey relationships, with the overall cyclical pattern that is observed in natural achieved through simulating creature movement and life itself rather than estimating population size change.

ContributorsPerry, Jordan (Author) / Burger, Kevin (Thesis director) / Miller, Phillip (Committee member) / Barrett, The Honors College (Contributor) / Department of Physics (Contributor) / Computer Science and Engineering Program (Contributor)
Created2023-05
Description

We implemented the well-known Ising model in one dimension as a computer program and simulated its behavior with four algorithms: (i) the seminal Metropolis algorithm; (ii) the microcanonical algorithm described by Creutz in 1983; (iii) a variation on Creutz’s time-reversible algorithm allowing for bonds between spins to change dynamically; and

We implemented the well-known Ising model in one dimension as a computer program and simulated its behavior with four algorithms: (i) the seminal Metropolis algorithm; (ii) the microcanonical algorithm described by Creutz in 1983; (iii) a variation on Creutz’s time-reversible algorithm allowing for bonds between spins to change dynamically; and (iv) a combination of the latter two algorithms in a manner reflecting the different timescales on which these two processes occur (“freezing” the bonds in place for part of the simulation). All variations on Creutz’s algorithm were symmetrical in time, and thus reversible. The first three algorithms all favored low-energy states of the spin lattice and generated the Boltzmann energy distribution after reaching thermal equilibrium, as expected, while the last algorithm broke from the Boltzmann distribution while the bonds were “frozen.” The interpretation of this result as a net increase to the system’s total entropy is consistent with the second law of thermodynamics, which leads to the relationship between maximum entropy and the Boltzmann distribution.

ContributorsLewis, Aiden (Author) / Chamberlin, Ralph (Thesis director) / Beckstein, Oliver (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Department of Physics (Contributor)
Created2023-05
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Description
In this project, we created a code that was able to simulate the dynamics of a three site Hubbard model ring connected to an infinite dissipative bath and driven by an electric field. We utilized the master equation approach, which will one day be able to be implemented efficiently on

In this project, we created a code that was able to simulate the dynamics of a three site Hubbard model ring connected to an infinite dissipative bath and driven by an electric field. We utilized the master equation approach, which will one day be able to be implemented efficiently on a quantum computer. For now we used classical computing to model one of the simplest nontrivial driven dissipative systems. This will serve as a verification of the master equation method and a baseline to test against when we are able to implement it on a quantum computer. For this report, we will mainly focus on classifying the DC component of the current around our ring. We notice several expected characteristics of this DC current including an inverse square tail at large values of the electric field and a linear response region at small values of the electric field.
ContributorsJohnson, Michael (Author) / Chamberlin, Ralph (Thesis director) / Ritchie, Barry (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / Department of Physics (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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Description

The goal of this project was to develop a prototype for an educational tool that will help users understand how the voting system deployed by a government can affect the outcomes of elections. This tool was developed in Java SE, consisting of a model for the simulation of elections capable

The goal of this project was to develop a prototype for an educational tool that will help users understand how the voting system deployed by a government can affect the outcomes of elections. This tool was developed in Java SE, consisting of a model for the simulation of elections capable of supporting various voting systems, along with a variety of fairness measures, and educational and explanatory material. While a completed version of this tool would ideally be fully self-contained, easily accessible in-browser, and provide detailed visualizations of the simulated elections, the current prototype version consists of a GitHub repository containing the code, with the educational material and explanations contained within the thesis paper. Ultimately, the goal of this project was to be a stepping stone on the path to create a tool that will instill a measure of systemic skepticism in the user; to give them cause to question why our systems are built the way they are, and reasons to believe that they could be changed for the better. In undertaking this project, I hope to help in providing people with the political education needed to make informed decisions about how they want the government to function. The GitHub repository containing all the code can be found at, https://github.com/SpencerDiamond/Votes_that_Count

ContributorsDiamond, Spencer (Author) / Sarjoughian, Hessam (Thesis director) / Hines, Taylor (Committee member) / Barrett, The Honors College (Contributor) / Department of Physics (Contributor) / Department of English (Contributor) / School of Mathematical and Statistical Sciences (Contributor)
Created2022-05
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Description

Plant-made virus-like particles (VLPs), composed of HIV-1 Gag and deconstructed gp41 proteins, have been shown to be safe and immunogenic in mice. Here, we report the successful production of HIV-1 Gag/dgp41 VLPs in Nicotiana benthamiana, using an enhanced geminivirus-based expression vector. This novel vector results in unique expression kinetics, with

Plant-made virus-like particles (VLPs), composed of HIV-1 Gag and deconstructed gp41 proteins, have been shown to be safe and immunogenic in mice. Here, we report the successful production of HIV-1 Gag/dgp41 VLPs in Nicotiana benthamiana, using an enhanced geminivirus-based expression vector. This novel vector results in unique expression kinetics, with peak protein accumulation and minimal necrosis achieved on day 4 post-infiltration. In comparing various purification strategies, it was determined that a 20% ammonium sulfate precipitation is an effective and efficient method for removing plant proteins and purifying the recombinant VLPs of interest. If further purification is required, this may be achieved through ultracentrifugation. VLPs are a useful platform for a variety of biomedical applications and developing the technology to efficiently produce VLPs in the plant expression system is of critical importance.

ContributorsFleming, Claire (Author) / Mor, Tsafrir (Thesis director) / Mason, Hugh (Committee member) / Kamzina, Aigerim (Committee member) / Barrett, The Honors College (Contributor) / Department of Physics (Contributor) / School of Life Sciences (Contributor)
Created2022-05