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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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Mutations in the DNA of somatic cells, resulting from inaccuracies in DNA<br/>replication or exposure to harsh conditions (ionizing radiation, carcinogens), may be<br/>loss-of-function mutations, and the compounding of these mutations can lead to cancer.<br/>Such mutations can come in the form of thymine dimers, N-𝛽 glycosyl bond hydrolysis,<br/>oxidation by hydrogen peroxide or

Mutations in the DNA of somatic cells, resulting from inaccuracies in DNA<br/>replication or exposure to harsh conditions (ionizing radiation, carcinogens), may be<br/>loss-of-function mutations, and the compounding of these mutations can lead to cancer.<br/>Such mutations can come in the form of thymine dimers, N-𝛽 glycosyl bond hydrolysis,<br/>oxidation by hydrogen peroxide or other radicals, and deamination of cytosine to uracil.<br/>However, many cells possess the machinery to counteract the deleterious effects of<br/>such mutations. While eukaryotic DNA repair enzymes decrease the incidence of<br/>mutations from 1 mistake per 10^7 nucleotides to 1 mistake per 10^9 nucleotides, these<br/>mutations, however sparse, are problematic. Of particular interest is a mutation in which<br/>uracil is incorporated into DNA, either by spontaneous deamination of cysteine or<br/>misincorporation. Such mutations occur about one in every 107 cytidine residues in 24<br/>hours. DNA uracil glycosylase (UDG) recognizes these mutations and cleaves the<br/>glycosidic bond, creating an abasic site. However, the rate of this form of DNA repair<br/>varies, depending on the nucleotides that surround the uracil. Most enzyme-DNA<br/>interactions depend on the sequence of DNA (which may change the duplex twist),<br/>even if they only bind to the sugar-phosphate backbone. In the mechanism of uracil<br/>excision, UDG flips the uracil out of the DNA double helix, and this step may be<br/>impaired by base pairs that neighbor the uracil. The deformability of certain regions of<br/>DNA may facilitate this step in the mechanism, causing these regions to be less<br/>mutable. In DNA, base stacking, a form of van der Waals forces between the aromatic<br/>nucleic bases, may make these uracil inclusions more difficult to excise. These regions,<br/>stabilized by base stacking interactions, may be less susceptible to repair by<br/>glycosylases such as UDG, and thus, more prone to mutation.

ContributorsUgaz, Bryan T (Author) / Levitus, Marcia (Thesis director) / Van Horn, Wade (Committee member) / Department of Physics (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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The COVID-19 pandemic has resulted in preventative measures and has led to extensive changes in lifestyle for the vast majority of the American population. As the pandemic progresses, a growing amount of evidence shows that minority groups, such as the Deaf community, are often disproportionately and uniquely affected. Deaf

The COVID-19 pandemic has resulted in preventative measures and has led to extensive changes in lifestyle for the vast majority of the American population. As the pandemic progresses, a growing amount of evidence shows that minority groups, such as the Deaf community, are often disproportionately and uniquely affected. Deaf people are directly affected in their ability to personally socialize and continue with daily routines. More specifically, this can constitute their ability to meet new people, connect with friends/family, and to perform in their work or learning environment. It also may result in further mental health changes and an increased reliance on technology. The impact of COVID-19 on the Deaf community in clinical settings must also be considered. This includes changes in policies for in-person interpreters and a rise in telehealth. Often, these effects can be representative of the pre-existing low health literacy, frequency of miscommunication, poor treatment, and the inconvenience felt by Deaf people when trying to access healthcare. Ultimately, these effects on the Deaf community must be taken into account when attempting to create a full picture of the societal shift caused by COVID-19.

ContributorsAsuncion, David Leonard Esquiera (Co-author) / Dubey, Shreya (Co-author) / Patterson, Lindsey (Thesis director) / Lee, Lindsay (Committee member) / Harrington Bioengineering Program (Contributor) / Department of Physics (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Stardust grains can provide useful information about the Solar System environment before the Sun was born. Stardust grains show distinct isotopic compositions that indicate their origins, like the atmospheres of red giant stars, asymptotic giant branch stars, and supernovae (e.g., Bose et al. 2010). It has been argued that some

Stardust grains can provide useful information about the Solar System environment before the Sun was born. Stardust grains show distinct isotopic compositions that indicate their origins, like the atmospheres of red giant stars, asymptotic giant branch stars, and supernovae (e.g., Bose et al. 2010). It has been argued that some stardust grains likely condensed in classical nova outbursts (e.g., Amari et al. 2001). These nova candidate grains contain 13C, 15N and 17O-rich nuclides which are produced by proton burning. However, these nuclides alone cannot constrain the stellar source of nova candidate grains. Nova ejecta is rich in 7Be that decays to 7Li (which has a half-life of ~53 days). I want to measure 6,7Li isotopes in nova candidate grains using the NanoSIMS 50L (nanoscale secondary ion mass spectrometry) to establish their nova origins without ambiguity. Several stardust grains that are nova candidate grains were identified in meteorite Acfer 094 on the basis of their oxygen isotopes. The identified silicate and oxide stardust grains are <500 nm in size and exist in the meteorite surrounded by meteoritic silicates. Therefore, 6,7Li isotopic measurements on these grains are hindered because of the large 300-500 nm oxygen ion beam in the NanoSIMS. I devised a methodology to isolate stardust grains by performing Focused Ion Beam milling with the FIB – Nova 200 NanoLab (FEI) instrument. We proved that the current FIB instrument cannot be used to prepare stardust grains smaller than 1 𝜇m due to lacking capabilities of the FIB. For future analyses, we could either use the same milling technique with the new and improved FIB – Helios 5 UX or use the recently constructed duoplasmatron on the NanoSIMS that can achieve a size of ~75 nm oxygen ion beam.

ContributorsDuncan, Ethan Jay (Author) / Bose, Miatrayee (Thesis director) / Starrfield, Sumner (Committee member) / Desch, Steve (Committee member) / School of Earth and Space Exploration (Contributor) / Department of Physics (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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This research endeavor explores the 1964 reasoning of Irish physicist John Bell and how it pertains to the provoking Einstein-Podolsky-Rosen Paradox. It is necessary to establish the machinations of formalisms ranging from conservation laws to quantum mechanical principles. The notion that locality is unable to be reconciled with the quantum

This research endeavor explores the 1964 reasoning of Irish physicist John Bell and how it pertains to the provoking Einstein-Podolsky-Rosen Paradox. It is necessary to establish the machinations of formalisms ranging from conservation laws to quantum mechanical principles. The notion that locality is unable to be reconciled with the quantum paradigm is upheld through analysis and the subsequent Aspect experiments in the years 1980-1982. No matter the complexity, any local hidden variable theory is incompatible with the formulation of standard quantum mechanics. A number of strikingly ambiguous and abstract concepts are addressed in this pursuit to deduce quantum's validity, including separability and reality. `Elements of reality' characteristic of unique spaces are defined using basis terminology and logic from EPR. The discussion draws directly from Bell's succinct 1964 Physics 1 paper as well as numerous other useful sources. The fundamental principle and insight gleaned is that quantum physics is indeed nonlocal; the door into its metaphysical and philosophical implications has long since been opened. Yet the nexus of information pertaining to Bell's inequality and EPR logic does nothing but assert the impeccable success of quantum physics' ability to describe nature.

ContributorsRapp, Sean R (Author) / Foy, Joseph (Thesis director) / Martin, Thomas (Committee member) / School of Earth and Space Exploration (Contributor) / Department of Physics (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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The use of enzyme-catalyst interfaces is underexplored in the field of biocatalysis, particularly in studies on enabling novel reactivity of enzymes. For this thesis, the HaloTag® protein tagging platform was proposed as a bioconjugation method for a pinacol coupling reaction using lipases, as a model for novel reactivities proceeding via

The use of enzyme-catalyst interfaces is underexplored in the field of biocatalysis, particularly in studies on enabling novel reactivity of enzymes. For this thesis, the HaloTag® protein tagging platform was proposed as a bioconjugation method for a pinacol coupling reaction using lipases, as a model for novel reactivities proceeding via ketyl radical intermediates and hydrogen-bonding-facilitated redox attenuation. After an initial lipase screening of 9 lipases, one lipase (Candida rugosa) was found to perform the pinacol coupling of p-anisaldehyde under standard conditions (fluorescein and 530nm light, 3% yield). Based on a retrosynthetic analysis for the photocatalyst-incorporated HaloTag® linker, the intermediates haloamine 1 and aldehyde 6 were synthesized. Further experiments are underway or planned to complete linker synthesis and conduct pinacol coupling experiments with a bioconjugated system. This project underscores the promising biocatalytic promiscuity of lipases for performing reactions proceeding through ketyl radical intermediates, as well as the underdeveloped potential of incorporating bioengineering principles like bioconjugation into biocatalysis to overcome kinetic barriers to electron transfer and optimize biocatalytic reactions.

ContributorsMcrae, Kenna Christine (Author) / Biegasiewicz, Kyle (Thesis director) / Ghirlanda, Giovanna (Committee member) / Moore, Ana (Committee member) / Department of Physics (Contributor) / School of Human Evolution & Social Change (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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The colossal global counterfeit market and advances in cryptography including quantum computing supremacy have led the drive for a class of anti-counterfeit tags that are physically unclonable. Dendrites, previously considered an undesirable side effect of battery operation, have promise as an extremely versatile version of such tags, with their fundamental

The colossal global counterfeit market and advances in cryptography including quantum computing supremacy have led the drive for a class of anti-counterfeit tags that are physically unclonable. Dendrites, previously considered an undesirable side effect of battery operation, have promise as an extremely versatile version of such tags, with their fundamental nature ensuring that no two dendrites are alike and that they can be read at multiple magnification scales. In this work, we first pursue a simulation for electrochemical dendrites that elucidates fundamental information about their growth mechanism. We then translate these results into physical dendrites and demonstrate methods of producing a hash from these dendrites that is damage-tolerant for real-world verification. Finally, we explore theoretical curiosities that arise from the fractal nature of dendrites. We find that uniquely ramified dendrites, which rely on lower ion mobility and conductive deposition, are particularly amenable to wavelet hashing, and demonstrate that these dendrites have strong commercial potential for securing supply chains at the highest level while maintaining a low price point.

ContributorsSneh, Tal (Author) / Kozicki, Michael (Thesis director) / Gonzalez-Velo, Yago (Committee member) / School of Molecular Sciences (Contributor) / Department of Physics (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Treatment log files for spot scanning proton therapy provide a record of delivery accuracy, but they also contain diagnostic information for machine performance. A collection of patient log files can identify machine performance trends over time. This facilitates the identification of machine issues before they cause downtime or degrade treatment

Treatment log files for spot scanning proton therapy provide a record of delivery accuracy, but they also contain diagnostic information for machine performance. A collection of patient log files can identify machine performance trends over time. This facilitates the identification of machine issues before they cause downtime or degrade treatment quality. At Mayo Clinic Arizona, all patient treatment logs are stored in a database. These log files contain information including the gantry, beam position, monitor units (MUs), and gantry angle. This data was analyzed to identify trends, which were then correlated with quality assurance measurements and maintenance records.

ContributorsGrayson, Madison Emily (Author) / Alarcon, Ricardo (Thesis director) / Robertson, Daniel (Committee member) / Department of Physics (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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HIV/AIDS is the sixth leading cause of death worldwide and the leading cause of death among women of reproductive age living in low-income countries. Clinicians in industrialized nations monitor the efficacy of antiretroviral drugs and HIV disease progression with the HIV-1 viral load assay, which measures the copy number of

HIV/AIDS is the sixth leading cause of death worldwide and the leading cause of death among women of reproductive age living in low-income countries. Clinicians in industrialized nations monitor the efficacy of antiretroviral drugs and HIV disease progression with the HIV-1 viral load assay, which measures the copy number of HIV-1 RNA in blood. However, viral load assays are not widely available in sub-Saharan Africa and cost between 50-$139 USD per test on average where available. To address this problem, a mixed-methods approach was undertaken to design a novel and inexpensive viral load diagnostic for HIV-1 and to evaluate barriers to its adoption in a developing country. The assay was produced based on loop-mediated isothermal amplification (LAMP). Blood samples from twenty-one individuals were spiked with varying concentrations of HIV-1 RNA to evaluate the sensitivity and specificity of LAMP. Under isothermal conditions, LAMP was performed with an initial reverse-transcription step (RT-LAMP) and primers designed for HIV-1 subtype C. Each reaction generated up to a few billion copies of target DNA within an hour. Presence of target was detected through naked-eye observation of a fluorescent indicator and verified by DNA gel electrophoresis and real-time fluorescence. The assay successfully detected the presence of HIV in samples with a broad range of HIV RNA concentration, from over 120,000 copies/reaction to 120 copies/reaction. In order to better understand barriers to adoption of LAMP in developing countries, a feasibility study was undertaken in Tanzania, a low-income country facing significant problems in healthcare. Medical professionals in Northern Tanzania were surveyed for feedback regarding perspectives of current HIV assays, patient treatment strategies, availability of treatment, treatment priorities, HIV transmission, and barriers to adoption of the HIV-1 LAMP assay. The majority of medical providers surveyed indicated that the proposed LAMP assay is too expensive for their patient populations. Significant gender differences were observed in response to some survey questions. Female medical providers were more likely to cite stigma as a source problem of the HIV epidemic than male medical providers while males were more likely to cite lack of education as a source problem than female medical providers.
ContributorsSalamone, Damien Thomas (Author) / Jacobs, Bertram L (Thesis advisor) / Marsiglia, Flavio (Committee member) / Stout, Valerie (Committee member) / Johnson, Crista (Committee member) / Arizona State University (Publisher)
Created2011
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Rhodoferax antarcticus strain ANT.BR, a purple nonsulfur bacterium isolated from a microbial mat in Ross Island, Antarctica, is the first described anoxygenic phototrophic bacterium that is adapted to cold habitats and is the first beta-proteobacterium to undergo complete genome sequencing. R. antarcticus has unique absorption spectra and there are no

Rhodoferax antarcticus strain ANT.BR, a purple nonsulfur bacterium isolated from a microbial mat in Ross Island, Antarctica, is the first described anoxygenic phototrophic bacterium that is adapted to cold habitats and is the first beta-proteobacterium to undergo complete genome sequencing. R. antarcticus has unique absorption spectra and there are no obvious intracytoplasmic membranes in cells grown phototrophically, even under low light intensity. Analysis of the finished genome sequence reveals a single chromosome (3,809,266 bp) and a large plasmid (198,615 bp) that together harbor 4,262 putative genes. The genome contains two types of Rubiscos, Form IAq and Form II, which are known to exhibit quite different kinetic properties in other bacteria. The presence of multiple Rubisco forms could give R. antarcticus high metabolic flexibility in diverse environments. Annotation of the complete genome sequence along with previous experimental results predict the presence of structural genes for three types of light-harvesting (LH) complexes, LH I (B875), LH II (B800/850), and LH III (B800/820). There is evidence that expression of genes for the LH II complex might be inhibited when R. antarcticus is under low temperature and/or low light intensity. These interesting condition-dependent light-harvesting apparatuses and the control of their expression are very valuable for the further understanding of photosynthesis in cold environments. Finally, R. antarcticus exhibits a highly motile lifestyle. The genome content and organization of all putative polar flagella genes are characterized and discussed.
ContributorsZhao, Tingting, M.S (Author) / Touchman, Jeffrey (Thesis advisor) / Rosenberg, Michael (Committee member) / Redding, Kevin (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2011