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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-đť›˝ 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-đť›˝ 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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Description
Natural photosynthesis features a complex biophysical/chemical process that requires sunlight to produce energy rich products. It is one of the most important processes responsible for the appearance and sustainability of life on earth. The first part of the thesis focuses on understanding the mechanisms involved in regulation of light harvesting,

Natural photosynthesis features a complex biophysical/chemical process that requires sunlight to produce energy rich products. It is one of the most important processes responsible for the appearance and sustainability of life on earth. The first part of the thesis focuses on understanding the mechanisms involved in regulation of light harvesting, which is necessary to balance the absorption and utilization of light energy and in that way reduce the effect caused by photooxidative damage. In photosynthesis, carotenoids are responsible not only for collection of light, but also play a major role in protecting the photosynthetic system. To investigate the role of carotenoids in the quenching of the excited state of cyclic tetrapyrroles, two sets of dyads were studied. Both sets of dyads contain zinc phthalocyanine (Pc) covalently attached to carotenoids of varying conjugation lengths. In the first set of dyads, carotenoids were attached to the phthalocyanine via amide linkage. This set of dyads serves as a good model for understanding the molecular "gear-shift" mechanism, where the addition of one double bond can turn the carotenoid from a nonquencher to a very strong quencher of the excited state of a tetrapyrrole. In the second set of dyads, carotenoids were attached to phthalocyanine via a phenyl amino group. Two independent studies were performed on these dyads: femtosecond transient absorption and steady state fluorescence induced by two-photon excitation. In the transient absorption study it was observed that there is an instantaneous population of the carotenoid S1 state after Pc excitation, while two-photon excitation of the optically forbidden carotenoid S1 state shows 1Pc population. Both observations provide a strong indication of the existence of a shared excitonic state between carotenoid and Pc. Similar results were observed in LHC II complexes in plants, supporting the role of such interactions in photosynthetic down regulation. In the second chapter we describe the synthesis of porphyrin dyes functionalized with carboxylate and phosphonate anchoring groups to be used in the construction of photoelectrochemical cells containing a porphyrin-IrO2·nH2O complex immobilized on a TiO2 electrode. The research presented here is a step in the development of high potential porphyrin-metal oxide complexes to be used in the photooxidation of water. The last chapter focuses on developing synthetic strategies for the construction of an artificial antenna system consisting of porphyrin-silver nanoparticle conjugates, linked by DNA of varied length to study the distance dependence of the interaction between nanoparticles and the porphyrin chromophore. Preliminary studies indicate that at the distance of about 7-10 nm between porphyrin and silver nanoparticle is where the porphyrin absorption leading to fluorescence shows maximum enhancement. These new hybrid constructs will be helpful for designing efficient light harvesting systems.
ContributorsPillai, Smitha (Author) / Moore, Ana (Thesis advisor) / Moore, Thomas (Committee member) / Gould, Ian (Committee member) / Arizona State University (Publisher)
Created2011
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This dissertation describes the work on two projects which involves measuring molecular conductance and studying their properties on the nanoscale using various Scanning Tunneling Microscopy (STM) techniques. The first molecule studied was a porphyrin-fullerene moiety known as a molecular Dyad for photovoltaic applications. This project is further divided into two

This dissertation describes the work on two projects which involves measuring molecular conductance and studying their properties on the nanoscale using various Scanning Tunneling Microscopy (STM) techniques. The first molecule studied was a porphyrin-fullerene moiety known as a molecular Dyad for photovoltaic applications. This project is further divided into two section, the first one involving the characterization of the Dyad monolayers and conductance measurement in the dark. The Dyads are designed to form charge separated states on illumination. The lifetime of the charged states have been measured efficiently but the single-molecule conductance through the molecules have yet to be characterized. The second part of the project describes the set-up of a novel sample stage which enables the study of molecular conductance under illumination. This part also describes the subsequent study of the molecule under illumination and the observation of a unique charge-separated state. It also contains the verification of the presence of this charge-separated using other characterization techniques like transient absorption spectroscopy. The second project described in the dissertation was studying and comparing the predicted rectifying nature of two molecules, identical in every way except for one stereocenter. This project describes the formation of monolayers of the molecule on gold and then studying and analyzing the current-voltage characteristics of the molecules and looking for rectification. Both the molecules proved to be rectifying, one more than the other as predicted by theoretical calculations.
ContributorsBhattacharyya, Shreya (Author) / Lindsay, Stuart (Thesis advisor) / Moore, Ana (Committee member) / Levitus, Marcia (Committee member) / Arizona State University (Publisher)
Created2011
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Description
Combretastatin A-4 (CA-4) represents one of the most promising antineoplastic and cancer vascular targeting stilbenes that have been isolated from the South African bush willow, Combretum Caffrum Kuntze. In order to further explore the bioactivity of this molecule, a diiodo derivative of CA-4, as well as its phosphate prodrug,

Combretastatin A-4 (CA-4) represents one of the most promising antineoplastic and cancer vascular targeting stilbenes that have been isolated from the South African bush willow, Combretum Caffrum Kuntze. In order to further explore the bioactivity of this molecule, a diiodo derivative of CA-4, as well as its phosphate prodrug, was synthesized and analyzed for its biological activity; although only a scale up synthesis of this compound was performed herein for ongoing analysis. In general, no increased specificity was noted for the human cancer cell lines. Antiangiogenic properties were similar to the untreated control. The diiodocombstatin was active against M. luteus, and its phosphate prodrugs were very active against N. gonorrhoeae. Combretastain A-2 is another biologically active stilbene isolated from Combretum Caffrum Kuntze. In an attempt to increase biological activity of this molecule both mono-iodo and diiodo derivatives have been partially synthesized. The initial step involving the iodination of piperonal utilizes a novel, cost effective and mild reaction. The iodo stilbenes were obtained via a Wittig reaction using phosphonium salts 25 and 27 along with 2,3-Bis-[tert-butyldimethylsiloxy]-4-methoxy benzaldehyde 29. Deprotection of the subsequent z-stilbenes, non-isolated mono-iodo stilbene and the diiodo 30 produced two synthetic objective z-stilbenes 16 and 17. Synthesis as well as biological analysis is ongoing.
ContributorsTrickey-Platt, Brindi Brooks (Author) / Pettit, George R. (Thesis advisor) / Moore, Ana (Committee member) / Skibo, Edward (Committee member) / Arizona State University (Publisher)
Created2011