Matching Items (17)
Filtering by
- All Subjects: Mathematical Modeling
- All Subjects: Sonoran Desert
- All Subjects: Genetics
- Creators: School of Mathematical and Natural Sciences
- Member of: Barrett, The Honors College Thesis/Creative Project Collection
Description
Veterans are approximately 30% more likely than non-veterans to suffer from severe hearing impairment. Tinnitus, or ringing in the ears, which is increasingly common among military service men and women, has been linked to significant cognitive and psychological impairment and can be worsened by the same sounds that trigger post-traumatic stress disorder (PTSD). In fact, tinnitus and PTSD often present as comorbidities, and recent studies suggest these two disorders may share a common neurological pathway. Additional studies are required to better understand the connection between hearing loss and impaired cognitive function such as that observed in with PTSD. Here, we use the fruit fly, Drosophila melanogaster, to explore the relationship between hearing loss and cognitive function. Negative geotaxis climbing assays and courtship behavior analysis were used to examine neurobehavioral changes induced by prolonged, intense auditory stimulation. Preliminary results suggest that exposure to loud noise for an extended period of time significantly affected Drosophila behavior, with males being more sensitive than females. Based on our results, there appears to be a potential connection between noise exposure and behavior, further suggesting that Drosophila could be an effective model to study the link between hearing loss and PTSD.
ContributorsMichael, Allison Faye (Author) / Hackney-Price, Jennifer (Thesis director) / Sellner, Erin (Committee member) / School of Social and Behavioral Sciences (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Bexarotene (Targretin®) is an FDA approved drug used to treat cutaneous T-cell lymphoma (CTCL), as well as off-label treatments for various cancers and neurodegenerative diseases. Previous research has indicated that bexarotene has a specific affinity for retinoid X receptors (RXR), which allows bexarotene to act as a ligand-activated-transcription factor and in return control cell differentiation and proliferation. Bexarotene targets RXR homodimerization to drive transcription of tumor suppressing genes; however, adverse reactions occur simultaneously when bound to other nuclear receptors. In this study, we used novel bexarotene analogs throughout 5 iterations synthesized in the laboratory of Dr. Wagner to test for their potency and ability to bind RXR. The aim of our study is to quantitatively measure RXR homodimerization driven by bexarotene analogs using a yeast two-hybrid system. Our results suggests there to be several compounds with higher protein activity than bexarotene, particularly in generations 3.0 and 5.0. This higher affinity for RXR homodimers may help scientists identify a compound that will minimize adverse effects and toxicity of bexarotene and serve as a better cancer treatment alternative.
ContributorsSeto, David Hua (Author) / Marshall, Pamela (Thesis director) / Wagner, Carl (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor) / School of Social and Behavioral Sciences (Contributor)
Created2015-05
Description
Bexarotene is a commercially produced drug commonly known as Targetin presecribed to treat cutaneous T-cell lymphoma (CTCL). Bex mimics the actions of natural 9-cis retinoic acid in the body, which are derived from Vitamin A in the diet and boost the immune system. Bex has been shown to be effective in the treatment of multiple types of cancer, including lung cancer. However, the disadvantages of using Bex include increased instances of hypothyroidism and excessive concentrations of blood triglycerides. If an analog of Bex can be developed which retains high affinity RXR binding similar to the 9-cis retinoic acid while exhibiting less interference for heterodimerization pathways, it would be of great clinical significance in improving the quality of life for patients with CTCL. This thesis will detail the biological profiling of additional novel (Generation Two) analogs, which are currently in submission for publication, as well as that of Generation Three analogs. The results from these studies reveal that specific alterations in the core structure of the Bex "parent" compound structure can have dramatic effects in modifying the biological activity of RXR agonists.
ContributorsYang, Joanna (Author) / Jurutka, Peter (Thesis director) / Wagner, Carl (Committee member) / Hibler, Elizabeth (Committee member) / Barrett, The Honors College (Contributor)
Created2012-05
Description
Virtually all animals require relatively predictable developmental schedules in order to fulfill the cycle of life. Cell death and severe inflammation alter steroid hormone production and can disrupt the timing of developmental transitions such as puberty. In the fruit fly, Drosophila melanogaster, injury to wing precursor tissues has been shown to result in decreased steroid hormone levels and delay development. The effects of damage to other tissues have not yet been explored. Here, the larval salivary glands were damaged in order to observe how injuring these specific tissues affect the timing of developmental transitions. Damage was induced by tissue-specific, temperature sensitive activation of cell death genes. The results indicated that death to salivary gland cells accelerates the Drosophila time to adult eclosion and that the observed acceleration of development is age-dependent. Insight into the effects of injury on development in Drosophila can potentially lead to information about development in other organisms, including humans, following injury or chronic inflammation.
ContributorsRippere, Alicia Leann (Author) / Hackney, Jennifer (Thesis director) / Marshall, Pamela (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor)
Created2015-05
Description
Cellular and molecular biologists often perform cellular assays to obtain a better understanding of how cells work. However, in order to obtain a measurable response by the end of an experiment, the cells must reach an ideal cell confluency. Prior to conducting the cellular assays, range-finding experiments need to be conducted to determine an initial plating density that will result in this ideal confluency, which can be costly. To help alleviate this common issue, a mathematical model was developed that describes the dynamics of the cell population used in these experiments. To develop the model, images of cells from different three-day experiments were analyzed in Photoshop®, giving a measure of cell count and confluency (the percentage of surface area covered by cells). The cell count data were then fitted into an exponential growth model and were correlated to the cell confluency to obtain a relationship between the two. The resulting mathematical model was then evaluated with data from an independent experiment. Overall, the exponential growth model provided a reasonable and robust prediction of the cell confluency, though improvements to the model can be made with a larger dataset. The approach used to develop this model can be adapted to generate similar models of different cell-lines, which will reduce the number of preliminary range-finding experiments. Reducing the number of these preliminary experiments can save valuable time and experimental resources needed to conduct studies using cellular assays.
ContributorsGuerrero, Victor Dominick (Co-author) / Guerrero, Victor (Co-author) / Watanabe, Karen (Thesis director) / Jurutka, Peter (Committee member) / School of Mathematical and Natural Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Since its isolation from a rhesus monkey in the Zika forest of Uganda in 1947, Zika virus (ZIKV) has spread into many parts of the world, causing major epidemics, notably in the Americas and some parts of Europe and Asia. The flavivirus ZIKV is primarily transmitted to humans via the bite of infectious adult female Aedes mosquitoes. In the absence of effective treatment or a safe and effective vaccine against the disease, control efforts are focused on effective vector management to reduce the mosquito population and limit human exposure to mosquito bites. The work in this thesis is based on the use of a mathematical model for gaining insight into the transmission dynamics of ZIKV in a population. The model, which takes the form of a deterministic system of nonlinear differential equations, is rigorously analyzed to gain insight into its basic qualitative features. In particular, it is shown that the disease-free equilibrium of the model is locally-asymptotically stable whenever a certain epidemiological quantity (known as the reproduction number, denoted by R0) is less than unity. The epidemiological implication of this result is that a small influx of ZIKV-infected individuals or vectors into the community will not generate a large outbreak if the anti-ZIKV control strategy (or strategies) adopted by the community can reduce and maintain R0 to a value less than unity. Numerical simulations of the model, using data relevant to ZIKV transmission dynamics in Puerto Rico, shows that a control strategy that solely focuses on killing immature mosquitoes (using highly efficacious larvicides) can lead to the elimination of ZIKV if the larvicide coverage (i.e., proportion of breeding sites treated with larvicides) is high enough (over 90%). Such elimination is also feasible using a control strategy that solely focuses on the use of insect repellents (as a means of personal protection against mosquito bites) if the coverage level of the insect repellent usage in the community is high enough (at least 70%). However, it is also shown that although the use of adulticides (i.e., using insecticides to kill adult mosquitoes) can reduce the reproduction number (hence, disease burden), it fails to reduce it to a value less than unity, regardless of coverage level. Thus, unlike with the use of larvicide-only or repellent-only strategies, the population-wide implementation of an adulticide-only strategy is unable to lead to ZIKV elimination. Finally, it is shown that the combined (integrated pest management) strategy, based on using all three aforementioned strategies, is the most effective approach for combatting ZIKV in the population. In particular, it is shown that even a moderately-effective level of this strategy, which entails using only 50% coverage of both larvicides and adulticides, together with about 45% coverage for a repellent strategy, will lead to ZIKV elimination. This moderately-effective combined strategy seems attainable in Puerto Rico.
ContributorsUrcuyo, Javier (Author) / Gumel, Abba (Thesis director) / Hackney Price, Jennifer (Committee member) / School of Mathematical and Natural Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Pharmacokinetics describes the movement and processing of a drug in a body, while Pharmacodynamics describes the drug's effect on a given subject. Pharmacokinetic/Pharmacodynamic(Pk/Pd) models have become a fundamental tool when predicting bacterial behavior and drug development. In November of 2009, Katsube et al. published their paper detailing their Pk/Pd model for the drug Doripenem and the bacteria P. aeruginosa. In their paper, they determined that there is a dependent relationship between the drug's effectiveness and the dosing strategy of the drug. Therefore, this thesis has applied optimal control in order to optimize the drug's effectiveness, while not burdening the subject with the side effects of the drug. Optimal Control is a mathematical tool used to balance two competing factors. As a result, it has become a useful tool used to make decisions involving complex behavior. By using Optimal Control, the model will maximize the drug's effect on the bacterial population of P. aeruginosa, while minimizing the drug concentration of Doripenem. In doing so, our research will enable doctors and clinicians to maximize a drug's effectiveness on the body, while minimizing side effects.
ContributorsSawkins, Bryan Thomas (Author) / Camacho, Erika (Thesis director) / Wirkus, Stephen (Committee member) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Desert ecosystems are one of the fastest urbanizing areas on the planet. This rapid shift has the potential to alter the abundances and species richness of herbivore and plant communities. Herbivores, for example, are expected to be more abundant in urban desert remnant parks located within cities due to anthropogenic activities that concentrate food resources and reduce native predator populations. Despite this assumption, previous research conducted around Phoenix has shown that top-down herbivory led to equally reduced plant biomass. It is unclear if this insignificant difference in herbivory at rural and urban sites is due to unaltered desert herbivore populations or altered activity levels that counteract abundance differences. Vertebrate herbivore populations were surveyed at four sites inside and four sites outside of the core of Phoenix during fall 2014 and spring 2015 in order to determine whether abundances and richness differ significantly between urban and rural sites. In order to survey species composition and abundance at these sites, 100 Sherman traps and 8 larger wire traps that are designed to attract and capture small vertebrates such as mice, rats, and squirrels, were set at each site for two consecutive trap nights. Results suggest that the commonly assumed effect of urbanization on herbivore abundances does not apply to small rodent herbivore populations in a desert city, as overall small rodent abundances were statistically similar regardless of location. Though a significant difference was not found for species richness, a significant difference between small rodent genera richness at these sites was observed.
ContributorsAlvarez Guevara, Jessica Noemi (Co-author) / Ball, Becky A. (Co-author, Thesis director) / Hall, Sharon J. (Co-author) / Bateman, Heather (Committee member) / School of Sustainability (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
The need for new tuberculocidal drugs is crucial with drug resistance on the rise as the tuberculosis epidemic rages on. One new potential drug target is the PrrAB two component system (TCS) since it does not exist in humans and is essential to viability in Mycobacterium tuberculosis. This project examines Mycobacterium smegmatis, and this nonpathogenic and fast-growing organism possesses two full length PrrAB orthologs, in addition to an orphaned PrrB sensor histidine kinase. While it was determined that PrrAB1 and PrrAB2 are nonessential, the lone PrrB3 is not yet characterized for essentiality. To confirm individual dispensability of PrrAB1 and PrrAB2 and investigate the essentiality of PrrB3 and the full M. smegmatis PrrAB multiplex, we utilized CRISPRi dCas9 to repress the expression (knockdown) of prrAB1 (MSMEG_5662-5663), prrAB2 (MSMEG_0244-0246), and the lone prrB3 (MSMEG_2793) in M. smegmatis independently and simultaneously. Repression of prrAB1 resulted in the greatest growth defect, with a lag of 17 cellular division cycles compared to the control, a strain generated with an empty vector. However, the knockdown of prrAB1 was not lethal to M. smegmatis. The inhibition of all three prrAB orthologs simultaneously, also known as a multiplex knockdown, lagged the control by 13 cellular division cycles. At the 48-hour point, both the single ortholog repression of prrAB1 as well as the whole prrAB system knockdown had a growth defect of 13 replication cycles behind the control. However, the multiplex knockdown stabilized growth at 48 hours, revealing a possible compensatory mechanism in M. smegmatis. Conclusively, we show that the PrrAB TCS is globally inessential for viability in M. smegmatis.
ContributorsHeiligenstein, Piper (Author) / Haydel, Shelley (Thesis director) / Shrivastava, Abhishek (Committee member) / Haller, Yannik (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / School of Mathematical and Natural Sciences (Contributor)
Created2023-12
Description
Pollution causes many health problems in the modern world and the desert climates struggle with pollution in unique ways. In the Sonoran Desert, the research was conducted with the purpose of expanding the knowledge of the topic in this area. A literature review was conducted based on air, soil and noise pollution in the region. The Sonoran Desert has high levels of carcinogenic elements along with other pollutants due to the main industries of mining, agriculture and manufacturing. Overall, these findings show people in desert climates deal with high levels of pollutants.
ContributorsWest, Katherine (Author) / Hackney Price, Jennifer (Thesis director) / Savalli, Udo (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor)
Created2023-05