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Description
Melanoma is a type of skin cancer that can metastasize in advanced stages to other organs such as the brain, lymph nodes, lungs and liver. Current standard treatment options include surgery, radiation therapy, chemotherapy, and immunotherapy. More recently, oncolytic virotherapy is being studied as a new strategy to fight cancer. Specifically, for melanoma, a herpes virus (T-VEC) was approved by the U.S Food and Drug Administration in 2015 to treat advanced disease. Oncolytic viruses have the capacity to replicate mostly in cancer cells while leaving healthy somatic cells free from infection. Additionally, most of these viruses have the ability to induce an immune response against the cancer as well. Myxoma virus (MYXV) causes myxomatosis in European rabbits but not in any other mammal. In humans, MYXV can infect and kill cancer cells acting as an oncolytic virus. However, the mechanisms behind how myxoma kills cancerous cells are not completely known. To investigate this, we treated melanoma murine cancer cells (B16F10) in vitro with different genetically modified myxoma virus mutants, as well as with a novel second mitochondria-derived activator of caspase mimicking drug SMAC-LCL161, to understand the mechanisms by which MYXV induces cell death. In parallel, B16F10 lacZ cells were subcutaneously injected into mice to engraft melanoma tumors. These tumors were treated with intratumoral injections of different viral mutants or armed viruses derived from MYXV along with SMAC-L61. After a period of treatment, the tumors were isolated. Cell death pathways in both cell culture and in tumors obtained from subcutaneous pathways were identified using different techniques. The study showed an increase in activated caspase 3 and cleaved PARP-1 activity in B16F10 lacZ cells from cell culture when compared to cells in vivo however the two apoptosis markers did not track with each other consistently.
ContributorsKien, Cassandra T (Author) / McFadden, Grant (Thesis director) / Franco Achury, Lina (Committee member) / Bertram, Jacobs (Committee member) / Hugh Downs School of Human Communication (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-12
Description
As the 7th leading cause of death in the world, with over 1.6 millions deaths attributed to it in 2016 alone, diabetes mellitus has been a rising global health concern. Type 1 diabetes is caused by lack of insulin production whereas type 2 diabetes is caused by insulin resistance. Both types of diabetes lead to increased glucose levels in the body if left untreated. This, in turn, leads to the development of a host of complications, one of which is ischemic heart disease. Accounting for the death of 16% of the world’s population, ischemic heart disease has been the leading cause of death since 2000. As of 2019, deaths from this disease have risen from 2 million to over 8.9 million globally. While medicine exists to counter the negative outcomes of diabetes mellitus, lower income nations suffer from the lack of availability and high costs of these medications. Therefore, this systematic review was performed to determine whether a non-medicinal treatment could provide similar therapeutic benefits for individuals with diabetes. Genistein is a phytoestrogen found in soy-based products, which has been potentially linked with preventing diabetes and improving diabetes-related symptoms such as hyperglycemia and abnormal insulin levels. We searched PubMed and SCOPUS using the terms ‘genistein’, ‘diabetes’, and ‘glucose’ and identified 32 peer-reviewed articles. In general, preclinical studies demonstrate that genistein decreases body weight as well as circulating glucose and triglycerides concentrations while increasing insulin levels and insulin sensitivity. It also delayed the onset of type 1 and type 2 diabetes. In contrast, clinical studies of genistein in general reported no significant relationship between genistein and body mass, circulating glucose, serum insulin, A1C concentrations, or onset of type 1 diabetes. However, genistein was found to improve insulin sensitivity, delay type 2 diabetes onset and improve serum triglyceride levels. In summary, preclinical and clinical studies suggest that genistein may help delay onset of type 2 diabetes and improve several symptoms associated with the disease. By translating these findings into clinical settings, genistein may offer a cost effective natural approach at mitigating complications associated with diabetes, although additional research is required to confirm these findings.
ContributorsJain, Rijul (Author) / Sweazea, Karen (Thesis director) / Al-Nakkash, Layla (Committee member) / Bolch, Charlotte (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-04-16
Description
Substance abuse costs the United States over $740 billion annually in healthcare, law enforcement, rehabilitation, and decreased work productivity costs. While there are certain clinical treatments for nicotine, opioid, and alcohol addiction, there is yet an equivalent treatment for psychostimulant addiction. The 5-HT7 receptor (5-HT7R) is one of the more recently discovered members of the serotonin receptor family. The involvement of 5-HT7Rs in thermoregulation, memory, and circadian rhythms, suggests that the receptor also plays a role in mood regulation, making it a potential target in the treatment of psychiatric disorders. Given’ the distribution of the 5-HT7Rs in the brain and its known cellular functions, the receptor has also been implicated in addiction processes. Most studies to date have mainly focused on psychiatric conditions like depression, having yet to explore the role of 5-HT7Rs in psycho-stimulant behaviors. In our study, the effects of SB 269970(SB), a selective antagonist for 5-HT7Rs, were tested on 8-OH-DPAT induced hypothermia, cocaine-induced locomotion, and fos expression in the nucleus accumbens. We found that SB effectively reversed 8-OH-DPAT induced hypothermia, indicating the drug is indeed binding to the 5-HT7R. However, while cocaine did increase locomotor activity and fos expression in the nucleus accumbens in rats, SB had no effect on either measure. These results suggest that 5-HT7Rs may work through pathways other than motor and should be explored through additional behavioral tests. Other brain regions should also be studied for fos expression to see if there is a region-specific effect of 5-HT7Rs and fos expression. The efficacy of SB to 5-HT7Rs and results of past studies on the drug suggests its potential as a pharmacological treatment for psychostimulant disorders.
ContributorsZheng, Margaret (Author) / Neisewander, Janet (Thesis director) / Olive, Michael (Committee member) / Garcia, Raul (Committee member) / School of Life Sciences (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Coral reefs are diverse marine ecosystems, where reef building corals provide both the structure of the habitat as well as the primary production through their symbiotic algae, and alongside algae living on the reef itself, are the basis of the food web of the reef. In this way, coral reefs are the ocean's "forests" and are estimated to support 25% of all marine species. However, due to the large size of a coral reef, the relative inaccessibility and the reliance on in situ surveying methods, our current understanding of reefs is spatially limited. Understanding coral reefs from a more spatially complete perspective will offer insight into the ecological factors that contribute to coral reef vitality. This has become a priority in recent years due to the rapid decline of coral reefs caused by mass bleaching. Despite this urgency, being able to assess the entirety of a coral reef is physically difficult and this obstacle has not yet been overcome. However, similar difficulties have been addressed in terrestrial ecosystems by using remote sensing methods, which apply hyperspectral imaging to assess large areas of primary producers at high spatial resolutions. Adapting this method of remote spectral sensing to assess coral reefs has been suggested, but in order to quantify primary production via hyper spectral imaging, light-use efficiencies (LUEs) of coral reef communities need to be known. LUEs are estimations of the rate of carbon fixation compared to incident absorbed light. Here, I experimentally determine LUEs and report on several parameters related to LUE, namely net productivity, respiration, and light absorbance for the main primary producers in coral reefs surrounding Bermuda, which consist of algae and coral communities. The derived LUE values fall within typical ranges for LUEs of terrestrial ecosystems, with LUE values for coral averaging 0.022 ± 0.002 mol O2 mol photons-1 day-1 at a water flow rate of 17.5 ± 2 cm s^(-1) and 0.049 ± 0.011 mol O2 mol photons-1 day-1 at a flow rate of 32 ± 4 cm s^(-1) LUE values for algae averaged 0.0335 ± 0.0048 mol O2 mol photons-1 day-1 at a flow rate of 17.5 ± 2 cm s^(-1). These values allow insight into coral reef productivity and opens the door for future remote sensing applications.
ContributorsFlesher, David A (Author) / Neuer, Susanne (Thesis director) / Redding, Kevin (Committee member) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
The gut microbiome of many termites consists of a diverse range of protists that aid in the digestion of food particles. One of these families of protists is Oxymonadida. This project focuses on finding the evolutionary relationship between oxymonads and their most recent common ancestor, Trimastigidae, by building phylogenetic trees. This project was important because there is a large amount of species of oxymonads. This is because oxymonads adapt to the particular termite it lives in, and there are many species of termites. Understanding each species relationship helps give more knowledge and insight as to where some of the unknown species may go, even though they may not have DNA sequences yet. One unpublished sequence for Microrhopalodina was used in this paper, which previously had no molecular data available. The trees retrieved in this project had some discrepancies compared to previous studies and found an interesting relationship for Microrhopalodina. Microrhopalodina was included in the Oxymonas clade, indicating a very close relationship between the two species. It may even suggest that Microrhopalodina should be considered part of the species Oxymonas. Furthermore, Streblomastix branched in between Monocercomonoides and Trimastigidae, which is a different result than previous papers have found. Streblomastix was previously found to branch between Blattamonas and Monocercomonoides. The most recent paper on Blattamonas stated that they were unsure what family this species belongs to due to its molecular diversity, but its appearance resembles Monocercomonoides which is part of the family Polymastigidae. The trees produced in this project may indicate that Blattamonas belongs in the Polymastigidae family after all.
ContributorsStotts, Cherise (Co-author, Co-author) / Jasso-Selles, Daniel E. (Co-author) / Gile, Gillian H. (Thesis director) / DeMartini, Francesca (Committee member) / Mee, Evan D. (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
With the coming advances of computational power, algorithmic trading has become one of the primary strategies to trading on the stock market. To understand why and how these strategies have been effective, this project has taken a look at the complete process of creating tools and applications to analyze and predict stock prices in order to perform low-frequency trading. The project is composed of three main components. The first component is integrating several public resources to acquire and process financial trading data and store it in order to complete the other components. Alpha Vantage API, a free open source application, provides an accurate and comprehensive dataset of features for each stock ticker requested. The second component is researching, prototyping, and implementing various trading algorithms in code. We began by focusing on the Mean Reversion algorithm as a proof of concept algorithm to develop meaningful trading strategies and identify patterns within our datasets. To augment our market prediction power (“alpha”), we implemented a Long Short-Term Memory recurrent neural network. Neural Networks are an incredibly effective but often complex tool used frequently in data science when traditional methods are found lacking. Following the implementation, the last component is to optimize, analyze, compare, and contrast all of the algorithms and identify key features to conclude the overall effectiveness of each algorithm. We were able to identify conclusively which aspects of each algorithm provided better alpha and create an entire pipeline to automate this process for live trading implementation. An additional reason for automation is to provide an educational framework such that any who may be interested in quantitative finance in the future can leverage this project to gain further insight.
ContributorsYurowkin, Alexander (Co-author) / Kumar, Rohit (Co-author) / Welfert, Bruno (Thesis director) / Li, Baoxin (Committee member) / Economics Program in CLAS (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
T cells, a component of the adaptive immune system, play an instrumental role in directing immune responses and direct cell killing in response to pathogens and cancers. T cells recognize and signal through the T cell receptor, a protein heterodimer on the surface of T cells. The T cell receptor is a highly variable structure formed via somatic recombination; the structure recognizes peptides presented on the surface of nucleated cells by major histocompatibility complex proteins in a specific receptor-restricted, peptide-restricted manner. This balance between T cell diversity and T cell specificity stands as a barrier to efficacious development of articificial T cell receptors capable of clearing disease. T cell receptors may be tailored to produce pathogen- or cancer-specific immune responses from autologous T cell populations. This necessitates a pipeline for amplification, cloning, and expression of antigen-specific T cell receptors. This study aims to utilize influenza-specific T cell receptor chains from healthy donor T cells to test a model for T cell receptor cloning and expression. This study utilizes Gateway recombination for high-throughput cloning into mammalian expression vectors. This study has successfully amplified and cloned T cell receptor chains from a population of influenza-specific T cells from donor cell transcripts into mammalian cell expression vectors. Additionally, CD8, a coreceptor for the T cell receptor complex, was successfully cloned and inserted into a vector for expression in mammalian cells. Sanger sequencing has confirmed sequences for influenza-specific T cell receptor chains and the CD8 chain. Future application of this project includes expression in mammalian non-T cells to test for efficacy of expression and, ultimately, expression in cytotoxic cells to create lymphocytes capable of antigen-specific recognition and cytolytic killing of cells of interest.
ContributorsVale, Nolan Richard (Author) / Anderson, Karen (Thesis director) / Blattman, Joseph (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
In the Alto Mayo Protection Forest (AMPF) of San Martín, Peru, unsustainable farming practices in coffee agroecosystems are the main drivers of deforestation and habitat loss. Previous studies indicate that across Latin American coffee farms, using shade-grown coffee result in higher biodiversity on the farms with a larger abundance of floral and faunal species. In AMPF, conservation agreements have been implemented between cultivators and Conservation International to ameliorate the environmental damages incurred by poor farming practices, as well as to increase cultivator livelihoods. To measure the effectiveness of these agreements, we compared camera trap data to drone-captured shade cover data to find the correlation between higher shade cover and biodiversity among subscriber plots. While our results showed no interrelationship between shade cover and species abundance or richness, this study was a small subset of the larger study, representing only 15% of the total subscriber plots and 24% of the overall sectors. Therefore, we predict that the results of the larger study will be more conclusive and will better indicate the predicted positive relationship between biodiversity and agroecology in AMPF.
ContributorsDelaune, Celeste Rose (Author) / Gerber, Leah (Thesis director) / Ahumada, Jorge (Committee member) / Summers, Percy (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
This thesis examines congressional discussions of media technologies at two distinct historical moments in order to see how Congress evaluated and sought to regulate technologies with the potential to reshape public modes of thought and communication. Specifically, it examines congressional discussions centered around Television and the Fairness Doctrine, as well as Facebook and the recent scandal involving Cambridge Analytica by asking how Congress has understood what is at stake while attempting to regulate emerging media technologies. Specifically, it probes questions such as: What is assumed about the technologies while attempting to legislate them? What is treated as subject to assessment and revision; what is given priority for consideration over other alternate angles? How do the legal and political contexts in which these discussions are framed impact legislative proceedings and society’s ways of knowing and relating to the world?
While these moments are only a subset of such moments in US history, and Congress is only one of a range of forums in which such political discussions can take place, the thesis focuses on these cases because not only are they important in themselves, but also they reveal issues and approaches that are not unique to these moments. The thesis draws on the on the work of Neil Postman, who argues that the emergence and subsequent dominance of media like television have the capacity to alter the manner in which we think and thus have profound effects on the texture and character of American civic life. In this vein it uses a comparison of how lawmakers attempted to regulate television and social media platforms like Facebook to explore whether and how lawmakers have attended to the capacity of these media to shape public thought.
The thesis demonstrates that understanding of media’s epistemological influence is only ever tacitly acknowledged by lawmakers and is not regarded as an important consideration during evaluative legislative efforts. Instead, Congress tends to focus on matters that are of immediate concern and pragmatic in nature, eclipsing questions about how these technologies fundamentally alter our perceptions of the world and the ways we as individuals and as a society relate to it. By not taking such questions into account during our legislative proceedings, the thesis argues, we cede opportunities to employ and regulate technologies to better serve our cultural ideals and remain susceptible to unwanted forms of cultural erosion mediated by technologies.
While these moments are only a subset of such moments in US history, and Congress is only one of a range of forums in which such political discussions can take place, the thesis focuses on these cases because not only are they important in themselves, but also they reveal issues and approaches that are not unique to these moments. The thesis draws on the on the work of Neil Postman, who argues that the emergence and subsequent dominance of media like television have the capacity to alter the manner in which we think and thus have profound effects on the texture and character of American civic life. In this vein it uses a comparison of how lawmakers attempted to regulate television and social media platforms like Facebook to explore whether and how lawmakers have attended to the capacity of these media to shape public thought.
The thesis demonstrates that understanding of media’s epistemological influence is only ever tacitly acknowledged by lawmakers and is not regarded as an important consideration during evaluative legislative efforts. Instead, Congress tends to focus on matters that are of immediate concern and pragmatic in nature, eclipsing questions about how these technologies fundamentally alter our perceptions of the world and the ways we as individuals and as a society relate to it. By not taking such questions into account during our legislative proceedings, the thesis argues, we cede opportunities to employ and regulate technologies to better serve our cultural ideals and remain susceptible to unwanted forms of cultural erosion mediated by technologies.
ContributorsOberhaus, Jack M (Author) / Hurlbut, J. Benjamin (Thesis director) / Zachary, Gregg (Committee member) / Maienschein, Jane (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
The objective of this study was to evaluate sustainability knowledge and practices in place at university-associated food pantries across the United States. A survey was sent to university- associated food pantries and responses were collected at a rate of 25% (n=84 of 326) to assess the knowledge and practices of this topic. The pantries surveyed were chosen solely based on ability to contact through email (emails were retrieved from online sources) and about 50% of the 680 university-associated pantries in the United States were sent the survey. The data was analyzed by quantifying the qualitative responses to the 9 sustainability- rated questions addressing zero- waste practice, barriers to offering sustainably sourced foods, types of sustainable donations, desire for sustainable products, and client demand for sustainable products and practices were posed to pantries. Results from this study provided insight into awareness of sustainability in these pantries and also assessed what sustainability practices are already being practiced by these pantries. Among those surveyed, a low percentage of university-associated pantries actually provide sustainably sourced foods (9.5%), but given the choice about a third (38.1%) would choose to offer these foods. It was reported that availability and cost were perceived as main barriers to providing sustainably sourced foods and that a small proportion of pantries teach their clients about zero waste practices, compost, and recycling. There is little client concern about this issue. Most pantries reported recycling more often than composting and also reported participating in some zero-waste practices. These results are unique to this study as not much research has been done in this area to assess environmental sustainability awareness in university-associated food pantries. Further research is required to further evaluate pantries across the nation as this sample size is approximately 12% of all university- associated pantries in the United States.
ContributorsCrowe, Alexandra B (Author) / Bruening, Meredith (Thesis director) / Payne-Sturges, Devon (Committee member) / School of Life Sciences (Contributor) / School of Sustainability (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05