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Modeling Cancer Using Li-Fraumeni Syndrome Patient-Derived Induced Pluripotent Stem Cells, Ruoji Zhou

Dissertations and Theses (Open Access)

Li-Fraumeni syndrome (LFS) is an autosomal dominant disease caused by germline mutations in the gene TP53, which predispose individuals to a wide range of malignancies, including osteosarcoma and breast cancer. In the previous study, our group developed a novel disease model platform by reprograming LFS patients' fibroblasts to induced pluripotent stem cells (iPSCs), and further differentiate these iPSCs into mesenchymal stem cells (MSCs) then to osteoblasts (OBs), the cells from which osteosarcomas originate. Interestingly, LFS iPSC-derived osteoblasts recapitulated the osteosarcoma phenotype, creating “a bone tumor in a dish”. This “tumor in a dish” platform proved that LFS is an …

Deubiquitinating Enzymes Promote Cancer Progression And Metastasis Via Regulating Protein Stability, Zhenna Xiao

Dissertations and Theses (Open Access)

Deubiquitinating enzymes (DUBs, also called deubiquitinases) are enzymes that remove monoubiquitin or polyubiquitin chains from target proteins. DUBs have critical roles in cell homeostasis and signal transduction, as they regulate protein degradation, subcellular localization, and protein-protein interaction. Deregulation of DUBs contributes substantially to tumor formation and progression, and therefore targeting DUBs may be a promising cancer therapy strategy. My dissertation focuses on identifying the DUBs of EZH2 and SNAI1, two proteins critical for cancer progression and metastasis, and establishing these DUBs as promising anti-cancer targets.

EZH2, the catalytic component of the PRC2 complex, silences gene transcription by histone methylation. High …

Quantifying Uncertainty In A Measurement-Based Assessment Of Relative Biological Effectiveness In Carbon Ion Radiotherapy, Shannon Hartzell

Dissertations and Theses (Open Access)

One of the largest inconsistencies in dose delivered during carbon ion therapy is due to uncertainties in relative biological effectiveness (RBE), a value that is calculated via one of several clinically implemented algorithms. This study investigates the uncertainty in measured microdosimetric parameters for RBE calculation by the Microdosimetric Kinetic Model (MKM), Repair Misrepair Fixation model (RMF), and Local Effect Model I (LEM) using a Tissue Equivalent Proportional Counter (TEPC).

Microdosimetric spectra, kinetic energy spectra, and dose fragment contributions were calculated using Monte Carlo (GEANT IV) for monoenergetic and SOBP carbon beams of clinical energy. From microdosimetric spectra, lineal energy values …

Dissecting The Roles Of Human Smc Complexes In Transcription Regulation And Chromatin Organization, Ruoyu Wang

Dissertations and Theses (Open Access)

Metazoans utilize a constellation of distal regulatory elements to control gene transcription, and therefore they have to forge highly complex chromatin loops to spatially bridge these regulatory elements and genes in the three-dimensional (3D) genome. However, the hierarchy of chromatin contacts and their underlying mechanisms are not well-understood. SMC complexes including Cohesin complex and Condensin complex has been widely proposed to organize 3D genome structure, and further regulate metazoans’ gene transcription. Here, we aim to dissect the direct functions of SMC complexes (both Cohesin and Condensin) in transcriptional regulation and 3D genome organization, by utilizing an inducible protein degradation system. …

P53r245w Mutation Elicits Metastatic Phenotype In Pten Deficient Prostate Cancer, Ky Pham

Dissertations and Theses (Open Access)

Trp53 mutations are the most frequent genetic alterations in prostate cancer and are associated with more aggressive disease and worse overall survival. The majority of Trp53 mutations in prostate cancer are missense mutations, resulting in amino acid substitutions with profound effect. In addition to the loss of wild type function, missense mutations in Trp53 result in a gain-of-function (GOF) phenotype. This GOF phenotype confers biologic advantages to the tumor cells, enabling them to metastasize and invade distant organs. In this study, we generated mice carrying a conditional prostate-specific p53R245W mutant and Pten deletion to access the role of this common …

Fasting Reduces Intestinal Radiotoxicity Enabling Dose-Escalated Radiotherapy For Pancreatic Cancer, Marimar De La Cruz Bonilla

Dissertations and Theses (Open Access)

Surgical resection is the only potentially curative treatment for pancreatic cancer, but only 15-20% of patients have resectable tumors. In unresectable cases, stereotactic body radiotherapy (SBRT) may be used to give tumor-directed radiotherapy (RT). Unfortunately, this can cause severe gastrointestinal (GI) toxicity due to proximity of the pancreatic head to the duodenum. Protecting the intestine from the toxic side-effects of radiation may enable dose-escalation that could achieve more effective local control of disease. We and others have previously shown that a fast of 24 hours protects mice from lethal doses of the DNA-damaging agent etoposide. In this study, we demonstrate …

Investigating The Role Of Cd109 In Pancreatic Ductal Adenocarcinoma, Mennatallah Shaheen

Dissertations and Theses (Open Access)

Pancreatic Ductal Adenocarcinoma (PDAC) is the 3rd leading cause of cancer death in the US. We performed loss of function genomic screening on a cohort of four patient derived PDAC cell populations and our data shows a cell surface receptor CD109 to be a common vulnerability, the biologic role of which in PDAC is yet unstudied and largely unknown. We hypothesized that CD109 expression provides PDAC cells with a survival advantage, and promotes cancer progression through activation of downstream signaling. We believe therefore that targeting CD109 could improve PDAC patients’ survival. Here we report that CD109 plays a role in …

Gcn5 Loss Impacts Myc-Driven Cancer In Mice And Human Cells, Aimee Farria

Dissertations and Theses (Open Access)

GCN5 is the catalytic subunit in the acetyltransferase module of SAGA and ATAC, multiprotein complexes involved in the modification of histone and nonhistone proteins. GCN5 is most recognized as a co-activator of gene transcription. The SAGA complex is recruited to chromatin by transcription factors such as MYC and E2F1 where GCN5 acetylates H3K9 leading to a more open and accessible chromatin structure. Previous research has demonstrated that GCN5 also acetylates MYC, a protein that amplifies the expression of cancer-promoting genes and is frequently dysregulated in cancer, increasing its stability. Our lab has found there is a significant overlap in the …

Molecular Consequences Of High Taz Expression In Gliomas, Visweswaran Ravikumar

Dissertations and Theses (Open Access)

Diffuse high grade gliomas are complex and lethal neoplasms of the adult central nervous system that are driven by a range of genetic and epigenetic alterations. Molecular classification of these tumors has identified different transcriptional subtypes, the most notable being Proneural (PN) and Mesenchymal (MES) classes. The most aggressive forms of the disease have a Mesenchymal expression signature, with reported PN-to-MES transition occurring with tumor progression. Master regulatory analysis has identified the transcriptional co-activator TAZ (WWTR1) as a major driver of the MES transition. Overexpression of this single protein in glioma stem cells has been shown to drive a transition …

Last Chance To See? Motivations And Outcomes Of Last Chance Tourism Experiences In Arctic Alaska, Tana Kay Wilson

All Theses

The tourism market for endangered places and their vulnerable resources are booming and widely referred to as last chance tourism (LCT). People are planning trips to experience places or see species they may never have wanted to see until learning that the option to witness it could disappear in their lifetime. The notion of LCT was first introduced by the tourism industry to describe increasing tourist interest to endangered destinations. Utilizing visitor surveys, the purpose of this study was to identify LCT participants and quantify experiential outcomes of LCT (e.g., awe, epiphany and ambassadorship). This study specifically takes place at …

An Ex Vivo Model Of Elastin Degradation In Porcine Carotid Arteries For The Study Of Abdominal Aortic Aneurysms, Hannah Gore

All Theses

Abdominal aortic aneurysms (AAA) are an area of dilation in the vessel that is greater than 3.0 cm in diameter or an area of the vessel that enlarged to greater than 50% of the vessel's original diameter. AAA are generally asymptomatic and if ruptured, have a mortality rate of 78-83%. AAA account for approximately 45,000 surgeries performed in the United States annually and are the 13th leading cause of death in the United States. Alterations of two extracellular matrix proteins, elastin and collagen, are associated with the formation of abdominal aortic aneurysms. AAA formation is marked by degradation of elastin …

Application Of Electrical Resistivity Geophysical Monitoring For Detection Of Preferential Flow, Jeffrey Britton Hundley Jr.

All Theses

Preferential flow is a common occurrence during infiltration yet is often not accounted for in predictive flow models. This has implications for contaminant transport in that the extent of constituent plumes are often underestimated, thereby reducing the effectiveness of any remediation efforts. Electrical resistivity monitoring could be a useful tool to determine if infiltration is bypassing parts of the subsurface through preferential flow pathways and to better inform predictive models. The viability of this method was evaluated through simple electrical simulations and with multiple column experiments across scales using advanced observation techniques like 4D computed tomography. Electrical resistivity was used …

Microfluidic Particle Separation Via Elasto-Inertial Focusing In Straight Rectangular Microchannels, Di Li

All Dissertations

Label-free separation of target particles or cells in a continuous flow is a crucial process in many commercial and industrial applications. Among the various particle and cell separation techniques, microfluidic separator based on elasto-inertial forces in the flow of non-Newtonian fluids has received increasing attention in the past decade. However, current studies have been mainly focused upon the use of viscoelastic forces to manipulate particles and cells. Little work has been done to obtain a fundamental understanding on how the fluid rheological properties, such as viscoelasticity and shear thinning, affect the motion of particles. This dissertation is aimed to address …

Modeling Electrostatics And Geometrical Quantities In Molecular Biophysics Using A Gaussian-Based Model Of Atoms, Arghya Chakravorty

All Dissertations

Electrostatic and geometric factors are critical to modeling the interactions and solvation effects of biomolecules in the aqueous environments of biological cells as they respectively influence the polar and non-polar components of the associated free energies. Conventional protocols use a hard-sphere model of atoms to devise and study the underlying thermodynamics. But this traditional model tends to overlook some of the important biophysical aspects at the cost of oversimplification of the representation of the solute-solvent environments. Here an alternative and physically appealing model of atoms – a Gaussian-based model, is presented which replaces the hard-sphere model with a smooth density-based …

Synthesis, Characterizations, And Study Of The Antioxidant Activity Of Novel Ruthenium-Thione And -Selone Complexes, Mohammed Abdulali Abbas

All Dissertations

Coordination chemistry of imidazole thione and selone compounds with 2nd and 3rd row d-block metals are of considerable interest due to their wide-ranging applications of reducing heavy metal toxicity, catalysis, and antimicrobial and antitumor activity. Antioxidant behavior of some imidazole thiones and selones is attributed to their ability to scavenge hydrogen peroxide or other reactive oxygen species as well as their coordination of redox-active iron and copper to prevent hydroxyl-radical-mediated DNA damage. Chapter 1 of this dissertation provides an overview of 2nd and 3rd row d-block metal complexes with imidazole thione and selone ligands and their applications.

Ruthenium complexes with …

Melt-Spinning And Properties Of Soy-Filled Polyethylene, Polypropylene, And Poly-(Lactic Acid) Fibers, Ozgun Guzdemir

All Dissertations

No abstract provided.

Self-Repair And Self-Cleaning Of The Lepidopteran Proboscis, Suellen Floyd Pometto

All Dissertations

The proboscis of butterflies and moths is a key innovation contributing to the high diversity of the order Lepidoptera. In addition to taking nectar from angiosperm sources, many species take up fluids from overripe or sound fruit, plant sap, animal dung, and moist soil. The proboscis is assembled after eclosion of the adult from the pupa by linking together two elongate galeae to form one tube with a single food canal. How do lepidopterans maintain the integrity and function of the proboscis while foraging from various substrates?

The research questions included whether lepidopteran species are capable of total self-repair, how …

The Below-Ground Competitive Ability And Allelopathic Potential Of Palmer Amaranth (Amaranthus Palmeri) In Soybean, Dwayne D. Joseph

All Dissertations

Palmer amaranth (Amaranthus palmeri S. Watson) has quickly become one of the most economically important weeds in South Carolina soybean production. Its ability to rapidly accumulate root and shoot biomass allows it to effectively compete with crops for light, nutrients and water. To better understand the below-ground competition dynamics between soybean and Palmer amaranth, greenhouse and field experiments were conducted. In 2016 and 2017, field studies were initiated with a split-plot 3x2x2 factorial treatment design. Treatments factors consisted of: neighbor (Palmer amaranth, soybean, none), divider (with and without) and irrigation (irrigated and non-irrigated). The response variables measured were soil …

Understanding The Warburg Phenotype And The Metabolic Plasticity Of Proliferative Mammalian Cells Using 13C Metabolic Flux Analysis, Daniel Odenwelder

All Dissertations

Proliferative cells, including many types of cancer and pluripotent stem cells, rely primarily on glycolysis and lactate metabolism for energy, regardless of oxygen availability. This metabolic phenotype – referred to as the Warburg effect – results in wasteful lactate accumulation. Although cancer cells and pluripotent stem cells share this central metabolic characteristic, the sensitivities of each of these cell types to lactate stress appear contradictory. While lactate accumulation is thought to adversely impact pluripotent stem cell proliferation and differentiation capacities, cancer cells have been shown to possess bioenergetic plasticity to utilize lactate catabolism for fuel. As a result, lactate buildup …

Development Of Peptides For Enantioselective Hypervalent Iodine(Iii)-Mediated Chemistry And Functional Materials For Environmental Remediation, Maria I. Swasy

All Dissertations

Within the field of asymmetric catalysis, many researchers have been inspired by the multifaceted structures and corresponding catalytic activity and selectivity of enzymes. One approach to mimicking the important characteristics of enzymes is to develop peptide-based catalysts for asymmetric transformations. Peptides containing even a small number of amino acids are able to provide an environment, rich with chiral information, that is adequate for the transfer of chirality. The overall goal of the presented research is to combine peptide-mediated asymmetric catalysis with hypervalent iodine (HI) chemistry in order to develop new and highly modular peptide catalysts for a variety of HI-mediated …

Advancing Molecular Simulations Of Crystal Nucleation: Applications To Clathrate Hydrates, Ryan Scott Defever

All Dissertations

Crystallization is a fundamental physical phenomenon with broad impacts in science and engineering. Nonetheless, mechanisms of crystallization in many systems remain incompletely understood. Molecular dynamics (MD) simulations are a powerful computational technique that, in principle, are well-suited to offer insights into the mechanisms of crystallization. Unfortunately, the waiting time required to observe crystal nucleation in simulated systems often falls far beyond the limits of modern MD simulations. This rare-event problem is the primary barrier to simulation studies of crystallization in complex systems. This dissertation takes a combined approach to advance simulation studies of nucleation in complex systems. First, we apply …

Discovery And Engineering Of An Endophytic Pseudomonas Strain From Taxus Chinensis For Efficient Production Of Zeaxanthin Diglucoside, Ozkan Fidan, Jixun Zhan

Biological Engineering Faculty Publications

Background

Endophytic microorganisms are a rich source of bioactive natural products. They are considered as promising biofertilizers and biocontrol agents due to their growth-promoting interactions with the host plants and their bioactive secondary metabolites that can help manage plant pathogens. Identification of new endophytes may lead to the discovery of novel molecules or provide new strains for production of valuable compounds.

Results

In this study, we isolated an endophytic bacterium from the leaves of Taxus chinensis, which was identified as Pseudomonas sp. 102515 based on the 16S rRNA gene sequence and physiological characteristics. Analysis of its secondary metabolites revealed …

Exploring The Moderating Effect Of Maternal Scaffolding On The Temperament - Language Development Relationship, Chelsea L. Robertson

Electronic Theses and Dissertations

Many studies have examined the relationship between a child’s temperament and its effect on his or her early language development. However, few studies have investigated the detrimental effects a child’s negative affectivity may have on their language development and potential ways these effects may be limited through parental behaviors. The current study aimed to investigate if physical or verbal maternal scaffolding behaviors moderated the effect negative affect has on language development. Although it was expected that maternal encouragement of physical activity would play a moderating role in the relationship between temperament and language development, no such relationship was found. One …

Self-Compassion And Suicide Risk In Veterans: Serial Effects Of Shame, Guilt, And Ptsd, Jessica Mckinney

Electronic Theses and Dissertations

Suicide is a significant public health concern and ranks as the 10^th leading cause of death in the U.S. Veterans are at a disproportionately higher risk for suicide, due to risk factors such as exposure to trauma and its negative cognitive-emotional sequalae, such as PTSD, shame, and guilt. However, not all veterans exposed to traumatic events, or who experience shame and guilt, die by suicide, perhaps as a result of the presence of individual-level protective factors such as self-compassion. Conceptualized as self-kindness, mindfulness and common humanity, self-compassion is beneficially associated with mental and physical health, including reduced suicide risk. …

Temperature Influence On Insecticide Resistance In Aedes Aegypti And Aedes Albopictus Mosquitoes From South Texas, Wendy Soledad Salinas

Theses and Dissertations

Aedes aegypti and Aedes albopictus are vectors for several emerging arboviruses including Zika, chikungunya and dengue. Both mosquitoes are found along the Rio Grande River in South Texas, along the border between Mexico and the United States of America. These mosquito species typically reside near human settlements. A preventative measure public health official use to help halt the spread of diseases is by controlling vector population with the use of insecticides, but as temperature vary, and with the constant exposure to commonly used insecticides, mosquitoes from South Texas may be developing a resistance to the insecticides. Resistance to insecticides may …

Evaluating Responses Of Benthic Macrofauna To Artificial Reef Presence In The Gulf Of Mexico, Douglas Faircloth

Theses and Dissertations

Artificial reef research has long concerned itself with the interactions of fishes and has tended to favor commercially valuable species. Because of this, a larger yet less known group that heavily benefits fishes have been overlooked; benthic macrofauna. Benthic macrofauna are marine invertebrates that live below the sediment-water interface and play many roles in the ecosystem. Macrofauna are important prey items, ecosystem engineers, and bioindicators, as well as being ubiquitous in the marine environment. Since macrofauna have been largely ignored in this field, not much is known regarding their interaction with the placement of artificial reefs. To try and fill …

Development And Analysis Of 3d-Printed Synthetic Vocal Fold Models, Ryan Gregory Romero

Theses and Dissertations

Vocal fold models are valuable for studying voice production. They provide an alternative method of studying the mechanics of the voice that does not require in vivo experimentation or the use of excised human or animal tissue. In this thesis, a new method of creating vocal fold models through additive manufacturing is described. The purpose of this research was to reduce model fabrication time, to decrease the number of model failures during manufacturing, and to lay the foundation for creating models with more lifelike geometric and material properties. This research was conducted in four stages. First, a suitable silicone additive …

Improving And Modeling Bacteria Recovery In Hollow Disk System, Clifton Anderson

Theses and Dissertations

Identifying antibiotic resistance in blood infections requires separating bacteria from whole blood. A hollow spinning disk rapidly removes suspended red blood cells by leveraging hydrodynamic differences between bacteria and whole blood components in a centrifugal field. Once the red cells are removed, the supernatant plasma which contains bacteria is collected for downstream antibiotic testing. This work improves upon previous work by modifying the disk design to maximize fractional plasma recovery and minimize fractional red cell recovery. V-shaped channels induce plasma flow and increase fractional plasma recovery. Additionally, diluting a blood sample spiked with bacteria prior to spinning it increased the …

General Catalog 2019-2020, Utah State University

University Catalogs

This catalog contains information on the Academic Departments and Programs as well as Course Descriptions for the above school year at Utah State University. To avoid large file downloads, the Academic Departments and Programs information is located in this file. The Course Description information is located in the secondary file.

Development Of Metals Corrosion Maps Of Arkansas And Maintenance Of Cross-Drains, Zahid Hossain, Ashraf Elsayed, Mdariful Hasan

Publications

Corrosion potential of metallic structures in alluvial soils is governed by chemical and electromagnetic properties of the soils. Geotechnical engineers are generally more concerned about different types of soils and their physical and mechanical properties than the chemical aspects. The main objective of this study is to analyze the geotechnical, electrochemical and electromagnetic properties of soils in Arkansas. Important parameters (e.g., soil resistivity) related to corrosion potential of metal culverts have been predicted through neural network (NN) models. The developed NN models have been trained and verified by using laboratory test results of soil samples collected from Arkansas Department of …