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Uncovering The Zeb1 Interactome To Identify Novel Regulators Of Metastatic Non-Small Cell Lung Cancer, Roxsan Manshouri

Dissertations and Theses (Open Access)

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the United States, due in part to the robust affinity of lung cancer cells to metastasize. Understanding the processes that contribute to metastasis provides promise for the discovery of novel therapeutic targets. Epithelial-tomesenchymal transition (EMT) is a proposed model for the initiation of metastasis. During EMT cell adhesion and polarity is reduced, allowing epithelial cancer cells to dissociate from the primary tumor and invade distant organs. The transcription factor zinc finger E-box-binding homeobox 1 (ZEB1) has been reported to uniquely correlate with NSCLC disease progression and to …

The Role Of Membrane Domains In Protein And Lipid Sorting During Endocytic Traffic, Blanca B. Diaz-Rohrer

Dissertations and Theses (Open Access)

The lipid and protein composition of the plasma membrane (PM) must be tightly controlled to maintain cellular functionality, despite constant, rapid endocytosis. Because de novo synthesis of proteins and lipids is energetically costly, the cell depends on active recycling to return endocytosed membrane components back to the PM. For most proteins, the mechanisms and pathways of their PM retention remain unknown. The work presented here shows that association with ordered membrane microdomains is fully sufficient for PM recycling and that abrogation of raft partitioning leads to their degradation in lysosomes. These findings support a model wherein ordered membrane domains mediate …

Identification And Molecular Analysis Of Dna In Exosomes, Jena Tavormina

Dissertations and Theses (Open Access)

Exosomes are heterogeneous nanoparticles 50-150nm in diameter. Exosomes contain many functional cargo components, such as protein, DNA, and RNA. While protein and RNA exosome content has been extensively studied, very little work has been done to characterize exosomal DNA. Here, we demonstrate that exosomal DNA is heterogeneous and its packaging into exosomes is dependent on the cell of origin. Furthermore, through a rigorous assessment of various isolation methods, we identify Size Exclusion Chromatography (SEC) as the best method for the isolation of exosomal DNA for downstream applications. Additionally, we evaluate the methylation status of exosomal DNA and demonstrate that exosomal …

A Signature Enrichment Design With Bayesian Adaptive Randomization For Cancer Clinical Trials, Fang Xia

Dissertations and Theses (Open Access)

Clinical trials in the era of precision medicine demand more flexible and efficient trial designs. Adaptive clinical trial designs allow pre-specified modifications of an on-going clinical trial and could shorten the trial duration. We reviewed five common types of adaptive clinical trials based on adaptation methods. In particular, outcome-randomization becomes more popular as it can assign more patients to the promising treatments based on the accumulated trial data. This data-driven allocation allows more patients to benefit from the trial, which is especially important for cancer patients. We compared different Bayesian outcome-adaptive randomization methods and discussed them from both methodological and …

Assessment Of New Innovations In Pet/Ct For Respiratory Motion Correction, Joseph Meier

Dissertations and Theses (Open Access)

In oncological imaging, Positron Emission Tomography/Computed Tomography (PET/CT) is a vital tool used for stating and treatment response assessment of patients due to its ability to visualize and accurately quantify the bio-distribution of radiolabeled pharmaceuticals. However, due to the long acquisition times, respiratory motion blur is unavoidable in PET images especially in the lower lung and upper abdomen. This leads to reductions in measured radiotracer concentration and lesion detectability all of which can potentially result in incorrect management of patients. Multiple methods exist to correct for respiratory motion but are rarely used in the routine clinical setting because of: 1) …

Deconvolute Brain Tumor Genomic Alterations Based On Dna Methylation, Jie Yang

Dissertations and Theses (Open Access)

Molecular classification based on mutations, expression subtypes, and copy number variants has improved diagnosis and treatment decision-making for patients with brain tumors, particularly malignant gliomas. However, the association between epigenetic signature and genetic alterations is poorly understood. For example, mutation of isocitrate dehydrogenase (IDH) is associated with genome-wide hypermethylation of CpG islands in gliomas. But other subtype-associated alterations, including telomerase reverse transcriptase (TERT) promoter mutation, alpha thalassemia/mental retardation syndrome X-linked (ATRX) mutation, chromosome 1p19q co-deletion (chr1p19q codel), and gene expression subtypes, have yet to be associated with any epigenetic signature. Therefore, we hypothesized that …

Relevance Of Fgfr1 And Its Isoforms In Prostate Cancer Bone Metastases, Estefania Labanca

Dissertations and Theses (Open Access)

The fibroblast growth factor receptor (FGFR) 1 is implicated in prostate cancer (PCa) progression. Various FGFR1 isoforms have been described and we demonstrate here that the well-characterized FGFR1 a and b isoforms are correlated with the expression of different genes and pathways in human PCa. Direct injection of PC3 PCa cells overexpressing FGFR1 isoforms into the femur of mice resulted in enhanced tumor growth and reduction in bone volume when compared with PC3 expressing empty vector. However, only PC3 overexpressing FGFR1 b was associated with increased osteoclast parameters, suggesting that each isoform may mediate diverse biological effects (similar findings were …

Neglecting Responsibilities: The Uniform Probate Code's Failure To Address Child Maltreatment And Poverty, Joshua Hamlet

Journal of Law and Policy

When a child or adolescent passes away, parents are typically stricken with grief and unable to cope with the devastation. Unfortunately, the emotional toll is not the only challenge parents face. Some are forced to handle legal battles regarding the administration of their deceased child’s estate. Since the majority of children do not have a will, state adoptions of the Uniform Probate Code dictate what happens to the child’s estate during these tragedies. But what happens in the event these parents abused or neglected their child while that child was still living? While the Uniform Probate Code advises that these …

The Hard Look Doctrine: How Disparate Impact Theory Can Inform Agencies On Proper Implementation Of Nepa Regulations, Monica Mercola

Journal of Law and Policy

Executive Order 12898—Federal Actions to Address Environmental Justice in Minority Populations and Low-Income Populations—was issued to achieve “environmental protection for all communities” by drawing federal agencies’ attention to the environmental and human health effects brought about by their actions. The National Environmental Policy Act (NEPA) sets forth a detailed process which aims to ensure that each agency will have available, and will consider, a carefully detailed compilation of information concerning significant environmental impacts resulting from federal actions before taking those actions. Realizing the Executive Order’s goal, however, is rendered problematic, in part because of the difficulty in challenging an Environmental …

Semantic Segmentation For Producing Nuclei Stained Images Using Conditional Generative Adversarial Networks, Tanmay Bhatia

All Theses

In order to discover nuclei of cells, biological scientist depend on various types of dyes, and coupled with the overall time involved in using these, it makes this a very inefficient process. Identifying nuclei with Deep Learning techniques can save a lot of time and can yield better accuracy.

Recent developments in Generative Adversarial Networks[1](GANs) have been shown to produce text, video and realistically looking synthetic images. We use the Conditional Generative Adversarial Networks[2] to produce Nuclei Stained images from label maps using two different Generator Architectures(U-Net and Encoder-Decoder with ResNet) and evaluate the performance of these networks. We also …

Bacterial Diversity Of The Gut Of Cotinis Nitida, Roy Attila Kucuk

All Theses

Adult and larval Holometabolous insects exhibit radically different gut morphologies tied to their differing natural histories. Additionally, like other animals, these organisms frequently show distinctive morphological and physiological partitioning of their digestive systems, and this reflects on resident microbial communities. A review of the literature reveals bacteria have formed various symbioses with holometabolous hosts, differing widely in the context of host-symbiont services and patterns of colonization. The significance of these organisms in shaping host evolution and vice-versa is, at present, unclear, but intriguing in the context of host phylogeny.

Using high throughput 16S amplicon sequencing, the bacterial community of the …

Microfabricated Substrate To Achieve In Vivo-Like Cardiomyocyte Morphology And Electrical Propagation In Neonatal Cell Culture, Tiffany Yu

All Theses

Because of the complexity of the in vivo environment, much physiological and pathological understanding of the human body is obtained through cell culture. To gain clinically relevant knowledge, having a cell culture model that mimics the corresponding in vivo tissue would be advantageous. For example, when studying the mechanical and electrical coupling between cardiac cells, imitating in vivo cellular morphology correlates with improved electrical coupling. This has applications within drug screening; by being able to test for cardiotoxicity with a cell culture model, this reduces the resources needed to screen pharmaceuticals for negative side effects. In conventional cardiomyocyte culture, cells …

Numerical Simulation Of Droplet Formation In A Microfluidic Ice Nucleating Particle Measurement Device, Ali Mohammadi Nafchi

All Theses

Ice nucleating particles have a great impact on weather and climate by affecting the freezing process of water in the atmosphere. Therefore, INP measurements are essential to developing more accurate climate models. Despite of the importance of INP measurements, available measurement techniques are costly, which leads to scarcity of available data. Microfluidic technology offers unique features including small scales and low fabrication costs; thus, can be used to design and develop an INP instrument with lower operation costs, which can enhance the number of INP measurements. In this study, we used a microfluidic platform that can be further developed to …

Barriers And Facilitators To Engagement With Environmental Education Field-Trips In The Congaree Biosphere Reserve: A Spatial Perspective, Toby Story

All Theses

This study was conducted in the Congaree Biosphere Reserve (CBR), a UNESCO designated Biosphere Reserve (BR), and is geographically situated at the nexus of conservation, sustainable development and Environmental Education (EE). We conducted semi-scripted interviews with providers of EE programs and administrators of middle schools in combination with Geographic Information System (GIS) analysis in a case study approach to elicit any barriers and facilitators to participation in EE field trips that exist in this specific context. We find that curriculum constraints, time, matters of human capacity, and access to finance and transportation present as barriers and are often interlinked. We …

Mammalian Artificial Chromosomes As A Synthetic Biology Tool For Transgene Expression, Charles Wang

All Theses

Mammalian artificial chromosomes, or MACs, have been studied as a potential avenue for hosting large numbers of transgenes in mammalian cells. MACs have several advantages over viral-based methods for transgene expression, including a lack of limits on loading capacity, which bypasses issues associated with integration into the genome. One area of research in which MACs can be applied is the biomanufacturing of protein-based therapeutics, where reported genome instability in Chinese hamster ovary (CHO) cells can lead to reduced product titer. MACs can potentially aid in solving this issue by providing alternate hosting sites for transgenes for integration of protein-based therapeutic …

Inflammation And Corrosion In Total Hip Prostheses: The Generation And Interaction Of Reactive Oxygen Species With Cocrmo Metallic Biomaterial Surfaces, Michael John Wiegand

All Dissertations

There are many molecules, species and mechanisms that contribute to the overall wear and degradation of biometallic alloys like cobalt-chromium-molybdenum (CoCrMo). Following implantation, orthopaedic alloys are subject to an encompassing inflammatory response that will either lead to foreign body giant cell formation and attachment to the surface or the fibrous tissue encapsulation, forming an inflamed periprosthetic joint. In addition to the inflammatory response, tribocorrosion-based processes of alloy-on-alloy or alloy-on-polymer couples release polymeric wear debris, oxides, hydroxides, and metal ions in response to excessive wear, loading and corrosion. It is hypothesized that these processes, biological and triboelectrochemical, are linked together in …

Assessing The Adsorption Of Various Proteins With Conformational Screening Utilizing K-Means Clustering And Charmm Potential Energy Calculations, Richard Edwin Overstreet

All Dissertations

Utilizing Quartz Crystal Microbalances (QCMB) to study the interaction of biochemical systems at interfaces is a diverse field with many potential applications. However, with an unfunctionalized surface, this technique suffers from a lack of known binding specificity which can denature the protein and result in a loss in activity. Under such conditions, investigating the adsorption mechanism of proteins to hydrophobic surfaces is difficult with traditional molecular dynamics simulations. In this work, we propose a screening model using geometric transformations, k-means clustering, and MD simulations to investigate the clustered orientations. In order to validate this model and predict the surface density …

Role Of Cryptococcus Neoformans Pyruvate Decarboxylase And Aldehyde Dehydrogenase Enzymes In Acetate Production And Virulence, Mufida Ahmed Nagi Ammar

All Dissertations

The basidiomycete Cryptococcus neoformans is is an invasive opportunistic pathogen of the central nervous system and the most frequent cause of fungal meningitis. C. neoformans enters the host by inhalation and protects itself from immune assault in the lungs by producing hydrolytic enzymes, immunosuppressants, and other virulence factors. C. neoformans also adapts to the environment inside the host, including producing metabolites that may confer survival advantages. One of these, acetate, can be kept in reserve as a carbon source or can be used to weaken the immune response by lowering local pH or as a key part of immunomodulatory molecules. …

The Effects Of Indirubin Derivative E804 On Inflammatory Profiles In Glioblastoma Multiforme Cell Lines And Subsequent Crosstalk Effect On Tumor Associated Thp-1 Macrophages, Micaela Ro Scobie

All Dissertations

Glioblastoma Multiforme (GBM) is a highly invasive brain tumor that affects approximately 18,000 people annually in the USA alone yet remains without curative treatment. Median survival with treatment is 14 months, with most treatments only prolonging life for several months while causing severe adverse side effects. There is a need for new therapeutic modalities. Herein I explore two small molecules that show promise in modulating inflammatory signaling in an in vitro GBM model. Indirubins E804 (indirubin-3’-(2,3 dihydroxypropyl)-oximether) and 7BIO (7-Bromoindirubin-3’-oxime) are synthetic derivatives of natural indirubin. Natural indirubin is a bisindole alkaloid derived from tryptophan precursors and is an agonist …

Stability And Toxicity Of Cerium Oxide Nanoparticles In Water-Soil-Plant Systems, Linlin Mu

All Dissertations

Cerium oxide nanoparticles (CeO2 NPs) are being increasingly used in industrial and consumer products and the release of CeO2 NPs into the air, water, and soil is an inevitable consequence. Once released into the environment, CeO2 NPs can have adverse impacts on the environment and human health. Thus, characterizing the environmental behavior and toxic effects of CeO2 NPs is important to protect the environment and human health. To assure such protection, the stability and phytotoxicity of CeO2 NPs need to be known because they are key to understanding their transport, toxicity and bioavailability in water and soil. The objective of …

Functional Morphology And Environmental Impacts On Migration-Relevant Performance Measures In Amphidromous Goby Fishes, Kelly Marie Diamond

All Dissertations

Animals engage in migrations for diverse reasons and over a variety of time periods. Moving between habitats introduces novel challenges that migrating organisms must overcome in order to reach their intended destination. Such challenges include attaining resources required for survival while also avoiding becoming a resource for other organisms. Another challenge is that environmental structure can act as a barrier between habitats. Amphidromous goby fishes provide an advantageous system in which to study several aspects of migration-related performance. As adults, these fishes live and lay eggs in freshwater streams. Upon hatching, larvae are swept downstream to the ocean. At the …

Evaluating And Enabling Scalable High Performance Computing Workloads On Commercial Clouds, Brandon M. Posey

All Dissertations

Performance, usability, and accessibility are critical components of high performance computing (HPC). Usability and performance are especially important to academic researchers as they generally have little time to learn a new technology and demand a certain type of performance in order to ensure the quality and quantity of their research results. We have observed that while not all workloads run well in the cloud, some workloads perform well. We have also observed that although commercial cloud adoption by industry has been growing at a rapid pace, its use by academic researchers has not grown as quickly. We aim to help …

The Impact Of An Intronic Dopamine Receptor Type-2 Single Nucleotide Polymorphism On Growth, Reproduction And Prolactin Gene Expression In Beef Bulls, Andrea Decarlo

All Dissertations

Prolactin (PRL) is a ~22 kDa peptide hormone reported to regulate over 300 distinct biological functions in vertebrates. Tonic inhibition of prolactin (PRL) by dopamine binding to dopamine receptor-type 2 (DRD2) is well established and changes in PRL serum concentration resulting in detrimental effects to male reproductive physiology have been observed. Release and synthesis of PRL may be altered due to a single nucleotide polymorphism (SNPs) in the DRD2 gene. The objective of these studies were to evaluate associations of a previously identified DRD2 SNP to PRL serum concentrations, growth traits, semen quality, and PRL gene expression in beef bulls. …

Systems Engineering Approaches To Minimize The Viral Spread Of Social Media Challenges, Amro Khasawneh

All Dissertations

Recently, adolescents’ and young adults’ use of social media has significantly increased. While this new landscape of cyberspace offers young internet users many benefits, it also exposes them to numerous risks. One such phenomenon receiving limited research attention is the advent and propagation of viral social media challenges. Several of these challenges entail self-harming behavior, which combined with their viral nature, poses physical and psychological risks for the participants and the viewers. One example of these viral social media challenges that could potentially be propagated through social media is the Blue Whale Challenge (BWC). In the initial study we investigate …

Social Competence And Attitude Towards School In Relation To Academic Achievements Of Students In Kosovo, Blerta Perolli Shehu

All Dissertations

The focus of the research was to determine the relationship among social competence, attitudes toward school and academic achievement of primary school students in Kosovo. Participants in the study were 206 students of 4th grade classes from five different schools in Kosovo, one of their parents and teachers. Parents completed a Survey of Students’ Characteristics, children completed a self-report measure on School Attitude, and teachers completed the Social Competency Rating Form and the School Attitude/Behavior Teacher Version for each of the children in their class. Teachers also assessed the children’s academic performance in 7-items Likert-type scale for each of the …

Conservation, Conflict, And Community Context: Insights From Indian Tiger Reserves, Devyani Singh

All Dissertations

Protected areas across the world have been established to preserve landscapes and conserve biodiversity. However, they also are crucial resources for nearby human populations who depend on them for subsistence and to fulfill social, economic, religious, and cultural needs. The contrasting ideologies of park use and conservation among diverse stakeholders (e.g. managers and local communities) make protected areas spaces of conflict. This mixed methods study aimed to gain a deeper, more comprehensive understanding of these complex conflicts and potential solutions by focusing on the social and ecological landscapes surrounding two Indian protected areas: Dudhwa National Park (DNP in Uttar Pradesh) …

Development Of Functionalized Capillary-Channeled Polymer (C-Cp) Fibers As Stationary Phase For Affinity Chromatography, Hung Khiem Trang

All Dissertations

At the heart of the chromatography technique, the stationary phase is the essential component that dictates multiple aspects of the separation process. Diverse chemistry of the stationary phases, in combination with the choice of appropriate base support materials, allows chromatography to be used in a wide range of applications ranging from the high-performance separations of trace analytes in complex biological samples for chemical detection and quantification to the large-scale purification of a recombinant protein from a complex media. Traditional chromatographic stationary phases mostly utilize porous materials for the high surface area and versatility for chemical modification. However, in many cases, …

Development Of A Nucleus Pulposus Implant For Intervertebral Disc Repair, Joshua Dillon Walters

All Dissertations

The intervertebral disc (IVD) is a fibrocartilaginous tissue connecting adjacent vertebrae in the spinal column. It comprises three distinct tissues: a gelatinous core known as the nucleus pulposus (NP), concentric fibrous rings encircling the NP known as the annulus fibrosus (AF), and the superior/inferior cartilaginous endplates (CEPs). The complex mechanical interplay of these tissues allows the IVD to withstand complex loading in the spine while maintaining trunk stability and flexibility. IVD pathologies, such as IVD degeneration (IDD) and herniation, are associated with cell-mediated inflammation in vivo. This inflammation creates a catabolic environment which degrades the extracellular matrix (ECM) of the …

The Impact Of Ergot Alkaloid Consumption During Gestation On Maternal Performance And Fetoplacental Development, Jessica Lynn Britt

All Dissertations

Tall fescue is the primary cool season perennial forage grass in southeastern US for grazing livestock. Tall fescue the is known to be drought tolerant , disease resistant, grazing tolerant and overall very hardy. Many of these attributes common to fescue are due to a symbiotic relationship between the fescue plant and an endophyte, Epichloë coenophiala , which produces a class of mycotoxins known as ergot alkaloids. These ergot alkaloids are similar in structure to several biogenic amines, such as epinephrine, norepinephrine, and dopamine. When consumed, ergot alkaloids cause a syndrome known as fescue toxicosis which causes problems with weight …

Probing Of Carbohydrate-Protein Interactions Using Galactonoamidine Inhibitors, Jessica B. Pickens

Graduate Theses and Dissertations

Glycoside hydrolases are ubiquitous and one of the most catalytically proficient enzymes known, and thus understanding their mechanisms are crucial. Most research has focused on the interaction of the glycon of substrates and their inhibitors within the active site of glycoside hydrolases. The inhibitors employed to probe these interactions generally had small aglycons (i.e. a hydrogen atom, amidines, small aliphatic groups, or benzyl groups). Here, the interactions of the aglycon with glycoside hydrolases are examined by probing the active sites with a library of 25 galactonoamidines. The studies described in this dissertation aim to increase the understanding of stabilization of …