Digital Commons Network^™

Spatial Control Of Cell Polarity And Cell Growth By Conserved Ndr Kinase Orb6, Illyce Nunez

Open Access Dissertations

During many cellular processes, such as cell morphogenesis, migration, and asymmetric cell division, eukaryotic cells modulate their growth and polarity. Understanding the molecular mechanisms that govern polarized cell growth has the potential to reveal important insights into diseases such as neurodegeneration, heart disease, and cancer. The model organism fission yeast Schizosaccharomyces pombe, with its cylindrical shape and bipolar growth zones, enables straightforward evaluation of changes in growth and polarity upon genetic or pharmacological manipulation. In addition, S. pombe has a characteristic response to nutrient starvation, which causes cells to alter their morphology by dividing at a shorter cell length and …

Functional Features Of Hyperactive Deg/Enac Channels Involved In Cell Death, Cristina Matthewman

Open Access Dissertations

Ion channels of the DEG/ENaC family can induce neurodegeneration under conditions in which they become hyperactivated. The C. elegans DEG/ENaC channel MEC-4(d) encodes a mutant channel with a substitution in the pore domain that causes swelling and death of the six touch neurons in which it is expressed. Dominant mutations in homolog channel UNC-8 result in uncoordinated movement. Here we show that this unc-8(d) movement defect is correlated with the selective death of cholinergic motor neurons in the ventral nerve cord, a milder toxicity compared with MEC-4(d). UNC-8(G387E), denoted UNC-8(d), and UNC-8(A586T) mutants encode hyperactivated channels that are strongly inhibited …

Opposing Functions Of Microglial And Macrophagic Tnfr2 In The Pathogenesis Of Experimental Autoimmune Encephalomyelitis, Han Gao

Open Access Dissertations

In multiple sclerosis (MS), soluble tumor necrosis factor (TNF) is detrimental via activation of TNF receptor 1 (TNFR1), whereas transmembrane TNF is beneficial primarily by activating TNF receptor 2 (TNFR2). Here we investigate the role of TNFR2 in microglia and monocytes/macrophages in experimental autoimmune encephalomyelitis (EAE), a model of MS, by cell-specific gene targeting. We show that TNFR2 ablation in microglia leads to early onset of EAE with increased leukocyte infiltration, T cell activation, and demyelination in the central nervous system (CNS). Conversely, TNFR2 ablation in monocytes/macrophages results in EAE suppression with impaired peripheral T cell activation, and reduced CNS …

Oxygen Concentration Modulates Cardiac Stem Cell Proliferation And Migration, Michael A. Bellio

Open Access Dissertations

Cardiac stem cells (CSCs) are being evaluated for their efficacy in the treatment of heart failure. However, numerous factors impair the exogenously delivered cells’ regenerative capabilities. Hypoxia is one stress that contributes to inadequate tissue repair. Here, we tested the hypothesis that hypoxia impairs cell proliferation, survival, and migration of human CSCs relative to physiological and room air oxygen concentrations. Human endomyocardial biopsy-derived CSCs were isolated, selected for c-Kit expression, and expanded in vitro at room air (21% O2). To assess the effect on proliferation, survival, and migration, CSCs were transferred to physiologic (5%) or hypoxic (0.5%) O2 concentrations. Physiologic …

On-Line Adaptive Dynamic Programming For Feedback Control, Xiangnan Zhong

Open Access Dissertations

Stability analysis and controller design are among the most important issues in feedback control problems. Usually, controller design for linear system can be obtained by solving the Riccati equation. However, when comes to the nonlinear control problem, Riccati equation becomes the well-known Hamilton-Jacobi-Bellman (HJB) equation which is difficult to tackle directly. Fortunately, adaptive dynamic programming (ADP) has been widely recognized as one of the “core methodologies” to achieve optimal control in stochastic process in a general case to achieve brain-like intelligent control. Extensive efforts and promising results have been achieved over the past decades. The achievements cover a large variety …

Assessing Hand Hygiene Compliance In Healthcare Workers To Reduce Infectious Disease, Ahmed Salem Alhasani

Open Access Dissertations

Hand hygiene is the first line of defense against the prevalence of infectious diseases in healthcare settings. Therefore, healthcare costs can be reduced. However, having rare incidents of healthcare-associated infections (HAI) does not always mean that hand hygiene compliance is high and at its desired level. This research study aims to develop multi-statistical measurements to assess hand hygiene compliance of the medical and nursing groups at the inpatient wards, 5B, 6B and ICU at the Providence Veterans Affairs Medical Center (PVAMC). The PVAMC was trying to identify whether the few cases or rare incidents of HAI that have been reported …

Direct Substrate Recognition By The Atp-Dependent Chaperone Protease Clpxp And Roles In Proteostasis, Marissa Grace Viola

Open Access Dissertations

The AAA+ (ATPases associated with a variety of cellular activities) protein superfamily includes approximately 30,000 molecular machines powered by adenosine triphosphate (ATP) binding and hydrolysis events, which are important for many cellular processes, including cell division, DNA replication, intracellular transport, and protein quality control. The bacterial AAA+ protein ClpXP is a two component ATP-dependent chaperone-protease that recognizes protein substrates bearing specific recognition signals, subsequently unfolding and degrading them to eliminate unnecessary or misfolded proteins. Since degradation is irreversible, highly specific recognition motifs are needed to ensure intentional engagement. A common strategy to facilitate recognition of substrates by AAA+ ATPases is …

Using Natural Products To Treat Resistant And Persistent Bacterial Infections, Robert W. Deering

Open Access Dissertations

Antimicrobial resistance is a growing threat to human health both worldwide and in the United States. Most concerning is the emergence of multi-drug resistant (MDR) bacterial pathogens, especially the ‘ESKAPE’ pathogens for which treatment options are dwindling. To complicate the problem, approvals of antibiotic drugs are extremely low and many research and development efforts in the pharmaceutical industry have ceased, leaving little certainty that critical new antibiotics are nearing the clinic. New antibiotics are needed to continue treating these evolving infections. In addition to antibiotics, approaches that aim to inhibit or prevent antimicrobial resistance could be useful. Also, studies that …

Biological Process: Characterization, Establishment Of Shelf Life And Optimizing Method Transfers, Syama S. Adhibhatta

Open Access Dissertations

Biological processes are complex and can be modeled using combination of linear and non-linear models. During the cell culture process, cells may change or evolve and it is extremely important to understand the variability of the process to manufacture consistent product. In order to maximize the output from the process, process parameters need to be characterized and optimized. Data from process involves linear and non-linear patterns and some of the parameters are auto-correlated. One of the objectives of study was to compare Unsupervised Dimesional Reduction methods to Supervised machine learning algorithms applied to biopharmaceutical manufacturing process data and suggest a …

Testing The Effectiveness Of Brief Psychoeducation To Improve Parent Problem Recognition, Caroline M. Segal

Open Access Dissertations

A significant discrepancy exists between the rate of mental health problems in children and adolescents and their engagement in mental health services. A major contributor to this problem is poor mental health literacy among parents. Parents are typically responsible for identifying mental health issues in their children, but studies show that they struggle with problem recognition. The current study is the first randomized controlled trial to assess the effectiveness of an intervention to increase parents’ recognition skills of children’s mental health problems. Participants included 298 participants recruited from community and online settings. Participants ranged in age from 24 to 58 …

Insights Into Chromatin Modification And Fancd2 Phosphorylation In Dna Damage Repair, David Vierra Ii

Open Access Dissertations

Fanconi Anemia (FA) is a rare autosomal X-linked recessive disorder, characterized by congenital abnormalities, pediatric bone marrow failure and cancer susceptibility. FA is caused by biallelic mutation in any one of 22 different genes. The main functions of the FA-BRCA pathway is the resolution of interstrand crosslinks (ICLs) within the DNA. The main activating step of the pathway is the monoubiquitination of the proteins FANCD2 and FANCI. In the first chapter of this dissertation I discuss how methylation and acetylation affect chromatin architecture and activation of the pathway. In the second chapter I will discuss the effects of FANCD2 phosphorylation …

Using The Energy Of Membrane-Associated Folding For Tumor Targeting And Intracellular Cargo Delivery, Linden C. Wyatt

Open Access Dissertations

Cancer is the second leading cause of death in the United States. Due to the increase in exposure to cancer-causing environmental factors, the presence of chronic conditions, and the increase in age-related mutations in normal tissue, cancer incidence is positively correlated with age. Because of the increase in life expectancy due to advances in medicine, the frequency of cancer incidence is expected to rise in the future. For these reasons, devising methods to efficiently diagnose and treat cancer is extremely important.

Effective targeting of cancer cells within tumors would allow for improvement in the efficacy of treatment and the reduction …

Molecular-Level Design Of Nanoscale Environments For Enhanced Single-Molecule Sensing, Julie Christine Whelan

Open Access Dissertations

Single molecule studies depend upon precise control over the chemical and physical structure of the nanoscale sensing instrumentation and environment, and this demand is particularly stringent in the case of nanopores, a unique tool for single-molecule sensing and manipulation. The size and shape of the nanopores are critical to their function, and each facet, alone, presents experimental hurdles; this dissertation contains an approach to address both, simultaneously. A method for electroless deposition of gold onto solid-state silicon nitride nanopores has been developed to provide a foundation for precision tailoring of surface properties and nanopore size to study single analyte molecules …

Investigation Of Novel Electrolyte Additives In Lithium Ion Batteries At Elevated Temperatures, Bo Zhang

Open Access Dissertations

Lithium-ion batteries (LIBs) are currently one of the leading energy storage systems behind our everyday portable devices, electric vehicles, and power grids. Due to global energy crisis and rising demands for alternative energy resources, state funded renewable energy programs and tax incentives have propelled a groundbreaking era of rapid research and development in LIBs. While we are witnessing the global shift away from conventional fossil fuels, a few major obstacles have undermined the scalability and reliability of lithium-ion batteries technology, including limited energy density, operational temperature, calendar life and safety concerns.

Among numerous attempts to circumvent the issues discussed above, …

Agency In Eating Disorders: American Literary And Visual Memoirs Of Anorexia And Bulimia, Jenny Platz

Open Access Dissertations

In my dissertation I examine the representation of self-creation through anorexia and bulimia in memoiristic narratives, blogs, and YouTube videos in contemporary American culture. I argue that the highly crafted characterizations and structures of the anorexic and bulimic memoirs and blogs implement the disorders into temporary tools of self-care that grant the subjects agency through their pursuits of maturation and identity creation and cannot be simplified into mere warnings and retellings of the dangers of the eating disorders. I am locating my research in the late twentieth and early twenty-first century to encompass the emergence of eating disorder memoirs, Ana …

A Study Of Chinese Consumer Preferences For Sustainably Farmed Seafood, Chao Zou

Open Access Dissertations

Sustainable seafood programs have developed and evolved for approximately two decades as a market-based mechanism to complement the traditional “command and control” fishery management scheme. In some cases, they have successfully incentivized fishmen/fish farmers around the world to implement more environmentally sustainable production practices. It is not a perfect system capable of solving every fishery management issue immediately, but it is unequivocally one of the most promising mechanisms to slow down the degradation of wild fishery stocks or reduce environmental impacts from aquaculture, while improving the resilience of coastal fishery communities. As wild fishery stocks continue to decline, aquaculture production …

Challenging And Supportive Factors Encountered By Underrepresented Minority Doctoral Students In Science, Technology, Engineering, And Mathematics, Tessy Tatiana Pumaccahua

Open Access Dissertations

The purpose of the present study was to examine the supportive and challenging factors underrepresented minority students encounter in an academic setting as they obtain doctoral degrees in STEM disciplines. The study also explored the impact of students’ multiple social identities on their educational experiences, as well as the recommendations these students would provide to incoming doctoral students of color in STEM. Participants in this study consisted of 12 self-identified students from underrepresented minority backgrounds enrolled in STEM doctoral degree programs at predominately White institutions in the U.S.. Qualitative methods were utilized in this study. Specifically, the data was obtained …

Understanding Pregnancy Centered Medications: Characterizing The Interactions Of A Series Of Sulfonylurea Analogs And The Atp Binding Cassette Transporter Proteins, P-Glycoprotein And Breast Cancer Resistance Protein, Samuel D. Bell

Open Access Dissertations

The oral hypoglycemic agent Glyburide has been shown to be actively transported from various biological tissues though a pronounced interaction with the ATP binding cassette (ABC) active transport proteins. Specifically, Glyburide is actively transported by the ABC proteins, P-glycoprotein (Pgp), Breast Cancer Resistance Protein (BCRP), and the Multidrug Resistance Proteins (MRP). This active transport occurs at various locations throughout the body but has been identified as being responsible for Glyburide’s unique placental transport behavior. Glyburide has been shown to not cross the placental barrier to any appreciable effect and will leave the placental barrier against the concentration gradient. Understanding this …

Tools To Fight The Terrorist Threat, Matthew Michael Porter

Open Access Dissertations

Chemical, biological, radiological, nuclear, and explosives (CBRNE) terrorist threats put law enforcement and soldiers at risk both at home and abroad. Law enforcement and soldiers must be provided with tools and knowledge to stay ahead of the capabilities of terrorists. Hexamethylene Triperoxide Diamine (HMTD) is a homemade explosive easily synthesized from hexamine, citric acid, and hydrogen peroxide. Although HMTD is very sensitive and prone to stability problems, it has a history of terrorists use, such as in the London bombing of 2005. Because law enforcement personnel must handle this material with no guarantee of purity nor indication of additives, for …

Speaking Truth To Power: Stand-Up Comedians As Sophists, Jesters, Public Intellectuals And Activists, Jillian Belanger

Open Access Dissertations

Stand-up comedians are rhetors who use humor as a rhetorical tool to inform and persuade mass audiences in the classical rhetorical tradition. In this dissertation, I work to recover the rhetorical motives of stand-up comedy, just as rhetoric and composition scholars before me have reread and recovered the legacy of the Sophists. To that end, I align stand-up comedians first with the historical heritage of Sophists and jesters, and then with the more contemporary tradition of public intellectuals and social activists. Using excerpts from stand-up comedy performances, I demonstrate how stand-up comedians are able to persuade and educate with humor. …

Greenhouse Gas Emissions From Biological Nutrient Removal During Wastewater Treatment, Elizabeth Quinn Brannon

Open Access Dissertations

Since the 1900s, humans have been altering the global nitrogen (N) cycle by industrially fixing N for fertilizer production. This reactive N is often released back to coastal environments through many mechanisms, including wastewater treatment, where it can lead to numerous consequences such as fish kills and algae blooms.

In many locations, wastewater treatment effluent is one of the largest sources of excess N to coastal environments. Although regulations limiting N loads in wastewater effluent in the U.S. were first developed in the 1970s, stricter regulations started to emerge in many states in the 2000s. In order to meet new …

Organellar Genome Evolution In Red Algal Parasites: Differences In Adelpho- And Alloparasites, Eric Salomaki

Open Access Dissertations

Parasitism is a common life strategy throughout the eukaryotic tree of life. Many devastating human pathogens, including the causative agents of malaria and toxoplasmosis, have evolved from a photosynthetic ancestor. However, how an organism transitions from a photosynthetic to a parasitic life history strategy remains mostly unknown. Parasites have independently evolved dozens of times throughout the Florideophyceae (Rhodophyta), and often infect close relatives. This framework enables direct comparisons between autotrophs and parasites to investigate the early stages of parasite evolution. Parasitic red algae have traditionally been defined as either ‘adelphoparasites’, which infect hosts within their same family or tribe, or …

The Effects Of Tca Cycle Mutations On The Virulence Of Vibrio Aguillarum Strains M93sm And Nb10sm, Edward Spinard

Open Access Dissertations

Vibrio anguillarum is an extracellular bacterial pathogen that is a causative agent of vibriosis in finfish and crustaceans. Mortality rates range from 30% to 100% and systemic infection usually causes fish to die within 1-4 days of initial infection. The primary routes of infections are through the skin, gills and intestines. Chemotactic motility and the metalloprotease EmpA have been shown to be important virulence factors during the invasion stage while the siderophore anguibactin, flagellin subunits and lipopolysaccharides were shown to be important for persistence in the host during the post-invasion stage. Three secreted proteins that are cytotoxic against epithelial cells …

High Throughput And Mechanistic Analysis Of The Hrd Motif Of Src Protein Tyrosine Kinase, Yixin Cui

Open Access Dissertations

Protein tyrosine kinases (PTK) play essential roles in cell signal transduction pathways. PTKs are associated with numerous diseases and promote oncogenic cell signal transduction in unregulated forms. Thus PTKs represent a large group of potential targets for anticancer drug discovery. Src was the first identified oncogene and has been intensively studied for decades. The work described in this dissertation studied the structure-function relationships of Src, to build a knowledge base for the function of conserved residues in the kinase domain. To accomplish this, the first focus of this dissertation was to develop a high throughput screening method to identify kinase …

Characterization Of A H4k20me2 Methyl-Binding Domain In The Fanconi Anemia Protein Fancd2, Karissa Lynn Paquin

Open Access Dissertations

Fanconi anemia (FA) is a rare genetic disease that results on early onset bone marrow failure, congenital defects, and increased cancer susceptibility. It is caused by mutation in any one of twenty two genes, whose protein products work in conjunction as part of the FA-BRCA pathway, a DNA repair pathway that specifically repairs DNA interstrand crosslinks (ICLs). One of the key steps in pathway activation is the monoubiquitination of the FANCD2 protein. Upon pathway activation, FANCD2 is recruited to sites of DNA damage, where is interacts with downstream repair protiens to promote DNA repair via homologous recombination (HR). How FANCD2 …

Characterization Of Cellulose Synthesis Complexes In Physcomitrella Patens, Xingxing Li

Open Access Dissertations

Due to the enormous economic value and significance of cellulose in human consumption and plant cell walls, production of cellulose microfibrils is considered to be one of the most critical biochemical processes in plant biology. In the past decades, cellulose biosynthesis has been extensively studied in vascular plants. More and more fundamental questions related to this key process are being answered. One such question is: What are the protein components of the enzymatic complex for cellulose synthesis? In seed plants, membrane-embedded rosette Cellulose Synthesis Complexes (CSCs) producing cellulose microfibrils are obligate hetero-oligomeric, being assembled from three functionally distinct and non-interchangeable …

Conformational Insights Into Aminobiphenyl-Modified Dna: Implications For Mutation And Repair, Ang Cai

Open Access Dissertations

Cancer is a major public health problem worldwide. An estimated 1.6 million new cases of cancer will be diagnosed in the United States in 2017. Most cancers are assumed to develop from the initiation of chemically induced DNA damages. Chemical carcinogens are genotoxic and they undergo enzymatic activation into reactive electrophilic species to form covalent bonds with the electron-rich DNA that form adducts. Aromatic amines are one of the most examined chemical carcinogens, and once activated, these amines attack the C-8 position of guanine to form C8-dG adducts (ABP [N-(2′-deoxyguanosin-8-yl)-2-aminobiphenyl], AF [N-(2′-deoxyguanosin-8-yl)-2-aminofluorene], and AAF [N-(2′-deoxyguanosin-8-yl)-2 acetylaminofluorene]); these formations result in …

Modeling Gas Budgets In Marginal Sea Ice Zones, Arash Bigdeli

Open Access Dissertations

Biogeochemical gas budgets at high-latitude regions and sea ice zones are a source of uncertainty in climate models. The four main processes that regulate these budgets include advection, ventilation, mixing, and accumulation/release from sea ice. Considering the scarcity of data in sea ice zones, specifically during winter time, the environment is too poorly sampled to constrain these processes through direct measurements; hence we proposed models to systematically investigate these processes. The models proposed in this dissertation consist of regional numerical ice-ocean models, 1D forward and inversion numerical models, and analytical models.

Manuscript I of this dissertation focuses on a 3D …

Bifurcations Of Some Planar Discrete Dynamical Systems With Applications, Toufik Khyat

Open Access Dissertations

The focus of this thesis is on some contemporary problems in the field of difference equations and discrete dynamical systems. The problems that I worked on range global attractivity results to all types of bifurcations for systems of difference equations in the plane.

The major goal was to investigate the impact of nonlinear perturbation and the introduction of quadratic terms on linear fractional difference equations such as the Beverton-Holt as well as the Sigmoid Beverton-Holt Model with delay that describes the growth or decay of single species.

The first Manuscript was on the study of the following equation:

[Mathematical equations …

Novel Methods For Delivering And Promoting The Endosomal Escape Of Nucleic Acid Based Drugs: Chiral Polyamines And Hydrophobic Nanoparticle-Containing Liposomes, Ruchi Verma

Open Access Dissertations

Nucleic acid based drugs such as plasmid DNA (pDNA), small interfering RNA (siRNA), short hairpin RNA (shRNA), micro RNA (miRNA), and both antisense and antigene oligonucleotides, are potentially potent and specific compounds for therapeutic applications. Many major life threatening ailments might be treated using these molecules, and many polynucleotide products are currently in advanced clinical development. However, their successful therapeutic application is hindered due to limited delivery to their site of action in either the cytosol or the nucleus of a cell. Some of the barriers in the path of successful delivery of these biomolecules to their site of action …