Digital Commons Network^™

Integral Measurement Of Atmospheric Particulate Matter (Pm), Di Liu

Theses and Dissertations

Atmospheric aerosol particles also known as atmospheric particulate matter or particulate matter (PM) are microscopic particles (solid or liquid) suspended in air, which is one of six air pollutants in US air quality standard. PM is classified as coarse particles with diameters between 2.5 to 10 mm, fine particles with a diameter less than 2.5 mm (PM_2.5), and ultrafine particles with the diameter less than 0.1 mm (PM_0.1). Epidemiological studies have already showed the adverse health effects (such as asthma, lung cancer and respiratory and cardiovascular disease) resulted from exposure to the fine and ultrafine particles. …

Role Of C121a In Mglur2 Homodimeric Expression And Function, Jong M. Shin

Theses and Dissertations

The group II metabotropic glutamate receptors are known for their involvement in various psychiatric disorders. The mGluR2 in particular is linked with etiology of schizophrenia especially in the context of crosstalk with 5-HT2A. Thus, the mGluR2 has attracted attentions for its potential therapeutic applications. Despite numerous physiological evidences on the actions of mGluR2, its mechanism is still unclear to this day. It is partially due to the lack of understanding in characteristics of mGluR2 homodimer which is its functionally active form. Therefore, the characterization of dimeric interaction serves as a foundation to advanced understanding of the role of mGluR2. On …

In Vitro Genetic Code Expansion And Selected Applications, Emil S. Iqbal

Theses and Dissertations

The ability of incorporation non-canonical amino acids (ncAAs) using translation offers researchers the ability of extend the functionality of proteins and peptides for many applications including synthetic biology, biophysical and structural studies, and discovery of novel ligands. Here we describe the three projects where the addition of ncAAs to in vitro translation systems creates useful chemical biology techniques. In the first, a fluorinated histidine derivative is used to create a novel affinity tag that allows for the selective purification of peptides from a complex mixture of proteins. In the second, the high promiscuity of an editing-deficient valine-tRNA synthetase (ValRS T222P) …

Investigating Racial Bias In Perceptions Of Free Will, Courtney J. Alderson

Theses and Dissertations

The overarching goal of this study was to examine whether perceptions of others’ free will would differ depending on perceiver race as well as target race. The current study proposed that such a racial bias may be one mechanism by which racial disparities in medical treatment recommendations arise. By bridging findings from four different lines of research (i.e., the literatures on racial health and medical treatment disparities, racial bias, free will beliefs, and social identity), it was hypothesized that: (1) participants would perceive greater amounts of free will for a hypothetical racial ingroup patient than an outgroup patient; (2) such …

An Investigation Of Electronic Cigarette Aerosol Mixture On Craniofacial Development In Mouse Embryos, Suraj Kandalam

Theses and Dissertations

E-cigarette (e-cig) use has increased in recent years among teenagers and young adults. E-cigs are battery-powered nicotine delivery systems that vaporize e-liquids, a solution composed of propylene glycol (PG), vegetable glycerin (VG), nicotine, flavoring, and coloring agents. The aim of this study was to determine the effects of exposure to e-cig aerosol mixtures (e-cigAMs) on proliferation, migration, and differentiation of NCCs in vitro and craniofacial development in mouse embryos in vivo. E-cigAM was produced by bubbling e-cig aerosol into saline. E-cigAMs were generated for unflavored e-liquid of increasing PG: VG ratio. Metabolic activity (MA), gene expression, migration, and proliferation …

Exploring Literacies In The Assemblage Of Adult Education English For Speakers Of Other Languages Classrooms, Susan Watson

Theses and Dissertations

The purpose of this dissertation is to provide a posthuman perspective of adult second language and literacy learning using the philosophy of Gilles Deleuze and his collaborative work with Félix Guattari, Masny’s (2005/6) multiple literacies theory or MLT, and DeLanda’s (2016) assemblage theory. Thinking with these scholars, I employ a post-qualitative, posthuman MLT conceptual framework to study literacy as a process that flows through and connects with globally-diverse students, languages, worldviews, and texts in the assemblage of adult education, English for speakers of other languages (ESOL) classrooms. I posit this assemblage as a remarkable and important context for literacy research …

Novel Insights Into The Contribution Of Cellular Senescence To Cancer Therapy: Reversibility, Dormancy And Senolysis., Tareq Saleh

Theses and Dissertations

Cellular senescence a specialized form of growth arrest that contributes to the pathogenesis of several aging-related disorders including cancer. While by definition tumor cells are considered immortalized, they can undergo senescence when exposed to conventional and targeted cancer therapy. Therapy-Induced Senescence (TIS) represents a fundamental response to therapy and impacts its outcomes. However, TIS has been considered a positive therapeutic goal since senescent tumor cells are expected to enter a state of permanent growth abrogation. In this work we examined the hypothesis that a subpopulation of senescent cells can re-acquire proliferative potential after a state of senescent dormancy, indicating that …

The Interaction Between Ceramide-1-Phosphate And Group Iva Cytosolic Phospholipase A2 And Its Role In Wound Healing, Patrick Macknight

Theses and Dissertations

The sphingolipid, ceramide-1-phosphate (C1P), directly binds and activates Group IVA cytosolic phospholipase A₂ (cPLA₂a) to generate eicosanoids. Due to the role of eicosanoids in wound healing, we choose to use our novel genetic mouse model expressing cPLA₂a with an ablated C1P interaction site (KI) to examine the cPLA₂a/C1P interaction in wound healing. Wound closure rate was not affected, but wound maturation was dramatically enhanced by loss of the C1P/cPLA₂α interaction based on the following findings. Wounds in KI mice displayed: i) increased infiltration of dermal fibroblasts into the wound environment; ii …

Impact Of Aerobic Exercise On Monocyte Subset Receptor Expression And Macrophage Polarization, Anson M. Blanks

Theses and Dissertations

Atherosclerotic cardiovascular disease (CVD) is hallmarked by inflammatory immune activation, particularly by the induction of a response by monocytes. Classical (CD14⁺⁺CD16^-) are anti-inflammatory mediators under homeostatic conditions, while intermediate (CD14⁺⁺CD16⁺) and non-classical (CD14^LowCD16⁺⁺) monocytes promote inflammation following activation. Monocyte activation and functionality is dependent upon receptor expression and ligand production by a variety of cells, including monocytes. Alterations in the expression of surface receptors often have a direct impact upon monocyte function, such as the increased pro-inflammatory cytokine production in response to activation that accompanies elevated CD14 expression …

Discovering Driver Mutations In Biological Data, Yahya Bokhari

Theses and Dissertations

Background

Somatic mutations accumulate in human cells throughout life. Some may have no adverse consequences, but some of them may lead to cancer. A cancer genome is typically unstable, and thus more mutations can accumulate in the DNA of cancer cells. An ongoing problem is to figure out which mutations are drivers - play a role in oncogenesis, and which are passengers - do not play a role. One way of addressing this question is through inspection of somatic mutations in DNA of cancer samples from a cohort of patients and detection of patterns that differentiate driver from passenger mutations. …

Trna Profiling Of Mesenchymal Stem Cell Exosome, Khin Mimi San

Theses and Dissertations

Background: Exosomes have great potential in regenerative medicine through the

transfer of their bioactive cargos, such as RNA. tRF RNA and tiRNA are tRNAderived

non-coding RNA. Here, we sought to identify the tRF/tiRNA profile in human

mesenchymal stem cell (hMSC) exosomes. Methods: Bone marrow hMSCs were

cultured with/without osteogenic differentiation medium and exosomes were

harvested. RNA was extracted from: 1) control cells (Cell-NT); 2) control exosomes

(EXO-NT); 3) differentiated cells (Cell-OM); 4) exosomes produced by differentiated

cells (EXO-OM). RNA was sequenced to profile the small RNA with a focus on

tRF/tiRNA. Results: tRF/tiRNA was highly enriched in hMSC exosomes. Less …

Genomic Instability In Severe Congenital Neutropenia, A Leukemia Predisposition Syndrome, Adya Sapra

Theses and Dissertations

Severe congenital neutropenia (SCN) is a rare blood disorder characterized by abnormally low levels of circulating neutrophils. Mutations in multiple genes like neutrophil elastase gene (ELANE) and granulocyte colony stimulating factor receptor (CSF3R) may cause SCN. The treatment of choice for SCN is the administration of granulocyte-colony stimulating factor (G-CSF) which elevates the neutrophil count and hence improves the survival and quality of life. Long term survivorship on G-CSF is however linked to development of MDS (myelodysplastic syndrome)/AML (acute myeloid leukemia). About 70% of MDS/AML patients acquire nonsense mutations affecting the cytoplasmic domain of CSF3R. …

Water Dynamics And The Effect Of Static And Alternating Electric Fields, Mohammadmahdi Shafiei Alavijeh

Theses and Dissertations

Having a net dipole moment, water molecules tend to align with an external electric field. The re-orientation of water molecules to align with the field direction can result in structural and dynamic changes in liquid water. Studying these changes can help us to understand the role of an E-field in many biological systems, chemical reactions, and many technological advancements.

In short, the application of static electric fields causes molecules to stay aligned with the field, so, fewer hydrogen bonds break, and molecules have slower dynamics. This type of field can be used when the mobility of water molecules needs to …

Lanthanide-Based Core-Shell Nanoparticles As Multifunctional Platforms For Targeted Radionuclide Therapy And Multimodal Molecular Imaging, Miguel Toro-Gonzalez

Theses and Dissertations

Lanthanide phosphate (LnPO₄) and lanthanide vanadate (LnVO₄) nanoparticles (NPs) are promising platforms for theranostic applications because of their chemical stability, low solubility, low toxicity, and unique luminescence and magnetic properties. Motivated by the high radiation resistance and ability to host actinides of naturally occurring lanthanide-based compounds, LnPO₄ and LnVO₄ NPs were studied as radionuclide carriers for targeted radionuclide therapy using in vivoα-generators, ²²³Ra, ²²⁵Ac, and ²²⁷Th. The implementation of these radionuclides has shown potential for the treatment of micrometastases and solid tumors as well as challenges in the retention of …

Quantitative And Molecular Analysis Of Habituation At The Maize R1 Locus, Robert C. Lindsay

Theses and Dissertations

Epigenetics is the study of heritable changes in phenotypes that are not the result of changes in DNA sequence. Examples of epigenetic affecters include methylation changes, chromatin modifications, transcription factors, and RNA-based changes. The molecular mechanisms behind epigenetic changes are not fully understood. Canalization is the buffering of gene expression against environmental changes over time, while habituation is semi-stable expression change over time due to selection. This work characterized the molecular changes associated with the kernel color changes of the R-sc:86-17pale allele at the maize red color1 (r1) locus to determine if the changes are epigenetic in nature. …

Alternative Splicing Of Cytoplasmic Polyadenylation Element Binding Protein 2 Is Modulated Via Serine Arginine Splicing Factor 3 In Cancer Metastasis, James T. Deligio, James Thomas Deligio

Theses and Dissertations

Our laboratory delineated a role for alternative pre-mRNA splicing (AS) in triple negative breast cancer (TNBC). We found the translational regulator cytosolic polyadenylation element binding protein 2 (CPEB2) which has two isoforms, CPEB2A and CPEB2B, is alternatively spliced during acquisition of anoikis resistance (AnR) and metastasis. The splicing event which determines the CPEB2 isoform is via inclusion/ exclusion of exon four in the mature mRNA transcript. The loss of CPEB2A with a concomitant increase in CPEB2B is required for TNBC cells to metastasize in vivo. We examined RNAseq profiles of TNBC cells which had CPEB2 isoforms specifically downregulated to …

Spatial Learning And Memory In Brain-Injured And Non-Injured Mice: Investigating The Roles Of Diacylglycerol Lipase-Α And -Β., Lesley D. Schurman

Theses and Dissertations

A growing body of evidence implicates the importance of the endogenous cannabinoid 2-arachidonyl glycerol (2-AG) in memory regulation. The biosynthesis of 2-AG occurs primarily through the diacylglycerol lipases (DAGL-α and -β), with 2-AG serving as a bioactive lipid to both activate cannabinoid receptors and as a rate limiting precursor for the production of arachidonic acid and subsequent pro-inflammatory mediators. Gene deletion of DAGL-α shows decrements in synaptic plasticity and hippocampal neurogenesis suggesting this biosynthetic enzyme may be important for processes of normal spatial memory. Additionally, 2-AG is elevated in response to pathogenic events such as traumatic brain injury (TBI), suggesting …

Snd1-Targeted Gene Therapy For Hepatocellular Carcinoma, Bryan D. Mckiver

Theses and Dissertations

Staphylococcal nuclease and tudor-domain containing 1 (SND1) is an oncogene for a wide variety of cancers, including hepatocellular carcinoma (HCC). SND1 is a multifunctional protein regulating gene expression of proto-oncogenes and tumor suppressor genes, making SND1 a prime target for developing cancer therapeutics. This notion is especially attributed to HCC as most patients are diagnosed in advanced stages and the therapeutic options available for these patients are severely limited. In this study, we evaluated the therapeutic potential of a replication-defective adenovirus vector delivering SND1 shRNA (Ad.SND1sh) to human HCC cell lines, HepG3, HuH-7, and Hep3B. Adenovirus infection in HCC cells …

The Role Of Adam10 And Adam17 In Humoral And Type 2 Immunity, Joseph C. Lownik

Theses and Dissertations

The proper regulation of inducible costimulator (ICOS) and its ligand (ICOSL) have been shown to be essential for maintaining immune homeostasis. Loss of either protein results in defective humoral immunity, and overexpression of ICOS results in aberrant antibody production resembling lupus. How ICOSL is regulated in response to ICOS interaction is still unclear. We demonstrate that ADAM10 is the primary physiological sheddase of ICOSL in both mouse and human. Using an in vivo system in which ADAM10 is deleted only on B cells (ADAM10^B-/-), elevated levels of ICOSL were seen. This increase is also seen when ADAM10 is …

Signaling Through Homomeric And Heteromeric Cannabinoid Cb1 Receptors, Guoqing Xiang

Theses and Dissertations

Cannabis (Marijuana) has multiple effects on the human body, such as analgesia, euphoria and memory impairment. Delta-9 tetrahydrocannabinol (D9-THC), the active ingredient in cannabis, binds to cannabinoid receptors, seven-transmembrane G protein-coupled receptors (GPCRs) that mediate a variety of physiological functions. GPCRs were believed to function only in homomeric forms, however, recent findings show that different GPCRs can also form heteromeric complexes that may expand their signaling properties. In this study, we focused on Cannabinoid CB1 receptor (CB1R) heteromers with the mu-opioid receptor (MOR) and the Dopamine type 2 receptor (D2R), respectively. We utilized a variety of techniques, such as the …

Effects Of Hiv-1 Tat And Drugs Of Abuse On Antiretroviral Penetration Inside Different Cns Cell Types, Sulay H. Patel

Theses and Dissertations

Human immunodeficiency (HIV) infection can result in neurocognitive deficits in about one-half of infected individuals. Despite excellent systemic effectiveness, restricted antiretroviral penetration across the blood-brain barrier (BBB) is a major limitation in fighting HIV infection within the central nervous system (CNS). Drug abuse exacerbates cognitive impairment and pathologic CNS changes in HIV-infected individuals. This work investigates the effects of the HIV-1 protein, Tat, and drugs of abuse on factors affecting drug penetration into the brain.

Firstly, an in vitro model of the blood-brain barrier was built to study effects of HIV-1 Tat and methamphetamine (Meth) on integrity and function of …

Relationship Between Patient-Health Coach Interactions And Changes In Markers Of Glucose Homeostasis, Jason P. Nagy

Theses and Dissertations

Diabetes and insulin resistance are on the rise in the United States. Early detection and deployment of therapies has allowed for the reversal of pancreatic beta cell damage. Unfortunately, not all providers can offer the support to facilitating the required life style modifications. The introduction of clinical health consultants (CHC) as supplemental care has improved patient health for a variety of chronic diseases. Missing in the literature are studies investigating the correlation between the number of CHC interactions and improvement in biomarkers.

The study utilized a non-experimental, retrospective study design to evaluate the relationship between the use between the use …

Family Planning And Hiv Interventions Among Women In Low-Income Settings, Steven P. Masiano

Theses and Dissertations

This dissertation examines the effectiveness of interventions related to family planning and the uptake of HIV-related preventive services among women in low-income settings. Women in low-income settings and living with HIV face many barriers to care, including limited access to services for family planning and HIV-related preventive care. At the same time, national, regional, and global efforts are looking for interventions to help control rapid population growth, create an HIV-free generation, and provide adequate preventive care for those living with HIV. This dissertation cuts across these issues and can help to inform debate and policies to address these issues.

This …

Drug Delivery With Light, Patrick S. Dupart

Theses and Dissertations

Cancer is responsible for about 25% of deaths in developed countries and for 15% of all deaths worldwide. Cancer is a devastating disease and while there have been great advances in the development of anticancer drugs, off-target toxicity is a major limitation with conventional cancer chemotherapy. The consequence of this form of treatment results in the killing of healthy and rapidly-growing non-cancerous cells including cells in the bone marrow; hair follicles; and cells in the mouth, digestive tract, and reproductive system. In addition to these general effects, certain anticancer drugs can have other associated toxicities. For instance, the anticancer drug …

"To Conceive With Child Is The Earnest Desire If Not Of All, Yet Of Most Women": The Advancement Of Prenatal Care And Childbirth In Early Modern England: 1500-1770, Victoria E.C. Glover

Theses and Dissertations

This thesis analyzes medical manuals published in England between 1500 and 1770 to trace developing medical understandings and prescriptive approaches to conception, pregnancy, and childbirth. While there have been plenty of books written regarding social and religious changes in the reproductive process during the early modern era, there is a dearth of scholarly work focusing on the medical changes which took place in obstetrics over this period. Early modern England was a time of great change in the field of obstetrics as physicians incorporated newly-discovered knowledge about the male and female body, new fields and tools, and new or revived …

Decoding The Signaling Of The D2r-2ar Heteromer: Relevance To Schizophrenia, Miao Huang

Theses and Dissertations

Schizophrenia is a severe mental disorder affecting ~1% of world population. Two G protein coupled receptors (GPCRs): Gi-coupled dopamine D2 receptor (D₂R), and Gq-coupled serotonin 2A receptor (2AR), are targeted by the typical and atypical antipsychotic drugs to treat schizophrenia. These two receptors have been shown to co-localize in brain regions relevant to schizophrenia, including the ventral tegmental area (VTA), striatum, and prefrontal cortex (PFC). Studies in our lab characterized the integrated signaling of the D₂R-2AR heteromer and found that both the Gi activity of D₂R and the Gq activity of 2AR were potentiated …

Effects Of A 2-Week Exercise Intervention On Heart Rate Variability In Individuals With Low And High Anxiety Sensitivity, Hannah M. Kotarski

Theses and Dissertations

Anxiety Sensitivity (AS), the belief that anxiety-related sensations may have harmful implications, can alter autonomic nervous system (ANS) function. Exercise has previously been shown to reduce AS; however, the effects of an exercise intervention on heart rate variability (HRV), a measure of ANS function, has not been evaluated in individuals with high AS. This study sought to 1) compare resting HRV in individuals with either low (LAS) or high AS (HAS) and 2) evaluate the effects of a 2-week exercise intervention on HRV and AS. Using the Anxiety Sensitivity Index (ASI-3), participants were identified as LAS (n=9; ASI-3=5.89±1.39) or HAS …

Nicotinic Acetylcholine Receptor Dependent Effects Of Nicotine On Hek293t And Hbo Cells, James D. Larsen

Theses and Dissertations

T2R receptors are the classical bitter taste receptors which detect and transduce bitter taste in a subset of taste receptor cells (TRCs). The TRPM5-dependent T2Rs are G-protein coupled receptors (GPCRs) and are linked to G protein, gustducin to initiate an intracellular signaling cascade for the transduction of bitter tastants. Nicotine is bitter. However, at present the transduction mechanisms for the detection of nicotine in are poorly understood. Previous studies from our laboratory using TRPM5 knockout (KO) mice demonstrated that the T2R pathway is insufficient in explaining the taste perception of nicotine. TRPM5 KO mice elicited chorda tympani (CT) taste nerve …

Toxicological Inhalation Effects Of Metal-Based Nanoparticle Aerosols As Studied By A Portable In Vitro Exposure Cassette, Lynn E. Secondo

Theses and Dissertations

The toxicology of aerosols in occupational settings is often performed through particle collection on a filter followed by reconstitution into cell culture media which can alter the biological effects. Current in vitro exposure systems require additional instruments to control temperature and humidity, making the system bulky and difficult to take to the field. The Portable In Vitro Exposure Cassette (PIVEC) was designed for personal monitoring, characterized using copper nanoparticles, tested with alveolar cells, and set-up for real-time monitoring. Three differently sized copper nanoparticles, 40-800 nm, were dispersed as a dry aerosol and measured gravimetrically and on a number concentration basis …

The Effect Of Biologic Materials And Oral Steroids On Radiographic And Clinical Outcomes Of Horizontal Alveolar Ridge Augmentation., Amy Reichert

Theses and Dissertations

The purpose of this study was to investigate if the addition of biologic materials and/or oral steroids would affect horizontal bone gain, or the bone density of the grafted bone in horizontal alveolar ridge augmentations. A retrospective chart review was completed to assess the clinical and radiographic outcomes of 53 ridge augmentation patients. An average bone gain of 3.6mm of width was found in our study based on radiographic analysis. There were no statistically significant differences found in the linear bone gain with the addition of biologic materials and steroids. A marginally statistically significant difference was found in the bone …