Master of Science, University of Toledo, 2019, Bioengineering

Musculoskeletal tissue injuries affect around 1 in 3 Americans and 1.7 billion people worldwide. This is a huge economic burden, costing an estimated $120 billion in the US alone. With limited success from surgery or subcutaneous injections of medicine, where only temporary relief or complications can occur, alternative measures should be explored. Injectable biologically-loaded hydrogels are one avenue and act as drug delivery systems. They provide a minimally invasive approach to release biologics in a sustained and controlled manner to provide long-lasting relief without toxic effects and with less risk of surgical complications. In this study, the immunological application of a previously-developed nanofibrous PCL-interspersed collagen hydrogel, (PNCOL) was explored by loading PNCOL with the cytokine IL-4 and identifying its effect upon macrophages. Furthermore, the effect of a simulated digestive inflammatory environment (DIE) had upon protein release kinetics as well as scaffold integrity were characterized. Genipin crosslinking was then explored to improve scaffold resistance to degradation, and an optimal genipin concentration was identified to impart sufficient scaffold crosslinking, increased mechanical strength, and a prolonged release profile, with minimal cytotoxic effects. Lastly, the immunomodulatory effect of IL-4 released from crosslinked and uncrosslinked scaffolds were investigated through identifying the impact of IL-4 on macrophage differentiation. The IL-4 released from PNCOL polarized macrophages toward an anti-inflammatory, pro-healing state, while genipin crosslinking with and without IL-4's presence appeared to lower macrophage activity.

Committee: Eda Yildirim-Ayan PhD (Advisor); Eda Yildirim-Ayan PhD (Committee Chair); Halim Ayan PhD (Committee Member); Arun Nadarajah PhD (Committee Member) Subjects: Biology; Biomedical Engineering; Biomedical Research; Cellular Biology; Materials Science

Master of Science (MS), Wright State University, 2019, Microbiology and Immunology

Macrophages are phagocytic cells located in tissues, organs and even circulated within our body as white blood cells. They are critical in detecting tissue damage and infection. Resident tissue macrophages initiate the signals for inflammation recruiting neutrophils and blood monocytes which mature into macrophages at sites of infection and in the resolution of inflammation. Based on the local cytokine milieu in tissue sites, macrophages may be polarized into pro-inflammatory M1 or anti-inflammatory M2 phenotypes. Receptor tyrosine kinase Mer (MERTK) helps in clearing dead neutrophils and other apoptotic cells from damaged tissue sites preventing chronic inflammation and autoimmune disorders. MERTK aids in the maintenance of tissue homeostasis and wound healing. Phosphatidylserine (PtdSer) present on the surface of apoptotic cells release “eat me” signals which are recognized by the two “bridging ligands” of MERTK receptor, Gas6 and ProS. The binding of the ligands to PtdSer initiates intracellular signals leading to phagocytosis of the cell. MERTK receptor is expressed mostly on M2c macrophages. The current study explores the expression rate of the phagocytic receptor MERTK, on macrophages polarized with either IL-10 (M2c ells) or IL-4 or IL-13 (M2a macrophages) following treatment with the suppressor of cytokine signaling SOCS3 in comparison with macrophage polarization with only IL-10 or IL-4 or IL-13 . The current study exhibits an enhancement in the expression of the phagocytic MERTK receptor on the surface of IL-10 polarized M2c macrophage when treated with SOCS3 in comparison to IL-10 polarized M2c macrophage, IL-4 polarized M2a macrophage and IL-13 treated M2a macrophage. IL-13 polarized M2a macrophage also shows an increase in the expression of MERTK receptor which is similar to a previous study where a similar receptor to MERTK termed “Axl receptor” is enhanced by IL-13 treatment on bone- marrow derived macrophage. SOCS3 when treated with IL-13 polar (open full item for complete abstract)

Committee: Nancy J. Bigley Ph.D. (Advisor); Dawn P. Wooley Ph.D. (Committee Member); Marjorie Markopoulos Ph.D. (Committee Member) Subjects: Immunology; Microbiology

Master of Science in Biomedical Engineering (MSBME), Wright State University, 2018, Biomedical Engineering

Modulation of macrophage polarization is required for effective tissue repair and regenerative therapies. Conversion of macrophages from inflammatory M1 to fibrotic M2 phenotype could help in diseases such as chronic wound which are stuck in inflammatory state. During the inflammatory phase, macrophages are of the inflammatory phenotype (M1) and distribute pro-inflammatory cytokines including TNF-a and IL1ß which are microbicidal and recruit/activate cells. In normal wound healing macrophages then switch to a fibrotic phenotype (M2) promoting wound closure by angiogenesis, and matrix deposition. Chronic wounds are a major biological and financial burden to both patients and the health care system, costing over $25 billion to Medicare annually. Natural wound healing proceeds through several largely overlapping phases that involve an inflammatory response and associated cellular migration, proliferation, matrix deposition, and tissue remodeling. The initial stages of the inflammatory response are dominated by neutrophils followed soon after by macrophages, which become prominent at the wound site. A sustained inflammation is an important aspect in the disruption of the normal healing process that can lead to a chronic condition. The chronic conditions start when the highly phagocytic M1 macrophages are done removing any infected or non-functional cells, and any damaged matrix or foreign debris and do not differentiate into an M2 phenotype. Thus, inducing these sustained M1 macrophages to differentiate into an M2 phenotype should correct this condition, and has been shown to improve wound healing. We suggest simultaneously using retinoic acid (RA) and mesenchymal stem cells (MSCs) to promote M1 to M2 transition. RA and MSCs have both shown to promote M1 to M2 transition, and in addition, MSCs can promote wound regeneration. We hypothesize that treating M1 macrophages with retinoic acid and mesenchymal stem cells loaded on a pullulan/gelatin scaffold will promote M1 (open full item for complete abstract)

Committee: Jaime Ramirez-Vick Ph.D. (Advisor); Nasim Nosoudi Ph.D. (Committee Member); Amir Zadeh Ph.D. (Committee Member) Subjects: Biomedical Engineering

Master of Science in Biomedical Sciences (MSBS), University of Toledo, 2017, Biomedical Sciences (Bioinformatics and Proteomics/Genomics)

Macrophages are critical cells in the immune system implicated in various diseases with a chronic inflammatory component, such as atherosclerosis. The dominant macrophage types, M1 and M2, play key roles in progression and regression of atherosclerotic plaques. In this study, we profiled the transcriptomes of these macrophage subsets using RNA-Seq and microarray to examine molecular signatures and distinctive pathways for each subset. RNA-Seq analysis revealed a total of 2,127 differentially expressed genes (including coding and non-coding transcripts) between the M1 and M2 subsets. Validation by qRT-PCR of 10 top differentially expressed genes showed that 8 of the upregulated and 9 of the downregulated genes followed the expected trend based on the RNA-Seq analysis. Subsequently, pathway analysis of the upregulated and downregulated gene sets showed M1 and M2 macrophages to be enriched in pathways such as the Th1 and glioma signaling respectively. Microarray analysis revealed a total of 163 differentially expressed circRNAs between the two macrophage subsets and predictions of circRNA/miRNA interactions. From these circRNA/miRNA interactions, a number of the differentially expressed circRNAs were predicted to target athero-relevant miRNAs. As examples, circRNA_41878 (gene Ankrd42) was predicted to target miR-382-5p while circRNA_19794 (gene Lmbrd1) was predicted to target miR-124-3p, miRNAs of recognized effects in atherosclerosis. Overall, this work provides insight into distinctive molecular signatures and pathways enriched in bone-marrow derived M1 and M2 macrophages, and reveals the presence and contribution of non-protein-coding RNAs to their transcriptomes. In addition, our circRNA results provide the basis for future studies on the function of circRNAs in the context of macrophage functions in atherosclerosis.

Committee: Guillermo Vazquez (Committee Chair); Bina Joe (Committee Member); Beata Lecka-Czernik (Committee Member); Sivarajan Kumarasamy (Committee Member) Subjects: Bioinformatics; Biomedical Research

Doctor of Philosophy (PhD), University of Toledo, 2017, Biomedical Sciences (Cardiovascular and Metabolic Diseases)

Atherosclerosis is the main cause of death due to cardiovascular disease in western societies with macrophages playing important roles in all stages of lesion development. Macrophages exhibit heterogeneity in plaques with M1 (inflammatory/classically activated) and M2 (anti-inflammatory/alternatively activated) phenotypes being found in both human and murine atherosclerotic lesions. Macrophage apoptosis determines the lesion progression, fate and endoplasmic reticulum (ER) stress is one of its major triggers. In the advanced lesions, macrophage apoptosis coupled with defective phagocytic clearance (a process called efferocytosis) leads to secondary necrosis, culminating in formation of areas of necrosis, key determinant of plaques to rupture. Therefore, identifying mechanisms regulating macrophage apoptosis represents an attractive area for novel therapeutic opportunities. The Transient Receptor Potential Canonical 3 (TRPC3) channel is a non-voltage gated; non-selective cation channel endowed with significant constitutive activity and is prominently expressed in central nervous and cardiovascular systems. Studies from our laboratory showed that macrophage deficiency of Trpc3 resulted in impaired survival signaling and increased apoptosis of naive or `M0' macrophages. As macrophage apoptosis influences lesion progression, we hypothesized that macrophage deficiency of Trpc3 would lead to increased apoptosis and necrosis in advanced atherosclerosis. Contrary to this, we found that advanced aortic root lesions of ApoE-/- mice (athero-prone background) transplanted with Trpc3 deficient bone marrow had reduced areas of necrosis and less apoptotic macrophages. These observations prompted us to speculate that TRPC3 might have a differential effect on apoptosis of naive (M0) vs. differentiated (M1 and M2) macrophages, latter phenotypes being predominant in atherosclerotic lesions. Also these studies made use of bone marrow donors which were global knockouts for Trpc3. Theref (open full item for complete abstract)

Committee: Guillermo Vazquez (Committee Chair); Viviana Ferreira (Committee Member); David Giovannucci (Committee Member); Bina Joe (Committee Member); Sivarajan Kumarasamy (Committee Member) Subjects: Biomedical Research

Doctor of Philosophy, Case Western Reserve University, 2016, Pathology

Inositol 1,4,5-trisphosphate receptors (IP3Rs) are channels located on the endoplasmic reticulum (ER) that release calcium (Ca2+) ions into the cytosol during intracellular signaling cascades. By initiating and shaping Ca2+ signals, IP3Rs play key roles in many essential processes. Consequently, cells have evolved complex mechanisms to control IP3R-mediated Ca2+ signals, including regulation by interacting proteins. In this dissertation, the regulation of IP3Rs by interacting proteins was investigated in order to: (1) further establish the identities and roles of IP3R-interacting proteins in controlling Ca2+ release and cell survival; and, (2) evaluate the possibility of targeting protein-IP3R interactions for the treatment of cancers. Reported herein is the discovery that the glycolytic enzyme pyruvate kinase M2 (PKM2) localizes in part to the ER and interacts with IP3Rs. By controlling IP3R-mediated Ca2+ release, IP3R-associated PKM2 governs Ca2+ transfer from ER to mitochondria, regulating cellular bioenergetics and suppressing Ca2+ signals capable of inducing cell death. The control of Ca2+ homeostasis by PKM2 is thus a novel mechanism by which PKM2 promotes cell survival. Notably, these findings suggest that PKM2 serves as a gatekeeper of the metabolic flux of pyruvate between oxidative metabolism in mitochondria versus fermentation to lactate in the cytoplasm, a novel regulatory function of PKM2 that may be especially important in promoting aerobic glycolysis (Warburg effect) in cancer cells. Also presented here is a study assessing the potential of targeting the interaction of the anti-apoptotic protein Bcl-2 with IP3Rs as a novel therapeutic approach for cancer. Bcl-2 inhibits pro-apoptotic Ca2+ release through interaction with IP3Rs via its BH4 domain, but this effect can be reversed by BIRD-2, a synthetic peptide inhibitor of Bcl-2-IP3R interaction, which induces selective apoptosis in malignant cells. The study demonstrates that BIRD-2 is an effective an (open full item for complete abstract)

Committee: Clark Distelhorst (Advisor) Subjects: Biochemistry; Biology; Biomedical Research; Cellular Biology; Molecular Biology; Pathology

PhD, University of Cincinnati, 2015, Engineering and Applied Science: Chemical Engineering

Direct ammoxidation of propane to acrylonitrile (ACN) has received significant attention of the scientific community in recent decades because propane is cheaper, more abundant and environmentally friendlier than the current propylene feedstock. The MoVTeNbOx M1 phase catalysts display the highest propane conversion and ACN yield (~ 60 mol. %). However, the ACN yield over the M1 phase is insufficiently high in order to replace the current Sohio process, employing the propylene feedstock to produce ACN with a ~ 81 mol. % yield. Therefore, there is currently a global effort in understanding the atomic structure and catalytic behavior of these catalysts in order to design improved M1 phase catalysts for propane ammoxidation. Accordingly, this PhD thesis aimed to pursue the following objectives: 1) improve the High-angle annular dark field scanning transmission electron microscopy (HAADF-STEM) image analysis and provide accurate metal site occupancies in the M1 phase; 2) develop new probability models which correlate the catalytic performance with metal distributions of the M1 phase; 3) elucidate the nature of M1/M2 phase cooperation for all chemical compositions. The HAADF-STEM image simulations were performed in order to determine accurate metal distributions in the MoVTeTaO M1 phase catalyst for propane ammoxidation. QSTEM simulation software was chosen due to the excellent agreement between experimental and simulated HAADF-STEM images. The QSTEM-based HAADF-STEM image analysis method successfully provided accurate metal distributions in the MoVTeTaO M1 phase as compared to previously reported metal occupancies determined by the Z2-based HAADF-STEM image analysis. Three probability models (Model 1-3) were advanced and investigated in this thesis based on metal distributions determined by the QSTEM-based HAADF-STEM image analysis. The correlations between the Mo/V distributions in MoVTeTaO M1 phase catalysts and their catalytic behavior in propane ammoxidation w (open full item for complete abstract)

Committee: Vadim Guliants Ph.D. (Committee Chair); Qian He Ph.D. (Committee Member); Ye Xu Ph.D. (Committee Member); Anastasios Angelopoulos Ph.D. (Committee Member); Peter Panagiotis Smirniotis Ph.D. (Committee Member) Subjects: Chemical Engineering

Master of Science (MS), Wright State University, 2014, Microbiology and Immunology

In this study, the human leukemic monocyte lymphoma cell line U-937 was used as an in vitro model for monitoring monocyte/macrophage differentiation. Phorbol 12- myristate (13) (PMA) was used to activate U-937 cells into macrophage-like cells (M0). After 24 hours of PMA treatment, non- adherent U-937 cells became tightly adherent to the culture plates forming M0 cells. M0 cells were then polarized into the M1 macrophage phenotype by treatment with LPS and IFN-¿ for another 24 hours. Each of the cytokines IL-4, IL-13, or IL-10 was applied separately to three M0 cultures for 24 hours to induce the M2 macrophage phenotype. M1 and M2 phenotypes displayed distinct morphological characteristics. M1 cells appeared large, with cellular processes (pseudopodia), and intracellular vacuoles while the M2 cells large aggregated into large masses. The undifferentiated U--937 cells expressed less CD206 and CD86 but greater amounts of CD163, CD80, and CD200R than did the differentiated U937 cells (M0 macrophages). These observations suggest that the differentiated M0 cells would be better at antigen presentation since they expressed a 6-fold increase the CD86 costimulatory molecule and half the amount of the CD80 costimulatory molecule as did undifferentiated U937 cells. M1 polarized macrophages expressed lesser amounts of CD14, CD86, CD80, CD163, CD206, and CD200R than M0 cells which may reflect the production of toxic substances such as reactive oxygen molecules, nitric oxide and TNF-a. Both the differentiation and polarization processes caused decreases in cell viability no difference seen between M0 and M1 populations at the 24 hour observation time. Marked differences in expression of these CD markers were obvious in the M2 subpopulations with the IL-4-polarized M2 cell showing marked elevations in expression of CD206 and CD86 and the IL-13-polarized M2 cells showing marked increase in expression of CD14. These differences highlight the plasticity of the macrophage in (open full item for complete abstract)

Committee: Nancy Bigley Ph.D. (Advisor); Barbara Hull Ph.D. (Advisor); Gerald Alter Ph.D. (Committee Member) Subjects: Immunology; Microbiology

Master of Science in Electrical Engineering, Cleveland State University, 2013, Fenn College of Engineering

VDL Mode 2 is the principal data communication technology for aeronautical communications implemented in the NextGen project for the National Airspace System (NAS), with potentially worldwide service. Aeronautical communications have strict transmission delay standards for safety considerations. Meeting the strict standards significantly drops the capacity of the number of aircraft that can communicate using the Very High Frequency (VHF) Data Radio (VDR). In this thesis, three methods of increasing the capacity while maintaining the strict standards are evaluated: transmit power control, load regulation and ground station placement. A simulation model using OPNET software is used for testing. Load regulation shows some improvement, while transmit power control is not beneficial. The best results are obtained from optimal ground station placement, with over 300 percent capacity improvement in certain scenarios.

Committee: Vijaya Konangi Ph.D. (Committee Chair); Fuqin Xiong Ph.D. (Committee Member); Nigamanth Sridhar Ph.D. (Committee Member) Subjects: Aerospace Engineering; Electrical Engineering; Engineering; Technical Communication

Master of Science (MS), Wright State University, 2012, Microbiology and Immunology

Macrophages are “first responders”, innate immune system cells which quickly arrive to a site of infection and injury, consuming cell debris and foreign matter and recruiting other immune system cells to the area. While historically they have been thought to react uniformly to all challenges, the discovery of toll-like receptors has shown that macrophages actually work closely with the adaptive immune system in fine-tuning the immune response. Furthermore, it has recently been discovered that macrophages can become polarized to one of two subtypes-M1 or M2. M1 macrophages are efficient producers of reactive oxygen species, nitrogen intermediates, and inflammatory cytokines. They are especially effective at mediating resistance against intracellular parasites and tumors. Arginine metabolism in M1 macrophages is characterized by high levels of inducible nitric oxide synthetase (iNos), and this is used as a marker for polarization of macrophages to the M1 phenotype. M2 macrophages, by contrast, produce anti-inflammatory molecules, have high levels of scavenger, mannose, and galactose-type receptors, and arginine metabolism is shifted to production of ornithine and polyamines via arginase. Arginase, encoded by the ARG1 gene, is considered to be one of the hallmarks of the M2 phenotype, and is one of the most specific markers used to determine polarization to that phenotype. Polarization to one phenotype or another is not permanent, and macrophages can be polarized directly from one state to the other directly by addition of appropriate cytokines (IFNy, LPS, TNFa for M1, IL-4, IL-13, IL-10, TGFb for M2). The state of macrophage polarization can be determined by examining a population of macrophages for tell-tale products of one state or another (ROS, RNS, TNFa, IL-1, IL-6, IL-12, or IL-23 for M1, IL-10, TGFb, PDGF, VEGF, EGF, and arginase for M2). Determining macrophage polarization has implications in health outcomes- M1 macrophages excel at fighting parasites and fig (open full item for complete abstract)

Committee: Nancy Bigley PhD (Committee Chair); Barbara Hull PhD (Committee Member); Thomas Brown PhD (Committee Member) Subjects: Microbiology

Master of Science (MS), Wright State University, 2012, Microbiology and Immunology

In our current study we examined the effects of HSV-1 challenge on J774A.1 macrophages polarized to either a proinflammatory (M1) or anti-inflammatory (M2) phenotype. Polarized J774A.1 macrophages were characterized using CD14-CD86 and SOCS1-SOCS3 expression levels. SOCS proteins are a family of proteins that are capable of inhibiting cytokine-signaling pathways. HSV-1 up regulates expression of SOCS1 protein levels in infected cells, inhibiting the ability of infected cells to produce proinflammatory products (Nowoslawski Akhtar and Benveniste, 2011). This study shows that signals within the microenvironment play a greater role in macrophage polarization, and SOCS1-SOCS3 expression levels, than does HSV-1 challenge. M1 macrophages showed morphological changes following polarization, a significant decrease in cell viability, a two-fold increase in the number of CD14+-CD86+ cells, similar levels of SOCS1 expression, and a 11-fold decrease in SOCS3 expression when compared to control cells. M2 macrophages also exhibited morphological changes, a slight decrease in cell viability, a 26.0% decrease in the number of CD14+-CD86+ cells, and SOCS1-SOCS3 expression levels similar to that of control cells. Following HSV-1 challenge (0.1 MOI), the majority of M1 macrophages and M2 macrophages appeared rounded, possibly due to disruption of actin filaments. Virus-infected M1 macrophages showed a slight decrease in cell viability when compared to uninfected M1 macrophages. Additionally, the number of CD14+-CD86+ cells of both M1 and M2 phenotypes decreased. M1 macrophages exhibited a 39.9% decrease, while M2 macrophages exhibited a 13.2% decrease. SOCS1 expression levels remained relatively unchanged in virus-infected M1 macrophages, while SOCS3 expression levels increased by 30.4% at 24 hours after infection. Increase in SOCS3 levels is hypothesized to be a protective response of infected M1 macrophages due to the release of high levels of proinflammatory molecules. Alternativel (open full item for complete abstract)

Committee: Nancy Bigley PhD (Advisor); Barbara Hull PhD (Committee Member); Julian Cambronero PhD (Committee Member) Subjects: Immunology; Microbiology

MS, University of Cincinnati, 2006, Engineering : Chemical Engineering

Recently discovered multi-component Mo-V-Te-Nb-O catalysts are very promising catalysts for propane ammoxidation to acrylonitrile. This mixed metal oxide system contains so-called “M1”, “M2” and rutile phases with orthorhombic, hexagonal and monoclinic structures, respectively, which were proposed to be active and selective in propane ammoxidation to acrylonitrile. In this study, the bulk mixed metal Mo-V-Te-Nb-O oxide catalysts with pure M1 and rutile structures were prepared separately in hydrothermal synthesis, followed by their calcination under nitrogen atmospheres. Novel approaches for the synthesis of mesoporous niobium oxide and niobium-based 4-component mesoporous Mo-V-Te-Nb-O phases were developed in the present work.. The novel thermally stable mesoporous Mo-V-Te-Nb-O phases were synthesized by evaporation-induced self-assembly EISA employing the mesoporous niobium oxide possessing a high Tammann temperature as a major framework component, followed by HT or dry gel conversion (DGC) treatment. In this work, the synthesis of bulk mesoporous and nanocrystalline orthorhombic (M1) catalysts inside the pore channels of ordered mesoporous hosts of SBA-15 silica was explored. The catalytic activity for propane ammoxidation to acrylonitrile was investigated for these three types of Mo-V-Te-Nb-O catalysts: dense, mesoporous bulk and SBA-15 supported mixed metal oxide catalysts.

Committee: Dr. Vadim Guliants (Advisor) Subjects: Engineering, Chemical

Master of Science, Miami University, 2002, Geology and Environmental Earth Science

This research is comprised of two projects involving the use of single crystal X-ray diffraction to for mineral structure determination. Chapter 1 involves determination of structural variation along the Mn ⇔ Fe solid solution of the lithiophilite-triphylite series, olivine structure types. Bond lengths and angle variance are examined to determine their variation along the Mn ⇔ Fe join and their relationships to other silicate and germanate olivine structures. The angle variance of the phosphate olivines was smaller in the M1 octahedron, which is in contrast to the other olivine structure phases examined in this study. In Chapter 2, diffraction data were collected on phenakite, danburite, spodumene, hambergite, lithiophilite, axinite, and prismatine, which are to be used as light element (Li, Be, and B) mineral standards. The data were used to determine the atomic positional parameters, site geometry, site occupancy, and polyhedral connectivity of each sample. This research is comprised of two projects involving the use of single crystal X-ray diffraction to for mineral structure determination. Chapter 1 involves determination of structural variation along the Mn ⇔ Fe solid solution of the lithiophilite-triphylite series, olivine structure types. Bond lengths and angle variance are examined to determine their variation along the Mn ⇔ Fe join and their relationships to other silicate and germanate olivine structures. The angle variance of the phosphate olivines was smaller in the M1 octahedron, which is in contrast to the other olivine structure phases examined in this study. In Chapter 2, diffraction data were collected on phenakite, danburite, spodumene, hambergite, lithiophilite, axinite, and prismatine, which are to be used as light element (Li, Be, and B) mineral standards. The data were used to determine the atomic positional parameters, site geometry, site occupancy, and polyhedral connectivity of each sample.

Committee: John Rakovan (Advisor) Subjects:

Master of Applied Communication Theory and Methodology, Cleveland State University, 2008, College of Liberal Arts and Social Sciences

The goal of the current study was to compare users from two distinct cultures to examine the extent to which they communicate differently through MySpace comments and to see how such differences might relate to their cultural background and biological sex. For this purpose, Hofstede's theories of individualism/collectivism and masculinity/femininity and Ting-Toomey's face negotiation theory were used as frameworks. Content analysis was performed on 150 Hungarian and 150 American randomly selected MySpace comments. One-way ANOVAs and crosstabulations showed some significant differences and similarities between Hungarian and American MySpace comments. Real-life cultural differences and sex-linked differences were found to be reflected in the comments. Thus, this study found mixed evidence for the existence of a global "MySpace culture" that includes both global linguistic features and reflects upon elements from users' own traditional culture.

Committee: Kimberly A. Neuendorf PhD (Advisor); Katheryn Maguire PhD (Committee Member); Paul D. Skalski PhD (Committee Member) Subjects: Communication

Doctor of Philosophy, University of Akron, 2005, Polymer Science

The effects of aging and aging under stress on the tear strength of filled natural rubber vulcanizates were investigated. Tear strengths were evaluated using a trouser tear geometry with a constrained tear path. Fracture energies and crack growth rates were determined. Four distinct cracking patterns were observed and characterized. Tear strength significantly decreased and crack deviation was absent at long cure times. Anaerobic heat aging at 120°C resulted in little change in the tear strength, while aging at 80°C, 100°C or 140°C resulted in a lowering of strength. Heat aging under stress (mechano-chemical) resulted in anisotropy. Tear results were assessed using double network concepts. After mechano-chemical aging at low strain, tear strength decreased slightly, but with enough deformation during aging, it decreased dramatically. In addition, the effect of various bonding agents on the fracture behavior was studied. A new commercial agent resulted in higher tear strengths than seen for traditional bonding agents.

Committee: Gary Hamed (Advisor) Subjects:

Master of Science (MS), Wright State University, 2013, Microbiology and Immunology

The U937 cell line is an oncogenic human monocyte cell line. These monocytes have the potential of differentiating into either macrophages or dendritic cells (Lawrence et al., 2011). This differentiation pattern depends on the characteristics of the tissue microenvironment (Kigerl et al., 2009). PMA (Phorbol 12-Myristate 13-Acetate) is a phorbol ester capable of transforming monocytic cells toward the macrophage pathway. Upon treatment with PMA, U937 cells under-go a series of morphological and functional changes. Traditionally monocytic cell lines are used as a model of macrophage function, because current human macrophage cell lines require a T-cell conditioned growth medium and contact with irradiated peripheral blood leukocytes (PBLs) to propagate (Lee et al., 1997). The PMA-treated monocyte is referred to as “macrophage-like,” meaning that the properties of the transformed cell line are not yet fully understood (Dockrell et al., 2010). These macrophages are clinically significant for possible cancer immunotherapy experimentation. Recently, two divergent macrophage subsets have been identified: M1 (pro-inflammatory) and M2 (anti-inflammatory). These macrophages are differentiated based on the cytokines present in the extracellular matrix (Kigerl et al., 2009). In order for the U937 cell line to be represented as an effective macrophage model, the ability of the cell line to polarize must be analyzed. This study is a review of the features necessary to convert the human U937 cell line into M1 or M2 morphological and functional subsets.

Committee: Nancy Bigley Ph.D. (Advisor); Barbara Hull Ph.D. (Committee Member); Gerald Alter Ph.D. (Committee Member) Subjects: Biochemistry; Biology; Immunology; Microbiology; Pathology

Master of Science (MS), Ohio University, 2013, Biomedical Engineering (Engineering and Technology)

Macrophages play an important role in the formation of atherosclerotic lesions and their progression. The presence of M1 and M2 macrophages in human atherosclerotic lesions has been suggested. Wnt5a is a noncanonical member of the wingless family of proteins that is expressed in human macrophages in different inflammatory diseases including atherosclerosis. These observations led us to hypothesize that Wnt5a secretion/expression is related to M1 and M2 subsets in atherosclerosis. To investigate this hypothesis, we performed immunohistochemical analysis using Wnt5a, CD68 (for macrophages) and CD163 (for M2 macrophages) in human atherosclerotic tissue sections derived from the carotid arteries of patients undergoing endarterectomy. We also performed immuno-fluorescence analysis to detect Wnt5a in human peripheral blood differentiated M1 and M2 macrophages. Our results suggest that Wnt5a secretion/protein expression is mainly associated with the M2 phenotype and shows the participation of other cells in Wnt5a protein expression in the atherosclerotic lesions.

Committee: Ramiro Malgor (Advisor) Subjects: Biomedical Engineering

Doctor of Philosophy, Case Western Reserve University, 2013, Neurosciences

Alzheimer's disease (AD) is characterized by the deposition of ¿¿-¿¿amyloid into plaques and neurofibrillary tangles in the brain that is accompanied by a robust immune response. Microglia, the tissue macrophages of the brain, detect and respond to deposited amyloid. Their response is coordinated by a cell surface receptor ensemble including CD36, CD47, SRA, ¿¿6¿¿1 integrin, TLR2, TLR4, TLR6, and CD14. The role of individual TLRs in the microglial response to A¿¿ has been controversial. Therefore we elected to inactivate the first kinase activated after TLR ligation, interleukin-¿¿¿1 receptor-¿¿associated kinase 4 (IRAK4), to investigate the role of all TLRs in the microglial response to A¿¿. Using mice where inactive IRAK4 had been knocked into the endogenous IRAK4 (IRAK4 KI) we found that IRAK4 is necessary for microglia to activate proinflammatory MAP kinases and generate reactive oxygen in response to fA¿¿42 in vitro. Furthermore, we analyzed the role of IRAK4 in vivo through use of the APPPS1 mouse model of Alzheimer's disease. APPPS1;IRAK4 KI animals displayed reductions in both soluble and insoluble A¿¿ by ELISA at 8 months of age and dense core A¿¿ as marked by thioS. At 8 months of age, APPPS1;IRAK4 KI animals had significant reductions in both microgliosis, as marked by iba1 staining, and astrogliosis, as marked by GFAP staining. qPCR analysis of microglial enriched isolates from the adult brain revealed dysregulation of the immune response as marked by transcript levels of ifn¿¿, il-¿¿1¿¿, tnf¿¿, il-¿¿10, il-¿¿4, and socs1. Importantly, this work implicated the interferon response factors (IRFs) in controlling the microglial response to A¿¿ that is, in part, regulated by IRAK4 kinase activity. Analysis of whole brain homogenates revealed significant reductions in the proinflammatory IRF5 and increases in the anti-¿¿inflammatory IRF4 in the APPPS1;IRAK4 KI animals. These changes were correlated with maintenance of A¿¿ clearance pathways and improvements in (open full item for complete abstract)

Committee: Gary Landreth (Advisor); Evan Deneris (Committee Chair); Bruce Lamb (Committee Member); George Dubyak (Committee Member); Xiaoxia Li (Committee Member); Sundararajan Sophia (Committee Member) Subjects: Biology; Immunology; Molecular Biology; Neurobiology; Neurosciences