Elevated blood pressure is associated with varying degrees of arterial remodeling. The mechanisms by which extracellular mechanical stress is converted into intracellular alterations in signal transduction and gene expression have yet to be fully elucidated. Our goal was to investigate the early events in the vascular smooth muscle response to acute hypertension and to identify mediators involved in long-term hypertensive remodeling. In the acute phase of hypertension we targeted cell surface integrin and growth factor...

This dissertation examines the research question "How do video game design principles affect learning outcomes in serious games?" This research first develops a theoretical foundation concerning the meaning of the terms "game" and "serious game". This conceptual clarification is broken down into analytic propositions, which state that games have participants, rules, goals and challenges, and synthetic propositions, which state that the games should be intrinsically compelling, provide meaningful choices, and be self encapsulated. Based on...

This dissertation examines how two different emotions—pride and guilt—experienced by managers influence their strategic decision-making. Four different aspects of strategic decisions are investigated: risk, comprehensiveness, speed, and resource commitment. The dissertation also investigates how culture moderates the relationship between emotions and different aspects of the strategic decision-making process. The hypotheses of this study were tested using a 2 x 2 experimental design with two emotions (guilt and pride) and two cultures (U.S. and China). The...

This dissertation discusses the modeling and simulation (M& S) research in the area of real-time virtual pathology using signal analysis and synthesis. The goal of this research is to contribute to the research in the M&S area of generating simulated outputs of medical diagnostics tools to supplement training of medical students with human patient role players. To become clinically competent physicians, medical students must become skilled in the areas of doctor-patient communication, eliciting the patient's...

The representation via simulation models can easily lead to simulation models too simple for their intended purpose, or with too much detail, making them hard to understand. This problem is related to limitations of the modeling and simulation methods. A multi-method Modeling and Simulation (M&S) approach has the potential for improved representation by taking advantage of methods' strengths and mitigating their weaknesses. Despite a high appeal for using multiple M&S methods, several related problems should...

Hypertension is one of the common complications of obesity. Using a rat model of diet induced obesity and hypertension we investigated some of the mechanisms that are involved in regulation of blood pressure in obesity. The first aim of this study was to determine the role of proximal tubule transporters on the renal sodium handling in obese hypertensive (OP) and lean normotensive (OR) rats. An acute increase in renal perfusion pressure resulted in a blunted...

Multidrug membrane transporters (efflux pumps) in both prokaryotes and eukaryotes are responsible for ineffective treatment of a wide variety of diseases, including infections and cancer, underscoring the importance of better understanding of their structures and functions for design of effective therapies. Despite extensive studies over decades, their underlying molecular mechanisms remain largely unknown. In this dissertation, we focus on the study of structures and functions of multidrug membrane transporters, including ATP-binding cassette transporter (BmrA) and...

Mammalian fertilization involves interactions of sperm surface receptors with the ligands of the zona pellucida, an extracellular matrix surrounding the ovulated oocytes. In humans, the zona pellucida is composed of three major glycoproteins. One of them, ZP3, participates in the primary sperm binding and in the subsequent triggering of the spermatozoa's acrosome reaction. Studies on the role of this specific protein in the human fertilization process are hampered by the limited amount of available biologically...

Recombinant human zona pellucida protein 3 (rhZP3), expressed. isolated and purified from PA-1 cells, is characterized for its biological activity and the role in the signal transduction pathway. Characterization of the biological activity of rhZP3 was detected by hemizona assay and immunofluorescence staining of acrosome reaction The results indicated that rhZP3 exhibited an inhibition in the binding assay (HZI 43.6 +/-3.3; n = 9; 30 ng/mL rhZP3) and induction of acrosome reaction (198.6% +/- 77.2%...

Muscle contraction is thought to be accomplished by sliding of myosin filaments along actin filaments. Although actomyosin naturally uses ATP as an energy source, it can also use other nucleoside triphosphates (NTP) as substrates. In this work, the dependence of rate and equilibrium constants of the various steps in the muscle contraction mechanism upon nucleotide structure was investigated to unravel the dependence of the mechanical properties of the muscle upon changes in different biochemical steps...

Cytomegalovirus (CMV) is a complex, ubiquitous herpesvirus that is characterized by acute, chronic, and latent infections. Monocytes-macrophages are the key target cell type involved in pathogenesis, which is most effectively studied using the murine model of CMV infection. Previously three murine CMV (MCMV) genes (M139, M140, and M141) were identified to regulate viral expression in cultured macrophages and in mice. These genes are members of the US22 gene family with respect to HCMV homology. There...

Prostate cancer (PCA) is the most common cancer and the second leading cause of death among American men. The high mortality is greatly attributed to the lack of early detection tools and effective treatment for metastasis and relapses. Biomarkers that can discriminate benign from malignant tumor and signal the development of androgen independent and metastatic tumor are needed. A biomarker designated prostate specific membrane antigen (PSMA) has the potential to fulfill this need. The objective...

Recent trends in design and manufacturing suggest a tendency toward multiple centers of specialty which results in a need for improved integration methodology for dissimilar finite element or CFD meshes. Since a typical finite element or CFD analysis requires about 50% of an engineers effort to be devoted to modeling and input, there is a need to advance the state-of-the-art in modeling, methodology. These two trends indicate a need to for the capability to combine...

A time-domain study of the random response of a laminated plate subjected to combined acoustic and thermal loads is carried out. The features of this problem also include given uniform static inplane forces. The formulation takes into consideration a possible initial imperfection in the flatness of the plate. High decibel sound pressure levels along with high thermal gradients across thickness drive the plate response into nonlinear regimes. This calls for the analysis to use von...

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine which demonstrates perplexing physiological effects. It has been demonstrated that LIF is essential for implantation in mice. Little is known relating to the manner by which LIF effects pre-implantation and post-implantation development. The objectives of this project were to determine the effects LIF on pre-implantation development, to determine the effects that it may have on implantation rates, successful pregnancy rates, and resorption rates, and to determine the...

There are 518 protein kinase genes in the human genome; this constitutes about 1.7% of all human genes. The cAMP-dependent protein kinase (PKA) serves as the prototypic model for the study of kinases because it contains a conserved catalytic core shared with all eukaryotic kinases, it is the simplest kinase, and it is one of the best-characterized serine/threonine kinases. PKA is ubiquitous in mammals and regulates multiple physiological mechanisms such as the cell cycle, apoptosis,...

The synuclein proteins α, β and γ which are located in the brain, have been a subject of intense research. Of particular interest is α-synuclein, which is found in misfolded forms in Lewy bodies that are associated with Parkinson's disease. Despite the efforts of researchers across the world, the physiological structure and function of the synucleins remains elusive. In recent years, highly controversial reports by some investigators indicate that in its natural form, α-synuclein exists...

The fast axonally transported proteins represent a subset of neuronal proteins that are conveyed anterogradely as secretory vesicle constituents from the perikarya. Although fast transport displays properties consistent with the general secretory pathway, neuronal structure presents special problems which may require modifications of the general pathway. The elucidation of these special modifications is essential for a more complete understanding of neuronal function both in normal and pathological conditions. In order to characterize the fast transported...