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<p><strong>Introduction: </strong>Obesity is associated with asthma and airway hyperresponsiveness, though the mechanisms behind this relationship remain unclear. It is unlikely to be due to a direct effect of leptin on human airway smooth muscle cells (ASMC) (Nair, <em>et al.</em>, 2009). Since adipocytes are known to produce a wide array of mediators, we hypothesized that adipocytes may directly modulate human ASMC biology.</p> <p><strong>Objectives:</strong> To determine and compare the effects of intra and extrathoracic adipocyte secretions on ASMC proliferation, chemotaxis, contractility and cytokine synthesis.</p> <p><strong>Methods:</strong> Human ASMC and human adipocytes were cultured from primary samples (intrathoracic or extrathoracic). Adipocyte-conditioned media was used as a treatment in proliferation cell count assays, Transwell migrations, muscle bath experiments and to induce interleukin (IL)-6, tumor necrosis factor (TNF)-α and eotaxin production (as measured with a Bioplex). The effects of adipocyte-myocyte co-culture were also investigated on the proliferation, migration and cytokine synthesis of the ASMC.</p> <p><strong>Results: </strong>Adipocyte supernatants and co-culture did not significantly affect the growth of ASMC in the presence of 10% fetal calf serum. The adipocyte supernatants were not chemotactic, and did not affect the migration of ASMC towards platelet derived growth factor (PDGF). Similarly, co-culture did not have any effect on ASMC chemotaxis. Cytokine synthesis was also unchanged by adipocytes. Adipocyte supernatants did not have any effect on the contractile or relaxant responses of bovine tracheal smooth muscle strips. There was no significant difference between adipocyte depot location, with intrathoracic and extrathoracic adipocytes having a similar effect.</p> <p><strong>Conclusion:</strong> Human adipocytes do not directly modulate airway smooth muscle proliferation, migration, contractility and cytokine synthesis. These data point to some other cause for the association between obesity and asthma, though the role of other cells present in the adipose tissue of obese individuals cannot be ruled out.</p> / Master of Science (MSc)

<p> Peroxynitrite is formed in blood vessels upon reaction of superoxide anion with nitric oxide (NO). It can oxidize proteins and thiols and nitrosylate free or protein bound thiols and tyrosine residues, thereby producing vascular dysfunction. Peroxynitrite therefore, may contribute to hypertension and cardiovascular diseases. We investigated the in vitro effects of commercially available peroxynitrite. De-endothelialized rings from the left descending coronary artery of pig were treated with peroxynitrite for 30 min, washed and then contracted with cyclopiazonic acid (CPA) or by membrane depolarization with KCl. Tissues pre-treated with peroxynitrite showed inhibition of the CPA-induced contraction with an IC50 of ≈100 uM but there was no effect on KCl-induced contraction. Peroxynitrite is stable only at alkaline pH and it may decompose to form superoxide and NO. However, including superoxide dismutase + catalase along with peroxynitrite did not change its effect.</p> <p> Next, we used the same protocol to compare the effects of peroxynitrite and NO generating agents: 3-morpholino sydnonimine (SIN-1), s-nitroso-N-acetylpenicilliamine (SNAP), sodium nitroprusside (SNP) and spermine nonoate. The effectiveness of these agents to inhibit the CPA-induced contraction was SNAP > spermine nonoate ≥ SIN-1 > SNP. SNAP was the most effective in inhibiting the KCl-induced contraction with spermine nononoate being less effective and SIN-1 and SNP not producing any significant inhibition. We further investigated the effect of SNAP. Catalase, superoxide dismutase or CPTIO (a NO scavenger) did not prevent the effects of SNAP on the KCl or the CPA-induced contractions. The guanylate cyclase inhibitor ODQ, partially reversed the effects of only low concentrations of SNAP. Thus, pretreatment with NO generating agents such as SNAP and spermine NONOate appear to be more effective in inhibiting the contraction of the pig coronary artery than with peroxynitrite or the peroxynitrite generating agent SIN-1. Since SIN-1, SNAP, SNP and NONOates produce different amounts of peroxynitrite, nitric oxide and S-nitrosylation products, their effects may be used to delineate the molecular basis of the actions of peroxynitrite and NO on the arterial function.</p> / Thesis / Master of Science (MSc)

Artificial neural network (ANNs) is an information processing paradigm inspired by the human brain. ANNs have been used in numerous applications to provide complex nonlinear input-output mappings. They have the ability to adapt and learn from observed data. The training of neural networks is an important area of research and consideration. Training techniques have to provide high accuracy, fast speed of convergence, and avoid premature convergence to local minima. In this thesis, a novel training method is proposed. This method is based on the relatively new Smooth Variable Structure filter (SVSF) and is formulated for feedforward multilayer perceptron training. The SVSF is a state and parameter estimation that is based on the Sliding Mode Concept and works in a predictor-corrector fashion. The SVSF applies a discontinuous corrective term to estimate state and parameters. Its advantages include guaranteed stability, robustness, and fast speed of convergence. The proposed training technique is applied to three real-world benchmark problems and to a fault detection application in a Ford diesel engine. SVSF-based training technique shows an excellent generalization capability and a fast speed of convergence. / Artificial neural network (ANNs) is an information processing paradigm inspired by the human brain. ANNs have been used in numerous applications to provide complex nonlinear input-output mappings. They have the ability to adapt and learn from observed data. The training of neural networks is an important area of research and consideration. Training techniques have to provide high accuracy, fast speed of convergence, and avoid premature convergence to local minima. In this thesis, a novel training method is proposed. This method is based on the relatively new Smooth Variable Structure filter (SVSF) and is formulated for feedforward multilayer perceptron training. The SVSF is a state and parameter estimation that is based on the Sliding Mode Concept and works in a predictor-corrector fashion. The SVSF applies a discontinuous corrective term to estimate state and parameters. Its advantages include guaranteed stability, robustness, and fast speed of convergence. The proposed training technique is applied to three real-world benchmark problems and to a fault detection application in a Ford diesel engine. SVSF-based training technique shows an excellent generalization capability and a fast speed of convergence. / Thesis / Master of Applied Science (MASc)

The vagina is an essential organ of the female reproductive system that has been largely understudied in the field of biomechanics. The ability of the vagina to contract gives rise to a set of active mechanical properties that contribute to the complex function of this organ in-vivo. After briefly reviewing experimental studies on the active properties of the vagina, including the differences in contractility with respect to anatomic regions and orientations, neural pathways, life events, pelvic floor disorders, and surgical mesh treatment, we present our novel experimental studies that aim toward filling existing knowledge gaps on vaginal tissue morphology and contractile function of the vagina. First, we quantified the large heterogeneous deformations that the vagina experiences during contractions for the first time. For this study, vaginal specimens were subjected to isometric planar biaxial tests, during which they were induced to contract via KCl at four applied equi-biaxial stretches. The digital image correlation method was used to perform full-field strain analysis during each contraction. The vagina was found to have anisotropic contractile behavior, generating higher forces and experiencing higher magnitude strains along the longitudinal direction (LD) than along the circumferential direction (CD) during contractions. Then, we performed the first detailed quantification of the distribution and alignment of vaginal smooth muscle and nerves throughout the vagina. Toward this goal, vaginas from adult female rats were subjected to a tissue clearing and immunohistochemistry protocol. Tissue clearing increased the transparency of the specimens such that organs could be imaged without sectioning, thus preserving the 3D architecture of the tissue. This analysis revealed a bimodal distribution of muscle alignment angles, with a significantly higher proportion of muscle oriented along the LD than along the CD of the organ. The morphologic and functional properties of the smooth muscle within the healthy vagina need to be fully investigated so that detrimental alterations in vaginal contractility, such as those caused by pelvic floor disorders and current treatment strategies, can be prevented. / Doctor of Philosophy / The vagina is an essential organ of the female reproductive system that has been largely understudied in the field of biomechanics. The ability of the vagina to contract gives rise to a set of active mechanical properties that contribute to the complex function of this organ in-vivo. After briefly reviewing experimental studies on the active properties of the vagina, including the differences in contractility with respect to anatomic regions and orientations, neural pathways, life events, pelvic floor disorders, and surgical mesh treatment, we present our novel experimental studies that aim toward filling existing knowledge gaps on vaginal tissue morphology and contractile function of the vagina. First, we quantified the large heterogeneous deformations that the vagina experiences during contractions for the first time. For this study, vaginal specimens were subjected to isometric planar biaxial tests, during which they were induced to contract via KCl at four applied equi-biaxial stretches. The digital image correlation method was used to perform full-field strain analysis during each contraction. The vagina was found to have anisotropic contractile behavior, generating higher forces and experiencing higher magnitude strains along the longitudinal direction (LD) than along the circumferential direction (CD) during contractions. Then, we performed the first detailed quantification of the distribution and alignment of vaginal smooth muscle and nerves throughout the vagina. Toward this goal, vaginas from adult female rats were subjected to a tissue clearing and immunohistochemistry protocol. Tissue clearing increased the transparency of the specimens such that organs could be imaged without sectioning, thus preserving the 3D architecture of the tissue. This analysis revealed a bimodal distribution of muscle alignment angles, with a significantly higher proportion of muscle oriented along the LD than along the CD of the organ. The morphologic and functional properties of the smooth muscle within the healthy vagina need to be fully investigated so that detrimental alterations in vaginal contractility, such as those caused by pelvic floor disorders and current treatment strategies, can be prevented.

The discussion in this paper focuses on how boundary based smooth shape design can be carried out. For this we treat surface generation as a mathematical boundary-value problem. In particular, we utilize elliptic Partial Differential Equations (PDEs) of arbitrary order. Using the methodology outlined here a designer can therefore generate the geometry of shapes satisfying an arbitrary set of boundary conditions. The boundary conditions for the chosen PDE can be specified as curves in 3-space defining the profile geometry of the shape. We show how a compact analytic solution for the chosen arbitrary order PDE can be formulated enabling complex shapes to be designed and manipulated in real time. This solution scheme, although analytic, satisfies exactly, even in the case of general boundary conditions, where the resulting surface has a closed form representation allowing real time shape manipulation. In order to enable users to appreciate the powerful shape design and manipulation capability of the method, we present a set of practical examples

Mesotrione is under evaluation for registration in turfgrass for weed control, but often requires repeat treatments. Previous research in agricultural crops indicates tank mixtures with mesotrione may improve weed control. Three field trials were conducted in 2005 and 2006 in Blacksburg, VA on smooth crabgrass in perennial ryegrass and tall fescue. Data indicate mesotrione applied in combination with bentazon, bromoxynil, or carfentrazone, controlled smooth crabgrass better than any of these herbicides applied alone at all sites. Adding mesotrione to MSMA and quinclorac improved smooth crabgrass on of three sites. Sequential mesotrione applications improved long term weed control. / Master of Science