There is good pharmacological evidence that cannabinoids caused cellular changes by interacting with specific cannabinoid receptors (CBR) (Klein et al., 2000). To date, two CBRs have been identified in the human body, designated Cannabinoid Receptor 1 (CB1) and Cannabinoid Receptor 2 (CB2) (Begg et al., 2005). Endogenously occurring compounds with action at the CBRs also exist and they are called endocannabinoids. One of the four known endocannabinoids is anandamide (AEA). The endocannabinoid system, present in the human body, plays a significant role in altering the physiology of the immune system. Enhancement of this system’s anti-inflammatory effect could possibly present a vital therapeutic target for central and peripheral inflammatory disorders. A number of synthetic CB1 or CB2 specific antagonists have been developed including the highly specific CB1 receptor antagonist/reverse agonist named Rimonabant/ SR141716A. SR compounds are considered unique because these compounds not only inhibit the binding and function of cannabimimetic agents, but also act as inverse agonists. Activation of CB1 receptors produces inappropriate CNS side effects including psychoactivity, dependence and sedation (Clayton et al., 2002) whereas CB1 receptor antagonists/inverse agonists avoid or prevent these side effects. Taking the above information into consideration, Rimonabant has the potential to offer an effective long term treatment of chronic inflammatory disorders without the serious side effects of commonly used treatments. The main aim of this study is to investigate the in vitro effects of Rimonabant alone and in combination with anandamide on inflammatory associated cytokine production by human umbilical vein endothelial cells (HUVEC) and macrophage cultures. After careful consideration of the evidence stating that endothelial cells produce several important molecules vital to the inflammatory response of the body and the confirmation that CB1 receptor mRNA is generally present in endothelial cells, the use of HUVEC was deemed to be satisfactory for this study. The first phase of the study was dedicated to establishing the technique to isolate HUVEC from fresh human umbilical cord within the local laboratory and to maintain these in culture for further use during experimental procedures to test the effects of CB1 ligands. The isolation procedure, trypsinising, freezing away and thawing methods used during this experiment produced healthy HUVEC in sufficient numbers for further use. The next step was to determine the maximum in vitro concentrations at which Rimonabant and anandamide had insignificant cytotoxic effect on selected human cells and in doing so, determine suitable concentrations for further experimentation. Both compounds had a dose related anti-proliferative response when tested on HUVEC. The same dose related response was observed during the Rimonabant exposure to human lymphocytes, but no decrease in lymphocyte viability was observed when treated with anandamide at the concentrations tested. It is evident from the results that there was an almost ten times difference in the IC50 value of the two different products (14.3 μM for Rimonabant and 124.2 μM for anandamide) which was statistically significant. Flow cytometry was used to determine the effects of Rimonabant and anandamide on the surface expression of the CR3 complement receptor by human neutrophils. Neither Rimonabant nor anandamide significantly affect CR3 expression on the surface of freshly isolated human neutrophils and would exclude the CR3 expression pathways as a potential mechanism of action for the anti-inflammatory effects of these compounds. The in vitro effect of Rimonabant and anandamide alone and in combination on the production of cytokines by human macrophages and by HUVEC was determined. Anandamide was shown to inhibit the production of all the detectable cytokines (IL-8, IL-1β and IL-6 in both cell types and IL-10 and TNF-α in macrophages). Furthermore this inhibitory effect was attenuated by pre-treatment Rimonabant. These results would suggest that anandamide could induce anti-inflammatory effects observed in macrophages and HUVEC, through cannabinoid receptors. Rimonabant also inhibited the production of all the detectable cytokines following treatment with 0.5 μM and 3 μM respectively. The anti-inflammatory effects of anandamide were attenuated when combined with 1 μM of Rimonabant. Throughout the various cytokine responses, the dose-response relationship appeared to follow a bell-shaped dose-response. This occurrence proposes that Rimonabant displaces anandamide and blocks the anti-inflammatory effects of the agonist. Flow cytometry was used to determine the effects of Rimonabant and anandamide alone and in combination on the extracellular surface expression of ICAM-1 by HUVEC. Neither Rimonabant nor anandamide had any significant inhibitory effect on the expression of ICAM-1 by HUVEC. Considering the low levels for ICAM-1 expressed by the HUVEC during this experiment and the literature supporting more effective methods of activating the ICAM-1 gene and subsequent up-regulation of ICAM-1 proteins, TNF-α stimulation of HUVEC might produce a different result compared to IL-1β stimulation. The final phase of the project was to determine the effects of Rimonabant and anandamide on the adhesion of human neutrophils to HUVEC. There was no significant difference with relation to the neutrophil adhesion to HUVEC following the treatment with various combination concentrations of the compounds, and also no significant effect following treatment with either test compound individually. Although a specific mechanism of action for Rimonabant could not be uncovered during this study, there is evidence that several possible mechanisms can be excluded. The results support observations made by other researchers and the hypothesis that Rimonabant has anti-inflammatory effects. The results provide motivation for further experimentation to better understand these anti-inflammatory actions of Rimonabant. / Dissertation (MSc)--University of Pretoria, 2012. / Pharmacology / unrestricted

No description available.

This thesis discusses a comparison of the differences in aerodynamic performance of wings designed with elliptical and bell-shaped lift distributions. The method uses a Standard Cirrus sailplane wing with a lift distribution associated with the induced drag benefits of an elliptical distribution (span efficiency = 0.96) as the basis of comparison. The Standard Cirrus is a standard class sailplane with 15-meter wingspan that was designed by Schempp-Hirth in 1969. This sailplane wing was modeled and analyzed in XFLR5, then validated against existing wind tunnel airfoil data, and Standard Cirrus flight test data. The root bending moment of the baseline wing was determined and used as the primary constraint in the design of two wings with bell-shaped lift distribution. These wings were modeled in XFLR5 by adjusting chord length and geometric twist respectively, and then they were studied using fixed speed lifting line analysis. Steady state cruise conditions for the Standard Cirrus sailplane were taken from the flight test data and applied for the analysis. The wing designed with chord variation posed incompatibilities with the lifting line method. The resulting planform was strongly tapered in the wingtip region and the reference chord length there was such that the software could not solve for a Reynolds number the magnitude resulting from two-dimensional airfoil analysis. However, the wing geometry provided insight into the design aspect of wings with bell-shaped lift distribution. Using chord variation to shape the lift distribution, the wing featured a 12% increase in wingspan but a 6.5% decrease in total wetted area when compared to the baseline. The results of the analysis of the wing designed with geometric twist indicate that induced drag decreased by 5% when compared to the baseline wing. The constraint on root bending moment resulted in a 12% increase in wingspan. Wetted area also increased by 14.8% over the baseline yielding an estimated 15% increase in skin friction.

The bell-shaped lift distribution (BSLD) wing design methodology advanced by Ludwig Prandtl in 1932 was proposed as providing the minimum induced drag. This study used this method as the basis to analyze its characteristics in two wing formation flight. Of specific interest are the potential efficiency savings and the optimal positioning for formation flight. Additional comparison is made between BSLD wings and bird flight in formation. This study utilized Computational Flow Dynamics (CFD) simulations on a geometric modeling of a BSLD wing, the Prandtl-D glider. The results were validated by modified equations published by Prandtl, by CFD modeling published by others, and by Trefftz plane analysis. For verification, the results were compared to formation flight research literature on aircraft and birds, as well as published research on non-formation BSLD flight. The significance of this research is two part. One is that the BSLD method has the potential for significant efficiency in formation flight. The optimal position for a trailing wing was determined to be partially overlapping the leading wing vortex core. For a BSLD wing these vortices are located inboard from the wingtips resulting in wingtip overlap and have a wider impact downstream than the elliptical lift distribution (ELD) wingtip vortices. A second aspect is that avian research has traditionally been studied assuming the ELD model for bird flight, whereas this study proposes that bird flight would be better informed using the BSLD.

The submitted thesis is focused on the development, optimization, testing and practical application of the new microextraction method called Bell Shaped Extraction Device assisted Liquid-Liquid Microextraction (BSED-LLME). The method is based on the application of a miniature bell-shaped extraction tool in which the extraction takes place, so that only minimal solvent losses can occur, and which allows a reproducible dosing and collection of a small volume of the extraction solvent. The BSED- LLME method was used to preconcentrate selected volatile and less volatile analytes from aqueous samples into organic solvents of a density lower than water. After the extraction, the analytes were determined by fast gas chromatography with flame ionization detection and gas chromatography with mass spectrometry. The statistical methods known as Design of Experiment (DOE) were used for determination of the optimal extraction conditions for BSED-LLME procedure. DOE is based on a mathematical description of the system and the prediction of the optimal setting of experimental parameters that may influence extraction efficiency. Factors such as extraction time, volume of extraction solvent, addition of sodium chloride (ionic strength), stirring rate and the diameter of the extraction vessel ect., have been tested....

The effects of metastable tetragonal zirconia on the properties of Ordinary Portland Cement were observed during which the effect of crystallite size pH on the preparation solution, precursor salt, and the presence of co-precipitates, Fe(OH)3, SnO2 and SiO2 on the crystallization temperature, enthalpy and crystal structure, immediately following the crystallization exothermic burst phenomenon in ZrO2 were measured. Thermal analysis and x-ray methods were used to determine crystallite sizes and structures immediately following the exothermic burst. Comparisons were made for zirconias prepared from oxychloride, chloride and nitrate solutions. The existence of tetrameric hydroxidecontaining ions in oxychloride precursor is used to rationalise low values of crystallization enthalpy. The position of the crystallization temperature, Tmax was not dependent on crystallite size alone but also on the pH at which the gel was made, the surface pH after washing, and the presence of diluent oxides. Enthalpy v r1/2 and Tmax v (diluent vol)1/3 relationships indicate that surface coverage effects dominate a surface nucleated phenomenon. The data established for ZrO2 systems was used to develop tetragonal-ZrO2-SnO2 powders capable of improving the mechanical properties of Ordinary Portland Cement discs. The ZrO2-OPC discs were prepared by powder mixing, water hydration and uniaxial pressing. Vicat needle tests showed that tetragonal-ZrO2 increases the initial setting rate. Microscopy indicated that porosity distribution changes near to ZrO2 particles. Zirconia has also been introduced into OPC discs by vacuum infiltration methods developed for solutions and colloidal suspensions. Comparisons between OPC discs and the OPCtetragonal ZrO2 composites have been made on the basis of diametral compression strength, Young’s modulus, hardness and toughness (K1c), as estimated by the cracked indentation method. Bell-shaped curves are found for the way the mechanical properties are changed as a function of Zirconia content.

Submitted by Edineia Teixeira (edineia.teixeira@unioeste.br) on 2018-03-05T18:27:51Z No. of bitstreams: 2 Fernando_Martins2017.pdf: 3146180 bytes, checksum: a1dcde101c1559cda9b93c488d0f17e9 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-03-05T18:27:51Z (GMT). No. of bitstreams: 2 Fernando_Martins2017.pdf: 3146180 bytes, checksum: a1dcde101c1559cda9b93c488d0f17e9 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-02-16 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / For species that do not exhibit parental care such as oviparous insects, choosing a favorable oviposition site is of utmost importance for brood success. Niche theory predicts that crickets should show a bell-shaped oviposition response to substrate humidity. However, at least one lab experiment with mole crickets (Orthoptera: Gryllotalpoidea) indicated a linear oviposition responses to substrate humidity. The house cricket Acheta domesticus (Orthoptera: Grylloidea) also shows a linear juvenile body growth response to substrate humidity, which suggests a positive relationship between humidity and oviposition preference. We evaluated the relationship between oviposition frequency and substrate humidity in forest litter- dwelling species, primarily composed of Ubiquepuella telytokous, using field experiments. We also tested oviposition responses of U. telytokous to substrate humidity in a laboratory experiment. We offered oviposition substrates that varied in humidity from zero percent to maximum substrate water absorption capacity. Oviposition preference was estimated using presence or absence of eggs as a binary response variable, adjusted logistic regression (GAMM) was used to test for non-linear responses, and GLMs were used to test linear responses. We found that oviposition probability increased linearly with substrate humidity for U. telytokous in both field and lab experiments. Our results demonstrate the importance of substrate humidity as an ecological niche requirement for this species. This work bolsters knowledge of litter cricket life history association with humidity, and suggests that litter crickets may be particularly threatened by changes in climate that favor habitat drying. / Para espécies que não apresentam cuidados parentais, tais como insetos ovíparos, a escolha de um local de oviposição favorável é de extrema importância para o sucesso da prole. A teoria do nicho prevê que a oviposição de grilos deve mostrar uma resposta em forma de sino à umidade do substrato. Entretanto, pelo menos um experimento de laboratório com paquinhas (Orthoptera: Gryllotalpoidea) indicou uma resposta de oviposição linear em relação a umidade do substrato. O grilo doméstico Acheta domesticus (Orthoptera: Grylloidea) também apresenta um crescimento corporal dos juvenis linear em relação a umidade do substrato, o que sugere uma relação positiva entre umidade e preferência de oviposição. Aqui testamos a relação entre a frequência de oviposição e a umidade do substrato, em espécies de grilos de serrapilheira florestal, primariamente compostas Ubiquepuella telytokous, utilizando experimentos de campo. Também testamos as respostas de oviposição de U. telytokous em experimentos de laboratório. Oferecemos substratos de oviposção que variaram a umidade de zero porcento até a capacidade máxima de absorção do substrato. A preferência de oviposição foi estimada utilizando presença ou ausência de ovos como uma variável resposta binária, regressão logística ajustada (GAMM) para testar respostas não lineares, e GLMs para testar respostas lineares. Verificamos que a probabilidade de oviposição aumenta linearmente com a umidade do substrato para U. telytokous, nos experimentos de campo e laboratório. Nossos resultados demonstram a importância da umidade do substrato como requisito de nicho ecológico para Ubiquepuella telytokous. Este trabalho reforça o conhecimento da associação de história de vida de grilos com a umidade, e sugere que esses organismos podem ser particularmente ameaçados por mudanças climáticas que tornam habitats áridos.

The effects of metastable tetragonal zirconia on the properties of Ordinary Portland Cement were observed during which the effect of crystallite size pH on the preparation solution, precursor salt, and the presence of co-precipitates, Fe(OH)3, SnO2 and SiO2 on the crystallization temperature, enthalpy and crystal structure, immediately following the crystallization exothermic burst phenomenon in ZrO2 were measured. Thermal analysis and x-ray methods were used to determine crystallite sizes and structures immediately following the exothermic burst. Comparisons were made for zirconias prepared from oxychloride, chloride and nitrate solutions. The existence of tetrameric hydroxidecontaining ions in oxychloride precursor is used to rationalise low values of crystallization enthalpy. The position of the crystallization temperature, Tmax was not dependent on crystallite size alone but also on the pH at which the gel was made, the surface pH after washing, and the presence of diluent oxides. Enthalpy v r1/2 and Tmax v (diluent vol)1/3 relationships indicate that surface coverage effects dominate a surface nucleated phenomenon. The data established for ZrO2 systems was used to develop tetragonal-ZrO2-SnO2 powders capable of improving the mechanical properties of Ordinary Portland Cement discs. The ZrO2-OPC discs were prepared by powder mixing, water hydration and uniaxial pressing. Vicat needle tests showed that tetragonal-ZrO2 increases the initial setting rate. Microscopy indicated that porosity distribution changes near to ZrO2 particles. Zirconia has also been introduced into OPC discs by vacuum infiltration methods developed for solutions and colloidal suspensions. Comparisons between OPC discs and the OPCtetragonal ZrO2 composites have been made on the basis of diametral compression strength, Young’s modulus, hardness and toughness (K1c), as estimated by the cracked indentation method. Bell-shaped curves are found for the way the mechanical properties are changed as a function of Zirconia content.