Malaria is caused by the Plasmodium sp. parasite that infects the red blood cells. Of the four types of malaria, the most serious type is transmitted by Plasmodium falciparum species. It can be life threatening. The other types of malaria (P. vivale, P. ovale and P. malariae) are generally less serious and are not life threatening. The existence of malaria as an enemy of humankind certainly predates written history. For thousands of years malaria has been a deadly scourge, and it remains one today. From American president John Adams who nearly succumbed to malaria in Amsterdam while on a diplomatic mission, back down to the timeline to the early Chinese, Indians, Greeks and Romans, malaria has not spared its victims, rich or poor. It wasn’t until the 19th Century that information about the true cause of malaria became known. Yet despite this knowledge, malaria still ravages Sub–Saharan Africa, South–East Asia and Latin America, taking as its victim’s mainly young children and pregnant women. However, without certain discoveries leading to a better understanding of malaria, new groundbreaking work wouldn’t be possible. Artemisinin and its derivatives are developing into a very important new class of antimalarial and their usage is becoming more common in the fight against malaria. The most commonly used and applied of these derivatives are artesunate, artemether, arteether and dihydroartemisinin. The discovery of artemisinin as the pharmacological active ingredient in an age old Chinese herb, Artemisia annua, was a major breakthrough in malaria chemotherapy. Discovery of qinghaosu in the 1970s sparked a new age for chemotherapy of malaria, and greatly inspired further research on organic peroxides. This generated widespread interest and led to the design and synthesis of organic peroxides into a highly active area of organic chemistry. The artemisinin derivatives act quickly and are eliminated quickly. Their rapid onset makes them especially effective against severe malaria. Their rapid disappearance may be a key reason why artemisinin resistance has been so slow to develop, and may be the reason why recrudences are so common when these drugs are used in monotherapy. Since their isolation, artemisinins have had a substantial impact on the treatment of malaria. Although very potent, the use of artemisinins as prophylactic antimalarials is not recommended. The aim of this study was to synthesise ester derivatives of artemisinin, determine certain physicochemical properties such as aqueous solubility and partition coefficient, and to evaluate their antimalarial activity in comparison to dihydroartemisinin and chloroquine. In this study eight esters of dihydroartemisinin (DHA) were synthesised by substitution at C– 10. The structures of the prepared derivatives were confirmed by nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). The new artemisinin esters were tested in vitro against the chloroquine sensitive strain of Plasmodium falciparum (D10). All the compounds tested showed activity against the D10 strain. All of the esters showed potency significantly better than chloroquine, except the octyl and decyl esters which were less active. The reason for the low activity could be ascribed to the fact that these two esters are both water immiscible oils, leading to solubility problems. The ethyl, butyl, phenyl and p–nitrophenyl esters all had similar IC50 values making their activity similar. The lowest IC50 value was displayed by the butyl ester with a value of 3.2 x 10– 3 uM. The poorest activity was recorded by the two oils, the octyl and decyl esters, with IC50 values of 38 x 10–3 uM and 90.2 x 10–3 uM respectively. All other compounds showed less antimalarial potency against the D10 strain compared with the other reference drug dihydroartemisinin, except the butyl ester. The butyl ester 12 displayed activity comparable to that of DHA (IC50; 3.2 x 10–3 uM versus 3.8 x 10–3 uM), and is thus worthwhile being further investigated in terms of pharmacokinetics in order to determine its half–life. Statistically it is impossible to make structure–activity relationship (SAR) deductions from the data received as the number of compounds in the series is too small. The butyl (12) (IC50 = 3.2 uM), 4–nitrobenzyl (16) (IC50 =15 uM), 2–(acetyloxy) acetyl (17) (IC50 = 8.6 uM), and 2–phenylacetyl (18) (IC50 = 12.4 uM) esters showed on a 0.05 level statistically significantly better activity against the chloroquine sensitive D10 strain of Plasmodium falciparum than chloroquine itself while the decyl ester (14) (IC50 = 90.2 uM) was statistically significantly less potent. The activity of the octyl (13) (IC50 = 38.0 uM) and benzyl (15) (IC50 = 25.7 uM) esters did not differ from that of chloroquine. In comparison to dihydroartemisinin the propyl (11) (IC50 = 24.1 uM), octyl (13) (IC50 = 38.0 uM), decyl (14) (IC50 = 90.0 uM), and benzyl (15) (IC50 = 25.7 uM) esters proved to be statistically significantly less potent than DHA while the activity of the butyl (12) (IC50 = 3.2 uM), 4– nitrobenzyl (16) (IC50 =15.3 uM), 2–(acetyloxy) acetyl (17) (IC50 = 8.6 uM), and 2–phenylacetyl (18) (IC50 = 12.4 uM) esters did not differ from that of DHA. / Thesis (M.Sc. (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2012.

Malaria is caused by the Plasmodium sp. parasite that infects the red blood cells. Of the four types of malaria, the most serious type is transmitted by Plasmodium falciparum species. It can be life threatening. The other types of malaria (P. vivale, P. ovale and P. malariae) are generally less serious and are not life threatening. The existence of malaria as an enemy of humankind certainly predates written history. For thousands of years malaria has been a deadly scourge, and it remains one today. From American president John Adams who nearly succumbed to malaria in Amsterdam while on a diplomatic mission, back down to the timeline to the early Chinese, Indians, Greeks and Romans, malaria has not spared its victims, rich or poor. It wasn’t until the 19th Century that information about the true cause of malaria became known. Yet despite this knowledge, malaria still ravages Sub–Saharan Africa, South–East Asia and Latin America, taking as its victim’s mainly young children and pregnant women. However, without certain discoveries leading to a better understanding of malaria, new groundbreaking work wouldn’t be possible. Artemisinin and its derivatives are developing into a very important new class of antimalarial and their usage is becoming more common in the fight against malaria. The most commonly used and applied of these derivatives are artesunate, artemether, arteether and dihydroartemisinin. The discovery of artemisinin as the pharmacological active ingredient in an age old Chinese herb, Artemisia annua, was a major breakthrough in malaria chemotherapy. Discovery of qinghaosu in the 1970s sparked a new age for chemotherapy of malaria, and greatly inspired further research on organic peroxides. This generated widespread interest and led to the design and synthesis of organic peroxides into a highly active area of organic chemistry. The artemisinin derivatives act quickly and are eliminated quickly. Their rapid onset makes them especially effective against severe malaria. Their rapid disappearance may be a key reason why artemisinin resistance has been so slow to develop, and may be the reason why recrudences are so common when these drugs are used in monotherapy. Since their isolation, artemisinins have had a substantial impact on the treatment of malaria. Although very potent, the use of artemisinins as prophylactic antimalarials is not recommended. The aim of this study was to synthesise ester derivatives of artemisinin, determine certain physicochemical properties such as aqueous solubility and partition coefficient, and to evaluate their antimalarial activity in comparison to dihydroartemisinin and chloroquine. In this study eight esters of dihydroartemisinin (DHA) were synthesised by substitution at C– 10. The structures of the prepared derivatives were confirmed by nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). The new artemisinin esters were tested in vitro against the chloroquine sensitive strain of Plasmodium falciparum (D10). All the compounds tested showed activity against the D10 strain. All of the esters showed potency significantly better than chloroquine, except the octyl and decyl esters which were less active. The reason for the low activity could be ascribed to the fact that these two esters are both water immiscible oils, leading to solubility problems. The ethyl, butyl, phenyl and p–nitrophenyl esters all had similar IC50 values making their activity similar. The lowest IC50 value was displayed by the butyl ester with a value of 3.2 x 10– 3 uM. The poorest activity was recorded by the two oils, the octyl and decyl esters, with IC50 values of 38 x 10–3 uM and 90.2 x 10–3 uM respectively. All other compounds showed less antimalarial potency against the D10 strain compared with the other reference drug dihydroartemisinin, except the butyl ester. The butyl ester 12 displayed activity comparable to that of DHA (IC50; 3.2 x 10–3 uM versus 3.8 x 10–3 uM), and is thus worthwhile being further investigated in terms of pharmacokinetics in order to determine its half–life. Statistically it is impossible to make structure–activity relationship (SAR) deductions from the data received as the number of compounds in the series is too small. The butyl (12) (IC50 = 3.2 uM), 4–nitrobenzyl (16) (IC50 =15 uM), 2–(acetyloxy) acetyl (17) (IC50 = 8.6 uM), and 2–phenylacetyl (18) (IC50 = 12.4 uM) esters showed on a 0.05 level statistically significantly better activity against the chloroquine sensitive D10 strain of Plasmodium falciparum than chloroquine itself while the decyl ester (14) (IC50 = 90.2 uM) was statistically significantly less potent. The activity of the octyl (13) (IC50 = 38.0 uM) and benzyl (15) (IC50 = 25.7 uM) esters did not differ from that of chloroquine. In comparison to dihydroartemisinin the propyl (11) (IC50 = 24.1 uM), octyl (13) (IC50 = 38.0 uM), decyl (14) (IC50 = 90.0 uM), and benzyl (15) (IC50 = 25.7 uM) esters proved to be statistically significantly less potent than DHA while the activity of the butyl (12) (IC50 = 3.2 uM), 4– nitrobenzyl (16) (IC50 =15.3 uM), 2–(acetyloxy) acetyl (17) (IC50 = 8.6 uM), and 2–phenylacetyl (18) (IC50 = 12.4 uM) esters did not differ from that of DHA. / Thesis (M.Sc. (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2012.

In this thesis the static and fatigue characteristics of glass filament wound plastic pipes and joints are examined by experiments and numerical analysis. A hydraulic fatigue test rig, capable of exerting static or cyclic pressures of up to 70 MPa, was designed and built to enable pressure tests to be carried out on glass reinforced epoxy and glass reinforced vinyl ester composite pipes incorporating various joints. Static weepage and burst tests were performed on tubular specimens with and without rubber liners to determine their weepage and burst strengths under internal hydraulic pressure and to investigate the influence of the joints. Fatigue weepage tests were performed to determine the fatigue life and failure modes of glass fibre/epoxy and glass fibre/vinyl ester pipes and joints. For each material system, three types of specimen were tested. These were plain pipes, pipes with coupler-bonded joints (or laminate joints in the case of vinyl ester resin based pipes) and pipes with spigot/socket bonded joints. All specimens were commercial products with nominal diameters of two inches (50 mm). A family of curves showing pressure versus life was obtained. It was observed that weepage mostly occurred close to the pipe joints when pipes were subjected to internal pressure. Optical microscopy was used to investigate the damage initiation and propagation mechanisms in the specimens after testing. Finally, two-dimensional and three-dimensional finite element analyses were carried out to calculate the stress and strain distributions, to predict the strength, to interpret the experimental results and to examine the failure modes of the specimens. Ply-by-ply stress analysis and the Tsai-Wu failure criterion were employed for the strength prediction.

[Abstract]: With the increasing use of fibre reinforced polymer (FRP) composites in civil engineering structures, there is a growing realisation of the need to develop newstructural systems which can utilise the unique characteristics of these materials in a more efficient and economical manner. In many instances this will require thedevelopment of new materials tailored to address the unique performance and economic parameters of mainstream construction. Over recent years, researchers at the University of Southern Queensland have pioneeredthe use of a new type of particulate filled polymer core material which greatly improves the robustness and cost effectiveness of FRP structural systems. These compositematerials are composed of small hollow spherical fillers (microspheres) in a thermosetting polymer matrix. Initial research into these materials, including theirfeasibility in prototype structural elements, have shown these materials to have major potential for widespread application in structural composite systems.One of the most promising classes of these materials investigated to date are vinyl ester / cenosphere composites, which utilise cenospheres derived from fly ash in a vinyl ester matrix. Previously reported studies into these materials have been restricted to initialsurveys of material behaviour which sought to identify key parameters in achieving desired performance outcomes in the composite. This dissertation presents the first in-depth investigation of these materials specifically as a core material option for civil infrastructure applications. The particular focus of this work is on the relationship of the vinyl ester matrix to the characteristics of the resultingcomposite. Several key matrix parameters were identified and assessed as to their influence on cure characteristics, fabrication operations, mechanical properties and theretention of such properties under elevated service temperatures. The outcomes of this work have significantly improved the understanding of matrix influences on the behaviour of these composite systems and have been drawn together to provide a number of recommendations on the application of this new technology to new structural systems.

Techn. Hochsch., Diss., 2004--Aachen.

As metabolic substrates, ketone bodies provide an alternative to glucose in order to pro- long survival during starvation. A low carbohydrate, high fat diet can be used to promote ketogenesis without fasting, but long-term compliance can be difficult. Dietary ketone bod- ies may be an alternative method to induce ketosis, so the aim of the work in this Thesis was to investigate the metabolism of exogenous ketones. In the first experimental Chap- ter, the effects of ketone ester and salt drinks on blood β-hydroxybutyrate (βHB), glucose, lipids, electrolytes and pH were determined in healthy humans at rest. Blood D-βHB levels were higher following ketone ester drinks, but it was found that total βHB levels with ke- tone salts were similar, as over 50% of βHB delivered in the salt was the L-isoform, which was only slowly removed from the blood. Circulating glucose and lipid concentrations fell following both ketone drinks. Blood pH fell following ketone ester consumption, but rose following ketone salt drinks, whilst both compounds raised blood sodium and chloride, and lowered potassium. Work in the second Chapter investigated the repeatability of ketone es- ter metabolism with food, successive drinks or continuous nasogastric (NG) infusion. Peak D-βHB levels were repeatable between- and within- subjects at rest but were lower after a meal, although blood acetoacetate, breath acetone and urine βHB were unaffected by feed- ing. βHB kinetic parameters were not altered by existing hyperketonemia from successive ketone ester drinks and total βHB uptake was identical when isovolumetric amounts of ketone ester were continuously infused through a NG tube. The third Chapter explored side-effects of ketone drinks: ketone ester drinks decreased appetite compared to isocaloric dextrose; which may have been linked to effects of βHB on enteroendocrine cells. Fur- thermore, both ester and salt drinks were found to be unpalatable, and to cause a few, mild gastro-intestinal effects that increased with intake. As exogenous ketones could be a per- formance enhancing supplement in sport, the fourth Chapter used a survey to investigate supplement use by endurance athletes. The results demonstrated widespread supplement use, which was highest at the elite level. In the final Chapter, the effect of glycogen lev- els on the oxidation of βHB was determined in isolated perfused rat hearts. Low cardiac glycogen levels decreased βHB oxidation and levels of the intermediates of glycolysis and the Krebs cycle, whilst increasing muscle amino acid levels, suggesting that low glycogen may have impaired anaplerosis. In conclusion, this work extends current understanding of the novel physiological ketosis that occurs following exogenous ketone consumption.

No description available.

Cyanate ester (PT-15, Lonza Corp) composites containing the inorganic-organic hybrid polyhedral oligomeric silsesquioxanes (POSS), octaaminophenyl(T8)POSS (C6H4NH2)8(SiO1.5)8, cyanopropylheptacyclopentyl(T8)POSS, (C5H9)7(SiO1.5)8(CH2) 3CN or TriSilanolPhenylPOSS (C42H38O12Si7), were synthesized respectively. These PT-15/POSS composites were characterized by FT-IR, X-ray diffraction (XRD), small-angle neutron scattering (SANS), scanning electron microscopy (SEM), X-ray energy dispersive spectroscopy (X-EDS), transmission electron microscopy (TEM), dynamic mechanical thermal analysis (DMTA) and three-point bending flexural tests. XRD, TEM and IR data are all consistent with molecular dispersion of octaaminophenyl(T8)POSS and TriSilanolPhenylPOSS due to the chemical bonding of the POSS macromer into the continuous cyanate ester network phase. In contrast to octaaminophenyl(T8) POSS and TriSilanolPhenylPOSS, cyanopropylheptacyclopentyl (T8)POSS has a low solubility in PT-15 and does not react with the resin before or during the cure. The TriSilanolPhenylPOSS (C42H38O12Si7) was incorporated into the aliphatic epoxy (Epoxy 9000, Clearstream Products, Inc.) in 99/1, 97/3, 95/5, 90/10 and 85/15 w/w ratios and cured. This same epoxy resin was also blended with an equal weight (50/50 w/w) of cyanate ester resin (PT-15, Lonza Corp) and TriSilanolPhenylPOSS was added in resin/POSS weight ratios of 99/1, 97/3, 95/5, 90/10 and 85/15 and cured. Both sets of composites were characterized by FT-IR, X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray energy dispersive spectroscopy (X-EDS), dynamic mechanical thermal analysis (DMTA) and three-point bending flexural tests. TriSilanolPhenyl-POSS was first thoroughly dispersed into the uncured liquid epoxy resin or the epoxy/PT-15 blend. XRD and X-EDS measurements after curing were consistent with partial molecular dispersion of the POSS units in the continuous matrix phase, while the remainder forms POSS aggregates. TEM and SEM show that POSS?enriched nanoparticles are present in the matrix resins of both the epoxy/POSS and epoxy-PT-15/POSS composites.

No description available.

No description available.