No description available.

No description available.

Methotrexate is a folic acid analogue widely used as a chemotherapeutic agent. It is known to be a potent inhibitor of the enzyme dihydrofolate reductase, therefore, perturbing intracellular pools of purine and pyrimidine bases for DNA synthesis, as well as pools of reduced folates used in a variety of metabolic reactions. It has been postulated, and subsequently widely accepted, that methotrexate kills cells by perturbing the intracellular ratio of dUTP:dTTP thereby leading to dUMP misincorporation into DNA. This would initiate an excision repair pathway designed to rid cellular DNA of this aberrant base. However, because of the imbalance of nucleotide pools, dUMP may well be re-incorporated during repair thus initiating a futile cycle of dUMP misincorporation and repair eventually leading to single-strand breaks in the DNA. From the results presented in this thesis, no evidence for dUMP misincorporation could be found in the two human cell lines studied (HeLa and CCRF-HSB2), despite the drug exhibiting dose-dependent cytotoxicity to both cell lines. This was true after a variety of methotrexate treatment times and at two different drug concentrations. Subsequent analysis of the drug treated cells, using the nucleoid sedimentation technique, for evidence of single-strand breaks in DNA yielded some anomalous results. Single-strand breaks, in the form of slower sedimenting nucleoids, were easily detectable after exposure of cells to low doses of methotrexate. However, treatment with higher doses resulted in the creation of faster sedimenting nucleoids. Subsequent analysis using other techniques showed that this faster sedimentation was occurring in the presence of DNA single-strand breaks. Collaborative work involving electron microscopy revealed methotrexate induced gross morphological changes in chromatin structure. Analogies with other unrelated anti-tumour agents interacting with topoisomerase enzymes are discussed.

No description available.

This work reported is divided into two parts: the first part deals with quinoxaline derivatives and includes the preparation and characterisation of novel linear tricyclic quinones 1,4-diazanthracen-9,10-diones, (54) and (55). The reaction of diazanaphthoquinones and 1-acetyl-1,3-butadiene are used to produce these quinones through the Diels-Alder reaction. In addition hexaazapentacyclic 5,6,7,12,13, 14-hexaazapentacene was prepared by the reaction ofbis(2-chloroquinoxalin-3-yl)sulfide with thioxamide and the reaction of the sulfide with amines was investigated. Two different approaches to 6,13-dibutyl-5,6,7,12,13,14-hexaazapentacene are given. Derivatives of the pentacyclic, 6-thia- 5,7,12,13,14-pentaazapentacene and the unsubstituted 6,13 -dihydro compound are described. The novel N-(2,5-dimethoxy-6-nitrophenyl)guanidine is used to obtain 3-amino-5,6-dimethoxy-1 ,2,4-benzotriazine-1-oxide and 4,7 -dimethoxy-1 ,2,3 -benzotriazole is shown to be second product. Second part of the work is concerned with the development of a preparative route to 2,6-diphenylpyridines substituted with different groups on the phenyl nuclei. Several approaches were attempted. Finally, success was achieved and a series of compounds having basic chains of different length on the phenyl groups was prepared. One chain in each case had a terminal primary amine. The binding constants of the primary amines and their N-acetyl derivatives with DNA were determined using fluorescence spectroscopy.

This thesis determined the feasibility of developing a 16-inch, gun-launched anti-satellite weapon. The general performance capability of rocket-and scramjet-boosted, gun-launched vehicles is examined with regards to propelling a miniature homing vehicle to a satellite intercept altitude. Rocket and scramjet boost vehicle performance is modeled and optimum trajectories are determined. A low gun elevation at launch and a pop-up manuever are required to maximize the scramjet boost vehicle acceleration potential. The rocket boost vehicle is capable of intercepting a low altitude satellite without a pop-up manuever from a gun elevation of 45 degrees. Both boost methods provide apogees consistent with the intercept of known Soviet Electronic Intelligence Ocean Reconnaissance satellites, EORSAT, and Radar Ocean Reconnaissance satellites, RORSAT.

No description available.

No description available.

Two species of desert truffles, Tirmania and Terfezia were collected from the Northern desert region in Saudi Arabia for antimicrobial and antioxidant activity testing. Both species were extracted with four types of extraction solutions, methanol, ethanol, ethyl acetate and water to test for antimicrobial activity and with three extraction solutions, methanol, ethanol and water for antioxidant activity. Using disc diffusion method, the extracts were subjected to twenty three different microorganisms to observe the antimicrobial activity by measuring clear zones. Methanol extract from Tirmania was the most effective, followed by those extracted with ethanol, water and ethyl acetate respectively. In Terfezia, ethanol extract was better than methanol extract in effectiveness. Ethyl acetate extracts were the least effective. The results indicate that truffles possess antimicrobial activity with broad spectrum effects against Gram positive, Gram negative, aerobic and anaerobic bacteria as well as Saccharomyces, while no effect was recorded with fungi. The results on antioxidant activity showed that truffles have very strong antioxidant property with 99.9% with ethanol extracts of Tirmania species and 95.5% with ethanol extract of Terfezia species using beta-carotene bleaching method and antioxidant property with 96.1% with ethanol extracts of Tirmania species and 95.3% with methanol extract of Terfezia species using DPPH free radical method.

Anti-icing agents are applied to road surfaces to prevent ice formation and to melt any hail or snow as it falls. The specific agent is selected to provide optimum anti-icing properties for the particular local climate in different municipalities taking into account cost, availability and properties. These anti-icing agents are generally applied in liquid form, and due to their low freezing temperatures, are able to remain liquid at the low ambient temperatures. Unfortunately, the negative aspect of the use of liquid agents is that they are able to penetrate concrete structures to a greater extent than can the solid de-icers, such as rock salt. Once the chloride solutions penetrate the concrete, they can have serious deleterious effects on both the reinforcing steel as well as the concrete [1]. It has been shown in previous studies that the cations of the solutions will tend to react with the cementitious materials to form precipitates of expansive nature. More specifically, the reaction of CaCl2 with Ca(OH)2 results in the formation of expansive calcium hydroxy-chloride [2]. The reaction of MgCl2 with Ca(OH)2 forms Mg(OH)2 in the capillary pores with CaCl2 as a by-product after which the MgCl2 can react with the calcium-silicate-hydrate to form magnesium-silicate-hydrate – a gel-like material with no inherent binding properties or strength. The calcium hydroxy-chloride and Mg(OH)2 precipitates can have a positive effect at early onset, but will eventually cause deterioration of concrete due to the internal forces applied by the precipitates as their volume increases. This can affect the strength and create notable interior strain in the concrete. There are a number of mechanical properties that can be analyzed using short-term testing that will help to determine any changes occurring due to salt solution exposure. To gain a general understanding of the effects of the salt solution exposure in this project, compressive strength, tensile strength, elastic modulus, and strain were measured using a number of exposure conditions. While the results of testing confirm that there are initial benefits beyond minimizing ice formation and bonding, there ultimately exist a number of concerns with respect to the reactions that occur between the salts and hardened cement paste. Although the formation of calcium hydroxy-chloride is known to be expansive [3], evidence of this compound was only seen indirectly through elevated strain and micro-cracking. There was no deterioration of compressive strength, tensile strength, or elastic modulus over the short-term testing. Similarly, and again due to the short testing period, the formation of magnesium-silicate-hydrate (M-S-H) is unlikely to have occurred, though its formation during long-term exposure can result in complete loss of binding strength [2]. However, the precipitation of Mg(OH)2 is believed to be responsible for the lower chloride diffusion rate as well as the increase in strength of the concrete exposed to MgCl2. The only agent which did not yield changes of concern with respect to concrete is the NaCl solution while CaCl2 produced the most deleterious effects.