This thesis examines a number of natural and anthropogenic disturbances within marine macrophyte habitats of the Caribbean. Understanding the effects of disturbance and the patterns associated with such dynamics is fundamental to ecological studies. Dynamics of interest included: interactions between populations; interactions between life history strategies; successional regimes; and alterations of community structure including loss of trophic heterogeneity and the possibility of "alternate" states. First I explored natural physical disturbance and succession. The dominance of macroalgae in the mid-shore, between areas of seagrass, challenged "classic" succession in such communities. I therefore proposed a model that included chronic "stress" by wave energy that could lead to a reversal in the climax state. Next, I investigated the importance of other grazers (i.e. trophic heterogeneity) in mediating the strength of trophic cascades (e.g. overgrazing). The enclosure experiments used suggested that different life history strategies respond differently to experimental conditions and that interference competition between specialist (conch) and generalist (urchins) grazers results in urchins switching to alternate resources and displaying lower condition. This dynamic may indirectly "buffer" the community against population expansions of urchins and overgrazing of diversity enhancing detritus. Under high nutrient enrichment, urchins maintained themselves, the trophic cascade and low diversity by switching to "expanded" autochthonous and "new" allochthonous resources. I continued to examine the effects of increasing nutrient enrichment, which correlated well with increasing human density, by examining eleven seagrass beds. The patterns of increasing consumer density and decreasing consumer diversity corresponded well to increasing enrichment and loss of autochthonous detritus. At high levels of enrichment, the community was dominated (> 90%) b

In New Zealand, native shrubs are considered an important potential carbon-sink in disturbed or abandoned land (e.g., pastoral land that is unsustainable for long-term pastoral agriculture). However, the impact of varying environmental drivers on carbon uptake from photosynthesis and carbon loss from respiration of a developing shrubland remains uncertain. In this study, the effects of both temperature and soil water content (θ) on photosynthesis and respiration were examined under controlled growth cabinet and field conditions in a pasture grass and the native shrub, kānuka (Kunzea ericoides var. ericoides). The purpose of the investigation was to assess the combined impacts of varying temperature and θ on canopy processes and to disentangle the effects of θ on photosynthesis and respiration for the two different plant types. A controlled growth cabinet study (Chapter 2) showed that θ had a greater effect on the short-term temperature response of photosynthesis than the temperature response of respiration. The optimum value of θ for net photosynthesis was around 30 % for both kānuka and the grass. Statistical analysis showed that the temperature sensitivity of photosynthetic parameters was similar for both plant types, but the sensitivity of respiratory parameters was different. Reduction in θ induced an inhibition of photosynthetic capacity in both plant types. The response of respiratory parameters to θ was not related to substrate limitations, however available evidence suggests that it is likely to be a species dependent plant mechanism in regulating the cost of maintenance due to reduced photosynthate assimilation and decreasing energy supply to support the activity of respiratory enzymes. Results obtained from a field study (Chapter 3) showed that photosynthesis and respiration in the grass and kānuka were sensitive to seasonal changes in temperature and θ. Photosynthetic parameters showed little acclimation following changes in seasonal growth conditions. In contrast, respiratory parameters tended to acclimate more strongly. Respiratory acclimation to multiple environmental conditions was characterised by changes in temperature sensitivity and a shift in the response of respiration to temperature, demonstrating the involvement of both ‘Type I’ and ‘Type II’ acclimation in both plant types. The results from controlled growth cabinet and field studies were used to drive a leaf level model that integrates the responses of photosynthesis and respiration to changes in temperature and θ and incorporates acclimation using variable photosynthetic and respiratory parameters (Chapter 4). This model was used to estimate the annual canopy carbon exchange of the grass and kānuka in response to seasonal changes and to predict changes in canopy carbon exchange under varying future climate change scenarios. The model highlighted the importance of considering seasonally-acclimated parameters in estimating canopy carbon exchange of both plant types to concurrent changes in multiple environmental variables. The overall results support the conclusion that understanding the combined effects of environmental variables on canopy processes is essential for predicting canopy net carbon exchange of a pasture-shrub system in a changing global environment. It has been shown here that the rate of increase in photosynthesis with increasing θ is greater than that of respiration which results in a progressively greater apparent carbon gain at moderate values of θ. Moreover, the impact of lower values of θ, which reduced the apparent sensitivity of respiration to temperature, may effectively decrease the rate of respiration during warmer summer months and enhance thermal acclimation via downregulation of respiration. Therefore, considering the influence of soil water conditions on the temperature sensitivity of photosynthetic and respiratory model parameters has important implications for precisely predicting the net carbon exchange of a pasture-shrub system.

‘FIELD WORKS’ explores landscape experiences that were once common to the tall grass prairie region of Manitoba. The route through this project winds in and out of urban surfaces to reveal memories embedded in the land. It documents forgotten and dormant prairie events so that they might be woven back into the fabric of the city. The purpose of this project is to transfer explored and speculative experience into a physical route through the urban prairie landscape. It is an effort to expose the layers clinging to physical memories rooted in the prairie.

No abstract available. / Thesis (Ph.D.)-University of Natal, Pietermaritzburg, 1984.

Video game journalism has been accused for lack in journalistic legitimacy for decades. The historical relation between video game journalists and video game publishers has always been problematic from an objective point of view, as publishers have the power to govern and dictate journalistic coverage by withdrawing financial funding and review material. This has consequently lead to lack in journalistic legitimacy when it comes to video game coverage. However, as the grass roots media movement gained popularity and attention in the mid 2000s, a new more direct and personal way of coverage became evident. Nowadays, grass roots media producers operate within the same field of practice as traditional journalists and the difference between entertainment and journalism has become harder than ever to distinguish. The aim of this master thesis is to discover if grass roots media is more critical than traditional video game journalism regarding industry coverage. The study combines Communication Power theory, Web 2.0 and Convergence Culture, as well as Alternative Media and Participatory Journalistic theory, to create an interdisciplinary theoretical framework. The theoretical framework also guides our choice in methodology as a grounded theory study, where the aim of analysis is to present or discover a new theory or present propositions grounded in our analysis. To reach this methodological goal, 10 different grass roots media producers were interviewed at 6 different occasions. The interviewees were asked about their opinions regarding grass roots media production, their own contribution, as well how they identified journalistic coverage. It was discovered that the grass roots media producers were not more critical than traditional video game journalists. This was because grass roots media producers operate under the rules of entertainment production. It was discovered that if grass roots media producers break out of the normative rules of entertainment production, they would either loose their autonomous freedom or funding, resulting in a catch-22 situation. Furthermore, it was found that grass roots media producers did not identify themselves as journalists; rather they identified themselves as game critics or reviewers. Thus, a video game journalist is categorised as an individual that report writes or edits video game news as an occupation, with formal journalistic training. However, since neither grass roots media producers nor industry veterans in general have journalistic training, it is still unclear who is a video game journalist. Lastly, we found that grass roots media producers have little possibility to influence traditional video game journalism. The only way to increase the status of journalistic legitimacy is by encouraging journalism itself, to engage in critical media coverage. As there is a public demand for industry coverage, and journalistic legitimacy is grounded on the normative democratic self-descriptions of the profession, video game journalism needs to move beyond entertainment and engage in democratically, constructive and critical coverage.

P-glycoprotein (Pgp), which leads to multidrug resistance in tumour cells, is an ATP-dependent secretory drug efflux pump. In the intestine, as well as at specific other epithelial and endothelial sites, P-glycoprotein expression is localised to the apical membrane, consistent with secretory detoxifying and absorption limitation functions. The primary function of Pgp is to clear the membrane lipid bilayer of lipophilic drugs. Results from in vitro studies with human Caco-2 cells provide direct evidence for Pgp limiting drug absorption. Limitation has non-linear dependence of absorption on substrate (eg. vinblastine) concentration, increased absorption upon saturation of secretion and increased absorption upon inhibition of Pgp function, with modulators such as verapamil. The aim of this study was to investigate the effect of a known Pgp inhibitor (verapamil) and grapefruit juice components (naringenin, quercetin and bergamottin) on the transport of Rhodamine 123 across rat jejunum and to compare these results with those obtained in similar studies done in Caco-2 cells and in rat intestine (monodirectional). Verapamil, naringenin (442 µM, 662 µM and 884 µM), quercetin (73 µM, 183 µM and 292 µM) and bergamottin (12 µM, 30 µM and 48 µM) were evaluated as modulators of rhodamine 123 transport across rat jejunum using Sweetana-Grass diffusion cells. This study was done bidirectionally, with three cells measuring transport in the apical to basolateral direction (AP / BL) and three cells measuring transport in the basolateral to apical direction (BL / AP). The rate of transport was expressed as the apparent permeability coefficient (Papp) and the extent of active transport was expressed by calculating the ratio of BL/AP to AP/BL. The BL-AP/AP-BL ratio calculated for Rhodamine 123 with no modulators added was 2.31. The known modulator verapamil decreased the BL-AP/AP-BL ratio to 1.52. This was statistically significant and inhibition of active transport was clearly demonstrated. All modulators inhibited active transport. Only naringenin 884 µM, quercetin 183 µM and bergamottin 30 µM did not show a statistically significant decrease in the BL-AP/AP-BL ratio. All three components of grapefruit juice showed inhibition of active transport and should have an effect on the bioavailability of the substrates of Pgp and other active transporters. The results obtained in this study are similar to the results found in Caco-2 cells, which suggests that Sweetana-Grass diffusion method can be used for diffusion studies. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.

Many orally administered drugs must overcome several barriers before reaching their target site. The first major obstacle to cross is the intestinal epithelium. Although lipophilic compounds may readily diffuse across the apical plasma membrane, their subsequent passage across the basolateral membrane and into blood is by no means guaranteed. Efflux proteins located at the apical membrane, which include P-glycoprotein (P-gp, MDR1) and Multidrug Resistance-associated Protein (MRP2), may drive compounds from inside the cell back into the intestinal lumen, preventing their absorption into the blood. Intestinal P-gp is localised to the villus tip enterocytes, i.e. the main site of absorption for orally administered compounds and in close proximity to the lumen. P-gp is therefore ideally positioned to limit the absorption of compounds by driving efflux back into the lumen. Drugs may also be modified by intracellular phase I and phase II metabolizing enzymes. This process may not only render the drug ineffective, but it may also produce metabolites that are themselves substrates for P-gp and/or MRP2. Drugs that reach the blood are then passed to the liver, where they are subjected to further metabolism and biliary excretion, often by a similar system of ATP binding cassette (ABC) transporters and enzymes to that present in the intestine. Thus a synergistic relationship exists between intestinal drug metabolizing enzymes and apical efflux transporters, a partnership that proves to be a critical determinant of oral bioavailability. Aim: The aim of this study was to investigate the effect of selected methoxy flavonoids (3-methoxyflavone, 5-methoxyflavone, 6-methoxyflavone and 7- methoxyflavone) on the mean ratio of Rhodamine123 (Rho 123) transport across rat intestine (jejunum) and to investigate structure activity relationships (SAR) of the selected flavonoids with reference to inhibition of P-gp. Methods: 3-Methoxyflavone, 5- methoxyflavone, 6-methoxyflavone and 7-methoxyflavone were evaluated at a concentration of 10μM and 20μM as modulators of Rho 123 transport across rat jejunum. The Sweetana-Grass diffusion cells were used to determine the transport of Rho 123. Each modulator was studied bidirectionally with two cells measuring transport in the apical to basolateral direction (AP/BL) and two cells measuring transport in the basolateral to apical direction (BUAP). The rate of transport was expressed as the apparent permeability coefficient (Papp)and the extent of active transport was expressed by calculating the ratio of BUAP to AP/BL. Each modulators Papp ratio was then compared with that of the control. Results: 3-Methoxyflavone decreased the Papp ratio from 3.34 (control) to 1.66 (10μM) and 1.33 (20μM) and showed statistical significant differences. 7-Methoxyflavone decreased the Papp ratio to 1.94 (10μM) and 1.55 (20μM) but only showed a statistical significant difference at 10μM. 5- Methoxyflavone decreased the Papp ratio to 2.41 (10μM) and 1.71 (20μM) and 6- methoxyflavone decreased the Papp to 3.03 (10μM) and 2.49 (20μM). Both 5- and 6- methoxyflavone showed no statistical significant differences from the control. The structure activity relationships with reference to P-gp inhibition clearly indicated that the C3 and C7 positioning of the methoxy-group on the A ring played a major role in the inhibition of Rho 123 transport. Conclusion: All the selected modulators showed inhibition of Rho 123 transport across the jejunum. This should affect the bioavailability of the substrates of P-gp and other active transporters. In summary, this study describe the inhibitory interaction of selected flavonoids with P-gp. Structure activity relationships were identified describing the inhibitory potency of the flavonoids based on methoxy groups positioning. The inhibitory potency results were 3-methoxyflavone > 7- methoxyflavone > 5-methoxyflavone> 6-methoxyflavone / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.

Background: Multidrug resistance (MDR) is resistance of cancer cells to multiple classes of chemotherapeutic drugs that can be structurally unrelated. MDR involves altered membrane transport that results in a lower cell concentration of cytotoxic drugs which plays an important role during cancer treatment. P-glycoprotein (Pgp) is localised at the apical surface of epithelial cell in the intestine and it functions as a biological barrier by extruding toxic substances and xenobiotics out of cells (Lin, 2003:54). The ATP-binding-cassette superfamily is a rapidly growing group of membrane transport proteins and are involved in diverse physiological processes which include antigen presentation, drug efflux from cancer cells, bacterial nutrient uptake and cystic fibrosis (Germann, 1996:928; Kerr, 2002:47). A number of drugs have been identified which are able to reverse the effects of Pgp, multidrug resistance protein (MRPI) and their associated proteins on multidrug resistance. The first MDR modulators discovered and studied during clinical trials were associated with definite pharmacological actions, but the doses required to overcome MDR were associated with the occurrence of unacceptable side effects. As a consequence, more attention has been given to the development of modulators with proper potency, selectivity and pharmacokinetic characteristics that it can be used at a lower dose. Several novel MDR reversing agents (also known as chemosensitisers) are currently undergoing clinical evaluation for the treatment of resistant tumours (Teodori et al., 2002:385). Aim: The aim of this study was to investigate the effect of selected flavonoids (morin, galangin, kaempferol and quercetin) at two different concentrations (10 μM and 20 μM) on the transport of a known Pgp substrate, Rhodamine 123 (Rho 123) across rat intestine (jejunum) and to investigate structure activity relationships (SAR) of the selected flavonoids with reference to the inhibition of Pgp. Methods: Morin, galangin, kaempferol and quercetin were evaluated as potential modulators of Rho 123 transport, each at a concentration of 10 μM and 20 μM across rat jejunum using Sweetana-Grass diffusion cells. This study was done bidirectionally, with two cells measuring transport in the apical to basolateral direction (AP-BL) and two cells measuring transport in the basolateral to apical direction (BL-AP). The rate of transport was expressed as the apparent permeability coefficient (Pap,) and the extent of active transport was expressed by calculating the ratio of BL-AP to AP-BL. Results: The BL-AP to AP-BL ratio calculated for Rho 123 with no modulators added was 3.29. Morin decreased the BL-AP to AP-BL ratio to 1.88 at a concentration of 10 μM and to 1.49 at a concentration of 20 μM. Galangin decreased the BL-AP to AP-BL ratio to 1.60 at a concentration of 20 μM. These two flavonoids showed statistically significant results and inhibition of active transport were clearly demonstrated. However, the other flavonoids inhibited active transport of Rho 123 but according to statistical analysis, the results were not significantly different. The two different concentrations (10 μM and 20 μM) indicated that galangin, kaempferol and quercetin showed practically significant differences according to the effect sizes. Morin, however, did not show any practically significant differences at the different concentrations. Regarding .the SAR, it was shown by Boumendjel and co-workers (2002:512) that the presence of a 5-hydroxyl group and a 3-hydroxyl group as well as the C2-C3 double bond are required for high potency binding to the nucleotide binding domain (NBD) of Pgp. All the flavonoids tested had the above-mentioned characteristics. Conclusion: All the selected flavonoids showed inhibition of active transport of Rho 123 and should have an effect on the bioavailability of the substrates of Pgp and other active transporters. This study described the inhibitory interaction of selected flavonoids on Pgp activity. Practical significant differences between the same modulator at different concentrations were also observed. Structure activity relationships were identified describing the inhibitory potency of the flavonoids based on hydroxyl group positioning / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.

The absorption enhancing ability of chitosan, a linear polysaccharide, is mediated by protonated amino groups on the C-2 position of the molecules that induce interaction with the anionic sites on the cell membranes to subsequently alter tight junction integrity. In neutral and basic environments, such as those found in the small and large intestines, most chitosan molecules will lose their charge and precipitate from solution rendering it ineffective as an absorption enhancer. To increase the solubility of this polymer, methylation of the amino groups on the C- 2 position was proposed. A partially quaternised and water soluble derivative of chitosan, N-trimethyl chitosan chloride (TMC), which exhibits superior solubility in a basic environment compared with other chitosan salts was synthesised and included in a chitosan microbead solid drug delivery system. Two TMC derivatives were synthesised by reductive methylation from high and medium molecular weight Chitoclear™ chitosan respectively. The degree of quaternisation calculated from the 1H-NMR spectra for the medium molecular weight TMC (TMC-M) and the high molecular weight TMC (TMC-H) polymers were 74.7 % and 48.5 % respectively. The mean molecular weights of the synthesised TMC-M and TMC-H polymers were 64 100 g/mole and 233 700 g/mole respectively. The effect of different concentrations TMC-M and TMC-H on chitosan microbeads was studied with results obtained from scanning electron microscopy (SEM), TMC loading capacity and microbead swelling behaviour. After selection of the most suitable TMC concentration, the effect of varying concentration (0.1, 0.2 and 0.5 %) additives on TMC and ibuprofen release was studied. Commonly used modified cellulose gum (Ac-di-sol®(ADS)), sodium starch glycolate (Explotab®(EXP)) and ascorbic acid (AA) were added as disintegrants to different microbead formulations to promote release of both the ibuprofen as model drug and TMC from the beads. It was noticed that the loading (% drug loading capacity) of TMC-M was much lower than that obtained with TMC-H while the inclusion of different additives in varying concentrations did not seem to have a profound influence on the loading of either TMC-M or TMC-H. It was further noticed from the fit factors (f1 and f2) for dissolution profiles of eighteen chitosan microbead variations that the formulation containing TMC-H and 0.5% (w/v) ascorbic acid was the only formulation with a significantly higher ibuprofen and TMC-H release profile compared to all other formulations tested. The chitosan microbead formulation containing 2%(w/v) TMC-H and 0.5 % (w/v) ascorbic acid (H-AA-0.5) was used for in vitro absorption studies through rat intestine in Sweetana-Grass diffusion chambers. Chitosan containing TMC-H (no ascorbic acid) (CHIT-H) only and a plain chitosan microbead (CHIT) formulation was used as control formulations during the in vitro studies. Although the H-AA-0.5 formulation exhibited the highest transport rate for ibuprofen, the mean rate of transport (P app) obtained from the two formulations containing TMCH (CHIT-H and H-AA-0.5) showed no significant difference in the transport rate of ibuprofen. Compared to the CHlT formulation as control, both formulations containing TMC-H exhibited increased ibuprofen transport across in vitro rat jejunum. However, a statistical significant increase in transport was obtained only from the H-AA-0.5 formulation in comparison with the CHlT formulation. It can be concluded that the combination of high molecular weight TMC with a low degree of quaternisation and ascorbic acid (0.5% w/v) in a chitosan microbead lead to a statistical significant increase in the in vitro transport rate of ibuprofen through rat jejunum. / Thesis (Ph.D. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2006.

‘FIELD WORKS’ explores landscape experiences that were once common to the tall grass prairie region of Manitoba. The route through this project winds in and out of urban surfaces to reveal memories embedded in the land. It documents forgotten and dormant prairie events so that they might be woven back into the fabric of the city. The purpose of this project is to transfer explored and speculative experience into a physical route through the urban prairie landscape. It is an effort to expose the layers clinging to physical memories rooted in the prairie.