No description available.

No description available.

DL-2-Amino-4-phosphonobutyric acid, an isostere of phosphoserine, was incorporated into the heptapeptide sequence, Leu-Arg-Arg-Ala-(DL-2-amino-4-phosphonobutyric acid)-Leu-Gly, for kinetic mechanistic studies of the cAMP-dependent protein kinase. To block the phosphono hydroxyl groups, methyl, ethyl and 4nitrobenzyl esters were studied as possible protecting groups. The phosphono diethyl ester of the N-Fmoc-protected amino acid was utilized in the synthesis of the heptapeptide. Two configurational forms of the protected peptide were obtained and were separated by C18-reverse phase HPLC. Characterization of the two isomeric forms was accomplished by 3 1P NMR, 1H NMR, 13C% NMR and amino acid analysis. The protecting groups of the isomeric phsophonopeptides were removed by HBr/AcOH and purified by cation exchange HPLC. Both phosphonopeptides were found to be inhibitors of the cAMP-dependent protein kinase, having Ki values of 0.6 mM (peptide A) and 1.9 mM (peptide B).

M.A. / The subject of this mini-dissertation is the social assessment of the proposed development of a campsite project by the Amangwane community. This project is proposed for the Cathedral Peak area of the Kwazulu Natal northern Drakensberg in partnership with the local conservation authority KZN Wildlife. As a result of the Business Plan process it was decided that participation of the wider community was necessary to obtain their input in designing the requirements for a successful campsite development. In this way the community needs will be met as far as possible. The purpose of undertaking the social assessment was twofold. Firstly, it was undertaken to establish what social structures exist within the community. This was done in order to identify and analyse the characteristics of the social structures in relation to the identified characteristics of the proposed campsite project and the possible impacts the project might have on the community. Secondly, it undertook to make suggestions in mitigation of potentially negative factors. A qualitative style of research was adopted due to the high level of involvement of the researcher in the community being studied. This close association helped in obtaining first-hand information and a practical, participatory approach, described as participatory action research, was followed. It is notable that no significant negative social impacts were recorded. The most noteworthy finding of the research was that the expectations of the community, in terms of positive impacts, were way beyond what the project could deliver. This is particularly true in terms of job creation. The main mitigation measure suggested in this respect relates to education and information dissemination. A number of other suggestions are also put forward that could positively influence the implementation of the project and the subsequent benefits to the community. / Prof. Tina Uys Prof. Anton Senekal

Parathyroid hormone (PTH) secretion maintains free-ionised extracellular calcium (Ca2+o) homeostasis under the control of the calcium-sensing receptor (CaR). In humans and dogs, blood acidosis and alkalosis is associated with increased or suppressed PTH secretion respectively. Furthermore, large (1.0 pH unit) changes in extracellular pH (pHo) alter Ca2+o sensitivity of the CaR in CaR-transfected HEK-293 cells (CaR-HEK). Indeed, it has been found in this laboratory that even pathophysiological acidosis (pH 7.2) renders CaR less sensitive to Ca2+o while pathophysiological alkalosis (pH 7.6) increases its Ca2+o sensitivity, both in CaR-HEK and parathyroid cells. If true in vivo, then CaR’s pHo sensitivity might represent a mechanistic link between metabolic acidosis and hyperparathyroidism in ageing and renal disease. However, in acidosis one might speculate that the additional H+ could displace Ca2+ bound to plasma albumin, thus increasing free-Ca2+ concentration and so compensating for the decreased CaR responsiveness. Therefore, I first demonstrated that a physiologically-relevant concentration of albumin (5% w/v) failed to overcome the inhibitory effect of pH 7.2 or stimulatory effect of pH 7.6 on CaR-induced intracellular Ca2+ (Ca2+i) mobilisation. Determining the molecular basis of CaR pHo sensitivity would help explain cationic activation of CaR and permit the generation of experimental CaR models that specifically lack pHo sensitivity. With extracellular histidine and free cysteine residues the most likely candidates for pHo sensing (given their sidechains’ pK values), all 17 such CaR residues were mutated to non-ionisable residues. However, none of the resulting CaR mutants exhibited significantly decreased CaR pHo sensitivity. Even co-mutation of the two residues whose individual mutation appeared to elicit modest reductions (CaRH429V and CaRH495V) failed to exhibit any change in CaR pHo sensitivity. I conclude therefore, that neither extracellular histidine nor free cysteine residues account for CaR pHo sensitivity. Next, it is known that cytosolic cAMP drives PTH secretion in vivo and that cAMP potentiates Ca2+o-induced Ca2+i mobilisation in CaR-HEK cells. Given the physiological importance of tightly controlled PTH secretion and Ca2+o homeostasis, here I investigated the influence of cAMP on CaR signalling in CaR-HEK cells. Agents that increase cytosolic cAMP levels such as forskolin and isoproterenol potentiated Ca2+o-induced Ca2+i mobilisation and lowered the Ca2+o threshold for Ca2+i mobilisation. Indeed, forskolin lowered the EC50 for Ca2+o on CaR (2.3 ± 0.1 vs. 3.0 ± 0.1 mM control, P<0.001). Forskolin also potentiated CaR-induced ERK phosphorylation; however protein kinase A activation appeared uninvolved in any of these effects. Pertussis toxin, used to block CaR-induced suppression of cAMP accumulation, also lowered the Ca2+o threshold for Ca2+i mobilisation though appeared to do so by increasing efficacy (Emax). Furthermore, mutation of the CaR’s two putative PKA consensus sequences (CaRS899 and CaRS900) to a non-phosphorylatable residue (alanine) failed to alter the potency of Ca2+o for CaR or attenuate the forskolin response. In contrast, phosphomimetic mutation of CaRS899 (to aspartate) did increase CaR sensitivity to Ca2+o. Together this suggests that PKA-mediated CaRS899 phosphorylation could potentiate CaR activity but that this does not occur following Ca2+o treatment in CaR-HEK cells. Together, these data show that cAMP regulates the Ca2+o threshold for Ca2+i mobilisation, thus helping to explain differential efficacy between CaR downstream signals. If true in vivo, this could help explain how multiple physiological signal inputs may be integrated in parathyroid cells.

Background After the 2010 earthquake in Haiti, there was a significant need for basic services such as health, water, food, sanitation, school, protection and security in the largest camp in Port-au-Prince, Park Jean Marie Vincent (PJMV). PJMV IDP camp was located in the commune of Cité Soleil; a slum in Haiti labeled as a red zone and widely regarded as the most insecure place on earth. As a result, the camp residents were left to live on their own contradicting the humanitarian principle of humanity and impartiality. Strong solidarity developed amongst camp residents leading them to organize themselves in order to decrease structural violence. Zanmi Lasante (ZL), a healthcare and human rights organization that works with poorest and most vulnerable communities in Central Plateau, would cross the red zone to accompany the camp residents by providing training, materials, and resources to set up aid activities. Using a qualitative methodology, this study will describe the activities ZL completed and present the outcomes of those activities. This study will argue that the ZL accompaniment helped to decrease structural violence and chaos and allowed the camp residents to persevere. Methods This study is based on a personal story and experience of the researcher in PJMV IDP camp after the 2010 Haitian earthquake. We collected data from semi-structured interviews with 5 ZL staff, 7 camp leaders, and 5 camp residents. The researcher conducted a narrative analysis to recreate a collective memory from four viewpoints: 1) Zanmi Lasante staff; 2) camp leaders; 3) IDP camp residents and 4) the researcher. The researcher used processual methods of qualitative research to identify themes and exemplar narratives to compare and contrast these multiple viewpoints. Results The interviews offered multiple viewpoints on the activities in the camp both before and during the time ZL was active. Activities included creating and staffing a health clinic, training community health workers, establishing a nutrition center, ensuring HIV-AIDS care, and launching a response to the cholera outbreak. In addition, ZL conducted other kinds of activities that put health in the social context, including building a water purification system, establishing a tent village, creating a school program, launching an initiative to protect women from sexual violence, and advocating for food and sanitation. The researcher finds that those additional activities generated good outcomes such as health, security, job creation, capacity building, community engagement and participation, and community empowerment. ZL used a collaborative approach, integrating accompaniment into all activities by working with local residents, leaders and other organizations. This accompaniment decreased structural violence and helped camp residents to be more self-sufficient. The study also explores the challenges of accompaniment as responsibilities for these activities were shifted from ZL to the camp residents and local leaders. Conclusions The goal of this study is to describe the activities conducted by ZL in PJMV from January 2010 to January 2012 and how the approach of offering aid using the accompaniment model impacted the social context in the camp. The researcher recommends that humanitarian aid from within and beyond a disaster affected community be geared toward supporting and partnering with local communities and local organizations. In this way, humanitarian aid will strengthen local communities in a way that may be sustained once these organizations leave.

No abstract available / Dissertation (MA(Fine Arts))--University of Pretoria, 2008. / Visual Arts / unrestricted

The West Ansil deposit was the first Cu discovery in 25 years in the Noranda Central Camp. It has a combined indicated and inferred resource of ~1.2 Mt. Grades for the indicated resource are 3.4% Cu, 0.4% Zn, 1.4 g/t Au and 9.2 g/t Ag. The bulk of the resource is located in three massive sulphide lenses (Upper, Middle and Lower) that are entirely within the Rusty Ridge Formation above the Lewis exhalite. The mineralization in all three ore lenses consists of massive pyrrhotite + chalcopyrite + magnetite. Semi-massive sphalerite is restricted to the upper and lower parts of the Middle lens. Massive magnetite occurs at the center of the Upper and Middle lenses, where it replaces massive pyrrhotite. A striking feature of West Ansil is the presence of abundant colloform and nodular pyrite (+marcasite) in the massive sulphides. Late-stage replacement of massive pyrrhotite by colloform pyrite and marcasite, occurs mostly along the upper and lower contacts of the lenses.

This thesis examined why NCAA Division 1 American football “linemen” experience greater heat strain than “backs” during summer training camps. In study #1, exercise at a heat production of 350 W/m2 in a hot environment (Tdb:32.4±1.0ºC; Twb:26.3±0.6ºC) resulted in greater local sweating on the upper body (head, arm, shoulder and chest; all <0.05) and a greater core temperature (P=0.033) in linemen despite a ~25% lower heat production per unit mass (L:6.0±0.5 W/kg; B:8.2±0.8 W/kg). In study #2, greater convective and evaporative heat transfer coefficients (P<0.05) were found in backs during live summer training camp drills, but these did not lead to a greater dry heat transfer or evaporative capacity. However, the maximum metabolic rate per unit mass was lower in linemen due to differences surface area-to-mass ratio. In conclusion, the greater heat strain previously reported in linemen likely arises, in part, from differences in sweating efficiency and body morphology.

Diploma thesis has a theoretical part that presents the chapters of the Project Management theory which are relevant for English Camps. Knowledge from the theoretical part is then in a practical part applied on a specific English Camp which was managed by author of this diploma thesis. Goal of the diploma thesis is to suggest a set of actions in specific spheres of the English Camp management that will eliminate past problems, lessen risk of unfavourable effects and create conditions for better achievement of project goals.