Molecular simulations of potential agents and targets of Alzheimer’s disease
- Authors: Joli, Luxolo
- Date: 2020
- Subjects: Alzheimer's disease -- Chemotherapy , Alzheimer's disease -- Treatment , Ligands (Biochemistry) , Proteins -- Chemistry , Molecular dynamics -- Simulation methods
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/146411 , vital:38523
- Description: Alzheimer's Disease (AD) is a neurodegenerative brain disorder that was first discovered in 1901 by Dr Aloïs Alzheimer and was later reported publicly in 1906. The German doctor had a 51-yearold woman patient called Auguste Deter, who was suffering from a rare brain disorder with early signs of memory loss and cognition. Alzheimer's Disease is the most common type of dementia that affects people with the age of 65 years and older. There is no single known cause of Alzheimer’s disease however, amyloid β-peptide (Aβ1–40/42) was found to be at the centre of AD pathogenesis and this connection was referred as “amyloid hypothesis”. It is suspected that an accumulation of amyloid β-peptide is a major contributor to neuronal dysfunction and degeneration. Alzheimer’s disease is complex and therefore, currently there is no medication available that treats the disease. However, there are approaches that focus on helping people maintain mental function, manage behavioral symptoms, and slow down the symptoms of disease. According to South Africa’s 2011 census, there are approximately 2.2 million people in South Africa with some form of dementia and therefore there is a need to find a treatment for the disease. This study aims to find agents and targets of Alzheimer’s Disease by using different computational techniques such as molecular modelling. The study will use compounds from the South African Compounds Database (SANCDB) and the following therapeutic targets α-, β- and γ-secretase, acetylcholinesterase, tau protein and neprilysin. A successful High-throughput Virtual Screening (HTVS) study to determine lead compounds was performed using a computational program called KNIME. Molecular docking was achieved with GLIDE as it allows for exhaustive ligand flexibility. The docking calculations were carried out using the high level of precision XP (extra precision) for enhanced docking accuracy. The binding affinities (docking scores) for the best bound ligands obtained from docking were in the order of -5 kcal/mol or less. The ligandSANC00370 was the best binding ligand against the protein 1J1C_B and had the best binding energy of -13.94 kcal/mol compared to others. The receptor-ligand complexes were analyzed using the interaction diagrams obtained from the Discovery Studio Visualizer and Maestro programs. Molecular Dynamics simulations were performed on the complexes obtained from docking to help in optimizing their interactions. The simulations were performed using the Desmond tool with the OPLS3 force field. 100 ns simulations were performed for six systems with the best docking score results epresenting each of the therapeutic targets and for the other complex systems, 50 ns simulations were performed. The Desmond simulations were analyzed using the Simulations Interaction Diagrams such as PL-RMSD, L-RMSF, P-RMSF, L-Torsions, P-SSE, LP-Contacts and L-Properties. Maestro was used to visualize the stability of the ligands in the active site during the simulation. All 13 Desmond simulations were successful however, there were 9 simulations which produced satisfactory results while the others were nsatisfactory. Based on the molecular docking and Molecular Dynamics results of this study, 9 potential targets and 6 potential agents were obtained successfully and can be studied further as therapeutics for Alzheimer’s Disease.
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- Date Issued: 2020
A critical analysis of selected teachers’ perceptions and experiences of the role that visualisation processes play in their Van Hiele level 1 teaching to migrate their learners to the next Van Hiele level
- Authors: Munichinga, Ben Muyambango
- Date: 2019
- Subjects: Hiele, Pierre M. van. Structure and insight , Visualization , Mathematics -- Study and teaching (Secondary) -- Namibia , Geometry -- Study and teaching (Secondary) -- Namibia , Mathematics -- Study and teaching (Secondary) -- Activity programs -- Namibia
- Language: English
- Type: text , Thesis , Masters , MEd
- Identifier: http://hdl.handle.net/10962/96735 , vital:31313
- Description: Learning is a process that involves building on prior knowledge, enriching and exchanging existing understanding where learners’ knowledge base is scaffolded in the construction of knowledge. Research on the teaching and learning of geometry in mathematics suggests that physical manipulation experiences, especially of shapes, is an important process in learning at all ages. The focus of the study was the migration of Grade 8 learners from one Van Hiele level to the next as a result of teachers incorporating visualisation processes and Van Hiele phases of instructions in their teaching. The study underpinned by the social constructivist’s theory, therefore aimed at teachers developing visual materials and using Van Hiele’s phases of instruction to teach two dimensional figures in Geometry. The study was carried out in Namibia, Zambezi region in Bukalo circuit. It involved four schools, with 93 learners and three teacher participants. The research is an interpretive case study of a planned intervention programme, which took a four weeks to complete. Participating learners wrote a Van Hiele Geometric test prior and post the intervention programme to determine their geometric level of thought. Participating teachers all received training on visualisation in mathematics and the Van Hiele theory before the intervention. During the intervention, teacher planned and each taught three lessons on two-dimensional figures. Qualitative data was collected from classroom observation, stimulus recall interviews and focus group interviews. Quantitative data came from the pre and post-test of learners. This study found that on average, Grade 8 learners who participated in the study were operating at levels lower than expected of pupils at their stage of schooling. This study also found that, visualisation processes and the Van Hiele phases are effective when used in geometry lessons to migrate learners from lower Van Hiele levels to higher. For teachers in the same circuit, partnership and planning of difficult topics on an agreed regular basis is recommended. When planning lessons teachers are encouraged to take advantage of the Van Hiele phases of instructions. This study thus recommends the incorporation of visualisation strategies of teaching geometry in particular at primary and lower secondary levels. Mathematics teachers are further encouraged to design visual materials such as Geoboards to use for every topic in geometry. Such visual materials should be carefully developed and evaluated to ensure that their use in the classroom is effectively linked to concepts under discussion in a given lesson.
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- Date Issued: 2019
Modelling storm-time TEC changes using linear and non-linear techniques
- Authors: Uwamahoro, Jean Claude
- Date: 2019
- Subjects: Magnetic storms , Astronomy -- Computer programs , Imaging systems in astronomy , Ionospheric storms , Electrons -- Measurement , Magnetosphere -- Observations
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/92908 , vital:30762
- Description: Statistical models based on empirical orthogonal functions (EOF) analysis and non-linear regression analysis (NLRA) were developed for the purpose of estimating the ionospheric total electron content (TEC) during geomagnetic storms. The well-known least squares method (LSM) and Metropolis-Hastings algorithm (MHA) were used as optimization techniques to determine the unknown coefficients of the developed analytical expressions. Artificial Neural Networks (ANNs), the International Reference Ionosphere (IRI) model, and the Multi-Instrument Data Analysis System (MIDAS) tomographic inversion algorithm were also applied to storm-time TEC modelling/reconstruction for various latitudes of the African sector and surrounding areas. This work presents some of the first statistical modeling of the mid-latitude and low-latitude ionosphere during geomagnetic storms that includes solar, geomagnetic and neutral wind drivers.Development and validation of the empirical models were based on storm-time TEC data derived from the global positioning system (GPS) measurements over ground receivers within Africa and surrounding areas. The storm criterion applied was Dst 6 −50 nT and/or Kp > 4. The performance evaluation of MIDAS compared with ANNs to reconstruct storm-time TEC over the African low- and mid-latitude regions showed that MIDAS and ANNs provide comparable results. Their respective mean absolute error (MAE) values were 4.81 and 4.18 TECU. The ANN model was, however, found to perform 24.37 % better than MIDAS at estimating storm-time TEC for low latitudes, while MIDAS is 13.44 % more accurate than ANN for the mid-latitudes. When their performances are compared with the IRI model, both MIDAS and ANN model were found to provide more accurate storm-time TEC reconstructions for the African low- and mid-latitude regions. A comparative study of the performances of EOF, NLRA, ANN, and IRI models to estimate TEC during geomagnetic storm conditions over various latitudes showed that the ANN model is about 10 %, 26 %, and 58 % more accurate than EOF, NLRA, and IRI models, respectively, while EOF was found to perform 15 %, and 44 % better than NLRA and IRI, respectively. It was further found that the NLRA model is 25 % more accurate than the IRI model. We have also investigated for the first time, the role of meridional neutral winds (from the Horizontal Wind Model) to storm-time TEC modelling in the low latitude, northern and southern hemisphere mid-latitude regions of the African sector, based on ANN models. Statistics have shown that the inclusion of the meridional wind velocity in TEC modelling during geomagnetic storms leads to percentage improvements of about 5 % for the low latitude, 10 % and 5 % for the northern and southern hemisphere mid-latitude regions, respectively. High-latitude storm-induced winds and the inter-hemispheric blows of the meridional winds from summer to winter hemisphere have been suggested to be associated with these improvements.
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- Date Issued: 2019
Teacher perspectives on value creation and learning in South African eco-schools: an evaluative review of teacher support processes in an eco-school professional learning community
- Authors: Khan, Anisa
- Date: 2018
- Subjects: Teachers -- In-service training -- South Africa , Environmental education -- Study and teaching -- South Africa , Continuing education , Teachers -- Attitudes , Communities of practice -- South Africa , Integrated Strategic Planning Framework for Teacher Education , Eco-schools
- Language: English
- Type: text , Thesis , Masters , MEd
- Identifier: http://hdl.handle.net/10962/62840 , vital:28300
- Description: The study is framed within the broader policy context of teacher professional development and the Department of Basic Education (DBE) and Department of Higher Education (DHET) strategy to support the development of Professional Learning Communities. Teacher Education and Development initiatives in South Africa face multiple challenges, with the Integrated Strategic Planning Framework for Teacher Education in South Africa: 2011-2025 (ISFPTED) (South Africa, DBE, 2011) providing guidance on priority interventions to address these, including guidance on continuous teacher professional development through teacher education support in professional learning communities. The Eco-Schools programme has, over its decade-long history, provided support to teachers in schools registered as Eco-Schools. The value created by the diverse support practices is not well known or understood. The study aimed to shed light on the support teachers in the Eco-Schools programme value and how this contributes to environmental learning and practice. Working with Wenger’s Communities of Practice theory (Wenger, 1998) as a conceptual framework and lens, the study set out to describe and explore the processes of teacher learning amongst a sample of teachers supported to function as a professional learning community within the Eco-Schools programme. The findings and recommendations made are in relation to the research goals which are to explore and describe the value being created by the patterns of teacher support in an Eco-Schools node/cluster. To this end, the evaluative study generated evidence in relation to what teachers derive value from through the support they receive; and assessed evidence on how teaching, learning, and practice are developing through participation in the Eco-Schools Professional Learning Community examined. The study was conducted in 2 phases, the first as a survey of the patterns of support in Eco-School clusters/ nodes. The descriptions enabled a mapping of the patterns of support in the “coordinator supported model” of Eco-Schools to understand how the coordinator supported model of Eco-Schools enables teacher collaboration and supports the development of an environment and sustainability community of practice between teachers from across the cluster/ node. The second part of the study explored teacher’s perspectives of value derived from participation in an expanded model of Eco-Schools support, using an appreciative inquiry methodology to extract teacher narrations of value creation and meaning-making. In relation to goal one, the main findings indicate that the patterns of support enabled teachers to develop confidence and skills for action taking and responding to local socio-economic and environmental challenges. The data also reflected local partnerships with other environmental knowledge organisations, thus adding value to the programme through an expanded network of environmental practice and provision of additional resources. In relation to goal 2 of the study, teachers experienced Eco-School practices as personally meaningful and connected to their identity. Teachers expressed value in the training they had received through the Fundisa for Change programme which deepened their understanding of the implementation requirements of the Curriculum and Assessment Policy Statements (CAPS) and helped to connect knowledge concepts in the curriculum with sustainability practices implemented as part of the Eco-Schools framework. In relation to goal 3, teachers gained confidence in “Teaching Biodiversity” through the Fundisa for Change training. Teachers were better able to understand the Specific Aims of the Biodiversity curriculum (CAPS) and to adapt their teaching methods to support the CAPS content and assessment requirements. Teacher portfolios also showed evidence of teachers developing skills in analysis of learner performance and an awareness of the need to adjust their teaching and assessment strategies to address “gaps” in learner understanding.
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- Date Issued: 2018
"Re-thinking" the Great Trek: a study of the nature and development of the Boer community in the Ohrigstad/Lydenburg area, 1845-1877
- Authors: Erasmus, Diderick Justin
- Date: 1995
- Subjects: South Africa -- History -- Great Trek, 1836-1840 , Afrikaners , Afrikaners -- South Africa -- Transvaal -- History
- Language: English
- Type: Thesis , Masters , MA
- Identifier: vital:2541 , http://hdl.handle.net/10962/d1002393 , South Africa -- History -- Great Trek, 1836-1840 , Afrikaners , Afrikaners -- South Africa -- Transvaal -- History
- Description: From the late 1830s Boer settlers conquered and settled vast new lands outside the Cape Colony. Although they more than doubled the area of European domination, historians have categorised Boer society outside the British colonies as primitive and dismissed the Boer conquests as an abberation from the broader process of European expansion. Such a distinction is no longer tenable. This study, which focuses on the Obrigstad/Lydenburg area, shows that the Boers were an integral part of European expansion in southern Africa. Settler expansion did not occur in a vacuum. Booming demand for commodities sparked economic growth across the sub-continent; the Boers were part of this process and consistently strove to produce for the region's expanding markets. In tandem with the expanding regional system, the Boer economy grew constantly. This was reflected in the centralisation of power in the Z.A.R. as Boer producers created formal political and administrative structures to further their economic interests. (A parallel process culminated in the Cape with colonists receiving representative government in March 1853.) This correlation between political and economic development was evident in the creation of a coercive labour system by the Boer state. Through their control of state structures, the Boers employed measures ranging from brute force to punitive taxation, legally enforceable contracts and pass laws to procure and control workers. It is important to note that the creation of a coercive labour system by the Boers paralleled similar developments in the Cape Colony. The speed with which the Boer economy expanded in comparison to the Cape, however, meant that stages in the development of an unfree labour force which had been chronologically distinct in the Cape coexisted within the Boer coercive system. Boer dependence on coerced labour made conflict with African groups inevitable. African groups in the eastern Transvaal had already been partly moulded by predatory economic forces emanating from the Portuguese settlements on the east coast since at least the 1750s. The arrival of the Boers in the 1840s greatly accelerated this process. Some groups were crushed, but others were able to obtain the means to resist Boer rule by interfacing with the settler economy. The economic forces which drove Boer settlement were thus not confined to the white settlers: Boer expansion was paralleled by the rise of African survivor states. The Dlamini, for example, built the powerful Swazi state by exchanging captives, ivory and cattle for guns and horses. Similarly, the Pedi, through the large scale expon of migrant labour, were able to acquire the means to challenge Boer authority in the late 1870s. Oearly then, the Boers 'Were not only representative of the wider settler social and economic order, but were acting in response to the same circumstances as the British settlers, Portuguese traders and African survivor states. It is thus impossible to continue to classify them as retrogressive and distinct from other groups in the region.
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- Date Issued: 1995