2 resultados para Two-level production planning

em Glasgow Theses Service


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Higher Education Institutes (HEIs) of any country could be a source of providing professionals to the country in many fields. By doing so, HEIs could play a pivotal role in the economic growth of the country. In Pakistan, it seems that, in the wake of this realization, steps have been taken to reform Higher Education. Drawing on the Triple I model of educational change covering Initiation, Implementation and Institutionalization (Fullan, 2007) this study focuses on the planning and implementation of reforms in the Education system of Pakistan at higher education level that have been introduced by the Higher Education Commission (HEC) since its inception in 2002. Kennedy’s model of hierarchical subsystems affecting innovation and Chin and Benne’s (1985) description of strategies for implementing change also provided guidelines for analyzing the changes in education in the country to highlight the role that the authorities expect the language teacher to play in the process of implementing these changes. A qualitative method is followed in this study to gather data from English language teachers at three universities of the Khyber Pakhtunkhwa province of Pakistan. A questionnaire was developed to look into the perceptions of English language teachers regarding the impact of these reforms. This was followed up by interviews. Responses from 28 teachers were received through questionnaire out of which 9 teachers were interviewed for detailed analysis of their perceptions. Thematic Content analysis was used to analyze and interpret the data. Some of the most significant changes that the respondents reported knowledge of included the introduction of Semester System, extending the Bachelors degree to four years from two years, promotion of research culture, and increased teachers’ autonomy in classroom practices. Implications of these reforms for English teachers’ professional development were also explored. The data indicate that the teachers generally have a positive attitude towards the changes. However, the data also show concerns that teachers have about the practical effectiveness of these changes in improving English language teaching and learning in Pakistani Universities. Some of the areas of concern are worries regarding resources, the assessment system, the number of qualified teachers, and instability in the educational policy. They are concerned about the training facilities and quality of the professional training available to them. Moreover, they report that training opportunities for their professional development are not available to all the teachers equally. Despite the HEC claims of providing regular training opportunities, the majority of the teachers did not receive any formal training in the last three years, while some teachers were able to access these opportunities multiple times. Through the recent reforms HEC has empowered the teachers in conducting the learning/teacher processes but this extra power has reduced their accountability and they can exercise these powers without any check on them. This empowerment is limited to the classroom and there appears to be no or minimal involvement in decision making at the top level of policy making. Such lack of involvement in the policy decisions seems to be generating a lack of sense of ownership among the teachers (Fullan 2003a:6). Although Quality Enhancement Cells have been developed in the universities to assure the desired quality of education, they might need a more active role to contribute in achieving the level of enhancement in education expected from them. Based on the perceptions of the respondents of this study and the review of the relevant literature, it is argued that it is unlikely for the reforms to be institutionalized if teachers are not given the right kind of awareness at the initiation stage and are not prepared at the implementation stage to cope with the challenge of a complex process. The teachers participating in this study, in general, have positive and enthusiastic attitudes towards most of the changes, in spite of some reservations. It could also be interesting to see if the power centers of the Pakistani Higher Education appreciate this enthusiasm and channel it for a strong Higher Education system in the country.

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Hypertension is the major risk factor for coronary disease worldwide. Primary hypertension is idiopathic in origin but is thought to arise from multiple risk factors including genetic, lifestyle and environmental influences. Secondary hypertension has a more definite aetiology; its major single cause is primary aldosteronism (PA), the greatest proportion of which is caused by aldosteroneproducing adenoma (APA), where aldosterone is synthesized at high levels by an adenoma of the adrenal gland. There is strong evidence to show that high aldosterone levels cause adverse effects on cardiovascular, cerebrovascular, renal and other systems. Extensive studies have been conducted to analyse the role that regulation of CYP11B2, the gene encoding the aldosterone synthase enzyme plays in determining aldosterone production and the development of hypertension. One significant regulatory factor that has only recently emerged is microRNA (miRNA). miRNAs are small non-coding RNAs, synthesized by a series of enzymatic processes, that negatively regulate gene expression at the posttranscriptional level. Detection and manipulation of miRNA is now known to be a viable method in the treatment, prevention and prognosis of certain diseases. The aim of the present study was to identify miRNAs likely to have a role in the regulation of corticosteroid biosynthesis. To achieve this, the miRNA profile of APA and normal human adrenal tissue was compared, as was the H295R adrenocortical cell line model of adrenocortical function, under both basal conditions and following stimulation of aldosterone production. Key differentially-expressed miRNAs were then identified and bioinformatic tools used to identify likely mRNA targets and pathways for these miRNAs, several of which were investigated and validated using in vitro methods. The background to this study is set out in Chapter 1 of this thesis, followed by a description of the major technical methods employed in Chapter 2. Chapter 3 presents the first of the study results, analysing differences in miRNA profile between APA and normal human adrenal tissue. Microarray was implemented to detect the expression of miRNAs in these two tissue types and several miRNAs were found to vary significantly and consistently between them. Furthermore, members of several miRNA clusters exhibited similar changes in expression pattern between the two tissues e.g. members of cluster miR-29b-1 (miR-29a-3p and miR-29b-3p) and of cluster miR-29b-2 (miR-29b-3p and miR-29c- 3p) are downregulated in APA, while members of cluster let-7a-1 (let-7a-5p and let-7d-5p), cluster let-7a-3 (let-7a-5p and let-7b-5p) and cluster miR-134 (miR- 134 and miR-382) are upregulated. Further bioinformatic analysis explored the possible biological function of these miRNAs using Ingenuity® Systems Pathway Analysis software. This led to the identification of validated mRNAs already known to be targeted by these miRNAs, as well as the prediction of other mRNAs that are likely targets and which are involved in processes relevant to APA pathology including cholesterol synthesis (HMGCR) and corticosteroidogenesis (CYP11B2). It was therefore hypothesised that increases in miR-125a-5p or miR- 335-5p would reduce HMGCR and CYP11B2 expression. Chapter 4 describes the characterisation of H295R cells of different strains and sources (H295R Strain 1, 2, 3 and HAC 15). Expression of CYP11B2 was assessed following application of 3 different stimulants: Angio II, dbcAMP and KCl. The most responsive strain to stimulation was Strain 1 at lower passage numbers. Furthermore, H295R proliferation increased following Angio II stimulation. In Chapter 5, the hypothesis that increases in miR-125a-5p or miR-335-5p reduces HMGCR and CYP11B2 expression was tested using realtime quantitative RT-PCR and transfection of miRNA mimics and inhibitors into the H295R cell line model of adrenocortical function. In this way, miR-125a-5p and miR-335-5p were shown to downregulate CYP11B2 and HMGCR expression, thereby validating certain of the bioinformatic predictions generated in Chapter 3. The study of miRNA profile in the H295R cell lines was conducted in Chapter 6, analysing how it changes under conditions that increase aldosterone secretion, including stimulation Angiotensin II, potassium chloride or dibutyryl cAMP (as a substitute for adrenocorticotropic hormone). miRNA profiling identified 7 miRNAs that are consistently downregulated by all three stimuli relative to basal cells: miR-106a-5p, miR-154-3p, miR-17-5p, miR-196b-5p, miR-19a-3p, miR-20b- 5p and miR-766-3p. These miRNAs include those derived from cluster miR-106a- 5p/miR-20b-5p and cluster miR-17-5p/miR-19a-3p, each producing a single polycistronic transcript. IPA bioinformatic analysis was again applied to identify experimentally validated and predicted mRNA targets of these miRNAs and the key biological pathways likely to be affected. This predicted several interactions between miRNAs derived from cluster miR-17-5p/miR-19a-3p and important mRNAs involved in cholesterol biosynthesis: LDLR and ABCA1. These predictions were investigated by in vitro experiment. miR-17-5p/miR-106a-p and miR-20b-5p were found to be consistently downregulated by stimulation of aldosterone biosynthesis. Moreover, miR-766-3p was upregulation throughout. Furthermore, I was able to validate the downregulation of LDLR by miR-17 transfection, as predicted by IPA. In summary, this study identified key miRNAs that are differentially-expressed in vivo in cases of APA or in vitro following stimulation of aldosterone biosynthesis. The many possible biological actions these miRNAs could have were filtered by bioinformatic analysis and selected interactions validated in vitro. While direct actions of these miRNAs on steroidogenic enzymes were identified, cholesterol handling also emerged as an important target and may represent a useful point of intervention in future therapies designed to modulate aldosterone biosynthesis and reduce its harmful effects.