Improving project management planning and control in service operations environment.

Projects have evidently become the core activity in most companies and organisations where they are investing significant amount of resources in different types of projects as building new services, process improvement, etc. This research has focused on service sector in attempt to improve project management planning and control activities. The research is concerned with improving the planning and control of software development projects. Existing software development models are analysed and their best practices identified and these have been used to build the proposed model in this research. The research extended the existing planning and control approaches by considering uncertainty in customer requirements, resource flexibility and risks level variability. In considering these issues, the research has adopted lean principles for planning and control software development projects. A novel approach introduced within this research through the integration of simulation modelling techniques with Taguchi analysis to investigate ‗what if‘ project scenarios. Such scenarios reflect the different combinations of the factors affecting project completion time and deliverables. In addition, the research has adopted the concept of Quality Function Deployment (QFD) to develop an automated Operations Project Management Deployment (OPMD) model. The model acts as an iterative manner uses ‗what if‘ scenario performance outputs to identify constraints that may affect the completion of a certain task or phase. Any changes made during the project phases will then automatically update the performance metrics for each software development phases. In addition, optimisation routines have been developed that can be used to provide management response and to react to the different levels of uncertainty. Therefore, this research has looked at providing a comprehensive and visual overview of important project tasks i.e. progress, scheduled work, different resources, deliverables and completion that will make it easier for project members to communicate with each other to reach consensus on goals, status and required changes. Risk is important aspect that has been included in the model as well to avoid failure. The research emphasised on customer involvement, top management involvement as well as team members to be among the operational factors that escalate variability levels 3 and effect project completion time and deliverables. Therefore, commitment from everyone can improve chances of success. Although the role of different project management techniques to implement projects successfully has been widely established in areas such as the planning and control of time, cost and quality; still, the distinction between the project and project management is less than precise and a little was done in investigating different levels of uncertainty and risk levels that may occur during different project phase.United Arab Emirates Governmen

Oral cancer via the bargain bin : the role of smokeless tobacco in the etiology of oral cancer

Background: Oral cancer combined with the other cancers of the head and neck region constitute the sixth most common cancer in the world. Oral cancer is a major public health challenge in South Asia. Pakistan, India, Bangladesh and Sri Lanka have some of the highest incidence and prevalence rates of oral cancer in the world. Approximately 16,000 new cases of oral cancer are diagnosed each year in Pakistan and around 6,000 Pakistanis lose their lives to this malignancy every year. There is a disconnect between the research findings from the developed countries and the developing countries, with regards to the risk of oral cancer associated with smokeless tobacco use. Given the differences in the composition of the smokeless tobacco products used in different parts of the world, it is imperative that the health risks related with each of these products are assessed on an individual basis. Methods: A case-control study was carried out in the Khyber Pakhtunkhwa province of Pakistan from September 2014 until May 2015, to quantify the risk of oral cancer associated with the use of Naswar (smokeless tobacco). Additionally, three systematic reviews (including meta-analyses) of observational studies and two narrative reviews were carried out to address the secondary objectives of this dissertation. Results: We found an increased risk of oral cancer associated with the use of smokeless tobacco products in South Asia. The use of smokeless tobacco was also associated with an elevated risk of oral potentially malignant disorders. In Khyber Pakhtunkhwa, Pakistan, Ever-users of Naswar had a 21-fold increase in the risk of oral cancer compared to Never-users Odds ratio (OR) =21.2 (95% Confidence Interval (CI), (8.4-53.8) . An elevated risk of oral cancer associated with Naswar use was found among both women and men. The risk of oral cancer increased with the increasing frequency, total duration, and the intensity of Naswar use. 70% of the oral cancer burden of Khyber Pakhtunkhwa was attributable to Naswar. Discussion: The findings of the systematic reviews and the case-control study on Naswar are comparable to the existing literature. The results clearly demonstrate a high risk of oral cancer and related disorders, associated with the use of smokeless tobacco products like Naswar, Betel quid, and Gutkha. There is a lack of oral cancer research in Pakistan and the tobacco control policies of the country largely focus on tobacco smoking while neglecting smokeless tobacco. In order to tackle the growing burden of oral cancer in South Asia in general and Pakistan in particular, policies need to be in place to curb the use of smokeless tobacco products. These products need to be regulated and brought under the tobacco tax-net. Changes to the composition of these products, to make them less harmful to health, should also be looked into as an intervention

The HBP1 tumor suppressor is a negative epigenetic regulator of MYCN driven neuroblastoma through interaction with the PRC2 complex

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Genes: Multigene Families, Control of Gene Expression, Genetic contributions to Human Diseases, including Chromosomal Fragile Sites and ‘Dynamic’ and ‘Non-self’ Mutations

The early work in this thesis utilizes the general approach of comparative analysis. In order to find out the relationship between entities (either functional or genetic) my colleagues and I have attempted to identify the important elements by detecting similarity between those entities that act in a similar manner. The philosophy behind this approach is simply that when two distinct objects perform a similar process then the requirements essential for that process will be revealed as similarities between those objects above a noise of difference between them. The use of comparative analysis in biological systems is an attempt to identify natural order from apparent chaos. This work includes but is not limited to :- 1. discovery of the family of kallikrein genes and exploration of their roles in biology, 2. identification of the DNA sequence elements required for hormonal and heavy metal control of metallothionein gene expression 3. discovery of at least some of the necessary and sufficient conditions for the appearance of fragile sites on chromosomes, and their consequent contributions to disease, 4. the molecular properties of repeat DNA sequence expansion that lead to dynamic mutation and consequent fragile site expression and / or disease pathogenesis. In a sense the use of genetic animal models in order to study gene function and pathogenesis follows similar logic of comparative analysis – the mutation of a single endogenous gene or the expression of a single introduced mutated gene in a (presumed) constant genetic background to enable the biological consequences of the genetic mutation or aberrant gene expression by comparing animals from the ‘wild-type’ or parent line with those that now carry the mutation or altered gene. This approach has been utilized in the most recent work contained herein as a means to determine gene function and / or to model human genetic disease pathogenesis, specifically pathogenic mechanisms of the protein WWOX in cancer and expanded repeat RNAs in neurodegenerative diseases. The culmination of this recent work is the development of an hypothesis – 4. that expanded repeat double-stranded RNA leads to neurodegeneration through its recognition by the RNA-binding pattern recognition receptors as a ‘non-self’ or foreign nucleic acid due to a paucity of RNA modification. The resultant pathogenic mechanism is therefore autoinflammatory disease. Given the wide range and variety of evidence of inflammatory activation in neurodegenerative diseases in general, this mechanism is therefore hypothesized to be the general causal mechanism for most (or all) of these diseases. A specific Introduction - highlighting the nature and significance of the work, and a Conclusion – of how this work has contributed to knowledge, are given at the start of each chapter, while the impact of the various components of this work is indicated by the number of citations for each of the included publications. Authorship contributions to each of the included publications in this work are also indicated with each specific reference.Thesis (DSc) -- University of Adelaide, School of Biological Sciences, 202

Extracellular vesicles from induced neurons trigger epigenetic silencing of a brain neurotransmitter.

Introduction: Antithrombin (AT) is a glycoprotein involved in the regulation of blood coagulation. It belongs to the family of serine-protease inhibitors and acts as the most important antagonist of different clot- ting factors. Two types of inherited AT deficiency can be distinguished: Type I (quantitative deficit), and Type II (qualitative deficit). The latter is characterized by an impaired inhibitory activity related to dysfunc- tional domains of the protein. Three Type II subtypes can be defined: Type IIa (reactive site defect), Type IIb (heparin binding site defect) and Type IIc (pleiotropic defect). This classification has clinical importance since these subtypes have a different thrombotic risk. No functional routine diagnostic assay, however, can be assumed to detect all forms of Type II deficiencies since false-negative results may hamper the diagnosis. Methods: We analysed the biochemical/biophysical association of ATT to EVs. We separated EVs from plasma of healthy or Type II affected patients or from cultured hepatocytes through differential ultracentrifu- gation followed by sucrose density gradient and/or immunoprecipitation. We next combined dot blot ana- lysis, WB, 2D electrophoresis and enzymatic assays to reveal the nature of ATT association to EVs. Results: We evidenced that ATT is associated to the external leaflet of EVs. We also found that specific ATT isoforms are enriched in EV preparations in respect to total plasma and that those isoforms are selectively associated to EVs when comparing healthy or ATT type II deficient patients. Summary/Conclusion: ATT selective association pat- tern to EVs might be related either to mutations in the primary sequence of the protein or alterations in the glycosylation process, hence experiments are ongoing to reveal the nature of this phenomenon. Our findings suggest that analysis of ATT enriched in EV prepara- tions might be useful to gain insights into the patho- genesis and be of support in the diagnostic algorithm of ATT deficiency. Funding: This work acknowledges FFABR (Fondo finanziamento attività Base di ricerca from MIUR, Ministry of Education, Universities and Research, Italy) for financial support