Tuberculosis (TB) is called a disease of poverty and is the main cause of death from infectious diseases among adults. In 1993 the World Health Organisation (WHO) declared TB to be a global emergency; however there were still approximately 1.4 million deaths due to TB in 2011. This thesis contains a detailed study of the existing literature regarding the global risk factors of TB. The risk factors identified from the literature review search which were also available from the NFHS-3 survey were then analysed to determine how well we could identify respondents who are at high risk of TB. We looked at the stigma and misconceptions people have regarding TB and include detailed reports from the existing literature of how a persons wealth, health, education, nutrition, and HIV status affect how likely the person is to have TB. The difference in the risk factor distribution for the TB and non-TB populations were examined and classification trees, nearest neighbours, and logistic regression models were trialled to determine if it was possible for respondents who were at high risk of TB to be identified. Finally gender-specific statistically likely directed acyclic graphs were created to visualise the most likely associations between the variables.

A mutation (CTG to TTG) of FeSOD gene was found in Escherichia coli. Since they both encode leucine, it is a silent mutation. Site-­‐directed mutagenesis was applied to correct the mutation, and the mutant FeSOD (before gene correction) and wild type FeSOD (after gene correction) were purified. The FeSODs from the two genes were Characterized using different assays and spectroscopic methods including EPR and CD. The requirement for the rare codon TTG may result in slowed translation and heavy demand on a scarce tRNA. Cultures expressing wild type FeSOD are better able to grow for long times after addition of IPTG and more mature to incorporate Fe atoms to the active sites than are cultures expressing the mutant gene. Moreover, the wild type FeSOD has more activity than the mutant. To our knowledge, this is the first time that a silent mutation has been demonstrated to affect metal incorporation into a metalloenzyme.

This work focuses on the use of a genetic algorithm for optimization in a search-based problem. The Genetic Algorithm (GA) is a subset of evolutionary algorithms that models biological processes to optimize highly complex functions. A GA allows a population composed of many individuals to evolve under specified selection rules to a state that maximizes the “fitness” (i.e. minimize the objective function). A major advantage of using GA over most stochastic techniques is its parallelism, which speeds up the simulation results leading to faster convergence. With mutation, the GA is also less likely to get stuck in local minima compared to other stochastic techniques. However, some notable drawbacks of the Standard GA (SGA) include slow convergence and a possibility of being stuck in local optimum solution. The SGA uses a random process to generate parameter values for the initial population generation, crossover and mutation processes. Random number generators are designed to result in either uniform distributions or Gaussian distributions. We conjecture that the evolutionary processes in genetics are driven by a random non-linear deterministic dynamic process rather than a random non-deterministic process. Therefore, in the GA evolutionary process, a chaotic map is incorporated into the initial population generation, the crossover and mutation processes of the SGA; this is termed the Chaotic GA (CGA). The properties of a chaotic system that provides additional benefits over randomly generated solutions are sensitivity to initial conditions, topological density and topological transitivity (robust diversity). These properties ensure that the CGA is able to explore the entire solution space. Introducing chaos into the whole process of a standard genetic algorithm may help improve convergence time and accuracy. Simulation was done using Matlab and Java.

The construction industry has had difficulty adopting project management software effectively and in a widespread manner. This thesis seeks to uncover common problems preventing the adoption of new software for construction project management, and to find a method to design more successful software. Construction project managers working at universities in the state of Georgia were selected as the specific group to study. To better define the functions of project management software, as well as uncover benefits both realized and anticipated, research was conducted. A Situation Awareness based approach was selected to result in proposing a prototype application that would specifically match the mental model of the study group. To define the mental model, a Goal Directed Task Analysis method was used by way of an online survey and in-person verification. In order to collect the survey data, a web based Goal Directed Task Analysis application was created and tested as a part of this thesis. Using the survey data, a proposed design for a prototype application was proposed. The application design was specifically made to fulfill the needs of project managers like those in the study group. The GDTA method proved effective in producing a software design. Recommendations to create and test the proposed prototype application are provided as a next step.

Die doel met hierdie navorsing was om ‘n analise van die selfgereguleerde leervaardighede van leerders in die BEd Honneurs Oopafstandsleerprogram te doen en ‘n onderrigmodel daar te stel om genoemde vaardighede te verbeter. Om hierdie doel te bereik is ‘n literatuurstudie onderneem ten einde a) leer te omskryf volgens die behavioristiese, sosiaal–kognitiewe, inligtingverwerkings, konstruktiwistiese teorieë en volwasse leerteorieë; b) selfgereguleerde leer te omskryf vanuit die behaviouristiese, fenomenologiese, Vygotskiaanse, kognitief–konstruktivistiese en sosiaal–kognitiewe beskouinge, met die klem op laasgenoemde beskouing en c) afstandsleer en die vereistes wat afstandsleer en selfgereguleerde leer aan afstandsleerders stel, te beskryf. Vanuit literatuur is bepaal dat effektiewe leer gedefinieer word vanuit die navorser se oriëntasie tot leer sowel as die aard van leer in ‘n spesifieke konteks. Die verskillende leerteorieë beklemtoon verskillende aspekte van leer en hou verskillende implikasies in vir programontwerp, rolle van onderriggewers, leermetodes en assessering. Verder dui literatuur op ‘n positiewe verband tussen selfgereguleerde leer en akademiese prestasie. Terselfdertyd dui bestaande literatuur daarop dat suksesvolle afstandsleerders selfregulerend moet kan leer en dus oor sodanige vaardighede moet beskik. Die navorsingspopulasie het bestaan uit BEd Honneurs oopafstandsleerders van Noordwes–Universiteit asook fleksieleerders van die Noordwes–Universiteit, Potchefstroomkampus wat alreeds eksamen afgelê het in die Leerperspektiewe module. Die teikengroep het bestaan uit leerders wat reeds vroeër eksamen afgelê het in die module LEON 611 en tydens kontaksessies in 2010 by spesifieke kontaksentrums en vakansieskole bygewoon en die vraelyste voltooi het (n=264). ‘n Multi–metode ontwerp is geïmplementeer waar ‘n kombinasie van kwantitatiewe en kwalitatiewe navorsing aangewend is om die navorsingsprobleem beter te verstaan. Kwantitatiewe data is ingesamel aan die hand van vier vraelyste waarná aanvullende kwalitatiewe data–insameling met semi–gestruktureerde onderhoude gevolg het. Kwantitatiewe navorsing het geskied aan die hand van ‘n ex post facto–benadering en data is statisties ontleed deur middel van a) faktoranalise, b) meervoudige regressie–analise, c) stapsgewyse regressie–analise en d) effekgroottes. Kwalitatiewe data is met behulp van ATLAS.ti.6.0 - ‘n rekenaarondersteunde stelsel, ontleed. Resultate van die ondersoek dui daarop dat deelnemers nie voldoen aan al die vereistes vir effektiewe afstandsleer nie. Bereiking van leerdoelwitte is in ‘n groot mate afhanklik van die steun van onderriggewers en porture. Hul beskik nie oor inligtingstegnologiese vaardighede nie en kan nie effektief leer waar nie–moedertaalonderrig ter sprake is nie. In teenstelling met bestaande literatuur dui kwantitatiewe en kwalitatiewe resultate op ‘n lae verband bestaan tussen afstandsleerders se selfgereguleerde leervaardighed en hul akademiese prestasie. Deelnemers maak selde gebruik van selfgereguleerde leervaardighede soos ter sprake tydens die voorafdenkfase maar meer tydens die wilsbeheer– en selfreaksiefases. ‘n Model is ontwikkel vir die verbetering van selfgereguleerde leervaardighede van oopafstandsleerders, inbegrepe deurlopende ontwikkeling van akademiese taalvaardigheid en inligtingstegnologiese vaardighede. Aanpassings in studiemateriaal en verandering van onderrigstrategieë en terugvoer is belangrike aspekte van die model. / Thesis (Ph.D. (Education))--North-West University, Potchefstroom Campus, 2011.

Die doel met hierdie navorsing was om ‘n analise van die selfgereguleerde leervaardighede van leerders in die BEd Honneurs Oopafstandsleerprogram te doen en ‘n onderrigmodel daar te stel om genoemde vaardighede te verbeter. Om hierdie doel te bereik is ‘n literatuurstudie onderneem ten einde a) leer te omskryf volgens die behavioristiese, sosiaal–kognitiewe, inligtingverwerkings, konstruktiwistiese teorieë en volwasse leerteorieë; b) selfgereguleerde leer te omskryf vanuit die behaviouristiese, fenomenologiese, Vygotskiaanse, kognitief–konstruktivistiese en sosiaal–kognitiewe beskouinge, met die klem op laasgenoemde beskouing en c) afstandsleer en die vereistes wat afstandsleer en selfgereguleerde leer aan afstandsleerders stel, te beskryf. Vanuit literatuur is bepaal dat effektiewe leer gedefinieer word vanuit die navorser se oriëntasie tot leer sowel as die aard van leer in ‘n spesifieke konteks. Die verskillende leerteorieë beklemtoon verskillende aspekte van leer en hou verskillende implikasies in vir programontwerp, rolle van onderriggewers, leermetodes en assessering. Verder dui literatuur op ‘n positiewe verband tussen selfgereguleerde leer en akademiese prestasie. Terselfdertyd dui bestaande literatuur daarop dat suksesvolle afstandsleerders selfregulerend moet kan leer en dus oor sodanige vaardighede moet beskik. Die navorsingspopulasie het bestaan uit BEd Honneurs oopafstandsleerders van Noordwes–Universiteit asook fleksieleerders van die Noordwes–Universiteit, Potchefstroomkampus wat alreeds eksamen afgelê het in die Leerperspektiewe module. Die teikengroep het bestaan uit leerders wat reeds vroeër eksamen afgelê het in die module LEON 611 en tydens kontaksessies in 2010 by spesifieke kontaksentrums en vakansieskole bygewoon en die vraelyste voltooi het (n=264). ‘n Multi–metode ontwerp is geïmplementeer waar ‘n kombinasie van kwantitatiewe en kwalitatiewe navorsing aangewend is om die navorsingsprobleem beter te verstaan. Kwantitatiewe data is ingesamel aan die hand van vier vraelyste waarná aanvullende kwalitatiewe data–insameling met semi–gestruktureerde onderhoude gevolg het. Kwantitatiewe navorsing het geskied aan die hand van ‘n ex post facto–benadering en data is statisties ontleed deur middel van a) faktoranalise, b) meervoudige regressie–analise, c) stapsgewyse regressie–analise en d) effekgroottes. Kwalitatiewe data is met behulp van ATLAS.ti.6.0 - ‘n rekenaarondersteunde stelsel, ontleed. Resultate van die ondersoek dui daarop dat deelnemers nie voldoen aan al die vereistes vir effektiewe afstandsleer nie. Bereiking van leerdoelwitte is in ‘n groot mate afhanklik van die steun van onderriggewers en porture. Hul beskik nie oor inligtingstegnologiese vaardighede nie en kan nie effektief leer waar nie–moedertaalonderrig ter sprake is nie. In teenstelling met bestaande literatuur dui kwantitatiewe en kwalitatiewe resultate op ‘n lae verband bestaan tussen afstandsleerders se selfgereguleerde leervaardighed en hul akademiese prestasie. Deelnemers maak selde gebruik van selfgereguleerde leervaardighede soos ter sprake tydens die voorafdenkfase maar meer tydens die wilsbeheer– en selfreaksiefases. ‘n Model is ontwikkel vir die verbetering van selfgereguleerde leervaardighede van oopafstandsleerders, inbegrepe deurlopende ontwikkeling van akademiese taalvaardigheid en inligtingstegnologiese vaardighede. Aanpassings in studiemateriaal en verandering van onderrigstrategieë en terugvoer is belangrike aspekte van die model. / Thesis (Ph.D. (Education))--North-West University, Potchefstroom Campus, 2011.

The problems of semantics and translation for concurrent programming languages are studied in this thesis. A structural operational approach is introduced to specify the semantics of parallelism and communication. Using this approach, semantics for the concurrent programming languages CSP (Hoare's Communicating Sequential Processes), multitasking and exception handling in Ada, Brinch-Hansen's Edison and CCS (Milner's Calculus of Communicating Systems) are defined and some of their properties are studied. An operational translation theory for concurrent programming languages is given. The concept of the correctness of a translation is formalised, the problem of composing transitions is studied and a composition theorem is proved. A set of sufficient conditions for proving the correctness of a translation is given. A syntax-directed translation from CSP to CCS is given and proved correct. Through this example the proof techniques of this approach is demonstrated. Finally, as an application of operational semantics and translation, a proposal for implementing multitasking in Ada is given via a two-step syntax-directed translation.

Ste2p and Ste3p are well-characterized yeast pheromone G-protein Coupled Receptors (GPCR) those are involved in the signaling of mating responses that lead to cell fusion. Their signaling–associated interactions with G-protein/MAPK signal transduction machinery are well established, homologous to those in mammalian systems, and serve as a simplified model system in GPCR research. While the arrestin- mediated biased signaling mechanism of mammalian GPCR has not been discovered for the pheromone receptors, a recent demonstration of α-arrestins being involved in the internalization of the pheromone GPCR, Ste2p was reported. The present study was designed to reevaluate and extend the alternate functionality for pheromone receptors and to determine the role of yeast arrestins in the yeast mating. Specific residues in the TM6 of Ste2p exhibiting strong mating and constitutive MAPK signaling were combined and investigated in terms of their effect on MAPK signal transduction leading to cell cycle arrest as well as their impact on downstream mating projection formation and zygote formation events. Our findings indicate that Ste2p possess as specific residues that govern its relative bias for mediating MAPK signaling or mating events. Relative dose response experiments accounting for systemic and observation bias for these mutations yielded evidence of mutational-derived functional biases for Ste2p and further validated the alternate pheromone dependent functionalities for Ste2p. Further, arrestin knockout and knock-in studies showed that Art1 (Ldb19) is selectively involved in the regulation of zygote formation but not MAPK signal transduction following the binding of ligand to Ste2p receptors. In addition, ligand stimulated selective localization of Art1 (Ldb19) to the mating projection, implicating it in the regulation of downstream mating functionalities. Overall, while leaving the full mechanism of alternate/biased Ste2p signaling to be elucidated, these results highlight the possibility of continued relevance of the yeast pheromone-mating pathway as a simplified model for GPCR research in the context of arrestin-mediated biased GPCR signaling.

Aim: This paper is a report on a study that explored the professional development of intensive care unit nurses in journal clubs. Background: Evidence-based practice is important in nursing care (Krom, Batten, & Bautista, 2010). However few nurses feel comfortable using evidence to guide their practice (Pravikoff, Tanner, & Pierce, 2005). Journal clubs are a way to establish science as conversation (Wright, 2004) and foster knowledge translation for evidence-based nursing practice (Goodfellow, 2004). Methods: Monthly journal club meetings were held with the participation of a total of 71 healthcare professionals (65 nurses, 2 physicians, 2 pharmacists, 1 physiotherapist, and 1 respiratory therapist), who worked in two intensive care units of an Ontario hospital. After six months of meetings, 21 individual interviews were conducted with nurses, physicians, pharmacists, and nurse educators. Additional data collection included two focus groups, surveys, a review of staff meeting minutes, and researcher field notes. Findings: Journal clubs provided nurses with incentive to read research articles, improved nurses’ confidence in reading research, created a community of peers who worked collaboratively to improve clinical practice, provided a structure for nurses to reflect-on-practice, and led to reported changes in clinical practice. However, the data suggests that any gains in competence of nurses with the critical appraisal of research articles were probably modest. Barriers to participating in journal clubs and evidence-based practice are also identified. Conclusion: Journal clubs can foster knowledge translation and evidence-based practice through creating a community of practice and by providing nurses with motivation, structure, and confidence to read research articles. However, nurses reported a lack of critical appraisal skills and uncertainty about how to implement evidence into practice. Journal clubs may have a greater impact when implemented alongside other knowledge translation strategies such as working with clinical nurse specialists in order to enhance evidence-based practice.

In this study, self-catalytic maturation of heterologously expressed pro-galactose oxidase was analysed in E.coli by altering some amino acids which were supposed to play a crucial role in pro-peptide removal. Galactose oxidase (GOase / EC 1.1.3.9) from Fusarium graminearum / having a molecular mass of 68kDa, is a monomeric, copper containing enzyme with an unusual thioether bond. The enzyme is produced as a precursor with an additional 8 amino acid pre- and a 17- amino acid pro-sequence at the N terminus. Previous work has shown that the pre-peptide is removed possibly by a protease during secretion, whereas the 17 amino acid pro-peptide is removed autocatalytically by the aerobic addition of Cu2+ to the precursor, preceding the formation of the thioether bond at the active site. The pro-gao gene was on ProGON1 and ProGOMN1 constructs which were previously established on pET101/D/lacZ vector in England by directed evolution. ProGON1 contains silent mutations at the N-terminus different from native galactose oxidase whereas ProGOMN1 has six further mutations within the mature enzyme, providing high expression. The cleavage site mutations R-1P/A1P, R-1X/A1X, S2A, and the H522A mutation just against the cleavage site in the three dimensional configuration, were carried out by site-directed mutagenesis. Those and some extra mutations were confirmed by DNA sequence analysis. Next, mutant galactose oxidases were expressed in E. coli BL21 Star (DE3), and were purified by Strep-Tactin&reg / Sepharose&reg / column, operating on the basis of affinity chromatography. Subsequently, SDS-PAGE was performed to analyze self-processing by detecting molecular mass difference of protein bands resulting from pro-sequence removal or existence. When the bands obtained in SDS-PAGE were compared, it was seen that the products of original recombinant plasmids, i.e. ProGON1, ProGOMN1 / and the mutational variants showed no difference in band size, all slightly above 70kDa / indicating pro-sequence presence on all constructs. Non-mutants and some of the mutants showed galactose oxidase activity, signifying proper active site construction by thioether bond formation. ProGOMN1 was submitted for N-terminal amino acid sequencing to be able to assert that a size above 70kDa is not solely due to the existence of a 1 kDa Strep-tag II at C-terminus. Sequencing data affirmed the presence of both the pre-peptide and the pro-preptide showing that processing has not occurred at the N-terminus. Accordingly, in this study, it was shown for the first time that the existence of a pre-pro-peptide at the N-terminus of galactose oxidase does not prevent thioether bond formation at the active site. Furthermore, since the pro-peptide is cleaved autocatalytically, the lack of removal of the pre-peptide in E.coli in the presence of Cu 2+ and oxygen is very likely to be the cause of lack of pro-peptide cleavage. In future studies the region corresponding to the pre-peptide will be deleted to prove this hypothesis.