Inter-molecular interaction is at the heart of biological function. Proteins can interact with ligands, peptides, small molecules, and other proteins to serve their structural or functional purpose. With advances in combinatorial chemistry and the development of high throughput binding assays, the available inter-molecular interaction data is increasing exponentially. As the space of testable compounds increases, the complexity and cost of finding a suitable inhibitor for a protein interaction increases. Computational drug discovery plays an important role in minimizing the time and cost needed to study the space of testable compounds. This work focuses on the usage of various computational methods in identifying protein interaction inhibitors and demonstrates the ability of computational drug discovery to contribute to the ever growing field of molecular interaction. A program to predict the location of binding surfaces on proteins, STP (Mehio et al., Bioinformatics, 2010, in press), has been created based on calculating the propensity of triplet-patterns of surface protein atoms that occur in binding sites. The use of STP in predicting ligand binding sites, allosteric binding sites, enzyme classification numbers, and binding details in multi-unit complexes is demonstrated. STP has been integrated into the in-house high throughput drug discovery pipeline, allowing the identification of inhibitors for proteins whose binding sites are unknown. Another computational paradigm is introduced, creating a virtual library of -turn peptidomimetics, designed to mimic the interaction of the Baff-Receptor (Baff-R) with the B-Lymphocyte Stimulator (Blys). LIDAEUS (Taylor, et al., Br J Pharmacol, 2008; 153, p. S55-S67) is used to identify chemical groups with favorable binding to Blys. Natural and non-natural sidechains are then used to create a library of synthesizable cyclic hexapeptides that would mimic the Blys:Baff-R interaction. Finally, this work demonstrates the usage and synergy of various in-house computational resources in drug discovery. The ProPep database is a repository used to study trends, motifs, residue pairing frequencies, and aminoacid enrichment propensities in protein-peptide interaction. The LHRLL protein-peptide interaction motif is identified and used with UFSRAT (S. Shave, PhD Thesis, University of Edinburgh, 2010) to conduct ligand-based virtual screening and generate a list of possible antagonists from the EDULISS (K. Hsin, PhD Thesis, University of Edinburgh, 2010) compound repository. A high throughput version of AutoDock (Morris, et al., J Comput Chem, 1998; 19, p. 1639-62) was adapted and used for precision virtual screening of these molecules, resulting in a list of compounds that are likely to inhibit the binding of this motif to several Nuclear Receptors.

Une évaluation longitudinale (de la 1ère à la 6ème année primaire) a été réalisée auprès d'enfants francophones apprenant le néerlandais comme langue seconde dans un contexte scolaire d'immersion linguistique. Leur développement linguistique a été comparé à celui d'enfants monolingues francophones et néerlandophones. Les objectifs de la recherche consistaient à déterminer (1) les conséquences positives ou négatives de la méthode immersive sur le développement linguistique des enfants dans leurs langues maternelle et seconde, (2) la langue la plus appropriée aux premiers pas dans l'acquisition de la lecture et de l'écriture (la langue maternelle ou la langue seconde caractérisée par un système écrit plus transparent), (3) les difficultés spécifiques rencontrées par ces enfants en immersion (acquisition de séquences phonologiques spécifiques à la langue seconde, interférences entre langues, etc.).

La problématique des contaminations croisées (transfert inter-lots de micro-ingrédients : additifs et/ou produits médicamenteux) dans le secteur de l'alimentation animale est entrée, depuis quelques décennies, au cœur des préoccupations de la profession. Ce phénomène se décompose en 2 phases : le dépôt de particules par un lot de fabrication et sa récupération par le/les lot(s) suivant(s). Plusieurs études expérimentales, ont incriminé l'élévateur à godets post-mélangeur dans l'augmentation du niveau de contamination d'une ligne de fabrication. Cet appareil de manutention achemine verticalement des mélanges pulvérulents de diverses matières premières, pouvant contenir, en particulier, des additifs ou des produits médicamenteux. L'objectif de ces travaux est de comprendre dans quelles mesures cet appareil est source de transfert inter-lots, et quels paramètres liés au procédé entrent en jeu. Plusieurs outils ont été mis en place et la réalisation d'un plan d'expériences a permis de mettre en lumière l'impact de certains facteurs sur la contamination croisée :d'une part, le mode de vidange (lié à la vitesse de la sangle) en tête de l'élévateur et l'angle de la bavette de jetée agissent sur la quantité de micro-ingrédient déposée lors du passage d'un lot, et d'autre part, l'espace autour des godets, modifie la capacité du lot suivant à collecter les reliquats.Ces informations définissent une position optimale des paramètres de l'élévateur qui, sur pilote, réduit le niveau de contaminations croisées de 9 à 7 %. Enfin, des observations des champs de vitesses pendant la jetée du produit ont apporté de éléments de compréhension sur mouvements d'air et d'aérosols à l'origine des contaminations.

Avec les larges déploiements de multiples technologies sans fil, les terminaux informatiques mobiles bénéficient d'une connectivité presque permanente, changeant de réseaux d'accès au gré de leurs déplacements. Ceci pose cependant le problème de la sélection de ces réseaux, afin de fournir les meilleures performances. Cette mobilité risque aussi d'impacter la qualité des applications, souvent en raison lors des " handovers " d'un réseau à l'autre, ou de la disparité des caractéristiques des réseaux d'accès. Pour aborder ces problèmes, cette thèse introduit trois éléments de contrôle (observation, décision, action) pour permettre une meilleure utilisation des ressources réseau par les équipements mobiles. Nous introduisons d'abord un mécanisme de décision qui utilise directement les métriques pertinentes pour les utilisateurs et les applications, plutôt que l'approche indirecte classique basée sur les métriques réseau. Ce mécanisme contrôle de manière coordonnée l'ensemble de la pile protocolaire, plutôt que des composants séparés, afin d'éviter des combinaisons conflictuelles. Nous démontrons que la flexibilité des paramètres applicatifs peut être exploitée et permet de maintenir une qualité élevée pour les applications tout en réduisant les coûts d'accès (énergétique et financier). Un élément d'action pour atténuer les perturbations lors des handovers est ensuite proposé sous la forme d'une extension au TCP-Friendly Rate Control mechanism (TFRC). Nous proposons de suspendre la transmission avant la déconnexion, puis de sonder le réseau après reconnexion. Nous montrons que cela permet un rétablissement plus rapide et une meilleure adaptabilité aux conditions du nouveau réseau. Son usage en combinaison avec le Datagram Congestion Control Protocol (DCCP) offre un meilleur support aux applications temps-réel, dont la qualité dépend de la vitesse de transmission immédiate. Finalement, nous proposons l'usage de la OMF Measurement Library (OML), une bibliothèque légère d'instrumentation et de rapport, comme élément d'observation. Pour évaluer la validité de cette proposition, nous étudions sa performance. Nous montrons qu'elle n'a pas d'impact significatif sur les applications instrumentées et qu'elle permet un suivi précis des métriques idoines.

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This dissertation aims at studying underlying cultural conflicts in Corinth and Paul's approach thereto. Firstly, the cultural underlays in the congregation of Corinth are revisited, with special reference to the presence of Greeks, Romans and Jews in the congregation which came into being there. This theme is explored by studying the meaning of culture, the archaeological data, as well as Biblical data and other historical data regarding these cultures and Corinth. Furthermore attention is given to the way in which these three cultures were reflected in Paul's own background. In conclusion Paul's approach to the conflict is delineated in terms of positive and negative renderings of the concept "becoming a slave to fellow humans". Special focus is given to 1 Corinthians 9:19-23 as a key pericope in this regard. The deduction made in this dissertation is that Paul disregards his own cultural heritage and makes himself a slave to people on behalf of winning people for Christ, without allowing people (or cultural groups) to rule him as masters. / Thesis (M.Th. (New Testament))--North-West University, Potchefstroom Campus, 2006

This project examines the medical management of pain and injury in British Olympic sport. By drawing upon the perspectives of health-care providers, it explores key developments such as the professionalisation, formalisation and bureaucratisation of sports medicine and the consequences of such developments on doctors' and physiotherapists' working practices, relationships with each other and on athlete care. A questionnaire about the backgrounds (e.g. the qualifications, experience and methods of recruitment and appointment) was sent to members of the British Olympic Association's Medical Committee and Physiotherapy Forum in November 2007 and in-depth, semi-structured interviews were conducted with 14 doctors and 14 physiotherapists between January and June 2008. Data indicate that attempts to professionalise sports medicine into a medical speciality have created fragmentation and resistance among the various groups involved in athlete care at this level. Whilst clinicians were committed by multi-disciplinary practice overall, data reveal qualitative differences between practitioners who have established themselves within bureaucratic organisations such as the English Institute of Sport (EIS) compared to those who provide largely voluntary medical services via National Governing Bodies of Sport (NGBs). Thus, practitioners in positions of managerial authority were constrained to negotiate the underlying amateur values of numerous sports medicine staff at the same time as striving for a professional ethos. Processes of professionalisation have also impacted upon the inter-professional relations between doctors and physiotherapists and the social organisation of athlete-care. As a consequence of their work setting, clinicians were constrained to adhere to the performance-motivated demands of their athlete and coach clients over longer-term health concerns. Because of their greater orientation towards performance, physiotherapists were able to effectively "compete" with doctors in a number of practice contexts and so claim considerable professional autonomy. This project adds to the existing body of knowledge on the medical practices of sports medicine clinicians in elite level sport and demonstrates the heterogeneity within this area of practice. Furthermore, the thesis highlights the importance of understanding clinicians working practices as a consequence of their particular work setting.

In the context of sustainable supply networks, this research analyzes the evolution of governance mechanisms and network structure, including the interplay between network conditions, context factors, positional power and managerial actions. The study reports on a longitudinal empirical research on a multi-stakeholder sustainable sourcing network established by Nespresso, Nestlé’s specialty coffee subsidiary. The research analyzes both dyadic and multi-actor network dynamics and proposes a framework to study network evolution. Social network analysis techniques are also used to measure evolution of the network's structure and complexity as well as positional power opportunities. The research shows that in the initial start-up phase, in a context marked by uncertainty, pre-existing commercial and personal relationships were favoured in the choice of partners. These pre-existing relationships were also influential in defining the initial network structure and supporting an initial phase of exploration. Governance mechanisms initially relied mostly on informal mechanisms, while formal mechanisms were incorporated over time to enable the supply chain network to grow and to provide clarity to all actors. As the sustainability programme network expanded in size and complexity, Nespresso, the lead organization, also acted on the network's structure by introducing regional offices, thus increasing network centralization and reducing complexity. Power derived by actors occupying central or brokerage positions in multiplex networks also influenced power relationships in the sustainability network by moderating or expanding the power opportunities available to central actors. The research has implications for both the Inter-organizational Relationship and the Social Network Theory literatures. In contrast with prior literature, the research proposes that in conditions of uncertainty, the use of informal governance mechanisms can facilitate a search and experimentation process. Formalization of governance mechanisms can be used, not as a repair mechanism, but rather as an enabler for further growth and efficiency. The research also extends the concept of network complexity and proposes that network managers can reduce this complexity by introducing or managing nodes that in turn contribute to the re-centralization of relationships towards specific nodes. Lastly, the research has implications for managers and proposes mapping of existing commercial and personal relationships as a potentially valuable tool in the creation and management of networks, adapting coordination mechanisms to the objectives of the relationship and actively managing the network's structure as a mechanism to enable network growth and efficiency.

The existing analyses in the literature of inter-regionalism focus on a macro perspective when they look at the relationship between inter-regional ties and global governance. They have not explored the European Union’s (EU) policy development toward the Association of South-East Asia Nations (ASEAN) in detail which affects the EU and ASEAN relationship. They have overlooked explanations and current empirical evidence regarding that relationship. This thesis analyses internal factors within the EU and external factors from ASEAN and outside of the EU which influence EU policies toward ASEAN. The internal factors are the relevant actors within the various institutional arrangements of the EU policy and the promotion of interests of the EU and those of its member states and to some extent of common EU values. The modes of engagement between the EU and ASEAN, the level of integration within ASEAN and the pressures and opportunities from ASEAN and outside the EU are the external factors. Then, this thesis assesses how, when and to what extent these factors influence the EU’s policy developments toward ASEAN and have implications for the inter-regional relationship between the two regions. I examine three EU policies toward ASEAN from 2001 to 2009:1) a new partnership with South-East Asia, 2) the joint EUASEAN monitoring mission in Aceh, and 3) an ASEAN-EU Free Trade Agreement (FTA).This thesis is based on a qualitative method of analysis and is part of problem-driven research. It employs inductive theory building from case studies as the research strategy and documents and interviews as methods of data collection. This thesis presents the variation in importance within factors which influence the EU’s policy development toward ASEAN. It highlights different kinds of interactions between factors which shape the success or failure of the EU’s policy development. The co-operative relationship between these factors is needed to conclude agreement between the two regions. However, the conflicting relationship between these factors can lead to the failure to reach agreement between them. With regard to internal factors, this thesis demonstrates that a shared common position between relevant and other related actors within each of the various institutional arrangements in the EU may assist in the conclusion of an agreement between the two regions. As EU interests takes precedence over values, the likelihood of achieving an agreement increases. With regard to external factors, this thesis argues that consultation and monitoring mechanisms have been used by the EU as its modes of engagement (as opposed to a negotiation) and they affect its policy development and enable it to reach an agreement with ASEAN. The conclusion of an agreement between the two regions can be easily achieved, when the level of integration within ASEAN remains static or weak. However, when the level of integration within ASEAN is stronger, the EU would be less likely to achieve its expected agreements with ASEAN. The conclusion of an agreement between the EU and ASEAN can be achieved when they can resolve these external pressures and take advantage of external opportunities. The trends in and implications for the EU and ASEAN relationship are as follows: first, the more the EU applies a balanced treatment of internal and external factors, then the more it will support the EU’s policy development and that will positively influence the EU and ASEAN relationship. Second, their relationship has been shifted from a hierarchical ex-colonial dynamic to a mutually interdependent partnership.

This work aimed to contribute to the understanding of tree - grass inter-cropping interactions so that the productivity and sustainability of extensive livestock husbandry can be increased. The work was carried out in the context of a small farm in Oaxaca, Mexico, where increases in productivity are limited by shortage of capital and where the tree component would be used as green manure. It is difficult to investigate the effectiveness of such a system by only using conventional field trials. I constructed a mathematical model to simulate how the main components of the system function under conditions that would not be evaluated in the field. Issues such as how many trees to plant and what tree species combine with grass cattle and environment, can be answered with the model. The particular features of the model are: 1) It describes an agro-ecosystem where trees perform several biological functions like nitrogen capture for use in the silvopastoral system, 2) It links grass and trees with the animal and 3) Nutrient availability depends mainly on soil organic matter decomposition and mineralisation rather than on external inputs. The present research consisted of 1) constructing the model prototype using data from the literature, 2) conducting field experiments to investigate the actual performance of the silvopastoral system, 3) perform laboratory research and greenhouse experiments complementarily to the field experiments and 4) elaborate on the carbon and nitrogen balance of the silvopastoral experiment, by combining research results and the mathematical model. The field experiment consisted of an array of 13 plots with one of the tree species Gliricidia sepium, Leucaena leucocephala, Delonix regia and Lysiloma auritum in a gradient of plant densities within a Brachiaria decumbens paddock. Results showed that the presence of trees in pastures is potentially useful for retaining nitrogen and carbon that would be lost in the grass mono-crop. Trees did not incorporate nitrogen through biological fixation, perhaps because the lack of adequate nodulation and they did not established their rooting systems to a depth beyond the grass roots (> 1.20m) so as to recover leached nutrients. However, trees produced mulch that was rich in nitrogen (3.8%) and whose decomposition rate ensures a slow release to prevent leaching. At the plant density used, the tree population caused no harm to grass as to production and nutritive value. Further increments in tree density in order to improve the potential for nitrogen capture should be evaluated in terms of the reduction of grass production. Several biological attributes of the species were determined, in some cases for the first time: biomass productivity, specific leaf area, nutritive value, phenolic content, root biomass, grass root longevity, root vertical distribution, etc. Such characterisation is useful for the understanding of the system inter-cropping and specially for the parameterisation of the silvopastoral model. Even though the mixtures proved able to survive for the span of the experiment, the sustainability of tree - grass inter-cropping as to the stabilisation of soil fertility requires longer monitoring. Other limiting factors such as phosphorus availability and the management of grazing systems have to be incorporated for an adequate evaluation of the silvopastoral system.