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Dans les cas de lymphopénie, les lymphocytes T résiduels prolifèrent exagérément dans un phénomène appelé «expansion homéostatique périphérique» (HPE), qui est efficace pour la régénération des T CD8+, mais inefficace pour les T CD4+. L’interleukine-7 (IL7) est une cytokine homéostatique utilisée afin d’augmenter les comptes lymphocytaires T des patients lymphopéniques. Toutefois, la raison de l’expansion préférentielle des lymphocytes T CD8+ par l’IL7 demeure toujours inconnue. Nous montrons que cette expansion est due au fait que l’IL7 induit une prolifération efficace des T CD8+ périphériques (CD8+PERI) ainsi que des émigrants thymiques CD8+ (CD8+RTEs). Par contre, l’effet prolifératif de l’IL7 est restreint presqu’uniquement aux CD4+RTEs même si les CD4+PERI survivent mieux que les CD4+RTEs. De plus faibles doses d’IL7 sont nécessaires aux CD4+RTEs afin de phosphoryler STAT5 ou de proliférer comparativement aux CD4+PERI et nous démontrons que les contacts TCR/CMHII sont nécessaires à la prolifération induite par l’IL7 des CD4+RTEs en périphérie. De fait, augmenter au Flt3 ligand le nombre de cellules dendritiques périphériques d’une souris donneuse, avant de transférer ses TPERI dans des souris receveuses traitées à l’IL7 induit une prolifération significative des CD4+PERI. Nos résultats indiquent donc que l’abondance des contacts TCR/CMHII reçus dans le thymus semble contrôler la sensibilité à l’IL7 des CD4+RTEs. Finalement, l’observation que les CD8+PERI et CD8+RTEs prolifèrent pareillement pendant la thérapie à l’IL7, alors que la prolifération des T CD4+ est largement restreinte aux RTEs expliquerait pourquoi, dans les cas de lymphopénie, la régénération des T CD4+ est aussi dépendante de la thymopoïèse. / In lymphopenic settings, residual T lymphocytes typically undergo exaggerated proliferation via homeostatic peripheral expansion (HPE). While HPE efficiently regenerates CD8+ T cells, it is unable to normalize CD4+ T-cell counts. Interleukin-7 (IL7) is a homeostatic cytokine, currently used in trials in order to increase T-cell counts in lymphopenic humans. Nowadays, it is still not known why IL7 therapy is more effective toward the expansion of CD8+ T cells rather than CD4+ T cells. Here we show that CD8+ T cells preferential expansion is due to IL7-induced efficient proliferation of peripheral CD8+ T cells (CD8+PERI) and CD8+ recent thymic emigrants (CD8+RTEs). In contrast, the proliferative action of IL7 is largely restricted to CD4+RTEs although CD4+PERI survive better than CD4+RTEs. Interestingly, CD4+RTEs require lower concentrations of IL7 in order to phosphorylate STAT5 or proliferate when compared to CD4+PERI, and we demonstrate the requirement for TCR/MHCII contacts to support the IL7-induced HPE of CD4+RTEs in the periphery. Furthermore, augmenting the number of MHCII expressing cells in the periphery of donor mice by treating them with Flt3 ligand (Flt3L) prior transferring their TPERI cells in IL7 therapy-treated recipients, significantly enhances the IL7-induced proliferation of CD4+PERI. Our results indicate so far that the abundance of TCR triggering occurring inside the thymus drives IL7 responsiveness of CD4+RTEs. Moreover, the observation that CD8+PERI and CD8+RTE proliferate similarly during IL7 therapy, while proliferation of CD4+ T cells is largely restricted to RTEs, may explain why CD4+ T cells regeneration in lymphopenic settings is highly dependent on thymopoiesis.

Pentecostalism has, in recent times, undeniably contributed towards the growth of the church as a whole. Public worship services inherently submit and contribute towards the meeting between man and God as well as fellowship between the people who form part of said service. Public services in honor of God speak to the purposes of God and man’s fundamental desire to meet with our Creator. Consequently, research into this phenomenon proves vital in determining and even extending the role of the Pentecostal ideology in correlation to the longevity of honorary public services. Chapters 2 through 4 shed light on some of the key concepts that clarifies the dynamic nature of these events, throughout the service wherein the radiant power of God touches the human heart in some astounding ways. Exegetic studies have been undertaken into 2 Chronicles 5-7 which examines these instances of divine meeting in the Old Testament while the second chapter of Acts deals with the event from a New Testament perspective. In addition to this, 1 Corinthians 11-14 was utilized to highlight the role of the Holy Ghost as the instigator for divine meeting. Specific issues addressed by the research include service preparation and the role of music and its contribution to ambience preceding a meeting between man and God. Moreover, a keen focus on the sermon and the delivery thereof as well as its progression leading up to the conclusion and summary in closing and prayer, are all dealt with as part of this study. This dynamic, in essence, becomes visible through the statement issued by the life of each disciple as a living testament to this consuming and changing event. Honorary public services fit the bill as an event to promote divine meeting. Chapter 5 delves into some of the auxiliary sciences i.e. sociology, communication science, psychology and the field of antropology. The principles in chapters 2 through 4 are affirmed by these aspects of science and provide perspective on the practical applications thereof. All these factors in relation to practice have also been scrutinized through empirical research. This research clearly places divine meeting as a central to and inseparable from perceiver experience. Chapter 7 provides practical guidelines to alternative approaches in practicum. The study proposes a model whereby certain aspects can be examined from a Pentecostal point of view in order to tailor services as a dais for divine meeting. Most importantly it should be evident in the life of the participant that they have truly encounter God. This meeting is the prime objective and at the heart of public service. It serves and should always serve as a doorway to Christian life. / PhD (Liturgics), North-West University, Potchefstroom Campus, 2014

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ABSTRACT This thesis describes an investigation into the role of acetylenic and allenic precursors in the formation of the important aroma compound β-damascenone (1). Chapter 1 provides an introduction to the subject, beginning with a brief history of the Australian wine industry which began with the first fleet’s arrival in 1788. Many of the various volatile compounds found in wine are then discussed, with particular emphasis on β-damascenone (1). Some previous syntheses of 1 are summarised, as well as the in vivo generation of this compound, and also the role of glycoconjugation in nature. The chapter concludes with the aims of the present work. Chapter 2 covers the synthesis of the suspected acetylenic precursor 9-hydroxymegastigma-3,5-dien-7-yne (36), which was prepared by the addition of 3-butyn-2-ol to 2,6,6-trimethylcyclohex-2-en-1-one, followed by a conjugate dehydration reaction. The synthetic sample of 36 was shown to be identical to a compound previously observed in the hydrolysate of 3,5,9-trihydroxymegastigma-6,7-diene (31). Upon acid hydrolysis, 36 produced > 90% β-damascenone (1). Chapter 3 outlines the synthesis and hydrolysis of the C9 glycoside 43, which was prepared by a modified Koenigs-Knorr procedure on aglycone 36. Diastereomerically pure samples of each of the two possible glycosides were synthesised from corresponding enantiomerically pure samples of 36, which in turn were prepared by the use of either (R) or (S) 3-butyn-2-ol. Detailed hydrolytic studies (at 25 ºC) were conducted on both the aglycone and the two glycosides: the half lives of conversion of 36 into 1 were 40 hours and 65 hours at pH 3.0 and pH 3.2 respectively; the (9R) diastereomer of 43 had half-lives of 3 days and 6 days, respectively at the same pH values, whereas the (9S) diastereomer had half lives of 3.5 days and 6.5 days, respectively at the same pH values. The synthesis of the other suspected precursor, megastigma-4,6,7-triene-3,9-diol (35) is covered in Chapter 4. This allene was prepared by addition of 3-butyn-2-ol to phorenol, with the allene function generated by reaction with lithium aluminium hydride. By using (3S)-phorenol and both (R) and (S) 3-butyn-2-ol, four different diastereomers of 35 were prepared and characterised. The (3S, 6R, 9S)-isomer of 35 was also found to be identical to a compound previously observed in the hydrolysate of (31). A detailed hydrolytic study of the four synthetic isomers of 35 is contained within Chapter 5. This study revealed that each of the four isomers underwent rapid epimerisation at 25 ºC and pH 3.0. Careful analysis of the four product mixtures by chiral GC-MS revealed that this epimerisation was occurring exclusively at C3. The complete absence of 3-hydroxydamascone (2) from any of the hydrolysates required a re-appraisal of the mechanism of in vivo formation of β-damascenone (1), which forms the focus of the second half of this chapter. The experimental procedures (materials and methods) for all work covered in chapters 2-5 are located in Chapter 6.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.

Résumé confidentiel / Résumé confidentiel

Les pouvoirs publics koweïtiens entendent créer un climat favorable aux investisseurs, en mettant l’accent notamment sur le partenariat entre public et privé. C’est ainsi qu’en 2008, le parlement koweitien a adopté la loi 7/2008 qui comporte une organisation générale des contrats de constructions, d’exploitation et de transfert (BOT). Le législateur a adopté par la suite la loi 116/2014 sur le partenariat qui reprend avec plus de détails les formes de coopération publique-privée. À cet effet, deux organes ont été créés : le Haut Comité et l’Autorité des projets, avec des compétences très étendues quant à la formation et à l’exécution du contrat BOT (appel d’offres, négociations, conclusion du contrat, sa durée, son financement, etc.). L’objectif de cette étude est de traiter, à partir de cette législation, la notion de contrat BOT que les spécialistes assimilent volontiers au terme de concession, ou à celui de délégation de service public. Dans cette perspective, il est nécessaire d’aborder le montage financier et la nature juridique du contrat BOT. La mise en œuvre du contrat BOT fait intervenir une diversité des parties contractantes (administration, partenaires privés, créditeurs, sociétés de construction, fournisseurs de matériels, investisseurs de capitaux, consommateurs utilisateurs des produits, etc.), cela rend la réalisation de ce type de contrat assez complexe. Cette complexité peut se poser de manière aiguë au Koweït, dans la mesure où le pays vient juste d’inaugurer cette procédure de passation de marché impliquant directement le public et le privéLe montage financier des contrats BOT, connu sous le nom de « projet de financement » repose presque totalement sur des acteurs privés. Dès lors, la question qui se pose est celle de la répartition des risques. À ce sujet, l’analyse cherche à comprendre pourquoi les risques liés au financement sont assumés essentiellement par l’opérateur privé, indirectement par la société de projet, et directement par le prêteur, en l’occurrence les banques. Reste que pour couvrir ces risques, le contrat BOT prévoit, au bénéfice des pourvoyeurs de fonds, un certain nombre de garanties portant aussi bien sur les actifs composant le projet (équipements, outillages, stocks, transmission de créances), que sur le projet lui-même (nantissement et hypothèques des actions de la société de projet, cession de revenus, substitution des banques au promoteur privé défaillant).La nature juridique du contrat BOT soulève deux interrogations majeures : la première est de savoir si ce type de contrat relève de droit administratif ou de droit civil. La seconde porte sur les litiges qui peuvent naître de ce type de contrat comportant un large éventail d’éléments d’extranéité (investissements extérieurs, transfert de technologie, etc.) et soumis à l’arbitrage international. À ce niveau, il convient de connaître le droit applicable : s’agit-il du droit interne ou droit international ? C’est à cet ensemble de questions que cette recherche tente d’apporter un début de réponse en prenant comme cadre de réflexion le contexte koweïtien. / The Public Authorities (Government) of Kuwait aim to create a favorable investor climate, with particular emphasis on public-private partnerships. Thus, in 2008, the Kuwaiti Parliament passed Law 7/2008, which includes a general organization of contracts of construction, exploitation and transfer (BOT) “Build, Operate and Transfer”. The legislator subsequently adopted the law 116/2014 on the partnership which repeats in more detail the forms of public-private cooperation. To this end, two bodies have been created: the High Committee and the Projects Authority, with extensive expertise in the training and execution of the BOT contract (call for tenders, negotiations, conclusion of the contract, its duration, financing, etc.). The objective of this study is to deal, from this legislation, with the concept of BOT contract that specialists readily assimilate to the term of concession, or that of public service delegation. In this perspective, it is necessary to address the financial arrangement and the legal nature of the BOT contract.The implementation of the BOT contract involves a diversity of contracting parties (administration, private partners, creditors, construction companies, equipment suppliers, capital investors, consumer users of products, etc.), which makes the implementation of this type of contract rather complex. This complexity can be seriously arisen in Kuwait, as the country has just inaugurated this procurement procedure directly involving the public and the private sector.The financial set-up of the BOT contracts, known as the "financing project", relies almost entirely on private actors. Therefore, the question that arises is that of the distribution of risks. In this regard, the analysis seeks to understand why financing risks are borne mainly by the private operator, indirectly by the project company, and directly by the lender, in this case the banks. However, to cover these risks, the BOT contract provides, for the benefit of fund providers, a number of guarantees covering both the project assets (equipment, tools, inventory, transfer of receivables) and the project itself (pledging and hypothecation of shares in the project company, transfer of income, substitution banks to the defaulting private promoter).The legal nature of the BOT contract raises two major questions: the first is whether this type of contract falls under administrative law or civil law. The second deals with disputes that may arise from this type of contract, which includes a wide range of foreign elements (outside investment, technology transfer, etc.) and is subject to international arbitration. At this level, one must know the applicable law: is it domestic law or international law? It is to this set of questions that this research tries to bring a beginning of answer by taking as a framework of reflection the Kuwaiti context.