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This paper critically analyses the use of anti-dumping regulation in the Southern African Customs Union (SACU) with specific reference to Botswana. Dumping takes place where products are introduced into the commerce of another country at less than its normal value, if the export price of the product exported from one country to another is less than the comparable price, in the ordinary course of trade, for the like product when destined for consumption in the exporting country. Anti-dumping duties are an internationally-recognised exception to three core WTO principles namely, bound tariff commitments, most-favoured-nation MFN) and national treatment. The use of anti-dumping in SACU has always been in accordance with existing WTO rules. The new SACU Agreement has important implications for the anti-dumping regime within the customs union. It changed the way in which tariff decisions, including anti-dumping tariffs, are made and it also requires member states to develop legislation on contingency trade remedies such as anti-dumping for the region and to establish national bodies to administer these remedies within different countries. The SACU council has given mandate to the International Trade Administration Commission of South Africa (ITAC) to undertake all trade remedies investigations and imposition of the necessary duties. From the inception of ITAC till now ninety-five percent (95%) of all anti-dumping applications filed at ITAC alleging dumping are instituted by South Africa industries. Thus, only five percent (5%) of all anti-dumping applications are from Botswana, Lesotho, Namibia and Swaziland (BLNS countries). The findings in this paper reveal that Botswana has never filed an application seeking protection of any of its industries. In terms of Article 14 of the SACU Agreement Botswana is in the process of establishing its national body like ITAC. The argument is that, since Botswana has never filed for any trade remedy how effective will this national body going to be? Therefore, critically analyzing the use of anti-dumping regulation is very crucial for Botswana as a SACU member. Such analysis will help assess the effectiveness of SACU institutions such as the tariff board and the Botswana national body to be established. / Dissertation (LLM)--University of Pretoria, 2010. / Centre for Human Rights / unrestricted

Les chimiokines sont des petites protéines secrétées dont la fonction principale est la stimulation de la migration de cellules immunitaires vers différents organes et tissus. Elles sont souvent impliquées lors des maladies inflammatoires, auto-immunes et des cancers. Ainsi, les chimiokines et leurs récepteurs couplés aux protéines G (RCPG) sont la cible pharmacologique de plusieurs molécules, actuellement testées en essais cliniques. Nous avons pris comme modèle, lors de notre étude, le récepteur atypique CXCR7. Ce récepteur est dit atypique, car il ne signalise pas via la voie classique des protéines G, mais plutôt via la voie de la β-arrestine. CXCR7 est impliqué dans de nombreux cancers, favorise la progression métastatique et est un co-récepteur pour le virus de l’immunodéficience humaine (VIH). Cependant, aucune donnée sur son mode de liaison avec ses ligands CXCL11/ITAC et CXCL12/SDF-1 n’existe à date. Nous pensons que cette information est essentielle pour le développement efficace d’agonistes et d’antagonistes, et nous nous sommes intéressés à identifier les résidus essentiels à la liaison des deux ligands de CXCR7 et à son activation par ces derniers. Pour cela, nous avons créé une série de mutants par substitution ou délétion d’acides aminés de la partie N-terminale, des boucles extracellulaires et des domaines transmembranaires du récepteur. Nous avons testé leur marquage en surface cellulaire par cytométrie en flux, leur liaison des deux ligands par expériences de radio-liaison, et leur capacité à recruter la β-arrestine en réponse aux ligands par essais BRET. Les résultats obtenus ont permis d’identifier des résidus importants à l’interaction des systèmes CXCR7/SDF-1 et CXCR7-ITAC et suggèrent des modes de liaison à CXCR7 différents entre ITAC et SDF-1. Tout comme la liaison d’ITAC à son autre récepteur CXCR3, sa liaison à CXCR7 suivrait le mode conventionnel de liaison en deux étapes des récepteurs de chimiokines. Cependant, la liaison de SDF-1 à CXCR7 suivrait un autre mode de liaison, contrairement à sa liaison à son autre récepteur, CXCR4. / Chemokines are small secreted proteins whose major function is to stimulate the migration of immune cells to different organs and tissues. They are often involved in inflammatory and auto-immune diseases as well as cancers. Thus, chemokines and their G proteins Coupled Receptors (GPCR) are the pharmacological target of multiples molecules, currently tested in clinical trials. The model of our study is the atypical receptor CXCR7. This receptor is called atypical because it doesn’t signalize through the classical G protein pathway but rather signalizes through the β-arrestin pathway. CXCR7 is involved in many cancers, promotes metastatic progression and is a co-receptor for human immunodeficiency virus (HIV). However, there are, to date, no data concerning its binding mode to its ligands CXCL11/ITAC and CXCL12/SDF-1. We think that this information is crucial for the efficient development of agonists and antagonists and thus decided to identify the residus that are important for the binding of the two ligands of CXCR7 to the receptor and its subsequent activation. For that, we created a set of mutants by substitution or deletion of amino acids of the N-terminus, extracellular loops and transmembrane domains of the receptor. We then tested their surface expression by antibody staining and flow cytometry, their binding of the two ligands by binding assays and their capability to recruit β-arrestin in response to the ligands by BRET assays. The results obtained allowed us to identify important residues for the interaction of the systems CXCR7/SDF-1 and CXCR7/ITAC. They also suggest different binding modes of the chemokines ITAC and SDF-1 to CXCR7. Just like the binding of ITAC to its other receptor CXCR3, the binding mode of ITAC to CXCR7 follows the conventional two steps binding model of chemokine receptors. However, the binding of SDF-1 to CXCR7 follows another binding mode than the classical two step model, unlike its binding to its other receptor CXCR4.