Bien que le traitement antirétroviral (ART) supprime efficacement la multiplication du VIH-1 chez les patients infectés, l’ART ne guérit pas l'infection. En effet, si l'ART est arrêté, nous observons un rebond viral. Celui–ci est principalement dû à l'activation stochastique de cellules latentes qui contiennent le génome viral intégré mais ne produisent pas de virus et ne sont donc pas ciblées par l'ART ou le système immunitaire. Ces cellules latentes sont peu nombreuses (1-10 par million de cellules T-CD4+ quiescentes) mais elles apparaissent rapidement après la primo infection et constituent donc un obstacle majeur à l'éradication virale. La stratégie la plus prometteuse pour supprimer ces cellules, dite "Shock and Kill", est de les réactiver pour qu'elles soient ensuite ciblées par l'ART et/ou lysées par les cellules T cytotoxiques. Un certain nombre d’agents de sortie de latence (LRAs) ont été mis au point pour réactiver ces cellules. Ils ciblent les protéines cellulaires telles que les Histone-désacétylases (HDAC) ou la protéine kinase C. La plupart d'entre eux présentent donc des effets non spécifiques et parfois une toxicité. Tat est la protéine du VIH-1 qui permet la transcription virale et favorise la traduction des gènes viraux. Tat est la protéine clé pour la levée de latence et l'initiation de la production des protéines virales par la cellule latente. Sur la base des structures RMN de Tat disponibles, nous avons identifié par dynamique moléculaire les conformations les plus stables de Tat. Cela nous a permis d'identifier par criblage in silico des ligands potentiels de Tat. Dix molécules ont été sélectionnées. Une molécule appelée D10 se fixe spécifiquement à la protéine Tat et augmente son activité de transactivation d'environ 4 fois. De plus, D10 présente une activité LRA sur les lignées cellulaires latentes JLat-9.2 et OM-10.1. L’activité LRA de D10 sur ces lignées représente 50 à 70% de celle du SAHA (vorinostat), un inhibiteur des HDAC candidat LRA en cours d’essais cliniques (Phase 2). Sur les cellules latentes de patients VIH traités, D10 à 50 nM a une activité LRA très efficace, 80% supérieure à celle de la bryostatine-1 qui agit sur la PKC et est considéré comme le LRA le plus prometteur actuellement. Le mécanisme d’action de D10, à semble être la stabilisation du complexe de transcription Tat-TAR. Cet effet est observé à 30 nM D10. En utilisant une approche chémoinformatique nous avons sélectionné 11 analogues de D10, dit N1-N11. Certains de ces analogues (N5, N8) montrent un effet plus fort que D10 sur l’augmentation de la transactivation de Tat ainsi que pour l’effet LRA sur les lignées cellulaires latentes. Ce résultat nous a permis d'ébaucher une relation structure chimique / activité LRA de ces molécules. Nous avons donc identifié de nouveaux agents de sortie de latence du VIH-1 ciblant Tat, plus spécifiques que les LRAs ciblant les protéines cellulaires. Ce sont les premiers activateurs de Tat identifiés. / Despite its efficiency to prevent viral multiplication, antiretroviral therapy (ART) is unable to cure patients with HIV-1. Indeed if ART is stopped, a viral rebound is observed. This increase in blood viral load is due to the activation of HIV-1 reservoirs, among which latently-infected memory CD4+ T cells. These cells are rare (1 per million of quiescent T cells) and appear very quickly following infection. To purge this long-lived reservoir the "Shock and Kill" approach was developed. This strategy relies on the use of latency reversing agents (LRAs) to induce reservoir activation. All LRAs developed until now target cellular proteins such as Histone deacetylases or protein kinase C. These LRAs are not specific for viral transcription and displayed modest effects ex vivo. Here we present a new LRA family that binds to and activates HIV-1 Tat which is the key regulator for viral transcription and latency reversal. These compounds are not cytotoxic and specifically activate Tat transcriptional activity. They were less efficient than available LRAs on HIV-1 latent cell lines. Nevertheless, when tested on latent T-cells from HIV-1 patients, the lead compound D10 was ~ 80% more efficient than bryostatin-1, one of the best LRA available to date. This effect was observed at 50 nM, which corresponds to the D10 concentration required for this compound to stabilize the Tat-TAR transcription complex. These molecules are the first Tat activators available.

Most widely used applications of quantitative past vegetation reconstruction are based on pollen-vegetation relationship functions. To carry out detail vegetation reconstruction using this method, large amount of geographic data pre-processing is necessary. For this reason, large scale vegetation reconstructions are extremely rare. In this study data processing is carried out using automated GIS tools. Application of GIS enabled precise and detail reconstruction of the Late Glacial and Holocene forest vegetation composition, as well as the development of vegetation in Lithuania. New pollen investigations from cores and outcrops, created Lithuanian pollen database, evaluation of pollen-vegetation relationship functions in the environment of Lithuania and reconstruction of main tree species composition in the Late Glacial and Holocene, according to pollen database and selected pollen-vegetation relationship function are presented in this study. The created palaeovegetation maps enbled considerable detalization of knowledge about past vegetation in Lithuania. Consequently, main vegetation migration and distribution patterns were defined. / Plačiausiai naudojami kiekybinio praeities augalijos taksonominės sudėties atkūrimo pagal žiedadukių duomenis metodai remiasi žiedadulkių-augalijos priklausomybės funkcijomis. Norint atlikti detalų augalijos sudėties atkūrimą šiuo metodu, reikalingos itin didelės apimties geografinių duomenų apdorojimo procedūros, todėl stambiu masteliu augalijos sudėtis atkūriama itin retai. Šiame darbe duomenų apdorojimas atliekamas automatizuotomis GIS priemonėmis. GIS panaudojimas leido tiksliai ir detaliai atkurti Lietuvos vėlyvojo ledynmečio ir holoceno miško augalijos taksonominę sudėtį bei augalijos vystymosi raidą. Disertaciniame darbe pristatomi nauji gręžinių ir atodangų nuosėdų žiedadulkių tyrimai, sudaryta Lietuvos žiedadulkių duomenų bazė, atliktas įvairių žiedadulkių-augalijos priklausomybės funkcijų įvertinimas Lietuvos sąlygose, žiedadulkių duomenų bazės pagrindu pagal pasirinktą priklausomybės funkciją atkurta pagrindinių medžių taksonų sudėtis eilei vėlyvojo ledynmečio ir holoceno laikotarpių. Sudarytais praeities augalijos paplitimo žemėlapiais reikšmingai detalizuotos žinios apie praeities augaliją Lietuvoje, nustatyti pagrindiniai augalijos migracijos keliai ir jos paplitimo dėsningumai.

Plačiausiai naudojami kiekybinio praeities augalijos taksonominės sudėties atkūrimo pagal žiedadukių duomenis metodai remiasi žiedadulkių-augalijos priklausomybės funkcijomis. Norint atlikti detalų augalijos sudėties atkūrimą šiuo metodu, reikalingos itin didelės apimties geografinių duomenų apdorojimo procedūros, todėl stambiu masteliu augalijos sudėtis atkūriama itin retai. Šiame darbe duomenų apdorojimas atliekamas automatizuotomis GIS priemonėmis. GIS panaudojimas leido tiksliai ir detaliai atkurti Lietuvos vėlyvojo ledynmečio ir holoceno miško augalijos taksonominę sudėtį bei augalijos vystymosi raidą. Disertaciniame darbe pristatomi nauji gręžinių ir atodangų nuosėdų žiedadulkių tyrimai, sudaryta Lietuvos žiedadulkių duomenų bazė, atliktas įvairių žiedadulkių-augalijos priklausomybės funkcijų įvertinimas Lietuvos sąlygose, žiedadulkių duomenų bazės pagrindu pagal pasirinktą priklausomybės funkciją atkurta pagrindinių medžių taksonų sudėtis eilei vėlyvojo ledynmečio ir holoceno laikotarpių. Sudarytais praeities augalijos paplitimo žemėlapiais reikšmingai detalizuotos žinios apie praeities augaliją Lietuvoje, nustatyti pagrindiniai augalijos migracijos keliai ir jos paplitimo dėsningumai. / Most widely used applications of quantitative past vegetation reconstruction are based on pollen-vegetation relationship functions. To carry out detail vegetation reconstruction using this method, large amount of geographic data pre-processing is necessary. For this reason, large scale vegetation reconstructions are extremely rare. In this study data processing is carried out using automated GIS tools. Application of GIS enabled precise and detail reconstruction of the Late Glacial and Holocene forest vegetation composition, as well as the development of vegetation in Lithuania. New pollen investigations from cores and outcrops, created Lithuanian pollen database, evaluation of pollen-vegetation relationship functions in the environment of Lithuania and reconstruction of main tree species composition in the Late Glacial and Holocene, according to pollen database and selected pollen-vegetation relationship function are presented in this study. The created palaeovegetation maps enbled considerable detalization of knowledge about past vegetation in Lithuania. Consequently, main vegetation migration and distribution patterns were defined.

Pollenanalyser har länge gjorts för att få en uppfattning om förflutna vegetationer. Men att återskapa olika miljöer med hjälp av pollen är svårt på grund av en rad olika faktorer. I Hemavan i norra Sverige har ett pollenprov tagits, vilket gör att det går att utforska möjligheterna huruvida det går att rekonstruera vegetationen där eller inte. För att försöka rekonstruera vegetationen kommer två metoder att användas, en kvalitativ beskrivande rekonstruktion samt en som är teoretiskt och baseras på Landscape Reconstruction Algorithm (LRA). Den kvalitativa beskrivande rekonstruktionen resulterade i fyra vegetationskartor under olika skeden från pollenprovet i Hemavan. Den teoretiska rekonstruktionen producerade inga konkreta resultat än hur en hypotetisk vegetationsrekonstruktion kan genomföras med LRA och geografiska informationssystem (GIS). Detta ledde till att det ansågs att den kvalitativa beskrivande rekonstruktionen var bättre lämpad för området i Hemavan, men även att det finns potential att utveckla den teoretiska LRA metoden.

South Africa’s labour legislation went through significant changes recently, with the changes to section 198 of the Labour Relations Act 66 of 1995 being the most contentious. The purpose of this research was to explore the perceptions of employees in the HR department of an integrated petroleum and chemical company regarding the changes to labour broking and the potential implications of these changes for an integrated petroleum and chemical company and its employees. The qualitative exploratory study was conducted with six employees of a large integrative petroleum and chemical company making use of labour brokers, until data saturation was reached. The data were collected by means of individual interviews and telephonic interviews. The results indicated that the changes to section 198 will have some positive and negative implications. The positive implications for an organisation included more productive employees and the ability to identify high-quality employees more easily. The positive implications for the company's employees are that the lower-income employees will be protected, the new legislation will provide permanent employment and there will be better dispute resolution procedures. The negative implications to the changes to section 198 for the organisation, include for instance higher costs, the drafting of new policies and guidelines and less employment flexibility. Negative implications for the employees include unemployment, negative attitudes towards the organisation, poor employability and a situation where the current and/or permanent employees have to do all the work. / Business Management / M. Com. (Business Management)

This study considers the role war victims empowerment has on peacebuilding. Even though the relation between empowerment and peacebuilding is well examined, the importance of involving war victims in the peacebuilding process has been given less attention. Through a qualitative case study on the NGO GWED-G’s interventions for young war victims in Gulu, Amuru, and Nwoya districts in Uganda, this study contributes to the discussion on the importance of empowering young war victims for improved peacebuilding efforts. The findings and analysis are based on two analytical frameworks, empowerment theory and the four dimensions of peacebuilding, as well as previous realized linkage between the two. Through these frameworks, it is clear that the empirical data collected in this study regarding the empowerment of young war victims are strongly correlated to the four dimensions of peacebuilding. When carrying out the research, it was also discovered that this linkage goes well beyond what previous research have stated. This study additionally discovered that the empowerment of young war victims has contributed to peacebuilding by impacting whole communities as well. By empowering these war victims, GWED-G has generated a ripple effect, the impact extended to families and entire communities of the empowered war victims and thereby more effectively contributed to peacebuilding.

Cette thèse donne un aperçu des différentes attaques que doivent contrer les implémentations et propose quelques solutions en distinguant trois niveaux, le niveau hardware, le niveau mathématique et le niveau algorithmique. L'état de l'art fait au chapitre 2 montre bien que les possibilités données à l'attaquant sont multiples et variées. Au niveau hardware, les résultats obtenus dans le projet ESPASS-IS ont motivé la définition de nouveaux projets entre le laboratoire TIMA, le LIRMM et STMicroelectronics . Au niveau mathématique, la mise en ÷uvre de LRA et la collaboration initiée avec le LIRMM a ouvert la voie à de nombreux sujets de recherches vers des arithmétiques à la fois rapides et compactes mais prenant en compte un nouvel élément d'optimisation : la robustesse aux injections de fautes et la minimisation des fuites au travers des canaux cachés. Au niveau algorithmique particulièrement, l'article publié à CHES'00 a fait parti de la toute première vague de travaux de sécurisation des implémentations des courbes elliptiques et constitue une publication très citée dans le domaine.

This thesis addresses accountability for mass atrocities. It presents a case study of Uganda that has undergone a two-decade conflict between the Lord’s Resistance Army (LRA) insurgent group and the national army, the Uganda People’s Defence Armed Forces (UPDF). The government of Uganda has initiated various accountability measures that include international and domestic prosecutions, truth telling, reparations and traditional justice to address international crimes and other human rights violations committed during the conflict. The thesis in particular investigates how all these mechanisms could be used in a way that ensures that Uganda fulfils its international obligations and that the different measures complement each other. The thesis traces the background to the conflict that began in 1986 and explores the consequences of the conflict on the civilian population in Uganda. It alludes to its spread from Uganda to South Sudan and since 2008, to the Democratic Republic of Congo (DRC) and Central African Republic. It argues that the significant and continuous involvement of the government of Sudan from 1994 to 2005 internationalised the LRA conflict. It further finds that both the LRA and the UPDF perpetrated war crimes and crimes against humanity during the conflict. The thesis further discusses the international obligation of Uganda to prosecute, punish and extradite persons responsible for the commission of international crimes and to ensure remedies to victims of such crimes and other human rights violations. It finds that the lapse of Part II of the Amnesty Act that allowed for a ‘blanket amnesty’ leaves room for Uganda to fulfil its international obligations. The thesis further investigates the Agreement on Accountability and Reconciliation and its Annexure reached between the government of Uganda and the LRA in Juba that ushers in the various accountability pursuits in Uganda. It argues that the implementation and successes of the Agreement depends on the consultations, legislations, policies and the establishment and workings of the institutions envisaged that could lead to justice, truth and reparations in Uganda. The thesis finds that the different accountability measures that Uganda is pursuing correspond to the political, social and historical conditions in Uganda, in particular, decades of armed conflict and human rights violations with impunity of perpetrators. It concludes that the success of the accountability undertakings will largely depend on the high calibre of officials and staff of the different institutions and their ability to deal wisely with challenges that will inevitably arise. It further finds that a political will and commitment is essential to ensure adequate investment in technical, material and financial resources and that non-interference of the government in the work of the institutions will ensure success. It concludes that such a political will and commitment, a robust consultation with stakeholders including victim groups and the creation of alliances locally, nationally, regionally and internationally, Uganda’s accountability pursuits will lead to the desired justice, truth and reparations. / Thesis (LLD)--University of Pretoria, 2012. / Centre for Human Rights / unrestricted

The level of brutality and violence against children abducted and forcefully conscripted by the Lord's Resistance Army (LRA) in northern Uganda pricked the conscience of humanity. The suffering of the people in northern Uganda was described by Jan Egeland, the former United Nations Under-Secretary for Humanitarian Affairs, as 'the biggest forgotten humanitarian crisis in the world'. This study is primarily concerned with the plight of child soldiers in northern Uganda and how their effective reintegration and rehabilitation (RR) could lead to successful peacebuilding. The study is premised on the hypothesis that 'the promotion of the RR of former child soldiers by providing psychosocial support based on traditional and indigenous resources may contribute to conditions of peace and stability in northern Uganda'. The main contribution of this research is that it explores the relevance of psychosocial support based on the traditional and indigenous resources to the RR of child soldiers and peacebuilding of war-torn societies. Psychosocial support based on traditional and indigenous resources as an element of peacebuilding has been the neglected element of peacebuilding by the liberal peacebuilding interventions in most war-torn societies. For example, while traditional and indigenous resources in northern Uganda have been instrumental in the RR of former child soldiers, most scholars and policy makers have largely paid attention to the usual official government and United Nations structured top-down interventions that emphasize Western approaches of peacebuilding. More so, the official approaches have tended to marginalize the plight of former child soldiers in the reconstruction and peacebuilding of northern Uganda. Yet, failing to pay sufficient attention to effective RR of child soldiers could undermine the peace dividends already achieved in northern Uganda. The study also analyses the limitations of psychosocial support based on traditional and indigenous resources in the RR of former child soldiers. It further examines why Western approaches of psychosocial support in the RR of child soldiers have remained in use in spite of the criticisms levelled against them. The study examines other peacebuilding interventions, both official and unofficial, that have been implemented in northern Uganda. In terms of key findings, the study establishes that traditional and indigenous resources are still popular and have been widely used in northern Uganda in the RR of child soldiers. Majority of former child soldiers who were interviewed observed that they found traditional and indigenous resources more helpful than the Western models of psychosocial support. However, it was also established that there is a significant section of former child soldiers who found Western models more relevant in their RR processes. Based on these findings, the study recommends an integrative and holistic model of psychosocial support that blends good elements from both traditional and indigenous resources and Western approaches with greater emphasis on the former.

The level of brutality and violence against children abducted and forcefully conscripted by the Lord¿s Resistance Army (LRA) in northern Uganda pricked the conscience of humanity. The suffering of the people in northern Uganda was described by Jan Egeland, the former United Nations Under- Secretary for Humanitarian Affairs, as ¿the biggest forgotten humanitarian crisis in the world¿. This study is primarily concerned with the plight of child soldiers in northern Uganda and how their effective reintegration and rehabilitation (RR) could lead to successful peacebuilding. The study is premised on the hypothesis that ¿the promotion of the RR of former child soldiers by providing psychosocial support based on traditional and indigenous resources may contribute to conditions of peace and stability in northern Uganda.¿ The main contribution of this research is that it explores the relevance of psychosocial support based on the traditional and indigenous resources to the RR of child soldiers and peacebuilding of war-torn societies. Psychosocial support based on traditional and indigenous resources as an element of peacebuilding has been the neglected element of peacebuilding by the liberal peacebuilding interventions in most war-torn societies. For example, while traditional and indigenous resources in northern Uganda have been instrumental in the RR of former child soldiers, most scholars and policy makers have largely paid attention to the usual official government and United Nations structured top-down interventions that emphasize Western approaches of peacebuilding. More so, the official approaches have tended to marginalize the plight of former child soldiers in the reconstruction and peacebuilding of northern Uganda. Yet, failing to pay sufficient attention to effective RR of child soldiers could undermine the peace dividends already achieved in northern Uganda. The study also analyses the limitations of psychosocial support based on traditional and indigenous resources in the RR of former child soldiers. It further examines why Western approaches of psychosocial support in the RR of child soldiers have remained in use in spite of the criticisms levelled against them. The study examines other peacebuilding interventions, both official and unofficial, that have been implemented in northern Uganda. In terms of key findings, the study establishes that traditional and indigenous resources are still popular and have been widely used in northern Uganda in the RR of child soldiers. Majority of former child soldiers who were interviewed observed that they found traditional and indigenous resources more helpful than the Western models of psychosocial support. However, it was also established that there is a significant section of former child soldiers who found Western models more relevant in their RR processes. Based on these findings, the study recommends an integrative and holistic model of psychosocial support that blends good elements from both traditional and indigenous resources and Western approaches with greater emphasis on the former. / Advocates Coalition for Development and Environment (ACODE)