The thesis poses the question of how one can stabilize a state through external intervention without destabilizing sovereignty. The study critically examines the justifications for international and regional interventions in the cases of Liberia and Burundi through a social constructivist framework. The main objective of the thesis is to enhance the understanding of how sovereignty is interpreted during non-aggressive interventions, both from a theoretical perspective through analysis of official discourses and from a practical perspective through interviews with external and internal actors in the field. The thesis argues that it may be more fruitful for future studies to question the aim of these interventions, rather than ask how to improve them. The study finds that rather than reinforce the sovereignty, these interventions neutralize states subject to external intervention in the sense that they become dependent on external capacity to maintain their stability, thereby maintaining peace and order in the international arena. The conclusion is that these interventions remain both controversial and paradoxical and the stated aim of reinforcing the state's sovereignty is questionable at best.

The ubiquitous enzyme dUTPase hydrolyzes dUTP into dUMP and pyrophosphate, preventing DNA fragmentation and cell death due to accumulation of dUTP. Inhibitors of dUTPase could serve as drugs in the treatment of cancers and infectious diseases. This thesis presents five studies. A mutational study on the Escherichia coli dUTPase (S72A) provides new insights about the catalytic principles of the homotrimeric dUTPases. A model is presented in which transition state formation is associated with a rotation of the conserved Ser72 side chain. The model can explain the strict order of deamination and hydrolysis catalyzed by the bifunctional dCTP deaminase:dUTPases. The S72A/D90N double mutant is currently investigated. Preliminary data indicate that this form preserves the binding properties of the S72A mutant but is completely inactive, making it attractive for structural studies. In the remaining studies we compare the binding of substrate analogues to the human, the E. coli and the equine infectious anemia virus (EIAV) homotrimeric dUTPases. One study concerns 2´,3´-dideoxy-UTP (ddUTP) and shows that removal of the 3´-hydroxyl group increases KM, ten times with the cellular dUTPases and fifty times with the viral dUTPase, but does not affect kcat with any of these enzymes. Another study concerns the inhibitory effects of 3´-azido-2´,3´-dideoxy-UTP. This derivative binds to the bacterial dUTPase but not to the other forms making it a potential lead for the development of antibacterial dUTPase inhibitors. Yet another study investigates two uracil derivatives. Both compounds are found to inhibit the human, the bacterial but not the viral dUTPase. The inhibition is shown to be competitive.

Control of mRNA stability is an important aspect in the regulation of gene expression. A well studied signal for rapid transcript decay in mammalian cells is the AU-rich element (ARE), which is found in the 3’ untranslated region (UTR) of many labile transcripts. These sequence elements confer destabilization of transcripts by binding to AU-binding proteins (AUBPs) that can recruit cellular decay enzymes. The stability of ARE-containing mRNAs can be regulated by extracellular stimuli, which allows for cells to adapt to the changing environment. AREs are found in many transcripts that encode for inflammatory genes, including TNF, GM-CSF, and IL-8. Pathogens evolve and devise mechanisms to subvert the immune response of the host to aid in its infection. Bacillus anthracis is one such infectious agent that can disable numerous arms of the host immune response. Its secreted toxin, anthrax lethal toxin (LeTx), causes the accelerated decay of the IL-8 mRNA. IL-8 is a dual function cytokine and chemokine that can recruit and activate neutrophils at the site of infection. Through the inactivation of MAPK pathways, LeTx activity causes the destabilization of IL-8 transcripts through its ARE. In this thesis, I show that an AUBP, TTP, is dephosphorylated by LeTx and MAPK inhibitors, and knock-down of its expression stabilized IL-8 transcripts. LeTx activity also increased the colocalization of TTP to P-bodies, cytoplasmic sites concentrated with RNA decay enzymes. This suggests that the post-translational modification of TTP induced by LeTx led to its enhanced destabilization function. Identified TTP-associated proteins, non-muscle myosin heavy chain 9 (myosin-9) and HSC-70, were examined for their role in IL-8 transcript decay. Knock-down of each protein led to a slower rate of IL-8 mRNA destabilization. However, treatment of LeTx continued to mediate accelerated destabilization of IL-8 in these siRNA-transfected cells. This suggests that LeTx, myosin-9, and HSC-70 modulate the destabilization function of TTP independently.

Control of mRNA stability is an important aspect in the regulation of gene expression. A well studied signal for rapid transcript decay in mammalian cells is the AU-rich element (ARE), which is found in the 3’ untranslated region (UTR) of many labile transcripts. These sequence elements confer destabilization of transcripts by binding to AU-binding proteins (AUBPs) that can recruit cellular decay enzymes. The stability of ARE-containing mRNAs can be regulated by extracellular stimuli, which allows for cells to adapt to the changing environment. AREs are found in many transcripts that encode for inflammatory genes, including TNF, GM-CSF, and IL-8. Pathogens evolve and devise mechanisms to subvert the immune response of the host to aid in its infection. Bacillus anthracis is one such infectious agent that can disable numerous arms of the host immune response. Its secreted toxin, anthrax lethal toxin (LeTx), causes the accelerated decay of the IL-8 mRNA. IL-8 is a dual function cytokine and chemokine that can recruit and activate neutrophils at the site of infection. Through the inactivation of MAPK pathways, LeTx activity causes the destabilization of IL-8 transcripts through its ARE. In this thesis, I show that an AUBP, TTP, is dephosphorylated by LeTx and MAPK inhibitors, and knock-down of its expression stabilized IL-8 transcripts. LeTx activity also increased the colocalization of TTP to P-bodies, cytoplasmic sites concentrated with RNA decay enzymes. This suggests that the post-translational modification of TTP induced by LeTx led to its enhanced destabilization function. Identified TTP-associated proteins, non-muscle myosin heavy chain 9 (myosin-9) and HSC-70, were examined for their role in IL-8 transcript decay. Knock-down of each protein led to a slower rate of IL-8 mRNA destabilization. However, treatment of LeTx continued to mediate accelerated destabilization of IL-8 in these siRNA-transfected cells. This suggests that LeTx, myosin-9, and HSC-70 modulate the destabilization function of TTP independently.

Given the potential political, economic and reputational costs for violating international norms of sovereignty, we should expect to only rarely observe the adoption by states of risky foreign policies like destabilization (which is defined as the policy of changing the balance of power between a target government and its domestic opposition, with the aim of effecting the downfall of that target government.) Yet, history demonstrates that states regularly adopt destabilization as a foreign policy. My research addresses this puzzle: Why, given the high potential costs of violation of international norms, do policymakers opt to do so anyway? I argue that the answer lies in the breadth and intensity of conflicts of interest between destabilizing states and their targets. To illustrate my theoretical argument, I hypothesize the following: When policy makers perceive a broad and intense conflict of security, economic and ideological interests, they will adopt destabilization as a policy. In this dissertation, I look at US relations with Latin American states during the Cold War. To demonstrate my hypothesis, I perform three comparative case studies. Each comparison examines two cases which are similar in most ways except, notably, the breadth of conflict of interest perceived by the US. In each negative case, I demonstrate that two, but not three types of conflicts were present and the US did not destabilize the target government, but instead chose different policy options. In the affirmative case, I demonstrate that all three types of conflicts were present, and the US destabilized the target government. I then briefly explore South African policy toward its neighbors, to illustrate that my theoretical explanation is plausible outside of the context of US-Latin American relations. I conclude with a brief discussion on extension of the theory and implications of this study for foreign policy analysis.

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Thesis (MEng.)--University of Stellenbosch, 2000. / ENGLISH ABSTRACT: The aim of the thesis was to investigate the use of flow destabilization methods, combined with permeate backflushing (BIF) or on their own, on flux recovery and maintenance in capillary UF membrane systems under cross-flow (XF) and dead-end (DE) operating conditions. Various hydraulic and mechanical methods have been used to remove the accumulated cake layer and improve steady state process flux. Permeate backflushing (B/F) is the most widely used but the drawbacks are loss of product and extensive down-time. In a pilot plant study for ultrafiltration of surface waters containing high NOM, turbidity and cation loads, the use of flow destabilization, or feed flow reversal (FFR) combined with cross-flow B/F was able to improve the normalised flux by 10.7 ± 3.4 %, compared with 3.2 ± 1.6 % improvement for BIF without FFR. When a second B/F included FFR, the flux improvement was 7.0 ± 2.0 % compared with 4.3 ± 2.5 % for a B/F without FFR. The hypothesis was proposed that the flow destabilization caused slight lifting of the oriented cake layer, while the cross-flow B/F was able to sweep the lifted cake out of the lumen. If the flow destabilization may be effected by a simple but effective and low-cost method, and if this flow destabilization may be combined with reverse flow for short durations, the "lift-and-sweep" approach will be the ideal method of maintaining process flux and increasing membrane life. Such a flow destabilization method, now named "reversepressure pulsing" (RIP), was developed. The method involves circulation of feed water in a recycle loop for 2 s to gain momentum, followed by closure of a fast-action valve upstream of the modules. The momentum of the water in the concentrate loop carries it into an air-filled feed accumulator, while concentrate and reverse-flow permeate (which also lifts the fouling layer) are discharged to the atmosphere using the recycle pump for 15 s. When the valve opens again, the air in the accumulator forces the water under pressure through the membrane lumens, causing a pressure pulse and flow perturbations that lift, shift and break up the fouling layer. During 3 such "lift-and-sweep" events, the cake is lifted and the debris is swept out of the lumen. Experimental results for uninterrupted dead-end filtration at a UF pilot plant using RIP only on a severely fouled membrane, indicated that the RIP increased the flux by 18.4 % and decreased the dP by 8.2 % over a 7.2 h period. The method is effective in removing the cake layer intermittently and no long-term flux decline occurred for a period of 555 h since the previous chemical cleaning. / AFRIKAANSE OPSOMMING: Die doel van die tesis was om die gebruik van vloei-destabiliserings metodes, alleen of gekombineer met permeaat-terugwas, op vloed-herwinning en instandhouding in kapillêre UF membraan-stelsels tydens kruisvloei en doodloop bedryf, te ondersoek. Verskeie meganiese en hidrouliese metodes word gebruik in membraan stelsels om die koeklaag op die membraan se oppervlak te verwyder en die gestadigde-toestand vloed te verbeter. Vanhierdie metodes word permeaat-terugwas die meeste gebruik, maar het sy nadele insluitend verlies van produk en produksietyd. In 'n loodsstudie vir die ultrafiltrasie van oppervlakwaters wat hoë beladings NOM, turbiditeit en katione bevat, is die waarneming gemaak dat kruisvloei terugwas met vloeidestabilisering (voerrigting-verandering) die genormaliseerde vloed met 10.7 ± 3.4 % kon verbeter, vergeleke met 'n 3.2 ± l.6 % verbetering sonder voerrigting-verandering. Vir 'n tweede terugwas was die verbetering 7.0 ± 2.0 % vergeleke met 4.3 ± 2.5 % sonder voerrigtingverandering. Die hipotese was voorgestel dat die vloei-destabilisering die geoiënteerde koeklaag van die oppervlak gelig het, en die kruisvloei terugwas die geligde koeklaag uit die lumen kon vee. Indien hierdie vloei-destabilisering bewerk kan word deur 'n eenvoudige maar effektiewe manier, en indien dit gekombineer kan word met terugvloei van produk vir kort tydperke, sal hierdie "lig-en-vee" benadering die ideale metode wees om die membrane se vloed te verbeter en leeftyd te verleng. So 'n vloei-destabiliseringsmetode, nou genoem "terugdruk-pulsering", is ontwikkel. Die metode behels die sirkuiering van voer-water vir 2 s in 'n hersirkulasielus om momentum op te bou, gevolg deur die toemaak van 'n snel-aksie klep stroom-op van die modules. Die water in die konsentraat-lus se momentum dra dit vorentoe tot in In lug-gevulde voer-akkumulator, terwyl konsentraat en terug-vloei permeaat (wat ook tot 'n mate die koeklaag lig) ook na die atmosfeer gewend word vir 15 s deur die hersirkulasiepomp. As die klep weer oopgaan, ontspan die lug in die akkumulator, en forseer die water daarin onder druk deur die membraan-lumens. Die druk-puls en vloei-perturbasies lig, skuif en breek die koeklaag op. Tydens 3 agtereenvolgende "lig-en-vee" aksies word die koeklaag effektief opgebreek en uit die lumen gevee. Eksperimentele uitslae vir ononderbroke doodloop bedryf op uitermate aangevuilde membrane van 'n ultrafiltrasie loodsaanleg toegerus met terugdruk-pulsering, het getoon dat die vloed met 18.4 % verbeter kon word en die dP met 8.2 % verminder kon word in slegs 7.2 h. Die metode breek die koeklaag effektief op, en geen langtermyn vloed-afname is waargeneem vir meer as 555 h sedert die vorige chemiese was-prosedure nie.

Deux émulsions cationiques modèles sont mises au contact avec un solide présentant une charge superficielle négative et avec une solution alcaline. Premièrement, lorsque des quantités déterminées de sable de Fontainebleau sont ajoutées sur une émulsion stabilisée par un ammonium quaternaire, la viscosité des émulsions résiduelles diminue avec l'addition de sable et l'hétérofloculation a lieu si nous ajoutons suffisamment de sable. Les résultats montrent que la concentration de la phase dispersée diminue et le processus dépends de la concentration de tensioactif dans la phase continue de l'émulsion. Etant donné que ni la taille des gouttes ni la distribution ne changent pendant l'addition des solides, nous proposons l'adsorption directe des gouttes sur la surface minérale, suivie par leur coalescence sur les particules de sable. Par ailleurs, lorsqu'une solution alcaline est rajoutée sur une émulsion stabilisée par une amine, l'équilibre chimique est rapidement perturbé. L'addition de NaOH implique la production d'amine, le volume effectif des gouttes diminue et le comportement rhéologique des émulsions évolue de rhéofluidifiant à Newtonien. La déstabilisation résultant de la remontée de pH est due à la coalescence des gouttes à cause de la déprotonation du tensioactif. La formulation interfaciale évolue à chaque addition de la solution alcaline et le système bascule vers la production d'une microémulsion très instable. Les conditions pour la déstabilisation des émulsions peuvent être optimisées par un suivi rhéologique, mais il est fondamental de tenir compte des diverses possibilités pouvant se présenter si le processus n'est pas contrôlé strictement / Two cationic model emulsions are contacted with a solid having a negative-charged surface and with a caustic soda solution. In one hand, emulsions stabilized by a quaternary ammonium are contacted with Fontainebleau sandstone, as a consequence, a viscosity reduction of the remaining emulsion is observed, as well as the emulsion break-up through a heteroflocculation mechanism provided the solid surface is large enough. Results show that the dispersed oil fraction decreases after addition of sandstone aliquots, and this depends on the concentration of surfactant in the continuous phase of the emulsion. As the droplet size and distribution remain constant during the process, it is assumed that the emulsion heteroflocculation is the result of direct oil droplets adhesion on the sand surface, followed by their coalescence around the sand particles. On the other hand, when an alkali solution is added to a model cationic oil-in-water emulsion, chemical equilibrium is rapidly affected. The effective droplets volume decreases and rheological behavior which firstly exhibits a shear-thinning behavior becomes gradually Newtonian. The abrupt emulsion destabilization by pH increase is the result of droplets coalescence as a consequence of electrostatic repulsions disappearance among droplets. The surfactant adsorption at the liquid-liquid interface changes, the optimal formulation is reached and emulsion becomes unstable. After all, the emulsion morphology, stability and even emulsion inversion are all controlled by pH. Emulsion destabilization can be studied by a rheological monitoring process but it is hardly recommended keep in mind all physicochemical phenomena if this method is not strictly controlled

Le permafrost de montagne est menacé par le réchauffement atmosphérique, une évolution qui s’accompagne de l’augmentation des phénomènes tels que les chutes de pierres, la formation de thermokarsts et l’accélération des glaciers rocheux. La déstabilisation des glaciers rocheux, qui compromet l’intégrité structurelle de ces formes, semble liée au réchauffement atmosphérique, et a suscité un intérêt grandissant au cours des dernières années. Ce phénomène, qui peut être provoqué par le réchauffement du pergélisol ou des contraintes mécaniques externes, est caractérisé par une accélération anormale des glaciers rocheux affectés, et par l’apparition des signes géomorphologiques telles que des fissures et des crevasses à sa surface. Bien que ce processus peut être transitoire, il peut déterminer une phase de crise amenant le glacier rocheux à un effondrement.Cet étude se préfixe de fournir une première évaluation des phénomènes de déstabilisation de glacier rocheux à l’échelle des Alpes françaises. Dans un premier temps, l’empreinte spatiale du pergélisol a été évaluée afin de produire une carte de répartition du pergélisol régionale, un outil nécessaire pour estimer l’état du permafrost dans les glaciers rocheux. La deuxième étape a consisté à identifier les formes déstabilisées grâce à une observation ponctuelle des images aériennes afin d’identifier les caractéristiques typiquement observables sur les glaciers rocheux déstabilisés. Il est alors possible de comprendre les conditions topoclimatiques typiques dans lesquelles se produit ce phénomène et de repérer les formes susceptibles de subir ce processus. Enfin, les efforts ont été concentrés sur le glacier rocheux du Lou, déstabilisé, qui, du fait d’un détachement de couche active, a conduit à une lave torrentielle en Août 2015. L’analyse a visé à mieux définir les circonstances de cet événement, en mettant l’accent sur les facteurs de préconditionnement, de préparation et de déclenchement et sur leur interaction avec le processus de déstabilisation.Les résultats ont fourni des informations riches sur la zone périglaciaire de la région. La modélisation de la répartition du pergélisol a mis en évidence les étendues de la zone périglaciaire dans la région qu’on peut trouver sur les pentes de débris au-dessus de 2300 - 2500 m.a.s.l. en fonction de l’exposition solaire et des caractéristiques régionales des précipitations. L’observation des photographies aériennes a permis d’observer 46 formes en cours de déstabilisation, soit 12% des glaciers rocheux actifs des Alpes françaises. Il apparaît que la déstabilisation est plus susceptible de se produire dans certaines conditions topoclimatiques locales spécifiques, en particulier dans des pentes exposées au nord, raides et convexes situées aux marges inférieures de la zone de pergélisol. Un grand nombre de glaciers rocheux ne présentant actuellement aucune déstabilisation sont donc susceptibles d’être affectés par une déstabilisation future. L’analyse du glacier rocheux du Lou a révélé que la déstabilisation est liée à une avancée rapide du front vers un ravin torrentiel. Ce processus semble avoir accru la prédisposition des matériaux détritiques du front à être mobilisés par du ruissellement, des précipitations relativement modérées ayant suffi à déclencher l’événement.Malgré les incertitudes liées aux méthodes impliquées, les résultats suggèrent que les conditions favorables à la déstabilisation sont fréquentes, et que cette dernière peut augmenter le niveau de risque si le site est connecté à des infrastructures humaines. Des efforts supplémentaires doivent donc être entrepris, afin d’améliorer la compréhension de ces processus, notamment par la surveillance des sites ainsi que par une évaluation locale complète des cascades de processus liés à ce phénomène. / As occurring to several geosystems on our planet, mountain permafrost is threatened by climate change as prolonged warming may compromise the geotechnical properties of the frozen ground. As result, increasing occurrence of rockfall activity, thermokarst formation and rock glacier acceleration was observed in the past decades. Rock glacier destabilization, a process that compromises the structural integrity of these landforms, seems to be linked to atmospheric warming, gaining interest in the past years. The destabilization, which may be triggered by warming permafrost or mechanical stress, is characterized by an anomalous acceleration of the landform and the occurrence of specific features such as cracks and crevasses on its surface. Although the occurrence of these processes is mostly transitory, determining a textit{crisis} phase of the landform, in exceptional cases it may lead the rock glacier to structural collapse.This PhD thesis provided an assessment on the occurrence and related processes of rock glacier destabilization in the French Alps. At first, the spatial occurrence of debris permafrost was assessed in order to provide the permafrost distribution map of the French Alps, a tool that was necessary to evaluate permafrost conditions at rock glaciers sites. The second step consisted in an identification of destabilized rock glaciers in the region, which was done by multiple orthoimages interpretation aimed to identify features typically observable on destabilized rock glacier. Once identified the destabilized rock glaciers it was possible to analyse the typical topographical settings in which destabilization occurs and to to spot those landforms that are susceptible to experience this phenomenon. After these efforts at the regional scale, the focus was shifted towards local scale investigations at the Lou rock glacier, a partially destabilized landform that, due to frontal failure, in August 2015 triggered a debris flow that caused significant damages to buildings. The analysis aimed to better define the circumstances of this event, focusing on preconditioning, preparatory and triggering factors and their interaction with the destabilization process.The results provided interesting insights on the issue of destabilizing rock glaciers in the region. Permafrost distribution modeling demonstrated the large extents of the periglacial zone in the region as it can be found in debris slopes above 2300 - 2900 m.a.s.l. depending upon solar exposure and regional precipitation characteristics. Rock glacier destabilization was observed on 46 landforms, i.e. the 12% of the active rock glaciers. Destabilization was found to be more likely to occur in specific local topo-climatic conditions, consisting of north facing, steep and convex slopes at the lower margins of the permafrost zone. A large number of rock glaciers currently not showing destabilization was found to be located in these conditions and suggested to be susceptible to future destabilization. As demonstrated by the Lou rock glacier analysis, destabilization was found to be a relevant phenomena in the context of permafrost hazards. At this site, rock glacier destabilization was linked to a rapid frontal advance towards a torrential gully. This process seemed to have increased the site predisposition to frontal failure as a mild rainstorm was sufficient to trigger the event.Despite methodological uncertainties, results indicated that destabilization occurrence is widespread and it may rise the hazard level of a site connected to human infrastructures. Therefore, it is suggested that, where it has been modelled and where stakes may be at risk downslope, rock glacier destabilization deserves to be more carefully investigated. In this sense further efforts should focus towards a better understanding of the destabilization process by site monitoring as well as towards a comprehensive hazard assessment linked to this phenomenon.

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