Masters in Public Administration - MPA / This mini-thesis seeks to understand why infrastructure projects fail to contribute effectively to poverty (rural) reduction. The thesis assumes that though infrastructure provision can impact positively on rural poverty reduction, the same infrastructure provision has worsened or put people in worse conditions of poverty. Therefore it is not automatic that infrastructure provision would reduce rural poverty as often held. The thesis goes on to postulate that a positive relationship between infrastructure and rural poverty reduction is best achieved within a broad or generic policy which provides the framework for providing such infrastructure. The thesis assesses these assertions empirically by first, testing the relationships between infrastructure and rural poverty reduction. Here a large scale infrastructure project in Ghana known as the Keta sea defence project serves as the case study. Secondly the thesis assesses Ghana's infrastructure provision policy environment and its implications on rural poverty reduction in the affected communities of the Keta sea defence project. / South Africa

By means of data-driven marketing as well as big data technology, this paper presents the investigation of a case study from travel industry implemented by a combination of propensity model and a business model “2W1H”. The business model “2W1H” represents the purchasing behavior “What to buy”, “When to buy”, and “How to buy”. This paper presents the process of building propensity models for the application in behavioral targeting in travel industry.     Combined the propensity scores from predictive analysis and logistic regression with proper marketing and CRM strategies when communicating with travelers, the business model “2W1H” can perform personalized targeting for evaluating of marketing strategy and performance. By analyzing the business model “2W1H” and the propensity model on each business model, both the validation of the model based on training model and test data set, and the validation of actual marketing activities, it has been proven that predictive analytics plays a vital role in the implementation of travelers’ purchasing behavioral targeting in marketing.

Influenza viruses are respiratory pathogens that are responsible for annual influenza epidemics and sporadic influenza pandemics. Oseltamivir (Tamiflu((R))) is currently the only FDA-approved oral drug that is available for the prevention and treatment of influenza virus infection. However, its narrow therapeutic window, coupled with the increasing incidence of drug resistance, calls for the next generation of influenza antivirals. In this study, we discovered hesperadin, an aurora B kinase inhibitor, as a broad-spectrum influenza antiviral through forward chemical genomics screening. Hesperadin inhibits multiple human clinical isolates of influenza A and B viruses with single to submicromolar efficacy, including oseltamivir-resistant strains. Mechanistic studies revealed that hesperadin inhibits the early stage of viral replication by delaying the nuclear entry of viral ribonucleoprotein complex, thereby inhibiting viral RNA transcription and translation as well as viral protein synthesis. Moreover, a combination of hesperadin with oseltamivir shows synergistic antiviral activity, therefore hesperadin can be used either alone to treat infections by oseltamivir-resistant influenza viruses or used in combination with oseltamivir to delay resistance evolution among oseltamivir-sensitive strains. In summary, the discovery of hesperadin as a broad-spectrum influenza antiviral offers an alternative to combat future influenza epidemics and pandemics.

This thesis analyses the influence of monetary policy on the general price level in Zimbabwe during periods of hyperinflation and dollarisation. The first part of the analysis covers the period January 2006 to July 2008 when the country experienced high inflation and ultimately hyperinflation. The second part covers the period 2009 to 2012, when the country adopted the multi-currency system and became fully dollarised. In terms of motivation, the study firstly sought to empirically examine the factors that led to hyperinflation in Zimbabwe, paying particular attention to the influence of monetary policy. Secondly, the thesis sought to determine the major factors that influenced price formation in a dollarised Zimbabwean economy; a completely new macro-economic environment. A significant development in this new macro-economic environment was the loss of monetary policy autonomy of the central bank, which also contributed to the relevance of the study. This thesis makes two contributions. The first contribution is the finding that hyperinflation in Zimbabwe was caused by expansionary monetary policy as a result of the activities of an unrestrained and unaccountable central bank. The second contribution was the empirical finding that in the fully dollarised economy inflation is largely determined by external factors. This implies that the domestic economy has no control over domestic inflation developments and as such, Zimbabwean authorities should formulate appropriate economic policies to respond to the impact of external shocks on domestic price formation when the need arises. The role of monetary policy in Zimbabwe’s hyperinflation episode is assessed using the Autoregressive Distributed Lag (ARDL) and the Error Correction Model (ECM) approaches with monthly data from January 2006 to July 2008. The impact of monetary policy on hyperinflation is captured by the coefficient of broad money supply and the interest rate. Results indicate that hyperinflation was caused by expansionary monetary policy, the exchange rate premium and inflation expectations for both the short and long term. Zimbabwe’s hyperinflation episode which peaked during the period 2007 to 2008 brings to the fore the importance of ensuring that the central bank is independent in executing its mandate of influencing the monetary policy process in a manner that ensures price stability. The ARDL and ECM approaches are also used to explore the dynamics of inflation in the dollarised Zimbabwean economy, with monthly data from January 2009 to December 2012. The main drivers of inflation under the multi-currency system were found to be the United States of America dollar/South African rand exchange rate, international oil prices, inflation expectations and the South African inflation rate. The findings contrast with the hyperinflationary era, where empirical studies have cited excessive money supply growth as the major driver of inflation dynamics in Zimbabwe. The results also suggest a higher exchange rate pass-through to domestic prices, consistent with empirical literature which postulates that inflation in dollarised economies is largely explained by movements in the exchange rate of major trading partners and international prices. The policy implication from the analysis is the need for policy makers to aggressively promote policies that ensure increased productivity of the economy. An improvement in productivity would influence the relative prices of tradable and non-tradable goods and ultimately the general price level in the economy. The study also quantified the independence of the Reserve Bank of Zimbabwe (RBZ) using the Mathew (2006), “new index for institutional quality” and the results showed that the RBZ is not an independent central bank. The central bank is found to have a low index of central bank independence (CBI), against a high level of inflation. While this relationship does not imply causality it can be inferred that the lack of independence of the RBZ could have influenced inflation dynamics in Zimbabwe. Only a subordinated central bank can be compelled to engage in inflationary deficit financing and also fund quasi-fiscal activities. The provisions of the RBZ Act [Chapter 22:15] in their current form make the central bank an appendage of the Ministry of Finance and Economic Development and this has, to a large extent, resulted in conflict between the political goals of government and the central bank’s primary objective of achieving price stability. In the event that Zimbabwe reintroduces its own currency in future, the achievement of the primary goal of price stability by the central bank will only be realised if the apex bank is given more autonomy.

Les SRPs (Small Rigid Platforms) sont des nanoparticules de taille inférieure à 5 nm, constituées d'une matrice de polysiloxane, à la surface de laquelle sont greffés de manière covalente des complexes de gadolinium. Les SRPs ont été développées pour des applications en imagerie multimodale, notamment en imagerie par résonance magnétique, en scintigraphie et en imagerie par fluorescence, ainsi que pour des applications en théranostic, et plus particulièrement, en radiosensibilisation. L'objectif de la thèse consiste à fonctionnaliser les SRPs par des entités de ciblage, capables d'identifier et de se lier à des récepteurs surexprimés par les tumeurs ou par l'endothélium qui leur est associé. Plus précisément, trois molécules ciblantes ont été retenues : (i) le c(RGDfK) – un pentapeptide cyclique contenant le motif Arg-Gly-Asp ciblant spécifiquement l'intégrine αuß3, récepteur de cellule endothéliale pour les protéines de la matrice extracellulaire et surexprimée par de nombreuses cellules cancéreuses, (ii) une molécule dérivée de la quinoxaline – ciblant la mélanine, sur-exprimée par de nombreux types de mélanomes (cancers de la peau), et (iii) un pyridinium – ciblant les protéoglycanes, sur-exprimés par le chondrosarcome (cancer du cartilage). Les différentes molécules ciblantes ont alors été greffées en surface des SRPs afin d'optimiser leur accumulation et leur rétention au sein des tumeurs, et par conséquent, d'augmenter le potentiel de ces SRPs en tant qu'agents théranostiques. Le couplage covalent des différents vecteurs aux SRPs et leur quantification ont été mis en évidence par diverses techniques de caractérisation physicochimiques et complémentaires. Enfin, le ciblage des nanoparticules vectorisées a été démontré par plusieurs tests in vitro et/ou in vivo lors de nombreuses collaborations pour les trois différents vecteurs / SRPs (Small Rigid Platforms) are sub-5 nanometre nanoparticles, composed of a polysiloxane network surrounded by gadolinium chelates. SRPs have previously demonstrated their efficiency for multimodal imaging and theranostic applications, especially magnetic resonance imaging, scintigraphy, fluorescence imaging, and radiosensitization. The purpose of this thesis deals with the functionalization of these SRPs by targeting entities able to recognize and to bind to receptors that are over-expressed by tumours or by the matching endothelium. More specifically, three targeting molecules drew our attention: (i) c(RGDfK) – a cyclic pentapeptide containing the Arg-Gly-Asp motif, able to target the αuß3 integrin, an endothelial cell receptor for the proteins of the extracellular matrix and frequently expressed by tumour cells, (ii) a quinoxaline derivative – targeting melanin, which is over-expressed by melanomas (skin cancers) and (iii) a pyridinium moiety – targeting proteoglycans, which are over-expressed in chondrosarcoma (cartilage cancer). The different targeting molecules were then grafted to the SRPs in order to maximize their accumulation and retention in tumours with the aim to enhance the SRP efficiency as theranostic agents. The covalent coupling of the different targeting molecules to the SRPs and their quantification were performed by various physicochemical characterization techniques. Finally, the targeting of the functionalized SRPs was highlighted by several in vitro and/or in vivo assays thanks to numerous successful collaborations

This paper examines Czech experience with inflation targeting. It tries to assess empirically character of deviations from inflation targets throughout the time. It assess situation also in an international context. Consequently it analyse ability of IT regime to anchor inflation expectations in context of CNB?s forecasting performance. Results imply that although deviations were quite frequent in the Czech Republic, their occurrence has not been a barrier for delivering lower inflation and its lower volatility. Notwithstanding, its volatility remains significantly above the range experienced in the EU and the EMU countries. Regarding the inflation expectations, monetary policy surprises tend to be smaller over time,signalising that IT regime is priced by the markets. Thus, credibility of the CNB, concerning anchoring of inflation expectations, seems to improve after introduction of IT regime. It also indicates that IT regime is a quite appropriate regime for the upcoming period of time, which will be end up by the entry in the EMU.

The degree work is focused on analysis of inflation with help of suitable econometric models. Inflation with it's forms and possibilities of measuring is described at the beginning of the paper. There is mentioned an importance of monitoring and analysing inflation in view of Czech national bank. Consequently there are described characteristics of time series, which are important from viewpoint of construction of econometric models. Next part of this paper is focused on characterization of econometrics models. At first there is vector autoregression model, in this connection there is discussed the essence of Granger causality and impulse reaction. There are also noticed both error correction model and vector error correction model. The empirical part of degree work involves the use of these models on selected macroeconomic time series of the Czech republic. The objective is to analyze the relationship between inflation and other individual macroeconomic quantities. There is established the optimal vector autoregressive model and the results of Granger causality and impulse reaction are interpretated. Both error correction model and vector error correction model examining cointegration are also applied.

Aim of this work is to answer question, if inflation targeting as a final goal of monetary policy, is possible in Islamic country with interest free financial system. Firs part of this work compares primer characteristics of Islamic financial system to conventional system of west countries. Second part focuses on possible macroeconomic model changes to correspond to Islamic system. Third part tests previous presumptions for inflation targeting. Final part proposes some measures to monetary policy performance.

La riboflavine (RF) est une vitamine essentielle pour la croissance et le développement cellulaire. Elle possède des propriétés physico-chimiques intéressantes et est internalisée dans les cellules par des transporteurs spécifiques. Le premier objectif de ce projet était de synthétiser des dérivés amphiphiles de la RF (RFA) et d'étudier leurs capacités d'auto-assemblages. Le second objectif était d'insérer les RFA dans des liposomes et d'évaluer leur efficacité de ciblage tumoral in vitro et in vivo. La préparation des différents RFA repose sur l'ajout d'un lipide en différentes positions de la RF. L’un d'eux, de type phospholipide (RfdiC14) a été capable de former des objets tridimensionnels de taille μm constitués de lamelles multicouches dont l’architecture et la dynamique sont très différentes de celles des phospholipides classiques. L’insertion de RfdiC14 dans des liposomes est efficace et n’influence pas leurs propriétés physico-chimiques. Les liposomes fonctionnalisés ont montré une internalisation cellulaire spécifique dans les lignées A431, PC3 et HUVECs. Afin de tester l’efficacité du ciblage tumoral in vivo, un analogue de RfdiC14 portant un espaceur PEG a été préparé puis inséré dans des liposomes péguylés. Grâce à un marquage adéquat (ICG et DiR), leur accumulation tumorale a été suivie par imagerie photoacoustique dans un modèle A431 et leur biodistribution évaluée par imagerie μCT/FMT dans un modèle PC3. Les résultats montrent une légère amélioration de l’accumulation tumorale dans les xénogreffes A431 et une augmentation du ciblage vasculaire dans le modèle tumoral PC3. La biodistribution globale des liposomes marqués est comparable à celle des contrôles. / Riboflavin (RF) is an essential vitamin for cell growth and development. It possesses interesting physicochemical properties and is internalized by the cells through specific transporters. The first aim of this study was to prepare amphiphile derivatives of RF (RFA) and study their auto-assembly. The second aim was to insert RFA into established drug delivery systems and test their tumour-targeting potential in vitro and in vivo. RFA were prepared by the molecule functionalization with lipid moieties in different positions. One of them, a phospholipid-like derivative (RfdiC14) was able to self-assembly in aqueous solutions into μm-sized 3D objects constituted from slightly curved multilayer lamellas. The bilayer architecture and dynamics were very different from ordinary phospholipids. In contrast, the insertion of small amount of RfdiC14 in a liposome did not influence membrane dynamics and physicochemical characteristics. RfdiC14-functionalised liposomes displayed high and specific uptake in vitro in A431, PC3 cells and HUVECs. The efficiency of RF targeting was also tested in vivo. For that purpose, liposome composition was optimized and a new RF amphiphile with a PEG spacer between RF and lipid was prepared. The tumour accumulation of the liposomes labelled with ICG was studied by photoacoustic imaging in A431 tumour model. The biodistribution of DiR labelled liposomes was accessed by combined μCT/FMT imaging in PC3 tumour model. The results show slight improvement of the tumour accumulation in A431 xenographts and the enhancement of vascular targeting in PC3 tumour model. The overall biodistribution of the RF-targeted liposomes was comparable to control.

Le mélanome métastatique reste à l’heure actuelle une pathologie dramatique avec une survie moyenne de 13 mois après diagnostic, démontrant l’échec des chimiothérapies. Ces travaux de thèse ont pour but de développer une stratégie alternative utilisant les siRNA (petits ARN interférents) encapsulés au sein de nanocapsules lipidiques (LNC) pour une injection intraveineuse. Les premiers travaux ont porté sur le développement et l’amélioration du procédé de formulation des LNC chargées en siRNA. Les résultats ont permis une encapsulation à hauteur de 35%, une stabilité prolongée supérieure à 3 mois et une efficacité d’extinction du gène cible dans les cellules de mélanome. La deuxième partie de la thèse s’est orientée sur les stratégies de ciblage du mélanome après administration systémique. Différentes modifications de surface des LNC à l’aide de polyéthylène glycol (PEG) et d’Affitins (peptide d’affinité) ont été mises au point. La biodistribution sur des animaux « sains » ou des animaux greffés en sous-cutanés (mélanome humain) a révélé des comportements distincts en fonction des recouvrements utilisés. Les formes pegylées ont montré une accumulation préférentielle au site tumoral en comparaison avec les formes non modifiées ou modifiées avec les Affitins. Dans une troisième partie, des études d’efficacité anti-tumorale ont été réalisées avec un siRNA ciblant la protéine Bcl-2 ou la sous unité alpha 1 de la pompe Na/K ATPase. Une réduction du volume tumoral de 25% est observée avec les LNC siRNA Bcl-2. Par ailleurs, l’association de nouvelles chimiothérapies, les ferrocifènes, et des siRNA Bcl-2, montrent grâce à leur co-encapsulation au sein des LNC, des effets prometteurs. Ces travaux démontrent ainsi la capacité des LNC à délivrer des siRNA par voie intraveineuse dans de nouvelles stratégies de ciblage du mélanome. / Metastatic melanoma represents the most aggressive form of skin cancer with a median survival around 13 months. The low efficacy of actual chemotherapy is explained by important resistance phenomenon. The objective of this work consists in developing a new alternative strategy based on siRNA (small interfering RNA) encapsulated into lipid nanocapsules (LNCs) for intravenous injection. Firstly, the experiments were focused on development and optimization of formulation process for the encapsulation of siRNA into LNCs. The result demonstrated an encapsulation efficiency evaluated at 35% by spectrophotometer analysis, an important stability at 4°C (for at less 3 month) and an efficient gene inhibition in melanoma cells. The second part of this work studied the melanoma targeting potential of surface modified LNCs after systemic injection. In this way, pegylation with different polymers and Affitin grafting (affinity peptide) was performed on siRNA LNCs. The biodistribution on healthy animals and subcutaneous melanoma tumor bearing mice revealed the distinct behavior of various modified LNCs. All pegylated LNCs showed a preferential accumulation in tumor site in comparison with non-modified or Affitins LNCs. In a third part, the anti-cancer efficacy was tested with siRNA targeting Bcl-2, an anti-apoptotic member, or Alpha 1 subunit of Na/K ATPase. A reduction of tumoral volume evaluated at 25% was observed for Bcl-2 siRNA LNC. Moreover, the association with new promising anticancerous drug, ferrocifens, and Bcl-2 siRNA co-encapsulated into LNCs evidenced promising effects. This work demonstrated the capacity of LNC to deliver siRNA into melanoma cells and tumor after systemic administration thank to new targeting strategies in melanoma