Estudos de metabolismo in vitro possuem o intuito de caracterizar e quantificar possíveis metabólitos, elucidar as vias metabólicas e sugerir modelos a serem seguidos para a realização de estudos in vivo. Com o intuito de estudar o metabolismo in vitro não estereosseletivo da rosiglitazona (RSG) empregando fração microssomal de fígado de ratos,foi desenvolvida uma metodologia por cromatografia líquida de alta eficiência (HPLC) com detecção UV em 245 nm, para analisar a RSG e seus principais metabólitos, p-hidroxi rosiglitazona (?-OH-R) e N-desmetil rosiglitazona (N-Dm-R). Os analitos foram separados em fase reversa, utilizando uma coluna X-Terra MS C-18 (partículas de 3,5 ?m) e fase móvel composta por água:acetonitrila:ácido acético (85:15:0,5, v/v/v), na vazão de 1 mL min-1. Matrizes biológicas contém um grande excesso de proteínas, lipídeos e outros materiais endógenos que interferem na análise de fármacos e metabólitos, tornando necessário um procedimento adequado de preparação das amostras antes da análise cromatográfica. A microextração em fase líquida com membrana cilíndrica oca (HF-LPME) é uma técnica promissora para a preparação de amostras em estudos de metabolismo in vitro, pois, além de promover o clean-up, promove também o enriquecimento dos analitos na amostra. A HF-LPME foi aplicada pela primeira vez para a extração simultânea desse fármaco e seus metabólitos. O sistema de três fases foi escolhido como o mais apropriado, empregando uma solução de ácido clorídrico como fase aceptora e 1-octanol como solvente orgânico. A otimização dos demais parâmetros foi realizada através de planejamento fatorial fracionário. O método foi validado e foi linear no intervalo de 50-6000 ng mL-1, apresentando limites de quantificação de 50 ng mL-1 e recuperações acima de 47 % para a RSG e seus metabólitos (?-OH-R e N-Dm-R). O método validado foi empregado em um estudo de metabolismo in vitro com fração microssomal de fígado de ratos. Nesse estudo, foi possível estimar as constantes de Michaelis-Menten (Km) e a velocidade inicial máxima (Vmax). N-Dm-R e ?-OH-R apresentaram valores de Vmax de 87,30 ± 8,04 e 51,64 ± 12,25 ?mol min-1 mg proteína-1, respectivamente, enquanto que os valores de Km foram de 58,14 ± 11,85 e 77,84 ± 36,77 mmol L-1, respectivamente. Outros metabólitos foram observados nos cromatogramas e a identificação foi feita por espectrometria de massas: ?rto-hidroxi-rosiglitazona e N-desmetil-hidroxi-rosiglitazona. A RSG é comercializada como uma mistura racêmica, apesar de possuir sua atividade antidiabética relacionada essencialmente com o enantiômero (S). O centro quiral desse fármaco possui um grupo carbonila, por isso, o enantiômero (R) pode se converter no enantiômero (S) ou vice-versa, via tautomerismo cetoenólico. Dados da literatura indicavam que essa racemização poderia ser lenta o suficiente para possibilitar o estudo dos enantiômeros isoladamente. Entretanto, até o momento não há dados sobre a disposição cinética ii e metabolismo enantiosseletivos desse fármaco. Sendo assim, propôs-se o desenvolvimento de metodologias analíticas para estudar a racemização da RSG e seus metabólitos e avaliar a possibilidade de estudar seu metabolismo in vitro de forma estereosseletiva. O método foi desenvolvido empregando HPLC com detecção em 245 nm. A separação dos enantiômeros do fármaco e metabólitos, também quirais, foi obtida empregando uma coluna Chiralcel OJ-H e fase móvel constituída por metanol:etanol (90:10; v/v), na vazão de 0,3 mL min-1. O estudo de racemização mostrou que o fármaco e seus metabólitos são racemizados nas condições em que o estudo de metabolismo é conduzido. Finalmente, para estudar o metabolismo in vitro da pioglitazona (PGZ), foi desenvolvido um método para análise desse fármaco e de seus principais metabólitos, a hidroxi-pioglitazona (M-IV) e a ceto-pioglitazona (M-III) empregando a eletroforese capilar (CE). As análises foram realizadas em capilar de sílica de 50 ?m de diâmetro interno e com comprimento efetivo de 40 cm, utilizando tampão fosfato de sódio 50 mmol L-1, pH 2,5, detecção em 190 nm, tensão de 30 kV e temperatura do capilar de 35 °C. A HF-LPME também foi empregada para a preparação das amostras. O sistema de três fases foi escolhido, empregando solução de ácido clorídrico como fase aceptora e o 1-octanol como solvente orgânico. A otimização dos demais parâmetros foi realizada através de planejamento fatorial fracionário. O método validado foi linear no intervalo de 200 - 25000 ng mL-1 para PGZ e 200 - 2000 ng mL-1 para os metabólitos, apresentando limites de quantificação de 200 ng mL-1 e recuperações acima de 19 % para a RSG e seus metabólitos M-IV e M-III. O método validado foi empregado em um estudo de metabolismo in vitro contendo fração microssomal de fígado de ratos, mas nesse estudo, não foi possível observar a formação dos metabólitos. Entretanto, esse método pode ser usado em outros modelos de metabolismo in vitro (microssomas humanos), nos quais se observa a formação desses metabólitos em concentrações maiores. / In vitro metabolism studies have been used to characterize and to quantify possible metabolites, to elucidate metabolic pathways and to suggest models to perform in vivo studies. So the purpose of this study was to evaluate the in vitro rosiglitazone (RSG) metabolism employing microsomal fraction obtained from rat livers. A high- performance liquid chromatography (HPLC) method with UV detection at 245 nm was developed to analyze RSG and the main metabolites, p-hydroxy rosiglitazone (?-OH-R) e N-desmethyl rosiglitazone (N-Dm-R). The analytes were separated under reversed phase conditions, using a X-Terra MS C-18 column (3.5 ?m particle size) and a mobile phase consisting of water:acetonitrile:acetic acid (85:15:0.5, v/v/v), at a flow rate of 1 mL min-1. Biological matrices contain a large excess of proteins, lipids and other endogenous compounds that interfere in the analysis of drugs and metabolites. So, a suitable sample preparation technique is required. Hollow-fiber liquid phase microextraction (HF-LPME) is a promising technique for the preparation of biological samples. Besides the clean-up, analytes enrichment is also achieved. HF-LPME for the simultaneous analysis of RSG and its main metabolites is described for the first time. The three-phase extraction was performed using hydrochloride acid solution as acceptor phase and 1-octanol as organic solvent. The other parameters were optimized by fractional factorial design. The method was validated and it was linear over the concentration range of 50-6000 ng mL-1, with quantification limits of 50 ng mL-1 and recoveries above 47 %. The validated method was used to estimate Michaelis-Menten (Km) constant and maximum initial velocity (Vmax). N-Dm-R e ?-OH-R showed Vmax values of 87.30 ± 8.04 and 51.64 ± 12.25 ?mol min-1 mg protein-1, respectively, while the Kmvalues were 58.14 ± 11.85 e 77.84 ± 36.77 mmol L-1, respectively. Other possible metabolites were observed in the chromatograms and they were identified by mass spectrometry: ?rtho-hydroxy-rosiglitazone e N-desmethyl-hydroxy-rosiglitazone. RSG is marketed as a racemic mixture although the antidiabetic activity is related essentially to the (S)-enantiomer. The chiral center has a carbonyl group, therefore the (R)-enantiomer could be transformed to the (S)-enantiomer or vice-versa by keto-enolic tautomerism. The literature indicates that this racemization is slow enough to allow the evaluation of the properties of the isolated enantiomers. However, there is no information in the literature about enantioselective RSG kinetic disposition and metabolism. Considering this facts, an analytical procedure was developed to study the racemization of RSG and its metabolites under different conditions and to determine if the enantioselective metabolism would be performed. The method was developed by HPLC with detection at 245 nm. The chiral separation of RSG and metabolites was achieved on a Chiralcel OJ-H column, with the mobile phase consisting of methanol:ethanol (90:10,v/v). The results obtained showed that the racemization occurs under the conditions used in in vitro iv metabolism studies. Finally, to study the in vitro metabolism of pioglitazone (PGZ), another method was developed by capillary electrophoresis (CE) to determine this drug and its main metabolites, hydroxy-pioglitazone (M-IV) and keto-pioglitazone (M-III). The analyses were conducted using a fused silica capillary (50 ?m inner diameter and 40 cm effective length), sodium phosphate buffer 50 mmol L-1, pH 2.5, detection at 190 nm, voltage of 30 kV and capillary temperature of 35°C. HF-LPME was also used for sample preparation with hydrochloride acid solution as acceptor phase and 1-octanol as organic solvent. The other parameters were optimized by fractional factorial design. The method was validated showing to be linear in the concentration range of 200 - 25000 ng mL-1 for PGZ and 200 - 2000 ng mL-1 for the metabolites. Quantification limits were 200 ng mL-1 for all analytes and the recoveries were higher than 19%. The validated method was used to study the in vitro metabolism of PGZ by rat liver microsomal fraction, but it was not possible to observe the formation of the metabolites in this study. However this method could be used in other in vitro metabolism models (human microssomes), in which higher concentrations of these metabolites are observed. Keywords:

This master’s thesis deals with jet streams. The exploration part describes conditions of jet stream formation, its characteristics, classification on the geographical basis and phenomena attendant on the jet streams. It also contains a description of jet stream measurement methods and methods of its interpretation in aeronautical meteorological charts. Organization of aeronautical traffic in the north Atlantic region within reach of the jet streams is further described. Practical part of this thesis contains author’s own research which compares time and economical profitability of transatlantic flights planned according to the jet streams. The principle of this evaluation was based on assessment of real flights and flights via shortest possible routes. It was proven, that profits mentioned above are gained only in the oceanic parts of flights.

The Czech Republic has committed itself to adopt the euro with joining the European union in 2004. Until today there has not been any political interest of setting the specific date of euro adoption due to low public approval. Currently, there is an increase of positive public opinion about euro so it is the right time to start an objective discussion. The thesis is divided into three parts. The First part describes the history and evolution of the European monetary union, Maastricht convergence criteria and the theory of optimal currency area. The second part presents possible economic benefits and costs of joining the monetary union. The third and the main part examines the real effects of euro adoption on sample of selected countries with similar characteristics. The impact of euro on main economic indicators was analysed and there has been carried out a comparison between these countries. Also the role of euro in trade of selected countries has been highlighted. Last but not least, the possible impact of euro on country competitivness has been analysed in the context of optimum currency area theory. It is expected that joining the monetary union leads to a boost of bilateral trade which harmonizes the economic cycles of trade partners. The main purpose of this part is to prove the increase of competitiveness of exporters gained from monetary union measured by the raise of the bilateral trade interconnection. Finally these two criteria - gross domestic product alignment and bilateral trade interconnection have been used to describe the suitability of Czech Republic as a candidate country for the European monetary union.

Η οικονομικη και νομισματικη ενωση (ονε) οδηγησε στην υιοθετηση του ενιαιου ευρωπαϊκου νομισματοσ, του ευρω, που αντικατεστησε τα εθνικα νομισματα των χωρων που συμμετεχουν στο συστημα αυτο. Το μεγεθοσ τησ επιδρασησ του ενιαιου νομισματοσ στο διμερεσ εμποριο μεταξυ των χωρων που το εχουν υιοθετησει εχει απασχολησει τη διεθνη βιβλιογραφια και εχουν προκυψει ποικιλα συμπερασματα. Ετσι, ορισμενοι συγγραφεισ βρισκουν πολυ μικρη επιδραση, ενω υπαρχουν και καποιοι, που μιλουν για τριπλασιασμο του εμποριου. Στην παρουσα μελετη, χρησιμοποιωντασ χωρεσ τησ εε οσο και εκτοσ αυτησ, εκτιμηθηκαν με τη μεθοδο ελαχιστων τετραγωνων (ols) δυο εναλλακτικα στατικα υποδειγματα, οπου μελετηθηκε η επιδραση του ευρω, σε συνδυασμο με αλλουσ παραγοντεσ, οπωσ για παραδειγμα τη γλωσσα, τη γεωγραφικη αποσταση, τη συναψη εμπορικων συμφωνιων. Διαπιστωθηκε μια θετικη και στατιστικα σημαντικη επιδραση του ενιαιου νομισματοσ, καθωσ και μια μικρη και αρνητικη επιρροη τησ μεταβλητικοτητασ των συναλλαγματικων ισοτιμιων στο διεθνεσ εμποριο. Ωστοσο, θα πρεπει να ειμαστε προσεκτικοι με τα ευρηματα αυτα, καθωσ απαιτειται βαθοσ χρονου, προκειμενου να διαφανει πληρωσ η επιδραση του ενιαιου νομισματοσ στισ εμπορικεσ συναλλαγεσ των χωρων που το χρησιμοποιουν. / The economic and monetary union (emu) led to the adoption of a single european currency, namely euro, that replaced the national currencies of the countries, which partipicate in this system. The magnitude of the effect of a single currency in the bilateral trade between the countries that have adopted it has been dealt with in the international bibliography, resulting in various conclusions. Thus, some authors find a very small effect, whereas others report a triplication of trade. In this study, by using both eu and non-eu countries, a pair of alternative static models were estimated, by means of the ols method. The effect of euro,in combination with other factors, for example the language, the geographical distance and free trade areas, was studied. It was found that there exists a positive and statistically significant effect of the single currency and a small and negative influence of the variability of exchange rates in the international trade. However, it would be wise to assess these findings with extra care, bearing in mind that a long period of time is required, for the effect of the single currency on the commercial transactions of the countries that have adopted it to be fully revealed.

Magister Economicae - MEcon / The research study investigated the potential impact that organisational capacity assessments can have on the long-term sustainability of non-profit organisations (NPOs). The researcher employed longitudinal research design as the main instrument in the collection of data. Data was collected from four local non-profit organisations in the Cullinan and Bronkhorstspruit areas of South Africa. These organisations were evaluated by means of a questionnaire, which was developed by the researcher. NPOs can only play a pivotal role in community and social services if management, leadership, governance and other elements of organisational capacity are well developed and continuously strengthened. This is critical for attracting local and international donors who provide crucial running costs and relieve national, provincial and local government departments of the financial burden. Currently, the South African government supports NPOs in South Africa. The legislative and registration aspects of NPOs are regulated by the NPO Act (Act 71 of 1997) and the Income Tax Act (Act 58 of 1962). The State of South African Registered NPOs Report 2010/2011 indicated a growth of the number of registrations to have increased by 8.3%. However, in the same financial year a total number of 468 NPOs were deregistered; 98% of these lost their registration due to non-compliance of regulatory requirements. According to the State of South African Registered NPOs Report (2016) the total number of applications received for the financial year was 16 726 (53.7%), however 4 421 (46%) did not meet the requirements of sections 12-13 of the NPO Act, an issue that would definitely affect the existence of non-compliant institutions.

The aim of this thesis is to define nominal and real convergence within the area of the European Union and to assess its development on the example of the Czech and Slovak Republics. This dissertation is divided into three integrated sections. The theoretical part analyses basic economic concepts related to the issue of convergence and stability of joint economic units. The topics covered include the Maastricht criteria, their relevance, currentness and possible conflict between nominal and real convergence with the accession of new countries, then the theory of optimum currency area (OCA), theory of endogeneity and exogeneity and the linkage on fiscal policy and fiscal discipline in the environment of the European Union and the eurozone. Special attention is focused on the development of fiscal policy following from the establishment of the Stability and Growth Pact, including its reforms and recent changes in the form of the Euro Plus Pact and the Fiscal Convention. To satisfy the need for quantitative evaluation of given hypotheses, the second (empirical and analytical) part offers two self-constructed indices - the index of real convergence and fiscal discipline index. Based on these indices, relationship between the performance criteria of nominal and the real economy is monitored in the evaluated cohort. The last part of this work is dedicated to synthesis and application of findings from the previous sections upon which conclusions and recommendations for possible entry of the Czech Republic into the euro area are made.

L’objectif de ce travail est d’analyser les implications du choix de régime de change dans les pays émergents et en développement, ainsi que d’apporter des éclaircissements sur les facteurs jouant un rôle important dans le déclenchement des crises (de change, bancaires, financières…) dans ces pays. Pour cela, l’analyse se tourne, dans un premier temps, vers la question du choix de régime de change optimal. Cette partie du travail s’appuie principalement sur un grand nombre de travaux théoriques et empiriques traitant de cette question, pour mettre en lumière les implications de ce choix, tout en tenant compte des particularités du groupe de pays qui font l’objet de cette étude. Dans une deuxième partie nous nous intéressons aux crises et les facteurs qui jouent un rôle majeur dans leur incidence. Ainsi, après une revue des différents modèles de crises afin d’identifier les variables d’intérêt, nous construisons deux modèles de prédiction des crises, ou « d’alarme précoce ». Enfin, la troisième partie du travail rassemble les enseignements tirés des deux parties précédentes pour traiter d’une question qui prend une ampleur croissante dans ces pays : étant donné la logique d’intégration financière mondiale et les avantages présentés par un régime de changes flottants dans un tel contexte, de quelle manière un pays envisageant un sortie vers ce régime de change peut-il la planifier, et à quel moment doit-il l’entreprendre, pour réussir une sortie sans crise majeure, que nous qualifions de sortie « ordonnée » ? Pour répondre à cette question, nous nous appuyons sur des expériences passées qui nous permettent de construire un modèle identifiant les variables susceptibles d’accroître la probabilité d’une sortie ordonnée. Nous complétons ce modèle par quelques considérations supplémentaires qui constituent des conditions importantes à la réussite d’une sortie ordonnée. L’objectif est d’apporter des recommandations susceptibles de faciliter cette transition. / The aim of this work is to analyze the implications of exchange rate regime choice in developing and emerging market economies, as well as highlight the factors that play a major role in the incidence of crises (currency, banking, financial…) in these countries. With this aim in mind, we start our analysis by turning to the question of the choice of the optimal exchange rate regime. This part of our work draws on a large number of both theoretical and empirical works evoking this question in order to determine the implications of this choice, all the while keeping in mind the fact that this particular group of countries present certain characteristics that are usually absent in their industrial counterparts. The second part of our work concentrates more specifically on crises and the factors that play a major role in their occurrence. Therefore, following a brief overview of different crisis models in order to identify the variables of interest, we propose two models for crisis prediction, or “Early Warning Systems”. Finally, the third and final part of our work brings together the conclusions of the earlier parts in order to address an issue that is becoming increasingly important in developing and emerging market economies: given their greater integration in international financial and capital markets, as well as the incontestable advantages of a floating exchange rate regime in such a context, how can a country wishing to exit to a more flexible exchange rate arrangement undertake such a transition, and when, in order to achieve an “orderly” exit, that is, an exit that is not accompanied by a crisis? To answer this question we draw on past experiences to construct a model indentifying the economic variables that might increase the probability of an orderly exit. We complete this model with a number of additional considerations that have recently emerged as important preconditions for an orderly exit, in order to provide some useful policy recommendations facilitating this transition.