La fiscalité et l'inflation au Rwanda: Une analyse empirique basée sur le modèle à correction d'erreur.

Rapport de recherche présenté à la Faculté des arts et des sciences en vue de l'obtenion du grade de Maîtrise en sciences économiques.

Drug-loaded nanocarriers : passive targeting and crossing of biological barriers

Poor bioavailability and poor pharmacokinetic characteristics are some of the leading causes of drug development failure. Therefore, poorly-soluble drugs, fragile proteins or nucleic acid products may benefit from their encapsulation in nanosized vehicles, providing enhanced solubilisation, protection against degradation, and increased access to pathological compartments. A key element for the success of drug-loaded nanocarriers (NC) is their ability to either cross biological barriers themselves or allow loaded drugs to traverse them to achieve optimal pharmacological action at pathological sites. Depending on the mode of administration, NC may have to cross different physiological barriers in their journey towards their target. In this review, the crossing of biological barriers by passive targeting strategies will be presented for intravenous delivery (vascular endothelial lining, particularly for tumour vasculature and blood-brain barrier targeting), oral administration (gastrointestinal lining) and upper airway administration (pulmonary epithelium). For each specific barrier, background information will be provided on the structure and biology of the tissues involved as well as available pathways for nano-objects or loaded drugs (diffusion and convection through fenestration, transcytosis, tight junction crossing, etc.). The determinants of passive targeting − size, shape, surface chemistry, surface patterning of nanovectors − will be discussed in light of current results. Perspectives on each mode of administration will be presented. The focus will be on polymeric nanoparticles and dendrimers although advances in liposome technology will be also reported as they represent the largest body in the drug delivery literature.

Manipulation der Aktin-Hülle später Endosomen durch ektopisches Protein-Targeting und Etablierung einer in vivo-Hierarchie cytoplasmatischer Targeting-Signalstärken

Der Endocytoseweg in Dictyostelium verläuft über definierte endosomale Reifestadien. Dabei werden die reifenden Endosomen im letzten Stadium durch eine Schicht aus filamentösem Aktin umhüllt. Über die biologische Funktion dieser Aktin-Hülle ist derzeit wenig bekannt. Zum weiteren Erkenntnisgewinn sollten daher unterschiedliche Aktin-interagierende Proteine an die endosomale Aktin-Hülle dirigiert und die sich daraus ergebenden Folgen untersucht werden. Dabei wurde der in Drengk et al., 2003 beschriebene Ansatz aufgegriffen, in dem Proteine durch die Fusion an Vacuolin an die späte endosomale Membran transportiert wurden. Die endosomale Lokalisation von DAip1 bewirkte den vollständigen Verlust der endosomalen Aktin-Hülle, ohne dabei das restliche zelluläre Cytoskelett zu beeinträchtigen. Dabei wird die Depolymerisation vermutlich über die nachgewiesene Interaktion von DAip1 mit dem Aktin-depolymerisierenden Protein Cofilin bewirkt. Einhergehend damit trat eine Aggregation der betroffenen Kompartimente, eine Verzögerung des endocytotischen Transits, sowie eine verstärkte Retention lysosomaler Enzyme auf. Diese Ergebnisse ließen auf eine Funktion der endosomalen Aktin-Hülle als Fusionsinhibitor oder in der Regulation von Recycling-Prozessen an späten Endosomen schließen. Die Verlängerung der endosomalen Verweilzeit des den Arp2/3-Komplex negativ regulierenden Proteins Coronin bewirkte dagegen keine offensichtlichen Veränderungen in den betroffenen Zellen. Diese Beoachtung könnte ein Indiz dafür sein, dass nach der Ausbildung der Aktin-Hülle keine weiteren essentiellen Arp2/3-abhängigen mehr an der endosomalen Membran auftreten. Die endosomale Lokalisation des Aktin-Crosslinkers ABP34 induzierte ebenfalls keine Abweichungen vom Wildtyp-Verhalten. Hierbei besteht allerdings die Möglichkeit, dass die Aktivität des Proteins durch die bereits zuvor beschriebene Calcium-Sensitivität beeintächtigt vorliegt. Eine Verstärkung der endosomalen Hülle konnte trotz der Verwendung unterschiedlicher Ansätze nicht hervorgerufen werden. Offensichtlich wirkt die zusätzliche Expression zentraler Regulatoren der Aktin-Polymerisation in der Zelle cytotoxisch. Die Bindung von VASP an die endosomale Membran bewirkte in den Zellen die Ausbildung voluminöser, cytoplasmatischer „Aktin-Bälle“. Diese riefen in den betroffenen Zellen Defekte in unterschiedlichen Aktin-abhängigen Prozessen, wie der Phago- und Pinocytose, sowie der Cytokinese hervor. Dabei gehen die beobachteten Veränderungen vermutlich auf die nachgewiesene Störung im Gleichgewicht zwischen G- und F-Aktin zurück. Obwohl die Aktin-Bälle an der endosomalen Membran entstehen, weisen sie nach vollendeter Entstehung keine inneren oder äußeren Membranen mehr auf und nehmen nicht mehr aktiv am endocytotischen Geschehen teil. Die nähere Charakterisierung offenbarte große Ähnlichkeit zu den mit unterschiedlichen neurodegenerativen Erkrankungen assoziierten Hirano-Bodies. Über das beobachtbare Lokalisationsverhalten der unterschiedlichen im ersten Teil der Arbeit eingesetzten Vacuolin-Hybridproteine ließ sich die Stärke der Lokalisationsinformationen der fusionierten Aktin-interagierenden Proteine miteinander vergleichen. Dies wurde verwendet, um die einzelnen Proteine gemäß ihres Targeting-Potenzials hierarchisch anzuordnen. Im zweiten Teil der Arbeit wurden dieser Hierarchie die beiden cytoplasmatischen Targeting-Signale für Peroxisomen (PTS1) und den Zellkern (SV40-NLS) hinzugefügt. Der vorgenommene Vergleich dieser in vivo gewonnen Daten aus Dictyostelium mit unterschiedlichen in vitro-Bindungsstudien mit homologen Proteinen anderer Organismen zeigte eine erstaunlich gute Übereinstimmung. Diese Beobachtung lässt auf vergleichbare Targeting-Affinitäten innerhalb der Eukaryoten schließen und belegt, dass die zelluläre Lokalisation eines Proteins relativ sicher anhand der in ihm vorhandenen Bindungs-Affinitäten vorhergesagt werden kann. Durch die Kombination der in vivo- und in vitro-Daten war es auch ohne Kenntnis des Oligomerisierungsgrades und des Interaktionspartners erstmals möglich, die Bindungsstärke von Vacuolin an der endosomalen Membran auf einen definierten Bereich einzugrenzen.

Individual Decision-Making and Inflation Persistence

The traditional task of a central bank is to preserve price stability and, in doing so, not to impair the real economy more than necessary. To meet this challenge, it is of great relevance whether inflation is only driven by inflation expectations and the current output gap or whether it is, in addition, influenced by past inflation. In the former case, as described by the New Keynesian Phillips curve, the central bank can immediately and simultaneously achieve price stability and equilibrium output, the so-called ‘divine coincidence’ (Blanchard and Galí 2007). In the latter case, the achievement of price stability is costly in terms of output and will be pursued over several periods. Similarly, it is important to distinguish this latter case, which describes ‘intrinsic’ inflation persistence, from that of ‘extrinsic’ inflation persistence, where the sluggishness of inflation is not a ‘structural’ feature of the economy but merely ‘inherited’ from the sluggishness of the other driving forces, inflation expectations and output. ‘Extrinsic’ inflation persistence is usually considered to be the less challenging case, as policy-makers are supposed to fight against the persistence in the driving forces, especially to reduce the stickiness of inflation expectations by a credible monetary policy, in order to reestablish the ‘divine coincidence’. The scope of this dissertation is to contribute to the vast literature and ongoing discussion on inflation persistence: Chapter 1 describes the policy consequences of inflation persistence and summarizes the empirical and theoretical literature. Chapter 2 compares two models of staggered price setting, one with a fixed two-period duration and the other with a stochastic duration of prices. I show that in an economy with a timeless optimizing central bank the model with the two-period alternating price-setting (for most parameter values) leads to more persistent inflation than the model with stochastic price duration. This result amends earlier work by Kiley (2002) who found that the model with stochastic price duration generates more persistent inflation in response to an exogenous monetary shock. Chapter 3 extends the two-period alternating price-setting model to the case of 3- and 4-period price durations. This results in a more complex Phillips curve with a negative impact of past inflation on current inflation. As simulations show, this multi-period Phillips curve generates a too low degree of autocorrelation and too early turnings points of inflation and is outperformed by a simple Hybrid Phillips curve. Chapter 4 starts from the critique of Driscoll and Holden (2003) on the relative real-wage model of Fuhrer and Moore (1995). While taking the critique seriously that Fuhrer and Moore’s model will collapse to a much simpler one without intrinsic inflation persistence if one takes their arguments literally, I extend the model by a term for inequality aversion. This model extension is not only in line with experimental evidence but results in a Hybrid Phillips curve with inflation persistence that is observably equivalent to that presented by Fuhrer and Moore (1995). In chapter 5, I present a model that especially allows to study the relationship between fairness attitudes and time preference (impatience). In the model, two individuals take decisions in two subsequent periods. In period 1, both individuals are endowed with resources and are able to donate a share of their resources to the other individual. In period 2, the two individuals might join in a common production after having bargained on the split of its output. The size of the production output depends on the relative share of resources at the end of period 1 as the human capital of the individuals, which is built by means of their resources, cannot fully be substituted one against each other. Therefore, it might be rational for a well-endowed individual in period 1 to act in a seemingly ‘fair’ manner and to donate own resources to its poorer counterpart. This decision also depends on the individuals’ impatience which is induced by the small but positive probability that production is not possible in period 2. As a general result, the individuals in the model economy are more likely to behave in a ‘fair’ manner, i.e., to donate resources to the other individual, the lower their own impatience and the higher the productivity of the other individual. As the (seemingly) ‘fair’ behavior is modelled as an endogenous outcome and as it is related to the aspect of time preference, the presented framework might help to further integrate behavioral economics and macroeconomics.

Poverty targeting and income impact of subsidised credit on accessed households in the Northern Mountainous Region of Vietnam

This paper uses the data of 1338 rural households in the Northern Mountainous Region of Vietnam to examine the extent to which subsidised credit targets the poor and its impacts. Principal Component Analysis and Propensity Score Matching were used to evaluate the depth of outreach and the income impact of credit. To address the problem of model uncertainty, the approach of Bayesian Model Average applied to the probit model was used. Results showed that subsidised credit successfully targeted the poor households with 24.10% and 69.20% of clients falling into the poorest group and the three bottom groups respectively. Moreover, those who received subsidised credit make up 83% of ethnic minority households. These results indicate that governmental subsidies are necessary to reach the poor and low income households, who need capital but are normally bypassed by commercial banks. Analyses also showed that ethnicity and age of household heads, number of helpers, savings, as well as how affected households are by shocks were all factors that further explained the probability at which subsidised credit has been assessed. Furthermore, recipients obtained a 2.61% higher total income and a 5.93% higher farm income compared to non-recipients. However, these small magnitudes of effects are statistically insignificant at a 5% level. Although the subsidised credit is insufficient to significantly improve the income of the poor households, it possibly prevents these households of becoming even poorer.

Military empowerment and civilian targeting in civil war

Civilians constitute a large share of casualties in civil wars across the world. They are targeted to create fear and punish allegiance with the enemy. This maximizes collaboration with the perpetrator and strengthens the support network necessary to consolidate control over contested regions. I develop a model of the magnitude and structure of civilian killings in civil wars involving two armed groups who Öght over territorial control. Armies secure compliance through a combination of carrots and sticks. In turn, civilians di§er from each other in their intrinsic preference towards one group. I explore the e§ect of the empowerment of one of the groups in the civilian death toll. There are two e§ects that go in opposite directions. While a direct e§ect makes the powerful group more lethal, there is an indirect e§ect by which the number of civilians who align with that group increases, leaving less enemy supporters to kill. I study the conditions under which there is one dominant e§ect and illustrate the predictions using sub-national longitudinal data for Colombiaís civil war.

Central Bank Independence and inflation: the case of Colombia. 1924 - 1998.

Este artículo evalúa el vínculo entre la independencia del banco central y la inflación, para el caso de Colombia. Se desarrolla un marco teórica relacionada con la independencia del Banco Central y la inflación. La conclusión es que la independencia del Banco Central es una característica importante de cara a la reducción de la inflación y con el fin de resolver parcialmente el problema de la inconsistencia temporal, y asumiendo la existencia de un régimen monetario dominante la independencia del Banco Central ha llevado a una reducción de la inflación y de su variabilidad en Colombia. No obstante, los resultados de la inflación en el último periodo no han sido tan impresionantes. Este artículo sugiere explicaciones alternativas a este resultado. La independencia real del Banco Central colombiano puede ser más baja que su independencia formal. Adicionalmente, otros factores pueden contribuir a explicar una inflación más elevada que la esperada, particularmente la existencia de un déficit fiscal financiado con recursos externos.

The simple macroeconomics of North and South in EMU. Bruegel Working Paper 2012/12, 30 July 2012

The euro area today consists of a competitive, moderately leveraged North and an uncompetitive, over-indebted South. Its main macroeconomic challenge is to carry out the adjustment required to restore the competitiveness of its southern part and eliminate its excessive public and private debt burden. This paper investigates the relationship between fiscal and competitiveness adjustment in a stylised model with two countries in a monetary union, North and South. To restore competitiveness, South implements a more restrictive fiscal policy than North. We consider two scenarios. In the first, monetary policy aims at keeping inflation constant in the North. The South therefore needs to deflate to regain competitiveness, which worsens the debt dynamics. In the second, monetary policy aims at keeping inflation constant in the monetary union as a whole. This results in more monetary stimulus, inflation in the North is higher, and this in turn helps the debt dynamics in the South. Our main findings are: •The differential fiscal stance between North and South is what determines real exchange rate changes. South therefore needs to tighten more. There is no escape from relative austerity. •If monetary policy aims at keeping inflation stable in the North and the initial debt is above a certain threshold, debt dynamics are perverse: fiscal retrenchment is self-defeating; •If monetary policy targets average inflation instead, which implies higher inflation in the North, the initial debt threshold above which the debt dynamics become perverse is higher. Accepting more inflation at home is therefore a way for the North to contribute to restoring debt sustainability in the South. •Structural reforms in the South improve the debt dynamics if the initial debt is not too high. Again, targeting average inflation rather than inflation in the North helps strengthen the favourable effects of structural reforms.