A diferenciação das células THP-1 em macrófagos, induzida por PMA, é associada ao aumento da expressão de PPAR. A UTR 5` de PPAR regula negativamente sua síntese, porém, o mecanismo molecular envolvido não foi esclarecido. Neste estudo, o estado traducional das células THP-1 diferenciadas por PMA foi investigado em associação à superprodução de PPAR. A presença de uORFs no transcrito de PPAR, contendo códons de iniciação compatíveis com seqüências de Kosak, poderia ser a causa do efeito inibitório da UTR 5`. A incorporação reduzida de L-[U-14C]leucina revelou que a superprodução de PPAR ocorre durante inibição global da tradução, confirmada pela redução dos polissomos. Além disso, desfosforilação de 4E-BP1 foi observada após tratamento com PMA e é associada a inibição da iniciação da tradução e estimulação da tradução dependente de IRES. De fato, a estrutura da UTR 5` de PPAR apresenta características de transcritos que formam IRES. Assim, a produção de PPAR pode ser regulada por IRES e ocorre concomitantemente com a inibição da tradução dependente de cap / The differentiation of THP-1 cells in macrophages, induced by PMA, is associated to overexpression of PPARb. Previous studies have shown that the PPARb 5\' UTR negatively regulates its expression. In our study the translational status of PMA-differentiated THP-1 cells was investigated in association to PPARb overexpression. Putative compatible Kosak initiation codons were identified in the PPARb uORFs and could be involved in the inhibitory effect of 5\' UTR. Decreased incorporation of L-[U-14C]leucine in proteins revealed that the overproduction of PPARb in PMA-differentiated THP-1 cells coincides with a global decrease in the protein synthesis process. Translation impairment was confirmed by polysome profile assay. An intense dephosphorylation of 4E-BP by PMA treatment was observed. Dephosphorylated 4E-BP causes inhibition of eIF4E cap-dependent translation initiation and favors IRES-dependent translation. The PPARb 5\' UTR structure has some characteristics that resemble the one described for IRES. Therefore, the PPARb production may be controlled by IRES

A diferenciação das células THP-1 em macrófagos, induzida por PMA, é associada ao aumento da expressão de PPAR. A UTR 5` de PPAR regula negativamente sua síntese, porém, o mecanismo molecular envolvido não foi esclarecido. Neste estudo, o estado traducional das células THP-1 diferenciadas por PMA foi investigado em associação à superprodução de PPAR. A presença de uORFs no transcrito de PPAR, contendo códons de iniciação compatíveis com seqüências de Kosak, poderia ser a causa do efeito inibitório da UTR 5`. A incorporação reduzida de L-[U-14C]leucina revelou que a superprodução de PPAR ocorre durante inibição global da tradução, confirmada pela redução dos polissomos. Além disso, desfosforilação de 4E-BP1 foi observada após tratamento com PMA e é associada a inibição da iniciação da tradução e estimulação da tradução dependente de IRES. De fato, a estrutura da UTR 5` de PPAR apresenta características de transcritos que formam IRES. Assim, a produção de PPAR pode ser regulada por IRES e ocorre concomitantemente com a inibição da tradução dependente de cap / The differentiation of THP-1 cells in macrophages, induced by PMA, is associated to overexpression of PPARb. Previous studies have shown that the PPARb 5\' UTR negatively regulates its expression. In our study the translational status of PMA-differentiated THP-1 cells was investigated in association to PPARb overexpression. Putative compatible Kosak initiation codons were identified in the PPARb uORFs and could be involved in the inhibitory effect of 5\' UTR. Decreased incorporation of L-[U-14C]leucine in proteins revealed that the overproduction of PPARb in PMA-differentiated THP-1 cells coincides with a global decrease in the protein synthesis process. Translation impairment was confirmed by polysome profile assay. An intense dephosphorylation of 4E-BP by PMA treatment was observed. Dephosphorylated 4E-BP causes inhibition of eIF4E cap-dependent translation initiation and favors IRES-dependent translation. The PPARb 5\' UTR structure has some characteristics that resemble the one described for IRES. Therefore, the PPARb production may be controlled by IRES

[pt] A crescente demanda energética verificada ao redor do mundo e a conscientização pública acerca dos efeitos deletérios do excesso de gases estufa na atmosfera vem colaborando para a articulação de compromissos de grande alcance em nome da adaptação das matrizes energéticas a formas ambiental e economicamente sustentáveis. A adesão à energias renováveis (como solar e eólica) e a descentralização da matriz energética por meio de tecnologias de geração distribuída (visando a melhoria da eficiência do uso da energia) são alguns dos movimentos mais relevantes realizados para fazer frente a essas demandas. Neste ínterim, o presente trabalho é dedicado à simulação numérica mediante o conceito 4E (Energy, Exergy, Environmental and Economic) de um sistema híbrido CHP (Combined Heat and Power) on-grid para atendimento de pequenas demandas residenciais ou industriais, tendo gás natural e energia solar como vetores energéticos preferenciais. O sistema inclui um reformador de gás natural para produção de gás de síntese rico em hidrogênio, uma célula a combustível com membrana de troca de prótons (PEM), painéis fotovoltaicos, baterias conectadas à rede elétrica por um inversor bidirecional, trocadores de calor e componentes auxiliares como compressores e boilers. Os componentes do sistema foram modelados separadamente com base em equações de conservação e seus modelos devidamente validados. Uma análise energética e exergética do reformador de gás natural foi conduzida mediante a metodologia de planejamento de experimentos a fim de avaliar a necessidade de considerar uma formulação complexa do combustível em vez de um substituto (metano puro). Posteriormente, estes modelos foram inseridos como módulos de uma rotina mais ampla destinada a simular o desempenho econômico do sistema integrado num intervalo de tempo de até 20 anos. Tal rotina, implementada no MATLAB, permite a flexibilização de critérios operacionais importantes como número de consumidores, configuração do sistema híbrido (armazenamento e participação de painéis fotovoltaicos), diferentes tipos de tarifa (convencional ou branca) e o possível uso de rejeito térmico para cogeração, enriquecendo o escopo de resultados obtidos. Paybacks entre 7 e 20 anos de operação do sistema foram alcançados para diferentes combinações dos parâmetros examinados considerando-se a adesão no ano de 2020, onde consumidores residenciais obtiveram resultados predominantemente melhores do que os industriais em virtude da demanda menos exigente dos primeiros. Foram também previstas reduções de até 50% no custo cumulativo total para consumidores residenciais referente a adesão ao sistema proposto por 20 anos, levando-se em conta a queda prevista nos custos de aquisição dos componentes para as próximas décadas. A avaliação do sistema em termos ambientais foi feita através da quantidade equivalente de CO2 por unidade de energia. Concluiu-se que a configuração completa, mesmo auxiliada por cogeração, supera a média de emissões da matriz energética brasileira (devido à alta participação das fontes renováveis nessa matriz), permanecendo, ainda assim, como uma opção melhor do que a combustão pura do gás natural, especialmente no que diz respeito ao atendimento de demanda térmica. / [en] The growing energy demand verified around the world and public awareness about the harmful effects of greenhouse gases excess in the atmosphere have been contributing to the articulation of far-reaching commitments in the name of adapt energy matrices to environmentally and economically sustainable ways. The adherence to renewable energy (such as solar and eolic) and descentralization of energy matrix through distributed generation technologies (aiming at the improvment of efficiency of energy use) are some of the more relevant movements done in order to deal with these demands. In the meantime, the present work is dedicated to numerical simulation using the 4E (Energy, Exergy, Environmental and Economic) concept of an on-grid hybrid CHP system to meet small residential or industrial demands, using natural gas and solar energy as preferred energy vectors. The system includes a natural gas reformer for the production of hydrogen-rich synthesis gas, a proton exchange membrane fuel cell (PEM), photovoltaic panels, batteries connected to the grid by a bidirectional inverter, heat exchanger and auxiliary componentes, such as compressors and boilers. The system components were modeled separately based on conservation equations and their models duly validated. An energy and exergy analysis of the natural gas reformer was conducted using design of experiment methodology in order to assess the necessity to consider a complex formulation of the fuel instead of a surrogate (pure methane). Subsequently, these models were inserted as modules of a broader routine designed to simulate the economic performance of the integrated system in a time interval of up to 20 years. This routine implemented in MATLAB allows for the flexibility of important operational criteria such as the number of consumers, configuration of the hybrid system (storage and participation of solar energy), different types of tariff (conventional or white) and the posible use of reject heat for cogeneration, enriching the scope of the results obtained. Paybacks between 7 and 20 years of system operation were achieved for different combinations of the examined parameters considering adherence in the year 2020, where residential consumers have predominantly obtained better results than industrial ones due to the less intense demand of the first ones. Reductions of up to 50% in the total cumulative cost related to adherence to the proposed system for 20 years for residential users were also foreseen, taking into account the expected drop in component acquisition costs over the next few decades. The evaluation of the system in environmental terms was assessed through equivalent amount of CO2 by energy unit. It was concluded that the complete configuration, even supported by cogeneration, exceeds the average of the brazilian energy matrix emissions (due to the high share of renewable sources in this matrix), nevertheless remaining as a better option than pure combustion of natural gas, specially for meeting thermal demand.

Das Eukaryotische-Initiations faktor-4E Bindungsprotein (4E-BP) ist ein Inhibitor der Translationsinitiation. Nicht-phosphoryliertes 4E-BP bindet an den eukaryotischen Initiationsfaktor 4E (eIF4E). Diese Bindung blockiert die Rekrutierung des Initiationskomplexes eIF4F an die Cap-Struktur des 5´Endes von eukaryotischen zellulären mRNAs, was die Initiation der Translation verhindert. Phosphorylierung von 4E-BP durch die mTOR Kinase führt zur Dissoziation des 4E-BP/eIF4E Komplexes und erhöht die Verfügbarkeit von eIF4E, dies wird mit Zellproliferation assoziiert. Die Aktivität von eIF4E wird nicht nur von 4E-BP, sondern auch durch Phosporylierung reguliert, welche wiederum durch die "MAP-Kinase-Interacting-Protein-Kinase" (MNK) reguliert wird. Drei Isoformen von 4E-BP sind bekannt: 4E-BP1, 4E-BP2 and 4E-BP3. 4E-BP1 und 4E-BP2 sind an oxidativem und adipogenetischen Stress beteiligt. Beide Proteine werden im h?matopoetischen System gleich exprimiert, wohingegen 4E-BP3 nicht detektiert wird. 4E-BP1 wird während der Erythroblasten-Proliferation phosphoryliert. Aus diesem Grund habe ich die Hämatopoese und die durch Phenylhydrazine (PHZ) induzierte Stress-Erythropoese in 4E-BP1 und 4E-BP2 Knock-Out Mäusen und 4E-BP1,2 Doppel-Knock-Out Mäusen analysiert. Ich konnte zeigen, dass die Hämatopoese in 4E-BPs defizienten Mäusen nicht beeinflusst wird. Allerdings zeigten 4E-BP1,2-/- und 4E-BP2-/- Mäuse eine verspätete Antwort auf Phenylhydrazin (PHZ) induzierten erythropoetischen Stress. Gleichzeitig war die mRNA Translation von GATA-1, ein essentieller erythropoetischer Transkriptionsfaktor in Erythroblasten runterreguliert. Die Signaltransduktionswege mTOR und MNK1 waren bei erythropoetischen Stress aktiviert. Diese Daten zeigen, dass 4E-BP2, aber nicht 4E-BP1, notwendig ist um auf erythropoetischen Stress zu reagieren und deuten an, dass die 4E-BP gesteuerte translations-regulierende Maschinerie eine Rolle in der Stress-Erythropoese spielt. / Translational regulation allows an organism to generate fast responses to environmental changes quickly. Eukaryotic initiation factor 4E binding protein (4E-BP) is an inhibitor of translation initiation. Unphosphorylated 4E-BP binds to eukaryotic initiation factor 4E (eIF4E) blocking recruitment of the initiation complex eIF4F to the cap structure at the 5´ terminus of eukaryotic cellular mRNAs. Thus initiation of translation is blocked. Phosphorylation of 4E-BP by the mTOR kinase causes disassociation of the 4E-BP/eIF4E complex and increases the availability of eIF4E. EIF4E activity is not only regulated by 4E-BP, but also phosphorylation which is regulated by MAP kinase - interacting protein kinase (MNK). Three isoforms of 4E-BP are known, termed 4E-BP1, 4E-BP2 and 4E-BP3. 4E-BP1 and 4E-BP2 are involved in oxidative and adipogenetic stresses in vivo. They are equally expressed in hematopoietic system, whereas 4E-BP3 is not detected. 4E-BP1 is phosphorylated during erythroblast proliferation. Erythroid differentiation is blocked by overexpresssion of eIF4E in tissue culture. These studies implied that 4E-BPs might play role in response to erythropoietic stress. I examined hematopoiesis and phenylhydrazine (PHZ) induced stress erythropoiesis in 4E-BP1 and 4E-BP2 individual knock out mice and 4E-BP1,2 compound knock out mice. I found that the hematopoiesis of 4E-BPs deficient mice were unaffected. However, 4E-BP1,2-/- and 4E-BP2-/- mice showed delayed response to phenylhydrazine (PHZ) induced erythropoietic stress. Simultaneously, the mRNA translation of GATA-1, which is the essential erythroid transcription factor, was downregulated in their erythroblasts. The signaling pathways through the mTOR and MNK1 were activated in erythropoietic stress. These data showed that 4E-BP2 but not 4E-BP1 was required for the response to erythropoietic stress and suggested that 4E-BP related translation regulatory machinery played a role in stress erythropoiesis.

The cells are capable of very quick and specific reactions on stress conditions. Influence of translation, specifically initiation of translation by inhibition factors, is one of the main regulatory process. Two of eIF4E-binding proteins (4E-BP), Eap1p and Caf20p, are known as cap-dependent translation repressors in yeast Saccharomyces cerevisiae. We used in vivo fluorescent microscopy analysis to show different reaction of Caf20p and Eap1p to heat stress. Protein Caf20p does not react on heat shock and stays difused in cytoplasm. Contrary to Caf20p reaction, protein Eap1p accumulates in cytoplasm close to stress granules (SGs). This work shows that Eap1p is involved in stress granules assembly. In the absence of Eap1p, yeast cells react to the heat stress with small and less focused SGs. Dele- tion of CAF20 does not affect SG assembly. This points to specific function of SG in distribution of factors connected with stress reaction. Polysomal analysis shows that deletion of one of initiation translation repressors does not affect heat induced global repression of translation. In permisive condition deletion of EAP1 may cause defect in addition of 60S ribosomal subunits. Absence of protein Eap1p causes morphological defect. That point to a different reactions of Eap1p and Caf20p on heat stress and possible...

Le contrôle traductionnel est une étape critique de la régulation de l'expression des gènes impliqués dans le développement embryonnaire et de nombreux processus cellulaires. Au cours de l'initiation de la traduction chez les eucaryotes, le facteur eIF4E (eukaryotic Initiation Factor 4E) fixe la coiffe des ARNm et recrute la protéine eIF4G pour former le complexe d'initiation. L' interaction eIF4E/eIF4G est une étape clé de la régulation traductionnelle, faisant du site de liaison à eIF4E un lieu de compétition entre eIF4G, le répresseur général de la traduction 4E-BP et d'autres régulateurs appelés 4E-IPs (4E-interacting partners), qui partagent avec eIF4G un motif consensus de liaison à eIF4E. Longtemps considérée comme une protéine désordonnée, nous avons montré au cours de cette thèse que 4E-BP adopte en réalité une conformation repliée lorsqu'il se lie à eIF4E, impliquant une surface d'interaction plus importante. Ces résultats ont apporté un nouveau regard sur les interactions qui s'établissent entre eIF4E et ses partenaires, et ont fourni des informations cruciales pour l'établissement de nouvelles thérapies, notamment celles développées dans le cadre des cancers. Mon travail de thèse a également permis l'établissement d'un criblage de nouvelles 4E-IPs, basé sur une approche alliant analyses structurales, bioinformatiques et biochimiques. Parmi les 4E-IPs détectées, nous avons caractérisé la protéine Angel1, membre d'une famille de déadénylases. Ces résultats ont ouvert de nombreuses perspectives pour la compréhension du métabolisme des ARNm mais aussi celle des régulations traductionnelles spécifiques prenant pour cible moléculaire eIF4E

abstract: Obesity impairs skeletal muscle maintenance and regeneration, a condition that can progressively lead to muscle loss, but the mechanisms behind it are unknown. Muscle is primarily composed of multinucleated cells called myotubes which are derived by the fusion of mononucleated myocytes. A key mediator in this process is the cellular fusion protein syncytin-1. This led to the hypothesis that syncytin-1 could be decreased in the muscle of obese/insulin resistant individuals. In contrast, it was found that obese/insulin resistant subjects had higher syncytin-1 expression in the muscle compared to that of the lean subjects. Across the subjects, syncytin-1 correlated significantly with body mass index, percent body fat, blood glucose and HbA1c levels, insulin sensitivity and muscle protein fractional synthesis rate. The concentrations of specific plasma fatty acids, such as the saturated fatty acid (palmitate) and monounsaturated fatty acid (oleate) are known to be altered in obese/insulin resistant humans, and also to influence the protein synthesis in muscle. Therefore, it was evaluated that the effects of palmitate and oleate on syncytin-1 expression, as well as 4E-BP1 phosphorylation, a key mechanism regulating muscle protein synthesis in insulin stimulated C2C12 myotubes. The results showed that treatment with 20 nM insulin, 300 µM oleate, 300 µM oleate +20 nM insulin and 300 µM palmitate + 300 µM oleate elevated 4E-BP1 phosphorylation. At the same time, 20 nM insulin, 300 µM palmitate, 300 µM oleate + 20 nM insulin and 300 µM palmitate + 300 µM oleate elevated syncytin-1 expression. Insulin stimulated muscle syncytin-1 expression and 4E-BP1 phosphorylation, and this effect was comparable to that observed in the presence of oleate alone. However, the presence of palmitate + oleate diminished the stimulatory effect of insulin on muscle syncytin-1 expression and 4E-BP1 phosphorylation. These findings indicate oleate but not palmitate increased total 4E-BP1 phosphorylation regardless of insulin and the presence of palmitate in insulin mediated C2C12 cells. The presence of palmitate inhibited the upregulation of total 4EB-P1 phosphorylation. Palmitate but not oleate increased syncytin-1 expression in insulin mediated C2C12 myotubes. It is possible that chronic hyperinsulinemia in obesity and/or elevated levels of fatty acids such as palmitate in plasma could have contributed to syncytin-1 overexpression and decreased muscle protein fractional synthesis rate in obese/insulin resistant human muscle. / Dissertation/Thesis / Masters Thesis Biology 2017

De frågeställningar som jag har utgått från är vem eller vilka personer, och vilka andra faktorer skapade superstjärnan Lady Gaga? Har Lady Gaga blivit framgångsrik på egen hand eller huvudsakligen som ett resultat av andra personer och deras inverkan? Syftet är att analysera bakgrunden till Lady Gagas enorma succé och utforska möjliga orsaker och förklaringar till den, för att sedan kunna använda och föra vidare kunskapen om dessa framgångsstrategier i musikbranschen. Jag har använt mig av kvalitativa intervjuer med fallstudien som metod. Intervjuerna är gjorda i New York, USA och omfattar inflytelserika personer från musik-, konst- och modevärlden, med inriktning på vilka faktorer och personer som varit viktiga och avgörande för Lady Gagas karriär. Analysen är baserad på en teori om Lady Gagas strategier kallad 4E efter ledorden emotions (känslor), erfarenhet, engagemang och exklusivitet. Intervjuerna och fallstudien bekräftar 4E-teorin på alla fyra punkter. Analysen visar att två ytterligare viktiga faktorer är vikten av stödjande grupper runt en ny okänd artist och New Yorks mångfald av artister, musiker och konstnärer.

Cette thèse vise à dégager les enjeux des rapports entre les différentes modalités d’enseignement et d’apprentissage des langues de statut différent en raison de l’évolution de l’environnement historico-culturel de la région du Banat. J’avance l’hypothèse que les ressources et les stratégies que les élèves utilisent dans l’environnement informel et non-formel des langues peuvent être mobilisées dans l’apprentissage formel des langues à certaines conditions : l’engagement de l’apprenant, le développement de son sentiment d’efficacité personnelle et l’aide de l’expert. L’apport des théories, notamment de la théorie écologique (Van Lier, 2004), m’a conduit à m’interroger sur l’existence potentielle d’un 4e environnement favorable à la mise en synergie des ressources et des stratégies présentes dans ces environnements. Pour étayer cette hypothèse, j’ai mis en place un protocole en deux étapes : tout d’abord, une enquête auprès d’élèves et d’enseignants de la région de Banat sous la forme d’un questionnaire adressé à cent élèves de collège et vingt professeurs, et une enquête qualitative au moyen de dix entretiens semi-directifs. Dans une seconde étape, j’ai mis en œuvre un scénario d’apprentissage de type blog dans ce 4e environnement avec un public de cinq élèves de 5e d’un collège de Timişoara. J’ai analysé les stratégies et l’engagement des élèves roumains pour démontrer comment une approche s’appuyant sur la prise de conscience de la pertinence de ressources et stratégies utilisées dans les environnements informels et non formels est susceptible d’optimiser les performances des élèves dans leur apprentissage d’une langue étrangère. / This doctoral dissertation is part of a systemic reflection and aims at identifying the relationship between different methods of teaching and learning languages due to the evolution of the historic-cultural environment of the Banat region. I put forward the hypothesis that the resources and the strategies used by the pupils within the informal and non-formal environment of languages can be mobilized within formal language learning under certain conditions: the pupil’s commitment, the development of his/her self-efficiency and the expert’s help. The contribution of theories, namely of the ecological theory (Van Lier, 2004), has lead me to question my thinking on the potential existence of a 4th environment favourable to the synergy of resources and strategies present within these environments.In order to support this hypothesis, I have established a two-stage protocol: firstly, an inquiry of pupils and teachers of the Banat region under the form of a questionnaire has been addressed to one hundred secondary school pupils and twenty teachers, and a qualitative inquiry through about ten semi-directive interviews. Secondly, I have established a learning device within this 4th environment, a blog, with an audience of five pupils from the fifth grade of a secondary school in Timişoara. I have thus analysed the strategies and the commitment of the Romanian pupils in order to demonstrate that an approach relying on the awareness of the relevance of the use of resources and strategies within the informal and non-formal environments is responsible for optimising the performances of pupils in foreign language.

Cette biographie est née d’une insatisfaction et d’un constat : insatisfaction devant une lecture de la carrière de Gaston Defferre (1910-1986) souvent réduite au «maire de Marseille » – ignorant le législateur, parlementaire durant plus de quarante ans, ministre sous la IVe et la Ve République, et responsable socialiste incontournable - constat paradoxal de la longévité d’une carrière politique qui ne lui permit cependant jamais de jouer les tous premiers rôles. Son échec cinglant à la présidentielle de 1969 constitua à cet égard un tournant, sonnant le glas de ses ambitions nationales, au moment même où son pouvoir local était à son apogée. L’intérêt d’une biographie de Defferre réside par conséquent dans cette tension entre ancrage local et carrière nationale – caractéristique de bien des hommes politiques français. Comprendre sa trajectoire politique, jusque dans son inachèvement, nécessite de penser l’articulation de ces deux dimensions de son action, sans jamais les isoler l’une de l’autre. Croisant les papiers privés de Defferre et les archives publiques, locales et nationales, cette thèse aborde ainsi quatre grandes questions : la Résistance comme matrice et expérience structurante dans la carrière de Defferre - l’enracinement local comme ressource – garantie de longévité politique et amortisseur d’échec – et contrainte – sensible dans la décision politique – - le rapport du bourgeois et du notable au socialisme comme idéologie ainsi qu’au parti socialiste – auquel il fut indéfectiblement fidèle - l’homme d’Etat, enfin, à travers son œuvre législative, son rapport aux institutions et la façon dont il conjugua intérêt général, engagement socialiste et intérêt local. / I began my work on Gaston Defferre for two main biographical reasons : first of all I was unsatisfied by the fact that Gaston Defferre’s political career was often reduced in public discourse to « the Mayor of marseille » – thus ignoring the policy maker, and Member of parliament for over 40 years, in charge of a ministery many times under the 4th and 5th Republics, and major socialist leader - the second element was the paradox of a very long political career that never gave him the occasion to play any major part un French politics. His failure at the 1969 presidential election is to be regarded as an important break in his career, that put a final dot to his national ambitions meanwhile his local leadership was getting to an edge. This dynamic gap between local and national career, comparable to that of many other political french leaders, makes this biographic research relevant - examining firmly the link between both aspects helps understand why this career remained unfulfilled. This work, proceeding through comparisons between local and national public documents, as well as private ones, uncovers four series of questions : the Resistance regarded as a matrix and a structuring experience in Defferre’s career - the local settings that gave him political longevity and a parachute in the event of failure, as well as a real restraint for political decisions - his relation to socialism as an ideology and to the socialist party – to which he always remained faithfull - the statesman, his reforms, his relation to the institutions, and the way he dealt with general interest, his socialist commitment to local interest.