Nous étudions les méthodes de management stratégique de l’entreprise familiale qui favorisent l’internationalisation performante et durable. Sur base de quatre cadres théoriques, la création de valeur économique durable, le socle stratégique, le modèle séquentiel d’Uppsala et l’apprentissage organisationnel, nous avons émis l’hypothèse qu’une stratégie d’internationalisation est performante et durable si les méthodes de management stratégique de l’entreprise familiale reposent sur des variables endogènes sociales et économiques. Au travers d’un cas longitudinal de recherche-intervention qualimétrique, nous avons ainsi identifié et mesuré les facteurs endogènes de performance durable de son internationalisation. Deux facteurs dominants de performance et deux de durabilité lui procurent un avantage concurrentiel : des pratiques de pilotage et de contrôle de trois natures incrémentales managériale, organisationnelle et informationnelle, la renégociation fréquente du « pacte organisationnel de vie commune », la mesure de ces facteurs incorporels et endogènes mobilisés et l’organisation de l’apprentissage tiré de l’expérience. / We study family businesses’ strategic management methods that promote sustainable and efficient internationalization. Based on four theoretical frameworks, sustainable economic value creation, strategic base, Uppsala’s sequential model, and organizational learning, we have ventured the following research hypothesis: the internationalization strategy boosts sustainable performance if family businesses’ strategic management methods rely on social and economic endogenous variables. Through a longitudinal intervention-research case, we have identified and measured its internationalization sustainable performance endogenous factors. Two main performance factors and two main sustainability factors provide competitive advantage for it: steering and controlling practices with three incremental functions (management, organization, and information), regular negotiation on “how to live together organizational agreement”, measurement of intangible and endogenous factors, and organization of experience-based learning.

Η αγγειογένεση ρυθμίζει πολλές φυσιολογικές και παθολογικές διαδικασίες. Έτσι είναι μεγάλου ενδιαφέροντος να ανακαλυφθούν μηχανισμοί που συμμετέχουν. Στο πρώτο μέρος της μεταπτυχιακής εργασίας πραγματοποιήθηκε η σύνθεση των τριών πεπτιδίων, ανάλογα ΤR1-41). Στην συνέχεια μελετήθηκε ο βιολογικός ρόλος του ΤR1-41. Είναι γνωστό ότι η θρομβίνη, η πρωτεάση σερίνης, έχει κεντρικό ρόλο στην αιμόσταση, και έχει προταθεί για να διαδραματίσει έναν σημαντικό ρόλο στην έναρξη της αγγειογέννεσης μέσω της μεταγωγής σήματος από τους PARs υποδοχέων. Οι PARs αποτελούνται μια νέα οικογένεια πρωτεϊνικών υποδοχέων των επτά διαμεμβρανικών τμημάτων (seven transmembrane domain receptor family) που διασυνδέονται με G πρωτεΐνες. Mοριακές και δομικές μελέτες του υποδοχέα της θρομβίνης, PAR-1, έδειξαν ότι το εξωκυτταρικό αμινοτελικό άκρο του είναι μακρύ και αποτελείται από 75 αμινοξέα. Επιπλέον, στην αλληλουχία του αμινοτελικού άκρου εντοπίστηκε μία θέση θετική για πέψη από τη θρομβίνη στη θέση μεταξύ της Arg41 και Ser42. Πράγματι η σύνδεση της θρομβίνης με τον PAR-1 έχει ως συνέπεια την εκλεκτική υδρόλυση του πεπτιδικού δεσμού LDPR41- S42FLLRN. Το αποτέλεσμα από την υδρόλυση αυτή, είναι η δημιουργία ενός ελεύθερου πεπτιδίου 41 αμινοξέων( Thrombin Receptor Peptide 1-41, TR1-41), και ενός νέου αμινοτελικού άκρου για τον υποδοχέα. Σε αντίθεση με το νέο αμινοτελικό άκρο του υποδοχέα της θρομβίνης (PAR-1), ο ρόλος του πεπτιδίου των 41 αμινοξέων (TR1-41) που αποκόπτεται με τη πρωτεολυτική δράση της θρομβίνης μεταξύ των αμινοξέων Arg41-Ser42 είναι σχεδόν άγνωστος. Στην παρούσα μελέτη, αξιολογήσαμε την επίδραση αυτού του πεπτιδίου (MGPRRLLLVAACFSLCGPLLSARTRARRPESKATNATLDPR) στα καλλιεργημένα ανθρώπινα ενδοθηλιακά κύτταρα. Η έκθεση των ενδοθηλιακών κυττάρων στο πεπτίδιο οδήγησε σε μια δοσοεξαρτώμενη αναστολή του πολλαπλασιασμού των κυττάρων, καθώς επίσης και της δράσης των bFGF και VEGF. Επίσης υπήρχε η ένδειξη ότι το πεπτίδιο TR1-41 αναστέλλει σε συνθήκες ορού 5% FBS, τη δράση bFGF μέσω του μονοπατιού της MAP-κινάσης και μέσω του Erk1/2. Αντίθετα, καμία επίδραση δεν παρατηρήθηκε στα κύτταρα στα οποία χορηγήθηκε το scrambled peptide (πεπτίδιο 41 αμινοξέων με αναγραμματισμένη σειρά αμινοξέων) ή και μικρότερα πεπτίδια αυτού (TRARRPESKATNATLDPR). Επίσης το πεπτίδιο TR1-41 παρουσιάζει ανασταλτική δράση στον πολλαπλασιασμό των HUVECs και άλλων κυτταρικών σειρών. Τέλος, το πεπτίδιο TR1-41 εμπόδισε τον σχηματισμό αγγείων στο in vitro σύστημα της αγγειογέννεσης με υπόστρωμα Matrigel. Tο δεύτερο μέρος του μεταπτυχιακού μελετήθηκε ο βιολογικός ρόλος της ορμόνης μελατονίνης. Η μελατονίνη είναι το σημαντικότερο εκκριτικό προϊόν του κωνοειδούς αδένα και σε γενικές γραμμές εμφανίζει ογκοστατικές, αντιγηραντικές, αντιοξειδωτικές, νευροπροστατευτικές, υπνωτικές, ορεξιογόνες, αναλγητικές, θερμορυθμιστικές,και καρδιαγγειακές ιδιότητες, ενώ παρουσιάζει ανασταλτική δράση στη διαδικασία της αναπαραγωγής και μετατοπίζει τις φάσεις του «βιολογικού ρολογιού». Από τα πειράματά μας στα πρωτογενή ανθρώπινα ενδοθηλιακά κύτταρα (HUVECs) η επίδραση της μελατονίνης φαίνεται διφασική. Στις χαμηλές συγκεντρώσεις μελατονίνης αυξάνεται ο πολλαπλασιασμός των HUVECς. Στις υψηλές συγκεντρώσεις αναστέλλει τον πολλαπλασιασμό των HUVECς. / Angiogenesis regulates many physiological and pathological processes, so it is of great interest to find out which mechanisms that are involved. In the first part of the project we synthesised three peptides, analogs of ΤR1-41 and we studied the biological role of the ΤR1-41. It is known that thrombin, the serine proteinase, best known for its pivotal role in haemostasis, has been proposed to play an important role in the initiation of angiogenesis by a mechanism most likely independent of its coagulant activity and more dependent on signaling via the protease-activated receptors (PARs). PARs consists a novel family of G protein-coupled receptors, which can be activated by proteolytic cleavage of their N-terminal extracellular domain. PAR-1 is the first member of this family to be cloned in which proteolytic cleavage at the R41/S42 bond by thrombin releases a 41 aminoacid peptide and unveils a tethered peptide ligand with the recognition sequence SFLLRN. Despite the wealth of information relating to the role of thrombin and PAR-1 innormal and disease states, a potential biological role of cleaved peptide remains unknown. In the present study, we evaluated the effect of the 41-amino-acid cleaved peptide, (MGPRRLLLVAACFSLCGPLLSARTRARRPESKATNATLDPR) in cultured human endothelial cells. Exposure of endothelial cells to this peptide resulted in a concentration-dependent inhibition of serum-mediated proliferation, as well as of bFGF- and VEGF-induced cell growth. There was the suspicion that the peptide blocked the serum, bFGF-triggered Erk1/2 activation. In contrast, no effect was observed in cells treated with a scramble peptide or with a shorter derivative of parstatin (TRARRPESKATNATLDPR). Finally, ΤR1-41 peptide abrogated tube formation in vitro Matrigel angiogenesis model. These results provide a plausible evidence for a negative role of PAR-1 cleaved peptide in angiogenic cascade and suggest parstatin as target for developing anti-angiogenic agents with potential therapeutic application in cancer and other angiogenesis-related diseases. The second part of the project was the biological role of melatonin. Melatonin is the major secretory product of the pineal gland and is considered an important natural oncostatic agent. From our experiments in human umbilical vein endothelial cells (HUVECs) the effect of melatonin seems to be biphasic. In low concentrations melatonin increased HUVEC proliferation, but in higher concentrations significantly decreased cell proliferation.

Nous étudions les méthodes de management stratégique de l’entreprise familiale qui favorisent l’internationalisation performante et durable. Sur base de quatre cadres théoriques, la création de valeur économique durable, le socle stratégique, le modèle séquentiel d’Uppsala et l’apprentissage organisationnel, nous avons émis l’hypothèse qu’une stratégie d’internationalisation est performante et durable si les méthodes de management stratégique de l’entreprise familiale reposent sur des variables endogènes sociales et économiques. Au travers d’un cas longitudinal de recherche-intervention qualimétrique, nous avons ainsi identifié et mesuré les facteurs endogènes de performance durable de son internationalisation. Deux facteurs dominants de performance et deux de durabilité lui procurent un avantage concurrentiel : des pratiques de pilotage et de contrôle de trois natures incrémentales managériale, organisationnelle et informationnelle, la renégociation fréquente du « pacte organisationnel de vie commune », la mesure de ces facteurs incorporels et endogènes mobilisés et l’organisation de l’apprentissage tiré de l’expérience. / We study family businesses’ strategic management methods that promote sustainable and efficient internationalization. Based on four theoretical frameworks, sustainable economic value creation, strategic base, Uppsala’s sequential model, and organizational learning, we have ventured the following research hypothesis: the internationalization strategy boosts sustainable performance if family businesses’ strategic management methods rely on social and economic endogenous variables. Through a longitudinal intervention-research case, we have identified and measured its internationalization sustainable performance endogenous factors. Two main performance factors and two main sustainability factors provide competitive advantage for it: steering and controlling practices with three incremental functions (management, organization, and information), regular negotiation on “how to live together organizational agreement”, measurement of intangible and endogenous factors, and organization of experience-based learning.

<p>The aim of the thesis is to quantitatively study the driving forces and mechanisms for regional growth from an endogenous and exogenous perspective and reveal the most important factors contributing to regional growth, by focusing on three aspects: local labour market, the supply side and the demand side of the labour market. The thesis is designed to use Swedish micro register data to develop spatial models with higher spatial resolution. It was found that endogenous factors are important and probably explain about at least one third of total regional economic growth. Among the endogenous factors, localised demographic composition, labour force and labour market, firms, and business environment have the strongest influence on regional economic growth. The findings from the Swedish context were briefly compared to China’s economic growth in the last fifty years.</p><p>The thesis consists of three related papers. The first paper studied the endogenous and exogenous factors in 108 Swedish LA regions during the 1990s. By using the SNI92 code, individual longitudinal data and an improved shift-share analysis method, it was found that the endogenous factor is important for regional economic growth because it is able to accelerate, decelerate or reverse the impact from exogenous factors during the period studied.</p><p>The second paper studied regional growth from the supply side of the labour market by focusing on population redistribution and place attractiveness. A ‘floating grid’ approach was developed to understand the factors shaping place attractiveness. The approach disregards administration zones by focusing on a small spatial unit—vicinity which is one kilometre square. Each unit has a unique set of surrounding zones that are local area and hinterland. By constructing spatial models, the total explained variance in place attractiveness was decomposed into partial explanatory effects that are assigned for physical attraction, demographic, service and labour market factors over the spatial scales. The finding is that the spatial scale of vicinity and demographic factors contribute most to place attractiveness.</p><p>The third paper studied regional growth from the demand side of the labour market by focusing on workplace and its economic performance. The ‘floating grid’ approach was once more applied while the basic analysis unit is a constructed workplace that holds working-square, local area and hinterland as surrounding zones. The economic performance of the workplace was attributed to external demand, local demand, business environment and labour force factors over different spatial scales. A method was developed to quantitatively identify intervals of partial explanatory effects that are components of the total explained variance. It was found that working-square and labour force factors contribute most to workplace economic performance.</p>

The aim of the thesis is to quantitatively study the driving forces and mechanisms for regional growth from an endogenous and exogenous perspective and reveal the most important factors contributing to regional growth, by focusing on three aspects: local labour market, the supply side and the demand side of the labour market. The thesis is designed to use Swedish micro register data to develop spatial models with higher spatial resolution. It was found that endogenous factors are important and probably explain about at least one third of total regional economic growth. Among the endogenous factors, localised demographic composition, labour force and labour market, firms, and business environment have the strongest influence on regional economic growth. The findings from the Swedish context were briefly compared to China’s economic growth in the last fifty years. The thesis consists of three related papers. The first paper studied the endogenous and exogenous factors in 108 Swedish LA regions during the 1990s. By using the SNI92 code, individual longitudinal data and an improved shift-share analysis method, it was found that the endogenous factor is important for regional economic growth because it is able to accelerate, decelerate or reverse the impact from exogenous factors during the period studied. The second paper studied regional growth from the supply side of the labour market by focusing on population redistribution and place attractiveness. A ‘floating grid’ approach was developed to understand the factors shaping place attractiveness. The approach disregards administration zones by focusing on a small spatial unit—vicinity which is one kilometre square. Each unit has a unique set of surrounding zones that are local area and hinterland. By constructing spatial models, the total explained variance in place attractiveness was decomposed into partial explanatory effects that are assigned for physical attraction, demographic, service and labour market factors over the spatial scales. The finding is that the spatial scale of vicinity and demographic factors contribute most to place attractiveness. The third paper studied regional growth from the demand side of the labour market by focusing on workplace and its economic performance. The ‘floating grid’ approach was once more applied while the basic analysis unit is a constructed workplace that holds working-square, local area and hinterland as surrounding zones. The economic performance of the workplace was attributed to external demand, local demand, business environment and labour force factors over different spatial scales. A method was developed to quantitatively identify intervals of partial explanatory effects that are components of the total explained variance. It was found that working-square and labour force factors contribute most to workplace economic performance.

This dissertation is divided into six chapters, as foHows: Chapter 1 of this dissertation discusses the growing significance of FDI for developing countries. It compares FDT in developed and developing countries and analyses recent evidence ofFDI flows to developing countries. Chapter 2 analyses the (endogenous and exogenous) detenninants ofFDI flows into developing countries. Chapter 3 discusses the importance of FDI flows, which are essential for new investments or for financing fortuitous deficits in host countries, and looks at the adjustment mechanisms for the equilibrium of the balance of payments. Chapter 4 gives attention to FDI flows, the liberalisation of financial markets and the financial account of the balance of payments in developing countries in providing more opportunities and mechanisms for development and economic growth. Finally, chapter S examines and compares FDI flows tu South Africa and Angola - the biggest FDI recipients on the African continent. / Economics / MCom (Economics)

This dissertation is divided into six chapters, as foHows: Chapter 1 of this dissertation discusses the growing significance of FDI for developing countries. It compares FDT in developed and developing countries and analyses recent evidence ofFDI flows to developing countries. Chapter 2 analyses the (endogenous and exogenous) detenninants ofFDI flows into developing countries. Chapter 3 discusses the importance of FDI flows, which are essential for new investments or for financing fortuitous deficits in host countries, and looks at the adjustment mechanisms for the equilibrium of the balance of payments. Chapter 4 gives attention to FDI flows, the liberalisation of financial markets and the financial account of the balance of payments in developing countries in providing more opportunities and mechanisms for development and economic growth. Finally, chapter S examines and compares FDI flows tu South Africa and Angola - the biggest FDI recipients on the African continent. / Economics / MCom (Economics)