Ce doctorat trouve son origine dans la compréhension des prises de décision et des comportements collectifs des animaux. Comment ces derniers parviennent-ils à effectuer des choix collectivement ? Comment les membres d’un groupe procèdent-ils pour synchroniser leurs comportements spatialement et temporellement ? Mon principal objectif a été de dégager, lors des déplacements collectifs et du fur rubbing chez le capucin moine, les évènements décisionnels dépendants de processus anonymes de ceux dépendants de processus liés à l’identité des individus et à leur réseau de relations sociales au sein du groupe. Dans les prises de décision collective relatives aux déplacements, les membres du groupe sont influencés dans leurs choix par leur identité sociale mais aussi par des mécanismes anonymes, de type mimétique. Le fur rubbing est également un comportement collectif dont les mécanismes sous-jacents incluent une dépendance interindividuelle de type mimétique. Des mécanismes similaires mettant en jeu des interactions entre individus basées sur des règles comportementales simples se retrouvent dans chacun des phénomènes collectifs étudiés. Ces résultats sont les premiers à démontrer l’émergence de prises de décision collective à partir de telles interactions anonymes dans un groupe de primates non humains. Ils permettent de faire le lien entre choix individuels et comportement collectif et de mieux concevoir comment un groupe de primates peut se coordonner, maintenir sa cohésion spatiale et synchroniser ses activités./How do animals reach collective consensus? How do group members spatially and temporally synchronise their behaviour? My main purpose was to demonstrate the respective roles of anonymous processes (contagion, mimetism) and individual-dependent processes (hierarchical rank, age, sex, kin, social relationships) in collective decision-making. During decision-making relating to collective movements, group members’ decisions depend on their social identity (individual-dependent mechanism) as well as anonymous processes. Fur rubbing is also a collective behaviour involving interindividual dependence with mimetic underlying mechanisms. We found similar mechanisms, involving interindividual interactions according to simple behavioural rules, in both collective phenomenon studied. These results are the first to demonstrate the emergence of collective decision-making based on anonymous interactions in a group of non human primates. They help to understand the link between individual choices and collective behaviour and to appreciate how a social group of primates maintain its spatial cohesion and synchronize its activities.

Ce travail a consisté à analyser, par des approches toxicocinétiques (TK) et mécanistiques, les effets oestrogéniques du Bisphenol A (BPA) sur un biomarqueur précoce et sensible : la sécrétion de l'hormone lutéinisante (LH) chez la brebis prépubère ovariectomisée. La plus faible concentration plasmatique en BPA induisant une inhibition de LH s'est avérée proche des concentrations maximales décrites chez l'Homme. Cette inhibition de LH pourrait impliquer une inhibition des systèmes neuronaux à kisspeptine. L'approche TK comparative d'espèces a montré que la clairance du BPA est toujours élevée, proche du débit sanguin hépatique. Pour une exposition à la dose journalière admissible, cette approche permet de prédire chez l'Homme des concentrations en BPA très inférieures à celles associées à une inhibition de LH dans notre modèle. / The goal of this thesis was to analyse through toxicokinetic (TK) and mechanistic approaches the estrogeno-mimetic effects of bisphenol A (BPA) on a precocious and sensitive biomarker: LH secretion in ovariectomized female lambs. The lowest plasma BPA concentrations associated to an inhibition of LH secretion appeared to be close to the highest one reported in human. LH suppression could be mediated by an inhibition of hypothalamic kisspeptin systems. The multispecies TK approach showed that BPA clearance is always high and equivalent to the liver blood flow. For an exposure scheme corresponding to the tolerable daily intake, this approach allows to predict human BPA concentration much lower than the one associated to LH inhibition in our highly sensitive lamb model.

Made available in DSpace on 2016-04-27T19:31:01Z (GMT). No. of bitstreams: 1 Maria Cristina Pereira Brandini.pdf: 7628674 bytes, checksum: 709d8294f83788820bb53a5dbcdee028 (MD5) Previous issue date: 2014-09-25 / The focus of this dissertation is the question of Tupinambá s body through the Jean de Léry s traveller seeing, in his writ, Histoire d un Voyage faict en la terre du Brésil, in other words, the traveller narration of the XVI century about the meeting with the New World and his contribuition for the body construction of the brasilian indian, the other. Opening in that way a discussion about the possibility of a control action or a domestication of the Tupinambá social body that could be hidden in Léry s writ with the intention for conquest. And even the dimension of Léry s contribuition for the construction through the verbal imagery about the indian social body during the begining of Brasil history and its continuities on ours contemporary time. And how this writ takes a handling of agent into the domestication mechanisms and european conquest on the question of the savage body construction. Particularizing what is envolving on the body knowledges that opening the modern concept found in the discourse of the traveller literature writing of the XVI century. A reflextion about a modern body historicity is opening with the New World discovery and how the process investigation lead to the question of the occidental body normatization, as well, to the meeting of others realities that concern about the relation between body and society, that promote a reation for separation and crash because of the unexpected and the impossibility of understanding the unknown. A game of assimilations and resistances emerges from the body policy executed between civilized and savage . The theoretical matter for this historygraphy investigation puts Léry into a dialogue between Michel de Certeau, Frank Lestringant and Tzvetan Todorov, upon the academic treatment about the meeting with the Tupinambá during the XVI century. We ll take too the study of the brazilian antropologist Eduardo Viveiros de Castro, who investigates the Araweté tribe of Amazônia, the last Tupinambá survivors during the XXI century. These authors refletion indicates a investigation that open specifics discussions: a brasilian state of exception established during the conquest period and his consequences above the construction of a imaginary ontology about the brasilian indian and in the manner how the savage body was simbolized, vestiges that are extended to the contemporary time / O objeto desta dissertação é a questão do corpo Tupinambá no olhar do viajante Jean de Léry, em sua escrita Histoire d un voyage faict en la terre du Brésil, ou seja, o relato de um viajante do século XVI sobre o encontro com o Novo Mundo e sua contribuição para a construção do corpo indígena brasileiro. Abre-se, assim, uma discussão sobre a possibilidade de controle, ou domesticação do corpo Tupinambá, que estaria nas entrelinhas da escrita conquistadora. Assim como a contribuição de Léry para engrossar a construção de um imaginário verbal sobre esse corpo social-outro nos primórdios do Brasil e de suas continuidades no contemporâneo. Ainda, a escrita recebe um tratamento de agente nos mecanismos de domesticação e conquista dos europeus na questão da construção do corpo selvagem, mais especificamente, no que envolve entendimentos de corpo que inauguram o conceito de modernidade no discurso escrito da literatura de viagem do século XVI. Fato que possibilita reflexão sobre a historicidade do corpo moderno dada pelo descobrimento do Novo Mundo. O processo de investigação leva a questão da normatização do corpo ocidental, bem como ao encontro de outras realidades , na relação entre corpo e sociedades que se chocam pelo inesperado e se distanciam pela impossibilidade de compreensão. Um jogo de assimilações e resistências emerge das políticas do corpo praticadas entre civilizado e selvagem . O aporte teórico para esta investigação historiográfica põe Léry num diálogo transdisciplinar com Michel de Certeau, Frank Lestringant e Tzvetan Todorov, para tratar do encontro com o Tupinambá no século XVI. Lançamos mão, também, no intuito de entendermos a corporalidade Tupinambá, do estudo do antropólogo Viveiros de Castro que pesquisou a tribo dos Araweté da Amazônia, último reduto dos Tupinambá no século XXI. O estudo dos autores citados encaminhou a pesquisa para discussões específicas, a saber: o estado de exceção instaurado durante o período da conquista e suas conseqüências na formação do imaginário e nos modos como o corpo foi simbolizado, traços que se estendem até a contemporaneidade

Nesta dissertação investigamos como a ficção envolve o leitor. Para isso, partimos da rejeição a Homero declarada por Calímaco, observando que a suposta diferença entre a literatura preferida pelo público e a literatura preferida pela crítica depende de dois fatores distintos. O primeiro é o simples fato de a crítica ler profissionalmente e o público ler por prazer. O segundo está relacionado à distinção entre recepção e uso da literatura proposta por C.S. Lewis. Na recepção, a obra tende a ser admirada por si; no uso, tende a ser instrumentalizada como suporte para um devaneio em que os desejos do próprio leitor são vicariamente satisfeitos. Observamos que essa devaneio, que Lewis chama de construção egoísta de castelos, e que inclui uma variante mórbida, tem um paralelo na noção girardiana do duplo angélico. Contudo, o devaneio depende da simpatia como definida por Adam Smith, a qual por sua vez depende de certa aprovação moral. Investigamos portanto o tipo de personagem que conquista a aprovação moral do leitor, contrastando os heróis homéricos com os cavaleiros cristãos a fim de verificar como o cristianismo dirige a aprovação moral para as vítimas, fazendo com que os heróis da ficção sejam pessoas perseguidas ou marginalizadas. / In this dissertation we investigate how fiction involves the reader. Starting Callimachuss rejection of Homer, we note that the supposed diference between the literature favoured by the public at large and the literature preferred by critics is actually twofold. First, critics read for business and the public reads for pleasure. Second, as proposed by C.S. Lewis, there is a distinction between the reception and use of literature. In reception, a work tends to be admired in itself, whereas in use it becomes a mere support for a sort of daydreaming in which the readers own desires are vicariously satisfied. We discuss this daydreaming called egotistic castle-building by Lewis, highlighting its morbid variant, which finds a parallel in the Girardian notion of the angelic double, developed from a reading of Proust. Now, as egotistic castle-building in its turn depends on sympathy as defined by Adam Smith, a concept which includes moral approval, we investigate the types of characters who obtain the moral approval of readers, contrasting the warriors from Homers poems with Christian knights in order to show that Christianity directs moral approval towards the victims. In a Christian society, fictional heroes must be people who are persecuted or at least marginalised.

Nous proposons dans ce mémoire de thèse une méthodologie permettant la résolution du problème de la décomposition de Hodge-Helmholtz discrète sur maillages polyédriques. Le défi de ce travail consiste à respecter les propriétés de la décomposition au niveau discret. Pour répondre à cet objectif, nous menons une étude bibliographique nous permettant d'identifier la nécessité de la mise en oeuvre de schémas numériques mimétiques. La description ainsi que la validation de la mise en oeuvre de ces schémas sont présentées dans ce mémoire. Nous revisitons et améliorons les méthodes de décomposition que nous étudions ensuite au travers d'expériences numériques. En particulier, nous détaillons le choix d'un solveur linéaire ainsi que la convergence des quantités extraites sur un ensemble varié de maillages polyédriques et de conditions aux limites. Nous appliquons finalement la décomposition de Hodge-Helmholtz à l'étude de deux écoulements turbulents : un écoulement en canal plan et un écoulement turbulent homogène isotrope. / We propose in this thesis a methodology to compute the Helmholtz-Hodge decomposition on discrete polyhedral meshes. The challenge of this work isto preserve the properties of the decomposition at the discrete level. In our literature survey, we have identified the need of mimetic schemes to achieve our goal. The description and validation of our implementation of these schemes are presented inthis document. We revisit and improve the methods of decomposition we then study through numerical experiments. In particular, we detail our choice of linear solvers and the convergence of extracted quantities on various series of polyhedral meshes and boundary conditions. Finally, we apply the Helmholtz-Hodge decomposition to the study of two turbulent flows: a turbulent channel flow and a homogeneous isotropic turbulent flow.

Additive manufacturing technologies are enabling newfound degrees of geometrical complexity to be realised, particularly with regards to internal structures. All of these manufacturing technologies are dependant on their prior design in an appropriate electronic form, either by reverse engineering, or, primarily, by computer-aided design. Within these emerging applications is the design of scaffolds with an intricate and controlled internal structure for bone tissue engineering. There is a consensus that ideal bone scaffold geometry is evident in biological trabecular structures. In their most basic topological form,these structures consist of the non-linear distribution of irregular interconnecting rods and plates of different size and shape. Complex and irregular architectures can be realised by several scaffold manufacturing techniques, but with little or no control over the main features of the internal geometry, such as size, shape and interconnectivity of each individual element. The combined use of computer aided design systems and additive manufacturing techniques allows a high degree of control over these parameters with few limitations in terms of achievable complexity. However, the design of irregular and intricate trabecular networks in computer aided design systems is extremely time-consuming since manually modelling an extraordinary number of different rods and plates, all with different parameters, may require several days to design an individual scaffold structure. In an attempt to address these difficulties, several other research efforts in this domain have largely focussed on techniques which result in designs which comprise of relatively regular and primitive shapes and do not represent the level of complexity seen biologically. Detailed descriptions of these methods are covered in chapter 1. An automated design methodology for trabecular structures is proposed by this research to overcome these limitations. This approach involves the investigation of novel software algorithms, which are able to interact with a conventional computer aided design program and permit the automated design of geometrical elements in the form of rods, each with a different size and shape. The methodology is described in chapter 2 and is tested in chapter 3. Applications of this methodology in anatomical designs are covered in chapter 4. Nevertheless, complex designed rod networks may still present very different properties compared to trabecular bone geometries due to a lack detailed information available which explicitly detail their geometry. The lack of detailed quantitative descriptions of trabecular bone geometries may compromise the validity of any design methodology, irrespective of automation and efficiency. Although flexibility of a design methodology is beneficial, this may be rendered inadequate when insufficient quantitative data is known of the target structure. In this work a novel analysis methodology is proposed in chapter 5, which may provide a significant contribution toward the characterisation and quantification of target geometries, with particular focus on trabecular bone structures. This analysis methodology can be used either to evaluate existing design techniques or to drive the development of new bio-mimetic design techniques. This work then progresses to a newly derived bio-mimetic automated design technique, driven by the newly produced quantitative data on trabecular bone geometries. This advanced design methodology has been developed and tested in chapter 6. This has demonstrated the validity of the technique and realised a significant stage of development in the context and scope of this work.

Η υπέρταση αποτελεί έναν από τους πλέον σημαντικότερους παράγοντες στην αύξηση των καρδιαγγειακών επεισοδίων τα οποία ευθύνονται περίπου για το ήμισυ των θανάτων στους ενηλίκους. To σύστημα ρενίνης-αγγειοτενσίνης (RAS), διαδραματίζει καθοριστικό ρόλο στη ρύθμιση της συστολικής και της διαστολικής πίεσης και για αυτό το λόγο η αναστολή του έχει αποτελέσει φαρμακολογικό στόχο για τη θεραπεία της υπέρτασης. Οι μη πεπτιδικοί ΑΤ1 ανταγωνιστές της Αγγειοτενσίνης ΙΙ αντιπροσωπεύουν τη νεότερη γενιά αντιϋπερτασικών φαρμάκων. Επιδρούν στο τελικό στάδιο του RAS, αποτελώντας μία αποτελεσματική θεραπευτική προσέγγιση της υπέρτασης. Με βάση το Losartan, τον πρώτο μη πεπτιδικό ΑΤ1 ανταγωνιστή της Αγγειοτενσίνης ΙΙ που κυκλοφόρησε στην αγορά το 1995, σχεδιάστηκαν δραστικότεροι και εκλεκτικότεροι ανταγωνιστές με παρατεταμένη βιολογική δράση. Στόχος της παρούσας ερευνητικής εργασίας και έχοντας ως βάση τα χαρακτηριστικά του Losartan, ήταν η σύνθεση μονοαλκυλιωμένων παραγώγων με βάση είτε το 2-βουτυλοϊμιδαζόλιο (ανάλογο 1),, είτε το 4-βουτυλοϊμιδαζόλιο (ανάλογο 2). Συγκεκριμένα, φέρουν τα ακόλουθα δομικά χαρακτηριστικά:  Ένα ιμιδαζολικό δακτύλιο υποκατεστημένο με την n-βουτυλ-ομάδα είτε στη θέση 2 (1), είτε στη θέση 4 (2) του ιμιδαζολίου, καθώς σύμφωνα με τη βιβλιογραφία η βουτυλ-ομάδα αυτή αλληλεπιδρά με τη λιπόφιλη περιοχή του υποδοχέα και διαθέτει το βέλτιστο μήκος, με απώτερο στόχο την εμφάνισης ή όχι βιολογικής δράσης.  Τη [2´-(2Η-τετραζολ-5-υλ)διφαινυλ-4-υλ]μεθυλ-ομάδα. / Hypertension is one of the most important factors resulting in the increase of cardiovascular episodes, which are responsible for approximately half of all deaths in adults. The Renin-Angiotensin System (RAS) plays a defining role in the regulation of systolic and diastolic pressure and its inhibition has been a pharmacological goal in the treatment of hypertension. Non peptide AT1 receptor Angiotensin II antagonists represent the latest generation of antihypertensive drugs. They interfere in the final blockade site of RAS thus being an effective therapeutic approach towards treating hypertension. Losartan was the first non peptide AT1 receptor angiotensin II antagonist to become available in the market in 1995. Using Losartan as a base, more potent and selective antagonists with prolonged biological action were designed. The goal of this thesis and using the characteristics of Losartan as basis, was the synthesis of monoalkylated products based on either 2-butylimidazole (analogue 1) or 4-butylimidazole (analogue 2). Το be more specific they had the following structural characteristics:  An imidazole ring substituted with the n-butyl group either at position 2 (1) or at position 4 (2) of imidazole, since according to existing literature this butyl group interacts with the lipofile area of the receptor and has the ideal size for the appearance of biological action.  The [2´-(2Η-tetrazol-5-yl)biphenyl-4-yl]methyl-group.

Η υπέρταση αποτελεί έναν από τους σημαντικότερους παράγοντες που αυξάνει τα καρδιαγγειακά επεισόδια τα οποία ευθύνονται περίπου για το ήμισυ των θανάτων στους ενηλίκους. To σύστημα ρενίνης-αγγειοτασίνης-αλδοστερόνης (RAAS) διαδραματίζει καθοριστικό ρόλο στη ρύθμιση της συστολικής και της διαστολικής πίεσης και η αναστολή του έχει αποτελέσει φαρμακολογικό στόχο για τη θεραπεία της υπέρτασης. Οι μη πεπτιδικοί ΑΤ1 ανταγωνιστές της Αγγειοτασίνη ΙΙ αντιπροσωπεύουν τη νεότερη γενιά αντιϋπερτασικών φαρμάκων. Επεμβαίνουν στο τελικό στάδιο του RAAS αποτελώντας μία αποτελεσματική θεραπευτική προσέγγιση της υπέρτασης. Με βάση το Losartan, τον πρώτο μη πεπτιδικό ΑΤ1 ανταγωνιστή της Αγγειοτασίνη ΙΙ που κυκλοφόρησε στην αγορά σχεδιάστηκαν δραστικότεροι και εκλεκτικοί ανταγωνιστές με παρατεταμένη βιολογική δράση. Στα πλαίσια της παρούσας ερευνητικής εργασίας έγινε σύνθεση διαλκυλιωμένων αναλόγων που φέρουν ως βάση τον ετεροκυκλικό ιμιδαζολικό δακτύλιο υποκατεστημένο στις θέσεις -4, -5. / Hypertension is one of the most important factors resulting in the increase of cardiovascular episodes, which are responsible for approximately half of all deaths in adults. The Renin-Angiotensin-Aldosterone System (RAAS) plays a defining role in the regulation of systolic and diastolic pressure and its inhibition has been a pharmacological goal in the treatment of hypertension. Non peptide AT1 receptor Angiotensin II antagonists represent the latest generation of antihypertensive drugs. They interfere in the final blockade site of RAAS thus being an effective therapeutic approach towards treating hypertension. Losartan was the first non peptide AT1 receptor angiotensin II antagonist to become available in the market. Using Losartan as a base, more potent and selective antagonists with prolonged biological action were designed. In the context of this thesis, the synthesis of dialkylated analogues based on the 4, 5 trisubstituted heterocyclic imidazole ring is described.

The arsenal of drugs available for treating Leishmania infections is limited and presents high toxicity. Therefore, new, effective, and less toxic leishmaniasis treatments are still needed. In this work, two series of derivatives, containing a semicarbazone or hydrazide-N- acylhydrazone scaffolds was designed and synthetized as protease inhibitors. From these series, derivatives LASSBio 1483, LASSBio 1705, LASSBio 1707 and LASSBio 1736 highlighted, showing in vitro and in vivo leishmanicidal activities. Thus, these derivatives presented a potent leishmanicidal activity against amastigotes of L. major (IC50 of 1.5 µΜ to LASSBio 1483, 8.5 µΜ to LASSBio 1705 and 1.,9 µΜ to LASSBio 1707) , L. amazonensis (IC50 of 3.5 µΜ to LASSBio 1483 and 84.0 µΜ to LASSBio 1736), L. braziliensis (IC50 of 31.7 µΜ to LASSBio 1483, 8.0 µΜ to LASSBio 1705 and 5.3 µΜ to LASSBio 1736) and L. chagasi (IC50 of 53.3 µΜ to LASSBio 1707 and 57,6 µΜ to LASSBio 1736). Also, the leishmanicidal activity of derivatives LASSBio-1483, LASSBio 1705, LASSBio 1707 and LASSBio 1736 were mediated via induction of apoptosis as evidenced by externalization of phospholipids, despolarization of mitochondrial membrane and elevation of activation of caspases. The ultrastructural morphological effects against the parasite of LASSBio 1483 and LASSBio 1736 against L. chagasi promastigotes were also verified. The treatment of L. amazonensis -infected BALB/c mice with derivatives LASSBio 1483 (effect of 30.5% and 33.3% in infected ear, by p.o and i.p., respectively), LASSBio 1705 1483 (effect of 58.5% in infected ear and 61.1% in lymph node, i.p.), LASSBio 1707 (effect of 56.5% in lymph node, i.p.) and LASSBio 1736 (effect of 53.6% in infected ear, i.p.)or the treatment of L. chagasi - infected hamsters with LASSBio 1707 (effect of 53.6, i.p.)and LASSBio 1736 (effect of 46.0%, i.p.) led to a significant reduction of parasite burden when compared to controls that received PBS. The treatment with these derivatives did not result in hepatic or renal toxicity in these animals models of leishmaniasis. These data make LASSBio 1483, LASSBio 1705, LASSBio 1707 and LASSBio 1736 new lead-candidates against cutaneous and visceral leishmaniasis. / Conselho Nacional de Desenvolvimento Científico e Tecnológico / O arsenal de fármacos disponíveis para o tratamento das infecções por Leishmania spp. é limitada e de elevada toxicidade. Portanto, novos tratamentos, eficazes e menos tóxicos para leishmaniose ainda são necessários. Neste trabalho, duas séries de derivados contendo as subunidades semicarbazona ou hidrazida-N-acilhidrazona foram desenhados e sintetizados como inibidores de proteases. A partir destas séries, os derivados LASSBio 1483, LASSBio 1705, LASSBio 1707 e LASSBio 1736 se destacaram, mostrando atividade leishmanicida in vitro e in vivo . Assim, esses derivados apresentaram atividade leishmanicida potente contra amastigotas de L. major (CI 50 de 1,5 µΜ para LASSBio 1483, 8,5 µΜ para LASSBio 1705 e 15,9 µΜ para LASSBio 1707) , L. amazonensis (CI 50 de 3,5 µΜ para LASSBio 1483 e 84,0 µΜ para LASSBio 1736) , L. braziliensis (CI 50 de 31,7 µΜ para LASSBio 1483, 8,0 µΜ para LASSBio 1705 e 5,3 µΜ para LASSBio 1736) e L. chagasi (CI 50 de 53,3 µΜ para LASSBio 1707 e 57,6 µΜ para LASSBio 1736). Além disso, a atividade leishmanicida dos derivados LASSBio 1483, LASSBio 1705, LASSBio1707 e LASSBio 1736 foi mediada via indução de apoptose como evidenciado pela externalização de fosfolipídeos de membrana, despolarização da membrana mitocondrial e ativação de caspases. Os efeitos morfológicos ultra-estruturais de LASSBio 1483 e LASSBio 1736 em promastigotas de L. chagasi também foram verificados. O tratamento de camundongos BALB/c infectados por L. amazonensis com os derivados LASSBio 1483 (efeito de 30,5% e 33,3% na orelha infectada, por v.o. e i.p., respectivamente), LASSBio 1705 (efeito de 58,1% na orelha infectada e de 61,1% no linfonodo, i.p.) , LASSBio 1707 (efeito de 56,5% no linfonodo, i.p.) e LASSBio 1736 (efeito de 38,8% na orelha infectada , i.p.) ou o tratamento de hamsters infectados por L. chagasi com LASSBio 1707 (efeito de 53,6%, i.p.) e LASSBio 1736 (efeito de 46,0%, i.p.), na dose de 30 µmols/kg/dia, levaram a uma redução significativa da carga parasitária quando comparados aos controles que receberam PBS. O tratamento com estes derivados não resultaram em toxicidade hepática ou renal nestes modelos animais de leishmaniose. Estes dados fazem de LASSBio-1483, LASSBio-1705, LASSBio-1707 e LASSBio-1736 novos candidatos a protótipos a fármacos contra leishmaniose cutânea e visceral

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Tereza SRA on 2017-06-28T00:37:06Z (GMT) / Submitted by Cláudia Sofia Frias Pinto (claudia.frias.pinto@gmail.com) on 2017-06-28T01:54:39Z No. of bitstreams: 1 Tese_versao final_3_Claudia Pinto.pdf: 798014 bytes, checksum: da2ed9bf3f1617241933592b84cc5356 (MD5) / Approved for entry into archive by Maria Tereza Fernandes Conselmo (maria.conselmo@fgv.br) on 2017-06-28T17:00:17Z (GMT) No. of bitstreams: 1 Tese_versao final_3_Claudia Pinto.pdf: 798014 bytes, checksum: da2ed9bf3f1617241933592b84cc5356 (MD5) / Made available in DSpace on 2017-06-28T19:23:56Z (GMT). No. of bitstreams: 1 Tese_versao final_3_Claudia Pinto.pdf: 798014 bytes, checksum: da2ed9bf3f1617241933592b84cc5356 (MD5) Previous issue date: 2017-05-31 / Este estudo baseia-se na Visão baseada em instituições para explicar as decisões de posse das multinacionais da América Latina em aquisições internacionais. Analisamos especificamente (1) o efeito da distância institucional na posse adquirida, (2) os comportamentos miméticos relacionados com a posse das multinacionais da América Latina quando realizam aquisições internacionais e (3) se adquirir um negócio relacionado tem impacto na força da distância institucional e do isomorfismo mimético. Investigamos quatro níveis de fontes de imitação, incluindo a experiência anterior da própria empresa, empresas domésticas e estrangeiras, e competidores da mesma indústria. Os resultados dos testes empíricos, usando uma análise de regressão logística em uma amostra de 1.334 aquisições internacionais efetuadas por multinacionais da América Latina e uma amostra transversal de 567 aquisições internacionais da indústria da manufatura, durante um período de mais de 20 anos (1995-2015), apoiam o quadro baseado em instituições, com diferentes influências nas escolhas da posse nas aquisições internacionais. Os resultados mostram evidências de que as multinacionais preferem adquirir posse total quando investem em países institucionalmente mais distantes. Mais, confirmamos que os comportamentos miméticos das multinacionais relacionados à posse em aquisições internacionais ocorrem nos quatro níveis. Finalmente, a influência da distância institucional, imitação das empresas estrangeiras e dos competidores da mesma indústria são fortalecidos pela aquisição de um negócio relacionado, enquanto que o efeito de imitar as experiências anteriores da própria empresa e das empresas domésticas é enfraquecido pela aquisição de um negócio relacionado. Contribuímos para a Visão baseada em instituições da Estratégia internacional identificando os comportamentos miméticos específicos à posse adquirida pelas empresas quando se internacionalizam. Além disso, também contribuímos para a crescente literatura sobre multinacionais da América Latina, ou multilatinas, fornecendo um melhor entendimento acerca das suas estratégias em aquisições intenacionais. Usamos uma abordagem multinível para trazer uma nova compreensão de como as multinacionais da América Latina imitam as decisões de posse em aquisições internacionais. Para o estudo da posse, e especificamente da posse em aquisições internacionais, contribuímos com uma interpretação comportamental e consideramos o isomorfismo entre multinacionais, indo além dos determinantes convencionais como custos de transação, assimetria informacional ou incerteza. / This study draws upon the institution-based view to explain the ownership decisions by Latin American multinationals (LAMNCs) in cross-border acquisitions (CBAs). We specifically examine (1) the effect of institutional distance on the ownership acquired, (2) the mimicking behaviors regarding ownership of MNCs from Latin American countries when undertaking CBAs and (3) if acquiring a related business impact the strength of institutional distance and mimetic isomorphism. We endeavor into investigating four levels of imitation sources, including firms own prior experience, home and foreign firms, and industry competitors. The results of the empirical tests, using a logistic regression analysis on a sample of 1,334 CBAs by LAMNCs and a cross-sectional sample of 567 CBAs from the manufacturing industry, over a 20-year period (1995-2015), support an institutional-based framework with different influences in the ownership choices in CBAs. Our findings provide evidence that MNCs prefer to acquire full ownership when investing in institutionally distant countries. Furthermore, we confirmed that the mimicking behavior of MNCs pertaining to ownership in CBAs occurs at four levels. Finally, the influence of institutional distance, mimicking of foreign fims and industry competitors are strengthened by the acquisition of a related business, albeit the effect of mimicking own firm prior experiences and home firms is weakened by the acquisition of a related business. We contribute to the institution-based view of international strategy identifying the specific mimetic behaviors of firms’ internationalization ownership in foreign operations. Moreover, we also contribute to the burgeoning literature on LAMNCs, or multilatinas, by providing a better understanding of their strategies regarding CBAs. We use a multi level approach to bring a new understanding of how LAMNCs mimic ownership decisions in CBAs. To the study on ownership, and specifically ownership in CBAs, we contribute for a behavioral interpretation and consider isomorphism between MNCs, going beyond conventional determinants such as transaction costs, informational asymmetry or uncertainty.