Les générateurs de nombres aléatoires sont des blocs destinés à produire des quantités numériques qui doivent être indépendantes et uniformément distribuées. Ces RNG sont utilisés dans des contextes sécuritaires où l'utilisation de nombres aléatoires est requise (génération de clefs cryptographiques, nonces des protocoles cryptographiques, marqueurs anti-rejeu, contre-mesures face aux attaques par canaux cachés) et où leur qualité est primordiale. Tous les composants électroniques ayant une fonction sécuritaire, comme par exemple les cartes à puces, incluent un ou plusieurs générateurs aléatoires (basés sur des principes physiques). En conséquence, le RNG est une brique centrale des applications sécuritaires et sa défaillance, totale ou partielle met donc en péril la fonctionnalité dans son ensemble. Ce travail de thèse porte sur l'étude des RNG physiques (PTRNG) et la modélisation de l'aléa à partir des caractérisations électroniques et mathématiques du circuit. Cette étude se place essentiellement dans le contexte de la norme AIS 31 du BSI* qui fait référence dans de nombreux pays européens. Cette norme est l‘une des rares qui impose des caractérisations sur les PTRNG, incluant notamment un modèle stochastique de ce dernier. Dans ce contexte, il est crucial de pouvoir valider la méthodologie d'évaluation proposée par ces normes et c'est sur ce point que j'ai focalisé mon travail de thèse.*Bundesamt für Sicherheit in der Informationstechnik, agence fédérale allemande chargée de la sécurité des technologies de l'information / Random number generators (RNG) are primitives that produce independent and uniformly distributed digital values, RNG are used in secure environments where the use of random numbers is required (generation of cryptographic keys, nonces in cryptographic protocols, padding values, countermeasures against side-channel attacks) and where the quality of the randomness is essential. All electronic components with a security function, such as smart cards, include one or more random generators (based on physical principles). Consequently, the RNG is an essential primitive for security applications. A flaw in security of the random number generation process directly impacts the security of the cryptographic system. This thesis focuses on the study of physical RNG (PTRNG), the modeling of its randomness and an electronic characterizations of the circuit. This study is in the context of the AIS-31 standard which is published by the BSI* and followed by many European countries. This standard is one of the few that require a characterizations of the PTRNG and a stochastic model. In this context, it is crucial to validate the evaluation methodology proposed by these standards and l focused on them during my thesis.*Bundesamt fiir Sicherheit in der Informationstechnik, federal agency German responsible for the security of information technology

Les nombres aléatoires sont indispensables dans de nombreuses applications notamment en cryptographie où l’aléa est utilisé dans les protocoles de sécurité. Les générateurs de nombres aléatoires, plus connus sous le nom de RNG comme “Random Number Generator” se déclinent en deux familles, les PRNG (Pseudo RNG) qui sont des générateurs de nombres aléatoires ayant des séquences déterministes et les TRNG (True RNG) qui sont des générateurs d’aléa “vrai”, donc non prédictibles. Les applications cryptographiques utilisent à la fois les TRNG et les PRNG. Un PRNG nécessite une valeur initiale, ou graine, qui peut être la sortie d’un TRNG. Les TRNG tirent profit de l’aléa des phénomènes physiques. Les TRNGs dans les technologies numériques comme les FPGAs font appel à des oscillateurs qui présentent l’inconvénient de pouvoir être attaqués par couplage harmonique. De façon à évaluer la qualité entropique d’un TRNG, des standards basés sur des tests statistiques ont été élaborés par des organismes de certification comme le NIST ou la BSI. Cependant, il est recommandé de formaliser, par le biais d’un modèle, le caractère stochastique de la génération d’aléa. Dans cette thèse, nous étudions une architecture de TRNG, peu coûteuse et robuste face aux attaques harmoniques car elle n’utilise pas d’oscillateurs. Ce TRNG extrait une variable aléatoire en exploitant à la fois les états métastables des bascules et les fluctuations temporelles (ou gigue) des signaux échantillonnés. Nous proposons par la suite un modèle stochastique qui nous permet de décrire le comportement aléatoire du TRNG indépendamment de la technologie ciblée. Les caractérisations et évaluations sur des circuits prototypes en technologies FPGA et ASIC montrent que l’architecture TRNG proposée génère de l’aléa de qualité et est robuste face aux variations environnementales / Random numbers are required in numerous applications namely in cryptography where randomness is used in security protocols. There are two main classes of Random Number Generators (RNG) : The Pseudo RNG (PRNG) which have a deterministic sequence, and the True RNG (TRNG) which generates unpredictable random numbers. Cryptographic applications use both TRNG and PRNG. The PRNG needs an initial value, or seed, which can be the output of a TRNG. In digital technologies, like FPGAs, TRNG are commonly based on oscillators which have the drawback of being biased by harmonic coupling. In order to assess the entropic quality of TRNGs, standards based on statistical tests have been elaborated by certification organisms namely the NIST and the BSI. However, it is recommended to formalize the stochastic behaviour of the randomness generation process. In this Ph.D, we address the design and quality evaluation of TRNGs in digital circuits. We study of a low-cost digital TRNG without oscillators, hence robust against harmonics attacks. The proposed TRNG exploits both the metastability phenomenon and the jitter noise in CMOS digital flip-flops to generate the random numbers. A stochastic model of this TRNG has been formalized. This model describes the random generation process regardless of the targeted technology. The characterization and evaluation on a prototype circuit, in FPGA and ASIC technologies, has shown that the proposed TRNG architecture generates randomness of good quality and is robust against environmental variations.

The human cognitive biases that result in anthropomorphism, the moral confusion surrounding the status of robots, and wider societal concerns related to the deployment of artificial intelligence at scale all motivate the study of robot transparency --- the design of robots such that they may be fully understood by humans. Based on the hypothesis that robot transparency leads to better (in the sense of more accurate) mental models of robots, I investigate how humans perceive and understand a robot when they encounter it, both in online video and direct physical encounter. I also use Amazon Mechanical Turk as a platform to facilitate online experiments with larger population samples. To improve transparency I use a visual real-time transparency tool providing a graphical representation of the internal processing and state of a robot. I also describe and deploy a vocalisation algorithm for transparency. Finally, I modify the form of the robot with a simple bee-like cover, to investigate the effect of appearance on transparency. I find that the addition of a visual or vocalised representation of the internal processing and state of a robot significantly improves the ability of a naive observer to form an accurate model of a robot's capabilities, intentions and purpose. This is a significant result across a diverse, international population sample and provides a robust result about humans in general, rather than one geographic, ethnic or socio-economic group in particular. However, all the experiments were unable to achieve a Mental Model Accuracy (MMA) of more than 59%, indicating that despite improved transparency of the internal state and processing, naive observers' models remain inaccurate, and there is scope for further work. A vocalising, or 'talking', robot greatly increases the confidence of naive observers to report that they understand a robot's behaviour when observed on video. Perhaps we might be more easily deceived by talking robots than silent ones. A zoomorphic robot is perceived as more intelligent and more likeable than a very similar mechanomorphic robot, even when the robots exhibit almost identical behaviour. A zoomorphic form may attract closer visual attention, and whilst this results in an improved MMA, it also diverts attention away from transparency measures, reducing their efficacy to further increase MMA. The trivial embellishment of a robot to alter its form has significant effects on our understanding and attitude towards it. Based on the concerns that motivate this work, together with the results of the robot transparency experiments, I argue that we have a moral responsibility to make robots transparent, so as to reveal their true machine nature. I recommend the inclusion of transparency as a fundamental design consideration for intelligent systems, particularly for autonomous robots. This research also includes the design and development of the 'Instinct' reactive planner, developed as a controller for a mobile robot of my own design. Instinct provides facilities to generate a real-time 'transparency feed'--- a real-time trace of internal processing and state. Instinct also controls agents within a simulation environment, the 'Instinct Robot World'. Finally, I show how two instances of Instinct can be used to achieve a second order control architecture.

<p>The principle of universal shipborne automatic identification system (AIS) is to allow automatic exchange of shipboard information between one vessel and another. Saab TransponderTech AB has an operating AIS transponder on the market and the purpose of this report is to investigate alternative technologies that could result in a highly integrated replacement for the existing hardware. </p><p>Design aspects of a system-on-chip are discussed, such as: available system-on- chip technologies, intellectual property, on-chip bus structures and development tools. This information is applied to the existing hardware and the integration possibilities of the various parts of the AIS transponder is investigated. </p><p>The focus will be on two main transponder parts that are possible to replace with highly integrated circuits. The first of these parts is the so-called digital part where system-on-chip platforms for different technologies have been investigated with a special interest in a highly integrated FPGA implementation. The second part is the radio frequency receivers where alternatives to the existing superheterodyne receiver are discussed. </p><p>The conclusion drawn is that there exist technologies for developing a highly integrated AIS transponder. An attractive highly integrated transponder could consist of a FPGA system-on-chip platform with subsampling digital receivers and additional components that are unsuitable for integration.</p>

El objetivo fundamental de este artículo es el de analizar, identificar y posteriormente cuantificar, las áreas de la costa Española Mediterránea, con mayor riesgo de sufrir un derrame de hidrocarburos procedente del tráfico marítimo de hidrocarburos. En el estudio que fundamenta este artículo, se han tomado en consideración una serie de variables, de entre las que destacamos, las peculiaridades geográficas, climáticas o la densidad de tráfico, que alimenten una función aleatoria. Esta función objetiva ponderará los diferentes puntos de la costa e identificando los que tengan una mayor probabilidad de riesgo.En la investigación aquí presentada, se pretende evidenciar dónde pueden ubicarse las áreas del Mediterráneo Occidental español donde puede haber mayor riesgo de derrame potencialmente.EL ESCENARIO GEOGRÁFICOEl Mar Mediterráneo se extiende sobre unos 3.800 Km. de Este a Oeste y unos 800 Km. de Norte a Sur, cubriendo una superficie aproximada de 2,5 millones de Km2, lo cual representa unas cinco veces la de España. Su cuenca alberga un volumen de 3,7 millones de Km3 con una profundidad media de unos 1.500 metros, la cual es claramente inferior a la media oceánica. Morfológicamente, el Mar Mediterráneo aparece separado del Océano Atlántico por el Estrecho de Gibraltar, de unos 14 Km. de anchura y 300 metros de profundidad. Otras comunicaciones, aunque menos importantes desde el punto de vista hidrológico, conectan el mar Mediterráneo con el Mar Negro y con el Océano Índico a través del Mar Rojo. Se trata, respectivamente de los estrechos del Bósforo y de los Dardanelos, entre los que queda delimitado el pequeño Mar de Mármara y el Canal de Suez, éste último de carácter artificial y de relativamente reciente apertura (1867). A grandes rasgos, podemos afirmar que el Mediterráneo está compuesto de dos grandes cuencas, separadas entre sí por el Canal de Sicilia y denominadas Cuenca Oriental y Cuenca Occidental.La cuenca Mediterránea se caracteriza por los limitados recursos agrícolas, forestales, ganaderos e incluso pesqueros. Por otro lado, también son limitados los recursos energéticos en la margen septentrional, aunque, por el contrario, hay una importante cantidad de gas natural e hidrocarburos en la margen meridional. Ante el mencionado panorama de recursos, nos encontramos con una importante población, la cual se prevé que rondará los 500 millones de habitantes y cerca de 300 millones de turistas anuales, a mediados de la próxima década.En la cuenca meridional se encuentran los principales puertos exportadores de hidrocarburos, destacando Libia como país mediterráneo con mayores reservas. En la margen europea, destaca el puerto de Marsella, con unas importaciones de crudo del orden de 65 millones de toneladas anuales, además de Italia, donde se localizan tres de los principales puertos en este tipo de tráficos, los cuales suman unas 90 millones de toneladas de crudo anuales. / Pollution risks coming from the shipping traffic is one of the real risks that Spanish coast can face. It is much closed the remember of the Fedra bulk carrier in the strait of Gibraltar, the Prestige tanker in Finisterre or the Castor near accident off the Almeria coast. The main objective of this paper is to analyse, identify and further to quantify, the areas in the Mediterranean Spanish coast, with biggest risk of suffering a hydrocarbons spill coming from the tankers maritime traffic. The study, in which this paper is based, has been considered a set of variables among which we can remark the geographic particularities, the climatic issues, the ships' age or the traffic density; that are going to feed an algorithm. This objective function will weight those different parameters in the entire coast and will identify the ones with the biggest risk probability. The results are going to put in evidence where are the most critical areas in the Spanish coast, when talking about its risk of spill.THE GEOGRAPHICAL SCENARIOThe Mediterranean Sea extends approximately on 3,800 km from East to West and 800 km from North to South, covering a surface of 2.5 millions of km2 which represents 5 times the surface of Spain. Its basin keeps a volume of 3.7 million of km3 with an average depth of 1,500 km which is clearly lower than the ocean average. The Mediterranean Sea is linked to the Atlantic Ocean through the Gibraltar Strait that is about 14 km wide and 300 metres deep. Other secondary passes from the hydrological point of view, is the connection with the Black Sea and the Indic Ocean through the Red Sea. From a general point of view we can identify two clear basins in the Mediterranean, limited by the Sicily canal and called Eastern and Western Mediterranean...The Mediterranean basin, is identified by the limited agricultural, forest, cattle and even fishing, resources, including the energetic ones at least in the Northern coast, but with large reserves of natural gas and hydrocarbons in the Southern coast. In a parallel sense we find a population of 500 millions of persons and around 300 millions of tourists per year that are expected in this decade. Also in this coast there are the main hydrocarbons export ports, most of all in Libya, the Mediterranean country with the biggest reserves. In the European coast we must remark the port of Marseilles, as the biggest import port in terms of volume, with 65 millions of metric tonnes per year or Italy where there are placed the three main ports of such kind of traffic, with an added volume of 90 millions of metric tonnes.The Mediterranean hydrocarbon traffic routes, from a internal point of view, are the ones from North to South and East to West, but we should add the crude oil traffic in transit that in the year 2006 sum up to 421 millions of metric tonnes only of crude oil, from which 72 millions where among non intra Mediterranean ports [1].

The principle of universal shipborne automatic identification system (AIS) is to allow automatic exchange of shipboard information between one vessel and another. Saab TransponderTech AB has an operating AIS transponder on the market and the purpose of this report is to investigate alternative technologies that could result in a highly integrated replacement for the existing hardware. Design aspects of a system-on-chip are discussed, such as: available system-on- chip technologies, intellectual property, on-chip bus structures and development tools. This information is applied to the existing hardware and the integration possibilities of the various parts of the AIS transponder is investigated. The focus will be on two main transponder parts that are possible to replace with highly integrated circuits. The first of these parts is the so-called digital part where system-on-chip platforms for different technologies have been investigated with a special interest in a highly integrated FPGA implementation. The second part is the radio frequency receivers where alternatives to the existing superheterodyne receiver are discussed. The conclusion drawn is that there exist technologies for developing a highly integrated AIS transponder. An attractive highly integrated transponder could consist of a FPGA system-on-chip platform with subsampling digital receivers and additional components that are unsuitable for integration.

An ethnographic study loosely informed by the theoretical framework of distributed cognition was carried out in order to describe how mariners have adopted the Automatic Identification System (AIS) in their work practice, or"made the technology their own". AIS is a transponder-based identification and communication system that allows ships to automatically identify and track each other. In addition to facilitating the identification and tracking of ships, objectives behind the introduction of AIS are to"simplify informational exchange", and"provide additional information to assist situation awareness". Participant observation and interviews were made at four different ships, as well as at two shore stations. A focus group was also held at a maritime conference. The study gave some interesting results. For example, a Problem of Public Information Loss was identified. It is tentatively suggested that this problem has been overlooked partly because of a widespread but impoverished model of communication which does not account for the role of side-participants in a conversation. It is concluded that more research needs to be done on maritime work and the use of new bridge technology.

Den tekniska utvecklingen har gjort att nya möjligheter har tillkommit för att säkra framförandet av fartyg och effektivisera ruttplaneringen. Ett av de effektiviseringssäten som för närvarande utvecklas är ruttutbyte. Syftet med studien är att med hjälp av ett simulerat scenario samt frågeformulär belysa eventuella risker förknippade med ruttutbyte till sjöss. Studien speglar deltagarnas upplevelse av den kritiska situationen som simuleringen återger och visar även skillnaden i beslutsfattandet mellan erfarna och oerfarna navigatörer. Tidigare forskning betonar till stor del fördelar med taktiskt ruttutbyte men mindre angående nackdelar med systemet. Med hjälp frågeformulär insamlades deltagarnas erfarenheter och upplevelser angående taktiskt ruttutbyte. Enligt scenariot var det planerat att ett av fartygen i trafikflödet skulle avvika från sin planerade rutt. Ruttutbyte har simulerats genom att visa fartygsrutter i ECDIS. Resultatet av studien visar att det finns ett klart mönster mellan olika gruppers beslutsfattande och graden av pålitlighet till de i ECDIS visade rutterna för andra fartyg. Studien visar även att det finns en påtaglig risk för kollision om navigatörer följer ruttutbytet utan vidare kritisk granskning på grund av falsk trygghet. / The technical advances in the maritime sector have led to new possibilities to secure the safe passage of the vessels and improve the process of route planning. One example of such advances is route exchange. The purpose of this study was by means of simulation to pinpoint whether there are any probable risks connected with the tactical route exchange. This study reflected the experience of the participants of the critical situation portrayed in the simulation. It also takes in to account the difference of the decision-making between the different groups. These groups are composed of experienced navigators and unexperienced navigators. The study also describes the simulation from a fact-based standpoint. Earlier research describes mostly advantages of the tactical route exchange and in less degree the disadvantages of the tactical route exchange. The study has been composed by means of simulation at several occasions. With the help of questionnaires, a general picture has been compiled of the participants’ background, experience and the general opinion about the tactical route exchange. According to the prepared scenario there was one vessel which was intended to deviate from its intended route. The route exchange was projected in the ECDIS console. The result shows that there is a pattern between the different groups´ decision-making and the degree of reliability of the projected routes. The study also points out the obvious risk of collision dependent on the incompleteness of the system and weaknesses for the worst-case scenario which should be taken into account in the future upgrades of the system.

Résumé Le cadre théorique de la contingence structurelle associe généralement « contexte, structure et performance » (Burns et Stalker, 1961; Woodward, 1965; Lawrence et Lorsch, 1967 ; Mintzberg, 1979).Le besoin de tester cette théorie dans l’environnement d’un pays sous développé (PSD) nous a conduit, dans cette recherche, à l’utilisation d’un cadre réduit basé uniquement sur des liens entre la technologie (remplacée par TI) et la structure (Galbraith, 1972 ; Lacrampe, 1974 ; Leifer, 1988). Notre cadre théorique s’appuie sur les approches managériales, économiques et organisationnelles des TI et de l’EDI (Leavitt, 1968 ; Scott Morton, 1991). Il utilise la théorie contingente de la gestion comptable (Otley, 1980; Chapman, 1997) et des systèmes d’information comptable AIS (Sutton, 1995; Maudlin et Ruchala, 1999; Baldwin et alii, 2000; Dunk, 2001) comme domaine d’opérationnalisation (système d’information fonctionnel). Ce travail commence par la constitution d’une boîte à outils contenant toutes les notions de base à utiliser (théories organisationnelles, TI - technologies de l'information, réseaux informatiques et EDI – échange des données informatisées), conformément aux principes fondateurs du MIS basés sur trois disciplines : Computer, Management et Organization Sciences (Culman et Swanson, 1986). La grille de lecture de la littérature est inspirée par la taxonomie de Urbaczenski, Jessup and Wheeler (2002) qui propose quatre catégories de recherche : économique, organisationnelle, technique et autre. Cette revue de la littérature permettra de proposer un modèle de recherche d’impact des TI et de l’EDI basé sur le cadre de référence structuro - fonctionnaliste et élaboré selon les principes de la théorie des systèmes. Le modèle de recherche utilise une structure causale conçue suivant l’impératif technologique (Markus et Robey, 1988). Il vise à expliquer l'impact organisationnel des TI à travers la stratégie (Porter et Millar, 1985; Wiseman, 1985 ; Palvia, Palvia et Zigli, 1990) sur la conception des MIS / AIS et des structures organisationnelles dans les entreprises d’un pays sous développé (PSD). Ce modèle d’impact organisationnel teste les hypothèses proposées, à partir des données d’une observation longitudinale (1970 à 2002) de quatorze (14) entreprises de la République Démocratique du Congo. Les entreprises échantillonnées de façon non probabiliste en deux catégories sont observées à travers l'introduction de l'EDI dans le système d’information comptable. Les tests de structure des données et de fonctionnement du modèle établissent l’impact des TI sur les structures organisationnelles et parfois sur les systèmes d’information, mais avec des nuances d’atténuation et de contribution suivant la nature de l’environnement ou l’usage de la stratégie. La conclusion de cette étude propose un processus d’apprentissage aux managers congolais pour éviter les dysfonctionnements organisationnels lors de l’adoption d’une nouvelle TI. Elle pose aussi le problème de validité des structures causales utilisées dans les recherches pour analyser l’impact organisationnel des TI. Abstract EDI adoption’s analysis in Congolese firms : an organizational structure impact of IT This research aims to identify the impact of IT (information technology) on organizational structure transformation in the firms of an under developed country. The framework of the contingency theory generally associates "context, structure and performance" (Burns and Stalker, 1961; Woodward, 1965; Lawrence and Lorsch, 1967; Mintzberg, 1979). The model of impact of TI and EDI suggested by this research uses a reduced framework only based on links between technology (replaced by IT) and structure (Galbraith, 1972; Lacrampe, 1974; Leifer, 1988). Based on the original paradigm of MIS, our theoretical framework uses managerial, economic and organizational approaches of IT and EDI (Leavitt, 1968; Scott Morton, 1991). It uses the contingent theory of accounting management (Otley, 1980; Chapman, 1997) and of accounting information systems (AIS - Sutton, 1995; Maudlin and Ruchala, 1999; Baldwin and alii, 2000; Dunk, 2001) as empirical field (functional information system). This workshop begins with the constitution of a toolbox containing all basic concepts to use (organization theories, IT - information technologies, computer networks and EDI – electronic data interchange), in accordance with the original MIS paradigm founded on three disciplines: Computer, Management and Organization Sciences (Culman and Swanson, 1986, p. 298). Then, we draw a theoretical framework of analysis which begins with a literature review inspired by Urbaczenski, Jessup and Wheeler’s taxonomy (2002). This literature review will allow to proposing a research model of IT and EDI designed according to the functionalist framework and system theory principles. The model of research uses a causal structure conceived according to the technological imperative (Markus and Robey, 1988). It aims at explaining the organizational impact of IT through the strategy (Porter and Millar, 1985; Wiseman, 1985; Palvia, Palvia and Zigli, 1990) on the design of MIS / AIS and the organizational structures in the companies of an under developed country (UDC). This study tests the hypotheses of the organizational impact‘s model suggested, basing from the data of a longitudinal observation (1970 to 2002) of fourteen (14) Congolese firms. The companies sampled by convenience in two layers are observed through the introduction of EDI into the accounting information system. The tests of data structure and of operating model performed on the introduction of accounting EDI, confirm the impact of IT on the organizational structures and sometimes on the information systems - IS. That with nuances of attenuation and contribution according to the nature of the environment or the use of the strategy. The conclusion of this study proposes a process of training to the congolese managers to avoid the organizational dysfunctions during the adoption of new IT. It poses also the problem of validity of the causal structures used in research to analyze the organizational impact of IT.

La scoliose idiopathique de l’adolescent (SIA) est définie comme une courbure de la colonne vertébrale supérieure à 10 degrés, qui est de cause inconnue et qui affecte de façon prépondérante les adolescents. Des études précédentes sur des modèles murins ont démontré une inactivation partielle du gène Pitx1. Cette inactivation partielle provoque une déformation spinale sévère lors du développement des souris Pitx1+/-, ce qui est grandement similaire au phénotype de la SIA. En se basant sur ces observations, nous postulons que la perte de fonction de Pitx1 pourrait avoir un rôle dans la SIA et pourrait être régulée par des mécanismes moléculaires spécifiques. En effet, des études faites sur l’expression de Pitx1 révèlent une perte de son expression dans les ostéoblastes dérivés de patients SIA au niveau de l’ARNm. Nous émettons l’hypothèse que la perte de Pitx1 dans la SIA pourrait être déclenchée par des facteurs hypoxiques puisqu’il est connu que Pitx1 est réprimé par l’hypoxie et que HIF-2 alpha est surexprimés dans les ostéoblastes des patients SIA même dans des conditions normoxiques. De plus, nous avons découvert une mutation dans le domaine ODD des HIF-1 alpha chez certains patients SIA (3,1%). Une fonction connue de ce domaine est de stabiliser et d’augmenter l’activité transcriptionnelle de HIF-1 alpha dans des conditions normoxiques. Nous avons confirmé, par la technique EMSA, l’existence d’un élément de réponse fonctionnel à l’hypoxie au niveau du promoteur de Pitx1. Cependant, des co-transfections avec des vecteurs d’expression pour HIF-1 alpha et HIF-2 alpha, en présence de leur sous-unité beta ARNT, ont conduit à une activation du promoteur de Pitx1 dans la lignée cellulaire MG-63 ainsi que dans les ostéoblastes des sujets contrôles. Il est intéressant de constater qu’aucune activité du promoteur de Pitx1 dans les ostéoblastes SIA n’a été observée, même après la co-expression de HIF-2 alpha et ARNT, confirmant le fait que l’expression de Pitx1 est abrogée dans la SIA. Dans l’ensemble, nos résultats démontrent un rôle important de Pitx1 dans la SIA et une possible régulation par des facteurs hypoxiques. / Adolescent Idiopathic Scoliosis is a lateral curvature of the spine greater than 10 degrees, with an unknown cause, affecting primarily adolescents. Previous mouse model studies showed that partial inactivation of Pitx1 gene resulted in the development of severe spinal deformities in Pitx1 +/- mice, which is strikingly similar to the AIS phenotype. Based on this observation, we postulated that loss of Pitx1 function might have a role in AIS and could be regulated through specific molecular mechanisms. Indeed, expression studies revealed a loss of Pitx1 expression in osteoblasts derived from AIS patients, at the mRNA level. We hypothesized that the loss of Pitx1 in AIS could be triggered by hypoxic factors, since Pitx1 is known to be repressed by hypoxia and that HIF-2 alpha was up regulated in AIS osteoblasts even under normoxic conditions. Also, we found a mutation in the ODD domain of HIF-1 alpha in some AIS patients (3.1%), which is known to stabilize and enhance HIF-1 alpha transcriptional activity in normoxic conditions. We confirmed through EMSA the existence of a functional hypoxia response element on Pitx1 promoter. However, co-transfection assays with HIF-1 alpha and HIF-2 alpha expression vectors in the presence of their beta subunit ARNT led to the activation of Pitx1 promoter in human osteoblast cell line MG-63 cells and osteoblasts from control subjects. Interestingly, no Pitx1 promoter activity was observed in AIS osteoblasts, even after the co expression of HIF2 alpha and ARNT, consolidating the fact that Pitx1 expression is abrogated in AIS. Taken together, our findings show an important role for Pitx1 in AIS and hypoxic factors could be one of its regulators.