Originally 2A was characterised in foot-and-mouth disease virus. Site directed mutagenesis identified a C-terminus consensus motif [D(V/I)ExNPGP] and it is proposed that 2A interacts with the exit tunnel of the ribosome in a way that a specific peptide bond is skipped between the last glycine of 2A and the proline of 2B, thus providing a discontinuity in translation, resulting in release of discrete proteins from one single ORF. 2A was also identified in other picornaviruses, positive, single and double-stranded RNA insect viruses and mammalian rotaviruses. A motif present at the C-terminus of the 2A oligopeptide [D(V/I)ExNPGP] is very highly, though not completely conserved . The sequence upstream of this motif shows, however, no apparent conservation between 2As of different viruses. In this study, extensive site-directed mutagenesis were performed on several 2A sequences and a series of ‘hybrid' 2As comprising different consensus motifs juxtaposed with different upstream contexts were created as part of a detailed analysis of the mechanism of 2A-mediated ribosome stalling. The results demonstrated that a minimal region of twenty to twenty-three amino acids interacts with the exit tunnel of the ribosome to bring about a pause in processivity, alter the peptidyl transferase centre geometry and restrict the ribosome A site via two distinctive stalling mechanisms. Other molecular analyses tested here will require further optimisations or alternative methods: a visual method to explore the dynamics of re-initiation of translation from proline codon, purification of the translation-regulating factors and structural resolution of 2A sequences. Previously, cellular 2As were identified in non-LTR retrotransposons of trypanosomes. It is reported here as part of two other cellular organisms Saccoglossus kowalevskii (acorn worm) and Branchiostoma floridae (amphioxus). In the acorn worm, the nucleotides sequences corresponding to 2A motifs were part of the untranslated genome. In amphioxus, three 2A elements were identified in hypothetical proteins, and at the N-terminus of twenty non-LTR retrotransposons.

Considerable variation exists both within and between species in nuclear DNA content. Despite there being no obvious functional role for much of this DNA, many studies have reported phenotypic correlations with genome size at various taxonomic levels. This suggests that DNA plays a functional role beyond the traditionally understood mechanisms. One such example of a phenotypic correlation with DNA content is present in the genus Silene, where a negative correlation between DNA content and flower size exists within and between species. This relationship is consistent with the direction of sexual dimorphism in DNA content (caused by heteromorphic sex-chromosomes) and flower size in the most studied species in the genus: S. latifolia. This thesis takes a comparative approach between two closely related species in the genus (S. latifolia and S. marizii), which differ markedly in their nuclear DNA content, in order to investigate the nature and phenotypic impacts of variation in DNA content. A phenotypic survey from a number of S. marizii populations reveals that the pattern of DNA content variation in this species is very different to that in S. latifolia. In particular, phenotypic correlations with DNA content appear be much weaker, whilst sexual dimorphism in DNA content, when present, appears to occur in either direction. A survey of interspecific hybrids suggests that this may be due to an enlarged S. marizii X-chromosome and that DNA content in hybrids may be biased with regard to their parents. Repetitive elements may be significant constituents of plant genomes. A study of Ty1-copia class retrotransposons in the two species reveals that they are present as a large and highly heterogeneous population. Phylogenetic analysis of these elements suggests a substantial degree of genetic isolation between the two species. Finally, an assessment of the flow-cytometric method, used to estimate DNA content, reveals substantial error associated with the method, but only limited evidence for stoichiometric effects.

A utilização de sistemas semi-ativos no controle de movimento e vibração vem crescendo muito nos últimos anos, e está se firmando como a opção mais econômica em muitas aplicações. Os sistemas de controle semi-ativos baseados em fluidos magneto-reológicos (MR) já são empregados no controle de vibrações desde máquinas de lavar a grandes pontes suspensas, e até mesmo no controle de vibração de edifícios sujeitos a abalos sísmicos. No controle de movimento, eles têm sido aplicados em aparelhos de fisioterapia, próteses de joelho humano e embreagens. No setor automobilístico, os sistemas semi-ativos são empregados em sistemas de controle da suspensão e sistemas anti-rolagem, e também no controle de sistemas de torque e tração. Visto a crescente importância dos sistemas de controle semi-ativo, este trabalho aborda este assunto dividindo-o em duas partes: a primeira, apresentada no volume 1, trata do projeto de atuadores magneto-reológicos e do seu modelamento dinâmico voltado para projetos de controle; e a segunda parte, apresentada no volume 2, trata de projeto de controladores para sistemas semi-ativos, mais especificamente voltados para o controle de suspensão veicular semi-ativa, buscando a melhoria do desempenho em conforto, segurança e dirigibilidade do veículo. Na primeira parte, a maior contribuição deste trabalho está em preencher uma lacuna na literatura no que diz respeito a uma técnica sistemática de projeto de atuadores magneto-reológicos e da forma mais adequada de sua representação dinâmica para projetos de controle, que é feita a partir de dados experimentais. Na segunda parte deste trabalho buscou-se desenvolver um sistema de controle economicamente viável para veículos utilitários (caminhonetes principalmente). Estes são os veículos que mais carecem de sistemas de suspensão capazes de atender a uma grande variedade de situações (variação de pista, variação de carga), e cujo mercado exige uma relação custo/benefício melhor que aquela dos mercados de carros de luxo, onde estes sistemas são empregados atualmente. Como resultados mais importantes deste trabalho têmse: uma proposição para o uso da lei de controle LQG/LTR em sistemas não estritamente próprios; um modelo de um veículo utilitário completo com sete graus de liberdade e capaz de representar as situações mais importantes do comportamento dinâmico deste tipo de veículo; o desenvolvimento de uma estratégia de controle robusto baseado na técnica LQG/LTR, adequada para trabalhar com atuadores semi-ativos, e que utiliza sensores de custo compatível com a aplicação. O sistema de controle proposto foi capaz de melhorar o desempenho em conforto e segurança, evitando situações de perda de aderência dos pneus e comportamentos dinâmicos indesejáveis destes veículos, que foi verificado experimentalmente e através de simulações em computador. / The application of semi-active systems to motion and vibration control has significantly grown during the last years, and it is becoming an economically viable option for several applications. Semi-active systems based on magneto-rheological (MR) fluids were applied to vibration control ranging from washing machines to suspended bridges, and also in vibration control of buildings under seismic tremors. Regarding the movement control, they have been used in gym apparati, human knee prosthesis and clutches. More specifically in the automotive industry, semi-active systems have been applied in suspension and anti-roll systems, and also in torque and traction control systems. This work treats this subject dividing it into two parts: the first one, presented in volume 1, deals with the design of semi-active actuators based on magneto-rheological fluids and dynamic modeling; and the second one, presented in volume 2, deals with the design of semi-active control for vehicular suspension systems. The control main objective is the performance improvement in comfort, safety and handling features of a vehicle. In the first part, the main contribution of this work is to fulfill a literature gap regarding a systematic procedure for design of magneto-rheological actuators and to find a better representation for the dynamic behavior regarding the control system development, which is done based on experimental data analysis. The second part of this work leaded with the development of a vehicular suspension system for utility vehicles (for SUVs, and mainly for light trucks), which need suspension systems able to face a great number of situations (road variation, load variation, etc.), and which present stability problems due to its high gravity center height. Important results of this work are: the development of a robust control strategy based on LQG/LTR techniques for non-strictly proper systems, the development of a dynamic model for light trucks and SUVs with seven degrees of freedom; the development of a robust control strategy based on the LQG/LTR synthesis, suit to work with semi-active actuators, and using sensors with costs compatible to the application. The proposed control system was able to improve the performance of comfort and safety, avoiding the loss of adherence between tires and the ground and other undesirable dynamic behaviors of these vehicles, that was verified experimentally and through computer simulations.

Le sepsis est défini par l’apparition de dysfonctions d’organes, multiples et mortelles, causées par une réponse de l’hôte dérégulée suite à une infection. L’hétérogénéité de la maladie représente un défi clinique majeur au regard de la prise en charge thérapeutique, et à ce jour les marqueurs proposés ne suffisent pas à stratifier les patients. Les rétrovirus endogènes humains (HERV) pourraient être des marqueurs pertinents,compte tenu des propriétés immunosuppressives de leurs enveloppes et de leur expression dans des maladies inflammatoires et auto-immunes. Cette thèse a pour objectif de savoir dans quelle mesure les HERV sont exprimés et modulés, dans des conditions d’inflammation et d’immunosuppression. Pour cela,nous avons utilisé une puce à ADN haute densité permettant (i) l’analyse de la transcription de 363 689HERV et 1500 gènes, et (ii) une lecture fonctionnelle de l’activité des LTR. L’expression des HERV a été objectivée (i) dans un modèle ex-vivo de tolérance à l’endotoxine sur des cellules mononuclées du sang périphérique (PBMC) d’individus sains et (ii) sur sang total provenant d’individus sains et de patients en choc septique, stratifiés ou non en fonction du statut immunitaire. (1) De 5,6% à 6,9% des HERV sont exprimés dans le compartiment sanguin et environ 20% des LTR possèdent une fonction promotrice ou polyA, les deux fonctions étant mutuellement exclusives. (2) Le contenu du transcriptome HERV est modulé ex vivo dans le contexte de tolérance à l’endotoxine laissant apparaitre deux grands phénotypes transcriptionnels. L’expression de certains loci HERV est corrélée au statut immunitaire de patient septique.L’évaluation d’une signature moléculaire complexe sur une cohorte de validation, permet la séparation en deux groupes présentant des critères de sévérité distincts, suggérant les HERV/MaLR comme biomarqueurs de stratification. (3) L’analyse de la co-expression des gènes et des HERV a permis d’intégrer ceux-ci au sein de réseaux associées à la réponse de l’hôte et de proposer des hypothèses fonctionnelles. / Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection.The heterogeneity of the disease present a major clinical challenge with regard to the therapeutic coverage,and this day the proposed markers are not enough to stratify patients. The human endogenous retrovirus(HERV) could be relevant markers, considering the immunosuppressives properties of their envelopes andtheir expression in inflammatory and autoimmune disease. The aim of this thesis is to know to what extentthe HERVs are expressed and modulated, in inflammatory and immunocompromised contexts. For this, weused a high density DNA chip allowing (i) the transcription analysis of 363,689 HERV and 1500 genes,and (ii) a functional reading of LTRs activities. The HERVs expression was objectified (i) in endotoxintolerance ex vivo model in peripheral blood mononuclear cells (PBMCs) of healthy volunteers and (ii) inwhole blood of healthy volunteers and septic shock patients, stratified or not according to immunity state.(1) Of 5,6% at 6,9% of HERVs are expressed in the blood compartment and around 20% of LTRs have apromoter or polyA function, both functions being mutually exclusive. (2) The HERV transcriptome ismodulated in ex vivo endotoxin tolerance model letting appear two higher transcriptional phenotypes. Theexpression of some HERVs loci are correlated of the immunity state of the septic shock patients. Theevaluation of molecular signature in validation cohort, allowed to separate in two patients groupspresenting different severity criteria, suggesting HERV/MaLR as biomarkers of stratification. (3) The coexpressedanalysis of genes and HERVs allowed to integrate these within signaling pathways associated atthe host immune response and to provide functional hypothesis.

Submitted by Cleide Dantas (cleidedantas@ufpa.br) on 2014-07-31T13:11:15Z No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_ControladoresRobustosTipo.pdf: 1406069 bytes, checksum: 94652acee018b9469e9601f509fb6582 (MD5) / Approved for entry into archive by Ana Rosa Silva (arosa@ufpa.br) on 2014-09-04T15:03:43Z (GMT) No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_ControladoresRobustosTipo.pdf: 1406069 bytes, checksum: 94652acee018b9469e9601f509fb6582 (MD5) / Made available in DSpace on 2014-09-04T15:03:43Z (GMT). No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_ControladoresRobustosTipo.pdf: 1406069 bytes, checksum: 94652acee018b9469e9601f509fb6582 (MD5) Previous issue date: 2014 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O objetivo principal desta dissertação é apresentar uma solução eficiente, prática e de simples implementação para um problema recorrente em projetos de controladores robustos multivariáveis do tipo LQG/LTR: a elevada ordem que estes controladores podem obter dependendo das complicações apresentadas pelo sistema dificultando para que este possa ser controlado de maneira satisfatória. Para que esta meta seja alcançada, é apresentada uma técnica de redução do modelo de sistemas com metodologia bastante descomplicada, dispensando qualquer necessidade de complexas programações para a sua utilização. Esta metodologia porém, é somente aplicável a uma classe bastante específica de sistema. Em suma, o sistema deve possuir variáveis de estado desacopladas do restante do sistema, ou seja, variáveis que não sofram influências de outras e que também não provoquem grande efeito nas saídas do sistema. Foi escolhido um sistema multivariável de sexta ordem, com duas entradas e duas saídas para que a técnica de redução de ordem de modelo seja testada. Este sistema possui as características especiais mencionadas anteriormente bem como exige o projeto de compensador dinâmico e a adição de integradores às suas saídas para que seja controlado adequadamente. Este trabalho pretende apresentar o procedimento de todo o projeto mencionado, desde a obtenção de um modelo de ordem reduzida até a implementação do controlador LQG/LTR. Em seguida, o controlador obtido é testado através de diversas simulações e os resultados encontrados são discutidos para a avaliação da eficácia e da praticidade do método proposto para obtenção de controladores de ordem reduzida. / This thesis’ main goal is to introduce an efficient, practical and easy to implement solution to a recurring problem in projects of LQG/LTR multivariable robust controllers: the high order these controllers may obtain depending on the complications presented by the system hampering its control in a satisfactory way. For this goal to be achieved, a system model reduction technique with very simple methodology is introduced, dispensing any needs of complex programming for its use. This methodology however, is only applicable to a very specific class of system. Summarizing, the system must have state variables decoupled from the rest of the system, that is, variables that don’t not influenced by others and that also don’t cause major effects on the system’s outputs. It was chosen a sixth order multivariable system having two inputs and two outputs for the model order reduction be tested. This system has the special characteristics mentioned before and also demands a dynamic compensator project as well as the integrators addition to its outputs so it can be controlled adequately. This text intends to show the procedure for the whole project, since the reduced order model achievement to the LQG/LTR controller implementation. Then, the obtained controller is tested through several simulations and the attained results are discussed for effectiveness and practicality evaluation of the proposed method for reduced order controller project.

Esta tese é estruturada em dois capítulos. O primeiro capítulo explora os retrotransposons com LTR (LTR-RT) em cana-de-açúcar e grande parte de seus resultados foram publicados no artigo \'\'Analysis of plant LTR-retrotransposons at the fine-scale family level reveals individual molecular patterns\'\'. Nossos resultados mostraram que as diferentes famílias de LTR-RT em cana-de-açúcar possuem estruturas e regulação distintas. O segundo capítulo desta tese visa responder a perguntas que surgiram durante a primeira metade deste trabalho, mas ao invés de focar no genoma de uma planta optamos por trabalhar com linhagem Del de LTR-RT em dez genomas de angiospermas sequenciados. Os resultados desta parte do trabalho foram submetidos para publicação no artigo intitulado \'\'Virus-like attachment sites and plastic CpG islands: landmarks of diversity in plant Del retrotransposons\'\'. Os resultados mostraram que a LTR é uma região dinâmica e importante para a evolução dos LTR-RTs. Nós especulamos que mudanças nas LTR atuem como gatilhos para a diversificação dos LTR-RTs. / This doctoral thesis is structured in two chapters. In the first chapter we explore the LTRretrotransposons (LTR-RT) in sugarcane, these results were published in an article entitled \'\'Analysis of plant LTR-etrotransposons at the fine-scale family level reveals individual molecular patterns\'\'. In this paper we show that different sugarcane LTR-RT families have distinct structure and are differentially regulated. In the second chapter we try to find answers to questions that came up in the first half of this work, but instead of focusing in one plant genome we chose to work with the Del lineage of LTR-RT in tem angiosperm sequenced genomes. These results are submitted to publication as an article entitled \'\'Virus-like attachment sites and plastic CpG islands: landmarks of diversity in plant Del retrotransposons\'\'. Our results indicate that the LTR region is dynamic and important in the evolution of LTR-retrotransposons, we speculate that it is a trigger for retrotransposon diversification.

Ce travail concerne la commande optimale robuste des systèmes hydrauliques à surface libre<br />(canaux d'irrigation). Nous nous sommes intéressés à deux approches de synthèse de<br />commande optimale. La première approche consiste à synthétiser une loi de commande<br />optimale LQG /H2-LTR (de dimension finie) avec pondérations fréquentielles robuste vis-àvis<br />des erreurs engendrées par la réduction à un modèle de dimension finie des équations de<br />Saint Venant. Le modèle réduit est obtenu par collocation orthogonale à partir du modèle<br />linéarisé tangent de Saint Venant. Un observateur est également proposé qui permet de<br />reconstruire l'état du système à partir des seuls états mesurés à l'amont et à l'aval de chaque<br />bief. Le régulateur optimal robuste et l'observateur ont été testés sur différents modèles de<br />référence ainsi que sur un micro-canal expérimental réel. Ils sont comparés aux résultats<br />obtenus par d'autres méthodes de régulation connues. La seconde approche de synthèse<br />consiste à faire l'approximation en dimension finie d'une loi de commande (de dimension<br />infinie) obtenue à partir des équations de Saint Venant linéarisées mais non réduites. Nous<br />présentons dans ce rapport des résultats liés à l'analyse et à la synthèse du régulateur optimal<br />LQ en dimension infinie appliquée aux équations de Saint Venant. Nous décrivons ensuite le<br />moyen d'obtenir une approximation en dimension finie du régulateur LQ sur la base de<br />l'équation de Riccati d'opérateurs associée au problème.

A utilização de sistemas semi-ativos no controle de movimento e vibração vem crescendo muito nos últimos anos, e está se firmando como a opção mais econômica em muitas aplicações. Os sistemas de controle semi-ativos baseados em fluidos magneto-reológicos (MR) já são empregados no controle de vibrações desde máquinas de lavar a grandes pontes suspensas, e até mesmo no controle de vibração de edifícios sujeitos a abalos sísmicos. No controle de movimento, eles têm sido aplicados em aparelhos de fisioterapia, próteses de joelho humano e embreagens. No setor automobilístico, os sistemas semi-ativos são empregados em sistemas de controle da suspensão e sistemas anti-rolagem, e também no controle de sistemas de torque e tração. Visto a crescente importância dos sistemas de controle semi-ativo, este trabalho aborda este assunto dividindo-o em duas partes: a primeira, apresentada no volume 1, trata do projeto de atuadores magneto-reológicos e do seu modelamento dinâmico voltado para projetos de controle; e a segunda parte, apresentada no volume 2, trata de projeto de controladores para sistemas semi-ativos, mais especificamente voltados para o controle de suspensão veicular semi-ativa, buscando a melhoria do desempenho em conforto, segurança e dirigibilidade do veículo. Na primeira parte, a maior contribuição deste trabalho está em preencher uma lacuna na literatura no que diz respeito a uma técnica sistemática de projeto de atuadores magneto-reológicos e da forma mais adequada de sua representação dinâmica para projetos de controle, que é feita a partir de dados experimentais. Na segunda parte deste trabalho buscou-se desenvolver um sistema de controle economicamente viável para veículos utilitários (caminhonetes principalmente). Estes são os veículos que mais carecem de sistemas de suspensão capazes de atender a uma grande variedade de situações (variação de pista, variação de carga), e cujo mercado exige uma relação custo/benefício melhor que aquela dos mercados de carros de luxo, onde estes sistemas são empregados atualmente. Como resultados mais importantes deste trabalho têmse: uma proposição para o uso da lei de controle LQG/LTR em sistemas não estritamente próprios; um modelo de um veículo utilitário completo com sete graus de liberdade e capaz de representar as situações mais importantes do comportamento dinâmico deste tipo de veículo; o desenvolvimento de uma estratégia de controle robusto baseado na técnica LQG/LTR, adequada para trabalhar com atuadores semi-ativos, e que utiliza sensores de custo compatível com a aplicação. O sistema de controle proposto foi capaz de melhorar o desempenho em conforto e segurança, evitando situações de perda de aderência dos pneus e comportamentos dinâmicos indesejáveis destes veículos, que foi verificado experimentalmente e através de simulações em computador. / The application of semi-active systems to motion and vibration control has significantly grown during the last years, and it is becoming an economically viable option for several applications. Semi-active systems based on magneto-rheological (MR) fluids were applied to vibration control ranging from washing machines to suspended bridges, and also in vibration control of buildings under seismic tremors. Regarding the movement control, they have been used in gym apparati, human knee prosthesis and clutches. More specifically in the automotive industry, semi-active systems have been applied in suspension and anti-roll systems, and also in torque and traction control systems. This work treats this subject dividing it into two parts: the first one, presented in volume 1, deals with the design of semi-active actuators based on magneto-rheological fluids and dynamic modeling; and the second one, presented in volume 2, deals with the design of semi-active control for vehicular suspension systems. The control main objective is the performance improvement in comfort, safety and handling features of a vehicle. In the first part, the main contribution of this work is to fulfill a literature gap regarding a systematic procedure for design of magneto-rheological actuators and to find a better representation for the dynamic behavior regarding the control system development, which is done based on experimental data analysis. The second part of this work leaded with the development of a vehicular suspension system for utility vehicles (for SUVs, and mainly for light trucks), which need suspension systems able to face a great number of situations (road variation, load variation, etc.), and which present stability problems due to its high gravity center height. Important results of this work are: the development of a robust control strategy based on LQG/LTR techniques for non-strictly proper systems, the development of a dynamic model for light trucks and SUVs with seven degrees of freedom; the development of a robust control strategy based on the LQG/LTR synthesis, suit to work with semi-active actuators, and using sensors with costs compatible to the application. The proposed control system was able to improve the performance of comfort and safety, avoiding the loss of adherence between tires and the ground and other undesirable dynamic behaviors of these vehicles, that was verified experimentally and through computer simulations.

Esta tese é estruturada em dois capítulos. O primeiro capítulo explora os retrotransposons com LTR (LTR-RT) em cana-de-açúcar e grande parte de seus resultados foram publicados no artigo \'\'Analysis of plant LTR-retrotransposons at the fine-scale family level reveals individual molecular patterns\'\'. Nossos resultados mostraram que as diferentes famílias de LTR-RT em cana-de-açúcar possuem estruturas e regulação distintas. O segundo capítulo desta tese visa responder a perguntas que surgiram durante a primeira metade deste trabalho, mas ao invés de focar no genoma de uma planta optamos por trabalhar com linhagem Del de LTR-RT em dez genomas de angiospermas sequenciados. Os resultados desta parte do trabalho foram submetidos para publicação no artigo intitulado \'\'Virus-like attachment sites and plastic CpG islands: landmarks of diversity in plant Del retrotransposons\'\'. Os resultados mostraram que a LTR é uma região dinâmica e importante para a evolução dos LTR-RTs. Nós especulamos que mudanças nas LTR atuem como gatilhos para a diversificação dos LTR-RTs. / This doctoral thesis is structured in two chapters. In the first chapter we explore the LTRretrotransposons (LTR-RT) in sugarcane, these results were published in an article entitled \'\'Analysis of plant LTR-etrotransposons at the fine-scale family level reveals individual molecular patterns\'\'. In this paper we show that different sugarcane LTR-RT families have distinct structure and are differentially regulated. In the second chapter we try to find answers to questions that came up in the first half of this work, but instead of focusing in one plant genome we chose to work with the Del lineage of LTR-RT in tem angiosperm sequenced genomes. These results are submitted to publication as an article entitled \'\'Virus-like attachment sites and plastic CpG islands: landmarks of diversity in plant Del retrotransposons\'\'. Our results indicate that the LTR region is dynamic and important in the evolution of LTR-retrotransposons, we speculate that it is a trigger for retrotransposon diversification.

Les rétrotransposons L1 (Long INterspersed Element-1) sont des éléments génétiques mobiles dont l'activité contribue à la dynamique du génome humain par mutagenèse insertionnelle. Les conséquences génétiques et épigénétiques d'une nouvelle insertion, et la capacité d'un L1 à être remobilisé, sont directement liées au site d’intégration dans le génome. Aussi, l’analyse des sites d’intégration des L1s est capitale pour comprendre leur impact fonctionnel - voire pathogène -, en particulier lors de la tumorigenèse ou au cours du vieillissement, et l’évolution de notre génome. Dans ce but, nous avons induit de façon expérimentale la rétrotransposition d'un élément L1 actif plasmidique dans des cellules en culture. Puis, nous avons cartographié les insertions obtenues de novo dans le génome humain grâce à une méthode de séquençage à haut-débit, appelée ATLAS-seq. Finalement, les sites pré-intégratifs identifiés par cette approche ont été analysés en relation avec un grand jeu de données publiques regroupant les caractéristiques structurales, génétiques ou épigénétiques de ces loci. Ces expériences ont révélé que les éléments L1 s’intègrent préférentiellement dans des régions de la chromatine faiblement exprimées et renfermant des activateurs faibles. Nous avons aussi trouvé plusieurs positions chromosomiques qui constituent des points chauds d'intégrations récurrentes. Nos résultats indiquent que la distribution des insertions de L1 de novo n’est pas aléatoire, que ce soit à l’échelle chromosomique ou à plus petite échelle, et ouvrent la porte à l'identification des déterminants moléculaires qui contrôlent la distribution chromosomique des L1s dans notre génome / Retrotransposons are mobile genetic elements that employ an RNA intermediate and a reverse transcription step for their replication. Long INterspersed Elements-1 (LINE-1 or L1) form the only autonomously active retrotransposon family in humans. Although most copies are defective due to the accumulation of mutations, each individual genome contains an average of 100 retrotransposition-competent L1 copies, which contribute to the dynamics of contemporary human genomes. L1 integration sites in the host genome directly determine the genetic consequences of the integration and the fate of the integrated copy. Thus, where L1 integrates in the genome, and whether this process is random, is critical to our understanding of human genome evolution, somatic genome plasticity in cancer and aging, and host-parasite interactions. To characterize L1 insertion sites, rather than studying endogenous L1 which have been subjected to evolutionary selective pressure, we induced de novo L1 retrotransposition by transfecting a plasmid-borne active L1 element into HeLa S3 cells. Then, we mapped de novo insertions in the human genome at nucleotide resolution by a dedicated deep-sequencing approach, named ATLAS-seq. Finally, de novo insertions were examined for their proximity towards a large number of genomic features. We found that L1 preferentially integrates in the lowly-expressed and weak enhancer chromatin segments. We also detected several hotspots of recurrent L1 integration. Our results indicate that the distribution of de novo L1 insertions is non-random both at local and regional scales, and pave the way to identify potential cellular factors involved in the targeting of L1 insertions