Conversion of membrane-bound Fas(CD95) ligand to its soluble form is associated with downregulation of its proapoptotic activity and loss of liver toxicity.

Human Fas ligand (L) (CD95L) and tumor necrosis factor (TNF)-alpha undergo metalloproteinase-mediated proteolytic processing in their extracellular domains resulting in the release of soluble trimeric ligands (soluble [s]FasL, sTNF-alpha) which, in the case of sFasL, is thought to be implicated in diseases such as hepatitis and AIDS. Here we show that the processing of sFasL occurs between Ser126 and Leu127. The apoptotic-inducing capacity of naturally processed sFasL was reduced by >1,000-fold compared with membrane-bound FasL, and injection of high doses of recombinant sFasL in mice did not induce liver failure. However, soluble FasL retained its capacity to interact with Fas, and restoration of its cytotoxic activity was achieved both in vitro and in vivo with the addition of cross-linking antibodies. Similarly, the marginal apoptotic activity of recombinant soluble TNF-related apoptosis-inducing ligand (sTRAIL), another member of the TNF ligand family, was greatly increased upon cross-linking. These results indicate that the mere trimerization of the Fas and TRAIL receptors may not be sufficient to trigger death signals. Thus, the observation that sFasL is less cytotoxic than membrane-bound FasL may explain why in certain types of cancer, systemic tissue damage is not detected, even though the levels of circulating sFasL are high.

Analysis of stop-gain and frameshift variants in human innate immunity genes.

Loss-of-function variants in innate immunity genes are associated with Mendelian disorders in the form of primary immunodeficiencies. Recent resequencing projects report that stop-gains and frameshifts are collectively prevalent in humans and could be responsible for some of the inter-individual variability in innate immune response. Current computational approaches evaluating loss-of-function in genes carrying these variants rely on gene-level characteristics such as evolutionary conservation and functional redundancy across the genome. However, innate immunity genes represent a particular case because they are more likely to be under positive selection and duplicated. To create a ranking of severity that would be applicable to innate immunity genes we evaluated 17,764 stop-gain and 13,915 frameshift variants from the NHLBI Exome Sequencing Project and 1,000 Genomes Project. Sequence-based features such as loss of functional domains, isoform-specific truncation and nonsense-mediated decay were found to correlate with variant allele frequency and validated with gene expression data. We integrated these features in a Bayesian classification scheme and benchmarked its use in predicting pathogenic variants against Online Mendelian Inheritance in Man (OMIM) disease stop-gains and frameshifts. The classification scheme was applied in the assessment of 335 stop-gains and 236 frameshifts affecting 227 interferon-stimulated genes. The sequence-based score ranks variants in innate immunity genes according to their potential to cause disease, and complements existing gene-based pathogenicity scores. Specifically, the sequence-based score improves measurement of functional gene impairment, discriminates across different variants in a given gene and appears particularly useful for analysis of less conserved genes.

Where will conflicts between alien and rare species occur after climate and land-use change? A test with a novel combined modelling approach

Protecting native biodiversity against alien invasive species requires powerful methods to anticipate these invasions and to protect native species assumed to be at risk. Here, we describe how species distribution models (SDMs) can be used to identify areas predicted as suitable for rare native species and also predicted as highly susceptible to invasion by alien species, at present and under future climate and land-use scenarios. To assess the condition and dynamics of such conflicts, we developed a combined predictive modelling (CPM) approach, which predicts species distributions by combining two SDMs fitted using subsets of predictors classified as acting at either regional or local scales. We illustrate the CPM approach for an alien invader and a rare species associated to similar habitats in northwest Portugal. Combined models predict a wider variety of potential species responses, providing more informative projections of species distributions and future dynamics than traditional, non-combined models. They also provide more informative insight regarding current and future rare-invasive conflict areas. For our studied species, conflict areas of highest conservation relevance are predicted to decrease over the next decade, supporting previous reports that some invasive species may contract their geographic range and impact due to climate change. More generally, our results highlight the more informative character of the combined approach to address practical issues in conservation and management programs, especially those aimed at mitigating the impact of invasive plants, land-use and climate changes in sensitive regions

Hierarchic species-area relationships and the management of forest habitat islands in intensive farmland

Habitat loss and fragmentation due to land use changes are major threats to biodiversity in forest ecosystems, and they are expected to have important impacts on many taxa and at various spatial scales. Species richness and area relationships (SARs) have been used to assess species diversity patterns and drivers, and thereby in the establishment of conservation and management strategies. Here we propose a hierarchical approach to achieve deeper insights on SARs in small forest islets in intensive farmland and to address the impacts of decreasing naturalness on such relationships. In the intensive dairy landscapes of Northwest Portugal, where small forest stands (dominated by pines, eucalypts or both) represent semi-natural habitat islands, 50 small forest stands were selected and surveyed for vascular plant diversity. A hierarchical analytical framework was devised to determine species richness and inter- and intra-patch SARs for the whole set of forest patches (general patterns) and for each type of forest (specific patterns). Differences in SARs for distinct groups were also tested by considering subsets of species (native, alien, woody, and herbaceous). Overall, values for species richness were confirmed to be different between forest patches exhibiting different levels of naturalness. Whereas higher values of plant diversity were found in pine stands, higher values for alien species were observed in eucalypt stands. Total area of forest (inter-patch SAR) was found not to have a significant impact on species richness for any of the targeted groups of species. However, significant intra-patch SARs were obtained for all groups of species and forest types. A hierarchical approach was successfully applied to scrutinise SARs along a gradient of forest naturalness in intensively managed landscapes. Dominant canopy tree and management intensity were found to reflect differently on distinct species groups as well as to compensate for increasing stand area, buffering SARs among patches, but not within patches. Thus, the maintenance of small semi-natural patches dominated by pines, under extensive practices of forest management, will promote native plant diversity while at the same time contributing to limit the expansion of problematic alien invasive species.

Adapting global conservation strategies to climate change at the European scale: the otter as a flagship species

Climate change has created the need for new strategies in conservation planning that account for the dynamics of factors threatening endangered species. Here we assessed climate change threat to the European otter, a flagship species for freshwater ecosystems, considering how current conservation areas will perform in preserving the species in a climatically changed future. We used an ensemble forecasting approach considering six modelling techniques applied to eleven subsets of otter occurrences across Europe. We performed a pseudo-independent and an internal evaluation of predictions. Future projections of species distribution were made considering the A2 and B2 scenarios for 2080 across three climate models: CCCMA-CGCM2, CSIRO-MK2 and HCCPR HAD-CM3. The current and the predicted otter distributions were used to identify priority areas for the conservation of the species, and overlapped to existing network of protected areas. Our projections show that climate change may profoundly reshuffle the otter's potential distribution in Europe, with important differences between the two scenarios we considered. Overall, the priority areas for conservation of the otter in Europe appear to be unevenly covered by the existing network of protected areas, with the current conservation efforts being insufficient in most cases. For a better conservation, the existing protected areas should be integrated within a more general conservation and management strategy incorporating climate change projections. Due to the important role that the otter plays for freshwater habitats, our study further highlights the potential sensitivity of freshwater habitats in Europe to climate change.

Evolutionary history and its relevance in understanding and conserving southern African biodiversity

Abstract : Understanding how biodiversity is distributed is central to any conservation effort and has traditionally been based on niche modeling and the causal relationship between spatial distribution of organisms and their environment. More recently, the study of species' evolutionary history and relatedness has permeated the fields of ecology and conservation and, coupled with spatial predictions, provides useful insights to the origin of current biodiversity patterns, community structuring and potential vulnerability to extinction. This thesis explores several key ecological questions by combining the fields of niche modeling and phylogenetics and using important components of southern African biodiversity. The aims of this thesis are to provide comparisons of biodiversity measures, to assess how climate change will affect evolutionary history loss, to ask whether there is a clear link between evolutionary history and morphology and to investigate the potential role of relatedness in macro-climatic niche structuring. The first part of my thesis provides a fine scale comparison and spatial overlap quantification of species richness and phylogenetic diversity predictions for one of the most diverse plant families in the Cape Floristic Region (CFR), the Proteaceae. In several of the measures used, patterns do not match sufficiently to argue that species relatedness information is implicit in species richness patterns. The second part of my thesis predicts how climate change may affect threat and potential extinction of southern African animal and plant taxa. I compare present and future niche models to assess whether predicted species extinction will result in higher or lower V phylogenetic diversity survival than what would be experienced under random extinction processes. l find that predicted extinction will result in lower phylogenetic diversity survival but that this non-random pattern will be detected only after a substantial proportion of the taxa in each group has been lost. The third part of my thesis explores the relationship between phylogenetic and morphological distance in southern African bats to assess whether long evolutionary histories correspond to equally high levels of morphological variation, as predicted by a neutral model of character evolution. I find no such evidence; on the contrary weak negative trends are detected for this group, as well as in simulations of both neutral and convergent character evolution. Finally, I ask whether spatial and climatic niche occupancy in southern African bats is influenced by evolutionary history or not. I relate divergence time between species pairs to climatic niche and range overlap and find no evidence for clear phylogenetic structuring. I argue that this may be due to particularly high levels of micro-niche partitioning. Résumé : Comprendre la distribution de la biodiversité représente un enjeu majeur pour la conservation de la nature. Les analyses se basent le plus souvent sur la modélisation de la niche écologique à travers l'étude des relations causales entre la distribution spatiale des organismes et leur environnement. Depuis peu, l'étude de l'histoire évolutive des organismes est également utilisée dans les domaines de l'écologie et de la conservation. En combinaison avec la modélisation de la distribution spatiale des organismes, cette nouvelle approche fournit des informations pertinentes pour mieux comprendre l'origine des patterns de biodiversité actuels, de la structuration des communautés et des risques potentiels d'extinction. Cette thèse explore plusieurs grandes questions écologiques, en combinant les domaines de la modélisation de la niche et de la phylogénétique. Elle s'applique aux composants importants de la biodiversité de l'Afrique australe. Les objectifs de cette thèse ont été l) de comparer différentes mesures de la biodiversité, 2) d'évaluer l'impact des changements climatiques à venir sur la perte de diversité phylogénétique, 3) d'analyser le lien potentiel entre diversité phylogénétique et diversité morphologique et 4) d'étudier le rôle potentiel de la phylogénie sur la structuration des niches macro-climatiques des espèces. La première partie de cette thèse fournit une comparaison spatiale, et une quantification du chevauchement, entre des prévisions de richesse spécifique et des prédictions de la diversité phylogénétique pour l'une des familles de plantes les plus riches en espèces de la région floristique du Cap (CFR), les Proteaceae. Il résulte des analyses que plusieurs mesures de diversité phylogénétique montraient des distributions spatiales différentes de la richesse spécifique, habituellement utilisée pour édicter des mesures de conservation. La deuxième partie évalue les effets potentiels des changements climatiques attendus sur les taux d'extinction d'animaux et de plantes de l'Afrique australe. Pour cela, des modèles de distribution d'espèces actuels et futurs ont permis de déterminer si l'extinction des espèces se traduira par une plus grande ou une plus petite perte de diversité phylogénétique en comparaison à un processus d'extinction aléatoire. Les résultats ont effectivement montré que l'extinction des espèces liées aux changements climatiques pourrait entraîner une perte plus grande de diversité phylogénétique. Cependant, cette perte ne serait plus grande que celle liée à un processus d'extinction aléatoire qu'à partir d'une forte perte de taxons dans chaque groupe. La troisième partie de cette thèse explore la relation entre distances phylogénétiques et morphologiques d'espèces de chauves-souris de l'Afrique australe. ll s'agit plus précisément de déterminer si une longue histoire évolutive correspond également à des variations morphologiques plus grandes dans ce groupe. Cette relation est en fait prédite par un modèle neutre d'évolution de caractères. Aucune évidence de cette relation n'a émergé des analyses. Au contraire, des tendances négatives ont été détectées, ce qui représenterait la conséquence d'une évolution convergente entre clades et des niveaux élevés de cloisonnement pour chaque clade. Enfin, la dernière partie présente une étude sur la répartition de la niche climatique des chauves-souris de l'Afrique australe. Dans cette étude je rapporte temps de divergence évolutive (ou deux espèces ont divergé depuis un ancêtre commun) au niveau de chevauchement de leurs niches climatiques. Les résultats n'ont pas pu mettre en évidence de lien entre ces deux paramètres. Les résultats soutiennent plutôt l'idée que cela pourrait être I dû à des niveaux particulièrement élevés de répartition de la niche à échelle fine.

Comparison of human chromosome 21 conserved nongenic sequences (CNGs) with the mouse and dog genomes shows that their selective constraint is independent of their genic environment.

The analysis of conservation between the human and mouse genomes resulted in the identification of a large number of conserved nongenic sequences (CNGs). The functional significance of this nongenic conservation remains unknown, however. The availability of the sequence of a third mammalian genome, the dog, allows for a large-scale analysis of evolutionary attributes of CNGs in mammals. We have aligned 1638 previously identified CNGs and 976 conserved exons (CODs) from human chromosome 21 (Hsa21) with their orthologous sequences in mouse and dog. Attributes of selective constraint, such as sequence conservation, clustering, and direction of substitutions were compared between CNGs and CODs, showing a clear distinction between the two classes. We subsequently performed a chromosome-wide analysis of CNGs by correlating selective constraint metrics with their position on the chromosome and relative to their distance from genes. We found that CNGs appear to be randomly arranged in intergenic regions, with no bias to be closer or farther from genes. Moreover, conservation and clustering of substitutions of CNGs appear to be completely independent of their distance from genes. These results suggest that the majority of CNGs are not typical of previously described regulatory elements in terms of their location. We propose models for a global role of CNGs in genome function and regulation, through long-distance cis or trans chromosomal interactions.

There and back again? Combining habitat suitability modelling and connectivity analyses to assess a potential return of the otter to Switzerland

After a steady decline in the early 20th century, several terrestrial carnivore species have recently recovered in Western Europe, either through reintroductions or natural recolonization. Because of the large space requirements of these species and potential conflicts with human activities, ensuring their recovery requires the implementation of conservation and management measures that address the environmental, landscape and social dimensions of the problem. Few examples exist of such integrated management. Taking the case of the otter (Lutra lutra) in Switzerland, we propose a multi-step approach that allows to (1) identify areas with potentially suitable habitat, (2) evaluate their connectivity, (3) verify the potentiality of the species recolonization from populations in neighbouring countries. We showed that even though suitable habitat is available for the species and the level of structural connectivity within Switzerland is satisfactory, the level of connectivity with neighbouring populations is crucial to prioritize strategies that favour the species recovery in the field. This research is the first example integrating habitat suitability and connectivity assessment at different scales with other factors in a multi-step assessment for species recovery.

Predicting potential distribution of the jaguar (Panthera onca) in Mexico: identification of priority areas for conservation

Aim The jaguar, Panthera onca, is a species of global conservation concern. In Mexico, the northernmost part of its distribution range, its conservation status, is particularly critical, while its potential and actual distribution is poorly known. We propose an ensemble model (EM) of the potential distribution for the jaguar in Mexico and identify the priority areas for conservation.Location Mexico.Methods We generated our EM based on three presence-only methods (Ecological Niche Factor Analysis, Mahalanobis distance, Maxent) and considering environmental, biological and anthropogenic factors. We used this model to evaluate the efficacy of the existing Mexican protected areas (PAs), to evaluate the adequacy of the jaguar conservation units (JCUs) and to propose new areas that should be considered for conservation and management of the species in Mexico.Results Our results outline that 16% of Mexico (c. 312,000 km2) can be considered as suitable for the presence of the jaguar. Furthermore, 13% of the suitable areas are included in existing PAs and 14% are included in JCUs (Sanderson et al., 2002).Main conclusions Clearly much more should be carried out to establish a proactive conservation strategy. Based on our results, we propose here new jaguar conservation and management areas that are important for a nationwide conservation blueprint.

Blocking hypoxia-induced autophagy in tumors restores cytotoxic T-cell activity and promotes regression.

The relationship between hypoxic stress, autophagy, and specific cell-mediated cytotoxicity remains unknown. This study shows that hypoxia-induced resistance of lung tumor to cytolytic T lymphocyte (CTL)-mediated lysis is associated with autophagy induction in target cells. In turn, this correlates with STAT3 phosphorylation on tyrosine 705 residue (pSTAT3) and HIF-1α accumulation. Inhibition of autophagy by siRNA targeting of either beclin1 or Atg5 resulted in impairment of pSTAT3 and restoration of hypoxic tumor cell susceptibility to CTL-mediated lysis. Furthermore, inhibition of pSTAT3 in hypoxic Atg5 or beclin1-targeted tumor cells was found to be associated with the inhibition Src kinase (pSrc). Autophagy-induced pSTAT3 and pSrc regulation seemed to involve the ubiquitin proteasome system and p62/SQSTM1. In vivo experiments using B16-F10 melanoma tumor cells indicated that depletion of beclin1 resulted in an inhibition of B16-F10 tumor growth and increased tumor apoptosis. Moreover, in vivo inhibition of autophagy by hydroxychloroquine in B16-F10 tumor-bearing mice and mice vaccinated with tyrosinase-related protein-2 peptide dramatically increased tumor growth inhibition. Collectively, this study establishes a novel functional link between hypoxia-induced autophagy and the regulation of antigen-specific T-cell lysis and points to a major role of autophagy in the control of in vivo tumor growth.

Pseudogenes in the ENCODE regions: consensus annotation, analysis of transcription, and evolution.

Arising from either retrotransposition or genomic duplication of functional genes, pseudogenes are "genomic fossils" valuable for exploring the dynamics and evolution of genes and genomes. Pseudogene identification is an important problem in computational genomics, and is also critical for obtaining an accurate picture of a genome's structure and function. However, no consensus computational scheme for defining and detecting pseudogenes has been developed thus far. As part of the ENCyclopedia Of DNA Elements (ENCODE) project, we have compared several distinct pseudogene annotation strategies and found that different approaches and parameters often resulted in rather distinct sets of pseudogenes. We subsequently developed a consensus approach for annotating pseudogenes (derived from protein coding genes) in the ENCODE regions, resulting in 201 pseudogenes, two-thirds of which originated from retrotransposition. A survey of orthologs for these pseudogenes in 28 vertebrate genomes showed that a significant fraction ( approximately 80%) of the processed pseudogenes are primate-specific sequences, highlighting the increasing retrotransposition activity in primates. Analysis of sequence conservation and variation also demonstrated that most pseudogenes evolve neutrally, and processed pseudogenes appear to have lost their coding potential immediately or soon after their emergence. In order to explore the functional implication of pseudogene prevalence, we have extensively examined the transcriptional activity of the ENCODE pseudogenes. We performed systematic series of pseudogene-specific RACE analyses. These, together with complementary evidence derived from tiling microarrays and high throughput sequencing, demonstrated that at least a fifth of the 201 pseudogenes are transcribed in one or more cell lines or tissues.

Beyond EA Frameworks: Towards an Understanding of the Adoption of Enterprise Architecture Management

Enterprise architectures (EA) are considered promising approaches to reduce the complexities of growing information technology (IT) environments while keeping pace with an ever-changing business environment. However, the implementation of enterprise architecture management (EAM) has proven difficult in practice. Many EAM initiatives face severe challenges, as demonstrated by the low usage level of enterprise architecture documentation and enterprise architects' lack of authority regarding enforcing EAM standards and principles. These challenges motivate our research. Based on three field studies, we first analyze EAM implementation issues that arise when EAM is started as a dedicated and isolated initiative. Following a design-oriented paradigm, we then suggest a design theory for architecture-driven IT management (ADRIMA) that may guide organizations to successfully implement EAM. This theory summarizes prescriptive knowledge related to embedding EAM practices, artefacts and roles in the existing IT management processes and organization.

Homeostatic proliferation and survival of naïve and memory T cells.

The immune system relies on homeostatic mechanisms in order to adapt to the changing requirements encountered during steady-state existence and activation by antigen. For T cells, this involves maintenance of a diverse repertoire of naïve cells, rapid elimination of effector cells after pathogen clearance, and long-term survival of memory cells. The reduction of T-cell counts by either cytotoxic drugs, irradiation, or certain viruses is known to lead to lymphopenia-induced proliferation and restoration of normal T-cell levels. Such expansion is governed by the interaction of TCR with self-peptide/MHC (p/MHC) molecules plus contact with cytokines, especially IL-7. These same ligands, i.e. p/MHC molecules and IL-7, maintain naïve T lymphocytes as resting cells under steady-state T-cell-sufficient conditions. Unlike naïve cells, typical "central" memory T cells rely on a combination of IL-7 and IL-15 for their survival in interphase and for occasional cell division without requiring signals from p/MHC molecules. Other memory T-cell subsets are less quiescent and include naturally occurring activated memory-phenotype cells, memory cells generated during chronic viral infections, and effector memory cells. These subsets of activated memory cells differ from central memory T cells in their requirements for homeostatic proliferation and survival. Thus, the factors controlling T-cell homeostasis can be seen to vary considerably from one subset to another as described in detail in this review.

Combining T2-preparation with spectral and spatial selectivity for improved coronary MRA

Cardiovascular disease is the leading cause of death worldwide. Within this subset, coronary artery disease (CAD) is the most prevalent. Magnetic resonance angiography (MRA) is an emerging technique that provides a safe, non-invasive way of assessing CAD progression. To generate contrast between tissues, MR images are weighted according to the magnetic properties of those tissues. In cardiac MRI, T2 contrast, which is governed by the rate of transverse signal loss, is often created through the use of a T2-Preparation module. T2-Preparation, or T2-Prep, is a magnetization preparation scheme used to improve blood/myocardium contrast in cardiac MRI. T2-Prep methods generally use a non-selective +90°, 180°, 180°, -90° train of radiofrequency (RF) pulses (or variant thereof), to tip magnetization into the transverse plane, allow it to evolve, and then to restore it to the longitudinal plane. A key feature in this process is the combination of a +90° and -90° RF pulse. By changing either one of these, a mismatch occurs between signal excitation and restoration. This feature can be exploited to provide additional spectral or spatial selectivity. In this work, both of these possibilities are explored. The first - spectral selectivity - has been examined as a method of improving fat saturation in coronary MRA. The second - spatial selectivity - has been examined as a means of reducing imaging time by decreasing the field of view, and as a method of reducing artefacts originating from the tissues surrounding the heart. Two additional applications, parallel imaging and self-navigation, are also presented. This thesis is thus composed of four sections. The first, "A Fat Signal Suppression for Coronary MRA at 3T using a Water-Selective Adiabatic T2-Preparation Technique", was originally published in the journal Magnetic Resonance in Medicine (MRM) with co-authors Ruud B. van Heeswijk and Matthias Stuber. The second, "Combined T2-Preparation and 2D Pencil Beam Inner Volume Selection", again with co-authors Ruud van Heeswijk and Matthias Stuber, was also published in the journal MRM. The third, "A cylindrical, inner volume selecting 2D-T2-Prep improves GRAPPA-accelerated image quality in MRA of the right coronary artery", written with co-authors Jerome Yerly and Matthias Stuber, has been submitted to the "Journal of Cardiovascular Magnetic Resonance", and the fourth, "Combined respiratory self-navigation and 'pencil-beam' 2D-T2 -Prep for free-breathing, whole-heart coronary MRA", with co¬authors Jerome Chaptinel, Giulia Ginami, Gabriele Bonanno, Simone Coppo, Ruud van Heeswijk, Davide Piccini, and Matthias Stuber, is undergoing internal review prior to submission to the journal MRM. -- Les maladies cardiovasculaires sont la cause principale de décès dans le monde : parmi celles-ci, les maladies coronariennes sont les plus répandues. L'angiographie par résonance magnétique (ARM) est une technique émergente qui fournit une manière sûre, non invasive d'évaluer la progression de la coronaropathie. Pour obtenir un contraste entre les tissus, les images d'IRM sont pondérées en fonction des propriétés magnétiques de ces tissus. En IRM cardiaque, le contraste en T2, qui est lié à la décroissance du signal transversal, est souvent créé grâce à l'utilisàtion d'un module de préparation T2. La préparation T2, ou T2-Prep, est un système de préparation de l'aimantation qui est utilisé pour améliorer le contraste entre le sang et le myocarde lors d'une IRM cardiaque. Les méthodes de T2-Prep utilisent généralement une série non-sélective d'impulsions de radiofréquence (RF), typiquement [+ 90°, 180°, 180°, -90°] ou une variante, qui bascule l'aimantation dans le plan transversal, lui permet d'évoluer, puis la restaure dans le plan longitudinal. Un élément clé de ce processus est la combinaison des impulsions RF de +90° et -90°. En changeant l'une ou l'autre des impulsions, un décalage se produit entre l'excitation du signal et de la restauration. Cette fonction peut être exploitée pour fournir une sélectivité spectrale ou spatiale. Dans cette thèse, les deux possibilités sont explorées. La première - la sélectivité spectrale - a été examinée comme une méthode d'améliorer la saturation de la graisse dans l'IRM coronarienne. La deuxième - la sélectivité spatiale - a été étudiée comme un moyen de réduire le temps d'imagerie en diminuant le champ de vue, et comme une méthode de réduction des artefacts provenant des tissus entourant le coeur. Deux applications supplémentaires, l'imagerie parallèle et la self-navigation, sont également présentées. Cette thèse est ainsi composée de quatre sections. La première, "A Fat Signal Suppression for Coronary MRA at 3T using a Water-Selective Adiabatic T2-Preparation Technique", a été publiée dans la revue médicale Magnetic Resonance .in Medicine (MRM) avec les co-auteurs Ruud B. van Heeswijk et Matthias Stuber. La deuxième, Combined T2-Preparation and 2D Pencil Beam Inner Volume Selection", encore une fois avec les co-auteurs Ruud van Heeswijk et Matthias Stuber, a également été publiée dans le journal MRM. La troisième, "A cylindrical, inner volume selecting 2D-T2-Prep improves GRAPPA- accelerated image quality in MRA of the right coronary artery", écrite avec les co-auteurs Jérôme Yerly et Matthias Stuber, a été présentée au "Journal of Cardiovascular Magnetic Resonance", et la quatrième, "Combined respiratory self-navigation and 'pencil-beam' 2D-T2 -Prep for free-breathing, whole-heart coronary MRA", avec les co-auteurs Jérôme Chaptinel, Giulia Ginami, Gabriele Bonanno , Simone Coppo, Ruud van Heeswijk, Davide Piccini, et Matthias Stuber, subit un examen interne avant la soumission à la revue MRM.