Direct visualization of the trimeric structure of the ASIC1a channel, using AFM imaging.

There has been confusion about the subunit stoichiometry of the degenerin family of ion channels. Recently, a crystal structure of acid-sensing ion channel (ASIC) 1a revealed that it assembles as a trimer. Here, we used atomic force microscopy (AFM) to image unprocessed ASIC1a bound to mica. We detected a mixture of subunit monomers, dimers and trimers. In some cases, triple-subunit clusters were clearly visible, confirming the trimeric structure of the channel, and indicating that the trimer sometimes disaggregated after adhesion to the mica surface. This AFM-based technique will now enable us to determine the subunit arrangement within heteromeric ASICs.

"In vitro" reconstitution of the fragmentation of vacuoles

Résumé La fragmentation des membranes est un processus commun à beaucoup d'organelles dans une cellule. Les mitochondries, le noyau, le réticulum endoplasmique, les phagosomes, les peroxisomes, l'appareil de Golgi et les lysosomes (vacuoles chez la levure) se fragmentent en plusieurs copies en réponse à des sitmulis environnementaux, tels que des stresses, ou dans une situtation normale durant le cycle cellulaire, afin d' être transférer dans les cellules filles. La fragmentation des membranes est également observée pendant le processus d'endocytose, lors de la formation de vésicules endocytiques, mais également dans tout le traffic intracellulaire, lors de la genèse d'une vésicule de transport. Le processus de fragmentation est donc généralement important. La découverte en 1991 d'une dynamin-like GTPase comme protéine impliquée dans la fragmentation de la membrane plasmique durant l'endocytose a ouvert ce domaine de recherche. Dès lors des dynamines ont été découvertes sur la pluspart des organelles, ce qui suggère un processus de fragmentation des membranes commun à l'ensemble de la cellule. Cependant, l'ensemble des protéines impliquées ainsi que le mécanisme de la fragmentation reste encore à élucider. Mon projet de thèse était d'établir un test in vitro de fragmentation des vacuoles utile à la compréhension du mécanisme de ce processus. Le choix de ce système est judicieux pour plusieurs raisons; premièrement les vacuoles fragmentent naturellement durant le cycle cellulaire, deuxièment leur taille permet de visualiser facilement leur morphologie par simple microscopie optique, finalement elles peuvent être isolées en quantité intéressante avec un haut degré de pureté. In vivo, les vacuoles peuvent être facilement fragmentées par un stress osmotique. Un tel test permet d'identifier des protéines impliquées dans le mécanisme comme dans le criblage que j'ai effectué sur l'ensemble de la collection de délétions des gènes non-essentiels chez la levure. Cependant un test in vitro est ensuite indispensable pour jouer avec les protéines découvertes afin d'en élucider le mécanisme. Avec mon test in vitro, j'ai confirmé l'implication des protéines SNAREs dans la fragmentation et j'ai permis de comprendre la régulation de la quantité de vacuoles et de leur taille par le complexe TORC1 dans une situation de stress. 7 Résumé large public Les cellules de chaque organisme sont composées de différents compartiments appelés organelles. Chacun possède une fonction bien définie afin de permettre la vie et la croissance de la cellule. Ils sont entourés de membrane, qui joue le role de barrière spécifiquement perméable, afin de garder l'intégrité de chacun. Dans des conditions de croissance normale, les cellules prolifèrent. Durant la division cellulaire amenant à la formation d'une nouvelle cellule, chaque organelle doit se diviser afin de fournir l'ensemble des organelles à la cellule fille. La division de chaque organelle nécessite la fragmentation de la membrane les entourant. Des protéines dynamine-like GTPase ont été découvertes sur presque l'ensemble des organelles d'une cellule. Elles sont impliquées dans les processus de fragmentation des membranes. Dès lors l'idée d'un mécanisme commun est apparu. Cependant cette réaction, par sa complexité, ne peut pas impliquer une protéine unique. La découverte d'autres facteurs et la compréhension du mécanisme reste à faire. La première étape peut se faire par étude in vivo, c'est-à-dire avec des cellules entières, la deuxième étape, quant à elle, nécessite d'isoler les protéines impliquées et de jouer avec les différents paramètres, ce qui signifie donc un travail in vitro, séparé des cellules. Mon travail a constisté à établir un procédé expérimental in vitro pour étudier la fragmentation des membranes. Je travaille avec des vacuoles de levures pour étudier les réactions membranaires. Les vacuoles sont les plus grandes organelles présentes dans les levures. Elles sont impliquées principalement dans la digestion. Comme toute organelle, elles se fragmentent durant la division cellulaire. Le procédé expérimental comporte une première étape, l'isolation des vacuoles et, deuxièmement, l'incubation de celles-ci avec des composés essentiels à la réaction. En parallèle, j'ai mis en évidence, par un travail in vivo, de nouvelles protéines impliquées dans le processus de fragmentation des membranes. Ceci a été fait en réalisant un criblage par microscopie d'une collection de mutants. Parmi ces mutants, j'ai cherché ceux qui présentaient un défaut dans la fragmentation des vacuoles. Ces deux procédés expérimentaux, in vitro et in vivo, m'ont permis de découvrir de nouvelles protéines impliquées dans cette réaction, ainsi que de mettre en évidence un mécanisme utlilisé par la cellule pour réguler la fragmentation des vacuoles. 8 Summary Fragmentation of membranes is common for many organelles in a cell. Mitochondria, nucleus, endoplasmic reticulum, phagosomes, peroxisomes, Golgi and lysosomes (vacuoles in yeast) fragment into multiple copies in response to environmental stimuli, such as stresses, or in a normal situation during the cell cycle in order to be transferred into the daughter cell. Fragmentation of membrane occurs during endocytosis, at the latest step in endocytic vesicle formation, and also in intracellular trafficking, when traffic vesicles bud. This field of research was opened in 1991 when a dynamin-like GTPase was found to be involved in fragmentation of the plasma membrane during endocytosis. Since dynamin-like GTPases have been found on most organelles, similarities in their mechanisms of fragmentation might exist. However, many proteins involved in the mechanism of fragmentation remain unknown. My thesis project was to establish an in vitro assay for membrane fragmentation in order to create a tool to study the mechanism of this process. I chose vacuoles as a model organelle for several reasons: first of all, vacuoles fragment under physiological conditions during cell cycle, secondly their size makes their morphology easily visible under the light microscope, and finally vacuoles can be isolated in good amounts with relatively high degrees of purity. In vivo, vacuole fragmentation can be induced with an osmotic shock. Such a simple assay facilitates the identification of new proteins involved in the process. I used this tool to screen of the entire knockout collection of non-essential genes in Saccharomyces cerevisiae for mutants defective in vacuole fragmentation. The in vitro system will be useful to characterize the mutants and to study the mechanism of fragmentation in detail. I used my in vitro assay to confirm the involvement of vacuolar SNARE proteins in fragmentation of the organelle and to uncover that number and size of vacuoles in the cell is regulated by the TORC1 complex via selective stimulation of fragmentation activity.

KnotProt: a database of proteins with knots and slipknots.

The protein topology database KnotProt, http://knotprot.cent.uw.edu.pl/, collects information about protein structures with open polypeptide chains forming knots or slipknots. The knotting complexity of the cataloged proteins is presented in the form of a matrix diagram that shows users the knot type of the entire polypeptide chain and of each of its subchains. The pattern visible in the matrix gives the knotting fingerprint of a given protein and permits users to determine, for example, the minimal length of the knotted regions (knot's core size) or the depth of a knot, i.e. how many amino acids can be removed from either end of the cataloged protein structure before converting it from a knot to a different type of knot. In addition, the database presents extensive information about the biological functions, families and fold types of proteins with non-trivial knotting. As an additional feature, the KnotProt database enables users to submit protein or polymer chains and generate their knotting fingerprints.

Investigating Gaze of Children with ASD in Naturalistic Settings.

BACKGROUND: Visual behavior is known to be atypical in Autism Spectrum Disorders (ASD). Monitor-based eye-tracking studies have measured several of these atypicalities in individuals with Autism. While atypical behaviors are known to be accentuated during natural interactions, few studies have been made on gaze behavior in natural interactions. In this study we focused on i) whether the findings done in laboratory settings are also visible in a naturalistic interaction; ii) whether new atypical elements appear when studying visual behavior across the whole field of view. METHODOLOGY/PRINCIPAL FINDINGS: Ten children with ASD and ten typically developing children participated in a dyadic interaction with an experimenter administering items from the Early Social Communication Scale (ESCS). The children wore a novel head-mounted eye-tracker, measuring gaze direction and presence of faces across the child's field of view. The analysis of gaze episodes to faces revealed that children with ASD looked significantly less and for shorter lapses of time at the experimenter. The analysis of gaze patterns across the child's field of view revealed that children with ASD looked downwards and made more extensive use of their lateral field of view when exploring the environment. CONCLUSIONS/SIGNIFICANCE: The data gathered in naturalistic settings confirm findings previously obtained only in monitor-based studies. Moreover, the study allowed to observe a generalized strategy of lateral gaze in children with ASD when they were looking at the objects in their environment.

Transgenic plant factories for the production of biopolymers and plateform chemicals

In the mid-to long-term, resource constraints will force society to cover a significant share of the future demand for fuels, materials and chemicals by renewable resources. This trend is already visible in the increasing conversion of carbohydrates and plant oils to fuels, chemicals, and polymers. In this perspective, we discuss current efforts and ideas to produce platform chemicals and polymers directly in transgenic plants.

Rules of origin : from analysis to reform

General Introduction This thesis can be divided into two main parts :the first one, corresponding to the first three chapters, studies Rules of Origin (RoOs) in Preferential Trade Agreements (PTAs); the second part -the fourth chapter- is concerned with Anti-Dumping (AD) measures. Despite wide-ranging preferential access granted to developing countries by industrial ones under North-South Trade Agreements -whether reciprocal, like the Europe Agreements (EAs) or NAFTA, or not, such as the GSP, AGOA, or EBA-, it has been claimed that the benefits from improved market access keep falling short of the full potential benefits. RoOs are largely regarded as a primary cause of the under-utilization of improved market access of PTAs. RoOs are the rules that determine the eligibility of goods to preferential treatment. Their economic justification is to prevent trade deflection, i.e. to prevent non-preferred exporters from using the tariff preferences. However, they are complex, cost raising and cumbersome, and can be manipulated by organised special interest groups. As a result, RoOs can restrain trade beyond what it is needed to prevent trade deflection and hence restrict market access in a statistically significant and quantitatively large proportion. Part l In order to further our understanding of the effects of RoOs in PTAs, the first chapter, written with Pr. Olivier Cadot, Celine Carrère and Pr. Jaime de Melo, describes and evaluates the RoOs governing EU and US PTAs. It draws on utilization-rate data for Mexican exports to the US in 2001 and on similar data for ACP exports to the EU in 2002. The paper makes two contributions. First, we construct an R-index of restrictiveness of RoOs along the lines first proposed by Estevadeordal (2000) for NAFTA, modifying it and extending it for the EU's single-list (SL). This synthetic R-index is then used to compare Roos under NAFTA and PANEURO. The two main findings of the chapter are as follows. First, it shows, in the case of PANEURO, that the R-index is useful to summarize how countries are differently affected by the same set of RoOs because of their different export baskets to the EU. Second, it is shown that the Rindex is a relatively reliable statistic in the sense that, subject to caveats, after controlling for the extent of tariff preference at the tariff-line level, it accounts for differences in utilization rates at the tariff line level. Finally, together with utilization rates, the index can be used to estimate total compliance costs of RoOs. The second chapter proposes a reform of preferential Roos with the aim of making them more transparent and less discriminatory. Such a reform would make preferential blocs more "cross-compatible" and would therefore facilitate cumulation. It would also contribute to move regionalism toward more openness and hence to make it more compatible with the multilateral trading system. It focuses on NAFTA, one of the most restrictive FTAs (see Estevadeordal and Suominen 2006), and proposes a way forward that is close in spirit to what the EU Commission is considering for the PANEURO system. In a nutshell, the idea is to replace the current array of RoOs by a single instrument- Maximum Foreign Content (MFC). An MFC is a conceptually clear and transparent instrument, like a tariff. Therefore changing all instruments into an MFC would bring improved transparency pretty much like the "tariffication" of NTBs. The methodology for this exercise is as follows: In step 1, I estimate the relationship between utilization rates, tariff preferences and RoOs. In step 2, I retrieve the estimates and invert the relationship to get a simulated MFC that gives, line by line, the same utilization rate as the old array of Roos. In step 3, I calculate the trade-weighted average of the simulated MFC across all lines to get an overall equivalent of the current system and explore the possibility of setting this unique instrument at a uniform rate across lines. This would have two advantages. First, like a uniform tariff, a uniform MFC would make it difficult for lobbies to manipulate the instrument at the margin. This argument is standard in the political-economy literature and has been used time and again in support of reductions in the variance of tariffs (together with standard welfare considerations). Second, uniformity across lines is the only way to eliminate the indirect source of discrimination alluded to earlier. Only if two countries face uniform RoOs and tariff preference will they face uniform incentives irrespective of their initial export structure. The result of this exercise is striking: the average simulated MFC is 25% of good value, a very low (i.e. restrictive) level, confirming Estevadeordal and Suominen's critical assessment of NAFTA's RoOs. Adopting a uniform MFC would imply a relaxation from the benchmark level for sectors like chemicals or textiles & apparel, and a stiffening for wood products, papers and base metals. Overall, however, the changes are not drastic, suggesting perhaps only moderate resistance to change from special interests. The third chapter of the thesis considers whether Europe Agreements of the EU, with the current sets of RoOs, could be the potential model for future EU-centered PTAs. First, I have studied and coded at the six-digit level of the Harmonised System (HS) .both the old RoOs -used before 1997- and the "Single list" Roos -used since 1997. Second, using a Constant Elasticity Transformation function where CEEC exporters smoothly mix sales between the EU and the rest of the world by comparing producer prices on each market, I have estimated the trade effects of the EU RoOs. The estimates suggest that much of the market access conferred by the EAs -outside sensitive sectors- was undone by the cost-raising effects of RoOs. The chapter also contains an analysis of the evolution of the CEECs' trade with the EU from post-communism to accession. Part II The last chapter of the thesis is concerned with anti-dumping, another trade-policy instrument having the effect of reducing market access. In 1995, the Uruguay Round introduced in the Anti-Dumping Agreement (ADA) a mandatory "sunset-review" clause (Article 11.3 ADA) under which anti-dumping measures should be reviewed no later than five years from their imposition and terminated unless there was a serious risk of resumption of injurious dumping. The last chapter, written with Pr. Olivier Cadot and Pr. Jaime de Melo, uses a new database on Anti-Dumping (AD) measures worldwide to assess whether the sunset-review agreement had any effect. The question we address is whether the WTO Agreement succeeded in imposing the discipline of a five-year cycle on AD measures and, ultimately, in curbing their length. Two methods are used; count data analysis and survival analysis. First, using Poisson and Negative Binomial regressions, the count of AD measures' revocations is regressed on (inter alia) the count of "initiations" lagged five years. The analysis yields a coefficient on measures' initiations lagged five years that is larger and more precisely estimated after the agreement than before, suggesting some effect. However the coefficient estimate is nowhere near the value that would give a one-for-one relationship between initiations and revocations after five years. We also find that (i) if the agreement affected EU AD practices, the effect went the wrong way, the five-year cycle being quantitatively weaker after the agreement than before; (ii) the agreement had no visible effect on the United States except for aone-time peak in 2000, suggesting a mopping-up of old cases. Second, the survival analysis of AD measures around the world suggests a shortening of their expected lifetime after the agreement, and this shortening effect (a downward shift in the survival function postagreement) was larger and more significant for measures targeted at WTO members than for those targeted at non-members (for which WTO disciplines do not bind), suggesting that compliance was de jure. A difference-in-differences Cox regression confirms this diagnosis: controlling for the countries imposing the measures, for the investigated countries and for the products' sector, we find a larger increase in the hazard rate of AD measures covered by the Agreement than for other measures.

A tumor-specific cellular environment at the brain invasion border of adamantinomatous craniopharyngiomas.

Craniopharyngiomas (CP) are benign epithelial tumors of the sellar region and can be clinicopathologically distinguished into adamantinomatous (adaCP) and papillary (papCP) variants. Both subtypes are classified according to the World Health Organization grade I, but their irregular digitate brain infiltration makes any complete surgical resection difficult to obtain. Herein, we characterized the cellular interface between the tumor and the surrounding brain tissue in 48 CP (41 adaCP and seven papCP) compared to non-neuroepithelial tumors, i.e., 12 cavernous hemangiomas, 10 meningiomas, and 14 metastases using antibodies directed against glial fibrillary acid protein (GFAP), vimentin, nestin, microtubule-associated protein 2 (MAP2) splice variants, and tenascin-C. We identified a specific cell population characterized by the coexpression of nestin, MAP2, and GFAP within the invasion niche of the adamantinomatous subtype. This was especially prominent along the finger-like protrusions. A similar population of presumably astroglial precursors was not visible in other lesions under study, which characterize them as distinct histopathological feature of adaCP. Furthermore, the outer tumor cell layer of adaCP showed a distinct expression of MAP2, a novel finding helpful in the differential diagnosis of epithelial tumors in the sellar region. Our data support the hypothesis that adaCP, unlike other non-neuroepithelial tumors of the central nervous system, create a tumor-specific cellular environment at the tumor-brain junction. Whether this facilitates the characteristic infiltrative growth pattern or is the consequence of an activated Wnt signaling pathway, detectable in 90% of these tumors, will need further consideration.

Kermit interacts with gαo, vang, and motor proteins in Drosophila planar cell polarity.

In addition to the ubiquitous apical-basal polarity, epithelial cells are often polarized within the plane of the tissue - the phenomenon known as planar cell polarity (PCP). In Drosophila, manifestations of PCP are visible in the eye, wing, and cuticle. Several components of the PCP signaling have been characterized in flies and vertebrates, including the heterotrimeric Go protein. However, Go signaling partners in PCP remain largely unknown. Using a genetic screen we uncover Kermit, previously implicated in G protein and PCP signaling, as a novel binding partner of Go. Through pull-down and genetic interaction studies, we find that Kermit interacts with Go and another PCP component Vang, known to undergo intracellular relocalization during PCP establishment. We further demonstrate that the activity of Kermit in PCP differentially relies on the motor proteins: the microtubule-based dynein and kinesin motors and the actin-based myosin VI. Our results place Kermit as a potential transducer of Go, linking Vang with motor proteins for its delivery to dedicated cellular compartments during PCP establishment.

Landmark detection for fusion of fundus and MRI toward a patient-specific multimodal eye model.

Ophthalmologists typically acquire different image modalities to diagnose eye pathologies. They comprise, e.g., Fundus photography, optical coherence tomography, computed tomography, and magnetic resonance imaging (MRI). Yet, these images are often complementary and do express the same pathologies in a different way. Some pathologies are only visible in a particular modality. Thus, it is beneficial for the ophthalmologist to have these modalities fused into a single patient-specific model. The goal of this paper is a fusion of Fundus photography with segmented MRI volumes. This adds information to MRI that was not visible before like vessels and the macula. This paper contributions include automatic detection of the optic disc, the fovea, the optic axis, and an automatic segmentation of the vitreous humor of the eye.

Cristallographie(s). (Montesquieu, Certeau, Deleuze, Foucault, Valéry)

Les imaginaires explorés par ce livre ont ceci de commun qu'ils tentent de s'en tenir à la matérialité du monde, de ses corps, de ses images, de ses lois. Ils affirment chacun à sa manière le monde et sa fable. Ils y construisent la figure d'un à-côté, d'une fuite, d'une déviation ou d'un renversement. Un coup d'oeil persan. Lois et calculs ; clôtures et braconnages ; lignes de fuites ; histoire(s). Les noms que ce livre convoque forment des cristaux, quelque(s) cristallographie(s). La lumière s'y dévie, s'y diffracte, révèle ses palettes de couleur, butte contre les grains obscurs de la matière, comme une matière elle-même concentrée et diffractée. Cette constellation se rend visible autant par la littérature (Kawabata, Kafka, Proust, etc.) que par la peinture (Bosch, Velàzquez, etc.), comme autant d'images projetées. Cette lumière prend des corps et une écriture, rythmicité opaque et clarifiante, sans mystères. Les cristaux qu'elle traverse sont des corps imaginaires, politiques, érotiques : la lumière s'y projette en corps à corps, à peau contre peau. Blessante, coupante, rasante, douce ou crue. Les catastrophes conceptuelles s'y aggravent ou en diffèrent. De Montesquieu à Valéry, de Certeau à Deleuze et à Foucault, les imaginaires (d'émancipation, de liberté, d'invention en jeux d'obsessions, de confrontations, de contraintes et de problèmes) se croisent et s'interrogent, se reflètent autrement (Spinoza, Kofman, Agamben, Malabou, Nietzsche, Derrida) se regardent sans se répondre, par des jeux de miroirs superposés. Une autre manière de partager, en rythmes et en images, quelques pratiques d'écriture et de pensée.

Characteristics and outcome of knee prosthetic joint infections (PJI): A 10-year cohort study (2000-2009)

Background: Prosthetic joint infections (PJI) lead to significant long-term morbidity with high cost of healthcare. We evaluated characteristics of infections and the infection and functional outcome of knee PJI over a 10-year period. Methods: All patients hospitalized at our institution from 1/2000 through 12/2009 with knee PJI (defined as growth of the same microorganism in ≥2 tissue or synovial fluid cultures, visible purulence, sinus tract or acute inflammation on tissue histopathology) were included. Patients, their relatives and/or treating physicians were contacted to determine the outcome. Results: During the study period, 61 patients with knee PJI were identified. The median age at the time of diagnosis of infection was 73 y (range, 53-94 y); 52% were men. Median hospital stay was 37 d (range, 1-145 d). Most reasons for primary arthroplasty was osteoarthritis (n = 48), trauma (n = 9) and rheumatoid arthritis (n = 4). 23 primary surgeries (40%) were performed at CHUV, 34 (60%) elsewhere. After surgery, 8 PJI were early (<3 months), 16 delayed (3-24 months) and 33 late (>24 months). PJI were treated with (i) open or arthroscopic debridement with prosthesis retention in 26 (46%), (ii) one-stage exchange in 1, (iii) two-stage exchange in 22 (39%) and (iv) prosthesis removal in 8 (14%). Isolated pathogens were S. aureus (13), coagulase-negative staphylococci (10), streptococci (5), enterococci (3), gram-negative rods (3) and anaerobes (3). Patients were followed for a median of 3.1 years, 2 patients died (unrelated to PJI). The outcome of infection was favorable in 50 patients (88%), whereas the functional outcome was favorable in 33 patients (58%). Conclusions: With the current treatment concept, the high cure rate of infection (88%) is associated with a less favorable functional outcome o 58%. Earlier surgical intervention and more rapid and improved diagnosis of infection may improve the functional outcome of PJI.

Partial melting of basic dykes in the contact aureoles of two shallow-level, gabbro-pyroxenite intrusions, Fuerteventura

THESIS ABSTRACT Low-pressure anatexis of basic dykes gave rise to unusual, zebra-like migmatites, in the contact metamorphic aureoles of two layered gabbro-pyroxenite intrusions, PXl and PX2, in the root zone of an ocean island, Fuerteventura Basal Complex (Canary Islands). This thesis focuses on the understanding of processes attributing to the partial melting and formation of these migmatites, characterised by a dense network of closely spaced, millimetre-wide leucocratic segregations with perfectly preserved igneous textures. The presence of fluids are required to decrease the solidus of basic igneous lithologies, to allow partial melting in such aloes-pressure (1-2 kb) environment. An oxygen isotope study was thus carried out on dykes inside and beyond the PX2 aureole, in order to decipher the nature and origin of such fluids. Low or negative δ18O values were obtained for whole rocks and mineral-separates, decreasing towards the contact, with the intrusion itself retaining fairly high values. This trend has been attributed to the advection of meteoric water during magma emplacement, with increasing fluid/rock ratios (higher dyke intensities towards the intrusion acting as fluid-pathways) and higher temperatures promoting increasing exchange during recrystallisation. A comparison of whole rock and mineral major- and trace- element data allowed the redistribution of elements .between different mineral phases and generations, during contact metamorphism and partial melting to be assessed. Certain trace-elements, e.g. Zr, Hf, Y, and REEs, were internally redistributed during contact metamorphic recrystallisation, causing- the enrichment of neocrystallised diopsides compared to relict phenocrysts. This has been assigned to the liberation of trace elements on the breakdown of primary minerals, kaersutite and sphene, on entering the thermal aureole. Major and trace element compositions of minerals in migmatite melanosomes and leucosomes are almost identical, pointing to a syn- or post- solidus reequilibration on cooling of the migmatite terrain. The mineralogical, textural and geochemical evolution of dykes in a contact metamorphic aureole, is recorded around an apophysis of the PX1 intrusion, where there is evidence of incipient partial melting. Hydrothermal mineral pseudomorphs in the outer parts of the aureole are progressively replaced by dry mineral assemblages, with increasingly recrystallised diopside and evidence of partial melting -the extent of which varies from one lithology to another. The appearance of more mafic lithologies towards the intrusion, with lower whole rock SiO2 and mobile element abundances, e.g. Rb, Cs, K, has been explained by the migration and accumulation of feldspathic material into leucosomes outside the samples. A micro-structural study of leucosomes and leucocratic pods, with the aid of high-resolution X-ray computed micro-tomography (HRXµCT), allowing the visualization and quantification of shapes and orientations, was carried out in order to better understand the processes of melt segregation in the PX1 aureole. Leucocratic pods, representing former amygdales, are considered as natural strain ellipsoids. Their short axes are oriented perpendicular to leucosome planes, which sub-parallel the intrusive contact. Leucosomes thus effectively represent foliation planes. This implies that the direction of maximum shortening, during migmatisation, was perpendicular to the orientation of leucosomes, contradicting earlier models that suggest leucosomes represent tension veins. RESUME DE LA THESE Un phénomène rare de fusion partielle de filons basiques à basse pression a été étudié dans les auréoles de contact de deux intrusions litées de gabbro-pyroxénite, PX1 et PX2, localisées dans le soubassement de l'île volcanique de Fuerteventura aux Canaries. Cette anatexie a engendré des migmatites finement zébrées d'aspect très inhabituel, dont les processus de formation ont été étudiés dans le présent travail. Ces roches sont caractérisées par un réseau dense de veinules leucocrates d'épaisseur millimétrique, dont les textures ignées sont parfaitement préservées. La fusion partielle de roches basiques à basse pression (1-2 kbar) requiert la présence d'eau afin d'abaisser le solidus du système à des températures géologiquement réalistes. Une étude comparative des isotopes de l'oxygène a ainsi été menée sur des filons respectivement affectés et non affectés par le métamorphisme de contact, afin de confirmer la présence de ces fluides, de déterminer l'importance de leur interaction avec les roches et leur origine. Des valeurs de δ180 basses ou négatives ont été mesurées sur roche totale et minéraux séparés, décroissantes en direction du contact, alors que l'intrusion elle-même a conservé des valeurs élevées. Ce gradient a été attribué à l'advection d'eau météorique durant la mise en place du magma, les températures les plus élevées favorisant d'autant plus la circulation des fluides et les échanges isotopiques durant la recristallisation des roches. Cette recristallisation engendré une redistribution chimique complète des éléments entre les différentes générations de minéraux résultant du métamorphisme de contact et de l'anatexie, mise en évidence par microanalyse. Certains éléments traces comme Zr, Hf, Y et les REE ont été concentrés dans le diopside néoformé consécutivement à la déstabilisation de minéraux primaires riches en ces éléments comme la kaersutite ou le sphène. Les compositions en éléments majeurs et traces des minéraux des mélanosomes et leucosomes des migmatites sont pratiquement identiques, indiquant une rééquilibration syn- à postsolidus lors du refroidissement de l'auréole de contact. La transformation progressive des filons basiques au niveau de leur minéralogie, textures et composition chimique a pu être observée en détail à l'approche du contact d'une apophyse de l'intrusion PX1. La paragenèse magmatique initiale n'est jamais préservée, les faciès les plus distants du contact étant constitués d'un assemblage pseudomorphique hydrothermal. Ce dernier est progressivement remplacé par des assemblages anhydres incluant du diopside néoformé, puis apparaissent les premiers signes de fusion partielle, dont l'importance varie fortement d'une lithologie à l'autre. L'apparition de faciès plus basiques en direction du contact, avec des teneurs réduites en SiO2 et en éléments incompatibles tels Rb, Cs, K, a été attribuée à l'échappement de leucosomes feldspathiques hors du système. Une étude microstructurale de la distribution spatiale du matériel leucocrate au sein des migmatites par microtomographie X de haute résolution (HRXµCT) a été menée pour mieux comprendre les processus de ségrégation des liquides dans l'auréole de PX1. De petites entités ovoïdes, représentant d'anciennes structures amygdalaires au sein des filons, ont été considérées comme des ellipsoïdes marqueurs de la déformation finie. Leur petit axe est orienté perpendiculairement aux plans définis par les leucosomes, eux-mêmes subparallèles au contact intrusif. Les leucosomes matérialisent donc des plans de clivage. Ainsi, la direction de raccourcissement maximum durant la fusion partielle était perpendiculaire à l'orientation des leucosomes, contrairement à ce qui a été dit dans de précédentes publications, qui suggéraient que les leucosomes représentaient des veines de tension. RESUME DE LA THESE (POUR LE GRAND PUBLIC) L'observation directe du soubassement d'une île volcanique est une occasion rare, accessible dans le «complexe de base » de l'île canarienne de Fuerteventura. Ce dernier a enregistré divers phénomènes magmatiques, métamorphiques et de fusion partielle induits par l'intrusion répétée de magmas alimentant des appareils volcaniques sus jacents, sous forme de petits plutons, essaims de filons et complexes annulaires de gabbros alcalins, pyroxénites, syénites et carbonatites. Dans ce contexte de flux de chaleur élevé, des filons basiques ont subi une fusion partielle au contact de deux intrusions de gabbro-pyroxénite, un phénomène extrêmement rare à une profondeur aussi réduite, estimée à quelque 3-6 km. Les produits de cette fusion partielle sont des liquides très riches en feldspath, concentrés en un réseau dense de veinules blanches (leucosomes) au sein du matériau résiduel sombre non fondu (mélanosome) pour former ce qu'on appelle des migmatites. Outre les aspects pétrologiques liés à la formation de ces migmatites, l'intérêt majeur du phénomène réside dans le fait qu'il puisse représenter la source des magmas évolués parfois observés sur les îles océaniques. A des pressions aussi faibles que dans le soubassement de Fuerteventura (1-2 Kbar), la présence de fluides abondants est nécessaire pour abaisser la température de début de fusion des roches (solidus) à des valeurs géologiquement réalistes. Des expériences ont montré que même en présence de plusieurs %-poids d'eau, une température de 1000°C était encore nécessaire pour obtenir une proportion de liquide équivalente à celle observée sur le terrain, soit 25%. Or les magmas alcalins des îles océaniques, bien qu'hydratés, n'en contiennent de loin pas autant, ce qui implique une source d'eau externe. Une étude isotopique de l'oxygène a été entreprise afin de tester cette hypothèse. Les valeurs obtenues en 5180 sont basses ou négatives et indiquent l'influence d'eau d'origine météorique. Cette eau de pluie se serait infiltrée le long des filons depuis la surface du volcan et les aurait complètement hydrothermalisés en profondeur (situation encore visible à l'extérieur de l'auréole de contact), leur permettant ainsi de stocker l'eau nécessaire à leur fusion partielle ultérieure. L'interaction entre eau de pluie et filons a été d'autant plus importante que ces derniers étaient proches du contact avec l'intrusion, ce qui suggère que la circulation de ces eaux et leur interaction avec les roches a été favorisée par la chaleur fournie par l'intrusion elle-même. Un autre aspect de ce travail s'est focalisé sur la redistribution des éléments traces au sein des minéraux des filons basiques durant le métamorphisme de contact et la fusion partielle. Ainsi, le pyroxène de seconde génération est-il sensiblement enrichi en traces telles Zr, Hf, Y et les terres rares, par rapport au pyroxène magmatique originel, en relation avec la déstabilisation de minéraux primaires riches en ces éléments tels le sphène et la kaersutite. Cependant, les compositions en éléments majeurs et traces des minéraux recristallisés des migmatites sont pratiquement les mêmes dans les leucosomes et les mélanosomes, suggérant une rééquilibration chimique complète durant le refroidissement de ces lithologies. Si certaines migmatites se sont comportées en système chimiquement fermé (hormis l'eau météorique), d'autres filons ont manifestement perdu une partie de leurs leucosomes, ainsi qu'en témoigne leur composition progressivement appauvrie en silice et autres éléments incompatibles mobiles, tels K et Rb à l'approche du contact de l'intrusion. Parallèlement à cette évolution chimique, les paragenèses hydrothermales distantes du contact sont progressivement remplacées par des paragenèses anhydres, puis par l'apparition des premiers leucosomes, tandis que les textures magmatiques initiales sont complètement effacées au profit d'une combinaison de textures magmatique dans les leucosomes et en mosaïque dans les mélanosomes. Enfin, la distribution spatiale des liquides de fusion partielle a été étudiée par microtomographie X de haute résolution, dans des filons contenant des entités ovoïdes leucocrates, sans doute d'anciennes amygdales à zéolites. Ces dernières ont été considérées comme des ellipsoïdes de la déformation finie. L'orientation de leur petit axe, perpendiculaire au plan défini par les veinules de leucosomes, indique que ces derniers représentent des plans de clivage perpendiculaires à la direction de raccourcissement maximum. Ainsi, la ségrégation des liquides de fusion partielle se serait faite dans les plans de compression et non dans des plans de dilatation, contrairement à ce que laisserait penser le sens commun.

Use of 2D Sensitivity Encoding for Slow-Infusion Contrast-Enhanced Isotropic 3-T Whole-Heart Coronary MR Angiography.

OBJECTIVE. The purpose of this study was to improve the blood-pool signal-to-noise ratio (SNR) and blood-myocardium contrast-to-noise ratio (CNR) of slow-infusion 3-T whole-heart coronary MR angiography (MRA).SUBJECTS AND METHODS. In 2D sensitivity encoding (SENSE), the number of acquired k-space lines is reduced, allowing less radiofrequency excitation per cardiac cycle and a longer TR. The former can be exploited for signal enhancement with a higher radiofrequency excitation angle, and the latter leads to noise reduction due to lower data-sampling bandwidth. Both effects contribute to SNR gain in coronary MRA when spatial and temporal resolution and acquisition time remain identical. Numeric simulation was performed to select the optimal 2D SENSE pulse sequence parameters and predict the SNR gain. Eleven patients underwent conventional unenhanced and the proposed 2D SENSE contrast-enhanced coronary MRA acquisition. Blood-pool SNR, blood-myocardium CNR, visible vessel length, vessel sharpness, and number of side branches were evaluated.RESULTS. Consistent with the numeric simulation, using 2D SENSE in contrast-enhanced coronary MRA resulted in significant improvement in aortic blood-pool SNR (unenhanced vs contrast-enhanced, 37.5 +/- 14.7 vs 121.3 +/- 44.0; p < 0.05) and CNR (14.4 +/- 6.9 vs 101.5 +/- 40.8; p < 0.05) in the patient sample. A longer length of left anterior descending coronary artery was visualized, but vessel sharpness, coronary artery coverage, and image quality score were not improved with the proposed approach.CONCLUSION. In combination with contrast administration, 2D SENSE was found effective in improving SNR and CNR in 3-T whole-heart coronary MRA. Further investigation of cardiac motion compensation is necessary to exploit the SNR and CNR advantages and to achieve submillimeter spatial resolution.

A collagen-poly(lactic acid-co-ɛ-caprolactone) hybrid scaffold for bladder tissue regeneration.

Scaffold materials should favor cell attachment and proliferation, and provide designable 3D structures with appropriate mechanical strength. Collagen matrices have proven to be beneficial scaffolds for tissue regeneration. However, apart from small intestinal submucosa, they offer a limited mechanical strength even if crosslinking can enhance their mechanical properties. A more cell-friendly way to increase material strength is to combine synthetic polymer meshes with plastic compressed collagen gels. This work describes the potential of plastic compressed collagen-poly(lactic acid-co-ɛ-caprolactone) (PLAC) hybrids as scaffolds for bladder tissue regeneration. Human bladder smooth muscle and urothelial cells were cultured on and inside collagen-PLAC hybrids in vitro. Scaffolds were analyzed by electron microscopy, histology, immunohistochemistry, and AlamarBlue assay. Both cell types proliferated in and on the hybrid, forming dense cell layers on top after two weeks. Furthermore, hybrids were implanted subcutaneously in the backs of nude mice. Host cell infiltration, scaffold degradation, and the presence of the seeded bladder cells were analyzed. Hybrids showed a lower inflammatory reaction in vivo than PLAC meshes alone, and first signs of polymer degradation were visible at six months. Collagen-PLAC hybrids have potential for bladder tissue regeneration, as they show efficient cell seeding, proliferation, and good mechanical properties.