Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project.

We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.

Species delimitation: A case study in a problematic ant taxon

Species delimitation has been invigorated as a discipline in systematics by an influx of new character sets, analytical methods, and conceptual advances. We use genetic data from 68 markers, combined with distributional, bioclimatic, and coloration information, to hypothesize boundaries of evolutionarily independent lineages (species) within the widespread and highly variable nominal fire ant species Solenopsis saevissima, a member of a species group containing invasive pests as well as species that are models for ecological and evolutionary research. Our integrated approach uses diverse methods of analysis to sequentially test whether populations meet specific operational criteria (contingent properties) for candidacy as morphologically cryptic species, including genetic clustering, monophyly, reproductive isolation, and occupation of distinctive niche space. We hypothesize that nominal S. saevissima comprises at least 4-6 previously unrecognized species, including several pairs whose parapatric distributions implicate the development of intrinsic premating or postmating barriers to gene flow. Our genetic data further suggest that regional genetic differentiation in S. saevissima has been influenced by hybridization with other nominal species occurring in sympatry or parapatry, including the quite distantly related Solenopsis geminata. The results of this study illustrate the importance of employing different classes of genetic data (coding and noncoding regions and nuclear and mitochondrial DNA [mtDNA] markers), different methods of genetic data analysis (tree-based and non-tree based methods), and different sources of data (genetic, morphological, and ecological data) to explicitly test various operational criteria for species boundaries in clades of recently diverged lineages, while warning against over reliance on any single data type (e.g., mtDNA sequence variation) when drawing inferences.

Species distribution models for conservation-oriented studies in Switzerland : filling data and tools gaps

SUMMARYSpecies distribution models (SDMs) represent nowadays an essential tool in the research fields of ecology and conservation biology. By combining observations of species occurrence or abundance with information on the environmental characteristic of the observation sites, they can provide information on the ecology of species, predict their distributions across the landscape or extrapolate them to other spatial or time frames. The advent of SDMs, supported by geographic information systems (GIS), new developments in statistical models and constantly increasing computational capacities, has revolutionized the way ecologists can comprehend species distributions in their environment. SDMs have brought the tool that allows describing species realized niches across a multivariate environmental space and predict their spatial distribution. Predictions, in the form of probabilistic maps showing the potential distribution of the species, are an irreplaceable mean to inform every single unit of a territory about its biodiversity potential. SDMs and the corresponding spatial predictions can be used to plan conservation actions for particular species, to design field surveys, to assess the risks related to the spread of invasive species, to select reserve locations and design reserve networks, and ultimately, to forecast distributional changes according to scenarios of climate and/or land use change.By assessing the effect of several factors on model performance and on the accuracy of spatial predictions, this thesis aims at improving techniques and data available for distribution modelling and at providing the best possible information to conservation managers to support their decisions and action plans for the conservation of biodiversity in Switzerland and beyond. Several monitoring programs have been put in place from the national to the global scale, and different sources of data now exist and start to be available to researchers who want to model species distribution. However, because of the lack of means, data are often not gathered at an appropriate resolution, are sampled only over limited areas, are not spatially explicit or do not provide a sound biological information. A typical example of this is data on 'habitat' (sensu biota). Even though this is essential information for an effective conservation planning, it often has to be approximated from land use, the closest available information. Moreover, data are often not sampled according to an established sampling design, which can lead to biased samples and consequently to spurious modelling results. Understanding the sources of variability linked to the different phases of the modelling process and their importance is crucial in order to evaluate the final distribution maps that are to be used for conservation purposes.The research presented in this thesis was essentially conducted within the framework of the Landspot Project, a project supported by the Swiss National Science Foundation. The main goal of the project was to assess the possible contribution of pre-modelled 'habitat' units to model the distribution of animal species, in particular butterfly species, across Switzerland. While pursuing this goal, different aspects of data quality, sampling design and modelling process were addressed and improved, and implications for conservation discussed. The main 'habitat' units considered in this thesis are grassland and forest communities of natural and anthropogenic origin as defined in the typology of habitats for Switzerland. These communities are mainly defined at the phytosociological level of the alliance. For the time being, no comprehensive map of such communities is available at the national scale and at fine resolution. As a first step, it was therefore necessary to create distribution models and maps for these communities across Switzerland and thus to gather and collect the necessary data. In order to reach this first objective, several new developments were necessary such as the definition of expert models, the classification of the Swiss territory in environmental domains, the design of an environmentally stratified sampling of the target vegetation units across Switzerland, the development of a database integrating a decision-support system assisting in the classification of the relevés, and the downscaling of the land use/cover data from 100 m to 25 m resolution.The main contributions of this thesis to the discipline of species distribution modelling (SDM) are assembled in four main scientific papers. In the first, published in Journal of Riogeography different issues related to the modelling process itself are investigated. First is assessed the effect of five different stepwise selection methods on model performance, stability and parsimony, using data of the forest inventory of State of Vaud. In the same paper are also assessed: the effect of weighting absences to ensure a prevalence of 0.5 prior to model calibration; the effect of limiting absences beyond the environmental envelope defined by presences; four different methods for incorporating spatial autocorrelation; and finally, the effect of integrating predictor interactions. Results allowed to specifically enhance the GRASP tool (Generalized Regression Analysis and Spatial Predictions) that now incorporates new selection methods and the possibility of dealing with interactions among predictors as well as spatial autocorrelation. The contribution of different sources of remotely sensed information to species distribution models was also assessed. The second paper (to be submitted) explores the combined effects of sample size and data post-stratification on the accuracy of models using data on grassland distribution across Switzerland collected within the framework of the Landspot project and supplemented with other important vegetation databases. For the stratification of the data, different spatial frameworks were compared. In particular, environmental stratification by Swiss Environmental Domains was compared to geographical stratification either by biogeographic regions or political states (cantons). The third paper (to be submitted) assesses the contribution of pre- modelled vegetation communities to the modelling of fauna. It is a two-steps approach that combines the disciplines of community ecology and spatial ecology and integrates their corresponding concepts of habitat. First are modelled vegetation communities per se and then these 'habitat' units are used in order to model animal species habitat. A case study is presented with grassland communities and butterfly species. Different ways of integrating vegetation information in the models of butterfly distribution were also evaluated. Finally, a glimpse to climate change is given in the fourth paper, recently published in Ecological Modelling. This paper proposes a conceptual framework for analysing range shifts, namely a catalogue of the possible patterns of change in the distribution of a species along elevational or other environmental gradients and an improved quantitative methodology to identify and objectively describe these patterns. The methodology was developed using data from the Swiss national common breeding bird survey and the article presents results concerning the observed shifts in the elevational distribution of breeding birds in Switzerland.The overall objective of this thesis is to improve species distribution models as potential inputs for different conservation tools (e.g. red lists, ecological networks, risk assessment of the spread of invasive species, vulnerability assessment in the context of climate change). While no conservation issues or tools are directly tested in this thesis, the importance of the proposed improvements made in species distribution modelling is discussed in the context of the selection of reserve networks.RESUMELes modèles de distribution d'espèces (SDMs) représentent aujourd'hui un outil essentiel dans les domaines de recherche de l'écologie et de la biologie de la conservation. En combinant les observations de la présence des espèces ou de leur abondance avec des informations sur les caractéristiques environnementales des sites d'observation, ces modèles peuvent fournir des informations sur l'écologie des espèces, prédire leur distribution à travers le paysage ou l'extrapoler dans l'espace et le temps. Le déploiement des SDMs, soutenu par les systèmes d'information géographique (SIG), les nouveaux développements dans les modèles statistiques, ainsi que la constante augmentation des capacités de calcul, a révolutionné la façon dont les écologistes peuvent comprendre la distribution des espèces dans leur environnement. Les SDMs ont apporté l'outil qui permet de décrire la niche réalisée des espèces dans un espace environnemental multivarié et prédire leur distribution spatiale. Les prédictions, sous forme de carte probabilistes montrant la distribution potentielle de l'espèce, sont un moyen irremplaçable d'informer chaque unité du territoire de sa biodiversité potentielle. Les SDMs et les prédictions spatiales correspondantes peuvent être utilisés pour planifier des mesures de conservation pour des espèces particulières, pour concevoir des plans d'échantillonnage, pour évaluer les risques liés à la propagation d'espèces envahissantes, pour choisir l'emplacement de réserves et les mettre en réseau, et finalement, pour prévoir les changements de répartition en fonction de scénarios de changement climatique et/ou d'utilisation du sol. En évaluant l'effet de plusieurs facteurs sur la performance des modèles et sur la précision des prédictions spatiales, cette thèse vise à améliorer les techniques et les données disponibles pour la modélisation de la distribution des espèces et à fournir la meilleure information possible aux gestionnaires pour appuyer leurs décisions et leurs plans d'action pour la conservation de la biodiversité en Suisse et au-delà. Plusieurs programmes de surveillance ont été mis en place de l'échelle nationale à l'échelle globale, et différentes sources de données sont désormais disponibles pour les chercheurs qui veulent modéliser la distribution des espèces. Toutefois, en raison du manque de moyens, les données sont souvent collectées à une résolution inappropriée, sont échantillonnées sur des zones limitées, ne sont pas spatialement explicites ou ne fournissent pas une information écologique suffisante. Un exemple typique est fourni par les données sur 'l'habitat' (sensu biota). Même s'il s'agit d'une information essentielle pour des mesures de conservation efficaces, elle est souvent approximée par l'utilisation du sol, l'information qui s'en approche le plus. En outre, les données ne sont souvent pas échantillonnées selon un plan d'échantillonnage établi, ce qui biaise les échantillons et par conséquent les résultats de la modélisation. Comprendre les sources de variabilité liées aux différentes phases du processus de modélisation s'avère crucial afin d'évaluer l'utilisation des cartes de distribution prédites à des fins de conservation.La recherche présentée dans cette thèse a été essentiellement menée dans le cadre du projet Landspot, un projet soutenu par le Fond National Suisse pour la Recherche. L'objectif principal de ce projet était d'évaluer la contribution d'unités 'd'habitat' pré-modélisées pour modéliser la répartition des espèces animales, notamment de papillons, à travers la Suisse. Tout en poursuivant cet objectif, différents aspects touchant à la qualité des données, au plan d'échantillonnage et au processus de modélisation sont abordés et améliorés, et leurs implications pour la conservation des espèces discutées. Les principaux 'habitats' considérés dans cette thèse sont des communautés de prairie et de forêt d'origine naturelle et anthropique telles que définies dans la typologie des habitats de Suisse. Ces communautés sont principalement définies au niveau phytosociologique de l'alliance. Pour l'instant aucune carte de la distribution de ces communautés n'est disponible à l'échelle nationale et à résolution fine. Dans un premier temps, il a donc été nécessaire de créer des modèles de distribution de ces communautés à travers la Suisse et par conséquent de recueillir les données nécessaires. Afin d'atteindre ce premier objectif, plusieurs nouveaux développements ont été nécessaires, tels que la définition de modèles experts, la classification du territoire suisse en domaines environnementaux, la conception d'un échantillonnage environnementalement stratifié des unités de végétation cibles dans toute la Suisse, la création d'une base de données intégrant un système d'aide à la décision pour la classification des relevés, et le « downscaling » des données de couverture du sol de 100 m à 25 m de résolution. Les principales contributions de cette thèse à la discipline de la modélisation de la distribution d'espèces (SDM) sont rassemblées dans quatre articles scientifiques. Dans le premier article, publié dans le Journal of Biogeography, différentes questions liées au processus de modélisation sont étudiées en utilisant les données de l'inventaire forestier de l'Etat de Vaud. Tout d'abord sont évalués les effets de cinq méthodes de sélection pas-à-pas sur la performance, la stabilité et la parcimonie des modèles. Dans le même article sont également évalués: l'effet de la pondération des absences afin d'assurer une prévalence de 0.5 lors de la calibration du modèle; l'effet de limiter les absences au-delà de l'enveloppe définie par les présences; quatre méthodes différentes pour l'intégration de l'autocorrélation spatiale; et enfin, l'effet de l'intégration d'interactions entre facteurs. Les résultats présentés dans cet article ont permis d'améliorer l'outil GRASP qui intègre désonnais de nouvelles méthodes de sélection et la possibilité de traiter les interactions entre variables explicatives, ainsi que l'autocorrélation spatiale. La contribution de différentes sources de données issues de la télédétection a également été évaluée. Le deuxième article (en voie de soumission) explore les effets combinés de la taille de l'échantillon et de la post-stratification sur le la précision des modèles. Les données utilisées ici sont celles concernant la répartition des prairies de Suisse recueillies dans le cadre du projet Landspot et complétées par d'autres sources. Pour la stratification des données, différents cadres spatiaux ont été comparés. En particulier, la stratification environnementale par les domaines environnementaux de Suisse a été comparée à la stratification géographique par les régions biogéographiques ou par les cantons. Le troisième article (en voie de soumission) évalue la contribution de communautés végétales pré-modélisées à la modélisation de la faune. C'est une approche en deux étapes qui combine les disciplines de l'écologie des communautés et de l'écologie spatiale en intégrant leurs concepts de 'habitat' respectifs. Les communautés végétales sont modélisées d'abord, puis ces unités de 'habitat' sont utilisées pour modéliser les espèces animales. Une étude de cas est présentée avec des communautés prairiales et des espèces de papillons. Différentes façons d'intégrer l'information sur la végétation dans les modèles de répartition des papillons sont évaluées. Enfin, un clin d'oeil aux changements climatiques dans le dernier article, publié dans Ecological Modelling. Cet article propose un cadre conceptuel pour l'analyse des changements dans la distribution des espèces qui comprend notamment un catalogue des différentes formes possibles de changement le long d'un gradient d'élévation ou autre gradient environnemental, et une méthode quantitative améliorée pour identifier et décrire ces déplacements. Cette méthodologie a été développée en utilisant des données issues du monitoring des oiseaux nicheurs répandus et l'article présente les résultats concernant les déplacements observés dans la distribution altitudinale des oiseaux nicheurs en Suisse.L'objectif général de cette thèse est d'améliorer les modèles de distribution des espèces en tant que source d'information possible pour les différents outils de conservation (par exemple, listes rouges, réseaux écologiques, évaluation des risques de propagation d'espèces envahissantes, évaluation de la vulnérabilité des espèces dans le contexte de changement climatique). Bien que ces questions de conservation ne soient pas directement testées dans cette thèse, l'importance des améliorations proposées pour la modélisation de la distribution des espèces est discutée à la fin de ce travail dans le contexte de la sélection de réseaux de réserves.

The different types of internal hernia after laparoscopic Roux-En-Y gastric by-pass for morbid obesity: MDCT features [C-419]

Learning Objectives: 1. To provide an overview of the different types of internal hernia (IH) occurring after laparoscopic Roux‑en‑Y gastric bypass (LRYGBP) for morbid obesity. 2. To describe correspondent MDCT features in relation with the underlying anatomical landmarks in order to differentiate their localisation and to direct the surgeon during following laparoscopic closure of mesenteric defects. Background: LRYGBP for morbid obesity is associated with less perioperative complications, shorter hospital stay and a more rapid recovery compared with the open surgical procedure. However, a relatively high incidence of IH is seen that may be due to the laparoscopic approach, but also caused by rapid weight loss with consecutive loosening of the mesenteric sutures. Procedure Details: After briefly reviewing the surgical procedure of LRYGBP (ante‑ versus retrocolic), we describe the exact anatomical landmarks of the different types of IH occurring at any time after operation: They are caused by surgical defects at the level of the transverse colon mesentery, at the Petersen's space, which represents an opening between the mesocolon and jejunal mesentery, or at the entero‑enterostomy site. Typical MDCT features of each IH type in axial and coronal planes as well as targeted vascular reconstructions are demonstrated. Conclusion: Exact knowledge about underlying pathophysiology and anatomical landmarks is essential for distinguishing the different types of IH occurring after LRYGBP on MDCT, since radiological features are difficult to recognize and may even overlap. The radiologist should be aware of the potential anatomic sites to ensure subsequent straightforward laparoscopic exploration.

Analyse systématique et permanente de la délinquance sérielle : place des statistiques criminelles ; apport des approches situationnelles pour un système de classification ; perspectives en matière de coopération

Résumé de la thèse L'évolution des systèmes policiers donne une place prépondérante à l'information et au renseignement. Cette transformation implique de développer et de maintenir un ensemble de processus permanent d'analyse de la criminalité, en particulier pour traiter des événements répétitifs ou graves. Dans une organisation aux ressources limitées, le temps consacré au recueil des données, à leur codification et intégration, diminue le temps disponible pour l'analyse et la diffusion de renseignements. Les phases de collecte et d'intégration restent néanmoins indispensables, l'analyse n'étant pas possible sur des données volumineuses n'ayant aucune structure. Jusqu'à présent, ces problématiques d'analyse ont été abordées par des approches essentiellement spécialisées (calculs de hot-sports, data mining, ...) ou dirigées par un seul axe (par exemple, les sciences comportementales). Cette recherche s'inscrit sous un angle différent, une démarche interdisciplinaire a été adoptée. L'augmentation continuelle de la quantité de données à analyser tend à diminuer la capacité d'analyse des informations à disposition. Un bon découpage (classification) des problèmes rencontrés permet de délimiter les analyses sur des données pertinentes. Ces classes sont essentielles pour structurer la mémoire du système d'analyse. Les statistiques policières de la criminalité devraient déjà avoir répondu à ces questions de découpage de la délinquance (classification juridique). Cette décomposition a été comparée aux besoins d'un système de suivi permanent dans la criminalité. La recherche confirme que nos efforts pour comprendre la nature et la répartition du crime se butent à un obstacle, à savoir que la définition juridique des formes de criminalité n'est pas adaptée à son analyse, à son étude. Depuis près de vingt ans, les corps de police de Suisse romande utilisent et développent un système de classification basé sur l'expérience policière (découpage par phénomène). Cette recherche propose d'interpréter ce système dans le cadre des approches situationnelles (approche théorique) et de le confronter aux données « statistiques » disponibles pour vérifier sa capacité à distinguer les formes de criminalité. La recherche se limite aux cambriolages d'habitations, un délit répétitif fréquent. La théorie des opportunités soutien qu'il faut réunir dans le temps et dans l'espace au minimum les trois facteurs suivants : un délinquant potentiel, une cible intéressante et l'absence de gardien capable de prévenir ou d'empêcher le passage à l'acte. Ainsi, le délit n'est possible que dans certaines circonstances, c'est-à-dire dans un contexte bien précis. Identifier ces contextes permet catégoriser la criminalité. Chaque cas est unique, mais un groupe de cas montre des similitudes. Par exemple, certaines conditions avec certains environnements attirent certains types de cambrioleurs. Deux hypothèses ont été testées. La première est que les cambriolages d'habitations ne se répartissent pas uniformément dans les classes formées par des « paramètres situationnels » ; la deuxième que des niches apparaissent en recoupant les différents paramètres et qu'elles correspondent à la classification mise en place par la coordination judiciaire vaudoise et le CICOP. La base de données vaudoise des cambriolages enregistrés entre 1997 et 2006 par la police a été utilisée (25'369 cas). Des situations spécifiques ont été mises en évidence, elles correspondent aux classes définies empiriquement. Dans une deuxième phase, le lien entre une situation spécifique et d'activité d'un auteur au sein d'une même situation a été vérifié. Les observations réalisées dans cette recherche indiquent que les auteurs de cambriolages sont actifs dans des niches. Plusieurs auteurs sériels ont commis des délits qui ne sont pas dans leur niche, mais le nombre de ces infractions est faible par rapport au nombre de cas commis dans la niche. Un système de classification qui correspond à des réalités criminelles permet de décomposer les événements et de mettre en place un système d'alerte et de suivi « intelligent ». Une nouvelle série dans un phénomène sera détectée par une augmentation du nombre de cas de ce phénomène, en particulier dans une région et à une période donnée. Cette nouvelle série, mélangée parmi l'ensemble des délits, ne serait pas forcément détectable, en particulier si elle se déplace. Finalement, la coopération entre les structures de renseignement criminel opérationnel en Suisse romande a été améliorée par le développement d'une plateforme d'information commune et le système de classification y a été entièrement intégré.

Transcriptional profiling reveals divergent roles of PPARalpha and PPARbeta/delta in regulation of gene expression in mouse liver.

Little is known about the role of the transcription factor peroxisome proliferator-activated receptor (PPAR) beta/delta in liver. Here we set out to better elucidate the function of PPARbeta/delta in liver by comparing the effect of PPARalpha and PPARbeta/delta deletion using whole genome transcriptional profiling and analysis of plasma and liver metabolites. In fed state, the number of genes altered by PPARalpha and PPARbeta/delta deletion was similar, whereas in fasted state the effect of PPARalpha deletion was much more pronounced, consistent with the pattern of gene expression of PPARalpha and PPARbeta/delta. Minor overlap was found between PPARalpha- and PPARbeta/delta-dependent gene regulation in liver. Pathways upregulated by PPARbeta/delta deletion were connected to innate immunity and inflammation. Pathways downregulated by PPARbeta/delta deletion included lipoprotein metabolism and various pathways related to glucose utilization, which correlated with elevated plasma glucose and triglycerides and reduced plasma cholesterol in PPARbeta/delta-/- mice. Downregulated genes that may underlie these metabolic alterations included Pklr, Fbp1, Apoa4, Vldlr, Lipg, and Pcsk9, which may represent novel PPARbeta/delta target genes. In contrast to PPARalpha-/- mice, no changes in plasma free fatty acid, plasma beta-hydroxybutyrate, liver triglycerides, and liver glycogen were observed in PPARbeta/delta-/- mice. Our data indicate that PPARbeta/delta governs glucose utilization and lipoprotein metabolism and has an important anti-inflammatory role in liver. Overall, our analysis reveals divergent roles of PPARalpha and PPARbeta/delta in regulation of gene expression in mouse liver.

Central and Cortical Gray Mater Segmentation of Magnetic Resonance Images of the Fetal Brain

Motivation. The study of human brain development in itsearly stage is today possible thanks to in vivo fetalmagnetic resonance imaging (MRI) techniques. Aquantitative analysis of fetal cortical surfacerepresents a new approach which can be used as a markerof the cerebral maturation (as gyration) and also forstudying central nervous system pathologies [1]. However,this quantitative approach is a major challenge forseveral reasons. First, movement of the fetus inside theamniotic cavity requires very fast MRI sequences tominimize motion artifacts, resulting in a poor spatialresolution and/or lower SNR. Second, due to the ongoingmyelination and cortical maturation, the appearance ofthe developing brain differs very much from thehomogenous tissue types found in adults. Third, due tolow resolution, fetal MR images considerably suffer ofpartial volume (PV) effect, sometimes in large areas.Today extensive efforts are made to deal with thereconstruction of high resolution 3D fetal volumes[2,3,4] to cope with intra-volume motion and low SNR.However, few studies exist related to the automatedsegmentation of MR fetal imaging. [5] and [6] work on thesegmentation of specific areas of the fetal brain such asposterior fossa, brainstem or germinal matrix. Firstattempt for automated brain tissue segmentation has beenpresented in [7] and in our previous work [8]. Bothmethods apply the Expectation-Maximization Markov RandomField (EM-MRF) framework but contrary to [7] we do notneed from any anatomical atlas prior. Data set &Methods. Prenatal MR imaging was performed with a 1-Tsystem (GE Medical Systems, Milwaukee) using single shotfast spin echo (ssFSE) sequences (TR 7000 ms, TE 180 ms,FOV 40 x 40 cm, slice thickness 5.4mm, in plane spatialresolution 1.09mm). Each fetus has 6 axial volumes(around 15 slices per volume), each of them acquired inabout 1 min. Each volume is shifted by 1 mm with respectto the previous one. Gestational age (GA) ranges from 29to 32 weeks. Mother is under sedation. Each volume ismanually segmented to extract fetal brain fromsurrounding maternal tissues. Then, in-homogeneityintensity correction is performed using [9] and linearintensity normalization is performed to have intensityvalues that range from 0 to 255. Note that due tointra-tissue variability of developing brain someintensity variability still remains. For each fetus, ahigh spatial resolution image of isotropic voxel size of1.09 mm is created applying [2] and using B-splines forthe scattered data interpolation [10] (see Fig. 1). Then,basal ganglia (BS) segmentation is performed on thissuper reconstructed volume. Active contour framework witha Level Set (LS) implementation is used. Our LS follows aslightly different formulation from well-known Chan-Vese[11] formulation. In our case, the LS evolves forcing themean of the inside of the curve to be the mean intensityof basal ganglia. Moreover, we add local spatial priorthrough a probabilistic map created by fitting anellipsoid onto the basal ganglia region. Some userinteraction is needed to set the mean intensity of BG(green dots in Fig. 2) and the initial fitting points forthe probabilistic prior map (blue points in Fig. 2). Oncebasal ganglia are removed from the image, brain tissuesegmentation is performed as described in [8]. Results.The case study presented here has 29 weeks of GA. Thehigh resolution reconstructed volume is presented in Fig.1. The steps of BG segmentation are shown in Fig. 2.Overlap in comparison with manual segmentation isquantified by the Dice similarity index (DSI) equal to0.829 (values above 0.7 are considered a very goodagreement). Such BG segmentation has been applied on 3other subjects ranging for 29 to 32 GA and the DSI hasbeen of 0.856, 0.794 and 0.785. Our segmentation of theinner (red and blue contours) and outer cortical surface(green contour) is presented in Fig. 3. Finally, torefine the results we include our WM segmentation in theFreesurfer software [12] and some manual corrections toobtain Fig.4. Discussion. Precise cortical surfaceextraction of fetal brain is needed for quantitativestudies of early human brain development. Our workcombines the well known statistical classificationframework with the active contour segmentation forcentral gray mater extraction. A main advantage of thepresented procedure for fetal brain surface extraction isthat we do not include any spatial prior coming fromanatomical atlases. The results presented here arepreliminary but promising. Our efforts are now in testingsuch approach on a wider range of gestational ages thatwe will include in the final version of this work andstudying as well its generalization to different scannersand different type of MRI sequences. References. [1]Guibaud, Prenatal Diagnosis 29(4) (2009). [2] Rousseau,Acad. Rad. 13(9), 2006, [3] Jiang, IEEE TMI 2007. [4]Warfield IADB, MICCAI 2009. [5] Claude, IEEE Trans. Bio.Eng. 51(4) (2004). [6] Habas, MICCAI (Pt. 1) 2008. [7]Bertelsen, ISMRM 2009 [8] Bach Cuadra, IADB, MICCAI 2009.[9] Styner, IEEE TMI 19(39 (2000). [10] Lee, IEEE Trans.Visual. And Comp. Graph. 3(3), 1997, [11] Chan, IEEETrans. Img. Proc, 10(2), 2001 [12] Freesurfer,http://surfer.nmr.mgh.harvard.edu.

Early expression of the type III secretion system of Parachlamydia acanthamoebae during a replicative cycle within its natural host cell Acanthamoeba castellanii.

The type three secretion system (T3SS) operons of Chlamydiales bacteria are distributed in different clusters along their chromosomes and are conserved at both the level of sequence and genetic organization. A complete characterization of the temporal expression of multiple T3SS components at the transcriptional and protein levels has been performed in Parachlamydia acanthamoebae, replicating in its natural host cell Acanthamoeba castellanii. The T3SS components were classified in four different temporal clusters depending on their pattern of expression during the early, mid- and late phases of the infectious cycle. The putative T3SS transcription units predicted in Parachlamydia are similar to those described in Chlamydia trachomatis, suggesting that T3SS units of transcriptional expression are highly conserved among Chlamydiales bacteria. The maximal expression and activation of the T3SS of Parachlamydia occurred during the early to mid-phase of the infectious cycle corresponding to a critical phase during which the intracellular bacterium has (1) to evade and/or block the lytic pathway of the amoeba, (2) to differentiate from elementary bodies (EBs) to reticulate bodies (RBs), and (3) to modulate the maturation of its vacuole to create a replicative niche able to sustain efficient bacterial growth.

Aging of myelinating glial cells predominantly affects lipid metabolism and immune response pathways.

Both the central and the peripheral nervous systems are prone to multiple age-dependent neurological deficits, often attributed to still unknown alterations in the function of myelinating glia. To uncover the biological processes affected in glial cells by aging, we analyzed gene expression of the Schwann cell-rich mouse sciatic nerve at 17 time points throughout life, from day of birth until senescence. By combining these data with the gene expression data of myelin mouse mutants carrying deletions of either Pmp22, SCAP, or Lpin1, we found that the majority of age-related transcripts were also affected in myelin mutants (54.4%) and were regulated during PNS development (59.5%), indicating a high level of overlap in implicated molecular pathways. The expression profiles in aging copied the direction of transcriptional changes observed in neuropathy models; however, they had the opposite direction when compared with PNS development. The most significantly altered biological processes in aging involved the inflammatory/immune response and lipid metabolism. Interestingly, both these pathways were comparably changed in the aging optic nerve, suggesting that similar biological processes are affected in aging of glia-rich parts of the central and peripheral nervous systems. Our comprehensive comparison of gene expression in three distinct biological conditions including development, aging, and myelin disease thus revealed a previously unanticipated relationship among themselves and identified lipid metabolism and inflammatory/immune response pathways as potential therapeutical targets to prevent or delay so far incurable age-related and inherited forms of neuropathies.

The Media and Socio-Cultural Regulation of Religion

(Résumé de l'ouvrage) Originale, insolite, renaissante, l'action religieuse émergente bouscule les habitudes, ébranle les certitudes, construit ici, maintenant, l'autre monde. Peut-on courir le risque? Voilà que la question se pose et se résout en rumeurs publiques, poursuites judiciaires et tensions scolaires, lesquelles mettent à nu des mécanismes inédits d'institutionnalisation de l'expérience religieuse en modernité. As new religious movements seek to carve out their own niche in society, public controversy and opposing beliefs can spark bitter debates, and can even lead to calls for state intervention. How then do new or borderline religious groups negotiate or mediate the building of public space?

Cost of Illness and Contingent Valuation : Controlling for the Motivations of Expressed Preferences in an Attempt to Avoid Double-Counting

This paper addresses the issue of double counting of health impacts in the context of cost of illness valuation. Double counting occurs when estimates are jointly used, which rely on valuation techniques that overlap. As a solution, we propose to limit the scope of each of the valuation method to a specific range of impacts. In order to limit the contingentvaluation method to the exclusive valuation of intangible costs, we propose a three steps approach : (1) leave the respondents free to valuate the consequences which matter to them, (2) elicit respondent's motivations, (3) control for the influence motivations have on elicited values. This procedure was applied in a Swiss contingent-valuation. An econometric treatment was applied in order to limit the scope of the estimates of the contingent valuation method to intangibles,therefore the possibility to a combination of methods with the risk of double-counting and underestimating costs being kept to a minimum.

Cutaneous plasmacytosis: an unusual presentation sharing features with POEMS syndrome?

Cutaneous plasmacytosis is a recently described skin disorder consisting of brown to red papules and nodules containing polyclonal plasmacytes. In this particular case, leg ulcers developed but also a diffuse patchy hyperpigmentation coexisting with a primary hypothyroidisim. The last two signs have only been described to date in POEMS syndrome, which is linked to monoclonal plasmacytic proliferation, and might suggest an overlap between these two entities.

Polar gradients of the DYRK-family kinase Pom1 couple cell length with the cell cycle.

Cells normally grow to a certain size before they enter mitosis and divide. Entry into mitosis depends on the activity of Cdk1, which is inhibited by the Wee1 kinase and activated by the Cdc25 phosphatase. However, how cells sense their size for mitotic commitment remains unknown. Here we show that an intracellular gradient of the dual-specificity tyrosine-phosphorylation regulated kinase (DYRK) Pom1, which emanates from the ends of rod-shaped Schizosaccharomyces pombe cells, serves to measure cell length and control mitotic entry. Pom1 provides positional information both for polarized growth and to inhibit cell division at cell ends. We discovered that Pom1 is also a dose-dependent G2-M inhibitor. Genetic analyses indicate that Pom1 negatively regulates Cdr1 and Cdr2, two previously described Wee1 inhibitors of the SAD kinase family. This inhibition may be direct, because in vivo and in vitro evidence suggest that Pom1 phosphorylates Cdr2. Whereas Cdr1 and Cdr2 localize to a medial cortical region, Pom1 forms concentration gradients from cell tips that overlap with Cdr1 and Cdr2 in short cells, but not in long cells. Disturbing these Pom1 gradients leads to Cdr2 phosphorylation and imposes a G2 delay. In short cells, Pom1 prevents precocious M-phase entry, suggesting that the higher medial Pom1 levels inhibit Cdr2 and promote a G2 delay. Thus, gradients of Pom1 from cell ends provide a measure of cell length to regulate M-phase entry.

Reconstructing the origins of high-alpine niches and cushion life form in the genus Androsace S.L. (Primulaceae).

Relatively, few species have been able to colonize extremely cold alpine environments. We investigate the role played by the cushion life form in the evolution of climatic niches in the plant genus Androsace s.l., which spreads across the mountain ranges of the Northern Hemisphere. Using robust methods that account for phylogenetic uncertainty, intraspecific variability of climatic requirements and different life-history evolution scenarios, we show that climatic niches of Androsace s.l. exhibit low phylogenetic signal and that they evolved relatively recently and punctually. Models of niche evolution fitted onto phylogenies show that the cushion life form has been a key innovation providing the opportunity to occupy extremely cold environments, thus contributing to rapid climatic niche diversification in the genus Androsace s.l. We then propose a plausible scenario for the adaptation of plants to alpine habitats.

Evaluating the ability of habitat suitability models to predict species presences.

Models predicting species spatial distribution are increasingly applied to wildlife management issues, emphasising the need for reliable methods to evaluate the accuracy of their predictions. As many available datasets (e.g. museums, herbariums, atlas) do not provide reliable information about species absences, several presence-only based analyses have been developed. However, methods to evaluate the accuracy of their predictions are few and have never been validated. The aim of this paper is to compare existing and new presenceonly evaluators to usual presence/absence measures. We use a reliable, diverse, presence/absence dataset of 114 plant species to test how common presence/absence indices (Kappa, MaxKappa, AUC, adjusted D-2) compare to presenceonly measures (AVI, CVI, Boyce index) for evaluating generalised linear models (GLM). Moreover we propose a new, threshold-independent evaluator, which we call "continuous Boyce index". All indices were implemented in the B10MAPPER software. We show that the presence-only evaluators are fairly correlated (p > 0.7) to the presence/absence ones. The Boyce indices are closer to AUC than to MaxKappa and are fairly insensitive to species prevalence. In addition, the Boyce indices provide predicted-toexpected ratio curves that offer further insights into the model quality: robustness, habitat suitability resolution and deviation from randomness. This information helps reclassifying predicted maps into meaningful habitat suitability classes. The continuous Boyce index is thus both a complement to usual evaluation of presence/absence models and a reliable measure of presence-only based predictions.