64 resultados para Layered and staggered structure
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This paper presents the underlying concepts developed by the Institute of Geography of the University of Lausanne (Switzerland) for a popularisation project of the geoheritage in the Tsanfleuron-Sanetsch area (Valais, Switzerland). Due to its wide scientific interest, the local geoheritage is of great value (Reynard, 2008). The article details the complementary links existing between the different parts of a geotourist project - databases, educational panels, educational material and geotourist map - developed for popularising the geoheritage value of the area. Each element of the project is briefly presented. Special focus is set on mapping questions: how cartographic design and information structure can be set in order to facilitate map's use and comprehension. In this way, the Tsanfleuron-Sanetsch map is presented as an applied example of the guiding principles proposed by Coratza and Regolini-Bissig (2009).
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The Polochic and Motagua faults define the active plate boundary between the North American and Caribbean plates in central Guatemala. A splay of the Polochic Fault traverses the rapidly growing city of San Miguel Uspantan that is periodically affected by destructive earthquakes. This fault splay was located using a 2D electrical resistivity tomography (ERT) survey that also characterized the fault damage zone and evaluated the thickness and nature of recent deposits upon which most of the city is built. ERT images show the fault as a similar to 50 m wide, near-vertical low-resistivity anomaly, bounded within a few meters by high resistivity anomalies. Forward modeling reproduces the key aspects of the observed electrical resistivity data with remarkable fidelity thus defining the overall location, geometry, and internal structure of the fault zone as well as the affected lithologies. Our results indicate that the city is constructed on a similar to 20 m thick surficial layer consisting of poorly consolidated, highly porous, water-logged pumice. This soft layer is likely to amplify seismic waves and to liquefy upon moderate to strong ground shaking. The electrical conductivity as well as the major element chemistry of the groundwater provides evidence to suggest that the local aquifer might, at least in part, be fed by water rising along the fault. Therefore, the potential threat posed by this fault splay may not be limited to its seismic activity per se, but could be compounded its potential propensity to enhance seismic site effects by injecting water into the soft surficial sediments. The results of this study provide the basis for a rigorous analysis of seismic hazard and sustainable development of San Miguel Uspantan and illustrate the potential of ERT surveying for paleoseismic studies.
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The genetic determinants and phenotypic traits which make a Staphylococcus aureus strain a successful colonizer are largely unknown. The genetic diversity and population structure of 133 S. aureus isolates from healthy, generally risk-free adult carriers were investigated using four different typing methods: multilocus sequence typing (MLST), amplified fragment length polymorphism analysis (AFLP), double-locus sequence typing (DLST), and spa typing were compared. Carriage isolates displayed great genetic diversity which could only be revealed fully by DLST. Results of AFLP and MLST were highly concordant in the delineation of genotypic clusters of closely related isolates, roughly equivalent to clonal complexes. spa typing and DLST provided considerably less phylogenetic information. The resolution of spa typing was similar to that of AFLP and inferior to that of DLST. AFLP proved to be the most universal method, combining a phylogeny-building capacity similar to that of MLST with a much higher resolution. However, it had a lower reproducibility than sequencing-based MLST, DLST, and spa typing. We found two cases of methicillin-resistant S. aureus colonization, both of which were most likely associated with employment at a health service. Of 21 genotypic clusters detected, 2 were most prevalent: cluster 45 and cluster 30 each colonized 24% of the carrier population. The number of bacteria found in nasal samples varied significantly among the clusters, but the most prevalent clusters were not particularly numerous in the nasal samples. We did not find much evidence that genotypic clusters were associated with different carrier characteristics, such as age, sex, medical conditions, or antibiotic use. This may provide empirical support for the idea that genetic clusters in bacteria are maintained in the absence of adaptation to different niches. Alternatively, carrier characteristics other than those evaluated here or factors other than human hosts may exert selective pressure maintaining genotypic clusters.
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PURPOSE: Small intestinal submucosa is a xenogenic, acellular, collagen rich membrane with inherent growth factors that has previously been shown to promote in vivo bladder regeneration. We evaluate in vitro use of small intestinal submucosa to support the individual and combined growth of bladder urothelial cells and smooth muscle cells for potential use in tissue engineering techniques, and in vitro study of the cellular mechanisms involved in bladder regeneration. MATERIALS AND METHODS: Primary cultures of human bladder urothelial cells and smooth muscle cells were established using standard enzymatic digestion or explant techniques. Cultured cells were then seeded on small intestinal submucosa at a density of 1 x 105 cells per cm.2, incubated and harvested at 3, 7, 14 and 28 days. The 5 separate culture methods evaluated were urothelial cells seeded alone on the mucosal surface of small intestinal submucosa, smooth muscle cells seeded alone on the mucosal surface, layered coculture of smooth muscle cells seeded on the mucosal surface followed by urothelial cells 1 hour later, sandwich coculture of smooth muscle cells seeded on the serosal surface followed by seeding of urothelial cells on the mucosal surface 24 hours later, and mixed coculture of urothelial cells and smooth muscle cells mixed and seeded together on the mucosal surface. Following harvesting at the designated time points small intestinal submucosa cell constructs were formalin fixed and processed for routine histology including Masson trichrome staining. Specific cell growth characteristics were studied with particular attention to cell morphology, cell proliferation and layering, cell sorting, presence of a pseudostratified urothelium and matrix penetrance. To aid in the identification of smooth muscle cells and urothelial cells in the coculture groups, immunohistochemical analysis was performed with antibodies to alpha-smooth muscle actin and cytokeratins AE1/AE3. RESULTS: Progressive 3-dimensional growth of urothelial cells and smooth muscle cells occurred in vitro on small intestinal submucosa. When seeded alone urothelial cells and smooth muscle cells grew in several layers with minimal to no matrix penetration. In contrast, layered, mixed and sandwich coculture methods demonstrated significant enhancement of smooth muscle cell penetration of the membrane. The layered and sandwich coculture techniques resulted in organized cell sorting, formation of a well-defined pseudostratified urothelium and multilayered smooth muscle cells with enhanced matrix penetration. With the mixed coculture technique there was no evidence of cell sorting although matrix penetrance by the smooth muscle cells was evident. Immunohistochemical studies demonstrated that urothelial cells and smooth muscle cells maintain the expression of the phenotypic markers of differentiation alpha-smooth muscle actin and cytokeratins AE1/AE3. CONCLUSIONS: Small intestinal submucosa supports the 3-dimensional growth of human bladder cells in vitro. Successful combined growth of bladder cells on small intestinal submucosa with different seeding techniques has important future clinical implications with respect to tissue engineering technology. The results of our study demonstrate that there are important smooth muscle cell-epithelial cell interactions involved in determining the type of in vitro cell growth that occurs on small intestinal submucosa. Small intestinal submucosa is a valuable tool for in vitro study of the cell-cell and cell-matrix interactions that are involved in regeneration and various disease processes of the bladder.
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La présente étude est à la fois une évaluation du processus de la mise en oeuvre et des impacts de la police de proximité dans les cinq plus grandes zones urbaines de Suisse - Bâle, Berne, Genève, Lausanne et Zurich. La police de proximité (community policing) est à la fois une philosophie et une stratégie organisationnelle qui favorise un partenariat renouvelé entre la police et les communautés locales dans le but de résoudre les problèmes relatifs à la sécurité et à l'ordre public. L'évaluation de processus a analysé des données relatives aux réformes internes de la police qui ont été obtenues par l'intermédiaire d'entretiens semi-structurés avec des administrateurs clés des cinq départements de police, ainsi que dans des documents écrits de la police et d'autres sources publiques. L'évaluation des impacts, quant à elle, s'est basée sur des variables contextuelles telles que des statistiques policières et des données de recensement, ainsi que sur des indicateurs d'impacts construit à partir des données du Swiss Crime Survey (SCS) relatives au sentiment d'insécurité, à la perception du désordre public et à la satisfaction de la population à l'égard de la police. Le SCS est un sondage régulier qui a permis d'interroger des habitants des cinq grandes zones urbaines à plusieurs reprises depuis le milieu des années 1980. L'évaluation de processus a abouti à un « Calendrier des activités » visant à créer des données de panel permettant de mesurer les progrès réalisés dans la mise en oeuvre de la police de proximité à l'aide d'une grille d'évaluation à six dimensions à des intervalles de cinq ans entre 1990 et 2010. L'évaluation des impacts, effectuée ex post facto, a utilisé un concept de recherche non-expérimental (observational design) dans le but d'analyser les impacts de différents modèles de police de proximité dans des zones comparables à travers les cinq villes étudiées. Les quartiers urbains, délimités par zone de code postal, ont ainsi été regroupés par l'intermédiaire d'une typologie réalisée à l'aide d'algorithmes d'apprentissage automatique (machine learning). Des algorithmes supervisés et non supervisés ont été utilisés sur les données à haute dimensionnalité relatives à la criminalité, à la structure socio-économique et démographique et au cadre bâti dans le but de regrouper les quartiers urbains les plus similaires dans des clusters. D'abord, les cartes auto-organisatrices (self-organizing maps) ont été utilisées dans le but de réduire la variance intra-cluster des variables contextuelles et de maximiser simultanément la variance inter-cluster des réponses au sondage. Ensuite, l'algorithme des forêts d'arbres décisionnels (random forests) a permis à la fois d'évaluer la pertinence de la typologie de quartier élaborée et de sélectionner les variables contextuelles clés afin de construire un modèle parcimonieux faisant un minimum d'erreurs de classification. Enfin, pour l'analyse des impacts, la méthode des appariements des coefficients de propension (propensity score matching) a été utilisée pour équilibrer les échantillons prétest-posttest en termes d'âge, de sexe et de niveau d'éducation des répondants au sein de chaque type de quartier ainsi identifié dans chacune des villes, avant d'effectuer un test statistique de la différence observée dans les indicateurs d'impacts. De plus, tous les résultats statistiquement significatifs ont été soumis à une analyse de sensibilité (sensitivity analysis) afin d'évaluer leur robustesse face à un biais potentiel dû à des covariables non observées. L'étude relève qu'au cours des quinze dernières années, les cinq services de police ont entamé des réformes majeures de leur organisation ainsi que de leurs stratégies opérationnelles et qu'ils ont noué des partenariats stratégiques afin de mettre en oeuvre la police de proximité. La typologie de quartier développée a abouti à une réduction de la variance intra-cluster des variables contextuelles et permet d'expliquer une partie significative de la variance inter-cluster des indicateurs d'impacts avant la mise en oeuvre du traitement. Ceci semble suggérer que les méthodes de géocomputation aident à équilibrer les covariables observées et donc à réduire les menaces relatives à la validité interne d'un concept de recherche non-expérimental. Enfin, l'analyse des impacts a révélé que le sentiment d'insécurité a diminué de manière significative pendant la période 2000-2005 dans les quartiers se trouvant à l'intérieur et autour des centres-villes de Berne et de Zurich. Ces améliorations sont assez robustes face à des biais dus à des covariables inobservées et covarient dans le temps et l'espace avec la mise en oeuvre de la police de proximité. L'hypothèse alternative envisageant que les diminutions observées dans le sentiment d'insécurité soient, partiellement, un résultat des interventions policières de proximité semble donc être aussi plausible que l'hypothèse nulle considérant l'absence absolue d'effet. Ceci, même si le concept de recherche non-expérimental mis en oeuvre ne peut pas complètement exclure la sélection et la régression à la moyenne comme explications alternatives. The current research project is both a process and impact evaluation of community policing in Switzerland's five major urban areas - Basel, Bern, Geneva, Lausanne, and Zurich. Community policing is both a philosophy and an organizational strategy that promotes a renewed partnership between the police and the community to solve problems of crime and disorder. The process evaluation data on police internal reforms were obtained through semi-structured interviews with key administrators from the five police departments as well as from police internal documents and additional public sources. The impact evaluation uses official crime records and census statistics as contextual variables as well as Swiss Crime Survey (SCS) data on fear of crime, perceptions of disorder, and public attitudes towards the police as outcome measures. The SCS is a standing survey instrument that has polled residents of the five urban areas repeatedly since the mid-1980s. The process evaluation produced a "Calendar of Action" to create panel data to measure community policing implementation progress over six evaluative dimensions in intervals of five years between 1990 and 2010. The impact evaluation, carried out ex post facto, uses an observational design that analyzes the impact of the different community policing models between matched comparison areas across the five cities. Using ZIP code districts as proxies for urban neighborhoods, geospatial data mining algorithms serve to develop a neighborhood typology in order to match the comparison areas. To this end, both unsupervised and supervised algorithms are used to analyze high-dimensional data on crime, the socio-economic and demographic structure, and the built environment in order to classify urban neighborhoods into clusters of similar type. In a first step, self-organizing maps serve as tools to develop a clustering algorithm that reduces the within-cluster variance in the contextual variables and simultaneously maximizes the between-cluster variance in survey responses. The random forests algorithm then serves to assess the appropriateness of the resulting neighborhood typology and to select the key contextual variables in order to build a parsimonious model that makes a minimum of classification errors. Finally, for the impact analysis, propensity score matching methods are used to match the survey respondents of the pretest and posttest samples on age, gender, and their level of education for each neighborhood type identified within each city, before conducting a statistical test of the observed difference in the outcome measures. Moreover, all significant results were subjected to a sensitivity analysis to assess the robustness of these findings in the face of potential bias due to some unobserved covariates. The study finds that over the last fifteen years, all five police departments have undertaken major reforms of their internal organization and operating strategies and forged strategic partnerships in order to implement community policing. The resulting neighborhood typology reduced the within-cluster variance of the contextual variables and accounted for a significant share of the between-cluster variance in the outcome measures prior to treatment, suggesting that geocomputational methods help to balance the observed covariates and hence to reduce threats to the internal validity of an observational design. Finally, the impact analysis revealed that fear of crime dropped significantly over the 2000-2005 period in the neighborhoods in and around the urban centers of Bern and Zurich. These improvements are fairly robust in the face of bias due to some unobserved covariate and covary temporally and spatially with the implementation of community policing. The alternative hypothesis that the observed reductions in fear of crime were at least in part a result of community policing interventions thus appears at least as plausible as the null hypothesis of absolutely no effect, even if the observational design cannot completely rule out selection and regression to the mean as alternative explanations.
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This study examines differences in sibling relationships among native Dutch and immigrant groups in the Netherlands. It uses a large national dataset to compare adult sibling relationships among Moroccan, Turkish, Caribbean and native Dutch groups, focusing on the varying importance of gender composition and age structure for the sibling relationship in the ethnic minority groups and the native Dutch families. Results show that, on average, ethnic minorities in the Netherlands have more involved sibling relationships in adulthood, with more contact, more emotional support, practical support (except Turks and Antilleans), a higher relationship quality, but also more conflict (among the Turks and Antilleans) compared to the Dutch. Gender constellation and hierarchical position were not of equal influence in all groups, although no clear patterns emerged.
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Eukaryotic gene expression depends on a complex interplay between the transcriptional apparatus and chromatin structure. We report here a yeast model system for investigating the functional interaction between the human estrogen receptor (hER) and CTF1, a member of the CTF/NFI transcription factor family. We show that a CTF1-fusion protein and the hER transactivate a synthetic promoter in yeast in a synergistic manner. This interaction requires the proline-rich transactivation domain of CTF1. When the natural estrogen-dependent vitellogenin B1 promoter is tested in yeast, CTF1 and CTF1-fusion proteins are unable to activate transcription, and no synergy is observed between hER, which activates the B1 promoter, and these factors. Chromatin structure analysis on this promoter reveals positioned nucleosomes at -430 to -270 (+/-20 bp) and at -270 to - 100 (+/-20 bp) relative to the start site of transcription. The positions of the nucleosomes remain unchanged upon hormone-dependent transcriptional activation of the promoter, and the more proximal nucleosome appears to mask the CTF/NFI site located at - 101 to -114. We conclude that a functional interaction of hER with the estrogen response element located upstream of a basal promoter occurs in yeast despite the nucleosomal organization of this promoter, whereas the interaction of CTF1 with its target site is apparently precluded by a nucleosome.
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BACKGROUND: Whether or not cognitive impairment and brain structure changes are trait characteristics of late-life depression is still disputed. Previous studies led to conflicting data possibly because of the difference in the age of depression onset. In fact, several lines of evidence suggest that late-onset depression (LOD) is more frequently associated with neuropsychological deficits and brain pathology than early-onset depression (EOD). To date, no study explored concomitantly the cognitive profile and brain magnetic resonance imaging (MRI) patterns in euthymic EOD and LOD patients. METHOD: Using a cross-sectional design, 41 remitted outpatients (30 with EOD and 11 with LOD) were compared to 30 healthy controls. Neuropsychological evaluation concerned working memory, episodic memory, processing speed, naming capacity and executive functions. Volumetric estimates of the amygdala, hippocampus, entorhinal and anterior cingulate cortex were obtained using both voxel-based and region of interest morphometric methods. White matter hyperintensities were assessed semiquantitatively. RESULTS: Both cognitive performance and brain volumes were preserved in euthymic EOD patients whereas LOD patients showed a significant reduction of episodic memory capacity and a higher rate of periventricular hyperintensities compared to both controls and EOD patients. CONCLUSION: Our results support the dissociation between EOD thought to be mainly related to psychosocial factors and LOD that is characterized by increasing vascular burden and episodic memory decline.
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In oviparous vertebrates vitellogenin, the precursor of the major yolk proteins, is synthesized in the liver of mature females under the control of estrogen. We have established the organization and primary structure of the 5' end region of the Xenopus laevis vitellogenin A2 gene and of the major chicken vitellogenin gene. The first three homologous exons have exactly the same length in both species, namely 53, 21 and 152 nucleotides, and present an overall sequence homology of 60%. In both species, the 5'-non-coding region of the vitellogenin mRNA measures only 13 nucleotides, nine of which are conserved. In contrast, the corresponding introns of the Xenopus and the chicken vitellogenin gene show no significant sequence homology. Within the 500 nucleotides preceding the 5' end of the genes, at least six blocks with sequence homologies of greater than 70% were detected. It remains to be demonstrated which of these conserved sequences, if any, are involved in the hormone-regulated expression of the vitellogenin genes.
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The Gene Ontology (GO) Consortium (http://www.geneontology.org) (GOC) continues to develop, maintain and use a set of structured, controlled vocabularies for the annotation of genes, gene products and sequences. The GO ontologies are expanding both in content and in structure. Several new relationship types have been introduced and used, along with existing relationships, to create links between and within the GO domains. These improve the representation of biology, facilitate querying, and allow GO developers to systematically check for and correct inconsistencies within the GO. Gene product annotation using GO continues to increase both in the number of total annotations and in species coverage. GO tools, such as OBO-Edit, an ontology-editing tool, and AmiGO, the GOC ontology browser, have seen major improvements in functionality, speed and ease of use.
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Joint inversion of crosshole ground-penetrating radar and seismic data can improve model resolution and fidelity of the resultant individual models. Model coupling obtained by minimizing or penalizing some measure of structural dissimilarity between models appears to be the most versatile approach because only weak assumptions about petrophysical relationships are required. Nevertheless, experimental results and petrophysical arguments suggest that when porosity variations are weak in saturated unconsolidated environments, then radar wave speed is approximately linearly related to seismic wave speed. Under such circumstances, model coupling also can be achieved by incorporating cross-covariances in the model regularization. In two case studies, structural similarity is imposed by penalizing models for which the model cross-gradients are nonzero. A first case study demonstrates improvements in model resolution by comparing the resulting models with borehole information, whereas a second case study uses point-spread functions. Although radar seismic wavespeed crossplots are very similar for the two case studies, the models plot in different portions of the graph, suggesting variances in porosity. Both examples display a close, quasilinear relationship between radar seismic wave speed in unconsolidated environments that is described rather well by the corresponding lower Hashin-Shtrikman (HS) bounds. Combining crossplots of the joint inversion models with HS bounds can constrain porosity and pore structure better than individual inversion results can.
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The capacity to interact socially and share information underlies the success of many animal species, humans included. Researchers of many fields have emphasized the evo¬lutionary significance of how patterns of connections between individuals, or the social networks, and learning abilities affect the information obtained by animal societies. To date, studies have focused on the dynamics either of social networks, or of the spread of information. The present work aims to study them together. We make use of mathematical and computational models to study the dynamics of networks, where social learning and information sharing affect the structure of the population the individuals belong to. The number and strength of the relationships between individuals, in turn, impact the accessibility and the diffusion of the shared information. Moreover, we inves¬tigate how different strategies in the evaluation and choice of interacting partners impact the processes of knowledge acquisition and social structure rearrangement. First, we look at how different evaluations of social interactions affect the availability of the information and the network topology. We compare a first case, where individuals evaluate social exchanges by the amount of information that can be shared by the partner, with a second case, where they evaluate interactions by considering their partners' social status. We show that, even if both strategies take into account the knowledge endowments of the partners, they have very different effects on the system. In particular, we find that the first case generally enables individuals to accumulate higher amounts of information, thanks to the more efficient patterns of social connections they are able to build. Then, we study the effects that homophily, or the tendency to interact with similar partners, has on knowledge accumulation and social structure. We compare the case where individuals who know the same information are more likely to learn socially from each other, to the opposite case, where individuals who know different information are instead more likely to learn socially from each other. We find that it is not trivial to claim which strategy is better than the other. Depending on the possibility of forgetting information, the way new social partners can be chosen, and the population size, we delineate the conditions for which each strategy allows accumulating more information, or in a faster way For these conditions, we also discuss the topological characteristics of the resulting social structure, relating them to the information dynamics outcome. In conclusion, this work paves the road for modeling the joint dynamics of the spread of information among individuals and their social interactions. It also provides a formal framework to study jointly the effects of different strategies in the choice of partners on social structure, and how they favor the accumulation of knowledge in the population. - La capacité d'interagir socialement et de partager des informations est à la base de la réussite de nombreuses espèces animales, y compris les humains. Les chercheurs de nombreux domaines ont souligné l'importance évolutive de la façon dont les modes de connexions entre individus, ou réseaux sociaux et les capacités d'apprentissage affectent les informations obtenues par les sociétés animales. À ce jour, les études se sont concentrées sur la dynamique soit des réseaux sociaux, soit de la diffusion de l'information. Le présent travail a pour but de les étudier ensemble. Nous utilisons des modèles mathématiques et informatiques pour étudier la dynamique des réseaux, où l'apprentissage social et le partage d'information affectent la structure de la population à laquelle les individus appartiennent. Le nombre et la solidité des relations entre les individus ont à leurs tours un impact sur l'accessibilité et la diffusion de l'informa¬tion partagée. Par ailleurs, nous étudions comment les différentes stratégies d'évaluation et de choix des partenaires d'interaction ont une incidence sur les processus d'acquisition des connaissances ainsi que le réarrangement de la structure sociale. Tout d'abord, nous examinons comment des évaluations différentes des interactions sociales influent sur la disponibilité de l'information ainsi que sur la topologie du réseau. Nous comparons un premier cas, où les individus évaluent les échanges sociaux par la quantité d'information qui peut être partagée par le partenaire, avec un second cas, où ils évaluent les interactions en tenant compte du statut social de leurs partenaires. Nous montrons que, même si les deux stratégies prennent en compte le montant de connaissances des partenaires, elles ont des effets très différents sur le système. En particulier, nous constatons que le premier cas permet généralement aux individus d'accumuler de plus grandes quantités d'information, grâce à des modèles de connexions sociales plus efficaces qu'ils sont capables de construire. Ensuite, nous étudions les effets que l'homophilie, ou la tendance à interagir avec des partenaires similaires, a sur l'accumulation des connaissances et la structure sociale. Nous comparons le cas où des personnes qui connaissent les mêmes informations sont plus sus¬ceptibles d'apprendre socialement l'une de l'autre, au cas où les individus qui connaissent des informations différentes sont au contraire plus susceptibles d'apprendre socialement l'un de l'autre. Nous constatons qu'il n'est pas trivial de déterminer quelle stratégie est meilleure que l'autre. En fonction de la possibilité d'oublier l'information, la façon dont les nouveaux partenaires sociaux peuvent être choisis, et la taille de la population, nous déterminons les conditions pour lesquelles chaque stratégie permet d'accumuler plus d'in¬formations, ou d'une manière plus rapide. Pour ces conditions, nous discutons également les caractéristiques topologiques de la structure sociale qui en résulte, les reliant au résultat de la dynamique de l'information. En conclusion, ce travail ouvre la route pour la modélisation de la dynamique conjointe de la diffusion de l'information entre les individus et leurs interactions sociales. Il fournit également un cadre formel pour étudier conjointement les effets de différentes stratégies de choix des partenaires sur la structure sociale et comment elles favorisent l'accumulation de connaissances dans la population.
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To determine the separate and interactive effects of fetal inflammation and neonatal hyperoxia on the developing lung, we hypothesized that: 1) antenatal endotoxin (ETX) causes sustained abnormalities of infant lung structure; and 2) postnatal hyperoxia augments the adverse effects of antenatal ETX on infant lung growth. Escherichia coli ETX or saline (SA) was injected into amniotic sacs in pregnant Sprague-Dawley rats at 20 days of gestation. Pups were delivered 2 days later and raised in room air (RA) or moderate hyperoxia (O₂, 80% O₂ at Denver's altitude, ∼65% O₂ at sea level) from birth through 14 days of age. Heart and lung tissues were harvested for measurements. Intra-amniotic ETX caused right ventricular hypertrophy (RVH) and decreased lung vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) protein contents at birth. In ETX-exposed rats (ETX-RA), alveolarization and vessel density were decreased, pulmonary vascular wall thickness percentage was increased, and RVH was persistent throughout the study period compared with controls (SA-RA). After antenatal ETX, moderate hyperoxia increased lung VEGF and VEGFR-2 protein contents in ETX-O₂ rats and improved their alveolar and vascular structure and RVH compared with ETX-RA rats. In contrast, severe hyperoxia (≥95% O₂ at Denver's altitude) further reduced lung vessel density after intra-amniotic ETX exposure. We conclude that intra-amniotic ETX induces fetal pulmonary hypertension and causes persistent abnormalities of lung structure with sustained pulmonary hypertension in infant rats. Moreover, moderate postnatal hyperoxia after antenatal ETX restores lung growth and prevents pulmonary hypertension during infancy.
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A workshop recently held at the Ecole Polytechnique Federale de Lausanne (EPFL, Switzerland) was dedicated to understanding the genetic basis of adaptive change, taking stock of the different approaches developed in theoretical population genetics and landscape genomics and bringing together knowledge accumulated in both research fields. Indeed, an important challenge in theoretical population genetics is to incorporate effects of demographic history and population structure. But important design problems (e.g. focus on populations as units, focus on hard selective sweeps, no hypothesis-based framework in the design of the statistical tests) reduce their capability of detecting adaptive genetic variation. In parallel, landscape genomics offers a solution to several of these problems and provides a number of advantages (e.g. fast computation, landscape heterogeneity integration). But the approach makes several implicit assumptions that should be carefully considered (e.g. selection has had enough time to create a functional relationship between the allele distribution and the environmental variable, or this functional relationship is assumed to be constant). To address the respective strengths and weaknesses mentioned above, the workshop brought together a panel of experts from both disciplines to present their work and discuss the relevance of combining these approaches, possibly resulting in a joint software solution in the future.
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Climate-driven range fluctuations during the Pleistocene have continuously reshaped species distribution leading to populations of contrasting genetic diversity. Contemporary climate change is similarly influencing species distribution and population structure, with important consequences for patterns of genetic diversity and species' evolutionary potential1. Yet few studies assess the impacts of global climatic changes on intraspecific genetic variation2, 3, 4, 5. Here, combining analyses of molecular data with time series of predicted species distributions and a model of diffusion through time over the past 21 kyr, we unravel caribou response to past and future climate changes across its entire Holarctic distribution. We found that genetic diversity is geographically structured with two main caribou lineages, one originating from and confined to Northeastern America, the other originating from Euro-Beringia but also currently distributed in western North America. Regions that remained climatically stable over the past 21 kyr maintained a high genetic diversity and are also predicted to experience higher climatic stability under future climate change scenarios. Our interdisciplinary approach, combining genetic data and spatial analyses of climatic stability (applicable to virtually any taxon), represents a significant advance in inferring how climate shapes genetic diversity and impacts genetic structure.