The role of transcription factories-mediated interchromosomal contacts in the organization of nuclear architecture.

Using numerical simulations, we investigate the underlying physical effects responsible for the overall organization of chromosomal territories in interphase nuclei. In particular, we address the following three questions: (i) why are chromosomal territories with relatively high transcriptional activity on average, closer to the centre of cell's nucleus than those with the lower activity? (ii) Why are actively transcribed genes usually located at the periphery of their chromosomal territories? (iii) Why are pair-wise contacts between active and inactive genes less frequent than those involving only active or only inactive genes? We show that transcription factories-mediated contacts between active genes belonging to different chromosomal territories are instrumental for all these features of nuclear organization to emerge spontaneously due to entropic effects arising when chromatin fibres are highly crowded.

Cannabinoid addiction: behavioral models and neural correlates

The use of cannabis sativa preparations as recreational drugs can be traced back to the earliest civilizations. However, animal models of cannabinoid addiction allowing the exploration of neural correlates of cannabinoid abuse have been developed only recently. We review these models and the role of the CB1 cannabinoid receptor, the main target of natural cannabinoids, and its interaction with opioid and dopamine transmission in reward circuits. Extensive reviews on the molecular basis of cannabinoid action are available elsewhere (Piomelli et al., 2000;Schlicker and Kathmann, 2001).

What can spike train distances tell us about the neural code?

Time scale parametric spike train distances like the Victor and the van Rossum distancesare often applied to study the neural code based on neural stimuli discrimination.Different neural coding hypotheses, such as rate or coincidence coding,can be assessed by combining a time scale parametric spike train distance with aclassifier in order to obtain the optimal discrimination performance. The time scalefor which the responses to different stimuli are distinguished best is assumed to bethe discriminative precision of the neural code. The relevance of temporal codingis evaluated by comparing the optimal discrimination performance with the oneachieved when assuming a rate code.We here characterize the measures quantifying the discrimination performance,the discriminative precision, and the relevance of temporal coding. Furthermore,we evaluate the information these quantities provide about the neural code. Weshow that the discriminative precision is too unspecific to be interpreted in termsof the time scales relevant for encoding. Accordingly, the time scale parametricnature of the distances is mainly an advantage because it allows maximizing thediscrimination performance across a whole set of measures with different sensitivitiesdetermined by the time scale parameter, but not due to the possibility toexamine the temporal properties of the neural code.

Towards a user-friendly webservice architecture for statistical machine translation in the PANACEA project

This paper presents a webservice architecture for Statistical Machine Translation aimed at non-technical users. A workfloweditor allows a user to combine different webservices using a graphical user interface. In the current state of this project,the webservices have been implemented for a range of sentential and sub-sententialaligners. The advantage of a common interface and a common data format allows the user to build workflows exchanging different aligners.

Functional architecture of olfactory ionotropic glutamate receptors.

Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate chemical communication between neurons at synapses. A variant iGluR subfamily, the Ionotropic Receptors (IRs), was recently proposed to detect environmental volatile chemicals in olfactory cilia. Here, we elucidate how these peripheral chemosensors have evolved mechanistically from their iGluR ancestors. Using a Drosophila model, we demonstrate that IRs act in combinations of up to three subunits, comprising individual odor-specific receptors and one or two broadly expressed coreceptors. Heteromeric IR complex formation is necessary and sufficient for trafficking to cilia and mediating odor-evoked electrophysiological responses in vivo and in vitro. IRs display heterogeneous ion conduction specificities related to their variable pore sequences, and divergent ligand-binding domains function in odor recognition and cilia localization. Our results provide insights into the conserved and distinct architecture of these olfactory and synaptic ion channels and offer perspectives into the use of IRs as genetically encoded chemical sensors. VIDEO ABSTRACT:

Wavelet analysis residual kriging vs. neural network residual kriging

This paper deals with the problem of spatial data mapping. A new method based on wavelet interpolation and geostatistical prediction (kriging) is proposed. The method - wavelet analysis residual kriging (WARK) - is developed in order to assess the problems rising for highly variable data in presence of spatial trends. In these cases stationary prediction models have very limited application. Wavelet analysis is used to model large-scale structures and kriging of the remaining residuals focuses on small-scale peculiarities. WARK is able to model spatial pattern which features multiscale structure. In the present work WARK is applied to the rainfall data and the results of validation are compared with the ones obtained from neural network residual kriging (NNRK). NNRK is also a residual-based method, which uses artificial neural network to model large-scale non-linear trends. The comparison of the results demonstrates the high quality performance of WARK in predicting hot spots, reproducing global statistical characteristics of the distribution and spatial correlation structure.

Dual functions of DP1 promote biphasic Wnt-on and Wnt-off states during anteroposterior neural patterning.

DP1, a dimerization partner protein of the transcription factor E2F, is known to inhibit Wnt/β-catenin signalling along with E2F, although the function of DP1 itself was not well characterized. Here, we present a novel dual regulatory mechanism of Wnt/β-catenin signalling by DP1 independent from E2F. DP1 negatively regulates Wnt/β-catenin signalling by inhibiting Dvl-Axin interaction and by enhancing poly-ubiquitination of β-catenin. In contrast, DP1 positively modulates the signalling upon Wnt stimulation, via increasing cytosolic β-catenin and antagonizing the kinase activity of NLK. In Xenopus embryos, DP1 exerts both positive and negative roles in Wnt/β-catenin signalling during anteroposterior neural patterning. From subcellular localization analyses, we suggest that the dual roles of DP1 in Wnt/β-catenin signalling are endowed by differential nucleocytoplasmic localizations. We propose that these dual functions of DP1 can promote and stabilize biphasic Wnt-on and Wnt-off states in response to a gradual gradient of Wnt/β-catenin signalling to determine differential cell fates.

Essays on the principles and adoption of entreprise-wide architecture

Enterprise-wide architecture has become a necessity for organizations to (re)align information technology (IT) to changing business requirements. Since a city planning metaphor inspired enterprise-wide architecture, this dissertation's research axes can be outlined by similarities between cities and enterprises. Both are characterized as dynamic super-systems that need to address the evolving interest of various architecture stakeholders. Further, both should simultaneously adhere to a set of principles to guide the evolution of architecture towards the expected benefits. The extant literature on enterprise-wide architecture not only disregards architecture adoption's complexities but also remains vague about how principles guide architecture evolution. To bridge this gap, this dissertation contains three interrelated research streams examining the principles and adoption of enterprise-wide architecture. The first research stream investigates organizational intricacies inherent in architecture adoption. It characterizes architecture adoption as an ongoing organizational adaptation process. By analyzing organizational response behaviors in this adaptation process, it also identifies four archetypes that represent very diverse architecture approaches. The second research stream ontologically clarifies the nature of architecture principles along with outlining new avenues for theoretical contributions. This research stream also provides an empirically validated set of principles and proposes a research model illustrating how principles can be applied to generate expected architecture benefits. The third research stream examines architecture adoption in multinational corporations (MNCs). MNCs are Specified by unique organizational characteristics that constantly strive for balancing global integration and local responsiveness. This research stream characterizes MNCs' architecture adoption as a continuous endeavor. This endeavor tries to constantly synchron ize architecture with stakeholders' beliefs about how to balance global integration and local responsiveness. To conclude, this dissertation provides a thorough explanation of a long-term journey in Which organizations learn over time to adopt an effective architecture approach. It also clarifies the role of principles to purposefully guide the aforementioned learning process. - L'Architecture d'Entreprise (AE) est devenue une nécessité pour permettre aux organisations de (ré)aligner les technologies de l'information (TI) avec les changements en termes de besoins métiers. En se basant sur la métaphore de la planification urbaine dont l'AE s'est inspirée, cette dissertation peut être présentée comme une comparaison entre les villes et les entreprises; les deux sont des super-systèmes dynamiques ayant besoin de répondre aux intérêts d'acteurs divers et variés en constants évolution. De plus, les deux devraient souscrire simultanément à un ensemble de principes afin de faire converger l'évolution de l'architecture vers les bénéfices attendus. La littérature sur l'AE, non seulement ne prend pas en considération les complexités de l'adoption d'architecture, mais aussi reste vague sur la manière dont les principes guident l'évolution de l'architecture. Pour pallier ce manque, cette dissertation est composée de trois volets de recherche étroitement liés examinant les principes et l'adoption de l'AE. Le premier volet examine la complexité organisationnelle inhérente à l'adoption de l'architecture. Il caractérise l'adoption de l'architecture en tant que processus d'adaptation continu. En analysant le comportement organisationnel en réponse à ce processus d'adaptation, ce volet distingue quatre archétypes représentant la diversité des approches de l'architecture. Le deuxième volet de recherche clarifie de manière ontologique la nature des principes d'architecture et envisage les contributions théoriques futures possibles. Cet axe de recherche fournit aussi un ensemble de principes, validés de manière empirique, et propose un modèle de recherche illustrant la manière dont ces principes peuvent être appliqués afin de générer les bénéfices attendus de l'architecture. Le troisième volet examine l'adoption de l'architecture dans les entreprises multinationales. Ces dernières possèdent des caractéristiques organisationnelles uniques et sont constamment à la recherche d'un équilibre entre une intégration globale et une flexibilité locale tout en prenant en compte les convictions des divers acteurs sur la manière d'atteindre cet équilibre. Pour conclure, cette dissertation fournit une explication sur le long voyage au cours duquel les entreprises apprennent à adopter une approche d'architecture efficace. Elle clarifie aussi le rôle des principes dans l'accompagnement de ce processus d'apprentissage.