Étude du rôle de la tyrosine kinase Src dans la régulation de la signalisation des récepteurs opioïdes delta (∆OR)

Les opioïdes sont les analgésiques les plus efficaces mais leur utilisation est limitée par la tolérance, un processus lié en partie à la désensibilisation des récepteurs. Le rôle de la présente étude était de mieux caractériser le processus de désensibilisation des récepteurs et plus particulièrement, d’étudier le rôle de la tyrosine kinase Src sur la régulation de la signalisation des récepteurs delta opioïdes. Nos résultats démontrent que l’inhibition pharmacologique avec PP2 (à faible concentration : 20- 40µM) ou encore l’inhibition moléculaire de la kinase avec de faibles concentrations d’ADN d’un mutant dominant inactif de Src (0,2µg/ml) potentialise l’amplitude et la durée de l’activation de la cascade ERK lorsqu’un agoniste, DPDPE (1µM; 5 min), se lie aux récepteurs. Nous avons également démontré que de fortes concentrations d’inhibiteurs de Src (80 et 100µM de PP2 ou 1µg/ml d’ADN du mutant dominant négatif) bloquent la cascade des MAPK suivant la stimulation de DOR par l’agoniste DPDPE. Ces observations indiquent que Src a un effet biphasique sur l’activité de ERK : l’inhibition complète de Src inhibe l’activité de la cascade MAPK alors qu’une inhibition modérée potentialise cette même cascade. Nous pensons aussi que de fortes concentrations des bloqueurs de Src interfèrent avec l’activation de ERK alors que de faibles concentrations interfèrent avec la désensibilisation des récepteurs. Cette possibilité a été testée à l’aide d’essais d’accumulation d’AMPc qui visaient à évaluer l’effet des bloqueurs de Src (PP2, 20 µM; 1h) sur la désensibilisation induite par un agoniste. L'activation de DOR par DPDPE inhibe la production d’AMPc, préalablement stimulée par du forskolin, de façon dose-dépendante. Le maximum d'inhibition observé est de 61%, mais lors d’un prétraitement au DPDPE (1 µM, 30 min) l’inhibition maximale est réduite à 72% de l’inhibition initiale observée. Cependant, un prétraitement des cellules au PP2 (20µM pendant 1 heure) avant d’effectuer la désensibilisation protège contre cette désensibilisation. L’effet protecteur des bloqueurs de Src n’entraîne pas de changement au niveau de l’internalisation des DOR mais l’altération de leur internalisation via un mutant tronqué du DOR ou via un milieu sucré hypertonique (0.4M de saccharose) réduit cette protection. Ces données suggèrent alors que l’internalisation optimale du récepteur est nécessaire pour que l’effet protecteur prenne place. Nous concluons donc que Src contribue à la désensibilisation de DOR après que l’internalisation du DOR soit survenue.

Interaction between Public Transportation and Urbanization in the Mexico City Metropolitan Area: an Expansive Model Reaching its Limits

In Metropolitan Area of Mexico City, most of urban displacements happen through semi formal public transportation: small and medium capacity vehicles operated by small private enterprises, through a concession scheme. This kind of public transportation has been playing a major role in the Mexican capital. On one hand, it has been one of the conditions for urbanization to be possible. On the other hand, despite its uncountable deficiencies, public transportation has allowed for a long time the whole population to be able to move within this huge metropolis. However, that important function with regards to integration has now reached its limits in the most recent suburbs of the city, where a new mode of urbanization is taking place, based on massive production of very big social housing gated settlements. Public transportation tends to constitute here a factor of exclusion and households meet with important difficulties for their daily mobility. 

Parallel and distributed computing with Java

The Java language first came to public attention in 1995. Within a year, it was being speculated that Java may be a good language for parallel and distributed computing. Its core features, including being objected oriented and platform independence, as well as having built-in network support and threads, has encouraged this view. Today, Java is being used in almost every type of computer-based system, ranging from sensor networks to high performance computing platforms, and from enterprise applications through to complex research-based.simulations. In this paper the key features that make Java a good language for parallel and distributed computing are first discussed. Two Java-based middleware systems, namely MPJ Express, an MPI-like Java messaging system, and Tycho, a wide-area asynchronous messaging framework with an integrated virtual registry are then discussed. The paper concludes by highlighting the advantages of using Java as middleware to support distributed applications.

The International Urban Energy Balance Models Comparison Project: First Results from Phase 1

A large number of urban surface energy balance models now exist with different assumptions about the important features of the surface and exchange processes that need to be incorporated. To date, no com- parison of these models has been conducted; in contrast, models for natural surfaces have been compared extensively as part of the Project for Intercomparison of Land-surface Parameterization Schemes. Here, the methods and first results from an extensive international comparison of 33 models are presented. The aim of the comparison overall is to understand the complexity required to model energy and water exchanges in urban areas. The degree of complexity included in the models is outlined and impacts on model performance are discussed. During the comparison there have been significant developments in the models with resulting improvements in performance (root-mean-square error falling by up to two-thirds). Evaluation is based on a dataset containing net all-wave radiation, sensible heat, and latent heat flux observations for an industrial area in Vancouver, British Columbia, Canada. The aim of the comparison is twofold: to identify those modeling ap- proaches that minimize the errors in the simulated fluxes of the urban energy balance and to determine the degree of model complexity required for accurate simulations. There is evidence that some classes of models perform better for individual fluxes but no model performs best or worst for all fluxes. In general, the simpler models perform as well as the more complex models based on all statistical measures. Generally the schemes have best overall capability to model net all-wave radiation and least capability to model latent heat flux.

Effect of phonetic complexity on word reading and repetition in deep dyslexia

This investigation moves beyond the traditional studies of word reading to identify how the production complexity of words affects reading accuracy in an individual with deep dyslexia (JO). We examined JO’s ability to read words aloud while manipulating both the production complexity of the words and the semantic context. The classification of words as either phonetically simple or complex was based on the Index of Phonetic Complexity. The semantic context was varied using a semantic blocking paradigm (i.e., semantically blocked and unblocked conditions). In the semantically blocked condition words were grouped by semantic categories (e.g., table, sit, seat, couch,), whereas in the unblocked condition the same words were presented in a random order. JO’s performance on reading aloud was also compared to her performance on a repetition task using the same items. Results revealed a strong interaction between word complexity and semantic blocking for reading aloud but not for repetition. JO produced the greatest number of errors for phonetically complex words in semantically blocked condition. This interaction suggests that semantic processes are constrained by output production processes which are exaggerated when derived from visual rather than auditory targets. This complex relationship between orthographic, semantic, and phonetic processes highlights the need for word recognition models to explicitly account for production processes.

Improving aircraft maintenance, repair, and overhaul: A novel text mining approach

Aircraft Maintenance, Repair and Overhaul (MRO) feedback commonly includes an engineer’s complex text-based inspection report. Capturing and normalizing the content of these textual descriptions is vital to cost and quality benchmarking, and provides information to facilitate continuous improvement of MRO process and analytics. As data analysis and mining tools requires highly normalized data, raw textual data is inadequate. This paper offers a textual-mining solution to efficiently analyse bulk textual feedback data. Despite replacement of the same parts and/or sub-parts, the actual service cost for the same repair is often distinctly different from similar previously jobs. Regular expression algorithms were incorporated with an aircraft MRO glossary dictionary in order to help provide additional information concerning the reason for cost variation. Professional terms and conventions were included within the dictionary to avoid ambiguity and improve the outcome of the result. Testing results show that most descriptive inspection reports can be appropriately interpreted, allowing extraction of highly normalized data. This additional normalized data strongly supports data analysis and data mining, whilst also increasing the accuracy of future quotation costing. This solution has been effectively used by a large aircraft MRO agency with positive results.

On climate change and cultural geography: farming on the Lizard Peninsula, Cornwall, UK

Climate change as a global problem has moved relatively swiftly into high profile political debates over the last 20 years or so, with a concomitant diffusion from the natural sciences into the social sciences. The study of the human dimensions of climate change has been growing in momentum through research which attempts to describe, evaluate, quantify and model perceptions of climate change, understand more about risk and assess the construction of policy. Cultural geographers’ concerns with the construction of knowledge, the workings of social relations in space and the politics and poetics of place-based identities provide a lens through which personal, collective and institutional responses to climate change can be evaluated using critical and interpretative methodologies. Adopting a cultural geography approach, this paper examines how climate change as a particular environmental discourse is constructed through memory, observation and conversation, as well as materialised in farming practices on the Lizard Peninsula, Cornwall, UK

Using lexical diversity measures to operationalise language dominance in bilinguals

Treffers-Daller and Korybski propose to operationalize language dominance on the basis of measures of lexical diversity, as computed, in this particular study, on transcripts of stories told by Polish-English bilinguals in each of their languages They compute four different Indices of Language Dominance (ILD) on the basis of two different measures of lexical diversity, the Index of Guiraud (Guiraud, 1954) and HD-D (McCarthy & Jarvis, 2007). They compare simple indices, which are based on subtracting scores from one language from scores for another language, to more complex indices based on the formula Birdsong borrowed from the field of handedness, namely the ratio of (Difference in Scores) / (Sum of Scores). Positive scores on each of these Indices of Language Dominance mean that informants are more English-dominant and negative scores that they are more Polish-dominant. The authors address the difficulty of comparing scores across languages by carefully lemmatizing the data. Following Flege, Mackay and Piske (2002) they also look into the validity of these indices by investigating to what extent they can predict scores on other, independently measured variables. They use correlations and regression analysis for this, which has the advantage that the dominance indices are used as continuous variables and arbitrary cut-off points between balanced and dominant bilinguals need not be chosen. However, they also show how the computation of z-scores can help facilitate a discussion about the appropriateness of different cut-off points across different data sets and measurement scales in those cases where researchers consider it necessary to make categorial distinctions between balanced and dominant bilinguals. Treffers-Daller and Korybski correlate the ILD scores with four other variables, namely Length of Residence in the UK, attitudes towards English and life in the UK, frequency of usage of English at home and frequency of code-switching. They found that the indices correlated significantly with most of these variables, but there were clear differences between the Guiraud-based indices and the HDD-based indices. In a regression analysis three of the measures were also found to be a significant predictor of English language usage at home. They conclude that the correlations and the regression analyses lend strong support to the validity of their approach to language dominance.

Is behavioral ecology important for understanding and predicting population dynamics?

Population ecology is a discipline that studies changes in the number and composition (age, sex) of the individuals that form a population. Many of the mechanisms that generate these changes are associated with individual behavior, for example how individuals defend their territories, find mates or disperse. Therefore, it is important to model population dynamics considering the potential influence of behavior on the modeled dynamics. This study illustrates the diversity of behaviors that influence population dynamics describing several methods that allow integrating behavior into population models and range from simpler models that only consider the number of individuals to complex individual-based models that capture great levels of detail. A series of examples shows the importance of explicitly considering behavior in population modeling to avoid reaching erroneous conclusions. This integration is particularly relevant for conservation, as incorrect predictions regarding the dynamics of populations of conservation interest can lead to inadequate assessment and management. Improved predictions can favor effective protection of species and better use of the limited financial and human conservation resources.

Planning in the face of ‘deep divisions’: a view from Beirut, Lebanon

This article discusses planning in the global South-East while focusing on the specific context of social divides, political turmoil and conflict situations. The article proposes a five-way framework based on political science and planning to theory to analyse such contexts. The article explores the case of Beirut, Lebanon that has undergone several episodes of internal and external conflicts resulting in a society splintered along sectarianism. Three Two case studies of open urban spaces and their public activities are analysed using the five-way framework The discussion indicates how economic liberalism that is prevalent in countries of the South-East, along with place-based identities, interest-based identities, consensus orientated processes and institutionalism might facilitate a cultivation of deep values away from a narrowly constructed identity. The article argues that planners should understand the options for positive action that aim to bridge deep divisions and suggests that the five-way framework provides a reference for contextualising in different ways to suit particular contexts. Therefore, the framework is not necessarily restricted to the South-East but could be applicable to any context which manifests deep divisions.

The web of connections between tourism companies: Structure and dynamics

Tourism destination networks are amongst the most complex dynamical systems, involving a myriad of human-made and natural resources. In this work we report a complex network-based systematic analysis of the Elba (Italy) tourism destination network, including the characterization of its structure in terms of several traditional measurements, the investigation of its modularity, as well as its comprehensive study in terms of the recently reported superedges approach. In particular, structural (the number of paths of distinct lengths between pairs of nodes, as well as the number of reachable companies) and dynamical features (transition probabilities and the inward/outward activations and accessibilities) are measured and analyzed, leading to a series of important findings related to the interactions between tourism companies. Among the several reported results, it is shown that the type and size of the Companies influence strongly their respective activations and accessibilities, while their geographical position does not seem to matter. It is also shown that the Elba tourism network is largely fragmented and heterogeneous, so that it could benefit from increased integration. (C) 2009 Elsevier B.V. All rights reserved.

Geometrical logarithmic and trigonometric hypercomplex functions of quaternionic type

Quaternionic theory has greatly been developed in recent years [1-12]. Thus, in our view, the study of trigonometric and logarithmic type quaternionic functions is important for the determination and realization of a hyper complex theory. In this paper, we intend to give a geometrical foundation for both logarithmic and trigonometric hyper complex functions based on the exponential function of quaternionic type recently introduced by Borges, Marão and Machado in their paper entitled Geometrical octonions II: Hyper regularity and hyper periodicity of the exponential function appearing. © 2011 Pushpa Publishing House.

Políticas públicas de educação para assentados da Reforma Agrária: o caso do PRONERA Saúde na Transamazônica

As ações dos Agentes Comunitários de Saúde são reconhecidas em sua relevância nas legislações brasileira que se concretiza em 2002 com a Lei nº 10.507 de 10 de Julho de 2002 que cria a Profissão do Agente Comunitário de Saúde e dá outras providências, posteriormente substituída pela Lei 11.350, de 05 de outubro de 2006. Contudo a história dos ACS‟s remonta períodos bem anteriores como à criação do Programa dos Agentes Comunitários de Saúde (PACS) em 1991, considerado começo da profissionalização do ACS‟s. Diante disso, o Programa Nacional de Educação na Reforma Agrária (PRONERA) vem para dar sua contribuição na formação de Técnicos Agentes Comunitários de Saúde (TACS‟s). De maneira concisa o PRONERA emerge como Política Pública Educacional em 2009, quando o mesmo se consolida no artigo 33 da Lei nº 11.947/09 e no final de 2010 onde é assinado o Decreto nº 7.352/10, que trata da educação do campo e institui formalmente o PRONERA no Ministério do Desenvolvimento Agrário (MDA). Assim, o PRONERA compõe a Política de Educação do Campo, ao mesmo tempo se caracteriza como Política Pública de Educação vinculada à Reforma Agrária. O PRONERA é um Programa do Governo Federal, através do Ministério de Desenvolvimento Agrário, coordenado pelo Instituto Nacional de Colonização e Reforma Agrária (INCRA) em convênio com as Universidades Públicas, em parceria com Movimentos Sociais e agentes governamentais estaduais e municipais. Oferece cursos de educação básica, técnica e tecnológica, ensino superior e pós graduação. Nosso objeto aqui está na análise do projeto “Saúde em movimento na Transamazônica: Curso de Formação Integrada em Técnico Agente Comunitário de Saúde (TACS) e Ensino Médio”, portanto no PRONERA Saúde que é apenas um dos projetos do PRONERA no Pará. Este abrange os municípios de Altamira, Senador José Porfírio, Medicilândia, Anapú e Pacajá, o curso foi projetado e aprovado em 2005 e começou em 2006 e finalizado em julho de 2011. Iniciou com 90 discentes todos ACS‟s das prefeituras parceiras (Altamira, Anapú, Medicilândia, Pacajá, Sen. José Porfírio). Esses discentes foram selecionados por uma equipe técnica do PRONERA, a partir das indicações dos Movimentos Sociais locais, principalmente dos Sindicatos dos Trabalhadores Rurais. Para o desenvolvimento dessa pesquisa utilizamos os Relatórios de Atividades do PRONERA Saúde e as entrevistas com os discentes (ACS‟s). A perspectiva teórico metodológica de análise das fontes para construção dissertativa se deu com base na teoria crítica marxista e nas leituras e contribuições da Educação Ambiental crítica, a relação saúde, meio ambiente e políticas públicas permeia a pesquisa e possibilita uma interação fundamental para busca de melhoria de vida desses agentes sociais.

Recursos alimentares e local de forrageio de três espécies de Helicops wagler, 1830 (Serpentes: Dipsadidae) na Amazônia Oriental, Brasil

Espécies filogeneticamente aparentadas, que coexistem no ambiente com semelhanças na utilização dos recursos, são potencialmente competidoras. Assim, espera-se que apresentem diferenciação em algum dos principais eixos do nicho ecológico. Helicops angulatus, H. hagmanni e H. polylepis são cobras d’água abundantes no estado do Pará, Amazônia Oriental, e podem ser sintópicas, o que sugere que estas espécies apresentem alguma variação na dieta ou no local de forrageio. Esse estudo teve o objetivo de verificar variações na composição da dieta, a amplitude e sobreposição de nicho trófico, bem como variações no local de forrageio, baseadas em características ecomorfológicas dos peixes consumidos por três espécies de cobras d’água na Amazônia Oriental, Pará. Verificamos que a dieta das três espécies de Helicops é semelhante, contudo, as proporções em que os itens são consumidos diferem. Helicops angulatus é a espécie mais generalista e H. hagmanni a mais especialista, e a sobreposição alimentar entre as três espécies foi intermediária. De acordo com os dados ecomorfológicos dos peixes consumidos por H. angulatus, H. hagmanni e H. polylepis pôde-se concluir que estas espécies forrageiam os mesmos ambientes em meio aquático, principalmente microhábitats de águas lênticas nos estratos médio e superior da coluna d’água. A coexistência dessas espécies pode estar sendo favorecida pela abundância dos recursos consumidos.

Lugar e não-lugar em Rondonópolis-MT: um estudo de cognição ambiental

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)