A dialética das restrições, ou como se faz a cidade

Opondo cultura da pureza e cultura da transformação, os conceitos de complexidade, caos e impureza são explorados como capazes de instrumentalizar a compreensão e a ação sobre a cidade. Ao considerá-Ia como produto permanentemente inacabado de um processo contínuo de restrições materiais e normativas, o autor afirma que a história e a representação das formas urbanas constituem o instrumento principal de análise da cidade. Refabricá-la, no entanto, deve também levar em consideração os fluxos e as redes, o espaçamento e a descontinuidade, ao se constatar que a acessibilidade é uma de suas questões centrais. Daí deriva a concepção do espaço coletivo atual enquanto movimento. A responsabilidade de projetá-to, apesar dos apelos da mídia, deve ser ancorada nos processos de construção da cidade sedimenta, paradigma da democracia

Estrogen/Estrogen Receptor Alpha Signaling in Mouse Posterofrontal Cranial Suture Fusion

BACKGROUND: While premature suture fusion, or craniosynostosis, is a relatively common condition, the cause is often unknown. Estrogens are associated with growth plate fusion of endochondral bones. In the following study, we explore the previously unknown significance of estrogen/estrogen receptor signaling in cranial suture biology. METHODOLOGY/PRINCIPAL FINDINGS: Firstly, estrogen receptor (ER) expression was examined in physiologically fusing (posterofrontal) and patent (sagittal) mouse cranial sutures by quantitative RT-PCR. Next, the cranial suture phenotype of ER alpha and ER beta knockout (alphaERKO, betaERKO) mice was studied. Subsequently, mouse suture-derived mesenchymal cells (SMCs) were isolated; the effects of 17-beta estradiol or the estrogen antagonist Fulvestrant on gene expression, osteogenic and chondrogenic differentiation were examined in vitro. Finally, in vivo experiments were performed in which Fulvestrant was administered subcutaneously to the mouse calvaria. Results showed that increased ERalpha but not ERbeta transcript abundance temporally coincided with posterofrontal suture fusion. The alphaERKO but not betaERKO mouse exhibited delayed posterofrontal suture fusion. In vitro, addition of 17-beta estradiol enhanced both osteogenic and chondrogenic differentiation in suture-derived mesenchymal cells, effects reversible by Fulvestrant. Finally, in vivo application of Fulvestrant significantly diminished calvarial osteogenesis, inhibiting suture fusion. CONCLUSIONS/SIGNIFICANCE: Estrogen signaling through ERalpha but not ERbeta is associated with and necessary for normal mouse posterofrontal suture fusion. In vitro studies suggest that estrogens may play a role in osteoblast and/or chondrocyte differentiation within the cranial suture complex

Cushing's Syndrome and Fetal Features Resurgence in Adrenal Cortex–Specific Prkar1a Knockout Mice

Carney complex (CNC) is an inherited neoplasia syndrome with endocrine overactivity. Its most frequent endocrine manifestation is primary pigmented nodular adrenocortical disease (PPNAD), a bilateral adrenocortical hyperplasia causing pituitary-independent Cushing's syndrome. Inactivating mutations in PRKAR1A, a gene encoding the type 1 α-regulatory subunit (R1α) of the cAMP–dependent protein kinase (PKA) have been found in 80% of CNC patients with Cushing's syndrome. To demonstrate the implication of R1α loss in the initiation and development of PPNAD, we generated mice lacking Prkar1a specifically in the adrenal cortex (AdKO). AdKO mice develop pituitary-independent Cushing's syndrome with increased PKA activity. This leads to autonomous steroidogenic genes expression and deregulated adreno-cortical cells differentiation, increased proliferation and resistance to apoptosis. Unexpectedly, R1α loss results in improper maintenance and centrifugal expansion of cortisol-producing fetal adrenocortical cells with concomitant regression of adult cortex. Our data provide the first in vivo evidence that loss of R1α is sufficient to induce autonomous adrenal hyper-activity and bilateral hyperplasia, both observed in human PPNAD. Furthermore, this model demonstrates that deregulated PKA activity favors the emergence of a new cell population potentially arising from the fetal adrenal, giving new insight into the mechanisms leading to PPNAD

Paris et la mer : la Seine est capitale

L’avenir du Grand Paris et de la France se joue à l’exacte croisée de la mer et de la capitale. L’histoire le montre : aucune métropole ne peut véritablement atteindre une échelle mondiale sans dimension maritime, et les villes-monde d’hier et de demain glissent toutes vers leurs ports. Entre Paris, où quelques pages parmi les plus riches de la culture humaine se sont écrites, et son estuaire, la vallée de la Seine constitue un atout majeur. Il est urgent de faire de Paris, le vrai « Grand Paris », la porte océane et la capitale naturelle de l’Europe occidentale. Cet ouvrage dirigé par Jacques Attali propose 50 projets pour y parvenir

Netquest: An Abstract Model for Pervasive Applications

International audienceOne of the barriers to the implementation and deployment of pervasive applications is the lack of a programming abstraction for ubiquitous computing. We propose a system (i) that supports a declarative programming language, Netlog, well suited to rapid prototyping of distributed applications, (ii) which relies on an embedded DBMS, which facilitates its implementation and its portability over heterogeneous devices, and (iii) supports important functionalities such as implicit routing or adaptive behavior

Netquest: An Abstract Model for Pervasive Applications

International audienceOne of the barriers to the implementation and deployment of pervasive applications is the lack of a programming abstraction for ubiquitous computing. We propose a system (i) that supports a declarative programming language, Netlog, well suited to rapid prototyping of distributed applications, (ii) which relies on an embedded DBMS, which facilitates its implementation and its portability over heterogeneous devices, and (iii) supports important functionalities such as implicit routing or adaptive behavior