936 resultados para French, Steven: Key concepts in philosophy
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A simple percolation theory-based method for determination of the pore network connectivity using liquid phase adsorption isotherm data combined with a density functional theory (DFT)-based pore size distribution is presented in this article. The liquid phase adsorption experiments have been performed using eight different esters as adsorbates and microporous-mesoporous activated carbons Filtrasorb-400, Norit ROW 0.8 and Norit ROX 0.8 as adsorbents. The density functional theory (DFT)-based pore size distributions of the carbons were obtained using DFT analysis of argon adsorption data. The mean micropore network coordination numbers, Z, of the carbons were determined based on DR characteristic plots and fitted saturation capacities using percolation theory. Based on this method, the critical molecular sizes of the model compounds used in this study were also obtained. The incorporation of percolation concepts in the prediction of multicomponent adsorption equilibria is also investigated, and found to improve the performance of the ideal adsorbed solution theory (IAST) model for the large molecules utilized in this study. (C) 2002 Elsevier Science B.V. All rights reserved.
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Sonic Hedgehog is a secreted morphogen involved in patterning a wide range of structures in the developing embryo. Disruption of the Hedgehog signalling cascade leads to a number of developmental disorders and plays a key role in the formation of a range of human cancers. The identification of genes regulated by Hedgehog is crucial to understanding how disruption of this pathway leads to neoplastic transformation. We have used a Sonic Hedgehog (Shh) responsive mouse cell line, C3H/10T1/2, to provide a model system for hedgehog target gene discovery. Following activation of cell cultures with Shh, RNA was used to interrogate microarrays to investigate downstream transcriptional consequences of hedgehog stimulation. As a result 11 target genes have been identified, seven of which are induced (Thrombomodulin, GILZ, BF-2, Nr4a1, IGF2, PMP22, LASP1) and four of which are repressed (SFRP-1, SFRP-2, Mip1-gamma, Amh) by Shh. These targets have a diverse range of putative functions and include transcriptional regulators and molecules known to be involved in regulating cell growth or apoptosis. The corroboration of genes previously implicated in hedgehog signalling, along with the finding of novel targets, demonstrates both the validity and power of the C3H/10T1/2 system for Shh target gene discovery.
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PRL and placental lactogen (PL) play key roles in maintaining the rodent corpus luteum through pregnancy. Suppressors of cytokine signaling (SOCS) have been shown to decrease cell sensitivity to cytokines, including PRL, and so here we have addressed the issue of whether luteolysis induced by prostaglandin F-2alpha (PGF(2alpha)) might up-regulate SOCS proteins to inhibit PRL signaling. In d 19 pregnant rats, cloprostenol, a PGF(2alpha) analog, rapidly induced transcripts for SOCS-3 and, to a lesser extent, SOCS-1. We also found increased SOCS-3 protein in the ovary by immunoblot and in the corpus luteum by immunohistochemistry. Increased SOCS-3 expression was preceded by an increase in STAT3 tyrosine phosphorylation 10 min after cloprostenol injection and was maintained for 4 h, as determined by gel shift and immunohistochemistry. Induction of SOCS-3 was accompanied by a sharp decrease in active STAT5, as determined by gel-shift assay and by loss of nuclear localized STAT5. Four hours after cloprostenol administration, the corpus luteum was refractory to stimulation of STAT5 by PRL administration, and this was not due to down-regulation of PRL receptor. Therefore, induction of SOCS-3 by PGF(2alpha) may be an important element in the initiation of luteolysis via rapid suppression of luteotropic support from PL.
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Many kinds of transcription factors and regulators play key roles in a variety of developmental processes. In the present survey, genes encoding proteins with conserved HMG-box, bZip domains, and some types of zinc finger motifs were surveyed in the completely sequenced genome of Ciona intestinalis. In the present analysis, 21 HMG-box-containing genes and 26 bZip genes were identified as well as four small groups of zinc finger genes in the Ciona genome. The results also showed that a less redundant set of genes is present in the Ciona genome compared with vertebrate genomes. In addition, cDNA clones for almost all genes identified have been cloned and distributed as a Ciona intestinalis Gene Collection Release I. The present comprehensive analysis therefore provides a means to study the role of these transcription factors in developmental processes of basal chordates.
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Sox8 is a member of the Sox family of developmental transcription factor genes and is closely related to Sox9, a key gene in the testis determination pathway in mammals. Like Sox9, Sox8 is expressed in the developing mouse testis around the time of sex determination, suggesting that it might play a role in regulating the expression of testis-specific genes. An early step in male sex differentiation is the expression of anti-Mullerian hormone (AMH) in Sertoli cells. Expression of the Amh gene during sex differentiation requires the interaction of several transcription factors, including SF1, SOX9, GATA4, WT1, and DAX1. Here we show that SOX8 may also be involved in regulating the expression of Amh. Expression of Sox8 begins just prior to that of Amh at 12 days post coitum (dpc) in mouse testes and continues beyond 16 dpc in Sertoli cells. In vitro assays showed that SOX8 binds specifically to SOX binding sites within the Amh minimal promoter and, like SOX9, acts synergistically with SF1 through direct protein-protein interaction to enhance Amh expression, albeit at lower levels compared with SOX9. SOX8 and SOX9 appear to have arisen from a common ancestral gene and may have retained some common functions during sexual development. Our data provide the first evidence that SOX8 may partially compensate for the reduced SOX9 activity in campomelic dysplasia and substitute for Sox9 where Sox9 is either not expressed or expressed too late to be involved in sex determination or regulation of Amh expression.
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Enzymic catalysis proceeds via intermediates formed in the course of substrate conversion. Here, we directly detect key intermediates in thiamin diphosphate (ThDP)-dependent enzymes during catalysis using H-1 NMR spectroscopy. The quantitative analysis of the relative intermediate concentrations allows the determination of the microscopic rate constants of individual catalytic steps. As demonstrated for pyruvate decarboxylase (PDC), this method, in combination with site-directed mutagenesis, enables the assignment of individual side chains to single steps in catalysis. In PDC, two independent proton relay systems and the stereochemical control of the enzymic environment account for proficient catalysis proceeding via intermediates at carbon 2 of the enzyme-bound cofactor. The application of this method to other ThDP-dependent enzymes provides insight into their specific chemical pathways.
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E2F regulation is essential for normal cell cycle progression. Therefore, it is not surprising that squamous cell carcinoma cell lines (SCC) overexpress E2F1 and exhibit deregulated E2F activity when compared with normal keratinocytes. Indeed, deliberate E2F1 deregulation has been shown to induce hyperplasia and skin tumor formation. In this study, we report on a dual role for E2F as a mediator of keratinocyte proliferation and modulator of squamous differentiation. Overexpression of E2F isoforms in confluent primary keratinocyte cultures resulted in suppression of differentiation-associated markers. Moreover, we found that the DNA binding domain and the trans-activation domain of E2F1 are important in mediating suppression of differentiation. Use of a dominant/negative form of E2F1 ( E2F d/n) found that E2F inhibition alone is sufficient to suppress the activity of proliferation-associated markers but is not capable of inducing differentiation markers. However, if the E2F d/n is expressed in differentiated keratinocytes, differentiation marker activity is further induced, suggesting that E2F may act as a modulator of squamous differentiation. We therefore examined the effects of E2F d/n in a differentiation- insensitive SCC cell line. We found that treatment with the differentiating agent, 12-O-tetradecanoyl- phorbol-13-acetate (TPA), or expression of E2F d/n alone had no effect on differentiation markers. However, a combination of E2F d/n + TPA induced the expression of differentiation markers. Combined, these data indicate that E2F may play a key role in keratinocyte differentiation. These data also illustrate the unique potential of anti-E2F therapies in arresting proliferation and inducing differentiation of SCCs.
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Activation of macrophages with lipopolysaccharide (LPS) induces the rapid synthesis and secretion of proinflammatory cytokines, such as tumor necrosis factor (TNFalpha), for priming the immune response [1, 2]. TNFalpha plays a key role in inflammatory disease [3]; yet, little is known of the intracellular trafficking events leading to its secretion. In order to identify molecules involved in this secretory pathway, we asked whether any of the known trafficking proteins are regulated by LPS. We found that the levels of SNARE proteins were rapidly and significantly up- or downregulated during macrophage activation. A subset of t-SNAREs (Syntaxin 4/SNAP23/Munc18c) known to control regulated exocytosis in other cell types [4, 5] was substantially increased by LPS in a temporal pattern coinciding with peak TNFalpha secretion. Syntaxin 4 formed a complex with Munc18c at the cell surface of macrophages. Functional studies involving the introduction of Syntaxin 4 cDNA or peptides into macrophages implicate this t-SNARE in a rate-limiting step of TNFalpha secretion and in membrane ruffling during macrophage activation. We conclude that in macrophages, SNAREs are regulated in order to accommodate the rapid onset of cytokine secretion and for membrane traffic associated with the phenotypic changes of immune activation. This represents a novel regulatory role for SNAREs in regulated secretion and in macrophage-mediated host defense.
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Inagaki and Hatano (2002) have argued that young children initially understand biological phenomena in terms of vitalism, a mode of construal in which life or life-force is the central causal-explanatory concept. This study investigated the development of vitalistic reasoning in young children's concepts of life, the human body and death. Sixty preschool children between the ages of 3 years, 7 months and 5 years, 11 months participated. All children were initially given structured interviews to assess their knowledge of (1) human body function and (2) death. From this sample 40 children in the Training group were taught about the human body and how it functions to maintain life. The Control group (n = 20) received no training. All 60 children were subsequently reassessed on their knowledge of human body function and death. Results from the initial interviews indicated that young children who spontaneously appealed to vitalistic concepts in reasoning about human body functioning were also more sophisticated in their understanding of death. Results from the posttraining interviews showed that children readily learned to adopt a vitalistic approach to human body functioning, and that this learning coincided with significant development in their understanding of human body function, and of death. The overall pattern of results supports the claim that the acquisition of a vitalistic causal-explanatory framework serves to structure children's concepts and facilitates learning in the domain of biology. (C) 2003 Elsevier Science (USA). All rights reserved.
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O objetivo deste texto ?? iniciar um levantamento da dificuldades impostas ?? reforma administrativa a partir da considera????o do problema da neutralidade da burocracia versus o requisito da autonomia de decis??o, elemento fundamental do Modelo de Administra????o P??blica Gerencial. Tal problema assume especial relev??ncia frente aos objetivos de aumentar a governan??a do Estado e constitui um dos desafios centrais do Plano Diretor da Reforma do Aparelho do Estado, particularmente no que diz respeito ?? forma de administra????o do chamado ???n??cleo estrat??gico??? ??? respons??vel pela defini????o das leis e pol??ticas p??blicas ??? e das ???atividades exclusivas de Estado??? ??? caracterizadas pelo exerc??cio do poder de legislar e tributar, fiscalizando, regulamentando e transferindo recursos. Para isso, a discuss??o est?? organizada em quatro se????es. Na primeira, s??o rapidamente apresentados os conceitos de governabilidade e governan??a, com ??nfase no fato de que a distin????o entre eles representa apenas um recurso anal??tico. Na segunda se????o, a partir das distin????es cl??ssicas de Max Weber entre pol??tica e administra????o, pol??ticos e burocratas, busca-se caracterizar a neutralidade burocr??tica e mostrar que representa, na realidade, apenas um dos elementos de uma constru????o t??pico ideal, cada vez mais distante de qualquer correspond??ncia com o mundo real. Em seguida, comenta-se rapidamente o processo de mudan??a do modelo de administra????o p??blica; e s??o apresentadas algumas das caracter??sticas do chamado Modelo de Administra????o P??blica Gerencial que, em lugar da neutralidade, implicam elevado grau de autonomia por parte dos agentes burocr??ticos. Por fim, s??o tecidas algumas considera????es, procurando mostrar que, da mesma maneira que a neutralidade, a autonomia burocr??tica apresenta dificuldades e que a proposta da ???autonomia imersa??? ou ???autonomia inserida??? exibe implica????es que merecem reflex??o mais demorada.
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Este trabalho ganha corpo a partir das experiências do antropólogo Carlos Castaneda. Além de ponto de partida para pensar as questões relativas ao corpo, o movimento e aprendizagem, as obras A Erva do diabo, Uma estranha realidade e Porta para o infinito, do autor mencionado, comparecem aqui para 1) investigarmos os relatos de experiência; 2) apresentarmos alguns conceitos-chaves, relativos a aprendizagem da “feitiçaria”, tal como a vontade. Vale frisar que nosso interesse na obra de Castaneda, não está nas questões místicas do xamanismo, nem mesmo nos pontos relativos ao campo da antropologia, mas na questão da aprendizagem. Para Dom Juan, o vellho índio feiticeiro e principal mestre de Carlos Castaneda, o propósito final do aprendizado da feitiçaria é justamente tornar-se um homem de conhecimento. Com o objetivo de analisar o lugar do movimento e do corpo no processo de aprendizagem, faremos o seguinte percurso analítico: de Skinner e Piaget abordaremos respectivamente a aprendizagem do comportamento operante e a aprendizagem em sentido amplo. Em seguida, apresentamos o pensamento de Francisco Varela e Bruno Latour, principalmente os conceitos de enação, corpos articulados e aprendizagem por afetação. Com Vincianne Despret discutiremos o aspecto afectivo, corporal e involuntário da aprendizagem. Com este apanhado conceitual, visamos então colocar em análise os efeitos ético-políticos dos modos de produção de conhecimento, efeitos irremediavelmente neste corpo-dissertação, e mais ainda efeitos na vida. Por fim, ao que parece, as modulações nos conceitos de corpo, movimento/ação, ao longo da exposição dos autores indicaram, por vezes, a participação de outros elementos, tais como a vontade e a percepção-atenção, implicando variações na forma de conceber a aprendizagem. Percebemos que de acordo com a formulação de aprendizagem e as nuances do movimento/ação e do corpo, isto implica produções diferenciadas de conhecimento e de realidade.
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Esta pesquisa analisa práticas e saberes da professora pomerana em uma escola do campo de ensino fundamental em Santa Maria de Jetibá/Estado do Espírito Santo/Brasil, para problematizar questões sobre cultura e interculturalidade. Aprofundam-se reflexões sobre quais têm sido as contribuições dessas práticas para uma educação escolar intercultural. Beneficia-se do estudo de caso para análise de documentos, observações de aulas, observações participantes em planejamentos, realização de entrevista semiestruturada com a professora e, anotações no diário de campo. Situam-se brevemente questões da história dos descendentes de pomeranos, bem como sobre as principais produções acadêmicas referentes à educação desse povo tradicional. Discussões teórico-metodológicas contribuem para compreensão e embasamento de alguns conceitos-chave, como: cultura(s) (THOMPSON, 1995; GEERTZ, 2012), interculturalismo (CANDAU, 2005; FORNET-BETANCOURT, 2004), cultura escolar e cultura da escola (FORQUIN, 1993), práticas docentes (FREIRE, 1996), saberes docentes (TARDIF, 2012), parceria (FOERSTE, 2005) etc. Aponta-se que as práticas da professora pomerana faziam parte do contexto escolar antes da implementação do Programa de Educação Escolar Pomerana (PROEPO) no que se refere ao uso oral da língua pomerana na sala de aula. As práticas da professora se ressignificam na interação com os saberes culturais, experienciais e coletivos produzidos na dinâmica escolar e comunitária. Essas práticas possibilitam o diálogo da cultura escolar com a cultura da escola, promovendo a vivência das experiências locais e o acesso ao saber universal. Pode-se afirmar que no contexto da escola investigada existem algumas condições que favorecem a dimensão da interculturalidade nos processos pedagógicos. Cabe aprofundar estudos sobre as contribuições da educação escolar para o ensino bilíngue e seus impactos à valorização da cultura pomerana e a consequente manutenção da língua deste povo tradicional. Tensões e conflitos foram identificados quanto ao enfoque do PROEPO ao desenvolvimento das habilidades de leitura e escrita em língua pomerana.
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Implementing multi-level governance has been a key priority in EU cohesion policy. This study assesses the perceived achievements and shortcomings in implementing European Social Fund by analyzing the deficits and weaknesses as well as the poor participation of local agents who are in direct contact with the beneficiaries in order to design and implement this fund, which is the main financial instrument of EU social policy.
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Gladiolus is an ornamental species produced for cut flowers and propagated by corms. The early flowering and increase in the number of flower buds, besides the production of commercial corms are constant challenges to be addressed in the crop improvement. Commercial production of ornamentals is technologically accelerated by means of growth regulators. Among them, the auxins stand out for their key role in the adventitious rooting and cell elongation. Alternatively, the humic substances present in the organic matter also have biostimulating effect, which is very similar to the auxinic effect. Therefore, this work aimed to study the growth and development of gladiolus in response to application of different concentrations of humic acids (HA) isolated from vermicompost. Corms were soaked for 24 hours in solutions containing 0, 10, 20, 30 and 40 mmol L-1 of C from HA. The corms were planted in 10-dm³ plastic bags filled with substrate and kept in a greenhouse. Growth of shoots and roots was evaluated. The results showed that the use of HA accelerates growth, and anticipates and increases flowering of Gladiolus.
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The increased integration of wind power into the electric grid, as nowadays occurs in Portugal, poses new challenges due to its intermittency and volatility. Wind power prediction plays a key role in tackling these challenges. The contribution of this paper is to propose a new hybrid approach, combining particle swarm optimization and adaptive-network-based fuzzy inference system, for short-term wind power prediction in Portugal. Significant improvements regarding forecasting accuracy are attainable using the proposed approach, in comparison with the results obtained with five other approaches.