934 resultados para 2,3-dimetoxy-8-oxoberberine


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Statins possess anti-inflammatory effects that may contribute to their ability to slow atherogenesis, whereas nitric oxide (NO) also influences inflammatory cell adhesion. This study aimed to determine whether a novel NO-donating pravastatin derivative, NCX 6550 [(1S-[1∝(ßS*,dS*),2∝,6a∝,8ß-(R*),8a∝]]-1,2,6,7,8,8a-hexahydro-ß,δ,6-trihydroxy-2-methyl-8-(2-methyl-1-oxobutoxy)-1-naphthalene-heptanoic acid 4-(nitrooxy)butyl ester)], has greater anti-inflammatory properties compared with pravastatin in normal and atherosclerotic apolipoprotein E receptor knockout (ApoE-/-) mice. C57BL/6 and ApoE-/- mice were administered pravastatin (40 mg/kg), NCX 6550 (48.5 mg/kg), or vehicle orally for 5 days. Ex vivo studies assessed splenocyte adhesion to arterial segments and splenocyte reactive oxygen species (ROS) generation. NCX 6550 significantly reduced splenocyte adhesion to artery segments in both C57BL/6 (8.8 ± 1.9% versus 16.6 ± 6.7% adhesion; P < 0.05) and ApoE-/- mice (9.3 ± 2.9% versus 23.4 ± 4.6% adhesion; P < 0.05) concomitant with an inhibition of endothelial intercellular adhesion molecule-1 expression. NCX 6550 also significantly reduced phorbol 12-myristate 13-acetate-induced ROS production that was enhanced in isolated ApoE-/- splenocytes. Conversely, pravastatin had no significant effects on adhesion in normal or ApoE-/- mice but reduced the enhanced ROS production from ApoE-/- splenocytes. In separate groups of ApoE-/- mice, NCX 6550 significantly enhanced endothelium-dependent relaxation to carbachol in aortic segments precon-tracted with phenylephrine (-logEC50, 6.37 ± 0.37) compared with both vehicle-treated (-logEC50, 5.81 ± 0.15; P < 0.001) and pravastatin-treated (-logEC50, 5.57 ± 0.45; P < 0.05) mice. NCX 6550 also significantly reduced plasma monocyte chemoattractant protein-1 levels (648.8 pg/ml) compared with both vehicle (1191.1 pg/ml; P < 0.001) and pravastatin (847 ± 71.0 pg/ml; P < 0.05) treatment. These data show that NCX 6550 exerts superior anti-inflammatory actions compared with pravastatin, possibly through NO-related mechanisms.

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The structure-activity relationship optimization of the pyrazoline template 3a resulted in novel 3-oxo-1,2-diphenyl-2,3-dihydro-1H-pyrazol-4-yl)-indole carboxamides 4a-4e. These non-peptidal CCK ligands have been shown to act as potent CCK 1 ligands in a [125]I-CCK-8 receptor binding assay. The best amides (4c and 4d) of this series displayed an IC50 of 20/25 CCK 1 for the CCK 1 receptor. In a subsequent in-vivo evaluation using various behaviour pharmacological assays, an anxiolytic effect of these novel 3-oxo-1,2-diphenyl-2,3-dihydro-1H-pyrazol-4-yl)-indole carboxamides was found at high doses in the elevated plus-maze. In the despair swimming test, a model for testing antidepressants, an ED50 of 0.33/0.41 mg kg -1 was determined for amide 4c/4d and the antidepressant effect had a magnitude comparable to desimipramine. © 2006 The Authors.

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myo-Inositol phosphates possessing the 1,2,3-trisphosphate motif share the remarkable ability to completely inhibit iron-catalysed hydroxyl radical formation. The simplest derivative, myo-inositol 1,2,3-trisphosphate [Ins(1,2,3)P3], has been proposed as an intracellular iron chelator involved in iron transport. The binding conformation of Ins(1,2,3)P3 is considered to be important to complex Fe3+ in a 'safe' manner. Here, a pyrene-based fluorescent probe, 4,6-bispyrenoyl-myo-inositol 1,2,3,5-tetrakisphosphate [4,6-bispyrenoyl Ins(1,2,3,5)P4], has been synthesised and used to monitor the conformation of the 1,2,3-trisphosphate motif using excimer fluorescence emission. Ring-flip of the cyclohexane chair to the penta-axial conformation occurs upon association with Fe3+, evident from excimer fluorescence induced by π-π stacking of the pyrene reporter groups, accompanied by excimer formation by excitation at 351 nm. This effect is unique amongst biologically relevant metal cations, except for Ca 2+ cations exceeding a 1:1 molar ratio. In addition, the thermodynamic constants for the interaction of the fluorescent probe with Fe3+ have been determined. The complexes formed between Fe 3+ and 4,6-bispyrenoyl Ins(1,2,3,5)P4 display similar stability to those formed with Ins(1,2,3)P3, indicating that the fluorescent probe acts as a good model for the 1,2,3-trisphosphate motif. This is further supported by the antioxidant properties of 4,6-bispyrenoyl Ins(1,2,3,5)P4, which closely resemble those obtained for Ins(1,2,3)P3. The data presented confirms that Fe3+ binds tightly to the unstable penta-axial conformation of myo-inositol phosphates possessing the 1,2,3-trisphosphate motif. © 2010 The Royal Society of Chemistry.

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DSDP 162 is located due north of DSDP 161 on the lower west flank of the East Pacific Rise about 3900 km west of the crest. It is in the Clarion-Clipperton block, about 80 km south of the Clarion Fracture Zone. The site lies at the extreme northern edge of the zone of thick sediments that parallels the equator in the Pacific and marks the region of high biological productivity.

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This paper reviews the state of the art in processing and extraction of ocean floor manganese nodules. It briefly reviews the mining sites where the abundant rich nodules occur and also discusses the metal distribution in nodules in view of economical processing and extraction of these metal values. The paper discloses in a detailed manner the physical and chemical characteristics of nodules, including porosity, surface area, water content and the effect of temperature on crystal structure of major constituents of nodules. In the extraction aspect of nodules, the paper reviews two different extraction schemes revealed in the literature, namely hydrometallurgical treatment and pyrometallurgical treatment. The hydrometallurgical treatments include acid leaching, ammonia leaching, leaching with reducing agents and leaching after high temperature pre-treatments such as in sulfating rousting, while the pyrometallurgical processes include smelting, chlorination-vaporization and segregation. The paper also covers metal recovery processes from leach liquor. An economic survey of processing nodules has been made in terms of problems associated with metal-marketing, and impact of metal production from nodules on mineral industries.

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The identification of transport parameters by inverse modeling often suffers from equifinality or parameter correlation when models are fitted to observations of the solute breakthrough in column outflow experiments. This parameters uncertainty can be approached by the application of multiple experimental designs such as column experiments in open-flow mode and the recently proposed closed-flow mode. Latter are characterized by the recirculation of the column effluent into the solution supply vessel that feeds the inflow. Depending on the experimental conditions, the solute concentration in the solution supply vessel and the effluent follows a damped sinusoidal oscillation. As a result, the closed-flow experiment provides additional observables in the breakthrough curve. The evaluation of these emergent features allows intrinsic control over boundary conditions and impacts the uncertainty of parameters in inverse modeling. We present a comprehensive sensitivity analysis to illustrate the potential application of closed-flow experiments. We show that the sensitivity with respect to the apparent dispersion can be controlled by the experimenter leading to a decrease in parameter uncertainty as compared to classical experiments by an order of magnitude for optimal settings. With these finding we are also able to reduce the equifinality found for situations, where rate-limited interactions impede a proper determination of the apparent dispersion and rate coefficients. Furthermore, we show the expected breakthrough curve for equilibrium and kinetic sorption, the latter showing strong similarities to the behavior found for completely mixed batch reactor experiments. This renders the closed-flow mode a useful complementary approach to classical column experiments.

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Background - Image blurring in Full Field Digital Mammography (FFDM) is reported to be a problem within many UK breast screening units resulting in significant proportion of technical repeats/recalls. Our study investigates monitors of differing pixel resolution, and whether there is a difference in blurring detection between a 2.3 MP technical review monitor and a 5MP standard reporting monitor. Methods - Simulation software was created to induce different magnitudes of blur on 20 artifact free FFDM screening images. 120 blurred and non-blurred images were randomized and displayed on the 2.3 and 5MP monitors; they were reviewed by 28 trained observers. Monitors were calibrated to the DICOM Grayscale Standard Display Function. T-test was used to determine whether significant differences exist in blurring detection between the monitors. Results - The blurring detection rate on the 2.3MP monitor for 0.2, 0.4, 0.6, 0.8 and 1 mm blur was 46, 59, 66, 77and 78% respectively; and on the 5MP monitor 44, 70, 83 , 96 and 98%. All the non-motion images were identified correctly. A statistical difference (p <0.01) in the blurring detection rate between the two monitors was demonstrated. Conclusions - Given the results of this study and knowing that monitors as low as 1 MP are used in clinical practice, we speculate that technical recall/repeat rates because of blurring could be reduced if higher resolution monitors are used for technical review at the time of imaging. Further work is needed to determine monitor minimum specification for visual blurring detection.

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O presente documento serve de reflexão sobre o processo de estágio, no ano letivo 2012-2013, exercido na EB 2,3 Eugénio dos Santos, tendo como referência o guia de estágio, no qual são definidas competências a desenvolver nas quatro áreas de intervenção: Organização e Gestão do Ensino e da aprendizagem, Inovação e Investigação Pedagógica, Participação na Escola e Relação com a Comunidade. Na área 1, fui responsável por uma turma de 7º ano muito heterogénea, com alunos oriundos de diversas turmas, cada um com as suas particularidades. Saliento a evolução ao nível do planeamento, refletida na condução e na avaliação formativa. Na área 2, desenvolvi, com o núcleo de estágio, um trabalho de investigação-ação sobre a “perceção dos professores acerca dos comportamentos em contexto de aula”. Aqui, aprofundei competências inerentes à investigação, nomeadamente a pesquisa bibliográfica. Na área 3, fui coadjuvante da professora orientadora no núcleo de desporto escolar de Patinagem, onde o desconhecimento traduziu-se numa maior experiência e gosto pela matéria. Organizei, com os colegas estagiários, a tradicional atividade “Dos 8 aos 80”, com participação da comunidade escolar e envolvente. Na área 4, evidencio o acompanhamento à direção de turma, como fonte dos conhecimentos inerentes à importância da relação escola-meio.

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O presente relatório tem como objetivo a explanação e a discussão de forma concisa da atividade docente desenvolvida no ano letivo 2012/2013, na Escola Básica 2,3/S Cunha Rivara de Arraiolos com as turmas do 8.º C e 11.º D nas disciplinas de Ciências Naturais e Saúde respetivamente, sob a orientação da Doutora Marília Cid. Apresentam-se os fundamentos teóricos que sustentaram o delineamento de todas as metodologias e estratégias de ensino no sentido de promover situações de aprendizagem significativa aos alunos das turmas referidas. Este é também um testemunho da participação ativa no projeto de educação para a saúde em colaboração com as entidades promotoras de saúde no Concelho de Arraiolos no sentido de organizar atividades extracurriculares propiciadoras da aprendizagem nesta dimensão, com a dinamização de sessões de esclarecimento de Educação Sexual a várias turmas da escola e a produção de um website informativo e de apoio aos alunos do 3.º Ciclo do Ensino Básico e do Ensino Secundário sobre Educação Sexual. Foi apanágio deste trabalho a análise e reflexão também evidenciadas no trabalho de investigação sobre as atividades desenvolvidas no âmbito da Educação para a Saúde mas também em toda a atividade de lecionação. Esta análise e reflexão, bem como a pesquisa individual e o trabalho colaborativo permitiram o desenvolvimento progressivo das minhas capacidades, da qualidade do trabalho desenvolvido e o melhoramento da formação académica. /ABSTRACT: This report aims at explaining concisely and discussion of teaching developed in the academic year 2012/2013, at Escola Básica 2,3 / S Cunha Rivara in Arraiolos with classes C from 8th grade class and D from 11th , in the disciplines of Natural Sciences and Health respectively under the guidance of PhD Teacher Marilia Cid. Here we present the theoretical foundations that supported the design of all methodologies and teaching strategies to promote meaningful learning situations for students of classes above. This is also a testament to the active participation in the design of health education in collaboration with the health promoters in the County of Arraiolos to organize extracurricular activities conducive learning these dimensions, the organization of information sessions to various Sex Education school classes and the production of an informational website to support the students of the 3rd cycle and Secondary Education on Sexual Education. It was the hallmark of this work, analysis and reflection evidenced in research work on the activities within the Health Education but also of the entire teaching activity. This analysis and reflection as well as individual research and collaborative work allowed the progressive development of my abilities, quality of work and the improvement of academic training.

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A Prática de Ensino Supervisionada desenvolveu-se no Agrupamento de Escolas nº 4 de Évora- EB 2,3 Conde Vilalva e na Escola Secundária André de Gouveia, com as turmas do 8º ano e 12° ano respectivamente. Para elucidar o trabalho realizado ao longo do ano desenvolvi o presente relatório onde abordei a preparação cientifica, pedagógica e didáctica que permitiu um conhecimento dos alunos e do currículo; a Planificação e condução das aulas e respectiva avaliação que faz referencia ao planeamento por etapas e às vantagens do mesmo e ainda à forma como foram leccionadas as aulas; uma análise da prática de ensino; a participação na escola e as actividades desenvolvidas nas mesmas; e o desenvolvimento profissional com referências ás competências que o professor deve assumir dentro da comunidade escolar. Com os parâmetros acima referidos demonstra-se a grande importância que o estágio teve na aquisição das competências essenciais inerentes à docência. ABSTRACT: Supervised Teaching Practice was developed in School Cluster nº 4 of Évora­ Elementary School Conde Vilalva and in Secondary School André de Gouveia, with classes of 8th and 12th grade, respectively. To elucidate the work I done over this school year, I developed this report which discussed the scientific, educational and teaching preparation, allowing an understanding of students and the curriculum; the planning and conduct of lessons and their assessment that refers to the planning stages, and to advantage of it and, on the other hand, the way that were taught lessons; an analysis of teaching practice; participation in school and activities carried therein; and professional development with reference to the competences that the teacher should take within the school community. With the above parameters is shown the importance of this stage in the acquisition of essential skills related to teaching.

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O presente relatório surge como um complemento à minha Prática de Ensino Supervisionada, realizada no ano lectivo de 2009/201O, visando essencialmente a reflexão e documentação do trabalho por mim desenvolvido ao longo deste ano. A minha Prática de Ensino Supervisionada debruçou-se sobre a disciplina de Educação Física, e decorreu na Escola EB 2,3 Conde de Vilalva, onde leccionei a disciplina a uma turma de 8° ano, e na Escola Secundária André de Gouveia, tendo leccionado a disciplina a um 12° ano. Durante este mesmo ano lectivo, leccionei ainda entre 8 intervenções a uma turma do 1° Ciclo de Ensino Básico, 1° ano; e 9 intervenções a uma turma do 2° Ciclo de Ensino Básico, o 5° ano. ABSTRACT: This document comes as a complement to my Supervised Teaching Practice, held in the 2009/201O academic year, aiming primarily to reflection and documentation of the work developed throughout this year. My Supervised Teaching Practice was focused on the discipline of Physical Education, and held at EB 2,3 Conde de Vilalva where I taught a class in 8th grade, and in high school André de Gouveia, where I taught the discipline to a class in 12th grade. During that same academic year, I taught between 8 and 1O interventions with a class of 1st cycle of education, 1st grade, and with a class of 2nd cycle of education, a 5th grade.

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In a study of socioeconomically disadvantaged children's acquisition of school literacies, a university research team investigated how a group of teachers negotiated critical literacies and explored notions of social power with elementary children in a suburban school located in an area of high poverty. Here we focus on a grade 2/3 classroom where the teacher and children became involved in a local urban renewal project and on how in the process the children wrote about place and power. Using the students' concerns about their neighborhood, the teacher engaged her class in a critical literacy project that not only involved a complex set of literate practices but also taught the children about power and the possibilities for local civic action. In particular, we discuss examples of children's drawing and writing about their neighborhoods and their lives. We explore how children's writing and drawing might be key elements in developing "critical literacies" in elementary school settings. We consider how such classroom writing can be a mediator of emotions, intellectual and academic learning, social practice, and political activism.

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In the title squaraine dye solvate, C26H24N2O2·2CHCl3, the dye molecule is essentially planar, except for the methyl groups, having a maximum deviation over the 26-membered delocalized bond system of 0.060 (2) Å. It possesses crystallographic twofold rotational symmetry with the indole ring systems adopting a syn conformation. The molecular structure features intramolecular N-HO hydrogen bonds enclosing conjoint S7 ring motifs about one of the dioxocyclobutene O atoms, while the two chloroform solvent molecules are linked to the second O atom through C-HO hydrogen bonds.

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The mineral amarantite Fe23+(SO4)O∙7H2O has been studied using a combination of techniques including thermogravimetry, electron probe analyses and vibrational spectroscopy. Thermal analysis shows decomposition steps at 77.63, 192.2, 550 and 641.4°C. The Raman spectrum of amarantite is dominated by an intense band at 1017 cm-1 assigned to the SO42- ν1 symmetric stretching mode. Raman bands at 1039, 1054, 1098, 1131, 1195 and 1233 cm-1 are attributed to the SO42- ν3 antisymmetric stretching modes. Very intense Raman band is observed at 409 cm-1 with shoulder bands at 399, 451 and 491 cm-1 are assigned to the v2 bending modes. A series of low intensity Raman bands are found at 543, 602, 622 and 650 cm-1 are assigned to the v4 bending modes. A very sharp Raman band at 3529 cm-1 is assigned to the stretching vibration of OH units. A series of Raman bands observed at 3025, 3089, 3227, 3340, 3401 and 3480 cm-1 are assigned to water bands. Vibrational spectroscopy enables aspects of the molecular structure of the mineral amarantite to be ascertained.