992 resultados para mk.66


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Trägerband: 15/474; Vorbesitzer: Dominikanerkloster Frankfurt am Main

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The receptor for calcitonin gene-related peptide (CGRP) has been the target for the development of novel small molecule antagonists for the treatment of migraine. Two such antagonists, BIBN4096BS and MK-0974, have shown great promise in clinical trials and hence a deeper understanding of the mechanism of their interaction with the receptor is now required. The structure of the CGRP receptor is unusual since it is comprised of a hetero-oligomeric complex between the calcitonin receptor-like receptor (CRL) and an accessory protein (RAMP1). Both the CLR and RAMP1 components have extracellular domains which interact with each other and together form part of the peptide-binding site. It seems likely that the antagonist binding site will also be located on the extracellular domains and indeed Trp-74 of RAMP1 has been shown to form part of the binding site for BIBN4096BS. However, despite a chimeric study demonstrating the role of the N-terminal domain of CLR in antagonist binding, no specific residues have been identified. Here we carry out a mutagenic screen of the extreme N-terminal domain of CLR (residues 23-63) and identify a mutant, Met-42-Ala, which displays 48-fold lower affinity for BIBN4096BS and almost 900-fold lower affinity for MK-0974. In addition, we confirm that the Trp-74-Lys mutation at human RAMP1 reduces BIBN4096BS affinity by over 300-fold and show for the first time a similar effect for MK-0974 affinity. The data suggest that the non-peptide antagonists occupy a binding site close to the interface of the N-terminal domains of CLR and RAMP1.

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The article expands existing categorisations of political and economic governance by including literature on less developed countries (LDCs). In four consecutive negotiations between the US multinational Kaisers and the US and Ghana governments in the early 1960s, it is argued that the company reached levels of influence that are at odds with existing explanations. In order to understand corporate political activities in LDCs, analysis needs to go beyond static factors (political risk) and include dynamic factors such as diplomatic relations and 'arenas of power', and consider the role of the investor's home country relative to the host economy.

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http://digitalcommons.fiu.edu/com_images/1071/thumbnail.jpg

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Trägerbände: Inc. qu. 979; Inc. oct. 271 Bd. 1; Vorbesitzer: Dominikanerkloster Frankfurt am Main

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Late Cretaceous and younger sediments dredged from the upper continental slope and canyon walls in the Great Australian Bight Basin between 126° and 136°E broadly confirm the stratigraphy which had been established previously from scattered exploration wells. Late Cretaceous to Early Eocene marine and marginal marine terrigenous sediments are overlain by Middle Eocene and younger pelagic carbonate (fine limestone and calcareous ooze). The samples provide the first evidence of truly marine Maastrichtian sedimentation, with abundant calcareous nannoplankton, on the southern margin of the continent. Other samples of interest include Precambrian sheared granodiorite on the upper slope south of Eyre Terrace, Paleocene phosphatic sediment in 'Eucla' Canyon at 128° 30'E, and terrigenous Early Miocene mudstone at 133° 20' and 134° 50'E. The mudstone is of note as an exception to the uniform pelagic carbonate wackestone and ooze which characterise Middle Eocene and younger sedimentation at all other sites. Fragments of alkali basalt lava of unknown age were recovered in 'Eucla' Canyon. Cores are mostly pelagic calcareous ooze, but those from submarine canyons include terrigenous turbidites.

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Composite materials arise from the need for lighter materials and with bigger mechanical and thermal resistance. The difficulties of discard, recycling or reuse are currently environmental concerns and, therefore, they are study object of much researches. In this perspective the feasibility of using loofahs (Luffa Cylindrica) for obtainment of a polymeric matrix composite was studied. Six formulations, with 4, 5 and 6 treated layers and untreated, were tested. The loofahs were treated in boiling water to remove lignins, waxes and impurities present in the fibers. After that, they were dried in a direct exposure solar dryer. For the characterization of the composite, thermal (thermal conductivity, thermal capacity, thermal diffusivity and thermal resistivity), mechanical (tensile and bending resistance) and physicochemical (SEM, XRD, density, absorption and degradation) properties were determined. The proposed composite has as advantage the low fiber density, which is around 0.66 g/cm³ (almost half of the polyester resin matrix), resulting in an average composite density of around 1.17g/cm³, 6.0 % lower in relation to the matrix. The treatment carried out in the loofahs increased the mechanical strength of the composite and decreased the humidity absorption. The composite showed lower mechanical behavior than the matrix for all the formulations. The composite also demonstrated itself to be feasible for thermal applications, with a value of thermal conductivity of less than 0.159 W/m.K, ranking it as a good thermal insulator. For all formulations/settings a low adherence between fibers and matrix occurred, with the presence of cracks, showing the fragility due to low impregnation of the fiber by the matrix. This composite can be used to manufacture structures that do not require significant mechanical strength, such as solar prototypes, as ovens and stoves.

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Composite materials arise from the need for lighter materials and with bigger mechanical and thermal resistance. The difficulties of discard, recycling or reuse are currently environmental concerns and, therefore, they are study object of much researches. In this perspective the feasibility of using loofahs (Luffa Cylindrica) for obtainment of a polymeric matrix composite was studied. Six formulations, with 4, 5 and 6 treated layers and untreated, were tested. The loofahs were treated in boiling water to remove lignins, waxes and impurities present in the fibers. After that, they were dried in a direct exposure solar dryer. For the characterization of the composite, thermal (thermal conductivity, thermal capacity, thermal diffusivity and thermal resistivity), mechanical (tensile and bending resistance) and physicochemical (SEM, XRD, density, absorption and degradation) properties were determined. The proposed composite has as advantage the low fiber density, which is around 0.66 g/cm³ (almost half of the polyester resin matrix), resulting in an average composite density of around 1.17g/cm³, 6.0 % lower in relation to the matrix. The treatment carried out in the loofahs increased the mechanical strength of the composite and decreased the humidity absorption. The composite showed lower mechanical behavior than the matrix for all the formulations. The composite also demonstrated itself to be feasible for thermal applications, with a value of thermal conductivity of less than 0.159 W/m.K, ranking it as a good thermal insulator. For all formulations/settings a low adherence between fibers and matrix occurred, with the presence of cracks, showing the fragility due to low impregnation of the fiber by the matrix. This composite can be used to manufacture structures that do not require significant mechanical strength, such as solar prototypes, as ovens and stoves.

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Fil: Buschini, José Daniel. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.

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Fil: Prego, Carlos Alberto. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.

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Fil: Buschini, José Daniel. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.