287 research outputs found

    Synthesis and biological evaluation of structurally simplified noscapine analogues as microtubule binding agents

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    This paper reports on the results of chemical synthesis and biological assays performed on several new analogues of noscapine. We have successfully synthesized four noscapine analogues called 1a–4a, as well as their four corresponding enantiomers called 1b–4b. The chemical pathway consisted of three steps with yields in excess of 60% in each step. Subsequently, we have performed biological activity assays intended to reveal the mode of action of these compounds on microtubules in buffer and in cancer cell lines. We have assayed fluorescence quenching effects in microtubule polymerization experiments, cytotoxicity evaluation in breast cancer cell lines, as well as microtubule dynamicity assessments, for each of the synthesized compounds. Finally, we performed computational docking simulations to two binding sites on β-tubulin: (a) the colchicine binding site and (b) the noscapine binding site. Our results indicate that these compounds have relatively low cytotoxicity profile and less pronounced effects on microtubule dynamics compared with noscapine. Our computational results indicate that these compounds bind to both putative binding sites but have higher affinity for the colchicine site. </jats:p

    La vida de Nuestra Señora (Ms. 2133)

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    Manuscrito número 2133 de la Biblioteca Histórica de la USAL2 h.+60 f.+3 h. : papel ; 207x145 mmObra póstuma. - Letra itálica. - En h. 2r: La vida de Nuestra Sra escripta por Don Antonio Hurtado de Mendoza secretario de camara de su Magd. En Barcelona el año de M DC LIII

    Scalling effects on the deformation behaviour of W/Cu composite materials under dynamic loading

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    Tungsten/copper (W/Cu) particle composites were used to investigate the scaling effects on their deformation and fracture behaviour. The effects of the volume fraction and the particle size of the reinforcement (tungsten particles) were studied. W/Cu-80/20, 70/30 and 60/40 wt.% each with tungsten particle size of 10 and 30 μ\mu m were tested under compression loading up to high strain rates. Cylindrical compression specimens with different volumes (Do=Ho)_{\rm o}= {\rm H}_{\rm o}) were investigated with strain rates between 0.001s1^{ - 1} and 6000 s1^{ - 1} at temperatures from 20°C to 800°C. A clear dependence of the flow stress on the deformed volume of the specimens was shown for compression loading.
An extensive metallographic investigation was carried out to determine a correlation between the deformation of the tungsten particles and the global deformation of the specimen. The contribution of the hard phase in the deformation process has shown to have an effective influence in the deformation process. The size of the deformed zone under compression loading showed an effect on the failure mechanism.
The material behaviour of the different W/Cu composites was described with material laws. The parameters of the material law were presented as a function of the strain rate, temperature, the volume fraction and the particle size of the tungsten. The mechanical behaviour of the composite materials was numerically computed with the previously determined material laws

    Melhoria da qualidade de filetes de tilápia do Nilo congelados com óleo de alecrim e tomilho

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    The food industry and the frozen fish sector in particular have benefitted greatly from advancements in food processing technologies. This study investigated the effect of adding natural antioxidants such as rosemary and thyme oil to frozen fillets of Nile tilapia (Oreochromis niloticus) in order to preserve their quality for consumers. Fillets were treated with rosemary and thyme at two concentrations (1% and 1.5%) and then were stored at 4°C. Samples were analyzed over 4 days for bacteriological (aerobic plate count, psychotropic count, and coliform count), chemical (determination of pH, thiobarbituric acid reactive substances-TBARS, and total volatile base nitrogen-TVB-N), and sensory quality examination (color, texture, and odor). Significant differences (P < 0.05) were observed among different groups in terms of aerobic plate count, psychotropic count, and coliform count during the storage. Moreover, pH, TVB-N, and TBARS mean values in the treated groups were lower than those in the untreated group. The best sensory quality was obtained at the highest concentrations (1.5%) of thyme and rosemary oil

    High Speed Forming of the Light-Weight Wrought Alloys

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    The deformation and fracture behaviour of the Al-alloy AA7075, Mg-alloy AZ80, and Tialloy Ti-6Al-4V were investigated in quasi-static and dynamic uniaxial compression and tension tests at strain rates in the range of 0.001 s^(-1) ≤ ε̇ ≤ 5000 s^(-1) and temperatures between 20°C and 500°C. Shear tests with hat shaped specimens of AZ80 were carried out by quasi-static and dynamic loading in the shear rate range of 0.01s^(-1) ≤ γ̇ ≤ 116000s^(-1) at a temperature of 20°C. For strain rates of ε̇ ≤ 10 s^(-1), the tests were carried out using a computer numerical controlled hydraulic testing machine. High strain rate experiments with ε̇ ≥ 1000 s^(-1) were performed on a Split Hopkinson Pressure Bar. Using the experimentally determined flow curves, the effect of strain rate and temperature on the compressive deformation at fracture was determined, showing that the forces required for forming as well as the limits of the possible deformation are controlled by strain rate und temperature. Under dynamic loading, both AA7075 and AZ80 show an increase of the deformation degree at fracture with increasing strain rate, whereas the Ti-6Al-4V shows a decrease of it. The investigated mechanical material behaviour (strain hardening, strain rate sensitivity, and thermal softening) and metallographic investigations of the deformed specimens in dynamic compression tests allow an explanation for character, formation, and evolution of damage in the deformed material. Constitutive material laws, whose parameters are determined from the experimental data, can be applied to describe the influence of strain rate and temperature on the mechanical material behaviour in compression, tension and shear tests. These material laws are to be implemented into the FE simulation, in order to determine the local state of stress and strain at time of the fracture. Through combination of experiment and simulation, a failure criterion for ductile fracture could be determined for AA7075 under quasi-static and dynamic tensile loading

    MODELING OF AN OSCILLATORY FREELY-ROTATING CUTTING BRUSH FOR STREET SWEEPING

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    Se desarrolla un modelo matemático de un cepillo lateral oscilatorio para barrido de calles en rotación libre. Las cerdas se modelan como vigas empotradas. La ecuación de movimiento se obtiene mediante la teoría de vibraciones forzadas de vigas, y la solución se basa en el método de modo normal. Se estudia una función sinusoidal y una novedosa función, llamada VAP. El modelo se valida mediante análisis de elementos finitos. Se identifican los efectos de los parámetros del cepillo sobre su dinámica. Para la función VAP, una condición similar a resonancia tiende a ocurrir en el plano fuerte para las deflexiones, cuando la frecuencia del cepillo es una fracción impar de una frecuencia natural de la cerda en dicho plano. El modelo sirve para estudiar las deflexiones pequeñas de una viga empotrada, sometida a vibraciones producidas por una onda sinusoidal, cuadrada, triangular o VAP
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