786 resultados para Michaelis-Menten


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The objective of this study was to examine the growth of Gracilaria cervicornis cultured in a shrimp (Litopenaeus vannamei) pond and to determine the absorption efficiency and the kinetics parameters (Vmax, Ks e Vmax:Ks) of this macroalgae for the nutrients N-NO3-, N-NH4+ and P-PO4-3, aiming at its use as bioremediatory of eutrophicated environments. For this study, two experiments (field and laboratory) were developed. In the field study, the seaweed was examined in relation to the growth and the biomass. In the laboratory experiment, the absorption efficiency of G. cervicornis was measured through the monitoring of the concentration of the three nutrients (N-NO3-, N-NH4+ e P-PO4-3) during 5 hours and the kinetic parameters were determined through the formula of Michaelis-Menten. The results obtained in this study demonstrated that G. cervicornis benefited from the available nutrients in the pond, increasing 52.4% of its biomass value after 30 days of culture. It was evidenced that the variability of the biomass could be explained through the salinity, availability of light (transparency and solid particle in suspension) and concentration of N-NO3- in the environment. In the laboratory experiment, the highest absorption efficiency was found in the treatments with low concentration (5 µmol.L-1), being evidenced a reduction of up to 85,3%, 97,5% and 81,2% of N-NH4+, N-NO3- and P-PO43-, respectively. Regarding the kinetic parameters, G. cervicornis presented better ability in absorbing N-NH4+ in high concentrations (Vmax = 158,5 µmol g-1 dry wt h-1) and P-PO43- in low concentrations (Ks = 5 µmol.L-1 e Vmax:Ks = 10,3). The results of this study show that G. cervicornis could be cultivated in shrimp ponds, presents a good capacity of absorption for the tested nutrients and is a promising candidate for biorremediation in shrimp pond effluent

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The phosphatidylinositide 3-kinases (PI3K) and mammalian target of rapamycin-1 (mTOR1) are two key targets for anti-cancer therapy. Predicting the response of the PI3K/AKT/mTOR1 signalling pathway to targeted therapy is made difficult because of network complexities. Systems biology models can help explore those complexities but the value of such models is dependent on accurate parameterisation. Motivated by a need to increase accuracy in kinetic parameter estimation, and therefore the predictive power of the model, we present a framework to integrate kinetic data from enzyme assays into a unified enzyme kinetic model. We present exemplar kinetic models of PI3K and mTOR1, calibrated on in vitro enzyme data and founded on Michaelis-Menten (MM) approximation. We describe the effects of an allosteric mTOR1 inhibitor (Rapamycin) and ATP-competitive inhibitors (BEZ2235 and LY294002) that show dual inhibition of mTOR1 and PI3K. We also model the kinetics of phosphatase and tensin homolog (PTEN), which modulates sensitivity of the PI3K/AKT/mTOR1 pathway to these drugs. Model validation with independent data sets allows investigation of enzyme function and drug dose dependencies in a wide range of experimental conditions. Modelling of the mTOR1 kinetics showed that Rapamycin has an IC50 independent of ATP concentration and that it is a selective inhibitor of mTOR1 substrates S6K1 and 4EBP1: it retains 40% of mTOR1 activity relative to 4EBP1 phosphorylation and inhibits completely S6K1 activity. For the dual ATP-competitive inhibitors of mTOR1 and PI3K, LY294002 and BEZ235, we derived the dependence of the IC50 on ATP concentration that allows prediction of the IC50 at different ATP concentrations in enzyme and cellular assays. Comparison of the drug effectiveness in enzyme and cellular assays showed that some features of these drugs arise from signalling modulation beyond the on-target action and MM approximation and require a systems-level consideration of the whole PI3K/PTEN/AKT/mTOR1 network in order to understand mechanisms of drug sensitivity and resistance in different cancer cell lines. We suggest that using these models in systems biology investigation of the PI3K/AKT/mTOR1 signalling in cancer cells can bridge the gap between direct drug target action and the therapeutic response to these drugs and their combinations.

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[Liber physiognomiae (latin). 1490]

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Collection : Italian books before 1601 ; 59.5

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[Liber physiognomiae (latin). 1490]

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[Liber physiognomiae (latin). 15..]

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Invocatio: Synergûntos tû Hypsístu [kreikkaa].