2 resultados para Non-linear dose-response curve


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In recent years modern numerical methods have been employed in the design of Wave Energy Converters (WECs), however the high computational costs associated with their use makes it prohibitive to undertake simulations involving statistically relevant numbers of wave cycles. Experimental tests in wave tanks could also be performed more efficiently and economically if short time traces, consisting of only a few wave cycles, could be used to evaluate the hydrodynamic characteristics of a particular device or design modification. Ideally, accurate estimations of device performance could be made utilizing results obtained from investigations with a relatively small number of wave cycles. However the difficulty here is that many WECs, such as the Oscillating Wave Surge Converter (OWSC), exhibit significant non-linearity in their response. Thus it is challenging to make accurate predictions of annual energy yield for a given spectral sea state using short duration realisations of that sea. This is because the non-linear device response to particular phase couplings of sinusoidal components within those time traces might influence the estimate of mean power capture obtained. As a result it is generally accepted that the most appropriate estimate of mean power capture for a sea state be obtained over many hundreds (or thousands) of wave cycles. This ensures that the potential influence of phase locking is negligible in comparison to the predictions made. In this paper, potential methods of providing reasonable estimates of relative variations in device performance using short duration sea states are introduced. The aim of the work is to establish the shortness of sea state required to provide statistically significant estimations of the mean power capture of a particular type of Wave Energy Converter. The results show that carefully selected wave traces can be used to reliably assess variations in power output due to changes in the hydrodynamic design or wave climate. 

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The efficacy of tyrosine kinase (TK) inhibitors on non-cycling acute myeloid leukaemia (AML) cells, previously shown to have potent tumourigenic potential, is unknown. This pilot study describes the first attempt to characterize non-cycling cells from a small series of human FMS-like tyrosine kinase 3 (FLT3) mutation positive samples. CD34+ AML cells from patients with FLT3 mutation positive AML were cultured on murine stroma. In expansion cultures, non-cycling cells were found to retain CD34+ expression in contrast to dividing cells. Leukaemic gene rearrangements could be detected in non-cycling cells, indicating their leukaemic origin. Significantly, the FLT3-internal tandem duplication (ITD) mutation was found in the non-cycling fraction of four out of five cases. Exposure to the FLT3-directed inhibitor TKI258 clearly inhibited the growth of AML CD34+ cells in short-term cultures and colony-forming unit assays. Crucially, non-cycling cells were not eradicated, with the exception of one case, which exhibited exquisite sensitivity to the compound. Moreover, in longer-term cultures, TKI258-treated non-cycling cells showed no growth impairment compared to treatment-naive non-cycling cells. These findings suggest that non-cycling cells in AML may constitute a disease reservoir that is resistant to TK inhibition. Further studies with a larger sample size and other inhibitors are warranted.