112 research outputs found
Insights into the behaviour of systems biology models from dynamic sensitivity and identifiability analysis: a case study of an NF-kB signaling pathway
Mathematical modelling offers a variety of useful techniques to help in understanding the intrinsic behaviour of complex signal transduction networks. From the system engineering point of view, the dynamics of metabolic and signal transduction models can always be described by nonlinear ordinary differential equations (ODEs) following mass balance principles. Based on the state-space formulation, many methods from the area of automatic control can conveniently be applied to the modelling, analysis and design of cell networks. In the present study, dynamic sensitivity analysis is performed on a model of the IB-NF-B signal pathway system. Univariate analysis of the Euclidean-form overall sensitivities shows that only 8 out of the 64 parameters in the model have major influence on the nuclear NF-B oscillations. The sensitivity matrix is then used to address correlation analysis, identifiability assessment and measurement set selection within the framework of least squares estimation and multivariate analysis. It is shown that certain pairs of parameters are exactly or highly correlated to each other in terms of their effects on the measured variables. The experimental design strategy provides guidance on which proteins should best be considered for measurement such that the unknown parameters can be estimated with the best statistical precision. The whole analysis scheme we describe provides efficient parameter estimation techniques for complex cell networks
I Going Away. I Going Home. : Austin Clarke\u27s Leaving this Island Place
Austin Clarkeâs âLeaving This Island Placeâ is one of scores of Caribbean autobiographical works that focus on a bright, young, lower-class islander leaving his/her small island place and setting out on âEldorado voyages.â The narrative of that journey away from home to Europe or Canada or the United States and the later efforts to return may be said to be the Caribbean story, as suggested in the subtitle of Wilfred Carteyâs study of Caribbean literature, Whispers from the Caribbean: I Going Away, I Going Home, which argues that while in Caribbean literature there is much movement away, there is also a body of literature in which âthe notion of âawayâ and images of movement out are replaced by images of returnâ (xvi). Traditionally, however, the first autobiographical works, such as George Lammingâs In the Castle of My Skin, V. S. Naipaulâs A House for Mr. Biswas, Merle Hodgeâs Crick Crack, Monkey, Jamaica Kincaidâs Annie John, Michelle Cliffâs No Telephone to Heaven, Edwidge Danticatâs Breath, Eyes, Memory, and Elizabeth Nunezâs Beyond the Limbo Silence, have focused on the childhood in the Caribbean and the journey awayâor at least the preparation for that journey. Such is the case with Clarkeâs âLeaving This Island Place.
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