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Point mutations in the influenza virus enzyme neuraminidase (NA) have been reported that lead to dramatic loss of activity for known NA inhibitors including the FDA approved sialic acid mimics zanamivir and oseltamivir. A more complete understanding of the molecular basis for such resistance is a critical component toward development of improved… (More)
The microscopically complicated real world exhibits behavior that often yields to simple yet quantitatively accurate descriptions. Predictions are possible despite large uncertainties in microscopic parameters, both in physics and in multiparameter models in other areas of science. We connect the two by analyzing parameter sensitivities in a prototypical… (More)
We explain that part of the reduction in the parameter uncertainties in the computations of Apgar et al. (Mol. Biosyst. 2010, 6, 1890-900) is due to a greatly increased number of effective data points.
We use an extension of the van der Pol oscillator as an example of a system with multiple time scales to study the susceptibility of its trajectory to polynomial perturbations in the dynamics. A striking feature of many nonlinear, multiparameter models is an apparently inherent insensitivity to large-magnitude variations in certain linear combinations of… (More)
We explain that part of the reduction in the parameter uncertainties in the computations of Apgar et al. (Mol. Biosyst. 2010, 6, 1890–900) is due to a greatly increased number of effective data points. In ''Sloppy models, parameter uncertainty, and the role of experimental design'', Apgar et al. 1 explore how experimental design can be used to constrain… (More)