Exploiting ecology in drug pulse sequences in favour of population reduction
Fig 1
Comparison of the lowest population minimum nmin for drug treatment sequences of constant overall duration τ = 60 providing the same total exposure to high stress tr and low stress τ − tr distributed over different numbers of identically-shaped pulses N.
Parameters τ and tr (x-axis), both given in units of growth rate, together with the skewness s, describing how tr is positioned within τ, (y-axis), determine a drug pulse (sketched on the right). The colour code signifies the optimal N-pulse sequence for a certain choice of parameters tr and s, and the shade indicates the value of the nmin. The coloured lines mark the skewnesses that give local minima for fixed tr corresponding to an optimal onset time for the respective number of pulses. In the non-blue regions a sequence of pulses is more effective than a single pulse, either because onset times are closer to the optimum value for higher number of pulses compared to one pulse (top left corner) or because the minimum nmin is reached in the last pulse of every sequence (bottom right corner; region surrounded by the black line).