If oscillations areviewed as a purely temporal pattern, it is not surprising that Formoterol Hemifumarate positive feedback enhances negative feedback oscillations. While we have focused here on understanding the role of positive feedback and suggesting its evolutionary purpose in easing oscillations by reducing the cooperativity requirements, our results can be also viewed in a prescriptive light. Given a model of an oscillatory biological phenomenon, unreasonably high cooperativity values within the model would suggest that one or several important positive feedback mechanisms have been overlooked in model construction. This might also direct further experimental work if evidence of such positive feedback is lacking. It has been also suggested that positive feedback provides robustness to the system. This robustness is measured using the fraction of random parameter choices within some space that result in stable oscillations. The idea being that this metric is a surrogate for the size of the parameter space where oscillations occur. The larger the parameter space with oscillations, the more robust the oscillations are to changes in parameter values. However, estimating the size of the parameter space using this approach is difficult, since models oscillate in different regions of parameter space and the size of a region of parameter space is meaningful only relative to the observed range of variation of that parameter that depends on the biological process it represents. Therefore, we did not test the ��robustness�� of the motifs in this work. We have elaborated on the qualitative role of positive feedback in reducing the nonlinearity necessary to produce oscillations using the simple Goodwin core motif. This three-component negative feedback is a common motif in several biochemical oscillators and more complex oscillators can be BRD73954 reduced to this threecomponent motif with positive feedback. We exploited the advantage of simple motifs to capture general functional roles of feedback structures, without the complexity that accompanies studies of specific systems.