The cross-activating motifs have been shown to produce oscillations under the alternative name of amplified negative feedback in. Marteil and Goldbeter use a combination of MM degradation of the inhibitor and cross-activation to reduce the cooperativity in the model for cAMP oscillations in slime mold to about 2. Alternative views on the BAR501 effect of positive feedback As is evident from our theoretical analysis and discussed earlier by Thron, one of the drivers of high cooperativity requirement is the mismatch between the effective degradation rates between the components, albeit measured at the Ipragliflozin critical point. Positive feedback reduces the needed cooperativity by reducing the mismatch between the component degradation rates. This is manifest as the prescription we presented that the positive feedback must be placed in the step with shortest half-life to obtain the best benefit. We might also speculate that such positive feedback on the fastest step would be favored by evolution as they produce oscillations most easily. Since positive feedback only has the ability to lengthen lifetimes, the mismatch can be reduced only by slowing down the fastest steps. In the case of the CA motifs, there are additional benefits of positive feedback in the form of reduction of the mismatch cost. It is well known that nonlinearity is critical to generating oscillatory phenomena. The measure of cooperativity can then be considered to be a measure of this nonlinearity required for oscillations. The positive feedback motifs in effect redistribute the ��total�� nonlinearity across multiple steps, which is apparent under the reaction order formulation of Thron for the MM and SA motifs. This distribution is further beneficial, since the effective reaction order of the system is a product rather than a sum of the individual reaction orders. Classical models of biological pattern formation work on the principle of short-range activation and long-range inhibition. Thus, spatio-temporal patterns are generated by auto-catalysis and long range inhibition.