An integral feedback model for damage response and homeostasis systems.

<p>(a) An increase of the input, , leads to a rise in the level of the output, , which, in turn triggers the production of the internal variable, , that lowers the output back to its original level. This feedback loop is at the heart of systems such as (b) the <i>E. coli</i> heat shock system - where the input is temperature, the internal variable is the amount of chaperones and the output is the level of unfolded proteins; and (c) the E coli SOS DNA repair system where the input is DNA damaging agents such as irradiation, the internal variable is DNA repair machinery and the output is the level of DNA damage. Another example is the regulation of the levels of calcium in the dairy cow (d) where the input is the calcium needed for milk production per day, the internal variable is calcium flux that goes into the blood from food, bone and other stores, and the output is flux of calcium that leaves the blood per day and is required for the activities of essential organs, such as heart and neurons.