  Monotone systems constitute one of the most important classes of dynamical
systems used in mathematical biology modeling. The objective of this paper is
to extend the notion of monotonicity to systems with inputs and outputs, a
necessary first step in trying to understand interconnections, especially
including feedback loops, built up out of monotone components. Basic
definitions and theorems are provided, as well as an application of a theorem
regarding negative feedback loops to the study of a model of one of the cell's
most important subsystems (MAPK cascades) .
