Multistability is an emergent dynamic property that has been invoked to explain multiple coexisting biological states. In this work, we investigate the origin of bistability in the lac operon. To do this, we develop a mathematical model for the regulatory pathway in this system and compare the model predictions with other experimental results in which a nonmetabolizable inducer was employed. We investigate the effect of lactose metabolism using this model, and show that it greatly modifies the bistable region in the external lactose (Le) versus external glucose (Ge) parameter space. The model also predicts that lactose metabolism can cause bistability to disappear for very low Ge. We have also carried out stochastic numerical simulations of the model for several values of Ge and Le. Our results indicate that bistability can help guarantee that Escherichia coli consumes glucose and lactose in the most efficient possible way. Namely, the lac operon is induced only when there is almost no glucose in the growing medium, but if Le is high, the operon induction level increases abruptly when the levels of glucose in the environment decrease to very low values. We demonstrate that this behavior could not be obtained without bistability if the stability of the induced and uninduced states is to be preserved. Finally, we point out that the present methods and results may be useful to study the emergence of multistability in biological systems other than the lac operon.

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We provide two algorithms for computing the volume of the convex polytope :The computational complexity of both algorithms is essentially described by n m , which makes them especially attractive for large n and relatively small m, when the other methods with O(m n ) complexity fail. The methodology, which differs from previous existing methods, uses a Laplace transform technique that is well suited to the half-space representation of .

We consider the problem of calculating a closed form expression for the integral of a real-valued function f : R n → R on a set S. We specialize to the particular cases when S is a convex polyhedron or an ellipsoid, and the function f is either a generalized polynomial, an exponential of a linear form (including trigonometric polynomials) or an exponential of a quadratic form. Laplace transform techniques allow us to obtain either a closed form expression, or a series representation that can be handled numerically. Finally, a methodology is proposed for multivariate functions f which have a (multidimensional) Laplace transform.

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