We describe conditions on the signed support, that is, on the set of the exponent vectors and on the signs of the coefficients, of a multivariate polynomial $f$ ensuring that the semi-algebraic set $\{ f < 0 \}$ defined in the positive orthant has at most one connected component. These results generalize Descartes' rule of signs in the sense that they provide a bound which is independent of the values of the coefficients and the degree of the polynomial. Based on how the exponent vectors lie on the faces of the Newton polytope, we give a recursive algorithm that verifies a sufficient condition for the set $\{ f < 0 \}$ to have one connected component. We apply the algorithm to reaction networks in order to prove that the parameter region of multistationarity of a ubiquitous network comprising phosphorylation cycles is connected.
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