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A formalism for calculating the open supermembrane contribution to the non-perturbative superpotential of moduli in heterotic M-theory is presented. This is explicitly applied to the Calabi-Yau (1,1)-moduli and the separation modulus of the end-of-the-world BPS three-branes, whose non-perturbative superpotential is computed. The role of gauge bundles on the boundaries of the open supermembranes is discussed in detail, and a topological criterion presented for the associated superpotential to be non-vanishing.

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