An analysis of the pion mass and pion decay constant is performed using mixed-action Lattice QCD calculations with domain-wall valence quarks on ensembles of rooted, staggered n_f = 2+1 MILC configurations. Calculations were performed at two lattice spacings of b~0.125 fm and b~0.09 fm, at two strange quark masses, multiple light quark masses, and a number of lattice volumes. The ratios of light quark to strange quark masses are in the range 0.1 <= m_l / m_s <= 0.6, while pion masses are in the range 235 < m_pi < 680 MeV. A two-flavor chiral perturbation theory analysis of the Lattice QCD calculations constrains the Gasser-Leutwyler coefficients bar{l}_3 and bar{l}_4 to be bar{l}_3 = 4.04(40)(+73-55) and bar{l}_4 = 4.30(51)(+84-60). All systematic effects in the calculations are explored, including those from the finite lattice space-time volume, the finite lattice spacing, and the finite fifth dimension in the domain-wall quark action. A consistency is demonstrated between a chiral perturbation theory analysis at fixed lattice spacing combined with a leading order continuum extrapolation, and the mixed-action chiral perturbation theory analysis which explicitly includes the leading order discretization effects. Chiral corrections to the pion decay constant are found to give f_pi / f = 1.062(26)(+42-40) where f is the decay constant in the chiral limit. The most recent scale setting by the MILC Collaboration yields a postdiction of f_pi = 128.2(3.6)(+4.4-6.0)(+1.2-3.3) MeV at the physical pion mass.
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