We critically examine uncertainties in parton distribution functions (PDFs) at large x arising from nuclear effects in deuterium F2 structure function data. Within a global PDF analysis, we assess the impact on the PDFs from uncertainties in the deuteron wave function at short distances and nucleon off-shell effects, the use of relativistic kinematics, as well as the use of less a restrictive parametrization of the d/u ratio. We find that in particular the d-quark and gluon PDFs vary significantly with the choice of nuclear model. We highlight the impact of these uncertainties on the determination of the neutron structure function, and on W boson production and parton luminosity at the Tevatron and the LHC. Finally, we discuss prospects for new measurements sensitive to the d-quark and gluon distributions but insensitive to nuclear corrections.
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