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Diesel combustion is a very complex process, involving a reacting, turbulent and multi-phase flow. Furthermore, heavy duty engines operate mainly at medium and high loads, where injection durations are very long and cylinder pressure is high. Within such context, proper CFD tools are necessary to predict mixing controlled combustion, heat transfer and, eventually, flame wall interaction which might result from long injection durations and high injection pressures. In particular, detailed chemistry seems to be necessary to estimate correctly ignition under a wide range of operating conditions and formation of rich combustion products which might lead to soot formation. This work is dedicated to the identification of suitable methodologies to predict combustion in heavy-duty diesel engines using detailed chemistry.