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In order to meet increasingly stringent emissions standards and lower the fuel consumption of heavy-duty (HD) vehicles, significant efforts have been made to develop high efficiency and clean diesel engines and aftertreatment systems. However, a trade-off between the actual engine efficiency and nitrogen oxides (NOx) emission remains to minimize the operational costs. In addition, the conversion efficiency of the diesel aftertreatment system decreases rapidly with lower exhaust gas temperatures (EGT), which occurs at low load operations. Thus, it is necessary to investigate the optimum combustion and engine control strategies that can lower the vehicle’s running costs by maintaining low engine-out NOx emissions while increasing the conversion efficiency of the NOx aftertreament system through higher EGTs.