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To achieve low tailpipe NOX emissions in Heavy-Duty engines, the rapid warm-up of the exhaust aftertreatment system (EAS) needs to be assisted by the adoption of new technologies to reduce engine-out emissions and increase the EAS conversion efficiency. Engine measures like cylinder deactivation, retarded start of the main injection, late intake valve closing, intake throttling and elevated idle speed can substantially increase the available exhaust gas enthalpy and temperature at the expense of additional fuel as has been shown in the literature. On the other hand, the exhaust system can be optimized in terms of hardware and controls, which is nowadays strongly supported by simulation. However, these simulation studies typically assume a fixed engine hardware and calibration and thus fixed engine-out simulation boundary conditions. Moving forward to tougher and real-world oriented legislation, the fixed cycle and engine-out boundary condition becomes insufficient.