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Fourth-generation wireless communication systems (4G) have totally different requirements than what front-end designers have been coping with up to now. Designs must be targeted to multi-mode and reconfigurability, leading to the concept of a "software-defined radio". A large part of such a radio will be integrated into a complex SoC, where the substrate noise coupling problem must be solved. However, for an optimal implementation of the complete system, including PA, RF filters and antenna, different technologies must be combined in a single package, merging the worlds of microwave 's-parameter' designers and IC 'spice' designers. Design and simulation environments efficiently combining the assets of both are needed. At the same time, optimized mixed-signal radio architecture including digital compensation techniques that overcome the limitations and inaccuracies of the analog front-end must be developed. Again, efficiently designing and simulating such mixed analog/digital architectures requires an optimized tool capable of combining RF simulation techniques with digital system model simulation.