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Summary form only given. In this talk, we discuss the cross-layer optimization issues in wireless networks by investigating the impact of physical (PHY) layers on the media access control (MAC) and higher protocol layers, or vice versa. In particular, we explore the benefits of cross-layer design for multi-user multi-input multi-output (MU-MIMO) cellular mobile networks, wireless local area networks (WLAN), and wireless sensor networks (WSN).In the first part of this talk, from the standpoint of the top-down design, i.e. from MAC layer to PHY layer, we introduce the concept of "soft coverage" in MU-MIMO cellular mobile systems. Specifically, the MAC layer multi-user scheduling algorithm is designed to improve the coverage of MIMO cellular mobile systems without increasing transmission power in the PHY layer. Next, we show that the multi-user scheduling algorithm can also simplify the design of MIMO receiver as well. It will be demonstrated that a simple zero-forcing MIMO receiver combined with appropriate multi-user scheduling algorithm can achieve the performance of the optimal MIMO receiver. In the second part of this talk, from the viewpoint of the bottom-up design, i.e., from PHY layer to higher protocol layer, we first discuss how radio propagation channels affect the design of rate adaptation schemes of WLAN. Specifically, we show that it is not necessary to adopt the complete eight modulation and coding (MCS) modes specified in IEEE 802.11 WLAN for various transmission rates in a Rayleigh fading. An efficient joint power and rate-adaptive IEEE 802.11 WLAN based on the concept of reduced-mode MCS will be discussed, which can avoid using inefficient MCS transmission modes by taking account of PHY layer effects. Next, for the power-sensitive WSN, we discuss how to develop a PHY/MAC/Network cross-layer analytical approach to determine the optimal number of clusters with minimal energy consumption in various radio propagation channel conditions.