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Nadal's loss in the Wimbledon final last month has to be the toughest loss for him in his career.
While Djokovic already took the No. 1 rankings in the computer just by virtue of getting to the finals of Wimbledon, the final match against Nadal was really going to determine who should be considered the best of the best. Djokovic was indeed able to defeat Nadal for the fifth time in 2011, cementing a changing of the guard in tennis.
Nadal will obviously then be looking to reassert his dominance both over Djokovic and men's tennis at the US Open. He will also be trying to repeat at a grand slam tournament for the first time in his career, other than at the French Open which he has done twice (2005-2008 and 2010-2011).
On the other side of the ball is Federer, who has looked pretty distant at times in some of his matches this season. His Wimbledon quarterfinal loss to Tsonga, when the Frenchman came back from down two sets, was an uncharacteristic lackluster performance by him on the big stage.
It makes you wonder if he is fully motivated at this point. He has accomplished just about everything possible in the sport and it would seem likely that his motivation would slip at least a little.