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The 14-time grand slam winner rallied to beat unheralded qualifier Tim Smyczek in five sets in the second round but he couldn't come back against a better opponent, Tomas Berdych, in the quarterfinals Tuesday.
Berdych crushed Nadal 6-2 6-0 7-6 (5) thanks to a fine display of power tennis to end a 17-match losing streak against the Spaniard. One of those losses came in the 2010 Wimbledon final.
Earlier Tuesday, Maria Sharapova set up a semifinal duel with fellow Russian Ekaterina Makarova when she eased past Eugenie Bouchard 6-3 6-2 and 10th-seed Makarova upset third-seed Simona Halep 6-4 6-0.
While Berdych barely missed on Rod Laver Arena, Nadal called his own display 'very bad' and said he helped Berdych by lacking in his trademark intensity.
'The third was the right set, the right game that I have to play,' Nadal told reporters. 'But is obvious that before I didn't play with the right confidence, with the right intensity, losing court, playing very short. I make him play very easy.
'So you cannot expect to win matches in quarterfinals of a grand slam helping the opponent to play well.'
Contributing to his fluctuating performances in Melbourne were a lack of match practice, added Nadal.
Entering the Australian Open, he'd only played eight tour-level matches since the middle of July because of a wrist injury, then appendicitis, in another long layoff.
Besides stuttering against Smyczek -- when Nadal was ill -- the third seed struggled at times in the third round against Dudi Sela. He turned it around against Kevin Anderson in the fourth round.
'When you are coming back from injuries you lose more easier the feeling than you do when you are on rhythm, when you are with no injuries, when you are confident in yourself that you played a lot of matches,' Nadal said. 'And that's the thing that happened, no?
'When I was playing well, I played well. But at the same time, against Sela I played well two sets, played bad the third. Against Anderson, was probably the only match I played regular. Played the right level during almost all the time.
'The rest of the matches have been lot of up and down.'
Berdych, however, did what he had to, hitting 46 winners and making only 21 unforced errors.
The tennis tour has seen a handful of retired grand slam winners return as coaches and Berdych attempted to lure eight-time grand slam champion Ivan Lendl -- Murray's former coach -- last year. But Lendl turned down the chance to work with his countryman because he was, according to Berdych, too busy.
Berdych instead opted for the 28-year-old Dani Vallverdu, Murray's former co-coach. Lendl and Vallverdu were by Murray's side when he opened his grand slam account at the 2012 U.S. Open before the Scot became the first British man in almost 80 years to win Wimbledon in 2013.
Berdych indeed admitted that Vallverdu helped him with his tactics against Nadal, and the effects were immediate.
'He changed a lot of things,' said Berdych, who next faces Murray. 'He changed a lot of positive things. And the best is I'm really able to execute them really, really quickly. That's how it should be.
'But ... it's not only about sitting on the table and talking about the tactics, it's also about you have to know what to do with that. If you have a plan it's a nice thing, but if you never tried it before or never practiced before, I mean, that's useless.'
The 29-year-old blasted past Nadal in an hour in the first two sets.
When Nadal elevated his game in the third set, Berdych didn't buckle even after he missed two match points on the Nadal serve at 6-5.
He stormed to a 5-1 lead in the tiebreak, a deficit that Nadal wasn't able to overcome.
Berdych saved all four break points he faced and pummeled Nadal's second serve, winning 71% of those points.
'Today I have the only time I can to enjoy the victory,' said Berdych. 'When I wake up tomorrow morning just all the focus goes for the next opponent and my next match.'
Murray ended the run of 19-year-old Aussie Nick Kyrgios, dampening the spirits of most of those on Rod Laver Arena who showed up for the night match.
Murray won 6-3 7-6 (5) 6-3, the turning point coming in the second-set tiebreak.
Kyrgios -- the first teenager on the men's tour to make multiple grand slam quarterfinals since Roger Federer -- led 4-3 with a mini-break but paid the price for two short approach shots, both punished by perfect Murray lobs.
'He was way too good for me,' Kyrgios said.
The other semifinal pairing will be determined Wednesday.
Novak Djokovic, trying for a fifth Australian Open crown, meets big-serving Canadian Milos Raonic, and defending champion Stan Wawrinka confronts U.S. Open finalist Kei Nishikori.
No problem for Maria
Sharapova needed three sets to battle past Bouchard at last year's French Open, but Tuesday was easier for the five-time grand slam winner. She was steady.
Bouchard, meanwhile, drowned in unforced errors, making 30 and chipping in only 13 winners.
'If I don't have enough time I probably go for riskier shots and that's why I would miss a few more,' Bouchard told reporters. 'That's why I think I made a few too many unforced errors. Just feeling under pressure, feeling I had to go for something.'
Sharapova has turned around her tournament since saving two match points in the second round against qualifier Alexandra Panova.
Her dad Yuri -- who no longer travels with Sharapova -- hasn't been shy to give her advice.
'When you're down and out like I was in the second match, it's like, I don't want to face that phone call with my father too many times during a tournament,' said Sharapova, who last won a major outside Roland Garros seven years ago. 'It's like, 'I better get my stuff together.'
'He told me that I was working much harder than I had to. If I was maybe a little bit smarter, did a few things maybe a little bit differently, maybe it could have been easier.'
Makarova may not be a household name but the left-hander has now reached consecutive grand slam semifinals.
She handled the occasion better than Halep, who lost last year's French Open final to Sharapova in three dramatic sets.
'I practiced very well in the morning, but maybe I was a little bit too stressed before I started the match,' Halep told reporters. 'Wasn't my good day. I had a bad day.'
In Wednesday's two other quarterfinals, top-seed Serena Williams faces 2014 finalist Dominika Cibulkova and Venus Williams battles Madison Keys in an all-American contest.
Read: Wawrinka's tiebreak magic