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Serena and Venus Williams moved into the quarterfinals of the Western & Southern Open by handling the afternoon heat, humidity and wind. The conditions were too much for Andy Murray.

Murray's off-day turned into the biggest upset of the tournament, a straight-sets loss Thursday that left him with hardly any hard-court time heading into the U.S. Open.

Murray lost 6-4, 6-4 to France's Jeremy Chardy, an opponent he'd beaten easily the four previous times they'd played. Murray had trouble controlling his shots on a breezy, 85-degree afternoon.

"I was a little bit uncomfortable with those balls bouncing extremely high," said Murray, who left the court as soon as the match ended and headed directly to the interview room. "It was fairly hard to control."

Roger Federer, Novak Djokovic, Mardy Fish and Juan Martin del Potro also reached the quarterfinals Thursday.

On the women's side, Serena Williams won her 19th straight match — her last 12 in straight sets — by beating Urszula Radwanska of Poland 6-4, 6-3. Williams hasn't lost a set since the Wimbledon final, which she won.

She returned to Wimbledon and won the gold medal in singles and in doubles with sister Venus. The travel and the hot conditions have worn her down.

"I have been playing a lot," she said. "Definitely (need) more energy. Been traveling a lot, been training a lot. You know, it's been a really big summer."

Venus Williams beat Sara Errani 6-3, 6-0, a quick match after two long ones the last two days.

"You know, I already got what I wanted at the Olympics this year, so everything else for me is like just amazing," Venus Williams said.

Murray left town with a little uncertainty.

He won a gold medal in the Olympics at Wimbledon by beating Federer, the highlight of his career. He went to Toronto last week hoping to get in shape for the hard-court season, but had to withdraw from the Rogers Cup because his left knee started hurting.

Murray felt good and moved well in an opening two-set win on center court Wednesday. Playing on the grandstand court a day later, the Scot never got into a rhythm.

Now, Murray heads to New York to practice for the U.S. Open, having played only three matches on hard courts since returning from Wimbledon's grass.

"I won't play any more matches," Murray said. "When going into the big tournaments, sometimes I've won tournaments in the buildup and it hasn't helped me. This year at Wimbledon, I lost in the first round at Queen's and made the final there for the first time. I have won Queen's before and not done well at Wimbledon.

"So it doesn't normally have that much bearing. But obviously I would have liked to have done a bit better this week."

Chardy got into the tournament as a replacement for John Isner, who had a sore back. The Frenchman won his opener over Andy Roddick, who developed back spasms during the match on Tuesday.

Chardy is the first injury replacement to reach an ATP Tour quarterfinal this season.

Federer beat Bernard Tomic 6-2, 6-4 on Thursday and has looked sharp in his two hard-court matches. Federer skipped the Rogers Cup last week.

"I feel like things are working really well for me," Federer said. "Regardless of what's going to happen, I'm feeling good, I'm healthy, I have no issues. I'm happy I got over the jet lag, and so the risk is less to get injured and all those things. So I'm in a good place right now."

Djokovic was on the court for only 30 minutes in the evening. Russia's Nikolay Davydenko quit after losing the first set 6-0, bothered by a sore right shoulder. He called the trainer over at the break, then decided not to continue.

Davydenko warmed up fine, but his serve quickly deteriorated. He had eight double faults, made 16 unforced errors and won only 16 points.

"You definitely don't want to win like this," Djokovic said. "Obviously he couldn't serve over 90 mph (by the end of the set) and he had a lot of double faults. Something was bothering his shoulder. Hopefully he'll be able to recover in time for the U.S. Open."

Fish, a two-time runner-up at the tournament in suburban Cincinnati, beat Radek Stepanek 6-3, 6-3, his first win over the Czech in five career matches. Fish celebrated his win with a leaping right fist pump.

"That was the monkey jumping off my back," Fish said. "He's been a tough opponent for me. Not only has he beaten me, but he's beaten me soundly."

Fish continues to improve after undergoing surgery in May to repair a heart condition.

"I feel fresher, stronger," he said. "The summer's gone well for me as far as getting my match fitness back."

On the women's side, top-seeded Agnieszka Radwanska overcame an unexpected challenge from wild-card Sloane Stephens before winning 6-1, 4-6, 6-4. Radwanska, who lost to Serena Williams in the Wimbledon final, reached the tournament's quarterfinal for the first time in three appearances.

Like Murray, she had trouble with the condition on the grandstand court.

"It was so hot and windy," she said. "I think that this court was slower than the center (court) and the ball didn't go at all. I was hitting as much as I could, but it just was hard to make winners there."

Rain forced suspension of sixth-seeded Caroline Wozniacki's match — she trailed Anastasia Pavlyuchenkova 6-4 after one set — and postponement of ninth-seeded Li Na's match against Johanna Larsson. They will play at 11 a.m. on Friday, with the winners having to play evening quarterfinal matches.

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AP freelancer Mark Schmetzer contributed to this report.