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By Paul Rincon
BBC News science reporter, at Kennedy Space Center
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The crew enjoyed cake before climbing aboard the shuttle
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The US space agency's first shuttle mission in over two years is all set to launch from the Kennedy Space Center.
The Discovery orbiter has been fuelled and lift-off at the Florida spaceport is timed for 1551 EDT (2051 BST).
The shuttle and its crew of seven will embark on a 12-day mission to deliver spare parts and essential supplies to the International Space Station.
It appears that only poor weather can delay the launch, with unfavourable cloud conditions forecast for the area.
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We have done everything that we know to do
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Meteorologists working at the KSC said the chances that cumulous clouds would disrupt the launch had gone up from 40% to 60%.
South-east winds that were expected to blow clouds away had now turned into south-west winds, they said.
Unfavourable cloud conditions are forecast
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The orbiter's external tank was loaded with two million litres (more than 500,000 gallons) of super-cold liquid oxygen and liquid hydrogen just after 0700 EDT.
The procedure, which was delayed slightly because of an equipment failure, took three hours to complete.
The Discovery crew, led by Commander Eileen Collins, was said by Nasa to have enjoyed the traditional pre-launch cake, which was decorated with the mission's insignia.
Collins and her team then walked out to the launch pad in the rain to get strapped into the orbiter.
Family support
The agency says it has learnt its lessons from the loss of Columbia, which broke apart as it came back into the Earth's atmosphere in February 2003.
Improvements to Discovery include a 50ft-long (15m) robotic arm that will inspect parts of the orbiter for damage once in orbit.
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SHUTTLE RETURN TO FLIGHT
Mission known as STS-114
Discovery's 31st flight
17th orbiter flight to ISS
Payload: Raffaello Multi-Purpose Logistics Module
Lift-off: 13 July, 1551 EDT
Location: Kennedy Space Center, Launch Pad 39B
Discovery crew: Collins, Kelly, Noguchi, Robinson, Thomas, Lawrence and Camarda
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The giant external tank has undergone modifications that should ensure it sheds little of its insulation foam on blast-off.
It was a suitcase-sized chunk of this material that crashed into Columbia's left wing, punching a large hole and leaving the orbiter open to the destructive super-heated gases of re-entry.
More cameras than ever before will be trained on Discovery during launch, to watch for any debris that could damage the spacecraft.
"It is utterly crucial for Nasa, for the nation, for our space programme, to fly a safe mission," Nasa Administrator Michael Griffin said on Tuesday.
"We have done everything that we know to do."
On Tuesday, family members of the Columbia crew issued a statement of support for Nasa's efforts to return the shuttle to flight.
Discovery's landing on 25 July, again at KSC, is set for 1101 EDT (1501 GMT; 1601 BST).