Biden told reporters at the New Castle Airport, not far from the debate site at Centre College in Danville, that he was ready to go at the Republican congressman from Wisconsin.
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"You ever see me rope-a-dope?" he responded when one reporter asked if he intended to stand back and let Ryan do himself in.
Ryan, meanwhile, was just as confident, after nine 90-minute prep sessions held across the country in recent days, Fox News reported.
"I know [Biden will] come and attack us," Ryan told CNN. "The problem he has is, he has Barack Obama's record he has to run on."
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President Barack Obama called Biden this afternoon to wish him luck in tonight's debate, according to Politico.
And the vice president probably needs it, as pressure mounts for him to stymie Mitt Romney's recent surge in the polls following Obama's lackluster performance in the first presidential debate.
Romney had been trailing in the polls, with basement-level likeability ratings and infinitesimal approval from women. But he is now virtually tied with the president in important swing states.
The latest NBC/WSJ/Marist poll shows Romney making significant gains in several states.
Tonight's debate airs nationally at 9 p.m. ET and will be moderated by ABC's Martha Raddatz. Watch live in the first video below: