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Back-to-back singles from Jeff Keppinger and Hunter Pence brought home Castro and Michael Bourn, who was hit by a pitch.
The Cubs scored three runs in the third, with the big blow coming on Byrd's two-out, two-run homer. It was Byrd's first home run since Aug. 11 and his 12th overall.
Cub right-hander Casey Coleman went six innings. He gave up four runs on eight hits and five walks. Astros lefty Wandy Rodriguez gave up four runs and eight hits in seven innings. He struck out six and walked one.
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