Dinara Safina was a 6-2, 6-3 winner over Italy's Flavia Pennetta on Wednesday.
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The sixth-seeded Russian registered a personal first at Flushing Meadows, reaching the US Open semi-finals for the first time.
The 22-year-old Safina, runner-up at the French Open and the Beijing Olympics, raced through the first set and came from a break down in the second to clinch a meeting with Serena.