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While Isner was almost delirious, Mahut, 28 and ranked 148 in the world, looked remarkably fresh, perhaps boosted by the knowledge he had won a match with Britain's Alex Bogdanovic in qualifying 24-22 in the final set.
BBC: Wimbledon 2010: Epic halted at 59-59 in fifth set
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Bogdanovic, three years Murray's senior, has had a more troubled time under Britain's Davis Cup umbrella.
BBC: SPORT | Tennis | What now for British tennis?
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Annacone, the LTA's head coach of men's tennis, was full of praise for Bogdanovic, who turned professional in 2002 and reached 108th in the world in June 2007, but is mystified by his lack of success.
BBC: Bogdanovic faces wildcard threat
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The absence of both Murray and Bogdanovic is very likely to mean a place in the singles squad for Scotland's Jamie Baker, plus Dan Evans and James Ward.
BBC: Andy Murray opts out of Davis Cup tie against Turkey
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"I probably won't get another wildcard and that's fair enough - I've had many chances, " said Bogdanovic, who partnered James Ward to victory over David Martin and Jean-Claude Scherrer in round one of the men's doubles.
BBC: Bogdanovic faces wildcard threat
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British number one Andy Murray has chosen to take a break from the Davis Cup while number two Alex Bogdanovic also opted not to take part in the tie, which is Leon Smith's first as captain.
BBC: Great Britain close in on Davis Cup victory