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New York - Defending champion Novak Djokovic and fellow two-time winner Rafael Nadal take centre stage on the Arthur Ashe Stadium on Wednesday looking to seal third round spots.
World No 1 Djokovic, who needed treatment on a right upper arm injury during his laboured four-set win over Poland's Jerzy Janowicz on Monday, faces Jiri Vesely of the Czech Republic.
Vesely inflicted a rare defeat on the Serb when he triumphed on clay at Monte Carlo in April.
"Different surface, different circumstances, best-of-five. But still, Vesely deserves respect," said Djokovic, the 2011 and 2015 champion in New York and looking for a third major of the year.
"He has a big game, big serve, big forehand, and moves well for his size. So let's see. Conditions are quite suitable to my style of the game. Hopefully I'll be able to slow his serve down a little bit and then take it from there."
Spanish fourth seed Nadal, the 2010 and 2013 champion, takes a 7-1 career record over Italy's Andreas Seppi into their night time clash.
Seppi, ranked at 87, has never got beyond the third round in New York but he is a former top 20 player who knocked Roger Federer out of the Australian Open two years ago.
Two-time Wimbledon champion Petra Kvitova gets play underway on Ashe against Turkey's Cagla Buyukakcay followed by Caroline Wozniacki, twice a runner-up in New York, facing former US and French Open champion Svetlana Kuznetsova.
Reigning Roland Garros champion and third seed Garbine Muguruza of Spain tackles Latvia's Anastasija Sevastova.
Muguruza needed three sets to see off Belgian qualifier Elise Mertens in a first round tie which also saw her need a medical timeout after suffering heat exhaustion.
Angelique Kerber, the second seeded Australian Open champion who could depose Serena Williams as world number one, faces 34-year-old Mirjana Lucic-Baroni.
The veteran Croatian made the last 16 in 2014 having played her first US Open back in 1997.
Italian seventh seed Roberta Vinci, last year's runner-up, faces Christina McHale of the United States.
Also on Louis Armstrong are US No 1 John Isner against Belgian qualifier Steve Darcis while compatriot Jack Sock clashes with German qualifier Mischa Zverev.
Two highly-fancied potential title winners are also in second round action.
Canadian fifth seed Milos Raonic, the Wimbledon runner-up, plays Ryan Harrison of the US.
In the women's draw, American eighth seed Madison Keys meets 16-year-old compatriot Kayla Day.Results from the second day of the 2016 US Open tennis championships at Flushing Meadows on Tuesday (x denotes seeded player):
Men
First round
Dominic Thiem (AUT x8) bt John Millman (AUS) 6-3, 2-6, 5-7, 6-4, 6-3
Ricardas Berankis (LTU) bt Malek Jaziri (TUN) 3-6, 7-6 (7/3), 6-4, 6-2
Pablo Carreno-Busta (ESP) bt Ilya Ivashka (BLR) 6-0, 7-5, 6-2
Janko Tipsarevic (SRB) bt Sam Querrey (USA x29) 7-6 (7/4), 6-7 (0/7), 6-3, 6-3
Steve Johnson (USA x19) bt Evgeny Donskoy (RUS) 4-6, 1-6, 7-6 (7/2), 6-3, 6-3
Juan Martin Del Potro (ARG) bt Diego Schwartzman (ARG) 6-4, 6-4, 7-6 (7/3)
Fabio Fognini (ITA) bt Teimuraz Gabashvili (RUS) 6-7 (9/11), 3-6, 7-6 (7/5), 7-5, 6-4
David Ferrer (ESP x11) bt Alexandr Dolgopolov (UKR) 6-5 - retired
Nick Kyrgios (AUS x14) bt Aljaz Bedene (GBR) 6-4, 6-4, 6-4
Horacio Zeballos (ARG) bt Florian Mayer (GER) 6-3, 6-4, 7-6 (9/7)
Illya Marchenko (UKR) bt Ivan Dodig (CRO) 6-3, 6-4, 6-7 (4/7), 7-5
Damir Dzumhur (BIH) bt Bernard Tomic (AUS x17) 6-4, 6-3, 4-6, 7-6 (7/0)
Alexander Zverev (GER x27) bt Daniel Brands (GER) 3-6, 6-1, 6-4, 7-6 (7/4)
Daniel Evans (GBR) bt Rajeev Ram (USA) 6-2, 4-6, 7-5, 6-1
Alessandro Giannessi (ITA) bt Denis Kudla (USA) 0-6, 6-4, 6-1, 1-6, 6-0
Stan Wawrinka (SUI x3) bt Fernando Verdasco (ESP) 7-6 (7/4), 6-4, 6-4
Kei Nishikori (JPN x6) bt Benjamin Becker (GER) 6-1, 6-1, 3-6, 6-3
Karen Khachanov (RUS) bt Thomas Fabbiano (ITA) 6-3, 6-3, 4-6, 6-3
Paul-Henri Mathieu (FRA) bt Christian Harrison (USA) 6-0, 6-2, 6-1
Nicolas Mahut (FRA) bt Philipp Kohlschreiber (GER x25) 6-3, 7-5, 1-0 - retired
Ivo Karlovic (CRO x21) bt Lu Yen-Hsun (TPE) 4-6, 7-6 (7/4), 6-7 (4/7), 7-6 (7/5), 7-5
Donald Young (USA) bt Jan-Lennard Struff (GER) 6-3, 7-5, 4-6, 7-5
Viktor Troicki (SRB) bt Radu Albot (MDA) 5-7, 3-6, 6-4, 6-4, 7-6 (7/5)
Jared Donaldson (USA) bt David Goffin (BEL x12) 4-6, 7-5, 6-4, 6-0
Feliciano Lopez (ESP x16) bt Borna Coric (CRO) 3-4 - retired
Joao Sousa (POR) bt Victor Estrella (DOM) 6-0, 6-1, 6-1
Jeremy Chardy (FRA) bt Michael Mmoh (USA) 6-4, 6-4, 6-1
Grigor Dimitrov (BUL x22) bt Inigo Cervantes (ESP) 6-2, 6-4, 7-6 (9/7)
Gilles Simon (FRA x30) bt Radek Stepanek (CZE) 6-3, 6-1, 6-4
Paolo Lorenzi (ITA) bt Carlos Berlocq (ARG) 6-4, 6-2, 6-1
Marcel Granollers (ESP) bt Juan Monaco (ARG) 7-6 (7/5), 7-6 (7/2), 6-4
Andy Murray (GBR x2) bt Lukas Rosol (CZE) 6-3, 6-2, 6-2
Women
First round
Serena Williams (USA x1) bt Ekaterina Makarova (RUS) 6-3, 6-3
Vania King (USA) bt Antonia Lottner (GER) 7-6 (7/2), 6-3
Johanna Larsson (SWE) bt Karin Knapp (ITA) 6-4, 6-2
Denisa Allertov (CZE) bt Ana Ivanovic (SRB x29) 7-6 (7/4), 6-1
Wang Qiang (CHN) bt Darya Kasatkina (RUS x23) 6-4, 2-6, 6-2
Yaroslava Shvedova (KAZ) bt Lara Arruabarrena (ESP) 6-2, 6-3
Zhang Shuai (CHN) bt Ellen Perez (AUS) 6-1, 6-1
Samantha Stosur (AUS x16) bt Camila Giorgi (ITA) 7-5, 6-7 (4/7), 6-1
Carla Suarez (ESP x11) bt Teliana Pereira (BRA) 6-0, 6-0
Jelena Jankovic (SRB) bt Mariana Duque (COL) 6-4, 6-1
Annika Beck (GER) bt Nadia Podoroska (ARG) 7-6 (8/6), 6-3
Elena Vesnina (RUS x19) bt Anett Kontaveit (EST) 7-6 (7/4), 4-6, 6-3
Timea Babos (HUN x31) bt Barbara Haas (AUT) 5-7, 6-3, 7-5
Richel Hogenkamp (NED) bt Heather Watson (GBR) 6-2, 7-5
Lucie Safarova (CZE) bt Daria Gavrilova (AUS) 6-4, 6-4
Simona Halep (ROM x5) bt Kirsten Flipkens (BEL) 6-0, 6-2
Agnieszka Radwanska (POL x4) bt Jessica Pegula (USA) 6-1, 6-1
Naomi Broady (GBR) bt Laura Robson (GBR) 6-7 (4/7), 6-3, 6-4
Katerina Siniakov (CZE) bt Eugenie Bouchard (CAN) 6-3, 3-6, 6-2
Caroline Garcia (FRA x25) bt Pauline Parmentier (FRA) 4-6, 6-3, 6-4
Ana Konjuh (CRO) bt Kiki Bertens (NED x20) 6-3, 2-6, 6-4
Kurumi Nara (JPN) bt Stefanie Voegele (SUI) 6-0, 7-5
Varvara Lepchenko (USA) bt Peng Shuai (CHN) 4-6, 7-6 (11/9), 6-3
Timea Bacsinszky (SUI x15) bt Vitalia Diatchenko (RUS) 6-1, 6-1
Karolina Pliskova (CZE x10) bt Sofia Kenin (USA) 6-4, 6-3
Montserrat Gonzalez (PAR) bt Danka Kovinic (MNE) 7-5, 6-2
Kristina Mladenovic (FRA) bt Nao Hibino (JPN) 6-4, 7-5
Anastasia Pavlyuchenkova (RUS x17) bt Louisa Chirico (USA) 6-1, 6-4
Laura Siegemund (GER x26) bt Patricia Tig (ROM) 3-6, 6-3, 6-2
Nicole Gibbs (USA) bt Aleksandra Krunic (SRB) 6-1, 6-0
Julia Gerges (GER) bt Yanina Wickmayer (BEL) 6-3, 6-2
Venus Williams (USA x6) bt Kateryna Kozlova (UKR) 6-2, 5-7, 6-4
