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| Dr. Leonard Hofstadter is a Caltech experimental physicist who shares an apartment with Dr. Sheldon Cooper in a building in Pasadena, California.
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| Dr. Sheldon Cooper is Leonard's best friend, roommate, and colleague. He is named after actor/producer Sheldon Leonard. He is calculating and cynical, believing that Leonard is only setting himself up for disappointment as he continues to have a crush on Penny.
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| Penny (the only character whose last name is unrevealed) is Leonard and Sheldon's neighbour across the hallway and is a "cheesecake-scented goddess" in the words of Wolowitz. Originally from Omaha, Nebraska, she is a beautiful waitress at the local Cheesecake Factory who apart from auditioning for several acting positions, is also writing a semi-autobiographical screenplay about a girl from Lincoln, Nebraska, who travels to Los Angeles to become an actress but ends up working at the Cheesecake Factory. Penny is very outgoing, kind, and assertive.
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| Howard Wolowitz is a Jewish engineer at Caltech's Department of Applied Physics who often hangs out at Leonard's and Sheldon's apartment. Jokingly, Wolowitz has stated that both he and Koothrappali visit Leonard and Sheldon's place because they like Leonard, not Sheldon.
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| Rajesh Koothrappali is Wolowitz's best friend and yet another genius. He also works in the Physics department at Caltech, where his area of expertise is particle astrophysics. He approaches women in the exact opposite way of Wolowitz: he is so shy that he is unable to speak to them unless he is intoxicated or does not feel he is directly addressing them. His social anxiety around women seems to be indicative of selective mutism, and is inspired by a former co-worker of Bill Prady's.
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| Leslie Winkle is another physicist who works in the same lab as Leonard, specializing in high energy physics, particularly super symmetry and dilepton calculations. She is essentially Leonard's female counterpart equipped with the black framed glasses and sweat jackets, with Penny saying they make a cute couple.
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