The episode opens with a short montage of clips from the series' twelve seasons, then segues to Sheldon and Amy, who are up late waiting for a call from the Nobel Committee. Following a prank call from Kripke, they are told they've won the Nobel Prize in Physics for their super-asymmetry work. The attention from the media and the university bothers Sheldon. Amy is saddened by an unflattering picture of her in a news report, so Raj convinces her to get a makeover. She loves her new look but Sheldon demands she change it back. Leonard calls him out for being rude, but Sheldon flees when he sees Penny emerge from the newly repaired elevator. Sheldon and Penny go to the Cheesecake Factory and Penny tells Sheldon that change is the only constant thing in life. On a TV, they see Bernadette and Howard take credit as Sheldon and Amy's best friends. Raj and Leonard defend Amy, with Leonard accidentally breaking Sheldon's DNA molecule model in Apartment 4A. Penny convinces Sheldon to ride in the elevator.
In the episode "The Launch Acceleration", Amy tries to use her "neurobiology bag of tricks" to increase the attraction between herself and Sheldon. In the final fifth-season episode "The Countdown Reflection", Sheldon takes Amy's hand as Howard is launched into space. In the sixth season first episode "The Date Night Variable", after a dinner in which Sheldon fails to live up to this expectation, Amy gives Sheldon an ultimatum that their relationship is over unless he tells her something from his heart. Amy accepts Sheldon's romantic speech even after learning that it is a line from the first Spider-Man movie. In "The Cooper/Kripke Inversion" Sheldon states that he has been working on his discomfort about physical contact and admits that "it's a possibility" that he could one day have sex with Amy. Amy is revealed to have similar feelings in "The Love Spell Potential". Sheldon explains that he never thought about intimacy with anyone before Amy.
Amy and Howard begin collaborating on a neuroprosthetics project, upsetting Sheldon and Raj, who feel they are not spending as much time with them. When they seek solace with an annoyed Bernadette, she exploits the situation to trick Sheldon into doing Howard's chores. Penny successfully employs the approaches recommended in one of Bernadette's parenting books to deal with Sheldon, but Leonard believes she is coddling Sheldon too much. Sheldon and Raj resolve the issue of missing their significant others by spending time together.
Sara Gilbert as Leslie Winkle (recurring season 1, starring season 2, guest seasons 3, 9): A physicist who works in the same lab as Leonard. In appearance, she is essentially Leonard's female counterpart and has conflicting scientific theories with Sheldon. Leslie has casual sex with Leonard and later Howard. Gilbert was promoted to a main cast member during the second season but resumed guest star status because producers could not come up with enough material for the character. Gilbert returned to The Big Bang Theory for its 200th episode.
The men are excited that Bill Gates is visiting Penny's pharmaceutical company, although she says that she cannot bring them along. Sheldon believes that it's an April Fools' Day prank. Leonard sees what hotel Gates is staying at on Penny's schedule, so he, Raj and Howard meet him in the lobby the day before. Once Sheldon sees proof, the men twice send him to the wrong hotel as real pranks. Penny says Leonard can meet Gates for real, so he fakes being sick to avoid him. When Penny puts Gates on a video call, he recognizes Leonard from the previous night. Meanwhile, Amy is tired of Bernadette only talking about her children, so Bernadette uses her expanded parental brain to learn random science facts.
Barry Kripke says that he can get proof that Pemberton plagiarized his thesis, which would destroy his chances at the Nobel Prize. Sheldon and Amy decide not to pursue this; they want to win on their own merits. Leonard decides to get the information from Kripke. Amy and Sheldon give it to Pemberton and Campbell, as they refuse to blackmail them. Campbell is furious that Pemberton's dishonesty could hurt his own career. It is revealed that Campbell is sleeping with Pemberton's ex-wife, causing the pair to brawl. Afterwards, Campbell exposes Pemberton, causing Pemberton to be fired. Amy and Sheldon reject a drunken Campbell's request to join their team. Bernadette tells Howard that another waitress at the Cheesecake Factory was attracted to him back in the day, so she said Howard had hepatitis to scare her off. Howard obsesses over who it was, until he tells Bernadette she is the only one that matters to him.
Kunal Nayyar as Rajesh Koothrappali: A particle astrophysicist originally from New Delhi, India. Raj is initially unable to talk to women unless he drinks alcohol. Raj also has very feminine tastes and often takes on a stereotypical female role in his friendship with Howard as well as in the group of four men. Raj later dates Lucy (Kate Micucci), who also suffers from social anxiety, but it eventually ends; he later speaks to Penny without alcohol and thus overcomes his selective mutism. He begins dating Emily and their relationship later becomes exclusive. Raj also has a Yorkshire Terrier named Cinnamon.
Raj meets with the woman his father set up for him, Anu. Her commanding personality and practical approach to marriage startle Raj but he agrees to go ahead with it. Howard criticizes him but apologizes; he just never expected Raj to give up on romance. Raj admits this to Anu so she proposes to him, and he says yes. Raj also sends out a relationship questionnaire to Leonard and Penny, which soon reveals that Penny does not think she ever wants kids, upsetting Leonard, who would like to have kids someday, and their friends selfishly badger them on the issue. After telling her father Wyatt who is also upset, Leonard tells Penny that he'll be okay with it, as he never thought he'd have her in his life. To get his mind off of it, Penny rents Leonard a Batmobile to drive in and have fun with for the day. Meanwhile, Stuart starts bringing home Denise at night, which is very uncomfortable for Howard and Bernadette. When they also try to have time to themselves, they wake up their kids.
Warner Bros. Television controls the online rights for the show. Full episodes are available at tv.com, while short clips and recently aired full episodes are available on cbs.com. In Canada, recent episode(s) and pictures are available on CTV.ca. Additionally in Canada, the first six seasons are available for streaming on Bell Media's CraveTV. After the show has aired in New Zealand the shows are available in full online at TVNZ's on demand web service.
Filming proceeds smoothly – makeup artists do touch-ups, a prop master replenishes the pickle supply – with humor and camaraderie between takes. When a reshoot is needed because Simon Helberg, who plays Howard, held his napkin in the wrong hand, Kaley Cuoco, who plays Penny, lifts her food box high and mockingly asks, “Does it go over my head? I don’t remember.”
"The Locomotive Manipulation" is the first episode in which Sheldon initiates a kiss with Amy. Although initially done in a fit of sarcasm, he discovers that he enjoys the feeling. Consequently, Sheldon slowly starts to open up over the rest of the season, and starts a more intimate relationship with Amy. However, in the season finale, Sheldon leaves temporarily to cope with several changes and Amy becomes distraught. However, in "The Prom Equivalency", he hides in his room to avoid going to a mock prom reenactment with her. In the resulting stand-off, Amy is about to confess that she loves Sheldon, but he surprises her by saying that he loves her too. This prompts Amy to have a panic attack.
Sheldon needs half a billion dollars to prove his latest concept of string theory, which the University cannot afford to fund. Crowdfunding and selling some of his most valuable comic books to Stuart give him a small start. When Raj mentions gambling in Las Vegas, Sheldon goes there but is caught calculating odds by security before he can make any bets. Meanwhile, Amy takes Penny and Bernadette shopping for her wedding dress. She loves an old-fashioned one that the other girls admit that they find ugly, though Penny assures Amy she can make her own decisions about her wedding. Sheldon, however, comes home and sees Amy in the dress and loves how she looks.