Although he outwardly considered their relationship "friends with benefits" and as such had no emotional connotation, Howard is feeling dejected after he is dumped by Leslie Winkle. Thinking he needs to do something fun to get over Leslie, Leonard and Raj decide to drag Howard to Las Vegas for a weekend getaway. Once there, Leonard and Raj learn that it will take more than just fun they can conjure up to get Howard out of his depression. They resort to professional help. Meanwhile, Sheldon is expecting to have a peaceful weekend alone in the apartment. Having locked himself out and with no superintendent to let him in, Sheldon is forced to stay the weekend with a less than happy Penny.

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It's "Anything Can Happen Thursday", the third Thursday in the month the guys have deemed the day to do something different to get out of their rut. Sheldon proposes that they go to the comic book store (as comic book store night is usually Wednesday). Penny tags along to buy a gift for her nephew. In addition to getting something for her nephew, she also gets something else: picked up, specifically by Stuart, the comic book store owner. Leonard has mixed emotions: he is buoyed by the fact that someone that is somewhat like him at first glance can get a girl like Penny, but is jealous that Penny picked Stuart instead of him. To get over this situation, Leonard, with Howard and Raj, decides to do what Howard suggested to get them out of their funk: go to a bar to pick up desperate women.

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In Sheldon's view, the tenants in the apartment directly above his and Leonard's are perfect neighbors since they never make any noise and he doesn't even know them. So he is horrified when he learns they are moving. Sheldon's fears are laid to rest when he questions the new tenant, Alicia, who is an aspiring actress like Penny and who answers all his questions on her living habits correctly to his specifications. Leonard, Howard and Raj, on the other hand, are more than happy as Alicia is a beautiful young woman. As Leonard, Howard and Raj fawn over Alicia, Penny becomes jealous. Penny does whatever she can to compete with Alicia and regain what she believes is the loss of her queen bee status within the group. But equally important, Penny wants to expose Alicia's motives for her friendship with the guys.

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Based on a some products that she made previously and sold to friends at a nominal profit, Penny is contemplating starting a home-based business called Penny Blossoms, in which she would make and sell flower shaped hair barrettes. Penny asks Sheldon for advice on the business aspects so that she can possibly turn this venture into a full time job. Sheldon agrees if only on the stipulation that she must listen to everything he says and not to make any sarcastic remarks. She agrees. But when Leonard, Howard and Raj get wind of what Sheldon and Penny are up to, the four guys collectively can't help but provide more than their two-cents worth of advice about every aspect of the business. The advice turns to total control. Problems arise because they forgot internal communication between departments of the business is key to success.

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Leonard, Sheldon, Howard and Raj are all taking a train trip to San Francisco to attend a symposium, at where the scheduled keynote speaker is Nobel Prize winning physicist Dr. George Smoot. Leonard, Howard and Raj, who all wanted to travel by plane instead, change their mind about taking the train when they see on board the beautiful Summer Glau, who they recognize from her role in Terminator: The Sarah Connor Chronicles (2008). Howard and Raj argue about who between the two has the right to hit on her, Raj who would need to take a trip to the bar car first. Meanwhile, Sheldon has forgotten an electronic file at the apartment he deems important for Dr. Smoot. After Leonard talks him out of getting off the train to go back to retrieve it, Sheldon decides on the slightly less abhorrent option of telephoning Penny to email it to him, which would entail Penny entering his (gasp) bedroom.

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Today Paul Does The Mailbag SOLO !!!

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During one of the more quiet moments of a paint-ball tournament where Leslie and Howard are alone in hiding waiting to be killed, they decide to make their final moment memorable by making out. This act is the beginning of a relationship of sorts between the two. Howard finds that one of the perks of being in a relationship with Leslie is that she has access to things at work that others don't, these things which she is willing to share with Howard, all at a time when the department budgets are being slashed around them. Howard learns that a relationship with Leslie has its gives and takes. Meanwhile, Penny accidentally shoot a paint-ball on Leonard and Sheldon's couch exactly on the spot where Sheldon sits. Will Sheldon notice that Penny has flipped the cushion over, and if he does, what will the collective do about fixing Sheldon's sitting spot both in the short term and the long term?

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Leonard is dreading a visit from his mother, famed scientific psychoanalyst Beverly Hofstadter. She has always driven Leonard crazy, much like Sheldon does now. It isn't surprising as Beverly and Sheldon are very much alike. Because of their similarities, Sheldon and Beverly hit it off. Beverly, however, extends her scientific psychoanalytical criticisms toward Howard, Raj and Penny, in addition to her son, the latter two who are driven to drink. In drowning their self-doubt in alcohol, Leonard and Penny have a special connection. Sheldon and Beverly also contemplate having a special connection.

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