A lot of speculation has been made about where Medford would be if it were real. It can be approximated by clues throughout the series. It's in east Texas, but far enough from Houston to make the trip a burden. During this episode, "Angelina County" was mentioned in the tornado alert on the Coopers' TV. This would suggest Lufkin, Texas, whose location, size and population would be very similar to Medford.
The name of the comic book featured in this episode is "Watchmen", by Alan Moore and Dave Gibbons.
Cal Tech and MIT, two colleges that would play a pivotal role in The Big Bang Theory (2007) (where Sheldon and the others work and Howard's alma-mater, respectively), are mentioned for the first time in the series.
Sheldon's complete confidence in knowing everything is tripped up in little ways throughout the series. Here, he claims that Harvard's school color is maroon, when, in fact, it's crimson.