Speed Limit: 45 MPH / Minimum: 65 MPH
This comic depicts a trio of road signs that provide legal instructions that are, in combination, impossible to follow: "Do not enter" precludes passing the point of the sign, the No U-Turn sign precludes turning around, and the "No Stopping Any Time" sign precludes both halting before the sign as well as reversing back (even ignoring that this is usually already illegal with or without signs explicitly forbidding it). A driver approaching this sign combo would seemingly be forced to violate at least one of the three, probably leading to the caption's concern expressed as "Oh no".
Of the three, "No U-Turn" is the one with the largest wiggle room, as it can be defined more narrowly/specifically as driving in a U-shape; thus, a driver might be able to get around it by drawing a more elaborate path. However, since the lane dividers on the road are solid until the signs, this potential loophole is preemptively closed.
Depending on the jurisdiction, signs may only apply to the road after them, so you could validly stop just before it.
This no-escape scenario could be done more easily with just "Stop" and "No Stopping Any Time" signs. But by combining 3 signs, the joke is presumably that it was done accidentally, without noticing the contradictions.
The title text adds even more to the dilemma, posting a 45 miles-per-hour maximum speed limit, but also a minimum required speed of 65 MPH. Since 45 is lower than 65,[citation needed] this is quite the perplexing contradiction.
For another of Randall's adventures in road signage (he does live in the Greater Boston area, after all), see 1116: Traffic Lights. For a similar contradiction, see the title text of 2179: NWS Warnings.