Yes. However, it is recommended to use them in numerical order for your first few games.
Are the abilities on the upgrade tiles,like the one that allows you to flip over a skill permanently) used only once?
Yes. You flip over a skill tile when you choose that upgrade. For the B-side of the player boards, this works differently. In this case, when rearranging your skills (e.g via the Q power) for any reason, the skill leaving the corresponding upgrade slot would flip back over to its non-upgraded” side and the incoming skill would upgrade.