Scott, my TIUs are original issue units. I have had no issues using the latest loader version. It's been awhile since I've had a laptop with a serial port, so I have a USB>serial converter cable.
I seem to recall that old loader versions will not work with 4.1 software.
I blew up the message in the picture on your first post, so now I see the problem. As recommended above, use Windows device manager and determine on what comm port the TIU is. The TIU must be turned on for this. When you determine the comm port, turn off the TIU and then start the loader program, click on options, and try to enter that port. Use a serial cable that has worked in the past, just in case you have one that's gone bad.