jccraig:
On my Windows 10 system, I solved this intermittent problem by going into Device Manager, finding "Ports (Com & LPT)" and then in that section locating the Arduino 101 labeled Serial Monitor port. Right-click and select "Disable" to disable that port. The, Right-click again and select "Enable". When I go back to the Arduino 101 IDE it now works. Also double check in the Tools menu to make sure the board and the port are still set to the Aruduino 101. This clears up the problems for me every time.
Thank you @jccraig!
I'll test it on my Windows 10 system! 8)