Wife has just got back from Philly, and understandably, the missing flight was a massive topic of conversation between her colleagues, the flight deck, and several nervous passengers.
Nothing about it makes sense, at all.
Rising to 45,000 feet is possible. Pilots swap off about an hour into the flight, right on the time frame we are looking at. Captain or co-pilot, whoever takes the controls, first checks and enters course, altitude, etc into the autopilot. Since cruising altitude is usually 35,000 feet, it's theoretically possible for someone to punch in 45,000 feet by mistake. Only one number off, and the keypad is not all that big. Entry is supposed to be cross checked, but if the captain handed off to the far less experienced co-pilot and went for a piss, it is conceivable that the cross check didn't happen. Standard climb rate on autopilot is 800 feet per minute, so it would be slow and gradual. So far - it could be pilot error. The last known communication from the plane could be used as evidence for this - a 777 is not going to keep viable oxygen pressure above 40,000 feet and the last words - Goodnight - are the sort of thing someone suffering from hypoxia would say. You simply fall asleep.
Except,the 777 is designed to be pretty much bullet proof and idiot proof, for exactly that reason. Cabin pressure drops, you get a siren screaming at you in the cockpit AND over the PA system, the stick shakes (same as the stall warning), the autopilot disengages, and oxygen is automatically deployed while the cabin lights strobe on and off. None of those can be switched off. Even the dopiest pilot is going to notice that.
Further, transponders run as long as there is power to them. They simply can not be turned off by any action of any member of crew or any passenger. You physically can not get to them - they are in the unpressurized hold. They work on the challenge/response system, usually every 15 minutes if you are not in crowded airspace. Normally it's basic stuff sent - challenge is "hey, 331, you still there?" Response is "Yep. 36,000 feet, heading whatever, air speed 500." Again, totally automatic and it can not be affected by anything other than a catastrophic power failure of both the gennies and the back up batteries. The only real way to make a plane "disappear" is if someone on the ground changes the challenge frequency. They are pretty idiot proof, but they only hear what they are told to hear. A nice analogy the Captain used is imagine it's a phone system. You grab the phone, punch in a number and the person you want to talk to answers (or you get voice mail). Punch numbers in at random and you will not get the person you mean to talk to.
Then there is the whole course change thing. You don't turn a plane on a dime. If it is on autopilot, the full weight of an unconscious person on the stick or the rudder pedals will do exactly nothing except irritate the machinery that has to keep ignoring the input.
ATC also has it's input. While they might not be the sweating, swearing types from the Airport movies, they do tend to notice if they have lost a plane. That is their job, and they are double checked, as everything to do with flying is. It is very formal. When you change control zones, you are formally handed off from one to the next - and the first thing you do is confirm your transponder code to the new ATC center and reset it to whatever code they request (only so many numbers available, someone else might be on the same frequency).
This adds little to the discussion, but I thought you might find it interesting. The missus has a good memory and they were talking about it over a coffee. Think I got it all - she talks fast and usually not in English!