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S21 is the Gain of the two port device! Pout/Pin
If it is a lossy or passsive device the gain will be zero or negative (Insertion Loss).
If it is an active device it should have some gain, making it a Positive S21
S11 is the Input ReturnLoss Looking in to Port 1 Pin(forward)/ Pin(reflected Back)
S22 is the Output Returnloss Looking in to Port 2 P(forward)/ P(reflected Back)
When S11 & S22 are Very Negative (dB) That means that none of the power going
in to the port get reflected out!