The Ionian cities that grew up in the wake of the Ionian migrations joined in a confederacy under the leadership of Ephesus. In the fourth century BCE, Lysimachos, one of the twelve generals of Alexander the Great, founded the new city of Ephesus, while leaving the old city around the Artemision. When Asia Minor was incorporated into the Roman Empire in 133 BCE, Ephesus was designated as the capital of the new province Asia. Criterion (iv): Ephesus as a whole is an outstanding example of a settlement landscape determined by environmental factors over time. Ephesus was also the leading political and intellectual centre, with the second school of philosophy in the Aegean, and Ephesus as a cultural and intellectual centre had great influence on philosophy and medicine.