The first Law of Thermodynamics states that the energy of a closed system remains constant. This is akin to the above law, but means that energy released by a chemical reaction will appear as heat and vice versa. The second Law states that the entropy of a system not at equilibrium will tend to increase until equilibrium is reached. This law has very major implications in biology as macromolecules will tend to degrade into smaller fragments (increasing the entropy), and energy must be expended to overcome the loss of entropy in creating them. The third law states that entropy will tend to decrease as temperature decreases (reaching a minimum at absolute zero). Hence, macromolecules are generally more stable at lower temperatures. This principle has also been applied to computer optimization techniques, the most common of which is simulated annealing.