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The most famous experiment that provided direct evidence for Einstein's mass-energy equivalence, as described by the equation E = mc^2, is the Annihilation of Matter and Antimatter.

In particle physics, it has been observed that when a particle and its corresponding antiparticle collide, they annihilate each other, resulting in the production of energy. This phenomenon demonstrates the conversion of mass into energy, in accordance with Einstein's equation.

One specific experiment that contributed to the confirmation of this principle was conducted at the Stanford Linear Accelerator Center (SLAC) in 1997. Scientists at SLAC collided electrons with their antimatter counterparts, called positrons, in a particle accelerator. The collision resulted in the annihilation of the particles, producing high-energy gamma rays. By measuring the energies and momenta of the incoming and outgoing particles, researchers were able to confirm that the energy produced from the annihilation process corresponded precisely to the mass lost according to E = mc^2.

It's important to note that while this experiment provided direct evidence for the mass-energy equivalence principle, Einstein's theory of relativity, which encompasses E = mc^2, has been extensively validated through numerous other experiments and observations in various domains of physics. These include experiments related to time dilation, length contraction, gravitational lensing, and the behavior of particles at high speeds, among others.

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