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"[T]he ... fermion minus sign problem ... is often misconcieved as a technical detail frustrating the careers of numerical simulators. It is much more. It is the nightmare of modern physics. At the moment one is dealing with an infinity of interacting fermions, it is a tragic fact that no methodology is available to handle the problem in a systematic, controlled fashion. The standard escapes are to either declare the non-interacting fermion gas to be the universal truth, or to suppose that fermions are completely eaten by collective bosonic fields. The devastating influences of the minus signs are most clearly felt in high Tc superconductivity, the subject of heavy fermions, and adjacent areas like the 2d metal-insulator transition. However, it permeates all of fundamental physics, from the nature of the core of neutron stars up to string theory. When you still think it is a non-existent problem, I am interested to hear your answer to the following simple question: can a state of matter exist, characterized by an irreducible sign problem in the scaling limit (i.e. it cannot be absorbed by an appropriate transformation) which cannot be adiabatically continued to the Fermi-gas?"
-- Jan Zaanen, http://www.lorentz.leidenuniv.nl/~jan/