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As the most abundant subtype in the central nervous system, the stoichiometric ratio differences between ( 4 2 ) 2 2 and ( 4 2 ) 2 4 of 4 2 nAChR determine receptor sensitivity and functional characteristics toward nicotine: The ( 4 2 ) 2 2 subtype exhibits high agonist affinity, whereas the ( 4 2 ) 2 4 subtype demonstrates 34-fold enhanced activation efficacy despite lower affinity, establishing a dual regulatory paradigm of high-affinity and high-efficacy ( 4 or 2 subunits completely blocks nicotine-induced burst firing of VTA dopamine neurons and dopamine release in the nucleus accumbens, while mice expressing hypersensitive 4 mutants exhibit exaggerated rewarding responses to low-dose nicotine (Maskos et al., 2005

However, the solution is not necessarily unique, as a space of alternative optimal solutions may exist

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Ozone wastewater treatment is now a mature technology used for municipal wastewater treatment in most of the worlds largest cities

Physical therapy helps but progress can be painfully slow