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We hypothesize that the failure of intrinsic-solubility approaches arises from inaccuracies in the predicted valuesalthough Starling is a state-of-the-art p K a -prediction model, it still routinely predicts values that are wrong by 0.51.0 p K a unit, which can correspond to a 10x difference in the predicted value

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Proc Natl Acad Sci USA 105:167316

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GERD develops when this sphincter weakens or relaxes inappropriately, allowing stomach acid to irritate the delicate esophageal lining