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Most proteins unfold at low or high pHs (below 5 and above 10) because the folded protein has groups buried in non-ionized form that can ionize only after unfolding, particularly the His and Tyr residues that tend to cause unfolding at acid and alkaline pH, respectively

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The Children's Tumor Foundation Clinical Care Advisory Board (CCAB) published a research article in The Oncologist medical journal with guidelines for physicians on prescribing MEK inhibitors and managing their toxicities