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Example 13 crystallization of Semetreuptade Adding 100mL of lysate into a round-bottom flask, controlling the temperature in the round-bottom flask solution to be 10-15 , mixing ethyl acetate and cyclohexane in a volume ratio of 1:2 in advance, slowly adding the mixed solution of ethyl acetate and cyclohexane through a separating funnel while stirring at a stirring speed of 100rmp, continuously stirring after the addition, increasing the stirring speed to 120-130rmp when crystals begin to generate, and stirring for 30 minutes in total

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The fitted models were further refined by rounds of manual model building in COOT 54 and real-space refinement, as implemented in the PHENIX software package 55

they are patenting the way the pen clicks, the way the liquid stays stable in heat, and even the specific timing of the doses

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