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It emerged from a body of protein-engineering work in the late 1980s and early 1990s much of it from the Australian laboratories associated with Francis, Ballard, and Wallace aimed at producing IGF analogs with reduced IGFBP affinity but preserved receptor activity, in order to study the relative contributions of binding-protein interaction versus receptor binding to biological potency

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In particular, the increased abundance of pro-inflammatory Th1 and Th17 cells has been associated with impaired embryo implantation and reduced implantation success 244,245

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