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Chang, T. M., Cooper, R. J. & Williams, E. R. Locating protonated amines in clathrates. J. Am. Chem. Soc. 135, 14821–14830 (2013).

Incidentally this was the paper that convinced me (not the work on progeria mice Josh has posted about previously) that epigenetic reprogramming might actually work in humans.

The Pharma Services business of Thermo Fisher Scientific will invest $150 Million at three facilities.

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Unfortunately pioglitazone is (weakly) associated with bladder cancer with long term use, look up free paper ‘Pioglitazone use and risk of bladder cancer: population based cohort study’. Although risk only increases from ~0.9% to 1.2% with over 2 years of use, and limiting factor that all users were diabetic, and other meta-studies have found no association, I believe small risk is probably real. PPAR gamma activation, which is causing desired adipogenesis is also active in the urinary bladder. So if one was to use pioglitazone, would have to use it for very limited period and have good cancer preventative regime in place. For more information see free paper ‘Deciphering the Roles of Thiazolidinediones and PPAR

Michael Fossel and Bioviva argue that it may well do that. But if senescence is not reversible and SC’s are not cleared, how will a healthy non inflammatory phenotype be restored?

I’ve read a couple of a papers that suggest you can improve on OSKM quite considerably by including some extra factors. According to this paper: ‘Two Supporting Factors Greatly Improve the Efficiency of Human iPSC Generation’, you can improve the efficiency of reprogramming by 100 times using either p53 siRNA or UTF1. Now I know you don’t want to go all the way back to pluripotency, but this might still be useful.

Accelerated Approval, which is described in 21 C.F.R. § 314.500 et seq., provides for approval of a new drug that is intended to treat a serious or life-threatening disease or condition and that fills an unmet medical need based on a surrogate endpoint. A surrogate endpoint is a laboratory measurement or physical sign used as an indirect or substitute measurement representing a clinically meaningful outcome. To be used in accelerated approval, a surrogate endpoint must be “reasonably likely, based on epidemiologic, therapeutic, pathophysiologic, or other evidence to predict benefit on irreversible morbidity or mortality.” The term “reasonably likely” implies that some uncertainty remains about the relationship of the surrogate to the clinical benefit to the patient. Therefore, accelerated approval is typically contingent on a sponsor’s agreement to conduct additional post-approval studies to verify and describe the drug’s clinical benefit. Accelerated Approval does not change the standards for approval, but by allowing a demonstration of efficacy based on a surrogate endpoint may expedite the approval process.

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