Nicotinamide Phosphoribosyltransferase Attenuates Methotrexate Response in Juvenile Idiopathic Arthritis and In Vitro

Variability in response to methotrexate (MTX) in the treatment of juvenile idiopathic arthritis (JIA) remains unpredictable and poorly understood. Based on previous studies implicating an interaction between nicotinamide phosphoribosyltransferase (NAMPT) expression and MTX therapy in inflammatory arthritis, we hypothesized that increased NAMPT expression would be associated with reduced therapeutic response to MTX in patients with JIA. A significant association was found between increased plasma concentrations of NAMPT and reduced therapeutic response in patients with JIA treated with MTX. Inhibition of NAMPT in cell culture by either siRNA-based gene silencing or pharmacological inhibition with FK-866 was found to result in a fourfold increase in the pharmacological activity of MTX. Collectively, these findings provide evidence that NAMPT inhibits the pharmacological activity of MTX and may represent a predictive biomarker of response, as well as a therapeutic target, in the treatment of JIA with MTX

Improved measurement results for the Avogadro constant using a 28Si-enriched crystal

New results are reported from an ongoing international research effort to accurately determine the Avogadro constant by counting the atoms in an isotopically enriched silicon crystal. The surfaces of two 28Si-enriched spheres were decontaminated and reworked in order to produce an outer surface without metal contamination and improved sphericity. New measurements were then made on these two reconditioned spheres using improved methods and apparatuses. When combined with other recently refined parameter measurements, the Avogadro constant derived from these new results has a value of $N_A = 6.022 140 76(12) \times 10^{23}$ mol$^{-1}$. The X-ray crystal density method has thus achieved the target relative standard uncertainty of $2.0 \times 10^{-8}$ necessary for the realization of the definition of the new kilogram.Comment: postprint, 22 page, 3 figures, 14 table

A new 28Si single crystal: counting the atoms for the new kilogram definition

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On the molar mass of silicon for a new Avogadro constant

An overview of the present results and status of the molar mass of a silicon crystal highly enriched in \ub2\u2078Si used for a new determination of the Avogadro constant is given with special emphasis on the cooperation between NIST, NRC, and PTB currently working on this topic. Using an experimental combination of multicollector ICP and isotope dilution mass spectrometry, a new approach developed by PTB for the measurement of the isotopic composition has been applied. It focuses on the isotope ratio treatment of \ub3\ub0Si/\ub2\u2079Si mainly, avoiding the more uncertain measurement of ratios related to the main isotope \ub2\u2078Si.Peer reviewed: YesNRC publication: Ye