Browsing by Subject "measurement"

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Open Access
Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells
(Nature Publishing Group, 2015) Küçük, C.; Jiang, B.; Hu X.; Zhang W.; Chan J.K.C.; Xiao W.; Lack, N.; Alkan, C.; Williams J.C.; Avery, K.N.; Kavak P.; Scuto, A.; Sen, E.; Gaulard P.; Staudt L.; Iqbal J.; Zhang W.; Cornish, A.; Gong Q.; Yang Q.; Sun H.; D'Amore F.; Leppä, S.; Liu W.; Fu, K.; De Leval L.; McKeithan, T.; Chan W.C.
Lymphomas arising from NK or γδ-T cells are very aggressive diseases and little is known regarding their pathogenesis. Here we report frequent activating mutations of STAT3 and STAT5B in NK/T-cell lymphomas (n=51), γδ-T-cell lymphomas (n=43) and their cell lines (n=9) through next generation and/or Sanger sequencing. STAT5B N642H is particularly frequent in all forms of γδ-T-cell lymphomas. STAT3 and STAT5B mutations are associated with increased phosphorylated protein and a growth advantage to transduced cell lines or normal NK cells. Growth-promoting activity of the mutants can be partially inhibited by a JAK1/2 inhibitor. Molecular modelling and surface plasmon resonance measurements of the N642H mutant indicate a marked increase in binding affinity of the phosphotyrosine-Y699 with the mutant histidine. This is associated with the prolonged persistence of the mutant phosphoSTAT5B and marked increase of binding to target sites. Our findings suggest that JAK-STAT pathway inhibition may represent a therapeutic strategy. © 2015 Macmillan Publishers Limited. All rights reserved.
Open Access
Application of a customized pathway-focused microarray for gene expression profiling of cellular homeostasis upon exposure to nicotine in PC12 cells
(2004) Konu Ö.; Xu X.; Ma J.Z.; Kane J.; Wang J.; Shi, S.J.; Li, M.D.
Maintenance of cellular homeostasis is integral to appropriate regulation of cellular signaling and cell growth and division. In this study, we report the development and quality assessment of a pathway-focused microarray comprising genes involved in cellular homeostasis. Since nicotine is known to have highly modulatory effects on the intracellular calcium homeostasis, we therefore tested the applicability of the homeostatic pathway-focused microarray on the gene expression in PC-12 cells treated with 1 mM nicotine for 48 h relative to the untreated control cells. We first provided a detailed description of the focused array with respect to its gene and pathway content and then assessed the array quality using a robust regression procedure that allows for the exclusion of unreliable measurements while decreasing the number of false positives. As a result, the mean correlation coefficient between duplicate measurements of the arrays used in this study (control vs. nicotine treatment, three samples each) has increased from 0.974±0.017 to 0.995±0.002. Furthermore, we found that nicotine affected various structural and signaling components of the AKT/PKB signaling pathway and protein synthesis and degradation processes in PC-12 cells. Since modulation of intracellular calcium concentrations ([Ca2+]i) and phosphatidylinositol signaling are important in various biological processes such as neurotransmitter release and tissue pathogenesis including tumor formation, we expect that the homeostatic pathway-focused microarray potentially can be used for the identification of unique gene expression profiles in comparative studies of drugs of abuse and diverse environmental stimuli, such as starvation and oxidative stress. © 2003 Elsevier B.V. All rights reserved.
Open Access
Is the largest Lyapunov exponent preserved in embedded dynamics?
(2000) Dechert W.Davis, Gençay, R.
The method of reconstruction for an n-dimensional system from observations is to form vectors of m consecutive observations, which for m > 2n, is generically an embedding. This is Takens' result. Our analytical examples show that it is possible to obtain spurious Lyapunov exponents that are even larger than the largest Lyapunov exponent of the original system. Therefore, we present examples where the largest Lyapunov exponent may not be preserved under Takens' embedding theorem. (C) 2000 Elsevier Science B.V.