TASK DEFINITION: Given a passage classify if the passage has a definite objective/aim/goal or not. Output '1' if the passage has a defininte objective/aim/goal and output '0' if the passage does not have a definite objective/aim/goal.
PROBLEM: Fibroblasts (FIBs) within the retro-orbital space of patients with Graves' disease (GOFs) express thyrotropin receptors (TSHRs) and are thought to be an orbital target of TSHR-stimulating autoantibodies in Graves' ophthalmopathy (GO). Recently, we developed a low molecular weight, drug-like TSHR antagonist (NCGC00229600) that inhibited TSHR activation in a model cell system overexpressing TSHRs and in normal human thyrocytes expressing endogenous TSHRs. Herein, we test the hypothesis that NCGC00229600 will inhibit activation of TSHRs endogenously expressed in GOFs.", 'Three strains of GOFs, previously obtained from patients with GO, were studied as undifferentiated FIBs and after differentiation into adipocytes (ADIPs), and another seven strains were studied only as FIBs. ADIP differentiation was monitored by morphology and measurement of adiponectin mRNA. FIBs and ADIPs were treated with the TSH- or TSHR-stimulating antibody M22 in the absence or presence of NCGC00229600 and TSHR activation was monitored by cAMP production.', 'FIBs contained few if any lipid vesicles and undetectable levels of adiponectin mRNA, whereas ADIPs exhibited abundant lipid vesicles and levels of adiponectin mRNA more than 250,000 times greater than FIBs; TSHR mRNA levels were 10-fold higher in ADIPs than FIBs. FIBs exhibited higher absolute levels of basal and forskolin-stimulated cAMP production than ADIPs. Consistent with previous findings, TSH stimulated cAMP production in the majority of ADIP strains and less consistently in FIBs. Most importantly, NCGC00229600 reduced both TSH- and M22-stimulated cAMP production in GOFs.

SOLUTION: 0

PROBLEM: The extent to which tolerance acquired in one motion environment can be transferred to another has not been fully elucidated. This study compares three provocative motion stimuli and whether tolerance acquired from cross-coupled motion and torso rotation can be transferred to simulated aircraft motion.', "There were 18 healthy subjects (9 men and 9 women), 18-44 yr of age, who were divided into 3 groups. Each group was exposed to the following desensitization procedure in a pseudo-random repeated measures design. In condition D1, subjects were exposed to 4 consecutive days of cross-coupling and on the 5th d they were exposed to simulated aircraft motion. In D2, subjects were exposed to 4 consecutive days of torso rotation and on the 5th day they were exposed to the simulated aircraft motion as in D1. In D3, subjects were exposed to 5 consecutive days of simulated aircraft motion. Based on Graybiel's diagnostic criteria, severity of motion sickness on the 1st and 5th day in D1, D2, and D3 were compared.", 'Cross-coupled motion was the most provocative stimulus followed by torso rotation and simulated aircraft motion. Within each motion stimulus, there was evidence of desensitization (p < 0.001) within 4 d. There were no significant differences in the severity of motion sickness observed on the 5th day regardless of the desensitization stimuli.

SOLUTION: 0

PROBLEM: H3K9 methylation is one of the essential histone post-translational modifications for heterochromatin formation and transcriptional repression. Recently, several studies have demonstrated that H3K9 methylation negatively regulates the type I interferon response.', 'We report the application of EHMT1 and EHMT2 specific chemical inhibitors to sensitize CML cell lines to interferon and imatinib treatments. Inhibition of EHMT1 and EHMT2 with BIX01294 enhances the cytotoxicity of IFN2a in four CML cell lines, K562, KCL22, BV173 and KT1 cells. Chromatin immunoprecipitation assay shows that BIX01294 treatment enhances type I interferon response by reducing H3K9me2 at the promoters of interferon-stimulated genes. Additionally, BIX01294 treatment augments IFN2a- and imatinib-mediated apoptosis in CML cell lines. Moreover, our data suggest that the expression level of EHMT1 and EHMT2 inversely correlates with the type I interferon responsiveness in CML cell lines.

SOLUTION:
0