This study characterizes in vitro production of autoantibodies by circulating B-lymphocytes from patients with TA. Differences in production from those with active versus inactive disease suggest that phenotypic alterations in this cell type may play an important role in pathogenesis.
SAA and C4BP may be useful biomarkers in determining the disease activity of TA. More work should be done to test these results in a large cohort of patients in a longitudinal manner.
Nucleoside triphosphate diphosphohydrolase1 (NTPDase1, CD39) inhibitors have potential as novel drugs for the (immuno)therapy of cancer. They increase the extracellular concentration of immunostimulatory ATP and reduce the formation of AMP, which can be further hydrolyzed by ecto-5'-nucleotidase (CD73) to immunosuppressive, cancer-promoting adenosine. In the present study, we synthesized analogs and derivatives of the standard CD39 inhibitor ARL67156, a nucleotide analog which displays a competitive mechanism of inhibition. Structure-activity relationships were analyzed at the human enzyme with respect to substituents in the N 6-and C8-position of the adenine core, and modifications of the triphosph(on)ate chain. Capillary electrophoresis coupled to laserinduced fluorescence detection employing a fluorescent-labeled ATP derivative was employed to determine the compounds' potency. Selected inhibitors were additionally evaluated in an orthogonal, malachite green assay versus the natural substrate ATP. The most potent CD39 inhibitors of the present series were ARL67156 and its derivatives 31 and 33 with K i values of around 1 µM. Selectivity studies showed that all three nucleotide analogs additionally blocked CD73 acting as dual-target inhibitors. Docking studies provided plausible binding modes to both targets. The present study provides a full characterization of the frequently applied CD39 inhibitor ARL67156, presents structureactivity relationships, and provides a basis for future optimization towards selective CD39 and dual CD39/CD73 inhibitors.
Both foil structure and surface texturing have been widely used to improve bearing performance. However, there is little research on their combination, namely, textured gas foil bearing. This paper adopts the Reynolds equation as the pressure governing equation of bump-type foil journal bearing to study the influence of textures located on the top foil. The Newton-Raphson iterative method and the perturbation method are employed to obtain static and dynamic characteristics, respectively. Thereafter, based on three texture distribution types, further analysis about the effect of the relative texture depth and the textured portion is carried out. The results indicate that an appropriate arrangement of textures could improve the performance of gas foil bearing. For #1 texture distribution, the maximum increment of load capacity could exceed 10% when ω = 1.4 × 105 r/min, ε = 0.2.
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