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31.
Rheumatoid arthritis (RA) is an autoimmune disease characterized by aggressive fibroblast-like synoviocytes (FLSs) and pannus formation. Various therapeutic strategies have been developed against inflammatory cytokines in RA in recent decades. Based on the migratory features of FLSs, we examined whether modulation of the migratory module attenuates RA severity. In this study, inflamed synovial fluid-stimulated FLSs exhibited enhanced migration and migratory apparatus expression, and sodium bicarbonate cotransporter n1 (NBCn1) was identified in primary cultured RA-FLSs for the first time. The NBC inhibitor S0859 attenuated the migration of FLSs induced with synovial fluid from patients with RA or with TNF-α stimulation. Inhibition of NBCs with S0859 in a collagen-induced arthritis (CIA) mouse model reduced joint swelling and destruction without blood, hepatic, or renal toxicity. Primary FLSs isolated from the CIA-induced mouse model also showed reduced migration in the presence of S0859. Our results suggest that inflammatory mediators in synovial fluid, including TNF-α, recruit NBCn1 to the plasma membrane of FLSs to provide dynamic properties and that modulation of NBCn1 could be developed into a therapeutic strategy for RA.Subject terms: Chemotaxis, Bone, Ion channel signalling, Rheumatoid arthritis, Drug development  相似文献   
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In this paper, dielectric properties of various thick PVP films cured at temperatures between 125° C and 200 °C are investigated. The thicknesses of PVP films are adjusted by varying their concentration in PGMEA solvent from 10 wt% to 2.5 wt%. Through FT-IR, CV, SEM, and AFM analyses, the optimum curing process temperatures (150 °C for 10 wt% and 7.5 wt% samples, and 175 °C for 5 wt% samples) where PET substrates can be thermally endured are proposed in terms of their low hysteresis voltage in the CV curve (1–2 V in 10 wt% samples, below 1 V in 7.5 wt% samples, and 0.5 V in 5 wt% samples).  相似文献   
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Numerical problems that are usually ignored in the dynamic analysis of hydraulic control valves are described, and an analysis of the effects of such problems on the numerical modeling is provided. Previous studies have ignored the effects of changes in the flow coefficient in the orifice, the solenoid force along the spool movement in the valve and an ascending tendency of pressure during reach to the steady state. To eliminate these problems, it was studied a method to substantiate the non-linearity of the pressure loss caused by passing between the orifice and port as well as that caused by interaction with the solenoid. Moreover, the movement of the spool and spring is expressed using the time-delay-element (TDE). The proposed numerical model has been used in the Bond graphs method of a hydraulic control valve and the simulation results have been shown to be accurate. It is known that differences between simulated and experimental results can have a considerable impact on the function of actual systems. The contribution of each parameter is measured separately for the transient state and steady state. Analysis standard observed the first peak value, pressure increase to the steady state and the settling time in the response results.  相似文献   
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Background  

Previous studies indicate that light information reaches the suprachiasmatic nucleus (SCN) through a subpopulation of retinal ganglion cells that contain both glutamate and pituitary adenylyl cyclase activating peptide (PACAP). While the role of glutamate in this pathway has been well studied, the involvement of PACAP and its receptors are only beginning to be understood. Speculating that PACAP may function to modulate how neurons in the suprachiasmatic nucleus respond to glutamate, we used electrophysiological and calcium imaging tools to examine possible cellular interactions between these co-transmitters.  相似文献   
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A compact, highly efficient, and passively assembled parallel optical-electrical convertor module (POECM) for active optical cable application is proposed. This paper presents our POECM structure, optical design simulation results, fabrication process, and data transmission test results, in sequence. The POECM has a compact size of \(18.5\hbox {mm} \times 10\hbox {mm} \times 2.8\hbox {mm}\) . We confirm a data rate of total throughput at 21.6 Gbps ( \(5.4\hbox {Gbps} \times 4\) channels) with a bit error rate of less than \(10^{-12}\) .  相似文献   
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