Dynamic synovial fibroblasts are modulated by NBCn1 as a potential target in rheumatoid arthritis

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     

Seven- and Eight-Membered Ring Conformations of Phosphorus Containing Heterocycles

Abstract

The conformational behaviour of seven- and eight-membered heterocycles based on their NMR spectrum and on a theoretical investigation is described. All possible basic conformations and their quantitative parameters have been considered. A molecular mechanics approach is applied to the calculation of the multidimensional maps of potential energy dependence on torsional angles.     

Curing temperature- and concentration-dependent dielectric properties of cross-linked poly-4-vinylphenol (PVP)

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, C–V, 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 C–V curve (1–2 V in 10 wt% samples, below 1 V in 7.5 wt% samples, and 0.5 V in 5 wt% samples).     

Hydrogels based on polycarboxylic acid-agar-agar complexes

IR spectroscopy and viscometry data have shown that poly(acrylic acid) and poly(methacrylic acid) form complexes with agar-agar in aqueous solutions as they do with other polysaccharides. The polyacid-agar-agar complexes are typical hydrogels. The swelling index of hydrogels based on the poly(methacrylic acid)-agar-agar complex has been found to be markedly lower than that of poly(acrylic acid)-agaragar complex. The hydrogels based on the complex of cross-linked poly(acrylic acid) with agar-agar can be of practical interest as polymeric carriers for drugs.     

Non-linear modeling and dynamic analysis of hydraulic control valve; effect of a decision factor between experiment and numerical simulation

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.     

Sodium self-diffusion coefficient in sodium silicate glass by quasielastic neutron scattering

Using pulsed neutrons of 19.8 Å wavelength a quasielastic line broadening as low as 0.03 eV (FWHM) has been observed due to Na⁺ diffusion in the glass Na₂O·2SiO₂. From the linewidths a Na⁺ self-diffusion coefficient of 3.1·10^–8 cm²/s at 420°C was obtained in excellent agreement with the diffusion coefficient determined for the same sample batch using²²Na radioactive tracers. The experimental Q dependence of the quasielasic linewidths gives a hint for deviations from a purely random walk in an ionic glass.     

Critical behavior of electric field gradient in MnSi studied by muon level-crossing resonance

The electric quadrupole interaction of⁵⁵Mn nuclei was studied in the weakly ferromagnetic system MnSi using muon level-crossing resonance (LCR) technique. The temperature dependence of the electric field gradient (EFG) shows a critical behavior near the ferromagnetic transition temperature, indicating that the EFG due to the conduction electron is strongly correlated with the magnetic susceptibility in the itinerant electron magnetism. The temperature dependence of EFG is in reasonable agreement with the self-consistent renormalization theory developed by Moriya and coworkers.We gratefully acknowledge helpful discussion with Dr. N. Nishida. We also wish to thank Keith Hoyle and Curtis Ballard for technical support.