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     

Improvement of Biological Effects of Root-Filling Materials for Primary Teeth by Incorporating Sodium Iodide

Therapeutic iodoform (CHI₃) is commonly used as a root-filling material for primary teeth; however, the side effects of iodoform-containing materials, including early root resorption, have been reported. To overcome this problem, a water-soluble iodide (NaI)-incorporated root-filling material was developed. Calcium hydroxide, silicone oil, and NaI were incorporated in different weight proportions (30:30:X), and the resulting material was denoted DX (D5~D30), indicating the NaI content. As a control, iodoform instead of NaI was incorporated at a ratio of 30:30:30, and the material was denoted I30. The physicochemical (flow, film thickness, radiopacity, viscosity, water absorption, solubility, and ion releases) and biological (cytotoxicity, TRAP, ARS, and analysis of osteoclastic markers) properties were determined. The amount of iodine, sodium, and calcium ion releases and the pH were higher in D30 than I30, and the highest level of unknown extracted molecules was detected in I30. In the cell viability test, all groups except 100% D30 showed no cytotoxicity. In the 50% nontoxic extract, D30 showed decreased osteoclast formation compared with I30. In summary, NaI-incorporated materials showed adequate physicochemical properties and low osteoclast formation compared to their iodoform-counterpart. Thus, NaI-incorporated materials may be used as a substitute for iodoform-counterparts in root-filling materials after further (pre)clinical investigation.     

马克思和阿伦特论“犹太人问题”

犹太人问题从来就不是一个固定的、指向明确的问题,但“犹太人问题”在历史上却始终是一个问题。如何解决“犹太人问题”？马克思从19世纪民族−国家的历史现实出发,对鲍威尔宗教的与世俗化的解决方式进行了反思和批判,进而得出解决犹太人问题必须在全人类解放的大背景下才能实现。通过将宗教问题还原为政治问题,将政治问题还原为市民社会对金钱的追求,马克思认为只有在实现了人的全面发展,也就是摆脱了资本的羁绊后,犹太人才可能获得真正的解放,这是一种“社会主义的解决方式”。而阿伦特则从对极权主义统治的反思,及构建一种“犹太家园”的可能方式出发,得出了一种基于“委员会制度”的“共和主义的解决方式”。在阿伦特看来,这种制度不仅是犹太人问题的解决方式,同时也是一种替代民族−国家和纳粹极权主义的政治形式的可能性,体现出一种新型政治哲学的内在希望。     

Leading order asymptotics in the Goldbeter–Koshland switch

An asymptotic analysis at leading order of the Goldbeter–Koshland switch, the simplest futile cycle, is carried out in detail. After a nondimensionalization of the problem, we find the leading order uniform expansions of the reactants, identifying the proper time scales in a total setting. Comparison with numerical integration confirms the goodness of our analysis.     

Spin-injection radiation of terahertz waves in ferromagnetic structures

We propose and discuss the mechanisms of terahertz sd exchange radiation during transmission of the spin-polarized current in a structure from a thin steel rod pressured to an ultrathin ferromagnetic film. The two mechanisms considered are quantum transitions between the quasi-Fermi levels in the film near the rod and precession of injected spins around the film magnetization.     

Calculation scheme of heavy-ion collisions within the framework of a modified hydrodinamic approach

A hydrodynamic approach to describing heavy-ion collisions with allowance for the emission of the secondary particles is developed. The compression, the expansion, and break-up stages of the resulting hotspot are considered. The formed shock wave has a time-dependent front. The calculated spectra of produced protons are compared with experimental data.     

Alpha decay in electron surrounding

The influence of atomic electron shells on the constant of alpha decay of heavy and mediummass nuclei was considered in detail. A method for simultaneously taking into account the change in the potential-barrier shape and the effect of reflection of a diverging Coulomb wave in the classically allowed region was developed. The ratios of decay probabilities per unit time for a bare nucleus and the respective neutral atom were found for some alpha-decaying isotopes.     

Ionization mechanism of the electrical degradation (breakdown) of polymer dielectric films

A physical mechanism is proposed explaining rapid (for a time of ～10^?7 s) increase in the current during an electrical breakdown of polymer dielectrics. Accumulation of positive molecular ions and electrons in a local region of a polymer as a result of field ionization of macromolecules is considered as the formation of quasi-neutral plasma in which the effect of Debye screening of charges occurs, leading to a decrease in the molecule ionization potential, which, in turn, accelerates the formation of unbound charges in the polymer. It is shown that the occurrence of these interrelated processes, the rates of which increase in time, leads, at a certain stage, to an explosive change in the polymer properties. A self-accelerating process has been revealed leading to an increase in the concentration of quasi-free charges, the development time of which is comparable to the time of breakdown evolution.     

Neural network correction of a vector gravitoinertial navigation system

The concept and model of correction of a 3D inertial navigation system capable of estimating earth’s gravitational field anomalies are suggested. The results of the computational experiment are presented.