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     

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).     

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.     

A Decision Criterion for the Optimal Number of Clusters in Hierarchical Clustering

Clustering has been widely used to partition data into groups so that the degree of association is high among members of the same group and low among members of different groups. Though many effective and efficient clustering algorithms have been developed and deployed, most of them still suffer from the lack of automatic or online decision for optimal number of clusters. In this paper, we define clustering gain as a measure for clustering optimality, which is based on the squared error sum as a clustering algorithm proceeds. When the measure is applied to a hierarchical clustering algorithm, an optimal number of clusters can be found. Our clustering measure shows good performance producing intuitively reasonable clustering configurations in Euclidean space according to the evidence from experimental results. Furthermore, the measure can be utilized to estimate the desired number of clusters for partitional clustering methods as well. Therefore, the clustering gain measure provides a promising technique for achieving a higher level of quality for a wide range of clustering methods.     

Issues on nanoimprint lithography with a single-layer resist structure

We summarize our key developments in nanoimprint lithography (NIL) that employs a single layer resist lift-off process: lowering of the imprint temperature (for thermal imprint) and pressure, achieving uniform resist thickness and low residual resist layer thickness in the trenches, and eliminating metal ‘rabbit ears’ for the single-layer lift-off. In thermal NIL, our requirements for lower operating temperature and pressure motivated us to develop an alternative resist that is a viscous fluid at room temperature and cures at a lower temperature of 70 °C than the operating temperature of the conventional thermal NIL (≈200 °C). For UV NIL, we devised a method to dispense the resist onto a hydrophobic mold and use the hydrophilic substrate surface to spread the resist via surface wetting to engineer a continuous and uniform film. We also explored the use of Si(110) substrates as molds to produce features with perfectly vertical side walls, and the use of aqua regia to directly etch away rabbit ears. PACS 86.65.+h; 81.16.Nd; 81.16.Rf     

Bandgap engineering of self-assembled InAs quantum dots with a thin AlAs barrier

We investigate the effects of a thin AlAs layer with different position and thickness on the optical properties of InAs quantum dots (QDs) by using transmission electron microscopy and photoluminescence (PL). The energy level shift of InAs QD samples is observed by introducing the thin AlAs layer without any significant loss of the QD qualities. The emission peak from InAs QDs directly grown on the 4 monolayer (ML) AlAs layer is blueshifted from that of reference sample by 219 meV with a little increase in FWHM from 42–47 meV for ground state. In contrast, InAs QDs grown under the 4 ML AlAs layer have PL peak a little redshifted to lower energy by 17 meV. This result is related to the interdiffusion of Al atom at the InAs QDs caused by the annealing effect during growing of InAs QDs on AlAs layer.     

Proton relaxation times in human red bone marrow by volume selective magnetic resonance spectroscopy

In hematological diseases the composition of red bone marrow shows alterations. The relaxation timesT ₁ andT ₂ of water and lipids in human hemopoietic bone marrow of 14 normal volunteers and 10 patients with acute leukemia and bone marrow carcinosis are determined using a double spin echo spectroscopy sequencein vivo. The volumes of interest (VOI) of (13 mm)³ in the center of vertebral bodies are examined using different measurement parameters. ForT ₁ measurements an inversion-recovery method is used.T ₂ is evaluated from spectra with differentTE. T ₁ (water) is found in a range between 1000 and 1700 ms,T ₁ (lipids) in a range between 260 and 320 ms in healthy volunteers.T ₂ (water) is determined between 32 and 65 ms. In some cases phase distortions of the water signals occur in the spectra. Water flow within the VOI may be a possible reason.T ₂ (lipids) is evaluated between 73 and 91 ms. The patients with acute leukemia exhibit clearly reduced lipid signals in their spectra. Lipid relaxation times could not be determined in these cases.T ₂ (water) is prolonged in acute leukemia to 51–98 ms.T ₁ (water) was not significantly different from values of healthy volunteers in our measurements. Results are discussed in comparison to relaxometric data from imaging and STEAM spectroscopic methods of other authors.