Observation of long-distance radial correlation in toroidal plasma turbulence.

This Letter presents the discovery of macroscale electron temperature fluctuations with a long radial correlation length comparable to the plasma minor radius in a toroidal plasma. Their spatiotemporal structure is characterized by a low frequency of ∼1-3 kHz, ballistic radial propagation, a poloidal or toroidal mode number of m/n=1/1 (or 2/1), and an amplitude of ∼2% at maximum. Nonlinear coupling between the long-range fluctuations and the microscopic fluctuations is identified. A change of the amplitude of the long-range fluctuation is transmitted across the plasma radius at the velocity which is of the order of the drift velocity.

Hypermethylation of serotonin transporter gene in bipolar disorder detected by epigenome analysis of discordant monozygotic twins.

Bipolar disorder (BD) is a severe mental disorder characterized by recurrent episodes of mania and depression. Serotonin transporter (HTT) is a target of antidepressants and is one of the strongest candidate molecules of mood disorder, however, genetic study showed equivocal results. Here, we performed promoter-wide DNA methylation analysis of lymphoblastoid cell lines (LCLs) derived from two pairs of monozygotic twins discordant for BD. To rule out the possible discordance of copy number variation (CNV) between twins, we performed CNV analysis and found the copy number profiles were nearly identical between the twin pairs except for immunoglobulin-related regions. Among the three genes we obtained as candidate regions showing distinct difference of DNA methylation between one of the two pairs, hypermethylation of SLC6A4, encoding HTT, in the bipolar twin was only confirmed by bisulfite sequencing. Then, promoter hypermethylation of SLC6A4 in LCLs of BD patients was confirmed in a case-control analysis. DNA methylation of SLC6A4 was significantly correlated with its mRNA expression level in individuals with the S/S genotype of HTTLPR, and mRNA expression level was lower in BD patients carrying the S/S genotype. Finally, DNA methylation of the same site was also higher in the postmortem brains of BD patients. This is the first study to report the role of epigenetic modification of SLC6A4 in BD using an unbiased approach, which provides an insight for its pathophysiology.

Induction of interleukin-23 p19 by serum amyloid A (SAA) in rheumatoid synoviocytes.

In this study, we investigated the roles of serum amyloid A (SAA) in T helper 17 (Th17)-related cytokine induction in rheumatoid arthritis (RA) synoviocytes. Synoviocytes isolated from rheumatoid arthritis (RA) patients were stimulated with recombinant SAA and IL-23 expression was investigated using reverse transcriptase-polymerase chain reaction and Western blot. The involvement of mitogen-activated protein kineases (MAPKs) and nuclear factor (NF)-κB in SAA-induced interleukin (IL)-23 p19 expression was investigated using pharmacological inhibitors. In RA synoviocytes, SAA induced the expression of IL-23 p19 and p40 mRNA expression. The SAA-stimulated expression of p19 was rapid (< 3 h), and insensitive to polymyxin B treatment. This SAA-stimulated expression of IL-23 p19 was inhibited completely by inhibitors of NF-κB, p38MAPK and dexamethasone. Interestingly, the SAA-induced IL-23, p19 and p40 production was accompanied by enhanced expression of IL-1ß, but not transforming growth factor-ß. These results indicate that SAA is a significant inducer of IL-23 and IL-1ß in RA synoviocytes and potentially activates the IL-23/IL-17 pathway in the RA synovium. Our data present a novel interaction between inflammation and autoimmunity by an acute-phase protein.

Observation of reversed-shear Alfvén eigenmodes excited by energetic ions in a helical plasma.

Reversed-shear Alfvén eigenmodes were observed for the first time in a helical plasma having negative q0'' (the curvature of the safety factor q at the zero shear layer). The frequency is swept downward and upward sequentially via the time variation in the maximum of q. The eigenmodes calculated by ideal MHD theory are consistent with the experimental data. The frequency sweeping is mainly determined by the effects of energetic ions and the bulk pressure gradient. Coupling of reversed-shear Alfvén eigenmodes with energetic ion driven geodesic acoustic modes generates a multitude of frequency-sweeping modes.

Potentiation of glucocorticoid receptor (GR)-mediated signaling by the immunosuppressant tacrolimus in rheumatoid synoviocytes.

OBJECTIVE: The immunosuppressant tacrolimus is known to enhance many aspects of glucocorticoid. In this study, we investigated the effects of tacrolimus on glucocorticoid receptor (GR) signaling using rheumatoid fibroblast-like synoviocytes (RA-FLS). METHODS: The nuclear translocation of GR was analyzed by immunocytochemistry. The DNA binding activity of p65 was assayed by a functional ELISA kit using nuclear extracts. GR-associated FK506-binding protein-51 (FKBP-51) was analyzed by Western blotting following immunoprecipitation of glucocorticoid receptor (GR) complexes. RESULTS: High concentrations (10-7M) of Dexamethasone (Dex) induced GR translocation to the nucleus in RA-FLS. However, the nuclear GR translocation did not occur with low concentrations of Dex (10-9M). Tacrolimus treatment of RA-FLS results in potentiation of GR translocation to the nucleus even in the presence of a low concentration of Dex (10-9M). GR-associated FKBP-51 decreased after tacrolimus treatment. Furthermore, tacrolimus also decreased the IL-1Beta-induced DNA binding activity of p65, a subunit of NF-KappaB, in the presence of 10-9 M of Dex. CONCLUSION: These data suggest that tacrolimus exerts anti-inflammatory properties by potentiating the GR signaling through the GR-immunosuppressant-binding proteins (immunophilins) interaction and its nuclear transport in rheumatoid synovium.

The observation of nonlinear ion cyclotron wave excitation during high-harmonic fast wave heating in the large helical device.

A wave detector, a newly designed magnetic probe, is installed in the large helical device (LHD). This wave detector is a 100-turn loop coil with electrostatic shield. Comparing a one-loop coil to this detector, this detector has roughly constant power coupling in the lower frequency range of 40 MHz, and it can easily detect magnetic wave in the frequency of a few megahertz. During high-harmonic fast wave heating, lower frequency waves (<10 MHz) were observed in the LHD for the first time, and for the power density threshold of lower frequency wave excitation (7.5 MHz) the power density of excited pumped wave (38.47 MHz) was approximately -46 dBmHz. These lower frequencies are kept constant for electron density and high energy particle distribution, and these lower frequency waves seem to be ion cyclotron waves caused by nonlinear wave-particle interaction, for example, parametric decay instability.

Determination of anti-cyclic citrullinated peptide antibodies in the sera of patients with liver diseases.

OBJECTIVE: To determine the frequency of anti-cyclic citrullinated peptide (anti-CCP) antibodies in patients with HCV infection, primary biliary cirrhosis (PBC) and type-I autoimmune hepatitis (AIH) to assess the specificity of anti-CCP antibodies. METHODS: Rheumatoid factor (RF) and anti-CCP antibodies were measured in the sera from patients with HCV infection (n=45), PBC (n=73), AIH (n=55) and rheumatoid arthritis (n=48), and also from the sera of healthy subjects (n=23). Anti-CCP antibodies were measured using a second generation enzyme-linked immunosorbent assay (ELISA). RESULTS: No sera with elevated anti-CCP were found in the patients with HCV infection. Two PBC patients (2.7%) and six AIH patients (10.5%) had anti-CCP antibodies. The seropositivity for anti-CCP in these autoimmune disease patients was associated with a high frequency of RA association [PBC; 100% (2/2), AIH; 86.4% (5/6)]. CONCLUSIONS: Although anti-CCP antibodies may be present in patients with autoimmune liver diseases, almost seropositive patients had concomitant RA. As a result, the measurement of anti-CCP antibodies may therefore be helpful for accurately diagnosing RA in patients with these liver diseases.

MEFV mutations in Japanese rheumatoid arthritis patients.

OBJECTIVE: Familiar Mediterranean Fever (FMF) is common among Mediterranean populations, while other populations are rarely affected. The aim of this study was to assess the involvement of MEFV gene mutations among Japanese rheumatoid arthritis patients with or without amyloid A (AA) amyloidosis. METHODS: The frequency of the MEFV mutations, which were identified in Japanese FMF patients, was determined in 126 Japanese RA patients and 76 Japanese healthy subjects. RESULTS: The M694I mutation was not observed among RA patients and healthy subjects. Allele frequency of R408Q, P369S, E148Q, L110P mutations account respectively for 3.3%, 3.9%, 23.7%, 9.2% in healthy subjects and 5.6%, 6.7%, 24.2%, 9.5% in RA patients. The overall mutation rate was comparable between the RA patients and healthy subjects, as well as between the RA patients with and without amyloidosis. CONCLUSION: This study shows the high prevalence of mutations of the MEFV genes in Japanese RA patients. However, our data suggest that the MEFV gene mutations may not be a genetic factor affecting the susceptibility of RA or the development of amyloidosis in a Japanese population.

Observation of stable superdense core plasmas in the large helical device.

In reduced recycling discharges in the Large Helical Device, a super dense core plasma develops when a series of pellets are injected. A core region with density as high as 4.5 x 10(20) m(-3) and temperature of 0.85 keV is maintained by an internal diffusion barrier with very high-density gradient. These results may extrapolate to a scenario for fusion ignition at very high density and relatively low temperature in helical devices.

Slow transition of energy transport in high-temperature plasmas.

A new slow transition process for energy transport in magnetically confined plasmas is reported. The slow transition is characterized by the change between two metastable transport conditions characterized by a weak and a strong electron temperature (Te) dependence of normalized heat flux. These two branches are found to merge at the critical gradient. In metastable transport, the derivative of normalized heat flux to the Te gradient, [EQUATION: SEE TEXT], is positive, while it becomes negative during the transition phase. The time for the transition increases as the normalized Te gradient is increased and exceeds the transport time scale characterized by the global energy confinement time.

Sawtooth oscillation in current-carrying plasma in the large helical device.

Sawtooth oscillations have been observed in current-carrying helical plasmas by using electron-cyclotron-emission diagnostics in the Large Helical Device. The plasma current, which is driven by neutral beam injection, reduces the beta threshold of the sawtooth oscillation. When the central q value is increased due to the plasma current, the core region crashes, and, when it is decreased, the edge region crashes annularly. Observed rapid mixture of the plasma in the limited region suggests that these sawtooth crashes are reconnection phenomena. Unlike previous experiments, no precursor oscillation has been observed.

Island dynamics in the large-helical-device plasmas.

In the Large Helical Device plasma discharges, the size of an externally imposed island with mode number ( n/m = 1/1) decreases substantially when the plasma is collisionless ( nu(*)< approximately 1) and the beta is finite ( > approximately 0.1%) at the island location. For the collisional plasmas with finite beta, on the other hand, the size of the island increases. However, there is a threshold in terms of the vacuum island size below which the island enlargement is not seen.

Observation of plasma flow at the magnetic island in the large helical device.

Radial profiles of ion temperature and plasma flow are measured at the n/m = 1/1 magnetic island produced by external perturbation coils in the Large Helical Device. The sheared poloidal flows and sheared radial electric field are observed at the boundaries of the magnetic island, because the poloidal flow vanishes inside the static magnetic island. When the width of the magnetic island becomes large, the flow along the magnetic flux surface inside the magnetic island appears around the O point in the direction which reduces the shear of the poloidal flow at the boundary of the magnetic island.

Observation of the "self-healing" of an error field island in the large helical device.

It was observed that the vacuum magnetic island produced by an external error magnetic field in the large helical device shrank in the presence of plasma. This was evidenced by the disappearance of flat regions in the electron temperature profile obtained by Thomson scattering. This island behavior depended on the magnetic configuration in which the plasmas were produced.

Orthodontic bracket bonding with a plasma-arc light and resin-reinforced glass ionomer cement.

Developments in light-curing technology have led to the introduction of a plasma-arc light-curing unit that delivers high-intensity output for faster curing. The purposes of this study were to determine the shear bond strengths of light-cured resin-reinforced glass ionomer cement cured with a plasma-arc light-curing unit and to evaluate the durability of the resultant bond strength with thermal cycling. Comparisons were made between light-cured resin-reinforced glass ionomer cement and light-cured composite resin. Two light-curing units were used in this study: a plasma-arc light-curing unit and a conventional light-curing unit. The mean shear bond strengths of light-cured resin-reinforced glass ionomer cement with the plasma-arc and the conventional light-curing units were 20.3 MPa and 26.0 MPa, respectively. An analysis of variance showed no statistically significant differences between the plasma-arc and the conventional light-curing units. Light-cured resin-reinforced glass ionomer cement and light-cured composite resin demonstrated similar bond strengths and exhibited no statistical differences. There was no statistical difference in bond strength between the teeth that were thermal cycled and those that were not. Failure sites for the brackets bonded with light-cured resin-reinforced glass ionomer cement appeared to be predominantly at the bracket-adhesive interface. The SDs of light-cured composite resin were high for both light-curing units. Whereas the coefficients of variation for light-cured resin-reinforced glass ionomer cement ranged from 20% to 30%, those of light-cured composite resin ranged from 40% to 60%. The bond strength of light-cured resin-reinforced glass ionomer cement cured with either a conventional light-curing unit or a plasma-arc light-curing unit surpassed the clinically required threshold. The plasma-arc light-curing unit may be an advantageous alternative to the conventional light-curing unit for orthodontic bracket bonding with both light-cured resin-reinforced glass ionomer cement and light-cured composite resin.

Reduction of ion thermal diffusivity associated with the transition of the radial electric field in neutral-beam-heated plasmas in the large helical device.

Recent large helical device experiments revealed that the transition from ion root to electron root occurred for the first time in neutral-beam-heated discharges, where no nonthermal electrons exist. The measured values of the radial electric field were found to be in qualitative agreement with those estimated by neoclassical theory. A clear reduction of ion thermal diffusivity was observed after the mode transition from ion root to electron root as predicted by neoclassical theory when the neoclassical ion loss is more dominant than the anomalous ion loss.

The translesion DNA polymerase zeta plays a major role in Ig and bcl-6 somatic hypermutation.

Ig somatic mutations would be introduced by a polymerase (pol) while repairing DNA outside main DNA replication. We show that human B cells constitutively express the translesion pol zeta, which effectively extends DNA past mismatched bases (mispair extender), and pol eta, which bypasses DNA lesions in an error-free fashion. Upon B cell receptor (BCR) engagement and coculture with activated CD4+ T cells, these lymphocytes upregulated pol zeta, downregulated pol eta, and mutated the Ig and bcl-6 genes. Inhibition of the pol zeta REV3 catalytic subunit by specific phosphorothioate-modified oligonucleotides impaired Ig and bcl-6 hypermutation and UV damage-induced DNA mutagenesis, without affecting cell cycle or viability. Thus, pol zeta plays a critical role in Ig and bcl-6 hypermutation, perhaps facilitated by the downregulation of pol eta.

Tensile bond strength of light-cured resin-reinforced glass ionomer cement with delayed light exposure.

In the clinical situations, the time intervals between material mixing and light exposure during bracket bonding, using light-cured resin-reinforced glass ionomer cement (LCGIC), may vary for each individual bracket. This study determined the tensile bond strengths of LCGIC subjected to various time intervals, and evaluated the durability with thermocycling. Comparisons were made between LCGIC and light-cured composite resin (LCR). Two hundred and forty bovine teeth were chosen as specimens. Light exposure was performed 5, 10, 20, and 40 min after the commencement of powder/liquid mixing. The durability was evaluated by thermocycling for 2000 times at temperatures between 5 degrees C and 55 degrees C, with a 30-s dwell time. Tensile bond strengths of LCGIC and LCR after 5 min, representing the general condition in clinical use, equaled 5.7 +/- 1.5 MPa and 5.1 +/- 2.6 MPa, respectively. For the LCGIC groups, no significant differences were seen between bond strengths with and without thermocycling. Also, no significant differences were noted among any time intervals. For the LCR groups, there were also no significant differences with and without thermocycling. The tensile bond strength of LCR showed highly significant differences within groups across time. Compared with LCR, the failure sites for brackets bonded with LCGIC appeared to be predominantly at the bracket/adhesive interface. The standard deviations of LCR were high when compared with those of LCGIC. The bond strength of LCGIC with or without thermocycling surpassed the clinically required minimum. LCGIC may be an advantageous alternative to LCR for orthodontic bracket bonding.

Energy confinement time and heat transport in initial neutral beam heated plasmas on the large helical device

The confinement characteristics of large net-current-free plasmas heated by neutral-beam injection have been investigated in the Large Helical Device (LHD). A systematic enhancement in energy-confinement times from the scaling derived from the medium-sized heliotron/torsatron experiments have been observed, which is attributed to the edge pedestal. The core confinement is scaled with the Bohm term divided by the square root of the gyro radii. The comparative analysis using a dimensionally similar discharge in the Compact Helical System indicates gyro-Bohm dependence in the core and transport improvement in the edge region of LHD plasmas.