Turbulence Transition in Magnetically Confined Hydrogen and Deuterium Plasmas.

In this study, we discovered a turbulence transition in a large helical device. The turbulence level and turbulence-driven energy transport decrease to a specific transition density and increase above it. The ruling turbulences below and above the transition density were ion-temperature gradient (ITG) and resistive-interchange (RI) turbulences, consistent with the predictions of gyrokinetic theory and two-fluid MHD model, respectively. Isotope experiments on hydrogen (H) and deuterium (D) clarified the role of transitions. In the ITG regime, turbulence levels and energy transport were comparable in the H and D plasmas. In contrast, in the RI regime, they were clearly suppressed in the D plasma. The results provide crucial knowledge for understanding isotope effects and future optimization of stellarator and heliotron devices.

Early postnatal GABAA receptor modulation reverses deficits in neuronal maturation in a conditional neurodevelopmental mouse model of DISC1.

Exploring drug targets based on disease-associated molecular mechanisms during development is crucial for the generation of novel prevention and treatment strategies for neurodevelopmental psychiatric conditions. We report that prefrontal cortex (PFC)-specific postnatal knockdown of DISC1 via in utero electroporation combined with an inducible knockdown expression system drives deficits in synaptic GABAA function and dendritic development in pyramidal neurons, as well as abnormalities in sensorimotor gating, albeit without profound memory deficits. We show for the first time that DISC1 is specifically involved in regulating cell surface expression of α2 subunit-containing GABAA receptors in immature developing neurons, but not after full maturation. Notably, pharmacological intervention with α2/3 subtype-selective GABAA receptor positive allosteric modulators during the early postnatal period ameliorates dendritic deficits and behavioral abnormalities induced by knockdown of DISC1. These findings highlight a critical role of DISC1-mediated disruption of postnatal GABA signaling in aberrant PFC maturation and function.

Establishment of functional imprinting of the H19 gene in human developing placentae.

We have found that the imprinted H19 gene can be expressed either biallelically or monoallelically in the developing human placentae. H19 biallelic expression is confined to the placenta until 10 weeks of gestation, after which it becomes exclusively maternal, and does not affect allele-specificity or levels of IGF2 expression. The promoter region of H19 is hypomethylated at all stages of placental development, while the 3' portion shows progressive methylation of the paternal allele with gestation. Our observations demonstrate that the establishment of functional H19 imprinting occurs during the early development of the placenta and provide an opportunity to understand the mechanism by which the H19 primary imprint is manifested in somatic cells.

Conceptual design and demonstration of a three-color laser interferometer for noise reduction in fusion plasma measurements.

A three-color laser interferometer consisting of three Mach-Zehnder-type, one-color laser interferometers with heterodyne detection and coaxial laser beams is demonstrated. The three-color laser interferometer is considered as three sets of a two-color laser interferometer. From the two sets of the two-color laser interferometer, the value consisting only of the noise floor can be assessed. The noise floor can be reduced by subtracting the value consisting only of the noise floor from the measurement value obtained with the other two-color laser interferometer. In the case of the three lasers with wavelengths 9.25 µm, 10.59 µm, and 532 nm, a 15% noise reduction was obtained compared to the two sets of the two-color laser interferometers contained in the three-color laser interferometer. The 100-Hz noise reduction by 53% was achieved, and the other frequency noises were equal to or less than the smallest noise achieved by the two-color laser interferometers. The 100-Hz noise floor is caused by the vibration noise, which remains because of the non-coaxiality of the three beams.

Reformation of the Electron Internal Transport Barrier with the Appearance of a Magnetic Island.

When realising future fusion reactors, their stationary burning must be maintained and the heat flux to the divertor must be reduced. This essentially requires a stationary internal transport barrier (ITB) plasma with a fast control system. However, the time scale for determining the position of the foot point of an ITB is not clearly understood even though its understanding is indispensable for fast profile control. In this study, the foot point of the electron ITB (eITB) was observed to be reformed at the vicinity of a magnetic island when the island started to form. In addition, the enhanced confinement region was observed to expand during the eITB formation according to the radial movement of the magnetic island toward the outer region. Compared to the time scales of the local heat transport, the faster time scales of the movement of the eITB foot point immediately after island formation (~0.5 ms) suggest the importance of the magnetic island for plasma profile control to maintain stationary burning.

Important roles of tachykinins in the development of allergic nasal hyperresponsiveness in guinea-pigs.

BACKGROUND: Although it has been suggested that the use of tachykinin receptor antagonists might prove to be an effective treatment for allergic rhinitis (AR), they are not used clinically. Therefore, we decided to examine the effects of tachykinin receptor antagonists on AR symptoms in an appropriate experimental model. OBJECTIVE: To evaluate newly developed tachykinin receptor antagonists in a Japanese cedar pollen-induced AR model and to determine their effect on allergen-induced sneezing, nasal blockage, and nasal hyperresponsiveness (NHR). METHODS: Sensitized guinea-pigs were challenged by forced inhalation of pollen once every week. Sneezing and nasal blockage were observed after pollen challenges. NHR (nasal blockage) to an intranasal application of leukotriene D(4) was assessed 2 days after an antigen challenge. We also evaluated whether intranasal dosing with a tachykinin causes NHR. NK(1) and NK(2) receptor antagonists were administered before an intranasal treatment with antigen or tachykinin. Amounts of tachykinins present in nasal cavity lavage fluid were measured by an enzyme immunoassay. RESULTS: Although an NK(1) and NK(2) receptor dual antagonist showed no effect on pollen-induced sneezing and biphasic nasal blockage, it did completely suppress the development of NHR. Experiments using specific NK(1) or NK(2) receptor antagonists revealed that NK(2) receptor activation was preferentially involved in the development of hyperresponsiveness. Increases in the levels of substance P (SP) and neurokinin A (NKA) in the nasal tissue were noted 20 min-1 h after the challenge. Intranasal instillation of either SP or NKA-induced NHR, which was almost completely inhibited by NK(2) receptor antagonists and partially inhibited by NK(1) receptor antagonists. CONCLUSIONS: SP and NKA, which are released early after the challenge, mediate the development of NHR by preferentially activating NK(2) receptors. Therefore, NK(2) receptor antagonists might prove to be effective treatment of AR.

Pathogenesis of cBFL in common with IPF? Correlation of IP-10/TARC ratio with histological patterns.

BACKGROUND: A Th1 predominant immune response has been shown in acute hypersensitivity pneumonitis. Predominance of Th2 appears to favour the development of pulmonary fibrosis through the profibrotic process and has been described as crucial in the progression of idiopathic pulmonary fibrosis. Chronic bird fancier's lung (cBFL) can present with a histological pattern of usual interstitial pneumonia (UIP)-like lesions. Little is known about the Th1/Th2 balance in the pathogenesis of cBFL. METHODS: To evaluate the relevance of Th1-type chemokines (interferon-inducible protein, IP-10) and Th2-type chemokines (thymus- and activation-regulated chemokine, TARC) and their receptors (CXCR3 and CCR4) to the histological patterns of cBFL, 40 patients with cBFL who underwent surgical lung biopsies, 12 with acute BFL (aBFL) and 10 healthy volunteers were analysed. IP-10 and TARC levels in serum and bronchoalveolar lavage (BAL) fluid were measured by ELISA. Immunohistochemistry for CXCR3 and CCR4 was performed on surgical lung specimens. RESULTS: The ratio of TARC to IP-10 in the serum of patients with UIP-like lesions was significantly higher than in patients with cNSIP/OP-like lesions, aBFL and healthy volunteers. The ratio of CCR4 to CXCR3 in patients with UIP-like lesions was significantly higher than in those with cNSIP/OP-like lesions and fNSIP-like lesions. The ratio of CCR4-positive to CXCR3-positive cells correlated with the ratio of TARC to IP-10 in serum. CONCLUSIONS: A Th2 predominant immune response may play an important role in the development of UIP-like lesions, as already observed in idiopathic pulmonary fibrosis. A Th1 predominance may play a role in the development of cNSIP/OP-like lesions in cBFL.

Development of thermal image plate using ceramic luminescence materials for aligning and stabilizing beam axis of CO2 laser.

A thermal image plate (TIP) using ceramic luminescence materials has been developed in order to visualize a beam spot of a CO2 laser which is used as a light source of an interferometer developed in JT-60SA. By using CaAlSiN3:Eu2+ (CASN), the TIP was developed, and its property was assessed. A CASN TIP was able to visualize the invisible CO2 laser beam as a negative image. The beam diameter and the stability of the beam axis measurement obtained with the CASN TIP were approximately the same as that obtained with a commercial TIP. Furthermore, the time response of the CASN TIP at the best was approximately the same as that of the commercial TIP. The CASN TIP which had the highest time response was applied to the beam axis stabilizer, and then the beam axis stabilization was successfully performed in 2 h.

Effect of a thin HA coating on the stress/strain distribution in bone around dental implants using three-dimensional finite element analysis.

Three-dimensional finite element analysis was performed for thin hydroxyapatite (HA) coated and titanium dental implants to study the effects on stress/strain distribution in the mandible with application of axial and oblique loads. The implants were of screw and cylinder types. With an axial load, the maximum equivalent bone stresses in the titanium implants were 21.5 and 29.0 MPa for the cylinder and screw types respectively, and the stress and strain distributions differed. For the cylinder type, the highest stress was located at the implant base, and for the screw type, it was located at the top edge of the first thread within the cortical bone. For the HA-coated cylinder and screw implants, the maximum equivalent bone stresses were 7.1 and 7.2 MPa respectively. The stress and strain distributions were similar, and the highest stress was located on the upper side of the cortical bone around the implant neck for both implants. Of the implants examined, the screw type HA-coated implant had the most uniform stress distribution in bone.

Faraday-cup-type lost fast ion detector on Heliotron J.

A Faraday-cup type lost-fast ion probe (FLIP) has been designed and installed in Heliotron J for the purpose of the studies of interaction between fast ions and MHD instabilities. The FLIP can measure the co-going fast ions whose energy is in the range of 1.7-42.5 keV (proton) and pitch angle of 90∘-140∘, especially for fast ions having the injection energy of neutral beam injection (NBI). The FLIP successfully measured the re-entering passing ions and trapped lost-fast ions caused by fast-ion-driven energetic particle modes in NBI heated plasmas.

IL-12 plays a pivotal role in LFA-1-mediated T cell adhesiveness by up-regulation of CCR5 expression.

The chemokine receptor CCR5 has been implicated in the recruitment of T cells to inflammatory sites. However, the regulation of CCR5 induction on T cells and its contribution to T cell adhesiveness are poorly understood. Using a Th1 clone, 2D6, that can be maintained with interleukin (IL)-12 or IL-2 alone (designated 2D6(IL-12) or 2D6(IL-2), respectively), we investigated how CCR5 is induced on T cells and whether CCR5 is responsible for up-regulating the function of adhesion molecules. 2D6(IL-12) grew, forming cell aggregates, in culture containing IL-12. This was due to lymphocyte function-associated antigen (LFA)-1-intercellular adhesion molecule (ICAM)-1 interaction, because 2D6(IL-12) expressed both LFA-1 and ICAM-1 and cell aggregation was inhibited by anti-ICAM-1 monoclonal antibody. Despite comparable levels of LFA-1 and ICAM-1 expression, 2D6(IL-2) cells did not aggregate in culture with IL-2. It is important that there was a critical difference in CCR5 expression between 2D6(IL-12) and 2D6(IL-2); the former expressed high levels of CCR5, and the latter expressed only marginal levels. Both types of cells expressed detectable albeit low levels of RANTES (regulated on activation, normal T expressed and secreted) mRNA. Unlike IL-12 or IL-2, IL-18 induced high levels of RANTES mRNA expression without modulating CCR5 expression. Therefore, combined stimulation with IL-12 and IL-18 strikingly up-regulated 2D6 cell aggregation. Notably, LFA-1-mediated aggregation of 2D6(IL-12) cells was suppressed by anti-CCR5 antibody. These results indicate that IL-12 plays a critical role in CCR5 expression on Th1 cells and consequently contributes to CCR5-mediated activation of LFA-1 molecules.

Localization of fractalkine and CX3CR1 mRNAs in rat brain: does fractalkine play a role in signaling from neuron to microglia?

Localization of the mRNAs for fractalkine, a CX3C chemokine, and for its receptor CX3CR1 was investigated in the rat brain. In situ hybridization study revealed that fractalkine mRNA was dominantly expressed in neuronal cells particularly in the olfactory bulb, cerebral cortex, hippocampus, caudate putamen and nucleus accumbens. In vitro study using enriched neuronal or glial culture supported the dominant expression of fractalkine mRNA in neurons. On the other hand, CX3CR1 mRNA was dominantly expressed in glial cells throughout the whole brain. The in vitro study suggested the cells expressing CX3CR1 mRNA are microglia, not astrocytes or neurons. Fractalkine appears to function as a signal molecule from neuron to microglia.

Renal handling of free and acylcarnitine in secondary carnitine deficiency.

Free and acylcarnitine in serum and urine samples were measured in miscellaneous diseases, including mitochondrial cytopathy with Fanconi's syndrome (MCFS). The urinary concentration of acylcarnitine always exceeded that of free carnitine, and a significant negative correlation was found between the ratio of serum free to acylcarnitine and the ratio of free to acylcarnitine clearance among control and test patients (p less than 0.005). A patient with MCFS excreted large amounts of free carnitine compared with acylcarnitine in urine, which may be attributable to decreased reabsorption of free carnitine in renal tubules.

Heterogeneous phenotypes of mitochondrial encephalomyopathy in a single kindred.

Five patients with mitochondrial disorders in a single family showed marked heterogeneity of clinical signs and symptoms. Two patients had the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes; one had blepharoptosis, seizures, and diabetes insipidus; and two had a nonspecific encephalomyopathic disorder. This family supports the concept of a "mitochondrial cytopathy."

Childhood-type myositis and linear scleroderma.

A 5-year-old girl had linear scleroderma on the flexor surface of the right arm; muscle wasting included the shoulder girdle. IgM fluorescence on blood vessels and along dermal-epidermal junction was observed by direct immunofluorescence in biopsied skin. Biceps muscle underlying the plaque of the scleroderma showed atrophy of entire fascicles, perifascicular atrophy, and cellular infiltration around blood vessels that are quite similar to those found in childhood-type dermatomyositis. In addition, various abnormalities, including edema and thickening of basal lamina, were found on blood vessels in muscle tissue. The results suggested that the autoimmune collagen vascular disorder is responsible for this condition.

Infantile glycogen storage myopathy in a girl with phosphorylase kinase deficiency.

A 19-month-old girl with moderate hypotonia was studied. Histochemical and electronmicroscopic findings revealed that many skeletal muscle fibers contained an excess amount of glycogen. The phosphorylase reaction was normalized only after activation with 5' AMP. Biochemical studies showed an increased glycogen content and decreased activities of phosphorylase "a" and an active form of phosphorylase kinase, whereas activities of total phosphorylase, total phosphorylase kinase, and cyclic AMP-dependent protein kinase were all in the normal range. Thus, phosphorylase kinase in the patient's muscle seemed to be a variant form, which was activated partially under the physiologic condition. This condition may be inherited as an X-linked recessive trait.

DF3 expression in human gallbladder carcinoma: significance for lymphatic invasion.

DF3 (MUC 1) is a member of a family of high molecular weight glycoproteins. Recent studies have demonstrated that DF3 is expressed in tumors of various human organs, and may function as an anti-adhesion molecule that inhibits cell-to-cell adhesion, inducing tumor metastasis. However, expression patterns of DF3 have not yet been established in human gallbladder carcinomas. In this study, we examined DF3 expression in human gallbladder adenocarcinoma and its clinicopathological significance. DF3 immunoreactivity was detected not only in the cancer cells (cytoplasmic type; 50.0%, 27/54) but also in the cancer stroma (stromal type; 46.3%, 25/54). According to TNM classification, 65.0% (26/40) of T2-4 gallbladder cancers showed cytoplasmic DF3, while 7.1% (1/14) of the T1 cancers were cytoplasmic DF3-positive (p<0.001). Stromal DF3 expression was detected in 62.5% (25/40) and none (0/14) of the T2-4 and T1 cancers, respectively (p<0.001). Lymph node metastasis was frequently found in the cytoplasmic DF3- and stromal DF3-positive gallbladder cancers (59.3% and 60.0%, respectively). These observations suggested that DF3 expression plays important roles in cancer cell growth and metastasis of human gallbladder adenocarcinomas.

CEA immunohistochemical localization is correlated with growth and metastasis of human gallbladder carcinoma.

Carcinoembryonic antigen (CEA) is a good marker of colorectal cancer. Recent studies have demonstrated that CEA may function as a metastatic potentiator by different pathways; i.e., modulation of immune responses, facilitation of intercellular adhesion and cellular migration. However, expression patterns of CEA have not yet been established in human gallbladder carcinomas. In this study, we examined CEA expression in human gallbladder adenocarcinomas and its clinicopathological significance. CEA immunoreactivity was detected not only in the cancer cells (cytoplasmic type: 63.0%, 34/54) but also in the cancer stroma (stromal type: 29.6%, 16/54). According to TNM classification, 75.0% (30/40) of T2-4 gallbladder cancers showed cytoplasmic CEA, while 28.6% (4/14) of the T1 cancers were cytoplasmic CEA-positive (p<0.05). Stromal CEA expression was detected in 40.0% (16/40) and none (0/14) of the T2-4 and T1 cancers, respectively (p<0.05). Lymph node metastasis was frequently found in the cytoplasmic CEA- and stromal CEA-positive gallbladder cancers (44.1% and 62.5%, respectively). These observations suggested that CEA expression plays important roles in cancer cell growth and metastasis of human gallbladder adenocarcinomas.

Stromal sialyl Le(a) expression is correlated with vascular invasion of human gallbladder adenocarcinoma.

Sialyl Le(a) antigen (CA19-9), a member of a family of high molecular weight glycoproteins, was originally described as a gastrointestinal- and pancreatic-specific tumor marker. Recent studies have demonstrated that sialyl Lea is a ligand for E-selectin and may play an important role in tumor metastasis. However, expression patterns of sialyl Le(a) have not yet been established in human gallbladder carcinomas. In this study, we examined sialyl Le(a) expression in human gallbladder adenocarcinoma and its clinicopathological significance. Sialyl Le(a) immunoreactivity was detected not only in cancer cells (cytoplasmic type; 68.5%, 37/54) but also in cancer stroma (stromal type; 46.3%, 24/54). According to TNM classification, stromal sialyl Le(a) expression was detected in 60. 0% (24/40) and 7.1% (1/14) of the T2-4 and T1 cancers, respectively (p<0.01). Stromal sialyl Le(a)-positive gallbladder cancers frequently showed lymphatic invasion, venous invasion and lymph node metastasis (62.9%, 62.5% and 70.0%, respectively) (p<0.01). These observations suggested that sialyl Le(a) expression plays important roles in vascular invasion and metastasis of human gallbladder adenocarcinomas.

Stromal expression of thrombospondin-1 is correlated with growth and metastasis of human gallbladder carcinoma.

Thrombospondin-1 (TSP1) is one of the extracellular matrix glycoproteins that affect cell adhesion, motility and growth. Based on its effects on tumors, TSP1 is thought to be a potential regulator of tumor growth and metastasis. In this study, we examined TSP1 expression in human gallbladder adenocarcinoma and its clinicopathological significance. TSP1 immunoreactivity was detected mainly in the cancer stroma and was observed infrequently in cancer cells. According to the TNM classification, 74.5% (29/39) of the T2 and T3 gallbladder cancers were TSP1-positive, while none (0/14) of the T1 cancers showed TSP1 expression (p<0.001). Lymph node metastasis and venous involvement were frequently found in the TSP1-positive cases (90.0% and 87.1%, respectively) of gallbladder adenocarcinoma (p<0.001). These observations suggested that TSP1 expression plays an important role in cancer cell growth and metastasis of human gallbladder adenocarcinomas, and that stromal TSP1 immunoreactivity is a good predictor of vascular involvement and lymph node metastasis.