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Abstract. The significance of serotonin in the pathogenesis of monocrotaline-induced pulmonary hypertension (MCT-PH) in rats, plasma serotonin concentrations, and the effect of a serotonin receptor antagonist administration in association with the number of proliferative cells were investigated. The thickness of the media of the small pulmonary arteries and the weight ratio of the RV to that of LV + S (RV/[LV + S] weight ratio) were used as indices of the severity of PH. Plasma serotonin concentrations were measured by high-performance liquid chromatography. Histopathologic analysis of the lung tissue was performed by hematoxylineosin and elastin van Gieson staining. Immunohistopathologic staining for proliferating cell nuclear antigen (PCNA) was performed to identify proliferative cells. The severity of PH as determined by the medial thickness of the small pulmonary arteries and RV/(LV + S) weight ratio in rats with MCT-PH was significantly reduced after treatment with MCI-9042 (p < 0.01 and p < 0.05, respectively). The serotonin concentration was significantly greater in MCT-PH rats than in normal control rats (p < 0.05). The scores for histopathologic changes, such as thickening of the alveolar walls and interstitial inflammatory cell infiltration in MCT-PH rats, were significantly reduced after treatment with MCI-9042 (p < 0.05 and p < 0.01, respectively). The number of PCNA-positive cells was significantly greater in MCT-PH rats than in normal control rats (p < 0.0001) and was reduced alter treatment with MCI-9042 (p < 0.0001). Treatment with MCI-9042 significantly inhibited the development... [ABSTRACT FROM AUTHOR]

The JT-60SA superconducting tokamak is being constructed under dual projects, the EU-JA international collaboration framework and Japanese national programme. To suppress magnetic field error to less than 0.01% with respect to the toroidal magnetic field for good confinement of plasma, QST has developed a precise onsite assembly technology of tokamak components such as vacuum vessel (VV) and toroidal magnetic field coils (TFC) with size of over 10-m scale. Prior to an onsite assembly, the assembly process is carefully simulated in a three dimension CAD model, through which the location and number of the reference points for the assembly are evaluated to determine each component position. In the onsite assembly, the tokamak components are positioned by measuring with the laser tracker of a 0.5 mm spatial resolution and assembled by adjusting with shims and splice plates. The onsite assembly of the VV 340° sector has been succeeded in an allowable accuracy of +8/−4 mm with the 10 m diameter by welding sectors, each of which was circumferentially segmented and manufactured by taking into account the deformation due to the welding. The remaining 20° sector will be installed after the TF coils installation. The metrology developed for the onsite assembly of the JT-60SA is expected to be applicable to ITER whose size is the double of JT-60SA. [ABSTRACT FROM AUTHOR]

In order to obtain information for control of JT-60SA plasma and physics research on the plasma, many types of magnetic sensors are developed. We have designed a new architecture of magnetic sensors and connection methods for JT-60SA taking installation and maintenance into account. The former include a newly designed Mirnov coil, a Rogowski coil and a diamagnetic loop. They enable us to make simple and robust sensors. The latter include a newly developed connector between a sensor and a mineral insulation cable, and a connection box. An unsealed connection box enables easy installation in a vacuum vessel; however, it should have a withstand voltage greater than 1 kV at intermediate gas pressures. We successfully achieved a high withstand voltage for the unsealed connection box in the gas pressure region around the Paschen minimum voltage. After R&D of JT-60SA magnetic sensors, almost all manufacturing steps are complete. This paper reports the manufacturing and tests of the magnetic sensors for JT-60SA. [ABSTRACT FROM AUTHOR]

JT-60SA has been designed and is being constructed to demonstrate and develop steady-state high-beta operation. Resistive wall mode (RWM) control, error field correction, and edge-localized mode (ELM) control will be performed using in-vessel coils. For these controls, we have developed a biaxial magnetic sensor to determine 3D magnetic configuration of the plasma. Moreover, for obtaining basic information about JT-60SA plasma, magnetic sensors, in particular, one-turn loops, Rogowski coils, diamagnetic loops, and saddle coils have been developed. Because the length of the vacuum vessel in the poloidal direction of JT-60SA is 16 m and almost twice as long as that of JT-60U, the length of the Rogowski coil and the diamagnetic loop of JT-60SA are also twice as long as those on JT-60U. We have devised new types of sensors and a connector for the mineral-insulated cable because construction and installation of these sensors are much more difficult in JT-60SA. We will report the design and specification of the magnetic sensors for JT-60SA from the physics and engineering aspects. [ABSTRACT FROM AUTHOR]

Disassembly of the JT-60U torus was started in 2009 after 18 years of D 2 operations and was completed in October 2012 for assembling the JT-60SA torus at the same position. The JT-60U torus was featured by the complicated and welded structure against the strong electromagnetic force, and by the radioactivation due to deuterium–deuterium (D–D) reactions. Since this work is the first experience of disassembling a large radioactivated fusion device in Japan, careful preparations of disassembly activities, including treatment of the radioactivated materials and safety work, have been made. During the disassembly period over 3 years, careful measures against exposure were taken and stringent control of exposure dose were implemented, and as a result, accumulated collective effective dose of ∼41,000 person-day to workers was only ∼22 mSv in total and no internal exposure was observed. About 13,000 components cut into pieces with measuring the contact dose were removed from the torus hall and stored safely in storage facilities. The total weight of the disassembly components reached up to ∼5400 tonnes. Most of the disassembly components will be treated as non-radioactive ones after the clearance level inspection under the Japanese regulations in the future. The assembly of JT-60SA has started in January 2013 after this disassembly of JT-60U torus. [ABSTRACT FROM AUTHOR]

Objectives: We investigated the alterations of acid-base characteristics of the blood cardioplegia (BCP) solution during aortic cross-clamping in hearts arrested with BCP and during in vitro-simulated ischemia. Methods: Following aortic cross-clamping, the hearts of 40 patients undergoing cardiac surgery were intermittently infused with an 18°C BCP solution and finally with a 34°C BCP solution prior to aortic cross-clamp release. We measured the pH, partial CO2 pressure (pCO2), [HCO3-], and [Cl-] of the coronary sinus effluent in the final BCP solution. The BCP solution was assessed under in vitro gassing at 34°C with 95% N2 + 5% CO2 (n = 6), 50% N2 + 50% CO2 (n = 3), or 100% CO2 (n = 6). Results: The coronary sinus effluent, compared with the preinfusion BCP solution, exhibited a significantly lower pH and a greater pCO2 with no change in the [HCO3-] level. In vitro, the 95% N2 + 5% CO2 gassing (simulated hypoxia) group exhibited a slight increase in [HCO3-] with no change in pCO2 or pH whereas the 50% N2 + 50% CO2 gassing and the 100% CO2 gassing (simulated hypoxia and hypercapnia) groups exhibited a significant increase in [HCO3-] under high pCO2-induced acidification. Conclusions: Under anoxia and CO2 retention during aortic cross-clamping, the BCP solution can be a bicarbonate donor to the myocardium. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Hepatocyte growth factor (HGF) is a potent angiogenic factor. The efficacy and safety of intramuscular injection of a naked plasmid encoding human HGF gene (beperminogene perplasmid, Collategene) was investigated in patients with critical limb ischemia (CLI) in a multicenter, randomized, double-blind, placebo-controlled trial. The randomization ratio for plasmid to placebo was 2:1. Injection sites were selected in each patient limb based on angiographic findings. Placebo or plasmid was injected on days 0 and 28. Evaluation of efficacy was carried out after 12 weeks. The primary end point was the improvement of rest pain in patients without ulcers (Rutherford 4) or the reduction of ulcer size in patients with ulcer(s) (Rutherford 5). Secondary end points were ankle-brachial pressure index, amputation, and quality of life (QOL). Forty-four patients were treated, and we performed interim analysis of efficacy in 40 patients. The overall improvement rate of the primary end point was 70.4% (19/27) in HGF group and 30.8% (4/13) in placebo group, showing a significant difference (P=0.014). In Rutherford 5 patients, HGF achieved a significantly higher improvement rate (100% [11/11]) than placebo (40% [2/5]; P=0.018). HGF plasmid also improved QOL. There were no major safety problems. HGF gene therapy is safe and effective for CLI. [ABSTRACT FROM AUTHOR]

Abstract: The tokamak machine monitoring and control system has been developed to avoid machine damages in JT-60 safety operation. It monitors the JT-60 mechanical structures and other sub-components to maintain their conditions. The system adopts the CAMAC digitizers, the Signal Transfer Unit (STU), and the hard-wired interlocks. Over 20 year, it has never been affected by any major troubles except a water leakage in toroidal field coil (TFC). The TFC monitoring system has been developed for the TFC safety with the water leakage from a cooling water channel. It has improved the reliability and efficiency of the TFC operation. [Copyright &y& Elsevier]

Dual-targeted therapy for antiangiogenesis and antilymphangiogenesis represents a potentially effective strategy for the treatment of various malignancies. Therefore, the goal of the present study was to identify genes that encode inhibitors of both angiogenesis and lymphangiogenesis. Using a cDNA library obtained from Lewis lung carcinoma (LL/2), a candidate gene was identified by the evaluation of growth inhibition in aortic and lymphatic endothelial cells (EC) as that coding for the mouse cold shock domain protein A (mCSDA). Overexpression of mCSDA significantly repressed cell proliferation and c-fos promoter activity in aortic, venous and lymphatic ECs. CSDA is a DNA-binding protein that binds to the hypoxia response element (HRE). Furthermore, of importance, we revealed that CSDA could directly bind to the serum response element (SRE) sequence, resulting in the inhibition of SRE activity, which may lead to growth inhibition in ECs. In an LL/2-inoculated mouse model, tumor growth was significantly repressed in an mCSDA-injected group. Histopathological analysis revealed that expression of blood and lymphatic EC markers was significantly decreased in mCSDA-injected groups. In conclusion, these data suggest that expression of CSDA can repress angiogenesis and lymphangiogenesis via direct binding to SRE in addition to HRE.Oncogene (2008) 27, 1821–1833; doi:10.1038/sj.onc.1210824; published online 15 October 2007 [ABSTRACT FROM AUTHOR]

Low-Z impurity (7Be) on the JT-60U divertor tiles was analyzed to study the impurity behavior in the divertor region. The amount of the 7Be increased approximately one hundred times after B4C-tile installation in the outer divertor. The 7Be was probably produced by 10B(p,α)7Be nuclear reaction on the divertor tiles in the hydrogen experiment with ion cyclotron range of frequency heating. The 7Be was distributed asymmetrically in the poloidal and the toroidal direction. The highest 7Be concentration was found at the inner divertor whose boron content (B/(B+C) ∼ 20%) was lower than the B4C tiles (B/(B+C) ∼ 80%) of the outer divertor. This result may imply impurity transport from the outer divertor to the inner divertor. [Copyright &y& Elsevier]

Study Objectives: To determine the significance of serotonin in the pathogenesis of interleukin (IL) 6-induced pulmonary hypertension (IL-6-PH) in rats, the plasma serotonin concentrations, and the effects of a specific antagonist of the serotonin (5-hydroxytryptamine [5-HT]) receptor, 1-[o-(m-methoxyphenyl)ethyl]phenoxy]-3-(dimethylamino)-2-propyl hydrogen succinate hydrochloride (MCI) on the degree of pulmonary hypertension (PH) were investigated in MCI-treated IL-6-PH (IL-6-MCI-PH) rats.Measurements: The thickness of the media of small pulmonary arteries and the ratio of the weight of the right ventricle free wall (RV) to that of the left ventricle with the septum (LV + S) were measured as indexes of the degree of PH. Serotonin concentrations in plasma and in supernatants of cultured vascular smooth muscle cells (VSMCs) stimulated by IL-6 were measured by high-performance liquid chromatography. The amplification of DNA encoding the 5-HT receptor in the lung specimen and VSMCs was performed by polymerase chain reaction.Results: The degree of PH, as determined by the medial thickness of small pulmonary arteries, was significantly increased in IL-6-PH rats as compared with normal control rats (p<0.05), and that in IL-6-MCI-PH rats was not significantly different from that in normal control rats. The RV/LV + S weight ratio in the IL-6-PH rats was significantly higher than that in normal control rats (p < 0.01). The RV/LV + S weight ratio in IL-6-MCI-PH rats was significantly lower than that in IL-6-PH rats (p < 0.01) and was not significantly different from that in normal control rats. The serotonin concentration was significantly higher in IL-6-PH rats than in normal control rats (p < 0.02), and the serotonin concentration in IL-6-MCI-PH rats was not significantly different from that in the normal control rats. The expression levels of the 5-HT receptor messenger RNA in the lung tissue tended to increase in IL-6-PH rats but was suppressed in IL-6-MCI-PH rats. IL-6 significantly increased the amount of serotonin released from VSMCs (p < 0.02). The expression of the 5-HT receptor messenger RNA was observed with IL-6 stimulation as was observed with serotonin stimulation in VSMCs.Conclusions: Serotonin receptor antagonists could be considered as potentially useful agents for the treatment of chronic thromboembolic PH, as well as for that of primary PH and PH associated with collagen vascular diseases. [ABSTRACT FROM AUTHOR]

Minimum sets of in-vessel components were installed for initial operation of JT-60SA in order to product and control the plasma and to know the plasma basic information, including inboard first wall, upper divertor, protection limiter, glow electrodes and magnetic sensors. All of magnetic sensors were installed within the required accuracy with in-situ measurement with laser tracker. The inboard first wall and the upper divertor were installed for the limiter configuration at the plasma initiation and the divertor configuration, respectively. They have carbon tiles as the first wall, which must be installed with accuracy of ± 1 mm in order to avoid the heat concentration. However, the vacuum-vessel wall had some deformation. Therefore, we measured in advance with laser tracker the position of the vacuum vessel where the bases of the inboard first wall and upper divertor would be welded. By using these position data and 3D CAD, we customized all bases. Owing to these procedures, we could install the first wall with required accuracy. Also, all other components were installed with required accuracy. [ABSTRACT FROM AUTHOR]