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The electrical insulation of the Megavolt ITER Injector and Concept Advancement (MITICA) beam source (BS) at 1 MV in vacuum is a challenging issue, which could not be fully addressed so far on the basis of experimental results and of theoretical models available in literature. A specific high-voltage (HV) test campaign is being prepared to validate and optimize the voltage holding capability of the BS insulation under realistic conditions, using full-size mockup electrodes reproducing in detail the geometry of the BS and accelerator. The proposed test strategy will address both the single-gap and the multistage insulation, so as to obtain a verification of voltage holding at 1 MV before the installation of the real components. This approach is intended to reduce the risk related to the HV insulation at 1 MV and, if necessary, to allow the development of effective corrections. In this article, the test motivations and requirements are defined, and the electrode implementation and diagnostic setup are described. Finally, the test configurations and the experimental procedure are discussed.

The origin of longitudinal beam non-uniformity, which is one of the key issues in large caesium (Cs)-seeded negative ion sources for fusion application, was experimentally investigated in the JAERI 10 A negative ion source. A sufficient caesium was seeded in the negative ion source to enhance the negative ion production. The beam intensity with Cs was typically four times higher than that without Cs, and was relatively high in the upper region where the electron temperature and plasma density were relatively high. This distribution was significantly different from that without Cs. From the correlation between the beam intensity and the plasma parameters, it was found that the beam non-uniformity was due to the localization of the plasma.

The present objective of the 1?MeV electrostatic accelerator R&D for the ITER NB system is the acceleration of ampere class negative ion beams at the required current density (200?A?m?2) up to the beam energy of 1?MeV. To produce such high current density H?ions, the KAMABOKO negative ion source was operated under high power arc discharge (?40?kW) and with Caesium seeding for enhancement of the negative ion surface production. The H?ion beams of 146?A?m?2(total ion current: 0.2?A) have been obtained stably at the beam energy of 836?keV (pulse length: ?0.2?s). The pulse length was limited due to the power density of the beams, which is more than twice as high as those of the existing negative ion based NB systems (JT-60U and LHD). A preliminary measurement of beam optics showed a beamlet divergence of ?5?mrad even in the beams of such high power density. The Bremsstrahlung generation as a consequence of electron acceleration was estimated. A discussion then follows for photoelectron production and possible breakdowns in insulators for the acceleration of higher current negative ions.

Major issues of neutral beam (NB) injector power supplies are high-speed switching, regulation and transmission of dc ultra-high voltage (UHV) and suppression of surge energy input to the beam source at high voltage breakdown. A gate turn-off thyristor inverter type power supply where the control is performed on the low voltage ac side was designed for the ITER NB. Based on the remarkable progress of a high power IEGT (injection enhanced gate transistor), the design of the inverter has been modified to increase efficiency and compactness using such new elements. The power loss in the inverter is reduced to 0.5?MW from 1.6?MW by adopting the IEGT inverter system at the same frequency of 150?Hz. Further, power supply performance has been studied for higher frequency operation of the inverter at 300?Hz. It was confirmed that the voltage regulation was stable even when the filter capacitor was reduced to 1/5 of the original value by circuit simulation. For the transmission line of the dc UHV with intermediate voltages, a disc shape multi-conductor bushing with a transmission line test chamber has been developed. The dimensions of the bushing are 1.8?m (diameter) and 140?mm (thickness) at the edge. Electric fields at the conductor surface and insulator surface were designed to be lower than 5?kV?mm?1and 7?kV?mm?1, respectively. An electric field at the bottom of the ground potential outer conductor was designed to be lower than 1.2?kV?mm?1to prevent particle levitation which triggers breakdown. The prototype transmission line has passed the lightning impulse test up to 1300?kV. A dc UHV up to 1175?kV was successfully sustained for 300?s. To prevent electric damage of the beam source at high voltage breakdown, core snubbers using Fe-based nanocrystalline soft magnetic materials have been adopted to dissipate the surge energy.

R&D pertaining to a 1 MeV accelerator and a large negative ion source has been carried out at the Japan Atomic Energy Research Institute for the ITER neutral beam system. The R&D is, at present, progressing towards: (1) 1 MeV acceleration of H⁻ ion beams at the ITER relevant current density of 200 A m⁻² and (2) improvement of uniform negative ion production over wide extraction area in large negative ion sources. Recently, H⁻ ion beams of 1 MeV and 140 mA level have been generated with a substantial beam current density (100 A m⁻²). In the uniformity study, it was clarified that the electron temperature in the ion extraction region was locally high (>1 eV), which resulted in the destruction of negative ions at a high reaction rate. Interception of fast electrons leaking through a transverse magnetic field called ‘magnetic filter’ has been found to be effective in lowering the local electron temperature, followed by an improvement of negative ion beam profile.

AbstractBackground/Aim: Brain atrophy is known to develop more rapidly in hemodialysis (HD) patients than other individuals. The present study was designed to examine the role of HD-related hypotension in brain atrophy in patients on chronic HD. Methods: By using magnetic resonance imaging, whole brain atrophy was assessed by the ventricular-brain ratio (VBR; ventricular area/whole brain area). Frontal brain atrophy was assessed by the frontal atrophy index (FAI; frontal brain area/intracranial frontal space). The number of lacunae was also counted. We studied 32 HD patients without symptomatic neurological abnormalities or diabetes mellitus: male/female ratio 19/13; mean age ± SD 53 ± 10 (range 28–77) years; mean HD duration ± SD 11 ± 6 (range 1–22) years. Magnetic resonance imagings were taken in 1995 and 1998. All dialysis-related hypotension episodes during the same period were identified from the medical records and counted. Results: The VBR ranged from 8.8 to 18.7% in 1995 (12.8 ± 2.2%) and was not different in 1998 (13.1 ± 2.7%). However, the VBR increased by more than 5% in 14 patients, and their HD duration of 13 ± 6 years was significantly longer than that of 18 patients with stable VBR (p < 0.05). The FAI in 1995 was 62.2 ± 4.2% (range 55.8–71.3%) and decreased significantly to 59.7 ± 4.7% (range 50.2–70.9%) in 1998 (p < 0.05). The change in FAI correlated significantly with both the total number of dialysis-related hypotension episodes (r = 0.45, p < 0.05) and the increase in number of lacunae (r = 0.42, p < 0.05). Conclusion: Our results suggest that dialysis-related hypotension plays a role in progressive frontal lobe atrophy in HD patients.Copyright © 2004 S. Karger AG, Basel

The injection performance of the negative-ion based NBI (N-NBI) system for JT-60U has been improved by correcting beamlet deflection and improving spatial uniformity of negative ion production. Beamlet deflection at the peripheral region of the grid segment due to the distorted electric field at the bottom of the extractor has been observed. This was corrected by modifying the surface geometry at the extractor to form a flat electric field. Moreover, beamlet deflection due to beamlet–beamlet repulsion caused by space charge was also compensated for by extruding the edge of the bottom extractor. This resulted in a reduction of the heat loading on the NBI port limiter. As a result of the improvement above, continuous injection of a 2.6 MW H⁰ beam at 355 keV has been achieved for 10 s. Thus, long pulse injection up to the nominal pulse duration of JT-60U was demonstrated. This has opened up the prospect of long pulse operation of the negative-ion based NBI system for a steady-state tokamak reactor. So far, a maximum injection power of 5.8 MW at 400 keV, with a deuterium beam, and 6.2 MW at 381 keV, with a hydrogen beam, have been achieved in the JT-60U N-NBI. Uniformity of negative ion production was improved by tuning the filament emission current so as to direct more arc power into the region where less negative ion current was extracted.

AbstractLong-term inhibition of nitric oxide synthase (NOS) in rats is known to cause systemic hypertension and renal parenchymal injury. We have previously reported that activation of intra-renal renin-angiotensin system was a major contributing factor for renal injury in chronically NOS-inhibited rats. Massive interstitial infiltration of monocytes/macrophages (M/M) was characteristically seen in this model. The present study was performed to elucidate the role of chemokines, RANTES and MCP-1, in promoting M/M recruitment into the renal cortex. The number of infiltrating ED-1-positive cells was examined in association with the level of expression of RANTES and MCP1 mRNAs in the renal cortex of rats treated orally for 12 weeks with L-NAME. Compared to controls rats, the number of infiltrating ED-1-positive cells was significantly higher in L-NAME-treated rats. The mRNA expressions of both RANTES and MCP-1 were significantly higher in L-NAME-treated rats than the control. In L-NAME-treated rats, the high number of ED-1-positive cells and increased expression of both RANTES and MCP-1 were suppressed by ACE inhibitor, but not by hydralazine. In contrast, neither ED-1 counts nor RANTES mRNA expression were affected by angiotensin (Ang) II type 1 receptor antagonist. These results suggest the likely involvement of RANTES and MCP-1 in the recruitment of M/M into the renal cortex of rats with chronic NOS inhibition. Furthermore, it is also indicated that Ang II stimulates MCP-1 expression via Ang II type 1 receptor, whereas RANTES expression is mediated via Ang II type 2 receptor.Copyright © 2002 S. Karger AG, Basel

The proteoglycan aggrecan is an important major component of cartilage matrix that gives articular cartilage the ability to withstand compression. Increased breakdown of aggrecan is associated with the development of arthritis and is considered to be catalyzed by aggrecanases, members of the ADAM-TS family of metalloproteinases. Four endogenous tissue inhibitors of metalloproteinases (TIMPs) regulate the activities of functional matrix metalloproteinases (MMPs), enzymes that degrade most components of connective tissue, but no endogenous factors responsible for the regulation of aggrecanases have been found. We show here that the N-terminal inhibitory domain of TIMP-3, a member of the TIMP family that has functional properties distinct from other TIMPs, is a strong inhibitor of human aggrecanases 1 and 2, with K(i) values in the subnanomolar range. This truncated inhibitor, which lacks the C-terminal domain that is responsible for interactions with molecules other than active metalloproteinases, is produced at high yield by bacterial expression and folding from inclusion bodies. This provides a starting point for developing a biologically available aggrecanase inhibitor suitable for the treatment of arthritis.

The eukaryotic cell cycle is regulated by cyclin-dependent kinases (CDKs). CDK4 and CDK6, which are activated by D-type cyclins during the G(1) phase of the cell cycle, are thought to be responsible for phosphorylation of the retinoblastoma gene product (pRb). The tumor suppressor p16(INK4A) inhibits phosphorylation of pRb by CDK4 and CDK6 and can thereby block cell cycle progression at the G(1)/S boundary. Phosphorylation of the carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase II by general transcription factor TFIIH is believed to be an important regulatory event in transcription. TFIIH contains a CDK7 kinase subunit and phosphorylates the CTD. We have previously shown that p16(INK4A) inhibits phosphorylation of the CTD by TFIIH. Here we report that the ability of p16(INK4A) to inhibit CDK7-CTD kinase contributes to the capacity to induce cell cycle arrest. These results suggest that p16(INK4A) may regulate cell cycle progression by inhibiting not only CDK4-pRb kinase activity but also by modulating CDK7-CTD kinase activity. Regulation of CDK7-CTD kinase activity by p16(INK4A) thus may represent an alternative pathway for controlling cell cycle progression.

A hierarchical interaction theory is presented, which can treat hydrodynamic interactions among a great number of bodies rigorously in the framework of linear potential theory. After checking numerical accuracy and convergence for a square array of 64 half-immersed spheres, the theory is applied to column-supported structures with 1280, 2880, and 5120 equally spaced circular cylinders as supporting columns. With the computed hydrodynamic and hydrostatic forces, the motion equation of an upper deck is solved using the mode-expansion method. Trapped-wave phenomena among a large number of columns are observed at relatively short waves, and numerical examples of those effects on the elastic deflection of the upper deck and the wave pattern around column-supported structures are also shown.

By using differential mRNA display to monitor the molecular alterations associated with adaptation of euryhaline eels to different salinities, we identified a cDNA fragment strongly induced in seawater eel gills. Cloning of a full-length cDNA and its expression in COS-7 cells indicated that the clone codes for an inward rectifier K+ channel (eKir) of 372 amino acid residues, which has two transmembrane segments and a typical pore-forming region (H5). Only low sequence similarities are present, except the H5 region, compared with other members of the inward rectifier K+ channel family (Kir). Consistent with this divergence in the amino acid sequence, a phylogenetic analysis indicated early divergence and independent evolution of eKir from other members; it is only distantly related to the Kir5.0 subfamily members. RNase protection analysis showed that eKir is highly expressed in the seawater eel gill, kidney, and posterior intestine but very weakly in freshwater eels. Immunohistochemistry of gill sections revealed dense localization of eKir in the chloride cells. Immunoelectron microscopy indicated that eKir is mainly present in the microtubular system in the chloride cell. This location and its salt-inducible nature suggest that the eKir channel cloned here is a novel member of the Kir5.0 subfamily of the Kir family and is implicated in osmoregulation.

Key words: acute renal failure; antipsychotic agents; computed tomography; magnetic resonance imaging; neuroleptic malignant syndrome; rhabdomyolysis

Objectives To identify the clinical, electrophysiological, histological, and genetic characteristics of a Japanese family with a muscle cramp syndrome. Methods Fourteen patients (eight men, six women) were studied in four generations of a single family. Electrophysiological examinations were performed in four cases and muscle and nerve biopsies were performed on the propositus. Results The mode of inheritance seemed to be autosomal dominant. The cramps occurred during both exertion and at rest, and during sleep. Electromyographic examination indicated a neurogenic aetiology. There was a decreased number of large myelinated fibres in the sural nerve, and fibre type grouping in the quadriceps femoris muscle biopsy. Conclusions The autosomal dominant muscle cramp syndrome in this family is probably caused by a polyneuropathy.

A novel galactosylalkylglycerol modified with a long-chain cyclic acetal at the sugar moiety, 3-O-(4'6'-plasmalogalactosyl) 1-O-alkylglycerol, was isolated from equine brain. The presence of cyclic acetal linkage, its linked position, and the length of the acetal chain of the natural plasmalo lipid were determined by proton NMR spectroscopy and fast-atom bombardment;-mass spectrometry, as well as gas chromatography;-mass spectrometry and gas;-liquid chromatography. To identify the isomeric stereostructure of the natural product, the plasmalo derivative was chemically synthesized from 3-O-galactosyl 2-O-acyl 1-O-alkyl glyceride through acetalization after deacylation. As a result, the direction and position of the acetal chain of the natural plasmalo lipid were characterized as an "endo"-type 4',6'-O-acetal derivative linked to galactoside by comparison with the NMR data of the synthesized product. The chain lengths of alkyl and acetal groups were C(14) for the former and C(16) and C(18) for the latter, and those for the latter group were mostly similar to those of plasmalogalactosyl ceramide, which was previously isolated from equine brain.

Abstract:: We report two patients with biopsy-proven focal myositis, successfully treated with a peripheral arterial injection of low-dose prednisolone. Spin-echo T2-weighted magnetic resonance images helped to identify affected muscles and proved to be useful for montoring treatment.

A highly potent cardiotonic polypeptide, anthopleurin‐A, was isolated from the sea anemone, Anthopleura xanthogrammica(Brandt), using solvent partition, gel permeation chromatography, and cation‐exchange chromatography. It is a pure basic polypeptide with a molecular weight of about 5500.

Modified galactosylceramide with a long-chain cyclic acetal at the sugar moiety, plasmalogalactosylceramide, was isolated from equine brain. To identify the isomeric stereostructure of the natural product, the plasmalo derivative was chemically synthesized from galactosylceramide through acetalization. The presence of cyclic acetal linkage, the linked position and length of the acetal chain of the synthesized and natural products were determined by proton nuclear magnetic resonance spectroscopy and fast-atom bombardment-mass spectrometry, as well as gas chromatography-mass spectrometry and gas-liquid chromatography. The orientation of the acetal chain linked to galactoside was characterized by connectivity between the cyclic acetal proton and ring proton(s) on the sugar moiety using the homonuclear Overhauser effect. This revealed that, of the two positional isomers of the acetal linkage with 4,6-O-acetal and 3,4-O-acetal derivatives obtained from the acetalization reaction, the former positional isomer, separated into two spots, was identified to 'endo'- and 'exo'-type acetal chains. In comparison to the NMR data of the synthesized derivative, equine brain acetalized lipid was found to be an 'endo'-type 4,6-O-acetal derivative.

BACKGROUND & AIMS: Urokinase plasminogen activator (uPA) regulates plasmin generation from plasminogen. The aim of this study was to analyze the role of the plasminogen activator/plasmin system in chronic pancreatitis (CP). METHODS: Using Northern blot analysis, in situ hybridization, and immunohistochemistry, the expression of uPA, its receptor (uPAR), plasminogen activator inhibitor 1 (PAI-1), and transforming growth factor beta 1 (TGF-beta 1) was studied in 14 patients undergoing pancreatic resection for CP. Normal control pancreatic tissue was obtained through an organ donor program. RESULTS: Eight of 14 CP samples showed concomitant increased expression (P < 0.001) of uPA (5.2-fold), uPAR (5.9-fold), and TGF-beta 1 (8.8-fold) messenger RNA (mRNA) compared with normal controls. PAI-1 mRNA expression was increased (6.5-fold; P < 0.001) in all CP samples. By in situ hybridization, moderate to strong mRNA staining of all four factors was present in acinar cells, some ductal cells, and areas with ductal metaplasia in CP samples. A similar staining pattern was found by immunohistochemistry. Intense mRNA and immunostaining for all of these factors in CP samples was associated with a higher degree of pancreatic damage. CONCLUSIONS: uPA and its receptor may contribute to the lytic damage observed in CP by plasmin generation. Similarly, increased amounts of plasmin may activate latent TGF-beta, thereby leading to the accumulation of fibrotic tissue. (Gastroenterology 1997 Sep;113(3):904-13)

Extracts of 107 marine alga specimens from Pacific islands were tested for P-388 lymphocytic leukemia and Ehrlich ascites tumor in mice. Several specimens showed high antitumor activity in both systems, with some featuring a notable lack of toxicity.

A total of 110 plant parts from 34 different species of medicinal and toxic plants was collected for pharmacological testing in or near the Lefaga District on the island of Upolu in Western Samoa. Voucher specimens of all species were also made. From the 110 plant parts, 211 different extracts were prepared and evaluated for antiviral, antibacterial, and anti-Ehrlich ascites tumor properties and for effects on blood pressure, heart rate, respiration, electrocardiogram, electroencephalogram, and gastric motility. Twelve extracts were effective in vitroas antibacterial agents and six inhibited Ehrlich ascites tumor growth in mice. Ninety-one extracts showed hypotensive properties, 31 for more than 30min.

Crude aqueous ethanol extracts of nine out of 12 species of anthozoans and the one scyphozoan examined showed varying degrees of positive inotropic and chronotropic effects on isolated rat atria. This is the first report of what may be rather widely occurring heart stimulants of possible practical utility among the Coelenterata.

Reaction of selenium with 2 equivalents of dimethyl acetylenedicarboxylate (I) produces the selenophentetracarboxylate (II).

The formation of shallow p+n junction with B+implantation in silicon was investigated. A rapid diffusion of implanted borons was observed in the initial stage of the annealing for activation (in 10 sec), and it was independent of the annealing temperature (600?1000°C) and determined the shallower limit of B+implanted p+n junction depth, 0.25 and 0.4 microns for the B+acceleration of 10 and 20 KV, respectively. Appropriate Si+implantation subsequent to B+implantation enabled the annealing temperature reduction to about 600°C with activation (sheet resistivity) and crystallinity (junction quality) comparable to those of high temperature annealing (900?1000°C). It is suggested that the rapid diffusion and the reduction in the annealing temperature resulted from the excess configuration entropy in the ion implanted layer which corresponded to high temperature situation in effect.