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Acral melanoma (AM) is an epidemiologically and molecularly distinct entity that is underrepresented in clinical trials on immunotherapy in melanoma. We aimed to analyze the efficacy of anti-programmed cell death 1 (anti-PD-1) antibodies in advanced AM.We retrospectively evaluated unresectable stage III or stage IV AM patients treated with an anti-PD-1 antibody in any line at 21 Japanese institutions between 2014 and 2018. The clinicobiologic characteristics, objective response rate (ORR, RECIST), survival estimated using Kaplan-Meier analysis, and toxicity (Common Terminology Criteria for Adverse Events 4.0.) were analyzed to estimate the efficacy of the anti-PD-1 antibodies.In total, 193 patients (nail apparatus, 70; palm and sole, 123) were included in the study. Anti-PD-1 antibody was used as first-line therapy in 143 patients (74.1%). Baseline lactate dehydrogenase (LDH) was within the normal concentration in 102 patients (52.8%). The ORR of all patients was 16.6% (complete response, 3.1%; partial response, 13.5%), and the median overall survival (OS) was 18.1 months. Normal LDH concentrations showed a significantly stronger association with better OS than abnormal concentrations (median OS 24.9 versus 10.7 months; P0.001). Although baseline characteristics were similar between the nail apparatus and the palm and sole groups, ORR was significantly lower in the nail apparatus group [6/70 patients (8.6%) versus 26/123 patients (21.1%); P = 0.026]. Moreover, the median OS in this group was significantly poorer (12.8 versus 22.3 months; P = 0.03).Anti-PD-1 antibodies have limited efficacy in AM patients. Notably, patients with nail apparatus melanoma had poorer response and survival, making nail apparatus melanoma a strong candidate for further research on the efficacy of novel combination therapies with immune checkpoint inhibitors.

In an attempt to study the gene products of the HLA complex, a monoclonal antibody, named HU-30, was produced by immunizing BALB/c mice with a cultured human B lymphoblastoid cell line, Shi-C3 (Aw24, Aw31, Bw51, Bw52, DR2, DR blank, MT1, MT2, MB3). HU-30 belonged to the IgG2 subclass and was active in complement dependent cytotoxicity. When the serological specificity was evaluated with a panel of 15 cultured human lymphoblastoid cell lines, it was found that HU-30 detected a polymorphic determinant, common to HLA-DR1 and 2, with much stronger cytotoxic activity against HLA-DR2 positive B cell lines. When HU-30 was tested against a panel of B cells from 84 healthy donors at a dilution of 2(-13), it gave positive reactions only with cells typed as HLA-DR2. Furthermore, sequential coprecipitation studies indicated that the HU-30 determinant was borne on the molecules carrying the HLA-DR determinants. Thus, HU-30 appears to be of great value as a tissue typing reagent monospecific for HLA-DR2.

We have performed soft X-ray angle-resolved photoemission spectroscopy (SXARPES) of a heavily boron-doped superconducting diamond film (Tc=7.2 K) in order to study the electronic structure near the Fermi level (EF). Careful determination of measured momentum space that across Γ point in the Brillouin zone (BZ) and increase of an energy resolution provide further spectroscopic evidence that EF is located at the highly dispersive diamond-like bands, indicating that holes at the top of the diamond-like valence band play an essential role for the conducting properties of the heavily boron-doped superconducting diamond for this boron-doping region (effective carrier concentration of 1.6%). The SXARPES intensities at EF were also mapped out over BZ to obtain experimental Fermi surface sheets and compared with calculations.

We have performed scanning tunneling microscopy/spectroscopy (STM/STS) experiments on (1 1 1)-oriented epitaxial films of heavily boron-doped diamond ( T c ∼5.4 K). We present that tunneling conductance spectra show temperature-dependent spatial variations. In the low-temperature region ( T =0.47 K), the tunneling spectra do not show strong spatial dependence and a superconducting energy gap is observed independent of the surface morphology. In the high-temperature region ( T =4.2 K), on the other hand, the tunneling conductance spectra show significant spatial dependence, indicating the inhomogeneous distribution of the superconducting property due to the distribution of boron atoms.

The JT-60 Super Advanced (JT-60SA) tokamak aims to perform the ITER support and to demonstrate steady-state high-beta plasma project with the collaboration between Japan and EU. To attain these objectives, the negative-ion-based NBI (N-NBI) system is required to inject 10 MW for 100 s at the beam energy of 500 keV. On JT-60U, the present N-NBI ion source has injected 3.2 MW for 21 s at 320 keV; however, three key issues should be solved for the JT-60SA N-NBI ion source. One is to improve the voltage holding capability of the large negative ion source, where the available acceleration voltage has been limited to less than ~400 kV due to breakdowns. The accelerator of the JT-60U ion source is composed of large three-stage grids and three fiberglass reinforced plastic (FRP) insulators. Recent R&D tests suggested that the FRP insulators were not the main factor to trigger the breakdowns at the early conditioning stage. The accelerator with a large area of grids and their supporting structure may need a high margin in the design of electric field and a long time for conditioning. The second issue is to reduce the power loading of the acceleration grids. It was found that some beamlets were strongly deflected due to beamlet-beamlet interaction and strike on the grounded grid in the accelerator. Moreover, the electrons generated in the accelerator caused the grid loading and the overheating of the beamline components. The acceleration grids for JT-60SA are to be designed by taking account of the beamlet-beamlet interaction and the applied magnetic field in 3-D simulation. Third is to maintain the D production for 100 s. Although a constant D- beam power was confirmed on JT-60U for 21 s, an active cooling system is required to keep the temperature of the plasma grid (PG) under optimum condition during 100-s operation. A simple cooling structure is proposed for the active cooled PG, where a key is the temperature gradient on the PG for uniform D- production. In the present schedule, design work, reflecting the latest R&D progress, will continue until ~2011. The modified N-NBI ion source will start on JT-60SA in 2015.

The control system of the cryogenic facility in the JT-60 NBI system has been replaced by employing the PLC (Programmable Logic Controller) and SCADA (Supervisory Control And Data Acquisition) system. The original control system was constructed about 20 years ago by specifying the DCS (Distributed Control System) computer to deal with ∼400 feedback loops. Recently, troubles on this control system have increased due to its age-induced deterioration. To maintain the high reliability of the cryogenic facility, a new control system has been planned with the PLC and SCADA systems. Their attractive features include high market availability and cost-effectiveness, however, the use of PLC for such a large facility with ∼400 feedback loops has not been established because of insufficient processing capability of the early PLC. Meanwhile, the recent progress in the PLC enables to use the FBD (function block diagram) programming language for 500 function blocks. By optimizing the function blocks and connecting them in the FBD language, the feedback loops have been successfully replaced from DCS to PLC without a software developer. Moreover, an oscillation of the liquid He level, which often occurs during the cooldown mode of the cryopumps, can be automatically stabilized by easily adding a new process program in the PLC. At present, the new control system has worked well.

Modification of JT-60U to a superconducting device (so called JT-60SA) has been planned to contribute to ITER and DEMO. The NBI system is required to inject D 0 beams of 34 MW for 100 s. The upgraded NBI system for JT-60SA consists of 12 positive-ion-based NBI (P-NBI) units and one negative-ion-based NBI (N-NBI) unit. The injection powers of each P-NBI and N-NBI units are 2 MW at 85 keV and 10 MW at 500 keV, respectively. On JT-60U, the long pulse operations of 30 s at 2 MW and 20 s at 3.2 MW have been achieved on the P-NBI and N-NBI units, respectively. Both units have demonstrated no injection power degradation for long pulse operation. It has been also found that the thermal time constants of the main key components with active cooling, such as the ion source of the present NBI system, are less than ∼20 s. Therefore, the pulse extension up to 100 s is expected to need some modifications mainly the power supply system. In addition, the voltage-holding capability of the negative ion source is required to be improved. The detailed technical design of the NBI system for JT-60SA is presented.

Superconductivity was achieved above 10 K in heavily boron-doped diamond thin films deposited by the microwave plasma-assisted chemical vapor deposition (CVD) method. Advantages of the CVD method are the controllability of boron concentration in a wide range, and a high boron concentration, compared to those obtained using the high-pressure high-temperature method. The superconducting transition temperatures of homoepitaxial (111) films are determined to be 11.4 K for TC onset and 8.4 K for zero resistance from transport measurements. In contrast, the superconducting transition temperatures of (100) films TC onset = 6.3 K and TC zero = 3.2 K were significantly suppressed.

The apoptosis-inducing Fas ligand (FasL) is expressed in a variety of human cancers and has been implicated in tumor immune evasion. Paradoxically, ectopic expression of FasL in experimental tumors triggers a neutrophil-mediated inflammatory response and tumor rejection. To resolve these conflicting findings, we have established B16 melanoma and P29 Lewis lung carcinoma lines expressing different levels of FasL and examined their tumorigenicity in vivo. While tumors with a high level of FasL were rapidly rejected as previously reported, those expressing a low level of FasL were not rejected but grew faster than did FasL-negative parental cells. The growth enhancement of FasL(low) tumors was not observed in T-cell-deficient nude mice, suggesting that FasL expressed in tumors at low levels counteracted against T-cell-dependent antitumor responses. In support of this notion, FasL(low) tumors were found to grow faster than parental cells in mice that had acquired tumor-specific immunity. Furthermore, histological examinations revealed apoptosis of lymphocytes in tissue sections of FasL(low) tumors. These results collectively suggest that FasL on tumors is a double-edged sword: at high levels it triggers tumor rejection whereas at low levels it facilitates tumor growth possibly by suppressing antitumor immune responses.

The 500 keV negative-ion based neutral beam injector for JT-60U started operations in 1996. The availability of the negative ion based neutral beam injection system has been improved gradually by modifying the ion source and optimizing its operation parameters. Recently, the extension of the pulse duration up to 30 s has been intended to study quasi-steady state plasma on JT-60U. The most serious issue is to reduce the heat load on the grids for long pulse operation. Two modifications have been proposed to reduce the heat load. One is to suppress the spread of beamlet-bundle which may be caused by beamlet–beamlet interaction in the multi-aperture grid due to the space charge force. Indeed, the investigation of the beam deflection, which was measured by the infrared camera on the target plate set 3.5 m away from the grid, indicates that the spread of beamlet-bundle is in proportion to the current density. Field-shaping plates were attached on the extraction grid to modify the local electric field. The plate thickness was optimized to steer the beamlet deflection. The other is to reduce the stripping loss, where the electron of the negative ion beam is stripped and accelerated in the accelerator and then collides with the grids. The ion source was modified to reduce the pressure in the accelerator column to suppress the beam-ion stripping loss. To date, long pulse injection of 19 s of 1.5–1.6 MW at a high energy beam of 360 keV, 9–10 A for D− has been obtained by one ion source with these modifications.

We have investigated the low-energy electronic state of boron-doped diamond thin film by the laser-excited photoemission spectroscopy. A clear Fermi-edge is observed for samples doped above the semiconductor–metal boundary, together with the characteristic structures at 150 � n meV possibly due to the strong electron–lattice coupling effect. In addition, for the superconducting sample, we observed a shift of the leading edge below T c indicative of a superconducting gap opening. We discuss the electron–lattice coupling and the superconductivity in doped diamond. r 2006 NIMS and Elsevier Ltd. All rights reserved.

The dispersion of acoustic and optical phonons in highly boron-doped diamond has been measured by inelastic X-ray scattering at an energy resolution of 6.4 meV. The sample is doped in the metallic regime and shows superconductivity below 4.2 K (midpoint). The data are compared to pure and nitrogen-doped diamond that represent the non-metallic state. No difference is found for the acoustic phonons in the three samples, while the optical phonons show a shift of the dispersion (softening) in qualitative agreement with earlier results from Raman spectroscopy. The presence of boron and nitrogen incorporated into the diamond lattice leads to structural disorder. Evidence for this is found both in the observation of otherwise symmetry-forbidded Bragg intensity at (0 0 2) and intensity from acoustic phonon modes in the vicinity of (0 0 2).

We have investigated an origin of the superconductivity discovered in boron (B)-doped diamonds by means of 11B-NMR on heteroepitaxially grown (111) and (100) films and polycrystalline film. The characteristic difference of B-NMR spectral shape for the (111Þ and (100) thin films is demonstrated as arising from the difference in the concentration (nB(1)) of boron substituted for carbon. It is revealed from a scaling between a superconducting transition temperature Tc and nB(1) that the holes doped into diamond via the substitution of boron for carbon ar responsible for the onset of superconductivity. The result suggests that the superconductivity in boron-doped diamond is mediated by the electron–phonon interaction brought about a high Debye temperature ˜ 1860 K characteristic for the diamond structure.

The steady and transient stress responses were investigated from lower shear rates to higher shear rates at a given strength of the electric field, and the individual experimental conditions were reduced to Mason number ( M n). The electro-rheological response was found in the region with higher M n of the order of 10, and the transient response became faster as the shear rate increased. These results show that the effect of chance of collision among the polarized particles would play an important role even in the region.

We describe two Japanese female patients with pigmented extramammary Paget’s disease (EMPD); one patient had a dark brown plaque and the other had a reddish patch with a pigmented area, both affecting the vulval region. Histochemical and immunohistochemical examinations confirmed EMPD with melanocyte colonization; plump tumour cells with a large nucleus and pale cytoplasm that were positive for CAM 5.2 and CEA proliferated singly or in nests in the epidermis, and scattered among the tumour cells were many dendritic cells with a large amount of melanin that were positive for HMB-45 and S-100 protein. Fontana–Masson (FM) stain showed many positive cells with well-developed dendritic processes within and around tumour nests. Histochemical and immunohistochemical studies of non-pigmented EMPD cases on the same region showed that HMB-45 positive cells were sparse or not detected at all, and that also FM staining-positive cells were decreased or not detected, and their dendritic processes were poorly formed. The present study suggests that there might be heterogeneity in EMPD in terms of relationships between Paget’s cells and melanocytes.

We report the case of a 22-year-old woman with a nevoid plaque that we termed localized follicular hamartoma. The plaque was noticed at puberty on a unilateral site of the face and scalp. Clinically, it revealed numerous, skin-colored to light brown papules alone and in groups, occasionally bearing a single hair. Histologically, branched epithelial nests of squamoid and/or basaloid cells were revealed in connection with the interfollicular epidermis and the upper portions of hair follicles, of which the lower portions showed normal structures. Immunohistochemically, the epithelial nests showed the keratin expression consisted with that of the infundibular epithelium. S-100-positive cells were found in the epithelial nests and the stroma. Factor XIIIa-positive dendritic cells were numerous in adjacent to the epithelial nests. Ultrastructurally, immature melanocytes with a small number of premelanosomes and Merkel cells were found in the nests. Stromal dendritic cells showed the adherent features of the cytoplasmic processes to anchoring fibrils or basal lamina of the epithelial nests. From these findings, our case is a hamartoma, which seems to be an abortive growth of secondary hair germs with a limited differentiation to the upper follicular portion.

Construction of the 500 keV negative-ion-based NBI system (N-NBI) with its maximum capability of 10 MW and 10 s for NB current drive and plasma core heating in high-density plasmas in JT-60 was completed in March 1996. The neutral beam injection into JT-60 with N-NBI has been performed since then. One of the key issues in the injection was how to control the bending magnetic field for residual ion beams. In N-NBI for JT-60, a stray magnetic field from the tokamak was actively used for bending of the residual ion beams. Combination of the stray magnetic field from JT-60 and the magnetic field of the deflecting coils was controlled sufficiently to successfully deposit residual ion beams at a constant point on the ion dump surface. The deposited positive and negative beam profiles on the ion dump were measured with an array of thermocouples brazed on the dump surface. This report describes the performance test of bending the residual ion beams and the measurement of the heat load on the ion dump for JT-60 N-NBI experiments.

A beam injection experiment with the negative-ion based NBI system (N-NBI) started in March 1996 on JT-60U. After achieving the first neutral beam injection of 180 keV, ∼0.1 MW for 0.4 s into the JT-60U plasmas, the operation parameters of the ion source and power supply had been optimized for increasing the beam energy and beam current. In September 1996, a deuterium neutral beam of 2.5 MW at 350 keV was injected into JT-60U using two ion sources. In the operation with hydrogen at the beginning of 1997, a negative ion beam current of 18.4 A at 350 keV has been obtained, and a neutral beam of 3.2 MW at 350 keV for 1 s has been injected into the plasma with one ion source. A neutralization efficiency of negative ion beam has been confirmed to be about 60% at the beam energies of 250–385 keV as predicted theoretically.

A case of angiolymphoid hyperplasia with eosinophilia arising on the face of a woman is reported. Histologically, the uniqueness of this case is the presence of multinucleated cells (MNCs), besides the conventional dermal changes. Electron microscopy showed that some of the apparent MNCs are clusters of endothelial cells forming immature vascular lumens with numerous microvilli, and the other MNCs displayed the recognized features of fibrohistiocytic or myofibroblastic cells. Immunohistochemically, some MNCs were positive for Ulex europaeus agglutinin and Factor VIII-related antigen. From these findings, some of the MNCs are histologically endothelial sprouts, and the others are fibrohistiocytic cells in the present case.

The elevated expression of the norA gene is responsible for efflux-mediated resistance to quinolones in Staphylococcus aureus (E.Y.W. Ng, M. Trucksis, and D.C. Hooper, Antimicrob. Agents Chemother. 38:1345-1355, 1994). For S. aureus transformed with a plasmid containing the cloned norA gene, SA113(pTUS20) (H. Yoshida, M. Bogaki, S. Nakamura, K. Ubukata, and M. Konno, J. Bacteriol. 172:6942-6949, 1990), and an overexpressed mutant, SA-1199B (G.W. Kaatz, S.M. Seo, and C.A. Ruble, J. Infect. Dis. 163:1080-1086, 1991), the MICs of norfloxacin increased 16 and 64 times compared with its MICs for the recipient and wild-type strains, SA113 and SA-1199, respectively. MICs of CS-940, however, increased only two and eight times, even though these two fluoroquinolones are similarly hydrophilic (apparent logPs of approximately -1). No good correlation was found, among 15 developed and developing quinolones, between the increment ratio in MICs and hydrophobicity (r = 0.61). Analysis of the quantitative structure-activity relationship among 40 fluoroquinolones revealed that the MIC increment ratio was significantly correlated with the bulkiness of the C-7 substituent and bulkiness and hydrophobicity of the C-8 substituent of fluoroquinolones (r = 0.87) and not with its molecular hydrophobicity (r = 0.47). Cellular accumulation of norfloxacin in SA-1199B was significantly lower than that in SA-1199, and it was increased by addition of carbonyl cyanide m-chlorophenyl hydrazone. On the other hand, accumulations of CS-940 in these strains were nearly identical, and they were not affected by addition of the protonophore.

Using Josephson chips maintained at 4.4 K by a closed-cycle 3-W desk-size refrigerator, the authors verified the correct operation of a 4-b Josephson microprocessor up to 1.1 GHz. Room temperature and liquid He temperature regions are connected with a 130-ps delay using I/O cables passing through sidewalls of a vacuum vessel. It is proposed that both semiconductor and Josephson devices can coexist on circuit boards that constitute the equivalent of a single board. >

Laser-excited photoemission spectroscopy is used to show that the doped carriers in metallic or superconducting diamond couple strongly to the lattice via high-energy ($\ensuremath{\sim}150\text{ }\text{ }\mathrm{meV}$) optical phonons, with direct observations of localized Franck-Condon multiphonon sidebands appearing as Fermi-edge replicas. It exhibits a temperature-dependent spectral weight transfer from higher to lower energy sidebands and zero-phonon Fermi-edge states. The quantified coupling strength shows a systematic increase on lowering temperature, implicating its relation to the normal state transport and superconductivity.

The first long pulse production of high power D(-) ion beams has been demonstrated in the JT-60 U negative ion sources, each of which was designed to produce 22 A, 500 keV D(-) ion beams. Voltage holding capability and the grid power loading were examined for long pulse production of high power D(-) ion beams. From the correlation between voltage holding and the light intensity of cathodoluminescence from the Fiber Reinforced Plastic insulators, the acceleration voltage for stable voltage holding capability was found to be less than 320-340 kV where the light was sufficiently suppressed. By tuning the extraction voltage, the grid power loadings in the ion sources were decreased to the allowable levels for long pulse injection without a significant reduction of the beam power. After tuning the acceleration and extraction voltages, D(-) ion beams of 12.5 and 9.8 A were produced at 340 keV with cesium seeding at a rate of approximately 14 microg/s into the ion sources. The pulse duration of these D(-) ion beams was extended step by step, and then was successfully extended up to 18 s without degradation of the negative ion production. The D(-) ion beams were neutralized to yield 3.6 MW D(0) beams by a gas cell, and then injected into the JT-60 U plasma. Further, a slight reduction of D(-) ion beam power allowed the longer injection duration of 21 s at a D(0) beam power of 3.2 MW. The success in the long pulse production of a high power D(-) ion beam shows that negative ion beams can be produced during a few tens of seconds without degradations of negative ion production and the voltage holding in a large Cs-seeded negative ion source.

T. Yokoya,1,2 E. Ikenaga,2 M. Kobata,2 H. Okazaki,1 K. Kobayashi,2 A. Takeuchi,2 A. Awaji,2 Y. Takano,3 M. Nagao,3 I. Sakaguchi,3 T. Takenouchi,4 K. Kobayashi,4 H. Kawarada,4 and T. Oguchi5 1The Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Okayama 700-8530, Japan 2Japan Synchrotron Radiation Research Institute (JASRI)/SPring-8, 1-1-1 Kouto, Sayo, Hyogo 679-5198, Japan 3National Institute for Materials Science, 1-2-1 Sengen, Tsukuba, Ibaraki 305-0047, Japan 4School of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku, Tokyo 169-8555, Japan 5Department of Quantum Matter, Graduate School of Advanced Sciences of Matter (ADSM), Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8526, Japan Received 7 November 2006; revised manuscript received 12 April 2007; published 21 May 2007

We observe strong softening of optical phonon modes in superconducting (Tc = 4.2 K) borondoped diamond near the Brillouin zone center using inelastic x-ray scattering from a CVD-grown highly oriented sample. The magnitude of the softening, and our observation that it becomes stronger approaching zone center, supports theoretical models suggesting a phonon-mediated pairing mechanism via coupling of optical phonon modes to Fermi surfaces around the zone center. The electron-phonon coupling parameter is determined as approximately λ = 0.33.

We have investigated the superconductivity discovered in boron-doped diamonds by means of $^{11}\mathrm{B}\text{\ensuremath{-}}\mathrm{NMR}$ on heteroepitaxially grown (111) and (100) films. $^{11}\mathrm{B}\text{\ensuremath{-}}\mathrm{NMR}$ spectra for all of the films are identified to arise from the substitutional B(1) site as single occupation and lower symmetric B(2) site substituted as $\text{boron}+\text{hydrogen}$ $(\mathrm{B}+\mathrm{H})$ complex, respectively. Clear evidence is presented that the effective carriers introduced by B(1) substitution are responsible for the superconductivity, whereas the charge neutral B(2) sites does not offer the carriers effectively. The result is also corroborated by the density of states deduced by $1∕{T}_{1}T$ measurement, indicating that the evolution of superconductivity is driven by the effective carrier introduced by substitution at B(1) site.

Heavily-boron-doped diamond films become superconducting with critical temperatures $T_c$ well above 4 K. Here we first measure the reflectivity of such a film down to 5 cm$^{-1}$, by also using Coherent Synchrotron Radiation. We thus determine the optical gap, the field penetration depth, the range of action of the Ferrell-Glover-Tinkham sum rule, and the electron-phonon spectral function. We conclude that diamond behaves as a dirty BCS superconductor., Comment: 4 pages including 3 figures

We have investigated the low energy electronic state of a boron-doped diamond thin film by the ultrahigh resolution laser-excited photoemission spectroscopy. We observed a clear shift of the leading edge below 11 K indicative of a superconducting gap opening ($\Delta \sim 0.78$ meV at 4.5 K). The gap feature is significantly broad and the well-defined quasiparticle peak is not recognizable even at the lowest temperature of measurement 4.5 K. We discuss our result in terms of possible disorder effect on superconductivity in this system., Comment: 12 pages, 4 figures

Recent photoemission studies on heavily boron-doped superconducting diamond films, reporting the electronic structure evolution as a function of boron concentrations, are reviewed. From soft X-ray angle-resolved photoemission spectroscopy, which directly measures electronic band dispersions, depopulation of electrons (or formation of hole pockets) at the top of the valence band were clearly observed. This indicates that the holes at the top of the valence bands are responsible for the metallic properties and hence superconductivity at lower temperatures. Hard X-ray photoemission spectroscopy observed shift of the main C 1s core level and intensity evolution of a lower binding energy additional structure, suggesting chemical potential shift, carrier doping efficiency by boron doping, and possibility of boron-related cluster formations.

The pulse duration of the negative ion based NBI system has been extended from 10 s to 25 s to study long pulse plasmas on JT-60U. A feedback control technique has been demonstrated to keep the arc power constant by controlling the filament voltage for long pulse operation. Thus it was clearly observed that the negative ion beam current increased with the temperature of the plasma grid at constant arc power. A tapered filament is employed to improve its durability for the next operational campaign. Moreover, a high voltage holding test indicates that the reduction in the outgassing from the FRP (fiberglass-reinforced plastic) insulator may be a key to suppress the breakdowns in the ion source

The recent discovery that heavily boron-doped diamond is a superconductor with a transition temperature of 7.4 K raises the prospect of superconducting devices with the unique properties of diamond. A study of the electronic structure responsible for superconductivity in heavily boron-doped diamond supports the idea that superconductivity is phonon-mediated, and provides information on the electronic structure that must be retained in order to harness this effect in practical devices. The physical properties of lightly doped semiconductors are well described by electronic band-structure calculations and impurity energy levels1. Such properties form the basis of present-day semiconductor technology. If the doping concentration n exceeds a critical value nc, the system passes through an insulator-to-metal transition and exhibits metallic behaviour; this is widely accepted to occur as a consequence of the impurity levels merging to form energy bands2. However, the electronic structure of semiconductors doped beyond nc have not been explored in detail. Therefore, the recent observation of superconductivity emerging near the insulator-to-metal transition3 in heavily boron-doped diamond4,5 has stimulated a discussion on the fundamental origin of the metallic states responsible for the superconductivity. Two approaches have been adopted for describing this metallic state: the introduction of charge carriers into either the impurity bands6 or the intrinsic diamond bands7,8,9. Here we show experimentally that the doping-dependent occupied electronic structures are consistent with the diamond bands, indicating that holes in the diamond bands play an essential part in determining the metallic nature of the heavily boron-doped diamond superconductor. This supports the diamond band approach and related predictions, including the possibility of achieving dopant-induced superconductivity in silicon and germanium7. It should also provide a foundation for the possible development of diamond-based devices10.

The negative-ion based NBI for JT-60U has been making efforts to increase beam power and beam energy since the operation started in March 1996. The NBI system has already operated negative ion beams of 14.3 A at 380 keV with deuterium and 18.4 A at 350 keV with hydrogen. In the beam injection into JT-60U, a deuterium neutral beam power of 3.6 MW at 350 keV has been injected for 0.9 sec, and plasma reactions against the high energy beam injection with the N-NBI have been confirmed to be in agreement with a theoretical prediction.

Induced stress and current response were investigated at higher shear rates for the electro-rheological (ER) suspensions. In relation between stress and shear rate for a typical ER suspension, the flow was well assumed to the Bingham flow with the yield stress depending on the strength of the electric field. On the other hand, the stress for a dilute suspension with a higher viscosity of continuous phase showed a remarkable dip behavior at higher shear rates: The stress decreased with an increase in the shear rate above a critical shear rate, and it gradually increased again. The apparent conductivity, which was investigated at the same time and closely related to the aggregated structure of polarized particles in the ER suspension, also probed the corresponding behavior to the dip of the stress. Applicability and limitation of the Bingham flow at the higher shear rates were also discussed using a dimensionless parameter.

We have examined the anti-tumor effect in nude mice caused by human pancreatic cancer cells (AsPC-1) modified to secrete IL-2 or IL-4. Loss of tumorigenicity of cytokine-producing, but not wild-type, cells was observed despite their unaltered in vitro proliferation rates; and these anti-tumor effects were dependent on the amount of cytokine released. Wild-type cells inoculated into mice which had rejected IL-2- or IL-4-producer cells showed significant growth retardation, while no retardation was detected when unrelated human colon carcinoma cells were inoculated. Histological examination of regressing IL-2- or IL-4-producing AsPC-1 tumors in nude mice revealed infiltration by CD11b-, but not CD90-, positive cells around the tumors. Treatment of nude mice with anti-asialoGM(1) antibody did not affect loss of tumorigenicity. Mice injected i.p. with IL-2- or IL-4-producing AsPC-1 cells did not die, in contrast to mice inoculated with wild-type cells. Injection of retrovirus-bearing IL-2, but not beta-galactosidase, gene into mice which had wild-type cells in the peritoneal cavity also significantly prolonged survival. Thus, expression of the IL-2 or IL-4 gene in AsPC-1 cells may generate tumor-specific acquired immunity, even in mature T cell-deficient conditions. An anti-tumor response can be induced by in vivo transfer of the IL-2 gene.

Several members of the epidermal growth factor (EGF) family of growth factors that contain EGF-like units at their carboxy portion have been isolated and characterized. Schwannoma-derived growth factor (SDGF) and amphiregulin (AR) are members of this family. SDGF has high sequence homology to AR, and is known to be not only a potent mitogen for astrocytes and fibroblasts but also a neurotrophic factor. We previously confirmed that the synthetic EGF-like peptides SDGF(38-80) and AR(44-84), corresponding to the EGF-like domain of mouse SDGF and human AR, respectively, formed similar disulfide bond patterns to that of EGF. In the present study, we further investigated the biological actions of these two EGF-like peptides on several cultured cell lines. We found that SDGF(38-80) and AR(44-84) have weak mitogenic activity in NIH/3T3 cells and weak binding affinity to the EGF receptor on the surface of A431 cells compared with EGF. However, SDGF(38-80) and EGF induced short neurite outgrowth in PC12 h cells, a subclone of PC12 cells, at 100 nM. In addition, a significant increase in acetylcholinesterase (AChE) activity induced by SDGF(38-80) was observed at a concentration similar range to that of EGF, which is known as a differentiation marker of these cells. The effect of AR(44-84) in PC12 h cells was weaker than those of SDGF(38-80) and EGF, but the AChE activity was significantly increased by the addition of 100 nM AR(44-84), which did not stimulate NIH/3T3 cell growth. These results also suggest that SDGF(38-80) and AR(44-84) may be effective for neuronal differentiation rather than proliferation.

A 75-year-old man was admitted because of non-Hodgkin's lymphoma (histology undetermined) of the rib. A complete remission was achieved after CHOP therapy and irradiation. One year later, high fever, thrombocytopenia and liver dysfunction developed. Bone marrow aspirate revealed a hypoplastic marrow with hemophagocytic histiocytes, and a diagnosis of hemophagocytic syndrome (HPS) was made. Although no lymphomatous lesions were detected, HPS due to relapsed lymphoma was strongly suspected. The patient received MEVP therapy including etoposide and prednisolone, but without any improvement. Soon after the initiation of CPT-11 and adriamycin (ADM) therapy, all symptoms of HPS disappeared. This combination chemotherapy was repeated over a three-week span, and the patient remained in partial remission for the next 10 months. In November 1997, a tumor developed in the paranasal sinus, and the patient died three months later. The autopsy disclosed many B lymphoma cells filling the small vessels of almost all organs, and a final diagnosis of intravascular lymphomatosis (IVL) was made. These findings indicate that combination CPT-11 and ADM therapy is effective for cases of IVL accompanied by HPS that are refractory to conventional chemotherapies.

We have performed scanning tunneling microscopy/spectroscopy (STM/STS) experiments on (1 1 1)-oriented epitaxial films of heavily boron-doped diamond at T = 0.47 K. The STM topography shows two kinds of atomic structures: a hydrogenated 1 × 1 structure, C(1 1 1)1 × 1:H, and an amorphous structure. On the C(1 1 1)1 × 1:H region, the tunneling spectra show superconducting property with the energy gap Δ = 0.83 meV. The obtained gap ratio 2 Δ / k B T c = 3.57 is consistent with the weak-coupling BCS theory.

We have examined the antitumor effect of human pancreatic carcinoma cells (AsPC-1) retrovirally transduced with mouse granulocyte macrophage-colony stimulating factor (GM-CSF) gene in nude mice. Growth retardation of the subcutaneous tumors of GM-CSF-producing AsPC-1 cells was observed, although their in vitro proliferation was not different from that of wild-type cells. Histological examination revealed infiltration of monocytic cells into the tumor of GM-CSF-producing cells, and they were shown to be mainly CD11b positive cells by immunohistochemical staining. The survival of the mice inoculated intraperitoneally with GM-CSF- producing AsPC-1 cells was significantly prolonged compared with that of the mice inoculated with wild-type AsPC-1 cells. Thus, the expression of GM-CSF gene in human pancreatic cells induced an antitumor effect in vivo even in the mature T cell-deficient condition.