[en] This paper reports the recent activity for the coated conductor in Superconductivity Research Laboratory (SRL), especially concerning to the ion beam assisted deposition (IBAD) and pulsed laser deposition (PLD) methods, which are considered to be the most promising from the recent achievements in terms of the length and critical current density. In SRL, we have recently introduced a reel-to-reel IBAD machine. The IBAD machine successfully brought about a textured Gd₂Zr₂O₇ layer on Hastelloy tapes. The degree of in-plane texturing, delta phi Δφ, of the samples was 13 deg. in a meter long conductor. This IBAD machine will be a strong tool to study a long YBCO coated conductor. The second recent result is the PLD-CeO₂ buffer layer on an IBAD tape. Being different from the conventional studies, the PLD-CeO₂ layer not only grew epitaxially but also developed its degree of texturing during the PLD deposition. The degree of texturing in the CeO₂ layer reached in the order of 2 deg. and 5 deg. on the IBAD tapes with Δφ around 10 deg. and 25 deg. , respectively. The texturing was so fast that we obtained a Δφ of 10 deg. in 1 min and 5-6 deg. in 6 min, starting from a thin IBAD substrate with a Δφ of 24-27 deg. . We can call this 'self-epitaxy' in the meaning of using no assist like Ar ion in the IBAD method. This new epitaxy phenomenon resulted in a small misorientation angles between grains and then reduced the weak-link induced degradation of J_c in the grain boundaries of the conductor. A PLD-YBCO layer on the above CeO₂ layer achieved a critical current density as high as 3.8 MA/cm² at 77 K and 0 T, which was not so largely degraded compared to the conventional coated conductors with the misorientation angles around 10 deg. and J_cs of 1-2 MA/cm². Therefore, 'self-epitaxy' is strongly expected to accelerate a practical conductor development due to its rapidly and highly texturing characteristic with the possibility to weaken the weak-link problem inherent in oxide superconductors

[en] In a clinical trial in which a 2-nitroimidazole radiosensitizer was administered repeatedly, the dose-limiting toxicity was found to be peripheral neuropathy. In the present study, the in vivo radiosensitizing activity of KU-2285 in combination with radiation dose fractionation, and the pharmacokinetics of cumulative dosing of KU-2285 in the peripheral nerves were examined. The ability of three nitroimidazoles, misonidazole (MISO), etanidazole (SR-2508) and KU-2285, to sensitize SCCVII tumors to radiation treatment has been compared for drug doses in the range 0-200 mg/kg. Single radiation doses or two different fractionation schedules (6 Gy/fractions x three fractions/48 h or 5 Gy/fractions x five fractions/48 h) were used; the tumor cell survival was determined using an in vivo/in vitro colony assay. The pharmacokinetics in the sciatic nerves were undertaken, when KU-2285 or etanidazole were injected at a dose of 200 mg/kg intravenously one, two, three, or four times at 2-h intervals. At less than 100 mg/kg, KU-2285 sensitized SCCVII tumors more than MISO and SR-2508 by fractionated irradiation. Evaluation of pharmacokinetics in the peripheral nerves showed that the apparent biological half-life of SR-2508 increased with the increases in the number of administrations, whereas that of KU-2285 became shorter. Since most clinical radiotherapy is given in small multiple fractions, KU-2285 appears to be a hypoxic cell radiosensitizer that could be useful in such regimens, and that poses no risk of chronic peripheral neurotoxicity. 12 refs., 5 figs., 1 tab

[en] Purpose: A new 2-nitroimidazole nucleoside radiosensitizer, PR-350 (1-[1',3',4'-trihydroxy-2'-butoxy]-methyl-2-nitroimidazole), has been reported to be as efficient as and less toxic than etanidazole. This compound is racemic, and it was recently optically resolved into two isomers, PR-68 (2'R,3'S type) and PR-69 (2'S,3'R type). The other two isomers, PR-28 (2'S,3'S type) and PR-44 (2'R,3'R type), were asymmetrically synthesized. In the present study, we investigated the properties, sensitizing activity, and toxicity of PR-350 and the four optical isomers in comparison with those of other 2-nitroimidazole hypoxic cell radiosensitizers, etanidazole, KU-2285, KIN-804, and RP-170. Because PR-350 and PR-28 can be industrially synthesized, we evaluated whether either of these two drugs are suitable for further investigation. Methods and Materials: In an in vitro study, EMT-6 cells were irradiated at a dose of 1-3 Gy under hypoxic conditions in the presence of the drugs at a concentration of 1 mM. A combined cytokinesis-block micronucleus and chromosomal aberration assay was performed. To assess the in vivo effects, colony assay and growth delay assay were performed using SCCVII tumor-bearing C³H mice. The mice received 16-24 Gy 10-40 min after administration of 50-200 mg/kg of the drugs. Toxicity and pharmacokinetics in mice were also investigated. Results: The sensitizer enhancement ratio (SER) in the in vitro cytokinesis-block micronucleus assay increased in the following order: PR-69 (1.27) ≅ PR-28 (1.31) ≅ PR-44 (1.38) ≅ PR-350 (1.41) ≅ PR-68 (1.47) < etanidazole (1.79) < KIN-804 (2.03) ≅ KU-2285 (2.30). The SER at a dose of 200 mg/kg and at an interval of 20 min (optimal interval) in the in vivo--in vitro colony assay increased as follows: PR-44 (1.26) ≅ PR-28 (1.29) < PR-69 (1.34) ≅ etanidazole (1.35) ≅ PR-350 (1.36) < RP-170 (1.41) ≅ PR-68 (1.41) < KU-2285 (1.49). The growth delay assay also showed that PR-350 was less efficient than KU-2285 and more efficient than PR-28. PR-350 and the four isomers had similar reduction potentials, but PR-28 and PR-44 were more hydrophilic than PR-68 and PR-69. The LD₅₀ in mice were 5.8 g/kg for PR-350, approximately 7 g/kg for PR-28, 4 g/kg for PR-68, and 6 g/kg for PR-44 and PR-69. The concentration of PR-28 in the murine sciatic nerve was lower than that of PR-350. Conclusion: In vivo radiosensitizing activity differed among the four optical isomers, which appeared to be due, at least in part, to differences in lipophilicity. Although PR-28 was the least toxic, its low sensitization efficiency does not warrant clinical trials. Among the PR compounds, PR-68 appears to be most efficient, but optical resolution of PR-68 from PR-350 is expensive, and asymmetrical synthesis of PR-68 is not established. Therefore, PR-350 seems to be most suitable for further investigation among the PR-350 series compounds, considering its higher efficiency compared with PR-28 and PR-44, and established synthesis

[en] CeO₂ buffer layers were deposited on IBAD-Gd₂Zr₂O₇ tapes by the pulsed laser deposition (PLD) method and were investigated especially in terms of the thickness dependence on the crystal grain alignment. The film thickness was varied from 10 to 1200 nm. The grain alignment of the CeO₂ layer on an IBAD tape was drastically improved with increasing its thickness. The Δphi value of the in-plane grain alignment decreased from 25.4 deg. for the Gd₂Zr₂O₇ layer of the IBAD tape to 4.9 deg. for the CeO₂ layer. Using this result, we demonstrated that the total production rate of the buffer layers process was enhanced drastically by the combination of a thinner Gd₂Zr₂O₇ layer by the IBAD method and a thicker CeO₂ layer by the PLD method. The improved in-plane grain alignment resulted in higher J_c in YBCO on the CeO₂ buffer layer

[en] We have proposed a self-epitaxy process for CeO₂ cap buffer layer deposition by using PLD in order to improve the deposition rate in the IBAD process. The process is combined with a thin IBAD buffer layer by a short time deposition and a self-epitaxy PLD cap layer by high rate deposition. The materials for both IBAD buffer layer and PLD cap layer were studied in terms of the grain alignment. Gd₂Zr₂O₇ (GZO) for the IBAD buffer layer and CeO₂ for the PLD cap layer are the best combination. It was estimated that a deposition time of the combination process could be about one-third of the conventional IBAD process. A 55 m long PLD-CeO₂ cap layer was fabricated at the tape transfer speed of 5 m/h on an IBAD-GZO tape by a reel to reel process. A PLD-CeO₂ cap layer improved the Δphi value of the buffer layer and also the uniformity of the Δphi values throughout the whole length. While the Δphi values of IBAD-GZO were in the range of 13.9 deg. and 18.8 deg., those of PLD-CeO₂ cap layer were improved to be in the range of 5.7 deg. and 8.7 deg.

[en] The in vitro and in vivo effects of two promising hypoxic cell radiosensitizers, KIN-804 (KIN) and KU-2285 (KU), were compared using four types of assays, and the acute toxicity and pharmacokinetics of KIN were investigated to evaluate the clinical applicability of the compounds. To evaluate the in vitro effect at low radiation doses (1-4.5 Gy), the cytokinesis-block micronucleus (MN) assay using SCCVII or EMT-6 cells and the chromosomal aberration (CA) assay using EMT-6 cells were performed. In addition, an in vivo-in vitro colony assay, a growth delay assay, and a pharmacokinetic study were performed using C3H mice bearing SCCVII tumors, and the LD_50/7 was determined in ICR mice. In the in vitro MN assay, the sensitizer enhancement ratio (SER) at 0.1, 0.25, 1, and 5 mM with SCCVII 2.59, 5.66, and 2.21 for KU. In the in vitro CA assay, the SER at 1 mM was 1.78 for KIN and 1.79 for KU. In the in vivo-in vitro colony assay, the SER of KIN at 50, 100, and 200 mg/kg was 1.24, 1.30, and 1.45, respectively, while the SER of KU at 100 mg/kg was 1.41. In the growth delay assay, the growth delay time for 100 and 200 mg/kg of the drug plus 20 Gy of radiation was respectively, 16.5 and 19.1 days for KIN, and 18.9 and 24.0 days for KU. In all experiments, the sensitizing effect of KIN was almost equal to that of KU. The LD_50/7 of KIN was 3.6 g/kg by intraperitoneal injection, while that of KU was 3.6 g/kg by intraperitoneal injection, and the pharmacokinetic study of KIN revealed a low uptake of the drug by the brain. Both KIN and KU had a definite sensitizing effect even at lower drug concentrations or doses, suggesting their potential usefulness in clinical radiotherapy. 11 refs., 6 figs

[en] To assess the effects of incorporation of a CF₂ group into the side chain of a 2-nitroimidazole derivative, the authors evaluated the in vitro and in vivo radiosensitizing activities of KU-2285 (a 2-nitroimidazole derivative with an N₁-substituent of -CH₂CF₂CONH(CH₂)nOH) and its related compounds in comparison with those of comparable nonfluorinated compounds. The pharmacokinetics of these compounds in murine tumors was also tested. KU-2285, KU-3202, and KU-3207 are fluorinated 2-nitroimidazole derivative compounds with similar structures. Etanidazole (a 2-nitroimidazole derivative with an N₁-substituent of -CH₂CONH(CH₂)nOH) and its related compounds, KU-3205 and KU-3206 were also tested. The in vivo radiosensitizing activities of each compound for hypoxic cells was evaluated with a standard colony formation method. The in vivo radiosensitizing activities of these compounds were tested in female C3H/He mice bearing SCCVII tumors using an in vivo/in vitro clonogenic assay. The pharmacokinetic studies were performed in C3H/He mice bearing the SCCVII tumor. Samples were analyzed by reversed-phase high-performance liquid chromatography. The in vitro radiosensitizing activities of fluorinated 2-nitroimidazoles were higher than those of the nonfluorinated compounds. Although the in vivo radiosensitizing activity of KU-2285 was higher than that of etanidazole, other fluorinated 2-nitroimidazoles showed less radiosensitizing activity than the comparable nonfluorinated compounds. The compound was eliminated from serum more rapidly with the increase in the number of CH₂ group in the side chain of the compound in each series. Although the in vitro sensitizing activity of the fluorinated compounds was higher than that of the comparable nonfluorinated compounds, the in vivo radiosensitizing activity of all fluorinated compounds but KU-2285 was lower than that of comparable etanidazole group compounds. 8 refs., 2 figs., 1 tab

[en] For Y Ba₂Cu₃O_7-x (YBCO) coated conductors with high J_c, we have been investigating pulsed laser deposition (PLD) processing using the 'self-epitaxial' PLD-CeO₂ layer on an ion beam assisted deposition (IBAD)-Gd₂Zr₂O₇ (GZO) buffered Hastelloy tape. In this study using short samples of 10 mm in length by 10 mm in width, a high critical current density, J_c, value of 4.4 MA cm^-2 was obtained for a substrate with the delta phi value of 2.4 deg. We also confirmed the relationship that the J_c value of YBCO increased exponentially with decreasing in-plane grain alignment of YBCO. Furthermore, we also succeeded in deposition of a high J_c and thick YBCO film; the thickness was 1.2 μm and the J_c value was 2.3 MA cm^-2. This value corresponds to 276 A/cm-width. Based on these results, a metre long YBCO coated conductor was fabricated using a reel-to-reel system. Consequently, J_c of 1 MA cm^-2 was obtained for a long coated conductor. Now, work is in progress to fabricate a longer and thicker YBCO coated conductor with high critical current, I_c

[en] We have fabricated RE₁Ba₂Cu₃O_7-δ (RE = Er, Dy, Gd) and YBa₂Cu₃O_7-δ (Y-123) superconductor films with various thickness on pulsed laser deposition (PLD)-CeO₂/ion-beam assisted deposition (IBAD)-Gd-Zr-oxide (GZO)/metal substrates by PLD method and investigated the dependence of critical current density (J _c) on applied magnetic field. In order to fabricate a practical high critical current (I _c) coated conductor, we used metal substrate tapes with Δφ value of 3.7 deg. -7.0 deg. fabricated by the technique of a self-epitaxy method. GdBa₂Cu₃O_7-δ (Gd-123) films showed higher J _c in magnetic fields than that for Y-123 films. J _c value of the Gd-123 film was 179,000 A/cm² at 3 T and 34,700 A/cm² at 6 T at 77 K. Transmission electron microscope (TEM) observation showed that Gd-123 film had a more defective structure than Y-123 film. These structures may be attributed to high J _c in high magnetic field

[en] Three types of YBCO films were deposited on metal tapes with biaxially textured CeO₂/Gd₂Zr₂O₇ multilayer. One YBCO film 4 μm in thickness was formed by pulsed-laser deposition (PLD) on the stationary substrate and another film 3 μm in thickness by PLD using a reel-to-reel substrate tape transferring system. I _c values of the films were 173 A and 293 A, respectively A further film 1 μm in thickness was fabricated by multiple-stage chemical vapor deposition (MSCVD). The I _c value of the MSCVD-YBCO film was 100 A. The microstructures of these YBCO films were characterized using transmission electron microscopy (TEM). In the PLD-YBCO films, the films less than 1 μm thick were predominantly composed of c-axis oriented grains which were considered to grow spirally, however, irregular instances of a-axis oriented grains were also found. The a-axis oriented grains size increased with increasing thickness of the YBCO films. In the 4 μm-thick PLD-YBCO film with an I _c value of 173 A, a-axis oriented grains were considered to nucleate on the CeO₂. We found many Y₂O₃ and cupper oxides at the boundaries between a- and c-axes oriented grains and the orientation relationships between YBCO and Y₂O₃ were determined to be as follows: (0 0 1)YBCO//(0 0 1)Y₂O₃ and (1 0 0)YBCO//(1 1 0)Y₂O₃. We also found many gaps and pores between YBCO grains. Nucleation of a-axis oriented grains was completely suppressed on the CeO₂ in the 3 μm-thick PLD-YBCO film with an I _c value of 293 A. In the MSCVD-YBCO film, the YBCO film mostly consisted of c-axis oriented grains, however a-axis oriented grains and polycrystal also formed in the film. As the MSCVD-YBCO film became thicker, the a-axis oriented grains grew large, as same as in the PLD-YBCO films. The growth rate of a-axis oriented grain along the substrate normal was much higher than that of c-axis oriented grains in comparison to the difference in the growth rate between a- and c-axes oriented grains in the PLD-YBCO. In these specimens, the grain growth of the a-axis oriented grains was considered to be one of the most significant causes of degradation of J _c values in the YBCO films