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We examined osteoporosis medication use and factors affecting persistence in 497 patients with fragility hip fractures. Only 25.5% of patients received continuous medication for 3 years, and 44.1% of patients received no treatment. Low Barthel index at discharge was a risk factor for both non-treatment and non-persistence to osteoporosis medication. Fragility hip fractures (FHF) caused by osteoporosis decrease the quality of life and worsen life expectancy. Use of osteoporosis medication may be an efficient method in the prevention of secondary FHF. However, previous studies have reported low rates of osteoporosis medication and persistence after FHF. This study aimed to evaluate osteoporosis medication use and factors affecting persistence in patients with FHF in the northern Kyushu area of Japan. A total of 497 FHF patients aged ≥ 60 years with a 3-year follow-up were included. We prospectively collected data from questionnaires sent every 6 months regarding compliance with osteoporosis medication. We compared baseline characteristics among three groups: no treatment (NT), no persistence (NP), and persistence (P), and conducted multivariable regression models to determine covariates associated with non-treatment (NT vs. NP/P) and non-persistence (NP vs. P). There were 219 (44.1%), 151 (30.4%), and 127 (25.5%) patients in the NT, NP, and P groups, respectively. Factors associated with non-treatment were male sex, chronic kidney disease, no previous osteoporosis treatment, and low Barthel index (BI) at discharge. The only factor associated with non-persistence was a low BI at discharge. Factors associated with a low BI at discharge were male sex, older age, trochanteric fracture, and surgical delay. Low BI at discharge is a risk factor for both non-treatment and non-persistence to osteoporosis medication. Therefore, appropriate interventions to improve BI may result in persistence to osteoporosis medication.

Background: Wedge-shaped bone grafts that are internally fixed by a Herbert-type screw are a well-established surgical treatment for scaphoid nonunion. A procedure using cylinder-shaped bone grafts was also reported, but preoperative wrist functions were not assessed. In addition, it was not reported whether the humpback deformity of the scaphoid nonunion was corrected. The purpose of the current study was to compare preoperative wrist functions in cases of scaphoid nonunion with those observed at final follow-up, using cylinder-shaped bone grafts The humpback deformity of the scaphoid nonunion was also evaluated.Methods: We conducted a retrospective study to examine operative outcomes from 2008 to 2015. Twelve wrists in 12 patients (average age, 41 years; range, 17–67), with a mean follow-up of 19 months, were included in the current study. Cylinder-shaped bone grafts were obtained from the iliac crest with a newly designed trephine and fixed with a Herbert-type screw. We reviewed both the preoperative wrist functions and those obtained at final follow-up.Results: Union was achieved in 11 of 12 nonunion cases. Preoperative wrist functions, except for the range of wrist motion, significantly improved by final follow-up.Conclusions: We conclude that the use of cylinder-shaped bone grafts improves preoperative wrist functions in cases of scaphoid nonunion.

This paper reports developments of indirectly cooled radiation-resistant magnet coils, which can be loaded with 2000-A dc. This current capacity is required for the most upstream magnets of a new high-momentum beam line to be constructed in the future extension of the J-PARC hadron experimental facility. Indirectly cooled coils using solid-conductor-type mineral insulation cables (MICs) and stainless-steel water pipes were adopted to achieve high radiation hardness. MICs were sandwiched by independent cooling water pipes and stacked in a casing, and the entire coil assembly was filled with solder. However, the maximum load applied to the indirectly cooled MIC coils was limited to 1000-A dc, mainly owing to a heat problem at the end parts of the coils. In pursuit of the required current capability, we have carried out load tests using a test sample of the end parts, which consists of MIC current leads and a copper bus bar connecting the MIC conductors, instead of a whole MIC coil. By improving the structure of the end parts, we have succeeded to operate the test piece stably with 2000-A dc in a vacuum.

An electrostatic separator is one of the key elements of a secondary beam line at the Hadron experimental hall of J-PARC. It generates a transverse electric field along the beam axis to separate particles of the same momentum by their mass differences. Two beam lines for charged secondary particles, K1.8 and K1.1BR, are constructed, to provide kaon beams with less contamination of pions. Three experimental areas, K1.8, K1.8BR and K1.1BR are available for nuclear and particle physics experiments. Two 6-m-separators and a 2-m-separator of a Wien filter type are installed for the K1.8 and the K1.1BR beam lines.

The target station in the hadron experimental facility at J-PARC consists of a production target and a huge vacuum chamber in which several secondary-beam-line magnets can work. This vacuum chamber system aims to remove the vacuum beam pipe from the magnet gap, because the cooling of the beam pipe is the most serious problem in the high intensity beam facility. We have developed indirectly cooled radiation-resistant magnets for the hadron target station. Their coils are made of solid-conductor type mineral-insulation cables and stainless-steel water pipes. They have the great advantages that electric circuits can be completely independent of water pass. The mechanical strength and the insulation performance of the coil are significantly improved also because the insulation water pipes can be avoided from the water pass. A C-type sector dipole and a figure-8-type quadrupole magnet have been fabricated by using indirectly cooled radiation-resistant magnet technology, and installed in the vacuum chamber. We have succeeded to operate them in vacuum stably with the current of DC 1000 A by improving the end structure of the MIC coils and increasing their emissivity. These magnets have been used for the real beam operation without any serious problems.

More than 50 radiation-resistant electromagnets were constructed for the primary proton and the secondary particle beam lines of the Hadron Experimental Hall of Japan Proton Accelerator Research Complex (J-PARC). The main radiation-resistant technologies we employed were the Polyimide-resin Insulation conductor for magnets at the relatively low radiation exposure and the Mineral Insulation Cable for magnets at the seriously high radiation environment. The remote handling and maintenance scheme of radiation-resistant magnets for seriously high radiation environment was developed also based on the Chimney magnet technology and applied to magnets near the production target in the Hadron Hall. On January 27th 2009, the first proton beam was successfully introduced to the Hadron Hall from the main accelerator of J-PARC, i.e. 50 GeV Proton Synchrotron. On February 10th, the secondary particles were extracted to the experimental area of the Hadron Hall through the secondary particle beam line. No serious problem happened on magnets of both primary proton and the secondary particle beam lines until the end of the beam operation scheduled on February 26th .

The new electrostatic (ES) separator to select and deliver 1–2 GeV/c kaon beams is made for the secondary beam line at the high intensity proton accelerator facility. The ES separator will generate a 75 kV/cm electrostatic field between parallel electrodes of 10 cm gap and 6 m in length along the beam direction. The K − /π − ratio of the line is expected to have a larger value than 1. It is designed so as to be radiation-proof and to lower spark rate comparing with the present separators.

The high intensity proton accelerator facility J-PARC is now in its final stage of construction. Soon intense primary proton beams will be slowly extracted to an experimental hall (HD-hall) and transported to a production target. Since the radiation level around the target will be very high, the beam line tunnel needs to be surrounded by 2.5 m-5 m thick concrete shields in the HD-hall. Radiation resistant magnets for handling high intensity beams are buried inside these thick concrete shields. This structure, however, brought us a problem of leading electric power lines to the magnets. For a solution to this problem, we have developed water cooled bus ducts penetrating radiation shield. These bus ducts enable us to connect the power supplies placed outside the shields to the magnets in the shortest power line length without any deterioration of protection ability of radiation shielding. The maximum power capacity of the bus duct is over 5000 A. The bus ducts plays an important part in our radiation resistant magnet system.

In a high-intensity proton beam facility, beam line elements downstream of a production target are exposed to a huge amount of radiation and heat. Beam pipes are closer to the beam than the magnet poles and more difficult to cool sufficiently without tritium production. Therefore, the magnets are placed in a large vacuum chamber, instead of using vacuum pipes located within the pole gaps. We have adopted indirect-cooling mineral-insulation-cable (MIC) coils for these magnets. They have a great advantage that the mechanical strength and the insulation performance can be significantly improved by avoiding the use of ceramic insulation pipes, because electric circuits are completely separated from water passages. We have made coils using 1000-A-class solid-conductor MICs and stainless-steel pipes, and tested magnet operation in vacuum. By improving the structure of end parts of MICs and increasing their emissivity, we have successfully fed the current of DC 1000 A to the solid-conductor MIC coils in vacuum.

In a high-intensity proton beam facility, beam line elements downstream of a production target are exposed to a huge amount of radiation and heat. A water-cooled beam collimator must be located between the target and the magnets, and the iron yokes of the magnets also have to be cooled by water. Moreover, beam pipes are closer to the beam than the magnet poles and more difficult to cool sufficiently without tritium production. Therefore, the magnets are placed in a large vacuum chamber, instead of using vacuum pipes located within the pole gaps. In order to reduce the residual radiation dose during maintenance, the chamber lid and feedthroughs are 4 meter above the beam line, and radiation-shielding blocks are also stacked in the chamber. We have tested magnet operation in vacuum using a dipole magnet with mineral-insulation-cable (MIC) coils and a nickel-coated yoke. A magnet with 2500-A-class hollow-conductor MIC coils has worked successfully with the current of DC 3000 A. The stability of operation in vacuum was confirmed by measuring the temperature with thermocouples and the magnetic field with a NMR probe. We have also succeeded in operating a 1000-A-class solid-conductor MIC coil in vacuum

Several species of radiation-resistant magnets were developed for J-PARC, a Japanese brand-new high-intensity accelerator complex, whose maximum beam power reaches 1 MW. The first development was polyimide insulation magnets. The ordinal epoxy resin was replaced by polyimide resin in order to improve its radiation lifetime up to $4 \times 10^8$ Gy. Most accelerator magnets of J-PARC were assembled with polyimide insulation coils. Peripherals of polyimide insulation magnets, such as insulation water tubes, water valves, water gaskets, etc., were replaced also by ones made of inorganic materials. The second development was mineral insulation magnets. Magnet excitation coils were made of “Mineral Insulation Cable (MIC).” The copper conductor of MIC was surrounded by a thin MgO insulation layer, and the MgO layer was covered by a copper sheath. Several sizes of MIC cross section were developed for large and small magnets with various maximum currents from 1000 to 3000 A. Peripherals of magnets assembled with MIC coils were also made of completely inorganic materials. These MIC magnets were used at the downstream part of beam loss points such as the secondary particle production target of Hadron Experimental Facility. The R&D stories of the radiation-resistant magnets, including the present status of the magnet operation, are briefly summarized.

The facility of the long baseline neutrino oscillation experiment using the J-PARC's 50 GeV-0.75 MW proton beam is now under way. The primary proton beam line consists of three sections, i.e. the first preparation (PP) section with normal conducting magnets, the second arc (ARC) section with superconducting magnets and the third final focus (FF) section with normal conducting magnets. In the PP section, we have to clean the primary proton beam extracted from the 50 GeV-PS and transport halo-less pure beam only to the ARC section. In the FF section the magnets have to be placed very close to the pion production target and horns. Therefore the normal conducting magnets have to work in the very high radioactive environment. The R&D works on the radiation resistant magnets for handling a high-intensity proton beam have already been continued at KEK as reported in . Another important point regarding high-intensity beam handling is to realize easy maintenance of the beam line. Any magnet experiencing trouble can be easily removed from beam line and repaired remotely. For this purpose, we developed new tools for the magnet maintenance. These are automatic sling apparatus, quick alignment and installation guide, and the quick disconnect devices of cooling water and electric power. In this paper, we will report the beam line maintenance scheme developed for the neutrino beam line, as well as the design of normal conducting magnet sections

Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that is overexpressed in several human cancers, and induces survival, proliferation and motility of cells in culture. Phosphorylation of FAK has been studied extensively in vitro, but little is known about its regulation during tumor invasion in vivo. In the current study, green fluorescent protein (GFP) was expressed stably in an invasive murine fibrosarcoma cell line for the purpose of discrimination between tumor and normal cells. Under fluorescence microscopy, the tumor was highly fluorescent, and the margin between the tumor and normal tissue was clearly demarcated. Using this invasion model, we showed localization of pY397-FAK expression in the infiltrative edge of tumors. We reproduced local invasion in vivo using a tumor tissue culture method in a three dimensional collagen gel. Phosphorylation of FAK is also upregulated in invading fibrosarcoma cells under in vitro conditions. Expression of the FAK C-terminal domain termed FRNK (FAK-related non-kinase) in 2,472 cells decreased FAK phosphorylation without changing total FAK levels. FRNK inhibited the motility of 2,472 cells, and reduced invasion in vitro. Although FRNK did not affect cell growth, it inhibited experimental metastases in syngenic mice. These results demonstrate that the phosphorylation of FAK might be specifically upregulated in invading fibrosarcoma cells and regulate their invasion and metastasis.

The J-PARC Neutrino Experiment, the construction of which starts in JFY 2004, will use a superconducting magnet system for its primary proton beam line. The system, which bends the 50 GeV 0.75 MW proton beam by about 80 degrees, consists of 28 superconducting combined function magnets. The magnets utilize single layer left/right asymmetric coils that generate a dipole field of 2.6 T and a quadrupole field of 18.6 T/m with the operation current of about 7.35 kA. The system also contains a few conduction cooled superconducting corrector magnets that serve as vertical and horizontal steering magnets. All the magnets are designed to provide a physical beam aperture of 130 mm in order to achieve a large beam acceptance. Extensive care is also required to achieve safe operation with the high power proton beam. The paper summarizes the system design as well as some safety analysis results.

We made a series of surveys to obtain neutrino beam line direction toward SuperKamiokande (SK) at a distance of 250 km for the long-baseline neutrino oscillation experiment at KEK. We found that the beam line is directed to SK within 0.03 mr and 0.09 mr (in sigma) in the horizontal and vertical directions, respectively. During beam operation, we monitored the muon distribution from secondary pions produced at the target and collected by a magnetic horn system. We found that the horn system functions like a lens of a point-to-parallel optics with magnification of approximately -100 and the focal length of 2.3 m. Namely, a small displacement of the primary beam position at the target is magnified about a factor -100 at the muon centroid, while the centroid position is almost stable against a change of the incident angle of the primary beam. Therefore, the muon centroid can be a useful monitor of the neutrino beam direction. We could determine the muon centroid within 6 mm and 12 mm in horizontal and vertical directions, respectively. This means that the neutrino beam direction could be controlled within 0.03 mr and 0.06 mr (in sigma) in the horizontal and vertical directions, respectively. We confirmed the beam direction with the neutrino distribution reconstructed at the near detector in KEK.

A series of the R&D works on the radiation resistant magnets for the Japan Hadron Facility (JHF) project has been continued at the High Energy Accelerator Research Organization (KEK). The JHF is a high-energy part of the Japanese high intensity Particle Accelerator Research Complex (J-PARC), which is Japanese next-generation high-intensity accelerator project. The main JHF accelerator is the 50 GeV proton synchrotron and will provide high intensity 15/spl mu/A proton beam for various nuclear and particle physics experiments. This time, the actual sized completely-inorganic radiation-resistant quadrupole magnet, designed for the 50 GeV proton beam transportation, was manufactured successfully by using mineral insulation magnet cable (MIC). The assembling procedure and the test results are presented in this issue.

As a part of the Japan Hadron Facility (JHF) Project, R&D on radiation-resistant magnets is being carried out at the High Energy Accelerator Research Organization (KEK). JHF is the Japanese next-generation high-intensity accelerator project, which will provide 1-MW proton beams of 3 GeV and 50 GeV for various fields of science.

Using modularized NaI(Tl) detectors, we carried out a high-statistics measurement of inclusive π o and η spectra in antiproton annihilation at rest in a liquid D 2 target. We obtained the following two-meson yields (branching ratios) per \bar p N ( N = p or n ) annihilation: 0.19± 0.09% for π o ω, 1.07±0.19% for π o ρ o , 0.057±0.018% for π o η, 0.0123±0.0055% for π o π o , 0.02±0.02% for π o ρ - , 0.202±0.031% for π o π - , 0.49±0.12% for ηω, 0.45±0.15% for ηρ o , and 0.91±0.22% for ηρ - .

For pt.I see Yamanoi et al., Proc. on Magnet Technology, p.711 (1997) We report on the status of the latest operation of the horn magnets. Our two types of large horn magnets were installed in the neutrino beam line at the KEK-12 GeV Proton Synchrotron (KEK-PS) and have been operated since March 1999. These two focusing magnets were designed to be excited at pulsed-high currents of up to 250 kA. One of the special characters of our horn magnet is a built-in pion-production target at the most upstream part of the inner conductor. This configuration enable us to increase the neutrino flux as high as possible with low-energy primary protons from the KEK-PS. Our horns have a coaxial-shape structure with a large diameter, i.e. a large volume of the magnetic field, in order to collect as many pions as possible. We estimate that the neutrino flux is enhanced by a factor of 14 by using this horn system. Both horns have been excited over 10/sup 6/ times at pulsed currents of 175 kA-250 kA. Some beginning problems were found in the peripheral apparatus of the horn magnets, and the built-in production target was found have a fatal mechanical damage. In the spring run, the performance of our horn magnet system was almost sufficient as a pion focusing device for a long-baseline neutrino oscillation experiment.

A soil-shielding benchmark experiment was conducted using secondary particles produced by 12 GeV protons, which were injected into an iron rod surrounded by soil. Induced activities of 22 Na in aluminium (Al) and soil samples were measured and the experiment was simulated by the MARS Monte Carlo code. The induced activities in Al samples were calculated using spallation cross sections and fluence, where the fluence was calculated by the MARS code. The relation between flux density and induced activities in soil was investigated using calculated flux densities: the distribution of the ratio of induced activities in soil samples to the flux densities showed the radial and axial independence. Both saturated activities and distribution coincide with experimental data within the estimated errors. These results indicate the successful simulation by the MARS code.

A positioning of the neutrino detector SuperKamiokande (SK) was made for a long-baseline neutrino oscillation experiment planned at KEK. For positioning, Global Positioning System (GPS) was employed. It has been demonstrated that GPS is of practical use for measuring the positions of SK and KEK, being 250 km distance from each other, to a better resolution. The geodetic coordinates at the SK center were obtained to be Lat. 36°25′32.5862″ N., Long. 137°18′37.1241″ E., H. 371.839 m in the global ellipsoidal coordinate system, WGS-84. The obtained coordinates are based on the coordinates given at a triangulation point at the KEK site. The present work will be fed back for constructing the neutrino beam line.

Using modularized NaI(Tl) detectors, we carried out a high statistics measurement of inclusive \ensuremath{\gamma}-ray, ${\ensuremath{\pi}}^{0}$, and \ensuremath{\eta} spectra, and determined the branching ratios or upper limits of Pontecorvo reactions $\mathrm{p\ifmmode\bar\else\textasciimacron\fi{}}d\ensuremath{\rightarrow}{\ensuremath{\pi}}^{0}n$, ${\ensuremath{\pi}}^{0}{\ensuremath{\Delta}}^{0}$, $\ensuremath{\eta}n$, and $\ensuremath{\eta}{\ensuremath{\Delta}}^{0}$ from the corresponding monochromatic peaks in them. The obtained branching ratios are $B(\mathrm{p\ifmmode\bar\else\textasciimacron\fi{}}d\ensuremath{\rightarrow}{\ensuremath{\pi}}^{0}n)=(1.03\ifmmode\pm\else\textpm\fi{}0.41)\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}5}$, $B(\mathrm{p\ifmmode\bar\else\textasciimacron\fi{}}d\ensuremath{\rightarrow}{\ensuremath{\pi}}^{0}{\ensuremath{\Delta}}^{0})=(4.67\ifmmode\pm\else\textpm\fi{}1.66)\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}5}$, $B(\mathrm{p\ifmmode\bar\else\textasciimacron\fi{}}d\ensuremath{\rightarrow}\ensuremath{\eta}n)l8.94\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}6}$ (95% C.L.), and $B(\mathrm{p\ifmmode\bar\else\textasciimacron\fi{}}d\ensuremath{\rightarrow}\ensuremath{\eta}{\ensuremath{\Delta}}^{0})l6.49\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}5}$ (95% C.L.).

A neutron beam line has been constructed at the KEK-proton synchrotron. Neutrons have been produced by the disintegration reactions of deuterons in a 6 cm thick beryllium target. Deuteron beams of 2–6 GeV have provided neutron beams of 1–3 GeV. The neutron flux increases with the deuteron energy. The typical beam intensities obtained were 1 × 108, 2 × 108, and 3 × 108 neutrons per 1011 deuterons of 2, 4, and 6 GeV, respectively. The neutron-momentum width, Δpp, was measured to be (4 ± 1) % in sigma at 1 GeV.

For pt. I see IEEE Trans. Magn., vo1.30, p.2511, (1994). We report here on R/D work concerning two types of radiation-resistant magnet coils, which were insulated using completely inorganic materials. Regarding the first coil, the electric insulator employed was a alumina long fiber and a ceramic binder. A new combination of adhesive agent, inorganic filler and alumina long fiber was found, which enabled us to form a strong insulation layer which does not peel off from a copper conductor. The magnet coil for 2000 A excitation current was produced using this insulation method. The second coil is a mineral insulated cable (MIG) with a 3000 A excitation current. This 3000 A-class MIC has been manufactured as a short sample, and was tested concerning its electric insulation both before and after bending.

A brief description of the primary beam line at the hadron experimental facility at the Japan Proton Accelerator Research Complex (J-PARC) is presented. The facility has been constructed in Tokai, Japan, and the first beam was successfully introduced into the experimental hall in January 2009. The facility utilizes a high-intensity proton beam with an energy of 50 GeV and a power of 750 kW and provides various secondary beams such as pions, kaons, and antiprotons for nuclear and particle physics experiments. We have developed beam-line components with sufficient radiation hardness and heat resistance to handle the high-power proton beam.

The asymmetry of positrons in the ${\mathit{K}}^{+}$\ensuremath{\rightarrow}${\mathrm{\ensuremath{\mu}}}^{+}$\ensuremath{\nu}, ${\mathrm{\ensuremath{\mu}}}^{+}$\ensuremath{\rightarrow}${\mathit{e}}^{+}$${\ensuremath{\nu}}_{\mathit{e}}$\ensuremath{\nu}${\mathrm{\ifmmode\bar\else\textasciimacron\fi{}}}_{\mathrm{\ensuremath{\mu}}}$ decay chain was measured in a search for right-handed weak currents in \ensuremath{\Delta}S=1 semileptonic decay. High-intensity low-background monoenergetic polarized muons of 236 MeV/c momentum resulting from kaon decay at rest were directly extracted from a primary production target which was hit by a proton beam of the KEK 12-GeV proton synchrotron. Muons were stopped in a pure-aluminum plate, and the energy-integrated asymmetry of the decay positrons with respect to the incoming muon direction was determined to high precision. The observed asymmetry yielded \ensuremath{\xi}${\mathit{P}}_{\mathrm{\ensuremath{\mu}}}$=-0.9996\ifmmode\pm\else\textpm\fi{}0.0030(stat)\ifmmode\pm\else\textpm\fi{}0.0048(syst). This result revealed no evidence of right-handed currents in this kaon-decay chain, and set a stringent bound on the mass of the right-handed weak boson.

Data of the ηπ− system were obtained in the reaction π−p → ηπ−p at 6.3 GeV/c beam momentum. About 17 k events of ηπ− were collected in the mass range 0.8 ⩽ Mηπ- ⩽ 1.8 GeV/c2 and in the range of the momentum transfer squared 0.075 ⩽ |t′| ⩽ 0.60 (GeV/c)2. A large forward-backward asymmetry was observed around 1.3 GeV/c2 in the Gottfried-Jackson frame of the ηπ− system. A partial wave analysis of the data was performed. A peak of the D+ wave attributed to a2 (1320) is clearly seen. An enhancement is observed around 1.3 GeV/c2 in the P+ wave.

Degradation of Gd 2 SiO 5 :Ce in optical transmittance due to proton irradiation was negligibly small below 10 6 rad, smaller than 2%/cm at 10 7 rad and large at 10 8 rad. The radiation hardness of 10 7 rad against protons is by two orders of magnitude smaller than against low energy γ-rays. Long term spontaneous recovery of the proton-induced damage is not large (10–20% of the initial degradation in 84 days). Recovery upon exposure to UV light occurs to some extent. Degradation due to thermal neutrons was negligibly small for a fluence of 10 14 n/cm 2 . No degradation was observed for exposure to fast neutrons of about 10 13 n/cm 2 during one year in the extracted beam tunnel of proton synchrotron.

We compared radiation damages of undoped CsI for 12 GeV protons and for 60Co γ-rays between 104 and 108 rad. Degradation in optical transmission was similar in magnitude both for protons and γ-rays; it is as small as 1–3% per 1 cm thickness at 104 rad, while it is as large as or larger than 5% above 105 rad. The above feature is different for BGO or GSO:Ce, whose radiation hardness is roughly two orders of magnitude smaller regarding protons than regarding γ-rays. Recovery of damage is qualitatively similar both for proton and γ-ray irradiations; spontaneous recovery is only partial and the annealing effect of UV exposure is negligibly small.

J‐PARC Hadron Experimental Facility is designed as a multi‐purpose experimental facility for particle and nuclear physics experiments using high‐intensity secondary particles (Kaons, pions, and so on) produced by 50 GeV‐15 μA (750 kW) primary proton beams. Currently, three secondary beam lines (K 1.8 BR, K 1.8, and KL) have been constructed. The first beam extraction from 50 GeV proton synchrotron was on January 27th, 2009, and the beam commissioning of the primary and secondary beam lines are on going. The present article reports construction status and beam commissioning of Hadron Experimental Facility in detail.

A new type of monochromatic μ + beam channel of high resolution was designed and constructed at the KEK 12 GeV proton synchrotron (KEK-PS). The principle of the channel is to transport 236 MeV/ c μ + emitted in the two body at rest decay of positive kaons, K + → μ + v , in the production target as a beam. In order to eliminate background μ + from in-flight π + decay, the channel has the following features. Firstly, the μ + beam is extracted at a backward angle of 147° from the direction of the 12 GeV primary proton beam, where the π + yield is relatively small. Secondly, the distance from the production target to the first bending magnet is designed to be as short as possible. Thirdly, the high momentum resolution of the beam channel also enables us to observe a very sharp peak in the μ + momentum spectrum, so that the background is efficiently subtracted. The typical intensity of the 236 MeV/ c monochromatic μ + is 3500 per 10 12 incident protons on a thin Pt target. The signal-to-background ratio finally achieved at the peak momentum was 60. This pure Kμ 2 muon beam was successfully utilized for an experiment designed to search for V + A currents in the weak interaction from a precise determination of the μ + longitudinal polarization.

The chromosomal translocation t(11;22)(q24;q12) generates the EWS-Fli1 fusion gene, which contributes to the development of Ewing Family Tumors (EFTs). Although p53 mutations are found only in 5-20% of EFTs, the p53 pathway is thought to be abrogated in EFTs. The role of EWS-Fli1 in the p53 pathway in the tumor is still poorly understood. In this study, using immunoprecipitation and co-localization, we show that EWS-Fli1 interacts with p53 within the nucleus in vivo. The introduction of EWS-Fli1 resulted in significant reduction of promoter activities and mRNA levels of p21 and mdm2, meanwhile it canceled p53-dependent growth suppression. In contrast, knockdown of EWS-Fli1 expression mediated by small interfering RNAs (siRNA) also augmented the induction of p21 and mdm2 in response to DNA damage. Furthermore, using serial deletion constructs of the EWS-Fli1 fusion protein, we determined that EWS-Fli1 binding to p53 as well as inhibition of p21 and mdm2 promoter activities was mediated by its N-terminal domain (amino acid residues 65-109). These observations suggest that the N-terminal region of EWS-Fli1 might associate with p53 and impair its transcriptional activity, subsequently inhibiting the expression of its downstream genes. These results might provide new insight into the oncogenesis of EFTs by EWS-Fli1 via the inhibition of p53 function.

This study evaluated the accuracy of an image-free navigated total knee arthroplasty (TKA) system when used to align deformed tibia bone models. The accuracy was assessed in normal, 10 degrees varus, 20 degrees varus, 10 degrees valgus, and 20 degrees valgus tibia bone models (a total of five tibial models) by direct measurement of the navigated cutting guide. The mean angular errors in the tibial mechanical axes of the normal, 10 degrees, and 20 degrees varus models, respectively, were 0.0 degree, 0.7 degree varus, and 2.4 degrees varus. Thus, the errors seen with the two varus models were significantly larger than that associated with the normal model. The mean angular errors were 0.1 degree varus and 0.4 degree valgus in the 10 degrees and 20 degrees valgus models, respectively. These errors were not significantly different from those obtained with the normal model. These results suggest that in varus-deformed knees, image-free navigation has a tendency to cut the tibia in varus. This fact is considered to be one of the reasons for the lack of superiority of TKA alignment in severely deformed knees when using image-free navigation. Therefore, special attention must be paid when using image-free navigation TKA in such cases.

Using modularized NaI(Tl) detectors, we have carried out a high-statistics measurement of inclusive {gamma}-ray spectra from {ital {bar p}d} annihilation at rest separately for each charge multiplicity of the final state. We have not seen, at statistical significance above 4{sigma}, any monochromatic {gamma}-ray peaks, which may be assigned to baryonium production {ital {bar p}p} or {ital {bar p}n}{r arrow}{gamma}{ital B} or to {ital {bar N}NN} bound-state production {ital {bar p}d}{r arrow}{gamma}({ital {bar N}NN}). The 4{sigma} upper limit for baryonium production per annihilation varied between 10{sup {minus}2} and 10{sup {minus}4} depending on baryonium mass of 1700 to 600 MeV/{ital c}{sup 2} and on the charge multiplicity. At (2--3){sigma} levels, however, five peaks were observed and three of them are located at the same position with the similar (2--3){sigma} peaks observed in {ital {bar p}p}{r arrow}{gamma}{ital B} and {ital {bar p}p}{r arrow}{pi}{sup 0}{ital B}.

Production cross sections of tritium in high energy nuclear reactions with 12 GeV protons were measured for Al, Co, Cu, Nb, Ag, In, Sn, Au and Pb targets. Large production cross sections of > 500 (mb) were obtained for Au and Pb targets. From their atomic weight dependence, tritium cross sections (σ) in mb can be expressed as a function of target atomic weight (A) by the following simple equation: σ(A) = 95 exp(A107), which should be useful for predicting unknown cross sections. Together with other existing data at different energies, the present data suggest that there is no energy dependence of tritium cross section at proton energies above several GeV.

Since chondrosarcoma has a high resistance to conventional chemotherapy and radiotherapy, surgical resection is currently the only effective treatment. Histone deacetylase (HDAC) inhibitor exert anticancer effects, but have not been tested in chondrosarcoma.We investigated the phenotypic change in chondrosarcoma cells treated with SAHA by cell viability assay, Western blot, flow cytometric analysis and electron microscopy.SAHA inhibited the growth of chondrosarcoma cell lines and induced apoptosis in SW1353 with a cleaved-PARP expression and sub-G1 fragmentation according to flow cytometric analysis. On the other hand, in RCS and OUMS-27, SAHA induced autophagy-associated cell death as shown by the detection of autophagosome-specific protein and specific ultrastructural morphology in the cytoplasm. In addition, SAHA significantly inhibited tumor growth in an in vivo xenograft model.These results suggest that SAHA might be a promising agent for performing clinically useful chemotherapy against chondrosarcomas.

This paper reports the present status of the development of computer-controlled magnet power supplies (12-phase thyristor converter) for the KEK 12 GeV proton-synchrotron beam lines. We have been developing a power supply in which an 8-bit microcomputer is embedded and which can be interfaced to a host computer. This power supply has the following advantages: (1) the load on the host computer is reduced; (2) maintenance of the power supplies becomes easier; and (3) the current control is carried out by a microcomputer program instead of conventional regulator circuits. At present a current stability of 2×10−4 has been achieved within 10 ms for a 1% change of line voltage. 2.5% of CPU time is used for this current control.

Multimodal therapies play important roles in the treatment of osteosarcoma (OS) and Ewing's family of tumors (EFTs), two most frequent malignant bone tumors. Although the clinical outcome of primary OS and EFTs is greatly improved, the relapsed cases often are associated with multidrug resistance of the tumors and the prognosis of these patients is still poor. Flavopiridol, a pan cyclin-dependent kinase (CDK) inhibitor is a novel antitumor agent that can induce cell cycle arrest and apoptosis in many cancer cells. However, there have been no studies about the effects of flavopiridol on drug-resistant OS and EFTs. Here, we demonstrated that flavopiridol induced the cleavage of poly-ADP-ribose polymerase (PARP) in a time and dose dependent manner in adriamycin-resistant OS and EFTs cells expressing P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP(1)) as effectively as in their parental cells. Our data also showed that flavopiridol caused the release of mitochondrial cytochrome c and the activation of caspase-9, caspase-8 and caspase-3, with an increase ratio of the proapoptotic protein level (Bax) to the antiapoptotic protein level (Bcl-2 and Bcl-X(L)), while apoptosis was inhibited by pan caspase inhibitor (Z-VAD-FMK) and caspase-3 inhibitor (Z-DEVD-FMK), not by caspase-8 inhibitor (Z-IETD-FMK). The treatment with flavopiridol further inhibited the tumor growth in mouse models of the drug-resistant OS and EFTs. These results suggest that flavopiridol might be promising in clinical therapy for the relapsed OS and EFTs.

We developed beam diagnosis devices, a residual gas ionization beam profile monitor (RGIPM) and an optical transition radiation (OTR) monitor, for a high power proton beam transfer line at the 50-GeV proton synchrotron (PS) of the Japan Proton Accelerator Research Complex (J-PARC). The RGIPM collects electrons produced by beam ionizing a residual gas in the vacuum beam pipe. Since the RGIPM is operated at a vacuum level of 1 Pa, a magnetic field is required to confine electrons around the magnetic field against the diffusion effect due to interactions of drift electrons to residual gas molecules. We, therefore, developed a magnet-built-in type of RGIPM. The OTR monitor observes OTR photons emitted at beam particles crossing a screen with a video camera. We demonstrated that the OTR can be measured even at the KEK 12-GeV proton synchrotron. In order to maintain radiation doses to imaging devices small, the devices are located at a distance of 5 m from the beam line. The OTR photons are collected by a Newtonian reflecting telescope.

Nondestructive beam profile monitor utilizing ionizations of residual gas has been developed for continuous monitoring of 3/spl times/10/sup 14/ protons at Japan Proton Accelerator Research Complex (J-PARC). Knock-on electrons produced in the ionizations of residual gas vacuumed to 1 Pa are collected with a uniform electric field applied between electrodes. Applying a uniform electric field parallel to the electric field is essential to reduce diffusion of electrons crossing over magnetic flux. A prototype monitor has been constructed and installed in EP2-C beam line at KEK 12 GeV proton synchrotron (12 GeV-PS). The profiles measured with the present monitor agree with the ones measured with the existing destructive profile monitor. The present monitor shows sufficient performances as a candidate of the profile monitor at J-PARC. In the present article, the working principle of the present monitor, the results of test experiments, and further developments are described in detail.

Superconducting combined function magnets will be utilized for the 50 GeV, 750 kW proton beam line for the J-PARC neutrino experiment. The magnet is designed to provide a dipole field of 2.6 T combined with a quadrupole field of 19 T/m in a coil aperture of 173.4 mm at a nominal current of 7345 A. Two full-scale prototype magnets to verify the magnet performance were successfully developed. The first prototype experienced no training quench during the excitation test and good field quality was confirmed.

We developed the optical transition radiation (OTR) monitor as a profile monitor for a high intensity (750 kW) slow-extraction beam line at the Japan Proton Accelerator Research Complex (J-PARC). The OTR monitor is considered to be one of good candidates for such a profile monitor, because the OTR light intensity only depends on the reflectivity of an OTR screen. We performed an experiment to test a prototype OTR monitor at the slow-extraction beam line of the KEK 12 GeV-PS. We succeeded to observe a beam profile clearly under the conditions of a low gamma factor of about 13.8, a low beam intensity of 4E11 protons per pulse, and a large beam loss of 1 W/m or more. We also checked a beam response, a background level, and a resistance to radiation of the monitor. We designed and developed two types of the image detecting system such as an optical fiber system and a optical system to enhance the S/N and reduce a radiation damage to the system.

In order to handle high intensity primary proton beam provided by Japan Proton Accelerator Research Complex (J-PARC), radiation-resistant beam lines have been constructed at Hadron Experimental Hall of J-PARC. The key technology of the radiation-resistant beam line is the radiation-resistant magnets. However all the peripheral devices of the magnets were designed and assembled as radiation-resistant ones since peripherals as well as magnets should be operated in very high radiation environment. In addition a safe operation and maintenance scheme of high intensity beam lines has been established based on the Chimney technology of radiation-resistant magnets including their peripherals. Then the beam lines in the Hadron Experimental Hall have been constructed with “radiation-resistant magnet system”.

The construction of the facility of the long baseline neutrino oscillation experiment using the J-PARC's 50 GeV-0.75 MW proton beam [1] was completed at the end of 2008. The number of radiation-resistant magnets we have prepared for the neutrino beamline of J-PARC were 15 with Polyimide resin Insulation (PI) against up to 108 Gy, and 4 magnets with completely Mineral Insulation Cable (MIC) for higher radiation dose up to 1011 Gy, and 2 magnets with Epoxy resin Insulation. All magnets were equipped with remote handling system, i.e. automated magnet lifts, quick alignment guides, water connectors, electric power connectors and interlock-signal connectors. On April 23rd 2009, the first proton beam was successfully introduced to the neutrino beamline from the main accelerator of J-PARC and the long baseline oscillation experiment, T2K, started. Now the beamline is operated with 135 kW (30 GeV-4.5 ) primary proton beam. No serious problem happened on magnets until the great East Japan earthquake on March 11th.

We have developed the most upstream dipole magnet K1.1D1 for a new secondary beam line at the hadron experimental hall in J-PARC. It is placed downstream of a production target and is close to the K1.8D1 magnet. Indirectly cooled coils using mineral insulation cables have been adopted for high radiation resistance. The coils have a slanting saddle shape in order to minimize the interference of the magnetic field between the two magnets. It has been operated during the beam time in the autumn of 2010 without any problems.

In connection with the Japanese Hadron Facility (JHF) project, the development of new types of radiation-resistant magnet coils has been continued at KEK. One major program is the design and production of a mineral insulation cable (MIC) with a larger maximum current. We have already developed a 2000A-class MIC having a square-cross-section hollow conductor. A sample magnet coil was fabricated with this MIC. Tests of its stability and reliability are under progress. We are now planning to develop a 3000A-class MIC. The other program is R/D work on a completely inorganic wrapping insulation material which can be used like the usual type glass-fiber tape pre-impregnated with epoxy-resin. After tests of the mechanical strength and electric insulation of many combinations of tapes and bonds, we found a pure (99%>) alumina-fiber tape pre-impregnated with inorganic cement that is suitable for a magnet coil insulator after thermal curing. >

A new counter experimental hall [K.H. Tanaka et al., IEEE Trans. Magn. 28 (1992) 697] was designed and constructed at the KEK 12-GeV Proton Synchrotron (KEK-PS). The extracted proton beam from the KEK-PS is introduced to the new hall through the newly-prepared primary beam line, EP1, and hits two production targets in cascade. The upstream target provides secondary particles to the low momentum ( 0.4–0.6 GeV c ) separated beam line, K5, and the downstream target is connected to the medium momentum (0.6–2.0 GeV/c) separated beam line, K6. Several new ideas were employed in the beam optical designs of EP1, K5 and K6 in order to increase the number and the purity of the short-lived secondary particles, such as kaons and pions, under the limited energy and intensity of the primary protons provided by the KEK-PS. These new ideas are described in this paper as well as the first commissioning results.