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The National Institute of Radiological Sciences has investigated multiple-ion therapy using energetic beams of helium, carbon, oxygen, and neon ions, to improve treatment outcomes of refractory cancer. For this therapy, it is necessary to ensure the helium-ion beam purity to avoid irradiation by unwanted ions. Here, we develop a measurement method for monitoring beam purity. This method can measure the charge number of the ions in a high-purity beam using an ionization chamber and Faraday cup. In addition, it can be used to detect the contamination of the clinical helium-ion beam. We perform beam experiments to evaluate our beam-purity monitoring method and predict that our method is capable of detecting contamination below 1%. [ABSTRACT FROM AUTHOR]

A study of multiple-ion therapy with charged heavy-ion beams was performed to improve outcomes of refractory cancer treatments. We proposed the accelerator operation method for applying the multiple-ion therapy, to quickly switch the ion species and energies of the output beams. In this method, the irradiation ion species can be changed only by switching the selected ion source and the injector parameters, and the output beam energies can be varied without changing the magnetic operation patterns of the synchrotron. We verified the effectiveness of our approach by conducting experiments at the Heavy Ion Medical Accelerator in Chiba (HIMAC) and confirmed that the approach can provide the fast switching of both the ion species and the beam energies. The experimental results also demonstrated that our approach will greatly reduce the commissioning time and the routine adjustments for multiple-ion beams. [ABSTRACT FROM AUTHOR]

An application of spin-torque oscillators (STOs) to high-signal-transfer-rate read heads beyond 3 Gbits/s is considered and the signal-to-noise ratios (SNRs) of the output signals under the thermal magnetization fluctuations are calculated by using the results of recent nonlinear theories. The STO head senses the media field as a modulation in the oscillation frequency, enabling high signal transfer rates beyond the limit of ferromagnetic relaxation. The output (digital) signal is obtained by frequency modulation (FM) detection, which is commonly used in communication technologies. As the problem of rapid phase diffusion in nonlinear STOs caused by the thermal fluctuations is overcome by employing a delay detection method, the sufficiently large SNRs are obtained even in nonlinear STOs less than 30×30 nm2 in size. [ABSTRACT FROM AUTHOR]

Analytical expressions of the phase and the amplitude noise spectra under the thermal fluctuation fields (i=x, y, z) are derived for a simplified model of spin-transfer oscillators within a small amplitude approximation. The line broadening caused by the transverse fluctuations hxT and hyT is calculated by using the linear phase-noise theories developed for electronic oscillators and that caused by the longitudinal fluctuation hzT is treated as a random walk problem well known in the theory of magnetic resonance. It is found that the linewidth caused by hxT and hyT is proportional to (αT/MV)(1/A2), where T is the temperature, α, M, and V are the Gilbert damping parameter, the saturation magnetization, and the volume of the free layer, respectively, and A is the amplitude of oscillation. On the other hand, the width caused by hzT is independent of the amplitude and is simply proportional to αT/MV. [ABSTRACT FROM AUTHOR]

Multiple-energy synchrotron operation was developed to realize fast 3D scanning irradiation for carbon-ion radiotherapy. This type of operation can output various carbon-ion beams with different energies in a single synchrotron cycle. The beam control system used in this kind of operation was developed to quickly provide the beam energy and intensity required from the irradiation control system. The performance of the system was verified by experimental tests. The system could output beams of 197 different energies in 63 s. The beam intensity could be controlled for all the output beams without large ripples or overshooting. The experimental test of irradiation for prostate cancer treatment was also successfully performed, and the test results proved that our system can greatly reduce the irradiation time. [ABSTRACT FROM AUTHOR]

The standard treatment for late-onset hypogonadism (LOH) is testosterone replacement therapy (TRT). In Japan, testosterone enanthate intramuscular injection is recommended for LOH. But it needs regular clinic visits every 2-3 week, and it elicit pain. The 2% testosterone gel (AndroForte2®) is available for treatment LOH. Because of imported drug, AndroForte2® (AF2) is expensive. We have created a 2 % novel testosterone gel (NTG). We hypothesized that our NTG improves Aging males' symptoms (AMS) scores, and serum testosterone in patients with LOH. In this active control equivalence, randomized, double-blind, crossover study, it enrolled that were men with low serum free-testosterone (defined as below 11.8pg/mL), and symptoms of androgen deficiency (defined as AMS scores more than 27). The patients were randomly divided into two groups (A group, men receiving the NTG first; and B group, men receiving the AF2 first). Men with LOH received 2% AF2 for 28 days or 2% NTG for another 28 days separated by a 14-day washout period. The AMS score and serum hormonal data, and adverse events were assessed. Twenty-three patients aged 42–71 years old were enrolled in and concluded the study with no adverse events experienced. Serum testosterone and free-testosterone concentrations were significantly higher with NTG and AF2. And more, both concentrations were significantly higher in NTG than AF2. The AMS total score, physical subscore, mental subscore, and sexual subscore were significantly improved with NTG, but not significant with AF2. This is the first study to show that our NTG may not be effective for improvement serum testosterone level but also for physical, mental, and sexual symptoms in patient with LOH. Work supported by industry: no. [ABSTRACT FROM AUTHOR]

Abstract: Multiple-energy synchrotron operation providing carbon-ion beams with various energies has been used for scanned particle therapy at NIRS. An energy range from 430 to 56MeV/u and about 200 steps within this range are required to vary the Bragg peak position for effective treatment. The treatment also demands the slow extraction of beam with highly reliable properties, such as spill, position and size, for all energies. We propose an approach to generating multiple-energy operation meeting these requirements within a short time. In this approach, the device settings at most energy steps are determined without manual adjustments by using systematic parameter tuning depending on the beam energy. Experimental verification was carried out at the HIMAC synchrotron, and its results proved that this approach can greatly reduce the adjustment period. [Copyright &y& Elsevier]

Abstract: A raster scanning method has been developed for cancer therapy at NIRS–HIMAC. This method requires a high-accuracy beam current control and fast beam-on/off switching. We have developed a feedback control system of the beam current with the RF-knockout slow extraction method. The system has allowed a stable response to beam-on/off switching using a feedback control delay function with a beam-current ripple of 7%. [Copyright &y& Elsevier]

Abstract: The betatron tune fluctuation due to current ripple from power supplies causes beam spill ripples in resonant slow extraction. The separatrix area variation due to the tune ripple depends on tune distance from the resonance and field strength of sextupole magnet in the third-integer resonant extraction. We proposed a method to increase tune distance while maintaining separatrix area by controlling sextupole field strength. We measured the correlation between beam spill ripple and tune distance using an artificial tune ripple, and verified the reduction of beam spill ripple below 50%. [Copyright &y& Elsevier]

Abstract: A 3D-scanning irradiation method gated with the patient''s respiration has been developed for the new Heavy Ion Medical Accelerator treatment facility in Chiba. The RF-knockout slow-extraction method has been used for fast on/off switching of the beam from the synchrotron during scanning irradiation. However, a small amount of beam that remained just inside the separatrix spilled out even without the transverse RF field, and limits the controllable low beam rate. We proposed to apply another transverse RF field with a frequency component matched with the betatron frequency of particles near the stopband in addition to the original transverse RF field. The particles just inside the separatrix can be selectively extracted during the irradiation, and the uncontrollable spilled beam can be suppressed. The spilled beam was measured with the ion chamber, and was reduced to 0.4% compared to the original method. [Copyright &y& Elsevier]

A nano-scale magnetic sensor, in which magnetic resonance is induced by the injection of spin fluctuation, is proposed. The device is composed of a thin ferromagnetic layer (FM), a non-magnetic layer and a synthetic antiferromagnet (SyAF). Transverse spin fluctuation in conduction electrons, generated by the thermal fluctuation of magnetization in FM, is injected by current into SyAF. The fluctuation induces magnetic resonance in SyAF under an appropriate external field. The increase in resistance by resonance absorption is estimated, assuming the effective-field type interaction in SyAF. Magnetoresistance of more than 100% is expected for a 30 nm×30 nm device. [Copyright &y& Elsevier]

Presents a study which formed a spin-valve transistor with an iron/gold/iron multilayer base on an n gallium arsenide (001) substrate. Experimental details; Results and discussion; Conclusions.

Examines the energy-dependent hot electron transport across a magnetic multilayer under an external magnetic field. Experiments on a magnetic multilayer using a wafer in a conventional vacuum evaporator; Results of the experiment; Conclusions.

Angular dependence of power spectra is measured for tunnel-type spin-transfer oscillators by changing the direction of the external field in the plane. The oscillation frequency shows the red shift with increasing the current in the case that the field directions are away from the hard axis of the free layer. The frequency shift changes from red to blue at a specific direction near the hard axis, where the linewidth is much reduced. These results are explained by taking into account the nonlinearity arising from the in-plane anisotropy as well as that arising from the demagnetizing effect. [ABSTRACT FROM AUTHOR]

A spin-valve transistor with an epitaxial Fe/Au/Fe(001) base was formed on n-GaAs, the characteristics of which were examined under a magnetic field for emitter voltages up to 3 V. The transfer ratio of the transistor, i.e., the ratio of collector-to-emitter current exceeded 10[sup -3] at 3 V, preserving the magnet current ratio, i.e., the ratio of collector current in the parallel-to-antiparallel magnetic configuration well above 100%. It was suggested that the transfer ratio would be further enhanced by improving the flatness of the tunnel junction for injecting electrons from the emitter into the base, as well as by increasing the electron transmittance at the base/collector interface. © 2001 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Radiotherapy using energetic carbon beams from the Heavy Ion Medical Accelerator in Chiba (HIMAC) has been carried out at the National Institutes of Quantum Science and Technology (QST) since June 1994. Based on positive clinical results, carbon-ion radiotherapy was authorized as an Advanced Medical Technology by Japanese government from 2003 and it was subsequently approved for inclusion in the Japanese National Health Insurance system from 2016. For the widespread use of carbon-ion radiotherapy, design studies as well as related research and development projects were conducted to develop a compact accelerator facility from 2004. Based on these studies, five compact facilities were constructed in Japan. However, since the accelerators are large in size, construction of these facilities is currently limited to university hospitals or large medical centers, and hence development of a more compact accelerator is desired. To further promote widespread proliferation of heavy-ion facilities and concurrently to maximize the potential of heavy-ion therapy, a project to develop a compact superconducting accelerator, the Quantum Scalpel project, was proposed. The compact accelerator employs superconducting technology to reduce the footprint of the entire accelerator system and the accelerator can provide various therapeutic beams of helium, carbon, oxygen, and neon ions having the energy of 56-430 MeV/ u to advanced heavy-ion therapy. In this article, we report the design of the compact superconducting accelerator for the advanced heavy-ion therapy and describe the progress of related research and development projects. [ABSTRACT FROM AUTHOR]

Since 2011, a three-dimensional (3D) scanning irradiation system has been utilized for treatments at the National Institute of Radiological Sciences-Heavy Ion Medical Accelerator in Chiba (NIRS-HIMAC). In 2012, a hybrid depth scanning method was introduced for the depth direction, in which 11 discrete beam energies are used in conjunction with the range shifter. To suppress beam spread due to multiple scattering and nuclear reactions, we then developed a full energy scanning method. Accelerator tuning and beam commissioning tests prior to a treatment with this method are time-consuming, however. We therefore devised a new approach to obtain the pencil beam dataset, including consideration of the contribution of large-angle scattered (LAS) particles, which reduces the time spent on beam data preparation. The accuracy of 3D dose delivery using this new approach was verified by measuring the dose distributions for different target volumes. Results confirmed that the measured dose distributions agreed well with calculated doses. Following this evaluation, treatments using the full energy scanning method were commenced in September 2015. [ABSTRACT FROM AUTHOR]

At Heavy Ion Medical Accelerator in Chiba (HIMAC) in National Institute of Radiological Sciences (NIRS), more than 9000 patients have been successfully treated by carbon ion beams since 1994. The successful results of treatments have led us to construct a new treatment facility equipped with a three-dimensional pencil beam scanning irradiation system, which is one of sophisticated techniques for cancer therapy with high energetic ion beam. This new facility comprises two treatment rooms having fixed beam lines and one treatment room having rotating gantry line. The challenge of this project is to realize treatment of a moving target by scanning irradiation. Thus, to realize this, the development of the fast scanning system is one of the most important issues in this project. After intense commissioning and quality assurance tests, the treatment with scanned ion beam was started in May 2011. After treatment of static target starts, we have developed related technologies. As a result, we can start treatment of moving target and treatment without range shifter plates since 2015. In this paper, the developments of the scanning irradiation system are described. [ABSTRACT FROM AUTHOR]

The electric properties of YBa2Cu3O7-δ/Au interfaces were investigated. An electric contact better than 108 Ω-1/cm2 was obtained at 4.2 K for the interface. There existed, however, a normal layer between the superconducting bulk and the gold electrode, preventing the observation of the proximity effect and the quasiparticle tunneling for this material. [ABSTRACT FROM AUTHOR]

Presents a study that investigated the electrical properties of barium-chromium-nitrogen films. Use of Hall effect measurements; Discussion on the development of semiconductor materials; Application of chemical vapor deposition.

Abstract: Analytical expressions of the output power spectra are derived for spin-transfer nano-oscillators, by using the phase-noise theories, which have been developed for electronic oscillators. The output spectra, which are proportional to the power spectra of transverse component of magnetization, are calculated under the thermal fluctuation with a small amplitude approximation. [Copyright &y& Elsevier]

Introduction: Premature ejaculation (PE) has negative personal consequences, such as distress, bother, frustration, and/or the avoidance of sexual intimacy. In Japan, no oral drugs or devices are approved or used clinically to treat PE. The Men's Training Cup Keep Training (MTCK), a masturbation aid, was developed for PE. MTCK offers 5 grades of tightness and strength. Objective: We aimed to investigate the efficacy of the MTCK in patients who are unable to delay ejaculation. Methods: Inclusion criteria were 20- to 60-year-old men feeling distressed and frustrated by PE and who had the same sexual partners throughout the study period. Exclusion criteria were neurologic disease and uncontrolled diabetes mellitus, as well as the use of antidepressants, α-blockers, and 5α-reductase inhibitors. The protocol comprised an 8-week training period with the MTCK from level 1 to level5, with each level used twice before moving to the next level. The main outcome measure was the extension of intravaginal ejaculation latency time (IELT). The secondary outcome measures were score improvements on the Premature Ejaculation Diagnostic Tool, Sexual Health Inventory for Men, Erection Hardness Score, and Difficulty in Performing Sexual Intercourse Questionnaire–5. Results: We enrolled 37 patients, and after 19 patients withdrew, 18 concluded the study without experiencing any adverse events. The mean patient age was 39.9 years. Geometric IELT after the 8 week training with the MTCK increased significantly (mean ± SE; 232.10 ± 72.16 seconds) vs baseline (103.91 ± 50.61 seconds, P=.006). Mean scores on the Premature Ejaculation Diagnostic Tool, Difficulty in Performing Sexual Intercourse Questionnaire–5, and Erection Hardness Score after 8-week training improved significantly vs the baseline values. The mean score on the Sexual Health Inventory for Men did not improve significantly after the 8-week training, but domain 1 did significantly improve after 8 weeks of MTCK use. Conclusions: The MTCK may be one possible treatment option for patients who are unable to delay ejaculation. Also, the MTCK may offer benefits for erectile function. Disclosure: No. [ABSTRACT FROM AUTHOR]

Introduction: Premature ejaculation (PE) has negative personal consequences, such as distress, bother, frustration, and/or the avoidance of sexual intimacy. In Japan, no oral drugs or devices are approved or used clinically to treat PE. The Men's Training Cup Keep Training (MTCK), a masturbation aid, was developed for PE. MTCK offers 5 grades of tightness and strength. Objective: We aimed to investigate the efficacy of the MTCK in patients who are unable to delay ejaculation. Methods: Inclusion criteria were 20- to 60-year-old men feeling distressed and frustrated by PE and who had the same sexual partners throughout the study period. Exclusion criteria were neurologic disease and uncontrolled diabetes mellitus, as well as the use of antidepressants, α-blockers, and 5α-reductase inhibitors. The protocol comprised an 8-week training period with the MTCK from level 1 to level5, with each level used twice before moving to the next level. The main outcome measure was the extension of intravaginal ejaculation latency time (IELT). The secondary outcome measures were score improvements on the Premature Ejaculation Diagnostic Tool, Sexual Health Inventory for Men, Erection Hardness Score, and Difficulty in Performing Sexual Intercourse Questionnaire–5. Results: We enrolled 37 patients, and after 19 patients withdrew, 18 concluded the study without experiencing any adverse events. The mean patient age was 39.9 years. Geometric IELT after the 8 week training with the MTCK increased significantly (mean ± SE; 232.10 ± 72.16 seconds) vs baseline (103.91 ± 50.61 seconds, P=.006). Mean scores on the Premature Ejaculation Diagnostic Tool, Difficulty in Performing Sexual Intercourse Questionnaire–5, and Erection Hardness Score after 8-week training improved significantly vs the baseline values. The mean score on the Sexual Health Inventory for Men did not improve significantly after the 8-week training, but domain 1 did significantly improve after 8 weeks of MTCK use. Conclusions: The MTCK may be one possible treatment option for patients who are unable to delay ejaculation. Also, the MTCK may offer benefits for erectile function. Disclosure: No. [ABSTRACT FROM AUTHOR]

Abstract: For the quality assurance (QA) of therapeutic scanned carbon-ion beams, QA tool having high spatial resolution is required. The radiochromic film (such as Gafchromic EBT2 film model) is a very useful tool because of its high spatial resolution, self-development, and near tissue equivalence. However, for a complex field in carbon-ion therapy, it is difficult to unambiguously determine the dose from the measured net optical density (OD). As a first approach, we investigated the response of EBT2 to carbon-ion beam at the Heavy Ion Medical Accelerator in Chiba (HIMAC) in Japan. Based on the measured results, we performed QA measurements independently of dose. We verified the QA measurements by EBT2 by comparing the ionization chamber and the fluorescent screen. The results obtained with EBT2 were in good agreement with those obtained with the other detector. In addition, to test the use in a complex field, we verified the OD distributions for moving and static target by means of a gamma index analysis. As a result, we confirmed that EBT2 could be used as a part of QA procedures for therapeutic scanned carbon-ion beams. [Copyright &y& Elsevier]

Abstract: In order to realize a precise dose distribution in heavy-ion cancer therapy, high beam stability is required for the accelerator complex. Owing to load fluctuation caused by the upper ring, which is one of the two rings in HIMAC, current dips of ≈5–10Hz were observed in the power supply for the bending/quadrupole magnet of the other lower ring. The parameters of the beam stability, such as the spill variation, the beam position, and the size, were adversely affected by the current dips. In order to suppress these current dips, we developed a new feed-forward system in the magnet power supply. We verified the performance of the feed-forward system by measuring the suppression of the current dips. We also performed beam experiments to measure the variation of the horizontal tune and the structure of the beam spill, which is slowly extracted by the resonance method. The experimental result showed that the current dips were successfully reduced by the system to ΔI/I ∼10−6. It was also confirmed that the horizontal tune and the spill structure could be stabilized by the current dip suppression. [Copyright &y& Elsevier]

Abstract: Power spectra of a spin-transfer nano-oscillator, in which a reflection layer is included, are measured for current densities up to 1.2×107 A/cm2. A clear oscillation peak, which is slightly asymmetric with respect to the peak frequency, is observed at 5GHz under the external field of 700Oe. The large red shift of the peak frequency on increasing the current, which has been reported in nano-contact devices, is not observed. The relatively low oscillation frequencies as well as the absence of the large red shift indicate the reduction in the demagnetizing field in the free layer. The linewidth decreases with the current and is inversely proportional to the square of the precession amplitude of magnetization in accordance with the recent linear theories. [Copyright &y& Elsevier]

Background Recent reports support the notion that patients with Crohn's disease have a dysregulated innate immune response to endogenous flora. Aim To reveal the distinct gene expression clusters of a lipopolysaccharide-stimulated pathway in the peripheral blood monocytes of Japanese patients with Crohn's disease. Materials and methods Total RNA was extracted from peripheral blood monocytes of four patients in the remission stage of Crohn's disease as well as four controls, and gene expression profiles before and after lipopolysaccharide stimulation were investigated using a high-density oligonucleotide probe array. To focus on innate immunity, the expression of genes to be studied was narrowed down to 118 probe sets which were selected using the following keywords: lipopolysaccharide, toll, myd and tir along with a software of NetAffx Analysis Center. Results Using hierarchical clustering analysis, we picked up to 44 and 36 probe sets for which expression had decreased before and after lipopolysaccharide stimulation, respectively, in patients with Crohn's disease compared with healthy volunteers. The expression of TLR5, 7, MyD88, SIGIRR, and Tollip was decreased both before and after lipopolysaccharide stimulation in patients with Crohn's disease. Conclusion We found several interesting clusters in monocytes before and after stimulation with lipopolysaccharide. These genes may have been responsible for the immunological differences between the Crohn's disease and control patients. [ABSTRACT FROM AUTHOR]

Background Recent reports support the notion that patients with Crohn's disease have a dysregulated innate immune response to endogenous flora. Aim To reveal the distinct gene expression clusters of a lipopolysaccharide-stimulated pathway in the peripheral blood monocytes of Japanese patients with Crohn's disease. Materials and methods Total RNA was extracted from peripheral blood monocytes of four patients in the remission stage of Crohn's disease as well as four controls, and gene expression profiles before and after lipopolysaccharide stimulation were investigated using a high-density oligonucleotide probe array. To focus on innate immunity, the expression of genes to be studied was narrowed down to 118 probe sets which were selected using the following keywords: lipopolysaccharide, toll, myd and tir along with a software of NetAffx Analysis Center. Results Using hierarchical clustering analysis, we picked up to 44 and 36 probe sets for which expression had decreased before and after lipopolysaccharide stimulation, respectively, in patients with Crohn's disease compared with healthy volunteers. The expression of TLR5, 7, MyD88, SIGIRR, and Tollip was decreased both before and after lipopolysaccharide stimulation in patients with Crohn's disease. Conclusion We found several interesting clusters in monocytes before and after stimulation with lipopolysaccharide. These genes may have been responsible for the immunological differences between the Crohn's disease and control patients. [ABSTRACT FROM AUTHOR]

We fabricate perpendicular magnetic recording media comprising two antiferromagnetically coupled Co/Pt multilayers and investigate its magnetic properties by ferromagnetic resonance (FMR) measurement. In such media, the magnetizations of the two perpendicular magnets are designed to compensate each other in the remanent state in order to reduce the dipolar field, which is a limiting factor in high-density magnetic recording devices. We measure FMR absorption spectra of the media and estimate the magnetic anisotropy and interlayer exchange coupling. We also demonstrate that FMR measurement can be employed to read out the magnetization direction. The principles behind this readout method are different from those behind the conventional method of detecting the stray field from the media by means of a magnetoresistive sensor; therefore, the proposed readout method is applicable to magnetic recording media having zero remanent magnetization. We expand this readout scheme to three-dimensional magnetic recording with several vertically stacked recording layers. By providing each recording layer with a different FMR frequency, we experimentally confirm that layer selective readout is possible. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) pencil-beam scanning is an ideal irradiation technique to make the best use of the characteristics of a carbon-ion beam and to provide flexible dose delivery. To suppress beam spread due to multiple scattering and nuclear reactions, we developed a full energy scanning method. In some cases, such as eye treatments, the irradiation fields are very small and short ranged. Accordingly, we prepared a minimum low-energy carbon-ion beam corresponding to water-equivalent residual ranges of less than 2 mm. We performed experimental verification for low-energy carbon-ion beams ranging from 55.6 to 96.0 MeV/u. The accuracy of 3D dose delivery with the low-energy carbon-ion beam was verified by measuring the dose distributions for different target volumes. The results confirmed that the measured dose distributions agree well with the calculated ones. Then, the first eye treatment with low-energy carbon-ion beam to a patient was performed in 2018. [ABSTRACT FROM AUTHOR]

Abstract: Background: Our genomewide association study documented an association between cold medicine‐related Stevens‐Johnson syndrome/toxic epidermal necrolysis (CM‐SJS/TEN) and Ikaros Family Zinc Finger 1 (IKZF1). Few studies examined biological and pathological functions of IKZF1 in mucosal immunity. We hypothesized that IKZF1 contributes to the mucocutaneous inflammation. Methods: Human skin and conjunctival tissues were obtained for immunohistological studies. Primary human conjunctival epithelial cells (PHCjECs) and adult human epidermal keratinocytes (HEKa) also used for gene expression analysis. We also generated K5‐Ikzf1‐EGFP transgenic mice (Ikzf1 Tg) by introducing the Ik1 isoform into cells expressing keratin 5, which is expressed in epithelial tissues such as the epidermis and conjunctiva, and then examined them histologically and investigated gene expression of the epidermis. Moreover, Ikzf1 Tg were induced allergic contact dermatitis. Results: We found that human epidermis and conjunctival epithelium expressed IKZF1, and in PHCjECs and HEKa, the expression of IKZF1 mRNA was upregulated by stimulation with polyI:C, a TLR3 ligand. In Ikzf1 Tg, we observed dermatitis and mucosal inflammation including the ocular surface. In contact dermatitis model, inflammatory infiltrates in the skin of Ikzf1 Tg were significantly increased compared with wild type. Microarray analysis showed that Lcn2, Adh7, Epgn, Ifi202b, Cdo1, Gpr37, Duoxa1, Tnfrsf4, and Enpp5 genes were significantly upregulated in the epidermis of Ikzf1 Tg compared with wild type. Conclusion: Our findings support the hypothesis that Ikaros might participate in mucocutaneous inflammation. [ABSTRACT FROM AUTHOR]

The HIMAC clinical study has been conducted with a carbon-ion beam since June 1994. Since 2006, as a new treatment research project, NIRS has developed both the accelerator and beam-delivery technologies for the sophisticated heavy-ion radiotherapy, which brings a pencil-beam 3D rescanning technology for both the static and moving-tumor treatments. In this technology, the depth-scanning technique was improved to the full-energy depth scanning by realizing a variable-energy operation of the HIMAC synchrotron itself. At present, a heavy-ion rotating gantry has been developed with the superconducting technology and is in a beam-commissioning stage. As a future plan, we just start a study of a multi-ions irradiation for more sophisticated LET-painting and a design study of a superconducting synchrotron for more compact heavy-ion radiotherapy facility. [ABSTRACT FROM AUTHOR]

A ridge filter (RGF), a beam energy modulation device, is usually used for particle radiotherapy with a pencil beam scanning system. The conventional RGF has a one-dimensional (1D) periodic laterally stepped structure in orthogonal plane with a central beam direction. The energy of a beam passing through the different thicknesses of the stepped RGF is modulated. Although the lateral pencil beam size is required to cover the several stepped RGF units to modulate its energy as designed, the current trend is to decrease lateral beam size to improve the scanning system. As a result, the beam size becomes smaller than the size of the individual RGF unit. The aim of this study was to develop a new RGF with two-dimensional (2D) honeycomb geometry to simultaneously achieve both a decrease in lateral beam size and the desired energy modulation. The conventional 1D-RGF and the 2D-RGF with honeycomb geometry were both designed so that the Bragg peak size of a 79 MeV/u carbon ion pencil beam in water was 1 mm RMS in the beam direction. To validate the design of the 2D-RGF, we calculated depth dose distributions in water using a simplified Monte Carlo method. In the calculations, we decreased the lateral pencil beam size at the entrance of the RGF and investigated the threshold of lateral beam size with which the pencil beam can reproduce the desired Bragg peak size for each type of RGF. In addition, we calculated lateral dose distributions in air downstream from the RGF and evaluated the inhomogeneity of the lateral dose distributions. Using the 2D-RGF, the threshold of lateral beam size with which the pencil beam can reproduce the desired Bragg peak size was smaller than that using the 1D-RGF. Moreover, the distance from the RGF at which the lateral dose distribution becomes uniform was shorter using the 2D-RGF than that using the 1D-RGF. These results indicate that when the periodic length of both RGFs is the same, the 2D-RGF allows use of a pencil beam with smaller lateral beam size and a shorter distance from the RGF to the target, resulting in improvement in the conformity of dose distribution in a tumor. [ABSTRACT FROM AUTHOR]

A superconducting rotating-gantry for carbon-ion radiotherapy was developed. This isocentric rotating gantry can transport carbon ions having the maximum kinetic energy of E = 430 MeV/ u to an isocenter with irradiation angles of over ±180°, and is further capable of performing three-dimensional raster-scanning irradiation. By using combined-function superconducting magnets, we could design a compact rotating gantry for carbon-ion radiotherapy. Construction of the gantry structure began since early 2014, and the installation of the entire gantry system to the Heavy Ion Medical Accelerator in Chiba (HIMAC) complex was completed by the end of September, 2015. Beam tuning subsequently began since October, 2015, and carbon ions, as accelerated by the HIMAC upper synchrotron, having kinetic energies of between E = 430–48 MeV/ u were successfully transported with the rotating gantry to the isocenter. The size and shape of the beam spots at the isocenter is being tuned over various combinations of the beam energies and the gantry angle. We will present the recent progress as well as the current status of the superconducting rotating-gantry. [ABSTRACT FROM AUTHOR]

At National Institute of Radiological Sciences (NIRS), we have been commissioning a rotating-gantry system for carbon-ion radiotherapy. This rotating gantry can transport heavy ions at 430 MeV/u to an isocenter with irradiation angles of ±180° that can rotate around the patient so that the tumor can be irradiated from any direction. A three-dimensional pencil-beam scanning irradiation system equipped with the rotating gantry enables the optimal use of physical characteristics of carbon ions to provide accurate treatment. To ensure the treatment quality using such a complex system, the calibration of the primary dose monitor, output check, range check, dose rate check, machine safety check, and some mechanical tests should be performed efficiently. For this purpose, we have developed a measurement system dedicated for quality assurance (QA) of this gantry system: the Daily QA system. The system consists of an ionization chamber system and a scintillator system. The ionization chamber system is used for the calibration of the primary dose monitor, output check, and dose rate check, and the scintillator system is used for the range check, isocenter, and gantry angle. The performance of the Daily QA system was verified by a beam test. The stability of the output was within 0.5%, and the range was within 0.5 mm. The coincidence of the coordinates between the patient-positioning system and the irradiation system was verified using the Daily QA system. Our present findings verified that the new Daily QA system for a rotating gantry is capable of verifying the irradiation system with sufficient accuracy. [ABSTRACT FROM AUTHOR]

Controlling beam position in three-dimensional pencil-beam scanning is important because errors in beam position disturb the uniformity of irradiated dose distribution. To suppress this, we have developed a simple procedure for beamline tuning. Beamline tuning is performed with steering magnets and fluorescent screen monitors to converge a beam’s trajectory to a central orbit. The misalignment between beam position and a reference axis is determined through a verification system, which consists of a screen monitor and an acrylic phantom. If beam position deviates from the reference axis, two pairs of steering magnets, which are placed downstream of the beam transport line, correct the beam. These adjustments are iterated until the deviations for 11 energies of the beam are within 0.5 mm of the reference axis. To demonstrate the success of the proposed procedure, we used it to perform beam commissioning at the Kanagawa Cancer Center.
 [ABSTRACT FROM AUTHOR]

A superconducting rotating-gantry for carbon-ion radiotherapy was developed. This isocentric gantry can transport carbon ions having kinetic energies of between E =430 and 48 MeV/ u to an isocenter over an angle of ±180°, and is further capable of performing three-dimensional raster-scanning irradiation. Construction of the entire rotating-gantry system was completed by the end of September 2015. Prior to beam commissioning, phase-space distributions of extracted carbon beams from the synchrotron were deduced by using an empirical method. In this method, phase-space distributions at the extraction channel of the synchrotron were modeled with 8 parameters, and the best parameters were determined so as to minimize a difference between the calculated and measured beam profiles by using a simplex method. Based on the phase-space distributions, beam optics through the beam-transport lines as well as the rotating gantry were designed. Since horizontal and vertical beam emittances, as extracted slowly from the synchrotron, generally differ with each other, a horizontal–vertical beam coupling would occur when the gantry rotates. Thus, the size and shape of beam spots at the isocenter should vary depending on the gantry angle. To compensate for the difference in the emittances, we employed a method to utilize multiple Coulomb scattering of the beam particles by a thin scatterer. Having compensated for the emittances and designed beam optics through the rotating gantry, beam commissioning over various combinations of gantry angles and beam energies was performed. By finely tuning the superconducting quadrupoles of the rotating gantry, we could successfully obtain the designed beam quality, which satisfies the requirements of scanning irradiation. [ABSTRACT FROM AUTHOR]

Energy barrier height for magnetization switching is theoretically studied for a system with uniaxial anisotropy in a circularly polarized microwave magnetic field. A formulation of the Landau-Lifshitz-Gilbert equation in a rotating frame introduces an effective energy that includes the effects of both the microwave field and static field. This allows the effective-energy profiles to rigorously describe the switching paths and corresponding barrier height, which govern thermally activated magnetization switching under microwave assistance. We show that fixed points and limit cycles in the rotating frame lead to various switching paths and that under certain conditions, switching becomes a two-step process with an intermediate state. [ABSTRACT FROM AUTHOR]

Abstract: The NIRS has carried out carbon-ion radiotherapy (RT) with HIMAC since 1994. On the basis of their ten-year HIMAC experience, NIRS has developed a standard-type CIRT facility in order to boost availability of carbon-ion RT in Japan. Work has been carried out at its pilot facility at Gunma University since 2010. The current projects of the pilot facility include Saga-HIMAT and i-ROCK, promoted by the Kanagawa prefectural cancer center. Toward the further sophisticated conformal carbon-ion RT with HIMAC, the NIRS has since 2006 been developing new treatment technologies, such as a fast 3D rescanning with a pencil beam and a compact rotating gantry. [Copyright &y& Elsevier]

Combined-function superconducting magnets are designed for a heavy-ion rotating gantry. The superconducting coils of these magnets have a surface winding coil structure. To minimize sagitta, the superconducting magnets as well as their coils have a curved shape. Ten superconducting magnets are installed on the rotating gantry. With the superconducting magnets, the rotating gantry can transport carbon ions having 430 MeV/u to a patient with irradiation angles of over \pm180 degrees, and is further capable of performing three-dimensional raster-scanning irradiation. Since the superconducting magnets would be rotated by \pm180 degrees, compact cryocoolers are employed for cooling of the superconducting coil. Because the coil has quadrupole and dipole layers, the superconducting magnets can provide both quadrupole and dipole magnetic field. Using the combined-function superconducting magnets, we can design a compact rotating gantry, while keeping a large scan size at the isocenter; the length and the radius of the gantry would be approximately 13 and 5.5 m, respectively, which are comparable to those for the existing proton gantries. In this paper, we report the design of the superconducting magnets as well as results of some tests. [ABSTRACT FROM PUBLISHER]

At the Heavy Ion Medical Accelerator in Chiba (HIMAC), more than 8000 patients have been successfully treated by carbon ion beams since 1994. The successful results of treatments have led us to construct a new treatment facility equipped with a 3-D pencil beam scanning irradiation system. For the implementation of this irradiation technique, we developed a fast scanning magnet and its power supply, which are required to have field ramp rate of more than 250 T/s. The scanning magnets set at the entrance of the irradiation system are two dipole magnets to scan the beam in both horizontal and vertical directions and used to form the irradiation field to be tumor shape. Before the installation, performance test including both static and dynamic field measurement was carried out. Severe delay of the field and temperature rise were not observed as expected. Measured field ramp rate reached up to 300 T/s. After the installation, we verified the accuracy and stability of the scanned ion beam through the commissioning with the beam. As a successful result of the commissioning, treatment using the new scanning system was started in 2011. [ABSTRACT FROM PUBLISHER]

Abstract: We introduce a method to read the data stored in a three-dimensional (3D) magnetic recording medium comprising plural storage layers. The readout is realized by selecting the storage layer with the ferromagnetic resonance frequency, and detecting the magnetization orientation with the ferromagnetic resonance absorption. This concept is experimentally confirmed with magnetic media comprising NiFe and CoFe layers. The feasibility of applying this method to a realistic 3D magnetic recording medium is discussed by calculating the absorption spectra of several storage layers with different perpendicular magnetic anisotropy constants. [Copyright &y& Elsevier]

Abstract: A flat radiation field for heavy ion beams is used in research experiments and clinical treatments. When a flat field is required, a beam spreading system must be installed for a beam line; thus a simple and affordable method is desirable. To achieve the carbon ion beam spreading, we employed a dual-ring double scattering method (DDSM), which consists of an initial scattering foil and a dual-ring subsequent scatterer. The scatterers for the DDSM were designed and tested to verify the flatness of the radiation field of the carbon ion beam. We obtained 100mm of the flat radiation field in the isocenter plane for the 2D radiation field, as expected. For the 3D radiation field, we obtained a field size of 80mm. With a 60-min setup time, using the DDSM system, and by placing only two scatterers, we can form the flat radiation field. [Copyright &y& Elsevier]

Abstract: Multiple-energy operation with extended flattops for synchrotron accelerators is being developed at HIMAC. This operation uses synchrotron operation-patterns having a stepwise flattop. With these patterns, a beam would be initially accelerated to the maximum energy, and then successively decelerated to lower energies. Having extended the flattops and extracted beams during these flattops, heavy ions with various energies can be provided in a single synchrotron cycle. Since the extraction energy can be quickly changed by the accelerator, itself, no energy degrader will be required to control the depth dose-distribution. By applying this multiple-energy operation to our fast raster-scanning irradiation, we can considerably reduce the total irradiation time, and concurrently obtain excellent depth dose-distributions. Beam acceleration and extraction tests using this operation were made. Successful results of the tests proved the effectiveness of this multiple-energy operation with extended flattops in heavy-ion therapy. [Copyright &y& Elsevier]