Enhanced Expression of Anti-CD19 Chimeric Antigen Receptor in piggyBac Transposon-Engineered T Cells

Adoptive T cell therapy using chimeric antigen receptor (CAR)-modified T cells is a promising cancer immunotherapy. We previously developed a non-viral method of gene transfer into T cells using a piggyBac transposon system to improve the cost-effectiveness of CAR-T cell therapy. Here, we have further improved our technology by a novel culture strategy to increase the transfection efficiency and to reduce the time of T cell manufacturing. Using a CH2CH3-free CD19-specific CAR transposon vector and combining irradiated activated T cells (ATCs) as feeder cells and virus-specific T cell receptor (TCR) stimulation, we achieved 51.4% ± 14% CAR+ T cells and 2.8-fold expansion after 14 culture days. Expanded CD19.CAR-T cells maintained a significant fraction of CD45RA+CCR7+ T cells and demonstrated potent antitumor activity against CD19+ leukemic cells both in vitro and in vivo. Therefore, piggyBac-based gene transfer may provide an alternative to viral gene transfer for CAR-T cell therapy

Observation of the “Self-Healing” of an Error Field Island in the Large Helical Device

It was observed that the vacuum magnetic island produced by an external error magnetic field in the large helical device shrank in the presence of plasma. This was evidenced by the disappearance of flat regions in the electron temperature profile obtained by Thomson scattering. This island behavior depended on the magnetic configuration in which the plasmas were produced

Measurement and comparison of individual external doses of high-school students living in Japan, France, Poland and Belarus -- the "D-shuttle" project --

Twelve high schools in Japan (of which six are in Fukushima Prefecture), four in France, eight in Poland and two in Belarus cooperated in the measurement and comparison of individual external doses in 2014. In total 216 high-school students and teachers participated in the study. Each participant wore an electronic personal dosimeter "D-shuttle" for two weeks, and kept a journal of his/her whereabouts and activities. The distributions of annual external doses estimated for each region overlap with each other, demonstrating that the personal external individual doses in locations where residence is currently allowed in Fukushima Prefecture and in Belarus are well within the range of estimated annual doses due to the background radiation level of other regions/countries

Compatibility between high energy particle confinement and magnetohydrodynamic stability in the inward-shifted plasmas of the Large Helical Device

The experimentally optimized magnetic field configuration of the Large Helical Device [A. Iiyoshi et al., Nucl. Fusion 39, 1245 (1999)], where the magnetic axis is shifted inward by 15 cm from the early theoretical prediction, reveals 50% better global energy confinement than the prediction of the scaling law. This configuration has been investigated further from the viewpoints of high energy particle confinement and magnetohydrodynamic (MHD) stability. The confinement of high energy ions is improved as expected. The minority heating of ion cyclotron range of frequency was successful and the heating efficiency was improved by the inward shift. The confinement of passing particles by neutral beam injection was also improved under low magnetic field strength, and there could be obtained an almost steady high beta discharge up to 3% in volume average. This was a surprising result because the observed pressure gradient exceeded the Mercier unstable limit. The observed MHD activities became as high as beta but they did not grow enough to deteriorate the confinement of high energy ions or the performance of the bulk plasma, which was still 50% better than the scaling. According to these favorable results, better performance would be expected by increasing the heating power because the neoclassical transport can also be improved there

Improved plasma performance on Large Helical Device

Since the start of the Large Helical Device (LHD) experiment, various attempts have been made to achieve improved plasma performance in LHD [A. Iiyoshi et al., Nucl. Fusion 39, 1245 (1999)]. Recently, an inward-shifted configuration with a magnetic axis position R_ax of 3.6 m has been found to exhibit much better plasma performance than the standard configuration with R_ax of 3.75 m. A factor of 1.6 enhancement of energy confinement time was achieved over the International Stellarator Scaling 95. This configuration has been predicted to have unfavorable magnetohydrodynamic (MHD) properties, based on linear theory, even though it has significantly better particle-orbit properties, and hence lower neoclassical transport loss. However, no serious confinement degradation due to the MHD activities was observed, resolving favorably the potential conflict between stability and confinement at least up to the realized volume-averaged beta of 2.4%. An improved radial profile of electron temperature was also achieved in the configuration with magnetic islands, minimized by an external perturbation coil system for the Local Island Divertor (LID). The LID has been proposed for remarkable improvement of plasma confinement like the high (H) mode in tokamaks, and the LID function was suggested in limiter experiments

Formation of electron internal transport barrier and achievement of high ion temperature in Large Helical Device

An internal transport barrier (ITB) was observed in the electron temperature profile in the Large Helical Device [O. Motojima et al., Phys. Plasmas 6, 1843 (1999)] with a centrally focused intense electron cyclotron resonance microwave heating. Inside the ITB the core electron transport was improved, and a high electron temperature, exceeding 10 keV in a low density, was achieved in a collisionless regime. The formation of the electron-ITB is correlated with the neoclassical electron root with a strong radial electric field determined by the neoclassical ambipolar flux. The direction of the tangentially injected beam-driven current has an influence on the electron-ITB formation. For the counter-injected target plasma, a steeper temperature gradient, than that for the co-injected one, was observed. As for the ion temperature, high-power NBI (neutral beam injection) heating of 9 MW has realized a central ion temperature of 5 keV with neon injection. By introducing neon gas, the NBI absorption power was increased in low-density plasmas and the direct ion heating power was much enhanced with a reduced number of ions, compared with hydrogen plasmas

Reduction of Ion Thermal Diffusivity Associated with the Transition of the Radial Electric Field in Neutral-Beam-Heated Plasmas in the Large Helical Device

Recent large helical device experiments revealed that the transition from ion root to electron root occurred for the first time in neutral-beam-heated discharges, where no nonthermal electrons exist. The measured values of the radial electric field were found to be in qualitative agreement with those estimated by neoclassical theory. A clear reduction of ion thermal diffusivity was observed after the mode transition from ion root to electron root as predicted by neoclassical theory when the neoclassical ion loss is more dominant than the anomalous ion loss

Thermal transport barrier in heliotron-type devices (Large Helical Device and Compact Helical System)

In the discharges of the Large Helical Device [O. Motojima et al., Proceedings of the 16th Conference on Fusion Energy, Montreal, 1996 (International Atomic Energy Agency, Vienna, 1997), Vol. 3, p. 437], a significant enhancement of the energy confinement has been achieved with an edge thermal transport barrier, which exhibits a sharp gradient at the edge. Key features associated with the barrier are quite different from those seen in tokamaks (i) almost no change in particle (including impurity) transport, (ii) a gradual formation of the barrier, (iii) a very high ratio of the edge temperature to the average temperature, (iv) no edge relaxation phenomenon. In the electron cyclotron heating (ECH) heated discharges in the Compact Helical System [K. Matsuoka et al., in Proceedings of the 12th International Conference on Plasma Physics and Controlled Nuclear Fusion Research, Nice, France, 1988 (International Atomic Energy Agency, Vienna, 1989), Vol. 2, p. 411], the internal electron transport barrier has been observed, which enhances the central electron temperature significantly. High shear of the radial electric field appears to suppress the turbulence in the core region and enhance the electron confinement there

Ion cyclotron range of frequency heating experiments on the large helical device and high energy ion behavior

Ion cyclotron range of frequency (ICRF) heating experiments on the Large Helical Device (LHD) [O. Motojima et al. Fus. Eng. Des. 20, 3 (1993)] achieved significant advances during the third experimental campaign carried out in 1999. They showed significant results in two heating modes; these are modes of the ICH-sustained plasma with large plasma stored energy and the neutral beam injection (NBI) plasma under additional heating. A long-pulse operation of more than 1 minute was achieved at a level of 1 MW. The characteristics of the ICRF heated plasma are the same as those of the NBI heated plasma. The energy confinement time is longer than that of International Stellarator Scaling 95. Three keys to successful ICRF heating are as follows: (1) an increase in the magnetic field strength, (2) the employment of an inward shift of the magnetic axis, (3) the installation of actively cooled graphite plates along the divertor legs. Highly energetic protons accelerated by the ICRF electric field were experimentally observed in the energy range from 30 to 250 keV and the tail temperature depended on the energy balance between the wave heating and the electron drag. The transfer efficiency from the high energy ions to the bulk plasma was deduced from the increase in the energy confinement time due to the high energy ions in the lower density discharge, which agrees fairly well with the result obtained by the Monte Carlo simulation. The transfer efficiency is expected to be 95% at an electron density of more than n_e=5.0×10^19 m^?3 even in the high power heating of 10 MW. The accumulation of impurities, e.g., FeXVI and OV was not observed in high rf power and long pulse operation. The well-defined divertor intrinsic to LHD is believed to be useful in reducing the impurity influx