Cytotoxic T Lymphocytes Regenerated from iPS Cells Have Therapeutic Efficacy in a Patient-Derived Xenograft Solid Tumor Model

Current adoptive T cell therapies conducted in an autologous setting are costly, time consuming, and depend on the quality of the patient's T cells. To address these issues, we developed a strategy in which cytotoxic T lymphocytes (CTLs) are regenerated from iPSCs that were originally derived from T cells and succeeded in regenerating CTLs specific for the WT1 antigen, which exhibited therapeutic efficacy in a xenograft model of leukemia. In this study, we extended our strategy to solid tumors. The regenerated WT1-specific CTLs had a strong therapeutic effect in orthotopic xenograft model using a renal cell carcinoma (RCC) cell line. To make our method more generally applicable, we developed an allogeneic approach by transducing HLA-haplotype homozygous iPSCs with WT1-specific TCR α/β genes that had been tested clinically. The regenerated CTLs antigen-specifically suppressed tumor growth in a patient-derived xenograft model of RCC, demonstrating the feasibility of our strategy against solid tumors

The ASTRO-H X-ray Observatory

The joint JAXA/NASA ASTRO-H mission is the sixth in a series of highly successful X-ray missions initiated by the Institute of Space and Astronautical Science (ISAS). ASTRO-H will investigate the physics of the high-energy universe via a suite of four instruments, covering a very wide energy range, from 0.3 keV to 600 keV. These instruments include a high-resolution, high-throughput spectrometer sensitive over 0.3-2 keV with high spectral resolution of Delta E < 7 eV, enabled by a micro-calorimeter array located in the focal plane of thin-foil X-ray optics; hard X-ray imaging spectrometers covering 5-80 keV, located in the focal plane of multilayer-coated, focusing hard X-ray mirrors; a wide-field imaging spectrometer sensitive over 0.4-12 keV, with an X-ray CCD camera in the focal plane of a soft X-ray telescope; and a non-focusing Compton-camera type soft gamma-ray detector, sensitive in the 40-600 keV band. The simultaneous broad bandpass, coupled with high spectral resolution, will enable the pursuit of a wide variety of important science themes.Comment: 22 pages, 17 figures, Proceedings of the SPIE Astronomical Instrumentation "Space Telescopes and Instrumentation 2012: Ultraviolet to Gamma Ray

Hitomi (ASTRO-H) X-ray Astronomy Satellite

The Hitomi (ASTRO-H) mission is the sixth Japanese x-ray astronomy satellite developed by a large international collaboration, including Japan, USA, Canada, and Europe. The mission aimed to provide the highest energy resolution ever achieved at E  >  2  keV, using a microcalorimeter instrument, and to cover a wide energy range spanning four decades in energy from soft x-rays to gamma rays. After a successful launch on February 17, 2016, the spacecraft lost its function on March 26, 2016, but the commissioning phase for about a month provided valuable information on the onboard instruments and the spacecraft system, including astrophysical results obtained from first light observations. The paper describes the Hitomi (ASTRO-H) mission, its capabilities, the initial operation, and the instruments/spacecraft performances confirmed during the commissioning operations for about a month

Rapid Coupled Flow and Geomechanics Simulation Using the Fast Marching Method

We present Fast Marching Method (FMM)-based, rapid coupled flow and geomechanics simulation (FMM-Geo), where FMM-based simulation refers to 1-D simulation along Diffusive Time-of-Flight (DTOF) coordinate that allows efficiently approximating full 3-D simulation with order-of-magnitude less computational time. FMM-based simulation is a technique originally developed for flow problem and it has been successfully applied to field-scale problems. The objective of this study is to extend the FMM-based simulation concepts to coupled flow and geomechanics, so that the coupled simulation can be utilized for high-resolution models, assisted history matching and optimization. Generally, coupled flow and geomechanics simulation has been too expensive to be applied for realistic problems, despite increasing demands for reservoir-geomechanical analysis. The efficacy of our rapid coupled flow and geomechanics simulation derives from the two computational load reduction mechanisms. First, geomechanics is solved for fewer variables through mean-stress based geomechanical formulation, hence the simulator primarily outputs pressure and mean stress. Typically, 3-D geomechanics is solved simultaneously for three components of a displacement vector and the number of variables can be considerably large when it is coupled with 3-D flow problem. By incorporating stress-tensor formulation, mean-stress based simulation is still capable of estimating each stress-tensor component. Secondly, original 3-D problem is transformed into the equivalent 1-D problem formulated along the DTOF coordinate and it leads to a significant reduction of the number of grid blocks. We show that these FMM-based simulation concepts are consistently extended to fully coupled flow and mean-stress based geomechanics, assuming pressure and mean-stress contours are aligned with DTOF contours. The DTOF represents the arrival time of the propagating pressure front that depends on reservoir heterogeneity, and it can be obtained by efficiently solving the Eikonal equation using the Fast Marching Method. The simulator was verified for a 2-D single-phase model against a mean-stress based benchmark simulator and achieved order-of-magnitude faster computation without compromising accuracy. Then we applied the simulator for an assisted history matching problem that integrates well data and surface subsidence data. With sufficient mass fluxes, it is possible that the corresponding pressure change induces detectable deformation at the surface. The history matching results suggest that subsidence data can be used auxiliary for estimating a permeability field in case of spatially limited production data. Finally, we introduce more generalized mean-stress based formulation in an attempt to remove initial/boundary condition related limitations for full 3-D problems. Preliminary results show that a 3-D case with initial stress gradient can be successfully solved in our 1-D simulation scheme by utilizing the generalized formulation. After thoroughly investigating the validity and theoretical limitations of FMM-Geo, we conclude that our rapid coupled flow and geomechanics simulation can be an extremely efficient simulation tool that can reasonably approximate full 3-D simulation for a transient period

Rapid Coupled Flow and Geomechanics Simulation Using the Fast Marching Method

We present Fast Marching Method (FMM)-based, rapid coupled flow and geomechanics simulation (FMM-Geo), where FMM-based simulation refers to 1-D simulation along Diffusive Time-of-Flight (DTOF) coordinate that allows efficiently approximating full 3-D simulation with order-of-magnitude less computational time. FMM-based simulation is a technique originally developed for flow problem and it has been successfully applied to field-scale problems. The objective of this study is to extend the FMM-based simulation concepts to coupled flow and geomechanics, so that the coupled simulation can be utilized for high-resolution models, assisted history matching and optimization. Generally, coupled flow and geomechanics simulation has been too expensive to be applied for realistic problems, despite increasing demands for reservoir-geomechanical analysis. The efficacy of our rapid coupled flow and geomechanics simulation derives from the two computational load reduction mechanisms. First, geomechanics is solved for fewer variables through mean-stress based geomechanical formulation, hence the simulator primarily outputs pressure and mean stress. Typically, 3-D geomechanics is solved simultaneously for three components of a displacement vector and the number of variables can be considerably large when it is coupled with 3-D flow problem. By incorporating stress-tensor formulation, mean-stress based simulation is still capable of estimating each stress-tensor component. Secondly, original 3-D problem is transformed into the equivalent 1-D problem formulated along the DTOF coordinate and it leads to a significant reduction of the number of grid blocks. We show that these FMM-based simulation concepts are consistently extended to fully coupled flow and mean-stress based geomechanics, assuming pressure and mean-stress contours are aligned with DTOF contours. The DTOF represents the arrival time of the propagating pressure front that depends on reservoir heterogeneity, and it can be obtained by efficiently solving the Eikonal equation using the Fast Marching Method. The simulator was verified for a 2-D single-phase model against a mean-stress based benchmark simulator and achieved order-of-magnitude faster computation without compromising accuracy. Then we applied the simulator for an assisted history matching problem that integrates well data and surface subsidence data. With sufficient mass fluxes, it is possible that the corresponding pressure change induces detectable deformation at the surface. The history matching results suggest that subsidence data can be used auxiliary for estimating a permeability field in case of spatially limited production data. Finally, we introduce more generalized mean-stress based formulation in an attempt to remove initial/boundary condition related limitations for full 3-D problems. Preliminary results show that a 3-D case with initial stress gradient can be successfully solved in our 1-D simulation scheme by utilizing the generalized formulation. After thoroughly investigating the validity and theoretical limitations of FMM-Geo, we conclude that our rapid coupled flow and geomechanics simulation can be an extremely efficient simulation tool that can reasonably approximate full 3-D simulation for a transient period

Pressure-induced incommensurate antiferromagnetic order in a ferromagnetic B-site ordered double-perovskite Lu2NiMnO6

We have investigated the pressure effect on magnetic ordering of the ferromagnetic double perovskite Lu 2 NiMnO 6 by magnetization, ac magnetic susceptibility, and neutron diffraction experiments up to 8.0 GPa in order to understand the ferromagnetic-to-antiferromagnetic phase transition by substitution of the A sites in A 2 NiMnO 6 from rare-earth to indium or scandium ions. Strong ferromagnetic spin correlation seen in the susceptibility at low pressure is significantly suppressed by increasing pressure. In a neutron diffraction experiment, the magnetic Bragg reflections associated with ferromagnetic ordering disappear above 4.5 GPa. For the high-pressure region above 4.5 GPa, an antiferromagnetic ordering with long-period incommensurate modulation appears, which is coexistent with ferromagnetic short-range order. From mean-field calculations, we infer that pressure modification of the delicate balance of the competing next-nearest-neighbor exchange interactions between Ni and Ni, or Mn and Mn, plays an important role in the phase transition from ferromagnetic to antiferromagnetic ordering in A 2 NiMnO 6