Application of gene gun for local-regional cancer

We studied the in vivo gene transfusion using a gene gun, formerly used in plants and culture cells. The hand-held type gene gun (Helios Gene Gun System) is simple and convenient for effective gene transfection in living animals. This method has some advantages in that there is no need for use of viral vector, independence on the cell cycle and local inducement of plural genes. There is a great possibility for application to local-regional cancer.     

Development of next generation PWR in Japan

The demand for energy in Japan is expected to increase steadily into the future, and it seems that the importance of nuclear power generation will be heightened more when the situation of our country which is not rich in energy resources is taken into account.

Furthermore, when we consider the present situation that the light water reactors have become common, recent outlook for the supply and demand for uranium resources, trends in the development of the fast breeder reactor technology, etc., the light water reactors are expected to remain dominant in the nuclear power generation of our country until at least the second half of the 21st century.

Based on such a background five PWR utilities in Japan (Hokkaido, Kansai, Shikoku, Kyushu, and the Japan Atomic Power), and Mitsubishi Heavy Industries, Ltd. have jointly started researching the Next Generation PWR which is expected to be the leading nuclear power plant taking place of APWR.     

Does mixed venous desaturation during a bed bath indicate cardiopulmonary decompensation in postoperative cardiac patients?]

The bed bath procedure consists of cleansing patients' body, passive position change, changing gown and making a bed. During the procedure, mixed venous desaturation was observed consistently in postoperative cardiac patients. We investigated the cause of the phenomenon in 22 patients undergoing cardiac surgery in their first postoperative day. The patients were breathing oxygen-enriched air via a Venturi mask. Cardiac index (CI), transluminal SvO2, arterial blood gas, Hb, DO2, VO2, FIO2, A-aDO2 and Qp/Qs were measured before and during the bed bath, while the patients were in the supine and left lateral position, respectively. Mean 8.5 +/- 1.5 minutes were required to complete the bed bath. During the bed bath, SvO2 decreased from 71 +/- 7% to 59 +/- 9% (P < 0.001), and returned to the baseline 6.5 +/- 7.4 minutes after the completion of the bed bath. VO2 increased markedly from 128 +/- 27 to 194 +/- 47 ml.min-1.m-2 (P < 0.001), while DO2 increased slightly from 480 +/- 91 to 513 +/- 110 ml.min-1.m-2 (P < 0.05). Among the determinants of DO2, CI increased slightly from 3.3 +/- 0.6 to 3.6 +/- 0.8 l.min-1.m-2, Hb remained unchanged and SaO2 decreased from 98.5 +/- 0.8 to 98.0 +/- 1.1%. FIO2 also decreased, while A-aDO2 and Qp/Qs remained unchanged. There was a negative correlation between VO2 change and SvO2 change, but no correlation between DO2 change and SvO2 change. There was a positive correlation between SaO2 change and SvO2 change, as well as between FIO2 change and SaO2 change. Therefore, the major cause of mixed venous desaturation was not the decreased DO2 or cardiopulmonary decompensation but the increased VO2 due to increased activity of the skeletal muscles. However, the decrease in SaO2 due to markedly increased O2 demand and the limited increase in CI might partially contribute to the marked decline in SvO2 through the limited increase in DO2.     

Slit flow of molten polyethylene filled with plastic flakes

The processability of polyethylene in sheet-extrusion or calendering may be improved by the addition of plastic flakes. The effects of plastic flake parameters and flow conditions on the viscosity and the die swell of the suspension were determined, and the structure in flow (morphology or dispersion state) and applications were discussed. Flakes of biaxially oriented polystyrene, high-impact polystyrene, polypropylene, polyamide or polypropylene spheres were dry-blended with polyethylene. The viscosity was determined by means of a slit or a capillary rheometer. The quenched extrudate was annealed and its die swell was measured. Flakes of biaxially oriented polystyrene shrunk into rod-like form during heating, but other plastics retained the flake-form. The relative viscosity and the swell ratio of the suspensions depended on the type of plastic and operating conditions. The rheological behavior of suspensions qualitatively suggested that polypropylene flakes deformed or crowded (including stacking), polyamide flakes deformed slightly, and polystyrene flakes were difficult to buckle, but crowded slightly. The thickness of extrudates can be controlled easily by flake addition due to decreased die swell, while the output would be reduced to some extent.     

Visualizing Intramolecular Dynamics of Membrane Proteins

Membrane proteins play important roles in biological functions, with accompanying allosteric structure changes. Understanding intramolecular dynamics helps elucidate catalytic mechanisms and develop new drugs. In contrast to the various technologies for structural analysis, methods for analyzing intramolecular dynamics are limited. Single-molecule measurements using optical microscopy have been widely used for kinetic analysis. Recently, improvements in detectors and image analysis technology have made it possible to use single-molecule determination methods using X-rays and electron beams, such as diffracted X-ray tracking (DXT), X-ray free electron laser (XFEL) imaging, and cryo-electron microscopy (cryo-EM). High-speed atomic force microscopy (HS-AFM) is a scanning probe microscope that can capture the structural dynamics of biomolecules in real time at the single-molecule level. Time-resolved techniques also facilitate an understanding of real-time intramolecular processes during chemical reactions. In this review, recent advances in membrane protein dynamics visualization techniques were presented.     

Combinatorial Measurement of CDKN1A/p21 and KIF20A Expression for Discrimination of DNA Damage-Induced Clastogenicity

In vitro mammalian cytogenetic tests detect chromosomal aberrations and are used for testing the genotoxicity of compounds. This study aimed to identify a supportive genomic biomarker could minimize the risk of misjudgments and aid appropriate decision making in genotoxicity testing. Human lymphoblastoid TK6 cells were treated with each of six DNA damage-inducing genotoxins (clastogens) or two genotoxins that do not cause DNA damage. Cells were exposed to each compound for 4 h, and gene expression was comprehensively examined using Affymetrix U133A microarrays. Toxicogenomic analysis revealed characteristic alterations in the expression of genes included in cyclin-dependent kinase inhibitor 1A (CDKN1A/p21)-centered network. The majority of genes included in this network were upregulated on treatment with DNA damage-inducing clastogens. The network, however, also included kinesin family member 20A (KIF20A) downregulated by treatment with all the DNA damage-inducing clastogens. Downregulation of KIF20A expression was successfully confirmed using additional DNA damage-inducing clastogens. Our analysis also demonstrated that nucleic acid constituents falsely downregulated the expression of KIF20A, possibly via p16 activation, independently of the CDKN1A signaling pathway. Our results indicate the potential of KIF20A as a supportive biomarker for clastogenicity judgment and possible mechanisms involved in KIF20A downregulation in DNA damage and non-DNA damage signaling networks.     

Time-minimal paths amidst moving obstacles in three dimensions

A path-planning problem is considered in the presence of moving polygonal obstacles in three dimensions. A particle is to be moved from a given initial position to a destination position amidst polygonal disjoint barriers moving along known linear trajectories. The particle can move in any direction in space with a single constraint that it cannot move faster than a given speed bound. All obstacles are slowly moving, i.e., their speeds are strictly slower than the maximum speed of the particle. The destination point is also permitted to move along a known trajectory and is assumed to be collision-free at all times. Three properties are stated and proved for a time-minimal path amidst moving polygonal barriers. A few extensions are considered, including piecewise linear motions of the obstacles.