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Purpose Gene therapy is a promising option for heart failure patients, but there remains a lack of effective delivery mechanisms. The Impella device is a heart pump that can increase coronary flow and pressure, important factors that determines efficacy of gene transduction when using intracoronary delivery. Because it also lends hemodynamic support, the Impella can be coupled with balloon coronary occlusion to increase cardiac vector dwell time. We hypothesized that use of the Impella offers safe and efficient delivery of genes using intracoronary administration of adeno-associated viral (AAV)-6. Methods AAV6 encoding luciferase gene (5.0 × 10E13) was injected into the coronary artery one week after MI induction in Yorkshire pigs. A total of twelve pigs were allocated to one of the following groups: slow antegrade delivery (n=3), slow antegrade delivery with Impella (n=3), delivery during coronary artery occlusion with Impella hemodynamic support (n=3), delivery during coronary artery and sinus occlusions with Impella hemodynamic support (CA + CS, n=3), Four weeks later, tissues were harvested from various heart regions and other organs to assess luciferase expression and viral uptake. Results Impella support offered safe vector delivery during 1-2 minutes of CA and CS occlusion. Impella + coronary artery block enhanced luciferase expression globally in the heart but not in non-cardiac tissues, such as liver, as compared to injection without coronary artery block. Impella with CA + CS block even further increased luciferase expression by increasing viral uptake, as evidenced by increased vector genome in the tissues detected by PCR. At the infarct border zone, an important area for cardiac gene therapy, CA + CS occlusion led to greater than 300-fold increase in luciferase (p=0.005) compared to viral injection alone. Conclusion Impella unloading with CA + CS occlusion dramatically improves AAV gene expression in the heart without increasing off-target expression; it is thus a promising method for clinical application of cardiac gene therapy.

[(18) F]-Fluorodeoxy-d-glucose (FDG) positron emission tomography-computed tomography (PET-CT) is known to be highly accurate in differentiating benign lesions from malignant lesions. In rare cases, benign tumours, viral infections and sarcoidosis of the skin have been reported to show FDG uptake, but the mechanism remains unclear. Here we report the first documented case of seborrhoeic keratosis (SK) showing increased FDG uptake. FDG PET-CT can be used to detect enhanced glycolysis of tumour cells by measuring increased levels of glucose transporters (GLUTs) indicative of higher glucose uptake. GLUT1 and GLUT3 expression in this case was compared with that in PET-negative SK and two normal skin samples using quantitative polymerase chain reaction with paraffin-embedded tissue. The expression of GLUT1 and GLUT3 was higher in PET-positive SK than in PET-negative SK or normal skin. More specifically, the expression of GLUT3 was observed only in the PET-positive case. This study revealed that high GLUT1 and GLUT3 expression in SK might be associated with the uptake of FDG.

To sustain plasmas with higher parameters and with longer pulse duration in LHD, ECH system has been upgraded by introducing newly developed 77 GHz gyrotrons. The designed output power and operation duration time are over 1 MW for several seconds and 0.3 MW for continuous operation, respectively. Owing to the upgrade of gyrotrons and improved power supply operation procedure, total injection power of EC-waves to LHD increased up to 3.7 MW at the last LHD experimental campaign in 2010. Application of the high-power 77 GHz EC-waves of 3.4 MW as focused beams to the center of plasma with low line-average electron density of ∼0.2×10 19m -3 causes highly steep electron temperature profile and the central electron temperature reached up to 20 keV, which highly exceeds the former record of 15 keV. At higher density region of 1×10 19m -3, central electron temperature reached 8.6 keV. Additional electron Bernstein wave heatings, O-X-B and slow X-B heatings, using a 77 GHz ECH system caused clear increase in plasma stored energy even for the high-density plasmas over plasma cutoff (>7. 35×10 19m -3) sustained with NBI. For the O-X-B scenario, the 77 GHz EC-wave was obliquely injected from low-field side in O-mode polarization, aiming at the point where high mode-conversion efficiency was expected. For realizing slow X-B scenario, new inner-vessel mirrors were installed in LHD just close to a helical coil, that is, at the high-field side (HFS) region. Using the inner-vessel mirror, X-mode waves were injected from HFS, showing evident increase in plasma stored energy. Oblique injection of long-pulse 0.77 MW/8 s 77 GHz wave with various N ∥ clearly demonstrated ECCD in LHD. The EC-driven current changes its direction with the sign of N ∥, and the highest EC-driven current reached up to 42 kA. © 2011 American Institute of Physics.

Electron Cyclotron Resonance Heating (ECRH) has contributed to the achievement of high performance plasma production, high electron temperature plasmas and sustainment of steady-state plasmas in the Large Helical Device (LHD). Our immediate targets of upgrading the ECRH system are 5 MW several seconds and 1 MW longer than one hour power injection into LHD. The improvement will greatly extend the plasma parameter regime. For that purpose, we have been promoting the development and installation of 77 GHz/1-1.5 MW/several seconds and 0.3 MW/CW gyrotrons in collaboration with University of Tsukuba. The transmission lines are re-examined and improved for high and CW power transmission. In the recent experimental campaign, two 77 GHz gyrotrons were operated. One more gyrotron, which was designed for 1.5 MW/2 s output, was constructed and is tested. We have been promoting to improve total ECRH efficiency for efficient gyrotron-power use and efficient plasma heating, e.g. a new waveguide alignment method and mode-content analysis and the feedback control of the injection polarization. In the last experimental campaign, the 77 GHz gyrotrons were used in combination with the existing 84 GHz range and 168 GHz gyrotrons. Multi-frequency ECRH system is more flexible in plasma heating experiments and diagnostics. A lot of experiments have been performed in relation to high electron temperature plasmas by realization of the core electron-root confinement (CERC), electron cyclotron current drive (ECCD), Electron Bernstein Wave heating, and steady-state plasma sustainment. Some of the experimental results are briefly described. © 2009 American Institute of Physics.

Three dimensional (3D) stacking of memory chips is a promising direction for implementing memory systems in mobile applications [1-2] and for low-cost high-performance computation [3]. The requirements are extremely low power consumption, high data bandwidth, stability and scalability of operation, as well as large storage capacity with a small footprint. A digital control chip at the base of the stack is needed to efficiently access the 3D memory hierarchy, as well as to emulate a standard memory interface for compatibility. The overall performance and yields of a 3D system are constrained by vertical communication channels among the stacked chips, as well as the connections to the PCB. However, the empirical models presently used in the design stage do not properly represent the electrical and mechanical properties and performance variations of through silicon vias (TSVs) and microbumps (μBumps). What is needed are circuit techniques that handle such uncertainties to enable the creation of robust 3D data links. This paper presents a complete test vehicle for TSV-based wide I/O data communication in a three-tier 3D chip stack assembled in a BGA package. In-place eye-diagram and waveform capturers are mounted in an active silicon interposer to characterize vertical signaling through the chain of TSVs and μBumps. © 2013 IEEE.

The 170 GHz gyrotron for ITER demonstrated the stable and steady state 1000s operation with the output power of 0.6 MW and the efficiency of 45% by depressed collector. The remarkable progress was obtained with optimization of a built-in launcher and mirrors for significant reduction of the stray radiation to ∼2% of the output power, improvement of electron beam quality for high oscillation efficiency and control of constant beam current for stable oscillation. The result indicates a promising prospect for development of a I MW-CW-50%, 170 GHz ITER gyrotron.

In GAMMA 10, the upgrade program of high power plug and central ECRH have started for the study of the physics of plasma potential and the demonstration of high plasma performance proving the tandem mirror advantage. A new high power (upgrade) gyrotron has been developed in collaboration with JAEA from 2003 for this purpose and now three upgrade gyrotrons were installed in GAMMA 10. The first gyro torn in 2004 outputted about 500 kW power at the gyrotron window, corresponding to 400kW injection power to plasma. In 2005, the power of 570 kW at the window was obtained from the second one, which was improved mainly in mode converter. These gyrotron were applied to plug cells and a new record value of ion confining potential Φ c = 3 kV was obtained at 470 kW injection, which is four times higher than the previous value before 2003. For the central ECRH system, the upgrade of DC power supply was conducted using the DC power supply from JFT-2M ECH system and the system outputted 400kW at MOU out with the upgrade gyrotron. The central ECRH has been conducted with the combination of the new efficient antenna, transmission line and the upgrade gyrotron, and the initial experiment resulted Te ≥ 500eV.

Generalized scaling laws for the formation of plasma confining potentials are investigated to find the physics essentials common to representative tandem-mirror operational modes in GAMMA 10. These modes are characterized in terms of (i) a high-potential mode and (ii) a hot-ion mode. The potential-formation scalings in these modes are consolidated and generalized on the basis of the consistency with finding of the wider validity of Cohen's strong electron-cyclotron heating (ECH) theory covering over both modes. A plateau-shaped electron distribution function is observed when a plug electron-confining potential is formed in the hot ion mode of GAMMA 10, as predicted in terms of the strong ECH theory.

(1) Four-time progress in ion-confining potentials Φ c to 3.0 kV in comparison to Φ c attained 1992-2002 is achieved in the hot-ion mode (T i =several keV). A scaling of Φ c , which favorably increases with plug electron-cyclotron heating (ECH) powers (P PECH ), is obtained. (2) The advance in Φ c leads to a finding of remarkable effects of radially sheared electric fields (dEr/dr) on turbulence suppression and transverse-loss reduction. (3) A weak decrease in Φ c with increasing n c to ∼10 19 m -3 with the recovery of Φ c with increasing P PECH is obtained. (4) The first achievement of active control and formation of an internal transport barrier (ITB) has been carried out with the improvement of transverse energy confinement. Off-axis ECH in an axisymmetric barrier mirror produces a cylindrical layer with energetic electrons, which flow through the central cell and into the end region. The layer, which produces a localized bumped ambipolar potential Φ c , generates a strong E r shear and peaked vorticity with the direction reversal of E r ×8 sheared flow near the Φ c peak. Intermittent vortex-like turbulent structures near the layer are suppressed in the central cell. This results in T e and T i rises surrounded by the layer. The phenomena are analogous to those in tokamaks with ITB. (5) Preliminary central ECH (170 kW, 20 ms) in a standard tandem-mirror operation raises T e0 from 70 to 300 eV together with T ι⊥0 from 4.5 to 6.1 keV, and T i//0 from 0.5 to 1.2 keV with τ P0 =95 ms for Φ c (=1.4 kV) trapped ions. The on-axis particle to energy confining ratio of τ P0 /τ E0 is observed to be 1.7 for Φ c trapped ions (consistent with Pastukhov's theory) and 2.4 for central mirror-trapped ions with 240-kW plug ECH and 90-kW ICH (η ICH ∼0.3; nl c =4.5×10 17 m -2 ). (6) Recently, a 200 kW central ECH with 430 kW plug ECH produces stable central-cell plasmas (T e =600 eV and T i =6.6 keV) with azimuthal E r ×B sheared flow. However, in the absence of the shear flow, hot plasmas migrate unstably towards vacuum wall with plasma degradation.

The dependence of the resonance position of the central-ECH (c-ECH) on plasma behavior was investigated using a fast camera. When the resonance positions were higher, low frequency fluctuation of ~...

An application of electron-cyclotron heating with an off-axis resonance location produces a cylindrical layer with energetic electrons and facilitates the formation for a profile of plasma rotation...

Along the upgrade program of ECRH system in GAMMA10, the gyrotron of 500kW level at 28GHz has been developed. The first 500kW gyrotron delivered 500kW at the windows and contributed to produce high ion confining potential. During the operation, it is found that there were some points to be improved: 1) Saturation level of output is smaller than expected. 2) Body current is large. 3) Beam over current occurs frequently. The second gyrotron was redesigned to improve these three points for stable operation. The second one has been changed in the design of internal mode converter, the shape of structure in collector and the slope of internal top roof of the collector. As a Result of 3 improved points, the maximum output power increased from 516kW to 570 kW, body current decreased from 5mA to 2mA, and the rate of beam over current decreased from 7% to 4%.

A new 28GHz 500kW gyrotron was developed for the electron cyclotron resonance heating system of tandem mirror GAMMA10. The maximum output power of 570 kW was obtained by experimental optimization. The efficiency of the gyrotron is 40∼50% in the power range of 300∼500 kW output with the optimization in spite of the restriction of the present magnet. The non-desirable influences caused by he leakage field of the magnet system of GAMM10 were minimized by the adjustment of gyrotron coil parameters and the minor change of the gyrotron and magnetic shield design.

Enhancement of the output power per gyrotron has been planned in the Large Helical Device (LHD). Three 77-GHz gyrotrons with an output power of more than 1 MW have been operated. In addition, a high power gyrotron with the frequency of 154 GHz (1 MW/5 s, 0.5 MW/CW) was newly installed in 2012 and the total injection power of ECRH reached 4.6 MW. The operational regime of ECRH plasma on the LHD has been extended due to the upgraded ECRH system such as the central electron temperature T{sub e0} = 13.5 keV with n{sub e} = 1×10{sup 19}m{sup −3}. In the LHD, an electron-internal-transport barrier (e-ITB) related to the production of high T{sub e} plasmas has been realized by strongly centre-focused ECRH. The electron thermal confinement clearly improved inside the e-ITB. The radial electric field was measured using the heavy ion beam probe. The formation of the positive E{sub r} was observed in the core region, which well agreed with the prediction of the neoclassical transport theory. The energy confinement characteristics have been investigated in the ECRH plasmas. It was found that higher plasma stored energy and lower radiation power was realized in the outward configuration. The plasma stored energy of 530more » kJ with n{sub e} = 3.2×10{sup 19}m{sup −3}, which is the 1.7 times larger than the previous record in the ECRH plasma in the LHD, has been successfully achieved.« less

Giant magnetoresistance (MR) effect has been investigated for Fe-rich FeCoNi(1.5 nm)/Cu(0.8 to 2.6 nm) multilayers deposited by rf magnetron sputtering method on MgO(100) or glass substrates with Fe buffer layers. The MR ratio, the antiferromagnetic coupling strength and the film structure were examined for the multilayers with the magnetic layers of Fe 56 Co 30 Ni 14 . The multilayers exhibit oscillatory MR as a function of Cu thicknesses in the same manner as Fe/Cu multilayers. The multilayer of glass/Fe/[Fe 56 Co 30 Ni 14 (1.5 nm)/Cu(1.3 nm)] 20 exhibited a large MR ratio of 24% at room temperature and 40% at 77 K. After annealing at 250°C, the MR ratio became still larger, 40% at RT and 67% at 77 K, which are comparable to those of Co/Cu multilayers.

Experiments were conducted to assess the effect of beta-mercaptoethanol (beta-ME) on the quality and viability of bovine blastocysts derived from in-vitro culture (IVC) of in-vitro matured and fertilized (TVM-IVF) oocytes during their transport between 2 distant places. Follicular oocytes were collected from ovaries obtained at a slaughterhouse and were cultured for 20 to 21 h in modified TCM-199. The IVM oocytes were fertilized in vitro with frozen-thawed spermatozoa. Fertilized oocytes were cultured for 7 d, and embryos that developed to the blastocyst stage were used for the experiments. The blastocysts, packed in straws with transportation medium that consisted of modified TCM-199 with HEPES equilibrated in air and supplemented with 20 % calf serum and 0, 10, 50, 100 or 150 microM beta-ME, were transported at 37 degrees C from Tokyo to Sapporo by air (18.3 h). The quality of blastocysts was assessed and ranked as excellent (A), good (B), fair (C) or poor (D) after transportation. The percentages of blastocysts ranked as A or B were significantly higher (P < 0.05) when the embryos were transported in beta-ME supplemented medium (80 to 100%) than when transported without beta-ME (54 %). Blastocysts ranked as A or B after transportation in medium with or without 150 microM beta-ME were nonsurgically transferred to synchronous recipients; 60 d after embryo transfer, 21/36 and 19/35 cows, respectively, were diagnosed as pregnant by palpation per rectum. These results indicate that beta-ME maintains the quality of bovine blastocysts in plastic straws for several hours without control of CO2 and that the concentration of beta-ME used in this experiment is not detrimental to the blastocysts.

Optical absorption spectra of CuInSe2 single crystals were measured for the samples with −0.150≤x≤0.053, where x represents a degree of nonstoichiometry in the formula Cu1−xIn1+xSe2. The Urbach’s tail was observed for all samples between 90 K and room temperature. The Urbach’s energy, which represents an arbitrary intensity of exciton–phonon interaction, was almost constant for the Cu‐rich samples (x

Idiopathic pulmonary haemosiderosis (IPH) is a rare cause of alveolar haemorrhage. Its management in pregnancy is complicated and little clinical data exist on outcomes or treatment. Two patients with IPH, one with a known diagnosis prior to pregnancy (patient A) and one presenting de novo during pregnancy (patient B) are reported. Both subjects became maximally symptomatic in the third trimester and were treated with corticosteroids. Despite steroid treatment patient A had continued symptoms and was treated with azathioprine. Both patients delivered healthy female infants at 32 weeks and 38 weeks gestation, respectively. Patient B's course was complicated by the development of fatal invasive pulmonary aspergillosis 4 weeks postpartum. With improved care, more patients with IPH survive to childbearing age. Patients become most symptomatic late in pregnancy, underscoring the need for careful third trimester monitoring. These cases demonstrate that steroids are safe and that azathioprine can be used as additional therapy. When considering treatment options it is important to weigh the benefits of these medications against the potential for maternal and foetal harm.

The Pentax-AWS (AWS(®)), a new video laryngoscope, has been shown to be useful in cases of difficult intubation. We hypothesized that the AWS(®) would be more useful in the settings of a narrow upper airway than the Macintosh laryngoscope. We compared each device in simulated scenarios of representative difficulty of tracheal intubation using a manikin. The primary endpoint was the rate of successful intubation.With each device, 23 anesthesiologists performed tracheal intubation in a SimMan(®) manikin in the following scenarios: (1) normal airway, (2) tongue edema, (3) cervical spine rigidity, (4) pharyngeal obstruction, (5) jaw trismus, (6) tongue edema with pharyngeal obstruction. The intubation time and success rate were measured. Each participant was asked to rate the difficulty of intubation (1=very easy; 5=very difficult).In the scenarios of tongue edema and tongue edema with pharyngeal obstruction, the AWS(®) yielded a higher success rate (100% vs. 34.8%; P0.001, 65.2% vs. 21.7%; P=0.006), a shorter intubation time [14.6 (7.0) vs. 33.4 (13.0) s; P0.001, 24.5 (12.0) vs. 37.6 (11.9); P=0.047; mean (standard deviation)], and a lower difficulty score [2 (1-4) vs. 5 (1-5); P0.001, 4 (2-5) vs. 5 (3-5); P0.001; median (range)], compared with the Macintosh laryngoscope.The AWS(®) has an advantage over the Macintosh laryngoscope in simulated tongue edema and tongue edema with pharyngeal obstruction. Further studies in a clinical setting are necessary to confirm these findings.

A twin-engine, low-wing transport model, with a supercritical wing designed for a cruise Mach number of0.77 and a lift coefficient of 0.55, was tested in the 16-Foot Transonic Tunnel at NASA Langley Research Center. The purpose of this test was to compare the wing/nacelle interference effects of superfans (very high bypass ratio turbofans, BPR ≈ 18) with the interference effects of advanced turbofans (BPR ≈ 6). Flow-through nacelles were used in this study. Forces and moments on the complete model were measured using a strain gage balance and extensive surface static pressure measuements (383 orifice locations) were made on the model’s wing, nacelles, and pylons. Data were taken at Mach numbers from 0.50 to 0.80 and model angle-of-attack was varied from −4 to +8 deg. Results of the investigation indicate that superfan nacelles can be installed with approximately the same drag penalty as conventional turbofan nacelles.

Second harmonic electron cyclotron resonance heating has been used for the production of hot electrons in an axisymmetric end mirror of the GAMMA 10 tandem mirror. Heating power is injected in the linearly polarized extraordinary mode into a limited area of the mirror field for the purpose of localized heating and temperature control. A ray tracing code and a Fokker-Planck code are used for a preparatory consideration of the heating configuration as well as for an interpretation of the experimental results. The path of the injected power flow is analysed with a simple model and the localized heating is confirmed. The electron temperature is controlled and the plasma in which the hot electrons form a substantial fraction of the total density (up to 0.8) is maintained macroscopically stable. The hot electron production rate is found to depend on the magnetic field strength, the target plasma density, the gas feed rate and the heating power. Several key factors that are important for successful results to be achieved are found. Experimental observations indicate that, essentially, the concept of quasi-linear diffusion of electrons in velocity space holds. It is also found that warm electrons play an important role in microwave absorption as well as in efficient hot electron production.

Intracellular dissolution of inhaled particles is an important pathway of clearance of potentially toxic materials. To study this process, monolayers of human and canine alveolar macrophages (AM) were maintained alive and functional in vitro for more than 2 wk. Complete phagocytosis of moderately soluble, monodisperse 57Co3O4 test particles of four different sizes was obtained by optimizing the cell density of the monolayer and the particle-to-cell ratio. The fraction of the initial particle mass that was soluble increased over time when the particles were ingested by AM but remained constant when in culture medium alone. Smaller particle sizes had a faster characteristic intracellular dissolution rate constant than did larger particles. The dissolution rates differed between AM obtained from two human volunteers as compared to those obtained from six mongrel dogs. These in vitro dissolution rates were very similar to in vivo translocation rates previously obtained from human and canine lung clearance studies after inhalation of the same or similar monodisperse, homogeneous 57Co3O4 test particles. We believe an important clearance mechanism for inhaled aerosol particles deposited in the lungs can be simulated in vitro in a cell culture system.

A steady-state operation of 1 MW/800 s with the efficiency of 55%, which exceeded 1 MW/400 s of the performance required in ITER, was demonstrated in 170 GHz gyrotron. The oscillation characteristics in the long pulse operation was clarified, and the advanced operation scenario of the gyrotron to the high efficiency oscillation was newly established by controlling a pitch factor of the electron beam and the cavity magnetic field in the long pulse operation. In the long pulse experiment, the steady state operation of 1 hour with the output power of 0.6 MW was also demonstrated.

A high power and long pulse gyrotron development has been carried out in JAERI for fusion application. The frequency is 170 GHz for ITER (International Thermonuclear Experiment Reactor) and 110 GHz for JT-60U tokamak of JAERI. Both gyrotrons have low loss diamond window. The outputs of 0.9 MW/9.2 sec and 0.5 MW/30 sec were demonstrated at 170 GHz with a depressed collector operation. It was proved that a pulse extension is possible without long time conditioning in principle. On 110 GHz gyrotron, 1.2 MW/4s ec and 1 MW/5 sec operation have been accomplished in the heating experiment of JT-60U.

A design and experimental results of a 110 GHz gyrotron with a single stage depressed collector are presented. By recovering a spent beam energy, efficiency of the gyrotron was improved from 30% to 50% with the RF output power of 610 kW and the pulse duration of 50 ms. A stable 5 sec oscillation was performed at 350 kW (output energy 1.75 MJ) with high efficiency of /spl sim/48% and the 420 kW-3.3 sec oscillation was also obtained. Conditioning time was short compared with the conventional gyrotron since a collector heat load was significantly reduced by the application of the beam retarding voltage. >

The high order mode escalation which reduces the heat load at the cavity of 170 GHz has succeeded without the adjacent mode competition. We performed 0.5 MW-0.75 sec and 0.175 MW-10 sec oscillation, but the output power was limited by the gyrotron window. For this solution, we have lately confirmed that the large size window disk of diamond manufactured by chemical vapor deposition (CVD) has the outstanding property; low loss tangent (tan/spl delta//spl les/1.4/spl times/10/sup -4/) and high thermal conductivity (1800 W m/sup -1/ K/sup -1/) and is available for 0.5 MW continuous wave (cw) transmission. On the basis of the result above, the modified 170 GHz 0.5 MW, long pulse gyrotron with the diamond window has been fabricated. We will also construct the 100 GHz range transmission line and the high power (1 MW level) and long pulse transmission experiment will be carried out.

As the mobile electronics equipment moves toward higher performance and miniaturizing, each IC package is required to be stacked for saving a package mounting area on a system board. This paper describes a newly developed 3-dimensional module package using the technology of the silicon device thinning, micro flip chip bonding and two types of via connection of print circuit board for vertical wirings. These technology has realized the high density packaging of over 4 ICs stacking for practical use.

Some infarcted myocytes undergo caspase-dependent DNA fragmentation, but serine protease-dependent DNA fragmentation may also be involved. There is controversy regarding whether caspase inhibitors can reduce infarct size, so the present study investigated whether serine protease inhibitor can reduce the DNA fragmentation of infarcted myocytes and whether serine protease or caspase inhibitors attenuates myocardial infarct size in Japanese white rabbits without collateral circulation. Rabbits were subjected to 30-min coronary occlusion followed by 48-h reperfusion. A vehicle (dimethylsulfoxide, control group, n=8) or Z-Val-Ala-Asp(Ome)-CH2F (ZVAD-fmk, a caspase inhibitor, ZVAD group, 0.8 mg/kg iv at 20 min before coronary occlusion and 0.8 mg/kg at 90 min after reperfusion, n=8) or 3,4-dichloroisocoumarin (DCI, a serine protease inhibitor, 2 mg/kg iv at 20 min before coronary occlusion, DCI group, n=8) was administered. Animals were killed at 48h after reperfusion for the detection of myocardial infarct size and at 4h after reperfusion for the detection of dUTP nick end-labeling (TUNEL)-positive myocytes, the electrophoretic pattern of DNA fragmentation and ultrastructural analysis. The left ventricle (LV) was excised and sliced. The myocardial infarct size as a percentage of the area at risk was assessed by triphenyltetrazolium chloride staining. DNA fragmentation was assessed by in situ TUNEL at the light microscopic level. ZVAD and DCI significantly reduced the mean blood pressure during reperfusion without affecting heart rate. There was no significant difference in the % area at risk (AAR) of LV among the 3 groups (control: 26.3+/-3.0%; ZVAD: 25.6+/-2.6%; DCI: 25.6+/-2.0%). The % infarct size as a percentage of the AAR in the ZVAD group (41.3+/-4.5%) and the DCI group (50.4+/-3.8%) was not significantly different from the control group (43.5+/-4.5%). However, the percent DNA fragmentation in the infarcted area in the ZVAD (3.5+/-0.8%) and DCI groups (4.2+/-0.9%) was significantly reduced compared with the control group (10.7+/-1.9%). The DNA ladder pattern observed in the control group was attenuated in both the ZVAD and DCI groups. There was no difference in electron microscopic changes among the 3 groups. Serine protease-dependent DNA fragmentation is present in infarcted myocytes, in addition to caspase-dependent DNA fragmentation, but an infarct-size reducing effect was not observed with either of these inhibitors.

A 40-year-old man was admitted with fever and purpura. He was diagnosed as having acute promyelocytic leukemia, and treated with all-trans retinoic acid. After achieving complete remission, he received consolidation therapy. During the chemotherapy, quadriplegia occurred three times. This was diagnosed as hypokalemic periodic paralysis because of the patient's low serum potassium level. Results of hormone and urine examinations showed no indication of secondary hypokalemia. However, the patient had a history of quadriplegia of unknown etiology at the age of 36. We speculated that in addition to the patient's predisposition to hypokalemic periodic paralysis, chemotherapy including prednisolone, and excessive ingestion of carbohydrate had induced his quadriplegia.

1. We investigated the effects of 1-(3-tert-butyl-2-hydroxy-5-methoxyphenyl)-3-(3-pyridylmethyl)urea hydrochloride (T-0162), a novel low-molecular weight free radical scavenger, on the generation of superoxide anions and hydroxyl radicals in vitro and in vivo and on myocardial infarct (MI) size in an in vivo model of MI in rabbits. 2. It was found that T-0162 scavenged both superoxide anions and hydroxyl radicals in a concentration-dependent manner in vitro. 3. In an in vivo rabbit model with 30 min coronary occlusion and 30min reperfusion, T-0162 scavenged hydroxyl radicals generated in the myocardium during reperfusion. 4. Anaesthetized open-chest Japanese white male rabbits were subjected to 30 min coronary occlusion and 48 h reperfusion. The control group (n = 10) was infused with 10% lecithin solution for 220 min from 10 min before occlusion to 180 min after reperfusion. The pretreatment group (n = 10) was infused with T-0162 dissolved in 10% lecithin solution for 220 min from 10 min before occlusion to 180 min after reperfusion at a rate of 400 microg/kg per min. The post-treatment group (n = 10) was injected with an i.v. bolus of 10 mg/kg T-0162 and was then infused with 400 microg/kg per min T-0162 for 190 min from 10 min before reperfusion to 180 min after reperfusion. After 48 h reperfusion, infarct size was measured histologically and expressed as a percentage of area at risk (AAR). 5. There was no significant difference in haemodynamic parameters among the three groups throughout the experimental period. The per cent infarct size of the AAR in the T-0162 groups (24.8+/-4.3 and 30.5+/-3.9% for pre- and posttreatment groups, respectively) was significantly reduced compared with control (44.7+/-4.1%; P0.05). There was no significant difference in the AAR among the three groups. 6. In conclusion, T-0162 reduces MI size through the inhibition of reperfusion injury.

A status of high power gyrotron development at JAERI is presented. Gyrotrons of 170 GHz and 110 GHz are under development for ITER (International Thermonuclear Experimental Reactor) and JT-60U, respectively. Both gyrotrons have a low loss synthetic diamond window that enables Gaussian beam output over 1 MW and a depressed collector. The output power of -1 MW/3 s was obtained for the 110 GHz gyrotron. A heating experiment was carried out using three 110 GHz gyrotrons on the JT-60U, and an effective local heating capability in plasma was demonstrated (e.g., attainment of 15 keV of electron temperature). As for 170 GHz device, an output power of 1.2 MW with electron beam of 85 kV/49 A was obtained for a short pulse (/spl sim/5 ms). The efficiency of /spl sim/52% was obtained at 1.0 MW with a depressed collector operation of 36.5 kV.

1. We examined whether N-hydroxyethyl-1-deoxynojirimycin (miglitol), a new human anti-diabetic drug with effects to inhibit alpha-1, 6-glucosidase glycogen debranching enzyme and reduce the glycogenolytic rate as well as to inhibit alpha-1,4-glucosidase, could reduce infarct size in the rabbit heart. Rabbits were subjected to 30-min coronary occlusion followed by 48-h reperfusion. 2. The infarct size as a percentage of area at risk was not reduced by pre-ischaemic treatment with 1 mg kg(-1) miglitol (42.7+/-4.0%, n=10) compared with the saline control group (41.7+/-2.3%, n=10). However, it was significantly and dose-dependently reduced by pre-ischaemic treatment with 5 or 10 mg kg(-1) of miglitol (25.7+/-4. 5%, n=10, and 14.6+/-2.4%, n=10, respectively) without altering the blood pressure, heart rate or blood glucose level. However, there was no evidence of an infarct-size reducing effect after pre-reperfusion treatment with 10 mg kg(-1) of miglitol (35.0+/-3.0%, n=10). 3. Another 40 rabbits given 1, 5 and 10 mg kg(-1) of miglitol or saline before ischaemia (n=10 in each) were sacrificed at 30 min of ischaemia for biochemical analysis. Miglitol preserved significantly the glycogen content, and attenuated significantly the lactate accumulation in a dose dependent manner in the ischaemic region at 30 min of ischaemia. 4. Pre-ischaemic treatment, but not pre-reperfusion treatment, with miglitol markedly reduced the myocardial infarct size, independently of blood pressure and heart rate. A dose-dependent effect of miglitol on infarct size, glycogenolysis and lactate formation suggests that the mechanism may be related to the inhibition of glycogenolysis. Thus, miglitol may be beneficial for coronary heart disease as well as diabetes mellitus.

To better understand the spread of hepatitis C virus (HCV) infection, we studied the association of HCV infection with similarly transmissible hepatitis B virus (HBV) infection and with hepatitis A virus (HAV) infection, which is supposed to be related to a nosocomial transmission of HCV. This was done by studying the presence or absence of antibodies to these viruses, as well as hepatitis B surface antigen, in a population of 1,398 inhabitants with abnormal liver function tests or history of liver disease and/or blood transfusion. This group was drawn from a group of 7,905 examinees screened for liver disease in 26 districts of Okayama prefecture, Japan. The prevalence of antibody-positive cases increased with age for those viruses. Small but significantly increased odds ratios were obtained among anti-HCV antibodies (HCVAb), anti-hepatitis B core antibodies (HBcAb) and anti-hepatitis A antibodies (HAVAb). After adjusting odds ratios by logistic regression analysis, a significant association was present only between HCVAb and HBcAb. The distribution of age-adjusted prevalences (AAP) of HCVAb in 26 districts was significantly wider than those of HBcAb or HAVAb. The district-based AAP of HCVAb, but not of HBcAb and HAVAb, correlated significantly with the district-based prevalence of infectious hepatitis having a tendency of chronicity reported in 1953-1955. Adjusted odds ratios calculated by logistic regression analysis of the virus markers showed that HCVAb was significantly associated with a past history of blood transfusion. Thus, the spread of HCV infection is speculated to have been triggered by blood transfusion, particularly from paid donors initially, followed by transmission by nosocomial or close person-to-person contact.

High-flow nasal canulae (HFNC) deliver high-flow humidified gas at up to 60 l/minute. There are two types of respiratory circuit to generate mix gas flow, Blender type (typeB) and Venturi type (typeV). The therapy is well established in the pediatric population and HFNC use has been described in the adult population. It has been reported that HFNC provide higher FIO2 compared with low-flow canulae, and also create mild positive pharyngeal airway pressure, but the effect on alveolar pressure is unknown. We aimed to investigate the effect of HFNC on alveolar pressure, by measuring intratracheal pressure in patients with a cricothyrotomy catheter (CTC). At the same time, we measured the actual gas flow rate (AGFR) by flowmeter and compared it with assumed flow.

Kariya and Tsuda (1995) demonstrated the predictive power of TDM (time dependent Markov) model for individual bond prices with the end-of-month price data of JG (Japanese Government) bonds with initial maturities of 10 years. The model predicted well the monthly term structure of the individual JG bond prices for the period 1991.1-1992.12 though there are only four parameters in the model, where there are about 80 bonds for each month. In fact, the prediction standard error for the period is 0.9 yen while the estimation standard error is less than 0.3 yen, where the face value of a JG bond is 100 yen. We again test the prediction power of the TDM model with the end-of-month price data of JG bonds for the period 1993.1-1995.12 when the interest rate level was low, and observe that the model loses the predictive power when interest rates change volatilly even though the overall performance is good. The observation follows from the fact that the VAR (vector autoregressive) model for predicting four time dependent parameters in the model, which is modelled based on the cross-sectionally estimated parameters, fails to keep a stable prediction power for months of volatile interest rates. It is remarked that the TDM model is proposed by Kariya and Tsuda (1994) as a time series extension of the CSM (Cross-Sectional Market) model for individual bond prices Kariya (1993) formulated.

The aim of the present study was to establish a reliable procedure with nocodazole treatment for the synchronous cleavage of blastomeres of bovine embryos used as nuclear donors for nuclear transfer. Sixteen-cell stage embryos derived from in vitro-maturation, fertilization and culture were used. In three initial experiments, embryos were incubated in mTCM-199+FCS with various concentrations (0-20 microM) of nocodazole under 5% CO2 in air. The concentrations required to arrest the blastomeres in the mitotic phase were examined. The effects of 10 microM nocodazole were also examined by observation of the division rate of blastomeres after the removal of nocodazole. Ninety percent (90%) of the blastomeres were arrested in the mitotic phase when embryos were exposed to 10 and 20 microM nocodazole. Exposure to 10 microM nocodazole had the highest blastomere-cleavage rate (47%). When the exposure period to 10 microM nocodazole was prolonged to 36 hr, the division rate of the blastomeres decreased. Furthermore, the effects of 2 culture conditions (mTCM-199 under 5% CO2 in air vs modified synthetic oviduct fluid medium under 5% CO2, 5% CO2 and 90% N2) were compared on the division rate of blastomeres of embryos exposed to 10 microM nocodazole for 12 hr. When the embryos were exposed to nocodazole in mSOF, the division rate of blastomeres was improved to about 60%. The blastomeres produced by this treatment condition were used as nuclear donors and the developmental potential of the reconstituted embryos was investigated. The developmental rate to the blastocyst stage was 30.1% (58/193). Five embryos were transferred to 5 recipient cows and 2 of the 5 recipients (40%) became pregnant. Subsequently, one normal calf was born.

Heterosexual chimerism among singleton females produced by multiple nonsexed embryo transfer (MNET singleton females) was investigated using chromosome typing and PCR (polymerase chain reaction)-amplification of male-specific DNA (msDNA). Of the 22 animals tested, 21 were classified as normal by both methods (i.e., showing no male cells among 100 metaphase spreads in chromosome typing and being msDNA negative in PCR). No morphological abnormalities of the genital organs were observed among 19 MNET single females. One MNET singleton female was, however, classified as a freemartin by PCR (male-specific DNA positive), but it was classified as normal cytogenetically. This individual probably had a low degree of heterosexual chimerism, and it seems that the chimerism derived from MNET was difficult to diagnose by chromosome typing, although it was detectable by PCR. The genital organs of this individual (15-mo-old Aberdeen Angus) were normal in form (both external and internal) and size. However, a very small structure, resembling seminiferous tubule, was found in the left ovary. It may be concluded that most MNET singleton females are expected to have normal reproductive function.