Turbulence Transition in Magnetically Confined Hydrogen and Deuterium Plasmas.

In this study, we discovered a turbulence transition in a large helical device. The turbulence level and turbulence-driven energy transport decrease to a specific transition density and increase above it. The ruling turbulences below and above the transition density were ion-temperature gradient (ITG) and resistive-interchange (RI) turbulences, consistent with the predictions of gyrokinetic theory and two-fluid MHD model, respectively. Isotope experiments on hydrogen (H) and deuterium (D) clarified the role of transitions. In the ITG regime, turbulence levels and energy transport were comparable in the H and D plasmas. In contrast, in the RI regime, they were clearly suppressed in the D plasma. The results provide crucial knowledge for understanding isotope effects and future optimization of stellarator and heliotron devices.

Impact of Magnetic Field Configuration on Heat Transport in Stellarators and Heliotrons.

We assess the magnetic field configuration in modern fusion devices by comparing experiments with the same heating power, between a stellarator and a heliotron. The key role of turbulence is evident in the optimized stellarator, while neoclassical processes largely determine the transport in the heliotron device. Gyrokinetic simulations elucidate the underlying mechanisms promoting stronger ion scale turbulence in the stellarator. Similar plasma performances in these experiments suggests that neoclassical and turbulent transport should both be optimized in next step reactor designs.

Isotope Effect on Energy Confinement Time and Thermal Transport in Neutral-Beam-Heated Stellarator-Heliotron Plasmas.

The isotope effect on energy confinement time and thermal transport has been investigated for plasmas confined by a stellarator-heliotron magnetic field. This is the first detailed assessment of an isotope effect in a stellarator heliotron. Hydrogen and deuterium plasmas heated by neutral beam injection on the Large Helical Device have exhibited no significant dependence on the isotope mass in thermal energy confinement time, which is not consistent with the simple gyro-Bohm model. A comparison of thermal diffusivity for dimensionally similar hydrogen and deuterium plasmas in terms of the gyroradius, collisionality, and thermal pressure has clearly shown robust confinement improvement in deuterium to compensate for the unfavorable mass dependence predicted by the gyro-Bohm model.

Suppression of Trapped Energetic Ions Driven Resistive Interchange Modes with Electron Cyclotron Heating in a Helical Plasma.

The resistive interchange mode destabilized by the resonant interaction with the trapped energetic ions is fully suppressed when the injected power of electron cyclotron heating exceeds a certain threshold. It is shown for the first time that the complete stabilization of the energetic-particle-driven mode without relaxing the energetic particle (EP) pressure gradient is possible by reducing the radial width of the eigenmodes δ_{w}, especially when δ_{w} narrows to a small enough value relative to the finite orbit width of EP.

Resistive interchange modes destabilized by helically trapped energetic ions in a helical plasma.

A new bursting m=1/n=1 instability (m,n: poloidal and toroidal mode numbers) with rapid frequency chirping down has been observed for the first time in a helical plasma with intense perpendicular neutral beam injection. This is destabilized in the plasma peripheral region by resonant interaction between helically trapped energetic ions and the resistive interchange mode. A large radial electric field is induced near the edge due to enhanced radial transport of the trapped energetic ions by the mode, and leads to clear change in toroidal plasma flow, suppression of microturbulence, and triggering an improvement of bulk plasma confinement.

Analysis of the Motional Stark Effect (MSE) diagnostic to measure the rotational transform and current profile in the Large Helical Device.

The analysis method of the Motional Stark Effect (MSE) diagnostic to measure the rotational transform and current profiles in the Large Helical Device has been improved. This was done by using the Variational Moments Equilibrium Code to calculate an equilibrium database for various pressure profiles and current profiles. This method looks for the radial profile of the rotational transform in the equilibrium database that gives the best fit to the polarization angle profiles measured with the MSE diagnostic. This analysis improves the measurements of rotational transform, especially near the magnetic axis, where the sensitivity of the polarization angle measurements becomes low and the uncertainty due to error in the estimation of the Pfirsch-Schlüter current becomes large. The radial profiles of the rotational transform and current profiles for Electron Cyclotron Current Drive and Neutral Beam Current Drive are obtained in the new analysis method with a sufficiently high accuracy to discuss the discrepancy of the current density profiles between the measurements and the calculations.

Prognostic significance of S-phase kinase-associated protein 2 and p27kip1 in patients with diffuse large B-cell lymphoma: effects of rituximab.

BACKGROUND: The F-box protein S-phase kinase-associated protein 2 (Skp2) positively regulates the G1-S transition by promoting degradation of the cyclin-dependent kinase inhibitor p27(kip1) (p27). Recent evidence has indicated an oncogenic role of Skp2 in not only carcinogenesis but also lymphomagenesis. MATERIALS AND METHODS: Clinicopathologic features and immunohistochemical expression of Skp2 and p27 were studied retrospectively in 671 patients treated with cyclophosphamide, vincristine, doxorubicin and prednisolone (CHOP) or cyclophosphamide, vincristine, doxorubicin and prednisolone plus rituximab (R-CHOP). The median follow-up periods were 43.2 months in the CHOP group (n = 425) and 24.0 months in the R-CHOP group (n = 246). RESULTS: High Skp2 or low p27 expression correlated significantly with poor overall survival (OS) and progression-free survival (P < 0.001) in both treatment groups. The prognostic value of Skp2 or p27 expression was independent of the parameters included in the International Prognostic Index by multivariate analysis. Patients with high Skp2 expression in combination with low p27 expression showed the worst survival. CONCLUSIONS: Addition of rituximab to the CHOP regimen did not provide a beneficial outcome to patients with diffuse large B-cell lymphoma with high Skp2 expression and low p27 expression. Skp2 and p27 may be useful prognostic markers in the rituximab era.

Use of TLR9 and TLR7/8 agonists in combination with d-galactosamine in exploring models for distinct severities of systemic inflammation relative to liver injury.

Challenges with various TLR ligands (TLRLs)in combination with D-galactosamine (GalN) in rodents may mimic diverse conditions of acute inflammation and organ failure. Here, we report that CpG (ODN1826, TLR9 agonist)/GalN induced a liver-specific injury with modest systemic effects, whereas R848 (resiquimod, TLR7/8 agonist)/GalN exhibited systemic and liver toxicity. We also observed the protective effect of Gr-1+ cells (the population containing neutrophils) against liver injury in both the R848/GalN and CpG/GalN models. In cytokine measurements, the intraperitoneal administration of antibodies showed a non-specific tolerance induction effect, which was more pronounced in the CpG/GalN than in the R848/GalN model. Cytokine analyses also suggested that the TLR9 agonist/GalN induced a limited degree of systemic inflammation compared to TLR7/8 agonist/GalN models. The relevance of this finding to the TLR9-mediated induction of stress tolerance (protective effect) in non-immune cells is discussed.

Performance of the newly installed vertical neutron cameras for low neutron yield discharges in the Large Helical Device.

Two new vertical neutron cameras characterized by high detection efficiency were developed on the Large Helical Device in order to observe poloidal structures of helically trapped beam ions created by the perpendicularly injected positive-ion based neutral beam (P-NB) and are newly operated since 2018. In this work, the neutron fields at the vertical neutron cameras are investigated using the Monte Carlo N-particle transport code to evaluate the performance of its collimators. The results indicate that neutrons are attenuated by the heavy concrete and are well collimated through the collimator to detectors. Neutron spectra at the detector position show over 99% of uncollided 2.45 MeV neutrons. Time evolution of neutron emission profiles during the short pulse of P-NB injection is measured by the vertical neutron cameras. Peaks on the neutron emission profiles corresponding to the helically trapped beam ion are successfully obtained, as designed. The decrease in line integrated neutron flux at the peak positions after the P-NB stops is consistent with the behavior of the total neutron emission rate measured by the neutron flux monitor.

Neutron-induced signal on the single crystal chemical vapor deposition diamond-based neutral particle analyzer.

A diamond-based neutral particle analyzer (DNPA) array composed of single-crystal chemical vapor deposition (sCVD) diamond detectors was installed on the Large Helical Device (LHD) for measuring the helically trapped energetic particles. In high neutron flux experiments, the unwanted neutron-induced pulse counting rate should be estimated using the neutron diagnostics because a diamond detector is sensitive to neutrons as well as energetic neutral particles. In order to evaluate the quantitative neutron-induced pulse counting rate on the DNPA, the response functions of the sCVD diamond detector for mono-energetic neutrons were obtained using accelerator-based D-D and D-7Li neutron sources in Fast Neutron Laboratory (FNL). As a result of the neutron flux estimation by the Monte Carlo N-Particle code at the NPA position in the LHD and the response function obtained in the FNL experiment, the counting rate of the neutron-induced signal was predicted to be 1.1 kcps for the source neutron emission rate of Sn = 1 × 1015 n/s. In the LHD experiment, the neutron-induced signals were observed by closing the gate valve during the plasma discharges. It is found that the counting rates of the neutron-induced signals proportional to Sn reached 1.1 kcps at Sn = 1 × 1015 n/s. As a result of the quantitative estimation of the neutron-induced signals on the DNPA using other neutron measurements, it has become possible to accurately measure energetic neutral particles in the high neutron flux experiment.

Prediction of functional outcome in stunned myocardium after myocardial infarction using BMIPP and tetrofosmin imaging.

The predictive value of combined (123)iodine-labelled 15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid imaging ((123)I-BMIPP) and early technetium-99m ((99m)Tc)-tetrofosmin imaging was compared with combined (123)I-BMIPP and delayed (99m)Tc-tetrofosmin or (123)I-BMIPP and thallium-201 ((201)Tl) imaging for functional outcome of stunned myocardium after acute myocardial infarction (AMI) in 37 patients with AMI. All patients underwent successful percutaneous coronary intervention with/without stenting within 24 h of symptoms. Resting (201)Tl, (99m)Tc-tetrofosmin and (123)I-BMIPP imaging were performed within 10 days of hospital admission; (99m)Tc-tetrofosmin imaging was also performed 6 months later. Segments were mismatched when the (123)I-BMIPP score was greater than the (99m)Tc-tetrofosmin or (201)Tl scores, and were matched when all scores were the same. Left ventricular function was estimated using wall motion score. Sensitivity and regional wall motion were significantly better in mismatching (99m)Tc-tetrofosmin-early/(123)I-BMIPP segments than mismatching (201)Tl/(123)I-BMIPP or (99m)Tc-tetrofosmin-delayed/(123)I-BMIPP segments. It is concluded that mismatching of (123)I-BMIPP and early (99m)Tc-tetrofosmin uptake can predict improvement in wall motion of stunned myocardium better than the other two imaging combinations.

Isotope effects in self-organization of internal transport barrier and concomitant edge confinement degradation in steady-state LHD plasmas.

The isotope effect, which has been a long-standing mystery in the turbulent magnetically confined plasmas, is the phenomena that the plasma generated with heavier hydrogen isotope show a mitigated transport. This is on the contrary to what is predicted with the simple scaling theory, in which the heavier ions easily diffuse because of its larger gyro-radius. Thanks to the newly developed analysis method and a comprehensive parameter scan experiment in the steady-state plasmas in the Large Helical Device (LHD), the isotope effect was clearly observed in the self-organized internal transport barrier (ITB) structure for the first time. Comparing the ITB intensity in deuterium (D) and hydrogen (H) plasmas, two distinct hydrogen isotope effects are found: stronger ITB is formed in D plasmas and a significant edge confinement degradation accompanied by the ITB formation emerges in H plasmas. This observation sheds light on a new aspect of the turbulent plasmas regarding how the basic properties of the fluid material affect the turbulent structure formation in the open-system.

Upstream Enhancer Elements of Shh Regulate Oral and Dental Patterning.

Sonic hedgehog ( Shh) is important in pattern formation during development. Shh transcription is modulated by a long-range regulatory mechanism containing a number of enhancers, which are spread over nearly 850 kb in the mouse genome. Shh enhancers in the nervous system have been found between intron and 430 kb upstream of Shh. Enhancers in the oral cavity, pharynx, lung, gut, and limbs have been discovered between 610 kb and 850 kb upstream of Shh. However, the intergenic region ranging from 430 to 610 kb upstream of Shh remains to be elucidated. In the present study, we found a novel long-range enhancer located 558 kb upstream of Shh. The enhancer showed in vivo activity in oral cavity and whiskers. A targeted deletion from the novel enhancer to mammal reptile conserved sequence 1 (MRCS1), which is a known enhancer of Shh in oral cavity, resulted in supernumerary molar formation, confirming the essential role of this intergenic region for Shh transcription in teeth. Furthermore, we clarified the binding of Lef1/Tcfs to the new enhancer and MRCS1, suggesting that Wnt/ß-catenin signaling regulates Shh signaling in the oral cavity via these enhancers.

Demonstration of reversed flow in segmental branches of the portal vein with hand-held color Doppler ultrasonography after hematopoietic stem cell transplantation.

Hepatic veno-occlusive disease (VOD) is a severe complication of hematopoietic stem cell transplantation (SCT). When monitored with hand-held color Doppler ultrasonography during day -7 to +35 around SCT, reversed blood flow in the segmental branches of the portal vein was detected in nine of 56 patients who had undergone SCT. Three of nine patients had clinical evidence of VOD, but six patients did not fulfill the criteria for diagnosis of VOD initially. Two patients progressed to clinical VOD at a later date and the reversed portal flow disappeared with or without treatment for VOD in the other four patients. Monitoring for reversed portal flow with color Doppler ultrasonography may be a useful tool for the early diagnosis of VOD, and may improve prognosis by allowing early initiation of treatment.

Mechanism of chromosomal integration of transgenes in microinjected mouse eggs: sequence analysis of genome-transgene and transgene-transgene junctions at two loci.

Production of transgenic animals is a key technique in modern biology, but the process of chromosomal integration of transgenes in microinjected eggs is still not fully understood. To gain information on the mechanisms involved in this process, we have cloned two transgene loci and their corresponding pre-integration sites and compared the junction sequences with the parental nucleotide (nt) sequences. No extensive DNA rearrangements were detected at these loci: only simple deletions (caused by the integration of the transgene concatemers) were present in the host genome. Analysis of three transgene-transgene junctions within the concatemers showed that 'nibbling' of ends (up to 3 nt) had occurred at some ends prior to joining. At all four genome-transgene junctions, short homologies of 1 to 3 nt were found, and at least three of these junctions were associated with the consensus sequence for topoisomerase-I cleavage sites. Moreover, three of the four integration junctions occurred in the terminal regions of the injected sequence, at positions only a few nt away from the ends. These results suggest that linear, but not circular, concatemers were preferentially integrated at their ends utilizing short homologies to the host genome.

Molecular cloning and expression of Caenorhabditis elegans ERp57-homologue with transglutaminase activity.

Formation of cross-linking between proteins via a gamma-glutamyl-epsilon-lysine residue is an important process in many biological phenomena including apoptosis. Formation of this linkage is catalyzed by the enzyme transglutaminase, which is widely distributed from bacteria to the animal kingdom. The simple multi-cellular organism Caenorhabditis elegans also possesses transglutaminase activity associated with apoptosis [Madi, A. et al. (1998) Eur. J. Biochem. 253, 583-590], but no gene with significant homology to vertebrate or bacterial transglutaminases has been found in the C. elegans genome sequence database. On the other hand, protein disulfide isomerases were recently recognized as a new family of transglutaminases [Chandrashekar, R. et al. (1998) Proc. Natl. Acad. Sci. USA 95, 531-536]. To identify the molecule with transglutaminase activity in C. elegans, we isolated from C. elegans a gene homologous to ERp57, which encodes a protein disulfide isomerase, expressed it in recombinant form, and characterized the transglutaminase and protein disulfide isomerase activities of the resultant protein. The C. elegans ERp57 protein had both enzyme activities, and the transglutaminase activity had similar characteristics to the activity in lysate of the whole worm. These results suggested that the ERp57 homologue was one of the substances with transglutaminase activity in C. elegans.

Determination of radionuclides induced by fast neutrons from the JCO criticality accident in Tokai-mura, Japan for estimating neutron doses.

A criticality accident occurred at a uranium conversion facility in Tokai-mura, Japan on September 30, 1999, and fission neutrons were continuously emitted for about 20 hours. Materials of stainless steel or iron, and chemical reagents were collected at places between 2 m and 270 m from the criticality accident site on October 25 and 26, 1999, November 27, 1999 and February 11, 2000. Neutron-induced radionuclides. such as 54Mn and 58Co, in the materials exposed to fast neutrons from the accident were measured to estimate the neutron fluences and energy distributions. Highly sensitive y-ray spectrometry with a well-type Ge detector was performed after radiochemical separation of Mn and Co from the materials. An instrumental neutron activation analysis was mainly applied for determinations of the target elements and chemical yields. The concentrations of 54Mn and 58Co in a mesh screen of stainless steel collected at a location 2.0 m from the accident site were determined. The total number of fission events was evaluated to be 2.5 x 10(18) by Monte-Carlo calculations of neutron transfer by considering the observed values of 54Mn and 58Co. The results presented here are fundamental to estimate the neutron doses at various distances.

Effects of invert soap with 0.05% sodium hydroxide on infectious bursal disease virus.

The effects of invert soaps with sodium hydroxide on infectious bursal disease virus (IBDV) were studied. Didecyldimethylammonium chloride was most effective, followed by alkylbenzyldimethylammonium chloride and [mono-bis(tri-methylammonium-methylene chloride)]-alkyl (C9-15) toluene. Dilutions without NaOH had little effect on virus titer. Didecyldimethylammonium chloride was further tested for its effects on IBDV by varying temperature, concentration of invert soap, and pH of the dilution. The effect of the invert soap was strong at 40 C, moderate at room temperature, and weak at 4 C. The concentration of invert soap influenced its efficacy at room temperature but not at 4 C. At pH values below 12.9, the invert soap showed decreased efficacy.

Scanning electron microscopic observations on vascular casts of ciliary processes in normal and topical epinephrine-treated rats.

Existence of neurohumoral control of the ciliary process blood flow was investigated in normal adult Wistar albino rats, utilizing the vascular casting method with a scanning electron microscope, comparing the ciliary process vessels in epinephrine-treated eyes to those in control eyes. The ciliary process microvasculature consisted of marginal capillaries, intraprocess capillaries and collecting veins. The supplying arterioles of the ciliary processes were derived from the iridociliary arterial circle. The arterioles were constricted or annularly impressed just before connecting with the marginal capillaries in the controls. The epinephrine instillation resulted in significant constriction of all the ciliary process vessels. Especially the ciliary process arterioles were narrowed in their full length in contrast to the focal constrictions in the controls. The diameter of the constricted arterioles in the epinephrine-treated eyes was the same as the focal constrictions in the controls. These results suggested that sphincter muscles existed in the wall of the ciliary process arterioles of the rat and that neurohumoral blood flow control was related to the constriction of the ciliary process arterioles resulting from the epinephrine administration.

Effects of quaternary ammonium compounds with 0.1% sodium hydroxide on swine vesicular disease virus.

The effects of quaternary ammonium compounds (QACs) with sodium hydroxide on swine vesicular disease virus (SVDV), an enterovirus were studied. Didecyldimethylammonium chloride (DDAC) with 0.1% NaOH showed a stronger effect against SVDV than other QACs with 0.1% NaOH. The effect of DDAC with 0.1% NaOH was strong at 40 degrees C. DDAC was effective against SVDV at pH values around 11.0, but not in the distilled water control. The effect of DDAC with 0.1% NaOH was already observed at 1 min after mixing of the DDAC with SVDV. Observation under an electron microscopy revealed that the probable mechanism of inactivation of DDAC with 0.1% NaOH is as follows: The virus particles were partially destroyed by 0.1% NaOH. DDAC gathered these affected particles and formed a micelle, then SVDV lost its infectivity. From these results, QACs with 0.1% NaOH are considered to be very effective against SVDV representing enteroviruses.