Receiver circuit improvement of dual frequency-comb ka-band Doppler backscattering system in the large helical device (LHD).

Doppler-backscattering (DBS) has been used in several fusion plasma devices because it can measure the perpendicular velocity of electron density perturbation v⊥, the radial electric field Er, and the perpendicular wavenumber spectrum S(k⊥) with high wavenumber and spatial resolution. In particular, recently constructed frequency comb DBS systems enable observation of turbulent phenomena at multiple observation points in the radial direction. A dual-comb microwave DBS system has been developed for the large helical device plasma measurement. Since it is desirable to control the gain of each frequency-comb separately, a frequency-comb DBS system was developed with a function to adjust the gain of the scattered signal intensity of each channel separately. A correction processing method was also developed to correct the amplitude ratio and the phase difference between the in-phase and quadrature-phase signals of the scattered signals. As a result, the error in Doppler-shift estimation required to observe vertical velocity and the radial electric field was reduced, which enables more precise measurements.

Hydrogen isotope effect on self-organized electron internal transport barrier criticality and role of radial electric field in toroidal plasmas.

Self-organized structure formation in magnetically confined plasmas is one of the most attractive subjects in modern experimental physics. Nonequilibrium media are known to often exhibit phenomena that cannot be predicted by superposition of linear theories. One representative example of such phenomena is the hydrogen isotope effect in fusion plasmas, where the larger the mass of the hydrogen isotope fuel is the better the plasma confinement becomes, contrary to what simple scaling models anticipate. In this article, threshold condition of a plasma structure formation is shown to have a strong hydrogen isotope effect. To investigate the underlying mechanism of this isotope effect, the electrostatic potential is directly measured by a heavy ion beam probe. It is elucidated that the core electrostatic potential transition occurs with less input power normalized by plasma density in plasmas with larger isotope mass across the structure formation. This observation is suggestive of the isotope effect in the radial electric field structure formation.

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.

W-band millimeter-wave back-scattering system for high wavenumber turbulence measurements in LHD.

A 90 GHz W-band millimeter-wave back-scattering system is designed and installed for measuring electron scale turbulence (k⊥ρs ∼ 40). A metal lens relay antenna is used for in-vessel beam focusing, and a beam diameter of less than 40 mm is achieved in the plasma core region. This antenna can be steered at an angle of 159° ± 6°, which almost covers the plasma radius. The estimated size of the scattering volume is ∼105 mm at the edge and 135 mm at the core, respectively. A 60 m corrugated waveguide is used to achieve a low transmission loss of ∼8 dB. A heterodyne detection system for millimeter-wave circuits with probing power modulation can distinguish the scattered signal from background noise.

Microwave frequency comb Doppler reflectometer applying fast digital data acquisition system in LHD.

We succeeded in increasing the radial observation points of the microwave frequency comb Doppler reflectometer system from 8 to 20 (or especially up to 45) using the high sampling rate of 40 GS/s digital signal processing. For a new acquisition system, the estimation scheme of the Doppler shifted frequency is constructed and compared with the conventional technique. Also, the fine radial profile of perpendicular velocity is obtained, and it is found that the perpendicular velocity profile is consistent with the E × B drift velocity one.

Cold thermal oral stimulation produces immediate excitability in human pharyngeal motor cortex.

BACKGROUND: Current strategies of swallowing therapy include facilitation of swallowing initiation by sensory modulation. Although thermal tactile oral stimulation is a common method to treat dysphagic patients to improve swallowing movement, little is known about the possible mechanisms. This study is aimed to investigate whether thermal oral (tongue) stimulation can modulate the cortico-pharyngeal neural motor pathway in humans. METHODS: Eighteen healthy volunteers participated and were intubated with an intraluminal catheter for recording pharyngeal electromyography. Each participant underwent baseline transcranial magnetic stimulation (TMS) cortico-pharyngeal motor evoked potential (MEP) measurements bilaterally. MEPs were then measured during thermal stimulation over the dorsal tongue, applied using the Peltier device at three different temperatures; 45°C, 37°C, and 15°C, in a pre-ordered manner. Each of the three temperatures was given twice with a 5-min resting time between each trial. Averaged MEP amplitude changes were analyzed using ANOVA and post-hoc t-tests. KEY RESULTS: Two-way repeated measures ANOVA with factors of Temperature × Trial in amplitude of MEP demonstrated a significant effect of Temperature both in the stronger (F2,34  = 5.775, P = .007) and weaker (F2,34  = 4.771, P = .017) pharyngeal hemispheres. Subsequent post-hoc tests showed the significant increase in pharyngeal MEPs at 15° compared to 37° in both hemispheres (P < .05). CONCLUSIONS & INFERENCES: Cold oral stimulation was able to induce significant changes in pharyngeal cortical excitability, demonstrating evidence for a sensorimotor interaction between oral and pharyngeal cortical areas.

Effect of body posture on chewing behaviours in healthy volunteers.

Mastication is essential to the eating process and forms an important part of feeding behaviour. Many factors related to the food bolus, such as bolus texture and size, are known to influence mastication. The aim of this study was to determine the effects of body posture on (i) chewing duration prior to the first swallow and (ii) patterns of mastication-related EMG activity. We asked 10 healthy adults to chew 8 g of steamed rice with barium sulphate while we recorded masseter, suprahyoid and infrahyoid muscle activity and simultaneously collected videofluorographic images. Participants chewed in either an upright or reclining position. Chewing duration, which was defined as the time from the start of mastication to the first swallow, was not different between the positions. However, the variability of chewing duration was larger in the upright versus reclining position, and the chewing duration in the reclining position was distributed around 15 s. Masseter activity gradually decreased in a time-dependent manner and was significantly larger at the early versus late stage of mastication. Suprahyoid activity was significantly larger at the early versus middle stage of mastication in the upright position only. Finally, masseter activity per second was negatively correlated with changes in chewing duration, that is, the larger the increase in chewing duration in the reclining position, the more the decrease in masseter activity per second. These results suggest that position-dependent changes in chewing behaviours, as described by chewing duration and EMG activity, may vary among participants.

Novel analysis technique for measuring edge density fluctuation profiles with reflectometry in the Large Helical Device.

A new method for measuring density fluctuation profiles near the edge of plasmas in the Large Helical Device (LHD) has been developed utilizing reflectometry combined with pellet-induced fast density scans. Reflectometer cutoff location was calculated by proportionally scaling the cutoff location calculated with fast far infrared laser interferometer (FIR) density profiles to match the slower time resolution results of the ray-tracing code LHD-GAUSS. Plasma velocity profile peaks generated with this reflectometer mapping were checked against velocity measurements made with charge exchange spectroscopy (CXS) and were found to agree within experimental uncertainty once diagnostic differences were accounted for. Measured density fluctuation profiles were found to peak strongly near the edge of the plasma, as is the case in most tokamaks. These measurements can be used in the future to inform inversion methods of phase contrast imaging (PCI) measurements. This result was confirmed with both a fixed frequency reflectometer and calibrated data from a multi-frequency comb reflectometer, and this method was applied successfully to a series of discharges. The full width at half maximum of the turbulence layer near the edge of the plasma was found to be only 1.5-3 cm on a series of LHD discharges, less than 5% of the normalized minor radius.

Expression of CD44 variant isoforms, CD44v3 and CD44v6, are associated with prognosis in nasopharyngeal carcinoma.

OBJECTIVE: The clinical and prognostic significance of CD44 variant isoform expression in nasopharyngeal carcinoma is not well known. This study aimed to clarify whether CD44 variant isoform expression serves as a prognostic factor in nasopharyngeal carcinoma. METHODS: Forty-two nasopharyngeal carcinoma patients, who underwent concurrent chemoradiotherapy as the initial treatment, were the subjects of investigation. Expression of CD44 variant isoforms, CD44v3, CD44v4, CD44v5, CD44v6 and CD44v7, in nasopharyngeal carcinoma was assessed in relation to concurrent chemoradiotherapy resistance and disease-specific survival of the patients. RESULTS AND CONCLUSION: The patients with CD44v6 high expression showed a clinically incomplete response to concurrent chemoradiotherapy at the primary site. The disease-specific survival rate was lower in patients with high expression of CD44v3 than in those with low expression. These results suggest that analysis of CD44v6 and CD44v3 expression is useful in estimating prognosis and determining effective treatment strategies in nasopharyngeal carcinoma.

Reconstruction of high temporal resolution Thomson scattering data during a modulated electron cyclotron resonance heating using conditional averaging.

This paper provides a software application of the sampling scope concept for fusion research. The time evolution of Thomson scattering data is reconstructed with a high temporal resolution during a modulated electron cyclotron resonance heating (MECH) phase. The amplitude profile and the delay time profile of the heat pulse propagation are obtained from the reconstructed signal for discharges having on-axis and off-axis MECH depositions. The results are found to be consistent with the MECH deposition.

LIM-domain protein AJUBA suppresses malignant mesothelioma cell proliferation via Hippo signaling cascade.

Malignant mesothelioma (MM) is one of the most aggressive neoplasms usually associated with asbestos exposure and is highly refractory to current therapeutic modalities. MMs show frequent activation of a transcriptional coactivator Yes-associated protein (YAP), which is attributed to the neurofibromatosis type 2 (NF2)-Hippo pathway dysfunction, leading to deregulated cell proliferation and acquisition of a malignant phenotype. However, the whole mechanism of disordered YAP activation in MMs has not yet been well clarified. In the present study, we investigated various components of the NF2-Hippo pathway, and eventually found that MM cells frequently showed downregulation of LIM-domain protein AJUBA, a binding partner of large tumor suppressor type 2 (LATS2), which is one of the last-step kinases of the NF2-Hippo pathway. Although loss of AJUBA expression was independent of the alteration status of other Hippo pathway components, MM cell lines with AJUBA inactivation showed a more dephosphorylated (activated) level of YAP. Immunohistochemical analysis showed frequent downregulation of AJUBA in primary MMs, which was associated with YAP constitutive activation. We found that AJUBA transduction into MM cells significantly suppressed promoter activities of YAP-target genes, and the suppression of YAP activity by AJUBA was remarkably canceled by knockdown of LATS2. In connection with these results, transduction of AJUBA-expressing lentivirus significantly inhibited the proliferation and anchorage-independent growth of the MM cells that harbored ordinary LATS family expression. Taken together, our findings indicate that AJUBA negatively regulates YAP activity through the LATS family, and inactivation of AJUBA is a novel key mechanism in MM cell proliferation.

Hedgehog signal activation in oesophageal cancer patients undergoing neoadjuvant chemoradiotherapy.

The zinc finger protein glioma-associated oncogene homologue 1 (Gli-1) is a critical component of the Hedgehog (Hh) signalling pathway, which is essential for morphogenesis and stem-cell renewal, and is dysregulated in many cancer types. As data were not available on the role of Gli-1 expression in oesophageal cancer progression, we analysed whether it could be used to predict disease progression and prognosis in oesophageal cancer patients undergoing neoadjuvant chemoradiotherapy (CRT). Among 69 patients with histologically confirmed oesophageal squamous cell carcinomas (ESCCs), 25 showed a pathological complete response after preoperative CRT. Overall survival (OS) was significantly associated with lymph-node metastasis, distant metastasis, and CRT, and was further correlated with the absence of both Gli-1 nuclear expression and residual tumour. All patients with Gli-1 nuclear expression (10.1%) had distant or lymph-node metastasis, and six out of seven died within 13 months. Furthermore, patients with Gli-1 nuclear-positive cancers showed significantly poorer prognoses than those without (disease-free survival: mean DFS time 250 vs 1738 months, 2-year DFS 0 vs 54.9%, P=0.009; OS: mean OS time 386 vs 1742 months, 2-year OS 16.7 vs 54.9%, P=0.001). Our study provides the first evidence that Gli-1 nuclear expression is a strong and independent predictor of early relapse and poor prognosis in ESCC after CRT. These findings suggest that Hh signal activation might promote cancer regrowth and progression after CRT.

Intraperitoneal injection of oxygenated perfluorochemical improves the outcome of intraportal islet transplantation in a rat model.

A 50% to 75% early graft loss upon engraftment has been suggested to in intraportal islet transplantation (IPIT). Hypoxia in the portal vein contributes to graft loss in immediately posttransplantation. Herein we examined the effect on the outcome of IPIT of intraperitoneal oxygenated perfluorochemical (PFC) as an oxygen carrier. Isolated Lewis rat islets were transplanted into the portal vein of a chemically induced diabetic syngeneic rat. First, 1500 IEQ was determined to be the optimal dose in this study. When oxygenated PFC (group 1) was intraperitoneally injected following IPIT of 1500 IEQ, the success rate of transplantation was 5/6, in contrast to 1/6 when PFC with no oxygen was injected (group 2) and 1/6 in IPIT without PFC, respectively. The area under the glucose profile curve on intraperitoneal glucose tolerance tests on posttransplant day 28 in group 1 was significantly smaller than that for group 2. In conclusion, intraperitoneal oxygenated PFC improved the outcome of IPIT.

Neuroendocrine differentiation of periodic-acid Schiff and Alcian blue-negative signet-ring cell-like cells and tubular adenocarcinoma cells within a gastric cancer.

A case of a Borrmann type 2 advanced gastric cancer with endocrine differentiation is described. Histologically, the cancer was either composed of cells arranged in a tubular pattern or formed solid nests of various sizes. The tubular pattern was composed of a moderately differentiated tubular adenocarcinoma. The histology showed partial carcinoid tumor-like features. Cancer cells inside solid nests had a signet-ring cell-like appearance. Periodic-acid Schiff (PAS) staining was positive in the cytoplasm of a few of the cells found in the tubular pattern and in the mucus in some lumens and on the apical surface of cells in some lumens, but PAS did not stain cancer cells in the solid nests. Neither cancer cells nor mucus in the lumens were stained with alcian blue. All cancer cells were strongly positive for Grimelius silver stain, and most of the cancer cells stained positively for chromogranin A. Electron microscopic examination showed electron dense neuroendocrine granules in the cytoplasm of cancer cells. Cancer cells were stained positively for pancytokeratin, cytokeratin 8/18 and carcinoembryonic antigen. Muc 1 mucin glycoprotein staining was positive along the cell surfaces of cancer cells, but Muc 2, 5AC and 6 stainings were negative, although Muc 3 stained positively in the cytoplasm of a few cancer cells. The present case is a gastric tubular adenocarcinoma with Muc 1-positive, neutral- and acid mucin-negative signet-ring cell-like cells, which is associated with neuroendocrine differentiation.

Resuscitation of the ischemically damaged human pancreas by the two-layer method prior to islet isolation.

A two-layer cold storage method (TLM) allows sufficient oxygen delivery to pancreata during preservation and resuscitates the viability of ischemically damaged pancreata. This study determined the effect of additional preservation of ischemically damaged human pancreata by the TLM before islet isolation. Human pancreata were procured from cadaveric organ donors and preserved by the TLM for 3.2 +/- 0.5 hours (mean +/- SEM) at 4 degrees C after 11.1 +/- 0.9 hours of cold storage in University of Wisconsin solution (UW) (TLM group), or by cold UW alone for 11.0 +/- 0.3 hours (UW group). Islet isolations of all pancreata were performed using the Edmonton protocol. Islet recovery and in vitro function of isolated islets were significantly increased in the TLM group compared with the UW group. In the metabolic assessment of human pancreata, ATP levels were significantly increased after the TLM preservation. This study showed that additional short-term preservation by the TLM resuscitates the viability of ischemically damaged human pancreata before islet isolation, leading to improvements in islet recovery and in vitro function of isolated islets.

Improvement of pancreatic islet isolation outcomes using glutamine perfusion during isolation procedure.

During procurement, isolation, and transplantation, islets are exposed to high levels of oxidative stress triggering a variety of signaling pathways that can ultimately lead to cell death. Glutamine is an important cellular fuel and an essential precursor for the antioxidant glutathione. The aim of this study was to examine the role of intraductal glutamine administration in facilitating recovery of isolated rat islets from pancreases subjected to a clinically relevant period of warm ischemia. Islets were isolated in Sprague-Dawley (SD) rats (n = 18 per group). Pancreata in groups 1 and 2 were procured immediately while groups 3 and 4 were subjected to 30-min warm ischemia. Groups 2 and 4 were treated intraductally with 5 mM glutamine prior to pancreatectomy. Exposure to 30-min warm ischemia significantly reduced islet yield [groups 1 & 2 (nonischemia): 503 +/- 29 islets/rat vs. groups 3 & 4 (ischemia): 247 +/- 26 islets/rat; p < 0.05]. Intraductal glutamine treatment significantly improved islet yield when pancreata were subjected to 30-min warm ischemia [144 +/- 16 islets/rat without glutamine (group 3) vs. 343 +/- 36 islets/rat with glutamine (group 4), p < 0.05]. Glutamine also significantly improved islet viability (values were 50 +/- 4% in group 4 vs. 27 +/- 3% in group 3, p < 0.05). Similarly, glutathione (reduced) levels were significantly elevated in both glutamine-treated groups; however, this increase was greatest in tissues exposed to ischemia (2.76 +/- 0.04 nmol/mg protein in group 4 vs. 1.66 +/- 0.04 nmol/mg protein in group 3, p < 0.05). Intraductal glutamine administration considerably improves the islet yield, viability, and augments endogenous glutathione levels in pancreata procured after a clinically relevant period of ischemia. Intraductal administration of glutamine at the time of digestive enzyme delivery into the harvested pancreas may represent a simple yet effective tool to improve islet yields in clinical isolations.

Improvement of Pancreatic Islet Isolation Outcomes Using Glutamine Perfusion during Isolation Procedure.

During procurement, isolation, and transplantation, islets are exposed to high levels of oxidative stress triggering a variety of signaling pathways that can ultimately lead to cell death. Glutamine is an important cellular fuel and an essential precursor for the antioxidant glutathione. The aim of this study was to examine the role of intraductal glutamine administration in facilitating recovery of isolated rat islets from pancreases subjected to a clinically relevant period of warm ischemia. Islets were isolated in Sprague-Dawley (SD) rats (n= 18 per group). Pancreata in groups 1 and 2 were procured immediately while groups 3 and 4 were subjected to 30-min warm ischemia. Groups 2 and 4 were treated intraductally with 5 mM glutamine prior to pancreatectomy. Exposure to 30-min warm ischemia significantly reduced islet yield [groups 1 & 2 (nonischemia): 503 ± 29 islets/rat vs. groups 3 & 4 (ischemia): 247 ± 26 islets/rat; p < 0.05]. Intraductal glutamine treatment significantly improved islet yield when pancreata were subjected to 30-min warm ischemia [144 ± 16 islets/rat without glutamine (group 3) vs. 343 ± 36 islets/rat with glutamine (group 4), p < 0.05]. Glutamine also significantly improved islet viability (values were 50 ± 4% in group 4 vs. 27 ± 3% in group 3, p < 0.05). Similarly, glutathione (reduced) levels were significantly elevated in both glutamine-treated groups; however, this increase was greatest in tissues exposed to ischemia (2.76 ± 0.04 nmol/mg protein in group 4 vs. 1.66 ± 0.04 nmol/mg protein in group 3, p < 0.05). Intraductal glutamine administration considerably improves the islet yield, viability, and augments endogenous glutathione levels in pancreata procured after a clinically relevant period of ischemia. Intraductal administration of glutamine at the time of digestive enzyme delivery into the harvested pancreas may represent a simple yet effective tool to improve islet yields in clinical isolations.

Interleukin-18 and interleukin-12 synergistically inhibit osteoclastic bone-resorbing activity.

The effect of interleukin (IL)-18 on osteoclastic bone-resorbing activity was investigated in vitro. Osteoclast-enriched cells, about 70% of which were tartrate-resistant acid phosphatase (TRAP)-positive, were cultured on dentine slices, and then the total volume of resorption pits on each dentine slice was measured as bone-resorbing activity. When the effects of IL-18 alone at 1, 10, 100, and 1000 ng/mL were examined, bone-resorbing activity was significantly reduced only at 1000 ng/mL, by about 50%. However, IL-18 plus IL-12 (10 ng/mL each) reduced bone-resorbing activity by about 70%, whereas IL-12 alone had no significant effect. When the concentration of interferon (IFN)-gamma in the medium was measured, IL-18 or IL-12 was found to increase it slightly, and the combination of these two cytokines synergistically increased it. The inhibitory effect of the combination of the two cytokines was completely abolished by the addition of an anti-IFN-gamma neutralizing antibody to the medium, but IFN-gamma by itself did not inhibit osteoclastic bone resorption. IL-18 alone or in combination with IL-12 did not affect the number of TRAP-positive cells in culture of osteoclast-enriched cells. Osteoclasts prepared from osteoclast-enriched cells expressed mRNAs of IL-18 receptor, MyD88, and cathepsin K. Furthermore, IL-18 receptor protein was detected on the cell surface of osteoclasts. The present results indicate that the combination of IL-18 and IL-12 synergistically inhibits osteoclastic bone-resorbing activity, suggesting that IFN-gamma participates in the mechanism underlying this inhibition.

Castration induces apoptosis in the male accessory sex organs of Fas-deficient lpr and Fas ligand-deficient gld mutant mice.

The role of the Fas ligand-Fas system in castration-induced apoptosis in the epithelia of the ventral prostate (VP), seminal vesicle (SV), coagulating gland (CG) and epididymis (Ep) was investigated using lpr/lpr, and gld/gld mutant mice which are deficient in Fas and Fas ligand, respectively. The degree of apoptosis in the epithelium was quantitatively estimated by an apoptotic index (a percentage of apoptotic cells). The weights (mg/10 g body weight) of the VP, SV, CG and Ep of lpr/lpr and gld/gld mice were similar to those of normal +/+ mice and castration decreased the weights of the VP, SV, CG and Ep in these three kinds of mice to similar levels. Castration also increased the apoptotic indices in these organs reaching maximum on days 2-6 after castration. There was no significant difference in the apoptotic index of these organs among +/+, lpr/lpr and gld/gld mice on days 0-8 after castration. Agarose gel electrophoresis of DNAs extracted from the VP, SV, CG and Ep of +/+, lpr/lpr and gld/gld mice on day 4 after castration showed a ladder pattern. The present results suggest that the Fas ligand-Fas system plays little role in castration-induced apoptosis in the mouse male accessory sex organs such as the VP, SV, CG and Ep.

Possible role of heat shock protein 60 in reducing ischemic-reperfusion injury in canine pancreas grafts after preservation by the two-layer method.

INTRODUCTION: Recently, results of the clinical application of the two-layer method have shown the morphologic quality of the human pancreas grafts after reperfusion to be excellent, although ischemia-reperfusion injury is related to early graft loss in pancreas transplantation. However, some reports have indicated that heat shock proteins (HSPs) have important functions in response to the stress-related events. AIM: To examine whether the two-layer method reduced ischemia-reperfusion injury in a canine pancreas autotransplantation model by investigating the expression of HSPs. METHODOLOGY: There were three experimental groups in which dogs received segmental autografts after preservation by the two-layer method using University of Wisconsin solution (UW) (group 1), simple storage in UW (group 2) for 24 hours, or no preservation (group 3). RESULTS: In group 1, pancreatic tissue perfusions were high, and pancreatic exocrine functions were well preserved after 1, 2, and 4 hours of reperfusion with low incidence of graft pancreatitis or vessel thrombosis compared with that in group 2. Moreover, ATP rapidly recovered, and HSP 60 was strongly enhanced after reperfusion in group 1. On the other hand, ATP recovery and the enhancement of HSP 60 were weak after reperfusion in group 2. CONCLUSION: The two-layer method reduced ischemia-reperfusion injury compared with UW simple storage in canine pancreas autotransplantation with a strong expression of HSP 60.