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Background Sarcopenia is a progressive condition that is characterized by decreases in skeletal muscle mass and function. Although sarcopenia is associated with lifestyle-related diseases (LSRD), the mechanisms underlying cell death in myoblasts, which differentiate to myotubes, remain unclear. We previously designated glyceraldehyde (an intermediate of glucose/fructose metabolism)-derived advanced glycation end-products (AGEs) as toxic AGEs (TAGE) because of their cytotoxicity and involvement in LSRD, and hypothesized that TAGE contribute to cell death in myoblasts. Methods C2C12 cells, which are murine myoblasts, were treated with 0, 0.5, 1, 1.5, and 2 mM glyceraldehyde for 24 h. Cell viability and intracellular TAGE were then assessed using 5-[2,4,-bis(sodioxysulfonyl)phenyl]-3-(2-methoxy-4-nitrophenyl)-2-(4-nitrophenyl)-2H-tetrazole-3-ium (WST-8) and slot blot assays. Cells were pretreated with 8 mM aminoguanidine, an inhibitor of AGE production, for 2 h, followed by 0, 1.5, and 2 mM glyceraldehyde for 24 h. Cell viability and intracellular TAGE levels were then assessed. Serum TAGE levels in STAM mice, in which there were four stages (no steatosis, simple steatosis, steatohepatitis, and fibrosis), were measured using a competitive enzyme-linked immunosorbent assay. Results were expressed as TAGE units (U) per milliliter of serum, with 1 U corresponding to 1.0 μg of glyceraldehyde-derived AGE-bovine serum albumin (BSA) (TAGE-BSA). The viability of cells treated with 20, 50, and 100 μg/mL non-glycated BSA and TAGE-BSA for 24 h was assessed using the WST-8 assay. Results In C2C12 cells treated with 1.5 and 2 mM glyceraldehyde, cell viability decreased to 47.7% (p = 0.0021) and 5.0% (p = 0.0001) and intracellular TAGE levels increased to 6.0 and 15.9 μg/mg protein, respectively. Changes in cell viability and TAGE production were completely inhibited by 8 mM aminoguanidine. Serum TAGE levels at the steatohepatitis and fibrosis stages were 10.51 ± 1.16 and 10.44 ± 0.95 U/mL, respectively, and were higher than those at the no steatosis stage (7.27 ± 0.18 U/mL). Cell death was not induced by 20 or 50 μg/mL TAGE-BSA. The viabilities of C2C12 cells treated with 100 μg/mL non-glycated BSA and TAGE-BSA were 105.0% (p = 0.2890) and 85.3% (p = 0.0217), respectively. Conclusion Intracellular TAGE strongly induced cell death in C2C12 cells and may also induce myoblast cell death in LSRD model mice.

In this presentation, we discuss noise floor comparisons of an optical displacement measuring interferometer between air and vacuum environments. A heterodyne interferometer and its phasemeter, with the resolution of 10-6 radian, implemented in a field programmable gate array (FPGA) are utilized for the comparison. A heterodyne laser source consists of a frequency stabilized He-Ne laser and two acoustic optic modulators (AOMs). The interferometer optics and a piezoelectric (PZT) flexure stage which drives the moving retroreflector of the interferometer are placed in a vacuum chamber. In the vacuum environment at 3 mPa, the noise floor of 1 pm/OHz or less is attained in the frequency range of 0.01 ~ 100 Hz.

Background 1,5-anhydroglucitol is a reduction product of 1,5-anhydrofructose. Circulating 1,5-anhydroglucitol is usually excreted by the kidneys and is reabsorbed via sodium-glucose co-transporter 4 in the renal tubules. In patients on hemodialysis, serum levels of 1,5-anhydroglucitol have been reported to be low; however, the underlying mechanism remains unclear. Methods We measured inter-dialysis changes in the levels of serum 1,5-anhydroglucitol and 1,5-anhydrofructose-derived advanced glycation end products (AGEs) in 78 patients on hemodialysis. Serum levels of 1,5-anhydrofructose-derived AGEs were also determined using a polyclonal antibody. Results The serum 1,5-anhydroglucitol level was decreased to as low as 2.0 μg/mL in the regular hemodialysis group; however, we could not verify changes in the serum 1,5-anhydroglucitol level during inter-dialysis days because of undetectable levels in 29 patients. The measured serum level of 1,5-anhydrofructose-derived AGEs was significantly increased in both patient groups. In addition, the 1,5-anhydrofructose-derived AGEs/1,5-anhydroglucitol ratio was higher in patients on hemodialysis than in controls. Conclusions Accelerated glycation of 1,5-anhydrofructose is one possible mechanism by which serum 1,5-anhydroglucitol levels are lowered in patients on HD, and we propose that the 1,5-anhydrofructose-derived AGEs/1,5-anhydroglucitol ratio should be measured in clinical settings in which patients have low serum levels of 1,5-AG.

Although dysfunction of the mesolimbic dopaminergic system has been implicated in chronic pain, the underlying mechanisms remain to be elucidated. We hypothesized that increased inhibitory inputs to the neuronal pathway from the dorsolateral bed nucleus of the stria terminalis (dlBNST) to the ventral tegmental area (VTA) during chronic pain may induce tonic suppression of the mesolimbic dopaminergic system. To test this hypothesis, male Sprague Dawley rats were subjected to spinal nerve ligation to induce neuropathic pain and then spontaneous IPSCs (sIPSCs) were measured in this neuronal pathway. Whole-cell patch-clamp electrophysiology of brain slices containing the dlBNST revealed that the frequency of sIPSCs significantly increased in VTA-projecting dlBNST neurons 4 weeks after surgery. Next, the role of corticotropin-releasing factor (CRF) signaling within the dlBNST in the increased sIPSCs was examined. CRF increased the frequency of sIPSCs in VTA-projecting dlBNST neurons in sham-operated controls, but not in chronic pain rats. By contrast, NBI27914, a CRF type 1 receptor antagonist, decreased the frequency of sIPSCs in VTA-projecting dlBNST neurons in the chronic pain rats, but not in the control animals. In addition, histological analyses revealed the increased expression of CRF mRNA in the dlBNST. Finally, bilateral injections of NBI27914 into the dlBNST of chronic pain rats activated mesolimbic dopaminergic neurons and induced conditioned place preference. Together, these results suggest that the mesolimbic dopaminergic system is tonically suppressed during chronic pain by enhanced CRF signaling within the dlBNST via increased inhibitory inputs to VTA-projecting dlBNST neurons.SIGNIFICANCE STATEMENTThe comorbidity of chronic pain and depression has long been recognized. Although dysfunction of the mesolimbic dopaminergic system has been implicated in both chronic pain and depression, the underlying mechanisms remain to be elucidated. Here, we show that the inhibitory inputs to the neuronal pathway from the dorsolateral bed nucleus of the stria terminalis (dlBNST) to the ventral tegmental area increase during chronic pain. This neuroplastic change is mediated by enhanced corticotropin-releasing factor signaling within the dlBNST that leads to tonic suppression of the mesolimbic dopaminergic system, which may be involved in the depressive mood and anhedonia under the chronic pain condition.

The main purpose of this study is to facilitate fragrance development on the basis of scientific knowledge. To this end, data on 314 perfumery raw materials (PRMs) showing the relationship between ...

Cardiovascular disease (CVD) is a lifestyle-related disease (LSRD) and one of the largest public health issues. Risk factors for CVD correlate with an excessive intake of glucose and/or fructose, which has been shown to induce the production of advanced glycation end-products (AGEs). We previously identified AGEs derived from glyceraldehyde and named them toxic AGEs (TAGE) due to their cytotoxicities and relationship with LSRD. We also reported that extracellular TAGE in the vascular system may promote CVD and that serum TAGE levels are associated with risk factors for CVD. The mechanisms responsible for the onset and/or progression of CVD by extracellular TAGE or the above risk factors involve vascular disorders. In the present study, we revealed that rat primary cultured cardiomyocytes generated intracellular TAGE, which decreased beating rates and induced cell death. LC3-II/LC3-I, a factor of autophagy, also decreased. Although intracellular TAGE may be targets of degradation as cytotoxic proteins via autophagy, they may inhibit autophagy. Furthermore, the mechanisms by which intracellular TAGE decrease beating rates and induce cell death may involve the suppression of autophagy. The present results suggest that intracellular TAGE are generated in cardiomyocytes and directly damage them, resulting in CVD.

We report the current status of the NASCO (NAnten2 Super CO survey as legacy) project which aims to provide all-sky CO data cube of southern hemisphere using the NANTEN2 4-m submillimeter telescope installed at the Atacama Desert through developing a new multi-beam receiver and a new telescope control system. The receiver consists of 5 beams. The four beams, located at the four corners of a square with the beam separation of 720′′, are installed with a 100 GHz band SIS receiver having 2-polarization sideband-separation filter. The other beam, located at the optical axis, is installed with a 200 GHz band SIS receiver having 2-polarization sideband-separation filter. The cooled component is modularized for each beam, and cooled mirrors are used. The IF bandwidths are 8 and 4 GHz for 100 and 200 GHz bands, respectively. Using XFFTS spectrometers with a bandwidth of 2 GHz, the lines of 12CO, 13CO, and C18O of J=1−0 or J=2−1 can be observed simultaneously for each beam. The control system is reconstructed on the ROS architecture, which is an open source framework for robot control, to enable a flexible observation mode and to handle a large amount of data. The framework is commonly used and maintained in a robotic field, and thereby reliability, flexibility, expandability, and efficiency in development are improved as compared with the system previously used. The receiver and control system are installed on the NANTEN2 telescope in December 2019, and its commissioning and science verification are on-going. We are planning to start science operation in early 2021.

Two-dimensional neutron detectors were developed for the extension of SENJU time-of-flight Laue single crystal neutron diffractometer in J-PARC MLF. The detectors are installed at the additional detector bank for the SENJU instrument. The detector module is made based on ZnS scintillator and wavelength-shifting fiber technology, where each detector module maintains a neutron-sensitive area of 256 × 256 mm with a pixel size of 4 × 4 mm. To meet the tight space limitation in the instrument, the detector was designed as compact as possible. The detector has a depth of 170 mm, which is about 40% smaller than that of the original SENJU detector. Moreover, new comparator electronics cards are implemented, which pick up signals with smaller heights and narrower time widths than the original ones. These cards help decrease in the applied PMT voltage and they improved count uniformity. All four produced detector exhibited similar detector performances: detection efficiency 50-60% for 2-A neutron, 60Co gamma-ray sensitivity 1×10−5, count uniformity 3-6%.

Background: Sarcopenia is a progressive disease that is characterized by decreases in skeletal muscle mass and function. Skeletal muscle consists of myotubes that differentiated from myoblasts. Although sarcopenia is associated with non-alcoholic steatohepatitis (NASH) and type 2 diabetes mellitus (T2DM), the underlying mechanisms remain unclear. We considered that glyceraldehyde (GA), a glucose/fructose metabolism intermediate, plays a crucial role in sarcopenia. We previously designated GA-derived advanced glycation end-products (AGEs) as toxic AGEs (TAGE) because of their cytotoxicity and involvement in lifestyle-related diseases (LSRD), such as NASH and T2DM. We hypothesized that TAGE induce cytotoxicity in myoblasts. Methods: C2C12 cells, which are murine myoblasts, were treated with 0, 0.5, 1, 1.5, and 2 mM GA for 24 h, and cell viability and intracellular TAGE were measured using WST-8 and slot blot assays. Cells were pretreated with 8 mM aminoguanidine (AG), an inhibitor of AGE production, for 2 h followed by 0, 1.5, and 2 mM GA for 24 h. Cell viability and intracellular TAGE were then measured. Serum TAGE levels in STAM mice, in which there were four stages (pre-simple steatosis, simple steatosis, steatohepatitis, and fibrosis), were measured using an enzyme-linked immunosorbent assay. Results were expressed as TAGE units (U) per milliliter of serum, with 1 U corresponding to 1.0 μg of GA-derived AGE-bovine serum albumin (BSA) (TAGE-BSA). The viabilities of cells treated with 20 μg/mL non-glycated BSA (NG-BSA) and TAGE-BSA for 24 h were assessed using the WST-8 assay. Results: In C2C12 cells treated with 1.5 and 2 mM GA, cell viability decreased to 47.7 and 5.0% and intracellular TAGE increased to 6.0 and 15.9 μg/mg protein, respectively. Decreases in cell viability and TAGE production were completely inhibited by 8 mM AG. Serum TAGE levels at the steatohepatitis and fibrosis stages were 10.51 ±1.16 and 10.44±0.95 U/mL, respectively, and increased from the pre-simple steatosis stage. The viabilities of C2C12 cells treated with 20 μg/mL NG-BSA and TAGE-BSA were 99.7 and 88.3%, respectively. Conclusion: Intracellular TAGE were generated in C2C12 cells and induced cell death more strongly than extracellular TAGE. Intracellular TAGE in myoblasts may cause sarcopenia in patients with LSRD.

Port structure in the JT-60SA is designed to access vacuum vessel inside for vacuum exhausts, plasma heating systems and diagnostics etc. from cryostat outside. The port consists of a rectangular pipe, bellows and additional materials such as electrical insulations and connection parts for onsite assembly. The vacuum space as the thermal insulation for superconducting coils is penetrated by the port as the vacuum interfaces between the vacuum vessel and the cryostat so that port structure is required to be structurally integrated against plasma and baking operations and accidental events. This structure must be installed in narrow space, and electrical insulation is functionally designed to avoid the unexpected large eddy current loop. This paper reports the design of port connection structure for the assembly. Port connection parts “Port Extension” and “adjustable plate” are introduced to absorb vertical of 10 mm, toroidal of 8 mm, and port axial of 10 mm error due to the manufacturing and assembly. The bellows are expected to absorb relative displacement of 39 mm only between the vacuum vessel and the cryostat during the operation. The structure is confirmed to withstand the load conditions because stress is estimated to be lower than allowable level by FEM analysis.

JT-60SA is a superconducting tokamak developed under the Satellite Tokamak Programme of the Broader Approach Agreement between EU and Japan, and the Japanese national programme. It is designed to operate in the break-even conditions for long pulse duration (typically 100 s), with a maximum plasma current of 5.5 MA. Its scientific aim is to contribute at early realization of fusion energy, in support to the ITER project and also to future DEMO devices by addressing key engineering and physical issues for advanced plasma operation. The JT-60SA Project has shown steady progress in the last years: from the design of the main components, started in 2007 in a close collaboration between EU and Japan, continuing through the assembly in the torus hall, started in January 2013 with the delivery of the first large European component, the Cryostat Base. Since then big milestones have been achieved, like the complete winding and pre-installation of the three lower Equilibrium Field (EF) coils, the welding of a 340° of the Vacuum Vessel sectors, and the completion of most of the Toroidal Field (TF) Coils. Outside the tokamak hall, large auxiliary plant like the Cryogenic System (CS) and the Quench Protection Circuits (QPC) have been fully installed and commissioned, while the Switching Network Units (SNU) and TF and EF coils Power Supplies (SCMPS) are completing installation on site. Other components such as Cryostat Vessel, Thermal Shields, In Vessel Components and so forth are being manufactured and being delivered to Naka site for installation and commissioning. This paper gives technical progress on fabrication, installation and assembly of tokamak components and ancillary systems, as well as progress of JT-60SA Research Plan being developed jointly by EU and Japanese fusion communities.

A large area, position-sensitive scintillation neutron detector was developed for upgrading the SENJU, a time-of-flight Laue single crystal neutron diffractometer, in J-PARC MLF. The detector has a neutron-sensitive area of 512 × 512 mm with a pixel size of 4 × 4 mm. The detector is to be installed below the new vacuum tank to enlarge its scattering angle coverage. A 6Li:ZnS (Ag) scintillator and wavelength-shifting fiber technology is employed to make the prototype detector. Each fiber channel is read out individually with a photon counting method. Detector electronics boards are implemented at the backside of the detector. This configuration enables the detector depth as short as 200 mm. The detector exhibits a detection efficiency of 45% for 1.8-A neutron. No degradation has been observed both in the fiber position and in the neutron sensitivity over one year after the detector assembly. The detector design and its performances are presented.

A real-time data display and storage device was developed for neutron scattering experiments. The device contains two sets of field programmable gate arrays and onboard microcomputers for data display and storage. The developed device can determine the time-of-flight and time- resolved neutron position data with a time range from 0 to 40 ms using a beam of pulsed neutrons at 25 Hz. It was confirmed by an operation test using burst and continuous test pulses that the device exhibited a pulse pair resolution of less than 1 μs and a counting rate capability of more than 1 Mcps.

Glucose/fructose in beverages/foods containing high-fructose corn syrup (HFCS) are metabolized to glyceraldehyde (GA) in the liver. We previously reported that GA-derived advanced glycation end-products (toxic AGEs, TAGE) are generated and may induce the onset/progression of non-alcoholic fatty liver disease (NAFLD). We revealed that the generation of TAGE in the liver and serum TAGE levels were higher in NAFLD patients than in healthy humans. Although we propose the intracellular generation of TAGE in the normal liver, there is currently no evidence to support this, and the levels of TAGE produced have not yet been measured. In the present study, male Wister/ST rats that drank normal water or 10% HFCS 55 (HFCS beverage) were maintained for 13 weeks, and serum TAGE levels and intracellular TAGE levels in the liver were analyzed. Rats in the HFCS group drank 127.4 mL of the HFCS beverage each day. Serum TAGE levels and intracellular TAGE levels in the liver both increased in the HFCS group. A positive correlation was observed between intracellular TAGE levels in the liver and serum TAGE levels. On the other hand, in male Wister/ST rats that drank Lactobacillus beverage for 12 weeks&mdash, a commercial drink that contains glucose, fructose, and sucrose&mdash, no increases were observed in intracellular TAGE or serum TAGE levels. Intracellular TAGE were generated in the normal rat liver, and their production was promoted by HFCS, which may increase the risk of NAFLD.

Objective: This study aimed to assess the dosimetric effect of intestinal gas of stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) on target and critical organs for pancreatic cancer without online electron density correction (EDC). Methods: Thirty pancreatic cancer patients who underwent online SMART were selected for this study. The treatment time of each stage and the total treatment time were recorded and analyzed. The concerned dose-volume parameters of target and organs-at-risk (OAR) were compared with and without an intestinal gas EDC using the Wilcoxon-signed rank test. Analysis items with p value < 0.05 were considered statistically significant. The relationships between dosimetric differences and intestinal gas volume variations were investigated using the Spearman test. Results: The average treatment time was 82 min, and the average EDC time was 8 min, which accounted for 10% of the overall treatment time. There were no significant differences in CTV (GTV), PTV, bowel, stomach, duodenum, and skin (p > 0.05) with respect to dose volume parameters. For the Dmax of gastrointestinal organs (p = 0.03), the mean dose of the liver (p = 0.002) and kidneys (p = 0.03 and p = 0.04 for the left and right kidneys, respectively), there may be a risk of slight overestimation compared with EDC, and for the Dmax of the spinal cord (p = 0.02), there may be a risk of slight underestimation compared with EDC. A weak correlation for D95 in the PTV and D0.5 cc in the duodenum was observed. Conclusion: For patients with similar inter-fractional intestinal gas distribution, EDC had little dosimetric effects on the D0.5 cc of all GI organs and dose volume parameters of target in most plans. Advances in knowledge: By omitting the EDC of intestinal gas, the online SMART treatment time can be shortened.

A two-dimensional scintillation neutron detector with a submillimeter spatial resolution was developed for time-of-flight neutron diffraction imaging in the J-PARC MLF. The detector comprised the thin, single ZnS/6LiF scintillator screen coupled with the crossed wavelength -shifting fiber array for light collection. For a high spatial resolution, the wavelength-shifting fibers with a diameter of 0.1 mm were used for assembling the light collection head. The prototype detector that has a neutron-sensitive area of 24 × 24 mm2 exhibited a spatial resolution of 0.20 ± 0.06 mm and 0.16 ± 0.06 mm for x and y directions, respectively. The detector had a detection efficiency of 7% for thermal neutron with a 60Co gamma-ray sensitivity in the order of 10-6. In this paper detector design and specifications are described together with experimental results using the pulsed neutron beam.

Background and study aims The aim of this study was tp compare the diagnostic efficiency of the PillCam SB3 capsule endoscopy (CE) system with the older system, PillCam SB2, taking into consideration the experience of the image reader. Patients and methods Small intestinal CE was conducted on 64 patients around May 2014 when the SB3 was introduced in our hospital. Data obtained from 20 patients (SB2: 10 and SB3: 10) based on transit time were assessed by junior (experience: 20 images), intermediate (> 50), and expert readers (> 600). Results Reading time with the CE down to the end of the small intestine was shorter in the SB3 group for each reader (SB2 vs. SB3: junior, 40.2 ± 10.1 vs. 23.7 ± 6.7 [P = 0.0009]; intermediate, 21.4 ± 4.9 vs. 10.3 ± 2.9 [P = 0.0003]; expert, 23.2 ± 5.6 vs. 11.1 ± 2.9 min [P = 0.0002]). Interpretation agreement rates between the findings by junior and intermediate readers and those by the expert reader were 84.6 % and 92.3 %, respectively. For the junior reader, rates of agreement using the SB2 and SB3 systems with those by the expert reader were 85.7 % and 83.3 %, respectively; no significant difference was noted between the two systems. Similarly, for the intermediate reader, the respective agreement rates using the SB2 and SB3 systems were 85.7 % and 100 %, respectively. Conclusions The PillCam SB3 reduces the time burden on readers irrespective of their experience.

The light transport properties of scintillator light inside alternative He-3 neutron detectors using scintillator sheets have been investigated by a ray-tracing simulation code. The detector consists of a light-reflecting tube, a thin rectangular ceramic scintillator sheet laminated on a glass plate, and two photo-multiplier tubes (PMTs) mounted at both ends of the detector tube. The flashes of light induced on the surface of the scintillator sheet via nuclear interaction between the scintillator and neutrons are detected by the two PMTs. The light output at both ends of various detectors in which the scintillator sheets are installed with several different arrangements were examined and evaluated in comparison with experimental results. The results derived from the simulation reveal that the light transport property is strongly dependent on the arrangement of the scintillator sheet inside the tube and the shape of the tube.

A novel ceramic-insulated detector element was developed for two-dimensional neutron measurement, and an irradiation experiment was performed using a Cf-252 neutron source. The element consisted of a ceramic insulator and a ball-shaped anode. It is estimated that a ceramic insulator can suppress the background noise caused by unintentionally scattered neutrons. An electrical field of 1.60×107 V/m was obtained based on a calculation at the top of the ball-shaped anode. Neutron signals were clearly observed using the detector element, thus validating its operation.

Nonalcoholic fatty liver disease (NAFLD) ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), leads to fibrosis and potentially cirrhosis, liver failure, and hepatocellular carcinoma, and is one of the most common causes of liver disease worldwide. NAFLD has also been implicated in other medical conditions such as insulin resistance, obesity, metabolic syndrome, hyperlipemia, hypertension, cardiovascular disease, and diabetes. Continuous hyperglycemia has been implicated in the pathogenesis of diabetic micro- and macro-vascular complications via various metabolic pathways, and numerous hyperglycemia-induced metabolic and hemodynamic conditions exist, including the increased generation of various types of advanced glycation end-products (AGEs). We recently demonstrated that glyceraldehyde-derived AGEs (Glycer-AGEs), the predominant components of toxic AGEs (TAGE), played an important role in the pathogenesis of angiopathy in diabetic patients. Moreover, a growing body of evidence suggests that the interaction between TAGE and the receptor for AGEs may alter intracellular signaling, gene expression, and the release of pro-inflammatory molecules and also elicits the generation of oxidative stress in numerous types of cells including hepatocytes and hepatic stellate cells. Serum levels of TAGE were significantly higher in NASH patients than in those with simple steatosis and healthy controls. Moreover, serum levels of TAGE inversely correlated with adiponectin (adiponectin is produced by adipose tissue and is an anti-inflammatory adipokine that can increase insulin sensitivity). Furthermore, immunohistochemical staining of TAGE showed intense staining in the livers of patients with NASH. Serum levels of TAGE may be a useful biomarker for discriminating NASH from simple steatosis. The administration of atorvastatin (10 mg daily) for 12 months significantly improved NASH-related metabolic parameters and significantly decreased serum levels of TAGE. The steatosis grade and NAFLD activity score were also significantly improved. These results demonstrated that atorvastatin decreased the serum levels of TAGE in NASH patients with dyslipidemia and suggest the usefulness of TAGE as a biomarker for the attenuation of NASH. Serum levels of TAGE were significantly higher in non-B or non-C hepatocellular carcinoma (NBNC-HCC) patients than in NASH subjects without HCC or control subjects. TAGE may be involved in the pathogenesis of NBNC-HCC, and could, therefore, be a biomarker that could discriminate NBNC-HCC from NASH. We propose that serum levels of TAGE are promising novel targets for the diagnosis of and therapeutic interventions against NASH.

Neutron devices such as neutron detectors, optical devices including supermirror devices and 3He neutron spin filters, and choppers are successfully developed and installed at the Materials Life Science Facility (MLF) of the Japan Proton Accelerator Research Complex (J-PARC), Tokai, Japan. Four software components of MLF computational environment, instrument control, data acquisition, data analysis, and a database, have been developed and equipped at MLF. MLF also provides a wide variety of sample environment options including high and low temperatures, high magnetic fields, and high pressures. This paper describes the current status of neutron devices, computational and sample environments at MLF.

Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are among the most common causes of chronic liver diseases in the westernized world. NAFLD and ALD are frequently accompanied by extrahepatic complications, including hepatocellular carcinoma and cardiovascular diseases, which have a negative impact on patient survival. The chronic ingestion of an excessive daily diet containing sugar/high-fructose corn syrup increases the level of the fructose/glucose metabolite, glyceraldehyde (GA), while the chronic consumption of an excessive number of alcoholic beverages increases the level of the alcohol metabolite, acetaldehyde (AA) in the liver. GA and AA are known to react non-enzymatically with the ε- or α-amino groups of proteins, thereby generating advanced glycation end-products (AGEs, GA-AGEs, and AA-AGEs, respectively) in vivo. The interaction between GA-AGEs and the receptor for AGEs (RAGE) alters intracellular signaling, gene expression, and the release of pro-inflammatory molecules and also elicits the production of reactive oxygen species by human hepatocytes and hepatic stellate cells, all of which may contribute to the pathological changes associated with chronic liver diseases. We herein discuss the pathophysiological roles of GA-AGEs and AA-AGEs (toxic AGEs, TAGE) and a related novel theory for preventing the onset/progression of NAFLD and ALD.

A neutron-sensitive ZnS/10B2O3 ceramic scintillator detector was developed as an alternative to a 3He-gas-based detector for use in a plutonium canister assay system. The detector has a modular structure, with a flat ZnS/10B2O3 ceramic scintillator strip that is installed diagonally inside a light-reflecting aluminium case with a square cross-section, and where the scintillation light is detected using two photomultiplier tubes attached at both ends of the case. The prototype detectors, which have a neutron-sensitive area of 30 mm×250 mm, exhibited a sensitivity of 21.7–23.4±0.1 cps/nv (mean±SD) for thermal neutrons, a 137Cs gamma-ray sensitivity of 1.1–1.9±0.2×10−7 and a count variation of less than 6% over the detector length. A trial experiment revealed a temperature coefficient of less than −0.24±0.05%/°C over the temperature range of 20–50 °C. The detector design and the experimental results are presented.

A position-sensitive tubular scintillator-based neutron detector is proposed as an alternative to a 3 He-gas-based detector. The detector has a neutron-detecting element constructed from rolled ZnS/ 6 LiF scintillator screens that sandwich wavelength-shifting (WLS) fibre coils (SFC element). Multiple SFC elements are enclosed in an aluminium tube in a row to form a one-dimensional position-sensitive neutron detector. The design of the WLS fibre coil, which was determined by performing basic experiments, comprised two 0.75-mm-diameter WLS fibres wound in parallel at a pitch of 1.5 mm. A 64-element detector with a pixel size of 22 mm×20 mm (width×length) successfully demonstrated the detection principle. The tubular shape of the new detector is similar to the usual 25-mm-diameter 3 He tube, making this an alternative detector with the potential to be installed in a vacuum tank for inelastic-neutron-scattering instruments.

A scintillator-based neutron-counting imaging detector with a sub-100-μm spatial resolution was developed for energy-selective neutron imaging. The detector head of the detector comprised a thin ZnS/6LiF scintillator screen, a fibre-optic taper and crossed wavelength-shifting (WLS) fibre arrays. A high spatial resolution was achieved by constructing the scintillator with a thickness of 100 μm and placing it in contact with the fibre-optic taper at a magnification ratio of 3.1:1. WLS fibres with a diameter of 100±5 μm (mean±SD) were specially made, and their dye content was optimized for use in crossed WLS-fibre arrays. The developed detector had a pixel size of 34 μm×34 μm, and exhibited spatial FWHM resolutions of 80±7 μm and 61±6 μm in the x and y directions, respectively. A small prototype detector demonstrated the capability of neutron imaging using Bragg edges of a Cu/Fe sample when using the pulsed-neutron source in the Materials and Life Science Experimental Facility at the Japan Proton Accelerator Research Complex.

The detector system of SENJU —a single-crystal time-of-flight neutron diffractometer—is described. SENJU is the first diffractometer employing a large-area two-dimensional wavelength-shifting fiber-based scintillator detector at the Materials and Life Science Experimental Facility at the Japan Proton Accelerator Research Complex. Thirty-seven detectors were installed in the instrument to cover a scattering angle of 30%. The detector modules exhibited a detector efficiency of 37–47±1% (mean±standard deviation) for thermal neutrons, a 60 Co gamma-ray sensitivity of 1.4–5.1±0.1×10 −6 , a background count rate of 2.1–3.8±1.0×10 −4 cps/cm 2 and a tolerance to stray magnetic fields up to 120 G. The detector exhibited stable performance under the operating conditions used, such as stable count rates over 400 days and a count temperature coefficient of −0.01±0.02%/°C at around 20 °C. The detector system and its performance metrics are presented together with the specific detector design.

Non-alcoholic fatty liver disease (NAFLD) is currently the most common feature of chronic liver disease. Non-alcoholic steatohepatitis (NASH) is a severe form of NAFLD, and one of its risk factors is hyperglycemia. The chronic ingestion of excessive amounts of high-fructose corn syrup is associated with an increased prevalence of fatty liver. Under hyperglycemic conditions, advanced glycation end-products (AGEs) are generated through a non-enzymatic glycation reaction between the ketone or aldehyde groups of sugars and amino groups of proteins. Glyceraldehyde (GA) is a metabolic intermediate of sugars, and GA-derived AGEs (known as toxic AGEs (TAGE)) have been implicated in the development of NASH. TAGE accumulates more in serum or liver tissue in NASH patients than in healthy controls or patients with simple steatosis. Furthermore, the TAGE precursor, GA, causes cell damage through protein dysfunctions by TAGE modifications and induces necrotic-type hepatocyte death. Intracellular TAGE may leak outside of necrotic-type cells. Extracellular TAGE then induce inflammatory or fibrotic responses related to the pathology of NASH in surrounding cells, including hepatocytes and hepatic stellate cells. This review focuses on the contribution of TAGE to the pathology of NASH, particularly hepatic cell death related to NASH.

JT-60SA is a superconducting tokamak to be assembled and operated at the JAEA laboratories in Naka (Japan) [1] . The tokamak has been designed to prepare, support and complement the ITER experimental programme and will be manufactured and operated under the funding of the Broader Approach Agreement (between the government of Japan and the European Commission) and of the Japan Fusion National Programme. Within the European contribution to JT-60SA, Spain has to provide the cryostat. Due to functional purposes, the cryostat has been divided in two large assemblies: the Cryostat Base (CB) and the Cryostat Vessel Body the latter subdivided into Cryostat Vessel Body Cylindrical Section (CVBCS) and the Top Lid. Spain is committed to provide the design and subsequent manufacturing of the CB and CVBCS (excluding the Top Lid) through the National Laboratory of Fusion at Ciemat. The design of both components has been concluded and the CB is currently being manufactured by a Spanish company, IDESA. This paper aims to present the status of the manufacturing and pre-assembly at the factory of the CB that has to be delivered in November 2012.

A multiwire-type two-dimensional neutron detector system with a sensitive area of 128×128 mm 2 is developed for use in the Materials and Life Science Experimental Facility at the Japan Proton Accelerator Research Complex. The system can achieve a short response time and high spatial resolution using the individual line readout method. Optical devices have been incorporated in the system for long-distance signal transmission and insulation between a detector head in the neutron shielding and signal processing circuits in the data acquisition room. The detector system exhibits a pulse-pair resolution of 1 μs, an average spatial resolution of less than 2 mm full width at half-maximum in the sensitive region, and a two-dimensional homogeneity of 8.3% in all pixels.

The JT-60SA cryostat is a stainless steel vacuum vessel (14 m diameter, 16 m height) which encloses the Tokamak providing the vacuum environment (10 −3 Pa) necessary to limit the transmission of thermal loads to the components at cryogenic temperature. It must withstand both external atmospheric pressure during normal operation and internal overpressure in case of an accident. The paper summarizes the structural analyses performed in order to validate the JT-60SA cryostat vessel body design. It comprises several analyses: a buckling analysis to demonstrate stability under the external pressure; an elastic and an elastic–plastic stress analysis according to ASME VIII rules, to evaluate resistance to plastic collapse including localized stress concentrations; and, finally, a detailed analysis with bolted fasteners in order to evaluate the behavior of the flanges, assuring the integrity of the vacuum sealing welds of the cryostat vessel body.

A scintillator-based gamma-ray detection system that uses a radiation-resistant optical fiber was developed. The system consisted of two radiation-resistant optical fibers—one, a fiber with a scintillator, and the other, a fiber without a scintillator—which were used to obtain the gamma-ray dose rate at the measurement point. This system demonstrated a linear response with respect to the gamma-ray dose rate from 0.005 to 1.5 Gy/h and a good radiation resistance over an absorbed dose of more than 300 kGy.

A ceramic-insulated ball-anode (CiB) element that consists of a ceramic insulator, cathode lines, ball-shaped anodes, and anode lines was developed, and an irradiation experiment was performed using a Cf-252 neutron source. An electric field simulation of CiB element was conducted and strong electric fields of more than 107 V/m was obtained by the calculation using the finite element method. The neutron-induced signals of all pixels were observed using 8 × 8 ch small-sized test element under Cf-252 neutron irradiation.

We have developed a position-sensitive tubular scintillation neutron detector as an alternative to a 3He gas based detector. The detector comprises a number of individual neutron-sensitive elements, where a pair of wound wavelength-shifting fiber coils is sandwiched with two rolled ZnS/6LiF scintillator screens in each element. Position-dependent neutron sensitivity within the scintillator / wavelength-shifting fiber coil (SFC) element was evaluated by using a collimated pulsed neutron beam at the J-PARC MLF. The collimated beam that has a size of 1 × 1 mm2 scanned over the SFC element. Neutron counts were recorded and plotted as a function of incident beam position. The scanning results showed less neutron sensitivity at the juncture of the rolled scintillator screens, which indicated a lack of scintillator materials due to imperfect manufacturing process.

Critical Dimension Uniformity (CDU) is one of the critical parameters to assure good performance and reliable functionality of sub 40 nm node logic process. CD uniformity control is also one of key issues in mass production. In this paper, we will introduce our latest software which is named CDU Master, The Nikon CDU Master can derive the optimal control parameters for each compensation function in the scanner using the exposure dose and focus correction data, the high degree of controllability of NSR-S620 scanner enables precise correction of the complicated CD error distribution. Finally, use this system, intra-wafer CDU of 40nm critical layer is improved by 34%, achieve the goal of the process control.

Design and manufacturing of the JT-60SA cryostat is being performed by CIEMAT, according to the Broader Approach Agreement between Japan and the European Commission. Taking into account both the limitations of transport and the assembly sequence of JT60-SA, the cryostat is divided in two main parts, namely the cryostat base and the cryostat vessel body. The paper is focused on the structural analyses carried out by CIEMAT to evaluate the mechanical behavior of the JT-60SA cryostat base final design, since the cryostat vessel body will be designed and manufactured in a subsequent stage. The overall structural integrity of the cryostat base has been verified and confirmed utilizing the ‘limit analysis’ procedure defined in ASME code 2007 Section VIII, Div. 2. The study has been complemented by further finite element analyses that include the detail of the bolted fastenings, aimed to evaluate the mechanical behavior of the bolted joints themselves, as well as the stresses and deformations in the overall cryostat base structure.

The effects of neutron and gamma-ray irradiation on a polymethylmethacrylate (PMMA) plastic optical fiber (POF) were investigated. An improvement in the optical transmission was observed at the beginning of irradiation, but radiation damage (radiation-induced transmission loss in the visible wavelength range) increased as the irradiation continued. To determine the effects of neutrons and gamma-rays, the amount of energy absorbed in the PMMA POF was calculated using the PHITS codes. Energy deposition in the fiber was calculated considering nuclear reactions listed in the nuclear data file used for the Monte Carlo N-particle transport code. The effects of neutron and gamma radiation were observed to be similar with absorbed energy less than 1.2 kGy. However, the transmission loss induced by neutrons was larger than that induced by gamma-rays when higher energy was deposited.

The IBARAKI biological crystal diffractometer, iBIX at BL03 [1] was constructed to meet demands on the structure analysis of biological macromolecules and organic compounds with unit cell dimensions up to 135 A. It is strenuous requirement that a detector covers a wide solid angle around a sample with less gap and has a spatial resolution of 1mm and a pulse pair resolution of 1 μsec.

〔目的〕本研究では超音波画像を用いた腰部多裂筋筋厚測定の検者内信頼性を級内相関係数（ICC）と最小可検変化量（MDC）により検討した．〔対象〕健常成人男性10名とした．〔方法〕測定課題は腰部多裂筋の機能である仙骨前屈運動を伴う骨盤前傾の静止性収縮とした．測定条件は活動強度と3つの異なる骨盤傾斜角度とした．左腰部多裂筋の筋厚を超音波画像診断装置を用いて測定した．同日内，異なる測定日間のそれぞれでICCとMDCの95%信頼区間（MDC95）を求め，検者内信頼性と測定誤差を検討した．〔結果〕同日内のICCは0.73-0.96，異なる測定日間のICCは骨盤中間位での最大収縮で低い値となったが，それ以外では0.67-0.93であった．MDC95 は同日内で0.8-2.7 mm，異なる測定日間で1.5-3.0 mmであった．〔結論〕超音波画像を用いた本実験肢位における腰部多裂筋の筋厚測定は，活動強度と骨盤傾斜角度を変化させても信頼性の高い測定が可能である．

The construction of The Engineering Materials Diffractometer, TAKUMI of J-PARC has been finished on March 2009, and the commissioning has been started from September 2008 being parallel with the final stage of the construction. In the commissioning, after checking the validity and the stability of the detectors and the data acquisition system, powder diffraction data of an austenitic steel alloy with 10 mm diameter without beam collimation (high intensity mode) was measured, and the resolution Δd/d of 0.4% was confirmed, as designed. Further commissioning was done also with 2 mm diameter of annealed piano wire with combination of beam collimation (high resolution mode), and the resolution Δd/d of less than 0.2% was confirmed to be achieved. TAKUMI adopted an event mode data recording method. It was found that the recording method is very useful to manipulate data as we like, for instance, detector range, time of flight binning width and time resolved data, even the experiment has been finished.

A gas-based neutron detection system with individual readout method and comprising a micro-pixel detector head was constructed, and preliminary experiments were conducted under neutrons irradiation. The detection system also consisted of a micro-pixel detector head, a gas chamber that had feedthrough lines of 541 channels, amplifier-shaper-discriminator boards, position encoders with field programmable gate arrays, and a device capable of fast data acquisition. The micro-pixel detector head exhibited a fast response time, and the full width at half maximum of the response time was 160 ns. Its gas gain was about 50 at an anode-cathode voltage of 560 V and a gas pressure of 0.5 MPa (0.45 MPa for He and 0.05 MPa for CF 4 ). Signal pulse peaks of neutrons could be identified and their output voltages at an anode and a cathode were 2.4 and 5.3 mV, respectively; on the other hand, the output voltage of all the anodes was 105 mV. The neutron detection system could easily distinguish neutron signals from the background noise, and the gas gain of the micro-pixel detector head did not changed.

A fibre-coded linear scintillator detector with a half-millimetre spatial resolution was developed with wavelength-shifting fibre read-out for neutron detection. The head of the detector comprised a ZnS/ 6 LiF scintillator placed on the ribbon of wavelength-shifting (WLS) fibres. Both ends of the fibres were coded to reduce the number of read-out photomultipliers and associated electronic circuitry. The prototype detector in which the fibre ribbon was sandwiched between two ZnS/ 6 LiF scintillators exhibited a spatial resolution of 0.5 mm, a detection efficiency of 35% for 1-A neutrons, and a gamma sensitivity of less than 10 −7 . This type of detector would be useful where a submillimetre spatial resolution is required with large detector coverage such as in neutron reflectometers.

This paper describes the conceptual design of cryostat for the JT-60SA, which is a research device for the commercial production of electricity from the controlled fusion reaction in the future. JT-60SA is designed to be a fully superconducting device and cryostat is one of the main components to allow the normal operation. Cryostat covers up the tokamak device, which is 15 m of total height and 7 m of radius, and supports the total weight of 25 MN. Cryostat components consist of vessel body, gravity support and auxiliary systems, such as 80 K thermal shield and vacuum exhaust. The functions required of cryostat are these three, thermal insulation for superconducting magnets, gravity support for the tokamak device, and bio-shielding. The design conditions for each cryostat component are outlined and the features of auxiliary systems such as capacity of vacuum exhaust related to 80 K thermal shield design are summarized.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The main etiologies of HCC are hepatitis B virus and hepatitis C virus (HCV), and non-hepatitis B/non-hepatitis C HCC (NBNC-HCC) has also been identified as an etiological factor. Although the incidence of HCV-related HCC in Japan has decreased slightly in recent years, that of NBNC-HCC has increased. The onset mechanism of NBNC-HCC, which has various etiologies, remains unclear; however, nonalcoholic steatohepatitis (NASH), a severe form of nonalcoholic fatty liver disease, is known to be an important risk factor for NBNC-HCC. Among the different advanced glycation end-products (AGEs) formed by the Maillard reaction, glyceraldehyde-derived AGEs, the predominant components of toxic AGEs (TAGE), have been associated with NASH and NBNC-HCC, including NASH-related HCC. Furthermore, the expression of the receptor for AGEs (RAGE) has been correlated with the malignant progression of HCC. Therefore, TAGE induce oxidative stress by binding with RAGE may, in turn, lead to adverse effects, such as fibrosis and malignant transformation, in hepatic stellate cells and tumor cells during NASH or NASH-related HCC progression. The aim of this review was to examine the contribution of the TAGE-RAGE axis in NASH-related HCC.