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Objective To investigate differences in uptake regions between methyl-11C-L-methionine positron emission tomography (11C-MET PET) and gadolinium (Gd)-enhanced MRI, and to examine the effects on dose distribution of changing the threshold value for definition of tumor boundaries.Methods Twenty consecutive patients with grade 3 or 4 glioma who had recurrence after postoperative RT between April 2016 and October 2017 were examined in the study. This study is simulation study assuming all patients received RT. Clinical target volume (CTV) was contoured using the Gd-enhanced region (CTV-Gd), T2-high region (CTV-T2), tumor/normal tissue (T/N) ratios of 11C-MET PET of 1.3 and 2.0 (CTV (T/N 1.3), CTV (T/N 2.0)), and the PET-edge method (CTV(P-E)) for stereotactic radiotherapy planning for recurrent malignant glioma after radiotherapy. Differences among CTVs were evaluated and the dose distribution for the normal brain was simulated for each CTV.Results The Jaccard index (JI) for concordance of CTV (Gd) with CTVs using 11C-MET PET was highest for CTV (T/N 2.0), with a value of 0.7. In a comparison of pixel values of MRI and PET, the correlation coefficient for cases with higher JI was significantly greater than that for lower JI cases (0.37 vs. 0.20, P = 0.007). D50% and D33% of the brain in radiotherapy planning using each CTV differed significantly (P = 0.03, P = 0.02) and those using CTV (T/N 1.3) were higher than with use of CTV (Gd). V90% and V95% for each CTV differed in a simulation study for actual treatment using CTV (Gd) (P = 1.0×10− 7, P = 3.0×10− 9) and those using CTV (T/N 1.3) and CTV (P-E) were lower than with CTV (Gd). Comparing with CTV (T2), the JI showed no significant difference with any CTV using PET. D50% and D33% of the brain were significantly higher than any CTV using PET.Conclusions The region of 11C-MET accumulation is not necessarily similar to the Gd-enhanced or T2 high region. A change of the tumor boundary using 11C-MET PET can cause significant changes in doses to the brain and the CTV.

INTRODUCTION To confirm the feasibility of hypofractionated proton beam therapy (PBT), we compared the acute adverse event rates and International Prostate Symptom Score (IPSS) in prostate cancer patients treated with hypofractionated versus conventionally fractionated (2.0 Gy relative biological effectiveness (RBE)/fraction) PBT. METHODS We reviewed 289 patients with prostate cancer, of whom 73, 100, and 116 patients were treated with 2.0, 2.5, and 3.0 Gy (RBE)/fraction, respectively. The endpoints were acute genitourinary and gastrointestinal toxicities and the IPSS, evaluated up to 6 months after PBT initiation. RESULTS No significant differences were found in acute toxicity rates or the IPSS among the fractionation schedules. Diabetes mellitus, age, and androgen deprivation therapy were not identified as factors associated with the IPSS. CONCLUSION There were no significant differences in adverse events or quality of life among the three fractionation schedules early after PBT.

BackgroundGlioblastoma peritumoral edema (PE) extent is associated with survival and progression pattern after tumor resection and radiotherapy (RT). To increase tumor control, proton beam was adopted to give high-dose boost (> 90 Gy). However, the correlation between PE extent and prognosis of glioblastoma after postoperative high-dose proton boost (HDPB) therapy stays unknown. We intend to utilize the PE status to classify the survival and progression patterns.MethodsPatients receiving HDPB (96.6 GyE) were retrospectively evaluated. Limited peritumoral edema (LPE) was defined as PE extent 1 cm from the tumor bed edge.ResultsAfter long-term follow-up (median 88.7, range 63.6–113.8 months) for surviving patients with (n = 13) and without (n = 32) LPE, the median overall survival (OS) and progression-free survival (PFS) were 77.2 vs. 16.7 months (p = 0.004) and 13.6 vs. 8.6 months (p = 0.02), respectively. In multivariate analyses combined with factors of performance, age, tumor maximum diameter, and tumor resection extent, LPE remained a significant factor for favorable OS and PFS. The rates of 5-year complete response, EPD, and distant metastasis with and without LPE were 38.5% vs. 3.2% (p = 0.005), 7.7% vs. 40.6% (p = 0.04), and 0% vs. 34.4% (p = 0.02), respectively.ConclusionsThe LPE status effectively identified patients with relative long-term control and specific progression patterns after postoperative HDPB for glioblastoma.

Activated charcoal (AC) is a potential candidate antidote against dioxins. However, it is difficult to take AC as a supplement on a daily basis, because its long-term ingestion causes side effects such as constipation and deficiency of fat-soluble essential nutrients and hypocholesterolemia. Alginate-coated AC, termed Health Carbon (HC), was developed to decrease the side effects of AC, but its pharmacological effects, including side effects, remains unclear. Here, we show that HC enhanced fecal excretion of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and decreased some side effects of unmodified AC, such as hypocholesterolemia, in male mice. Basal diet mixed with HC or unmodified AC at various concentrations was fed to mice for 16 days following a single intraperitoneal administration of [3H]TCDD. Both HC and unmodified AC at 3% or more significantly increased fecal excretion of [3H]TCDD in comparison with the control basal diet. Consistent with this, [3H]TCDD radioactivity in the liver-a major TCDD storage organ-was markedly decreased by HC at concentrations of 3% and 10%. In an examination of potential side effects, unmodified AC at 10% or more caused significant body weight reduction and at 20% caused significant hypocholesterolemia. In contrast, HC caused weight gain reduction only at a concentration of 20%, and there was no evidence of hypocholesterolemia at any dietary HC concentration. HC not only retains the ability of AC to enhance fecal excretion of TCDD but also reduces some of the side effects of AC.

The Rho-associated coiled-coil-containing protein kinase (ROCK) pathway is known to influence metastasis in several cancers; however, the impact of the pathway on clinical outcomes in patients undergoing radiotherapy remains unknown. In the present study, the expression of RhoA, RhoC, ROCK-1, ROCK-2 and p53 was immunohistochemically evaluated using biopsy specimens obtained from 49 patients with stage II–III cervical squamous cell carcinoma treated with concurrent chemoradiotherapy (CCRT). The relationship between the expression of these proteins and patient outcomes was investigated. RhoA overexpression was associated with significantly impaired disease-free survival and distant metastasis-free survival (P = 0.045 and P = 0.041, respectively) in stage III cancer patients. No differences in survival were observed based on the expression of the other proteins among stage III cancer patients. In stage II cancer patients, no differences in survival were noted based on the expression of any of the proteins. The expression of RhoA was able to successfully differentiate cervical cancer patients with distant metastasis after CCRT. This information may help stratify patients according to the risk of metastasis, thereby leading to the potential to provide individualized treatment.

Neuroblastoma (NB) predominantly presents as high-risk disease, requiring intensive multimodal therapy. Proton beam therpy (PBT) is a promising option for many childhood cancers, but is not widely available. Patients with NB hoping to receive PBT may therefore need to be transferred between institutions during intensive multimodal therapy, risking undesirable effects. We evaluated patients with high-risk NB who received PBT at our institute as part of first-line therapy, mainly focusing on the safety and feasibility of mid-treatment patient transfer. Eighteen patients with newly diagnosed high-risk NB who received PBT between April 2010 and June 2016 were retrospectively analyzed for local control, outcomes, and toxicity. Survival (3-y overall survival 71%±11%; 3-y event-free survival 44%±12%) and local control rate (100%) were comparable with previous studies. Few acute adverse events were recorded, and all patients completed PBT without treatment delay. PBT for high-risk NB was safe and feasible for patients requiring mid-treatment interinstitutional transfer.

A scanning electron microscope transition edge sensor has been developed to analyze the minor or trace constituents contained in a bulk sample and small particles on the sample under a low accelerating voltage (typically

Fourier transform microwave spectra for the J = 1 ← 0 and 2 ← 1 rotational transitions of the SiCl+ ion were observed for two isotopologues ( 35 Cl and 37 Cl) in the ground and the first excited vibrational states of the ground 1 Σ + electronic state. Thanks to the high resolution of the FTMW spectrometer, hyperfine structures due to the quadrupole moment of the chlorine nucleus and the nuclear spin-rotation interaction were fully resolved. The observed FTMW spectra were combined with previously reported MMW and diode laser spectra in an analysis to determine the mass-independent Dunham coefficients U k , l as well as a mass scaling parameter Δ 01 Cl = - 0.856 ( 30 ) . The equilibrium bond length of SiCl+ determined is r e = 1.9439729 ( 10 ) A and the nuclear quadrupole coupling constant of Si 35 Cl+ is eQq e = - 11.8788 ( 23 ) MHz.

Accepted: 2017-12-12, 資料番号: SA1170295000

Objective: Proton beam therapy (PBT) may provide good local control for skull base chordoma and reduced toxicities, especially for pediatric patients. Methods: We evaluated the efficacy and safety of hyperfractionated high-dose PBT in6 pediatric patients with newly-diagnosed skull basechordoma who were treated with PBT at our institute from 2011 to 2015. The patients were 5 males and one female, and the median age was 9 years old (range: 5 - 13). All patients received surgery before PBT. The median period between surgery and PBT was 57 days (range: 34 - 129 days). The treatment dose was 78.4 GyE in 56 fractions (twice per day). Results: All patients received PBT without severe acute toxicity. The median follow-up period was 27 months (range: 21 - 71 months). At the last follow-up, all patients were alive and all tumors were well controlled. Acute and late toxicities were generally acceptable, with only grade 1 and 2 events. Late toxicities included growth hormone abnormality and cortical hormone abnormality. One patient needed growth hormone and cortical hormone replacement therapy. Conclusion: Although the number of pediatric patients was small, our overall findings in the 6 cases indicate that hyperfractionated high-dose PBT is safe and effective for pediatric patients with skull base chordoma.

The millimeter-wave spectrum of the SiCl + ion in the ground and first excited vibrational states was observed for the two isotopic ( 35 Cl and 37 Cl) species. The ion was generated in a free-space absorption cell by a hollow cathode discharge of SiCl 4 diluted with He and discriminated from neutral species by the magnetic field effect on the absorption lines. The observed millimeter-wave spectrum was combined with a previously reported diode laser spectrum in an analysis to determine mass-independent Dunham coefficients as well as the mass scaling parameters. The equilibrium bond length of SiCl + determined is r e = 1.943 978(2) A.

Introduction: The aim of this study was to observe an inhibition of bone resorption and osteoclastogenesis by iguratimod (IGU, T-614), a disease-modifying anti-rheumatic drug, using adjuvant-induced arthritis (AIA) rats and receptor activator of nuclear factor kappa-B ligand (RANKL)-stimulated RAW264.7 cells. Methods: The bone mineral density and 3D morphometric parameters of hind paws in AIA rats were measured using micro computed tomography (μCT) imaging. The activity of osteoclast cells was estimated based on tartrate-resistant acid phosphatase (TRAP) staining in specimens from the rats. In vitro TRAP activity was investigated using RANKL-stimulated RAW264.7 cells. The amount of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) protein was measured by western blot analysis. The expression of Nfatc1, its regulator genes, its upstream factors, and osteoclast-functional genes were investigated. Results: In addition to the suppression of bone resorption and lesions of bone trabeculae of AIA rats, IGU significantly decreased the number of TRAP-positive cells in the calcaneal bones. Moreover, this drug inhibited the differentiation of RANKL-stimulated RAW264.7 cells into osteoclasts, which were identified morphologically and functionally. IGU decreased the amount of NFATc1 protein and improved the altered expression of NFATc1-associated genes and osteoclast-functional genes. Conclusions: IGU suppressed osteoclastogenesis and bone resorption via the RANKL-NFATc1 pathway, suggesting such effect would be expected in clinical use.

Accepted: 2015-06-18, 資料番号: SA1150096000

The major route of cadmium (Cd) intake by non-smokers is through food ingestion. Cd is a non-essential metal absorbed through one or more transporters of essential metal ions. Expression of these transporters is affected by nutritional status. To investigate the risk factors for Cd toxicity, the effects of deficiency of essential metals on hepatic and renal accumulation of Cd were studied in mice of different ages. Mice were administered a control diet or one of the essential metal-deficient diets, administered Cd by gavage for 6 weeks, and killed; then, Cd accumulation was evaluated. Iron deficiency (FeDF) or calcium deficiency (CaDF) resulted in remarkable increases in hepatic and renal Cd accumulation compared with control-diet mice and other essential metal-deficient mice. Cd accumulation in hepatic and renal tissue was increased significantly at all ages tested in FeDF and CaDF mice. Renal Cd concentrations were higher in 4-week-old mice than in 8- and 25-week-old mice. Increase in intestinal mRNA expression of calcium transporter (CaT)1, divalent metal ion transporter-1, and metallothionein (MT)1 was also higher in 4-week-old mice than in other mice. Renal accumulation of Cd showed strong correlation with intestinal mRNA expression of CaT1 and MT1. These data suggest that CaDF and FeDF at younger ages can be a risk factor for Cd toxicity.

High resolution Fourier transform emission spectroscopy of the A∼

Patients with rheumatoid arthritis experience nociceptive as well as neuropathic pain. The effect of iguratimod (IGU), a disease-modifying anti-rheumatic drug, on neuropathic pain in a rat model of chronic constriction injury (CCI) was examined in this study. CCI was induced by making four ligations on the left sciatic nerve. Rats with stable signs of static allodynia were selected 2 weeks after the surgery and drug treatments were started (day 0). The test drugs were orally administered once daily for 15 days. The threshold of mechanical pain response in the hind paw was evaluated by the von Frey hair test in a blinded manner. To observe histological changes in the spinal cord, the L4 region was subjected to immunohistochemical analysis for the detection of microglial cells. IGU showed an anti-allodynic effect on CCI-induced neuropathic pain at days 6 and 14, but not at 90 min after the first administration of IGU. This effect of IGU was observed until day 21. Furthermore, IGU decreased the number of Iba-1-positive cells, which had been increased at the ipsilateral side of the dorsal horn by CCI. These results suggest that IGU suppresses neuropathic pain via a different mechanism from that of current therapeutics.

Accepted: 2014-08-18, 資料番号: SA1150040000

The stochastic volatility model of Heston (Rev Financ Stud 6(2):327–343, 1993) has found difficulty in describing some of the important features of implied volatility dynamics, leading to a quest for multifactor extensions as well as the incorporation of time-dependent model parameters. In this paper, an asymptotic expansion approach to the multifactor Heston model with time-dependent parameters is developed. The results of Benhamou et al. (SIAM J Financ Math 1(1):289–325, 2010) are extended and it is shown that the extension to the multifactor model involves an extra expansion term that captures the interaction between variance factors. The expansion formula under constant parameters can be explicitly computed and the incorporation of time-dependent parameters is straightforward under the framework. As illustration, a two-factor model is calibrated to data of index options and variance swaps and it is found that it is possible to distinguish a short-term and long-term variance factor from the implied volatility surface and variance swap rates. Moreover, the two-factor model is able to reproduce the shapes of the implied volatility surface during various market scenarios.

The microcalorimeter detects the energy of incidentX-ray photon by the slight temperature rise of a device at a very low temperature, and the detector of a superconducting transition-edge sensor (TES) microcalorimeter has been developed for the measurement of energy dispersive X-ray photons of the energy of 10 to 20 keV with the energy resolution better than 100 eV of FWHM value by having the counting rate over 100 counts per second. A FE-SEM with a detector of TES microcalorimeter (SEM-TES) has already been developed for the extra-high resolution energy-dispersive X-ray spectrometry system to apply in electron-microprobe chemical analyses. Recently, we developed the sensitive correct function on the observed X-ray intensity data measured in the system. Then, the high energy resolution of revised SEM-TES system is precisely able to determine the element contents on the sample. In addition, the chemical bonding states can be clarified by the fluorescent X-ray intensities in the lower energy region derived with a low accelerating voltage of SEM-TES system. We applied the revised SEM-TES system to analyze chemical state on the electrode of nanosheets-derived Hx(Ni1/3Co1/3Mn1/3)O2 for newly developing electrochemical capacitors. We investigated the chemicalstate of cations by not the M-lines but the L-beta and L-alpha lines as the lower energy lines having relative large contribution on chemical bonding. As a result, we revealed a specific chemical state of the Mn different from that of Li(Ni1/3Co1/3Mn1/3)O2 electrode in LiB, that was supported by the result of TEM-EELS analysis. These results show that the SEM-TES system can be a useful analytical tool for the chemical bonding state and electronic structure determinations in a wide range of materials.

Transition Edge Sensor (TES) is an energy dispersive X-ray detecting system with high energy resolution. The energy resolution of this system depends on the steepness of superconducting transition curve from normal to superconducting state, heat capacitance and the operating temperature. The TES is based on the dilution refrigerator cooled by about 100 mK. The energy resolution is calculated about 1-2 eV for the detector with maximum detecting energy as 10 eV. The energy resolution also depends on the superconducting current flowing through the TES device because the superconducting current is affected by the temperature stability of the refrigerator. The fluctuation of the superconducting current means the fluctuation of the X-ray spectrum peak center. We have developed the sensitivity correction system to stabilize the peak center of the X-ray spectrum. The peak center of X-ray spectrum correlates with heater power to keep the base temperature of TES device at a constant temperature. The peak center of X-ray spectrum is calibrated by monitoring the heater power at constant time interval using the correlation curve between the peak center of X-ray spectrum and heater power.

The multi-fluids mixer patented by Sadatomi & Kawahara (2012) can be utilized as a twin-fluid atomizer, in which liquid atomization is implemented by supplying compressed gas into a mixing chamber, and water is sucked automatically due to a vacuum pressure induced by an orifice. A series of experiments were conducted to study the effects of the geometries (i.e., size of atomizer, orifice shape) on spray performance. From a comparative analysis of the experiments, the effects of the geometrical parameters on spray characteristics, such as mist generation rate, atomization efficiency, Sauter mean diameter of atomized water droplets, etc., were clarified. Finally, the CO2 elimination capacity of the mist sprayed by the atomizer with the optimum specification was tested in a closed room with different spray time and different methods. The results showed that, the maximum capacity of CO2 elimination was obtained by spraying mist for 5 minutes with a PET propeller, and the CO2 concentration could be reduced from 1000 ppm to 800 ppm.

[Objectives] The combined effects of a new antirheumatic drug, iguratimod (IGU) with antitumor necrosis factor (TNF)α antibody (aTNFAb) were examined in two mouse models of arthritis. [Methods] In collagen-induced arthritis (CIA) model, arthritis was induced by immunization with type II collagen on day 0 and 21. IGU was orally administrated once daily and aTNFAb was intraperitoneally injected twice a week from day 25 to day 34. In glucose-6-phosphate isomerase (GPI)-induced arthritis model, arthritis was induced by immunization with recombinant GPI on day 0 and the treatments were started on day 5. IGU was orally administrated daily and aTNFAb was intravenously injected every other day to day 14. Efficacy was evaluated using arthritis scores, articular destruction scores, and blood biochemical analyses. [Results] In the CIA model, the combination of IGU and aTNFAb significantly inhibited the arthritis and articular destruction more effectively than as monotherapies. Serum interleukin (IL)-1β and IL-6 levels were also reduced significantly with combined treatment. The decline in serum levels of cartilage oligomeric matrix protein (COMP) and matrix metalloproteinase (MMP)3 was significantly enhanced with the IGU/aTNFAb combination. In the GPI-induced arthritis model, IGU and aTNFAb lowered the arthritis scores and the combination of both treatments showed a significant effect compared with IGU alone. Regarding anti-GPI titers on day 14, IGU and/or aTNFAb showed no significant effect. [Conclusion] In the two mouse models, the combination of IGU and aTNFAb showed greater benefit than either monotherapy, suggesting such combination therapy would be effective in clinical use.

Leptin is an adipose-derived hormone that primarily regulates energy balance in response to nutrition. Human placental cells produce leptin, whereas murine placental cells produce soluble leptin receptors (Ob-R). However, the roles of these proteins during pregnancy have not been elucidated completely. As an essential metal, zinc (Zn) is central to insulin biosynthesis and energy metabolism. In the present study, the effects of Zn deficiency and supplementation on maternal plasma leptin and soluble Ob-R regulation in pregnant mice placentas were examined using enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, and Western blotting. Nutritional Zn deficiency significantly reduced plasma insulin concentrations and fetal and placental weights in pregnant mice. Plasma leptin concentrations in pregnant mice also increased 20- to 40-fold compared with those in non-pregnant mice. Although dietary Zn deficiency and supplementation did not affect plasma leptin concentrations in non-pregnant mice, Zn-deficient pregnant mice had significantly reduced plasma leptin concentrations and adipose leptin mRNA expression. In contrast, Zn-supplemented pregnant mice had increased plasma leptin concentrations without increased adipose leptin mRNA expression. Placental soluble Ob-R mRNA expression also decreased in Zn-deficient mice and tended to increase in Zn-supplemented mice. These results indicate that Zn influences plasma leptin concentrations by modulating mRNA expression of soluble Ob-R in the placenta, and leptin in visceral fat during pregnancy. These data suggest that both adipose and placenta-derived leptin system are involved in the regulation of energy metabolism during fetal growth.

It has been reported that the activity of mitochondrial aconitase (m-aconitase) is rapidly inhibited in a variety of cells when exposed to nitric oxide (NO). In present study, we found that NO significantly increased the number of surviving neurons via enhanced mitochondrial functions with simultaneous addition of the [Fe(II)(β-citryl-L-glutamate; β-CG)] complex. In vitro, a variety of aconitase-inhibitors, such as fluorocitrate, cyanide ion, ferricyanide ([Fe(CN)6]), and various oxidants including superoxide anion, inhibited the activity of m-aconitase even in the presence of Fe(II), whereas a NO-donor, nitroprusside (SNP) ([Fe(CN)5NO]), was the only agent that significantly increased activity of that enzyme. Therefore, it is reasonable to assume that NO released from SNP promotes Fe-dependent activation of aconitase. All other tested NO-donors, including 3-morpholino-sydnonimine (SIN), Deta NONOate (NOC18), and NaNO2, also promoted activation of m-aconitase in time- and dose-dependent manners in the presence of Fe(II). The promoting effects of the NO-donors on activation disappeared with the addition of NO-scavengers. In intact mitochondria, all tested NO-donors promoted reactivation of aconitase in a dose-dependent manner in the presence of Fe(II), whereas that was not seen in its absence. These findings suggest that NO released from NO-donors promotes Fe-dependent activation of aconitase. In mixed neuronal and glial cultures, NO-donors except for SNP enhanced mitochondrial activity at low concentrations. Furthermore, simultaneous addition of the [Fe(II)(β-CG)] complex significantly enhanced those activities and greatly increased the number of surviving neurons. Thus, NO can carry Fe ions into m-aconitase via the guide of the tag of β-CG addressed to the enzyme.