Conceptual design of a collimator for the neutron emission profile monitor in JT-60SA using Monte Carlo simulations.

Materials and structures of a collimator for a new neutron emission profile monitor in JT-60SA are examined through Monte Carlo simulations using the Monte Carlo N-Particle transport code. First, the shielding properties of various material combinations are compared in order to determine a combination with high shielding performances against both neutrons and gamma-rays. It is found that a collimator consisting of borated polyethylene and lead has a high shielding performance against neutrons. Moreover, a high shielding performance against gamma-rays is obtained when a lead pipe with a radial thickness of 0.01 m is inserted into a collimation tube. Second, we demonstrate that it is possible to improve the spatial resolution to a desired level by installing a thin tubular extension structure that fits into the limited space available between the main collimator block and the tokamak device. Finally, the collimator structures that meet both the targeted spatial resolutions (<10% of the plasma minor radius) and the targeted counting rate (105 cps order) are discussed.

Design optimization of a fast-neutron detector with scintillating fibers for triton burnup experiments at fusion experimental devices.

Time-resolved triton burnup studies have been carried out to estimate the behavior of alpha particles in DD fusion experimental devices. In those studies, 14 MeV neutrons emitted through DT reactions in DD plasmas should be measured selectively in the backgrounds of DD neutrons and gamma rays. For this purpose, a scintillating-fiber (Sci-Fi) based fast-neutron detector has been adapted because of its advantages such as fast response, design flexibility in detection efficiency by changing the number of Sci-Fi, and discrimination property against 2.4 MeV neutrons produced through DD reactions and gamma rays. However, its length had conventionally been set to around 10 cm without an optimization study of its design parameters to meet the requirements as 14 MeV neutron detector. In the present study, we tested three types of Sci-Fi detectors with three different lengths and compared with the simulated results of energy deposition, through which we tried to understand the phenomena in the detection process of fast neutrons. From the results, it has been shown that, due to the self-shielding of neutrons by Sci-Fi and the attenuation of scintillation photons during the transmission process to the photomultiplier tube, the optimal length of Sci-Fi is concluded to be about 6 cm.

ICTV Virus Taxonomy Profile: Filoviridae.

Members of the family Filoviridae produce variously shaped, often filamentous, enveloped virions containing linear non-segmented, negative-sense RNA genomes of 15-19 kb. Several filoviruses (e.g., Ebola virus) are pathogenic for humans and are highly virulent. Several filoviruses infect bats (e.g., Marburg virus), whereas the hosts of most other filoviruses are unknown. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on Filoviridae, which is available at www.ictv.global/report/filoviridae.

Probabilistic n/γ discrimination with robustness against outliers for use in neutron profile monitors.

A method to stochastically discriminate neutron and γ-ray signals measured with a stilbene organic scintillator is proposed. Each pulse signal was stochastically categorized into two groups: neutron and γ-ray. In previous work, the Expectation Maximization (EM) algorithm was used with the assumption that the measured data followed a Gaussian mixture distribution. It was shown that probabilistic discrimination between these groups is possible. Moreover, by setting the initial parameters for the Gaussian mixture distribution with a k-means algorithm, the possibility of automatic discrimination was demonstrated. In this study, the Student's t-mixture distribution was used as a probabilistic distribution with the EM algorithm to improve the robustness against the effect of outliers caused by pileup of the signals. To validate the proposed method, the figures of merit (FOMs) were compared for the EM algorithm assuming a t-mixture distribution and a Gaussian mixture distribution. The t-mixture distribution resulted in an improvement of the FOMs compared with the Gaussian mixture distribution. The proposed data processing technique is a promising tool not only for neutron and γ-ray discrimination in fusion experiments but also in other fields, for example, homeland security, cancer therapy with high energy particles, nuclear reactor decommissioning, pattern recognition, and so on.

Identification of a TLR2-regulated gene signature associated with tumor cell growth in gastric cancer.

Toll-like receptors (TLRs) are key regulators of innate immune responses, and their dysregulation is observed in numerous inflammation-associated malignancies, including gastric cancer (GC). However, the identity of specific TLRs and their molecular targets which promote the pathogenesis of human GC is ill-defined. Here, we sought to determine the clinical utility of TLR2 in human GC. TLR2 mRNA and protein expression levels were elevated in >50% of GC patient tumors across multiple ethnicities. TLR2 was also widely expressed among human GC cell lines, and DNA microarray-based expression profiling demonstrated that the TLR2-induced growth responsiveness of human GC cells corresponded with the up-regulation of six anti-apoptotic (BCL2A1, BCL2, BIRC3, CFLAR, IER3, TNFAIP3) and down-regulation of two tumor suppressor (PDCD4, TP53INP1) genes. The TLR2-mediated regulation of these anti-apoptotic and tumor suppressor genes was also supported by their increased and reduced expression, respectively, in two independent genetic GC mouse models (gp130F/F and Gan) characterized by high tumor TLR2 expression. Notably, enrichment of this TLR2-regulated gene signature also positively correlated with augmented TLR2 expression in human GC tumors, and served as an indicator of poor patient survival. Furthermore, treatment of gp130F/F and cell line-derived xenograft (MKN1) GC mouse models with a humanized anti-TLR2 antibody suppressed gastric tumor growth, which was coincident with alterations to the TLR2-driven gene signature. Collectively, our study demonstrates that in the majority of GC patients, elevated TLR2 expression is associated with a growth-potentiating gene signature which predicts poor patient outcomes, thus supporting TLR2 as a promising therapeutic target in GC.

Progress in development of the neutron profile monitor for the large helical device.

The neutron profile monitor stably operated at a high-count-rate for deuterium operations in the Large Helical Device has been developed to enhance the research on the fast-ion confinement. It is composed of a multichannel collimator, scintillation-detectors, and a field programmable gate array circuit. The entire neutron detector system was tested using an accelerator-based neutron generator. This system stably acquires the pulse data without any data loss at high-count-rate conditions up to 8 × 10(5) counts per second.

A study on fast digital discrimination of neutron and gamma-ray for improvement neutron emission profile measurement.

Neutron and γ-ray (n-γ) discrimination with a digital signal processing system has been used to measure the neutron emission profile in magnetic confinement fusion devices. However, a sampling rate must be set low to extend the measurement time because the memory storage is limited. Time jitter decreases a discrimination quality due to a low sampling rate. As described in this paper, a new charge comparison method was developed. Furthermore, automatic n-γ discrimination method was examined using a probabilistic approach. Analysis results were investigated using the figure of merit. Results show that the discrimination quality was improved. Automatic discrimination was applied using the EM algorithm and k-means algorithm.

ANGPTL4 is a secreted tumor suppressor that inhibits angiogenesis.

Tumor suppressors with extracellular function are likely to have advantages as targets for cancer therapy, but few are known. Here, we focused on angiopoietin-like 4 (ANGPTL4), which is a secreted glycoprotein involved in lipoprotein metabolism and angiogenesis, is methylation-silenced in human cancers, but has unclear roles in cancer development and progression. We found a deletion mutation in its coiled-coil domain at its N-terminal in human gastric cancers, in addition to hypermethylation of the ANGPTL4 promoter CpG islands. Forced expression of wild-type ANGPTL4, but not ANGPTL4 with the deletion, at physiological levels markedly suppressed in vivo tumorigenicity and tumor angiogenesis, indicating that the latter caused the former. Tumor-derived ANGPTL4 suppressed in vitro vascular tube formation and proliferation of human umbilical vascular endothelial cells, partly due to suppression of ERK signaling. These showed that ANGPTL4 is a genetically and epigenetically inactivated secreted tumor suppressor that inhibits tumor angiogenesis.

FHL1 on chromosome X is a single-hit gastrointestinal tumor-suppressor gene and contributes to the formation of an epigenetic field defect.

Tumor-suppressor genes on chromosome X can be inactivated by a single hit, any of the point mutations, chromosomal loss and aberrant DNA methylation. As aberrant DNA methylation can be induced frequently, we here aimed to identify a tumor-suppressor gene on chromosome X inactivated by promoter DNA methylation. Of 69 genes on chromosome X upregulated by treatment of a gastric cancer cell line with a DNA-demethylating agent, 5-aza-2'-deoxycytidine, 11 genes had low or no expression in the cell line and abundant expression in normal gastric mucosae. Among them, FHL1 was frequently methylation-silenced in gastric and colon cancer cell lines, and methylated in primary gastric (21/80) and colon (5/50) cancers. Knockdown of the endogenous FHL1 in two cell lines by two kinds of shRNAs significantly increased cell growth in vitro and sizes of xenografts in nude mice. Expression of exogenous FHL1 in a non-expressing cell line significantly reduced its migration, invasion and growth. Notably, a somatic mutation (G642T; Lys214Asn) was identified in one of 144 colon cancer specimens, and the mutant FHL1 was shown to lack its inhibitory effects on migration, invasion and growth. FHL1 methylation was associated with Helicobacter pylori infection and accumulated in normal-appearing gastric mucosae of gastric cancer patients. These data showed that FHL1 is a methylation-silenced tumor-suppressor gene on chromosome X in gastrointestinal cancers, and that its silencing contributes to the formation of an epigenetic field for cancerization.

Fusion product diagnostics planned for Large Helical Device deuterium experiment.

Deuterium experiment on the Large Helical Device (LHD) is now being planned at the National Institute for Fusion Science. The fusion product diagnostics systems currently considered for installation on LHD are described in this paper. The systems will include a time-resolved neutron yield monitor based on neutron gas counters, a time-integrated neutron yield monitor based on activation techniques, a multicollimator scintillation detector array for diagnosing spatial distribution of neutron emission rate, 2.5 MeV neutron spectrometer, 14 MeV neutron counter, and prompt γ-ray diagnostics.

Carbon-ion radiotherapy: clinical aspects and related dosimetry.

The features of relativistic carbon-ion beams are attractive from the viewpoint of radiotherapy. They exhibit not only a superior physical dose distribution but also an increase in biological efficiency with depth, because energy loss of the beams increases as they penetrate the body. This paper reviews clinical aspects of carbon-beam radiotherapy using the experience at the National Institute of Radiological Sciences. The paper also outlines the dosimetry related to carbon-beam radiotherapy, including absolute dosimetry of the carbon beam, neutron measurements and radiation protection measurements.

Polarization control in three-dimensional resonant coherent excitation.

We present an experimental demonstration of an ingenious technique to control the alignment of the atomic internal state in the x-ray region using a periodic crystal field. The alignment directions of Ar16+ and Fe24+ ions were readily controlled by selecting the array of atomic planes using three-dimensional resonant coherent excitation, and were probed via the anisotropy of the deexcitation x-ray emission. We applied this method to a double resonance experiment, and succeeded in controlling the population of the specific magnetic substate in a Lambda-type three-level configuration.

Dressed atoms in flight through a periodic crystal field: X-VUV double resonance.

We report the Autler-Townes doublet demonstrating a novel type of coherent interaction of atoms not with photons but with a periodic crystal field when the atom is in flight through a crystal at high velocity. It was observed by the nonoptical X-VUV (vacuum-ultraviolet) double resonance of three-dimensional resonant coherent excitation with good coherence. The states strongly coupled in the VUV region were probed by the excitation in the x-ray region. The characteristic spectra are well interpreted by an analogy of the dressed atom concept often adopted for the atom-photon interaction.

Anisotropic x-ray emission from heliumlike Fe24+ ions aligned by resonant coherent excitation with a periodic crystal potential.

We have measured deexcitation x rays emitted from the resonant coherently excited 2(1)P(1) state of heliumlike Fe24+ ions of 423 MeV/amu, planar channeling through a Si crystal. Large anisotropy in the angular distribution of deexcitation x-ray emission is observed: the x-ray emission in the direction parallel to the channeling plane is favored by a factor of 2 compared to the perpendicular direction. This anisotropy originates from the direction of the periodic crystal field, which populates specific m states in resonant coherent excitation and aligns the excited states.

Three-dimensional resonant coherent excitation of nonchanneling ions in a crystal.

We have observed resonant coherent excitation (RCE) of H-like Ar(17+) ions traveling through a 1 microm-thick Si crystal at an energy of 391 MeV/u in the nonchanneling condition. A three-dimensional periodic array of atomic planes induces RCE of the nonchanneling ions. The high energy heavy ions together with the thin crystal allow us to observe this new RCE through the measurements of the charge-state distribution of the emerging ions. The observed resonances are much narrower than those of planar-channeling ions due to the absence of the large Stark shift caused by the planar potential.

Nicotine inhibits the production of proinflammatory mediators in human monocytes by suppression of I-kappaB phosphorylation and nuclear factor-kappaB transcriptional activity through nicotinic acetylcholine receptor alpha7.

Macrophages/monocytes and the proinflammatory mediators, such as tumour necrosis factor (TNF)-alpha, prostaglandin E(2) (PGE(2)), macrophage inflammatory protein (MIP)-1alpha and MIP-1alpha, play a critical role in the progression of immunological disorders including rheumatoid arthritis, Behçet's disease and Crohn's disease. In addition, the nicotinic acetylcholine receptor-alpha7 (alpha7nAChR) subunit is an essential regulator of inflammation. In this study, we evaluated the expression of the alpha7nAChR subunit on human peripheral monocytes and the effect of nicotine on the production of these proinflammatory mediators by activated monocytes. Fluorescein isothiocyanate (FITC)-labelled alpha-bungarotoxin demonstrated the cell surface expression of the alpha7nAchR subunit. Pretreatment with low-dose nicotine caused inhibition of TNF-alpha, PGE(2), MIP-1alpha and MIP-1alpha production, and mRNA expression of TNF-alpha, MIP-1alpha and MIP-1alpha and COX-2 in lipopolysaccharide (LPS)-activated monocytes. These suppressive effects of nicotine were caused at the transcriptional level and were mediated through alpha7nAChR. Nicotine suppressed the phosphorylation of I-kappaB, and then inhibited the transcriptional activity of nuclear factor-kappaB. These immunosuppressive effects of nicotine may contribute to the regulation of some immune diseases.

Decreased fidelity in replicating DNA methylation patterns in cancer cells leads to dense methylation of a CpG island.

Cancer cells that have a large number of aberrantly methylated CpG islands (CGIs) are known to have CpG island methylator phenotype (CIMP), and decreased fidelity in replicating methylation patters has been analyzed as an underlying mechanism. First we developed a method to analyze the number of errors in replicating CpG methylation patterns in a defined period. A single cell was expanded into 106 cells, and the number of errors during the culture was measured by counting the deviation from the original methylation patterns. It was shown that methylated status of a CpG site was more stably inherited than unmethylated status, suggesting that the genome is constantly exposed to de novo methylation. Promoter CGIs showed higher fidelities than CGIs outside promoter regions. We then analyzed error rates in two gastric cancer cell lines without CIMP and two with CIMP for five promoter CGIs. Two CIMP(-) cell lines showed error rates smaller than 1.0x10(-3) errors per site per generation (99.90%-100% fidelity) for all the five CGIs. In contrast, AGS cells showed significantly elevated error rates, mainly due to increased de novo methylation, in three CGIs (1.6- to 3.2-fold), and KATOIII cells showed a significantly elevated error rate in one CGI (2.2-fold). Presence of densely methylated DNA molecules was observed only in KATOIII and AGS. These data demonstrated that some cancer cells have decreased fidelity in replicating CpG methylation patterns that underlie CIMP.

Excessive expression of Txk, a member of the Tec family of tyrosine kinases, contributes to excessive Th1 cytokine production by T lymphocytes in patients with Behcet's disease.

Excessive Th1 cell function is importantly involved in the pathogenesis of Behcet's disease (BD). We previously found that Txk, a member of the Tec family of tyrosine kinases, acts as a Th1 cell specific transcription factor. To investigate immune aberration in the pathogenesis of BD, we studied the expression of Txk and Th1 cytokines in peripheral blood lymphocytes (PBL) and skin lesions in patients with BD. Cytokine production by the lymphocytes was assessed using ELISA. PBL produced excessive Th1 associated cytokines including IFN-gamma and IL-12 spontaneously and in response to exogenous HSP60-derived peptide stimulation, which was shown to induce proliferation of PBL, in patients with BD. Circulating CD4+ T cells expressed excessive Txk protein. A majority of cells infiltrating into skin lesions expressed IFN-gamma in the BD specimens. IL-12 and IL-18 were also expressed in the mononuclear cell aggregates. Lymphocytes accumulating in the skin lesion expressed higher levels of Txk as compared with atopic dermatitis lesions, a typical Th2 disease. IFN-gamma, IL-18 and Il-12 were detected in the BD skin lesions, which may induce preferential development of Th1 cells in patients with BD. The mononuclear cell aggregates contained Txk expressing cells in such skin lesions. Collectively, Txk expressing Th1 cells and the Th1 associated cytokines may play a critical role in the development of skin lesions in BD.

Involvement of Th1 cells and heat shock protein 60 in the pathogenesis of intestinal Behcet's disease.

Involvement of excessive Th1 cell functions and heat shock protein expression in the pathogenesis of Behcet's disease (BD) has been reported. In this study we have characterized immune responses in intestinal lesions of BD. Peripheral blood lymphocytes (PBL) of BD and healthy controls (HC) and tissue specimens of intestinal Behcet's disease (intestinal BD), Crohn's disease (CD) and ulcerative colitis (UC) were analysed for mRNA and protein expression by reverse transcriptase-polymerase chain reaction (PCR) and immunohistochemistry, respectively. PBL of BD patients expressed the Th1-related chemokine receptor, CCR5 and CXCR3 preferentially compared with those of healthy controls. Intestinal lesions of BD expressed interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha and interleukin (IL)-12 mRNA, indicating Th1 skewed responses in vivo. mRNA of Txk, a Tec family tyrosine kinase specific to Th1 cells, was expressed in the lesions, suggesting its contribution to the Th1-dominant responses. In the intestinal samples, CCR5 was detected in all the cases with BD, whereas Th2-related CCR3 and CCR4 were detected randomly, mainly in the cases with inactive BD and those receiving large amounts of prednisolone, indicating the Th1-dominant immune responses in the intestinal lesions. As the ligands of CCR5, MIP1alpha and MIP1beta were detected, whereas RANTES was not. Heat shock protein (HSP) 60 was expressed in PBL and intestinal tissues of BD. Th1-dominant immune responses and HSP60 expression may induce the inflammatory responses and thus be associated with the pathogenesis of intestinal BD.

Consideration of physical condition in estimation of blood glucose via data mining.

Many diabetics carry a portable-type blood glucose monitor and collect their own blood to examine their blood glucose levels daily (self monitoring of blood glucose, SMBG). The use of a physical condition variable was suggested in order to estimate the blood glucose level for diabetics. Four sets of data, including FBG, food intake, metabolic rate and physical condition, were collected from four Type 1 diabetics over a five-month period. Using these data, an increasing or decreasing tendency for FBG for the next day was estimated using the data mining method. The results revealed that the estimation accuracy was improved when a physical condition variable was used. An average correspondence rate of 81 % was observed, with a maximum of 90 %. These results indicated that the data mining method could be effective in the estimation of blood glucose levels.