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.

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.

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.

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.

Participation of Bax-alpha in IFN-alpha-mediated apoptosis in Daudi B lymphoma cells.

Although interferon-alpha (IFN-alpha) has proved beneficial in the treatment of some tumors, the basis for this is still uncertain. In this study, we examined the effects of IFN-alpha on the growth of tumor cells in vitro, using the Daudi line of B lymphoma cells as a model. There was a dose-dependent accumulation of these cells in the G1 phase of the cell cycle 24-48 h from the time of exposure to IFN-alpha. This was followed between 48 h and 96 h by an increasing degree of apoptosis, as assessed by cell survival, propidium iodine staining, and transmission electron microscopy. Concomitantly with the apoptosis, there was the appearance of pl8 Bax-alpha, an apparently novel variant low molecular weight form of the p21 Bax-alpha found in normal cells. There was also a slight diminution in Bcl-xL, with a resultant drop in the Bcl-xL:Bax-alpha ratio. Treatment of cells with CD40-L partially inhibited the development of apoptosis in response to IFN-alpha. At the same time, generation of p18 Bax-alpha was reduced, which suggests that this plays a part in the apoptotic process. These findings may throw light on the development of lymphomas and perhaps point to future ways of improving therapy with IFN-alpha.

Dosimetry and measured differential W values of air for heavy ions.

Heavy-ion irradiation systems were designed and constructed at two cyclotron facilities in Japan for use in various fields of radiation physics and radiation biology. A 135 MeV/u carbon beam as well as 12 MeV/u carbon and helium-3 beams were first used in experiments. We have established a systematic method for heavy-ion dosimetry at both high and low incident energies involving measurements of fluences. We also obtained differential W values (w) of air for those beams by comparing the results of fluence measurement dosimetry with ionization chamber dosimetry. The differential W values of air were found to be 36.2 +/- 1.0, 34.5 +/- 1.0, and 33.7 +/- 0.9 eV for 6.7 MeV/u carbon ions, 10.3 MeV/u 3He ions, and 129.4 MeV/u carbon ions, respectively. The w value for high-energy heavy ions approaches the W value for high-energy electron or photon beams. In ionization chamber dosimetry for a heavy-ion beam, we found a track-size effect. A difference in the track sizes of heavy ions in the gas and solid phases affected the output current of the ion chamber in the case of high-energy heavy ions.

Cleavage of Bax-alpha and Bcl-x(L) during carboplatin-mediated apoptosis in squamous cell carcinoma cell line.

Although carboplatin (CBDCA) has been used for the treatment of several types of tumors, the complete response rate has been limited, probably because of inherent or CBDCA-induced resistance. As a first step to overcome these problems, we tried to elucidate the mechanisms of CBDCA-mediated cytotoxicity in the squamous cell carcinoma cell line MIT7. The treatment of cells with CBDCA resulted in apoptosis in a dose-dependent manner, as assessed by the propidium iodide staining method and DNA degradation in a nucleosomal pattern. The induction of apoptosis was accompanied by the decline of mitochondrial membrane potential (Deltapsi(m) ) at 12 h following CBDCA stimulation. Variant forms of p18 Bax-alpha and p16 Bcl-x(L) were generated with the down-regulation of both Bax-alpha (p21) and Bcl-x(L) (p31) at 36 and 48 h following CBDCA stimulation, suggesting that the modulation of Bcl-2 family proteins Bax-alpha and Bcl-x(L) play some role in CBDCA-mediated apoptosis. The activation of caspase-3 and -8 occurred at 12 and 24 h following the stimulation, respectively. The pretreatment of cells with pan-caspase inhibitor Z-VAD-fmk markedly prevented CBDCA-mediated cytotoxicity/apoptosis and the modulation of Bcl-2 family proteins (generation of p18 Bax-alpha and p16 Bcl-x(L) ) with only slight prevention of decline of Deltapsi(m). Taken together, these results may suggest that activation of several caspases, including caspase-3 and -8, plays some role in CBDCA-mediated apoptosis, probably through the modification of Bcl-2 family proteins, Bax-alpha and Bcl-x(L). Moreover, caspase activation may occur downstream of membrane depolarization.

Neuropathology of infant with Pena-Shokeir I syndrome.

In an infant with clinical features of Pena-Shokeir I syndrome, who survived for 182 days, neuropathologic examination revealed little myelination in peripheral nerves with group atrophy of muscle fibers, dysplasia of inferior olivary and dentate nuclei, and leptomeningeal heterotopia. Congenital peripheral neuropathy associated with minor brain anomalies is characteristic in this patient, and may cause absence of fetal movements leading to ankylosis of multiple joints, absence of breathing in association with pulmonary hypoplasia, absence of swallowing causing polyhydramnios, and absence of movements of facial muscles causing craniofacial anomalies.

West syndrome with periventricular leukomalacia: a morphometric MRI study.

A morphometric magnetic resonance imaging study was performed, and the results were compared among three groups (group 1, periventricular leukomalacia patients with West syndrome; group 2, periventricular leukomalacia patients without West syndrome; and group 3, control patients) to clarify the characteristics and cause of West syndrome. This study included 21 infants (11 males and 10 females, 7 months to 2 years 8 months old) born at 24-32 weeks of gestation and weighing 625-1,908 gm. The Evans ratio, ratio of the posterior horns, Cella media index, width of the third ventricle, and the areas of the midbrain, pons, and medulla oblongata were measured and compared among the three groups. There were no differences of gestation or birth weight among the three groups. The Evans ratio, ratio of the posterior horns, Cella media index, and width of the third ventricle were larger in group 1 than in groups 2 and 3. The ratio of the posterior horns and Cella media index were larger in group 2 than in group 3, although the width of the third ventricle was not. Myelination was delayed in all patients in group 1 and in two patients in group 2. In group 1 the areas of the midbrain and pons were smaller than in groups 2 and 3 and the medulla oblongata was smaller than in group 3, although there were no differences in midbrain, pons, and medulla oblongata between groups 2 and 3. Although the infants with periventricular leukomalacia and West syndrome frequently demonstrated marked ventricular dilatation and delayed myelination, the atrophy of midbrain and pons was the most characteristic, and the damage may cause West syndrome.

Diagnostic imaging by energetic radioactive particle beams: applications in Bragg Peak cancer therapy.

NASA: Researchers explore the use of Bragg Ionization Peak in radiotherapy for tumors. Considerations for the production of a high quality radioactive beam include secondary beam production efficiency, primary beam survival, and multiple scattering. A Positron Emitting Beam Analyzing camera was developed and tested at BEVALAC using a neon-19 beam stopping point. Results indicate that in homogeneous brain tissues, CT measurements and radioactive beam measurements are between 1-2 mm; there can be substantial difference between CT measurements and radioactive beam estimates if the beam stopping point crosses the fossae; random coincidences due to detector activation also appear as diffused images in the image plane of the beam stopping point; and further enhancements are necessary to make reliable measurements in the human trunk and complex brain regions.^ieng

Fine needle aspiration of toxoplasmic lymphadenitis in an intramammary lymph node. A case report.

BACKGROUND: Cytologic findings of toxoplasmic lymphadenitis (TL) have been only sporadically reported. Intramammary lymph node is an extremely rare site for TL. CASE: A 47-year-old, healthy, female presented with a breast tumor, which was aspirated. The cytomorphologic features were interpreted as suggestive of TL. Histopathology of the excisional biopsy specimen and subsequent serologic examination confirmed the diagnosis. CONCLUSION: We obtained several characteristic findings in aspiration of TL. Of these, epithelioid cell clusters and monocytoid cells were the most diagnostic.

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.