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Sample records for u-87 astrocytoma risc

  1. The microRNA and messengerRNA profile of the RNA-induced silencing complex in human primary astrocyte and astrocytoma cells.

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    Moser, Joanna J; Fritzler, Marvin J

    2010-10-18

    GW/P bodies are cytoplasmic ribonucleoprotein-rich foci involved in microRNA (miRNA)-mediated messenger RNA (mRNA) silencing and degradation. The mRNA regulatory functions within GW/P bodies are mediated by GW182 and its binding partner hAgo2 that bind miRNA in the RNA-induced silencing complex (RISC). To date there are no published reports of the profile of miRNA and mRNA targeted to the RISC or a comparison of the RISC-specific miRNA/mRNA profile differences in malignant and non-malignant cells. RISC mRNA and miRNA components were profiled by microarray analysis of malignant human U-87 astrocytoma cells and its non-malignant counterpart, primary human astrocytes. Total cell RNA as well as RNA from immunoprecipitated RISC was analyzed. The novel findings were fourfold: (1) miRNAs were highly enriched in astrocyte RISC compared to U-87 astrocytoma RISC, (2) astrocytoma and primary astrocyte cells each contained unique RISC miRNA profiles as compared to their respective cellular miRNA profiles, (3) miR-195, 10b, 29b, 19b, 34a and 455-3p levels were increased and the miR-181b level was decreased in U-87 astrocytoma RISC as compared to astrocyte RISC, and (4) the RISC contained decreased levels of mRNAs in primary astrocyte and U-87 astrocytoma cells. The observation that miR-34a and miR-195 levels were increased in the RISC of U-87 astrocytoma cells suggests an oncogenic role for these miRNAs. Differential regulation of mRNAs by specific miRNAs is evidenced by the observation that three miR34a-targeted mRNAs and two miR-195-targeted mRNAs were downregulated while one miR-195-targeted mRNA was upregulated. Biological pathway analysis of RISC mRNA components suggests that the RISC plays a pivotal role in malignancy and other conditions. This study points to the importance of the RISC and ultimately GW/P body composition and function in miRNA and mRNA deregulation in astrocytoma cells and possibly in other malignancies.

  2. The microRNA and messengerRNA profile of the RNA-induced silencing complex in human primary astrocyte and astrocytoma cells.

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    Joanna J Moser

    2010-10-01

    Full Text Available GW/P bodies are cytoplasmic ribonucleoprotein-rich foci involved in microRNA (miRNA-mediated messenger RNA (mRNA silencing and degradation. The mRNA regulatory functions within GW/P bodies are mediated by GW182 and its binding partner hAgo2 that bind miRNA in the RNA-induced silencing complex (RISC. To date there are no published reports of the profile of miRNA and mRNA targeted to the RISC or a comparison of the RISC-specific miRNA/mRNA profile differences in malignant and non-malignant cells.RISC mRNA and miRNA components were profiled by microarray analysis of malignant human U-87 astrocytoma cells and its non-malignant counterpart, primary human astrocytes. Total cell RNA as well as RNA from immunoprecipitated RISC was analyzed. The novel findings were fourfold: (1 miRNAs were highly enriched in astrocyte RISC compared to U-87 astrocytoma RISC, (2 astrocytoma and primary astrocyte cells each contained unique RISC miRNA profiles as compared to their respective cellular miRNA profiles, (3 miR-195, 10b, 29b, 19b, 34a and 455-3p levels were increased and the miR-181b level was decreased in U-87 astrocytoma RISC as compared to astrocyte RISC, and (4 the RISC contained decreased levels of mRNAs in primary astrocyte and U-87 astrocytoma cells.The observation that miR-34a and miR-195 levels were increased in the RISC of U-87 astrocytoma cells suggests an oncogenic role for these miRNAs. Differential regulation of mRNAs by specific miRNAs is evidenced by the observation that three miR34a-targeted mRNAs and two miR-195-targeted mRNAs were downregulated while one miR-195-targeted mRNA was upregulated. Biological pathway analysis of RISC mRNA components suggests that the RISC plays a pivotal role in malignancy and other conditions. This study points to the importance of the RISC and ultimately GW/P body composition and function in miRNA and mRNA deregulation in astrocytoma cells and possibly in other malignancies.

  3. Errantum: Treatment of human astrocytoma U87 cells with silicon dioxide nanoparticles lowers their survival and alters their expression of mitochondrial and cell signaling proteins

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    Lai JCK

    2010-12-01

    Full Text Available Lai JCK, Ananthakrishnan G, Jandhyam S, et al. Treatment of human astrocytoma U87 cells with silicon dioxide nanoparticles lowers their survival and alters their expression of mitochondrial and cell signaling proteins. Int J Nanomedicine. 2010;5:715–723.The wrong image was used in Figure 5 on page 719.

  4. Inhibition of STAT3 reduces astrocytoma cell invasion and constitutive activation of STAT3 predicts poor prognosis in human astrocytoma.

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    Qinchuan Liang

    Full Text Available Astrocytoma cells characteristically possess high invasion potentials. Recent studies have revealed that knockdown of signal transducers and activators of transcription 3 (STAT3 expression by RNAi induces apoptosis in astrocytoma cell. Nevertheless, the distinct roles of STAT3 in astrocytoma's invasion and recurrence have not been elucidated. In this study, we silenced STAT3 using Small interfering RNAs in two human glioblastoma multiforme (GBM cell lines (U251 and U87, and investigated the effect on GBM cell adhesion and invasion. Our results demonstrate that disruption of STAT3 inhibits GBM cell's adhesion and invasion. Knockdown of STAT3 significantly increased E-cadherin but decreased N-cadherin, vascular endothelial growth factor, matrix metalloproteinase 2 and matrix metalloproteinase 9. Additionally, expression of pSTAT3(Tyr705 correlates with astrocytoma WHO classification, Karnofsky performance status scale score, tumor recurrence and survival. Furthermore, pSTAT3(Tyr705 is a significant prognostic factor in astrocytoma. In conclusion, STAT3 may affect astrocytoma invasion, expression of pSTAT3(Tyr705 is a significant prognostic factor in tumor recurrence and overall survival in astrocytoma patients. Therefore, STAT3 may provide a potential target for molecular therapy in human astrocytoma, and pSTAT3(Tyr705could be an important biomarker for astrocytoma prognosis.

  5. Expression of delta-catenin is associated with progression of human astrocytoma

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    MingHao, Wang; Qianze, Dong; Di, Zhang; YunJie, Wang

    2011-01-01

    δ-Catenin (CTNND2), which encodes a scaffold protein in humans, has been found in a few malignancies. However, the expression pattern and contribution of δ-catenin to astrocytoma progression are unclear. We investigated δ-catenin expression in human astrocytoma samples and its function in astrocytoma cell lines using immunohistochemistry, siRNA knockdown, transfection, MTT, transwell migration and Rac1 pulldown techniques. δ-Catenin protein expression was detected in cytoplasm of astrocytoma cells by immunohistochemistry. Analysis showed that grade I astrocytoma (0%, 0/11) and glial cells from normal brain tissue exhibited negative staining. δ-Catenin expression was significantly higher in grade III-IV (35%, 29/84) compared to grade II astrocytoma cells (18%, 11/61); p < 0.01). In addition, CTNND2 overexpression promoted proliferation, invasion and Rac1 activity of U251 astrocytoma cells. Treatment of δ-catenin-transfected cells with a Rac1 inhibitor decreased Rac1 activity and invasion. δ-Catenin knockdown in U87 glioblastoma cell decreased cell proliferation, invasion and Rac1 activity. The results suggest that δ-catenin expression is associated with the malignant progression of astrocytoma and promotes astrocytoma cell invasion through upregulation of Rac1 activity. δ-Catenin expression levels may serve as a useful marker of the biological behavior of astrocytoma cells

  6. Resveratrol represses YKL-40 expression in human glioma U87 cells

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    Zhang, Wei; Tamiya, Takashi; Murao, Koji; Zhang, Xiang; Matsumoto, Kensuke; Diah, Suwarni; Okada, Masaki; Miyake, Keisuke; Kawai, Nobuyuki; Fei, Zhou

    2010-01-01

    Glioblastoma multiforme (GBM) is the most malignant intracranial tumour that develops in both adults and children. Microarray gene analyses have confirmed that the human YKL-40 gene is one of the most over-expressed genes in these tumours but not in normal brain tissue. Clinical studies have shown that serum YKL-40 levels are positively correlated with tumour burden in addition to being an independent prognostic factor of a short relapse-free interval as well as short overall survival in patients with various cancers. Our previous study revealed that YKL-40 was closely correlated with the pathological grades of human primary astrocytomas and played a crucial role in glioma cell proliferation. Hence, YKL-40 could be an attractive target in the design of anti-cancer therapies. Cell viability and invasion assays were performed to detect the cell proliferation and invasive ability of U87 cells induced by resveratrol (3, 5, 4'-trihydroxystilbene; Res) or YKL-40 small-interfering RNAs (siRNAs). In addition, the luciferase assay, real-time RT-PCR, western blotting, and ELISA were used to measure YKL-40 promoter activity, mRNA, and protein expression, respectively. The expressions of phosphor-ERK1/2 and ERK1/2 were determined by western blotting. Res inhibited U87 cell proliferation and invasion in vitro and repressed YKL-40 in U87 cells by decreasing the activity of its promoter and reducing mRNA transcription and protein expression in vitro. YKL-40 siRNA treatment also impaired the invasiveness of U87 cells. When U87 cells were cultured with 20 μM PD98059 (an ERK1/2 inhibitor) alone, with 20 μM PD98059 and 100 μM Res, or with 100 μM Res alone for 48 h, YKL-40 protein expression decreased most significantly in the Res-treated group. PD98059 partially reversed the decrease of YKL-40 protein expression induced by Res. Furthermore, phosphor-ERK1/2 expression was reduced by Res treatment in a time-dependent manner. We demonstrated for the first time that Res

  7. Xenograft transplantation of human malignant astrocytoma cells into immunodeficient rats: an experimental model of glioblastoma.

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    Miura, Flávio Key; Alves, Maria Jose Ferreira; Rocha, Mussya Cisotto; da Silva, Roseli; Oba-Shinjo, Sueli Mieko; Marie, Suely Kazue Nagahashi

    2010-03-01

    Astrocytic gliomas are the most common intracranial central nervous system neoplasias, accounting for about 60% of all primary central nervous system tumors. Despite advances in the treatment of gliomas, no effective therapeutic approach is yet available; hence, the search for a more realistic model to generate more effective therapies is essential. To develop an experimental malignant astrocytoma model with the characteristics of the human tumor. Primary cells from subcutaneous xenograft tumors produced with malignant astrocytoma U87MG cells were inoculated intracerebrally by stereotaxis into immunosuppressed (athymic) Rowett rats. All four injected animals developed non-infiltrative tumors, although other glioblastoma characteristics, such as necrosis, pseudopalisading cells and intense mitotic activity, were observed. A malignant astrocytoma intracerebral xenograft model with poorly invasive behavior was achieved in athymic Rowett rats. Tumor invasiveness in an experimental animal model may depend on a combination of several factors, including the cell line used to induce tumor formation, the rat strains and the status of the animal's immune system.

  8. EMMPRIN expression positively correlates with WHO grades of astrocytomas and meningiomas.

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    Tsai, Wen-Chiuan; Chen, Ying; Huang, Li-Chun; Lee, Herng-Sheng; Ma, Hsin-I; Huang, Shih-Ming; Sytwu, Huey-Kang; Hueng, Dueng-Yuan

    2013-09-01

    High-grade primary brain tumors possessed poor outcome due to invasiveness. Extracellular matrix metalloproteinase inducer (EMMPRIN) stimulates peri-tumoral fibroblasts to secrete matrix metalloproteinase and promote invasiveness. This study hypothesized that high-grade brain tumors overexpress EMMPRIN. Analyzing the public delinked database from the Gene Expression Omnibus profile, the results showed that the EMMPRIN mRNA level was higher in WHO grade IV (n = 81) than in grade III (n = 19, p EMMPRIN levels positively correlated with WHO grades for astrocytomas (p = 0.008) and meningiomas (p = 0.048). EMMPRIN mRNA levels in conventional glioma cell lines (n = 36) was not less than those in glioma primary culture cells (n = 27) and glioblastoma stem-like cells (n = 12). The GBM8401, U87MG, and LN229 human glioma cell lines also overexpressed EMMPRIN. Hematoxylin and eosin, IHC, and immunofluorescence staining of xenografts confirmed that high-grade brain tumors overexpressed EMMPRIN. Lastly, Kaplan-Meier analysis revealed poorer survival in WHO grade IV (n = 56) than in grade III astrocytomas (n = 21, by log-rank test; p = 0.0001, 95 % CI: 1.842-3.053). However, in high-grade astrocytomas, there was no difference in survival between high and low EMMPRIN mRNA levels. Thus, this study identified that high-grade brain tumors overexpress EMMPRIN, which positively correlates with WHO grades in human astrocytomas and meningiomas, and suggests that EMMPRIN may be a therapeutic target of brain tumor.

  9. Making RISC.

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    Kawamata, Tomoko; Tomari, Yukihide

    2010-07-01

    It is well established that 20- to 30-nt small RNAs, including small interfering RNAs, microRNAs and Piwi-interacting RNAs, play crucial roles in regulating gene expression and control a surprisingly diverse array of biological processes. These small RNAs cannot work alone: they must form effector ribonucleoprotein complexes - RNA-induced silencing complexes (RISCs) - to exert their function. Thus, RISC assembly is a key process in small RNA-mediated silencing. Recent biochemical analyses of RISC assembly, together with new structural studies of Argonaute, the core protein component of RISC, suggest a revised view of how mature RISC, which contains single-stranded guide RNA, is built from small RNAs that are born double-stranded. Copyright 2010 Elsevier Ltd. All rights reserved.

  10. Native gel analysis for RISC assembly.

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    Kawamata, Tomoko; Tomari, Yukihide

    2011-01-01

    Small-interfering RNAs (siRNAs) and microRNAs (miRNAs) regulate expression of their target mRNAs via the RNA-induced silencing complex (RISC). A core component of RISC is the Argonaute (Ago) protein, which dictates the RISC function. In Drosophila, miRNAs and siRNAs are generally loaded into Ago1-containing RISC (Ago1-RISC) and Ago2-containing RISC (Ago2-RISC), respectively. We developed a native agarose gel system to directly detect Ago1-RISC, Ago2-RISC, and their precursor complexes. Methods presented here will provide powerful tools to biochemically dissect the RISC assembly pathways.

  11. Human U87 astrocytoma cell invasion induced by interaction of βig-h3 with integrin α5β1 involves calpain-2.

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    Jie Ma

    Full Text Available It is known that βig-h3 is involved in the invasive process of many types of tumors, but its mechanism in glioma cells has not been fully clarified. Using immunofluorescent double-staining and confocal imaging analysis, and co-immunoprecipitation assays, we found that βig-h3 co-localized with integrin α5β1 in U87 cells. We sought to elucidate the function of this interaction by performing cell invasion assays and gelatin zymography experiments. We found that siRNA knockdowns of βig-h3 and calpain-2 impaired cell invasion and MMP secretion. Moreover, βig-h3, integrins and calpain-2 are known to be regulated by Ca(2+, and they are also involved in tumor cell invasion. Therefore, we further investigated if calpain-2 was relevant to βig-h3-integrin α5β1 interaction to affect U87 cell invasion. Our data showed that βig-h3 co-localized with integrin α5β1 to enhance the invasion of U87 cells, and that calpain-2, is involved in this process, acting as a downstream molecule.

  12. Down-regulation of 14-3-3β exerts anti-cancer effects through inducing ER stress in human glioma U87 cells: Involvement of CHOP–Wnt pathway

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    Cao, Lei; Lei, Hui; Chang, Ming-Ze; Liu, Zhi-Qin [Department of Neurological Disease, Xi' an Central Hospital, Xi' an Jiaotong University, Xi' an, Shaanxi 710000 (China); Bie, Xiao-Hua, E-mail: biexiaohua_xjtu@126.com [Department of Functional Neurosurgery, Xi' an Red Cross Hospital, Xi' an Jiaotong University, Xi' an, Shaanxi 710054 (China)

    2015-07-10

    We previously identified 14-3-3β as a tumor-specific isoform of 14-3-3 protein in astrocytoma, but its functional role in glioma cells and underlying mechanisms are poorly understood. In the present study, we investigated the effects of 14-3-3β inhibition in human glioma U87 cells using specific targeted small interfering RNA (siRNA). The results showed that 14-3-3β is highly expressed in U87 cells but not in normal astrocyte SVGp12 cells. Knockdown of 14-3-3β by Si-14-3-3β transfection significantly decreased the cell viability but increased the LDH release in a time-dependent fashion in U87 cells, and these effects were accompanied with G0/G1 cell cycle arrest and apoptosis. In addition, 14-3-3β knockdown induced ER stress in U87 cells, as evidenced by ER calcium release, increased expression of XBP1S mRNA and induction of ER related pro-apoptotic factors. Down-regulation of 14-3-3β significantly decreased the nuclear localization of β-catenin and inhibited Topflash activity, which was shown to be reversely correlated with CHOP. Furthermore, Si-CHOP and sFRP were used to inhibit CHOP and Wnt, respectively. The results showed that the anti-cancer effects of 14-3-3β knockdown in U87 cells were mediated by increased expression of CHOP and followed inhibition of Wnt/β-catenin pathway. In summary, the remarkable efficiency of 14-3-3β knockdown to induce apoptotic cell death in U87 cells may find therapeutic application for the treatment of glioma patients. - Highlights: • Knockdown of 14-3-3β leads to cytotoxicity in human glioma U87 cells. • Knockdown of 14-3-3β induces cell cycle arrest and apoptosis in U87 cells. • Knockdown of 14-3-3β results in ER stress in U87 cells. • Knockdown of 14-3-3β inhibits Wnt/β-catenin pathway via CHOP activation.

  13. Down-regulation of 14-3-3β exerts anti-cancer effects through inducing ER stress in human glioma U87 cells: Involvement of CHOP–Wnt pathway

    International Nuclear Information System (INIS)

    Cao, Lei; Lei, Hui; Chang, Ming-Ze; Liu, Zhi-Qin; Bie, Xiao-Hua

    2015-01-01

    We previously identified 14-3-3β as a tumor-specific isoform of 14-3-3 protein in astrocytoma, but its functional role in glioma cells and underlying mechanisms are poorly understood. In the present study, we investigated the effects of 14-3-3β inhibition in human glioma U87 cells using specific targeted small interfering RNA (siRNA). The results showed that 14-3-3β is highly expressed in U87 cells but not in normal astrocyte SVGp12 cells. Knockdown of 14-3-3β by Si-14-3-3β transfection significantly decreased the cell viability but increased the LDH release in a time-dependent fashion in U87 cells, and these effects were accompanied with G0/G1 cell cycle arrest and apoptosis. In addition, 14-3-3β knockdown induced ER stress in U87 cells, as evidenced by ER calcium release, increased expression of XBP1S mRNA and induction of ER related pro-apoptotic factors. Down-regulation of 14-3-3β significantly decreased the nuclear localization of β-catenin and inhibited Topflash activity, which was shown to be reversely correlated with CHOP. Furthermore, Si-CHOP and sFRP were used to inhibit CHOP and Wnt, respectively. The results showed that the anti-cancer effects of 14-3-3β knockdown in U87 cells were mediated by increased expression of CHOP and followed inhibition of Wnt/β-catenin pathway. In summary, the remarkable efficiency of 14-3-3β knockdown to induce apoptotic cell death in U87 cells may find therapeutic application for the treatment of glioma patients. - Highlights: • Knockdown of 14-3-3β leads to cytotoxicity in human glioma U87 cells. • Knockdown of 14-3-3β induces cell cycle arrest and apoptosis in U87 cells. • Knockdown of 14-3-3β results in ER stress in U87 cells. • Knockdown of 14-3-3β inhibits Wnt/β-catenin pathway via CHOP activation

  14. RISC vs. Non-RISC Schools: A Comparison of Student Proficiencies for Reading, Writing, and Mathematics

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    Haystead, Mark W.

    2010-01-01

    This report describes the findings for an analysis of data provided by the Re-Inventing Schools Coalition (RISC). A comparison was made between schools at seven districts that employ the RISC model and eight non-RISC districts (hereinafter referred to as RISC and non-RISC schools) on the percentages of students who scored proficient or above on…

  15. Epigenetic Silencing of the Protocadherin Family Member PCDH-γ-All in Astrocytomas

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    Anke Waha

    2005-03-01

    Full Text Available In a microarray-based methylation analysis of astrocytomas [World Health Organization (WHO grade II], we identified a CpG island within the first exon of the protocadherin-γ subfamily A11 (PCDH-γ-A11 gene that showed hypermethylation compared to normal brain tissue. Bisulfite sequencing and combined bisulfite restriction analysis (COBRA was performed to screen low- and high-grade astrocytomas for the methylation status of this CpG island. Hypermethylation was detected in 30 of 34 (88% astrocytomas (WHO grades II and III, 20 of 23 (87% glioblastomas (WHO grade IV, 8 of 8 (100% glioma cell lines. There was a highly significant correlation (P = .00028 between PCDH-γ-A11 hypermethylation and decreased transcription as determined by competitive reverse transcription polymerase chain reaction in WHO grades II and III astrocytomas. After treatment of glioma cell lines with a demethylating agent, transcription of PCDH-γ-A11 was restored. In summary, we have identified PCDH-γ-A11 as a new target silenced epigenetically in astrocytic gliomas. The inactivation of this cell-cell contact molecule might be involved in the invasive growth of astrocytoma cells into normal brain parenchyma.

  16. Conversion of pre-RISC to holo-RISC by Ago2 during assembly of RNAi complexes

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    Kim, Kevin; Lee, Young Sik; Carthew, Richard W.

    2007-01-01

    In the Drosophila RNA interference (RNAi) pathway, small interfering RNAs (siRNAs) direct Argonaute2 (Ago2), an endonuclease, within the RNA-induced silencing complex (RISC) to cleave complementary mRNA targets. In vitro studies have shown that, for each siRNA duplex, RISC retains only one strand, the guide, and releases the other, the passenger, to form a holo-RISC complex. Here, we have isolated a new Ago2 mutant allele and provide, for the first time, in vivo evidence that endogenous Ago2 slicer activity is important to mount an RNAi response in Drosophila. We demonstrate in vivo that efficient removal of the passenger strand from RISC requires the cleavage activity of Ago2. We have also identified a new intermediate complex in the RISC assembly pathway, pre-RISC, in which Ago2 is stably bound to double-stranded siRNA. PMID:17123955

  17. ATP-dependent human RISC assembly pathways.

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    Yoda, Mayuko; Kawamata, Tomoko; Paroo, Zain; Ye, Xuecheng; Iwasaki, Shintaro; Liu, Qinghua; Tomari, Yukihide

    2010-01-01

    The assembly of RNA-induced silencing complex (RISC) is a key process in small RNA-mediated gene silencing. In humans, small interfering RNAs (siRNAs) and microRNAs (miRNAs) are incorporated into RISCs containing the Argonaute (AGO) subfamily proteins Ago1-4. Previous studies have proposed that, unlike Drosophila melanogaster RISC assembly pathways, human RISC assembly is coupled with dicing and is independent of ATP. Here we show by careful reexamination that, in humans, RISC assembly and dicing are uncoupled, and ATP greatly facilitates RISC loading of small-RNA duplexes. Moreover, all four human AGO proteins show remarkably similar structural preferences for small-RNA duplexes: central mismatches promote RISC loading, and seed or 3'-mid (guide position 12-15) mismatches facilitate unwinding. All these features of human AGO proteins are highly reminiscent of fly Ago1 but not fly Ago2.

  18. Prognostic parameters in benign astrocytomas

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    Westergaard, L; Gjerris, F; Klinken, L

    1993-01-01

    astrocytomas treated in the period 1956 to 1991. The pilocytic type of astrocytoma was found to have an outstandingly good prognosis and should be regarded as a distinct nosological entity. For the non-pilocytic supratentorial astrocytomas, a multivariate regression analysis showed that age, tumour site...

  19. The inhibitory effect of CIL-102 on the growth of human astrocytoma cells is mediated by the generation of reactive oxygen species and induction of ERK1/2 MAPK

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    Teng, Chih-Chuan [Institute of Nursing and Department of Nursing, Chang Gung University of Science and Technology, Chronic Diseases and Health Promotion Research Center, CGUST, Taiwan (China); Institute of Basic Medicine Science, National Cheng Kung University, Tainan, Taiwan (China); Kuo, Hsing-Chun [Institute of Nursing and Department of Nursing, Chang Gung University of Science and Technology, Chronic Diseases and Health Promotion Research Center, CGUST, Taiwan (China); Cheng, Ho-Chen [Department of General Education, Chang Gung University of Science and Technology, CGUST, Taiwan (China); Wang, Ting-Chung [Department of Neurosurgery, Chang Gung Memorial Hospital, Chia-Yi Center, Chiayi, Taiwan (China); Graduate Institute of Clinical Medical Sciences, Chang Gung University, Gueishan, Taiwan (China); Sze, Chun-I, E-mail: szec@mail.ncku.edu.tw [Institute of Basic Medicine Science, Department of Cell Biology and Anatomy and Pathology, National Cheng Kung University, Tainan, Taiwan (China)

    2012-08-15

    CIL-102 (1-[4-(furo[2,3-b]quinolin-4-ylamino)phenyl]ethanone) is the major active agent of the alkaloid derivative of Camptotheca acuminata, with multiple pharmacological activities, including anticancer effects and promotion of apoptosis. The mechanism by which CIL-102 inhibits growth remains poorly understood in human astrocytoma cells. Herein, we investigated the molecular mechanisms by which CIL-102 affects the generation of reactive oxygen species (ROS) and cell cycle G2/M arrest in glioma cells. Treatment of U87 cells with 1.0 μM CIL-102 resulted in phosphorylation of extracellular signal-related kinase (ERK1/2), downregulation of cell cycle-related proteins (cyclin A, cyclin B, cyclin D1, and cdk1), and phosphorylation of cdk1Tyr{sup 15} and Cdc25cSer{sup 216}. Furthermore, treatment with the ERK1/2 inhibitor PD98059 abolished CIL-102-induced Cdc25cSer{sup 216} expression and reversed CIL-102-inhibited cdk1 activation. In addition, N-acetyl cysteine (NAC), an ROS scavenger, blocked cell cycle G2/M arrest and phosphorylation of ERK1/2 and Cdc25cSer{sup 216} in U87 cells. CIL-102-mediated ERK1/2 and ROS production, and cell cycle arrest were blocked by treatment with specific inhibitors. In conclusion, we have identified a novel CIL-102-inhibited proliferation in U87 cells by activating the ERK1/2 and Cdc25cSer{sup 216} cell cycle-related proteins and inducing ROS production; this might be a new mechanism in human astrocytoma cells. -- Highlights: ► We show the effects of CIL-102 on the G2/M arrest of human astrocytoma cells. ► ROS and the Ras/ERK1/2 triggering pathways are involved in the CIL-102 treatment. ► CIL-102 induces sustained activation of ERK1/2 and Cdc25c and ROS are required.

  20. The inhibitory effect of CIL-102 on the growth of human astrocytoma cells is mediated by the generation of reactive oxygen species and induction of ERK1/2 MAPK

    International Nuclear Information System (INIS)

    Teng, Chih-Chuan; Kuo, Hsing-Chun; Cheng, Ho-Chen; Wang, Ting-Chung; Sze, Chun-I

    2012-01-01

    CIL-102 (1-[4-(furo[2,3-b]quinolin-4-ylamino)phenyl]ethanone) is the major active agent of the alkaloid derivative of Camptotheca acuminata, with multiple pharmacological activities, including anticancer effects and promotion of apoptosis. The mechanism by which CIL-102 inhibits growth remains poorly understood in human astrocytoma cells. Herein, we investigated the molecular mechanisms by which CIL-102 affects the generation of reactive oxygen species (ROS) and cell cycle G2/M arrest in glioma cells. Treatment of U87 cells with 1.0 μM CIL-102 resulted in phosphorylation of extracellular signal-related kinase (ERK1/2), downregulation of cell cycle-related proteins (cyclin A, cyclin B, cyclin D1, and cdk1), and phosphorylation of cdk1Tyr 15 and Cdc25cSer 216 . Furthermore, treatment with the ERK1/2 inhibitor PD98059 abolished CIL-102-induced Cdc25cSer 216 expression and reversed CIL-102-inhibited cdk1 activation. In addition, N-acetyl cysteine (NAC), an ROS scavenger, blocked cell cycle G2/M arrest and phosphorylation of ERK1/2 and Cdc25cSer 216 in U87 cells. CIL-102-mediated ERK1/2 and ROS production, and cell cycle arrest were blocked by treatment with specific inhibitors. In conclusion, we have identified a novel CIL-102-inhibited proliferation in U87 cells by activating the ERK1/2 and Cdc25cSer 216 cell cycle-related proteins and inducing ROS production; this might be a new mechanism in human astrocytoma cells. -- Highlights: ► We show the effects of CIL-102 on the G2/M arrest of human astrocytoma cells. ► ROS and the Ras/ERK1/2 triggering pathways are involved in the CIL-102 treatment. ► CIL-102 induces sustained activation of ERK1/2 and Cdc25c and ROS are required.

  1. DNA methylation analysis of paediatric low-grade astrocytomas identifies a tumour-specific hypomethylation signature in pilocytic astrocytomas.

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    Jeyapalan, Jennie N; Doctor, Gabriel T; Jones, Tania A; Alberman, Samuel N; Tep, Alexander; Haria, Chirag M; Schwalbe, Edward C; Morley, Isabel C F; Hill, Alfred A; LeCain, Magdalena; Ottaviani, Diego; Clifford, Steven C; Qaddoumi, Ibrahim; Tatevossian, Ruth G; Ellison, David W; Sheer, Denise

    2016-05-27

    Low-grade gliomas (LGGs) account for about a third of all brain tumours in children. We conducted a detailed study of DNA methylation and gene expression to improve our understanding of the biology of pilocytic and diffuse astrocytomas. Pilocytic astrocytomas were found to have a distinctive signature at 315 CpG sites, of which 312 were hypomethylated and 3 were hypermethylated. Genomic analysis revealed that 182 of these sites are within annotated enhancers. The signature was not present in diffuse astrocytomas, or in published profiles of other brain tumours and normal brain tissue. The AP-1 transcription factor was predicted to bind within 200 bp of a subset of the 315 differentially methylated CpG sites; the AP-1 factors, FOS and FOSL1 were found to be up-regulated in pilocytic astrocytomas. We also analysed splice variants of the AP-1 target gene, CCND1, which encodes cell cycle regulator cyclin D1. CCND1a was found to be highly expressed in both pilocytic and diffuse astrocytomas, but diffuse astrocytomas have far higher expression of the oncogenic variant, CCND1b. These findings highlight novel genetic and epigenetic differences between pilocytic and diffuse astrocytoma, in addition to well-described alterations involving BRAF, MYB and FGFR1.

  2. Childhood Astrocytoma Treatment (PDQ®)—Patient Version

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    Childhood astrocytomas can be benign (not cancer) or malignant (cancer). Learn more about the types of astrocytoma, signs and symptoms, diagnosis, prognosis, and treatment of astrocytomas that are newly diagnosed or have come back after treatment in this expert-reviewed summary.

  3. Development of Novel Antisense Oligonucleotides for the Functional Regulation of RNA-Induced Silencing Complex (RISC) by Promoting the Release of microRNA from RISC.

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    Ariyoshi, Jumpei; Momokawa, Daiki; Eimori, Nao; Kobori, Akio; Murakami, Akira; Yamayoshi, Asako

    2015-12-16

    MicroRNAs (miRNAs) are known to be important post-transcription regulators of gene expression. Aberrant miRNA expression is associated with pathological disease processes, including carcinogenesis. Therefore, miRNAs are considered significant therapeutic targets for cancer therapy. MiRNAs do not act alone, but exhibit their functions by forming RNA-induced silencing complex (RISC). Thus, the regulation of RISC activity is a promising approach for cancer therapy. MiRNA is a core component of RISC and is an essential to RISC for recognizing target mRNA. Thereby, it is expected that development of the method to promote the release of miRNA from RISC would be an effective approach for inhibition of RISC activity. In this study, we synthesized novel peptide-conjugated oligonucleotides (RINDA-as) to promote the release of miRNA from RISC. RINDA-as showed a high rate of miRNA release from RISC and high level of inhibitory effect on RISC activity.

  4. Investigation of platinum nanoparticle properties against U87 glioblastoma multiforme

    DEFF Research Database (Denmark)

    Kutwin, Marta; Sawosz, Ewa; Jaworski, Slawomir

    2017-01-01

    a harmful influence on viability of U87 glioblastoma multiforme (GBM) cells, but also showed genotoxic properties as well as a pro-apoptotic effect on cancer cells. It was found that NP-Pt decreased the weight and volume of U87 GBM tumor tissue and caused pathomorphological changes in the ultrastructure...

  5. Pilocytic astrocytoma

    Directory of Open Access Journals (Sweden)

    Yu-wei CONG

    2015-03-01

    Full Text Available Background Pilocytic astrocytoma (PA is a low-grade glioma that occurs mainly in children and young adults. The histomorphology of PA located in the cerebellum (WHOⅠ is very typical. This article is to report one case of PA in the cerebellum of an 8-year-old child, and to discuss the clinical, imaging and pathological features of PA and clinicopathological differentiations from relevant tumors.  Methods and Results An 8-year-old girl presented intermittent headache for one month and the headache was aggravated for 7 d. MRI showed circular space-occupying lesion in the left cerebellar hemisphere and cerebellar vermis, and the lesion revealed uneven signals. During the surgery, the tumor was soft and jellylike, with poor blood supply. Histologically, tumor cell nuclei were round or oval; cytoplasmic projections on both ends were slender hair-like, and were arranged around the blood vessels. Part of tumor cells had spindle nuclei, and showed fascicular compact arrangement or loose reticular arrangement. The pathomorphism of this tumro was slightly different from that of typical PA. It had unusually rich blood vessels, and Rosenthal fibers and eosinophilic granules were not obvious. Tumor cells were diffusely positive for glial fibrillary acidic protein (GFAP, synaptophysin (Syn, vimentin (Vim and P53, but negative for cytokeratin (CK, neuronal nuclei (NeuN and neurofilament protein (NF. Ki-67 index was 2%-5%. Vascular endothelial cells were positive for CD34, and scatteredly expressed CD68. Pathological diagosis was pilocytic astrocytoma (WHOⅠ.  Conclusions Pilocytic astrocytoma usually happens in children and adolescents and often occurs in the cerebellum. Rosenthal fibers and eosinophilic granules are helpful to make a clear diagnosis, but they are not necessary conditions of diagnosis. Differential diagnoses should be paid attention, such as pilomyxoid astrocytoma, angiocentric glioma and dysembryoplastic neuroepithelial tumor (DNT

  6. Clarifying mammalian RISC assembly in vitro

    Directory of Open Access Journals (Sweden)

    Metzler David

    2011-04-01

    Full Text Available Abstract Background Argonaute, the core component of the RNA induced silencing complex (RISC, binds to mature miRNAs and regulates gene expression at transcriptional or post-transcriptional level. We recently reported that Argonaute 2 (Ago2 also assembles into complexes with miRNA precursors (pre-miRNAs. These Ago2:pre-miRNA complexes are catalytically active in vitro and constitute non-canonical RISCs. Results The use of pre-miRNAs as guides by Ago2 bypasses Dicer activity and complicates in vitro RISC reconstitution. In this work, we characterized Ago2:pre-miRNA complexes and identified RNAs that are targeted by miRNAs but not their corresponding pre-miRNAs. Using these target RNAs we were able to recapitulate in vitro pre-miRNA processing and canonical RISC loading, and define the minimal factors required for these processes. Conclusions Our results indicate that Ago2 and Dicer are sufficient for processing and loading of miRNAs into RISC. Furthermore, our studies suggest that Ago2 binds primarily to the 5'- and alternatively, to the 3'-end of select pre-miRNAs.

  7. MR imaging characteristics of protoplasmic astrocytomas

    Energy Technology Data Exchange (ETDEWEB)

    Tay, Kevin L. [Royal Melbourne Hospital, Department of Radiology, Parkville, Victoria (Australia); Royal North Shore Hospital, Department of Radiology, St Leonards, New South Wales (Australia); Tsui, Alpha [Royal Melbourne Hospital, Department of Pathology, Parkville, Victoria (Australia); Phal, Pramit M.; Tress, Brian M. [Royal Melbourne Hospital, Department of Radiology, Parkville, Victoria (Australia); Drummond, Katharine J. [Royal Melbourne Hospital, Department of Neurosurgery, Parkville, Victoria (Australia)

    2011-06-15

    Protoplasmic astrocytomas are a poorly recognized and uncommon subtype of astrocytoma. While usually categorized with other low-grade gliomas, there is literature to suggest that protoplasmic astrocytomas have differences in biology compared to other gliomas in this group. This paper presents the MR imaging characteristics of a series of eight protoplasmic astrocytomas. We retrospectively reviewed MR images and histopathology of eight consecutive cases of histologically proven protoplasmic astrocytomas. Patients ranged from 17 to 51 years of age with a 5:3 male to female ratio. The tumors were located in the frontal or temporal lobes and tended to be large, well defined, and had a very high signal on T2 (close to cerebrospinal fluid). Generally, a large proportion of the tumor showed substantial signal suppression on T2 fluid-attenuated inversion recovery (FLAIR). Six of the eight lesions also demonstrated a partial or complete rim of reduced apparent diffusion coefficient (ADC) around the T2 FLAIR suppressing portion. The possibility that a primary cerebral neoplasm represents a protoplasmic astrocytoma should be considered in a patient with a large frontal or temporal tumor that has a very high signal on T2 with a large proportion of the tumor showing substantial T2 FLAIR suppression. A further clue is a partial or complete rim of reduced ADC. (orig.)

  8. Dicer is dispensable for asymmetric RISC loading in mammals.

    Science.gov (United States)

    Betancur, Juan G; Tomari, Yukihide

    2012-01-01

    In flies, asymmetric loading of small RNA duplexes into Argonaute2-containing RNA-induced silencing complex (Ago2-RISC) requires Dicer-2/R2D2 heterodimer, which acts as a protein sensor for the thermodynamic stabilities of the ends of small RNA duplexes. However, the mechanism of small RNA asymmetry sensing in mammalian RISC assembly remains obscure. Here, we quantitatively examined RISC assembly and target silencing activity in the presence or absence of Dicer in mammals. Our data show that, unlike the well-characterized fly Ago2-RISC assembly pathway, mammalian Dicer is dispensable for asymmetric RISC loading in vivo and in vitro.

  9. Focusing on RISC assembly in mammalian cells.

    Science.gov (United States)

    Hong, Junmei; Wei, Na; Chalk, Alistair; Wang, Jue; Song, Yutong; Yi, Fan; Qiao, Ren-Ping; Sonnhammer, Erik L L; Wahlestedt, Claes; Liang, Zicai; Du, Quan

    2008-04-11

    RISC (RNA-induced silencing complex) is a central protein complex in RNAi, into which a siRNA strand is assembled to become effective in gene silencing. By using an in vitro RNAi reaction based on Drosophila embryo extract, an asymmetric model was recently proposed for RISC assembly of siRNA strands, suggesting that the strand that is more loosely paired at its 5' end is selectively assembled into RISC and results in target gene silencing. However, in the present study, we were unable to establish such a correlation in cell-based RNAi assays, as well as in large-scale RNAi data analyses. This suggests that the thermodynamic stability of siRNA is not a major determinant of gene silencing in mammalian cells. Further studies on fork siRNAs showed that mismatch at the 5' end of the siRNA sense strand decreased RISC assembly of the antisense strand, but surprisingly did not increase RISC assembly of the sense strand. More interestingly, measurements of melting temperature showed that the terminal stability of fork siRNAs correlated with the positions of the mismatches, but not gene silencing efficacy. In summary, our data demonstrate that there is no definite correlation between siRNA stability and gene silencing in mammalian cells, which suggests that instead of thermodynamic stability, other features of the siRNA duplex contribute to RISC assembly in RNAi.

  10. Focusing on RISC assembly in mammalian cells

    International Nuclear Information System (INIS)

    Hong Junmei; Wei Na; Chalk, Alistair; Wang Jue; Song, Yutong; Yi Fan; Qiao Renping; Sonnhammer, Erik L.L.; Wahlestedt, Claes; Liang Zicai; Du, Quan

    2008-01-01

    RISC (RNA-induced silencing complex) is a central protein complex in RNAi, into which a siRNA strand is assembled to become effective in gene silencing. By using an in vitro RNAi reaction based on Drosophila embryo extract, an asymmetric model was recently proposed for RISC assembly of siRNA strands, suggesting that the strand that is more loosely paired at its 5' end is selectively assembled into RISC and results in target gene silencing. However, in the present study, we were unable to establish such a correlation in cell-based RNAi assays, as well as in large-scale RNAi data analyses. This suggests that the thermodynamic stability of siRNA is not a major determinant of gene silencing in mammalian cells. Further studies on fork siRNAs showed that mismatch at the 5' end of the siRNA sense strand decreased RISC assembly of the antisense strand, but surprisingly did not increase RISC assembly of the sense strand. More interestingly, measurements of melting temperature showed that the terminal stability of fork siRNAs correlated with the positions of the mismatches, but not gene silencing efficacy. In summary, our data demonstrate that there is no definite correlation between siRNA stability and gene silencing in mammalian cells, which suggests that instead of thermodynamic stability, other features of the siRNA duplex contribute to RISC assembly in RNAi

  11. RISC-interacting clearing 3'- 5' exoribonucleases (RICEs) degrade uridylated cleavage fragments to maintain functional RISC in Arabidopsis thaliana.

    Science.gov (United States)

    Zhang, Zhonghui; Hu, Fuqu; Sung, Min Woo; Shu, Chang; Castillo-González, Claudia; Koiwa, Hisashi; Tang, Guiliang; Dickman, Martin; Li, Pingwei; Zhang, Xiuren

    2017-05-02

    RNA-induced silencing complex (RISC) is composed of miRNAs and AGO proteins. AGOs use miRNAs as guides to slice target mRNAs to produce truncated 5' and 3' RNA fragments. The 5' cleaved RNA fragments are marked with uridylation for degradation. Here, we identified novel cofactors of Arabidopsis AGOs, named RICE1 and RICE2. RICE proteins specifically degraded single-strand (ss) RNAs in vitro; but neither miRNAs nor miRNA*s in vivo. RICE1 exhibited a DnaQ-like exonuclease fold and formed a homohexamer with the active sites located at the interfaces between RICE1 subunits. Notably, ectopic expression of catalytically-inactive RICE1 not only significantly reduced miRNA levels; but also increased 5' cleavage RISC fragments with extended uridine tails. We conclude that RICEs act to degrade uridylated 5' products of AGO cleavage to maintain functional RISC. Our study also suggests a possible link between decay of cleaved target mRNAs and miRNA stability in RISC.

  12. Spontaneous anaplasia in pilocytic astrocytoma of cerebellum.

    Science.gov (United States)

    Lach, B; Al Shail, E; Patay, Z

    2003-06-01

    We report a cystic cerebellar astrocytoma with a mural nodule that contained an additional focus of astrocytoma with the histological features of anaplasia, and showed up to 48% of aneuploid and 3% S-phase cells on flow cytometry. This focus was detectable on the enhanced, as well as non-enhanced T1 and T2 images. This appears to be the first case of pilocytic astrocytoma of cerebellum with focal anaplasia detected on histological and radiological studies.

  13. Conformal proton radiation therapy for pediatric low-grade astrocytomas

    International Nuclear Information System (INIS)

    Hug, E.B.; Loma Linda Univ. Medical Center, Loma Linda, CA; Darthmouth-Hitchcock Medical Center, Lebanon, New Hampshire; Muenter, M.W.; Archambeau, J.O.; DeVries, A.; Loredo, L.N.; Grove, R.I.; Slater, J.D.; Liwnicz, B.

    2002-01-01

    Background: To evaluate the safety and efficacy of proton radiation therapy (PRT) for intracranial low-grade astrocytomas, the authors analyzed the first 27 pediatric patients treated at Loma Linda University Medical Center (LLUMC). Patients and Method: Between September 1991 and August 1997, 27 patients (13 female, 14 male) underwent fractionated proton radiation therapy for progressive or recurrent low-grade astrocytoma. Age at time of treatment ranged from 2 to 18 years (mean: 8.7 years). Tumors were located centrally (diencephatic) in 15 patients, in the cerebral and cerebellar hemispheres in seven patients, and in the brainstem in five patients. 25/27 patients (92%) were treated for progressive, unresectable, or residual disease following subtotal resection. Tissue diagnosis was available in 23/27 patients (85%). Four patients with optic pathway tumors were treated without histologic confirmation. Target doses between 50.4 and 63.0 CGE (cobalt gray equivalent, mean: 55.2 CGE) were prescribed at 1.8 CGE per fraction, five treatments per week. Results: At a mean follow-up period of 3.3 years (0.6-6.8 years), 6/27 patients experienced local failure (all located within the irradiated field), and 4/27 patients had died. By anatomic site these data translated into rates of local control and survival of 87% (13/15 patients) and 93% (14/15 patients) for central tumors, 71% (5/7 patients) and 86% (6/7 patients) for hemispheric tumors, and 60% (3/5 patients) and 60% (3/5 patients) for tumors located in the brainstem. Proton radiation therapy was generally well tolerated. All children with local control maintained their performance status. One child with associated neurofibromatosis, Type 1, developed Moyamoya disease. All six patients with optic pathway tumors and useful vision maintained or improved their visual status. Conclusions: This report on pediatric low-grade astrocytomas confirms proton radiation therapy as a safe and efficacious 3-D conformal treatment

  14. RISC assembly: Coordination between small RNAs and Argonaute proteins.

    Science.gov (United States)

    Kobayashi, Hotaka; Tomari, Yukihide

    2016-01-01

    Non-coding RNAs generally form ribonucleoprotein (RNP) complexes with their partner proteins to exert their functions. Small RNAs, including microRNAs, small interfering RNAs, and PIWI-interacting RNAs, assemble with Argonaute (Ago) family proteins into the effector complex called RNA-induced silencing complex (RISC), which mediates sequence-specific target gene silencing. RISC assembly is not a simple binding between a small RNA and Ago; rather, it follows an ordered multi-step pathway that requires specific accessory factors. Some steps of RISC assembly and RISC-mediated gene silencing are dependent on or facilitated by particular intracellular platforms, suggesting their spatial regulation. In this review, we summarize the currently known mechanisms for RISC assembly of each small RNA class and propose a revised model for the role of the chaperone machinery in the duplex-initiated RISC assembly pathway. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. 201Thallium SPECT, accuracy in astrocytoma diagnosis and treatment evaluation

    International Nuclear Information System (INIS)

    Kaellen, K.

    1999-10-01

    The aims of the studies included in this thesis were: - to investigate the reliability of 201 Thallium single photon emission computed tomography. Tl SPECT for preoperative diagnosis and histological staging of malignant astrocytomas in comparison with CT; - to develop a method for quantification of cerebral thallium uptake, and to evaluate the quantitative measurement in comparison with CT, for astrocytoma treatment follow-up purposes; - to compare quantitative Tl SPECT and proton magnetic resonance spectroscopy (H-MRS) with conventional MR imaging for astrocytoma monitoring, and to evaluate associations between change of morphological tumour characteristics during treatment and changes of cerebral thallium uptake and metabolic ratios. Results and conclusions: - High TI-index, calculated as a ratio comparing tumour uptake to uptake in the contralateral hemisphere, is an indicator of highly malignant astrocytoma. Differentiation between the high-grade astrocytomas, the low-grade astrocytomas, and infectious lesions is only partial, with an overlap of Tl-indexes between these groups. High-grade astrocytomas that do not show contrast enhancement on CT, and astrocytomas with central necrosis and moderate ring-enhancement, tend to be underestimated when evaluated by Tl-index calculation. Tl SPECT is not a reliable method for non-invasive tumour staging among the group of highly malignant astrocytomas. - Quantification of cerebral TI-uptake, defining the volume of viable tumour tissue, is a new method for astrocytoma chemotherapy monitoring. Results suggest that the method provides prognostic information, and information of treatment efficacy, at an earlier stage than CT. - We did not find a higher accuracy of quantitative Tl SPECT than of MR for monitoring purposes and our results indicated that treatment induced MR changes were interrelated with TI-uptake variations. - Multi-voxel H-MRS was difficult to apply for astrocytoma treatment monitoring, due to the anatomical

  16. Slicing-independent RISC activation requires the argonaute PAZ domain.

    Science.gov (United States)

    Gu, Shuo; Jin, Lan; Huang, Yong; Zhang, Feijie; Kay, Mark A

    2012-08-21

    Small RNAs regulate genetic networks through a ribonucleoprotein complex called the RNA-induced silencing complex (RISC), which, in mammals, contains at its center one of four Argonaute proteins (Ago1-Ago4). A key regulatory event in the RNA interference (RNAi) and microRNA (miRNA) pathways is Ago loading, wherein double-stranded small-RNA duplexes are incorporated into RISC (pre-RISC) and then become single-stranded (mature RISC), a process that is not well understood. The Agos contain an evolutionarily conserved PAZ (Piwi/Argonaute/Zwille) domain whose primary function is to bind the 3' end of small RNAs. We created multiple PAZ-domain-disrupted mutant Ago proteins and studied their biochemical properties and biological functionality in cells. We found that the PAZ domain is dispensable for Ago loading of slicing-competent RISC. In contrast, in the absence of slicer activity or slicer-substrate duplex RNAs, PAZ-disrupted Agos bound duplex small interfering RNAs, but were unable to unwind or eject the passenger strand and form functional RISC complexes. We have discovered that the highly conserved PAZ domain plays an important role in RISC activation, providing new mechanistic insights into how miRNAs regulate genes, as well as new insights for future design of miRNA- and RNAi-based therapeutics. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. 13N-NH3 PET in the diagnosis of astrocytomas: preliminary result

    International Nuclear Information System (INIS)

    Zhang Xiangsong; He Zuoxiang; Tang Anwu

    2004-01-01

    Objective: To evaluate the feasibility of diagnosing the astrocytoma with 13N-NH3 PET imaging. Methods 13N-NH3 and 18F-fluorodeoxyglucose (FDG) PET imaging were performed in seven cases of astrocytomas including 3 anteoperative astrocytomas, 2 recurrent astrocytomas, 2 brain injury or necrosis after the operation and radiotherapy. The radioactivity ratios of the tumor and normal white matter (T/WM) were calculated. Results: The tumor lesions in 3 anteoperative astrocytomas and 2 recurrent astrocytomas all uptake 13N-NH3. The average T/WM on 13N-NH3 images was 1.82±0.21, and T/WM on 13N-NH3 and 18F-FDG images were 1.98 and 0.97 for one case with grade 1 astrocytoma. 13N-NH3 and 18F-FDG PET imaging both showed decreased uptake in 2 brain injury or necrosis after the operation and radiotherapy of astrocytomas. Conclusions: 13N-NH3 was uptaken in astrocytomas. 13N-NH3 can be useful in the diagnosis of astrocytoma, and potentially improve diagnostic accuracy of astrocytoma, especially in low-grade astrocytoma. (authors)

  18. 13N-NH3 PET in the diagnosis of astrocytomas: preliminary result

    International Nuclear Information System (INIS)

    Zhang Xiangsong; He Zuoxiang; Tang Anwu

    2004-01-01

    Objective: To evaluate the feasibility of diagnosing the astrocytoma with 13N-NH3 PET imaging. Methods: 13N-NH3 and 18F-fluorodeoxyglucose (FDG) PET imaging were performed in seven cases of astrocytomas including 3 anteoperative astrocytomas, 2 recurrent astrocytomas, 2 brain injury or necrosis after the operation and radiotherapy. The radioactivity ratios of the tumor and normal white matter (T/WM) were calculated. Results: The tumor lesions in 3 anteoperative astrocytomas and 2 recurrent astrocytomas all uptake 13N-NH3 .The average T/WM on 13N-NH3 images was 1.82±0.21, and T/WM on 13N-NH3 and 18F-FDG images were 1.98 and 0.97 for one case with grade 1 astrocytoma. 13N-NH3 and 18F-FDG PET imaging both showed decreased uptake in 2 brain injury or necrosis after the operation and radiotherapy of astrocytomas. Conclusions: 13N-NH3 was uptaken in astrocytomas. 13N-NH3 can be useful in the diagnosis of astrocytoma, and potentially improve diagnostic accuracy of astrocytoma, especially in low-grade astrocytoma. (authors)

  19. 3' fragment of miR173-programmed RISC-cleaved RNA is protected from degradation in a complex with RISC and SGS3.

    Science.gov (United States)

    Yoshikawa, Manabu; Iki, Taichiro; Tsutsui, Yasuhiro; Miyashita, Kyoko; Poethig, R Scott; Habu, Yoshiki; Ishikawa, Masayuki

    2013-03-05

    trans-acting small interfering RNAs (tasiRNAs) are plant-specific endogenous siRNAs produced via a unique pathway whose first step is the microRNA (miRNA)-programmed RNA-induced silencing complex (RISC)-mediated cleavage of tasiRNA gene (TAS) transcripts. One of the products is subsequently transformed into tasiRNAs by a pathway that requires several factors including SUPPRESSOR OF GENE SILENCING3 (SGS3) and RNA-DEPENDENT RNA POLYMERASE6. Here, using in vitro assembled ARGONAUTE (AGO)1-RISCs, we show that SGS3 is recruited onto RISCs only when they bind target RNA. Following cleavage by miRNA173 (miR173)-programmed RISC, SGS3 was found in complexes containing cleaved TAS2 RNA and RISC. The 3' cleavage fragment (the source of tasiRNAs) was protected from degradation in this complex. Depletion of SGS3 did not affect TAS2 RNA cleavage by miR173-programmed RISC, but did affect the stability of the 3' cleavage fragment. When the 3' nucleotide of 22-nt miR173 was deleted or the corresponding nucleotide in TAS2 RNA was mutated, the complex was not observed and the 3' cleavage fragment was degraded. Importantly, these changes in miR173 or TAS2 RNA are known to lead to a loss of tasiRNA production in vivo. These results suggest that (i) SGS3 associates with AGO1-RISC via the double-stranded RNA formed by the 3'-terminal nucleotides of 22-nt miR173 and corresponding target RNA, which probably protrudes from the AGO1-RISC molecular surface, (ii) SGS3 protects the 3' cleavage fragment of TAS2 RNA from degradation, and (iii) the observed SGS3-dependent stabilization of the 3' fragment of TAS2 RNA is key to tasiRNA production.

  20. Prognosis and Treatment of Spinal Cord Astrocytoma

    International Nuclear Information System (INIS)

    Minehan, Kiernan J.; Brown, Paul D.; Scheithauer, Bernd W.; Krauss, William E.; Wright, Michael P.

    2009-01-01

    Purpose: To identify the prognostic factors for spinal cord astrocytoma and determine the effects of surgery and radiotherapy on outcome. Methods and Materials: This retrospective study reviewed the cases of consecutive patients with spinal cord astrocytoma treated at Mayo Clinic Rochester between 1962 and 2005. Results: A total of 136 consecutive patients were identified. Of these 136 patients, 69 had pilocytic and 67 had infiltrative astrocytoma. The median follow-up for living patients was 8.2 years (range, 0.08-37.6), and the median survival for deceased patients was 1.15 years (range, 0.01-39.9). The extent of surgery included incisional biopsy only (59%), subtotal resection (25%), and gross total resection (16%). Patients with pilocytic tumors survived significantly longer than those with infiltrative astrocytomas (median overall survival, 39.9 vs. 1.85 years; p < 0.001). Patients who underwent resection had a worse, although nonsignificant, median survival than those who underwent biopsy only (pilocytic, 18.1 vs. 39.9 years, p = 0.07; infiltrative, 19 vs. 30 months, p = 0.14). Postoperative radiotherapy, delivered in 75% of cases, gave no significant survival benefit for those with pilocytic tumors (39.9 vs. 18.1 years, p = 0.33) but did for those with infiltrative astrocytomas (24 vs. 3 months; Wilcoxon p = 0.006). On multivariate analysis, pilocytic histologic type, diagnosis after 1984, longer symptom duration, younger age, minimal surgical extent, and postoperative radiotherapy predicted better outcome. Conclusion: The results of our study have shown that histologic type is the most important prognostic variable affecting the outcome of spinal cord astrocytomas. Surgical resection was associated with shorter survival and thus remains an unproven treatment. Postoperative radiotherapy significantly improved survival for patients with infiltrative astrocytomas but not for those with pilocytic tumors

  1. In vitro reconstitution of chaperone-mediated human RISC assembly.

    Science.gov (United States)

    Naruse, Ken; Matsuura-Suzuki, Eriko; Watanabe, Mariko; Iwasaki, Shintaro; Tomari, Yukihide

    2018-01-01

    To silence target mRNAs, small RNAs and Argonaute (Ago) proteins need to be assembled into RNA-induced silencing complexes (RISCs). Although the assembly of Drosophila melanogaster RISC was recently reconstituted by Ago2, the Dicer-2/R2D2 heterodimer, and five chaperone proteins, the absence of a reconstitution system for mammalian RISC assembly has posed analytical challenges. Here we describe reconstitution of human RISC assembly using Ago2 and five recombinant chaperone proteins: Hsp90β, Hsc70, Hop, Dnaja2, and p23. Our data show that ATP hydrolysis by both Hsp90β and Hsc70 is required for RISC assembly of small RNA duplexes but not for that of single-stranded RNAs. The reconstitution system lays the groundwork for further studies of small RNA-mediated gene silencing in mammals. © 2018 Naruse et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  2. Single-Molecule Analysis for RISC Assembly and Target Cleavage.

    Science.gov (United States)

    Sasaki, Hiroshi M; Tadakuma, Hisashi; Tomari, Yukihide

    2018-01-01

    RNA-induced silencing complex (RISC) is a small RNA-protein complex that mediates silencing of complementary target RNAs. Biochemistry has been successfully used to characterize the molecular mechanism of RISC assembly and function for nearly two decades. However, further dissection of intermediate states during the reactions has been warranted to fill in the gaps in our understanding of RNA silencing mechanisms. Single-molecule analysis with total internal reflection fluorescence (TIRF) microscopy is a powerful imaging-based approach to interrogate complex formation and dynamics at the individual molecule level with high sensitivity. Combining this technique with our recently established in vitro reconstitution system of fly Ago2-RISC, we have developed a single-molecule observation system for RISC assembly. In this chapter, we summarize the detailed protocol for single-molecule analysis of chaperone-assisted assembly of fly Ago2-RISC as well as its target cleavage reaction.

  3. Cystic astrocytomas in children. The contribution of MRI

    International Nuclear Information System (INIS)

    Vilgrain, V.; Sellier, N.; Lalande, G.; Demange, P.; Kalifa, G.

    1988-01-01

    Three cases of cystic astrocytomas are reported in children. Two are supratentorial and one is a cerebellar tumor. The authors insist on the difficulties of the diagnosis. They emphasize the role of NMR which enables distinction between cystic astrocytomas and other cysts. In agreement with Kjos, the 3 cystic astrocytomas demonstrate an increased T1 and T2 and belong to the group of cystic tumors (type II) [fr

  4. Postradiation astrocytoma. Report of two cases

    International Nuclear Information System (INIS)

    Kitanaka, C.; Shitara, N.; Nakagomi, T.; Nakamura, H.; Genka, S.; Nakagawa, K.; Akanuma, A.; Aoyama, H.; Takakura, K.

    1989-01-01

    The authors describe two cases of malignant astrocytomas associated with previous radiation therapy in childhood for intracranial germinoma and craniopharyngioma. In both patients, there was no recurrence at the primary tumor site. Because of a geometric coincidence between the tumor location and the radiation field, radiotherapy was strongly implicated as a cause of these two astrocytomas.33 references

  5. Expression of aquaporin8 in human astrocytomas: Correlation with pathologic grade

    International Nuclear Information System (INIS)

    Zhu, Shu-juan; Wang, Ke-jian; Gan, Sheng-wei; Xu, Jin; Xu, Shi-ye; Sun, Shan-quan

    2013-01-01

    Highlights: •AQP8 is mainly distributed in the cytoplasm of human astrocytoma cells. •AQP8 over-expressed in human astrocytomas, especially glioblastoma. •The up-regulation of AQP8 is related to the pathological grade of human astrocytomas. •AQP8 may contribute to the growth and proliferation of astrocytomas. -- Abstract: Aquaporin8 (AQP8), a member of the aquaporin (AQP) protein family, is weakly distributed in mammalian brains. Previous studies on AQP8 have focused mainly on the digestive and the reproductive systems. AQP8 has a pivotal role in keeping the fluid and electrolyte balance. In this study, we investigated the expression changes of AQP8 in 75 cases of human brain astrocytic tumors using immunohistochemistry, Western blotting, and reverse transcription polymerase chain reaction. The results demonstrated that AQP8 was mainly distributed in the cytoplasm of astrocytoma cells. The expression levels and immunoreactive score of AQP8 protein and mRNA increased in low-grade astrocytomas, and further increased in high-grade astrocytomas, especially in glioblastoma. Therefore, AQP8 may contribute to the proliferation of astrocytomas, and may be a biomarker and candidate therapy target for patients with astrocytomas

  6. Expression of aquaporin8 in human astrocytomas: Correlation with pathologic grade

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Shu-juan; Wang, Ke-jian; Gan, Sheng-wei; Xu, Jin; Xu, Shi-ye; Sun, Shan-quan, E-mail: sunsq2151@cqmu.edu.cn

    2013-10-11

    Highlights: •AQP8 is mainly distributed in the cytoplasm of human astrocytoma cells. •AQP8 over-expressed in human astrocytomas, especially glioblastoma. •The up-regulation of AQP8 is related to the pathological grade of human astrocytomas. •AQP8 may contribute to the growth and proliferation of astrocytomas. -- Abstract: Aquaporin8 (AQP8), a member of the aquaporin (AQP) protein family, is weakly distributed in mammalian brains. Previous studies on AQP8 have focused mainly on the digestive and the reproductive systems. AQP8 has a pivotal role in keeping the fluid and electrolyte balance. In this study, we investigated the expression changes of AQP8 in 75 cases of human brain astrocytic tumors using immunohistochemistry, Western blotting, and reverse transcription polymerase chain reaction. The results demonstrated that AQP8 was mainly distributed in the cytoplasm of astrocytoma cells. The expression levels and immunoreactive score of AQP8 protein and mRNA increased in low-grade astrocytomas, and further increased in high-grade astrocytomas, especially in glioblastoma. Therefore, AQP8 may contribute to the proliferation of astrocytomas, and may be a biomarker and candidate therapy target for patients with astrocytomas.

  7. De predictieve validiteit van de Recidive Inschattingsschalen (RISc)

    NARCIS (Netherlands)

    Knaap, L.M. van der; Alberda, D.L.

    2009-01-01

    Om inzichten te krijgen in criminogene factoren van delinquenten is het screeningsinstrument 'Recidive Inschattingsschalen' (RISc) ontwikkeld. De betrouwbaarheid en validiteit van dit instrument zijn al onderzocht en positief bevonden. Dit onderzoek gaat na of de RISc geschikt is als

  8. {sup 201}Thallium SPECT, accuracy in astrocytoma diagnosis and treatment evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Kaellen, K

    1999-10-01

    The aims of the studies included in this thesis were: - to investigate the reliability of {sup 201}Thallium single photon emission computed tomography. Tl SPECT for preoperative diagnosis and histological staging of malignant astrocytomas in comparison with CT; - to develop a method for quantification of cerebral thallium uptake, and to evaluate the quantitative measurement in comparison with CT, for astrocytoma treatment follow-up purposes; - to compare quantitative Tl SPECT and proton magnetic resonance spectroscopy (H-MRS) with conventional MR imagingfor astrocytoma monitoring, and to evaluate associations between change of morphological tumour characteristics during treatment and changes of cerebral thallium uptake and metabolic ratios. Results and conclusions: - High TI-index, calculated as a ratio comparing tumour uptake to uptake in the contralateral hemisphere, is an indicator of highly malignant astrocytoma. Differentiation between the high-grade astrocytomas, the low-grade astrocytomas, and infectious lesions is only partial, with an overlap of Tl-indexes between these groups. High-grade astrocytomas that do not show contrast enhancement on CT, and astrocytomas with central necrosis and moderate ring-enhancement, tend to be underestimated when evaluated by Tl-index calculation. Tl SPECT is not a reliable method for non-invasive tumour staging among the group of highly malignant astrocytomas. - Quantification of cerebral TI-uptake, defining the volume of viable tumour tissue, is a new method for astrocytoma chemotherapy monitoring. Results suggest that the method provides prognostic information, and information of treatment efficacy, at an earlier stage than CT. - We did not find a higher accuracy of quantitative Tl SPECT than of MR for monitoring purposes and our results indicated that treatment induced MR changes were interrelated with TI-uptake variations. - Multi-voxel H-MRS was difficult to apply for astrocytoma treatment monitoring, due to the

  9. RNA helicase A is not required for RISC activity.

    Science.gov (United States)

    Liang, Xue-Hai; Crooke, Stanley T

    2013-10-01

    It has been shown that siRNAs can compete with each other or with endogenous miRNAs for RISC components. This competition may complicate the interpretations of phenotypes observed through siRNA-mediated knockdown of genes, especially those genes implicated in the RISC pathway. In this study, we re-examined the function of RNA helicase A (RHA), which has been previously proposed to function in RISC loading based on siRNA-mediated knockdown studies. Here we show that reduced RISC activity or loading of siRNAs was observed only in cells depleted of RHA using siRNA, but not using RNaseH-dependent antisense oligonucleotides (ASOs), suggesting that the impaired RISC function stems from the competition between pre-existing and newly transfected siRNAs, but not from reduction of the RHA protein. This view is further supported by the findings that cells depleted of a control protein, NCL1, using siRNA, but not ASO, exhibited similar defects on the loading and activity of a subsequently transfected siRNA. Transfection of RHA or NCL1 siRNAs, but not ASOs, reduced the levels of endogenous miRNAs, suggesting a competition mechanism. As a positive control, we showed that reduction of MOV10 by either siRNA or ASO decreased siRNA activity, confirming its role in RISC function. Together, our results indicate that RHA is not required for RISC activity or loading, and suggest that proper controls are required when using siRNAs to functionalize genes to avoid competition effects. © 2013. Published by Elsevier B.V. All rights reserved.

  10. Functional Verification of Enhanced RISC Processor

    OpenAIRE

    SHANKER NILANGI; SOWMYA L

    2013-01-01

    This paper presents design and verification of a 32-bit enhanced RISC processor core having floating point computations integrated within the core, has been designed to reduce the cost and complexity. The designed 3 stage pipelined 32-bit RISC processor is based on the ARM7 processor architecture with single precision floating point multiplier, floating point adder/subtractor for floating point operations and 32 x 32 booths multiplier added to the integer core of ARM7. The binary representati...

  11. Integrated analysis of mismatch repair system in malignant astrocytomas.

    Directory of Open Access Journals (Sweden)

    Irene Rodríguez-Hernández

    Full Text Available Malignant astrocytomas are the most aggressive primary brain tumors with a poor prognosis despite optimal treatment. Dysfunction of mismatch repair (MMR system accelerates the accumulation of mutations throughout the genome causing uncontrolled cell growth. The aim of this study was to characterize the MMR system defects that could be involved in malignant astrocytoma pathogenesis. We analyzed protein expression and promoter methylation of MLH1, MSH2 and MSH6 as well as microsatellite instability (MSI and MMR gene mutations in a set of 96 low- and high-grade astrocytomas. Forty-one astrocytomas failed to express at least one MMR protein. Loss of MSH2 expression was more frequent in low-grade astrocytomas. Loss of MLH1 expression was associated with MLH1 promoter hypermethylation and MLH1-93G>A promoter polymorphism. However, MSI was not related with MMR protein expression and only 5% of tumors were MSI-High. Furthermore, the incidence of tumors carrying germline mutations in MMR genes was low and only one glioblastoma was associated with Lynch syndrome. Interestingly, survival analysis identified that tumors lacking MSH6 expression presented longer overall survival in high-grade astrocytoma patients treated only with radiotherapy while MSH6 expression did not modify the prognosis of those patients treated with both radiotherapy and chemotherapy. Our findings suggest that MMR system alterations are a frequent event in malignant astrocytomas and might help to define a subgroup of patients with different outcome.

  12. The molecular biology of WHO grade I astrocytomas.

    Science.gov (United States)

    Marko, Nicholas F; Weil, Robert J

    2012-12-01

    World Health Organization (WHO) grade I astrocytomas include pilocytic astrocytoma (PA) and subependymal giant cell astrocytoma (SEGA). As technologies in pharmacologic neo-adjuvant therapy continue to progress and as molecular characteristics are progressively recognized as potential markers of both clinically significant tumor subtypes and response to therapy, interest in the biology of these tumors has surged. An updated review of the current knowledge of the molecular biology of these tumors is needed. We conducted a Medline search to identify published literature discussing the molecular biology of grade I astrocytomas. We then summarized this literature and discuss it in a logical framework through which the complex biology of these tumors can be clearly understood. A comprehensive review of the molecular biology of WHO grade I astrocytomas is presented. The past several years have seen rapid progress in the level of understanding of PA in particular, but the molecular literature regarding both PA and SEGA remains nebulous, ambiguous, and occasionally contradictory. In this review we provide a comprehensive discussion of the current understanding of the chromosomal, genomic, and epigenomic features of both PA and SEGA and provide a logical framework in which these data can be more readily understood.

  13. 3′ fragment of miR173-programmed RISC-cleaved RNA is protected from degradation in a complex with RISC and SGS3

    Science.gov (United States)

    Yoshikawa, Manabu; Iki, Taichiro; Tsutsui, Yasuhiro; Miyashita, Kyoko; Poethig, R. Scott; Habu, Yoshiki; Ishikawa, Masayuki

    2013-01-01

    trans-acting small interfering RNAs (tasiRNAs) are plant-specific endogenous siRNAs produced via a unique pathway whose first step is the microRNA (miRNA)-programmed RNA-induced silencing complex (RISC)–mediated cleavage of tasiRNA gene (TAS) transcripts. One of the products is subsequently transformed into tasiRNAs by a pathway that requires several factors including SUPPRESSOR OF GENE SILENCING3 (SGS3) and RNA-DEPENDENT RNA POLYMERASE6. Here, using in vitro assembled ARGONAUTE (AGO)1–RISCs, we show that SGS3 is recruited onto RISCs only when they bind target RNA. Following cleavage by miRNA173 (miR173)-programmed RISC, SGS3 was found in complexes containing cleaved TAS2 RNA and RISC. The 3′ cleavage fragment (the source of tasiRNAs) was protected from degradation in this complex. Depletion of SGS3 did not affect TAS2 RNA cleavage by miR173-programmed RISC, but did affect the stability of the 3′ cleavage fragment. When the 3′ nucleotide of 22-nt miR173 was deleted or the corresponding nucleotide in TAS2 RNA was mutated, the complex was not observed and the 3′ cleavage fragment was degraded. Importantly, these changes in miR173 or TAS2 RNA are known to lead to a loss of tasiRNA production in vivo. These results suggest that (i) SGS3 associates with AGO1–RISC via the double-stranded RNA formed by the 3′-terminal nucleotides of 22-nt miR173 and corresponding target RNA, which probably protrudes from the AGO1–RISC molecular surface, (ii) SGS3 protects the 3′ cleavage fragment of TAS2 RNA from degradation, and (iii) the observed SGS3-dependent stabilization of the 3′ fragment of TAS2 RNA is key to tasiRNA production. PMID:23417299

  14. RISC-interacting clearing 3’- 5’ exoribonucleases (RICEs) degrade uridylated cleavage fragments to maintain functional RISC in Arabidopsis thaliana

    Science.gov (United States)

    Zhang, Zhonghui; Hu, Fuqu; Sung, Min Woo; Shu, Chang; Castillo-González, Claudia; Koiwa, Hisashi; Tang, Guiliang; Dickman, Martin; Li, Pingwei; Zhang, Xiuren

    2017-01-01

    RNA-induced silencing complex (RISC) is composed of miRNAs and AGO proteins. AGOs use miRNAs as guides to slice target mRNAs to produce truncated 5' and 3' RNA fragments. The 5' cleaved RNA fragments are marked with uridylation for degradation. Here, we identified novel cofactors of Arabidopsis AGOs, named RICE1 and RICE2. RICE proteins specifically degraded single-strand (ss) RNAs in vitro; but neither miRNAs nor miRNA*s in vivo. RICE1 exhibited a DnaQ-like exonuclease fold and formed a homohexamer with the active sites located at the interfaces between RICE1 subunits. Notably, ectopic expression of catalytically-inactive RICE1 not only significantly reduced miRNA levels; but also increased 5' cleavage RISC fragments with extended uridine tails. We conclude that RICEs act to degrade uridylated 5’ products of AGO cleavage to maintain functional RISC. Our study also suggests a possible link between decay of cleaved target mRNAs and miRNA stability in RISC. DOI: http://dx.doi.org/10.7554/eLife.24466.001 PMID:28463111

  15. An antiviral RISC isolated from Tobacco rattle virus-infected plants.

    Science.gov (United States)

    Ciomperlik, Jessica J; Omarov, Rustem T; Scholthof, Herman B

    2011-03-30

    The RNAi model predicts that during antiviral defense a RNA-induced silencing complex (RISC) is programmed with viral short-interfering RNAs (siRNAs) to target the cognate viral RNA for degradation. We show that infection of Nicotiana benthamiana with Tobacco rattle virus (TRV) activates an antiviral nuclease that specifically cleaves TRV RNA in vitro. In agreement with known RISC properties, the nuclease activity was inhibited by NaCl and EDTA and stimulated by divalent metal cations; a novel property was its preferential targeting of elongated RNA molecules. Intriguingly, the specificity of the TRV RISC could be reprogrammed by exogenous addition of RNA (containing siRNAs) from plants infected with an unrelated virus, resulting in a newly acquired ability of RISC to target this heterologous genome in vitro. Evidently the virus-specific nuclease complex from N. benthamiana represents a genuine RISC that functions as a readily employable and reprogrammable antiviral defense unit. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. AGO/RISC-mediated antiviral RNA silencing in a plant in vitro system.

    Science.gov (United States)

    Schuck, Jana; Gursinsky, Torsten; Pantaleo, Vitantonio; Burgyán, Jozsef; Behrens, Sven-Erik

    2013-05-01

    AGO/RISC-mediated antiviral RNA silencing, an important component of the plant's immune response against RNA virus infections, was recapitulated in vitro. Cytoplasmic extracts of tobacco protoplasts were applied that supported Tombusvirus RNA replication, as well as the formation of RNA-induced silencing complexes (RISC) that could be functionally reconstituted with various plant ARGONAUTE (AGO) proteins. For example, when RISC containing AGO1, 2, 3 or 5 were programmed with exogenous siRNAs that specifically targeted the viral RNA, endonucleolytic cleavages occurred and viral replication was inhibited. Antiviral RNA silencing was disabled by the viral silencing suppressor p19 when this was present early during RISC formation. Notably, with replicating viral RNA, only (+)RNA molecules were accessible to RISC, whereas (-)RNA replication intermediates were not. The vulnerability of viral RNAs to RISC activity also depended on the RNA structure of the target sequence. This was most evident when we characterized viral siRNAs (vsiRNAs) that were particularly effective in silencing with AGO1- or AGO2/RISC. These vsiRNAs targeted similar sites, suggesting that accessible parts of the viral (+)RNA may be collectively attacked by different AGO/RISC. The in vitro system was, hence, established as a valuable tool to define and characterize individual molecular determinants of antiviral RNA silencing.

  17. Structural determinants of miRNAs for RISC loading and slicer-independent unwinding.

    Science.gov (United States)

    Kawamata, Tomoko; Seitz, Hervé; Tomari, Yukihide

    2009-09-01

    MicroRNAs (miRNAs) regulate expression of their target mRNAs through the RNA-induced silencing complex (RISC), which contains an Argonaute (Ago) family protein as a core component. In Drosophila melanogaster, miRNAs are generally sorted into Ago1-containing RISC (Ago1-RISC). We established a native gel system that can biochemically dissect the Ago1-RISC assembly pathway. We found that miRNA-miRNA* duplexes are loaded into Ago1 as double-stranded RNAs in an ATP-dependent fashion. In contrast, unexpectedly, unwinding of miRNA-miRNA* duplexes is a passive process that does not require ATP or slicer activity of Ago1. Central mismatches direct miRNA-miRNA* duplexes into pre-Ago1-RISC, whereas mismatches in the seed or guide strand positions 12-15 promote conversion of pre-Ago1-RISC into mature Ago1-RISC. Our findings show that unwinding of miRNAs is a precise mirror-image process of target recognition, and both processes reflect the unique geometry of RNAs in Ago proteins.

  18. Cyclophilin 40 facilitates HSP90-mediated RISC assembly in plants.

    Science.gov (United States)

    Iki, Taichiro; Yoshikawa, Manabu; Meshi, Tetsuo; Ishikawa, Masayuki

    2012-01-18

    Posttranscriptional gene silencing is mediated by RNA-induced silencing complexes (RISCs) that contain AGO proteins and single-stranded small RNAs. The assembly of plant AGO1-containing RISCs depends on the molecular chaperone HSP90. Here, we demonstrate that cyclophilin 40 (CYP40), protein phosphatase 5 (PP5), and several other proteins with the tetratricopeptide repeat (TPR) domain associates with AGO1 in an HSP90-dependent manner in extracts of evacuolated tobacco protoplasts (BYL). Intriguingly, CYP40, but not the other TPR proteins, could form a complex with small RNA duplex-bound AGO1. Moreover, CYP40 that was synthesized by in-vitro translation using BYL uniquely facilitated binding of small RNA duplexes to AGO1, and as a result, increased the amount of mature RISCs that could cleave target RNAs. CYP40 was not contained in mature RISCs, indicating that the association is transient. Addition of PP5 or cyclophilin-binding drug cyclosporine A prevented the association of endogenous CYP40 with HSP90-AGO1 complex and inhibited RISC assembly. These results suggest that a complex of AGO1, HSP90, CYP40, and a small RNA duplex is a key intermediate of RISC assembly in plants.

  19. Radiotherapy Results of Brain Astrocytoma and Glioblastoma Multiforme

    International Nuclear Information System (INIS)

    Choi, Doo Ho; Kim, Il Han; Ha, Sung Whan; Chi, Je Geun

    1988-01-01

    A retrospective analysis was performed on 49 patients with astrocytoma of glioblastoma multiforme of brain who received postoperative radiotherapy in the period between February 1979 and December 1985. Fourteen patients had grade I astrocytoma, 11 patients grade II, 14 patients grade III, and 10 patients glioblastoma multiforme. Three year actuarial survival rates were 85.7%, 44.6% and 23.1% for grade I, II, and III astrocytomas, respectively. One and 2 year actuarial survival rates for patients with glioblastoma multiforme were 54.5% and 27.3%, respectively. Histologic grade, age, extent of operation and tumor location were revealed to be prognosticators

  20. Nitroproteins in Human Astrocytomas Discovered by Gel Electrophoresis and Tandem Mass Spectrometry

    Science.gov (United States)

    Peng, Fang; Li, Jianglin; Guo, Tianyao; Yang, Haiyan; Li, Maoyu; Sang, Shushan; Li, Xuejun; Desiderio, Dominic M.; Zhan, Xianquan

    2015-12-01

    Protein tyrosine nitration is involved in the pathogenesis of highly fatal astrocytomas, a type of brain cancer. To understand the molecular mechanisms of astrocytomas and to discover new biomarkers/therapeutic targets, we sought to identify nitroproteins in human astrocytoma tissue. Anti-nitrotyrosine immunoreaction-positive proteins from a high-grade astrocytoma tissue were detected with two-dimensional gel electrophoresis (2DGE)-based nitrotyrosine immunoblots, and identified with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Fifty-seven nitrotyrosine immunopositive protein spots were detected. A total of 870 proteins (nitrated and non-nitrated) in nitrotyrosine-immunopositive 2D gel spots were identified, and 18 nitroproteins and their 20 nitrotyrosine sites were identified with MS/MS analysis. These nitroproteins participate in multiple processes, including drug-resistance, signal transduction, cytoskeleton, transcription and translation, cell proliferation and apoptosis, immune response, phenotypic dedifferentiation, cell migration, and metastasis. Among those nitroproteins that might play a role in astrocytomas was nitro-sorcin, which is involved in drug resistance and metastasis and might play a role in the spread and treatment of an astrocytoma. Semiquantitative immune-based measurements of different sorcin expressions were found among different grades of astrocytomas relative to controls, and a semiquantitative increased nitration level in high-grade astrocytoma relative to control. Nitro-β-tubulin functions in cytoskeleton and cell migration. Semiquantitative immunoreactivity of β-tubulin showed increased expression among different grades of astrocytomas relative to controls and semiquantitatively increased nitration level in high-grade astrocytoma relative to control. Each nitroprotein was rationalized and related to the corresponding functional system to provide new insights into tyrosine nitration and its potential role in the

  1. The Resilient Schools Consortium (RiSC): Linking Climate Literacy, Resilience Thinking and Service Learning

    Science.gov (United States)

    Branco, B. F.; Fano, E.; Adams, J.; Shon, L.; Zimmermann, A.; Sioux, H.; Gillis, A.

    2017-12-01

    Public schools and youth voices are largely absent from climate resilience planning and projects in New York City. Additionally, research shows that U.S. science teachers' understanding of climate science is lacking, hence there is not only an urgent need to train and support teachers on both the science and pedagogy of climate change, but to link climate literacy, resilience thinking and service learning in K-12 education. However, research on participation of students and teachers in authentic, civic-oriented experiences points to increased engagement and learning outcomes in science. The Resilient Schools Consortium (RiSC) Project will address all these needs through an afterschool program in six coastal Brooklyn schools that engages teachers and urban youth (grades 6-12), in school and community climate resilience assessment and project design. The RiSC climate curriculum, co-designed by New York City school teachers with Brooklyn College, the National Wildlife Federation, New York Sea Grant and the Science and Resilience Institute at Jamaica Bay, will begin by helping students to understand the difference between climate and weather. The curriculum makes extensive use of existing resources such as NOAA's Digital Coast and the Coastal Resilience Mapping Portal. Through a series of four modules over two school years, the six RiSC teams will; 1. explore and understand the human-induced drivers of climate change and, particularly, the significant climate and extreme weather related risks to their schools and surrounding communities; 2. complete a climate vulnerability assessment within the school and the community that is aligned to OneNYC - the city's resilience planning document; 3. design and execute a school-based resilience project; and 4. propose resilience guidelines for NYC Department of Education schools. At the end of each school year, the six RiSC teams will convene a RiSC summit with city officials and resilience practitioners to share ideas and

  2. Proposta e simulação de uma arquitetura RISC

    OpenAIRE

    Fredy Joao Valente

    1991-01-01

    RISC - Uma nova tendência em arquitetura de computadores. Este trabalho apresenta um estudo de como surgiu esta nova arquitetura, e suas características básicas, que a diferencia das arquiteturas convencionais. Uma proposta de microprocessador RISC é apresentada, com sua rota de dados completamente detalhada. Um simulador para arquitetura RISC foi então construído, para se testar este microprocessador. Para validar o simulador, que é a idéia principal deste trabalho, e para se avaliar a arqui...

  3. The Radiation, Interplanetary Shocks, and Coronal Sources (RISCS) Toolset

    Science.gov (United States)

    Zank, G. P.; Spann, James F.

    2014-01-01

    The goal of this project is to serve the needs of space system designers and operators by developing an interplanetary radiation environment model within 10 AU:Radiation, Interplanetary Shocks, and Coronal Sources (RISCS) toolset: (1) The RISCS toolset will provide specific reference environments for space system designers and nowcasting and forecasting capabilities for space system operators; (2) We envision the RISCS toolset providing the spatial and temporal radiation environment external to the Earth's (and other planets') magnetosphere, as well as possessing the modularity to integrate separate applications (apps) that can map to specific magnetosphere locations and/or perform the subsequent radiation transport and dosimetry for a specific target.

  4. Multilayer checkpoints for microRNA authenticity during RISC assembly.

    Science.gov (United States)

    Kawamata, Tomoko; Yoda, Mayuko; Tomari, Yukihide

    2011-09-01

    MicroRNAs (miRNAs) function through the RNA-induced silencing complex (RISC), which contains an Argonaute (Ago) protein at the core. RISC assembly follows a two-step pathway: miRNA/miRNA* duplex loading into Ago, and separation of the two strands within Ago. Here we show that the 5' phosphate of the miRNA strand is essential for duplex loading into Ago, whereas the preferred 5' nucleotide of the miRNA strand and the base-pairing status in the seed region and the middle of the 3' region function as additive anchors to Ago. Consequently, the miRNA authenticity is inspected at multiple steps during RISC assembly.

  5. Multiple solid pilocytic astrocytomas in cerebleiium with neurofibromatosis type: A case report

    International Nuclear Information System (INIS)

    Choi, Seo Young; Kim, Myung Soon; Kim, Young Ju

    2014-01-01

    Pilocytic astrocytoma usually has a classic imaging manifestation of a solitary, cyst-like mass with a strong contrast-enhancing mural nodule. There is only one published report so far of multiple solid and cyst type pilocytic astrocytomas in the cerebellum in neurofibromatosis type 1 (NF1) patient from the United States in 2007. We report a case of pilocytic astrocytoma presenting with only solid, multiple pilocytic astrocytomas in the cerebellum in NF1 patient.

  6. Identification of astrocytoma associated genes including cell surface markers

    International Nuclear Information System (INIS)

    Boon, Kathy; Edwards, Jennifer B; Eberhart, Charles G; Riggins, Gregory J

    2004-01-01

    Despite intense effort the treatment options for the invasive astrocytic tumors are still limited to surgery and radiation therapy, with chemotherapy showing little or no increase in survival. The generation of Serial Analysis of Gene Expression (SAGE) profiles is expected to aid in the identification of astrocytoma-associated genes and highly expressed cell surface genes as molecular therapeutic targets. SAGE tag counts can be easily added to public expression databases and quickly disseminated to research efforts worldwide. We generated and analyzed the SAGE transcription profiles of 25 primary grade II, III and IV astrocytomas [1]. These profiles were produced as part of the Cancer Genome Anatomy Project's SAGE Genie [2], and were used in an in silico search for candidate therapeutic targets by comparing astrocytoma to normal brain transcription. Real-time PCR and immunohistochemistry were used for the validation of selected candidate target genes in 2 independent sets of primary tumors. A restricted set of tumor-associated genes was identified for each grade that included genes not previously associated with astrocytomas (e.g. VCAM1, SMOC1, and thymidylate synthetase), with a high percentage of cell surface genes. Two genes with available antibodies, Aquaporin 1 and Topoisomerase 2A, showed protein expression consistent with transcript level predictions. This survey of transcription in malignant and normal brain tissues reveals a small subset of human genes that are activated in malignant astrocytomas. In addition to providing insights into pathway biology, we have revealed and quantified expression for a significant portion of cell surface and extra-cellular astrocytoma genes

  7. [RITA combined with temozolomide inhibits the proliferation of human glioblastoma U87 cells].

    Science.gov (United States)

    He, Xiao-Yan; Feng, Xiao-Li; Song, Xin-Pei; Zeng, Huan-Chao; Cao, Zhong-Xu; Xiao, Wei-Wei; Zhang, Bao; Wu, Qing-Hua

    2016-10-20

    To observe the effect of RITA, a small molecule that targets p53, combined with temozolomide (TMZ) on proliferation, colony formation and apoptosis of human glioblastoma U87 cells and explore the underlying mechanism. Cultured U87 cells were treated with RITA (1, 5, 10, 20 µmol/L), TMZ, or RITA+TMZ (half dose) for 24, 48 or 72 h. MTS assay were used to detect the cell proliferation, and the cell proliferation rate and inhibitory rate were calculated. The effect of combined treatments was evaluated by the q value. The expressions of p53, p21 and other apoptosis-associated genes were detected by qRT-PCR and Western blotting; cell apoptosis was assayed using flow cytometry with Annexin V/PI double staining; colony formation of the cells was detected with crystal violet staining. MTS assay showed that RITA at the 4 doses more potently inhibited U87 cell viability than TMZ at 72 h (P=0.000) with inhibitory rates of 25.94%-41.38% and 3.84%-8.20%, respectively. RITA combined with TMZ caused a more significant inhibition of U87 cells (29.21%-52.11%) than RITA (PRITA+TMZ for 48 h resulted in q values exceeding 1.2 and showed an obvious synergistic effect of the drugs. Both RITA and TMZ, especially the latter, significantly increased the expressions of p53, p21, puma, and other apoptosis-associated genes to accelerate apoptosis and inhibit the growth and colony formation of U87 cells, and the effect was more obvious with a combined treatment. RITA inhibits the growth of human glioblastoma cells and enhance their sensitivity to TMZ by up-regulating p53 expression, and when combined, RITA and TMZ show a synergistic effect to cause a stronger cell inhibition.

  8. An in vitro reprogrammable antiviral RISC with size-preferential ribonuclease activity.

    Science.gov (United States)

    Omarov, Rustem T; Ciomperlik, Jessica; Scholthof, Herman B

    2016-03-01

    Infection of Nicotiana benthamiana plants with Tomato bushy stunt virus (TBSV) mutants compromised for silencing suppression induces formation of an antiviral RISC (vRISC) that can be isolated using chromatography procedures. The isolated vRISC sequence-specifically degrades TBSV RNA in vitro, its activity can be down-regulated by removing siRNAs, and re-stimulated by exogenous supply of siRNAs. vRISC is most effective at hydrolyzing the ~4.8kb genomic RNA, but less so for a ~2.2kb TBSV subgenomic mRNA (sgRNA1), while the 3' co-terminal sgRNA2 of ~0.9kb appears insensitive to vRISC cleavage. Moreover, experiments with in vitro generated 5' co-terminal viral transcripts show that RNAs of ~2.7kb are efficiently cleaved while those of ~1.1kb or shorter are unaffected. The isolated antiviral ribonuclease complex fails to degrade ~0.4kb defective interfering RNAs (DIs) in vitro, agreeing with findings that in plants DIs are not targeted by silencing. Copyright © 2016. Published by Elsevier Inc.

  9. Pilocytic Astrocytoma Presenting as an Orbital Encephalocele: A Case Report

    Directory of Open Access Journals (Sweden)

    Amy Bruzek

    2015-04-01

    Full Text Available We describe the case of a 29-year-old male who presented with new-onset seizures. He was subsequently found to have an orbital encephalocele containing a focus of pilocytic astrocytoma. We believe that this is the first report of a pilocytic astrocytoma located within the orbit that did not originate from the optic pathway. It is also the first case of a pilocytic astrocytoma completely contained within an encephalocele. This case suggests a close pathological examination of encephaloceles for underlying diseases.

  10. Computed tomography of benign supratentorial astrocytomas of infancy and childhood

    International Nuclear Information System (INIS)

    Pedersen, H.; Gjerris, F.; Klinken, L.

    1981-01-01

    The CT findings of 15 benign supratentorial astrocytomas in children less than 15 years of age are compared with the CT findings of 19 supratentorial tumors of other histological types in the same age group. Astrocytomas were more often hypodense, lacked calcification and showed greater contrast enhancement than other tumors. Seven of the 15 astrocytomas were hypodense, without calcification and showed contrast enhancement of more than 10 Hounsfield units, whereas this coexistence was not present in any of the 19 tumors of the other histological types. (orig.)

  11. [Cell-ELA-based determination of binding affinity of DNA aptamer against U87-EGFRvIII cell].

    Science.gov (United States)

    Tan, Yan; Liang, Huiyu; Wu, Xidong; Gao, Yubo; Zhang, Xingmei

    2013-05-01

    A15, a DNA aptamer with binding specificity for U87 glioma cells stably overexpressing the epidermal growth factor receptor variant III (U87-EGFRvIII), was generated by cell systematic evolution of ligands by exponential enrichment (cell-SELEX) using a random nucleotide library. Subsequently, we established a cell enzyme-linked assay (cell-ELA) to detect the affinity of A15 compared to an EGFR antibody. We used A15 as a detection probe and cultured U87-EGFRvIII cells as targets. Our data indicate that the equilibrium dissociation constants (K(d)) for A15 were below 100 nmol/L and had similar affinity compared to an EGFR antibody for U87-EGFRvIII. We demonstrated that the cell-ELA was a useful method to determine the equilibrium dissociation constants (K(d)) of aptamers generated by cell-SELEX.

  12. 16-Bit RISC Processor Design for Convolution Application

    OpenAIRE

    Anand Nandakumar Shardul

    2013-01-01

    In this project, we propose a 16-bit non-pipelined RISC processor, which is used for signal processing applications. The processor consists of the blocks, namely, program counter, clock control unit, ALU, IDU and registers. Advantageous architectural modifications have been made in the incremented circuit used in program counter and carry select adder unit of the ALU in the RISC CPU core. Furthermore, a high speed and low power modified modifies multiplier has been designed and introduced in ...

  13. Differential RISC association of endogenous human microRNAs predicts their inhibitory potential.

    Science.gov (United States)

    Flores, Omar; Kennedy, Edward M; Skalsky, Rebecca L; Cullen, Bryan R

    2014-04-01

    It has previously been assumed that the generally high stability of microRNAs (miRNAs) reflects their tight association with Argonaute (Ago) proteins, essential components of the RNA-induced silencing complex (RISC). However, recent data have suggested that the majority of mature miRNAs are not, in fact, Ago associated. Here, we demonstrate that endogenous human miRNAs vary widely, by >100-fold, in their level of RISC association and show that the level of Ago binding is a better indicator of inhibitory potential than is the total level of miRNA expression. While miRNAs of closely similar sequence showed comparable levels of RISC association in the same cell line, these varied between different cell types. Moreover, the level of RISC association could be modulated by overexpression of complementary target mRNAs. Together, these data indicate that the level of RISC association of a given endogenous miRNA is regulated by the available RNA targetome and predicts miRNA function.

  14. Effects of diphenylhydantoin on murine astrocytoma radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Lordo, C.D.; Stroude, E.C.; Del Maestro, R.F.

    1987-01-01

    Diphenylhydantoin is a well known anticonvulsant used primarily in the treatment of epilepsy. The prophylactic use of diphenylhydantoin has been suggested for certain cerebral metastases, and it is routinely administered to prevent seizures induced by intracranial neoplasms and/or surgery. Patients with malignant gliomas treated with diphenylhydantoin frequently receive radiation therapy. The effects of a clinical concentration of diphenylhydantoin in combination with gamma radiation was investigated using the C6 astrocytoma cell line in both monolayer and three dimensional multicellular spheroid cultures. Diphenylhydantoin at 7.2 X 10(-5) M (20 micrograms/ml) significantly increased the doubling time (23%) of the C6 astrocytoma cells in monolayer, but did not affect their survival as measured by plating efficiency. No changes were seen in spheroid growth or plating efficiency of the cells dissociated from spheroids at this concentration. Diphenylhydantoin at the clinical concentration tested was not associated with an alteration in radiation sensitivity of C6 astrocytoma cells in monolayer or three dimensional multicellular spheroid cultures.

  15. RISC RNA sequencing for context-specific identification of in vivo microRNA targets.

    Science.gov (United States)

    Matkovich, Scot J; Van Booven, Derek J; Eschenbacher, William H; Dorn, Gerald W

    2011-01-07

    MicroRNAs (miRs) are expanding our understanding of cardiac disease and have the potential to transform cardiovascular therapeutics. One miR can target hundreds of individual mRNAs, but existing methodologies are not sufficient to accurately and comprehensively identify these mRNA targets in vivo. To develop methods permitting identification of in vivo miR targets in an unbiased manner, using massively parallel sequencing of mouse cardiac transcriptomes in combination with sequencing of mRNA associated with mouse cardiac RNA-induced silencing complexes (RISCs). We optimized techniques for expression profiling small amounts of RNA without introducing amplification bias and applied this to anti-Argonaute 2 immunoprecipitated RISCs (RISC-Seq) from mouse hearts. By comparing RNA-sequencing results of cardiac RISC and transcriptome from the same individual hearts, we defined 1645 mRNAs consistently targeted to mouse cardiac RISCs. We used this approach in hearts overexpressing miRs from Myh6 promoter-driven precursors (programmed RISC-Seq) to identify 209 in vivo targets of miR-133a and 81 in vivo targets of miR-499. Consistent with the fact that miR-133a and miR-499 have widely differing "seed" sequences and belong to different miR families, only 6 targets were common to miR-133a- and miR-499-programmed hearts. RISC-sequencing is a highly sensitive method for general RISC profiling and individual miR target identification in biological context and is applicable to any tissue and any disease state.

  16. Epigallocatechin-3-gallate increases intracellular [Ca2+] in U87 cells mainly by influx of extracellular Ca2+ and partly by release of intracellular stores.

    Science.gov (United States)

    Kim, Hee Jung; Yum, Keun Sang; Sung, Jong-Ho; Rhie, Duck-Joo; Kim, Myung-Jun; Min, Do Sik; Hahn, Sang June; Kim, Myung-Suk; Jo, Yang-Hyeok; Yoon, Shin Hee

    2004-02-01

    Green tea has been receiving considerable attention as a possible preventive agent against cancer and cardiovascular disease. Epigallocatechin-3-gallate (EGCG) is a major polyphenol component of green tea. Using digital calcium imaging and an assay for [3H]-inositol phosphates, we determined whether EGCG increases intracellular [Ca2+] ([Ca2+]i) in non-excitable human astrocytoma U87 cells. EGCG induced concentration-dependent increases in [Ca2+]i. The EGCG-induced [Ca2+]i increases were reduced to 20.9% of control by removal of extracellular Ca2+. The increases were also inhibited markedly by treatment with the non-specific Ca2+ channel inhibitors cobalt (3 mM) for 3 min and lanthanum (1 mM) for 5 min. The increases were not significantly inhibited by treatment for 10 min with the L-type Ca2+ channel blocker nifedipine (100 nM). Treatment with the inhibitor of endoplasmic reticulum Ca2+-ATPase thapsigargin (1 micro M) also significantly inhibited the EGCG-induced [Ca2+]i increases. Treatment for 15 min with the phospholipase C (PLC) inhibitor neomycin (300 micro M) attenuated the increases significantly, while the tyrosine kinase inhibitor genistein (30 micro M) had no effect. EGCG increased [3H]-inositol phosphates formation via PLC activation. Treatment for 10 min with mefenamic acid (100 micro M) and flufenamic acid (100 micro M), derivatives of diphenylamine-2-carboxylate, blocked the EGCG-induced [Ca2+]i increase in non-treated and thapsigargin-treated cells but indomethacin (100 micro M) did not affect the increases. Collectively, these data suggest that EGCG increases [Ca2+]i in non-excitable U87 cells mainly by eliciting influx of extracellular Ca2+ and partly by mobilizing intracellular Ca2+ stores by PLC activation. The EGCG-induced [Ca2+]i influx is mediated mainly through channels sensitive to diphenylamine-2-carboxylate derivatives.

  17. Imaging characteristics of pilomyxoid astrocytomas in comparison with pilocytic astrocytomas

    International Nuclear Information System (INIS)

    Lee, In Ho; Kim, Ji Hye; Suh, Yeon-Lim; Eo, Hong; Shin, Hyung Jin; Yoo, So-Young; Lee, Kyung Soo

    2011-01-01

    Purpose: Pilomyxoid astrocytoma (PMA) is a recently described astrocytic tumor that has been previously diagnosed as pilocytic astrocytoma (PA). The purpose of this study was to describe the imaging features of PMAs in comparison with PAs. Materials and methods: We retrospectively reviewed CT/MR images and medical records of 10 patients with PMA and 38 patients with PA. The mean ages of patients with PMA and PA were 10 and 15 years, respectively. Imaging features including location, composition, enhancement pattern, presence of calcification, hemorrhage, and leptomeningeal dissemination were compared in patients with two tumor types. Results: Six PMAs (60%) occurred at the suprasellar area and the cerebellum was the most common (45%) site of PA. Solid component was dominant in eight PMAs (80%) and in 19 PAs (50%). All of the PMAs containing solid mass (n = 8) included non-enhancing portion while 12/37 (32%) PAs included non-enhancing solid portion (p < 0.05). Leptomeningeal dissemination was noted in five PMAs (50%) and one PA (3%) (p < 0.05). Other imaging findings were not significantly different. Conclusion: A younger age, more frequent occurrence at the suprasellar area, mainly solid mass containing non-enhancing portion, and more frequent leptomeningeal dissemination are helpful differential features of PMAs as compared to PAs.

  18. C3PO, an endoribonuclease that promotes RNAi by facilitating RISC activation.

    Science.gov (United States)

    Liu, Ying; Ye, Xuecheng; Jiang, Feng; Liang, Chunyang; Chen, Dongmei; Peng, Junmin; Kinch, Lisa N; Grishin, Nick V; Liu, Qinghua

    2009-08-07

    The catalytic engine of RNA interference (RNAi) is the RNA-induced silencing complex (RISC), wherein the endoribonuclease Argonaute and single-stranded small interfering RNA (siRNA) direct target mRNA cleavage. We reconstituted long double-stranded RNA- and duplex siRNA-initiated RISC activities with the use of recombinant Drosophila Dicer-2, R2D2, and Ago2 proteins. We used this core reconstitution system to purify an RNAi regulator that we term C3PO (component 3 promoter of RISC), a complex of Translin and Trax. C3PO is a Mg2+-dependent endoribonuclease that promotes RISC activation by removing siRNA passenger strand cleavage products. These studies establish an in vitro RNAi reconstitution system and identify C3PO as a key activator of the core RNAi machinery.

  19. The nitric oxide donor JS-K sensitizes U87 glioma cells to repetitive irradiation.

    Science.gov (United States)

    Heckler, Max; Osterberg, Nadja; Guenzle, Jessica; Thiede-Stan, Nina Kristin; Reichardt, Wilfried; Weidensteiner, Claudia; Saavedra, Joseph E; Weyerbrock, Astrid

    2017-06-01

    As a potent radiosensitizer nitric oxide (NO) may be a putative adjuvant in the treatment of malignant gliomas which are known for their radio- and chemoresistance. The NO donor prodrug JS-K (O2-(2.4-dinitrophenyl) 1-[(4-ethoxycarbonyl) piperazin-1-yl] diazen-1-ium-1,2-diolate) allows cell-type specific intracellular NO release via enzymatic activation by glutathione-S-transferases overexpressed in glioblastoma multiforme. The cytotoxic and radiosensitizing efficacy of JS-K was assessed in U87 glioma cells in vitro focusing on cell proliferation, induction of DNA damage, and cell death. In vivo efficacy of JS-K and repetitive irradiation were investigated in an orthotopic U87 xenograft model in mice. For the first time, we could show that JS-K acts as a potent cytotoxic and radiosensitizing agent in U87 cells in vitro. This dose- and time-dependent effect is due to an enhanced induction of DNA double-strand breaks leading to mitotic catastrophe as the dominant form of cell death. However, this potent cytotoxic and radiosensitizing effect could not be confirmed in an intracranial U87 xenograft model, possibly due to insufficient delivery into the brain. Although NO donor treatment was well tolerated, neither a retardation of tumor growth nor an extended survival could be observed after JS-K and/or radiotherapy.

  20. Methylation profiles of thirty four promoter-CpG islands and concordant methylation behaviours of sixteen genes that may contribute to carcinogenesis of astrocytoma

    Directory of Open Access Journals (Sweden)

    Wang Yifei

    2004-09-01

    Full Text Available Abstract Background Astrocytoma is a common aggressive intracranial tumor and presents a formidable challenge in the clinic. Association of altered DNA methylation patterns of the promoter CpG islands with the expression profile of cancer-related genes, has been found in many human tumors. Therefore, DNA methylation status as such may serve as an epigenetic biomarker for both diagnosis and prognosis of human tumors, including astrocytoma. Methods We used the methylation specific PCR in conjunction with sequencing verification to establish the methylation profile of the promoter CpG island of thirty four genes in astrocytoma tissues from fifty three patients (The WHO grading:. I: 14, II: 15, III: 12 and IV: 12 cases, respectively. In addition, compatible tissues (normal tissues distant from lesion from three non-astrocytoma patients were included as the control. Results Seventeen genes (ABL, APC, APAF1, BRCA1, CSPG2, DAPK1, hMLH1, LKB1, PTEN, p14ARF, p15INK4b, p27KIP1, p57KIP2, RASSF1C, RB1, SURVIVIN, and VHL displayed a uniformly unmethylated pattern in all the astrocytoma and non-astrocytoma tissues examined. However, the MAGEA1 gene that was inactivated and hypermethylated in non-astrocytoma tissues, was partially demethylated in 24.5% of the astrocytoma tissues (co-existence of the hypermethylated and demethylated alleles. Of the astrocytoma associated hypermethylated genes, the methylation pattern of the CDH13, cyclin a1, DBCCR1, EPO, MYOD1, and p16INK4a genes changed in no more than 5.66% (3/53 of astrocytoma tissues compared to non-astrocytoma controls, while the RASSF1A, p73, AR, MGMT, CDH1, OCT6,, MT1A, WT1, and IRF7 genes were more frequently hypermethylated in 69.8%, 47.2%, 41.5%, 35.8%, 32%, 30.2%, 30.2%, 30.2% and 26.4% of astrocytoma tissues, respectively. Demethylation mediated inducible expression of the CDH13, MAGEA1, MGMT, p73 and RASSF1A genes was established in an astrocytoma cell line (U251, demonstrating that expression of

  1. Evaluation of miR-362 Expression in Astrocytoma of Human Brain Tumors

    Directory of Open Access Journals (Sweden)

    Majid Kheirollahi

    2017-01-01

    Full Text Available Background: Patients affected by gliomas have a poor prognosis. Astrocytoma is a subtype of glioma. Identification of biomarkers could be an effective way to an early diagnosis of tumor or to distinguish more aggressive tumors that need more intensive therapy. In this study, we investigated whether the expression of miR-362 was increased or decreased in patients with different grades of astrocytoma. Materials and Methods: miR-362 expression was compared in 25 patients with astrocytoma with that of 4 normal nonneoplastic brain tissues. Results: In all tumor tissues, the expression of miR-362 was significantly decreased relative to its expression in normal brain tissues. However, there was no significant difference between miR-362 expressions in high and low grades of astrocytoma. Conclusions: In conclusion, miR-362 showed a down-regulation pattern in astrocytoma tissues that was different from the pattern obtained from previously published microarray studies.

  2. Autoantigen La promotes efficient RNAi, antiviral response, and transposon silencing by facilitating multiple-turnover RISC catalysis.

    Science.gov (United States)

    Liu, Ying; Tan, Huiling; Tian, Hui; Liang, Chunyang; Chen, She; Liu, Qinghua

    2011-11-04

    The effector of RNA interference (RNAi) is the RNA-induced silencing complex (RISC). C3PO promotes the activation of RISC by degrading the Argonaute2 (Ago2)-nicked passenger strand of duplex siRNA. Active RISC is a multiple-turnover enzyme that uses the guide strand of siRNA to direct the Ago2-mediated sequence-specific cleavage of complementary mRNA. How this effector step of RNAi is regulated is currently unknown. Here, we used the human Ago2 minimal RISC system to purify Sjögren's syndrome antigen B (SSB)/autoantigen La as an activator of the RISC-mediated mRNA cleavage activity. Our reconstitution studies showed that La could promote multiple-turnover RISC catalysis by facilitating the release of cleaved mRNA from RISC. Moreover, we demonstrated that La was required for efficient RNAi, antiviral defense, and transposon silencing in vivo. Taken together, the findings of C3PO and La reveal a general concept that regulatory factors are required to remove Ago2-cleaved products to assemble or restore active RISC. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Postoperative irradiation of incompletely excised gemistocytic astrocytomas. Clinical outcome and prognostic factors

    International Nuclear Information System (INIS)

    Nowak-Sadzikowska, J.; Glinski, B.; Szpytma, T.; Pluta, E.

    2005-01-01

    Background and purpose: although gemistocytic astrocytomas are considered slow-growing tumors, they often behave aggressively and carry the least favorable prognosis among low-grade astrocytomas. The aim of this study is to evaluate the outcomes and prognostic factors of patients with incompletely excised gemistocytic astrocytomas irradiated postoperatively. Patients and methods: records of 48 patients with incompletely excised gemistocytic astrocytoma, irradiated between 1976 and 1998 at the department of radiation oncology, Maria Sklodowska-curie Memorial Cancer Center, Cracow, Poland, were reviewed. The total dose ranged from 50 to 60 Gy (mean: 59.35, median: 60 Gy) delivered in daily fractions of 2 Gy, 5 days a week. The treatment volume covered the residual tumor with a margin of 1-2 cm. Results: toxicity was acceptable. The overall actuarial survival rates at 5 and 10 years were 30% and 17%, respectively. Age and gender had an influence on overall survival by univariate and multivariate analysis (p < 0.05). Patients ≤ 35 years of age and female patients carried the best prognosis. Conclusion: in most patients with gemistocytic astrocytoma, combined surgery and postoperative radiotherapy result in only short-term survival. Older age is the most important unfavorable prognostic factor in patients with gemistocytic astrocytoma. (orig.)

  4. A scoring system for ascertainment of incident stroke; the Risk Index Score (RISc).

    Science.gov (United States)

    Kass-Hout, T A; Moyé, L A; Smith, M A; Morgenstern, L B

    2006-01-01

    The main objective of this study was to develop and validate a computer-based statistical algorithm that could be translated into a simple scoring system in order to ascertain incident stroke cases using hospital admission medical records data. The Risk Index Score (RISc) algorithm was developed using data collected prospectively by the Brain Attack Surveillance in Corpus Christi (BASIC) project, 2000. The validity of RISc was evaluated by estimating the concordance of scoring system stroke ascertainment to stroke ascertainment by physician and/or abstractor review of hospital admission records. RISc was developed on 1718 randomly selected patients (training set) and then statistically validated on an independent sample of 858 patients (validation set). A multivariable logistic model was used to develop RISc and subsequently evaluated by goodness-of-fit and receiver operating characteristic (ROC) analyses. The higher the value of RISc, the higher the patient's risk of potential stroke. The study showed RISc was well calibrated and discriminated those who had potential stroke from those that did not on initial screening. In this study we developed and validated a rapid, easy, efficient, and accurate method to ascertain incident stroke cases from routine hospital admission records for epidemiologic investigations. Validation of this scoring system was achieved statistically; however, clinical validation in a community hospital setting is warranted.

  5. Malignant transformation of a chiasmatic pilocytic astrocytoma in a patient with diencephalic syndrome

    International Nuclear Information System (INIS)

    Wal, Ester P.J. van der; Edwards-Brown, Mary; Azzarelli, Biagio

    2003-01-01

    Chiasmatic gliomas with metastatic spread are rare in children and are usually associated with diencephalic syndrome. They are mostly pilocytic astrocytomas and their transformation to high-grade astrocytomas has never previously been reported in the pediatric population. We report leptomeningeal spread of a chiasmatic pilocytic astrocytoma in a child presenting with diencephalic syndrome. He was treated with chemotherapy and radiation. The tumor recurred with transformation into a high-grade astrocytoma. Radiation therapy may have played a role in transformation of the tumor, but more research is needed to further clarify the biological behavior of this tumor. (orig.)

  6. A study on the effectiveness of lockup-free caches for a Reduced Instruction Set Computer (RISC) processor

    OpenAIRE

    Tharpe, Leonard.

    1992-01-01

    Approved for public release; distribution is unlimited This thesis presents a simulation and analysis of the Reduced Instruction Set Computer (RISC) architecture and the effects on RISC performance of a lockup-free cache interface. RISC architectures achieve high performance by having a small, but sufficient, instruction set with most instructions executing in one clock cycle. Current RISC performance range from 1.5 to 2.0 CPI. The goal of RISC is to attain a CPI of 1.0. The major hind...

  7. Metabolic impact of anti-angiogenic agents on U87 glioma cells.

    Directory of Open Access Journals (Sweden)

    Tanja Mesti

    Full Text Available BACKGROUND: Glioma cells not only secrete high levels of vascular endothelial growth factor (VEGF but also express VEGF receptors (VEGFR, supporting the existence of an autocrine loop. The direct impact on glioma cells metabolism of drugs targeting the VEGF pathway, such as Bevacizumab (Bev or VEGFR Tyrosine Kinase Inhibitor (TKI, is poorly known. MATERIAL AND METHODS: U87 cells were treated with Bev or SU1498, a selective VEGFR2 TKI. VEGFR expression was checked with FACS flow cytometry and Quantitative Real-Time PCR. VEGF secretion into the medium was assessed with an ELISA kit. Metabolomic studies on cells were performed using High Resolution Magic Angle Spinning Spectroscopy (HR-MAS. RESULTS: U87 cells secreted VEGF and expressed low level of VEGFR2, but no detectable VEGFR1. Exposure to SU1498, but not Bev, significantly impacted cell proliferation and apoptosis. Metabolomic studies with HR MAS showed that Bev had no significant effect on cell metabolism, while SU1498 induced a marked increase in lipids and a decrease in glycerophosphocholine. Accordingly, accumulation of lipid droplets was seen in the cytoplasm of SU1498-treated U87 cells. CONCLUSION: Although both drugs target the VEGF pathway, only SU1498 showed a clear impact on cell proliferation, cell morphology and metabolism. Bevacizumab is thus less likely to modify glioma cells phenotype due to a direct therapeutic pressure on the VEGF autocrine loop. In patients treated with VEGFR TKI, monitoring lipids with magnetic resonance spectroscopic (MRS might be a valuable marker to assess drug cytotoxicity.

  8. Increased RNA-induced silencing complex (RISC) activity contributes to hepatocellular carcinoma.

    Science.gov (United States)

    Yoo, Byoung Kwon; Santhekadur, Prasanna K; Gredler, Rachel; Chen, Dong; Emdad, Luni; Bhutia, Sujit; Pannell, Lewis; Fisher, Paul B; Sarkar, Devanand

    2011-05-01

    There is virtually no effective treatment for advanced hepatocellular carcinoma (HCC) and novel targets need to be identified to develop effective treatment. We recently documented that the oncogene Astrocyte elevated gene-1 (AEG-1) plays a seminal role in hepatocarcinogenesis. Employing yeast two-hybrid assay and coimmunoprecipitation followed by mass spectrometry, we identified staphylococcal nuclease domain containing 1 (SND1), a nuclease in the RNA-induced silencing complex (RISC) facilitating RNAi-mediated gene silencing, as an AEG-1 interacting protein. Coimmunoprecipitation and colocalization studies confirmed that AEG-1 is also a component of RISC and both AEG-1 and SND1 are required for optimum RISC activity facilitating small interfering RNA (siRNA) and micro RNA (miRNA)-mediated silencing of luciferase reporter gene. In 109 human HCC samples SND1 was overexpressed in ≈74% cases compared to normal liver. Correspondingly, significantly higher RISC activity was observed in human HCC cells compared to immortal normal hepatocytes. Increased RISC activity, conferred by AEG-1 or SND1, resulted in increased degradation of tumor suppressor messenger RNAs (mRNAs) that are target of oncomiRs. Inhibition of enzymatic activity of SND1 significantly inhibited proliferation of human HCC cells. As a corollary, stable overexpression of SND1 augmented and siRNA-mediated inhibition of SND1 abrogated growth of human HCC cells in vitro and in vivo, thus revealing a potential role of SND1 in hepatocarcinogenesis. We unravel a novel mechanism that overexpression of AEG-1 and SND1 leading to increased RISC activity might contribute to hepatocarcinogenesis. Targeted inhibition of SND1 enzymatic activity might be developed as an effective therapy for HCC. Copyright © 2011 American Association for the Study of Liver Diseases.

  9. RTEL1 and TERT polymorphisms are associated with astrocytoma risk in the Chinese Han population.

    Science.gov (United States)

    Jin, Tian-Bo; Zhang, Jia-Yi; Li, Gang; Du, Shu-Li; Geng, Ting-Ting; Gao, Jing; Liu, Qian-Ping; Gao, Guo-Dong; Kang, Long-Li; Chen, Chao; Li, Shan-Qu

    2013-12-01

    Common variants of multiple genes play a role in glioma onset. However, research related to astrocytoma, the most common primary brain neoplasm, is rare. In this study, we chose 21 tagging SNPs (tSNPs), previously reported to be associated with glioma risk in a Chinese case-control study from Xi'an, China, and identified their contributions to astrocytoma susceptibility. We found an association with astrocytoma susceptibility for two tSNPs (rs6010620 and rs2853676) in two different genes: regulator of telomere elongation helicase 1 (RTEL1) and telomerase reverse transcriptase (TERT), respectively. We confirmed our results using recessive, dominant, and additive models. In the recessive model, we found two tSNPs (rs2297440 and rs6010620) associated with increased astrocytoma risk. In the dominant model, we found that rs2853676 was associated with increased astrocytoma risk. In the additive model, all three tSNPs (rs2297440, rs2853676, and rs6010620) were associated with increased astrocytoma risk. Our results demonstrate, for the first time, the potential roles of RTEL1 and TERT in astrocytoma development.

  10. A case of astrocytoma, 19 year history after BNCT

    International Nuclear Information System (INIS)

    Kamano, Shuji

    2006-01-01

    A 39-year-old man had received Boron Neutron Capture Therapy (BNCT) in 1987 for a Grade II Astrocytoma. He gradually exacerbated and received a second operation in 1994. The mass taken in the second operation is almost competent with radiation necrosis. Following that, he shows no signs of recurrence. Currently, he has returned to full time employment in physical labor. This case suggests effectiveness of BNCT for rather low-grade astrocytomas. (author)

  11. Modeled microgravity suppressed invasion and migration of human glioblastoma U87 cells through downregulating store-operated calcium entry

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Zi-xuan [Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 (China); Rao, Wei [Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 (China); Wang, Huan [Department of Dermatology, Tangdu Hospital, Fourth Military Medical University, Xi' an, 710032 (China); Wang, Nan-ding [Department of Cardiology, Xi' an Traditional Chinese Medicine Hospital, Xi' an, 710032 (China); Si, Jing-Wen; Zhao, Jiao; Li, Jun-chang [Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 (China); Wang, Zong-ren, E-mail: zongren@fmmu.edu.cn [Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 (China)

    2015-02-13

    Glioblastoma is the most common brain tumor and is characterized with robust invasion and migration potential resulting in poor prognosis. Previous investigations have demonstrated that modeled microgravity (MMG) could decline the cell proliferation and attenuate the metastasis potential in several cell lines. In this study, we studied the effects of MMG on the invasion and migration potentials of glioblastoma in human glioblastoma U87 cells. We found that MMG stimulation significantly attenuated the invasion and migration potentials, decreased thapsigargin (TG) induced store-operated calcium entry (SOCE) and downregulated the expression of Orai1 in U87 cells. Inhibition of SOCE by 2-APB or stromal interaction molecule 1 (STIM1) downregulation both mimicked the effects of MMG on the invasion and migration potentials in U87 cells. Furthermore, upregulation of Orai1 significantly weakened the effects of MMG on the invasion and migration potentials in U87 cells. Therefore, these findings indicated that MMG stimulation inhibited the invasion and migration potentials of U87 cells by downregulating the expression of Orai1 and sequentially decreasing the SOCE, suggesting that MMG might be a new potential therapeutic strategy in glioblastoma treatment in the future. - Highlights: • Modeled microgravity (MMG) suppressed migration and invasion in U87 cells. • MMG downregulated the SOCE and the expression of Orai1. • SOCE inhibition mimicked the effects of MMG on migration and invasion potentials. • Restoration of SOCE diminished the effects of MMG on migration and invasion.

  12. Modeled microgravity suppressed invasion and migration of human glioblastoma U87 cells through downregulating store-operated calcium entry

    International Nuclear Information System (INIS)

    Shi, Zi-xuan; Rao, Wei; Wang, Huan; Wang, Nan-ding; Si, Jing-Wen; Zhao, Jiao; Li, Jun-chang; Wang, Zong-ren

    2015-01-01

    Glioblastoma is the most common brain tumor and is characterized with robust invasion and migration potential resulting in poor prognosis. Previous investigations have demonstrated that modeled microgravity (MMG) could decline the cell proliferation and attenuate the metastasis potential in several cell lines. In this study, we studied the effects of MMG on the invasion and migration potentials of glioblastoma in human glioblastoma U87 cells. We found that MMG stimulation significantly attenuated the invasion and migration potentials, decreased thapsigargin (TG) induced store-operated calcium entry (SOCE) and downregulated the expression of Orai1 in U87 cells. Inhibition of SOCE by 2-APB or stromal interaction molecule 1 (STIM1) downregulation both mimicked the effects of MMG on the invasion and migration potentials in U87 cells. Furthermore, upregulation of Orai1 significantly weakened the effects of MMG on the invasion and migration potentials in U87 cells. Therefore, these findings indicated that MMG stimulation inhibited the invasion and migration potentials of U87 cells by downregulating the expression of Orai1 and sequentially decreasing the SOCE, suggesting that MMG might be a new potential therapeutic strategy in glioblastoma treatment in the future. - Highlights: • Modeled microgravity (MMG) suppressed migration and invasion in U87 cells. • MMG downregulated the SOCE and the expression of Orai1. • SOCE inhibition mimicked the effects of MMG on migration and invasion potentials. • Restoration of SOCE diminished the effects of MMG on migration and invasion

  13. Evaluation of invasiveness of astrocytoma using 1H-magnetic resonance spectroscopy: correlation with expression of matrix metalloproteinase-2

    International Nuclear Information System (INIS)

    Zhang, Kai; Li, Chuanfu; Ma, Xiangxing; Meng, Xiangshui; Feng, Dechao; Liu, Ying; Li, Li

    2007-01-01

    Even low-grade astrocytomas infiltrate the entire brain, a feature that precludes their successful therapy. So to assess the invasive potential of astrocytoma is very important. The aim of this study was determine whether there is a significant correlation between the results of 1 H-magnetic resonance spectroscopy ( 1 H-MRS) and tumor invasive potential of astrocytoma, which is reflected by expression of matrix metalloproteinase-2 (MMP-2). The 1 H-MRS spectra of 41 histologically verified astrocytomas were obtained on a 3-T MR scanner. According to the World Health Organization classification criteria for central nervous system tumors, there were 16 low-grade astrocytomas (2 pilocytic astrocytomas, 14 grade II astrocytomas) and 25 high-grade astrocytomas (5 anaplastic astrocytomas, 20 glioblastomas).The choline/N-acetylaspartate (Cho/NAA) and choline/creatine (Cho/Cr) ratios were calculated. Of the 41 astrocytomas, 19 (8 low-grade and 11 high-grade) were analyzed immunohistochemically. Expression of MMP-2 was determined using streptavidin-peroxidase complex (SP) staining which was quantified by calculating its calibrated opacity density (COD) using an image analysis system. The correlations between metabolite ratios and the quantitative data from the immunohistochemical tests in the 19 astrocytomas were determined. The Cho/NAA and Cho/Cr ratios of high-grade astrocytoma were both significantly greater than those of low-grade astrocytoma (t = -6.222, P = 0.000; t = -6.533, P = 0.000, respectively). MMP-2 COD values of high-grade astrocytomas were also significantly greater than those of low-grade astrocytomas (t = -5.892, P 0.000). There were strong positive correlations between Cho/NAA ratio and MMP-2 COD (r = 0.669, P = 0.002), and between Cho/Cr ratio and MMP-2 COD (r = 0.689, P = 0.001). 1 H-MRS is helpful in evaluating the invasiveness of astrocytomas and predicting prognosis preoperatively by determining the Cho/NAA and Cho/Cr ratios. (orig.)

  14. ADAR2 editing activity in newly diagnosed versus relapsed pediatric high-grade astrocytomas

    International Nuclear Information System (INIS)

    Tomaselli, Sara; Galeano, Federica; Massimi, Luca; Di Rocco, Concezio; Lauriola, Libero; Mastronuzzi, Angela; Locatelli, Franco; Gallo, Angela

    2013-01-01

    High-grade (WHO grade III and IV) astrocytomas are aggressive malignant brain tumors affecting humans with a high risk of recurrence in both children and adults. To date, limited information is available on the genetic and molecular alterations important in the onset and progression of pediatric high-grade astrocytomas and, even less, on the prognostic factors that influence long-term outcome in children with recurrence. A-to-I RNA editing is an essential post-transcriptional mechanism that can alter the nucleotide sequence of several RNAs and is mediated by the ADAR enzymes. ADAR2 editing activity is particularly important in mammalian brain and is impaired in both adult and pediatric high-grade astrocytomas. Moreover, we have recently shown that the recovered ADAR2 activity in high-grade astrocytomas inhibits in vivo tumor growth. The aim of the present study is to investigate whether changes may occur in ADAR2-mediated RNA editing profiles of relapsed high-grade astrocytomas compared to their respective specimens collected at diagnosis, in four pediatric patients. Total RNAs extracted from all tumor samples and controls were tested for RNA editing levels (by direct sequencing on cDNA pools) and for ADAR2 mRNA expression (by qRT-PCR). A significant loss of ADAR2-editing activity was observed in the newly diagnosed and recurrent astrocytomas in comparison to normal brain. Surprisingly, we found a substantial rescue of ADAR2 editing activity in the relapsed tumor of the only patient showing prolonged survival. High-grade astrocytomas display a generalized loss of ADAR2-mediated RNA editing at both diagnosis and relapse. However, a peculiar Case, in complete remission of disease, displayed a total rescue of RNA editing at relapse, intriguingly suggesting ADAR2 activity/expression as a possible marker for long-term survival of patients with high-grade astrocytomas

  15. Optical RISC computer

    Science.gov (United States)

    Guilfoyle, Peter S.; Stone, Richard V.; Hessenbruch, John M.; Zeise, Frederick F.

    1993-07-01

    A second generation digital optical computer (DOC II) has been developed which utilizes a RISC based operating system as its host. This 32 bit, high performance (12.8 GByte/sec), computing platform demonstrates a number of basic principals that are inherent to parallel free space optical interconnects such as speed (up to 1012 bit operations per second) and low power 1.2 fJ per bit). Although DOC II is a general purpose machine, special purpose applications have been developed and are currently being evaluated on the optical platform.

  16. Complement activation in astrocytomas: deposition of C4d and patient outcome

    International Nuclear Information System (INIS)

    Mäkelä, Katri; Helén, Pauli; Haapasalo, Hannu; Paavonen, Timo

    2012-01-01

    C4d is a cleavage product of complement component C4 and is considered to serve as a marker for the site of complement activation. In this study C4d staining of grade I-IV astrocytic tumors was studied to explore if there is an association between complement activation and the grade of tumor, or patient survival. Tissue micro-array samples of 102 astrocytomas were stained immunohistochemically. The material consisted of 9 pilocytic astrocytomas and 93 grade II-IV astrocytomas, of which 67 were primary resections and 26 recurrent tumors. The intensity of C4d staining as well as extent of C4d and CD34 staining were evaluated. The intensity of C4d staining was scored semiquantitatively. The extent of the staining was counted morphometrically with a point counting grid yielding a percent of C4d and CD34 positive area of the sample. The intensity and extent of C4d staining increased in grade II-IV diffusely infiltrating astrocytoma tumors in line with the malignancy grade (p = 0.034 and p = 0.016, respectively, Kruskal-Wallis test). However, C4d positive tumor area percentages were higher in grade I pilocytic astrocytomas than in grade II-IV diffusely infiltrating astrocytomas (p = 0.041, Mann–Whitney test). There was a significant correlation between CD34 positive and C4d positive endothelial area fraction in diffusely infiltrating astrocytomas (p < 0.001, Pearson correlation). In these tumors, the increasing intensity of C4d staining was also associated with worsened patient outcome (p = 0.014, log-rank test). The worsening of patient outcome and malignant progression of tumor cells seem to be connected to microenvironmental changes evoked by chronically activated complement

  17. Argonaute pull-down and RISC analysis using 2'-O-methylated oligonucleotides affinity matrices.

    Science.gov (United States)

    Jannot, Guillaume; Vasquez-Rifo, Alejandro; Simard, Martin J

    2011-01-01

    During the last decade, several novel small non-coding RNA pathways have been unveiled, which reach out to many biological processes. Common to all these pathways is the binding of a small RNA molecule to a protein member of the Argonaute family, which forms a minimal core complex called the RNA-induced silencing complex or RISC. The RISC targets mRNAs in a sequence-specific manner, either to induce mRNA cleavage through the intrinsic activity of the Argonaute protein or to abrogate protein synthesis by a mechanism that is still under investigation. We describe here, in details, a method for the affinity chromatography of the let-7 RISC starting from extracts of the nematode Caenorhabditis elegans. Our method exploits the sequence specificity of the RISC and makes use of biotinylated and 2'-O-methylated oligonucleotides to trap and pull-down small RNAs and their associated proteins. Importantly, this technique may easily be adapted to target other small RNAs expressed in different cell types or model organisms. This method provides a useful strategy to identify the proteins associated with the RISC, and hence gain insight in the functions of small RNAs.

  18. Expression and prognostic impact of matrix metalloproteinase-2 (MMP-2) in astrocytomas

    DEFF Research Database (Denmark)

    Ramachandran, Rahimsan K.; Sørensen, Mia D.; Aaberg-Jessen, Charlotte

    2017-01-01

    with diffuse astrocytoma, anaplastic astrocytoma and glioblastoma were stained immunohistochemically using a monoclonal MMP-2 antibody. The MMP-2 intensity in cytoplasm/membrane was quantified by a trained software-based classifier using systematic random sampling in 10% of the tumor area. We found MMP-2...... of this tumor. Matrix metalloproteinase-2 (MMP-2) is an extracellular matrix degrading enzyme which has been shown to play important roles in different cancers. The aim of this study was to investigate the expression and prognostic potential of MMP-2 in astrocytomas. Tissue samples from 89 patients diagnosed...

  19. The RISC-spectrometer experiment

    International Nuclear Information System (INIS)

    Pinter, Gy.

    1981-01-01

    The RISC (Relativistic Ionising Streamer Chamber) spectrometer (situated at Protvino, joining the accelerator) is discussed, and the experiment carried out in international cooperation is presented. The beam monitor, the trigger system and the control and data recording system as well as the streamer spark chamber are detailed (the latter is the largest of our time). Examples of the main experiments as well as the work carried out in Budapest are discussed briefly. (Sz.J.)

  20. Anorexia: an early sign of fourth ventricle astrocytoma in children.

    Science.gov (United States)

    Leroy, Henri-Arthur; Baroncini, Marc; Delestret, Isabelle; Florent, Vincent; Vinchon, Matthieu

    2014-12-01

    Paediatric low-grade astrocytomas of the fourth ventricle are rare tumours, generally revealed by hydrocephalus. However, some patients present with a history of severe anorexia. It might be a harbinger, which if recognized, could lead to earlier diagnosis. We decided to examine our database in order to evaluate the incidence and signification of anorexia in this context. Retrospective monocentric study of cases of low-grade astrocytomas of the fourth ventricle operated between 1991 and 2012 in our paediatric neurosurgery department. We particularly observed the clinical presentation and long-term clinical, oncological and radiological evolution. Non-parametrical tests were used (Mann-Whitney, Fisher). We reviewed 34 cases, 31 pilocytic astrocytomas and 3 diffuse astrocytomas, 16 boys and 18 girls, (M/F ratio 0.89). Mean age at diagnosis was 8 years old. Seven presented with notable anorexia, the average BMI in this group was ≤2 standard deviation (SD); with clinical signs evolving for 11.5 months. Twenty-seven children had no anorexia; average BMI in this group was +1 SD, with clinical evolution for 6 months on an average of p anorexia, body mass index improved markedly in the postoperative follow-up, which lasted, on average, for 6 years. Anorexia with stunted body weight curve is a non-exceptional presentation in children with low-grade astrocytomas of the fourth ventricle. Unexplained or atypical anorexia with negative etiologic assessment should prompt cerebral imaging. Clinical improvement after surgical resection, could suggest a possible interaction between tumour tissue and appetite-suppressing peptide secretion.

  1. Retinal astrocytoma in a dog.

    Science.gov (United States)

    Kuroki, Keiichi; Kice, Nathan; Ota-Kuroki, Juri

    2017-09-01

    A miniature schnauzer dog presenting with hyphema and glaucoma of the right eye had a retinal neoplasm. Neoplastic cells stained positively for glial fibrillary acidic protein, vimentin, and S-100 and largely negatively for oligodendrocyte transcription factor 2 by immunohistochemistry. The clinical and histopathological features of canine retinal astrocytomas are discussed.

  2. Anatomy of RISC: how do small RNAs and chaperones activate Argonaute proteins?

    Science.gov (United States)

    Nakanishi, Kotaro

    2016-09-01

    RNA silencing is a eukaryote-specific phenomenon in which microRNAs and small interfering RNAs degrade messenger RNAs containing a complementary sequence. To this end, these small RNAs need to be loaded onto an Argonaute protein (AGO protein) to form the effector complex referred to as RNA-induced silencing complex (RISC). RISC assembly undergoes multiple and sequential steps with the aid of Hsc70/Hsp90 chaperone machinery. The molecular mechanisms for this assembly process remain unclear, despite their significance for the development of gene silencing techniques and RNA interference-based therapeutics. This review dissects the currently available structures of AGO proteins and proposes models and hypotheses for RISC assembly, covering the conformation of unloaded AGO proteins, the chaperone-assisted duplex loading, and the slicer-dependent and slicer-independent duplex separation. The differences in the properties of RISC between prokaryotes and eukaryotes will also be clarified. WIREs RNA 2016, 7:637-660. doi: 10.1002/wrna.1356 For further resources related to this article, please visit the WIREs website. © 2016 The Authors. WIREs RNA published by Wiley Periodicals, Inc.

  3. Wnt/β-catenin pathway involvement in ionizing radiation-induced invasion of U87 glioblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Zhen [Huazhong University of Science and Technology, Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Wuhan (China); Zhou, Lin [Huazhong University of Science and Technology, Department of Histoembryology, Tongji Medical College, Wuhan (China); Han, Na; Zhang, Mengxian [Huazhong University of Science and Technology, Department of Oncology, Tongji Hospital, Tongji Medical College, Wuhan (China); Lyu, Xiaojuan [Huazhong University of Science and Technology, Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Wuhan (China)

    2015-08-15

    Radiotherapy has been reported to promote the invasion of glioblastoma cells; however, the underlying mechanisms remain unclear. Here, we investigated the role of the Wnt/β-catenin pathway in radiation-induced invasion of glioblastoma cells. U87 cells were irradiated with 3 Gy or sham irradiated in the presence or absence of the Wnt/β-catenin pathway inhibitor XAV 939. Cell invasion was determined by an xCELLigence real-time cell analyser and matrigel invasion assays. The intracellular distribution of β-catenin in U87 cells with or without irradiation was examined by immunofluorescence and Western blotting of nuclear fractions. We next investigated the effect of irradiation on Wnt/β-catenin pathway activity using TOP/FOP flash luciferase assays and quantitative polymerase chain reaction analysis of β-catenin target genes. The expression levels and activities of two target genes, matrix metalloproteinase (MMP)-2 and MMP-9, were examined further by Western blotting and zymography. U87 cell invasiveness was increased significantly by ionizing radiation. Interestingly, ionizing radiation induced nuclear translocation and accumulation of β-catenin. Moreover, we found increased β-catenin/TCF transcriptional activities, followed by up-regulation of downstream genes in the Wnt/β-catenin pathway in irradiated U87 cells. Importantly, inhibition of the Wnt/β-catenin pathway by XAV 939, which promotes degradation of β-catenin, significantly abrogated the pro-invasion effects of irradiation. Mechanistically, XAV 939 suppressed ionizing radiation-triggered up-regulation of MMP-2 and MMP-9, and inhibited the activities of these gelatinases. Our data demonstrate a pivotal role of the Wnt/β-catenin pathway in ionizing radiation-induced invasion of glioblastoma cells, and suggest that targeting β-catenin is a promising therapeutic approach to overcoming glioma radioresistance. (orig.) [German] Studien haben gezeigt, dass eine Strahlentherapie die Invasivitaet von

  4. Holocord low grade astrocytoma - Role of radical irradiation and chemotherapy

    International Nuclear Information System (INIS)

    Goyal, S.; Puri, T.; Julka, R.K.

    2015-01-01

    Spinal intradural tumors, especially those extending along the entire length of the spinal cord, termed as ‘holocord’ tumors are uncommon. Most of these are gliomas, with astrocytomas (low grade) predominating in children and ependymomas in adults. Other histologies, though reported, are even rarer. Management is debatable, with both surgery and radiotherapy of such extensive tumors posing challenges. We describe a case of a 14-year-old girl with holocord astrocytoma extending from cervicomedullary junction till lumbar spine, who recovered full neurological function following radical irradiation of entire spine followed by temozolomide-based chemotherapy. No grade 3/4 bone marrow morbidity was seen. Five years following treatment, she maintained normal neurological function and apparently normal pubertal and skeletal growth despite residual disease visible on imaging. Literature review of existing reports of holocord astrocytomas highlighting management and outcome is presented.

  5. Psychometrische kwaliteiten van de Recidive Inschattingsschalen (RISc) : Interbeoordelaarsbetrouwbaarheid, interne consistentie en congruente validiteit

    NARCIS (Netherlands)

    Knaap, L.M. van der; Leenarts, L.E.W.; Nijssen, L.T.J.

    2007-01-01

    Het instrument Recidive Inschattings Schalen (RISc) is gebaseerd op een Engelstalig instrument (OASys). Tijdens de ontwikkeling van de RISc is aandacht besteed aan de vertaling van het instrument, aan de kwaliteit van de items en aan de interne consistentie van de schalen van het instrument. Verder

  6. Slicer-independent mechanism drives small-RNA strand separation during human RISC assembly.

    Science.gov (United States)

    Park, June Hyun; Shin, Chanseok

    2015-10-30

    Small RNA silencing is mediated by the effector RNA-induced silencing complex (RISC) that consists of an Argonaute protein (AGOs 1-4 in humans). A fundamental step during RISC assembly involves the separation of two strands of a small RNA duplex, whereby only the guide strand is retained to form the mature RISC, a process not well understood. Despite the widely accepted view that 'slicer-dependent unwinding' via passenger-strand cleavage is a prerequisite for the assembly of a highly complementary siRNA into the AGO2-RISC, here we show by careful re-examination that 'slicer-independent unwinding' plays a more significant role in human RISC maturation than previously appreciated, not only for a miRNA duplex, but, unexpectedly, for a highly complementary siRNA as well. We discovered that 'slicer-dependency' for the unwinding was affected primarily by certain parameters such as temperature and Mg(2+). We further validate these observations in non-slicer AGOs (1, 3 and 4) that can be programmed with siRNAs at the physiological temperature of humans, suggesting that slicer-independent mechanism is likely a common feature of human AGOs. Our results now clearly explain why both miRNA and siRNA are found in all four human AGOs, which is in striking contrast to the strict small-RNA sorting system in Drosophila. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  7. RISC-Target Interaction: Cleavage and Translational Suppression

    Science.gov (United States)

    van den Berg, Arjen; Mols, Johann; Han, Jiahuai

    2008-01-01

    Summary Small RNA molecules have been known and utilized to suppress gene expression for more than a decade. The discovery that these small RNA molecules are endogenously expressed in many organisms and have a critical role in controlling gene expression have led to the arising of a whole new field of research. Termed small interfering RNA (siRNA) or microRNA (miRNA) these ~22 nt RNA molecules have the capability to suppress gene expression through various mechanisms once they are incorporated in the multi-protein RNA-Induced Silencing Complex (RISC) and interact with their target mRNA. This review introduces siRNAs and microRNAs in a historical perspective and focuses on the key molecules in RISC, structural properties and mechanisms underlying the process of small RNA regulated post-transcriptional suppression of gene expression. PMID:18692607

  8. Expression of estrogen and progesterone receptors in astrocytomas: a literature review

    Directory of Open Access Journals (Sweden)

    Cléciton Braga Tavares

    Full Text Available Gliomas are the most common type of primary central nervous system neoplasm. Astrocytomas are the most prevalent type of glioma and these tumors may be influenced by sex steroid hormones. A literature review for the presence of estrogen and progesterone receptors in astrocytomas was conducted in the PubMed database using the following MeSH terms: “estrogen receptor beta” OR “estrogen receptor alpha” OR “estrogen receptor antagonists” OR “progesterone receptors” OR “astrocytoma” OR “glioma” OR “glioblastoma”. Among the 111 articles identified, 13 studies met our inclusion criteria. The majority of reports showed the presence of estrogen and progesterone receptors in astrocytomas. Overall, higher tumor grades were associated with decreased estrogen receptor expression and increased progesterone receptor expression.

  9. Expression of estrogen and progesterone receptors in astrocytomas: a literature review

    Science.gov (United States)

    Tavares, Cléciton Braga; Gomes-Braga, Francisca das Chagas Sheyla Almeida; Costa-Silva, Danylo Rafhael; Escórcio-Dourado, Carla Solange; Borges, Umbelina Soares; Conde, Airton Mendes; da Conceição Barros-Oliveira, Maria; Sousa, Emerson Brandão; da Rocha Barros, Lorena; Martins, Luana Mota; Facina, Gil; da-Silva, Benedito Borges

    2016-01-01

    Gliomas are the most common type of primary central nervous system neoplasm. Astrocytomas are the most prevalent type of glioma and these tumors may be influenced by sex steroid hormones. A literature review for the presence of estrogen and progesterone receptors in astrocytomas was conducted in the PubMed database using the following MeSH terms: “estrogen receptor beta” OR “estrogen receptor alpha” OR “estrogen receptor antagonists” OR “progesterone receptors” OR “astrocytoma” OR “glioma” OR “glioblastoma”. Among the 111 articles identified, 13 studies met our inclusion criteria. The majority of reports showed the presence of estrogen and progesterone receptors in astrocytomas. Overall, higher tumor grades were associated with decreased estrogen receptor expression and increased progesterone receptor expression. PMID:27626480

  10. A Fault-tolerant RISC Microprocessor for Spacecraft Applications

    Science.gov (United States)

    Timoc, Constantin; Benz, Harry

    1990-01-01

    Viewgraphs on a fault-tolerant RISC microprocessor for spacecraft applications are presented. Topics covered include: reduced instruction set computer; fault tolerant registers; fault tolerant ALU; and double rail CMOS logic.

  11. Ammonium-induced calcium mobilization in 1321N1 astrocytoma cells

    International Nuclear Information System (INIS)

    Hillmann, Petra; Koese, Meryem; Soehl, Kristina; Mueller, Christa E.

    2008-01-01

    High blood levels of ammonium/ammonia (NH 4 + /NH 3 ) are associated with severe neurotoxicity as observed in hepatic encephalopathy (HE). Astrocytes are the main targets of ammonium toxicity, while neuronal cells are less vulnerable. In the present study, an astrocytoma cell line 1321N1 and a neuroblastoma glioma hybrid cell line NG108-15 were used as model systems for astrocytes and neuronal cells, respectively. Ammonium salts evoked a transient increase in intracellular calcium concentrations ([Ca 2+ ] i ) in astrocytoma (EC 50 = 6.38 mM), but not in NG108-15 cells. The ammonium-induced increase in [Ca 2+ ] i was due to an intracellular effect of NH 4 + /NH 3 and was independent of extracellular calcium. Acetate completely inhibited the ammonium effect. Ammonium potently reduced calcium signaling by G q protein-coupled receptors (H 1 and M3) expressed on the cells. Ammonium (5 mM) also significantly inhibited the proliferation of 1321N1 astrocytoma cells. While mRNA for the mammalian ammonium transporters RhBG and RhCG could not be detected in 1321N1 astrocytoma cells, both transporters were expressed in NG108-15 cells. RhBG and RhBC in brain may promote the excretion of NH 3 /NH 4 + from neuronal cells. Cellular uptake of NH 4 + /NH 3 was mainly by passive diffusion of NH 3 . Human 1321N1 astrocytoma cells appear to be an excellent, easily accessible human model for studying HE, which can substitute animal studies, while NG108-15 cells may be useful for investigating the role of the recently discovered Rhesus family type ammonium transporters in neuronal cells. Our findings may contribute to the understanding of pathologic ammonium effects in different brain cells, and to the treatment of hyperammonemia

  12. Current treatment of low grade astrocytoma

    DEFF Research Database (Denmark)

    Pedersen, Christina Louise; Romner, Bertil

    2013-01-01

    Through a comprehensive review of the current literature, the present article investigates several aspects of low grade astrocytomas (LGA), including prognostic factors, treatment strategies and follow-up regimes. LGA are in general relatively slow-growing primary brain tumours, but they have a v...... effective in discriminating between tumour progression and radiation necrosis. The research into biomarkers is currently limited with regards to their applications in LGA diagnostics, and therefore further studies including larger patient populations are needed.......Through a comprehensive review of the current literature, the present article investigates several aspects of low grade astrocytomas (LGA), including prognostic factors, treatment strategies and follow-up regimes. LGA are in general relatively slow-growing primary brain tumours, but they have...... as the course of disease. The current literature seems to support the idea that treatment with radical tumour resection, where possible, yields better long term outcome for patients with LGA. However, adjuvant therapy is often necessary. Administering early postoperative radiotherapy to patients with partially...

  13. Psychometric Evaluation of the Connor-Davidson Resilience Scale (CD-RISC) Using Iranian Students

    Science.gov (United States)

    Khoshouei, Mahdieh Sadat

    2009-01-01

    The purpose of this study was to evaluate the psychometric properties of the Persian version of the Connor-Davidson Resilience Scale (CD-RISC). The CD-RISC was completed by a sample of 323 Isfahan university students (168 females, 155 males) aged 19-34 years. A maximum likelihood method with an oblique solution resulted in four factors…

  14. AVR RISC microcontroller handbook

    CERN Document Server

    Kuhnel, Claus

    1998-01-01

    The AVR RISC Microcontroller Handbook is a comprehensive guide to designing with Atmel's new controller family, which is designed to offer high speed and low power consumption at a lower cost. The main text is divided into three sections: hardware, which covers all internal peripherals; software, which covers programming and the instruction set; and tools, which explains using Atmel's Assembler and Simulator (available on the Web) as well as IAR's C compiler.Practical guide for advanced hobbyists or design professionalsDevelopment tools and code available on the Web

  15. RISC processing in Fastbus

    International Nuclear Information System (INIS)

    Atiya, M.; Haggerty, J.; Ng, C.; Sambamurti, A.; Strzelinski, R.

    1990-01-01

    This paper reports on the designed, construction and testing microprocessor based controller for data acquisition and analysis conforming to the IEEE-960 Fastbus standard. The controller uses the RISC AM29000 processor and the Am29027 floating point co-processor. The module functions as a Fastbus slave and is used for analysis and filtering of digitially sampled waveforms acquired in a large system of high performance transient digitizers (over 200 channels, each sampling at 500 MHz. with 8 bits of dynamic range). With modifications the module can operate as a Fastbus master

  16. Prognostic relevance of gemistocytic grade II astrocytoma: gemistocytic component and MR imaging features compared to non-gemistocytic grade II astrocytoma

    Energy Technology Data Exchange (ETDEWEB)

    Heo, Young Jin [Inje University, Busan Paik Hospital, Department of Radiology, Busan (Korea, Republic of); Park, Ji Eun; Kim, Ho Sung; Lee, Ji Ye; Jung, Seung Chai; Choi, Choong Gon; Kim, Sang Joon [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Nam, Soo Jeong [University of Ulsan College of Medicine, Asan Medical Center, Department of Pathology, Seoul (Korea, Republic of)

    2017-07-15

    To determine if gemistocytic grade II astrocytoma (GemA) and its MR imaging characteristics are associated with a shorter time-to-progression (TTP) compared with non-gemistocytic grade II astrocytoma (non-GemA). We enrolled 78 patients who were followed up more than 5 years (29 pathologically proven GemA and 49 non-GemA) during a 10-year period. Contrast-enhanced T1-weighted, diffusion-weighted imaging (DWI), dynamic susceptibility contrast (DSC), and MR spectroscopy (MRS) and clinical data were retrospectively reviewed. Clinical and MR imaging features were analyzed as possible prognostic factors of high-grade transformation, and multivariate analysis of TTP was performed using Cox proportional modeling. GemA showed more frequent high-grade features than non-GemA, including diffusion restriction (P <.001), increased choline/creatine (P =.02), and increased choline/NAA ratio (P =.015). Patients with GemA had a significantly shorter median TTP (53.1 vs 68 months; P <.001). A gemistocytic histopathology (hazard ratio = 3.42; P =.015) and low ADC (hazard ratio = 3.61; P =.001) were independently associated with a shorter TTP. GemA can present with MR imaging findings mimicking high-grade glioma at initial diagnosis and transforms to high-grade disease earlier than non-GemA. Low ADC on DWI might be useful in stratifying the risk of progression in patients with grade II astrocytoma. (orig.)

  17. Neurotrophin receptors expression and JNK pathway activation in human astrocytomas

    Directory of Open Access Journals (Sweden)

    Maraziotis Theodore

    2007-10-01

    Full Text Available Abstract Background Neurotrophins are growth factors that regulate cell growth, differentiation and apoptosis in the nervous system. Their diverse actions are mediated through two different transmembrane – receptor signaling systems: Trk receptor tyrosine kinases (TrkA, TrkB, TrkC and p75NTR neurotrophin receptor. Trk receptors promote cell survival and differentiation while p75NTR induces, in most cases, the activity of JNK-p53-Bax apoptosis pathway or suppresses intracellular survival signaling cascades. Robust Trk activation blocks p75NTR -induced apoptosis by suppressing the JNK-p53-Bax pathway. The aim of this exploratory study was to investigate the expression levels of neurotrophin receptors, Trks and p75NTR, and the activation of JNK pathway in human astrocytomas and in adjacent non-neoplastic brain tissue. Methods Formalin-fixed paraffin-embedded serial sections from 33 supratentorial astrocytomas (5 diffuse fibrillary astrocytomas, WHO grade II; 6 anaplastic astrocytomas, WHO grade III; 22 glioblastomas multiforme, WHO grade IV were immunostained following microwave pretreatment. Polyclonal antibodies against TrkA, TrkB, TrkC and monoclonal antibodies against p75NTR and phosphorylated forms of JNK (pJNK and c-Jun (pc-Jun were used. The labeling index (LI, defined as the percentage of positive (labeled cells out of the total number of tumor cells counted, was determined. Results Moderate to strong, granular cytoplasmic immunoreactivity for TrkA, TrkB and TrkC receptors was detected in greater than or equal to 10% of tumor cells in the majority of tumors independently of grade; on the contrary, p75NTR receptor expression was found in a small percentage of tumor cells (~1% in some tumors. The endothelium of tumor capillaries showed conspicuous immunoreactivity for TrkB receptor. Trk immunoreactivity seemed to be localized in some neurons and astrocytes in non-neoplastic tissue. Phosphorylated forms of JNK (pJNK and c-Jun (pc-Jun were

  18. Wnt/β-catenin pathway involvement in ionizing radiation-induced invasion of U87 glioblastoma cells

    International Nuclear Information System (INIS)

    Dong, Zhen; Zhou, Lin; Han, Na; Zhang, Mengxian; Lyu, Xiaojuan

    2015-01-01

    Radiotherapy has been reported to promote the invasion of glioblastoma cells; however, the underlying mechanisms remain unclear. Here, we investigated the role of the Wnt/β-catenin pathway in radiation-induced invasion of glioblastoma cells. U87 cells were irradiated with 3 Gy or sham irradiated in the presence or absence of the Wnt/β-catenin pathway inhibitor XAV 939. Cell invasion was determined by an xCELLigence real-time cell analyser and matrigel invasion assays. The intracellular distribution of β-catenin in U87 cells with or without irradiation was examined by immunofluorescence and Western blotting of nuclear fractions. We next investigated the effect of irradiation on Wnt/β-catenin pathway activity using TOP/FOP flash luciferase assays and quantitative polymerase chain reaction analysis of β-catenin target genes. The expression levels and activities of two target genes, matrix metalloproteinase (MMP)-2 and MMP-9, were examined further by Western blotting and zymography. U87 cell invasiveness was increased significantly by ionizing radiation. Interestingly, ionizing radiation induced nuclear translocation and accumulation of β-catenin. Moreover, we found increased β-catenin/TCF transcriptional activities, followed by up-regulation of downstream genes in the Wnt/β-catenin pathway in irradiated U87 cells. Importantly, inhibition of the Wnt/β-catenin pathway by XAV 939, which promotes degradation of β-catenin, significantly abrogated the pro-invasion effects of irradiation. Mechanistically, XAV 939 suppressed ionizing radiation-triggered up-regulation of MMP-2 and MMP-9, and inhibited the activities of these gelatinases. Our data demonstrate a pivotal role of the Wnt/β-catenin pathway in ionizing radiation-induced invasion of glioblastoma cells, and suggest that targeting β-catenin is a promising therapeutic approach to overcoming glioma radioresistance. (orig.) [de

  19. The co-chaperones Fkbp4/5 control Argonaute2 expression and facilitate RISC assembly.

    Science.gov (United States)

    Martinez, Natalia J; Chang, Hao-Ming; Borrajo, Jacob de Riba; Gregory, Richard I

    2013-11-01

    Argonaute2 (Ago2) protein and associated microRNAs (miRNAs) or small interfering RNAs (siRNAs) form the RNA-induced silencing complex (RISC) for target messenger RNA cleavage and post-transcriptional gene silencing. Although Ago2 is essential for RISC activity, the mechanism of RISC assembly is not well understood, and factors controlling Ago2 protein expression are largely unknown. A role for the Hsc70/Hsp90 chaperone complex in loading small RNA duplexes into the RISC has been demonstrated in cell extracts, and unloaded Ago2 is unstable and degraded by the lysosome in mammalian cells. Here we identify the co-chaperones Fkbp4 and Fkbp5 as Ago2-associated proteins in mouse embryonic stem cells. Pharmacological inhibition of this interaction using FK506 or siRNA-mediated Fkbp4/5 depletion leads to decreased Ago2 protein levels. We find FK506 treatment inhibits, whereas Fkbp4/5 overexpression promotes, miRNA-mediated stabilization of Ago2 expression. Simultaneous treatment with a lysosome inhibitor revealed the accumulation of unloaded Ago2 complexes in FK506-treated cells. We find that, consistent with unloaded miRNAs being unstable, FK506 treatment also affects miRNA abundance, particularly nascent miRNAs. Our results support a role for Fkbp4/5 in RISC assembly.

  20. Prevention against diffuse spinal cord astrocytoma: can the Notch pathway be a novel treatment target?

    Directory of Open Access Journals (Sweden)

    Jian-jun Sun

    2015-01-01

    Full Text Available This study was designed to investigate whether the Notch pathway is involved in the development of diffuse spinal cord astrocytomas. BALB/c nude mice received injections of CD133 + and CD133− cell suspensions prepared using human recurrent diffuse spinal cord astrocytoma tissue through administration into the right parietal lobe. After 7-11 weeks, magnetic resonance imaging was performed weekly. Xenografts were observed on the surfaces of the brains of mice receiving the CD133 + cell suspension, and Notch-immunopositive expression was observed in the xenografts. By contrast, no xenografts appeared in the identical position on the surfaces of the brains of mice receiving the CD133− cell suspension, and Notch-immunopositive expression was hardly detected either. Hematoxylin-eosin staining and immunohistochemical staining revealed xenografts on the convex surfaces of the brains of mice that underwent CD133 + astrocytoma transplantation. Some sporadic astroglioma cells showed pseudopodium-like structures, which extended into the cerebral white matter. However, it should be emphasized that the subcortex xenograft with Notch-immunopositive expression was found in the fourth mouse received injection of CD133− astrocytoma cells. However, these findings suggest that the Notch pathway plays an important role in the formation of astrocytomas, and can be considered a novel treatment target for diffuse spinal cord astrocytoma.

  1. MicroRNA-223 Enhances Radiation Sensitivity of U87MG Cells In Vitro and In Vivo by Targeting Ataxia Telangiectasia Mutated

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Liping; Zhu, Ji [Departments of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Zaorsky, Nicholas G. [Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Deng, Yun [Departments of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Wu, Xingzhong [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai (China); Liu, Yong [Departments of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Liu, Fangqi; Cai, Guoxiang; Gu, Weilie [Department of Colorectal Cancer, Fudan University, Shanghai Cancer Center, Shanghai (China); Shen, Lijun [Departments of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Zhang, Zhen, E-mail: zhenzhang6@hotmail.com [Departments of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China)

    2014-03-15

    Purpose: Ataxia telangiectasia mutated (ATM) protein is important in the DNA damage response because it repairs radiation-induced damage in cancers. We examined the effect of microRNA-223 (miR-223), a regulator of ATM expression, on radiation sensitivity of cancer cells. Methods and Materials: Human embryonic kidney 293 T (293T) cells were infected with pLL3.7-miR-223 plasmid to generate the pLL3.7-miR-223 and -empty virus (EV) lentivirus (miR-223 and EV). A dual luciferase assay in which the reporter contained wild-type 3′ untranslated region (UTR) of ATM was performed. U87MG cells were infected with miR-223 or EV to establish the overexpressed stable cell lines (U87-223 or U87-EV, respectively). Cells were irradiated in vitro, and dose enhancement ratios at 2 Gy (DER{sub 2}) were calculated. Hind legs of BALB/c athymic mice were injected with U87-223 or U87-EV cells; after 2 weeks, half of the tumors were irradiated. Tumor volumes were tracked for a total of 5 weeks. Results: The dual luciferase reporter assay showed a significant reduction in luciferase activity of 293T cells cotransfected with miR-223 and the ATM 3′UTR compared to that in EV control. Overexpression of miR-223 in U87MG cells showed that ATM expression was significantly downregulated in the U87-223 cells compared to that in U87-EV (ATM/β-actin mRNA 1.0 vs 1.5, P<.05). U87-223 cells were hypersensitive to radiation compared to U87-EV cells in vitro (DER{sub 2} = 1.32, P<.01). Mice injected with miR-223-expressing tumors had almost the same tumors after 3 weeks (1.5 cm{sup 3} vs 1.7 cm{sup 3}). However, irradiation significantly decreased tumor size in miR-223-expressing tumors compared to those in controls (0.033 cm{sup 3} vs 0.829 cm{sup 3}). Conclusions: miR-223 overexpression downregulates ATM expression and sensitizes U87 cells to radiation in vitro and in vivo. MicroRNA-223 may be a novel cancer-targeting therapy, although its cancer- and patient-specific roles are

  2. Adult Pilomyxoid Astrocytoma Mimicking a Cortical Brain Tumor: MR Imaging Findings

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Jong Chang; Weon, Young Cheol; Suh, Jae Hee; Kim, Young; Hwang, Jae Cheol [Ulsan University Hospital, Ulsan (Korea, Republic of)

    2010-08-15

    A pilomyxoid astrocytoma (PMA) is a recently identified low-grade neoplasm that was previously classified as a pilocytic astrocytoma (PA), yet demonstrates unique histological features and more aggressive behavior. Although a PMA is generally a tumor of early childhood and typically occurs in the hypothalamic/chiasmatic region, it can mimic cortical tumors, especially in adults. We report the MR findings of a PMA presenting as a cortical brain tumor in an adult with neurofibromatosis 1 (NF1)

  3. TAF11 assembles RISC loading complex to enhance RNAi efficiency

    Science.gov (United States)

    Liang, Chunyang; Wang, Yibing; Murota, Yukiko; Liu, Xiang; Smith, Dean; Siomi, Mikiko C.; Liu, Qinghua

    2015-01-01

    SUMMARY Assembly of the RNA-induced silencing complex (RISC) requires formation of the RISC loading complex (RLC), which contains Dicer-2(Dcr-2)-R2D2 complex and recruits duplex siRNA to Ago2 in Drosophila melanogaster. However, the precise composition and action mechanism of Drosophila RLC remain unclear. Here, we identified the missing factor of RLC as TATA-binding protein associated factor 11 (TAF11) by genetic screen. Although an annotated nuclear transcription factor, we found that TAF11 also associated with Dcr-2/R2D2 and localized to cytoplasmic D2 bodies. Consistent with defective RLC assembly in taf11−/− ovary extract, we reconstituted the RLC in vitro using recombinant Dcr-2-R2D2 complex, TAF11, and duplex siRNA. Furthermore, we showed that TAF11 tetramer facilitates Dcr-2-R2D2 tetramerization to enhance siRNA binding and RISC loading activities. Together, our genetic and biochemical studies define the molecular nature of Drosophila RLC and elucidate a novel cytoplasmic function of TAF11 in organizing RLC assembly to enhance RNAi efficiency. PMID:26257286

  4. Clinical Implications of the Epidermal Growth Factor Receptor overexpression in the High-grade Astrocytomas

    International Nuclear Information System (INIS)

    Hong, Seong Eon; Kang, Jin Oh; Lee, Hye Kyoung; Yang, Moon Ho; Leem, Won; Cho, Kyung Sam

    1996-01-01

    To determine the incidence and prognostic effects of EGFR overexpression in the high-grade astrocytomas. With 23 paraffin blocks of the high-garde astrocytomas, expression of EGFR were evaluated by immunohistochemical staining employing polyclonal antibody raised to short cytoplasmic domain of the molecule. Two out of 7 anaplastic astrocytomas and 9 out of 16 glioblastoma multiform patients showed overexpression of EGFR(p=0.44). Three out of 11 patients of age below 55 and 8 out of 12 patients of age over 54 showed EGFR overexpression(p=0.141). Median survival of the EGFR negative anaplastic astrocytoma patient was 37 months. Median survival of the glioblastoma multiform patients were 11 months in EGFR negative group and 7 months in EGFR positive group. But survival difference was not significant(p=0.17). There was a marked trend of increasing overexpression of EGFR in older patients. But survival of the glioblastoma multiform decreased by the overexpression of the EGFR without significant

  5. Clinical significance of changes of serum expression of IGF-I in patients with astrocytoma

    International Nuclear Information System (INIS)

    Liu Jianbo; Ding Dongmei; Yang Fubing

    2005-01-01

    Objective: To investigate the serum expression of IGF-I in patients with astrocytoma of different degrees of malignancy as well as the changes of levels after operative removal of the tumor. Methods: Serum IGF-I contents were measured with IRMA in 16 patients with Grade I-II astrocytoma and 14 patients with Grade III-IV astrocytoma both before and after operation as well as in 30 controls. Results: The serum contents of IGF-I in both groups of patients were significantly higher than those in controls (P<0.05). The levels in Grade III-IV patients were significantly higher than those in Grade I-II patients (P < 0.05 ). After operation, the levels dropped significantly (vs before operation, P<0.05). Conclusion: The serum contents of IGF - I in patients with astrocytoma were positively correlated with the degree of malignancy. Post-operative decrease of IGF-I contents was related to the decrease of tumor burden. (authors)

  6. [Diagnostic imaging of high-grade astrocytoma: heterogeneity of clinical manifestation, image characteristics, and histopathological findings].

    Science.gov (United States)

    Okajima, Kaoru; Ohta, Yoshio

    2012-10-01

    Recent developments in diagnostic radiology, which have enabled accurate differential diagnoses of brain tumors, have been well described in the last three decades. MR and PET imaging can also provide information to predict histological grades and prognoses that might influence treatment strategies. However, high-grade astrocytomas consist of many different subtypes that are associated with different imaging and histological characteristics. Hemorrhage and necrosis results in a variety of imaging features, and infiltrative tumor growth entrapping normal neurons may cause different clinical manifestations. We reviewed patients with high-grade astrocytomas that showed various imaging characteristics, with special emphasis on initial symptoms and histological features. Clinicopathological characteristics of astrocytomas were also compared with other malignant tumors. Neurological deficits were not notable in patients with grade 3-4 astrocytomas when they showed infiltrative tumor growth, while brain metastases with compact cellular proliferation caused more neurological symptoms. Infiltrative tumors did not show any enhancing masses on MR imaging, but these tumors may show intratumor heterogeneity. Seizures were reported to be more frequent in low-grade glioma and in secondary glioblastoma. Tumor heterogeneity was also reported in molecular genetic profile, and investigators identified some subsets of astrocytomas. They investigated IHD1/2 mutation, EGFR amplification, TP53 mutation, Ki-67 index, etc. In summary, high-grade astrocytomas are not homogenous groups of tumors, and this is associated with the heterogeneity of clinical manifestation, image characteristics, and histopathological findings. Molecular studies may explain the tumor heterogeneity in the near future.

  7. Neurotrophin receptors expression and JNK pathway activation in human astrocytomas

    International Nuclear Information System (INIS)

    Assimakopoulou, Martha; Kondyli, Maria; Gatzounis, George; Maraziotis, Theodore; Varakis, John

    2007-01-01

    Neurotrophins are growth factors that regulate cell growth, differentiation and apoptosis in the nervous system. Their diverse actions are mediated through two different transmembrane – receptor signaling systems: Trk receptor tyrosine kinases (TrkA, TrkB, TrkC) and p75 NTR neurotrophin receptor. Trk receptors promote cell survival and differentiation while p75 NTR induces, in most cases, the activity of JNK-p53-Bax apoptosis pathway or suppresses intracellular survival signaling cascades. Robust Trk activation blocks p75 NTR -induced apoptosis by suppressing the JNK-p53-Bax pathway. The aim of this exploratory study was to investigate the expression levels of neurotrophin receptors, Trks and p75 NTR , and the activation of JNK pathway in human astrocytomas and in adjacent non-neoplastic brain tissue. Formalin-fixed paraffin-embedded serial sections from 33 supratentorial astrocytomas (5 diffuse fibrillary astrocytomas, WHO grade II; 6 anaplastic astrocytomas, WHO grade III; 22 glioblastomas multiforme, WHO grade IV) were immunostained following microwave pretreatment. Polyclonal antibodies against TrkA, TrkB, TrkC and monoclonal antibodies against p75 NTR and phosphorylated forms of JNK (pJNK) and c-Jun (pc-Jun) were used. The labeling index (LI), defined as the percentage of positive (labeled) cells out of the total number of tumor cells counted, was determined. Moderate to strong, granular cytoplasmic immunoreactivity for TrkA, TrkB and TrkC receptors was detected in greater than or equal to 10% of tumor cells in the majority of tumors independently of grade; on the contrary, p75 NTR receptor expression was found in a small percentage of tumor cells (~1%) in some tumors. The endothelium of tumor capillaries showed conspicuous immunoreactivity for TrkB receptor. Trk immunoreactivity seemed to be localized in some neurons and astrocytes in non-neoplastic tissue. Phosphorylated forms of JNK (pJNK) and c-Jun (pc-Jun) were significantly co-expressed in a tumor

  8. Treatment results of non-pilocytic cerebral astrocytomas in adults treated by surgery, radiation therapy and chemotherapy

    International Nuclear Information System (INIS)

    Matsutani, Masao; Nishikawa, Ryo; Sugiyama, Satoshi; Fujimaki, Takamitsu; Nakamura, Osamu

    1999-01-01

    Non-pilocytic cerebral astrocytomas in adults are oncopathologically defined as well-differentiated carcinoma of the brain. They grow invasively and can not be cured by extensive surgery followed by radiation therapy. We performed multidisciplinary treatments consisting of surgery, radiation therapy and chemotherapy in 26 adult patients with non-pilocytic cerebral astrocytomas. The 5- and 10-year survival rates of the patients were 90.9% and 75.6%, respectively; these were better than reported survival rates of patients treated by postoperative radiation therapy alone. Precise analysis of clinical findings of astrocytic tumors suggested that glioblastomas growing superficially might be derived from preexisting astrocytomas. This hypothesis proposes that multidisciplinary treatments for astrocytomas in early stages could cure the disease and could ultimately decrease a number of glioblastomas. (author)

  9. Spanish validation of the 10-item Connor-Davidson Resilience Scale (CD-RISC 10) with non-professional caregivers.

    Science.gov (United States)

    Blanco, Vanessa; Guisande, María Adelina; Sánchez, María Teresa; Otero, Patricia; Vázquez, Fernando L

    2017-11-08

    Despite the importance of resilience in populations under stress, and the fact that the 10-item version Connor-Davidson Resilience Scale (CD-RISC 10) is the shortest instrument for reliable and valid evaluation of resilience, there are no data on their psychometric properties in non-professional caregivers. The aim of this study was to analyze the psychometric properties and factorial structure of the spanish version of the CD-RISC 10 in non-professional caregivers. Independently trained assessors evaluated resilience, self-esteem, social support, emotional distress and depression in a sample of 294 caregivers (89.8% women, mean age 55.3 years). The internal consistency of CD-RISC 10 was α = .86. A single factor was found that accounted for 44.7% of the total variance. Confirmatory factor analysis corroborated this unifactorial model. The CD-RISC 10 was significantly correlated with the self-esteem (r = .416, p caregivers with depression (sensitivity = 70.0%, specificity = 68.2%). The CD-RISC 10 is a reliable and valid instrument to evaluate resilience in the caregiver population.

  10. Rab23 is overexpressed in human astrocytoma and promotes cell migration and invasion through regulation of Rac1.

    Science.gov (United States)

    Wang, Minghao; Dong, Qianze; Wang, Yunjie

    2016-08-01

    Rab23 overexpression has been implicated in several human cancers. However, its biological roles and molecular mechanism in astrocytoma have not been elucidated. The aim of this study is to explore clinical significance and biological roles of Rab23 in astrocytoma. We observed negative Rab23 staining in normal astrocytes and positive staining in 39 out of 86 (45 %) astrocytoma specimens using immunohistochemistry. The positive rate of Rab23 was higher in grades III and IV (56.5 %, 26/46) than grades I + II astrocytomas (32.5 %, 13/40, p Rac1 activity. Treatment of transfected cells with a Rac1 inhibitor decreased Rac1 activity and invasion. In conclusion, Rab23 serves as an important oncoprotein in human astrocytoma by regulating cell invasion and migration through Rac1 activity.

  11. Conformal proton radiation therapy for pediatric low-grade astrocytomas

    Energy Technology Data Exchange (ETDEWEB)

    Hug, E.B. [Loma Linda Univ. Medical Center, Loma Linda, CA (United States). Dept. of Radiation Medicine; Loma Linda Univ. Medical Center, Loma Linda, CA (United States). Dept. of Pediatrics and Dept. of Pathology; Darthmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States). Section of Radiation Oncology; Muenter, M.W.; Archambeau, J.O.; DeVries, A.; Loredo, L.N.; Grove, R.I.; Slater, J.D. [Loma Linda Univ. Medical Center, Loma Linda, CA (United States). Dept. of Radiation Medicine; Liwnicz, B. [Loma Linda Univ. Medical Center, Loma Linda, CA (United States). Dept. of Pathology

    2002-01-01

    Background: To evaluate the safety and efficacy of proton radiation therapy (PRT) for intracranial low-grade astrocytomas, the authors analyzed the first 27 pediatric patients treated at Loma Linda University Medical Center (LLUMC). Patients and Method: Between September 1991 and August 1997, 27 patients (13 female, 14 male) underwent fractionated proton radiation therapy for progressive or recurrent low-grade astrocytoma. Age at time of treatment ranged from 2 to 18 years (mean: 8.7 years). Tumors were located centrally (diencephatic) in 15 patients, in the cerebral and cerebellar hemispheres in seven patients, and in the brainstem in five patients. 25/27 patients (92%) were treated for progressive, unresectable, or residual disease following subtotal resection. Tissue diagnosis was available in 23/27 patients (85%). Four patients with optic pathway tumors were treated without histologic confirmation. Target doses between 50.4 and 63.0 CGE (cobalt gray equivalent, mean: 55.2 CGE) were prescribed at 1.8 CGE per fraction, five treatments per week. Results: At a mean follow-up period of 3.3 years (0.6-6.8 years), 6/27 patients experienced local failure (all located within the irradiated field), and 4/27 patients had died. By anatomic site these data translated into rates of local control and survival of 87% (13/15 patients) and 93% (14/15 patients) for central tumors, 71% (5/7 patients) and 86% (6/7 patients) for hemispheric tumors, and 60% (3/5 patients) and 60% (3/5 patients) for tumors located in the brainstem. Proton radiation therapy was generally well tolerated. All children with local control maintained their performance status. One child with associated neurofibromatosis, Type 1, developed Moyamoya disease. All six patients with optic pathway tumors and useful vision maintained or improved their visual status. Conclusions: This report on pediatric low-grade astrocytomas confirms proton radiation therapy as a safe and efficacious 3-D conformal treatment

  12. Malignant astrocytoma following radiotherapy for craniopharyngioma

    Energy Technology Data Exchange (ETDEWEB)

    Maat-Schieman, M.L.C.; Bots, G.T.A.M.; Thomeer, T.W.M.; Vielvoye, G.J. (Rijksuniversiteit Leiden (Netherlands). Hospital)

    1985-05-01

    The case report describes a boy with a malignant astrocytoma in the mid-line of the cerebellum 14 years after X-ray therapy for craniopharyngioma. In Leiden University Hospital this is the first case of a suspected radiation-induced brain tumour in 66 patients treated for cranial lesions by radiotherapy between 1969 and 1979 who have survived more than 5 years.

  13. Malignant astrocytoma following radiotherapy for craniopharyngioma

    International Nuclear Information System (INIS)

    Maat-Schieman, M.L.C.; Bots, G.T.A.M.; Thomeer, T.W.M.; Vielvoye, G.J.

    1985-01-01

    The case report describes a boy with a malignant astrocytoma in the mid-line of the cerebellum 14 years after X-ray therapy for craniopharyngioma. In Leiden University Hospital this is the first case of a suspected radiation-induced brain tumour in 66 patients treated for cranial lesions by radiotherapy between 1969 and 1979 who have survived more than 5 years. (author)

  14. GLUT-1-independent infection of the glioblastoma/astroglioma U87 cells by the human T cell leukemia virus type 1

    International Nuclear Information System (INIS)

    Jin Qingwen; Agrawal, Lokesh; VanHorn-Ali, Zainab; Alkhatib, Ghalib

    2006-01-01

    The human glucose transporter protein 1 (GLUT-1) functions as a receptor for human T cell leukemia virus (HTLV). GLUT-1 is a twelve-transmembrane cell surface receptor with six extracellular (ECL) and seven intracellular domains. To analyze HTLV-1 cytotropism, we utilized polyclonal antibodies to a synthetic peptide corresponding to the large extracellular domain of GLUT-1. The antibodies caused significant blocking of envelope (Env)-mediated fusion and pseudotyped virus infection of HeLa cells but had no significant effect on infection of U87 cells. This differential effect correlated with the detection of high-level surface expression of GLUT-1 on HeLa cells and very weak staining of U87 cells. To investigate this in terms of viral cytotropism, we cloned GLUT-1 cDNA from U87 cells and isolated two different versions of cDNA clones: the wild-type sequence (encoding 492 residues) and a mutant cDNA with a 5-base pair deletion (GLUT-1Δ5) between nucleotides 1329 and 1333. The deletion, also detected in genomic DNA, resulted in a frame-shift and premature termination producing a truncated protein of 463 residues. Transfection of the wild-type GLUT-1 but not GLUT-1Δ5 cDNA into CHO cells resulted in efficient surface expression of the human GLUT-1. Co-expression of GLUT-1 with GLUT-1Δ5 produces a trans-inhibition by GLUT-1Δ5 of GLUT-1-mediated HTLV-1 envelope (Env)-mediated fusion. Co-immunoprecipitation experiments demonstrated physical interaction of the wild-type and mutant proteins. Northern blot and RT-PCR analyses demonstrated lower GLUT-1 RNA expression in U87 cells. We propose two mechanisms to account for the impaired cell surface expression of GLUT-1 on U87 cells: low GLUT-1 RNA expression and the formation of GLUT-1/GLUT-1Δ5 heterodimers that are retained intracellularly. Significant RNAi-mediated reduction of endogenous GLUT-1 expression impaired HTLV-1 Env-mediated fusion with HeLa cells but not with U87 cells. We propose a GLUT-1-independent mechanism

  15. Primary ciliogenesis defects are associated with human astrocytoma/glioblastoma cells

    Directory of Open Access Journals (Sweden)

    Rattner Jerome B

    2009-12-01

    Full Text Available Abstract Background Primary cilia are non-motile sensory cytoplasmic organelles that have been implicated in signal transduction, cell to cell communication, left and right pattern embryonic development, sensation of fluid flow, regulation of calcium levels, mechanosensation, growth factor signaling and cell cycle progression. Defects in the formation and/or function of these structures underlie a variety of human diseases such as Alström, Bardet-Biedl, Joubert, Meckel-Gruber and oral-facial-digital type 1 syndromes. The expression and function of primary cilia in cancer cells has now become a focus of attention but has not been studied in astrocytomas/glioblastomas. To begin to address this issue, we compared the structure and expression of primary cilia in a normal human astrocyte cell line with five human astrocytoma/glioblastoma cell lines. Methods Cultured normal human astrocytes and five human astrocytoma/glioblastoma cell lines were examined for primary cilia expression and structure using indirect immunofluorescence and electron microscopy. Monospecific antibodies were used to detect primary cilia and map the relationship between the primary cilia region and sites of endocytosis. Results We show that expression of primary cilia in normal astrocytes is cell cycle related and the primary cilium extends through the cell within a unique structure which we show to be a site of endocytosis. Importantly, we document that in each of the five astrocytoma/glioblastoma cell lines fully formed primary cilia are either expressed at a very low level, are completely absent or have aberrant forms, due to incomplete ciliogenesis. Conclusions The recent discovery of the importance of primary cilia in a variety of cell functions raises the possibility that this structure may have a role in a variety of cancers. Our finding that the formation of the primary cilium is disrupted in cells derived from astrocytoma/glioblastoma tumors provides the first

  16. Study on the correlation between VEGF and peritumoral edema and tumor border in astrocytoma by CT

    International Nuclear Information System (INIS)

    Ye Yuxiang; Tan Siping; Liu Bo; Liu Guorui; Zhen Zhichao; Fan Miao

    2004-01-01

    Objective: To study the correlation between VEGF and peritumoral edema and tumor border in human astrocytoma, investigate the significance of its CT features in molecular-biology. Methods: The VEGF was examined by means of SP immunohistochemical technique in 52 cases of astrocytoma proved by pathology. The correlation of tumor VEGF with peritumoral edema, and tumor border was analyzed. Results: The peritumoral edema, tumor border and mass effect of astrocytoma was positively correlated with its VEGF. The VEGF increased with peritumoral edema and mass effect (P<0.01). VEGF were significantly higher in uncertain border group than those the clear border group (P<0.05), which VEGF were 69.2 ± 19.0. Conclusion: The over expression of VEGF obviously effect CT features in astrocytoma, such as peritumoral edema and tumor border

  17. TAF11 Assembles the RISC Loading Complex to Enhance RNAi Efficiency.

    Science.gov (United States)

    Liang, Chunyang; Wang, Yibing; Murota, Yukiko; Liu, Xiang; Smith, Dean; Siomi, Mikiko C; Liu, Qinghua

    2015-09-03

    Assembly of the RNA-induced silencing complex (RISC) requires formation of the RISC loading complex (RLC), which contains the Dicer-2 (Dcr-2)-R2D2 complex and recruits duplex siRNA to Ago2 in Drosophila melanogaster. However, the precise composition and action mechanism of Drosophila RLC remain unclear. Here we identified the missing factor of RLC as TATA-binding protein-associated factor 11 (TAF11) by genetic screen. Although it is an annotated nuclear transcription factor, we found that TAF11 also associated with Dcr-2/R2D2 and localized to cytoplasmic D2 bodies. Consistent with defective RLC assembly in taf11(-/-) ovary extract, we reconstituted the RLC in vitro using the recombinant Dcr-2-R2D2 complex, TAF11, and duplex siRNA. Furthermore, we showed that TAF11 tetramer facilitates Dcr-2-R2D2 tetramerization to enhance siRNA binding and RISC loading activities. Together, our genetic and biochemical studies define the molecular nature of the Drosophila RLC and elucidate a cytoplasmic function of TAF11 in organizing RLC assembly to enhance RNAi efficiency. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. astrocytoma – diagnostic pitfalls. A review

    Directory of Open Access Journals (Sweden)

    Ewa Matyja

    2016-10-01

    Full Text Available Pilocytic astrocytomas (PAs are the most frequent primary astroglial tumours affecting children and adolescents. They occur sporadically or in association with a genetically determined syndrome – neurofibromatosis type 1. Classic PA usually manifests as a well-circumscribed, often cystic, slowly growing tumour, which corresponds to WHO grade I. The majority of pilocytic tumours arise along the neuraxis, predominantly in the cerebellum. They are associated with favourable long-term outcome or spontaneous regression, even after incomplete resection. However, the behaviour and prognosis might also be related to tumour histology and location. Pilomyxoid astrocytoma (PMA represents a variant of classical PA with more invasive growth and increased risk of recurrences and dissemination. Typically, PAs exhibit distinct histology with biphasic architecture of loose, microcystic and compact, fibrillary areas. However, some tumours arise in an uncommon location and display heterogeneous histopathological appearance. The morphological pattern of PA can mimic some other glial neoplasms, including oligodendroglioma, pleomorphic xanthoastrocytoma, ependymoma or diffuse astrocytoma. Not infrequently, the advanced degenerative changes, including vascular fibrosis, and recent and old haemorrhages, may mimic vascular pathology. Sometimes, the neoplastic piloid tissue can resemble reactive gliosis, related to long-standing non neoplastic lesions. Not infrequently, PA exhibits histological features typical for anaplasia, including necrosis, mitoses and glomeruloid vascular proliferation that can suggest a diffuse high-grade glioma. However, even those PAs that lack distinct histological features of anaplasia can behave unpredictably, in a more aggressive manner, with leptomeningeal spreading. Genetic alterations resulting in aberrant signalling of the mitogen-activated protein kinase (MAPK pathway have been considered to underlie the development of PAs. The most

  19. Childhood Astrocytomas Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Astrocytoma is the most common type of glioma in children. Get detailed information about the clinical features, molecular and diagnostic evaluation, classification, prognosis, and treatment of newly diagnosed and recurrent disease low-grade and high-grade gliomas in this comprehensive summary for clinicians.

  20. Optimization of Particle-in-Cell Codes on RISC Processors

    Science.gov (United States)

    Decyk, Viktor K.; Karmesin, Steve Roy; Boer, Aeint de; Liewer, Paulette C.

    1996-01-01

    General strategies are developed to optimize particle-cell-codes written in Fortran for RISC processors which are commonly used on massively parallel computers. These strategies include data reorganization to improve cache utilization and code reorganization to improve efficiency of arithmetic pipelines.

  1. Anaplasia in pilocytic astrocytoma predicts aggressive behavior.

    Science.gov (United States)

    Rodriguez, Fausto J; Scheithauer, Bernd W; Burger, Peter C; Jenkins, Sarah; Giannini, Caterina

    2010-02-01

    The clinical significance of anaplastic features, a rare event in pilocytic astrocytoma (PA), is not fully established. We reviewed 34 PA with anaplastic features (Male = 21, Female = 13; median age 35 y, 5 to 75) among approximately 2200 PA cases (1.7%). Tumors were included which demonstrated brisk mitotic activity [at least 4 mitoses/10 high power fields (400 x )], in addition to hypercellularity and moderate-to-severe cytologic atypia, with or without necrosis. The tumors either had a PA precursor, coexistent (n = 14) (41%) or documented by previous biopsy (n = 10) (29%), or exhibited typical pilocytic features in an otherwise anaplastic astrocytoma (n = 10) (29%). Clinical features of neurofibromatosis type-1 were present in 24% and a history of radiation for PA precursor in 12%. Histologically, the anaplastic component was classified as pilocytic like (41%), small cell (32%), epithelioid (15%), or fibrillary (12%). Median MIB1 labeling index was 24.7% in the anaplastic component and 2.6% in the precursor, although overlapping values were present. Strong p53 staining (3+) was limited to areas with anaplasia (19%), with overlapping values for 1 and 2+ in areas without anaplasia. Median overall and progression-free survivals after diagnosis for the entire study group were 24 and 14 months, respectively. Overall and progression-free survivals were shorter in the setting of prior radiation for a PA precursor (P = 0.007, 0.028), increasing mitotic activity (P = 0.03, 0.02), and presence of necrosis (P = 0.02, 0.02), after adjusting for age and site. The biologic behavior of PAs with high-mitotic rates and those with necrosis paralleled that of St Anne-Mayo grades 2 and 3 diffuse astrocytomas, respectively. In summary, PA with anaplastic features exhibits a spectrum of morphologies and is associated with decreased survival when compared with typical PA.

  2. Performance awareness execution performance of HEP codes on RISC platforms,issues and solutions

    CERN Document Server

    Yaari, R; Yaari, Refael; Jarp, Sverre

    1995-01-01

    The work described in this paper was started during the migration of Aleph's production jobs from the IBM mainframe/CRAY supercomputer to several RISC/Unix workstation platforms. The aim was to understand why Aleph did not obtain the performance on the RISC platforms that was "promised" after a CERN Unit comparison between these RISC platforms and the IBM mainframe. Remedies were also sought. Since the work with the Aleph jobs in turn led to the related task of understanding compilers and their options, the conditions under which the CERN benchmarks (and other benchmarks) were run, kernel routines and frequently used CERNLIB routines, the whole undertaking expanded to try to look at all the factors that influence the performance of High Energy Physics (HEP) jobs in general. Finally, key performance issues were reviewed against the programs of one of the LHC collaborations (Atlas) with the hope that the conclusions would be of long- term interest during the establishment of their simulation, reconstruction and...

  3. Glioblastomas, astrocytomas and oligodendrogliomas linked to Lynch syndrome

    DEFF Research Database (Denmark)

    Therkildsen, C; Ladelund, S; Rambech, E

    2015-01-01

    .5%) in MSH2 gene mutation carriers compared to patients with mutations in MLH1 or MSH6. Glioblastomas predominated (56%), followed by astrocytomas (22%) and oligodendrogliomas (9%). MMR status was assessed in 10 tumors, eight of which showed MMR defects. None of these tumors showed immunohistochemical...

  4. Combined value of susceptibility weighted imaging and dynamic susceptibility-weighted contrast-enhanced MR perfusion-weighted imaging in brain astrocytoma grading

    International Nuclear Information System (INIS)

    Wang Xiaochun; Zhang Hui; Qin Jiangbo; Wang Le; Wu Xiaofeng

    2012-01-01

    Objective: To assess the value of combination of susceptibility weighted imaging (SWI) and dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion-weighted magnetic resonance imaging in astrocytoma grading. Methods: SWI and DSC scans were performed in 82 patients with pathologically confirmed astrocytoma. The patient group consisted of grade Ⅱ (15), grade Ⅲ (10), and grade Ⅳ (57). The intratumoral susceptibility signal intensity (ITSS) and relative cerebral blood volume (rCBV) max were used to determine the grade of astrocytomas by Kruskal Wallis test, Welch test, Spearman correlation coefficients, Pearson correlation coefficients, and receiver operating characteristic curve (ROC)statistic methods. Results: There were no ITSS in 14 cases of low-grade astrocytomas, the degree of ITSS were grade 1 to 3 in anaplastic astrocytomas, the degree of ITSS were grade 3 in all of the glioblastomas, the degree of ITSS were significant difference in all grades (H=71.96, P<0.01). rCBV max in grade Ⅱ, grade Ⅲ and grade Ⅳ astrocytomas were 1.26 ± 0.42, 3.59 ± 2.09 and 8.34 ± 1.16 respectively, rCBV max were significant difference in all grades (F'=681.72, P<0.01). ITSS showed significant correlation with rCBV max (r=0.72, P<0.01) and tumor grades (r=0.89, P<0.01), and rCBV and tumor grades showed significant correlation (r=0.78, P<0.01). Area under the ROC curve application SWI, DSC, SWI and DSC in differentiation of the grade Ⅱ and grade Ⅲ astrocytomas were 0.99, 0.93, 1.00, differentiate grade Ⅲ from grade Ⅳ were 0.70, 0.94, 0.94, and differentiate high-grade from low-grade astrocytomas were 1.00, 0.99, 1.00. Conclusions: ITSS is helpful to determine the grade of astrocytomas. The use of SWI in combination with DSC may improve the diagnostic accuracy of astrocytoma grading. (authors)

  5. Dysregulated RNA-Induced Silencing Complex (RISC) Assembly within CNS Corresponds with Abnormal miRNA Expression during Autoimmune Demyelination.

    Science.gov (United States)

    Lewkowicz, Przemysław; Cwiklińska, Hanna; Mycko, Marcin P; Cichalewska, Maria; Domowicz, Małgorzata; Lewkowicz, Natalia; Jurewicz, Anna; Selmaj, Krzysztof W

    2015-05-13

    MicroRNAs (miRNAs) associate with Argonaute (Ago), GW182, and FXR1 proteins to form RNA-induced silencing complexes (RISCs). RISCs represent a critical checkpoint in the regulation and bioavailability of miRNAs. Recent studies have revealed dysregulation of miRNAs in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE); however, the function of RISCs in EAE and MS is largely unknown. Here, we examined the expression of Ago, GW182, and FXR1 in CNS tissue, oligodendrocytes (OLs), brain-infiltrating T lymphocytes, and CD3(+)splenocytes (SCs) of EAE mic, and found that global RISC protein levels were significantly dysregulated. Specifically, Ago2 and FXR1 levels were decreased in OLs and brain-infiltrating T cells in EAE mice. Accordingly, assembly of Ago2/GW182/FXR1 complexes in EAE brain tissues was disrupted, as confirmed by immunoprecipitation experiments. In parallel with alterations in RISC complex content in OLs, we found downregulation of miRNAs essential for differentiation and survival of OLs and myelin synthesis. In brain-infiltrating T lymphocytes, aberrant RISC formation contributed to miRNA-dependent proinflammatory helper T-cell polarization. In CD3(+) SCs, we found increased expression of both Ago2 and FXR1 in EAE compared with nonimmunized mice. Therefore, our results demonstrate a gradient in expression of miRNA between primary activated T cells in the periphery and polarized CNS-infiltrating T cells. These results suggest that, in polarized autoreactive effector T cells, miRNA synthesis is inhibited in response to dysregulated RISC assembly, allowing these cells to maintain a highly specific proinflammatory program. Therefore, our findings may provide a mechanism that leads to miRNA dysregulation in EAE/MS. Copyright © 2015 the authors 0270-6474/15/357521-17$15.00/0.

  6. [Overexpressed miRNA-134b inhibits proliferation and invasion of CD133+ U87 glioma stem cells].

    Science.gov (United States)

    Liu, Yifeng; Zhang, Baochao; Wen, Changming; Wen, Gongling; Zhou, Guoping; Zhang, Jingwei; He, Haifa; Wang, Ning; Li, Wei

    2017-05-01

    Objective To investigate the role of microRNA-134b (miR-134b) in the tumorigenesis of glioma stem cells (GSCs) and the possible molecular mechanism. Methods Real-time quantitative PCR (qRT-PCR) was used to evalate the expression of miR-134b in CD133 + and CD133 - U87 GSCs. A lentiviral vector overexpressing miR-134b in U87 GSCs was constructed, and the effect of miR-134b overexpression on matrix metalloproteinase-2 (MMP-2), MMP-9 and MMP-12 expressions at both mRNA and protein levels were detected by qRT-PCR and Western blotting, respectively. Transwell TM assay was performed to determine the effect of miR-134b overexpression on GSCs invasion ability. Tumor xenograft models in nude mice were established to evaluate the effect of miR-134b overexpression on tumorgenesis in vivo. Results The qRT-PCR showed that, compared with CD133 - cells, miR-134b was significantly down-regulated in CD133 + cells. Cell line over-expressing miR-134b was successfully established, and miR-134b was up-regulated significantly compared with empty vector control. Overexpression of miR-134b remarkably inhibited the invasion of U87 GSCs and the expression of MMP-12. However, overexpression of miR-134b did not affect MMP-2 and MMP-9 expressions. miR-134b also suppressed U87 GSCs xenograft growth in vivo. Tumor volume in tumor xenograft model group was significantly lower than that in control group, and tumor weight decreased by 42% in the former group. Conclusion Overexpression of miR-134b inhibits the growth and invasion of CD133 + GSCs.

  7. Design of RISC Processor Using VHDL and Cadence

    Science.gov (United States)

    Moslehpour, Saeid; Puliroju, Chandrasekhar; Abu-Aisheh, Akram

    The project deals about development of a basic RISC processor. The processor is designed with basic architecture consisting of internal modules like clock generator, memory, program counter, instruction register, accumulator, arithmetic and logic unit and decoder. This processor is mainly used for simple general purpose like arithmetic operations and which can be further developed for general purpose processor by increasing the size of the instruction register. The processor is designed in VHDL by using Xilinx 8.1i version. The present project also serves as an application of the knowledge gained from past studies of the PSPICE program. The study will show how PSPICE can be used to simplify massive complex circuits designed in VHDL Synthesis. The purpose of the project is to explore the designed RISC model piece by piece, examine and understand the Input/ Output pins, and to show how the VHDL synthesis code can be converted to a simplified PSPICE model. The project will also serve as a collection of various research materials about the pieces of the circuit.

  8. Structural insights into RISC assembly facilitated by dsRNA-binding domains of human RNA helicase A (DHX9).

    Science.gov (United States)

    Fu, Qinqin; Yuan, Y Adam

    2013-03-01

    Intensive research interest has focused on small RNA-processing machinery and the RNA-induced silencing complex (RISC), key cellular machines in RNAi pathways. However, the structural mechanism regarding RISC assembly, the primary step linking small RNA processing and RNA-mediated gene silencing, is largely unknown. Human RNA helicase A (DHX9) was reported to function as an RISC-loading factor, and such function is mediated mainly by its dsRNA-binding domains (dsRBDs). Here, we report the crystal structures of human RNA helicase A (RHA) dsRBD1 and dsRBD2 domains in complex with dsRNAs, respectively. Structural analysis not only reveals higher siRNA duplex-binding affinity displayed by dsRBD1, but also identifies a crystallographic dsRBD1 pair of physiological significance in cooperatively recognizing dsRNAs. Structural observations are further validated by isothermal titration calorimetric (ITC) assay. Moreover, co-immunoprecipitation (co-IP) assay coupled with mutagenesis demonstrated that both dsRBDs are required for RISC association, and such association is mediated by dsRNA. Hence, our structural and functional efforts have revealed a potential working model for siRNA recognition by RHA tandem dsRBDs, and together they provide direct structural insights into RISC assembly facilitated by RHA.

  9. Simty: generalized SIMT execution on RISC-V

    OpenAIRE

    Collange , Sylvain

    2017-01-01

    International audience; We present Simty, a massively multi-threaded RISC-V processor core that acts as a proof of concept for dynamic inter-thread vector-ization at the micro-architecture level. Simty runs groups of scalar threads executing SPMD code in lockstep, and assembles SIMD instructions dynamically across threads. Unlike existing SIMD or SIMT processors like GPUs or vector processors, Simty vector-izes scalar general-purpose binaries. It does not involve any instruction set extension...

  10. Management of Pediatric Spinal Cord Astrocytomas: Outcomes With Adjuvant Radiation

    International Nuclear Information System (INIS)

    Guss, Zachary D.; Moningi, Shalini; Jallo, George I.; Cohen, Kenneth J.; Wharam, Moody D.; Terezakis, Stephanie A.

    2013-01-01

    Purpose: Pediatric intramedullary spinal cord tumors are exceedingly rare; in the United States, 100 to 200 cases are recognized annually, of these, most are astrocytomas. The purpose of this study is to report the outcomes in pediatric patients with spinal cord astrocytomas treated at a tertiary care center. Methods and Materials: An institutional review board-approved retrospective single-institution study was performed for pediatric patients with spinal cord astrocytomas treated at our hospital from 1990 to 2010. The patients were evaluated on the extent of resection, progression-free survival (PFS), and development of radiation-related toxicities. Kaplan-Meier curves and multivariate regression model methods were used for analysis. Results: Twenty-nine patients were included in the study, 24 with grade 1 or 2 (low-grade) tumors and 5 with grade 3 or 4 (high-grade) tumors. The median follow-up time was 55 months (range, 1-215 months) for patients with low-grade tumors and 17 months (range, 10-52 months) for those with high-grade tumors. Thirteen patients in the cohort received chemotherapy. All patients underwent at least 1 surgical resection. Twelve patients received radiation therapy to a median radiation dose of 47.5 Gy (range, 28.6-54.0 Gy). Fifteen patients with low-grade tumors and 1 patient with a high-grade tumor exhibited stable disease at the last follow-up visit. Acute toxicities of radiation therapy were low grade, whereas long-term sequelae were infrequent and manageable when they arose. All patients with low-grade tumors were alive at the last follow-up visit, compared with 1 patient with a high-grade tumor. Conclusion: Primary pediatric spinal cord astrocytomas vary widely in presentation and clinical course. Histopathologic grade remains a major prognostic factor. Patients with low-grade tumors tend to have excellent disease control and long-term survival compared to those with high-grade tumors. This experience suggests that radiation therapy

  11. Management of Pediatric Spinal Cord Astrocytomas: Outcomes With Adjuvant Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Guss, Zachary D.; Moningi, Shalini [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Hospital, Baltimore, Maryland (United States); Jallo, George I. [Department of Neurosurgery, Johns Hopkins Hospital, Baltimore, Maryland (United States); Cohen, Kenneth J. [Division of Pediatric Oncology, Johns Hopkins Hospital, Baltimore, Maryland (United States); Wharam, Moody D. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Hospital, Baltimore, Maryland (United States); Terezakis, Stephanie A., E-mail: stereza1@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Hospital, Baltimore, Maryland (United States)

    2013-04-01

    Purpose: Pediatric intramedullary spinal cord tumors are exceedingly rare; in the United States, 100 to 200 cases are recognized annually, of these, most are astrocytomas. The purpose of this study is to report the outcomes in pediatric patients with spinal cord astrocytomas treated at a tertiary care center. Methods and Materials: An institutional review board-approved retrospective single-institution study was performed for pediatric patients with spinal cord astrocytomas treated at our hospital from 1990 to 2010. The patients were evaluated on the extent of resection, progression-free survival (PFS), and development of radiation-related toxicities. Kaplan-Meier curves and multivariate regression model methods were used for analysis. Results: Twenty-nine patients were included in the study, 24 with grade 1 or 2 (low-grade) tumors and 5 with grade 3 or 4 (high-grade) tumors. The median follow-up time was 55 months (range, 1-215 months) for patients with low-grade tumors and 17 months (range, 10-52 months) for those with high-grade tumors. Thirteen patients in the cohort received chemotherapy. All patients underwent at least 1 surgical resection. Twelve patients received radiation therapy to a median radiation dose of 47.5 Gy (range, 28.6-54.0 Gy). Fifteen patients with low-grade tumors and 1 patient with a high-grade tumor exhibited stable disease at the last follow-up visit. Acute toxicities of radiation therapy were low grade, whereas long-term sequelae were infrequent and manageable when they arose. All patients with low-grade tumors were alive at the last follow-up visit, compared with 1 patient with a high-grade tumor. Conclusion: Primary pediatric spinal cord astrocytomas vary widely in presentation and clinical course. Histopathologic grade remains a major prognostic factor. Patients with low-grade tumors tend to have excellent disease control and long-term survival compared to those with high-grade tumors. This experience suggests that radiation therapy

  12. Outcome of Patients With Pilocytic Astrocytoma and Leptomeningeal Dissemination

    Energy Technology Data Exchange (ETDEWEB)

    Mazloom, Ali; Hodges, Joseph C.; Teh, Bin S. [Department of Radiation Oncology, Methodist Hospital, Houston, TX (United States); Chintagumpala, Murali [Department of Pediatrics, Baylor College of Medicine, Houston, TX (United States); Paulino, Arnold C., E-mail: apaulino@tmhs.org [Department of Radiation Oncology, Methodist Hospital, Houston, TX (United States); Department of Pediatrics, Baylor College of Medicine, Houston, TX (United States)

    2012-10-01

    Purpose: To determine the patient, tumor, and treatment characteristics of patients with pilocytic astrocytoma (PA) and leptomeningeal dissemination (LMD). Methods and Materials: A PubMed search of English-language studies pertaining to PA with LMD was performed using a combination of keywords that included juvenile pilocytic astrocytoma, low-grade astrocytoma, low-grade glioma, leptomeningeal dissemination, neuraxis spread, and radiotherapy. We found 26 studies with 58 patients between 1976 and 2005 that met these criteria. Results: The median survival for PA patients with LMD was 65 months. The 1-, 2-, and 5-year overall survival (OS) rate after the diagnosis of LMD was 81.1%, 75.7%, and 55.5%. The 1-, 2-, and 5-year progression-free survival (PFS) rate after the diagnosis of LMD was 69.3%, 66.5%, and 34.6%, respectively. Age, gender, primary site location, timing of LMD presentation (synchronous vs. metachronous), and LMD location did not significantly influence OS or PFS. No statistically significant difference was found in OS or PFS between the chemotherapy and radiotherapy groups. Likewise, no difference was found in OS or PFS according to the use of craniospinal irradiation vs. less extensive RT fields. Conclusions: Approximately one-half of PA patients were alive 5 years after the diagnosis of LMD. Both chemotherapy and radiotherapy have efficacy against LMD. Although the use of craniospinal irradiation did not have an effect on PFS, the patient numbers were small and a larger number treated with craniospinal irradiation is needed to determine its efficacy.

  13. Leptomeningeal dissemination of an astrocytoma causing hypophyseal insufficiency

    International Nuclear Information System (INIS)

    Suzan, S.; Cigdem, O.; Furkan, U.; Baki, A.

    2012-01-01

    Full text: Introduction: Hypophyseal insufficiency is an unusual clinical presentation of metastatic disease. Objectives: In this report, a case of leptomeningeal metastasis of an astrocytoma to the infundibular recess, causing hypophyseal insufficiency is presented with its magnetic resonance imaging (MRI) findings. Materials and methods: A 27-year-old woman presented with nausea, vomiting and generalized weakness. Her laboratory results were consistent with hypopituitarism. She had an operation history for astrocytoma. She was referred to radiology department for brain MRI study. Contrast-enhanced MRI scan showed extensive wall enhancement of ventricles consistent with leptomeningeal metastases. A nodular mass with pronounced contrast enhancement was also detected at the infundibular stalk. Results: Because suprasellar cistern was normal and extensive leptomeningeal metastases was detected, the nodular mass at the infundibular stalk thought to be secondary to leptomeningeal involvement of the infundibular recess. Conclusion: When a patient with a known malignancy presented with hypophyseal insufficiency, it should be thought that leptomeningeal metastases to the infundibular recess may also be a cause. The neuroimaging, especially contrast-enhanced studies, is necessary for the confirmation

  14. Schizotypal Estimators in Adolescence: The Concurrent Validity of the RISC.

    Science.gov (United States)

    Rust, John; Chiu, Herbert

    1988-01-01

    Administered Minnesota Counseling Inventory and Rust Inventory of Schizotypal Cognition (RISC) to 174 adolescents in Hong Kong. Results showed that negative schizophrenic symptoms of social dysfunction and emotional instability as measured by Minnesota Counseling Inventory were positively and significantly correlated with positive schizotypal…

  15. siRNAs targeted to certain polyadenylation sites promote specific, RISC-independent degradation of messenger RNAs.

    Science.gov (United States)

    Vickers, Timothy A; Crooke, Stanley T

    2012-07-01

    While most siRNAs induce sequence-specific target mRNA cleavage and degradation in a process mediated by Ago2/RNA-induced silencing complex (RISC), certain siRNAs have also been demonstrated to direct target RNA reduction through deadenylation and subsequent degradation of target transcripts in a process which involves Ago1/RISC and P-bodies. In the current study, we present data suggesting that a third class of siRNA exist, which are capable of promoting target RNA reduction that is independent of both Ago and RISC. These siRNAs bind the target messenger RNA at the polyA signal and are capable of redirecting a small amount of polyadenylation to downstream polyA sites when present, however, the majority of the activity appears to be due to inhibition of polyadenylation or deadenylation of the transcript, followed by exosomal degradation of the immature mRNA.

  16. Hsc70/Hsp90 chaperone machinery mediates ATP-dependent RISC loading of small RNA duplexes.

    Science.gov (United States)

    Iwasaki, Shintaro; Kobayashi, Maki; Yoda, Mayuko; Sakaguchi, Yuriko; Katsuma, Susumu; Suzuki, Tsutomu; Tomari, Yukihide

    2010-07-30

    Small silencing RNAs--small interfering RNAs (siRNAs) or microRNAs (miRNAs)--direct posttranscriptional gene silencing of their mRNA targets as guides for the RNA-induced silencing complex (RISC). Both siRNAs and miRNAs are born double stranded. Surprisingly, loading these small RNA duplexes into Argonaute proteins, the core components of RISC, requires ATP, whereas separating the two small RNA strands within Argonaute does not. Here we show that the Hsc70/Hsp90 chaperone machinery is required to load small RNA duplexes into Argonaute proteins, but not for subsequent strand separation or target cleavage. We envision that the chaperone machinery uses ATP and mediates a conformational opening of Ago proteins so that they can receive bulky small RNA duplexes. Our data suggest that the chaperone machinery may serve as the driving force for the RISC assembly pathway. Copyright 2010 Elsevier Inc. All rights reserved.

  17. 24 CFR 87.105 - Definitions.

    Science.gov (United States)

    2010-04-01

    ... services in the private sector. (o) Recipient includes all contractors, subcontractors at any tier, and... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Definitions. 87.105 Section 87.105... RESTRICTIONS ON LOBBYING General § 87.105 Definitions. For purposes of this part: (a) Agency, as defined in 5 U...

  18. A RISC/UNIX workstation second stage trigger

    International Nuclear Information System (INIS)

    Foreman, W.M.; Amann, J.F.; Fu, S.; Kozlowski, T.; Naivar, F.J.; Oothoudt, M.A.; Shelley, F.

    1992-01-01

    Recent advances in Reduced Instruction Set Computer (RISC) workstations have greatly altered the economics of processing power available for experiments. In addition VME interfaces available for many of these workstations make it possible to use them in experiment frontends for filtering and compressing data. Such a second stage trigger has been implemented at LAMPF using a commercially available workstation and VME interface. The implementation is described and measurements of data transfer speeds are presented in this paper

  19. RISC & DSP System Application Design using VHDL

    OpenAIRE

    Rachana Solanki; Vinay Gupta

    2014-01-01

    The Reduced Instruction Set Computer (RISC) processor use fewer instructions with simple constructs, therefore they can be executed much faster within the CPU without having to use memory as often. It reduce execution time by simplifying the instruction set of the computer. The DSP processors are perform the operation such as Discrete Cosine transform (DCT), Inverse DCT, Discrete Fourier Transform (DFT) and Fast Fourier Transform (FFT) are performed by DSP system. This paper represent the des...

  20. Association of invasive breast carcinoma and multicentric high grade astrocytoma: a case report with a review.

    Science.gov (United States)

    Pour, P Hossein; Forouzandeh, M; Beni, A Naderi; Beni, Z Naderi; Hoseinpour, P

    2011-03-01

    Breast cancer is the most common cancer in women. Multicentric gliomas are uncommon lesions of the central nervous system (CNS) with an unprecise rate of occurrence that diffusely infiltrate large portions of the brain. High grade astrocytoma is the most agressive form of gliomas and often has a distinct neuroimaging pattern with a poor prognosis. We report a case of a 29-year-old woman patient with primary breast carcinoma and high grade astrocytoma subsequently developed. The woman was treated by mastectomy and 20 months post-diagnosis of the cancer she exhibited a transient facial paralysis. Magnetic resonance imaging (MRI) revealed two cranial masses suspicious of metastasis. A complete tumor removal from the brain was performed. On histological examination, this tumor was a high grade astrocytoma.

  1. Fluorescence correlation spectroscopy and fluorescence cross-correlation spectroscopy reveal the cytoplasmic origination of loaded nuclear RISC in vivo in human cells.

    Science.gov (United States)

    Ohrt, Thomas; Mütze, Jörg; Staroske, Wolfgang; Weinmann, Lasse; Höck, Julia; Crell, Karin; Meister, Gunter; Schwille, Petra

    2008-11-01

    Studies of RNA interference (RNAi) provide evidence that in addition to the well-characterized cytoplasmic mechanisms, nuclear mechanisms also exist. The mechanism by which the nuclear RNA-induced silencing complex (RISC) is formed in mammalian cells, as well as the relationship between the RNA silencing pathways in nuclear and cytoplasmic compartments is still unknown. Here we show by applying fluorescence correlation and cross-correlation spectroscopy (FCS/FCCS) in vivo that two distinct RISC exist: a large approximately 3 MDa complex in the cytoplasm and a 20-fold smaller complex of approximately 158 kDa in the nucleus. We further show that nuclear RISC, consisting only of Ago2 and a short RNA, is loaded in the cytoplasm and imported into the nucleus. The loaded RISC accumulates in the nucleus depending on the presence of a target, based on an miRNA-like interaction with impaired cleavage of the cognate RNA. Together, these results suggest a new RISC shuttling mechanism between nucleus and cytoplasm ensuring concomitant gene regulation by small RNAs in both compartments.

  2. [Familial astrocytoma associated with von Recklinghausen's disease: report of two cases].

    Science.gov (United States)

    Ito, Y; Oki, S; Mikami, T; Ogasawara, H; Kawamoto, Y; Sato, H; Yamaguchi, S; Hayashi, Y; Shindo, H

    1997-03-01

    Two cases of astrocytoma associated with von Recklinghausen's disease (neurofibromatosis type; NF-1) were reported. The first case wes a 60-year-old man who had been diagnosed as von Recklinghausen's disease on the basis of skin findings. Magnetic resonance imaging (MRI) showed a tumor in the left temporal lobe. Partial removal was performed with neuronavigator, and because of the existence of Rosenthal fiber the histological diagnosis was pilocytic astrocytoma. Radiation therapy was performed. The second case was a 6-year-old boy suffering from headache and left hemiparesis including his face. MRI showed a tumor with a cyst in the right thalamus and obstructive hydrocephalus. Initially CT-guided stereotactic biopsy was performed, and the histological diagnosis, on the basis of increased cellularity, pleomorphism and nuclear atypia without necrosis or vascular proliferation, was anaplastic astrocytoma. Radiation and chemo-immuno therapy were carried out after V-P shunt. It is well known that von Recklinghausen's disease (NF-1) is often associated with optic glioma (5-36%). In the literature, the glioma seldom occurs in other parts of the brain, supratentorial glioma especially is rare. Only two familial cases of supratentorial glioma associated with von Recklinghausen's disease have been reported. The prognosis of supratentorial glioma associated with NF-1 was poor in these reports. In this paper, the diagnostic and therapeutic problems are discussed.

  3. Polish natural bee honeys are anti-proliferative and anti-metastatic agents in human glioblastoma multiforme U87MG cell line.

    Directory of Open Access Journals (Sweden)

    Justyna Moskwa

    Full Text Available Honey has been used as food and a traditional medicament since ancient times. However, recently many scientists have been concentrating on the anti-oxidant, anti-proliferative, anti-inflammatory and other properties of honey. In this study, we investigated for the first time an anticancer effect of different honeys from Poland on tumor cell line - glioblastoma multiforme U87MG. Anti-proliferative activity of honeys and its interferences with temozolomide were determined by a cytotoxicity test and DNA binding by [H3]-thymidine incorporation. A gelatin zymography was used to conduct an evaluation of metalloproteinases (MMP-2 and MMP-9 expression in U87MG treatment with honey samples. The honeys were previously tested qualitatively (diastase activity, total phenolic content, lead and cadmium content. The data demonstrated that the examined honeys have a potent anti-proliferative effect on U87MG cell line in a time- and dose-dependent manner, being effective at concentrations as low as 0.5% (multifloral light honey - viability 53% after 72 h of incubation. We observed that after 48 h, combining honey with temozolomide showed a significantly higher inhibitory effect than the samples of honey alone. We observed a strong inhibition of MMP-2 and MMP-9 for the tested honeys (from 20 to 56% and from 5 to 58% compared to control, respectively. Our results suggest that Polish honeys have an anti-proliferative and anti-metastatic effect on U87MG cell line. Therefore, natural bee honey can be considered as a promising adjuvant treatment for brain tumors.

  4. Vascular endothelial growth factor and basic fibroblast growth factor expression positively correlates with angiogenesis and peritumoural brain oedema in astrocytoma

    International Nuclear Information System (INIS)

    Jang, F.F.; Wei, W.

    2008-01-01

    Astrocytoma is the most malignant intracranial neoplasm and is characterized by high neovascularization and peritumoural brain oedema. Angiogenesis is a complicated process in oncogenesis regulated by the balance between angiogenic and antiangiogenic factors. The expression of two angiogenic growth factors, vascular endothelial growth factor and basic fibroblast growth factor were investigated using immunohistochemistry for astrocytoma from 82 patients and 11 normal human tissues. The expression of vascular endothelial growth factor and basic fibroblast growth factor positively correlate with the pathological grade of astrocytoma, microvessel density numbers and brain oedema, which may be responsible for the increased tumour neovascularization and peritumoural brain oedema. The results support the idea that inhibiting vascular endothelial growth factor and basic fibroblast growth factor are useful for the treatment of human astrocytoma and to improve patient's clinical outcomes and prognosis. (author)

  5. Proliferative and Invasive Effects of Progesterone-Induced Blocking Factor in Human Glioblastoma Cells

    Directory of Open Access Journals (Sweden)

    Araceli Gutiérrez-Rodríguez

    2017-01-01

    Full Text Available Progesterone-induced blocking factor (PIBF is a progesterone (P4 regulated protein expressed in different types of high proliferative cells including astrocytomas, the most frequent and aggressive brain tumors. It has been shown that PIBF increases the number of human astrocytoma cells. In this work, we evaluated PIBF regulation by P4 and the effects of PIBF on proliferation, migration, and invasion of U87 and U251 cells, both derived from human glioblastomas. PIBF mRNA expression was upregulated by P4 (10 nM from 12 to 24 h. Glioblastoma cells expressed two PIBF isoforms, 90 and 57 kDa. The content of the shorter isoform was increased by P4 at 24 h, while progesterone receptor antagonist RU486 (10 μM blocked this effect. PIBF (100 ng/mL increased the number of U87 cells on days 4 and 5 of treatment and induced cell proliferation on day 4. Wound-healing assays showed that PIBF increased the migration of U87 (12–48 h and U251 (24 and 48 h cells. Transwell invasion assays showed that PIBF augmented the number of invasive cells in both cell lines at 24 h. These data suggest that PIBF promotes proliferation, migration, and invasion of human glioblastoma cells.

  6. Development of a data acquisition system using a RISC/UNIXTM workstation

    International Nuclear Information System (INIS)

    Takeuchi, Y.; Tanimori, T.; Yasu, Y.

    1993-01-01

    We have developed a compact data acquisition system on RISC/UNIX workstations. A SUN TM SPARCstation TM IPC was used, in which an extension bus 'SBus TM ' was linked to a VMEbus. The transfer rate achieved was better than 7 Mbyte/s between the VMEbus and the SUN. A device driver for CAMAC was developed in order to realize an interruptive feature in UNIX. In addition, list processing has been incorporated in order to keep the high priority of the data handling process in UNIX. The successful developments of both device driver and list processing have made it possible to realize the good real-time feature on the RISC/UNIX system. Based on this architecture, a portable and versatile data taking system has been developed, which consists of a graphical user interface, I/O handler, user analysis process, process manager and a CAMAC device driver. (orig.)

  7. Lack of prognostic significance of C-erbB-2 expression in low- and high- grade astrocytomas.

    Science.gov (United States)

    Muallaoglu, Saik; Besen, Ali Ayberk; Ata, Alper; Mertsoylu, Huseyin; Arican, Ali; Kayaselcuk, Fazilet; Ozyilkan, Ozgur

    2014-01-01

    Astrocytic tumors, the most common primary glial tumors of the central nervous system, are classified from low to high grade according to the degree of anaplasia and presence of necrosis. Despite advances in therapeutic management of high grade astrocytic tumors, prognosis remains poor. In the present study, the frequency and prognostic significance of c-erb-B2 in astrocytic tumors was investigated. Records of 72 patients with low- and high-grade astrocytic tumors were evaluated. The expression of C-erbB-2 was determined immunohistochemically and intensity was recorded as 0 to 3+. Tumors with weak staining (1+) or no staining (0) were considered Her-2 negative, while tumors with moderate (2+) and strong (3+) staining were considered Her-2 positive. Of the 72 patients, 41 (56.9%) had glioblastoma (GBM), 10 (13.9%) had diffuse astrocytoma, 15 (20.8%) had anaplastic astrocytoma, 6 (8.3%) had pilocytic astrocytoma. C-erbB-2 overexpression was detected in the tumor specimens of 17 patients (23.6%). Six (8.3%) tumors, all GBMs, exhibited strong staining, 2 (2.7%) specimens, both GBMs, exhibited moderate staining, and 9 specimens, 5 of them GBMs (12.5%), exhibited weak staining. No staining was observed in diffuse astrocytoma and pilocytic astrocytoma specimens. Median overall survival of patients with C-erbB-2 negative and C-erbB-2 positive tumors were 30 months (95%CI: 22.5-37.4 months) and 16.9 months (95%CI: 4.3-29.5 months), respectively (p=0.244). Although there was no difference in survival, C-erbB-2 overexpression was observed only in the GBM subtype.

  8. RNA-induced silencing complex (RISC) Proteins PACT, TRBP, and Dicer are SRA binding nuclear receptor coregulators.

    Science.gov (United States)

    Redfern, Andrew D; Colley, Shane M; Beveridge, Dianne J; Ikeda, Naoya; Epis, Michael R; Li, Xia; Foulds, Charles E; Stuart, Lisa M; Barker, Andrew; Russell, Victoria J; Ramsay, Kerry; Kobelke, Simon J; Li, Xiaotao; Hatchell, Esme C; Payne, Christine; Giles, Keith M; Messineo, Adriana; Gatignol, Anne; Lanz, Rainer B; O'Malley, Bert W; Leedman, Peter J

    2013-04-16

    The cytoplasmic RNA-induced silencing complex (RISC) contains dsRNA binding proteins, including protein kinase RNA activator (PACT), transactivation response RNA binding protein (TRBP), and Dicer, that process pre-microRNAs into mature microRNAs (miRNAs) that target specific mRNA species for regulation. There is increasing evidence for important functional interactions between the miRNA and nuclear receptor (NR) signaling networks, with recent data showing that estrogen, acting through the estrogen receptor, can modulate initial aspects of nuclear miRNA processing. Here, we show that the cytoplasmic RISC proteins PACT, TRBP, and Dicer are steroid receptor RNA activator (SRA) binding NR coregulators that target steroid-responsive promoters and regulate NR activity and downstream gene expression. Furthermore, each of the RISC proteins, together with Argonaute 2, associates with SRA and specific pre-microRNAs in both the nucleus and cytoplasm, providing evidence for links between NR-mediated transcription and some of the factors involved in miRNA processing.

  9. MRS of pilocytic astrocytoma: The peak at 2 ppm may not be NAA.

    Science.gov (United States)

    Tamrazi, Benita; Nelson, Marvin D; Blüml, Stefan

    2017-08-01

    To determine whether the chemical shift of residual N-acetylaspartate (NAA) signal in pilocytic astrocytomas (PA) is consistent with the position of the NAA peak in controls. MR spectra from 27 pediatric World Health Organization (WHO) grade I pilocytic astrocytoma patients, fifteen patients with WHO grade II and high-grade (III-IV) astrocytomas, and 36 controls were analyzed. All spectra were acquired with a short echo time (35 ms), single voxel point-resolved spectroscopy sequence on clinical 3 tesla scanners. Fully automated LCModel software was used for processing, which included the fitting of peak positions for NAA and creatine (Cr). The chemical shift difference between the NAA and Cr peaks was significantly smaller (by 0.016 ± 0.005 parts per million, P NAA peak in PAs is not consistent with NAA. The signal likely originates from an N-acetyl group of one or more other chemicals such as N-acetylated sugars. Magn Reson Med 78:452-456, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  10. Competition between alliance blocks : the case of the RISC microprocessor technology

    NARCIS (Netherlands)

    Vanhaverbeke, W.P.M.; Noorderhaven, N.G.

    2001-01-01

    Competition between alliance blocks is a new form of rivalry: groups of firms link together for a common purpose by means of strategic alliances, and competition between alliance blocks is superimposed on competition between individual firms. This paper focuses on alliance blocks in the RISC

  11. Molecular analysis of pediatric brain tumors identifies microRNAs in pilocytic astrocytomas that target the MAPK and NF-κB pathways.

    Science.gov (United States)

    Jones, Tania A; Jeyapalan, Jennie N; Forshew, Tim; Tatevossian, Ruth G; Lawson, Andrew R J; Patel, Sheena N; Doctor, Gabriel T; Mumin, Muhammad A; Picker, Simon R; Phipps, Kim P; Michalski, Antony; Jacques, Thomas S; Sheer, Denise

    2015-12-18

    Pilocytic astrocytomas are slow-growing tumors that usually occur in the cerebellum or in the midline along the hypothalamic/optic pathways. The most common genetic alterations in pilocytic astrocytomas activate the ERK/MAPK signal transduction pathway, which is a major driver of proliferation but is also believed to induce senescence in these tumors. Here, we have conducted a detailed investigation of microRNA and gene expression, together with pathway analysis, to improve our understanding of the regulatory mechanisms in pilocytic astrocytomas. Pilocytic astrocytomas were found to have distinctive microRNA and gene expression profiles compared to normal brain tissue and a selection of other pediatric brain tumors. Several microRNAs found to be up-regulated in pilocytic astrocytomas are predicted to target the ERK/MAPK and NF-κB signaling pathways as well as genes involved in senescence-associated inflammation and cell cycle control. Furthermore, IGFBP7 and CEBPB, which are transcriptional inducers of the senescence-associated secretory phenotype (SASP), were also up-regulated together with the markers of senescence and inflammation, CDKN1A (p21), CDKN2A (p16) and IL1B. These findings provide further evidence of a senescent phenotype in pilocytic astrocytomas. In addition, they suggest that the ERK/MAPK pathway, which is considered the major driver of these tumors, is regulated not only by genetic aberrations but also by microRNAs.

  12. Exposure to 60-Hz magnetic fields and proliferation of human astrocytoma cells in vitro.

    Science.gov (United States)

    Wei, M; Guizzetti, M; Yost, M; Costa, L G

    2000-02-01

    Epidemiological studies have suggested that exposure to electric and magnetic fields (EMF) may be associated with an increased incidence of brain tumors, most notably astrocytomas. However, potential cellular or molecular mechanisms involved in these effects of EMF are not known. In this study we investigated whether exposure to 60-Hz sinusoidal magnetic fields (0.3-1.2 G for 3-72 h) would cause proliferation of human astrocytoma cells. Sixty-Hertz magnetic fields (MF) caused a time- and dose-dependent increase in proliferation of astrocytoma cells, measured by (3)H-thymidine incorporation and by flow cytometry, and strongly potentiated the effect of two agonists (the muscarinic agonist carbachol and the phorbol ester PMA). However, MF had no effect on DNA synthesis of rat cortical astrocytes, i.e., of similar, nontransformed cells. To determine the amount of heating induced by MF, temperatures were also recorded in the medium. Both 1.2 G MF and a sham exposure caused a 0.7 degrees C temperature increase in the medium; however, (3)H-thymidine incorporation induced by sham exposure was significantly less than that caused by MF. GF 109203X, a rather specific protein kinase C (PKC) inhibitor, and down-regulation of PKC inhibited the effect of MF on basal and on agonist-stimulated (3)H-thymidine incorporation. These data indicate that MF can increase the proliferation of human astrocytoma cells and strongly potentiate the effects of two agonists. These findings may provide a biological basis for the observed epidemiological associations between MF exposure and brain tumors. Copyright 2000 Academic Press.

  13. Astrocytoma of the pituitary gland (pituicytoma): case report

    International Nuclear Information System (INIS)

    Uesaka, T.; Miyazono, M.; Nishio, S.; Iwaki, T.

    2002-01-01

    A 34-year-old man presented with a 4-month history of visual obscuration. Magnetic resonance imaging showed a solid, discrete, contrast-enhancing pituitary mass with suprasellar extension. Surgery, which was performed via a transsphenoidal approach, disclosed the pituitary tumor to be a fibrillary astrocytoma (pituicytoma). This case report contains the clinical and neuroimaging features of this rare tumor of the neurohypophysis, which masqueraded as a pituitary adenoma. (orig.)

  14. Saponin 6 derived from Anemone taipaiensis induces U87 human malignant glioblastoma cell apoptosis via regulation of Fas and Bcl‑2 family proteins.

    Science.gov (United States)

    Ji, Chen-Chen; Tang, Hai-Feng; Hu, Yi-Yang; Zhang, Yun; Zheng, Min-Hua; Qin, Hong-Yan; Li, San-Zhong; Wang, Xiao-Yang; Fei, Zhou; Cheng, Guang

    2016-07-01

    Glioblastoma multiforme (GBM) is the most common and aggressive type of brain tumor, and is associated with a poor prognosis. Saponin 6, derived from Anemone taipaiensis, exerts potent cytotoxic effects against the human hepatocellular carcinoma HepG2 cell line and the human promyelocytic leukemia HL‑60 cell line; however, the effects of saponin 6 on glioblastoma remain unknown. The present study aimed to evaluate the effects of saponin 6 on human U87 malignant glioblastoma (U87 MG) cells. The current study revealed that saponin 6 induced U87 MG cell death in a dose‑ and time‑dependent manner, with a half maximal inhibitory concentration (IC50) value of 2.83 µM after treatment for 48 h. However, saponin 6 was needed to be used at a lesser potency in HT‑22 cells, with an IC50 value of 6.24 µM. Cell apoptosis was assessed by flow cytometry using Annexin V‑fluorescein isothiocyanate/propidium iodide double staining. DNA fragmentation and alterations in nuclear morphology were examined by terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling and transmission electron microscopy, respectively. The present study demonstrated that treatment with saponin 6 induced cell apoptosis in U87 MG cells, and resulted in DNA fragmentation and nuclear morphological alterations typical of apoptosis. In addition, flow cytometric analysis revealed that saponin 6 was able to induce cell cycle arrest. The present study also demonstrated that saponin 6‑induced apoptosis of U87 MG cells was attributed to increases in the protein expression levels of Fas, Fas ligand, and cleaved caspase‑3, ‑8 and ‑9, and decreases in the levels of B‑cell lymphoma 2. The current study indicated that saponin 6 may exhibit selective cytotoxicity toward U87 MG cells by activating apoptosis via the extrinsic and intrinsic pathways. Therefore, saponin 6 derived from A. taipaiensis may possess therapeutic potential for the treatment of GBM.

  15. Anti-Cancer Effect of Metabotropic Glutamate Receptor 1 Inhibition in Human Glioma U87 Cells: Involvement of PI3K/Akt/mTOR Pathway

    Directory of Open Access Journals (Sweden)

    Chi Zhang

    2015-01-01

    Full Text Available Background: Metabotropic glutamate receptors (mGluRs are G-protein-coupled receptors that mediate neuronal excitability and synaptic plasticity in the central nervous system, and emerging evidence suggests a role of mGluRs in the biology of cancer. Previous studies showed that mGluR1 was a potential therapeutic target for the treatment of breast cancer and melanoma, but its role in human glioma has not been determined. Methods: In the present study, we investigated the effects of mGluR1 inhibition in human glioma U87 cells using specific targeted small interfering RNA (siRNA or selective antagonists Riluzole and BAY36-7620. The anti-cancer effects of mGluR1 inhibition were measured by cell viability, lactate dehydrogenase (LDH release, TUNEL staining, cell cycle assay, cell invasion and migration assays in vitro, and also examined in a U87 xenograft model in vivo. Results: Inhibition of mGluR1 significantly decreased the cell viability but increased the LDH release in a dose-dependent fashion in U87 cells. These effects were accompanied with the induction of caspase-dependent apoptosis and G0/G1 cell cycle arrest. In addition, the results of Matrigel invasion and cell tracking assays showed that inhibition of mGluR1 apparently attenuated cell invasion and migration in U87 cells. All these anti-cancer effects were ablated by the mGluR1 agonist L-quisqualic acid. The results of western blot analysis showed that mGluR1 inhibition overtly decreased the phosphorylation of PI3K, Akt, mTOR and P70S6K, indicating the mitigated activation of PI3K/Akt/mTOR pathway. Moreover, the anti-tumor activity of mGluR1 inhibition in vivo was also demonstrated in a U87 xenograft glioma model in athymic nude mice. Conclusion: The remarkable efficiency of mGluR1 inhibition to induce cell death in U87 cells may find therapeutic application for the treatment of glioma patients.

  16. Structural insights into RNA processing by the human RISC-loading complex.

    Science.gov (United States)

    Wang, Hong-Wei; Noland, Cameron; Siridechadilok, Bunpote; Taylor, David W; Ma, Enbo; Felderer, Karin; Doudna, Jennifer A; Nogales, Eva

    2009-11-01

    Targeted gene silencing by RNA interference (RNAi) requires loading of a short guide RNA (small interfering RNA (siRNA) or microRNA (miRNA)) onto an Argonaute protein to form the functional center of an RNA-induced silencing complex (RISC). In humans, Argonaute2 (AGO2) assembles with the guide RNA-generating enzyme Dicer and the RNA-binding protein TRBP to form a RISC-loading complex (RLC), which is necessary for efficient transfer of nascent siRNAs and miRNAs from Dicer to AGO2. Here, using single-particle EM analysis, we show that human Dicer has an L-shaped structure. The RLC Dicer's N-terminal DExH/D domain, located in a short 'base branch', interacts with TRBP, whereas its C-terminal catalytic domains in the main body are proximal to AGO2. A model generated by docking the available atomic structures of Dicer and Argonaute homologs into the RLC reconstruction suggests a mechanism for siRNA transfer from Dicer to AGO2.

  17. Effects of the nitric oxide donor JS-K on the blood-tumor barrier and on orthotopic U87 rat gliomas assessed by MRI.

    Science.gov (United States)

    Weidensteiner, Claudia; Reichardt, Wilfried; Shami, Paul J; Saavedra, Joseph E; Keefer, Larry K; Baumer, Brunhilde; Werres, Anna; Jasinski, Robert; Osterberg, Nadja; Weyerbrock, Astrid

    2013-04-01

    Nitric oxide (NO) released from NO donors can be cytotoxic in tumor cells and can enhance the transport of drugs into brain tumors by altering blood-tumor barrier permeability. The NO donor JS-K [O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate] releases NO upon enzymatic activation selectively in cells overexpressing glutathione-S-transferases (GSTs) such as gliomas. Thus, JS-K-dependent NO effects - especially on cell viability and vascular permeability - were investigated in U87 glioma cells in vitro and in an orthotopic U87 xenograft model in vivo by magnetic resonance imaging (MRI). In vitro experiments showed dose-dependent antiproliferative and cytotoxic effects in U87 cells. In addition, treatment of U87 cells with JS-K resulted in a dose-dependent activation of soluble guanylate cyclase and intracellular accumulation of cyclic guanosine monophosphate (cGMP) which was irreversibly inhibited by the selective inhibitor of soluble guanylate cyclase ODQ (1H-[1,2,4]oxadiazolo(4,3a)quinoxaline-1-one). Using dynamic contrast enhanced MRI (DCE-MRI) as a minimally invasive technique, we demonstrated for the first time a significant increase in the DCE-MRI read-out initial area under the concentration curve (iAUC60) indicating an acute increase in blood-tumor barrier permeability after i.v. treatment with JS-K. Repeated MR imaging of animals with intracranial U87 gliomas under treatment with JS-K (3.5 μmol/kg JS-K 3×/week) and of untreated controls on day 12 and 19 after tumor inoculation revealed no significant changes in tumor growth, edema formation or tumor perfusion. Immunohistochemical workup of the brains showed a significant antiproliferative effect of JS-K in the gliomas. Taken together, in vitro and in vivo data suggest that JS-K has antiproliferative effects in U87 gliomas and opens the blood-tumor barrier by activation of the NO/cGMP signaling pathway. This might be a novel approach to facilitate entry of therapeutic

  18. FLAIR MR sequence in the diagnosis and follow-up of low-grade astrocytomas

    Directory of Open Access Journals (Sweden)

    Stošić-Opinćal Tatjana

    2005-01-01

    Full Text Available Aim. To evaluate the sensitivity of fluid-attenuated inversion recovery (FLAIR sequence in the diagnosis and follow-up of the patients with low-grade astrocytomas compared with T2-weighted (T2W sequence. Methods. Twenty-four patients with biopsy- confirmed low-grade astrocytoma (age range, 15-66 years underwent T1- weighted (T1W, T2W and FLAIR imaging with a superconducting unit 1.0 T. FLAIR images were qualitatively evaluated by comparison with T2W images by the three experienced neuroradiologists. To evaluate the diagnostic value of FLAIR, the neuroradiologists individually assessed the possibilities of the detection of lesions, as well as the possibilities of the differentiation of tumor from the surrounding edema on FLAIR vs. T2W images. Every examiner ranked FLAIR sequence vs. T2W in three degrees: worse, equal and better. Results. The comparison of FLAIR with T2W spin-echo (SE images with regard to the detection of the lesions showed that 82.8% of FLAIR studies were superior, 17.2% were of similar diagnostic value, and none was inferior to the T2W images. The comparison of images with regard to the differentiation of tumor boundaries vs. surrounding edema showed that 92.5% of FLAIR studies were superior, 7.5% were of similar diagnostic value, and none was inferior to the T2W images. Conclusion. Our results were similar to the previous studies' results concerning the advantages of FLAIR sequence in the diagnosis of low grade astrocytomas over T2W sequence. FLAIR was better at showing different tumor components, and at distinguishing CSF from the cystic component, and the postoperative cavity, compared with T2W images. Our conclusion was that FLAIR could be routinely used in the evaluation and follow-up of low-grade astrocytomas.

  19. Single-molecule fluorescence measurements reveal the reaction mechanisms of the core RISC, composed of human Argonaute 2 and a guide RNA.

    Science.gov (United States)

    Jo, Myung Hyun; Song, Ji-Joon; Hohng, Sungchul

    2015-12-01

    In eukaryotes, small RNAs play important roles in both gene regulation and resistance to viral infection. Argonaute proteins have been identified as a key component of the effector complexes of various RNA-silencing pathways, but the mechanistic roles of Argonaute proteins in these pathways are not clearly understood. To address this question, we performed single-molecule fluorescence experiments using an RNA-induced silencing complex (core-RISC) composed of a small RNA and human Argonaute 2. We found that target binding of core-RISC starts at the seed region of the guide RNA. After target binding, four distinct reactions followed: target cleavage, transient binding, stable binding, and Argonaute unloading. Target cleavage required extensive sequence complementarity and accelerated core-RISC dissociation for recycling. In contrast, the stable binding of core-RISC to target RNAs required seed-match only, suggesting a potential explanation for the seed-match rule of microRNA (miRNA) target selection.

  20. Burden to importance ratio as a quantitative measure to validate the RISC-3 SSC in OPTION-2

    International Nuclear Information System (INIS)

    Ha, J. S.; Sung, P. H.

    2004-01-01

    A Risk-Informed Safety Significance Categorization (RISSC) is to categorize structures, systems, or components (SSCs) of a Nuclear Power Plant (NPP) into two or more groups, according to their safety significance using both probabilistic and deterministic insights. Recently, OPTION-2 (which is an emerging risk-informed paradigm) recommends that SSCs should be categorized into four groups according to whether they are safety-related or not as well as their safety significance. With the change of 10 CFR 50, safety-related components which categorized into low safety significant SSC (RISC-3 SSC) can be exempted from the existing conservative requirements. Consequently, as OPTION-2 paradigm is applied, a validation process focused on the RISC-3 SSC is needed to assure the categorization results, because most of existing RISSC methods focused on the categorization of the whole SSCs of NPPs based on importance measures obtained from probabilistic and deterministic insights. In this work, Burden to Importance Ratio (BIR) is utilized as a measure for the validation of RISC-3 SSC in OPTION-2. To demonstrate the usefulness of the proposed approach, the approach is applied to 22 components selected from 512 In-Service Test (IST) components of Ulchin unit 3. The results of the application show that the proposed approach is useful for the validation of RISC-3 SSC in OPTION-2

  1. circ-SHKBP1 Regulates the Angiogenesis of U87 Glioma-Exposed Endothelial Cells through miR-544a/FOXP1 and miR-379/FOXP2 Pathways

    Directory of Open Access Journals (Sweden)

    Qianru He

    2018-03-01

    Full Text Available Circular RNAs (circRNAs are a type of endogenous non-coding RNAs, which have been considered to mediate diverse tumorigenesis including angiogenesis. The present study aims to elucidate the potential role and molecular mechanism of circ-SHKBP1 in regulating the angiogenesis of U87 glioma-exposed endothelial cells (GECs. The expression of circ-SHKBP1, but not linear SHKBP1, was significantly upregulated in GECs compared with astrocyte-exposed endothelial cells (AECs. circ-SHKBP1 knockdown inhibited the viability, migration, and tube formation of GECs dramatically. The expressions of miR-379/miR-544a were downregulated in GECs, and circ-SHKBP1 functionally targeted miR-544a/miR-379 in an RNA-induced silencing complex (RISC manner. Dual-luciferase reporter assay demonstrated that forkhead box P1/P2 (FOXP1/FOXP2 were targets of miR-544a/miR-379. The expressions of FOXP1/FOXP2 were upregulated in GECs, and silencing of FOXP1/FOXP2 inhibited the viability, migration, and tube formation of GECs. Meanwhile, FOXP1/FOXP2 promoted angiogenic factor with G patch and FHA domains 1 (AGGF1 expression at the transcriptional level. Furthermore, knockdown of AGGF1 suppressed the viability, migration, and tube formation of GECs via phosphatidylinositol 3-kinase (PI3K/AKT and extracellular signal-regulated kinase (ERK1/2 pathways. Taken together, the present study demonstrated that circ-SHKBP1 regulated the angiogenesis of GECs through miR-544a/FOXP1 and miR-379/FOXP2 pathways, and these findings might provide a potential target and effective strategy for combined therapy of gliomas.

  2. Phase II trial of carmustine, cisplatin, and oral etoposide chemotherapy before radiotherapy for grade 3 astrocytoma (anaplastic astrocytoma): Results of North Central Cancer Treatment Group trial 98-72-51

    International Nuclear Information System (INIS)

    Rao, Ravi D.; Krishnan, Sunil; Fitch, Tom R.; Schomberg, Paula J.; Dinapoli, Robert P.; Nordstrom, Kathleen; Scheithauer, Bernd; O'Fallon, Judith R.; Maurer, Matthew J. M.S.; Buckner, Jan C.

    2005-01-01

    Purpose: To evaluate the efficacy of preradiotherapy (RT) chemotherapy with carmustine, cisplatin, and oral etoposide combined with RT in the treatment of newly diagnosed anaplastic astrocytoma. Methods and materials: Therapy consisted of carmustine (40 mg/m 2 /d) on Days 1-3, oral etoposide (50 mg/d) on Days 1-21 and 29-49, and cisplatin (20 mg/m 2 /d i.v.) on Days 1-3 and 29-31. The regimen was repeated every 8 weeks for three cycles, with conventionally fractionated RT (5000 cGy with a 1000-cGy boost) delivered concurrently with the third cycle. Results: A total of 29 patients were enrolled between December 1999 and March 2001. For varying reasons (e.g., progression, refusal, death, or toxicity), only 48% completed the chemotherapy regimen and 76% completed RT. Grade 3-4 toxicities were observed in 14 patients (48%). The primary study endpoint was the 23-month (700-day) survival, the median survival of patients with anaplastic astrocytoma in a previous North Central Cancer Treatment Group trial. To be considered an active treatment, a maximum of 9 patient deaths (of the first 25) were allowed before 700 days. However, 14 patients had died by 700 days after therapy. Conclusion: Our results have demonstrated that pre-RT chemotherapy with this regimen is insufficiently active in patients with anaplastic astrocytoma

  3. Transcriptional profiles of pilocytic astrocytoma are related to their three different locations, but not to radiological tumor features

    International Nuclear Information System (INIS)

    Zakrzewski, Krzysztof; Jarząb, Michał; Pfeifer, Aleksandra; Oczko-Wojciechowska, Małgorzata; Jarząb, Barbara; Liberski, Paweł P.; Zakrzewska, Magdalena

    2015-01-01

    Pilocytic astrocytoma is the most common type of brain tumor in the pediatric population, with a generally favorable prognosis, although recurrences or leptomeningeal dissemination are sometimes also observed. For tumors originating in the supra-or infratentorial location, a different molecular background was suggested, but plausible correlations between the transcriptional profile and radiological features and/or clinical course are still undefined. The purpose of this study was to identify gene expression profiles related to the most frequent locations of this tumor, subtypes based on various radiological features, and the clinical pattern of the disease. Eighty six children (55 males and 31 females) with histologically verified pilocytic astrocytoma were included in this study. Their age at the time of diagnosis ranged from fourteen months to seventeen years, with a mean age of seven years. There were 40 cerebellar, 23 optic tract/hypothalamic, 21 cerebral hemispheric, and two brainstem tumors. According to the radiological features presented on MRI, all cases were divided into four subtypes: cystic tumor with a non-enhancing cyst wall; cystic tumor with an enhancing cyst wall; solid tumor with central necrosis; and solid or mainly solid tumor. In 81 cases primary surgical resection was the only and curative treatment, and in five cases progression of the disease was observed. In 47 cases the analysis was done by using high density oligonucleotide microarrays (Affymetrix HG-U133 Plus 2.0) with subsequent bioinformatic analyses and confirmation of the results by independent RT-qPCR (on 39 samples). Bioinformatic analyses showed that the gene expression profile of pilocytic astrocytoma is highly dependent on the tumor location. The most prominent differences were noted for IRX2, PAX3, CXCL14, LHX2, SIX6, CNTN1 and SIX1 genes expression even within different compartments of the supratentorial region. Analysis of the genes potentially associated with radiological

  4. Sublethal dose of irradiation enhances invasion of malignant glioma cells through p53-MMP 2 pathway in U87MG mouse brain tumor model

    International Nuclear Information System (INIS)

    Pei, Jian; Park, In-Ho; Ryu, Hyang-Hwa; Li, Song-Yuan; Li, Chun-Hao; Lim, Sa-Hoe; Wen, Min; Jang, Woo-Youl; Jung, Shin

    2015-01-01

    Glioblastoma is a highly lethal neoplasm that frequently recurs locally after radiotherapy, and most of these recurrences originate from near the irradiated target field. In the present study, we identified the effects of radiation on glioma invasion and p53, TIMP-2, and MMP-2 expression through in vitro and in vivo experiments. The U87MG (wt p53) and U251 (mt p53) human malignant glioma cell lines were prepared, and the U2OS (wt 53) and Saos2 (del p53) osteosarcoma cell lines were used as p53 positive and negative controls. The four cell lines and p53 knock-downed U87MG cells received radiation (2–6 Gy) and were analyzed for expression of p53 and TIMP-2 by Western blot, and MMP-2 activity was detected by zymography. In addition, the effects of irradiation on directional invasion of malignant glioma were evaluated by implanting nude mice with bioluminescent u87-Fluc in vivo followed by MMP-2, p53, and TIMP-2 immunohisto-chemistry and in situ zymography. MMP-2 activity and p53 expression increased in proportional to the radiation dose in cell lines with wt p53, but not in the cell lines with del or mt p53. TIMP-2 expression did not increase in U87MG cells. MMP-2 activity decreased in p53 knock-downed U87MG cells but increased in the control group. Furthermore, radiation enhanced MMP-2 activity and increased tumor margin invasiveness in vivo. Tumor cells invaded by radiation overexpressed MMP-2 and p53 and revealed high gelatinolytic activity compared with those of non-radiated tumor cells. Radiation-induced upregulation of p53 modulated MMP-2 activity, and the imbalance between MMP-2 and TIMP-2 may have an important role in glioblastoma invasion by degrading the extracellular matrix. Bioluminescent “U87-Fluc”was useful for observing tumor formation without sacrifice after implanting tumor cells in the mouse brain. These findings suggest that the radiotherapy involved field for malignant glioma needs to be reconsidered, and that future trials should investigate

  5. The emerging role of m-TOR up-regulation in brain Astrocytoma.

    Science.gov (United States)

    Ryskalin, Larisa; Limanaqi, Fiona; Biagioni, Francesca; Frati, Alessandro; Esposito, Vincenzo; Calierno, Maria Teresa; Lenzi, Paola; Fornai, Francesco

    2017-05-01

    The present manuscript is an overview of various effects of mTOR up-regulation in astrocytoma with an emphasis on its deleterious effects on the proliferation of Glioblastoma Multiforme. The manuscript reports consistent evidence indicating the occurrence of mTOR up-regulation both in experimental and human astrocytoma. The grading of human astrocytoma is discussed in relationship with mTOR up-regulation. In the second part of the manuscript, the biochemical pathways under the influence of mTOR are translated to cell phenotypes which are generated by mTOR up-regulation and reverted by its inhibition. A special section is dedicated to the prominent role of autophagy in mediating the effects of mTOR in glioblastoma. In detail, autophagy inhibition produced by mTOR up-regulation determines the fate of cancer stem cells. On the other hand, biochemical findings disclose the remarkable effects of autophagy activators as powerful inducers of cell differentiation with a strong prevalence towards neuronal phenotypes. Thus, mTOR modulation acts on the neurobiology of glioblastoma just like it operates in vivo at the level of brain stem cell niches by altering autophagy-dependent cell differentiation. In the light of such a critical role of autophagy we analyzed the ubiquitin proteasome system. The merging between autophagy and proteasome generates a novel organelle, named autophagoproteasome which is strongly induced by mTOR inhibitors in glioblastoma cells. Remarkably, when mTOR is maximally inhibited the proteasome component selectively moves within autophagy vacuoles, thus making the proteasome activity dependent on the entry within autophagy compartment.

  6. Arabidopsis ARGONAUTE7 selects miR390 through multiple checkpoints during RISC assembly.

    Science.gov (United States)

    Endo, Yayoi; Iwakawa, Hiro-oki; Tomari, Yukihide

    2013-07-01

    Plant ARGONAUTE7 (AGO7) assembles RNA-induced silencing complex (RISC) specifically with miR390 and regulates the auxin-signalling pathway via production of TAS3 trans-acting siRNAs (tasiRNAs). However, how AGO7 discerns miR390 among other miRNAs remains unclear. Here, we show that the 5' adenosine of miR390 and the central region of miR390/miR390* duplex are critical for the specific interaction with AGO7. Furthermore, despite the existence of mismatches in the seed and central regions of the duplex, cleavage of the miR390* strand is required for maturation of AGO7-RISC. These findings suggest that AGO7 uses multiple checkpoints to select miR390, thereby circumventing promiscuous tasiRNA production.

  7. RISC-mediated control of selected chromatin regulators stabilizes ground state pluripotency of mouse embryonic stem cells.

    Science.gov (United States)

    Pandolfini, Luca; Luzi, Ettore; Bressan, Dario; Ucciferri, Nadia; Bertacchi, Michele; Brandi, Rossella; Rocchiccioli, Silvia; D'Onofrio, Mara; Cremisi, Federico

    2016-05-06

    Embryonic stem cells are intrinsically unstable and differentiate spontaneously if they are not shielded from external stimuli. Although the nature of such instability is still controversial, growing evidence suggests that protein translation control may play a crucial role. We performed an integrated analysis of RNA and proteins at the transition between naïve embryonic stem cells and cells primed to differentiate. During this transition, mRNAs coding for chromatin regulators are specifically released from translational inhibition mediated by RNA-induced silencing complex (RISC). This suggests that, prior to differentiation, the propensity of embryonic stem cells to change their epigenetic status is hampered by RNA interference. The expression of these chromatin regulators is reinstated following acute inactivation of RISC and it correlates with loss of stemness markers and activation of early cell differentiation markers in treated embryonic stem cells. We propose that RISC-mediated inhibition of specific sets of chromatin regulators is a primary mechanism for preserving embryonic stem cell pluripotency while inhibiting the onset of embryonic developmental programs.

  8. Journal of Chemical Sciences | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Compounds 3 and 4 were screened for selective antiproliferative activity in three cancer cell lines of different tissue types (COLO 205 (human colorectal adenocarcinoma),U87 MG (glioblastoma astrocytoma) and MIAPaCa-2 (human pancreatic carcinoma). Geometry-optimized structures for tautomers 3 and 4 (3′ and 4′ ...

  9. An infant with hyperalertness, hyperkinesis, and failure to thrive: a rare diencephalic syndrome due to hypothalamic anaplastic astrocytoma.

    Science.gov (United States)

    Stival, Alessia; Lucchesi, Maurizio; Farina, Silvia; Buccoliero, Anna Maria; Castiglione, Francesca; Genitori, Lorenzo; de Martino, Maurizio; Sardi, Iacopo

    2015-09-04

    Diencephalic Syndrome is a rare clinical condition of failure to thrive despite a normal caloric intake, hyperalertness, hyperkinesis, and euphoria usually associated with low-grade hypothalamic astrocytomas. We reported an unusual case of diencephalic cachexia due to hypothalamic anaplastic astrocytoma (WHO-grade III). Baseline endocrine function evaluation was performed in this patient before surgery. After histological diagnosis, he enrolled to a chemotherapy program with sequential high-dose chemotherapy followed by hematopoietic stem cell rescue. The last MRI evaluation showed a good response. The patient is still alive with good visual function 21 months after starting chemotherapy. Diencephalic cachexia can rarely be due to high-grade hypothalamic astrocytoma. We suggest that a nutritional support with chemotherapy given to high doses without radiotherapy could be an effective strategy for treatment of a poor-prognosis disease.

  10. Low-Grade Astrocytoma Associated with Abscess Formation: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Tai-Hsin Tsai

    2008-05-01

    Full Text Available A rare case of low-grade astrocytoma associated with abscess formation occurred in a 52-year-old man presenting with Broca's aphasia. He underwent craniotomy and tumor removal under the impression of brain tumor with necrotic cystic change. Abscess accumulation within the intra-axial tumor was found intraoperatively. Literature related to brain abscess with brain tumor is reviewed, with an emphasis on abscesses with astrocytoma. We discuss the common brain tumors that are associated with abscess, pathogens that coexist with brain tumor, and the pathogeneses of coexisting brain abscess and tumor. It is very important to know how to differentiate between and diagnose a brain abscess and tumor, or brain abscess with tumor, preoperatively from clinical presentation and through the use of computed tomography, conventional magnetic resonance imaging, diffusion-weighted imaging or magnetic resonance spectroscopy.

  11. Polerovirus protein P0 prevents the assembly of small RNA-containing RISC complexes and leads to degradation of ARGONAUTE1.

    Science.gov (United States)

    Csorba, Tibor; Lózsa, Rita; Hutvágner, György; Burgyán, József

    2010-05-01

    RNA silencing plays an important role in plants in defence against viruses. To overcome this defence, plant viruses encode suppressors of RNA silencing. The most common mode of silencing suppression is sequestration of double-stranded RNAs involved in the antiviral silencing pathways. Viral suppressors can also overcome silencing responses through protein-protein interaction. The poleroviral P0 silencing suppressor protein targets ARGONAUTE (AGO) proteins for degradation. AGO proteins are the core component of the RNA-induced silencing complex (RISC). We found that P0 does not interfere with the slicer activity of pre-programmed siRNA/miRNA containing AGO1, but prevents de novo formation of siRNA/miRNA containing AGO1. We show that the AGO1 protein is part of a high-molecular-weight complex, suggesting the existence of a multi-protein RISC in plants. We propose that P0 prevents RISC assembly by interacting with one of its protein components, thus inhibiting formation of siRNA/miRNA-RISC, and ultimately leading to AGO1 degradation. Our findings also suggest that siRNAs enhance the stability of co-expressed AGO1 in both the presence and absence of P0.

  12. RISC mezzanines for controlling data acquisition in the NA48 experiment at CERN

    International Nuclear Information System (INIS)

    Guzik, Z.; Chlopik, A.; Bal, Fr.; Formenti, F.; Lacourt, A.

    2000-01-01

    A part of the LKr calorimeter data acquisition system of the NA48 experiment (a precision measurements of ε/ε' in CP violating; K 0 →2π decays) is described. The experiment runs on the SPS north area in CERN. This paper presents some aspects of controlling the NA48 readout process based on commercial RIO 8260 RISC processors, which were used as a core for maintaining control algorithms. Several RISC processors were equipped with custom-made VME mezzanine boards providing interfacing, pre-processing and data formatting. These mezzanines are subjects of this paper. They are: RIO-TIC/DAT - time stamp distributor and buffered DT-bus interface, FOL-RIO - optical data formatter and event merger and 'TAXI receiver' - handling trigger data of the NA48 Level 2 trigger supervisor. Also the interface between DT-bus and S-link/PCI is described

  13. A fastbus master based on a risc microprocessor

    International Nuclear Information System (INIS)

    Cerrito, L.; Chorowicz, V.; Lebbolo, H.; Vallereau, A.

    1990-01-01

    SISIFUS is a general purpose Fastbus Master and Slave able to perform any operation on both Fastbus segments. Master operations are directed either by the processor or by two fast sequencers. A Block Mover function is implemented allowing direct data block transfers between two Slaves. SISIFUS uses the AM 29000 RISC microprocessor which can execute every assembler instruction in 40ns. The on-board monitor/debugger allows programs to be written in assembler from a terminal connected to the module or written in C and cross compiled on a host computer (PC)

  14. RhoE interferes with Rb inactivation and regulates the proliferation and survival of the U87 human glioblastoma cell line

    International Nuclear Information System (INIS)

    Poch, Enric; Minambres, Rebeca; Mocholi, Enric; Ivorra, Carmen; Perez-Arago, Amparo; Guerri, Consuelo; Perez-Roger, Ignacio; Guasch, Rosa M.

    2007-01-01

    Rho GTPases are important regulators of actin cytoskeleton, but they are also involved in cell proliferation, transformation and oncogenesis. One of this proteins, RhoE, inhibits cell proliferation, however the mechanism that regulates this effect remains poorly understood. Therefore, we undertook the present study to determine the role of RhoE in the regulation of cell proliferation. For this purpose we generated an adenovirus system to overexpress RhoE in U87 glioblastoma cells. Our results show that RhoE disrupts actin cytoskeleton organization and inhibits U87 glioblastoma cell proliferation. Importantly, RhoE expressing cells show a reduction in Rb phosphorylation and in cyclin D1 expression. Furthermore, RhoE inhibits ERK activation following serum stimulation of quiescent cells. Based in these findings, we propose that RhoE inhibits ERK activation, thereby decreasing cyclin D1 expression and leading to a reduction in Rb inactivation, and that this mechanism is involved in the RhoE-induced cell growth inhibition. Moreover, we also demonstrate that RhoE induces apoptosis in U87 cells and also in colon carcinoma and melanoma cells. These results indicate that RhoE plays an important role in the regulation of cell proliferation and survival, and suggest that this protein may be considered as an oncosupressor since it is capable to induce apoptosis in several tumor cell lines

  15. The value of diffusion weighted imaging in differentiating intracranial tuberculomas from high-grade astrocytomas and metastases

    International Nuclear Information System (INIS)

    Peng Juan; Luo Tianyou; Lv Fajin; Fang Weidong; Wu Jingquan; Ouyang Yu; Li Yongmei

    2007-01-01

    Objective: To explore the value of diffusion weighted imaging (DWI) in differentiating intracranial tuberculomas from high-grade astrocytomas and metastases. Methods: The conventional MR imaging and DWI were performed in 50 eases (14 cases with intracranial tuberculomas, 15 cases with high- grade astrocytomas, and 21 cases with metastases) before treatment or operation. The mean apparent diffusion coefficient (ADC) values and relative apparent diffusion coefficient (rADC) values were calculated from the mass as well as from the peripheral edema regions of intracranial lesions. Results: The mean ADC values and rADC values were (1.2±0.2) x 10 -3 mm 2 ·s -1 and 1.6±0.3 in the mass of intracranial tuberculomas respectively; (0.8±0.1) x 10 -3 mm 2 ·s -1 and 1.1±0.1 in the parenehyma of high-grade astrocytomas; (0.8±0.1) x 10 -3 mm 2 ·s -1 and 1.0±0.2 in the parenchyma of metastases. There was significant difference of the mean ADC values (F=33.57, P -3 mm 2 ·s -1 and 2.5±0.2 in the peripheral edema regions of intracranial tuberculomas respectively; (1.4±0.2) x 10 -3 mm 2 ·s -1 and 1.8±0.3 in the peripheral edema regions of high-grade astrocytomas; and (1.9±0.2) x 10 -3 mm 2 ·s -1 and 2.3±0.5 in the peripheral edema regions of metastases. There was also significant difference in the mean ADC values (F23.17, P<0.01) or rADC values (F=5.94, P<0.01) among the peripheral edema regions of the three groups. Conclusion: The ADC values and rADC values are quite effective in differentiating intracranial tuberculoma from high-grade astrocytoma and metastasis. (authors)

  16. MR signal of the solid portion of pilocytic astrocytoma on T2-weighted images: is it useful for differentiation from medulloblastoma?

    International Nuclear Information System (INIS)

    Arai, Kiyokazu; Yagi, Akiko; Taketomi-Takahashi, Ayako; Morita, Hideo; Koyama, Yoshinori; Endo, Keigo; Sato, Noriko; Aoki, Jun; Oba, Hiroshi; Ishiuchi, Shogo; Saito, Nobuhito

    2006-01-01

    Background and purpose: Although imaging features of cerebellar pilocytic astrocytoma and medulloblastoma have been described in many texts, original comparisons of magnetic resonance intensity between these two tumours are limited. In the present study the results of magnetic resonance imaging (MRI) were reviewed, focusing especially on the signal intensity of the solid portion of these neoplasms. Methods: MR images of ten cerebellar pilocytic astrocytomas and ten medulloblastomas were reviewed. The signal intensities of the solid components were graded on a scale of 1 to 5, with higher scores indicating a signal intensity closer to that of water. The degree of enhancement, tumour cysts and peripheral oedema were evaluated on MR images. When the solid portion was heterogeneous (i.e. mixed signal intensity or degree of enhancement), the dominant area was selected for evaluation. On T2-weighted images, the signal intensity of the solid portion was equal to that of cerebrospinal fluid (CSF) in 50% of pilocytic astrocytomas. No medulloblastomas showed such hyperintensity. Most medulloblastomas (80%) were isointense to grey matter. On T1-weighted images, the signal intensity varied widely in pilocytic astrocytomas; however, all medulloblastomas were iso- or hypointense to grey matter. The MR enhancement pattern, cystic component and peripheral oedema all varied in both tumour types and no specific features were identified. A signal intensity of the solid portion isointense to CSF on T2-weighted images was characteristic of cerebellar pilocytic astrocytomas; this was not observed in medulloblastomas. Attention to T2-weighted imaging of the solid portions of a tumour is easy and helpful in differentiating between cerebellar pilocytic astrocytoma and medulloblastoma. (orig.)

  17. miR-106a-5p inhibits the proliferation and migration of astrocytoma cells and promotes apoptosis by targeting FASTK.

    Directory of Open Access Journals (Sweden)

    Feng Zhi

    Full Text Available Astrocytomas are common malignant intracranial tumors that comprise the majority of adult primary central nervous system tumors. MicroRNAs (miRNAs are small, non-coding RNAs (20-24 nucleotides that post-transcriptionally modulate gene expression by negatively regulating the stability or translational efficiency of their target mRNAs. In our previous studies, we found that the downregulation of miR-106a-5p in astrocytomas is associated with poor prognosis. However, its specific gene target(s and underlying functional mechanism(s in astrocytomas remain unclear. In this study, we used mRNA microarray experiments to measure global mRNA expression in the presence of increased or decreased miR-106a-5p levels. We then performed bioinformatics analysis based on multiple target prediction algorithms to obtain candidate target genes that were further validated by computational predictions, western blot analysis, quantitative real-time PCR, and the luciferase reporter assay. Fas-activated serine/threonine kinase (FASTK was identified as a direct target of miR-106a-5p. In human astrocytomas, miR-106a-5p is downregulated and negatively associated with clinical staging, whereas FASTK is upregulated and positively associated with advanced clinical stages, at both the protein and mRNA levels. Furthermore, Kaplan-Meier analysis revealed that the reduced expression of miR-106a-5p or the increased expression of FASTK is significantly associated with poor survival outcome. These results further supported the finding that FASTK is a direct target gene of miR-106a-5p. Next, we explored the function of miR-106a-5p and FASTK during astrocytoma progression. Through gain-of-function and loss-of-function studies, we demonstrated that miR-106a-5p can significantly inhibit cell proliferation and migration and can promote cell apoptosis in vitro. The knockdown of FASTK induced similar effects on astrocytoma cells as those induced by the overexpression of miR-106a-5p. These

  18. First-line nitrosourea-based chemotherapy in symptomatic non-resectable supratentorial pure low-grade astrocytomas.

    Science.gov (United States)

    Frenay, M P; Fontaine, D; Vandenbos, F; Lebrun, C

    2005-09-01

    At the present time, there are no proven beneficial effects of chemotherapy (CT) for the treatment of pure low-grade astrocytomas. Brain radiotherapy (RT) still remains the standard treatment in order to reduce or delay tumor progression or symptoms, despite possible long-term neurologic complications. We report 10 patients, with histologically proven pure low-grade fibrillary astrocytomas, to which we administered a first-line nitrosourea-based CT. All patients were symptomatic with pharmaco-resistant epilepsy or neurologic symptoms, and had been rejected for neurosurgical resection. All patients with epilepsy had a clinical improvement with reduction in seizure frequency and 60% became seizure-free. CT was well tolerated; all patients developed myelosuppression with 40% of grade III/IV hematotoxicity. Seven were alive at the time of writing with a mean follow-up of 6.5 years (3.5-12) from first recorded symptoms. The three deceased patients died 7.5, 7.5, and 8.5 years from first symptoms. These results demonstrate that some patients with symptomatic non-resectable fibrillary low-grade astrocytomas can be treated with up-front CT to improve their neurologic status. This report suggests that benefits of CT on symptoms, survival, and quality of life should be prospectively compared with RT.

  19. Kaurene diterpene induces apoptosis in U87 human malignant glioblastoma cells by suppression of anti-apoptotic signals and activation of cysteine proteases

    Energy Technology Data Exchange (ETDEWEB)

    Lizarte, F.S. Neto; Tirapelli, D.P.C. [Universidade de São Paulo, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Ambrosio, S.R. [Universidade de Franca, Núcleo de Pesquisa em Ciências e Tecnologia, Franca, SP (Brazil); Tirapelli, C.R. [Universidade de São Paulo, Laboratório de Farmacologia, Departamento de Enfermagem Psiquiátrica e Ciências Humanas, Escola de Enfermagem de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Oliveira, F.M. [Universidade de São Paulo, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Novais, P.C. [Universidade de São Paulo, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Peria, F.M.; Oliveira, H.F. [Universidade de São Paulo, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Carlotti, C.G. Junior; Tirapelli, L.F. [Universidade de São Paulo, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP (Brazil)

    2013-01-11

    Gliomas are the most common and malignant primary brain tumors in humans. Studies have shown that classes of kaurene diterpene have anti-tumor activity related to their ability to induce apoptosis. We investigated the response of the human glioblastoma cell line U87 to treatment with ent-kaur-16-en-19-oic acid (kaurenoic acid, KA). We analyzed cell survival and the induction of apoptosis using flow cytometry and annexin V staining. Additionally, the expression of anti-apoptotic (c-FLIP and miR-21) and apoptotic (Fas, caspase-3 and caspase-8) genes was analyzed by relative quantification (real-time PCR) of mRNA levels in U87 cells that were either untreated or treated with KA (30, 50, or 70 µM) for 24, 48, and 72 h. U87 cells treated with KA demonstrated reduced viability, and an increase in annexin V- and annexin V/PI-positive cells was observed. The percentage of apoptotic cells was 9% for control cells, 26% for cells submitted to 48 h of treatment with 50 µM KA, and 31% for cells submitted to 48 h of treatment with 70 µM KA. Similarly, in U87 cells treated with KA for 48 h, we observed an increase in the expression of apoptotic genes (caspase-8, -3) and a decrease in the expression of anti-apoptotic genes (miR-21 and c-FLIP). KA possesses several interesting properties and induces apoptosis through a unique mechanism. Further experiments will be necessary to determine if KA may be used as a lead compound for the development of new chemotherapeutic drugs for the treatment of primary brain tumors.

  20. Kaurene diterpene induces apoptosis in U87 human malignant glioblastoma cells by suppression of anti-apoptotic signals and activation of cysteine proteases

    International Nuclear Information System (INIS)

    Lizarte, F.S. Neto; Tirapelli, D.P.C.; Ambrosio, S.R.; Tirapelli, C.R.; Oliveira, F.M.; Novais, P.C.; Peria, F.M.; Oliveira, H.F.; Carlotti, C.G. Junior; Tirapelli, L.F.

    2013-01-01

    Gliomas are the most common and malignant primary brain tumors in humans. Studies have shown that classes of kaurene diterpene have anti-tumor activity related to their ability to induce apoptosis. We investigated the response of the human glioblastoma cell line U87 to treatment with ent-kaur-16-en-19-oic acid (kaurenoic acid, KA). We analyzed cell survival and the induction of apoptosis using flow cytometry and annexin V staining. Additionally, the expression of anti-apoptotic (c-FLIP and miR-21) and apoptotic (Fas, caspase-3 and caspase-8) genes was analyzed by relative quantification (real-time PCR) of mRNA levels in U87 cells that were either untreated or treated with KA (30, 50, or 70 µM) for 24, 48, and 72 h. U87 cells treated with KA demonstrated reduced viability, and an increase in annexin V- and annexin V/PI-positive cells was observed. The percentage of apoptotic cells was 9% for control cells, 26% for cells submitted to 48 h of treatment with 50 µM KA, and 31% for cells submitted to 48 h of treatment with 70 µM KA. Similarly, in U87 cells treated with KA for 48 h, we observed an increase in the expression of apoptotic genes (caspase-8, -3) and a decrease in the expression of anti-apoptotic genes (miR-21 and c-FLIP). KA possesses several interesting properties and induces apoptosis through a unique mechanism. Further experiments will be necessary to determine if KA may be used as a lead compound for the development of new chemotherapeutic drugs for the treatment of primary brain tumors

  1. Differential prefrontal-like deficit in children after cerebellar astrocytoma and medulloblastoma tumor

    Directory of Open Access Journals (Sweden)

    Quintero Eliana A

    2008-04-01

    Full Text Available Abstract Background This study was realized thanks to the collaboration of children and adolescents who had been resected from cerebellar tumors. The medulloblastoma group (CE+, n = 7 in addition to surgery received radiation and chemotherapy. The astrocytoma group (CE, n = 13 did not receive additional treatments. Each clinical group was compared in their executive functioning with a paired control group (n = 12. The performances of the clinical groups with respect to controls were compared considering the tumor's localization (vermis or hemisphere and the affectation (or not of the dentate nucleus. Executive variables were correlated with the age at surgery, the time between surgery-evaluation and the resected volume. Methods The executive functioning was assessed by means of WCST, Complex Rey Figure, Controlled Oral Word Association Test (letter and animal categories, Digits span (WISC-R verbal scale and Stroop test. These tests are very sensitive to dorsolateral PFC and/or to medial frontal cortex functions. The scores for the non-verbal Raven IQ were also obtained. Direct scores were corrected by age and transformed in standard scores using normative data. The neuropsychological evaluation was made at 3.25 (SD = 2.74 years from surgery in CE group and at 6.47 (SD = 2.77 in CE+ group. Results The Medulloblastoma group showed severe executive deficit (≤ 1.5 SD below normal mean in all assessed tests, the most severe occurring in vermal patients. The Astrocytoma group also showed executive deficits in digits span, semantic fluency (animal category and moderate to slight deficit in Stroop (word and colour tests. In the astrocytoma group, the tumor's localization and dentate affectation showed different profile and level of impairment: moderate to slight for vermal and hemispheric patients respectively. The resected volume, age at surgery and the time between surgery-evaluation correlated with some neuropsychological executive variables

  2. RISC mezzanines for controlling data acquisition in the NA48 experiment at CERN

    CERN Document Server

    Guzik, Z; Bal, F; Formenti, F; Lacourt, A

    2000-01-01

    A part of the LKr calorimeter data acquisition system of the NA48 experiment (a precision measurements of epsilon / epsilon ' in CP- violating K/sup 0/ to 2 pi decays) is described. The experiment runs on the SPS north area in CERN. This paper presents some aspects of controlling the NA48 readout process based on commercial RIO 8260 RISC processors, which were used as a core for maintaining control algorithms. Several RISC processors were equipped with custom-made VME mezzanine boards providing interfacing, pre-processing and data formatting. These mezzanines are the subjects of this paper. They are: RIO-TIC/DAT (a time-stamp distributor and buffered DT-bus interface), FOL-RIO (an optical data formatter and event merger) and "TAXI receiver" (for handling trigger data of the NA48 Level-2 trigger supervisor). Also, the interface between the DT-bus and S- link/PCI is described. (8 refs).

  3. RISC Processors and High Performance Computing

    Science.gov (United States)

    Bailey, David H.; Saini, Subhash; Craw, James M. (Technical Monitor)

    1995-01-01

    This tutorial will discuss the top five RISC microprocessors and the parallel systems in which they are used. It will provide a unique cross-machine comparison not available elsewhere. The effective performance of these processors will be compared by citing standard benchmarks in the context of real applications. The latest NAS Parallel Benchmarks, both absolute performance and performance per dollar, will be listed. The next generation of the NPB will be described. The tutorial will conclude with a discussion of future directions in the field. Technology Transfer Considerations: All of these computer systems are commercially available internationally. Information about these processors is available in the public domain, mostly from the vendors themselves. The NAS Parallel Benchmarks and their results have been previously approved numerous times for public release, beginning back in 1991.

  4. The microelectronic and photonic test bed RISC processor and DRAM memory stack experiments

    International Nuclear Information System (INIS)

    Clark, K.A.; Meehan, T.J.

    1999-01-01

    This paper reports on the on-orbit data obtained from the MPTB RISC Processor Experiment, containing three Integrated Device Technologies R3081 processors. During operations, nine SEUs were observed in the processors, and four SEUs were observed in the memory and/or support circuitry. (authors)

  5. Generation of HIV-1 primary isolates representative of plasma variants using the U87.CD4 cell line

    NARCIS (Netherlands)

    Heeregrave, Edwin J.; Ampofo, William K.; Tetteh, John K. A.; Ofori, Michael; Ofori, Sampson B.; Shah, Akram S.; Pollakis, Georgios; Paxton, William A.

    2010-01-01

    In order to obtain HIV-1 primary isolates in settings with limited access to donor PBMCs, a culture method was developed where patient PBMCs infected with HIV-1 were cultured together with U87.CD4 cells. Using this non-laborious method, it is possible to harvest virus solely on the basis of syncytia

  6. The value of multi ultra high-b-value DWI in grading cerebral astrocytomas and its association with aquaporin-4.

    Science.gov (United States)

    Tan, Yan; Zhang, Hui; Wang, Xiao-Chun; Qin, Jiang-Bo; Wang, Le

    2018-06-01

    To investigate the value of multi-ultrahigh-b-value diffusion-weighted imaging (UHBV-DWI) in differentiating high-grade astrocytomas (HGAs) from low-grade astrocytomas (LGAs), analyze its association with aquaporin (AQP) expression. 40 astrocytomas divided into LGAs (N = 15) and HGAs (N = 25) were studied. Apparent diffusion coefficient (ADC) and UHBV-ADC values in solid parts and peritumoral edema were compared between LGAs and HGAs groups by the t-test. Using receiver operating characteristic curves to identify the better parameter. Using real time polymerase chain reaction to assess AQP messenger ribonucleic acid (mRNA). Using spearman correlation analysis to assess the correlation of AQP mRNA with each parameter. ADC values in solid parts of HGAs were significantly lower than LGAs (p = 0.02), while UHBV-ADC values of HGAs were significantly higher than LGAs (p  0.05); ADC value showed a negative correlation with AQP4 mRNA (r = -0.357; p = 0.024). UHBV-ADC value positively correlated with the AQP4 mRNA (r = 0.646; p value may be related with the AQP4 mRNA levels. UHBV-DWI could be of value in the assessment of astrocytoma. Advances in knowledge: UHBV-DWI generated by multi UHBV could have particular value for astrocytoma grading, and the level of AQP4 mRNA might be potentially linked to the change of UHBV-DWI parameter, and we might find the exact reason for the difference of UHBV-ADC between the LGAs and HGAs.

  7. Gemistocytic astrocytoma in the spinal cord in a dog: a case report

    Directory of Open Access Journals (Sweden)

    R.O. Chaves

    2016-08-01

    Full Text Available ABSTRACT This paper reports a case of a rare variant of the cervical spinal cord astrocytoma diagnosed in a dog with progressive neurological signs, initially asymmetrical, not ambulatory tetraparesis, segmental reflexes and normal muscle tone in all four limbs and absence of pain upon palpation of the cervical spine. Myelography revealed attenuation of the ventral and dorsal contrast line in the third region of the fifth cervical vertebra. At necropsy intramedullary cylindrical mass that stretched from the third to the sixth cervical vertebra, which replaced all the gray matter of the spinal cord was observed. In the histological study, there was the replacement of the substance by neoplastic cells mantle arranged loosely. The cells were large and slightly rounded. The eosinophilic cytoplasm was well defined, sometimes forming processes interconnecting cells. The nucleus was eccentric, round, oval or kidney-shaped, and the nucleolus was evident. Thus, the microscopic changes observed in the cervical spinal cord were consistent with gemistocytic astrocytoma.

  8. 234U/238U and δ87Sr in peat as tracers of paleosalinity in the Sacramento-San Joaquin Delta of California, USA

    International Nuclear Information System (INIS)

    Drexler, J.Z.; Paces, J.B.; Alpers, C.N.; Windham-Myers, L.; Neymark, L.A.; Bullen, T.D.; Taylor, H.E.

    2014-01-01

    Highlights: • Concentrations and isotopic values of Sr and U in peat were used to trace paleosalinity. • A three-end-member mixing model was constructed using values from water sources. • Paleosalinity of peat samples was determined relative to that of end members. • δ 87 Sr values were altered during and after the California Gold Rush period. • Oligohaline and freshwater marshes have long existed in the Sacramento-San Joaquin Delta. - Abstract: The purpose of this study was to determine the history of paleosalinity over the past 6000+ years in the Sacramento-San Joaquin Delta (the Delta), which is the innermost part of the San Francisco Estuary. We used a combination of Sr and U concentrations, δ 87 Sr values, and 234 U/ 238 U activity ratios (AR) in peat as proxies for tracking paleosalinity. Peat cores were collected in marshes on Browns Island, Franks Wetland, and Bacon Channel Island in the Delta. Cores were dated using 137 Cs, the onset of Pb and Hg contamination from hydraulic gold mining, and 14 C. A proof of concept study showed that the dominant emergent macrophyte and major component of peat in the Delta, Schoenoplectus spp., incorporates Sr and U and that the isotopic composition of these elements tracks the ambient water salinity across the Estuary. Concentrations and isotopic compositions of Sr and U in the three main water sources contributing to the Delta (seawater, Sacramento River water, and San Joaquin River water) were used to construct a three-end-member mixing model. Delta paleosalinity was determined by examining variations in the distribution of peat samples through time within the area delineated by the mixing model. The Delta has long been considered a tidal freshwater marsh region, but only peat samples from Franks Wetland and Bacon Channel Island have shown a consistently fresh signal (<0.5 ppt) through time. Therefore, the eastern Delta, which occurs upstream from Bacon Channel Island along the San Joaquin River and its

  9. 25 CFR 87.11 - Investment of judgment funds.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Investment of judgment funds. 87.11 Section 87.11 Indians... JUDGMENT FUNDS § 87.11 Investment of judgment funds. As soon as possible after the appropriation of... distribution of the funds, the Commissioner shall invest such funds pursuant to 25 U.S.C. 162a. Investments of...

  10. A general model of concurrency and its implementation as many-core dynamic RISC processors

    NARCIS (Netherlands)

    Bernard, T.; Bousias, K.; Guang, L.; Jesshope, C.R.; Lankamp, M.; van Tol, M.W.; Zhang, L.

    2008-01-01

    This paper presents a concurrent execution model and its micro-architecture based on in-order RISC processors, which schedules instructions from large pools of contextualised threads. The model admits a strategy for programming chip multiprocessors using parallelising compilers based on existing

  11. RISC. A new style in the design of architectures

    International Nuclear Information System (INIS)

    Cortadella, J.; Gonzalez, A.; Llaberia, J.M.

    1988-01-01

    In the 80's a new architecture design and implementation style has appeared: the RISC style. It proposes an overall view of the system were the processor is included. For each function, an extensive analysis has to be performed in order to evaluate the advantages and disadvantages that hardware and software introduce in the design. An optimum design involved an agreement between both levels and has to take into account cost, performance, and technological factors. In this paper, the main features of this new architecture design style are presented. (Author)

  12. Tuberous schlerosis complex and astrocytoma: a case report, Hiroshima

    Energy Technology Data Exchange (ETDEWEB)

    Rudnick, P A; Hoshino, N; Kitaoka, T; Miura, M

    1961-02-10

    This case report concerned a young woman with cutaneous, osseous, and retinal changes of tuberous sclerosis, referred to ABCC for evaluation of blindness and increased intracranial pressure. A right lateral ventricle astrocytoma was successfully removed, but the patient's sight was not restored. The development of cerebral neoplasms in these patients is discussed. A careful search for resectable brain lesions should be made in all patients with tuberous sclerosis who have signs and symptoms of increased intracranial pressure. 14 references, 6 figures.

  13. Tuberous schlerosis complex and astrocytoma: a case report, Hiroshima

    Energy Technology Data Exchange (ETDEWEB)

    Rudnick, P.A.; Hoshino, N.; Kitaoka, T.; Miura, M.

    1961-02-10

    This case report concerned a young woman with cutaneous, osseous, and retinal changes of tuberous sclerosis, referred to ABCC for evaluation of blindness and increased intracranial pressure. A right lateral ventricle astrocytoma was successfully removed, but the patient's sight was not restored. The development of cerebral neoplasms in these patients is discussed. A careful search for resectable brain lesions should be made in all patients with tuberous sclerosis who have signs and symptoms of increased intracranial pressure. 14 references, 6 figures.

  14. Putative Structural and Functional Coupling of the Mitochondrial BKCa Channel to the Respiratory Chain.

    Directory of Open Access Journals (Sweden)

    Piotr Bednarczyk

    Full Text Available Potassium channels have been found in the inner mitochondrial membranes of various cells. These channels regulate the mitochondrial membrane potential, the matrix volume and respiration. The activation of these channels is cytoprotective. In our study, the single-channel activity of a large-conductance Ca(2+-regulated potassium channel (mitoBKCa channel was measured by patch-clamping mitoplasts isolated from the human astrocytoma (glioblastoma U-87 MG cell line. A potassium-selective current was recorded with a mean conductance of 290 pS in symmetrical 150 mM KCl solution. The channel was activated by Ca(2+ at micromolar concentrations and by the potassium channel opener NS1619. The channel was inhibited by paxilline and iberiotoxin, known inhibitors of BKCa channels. Western blot analysis, immuno-gold electron microscopy, high-resolution immunofluorescence assays and polymerase chain reaction demonstrated the presence of the BKCa channel β4 subunit in the inner mitochondrial membrane of the human astrocytoma cells. We showed that substrates of the respiratory chain, such as NADH, succinate, and glutamate/malate, decrease the activity of the channel at positive voltages. This effect was abolished by rotenone, antimycin and cyanide, inhibitors of the respiratory chain. The putative interaction of the β4 subunit of mitoBKCa with cytochrome c oxidase was demonstrated using blue native electrophoresis. Our findings indicate possible structural and functional coupling of the mitoBKCa channel with the mitochondrial respiratory chain in human astrocytoma U-87 MG cells.

  15. Cerebral hemisphere astrocytoma: Treatment results

    International Nuclear Information System (INIS)

    Boyages, J.; Tiver, K.W.

    1987-01-01

    Eighty two adult patients with histologically proven cerebral astrocytomas of grades I to IV received post-operative radiotherapy at Westmead Hospital between January 1980 and February 1985. Seventy one patients completed a course of megavoltage irradiation, the majority having received a tumour dose of at least 60 Gy. Patients who underwent surgical resection had a greater median survival than those undergoing biopsy, but the difference was not statistically significant. By grade, the difference reached statistical significance only for grade III tumours. Patients with high grade tumours had a significantly lower survival than those patients with tumours of low grade. After adjustment for grade, various dosage levels did not significantly affect survival, although there was a trend towards improved median survival with higher doses in grade III tumours. When included in a multivariate analysis, the extent of surgery did not significantly influence survival, but increasing tumour grade and increasing age were significant adverse prognostic factors. (Auth.)

  16. Outcome and patterns of failure following limited-volume irradiation for malignant astrocytomas

    Energy Technology Data Exchange (ETDEWEB)

    Garden, A.S.; Maor, M.H.; Yung, W.K.A.; Bruner, J.M.; Woo, Shiao Y.; Moser, R.P.; Lee, Ya-Yen (Anderson (M.D.) Hospital and Tumor Inst., Houston, TX (USA))

    1991-02-01

    Between January 1982 and June 1986, 60 consecutive patients with high-grade astrocytomas (39 glioblastoma multiforme (GBM), 21 anaplastic astrocytoma (AA)) were treated with radiation therapy after biopsy (13 patients) or resection (47 patients). 53 patients were treated with limited-volume irradiation, 7 received whole-brain irradiation. The mean tumor dose was 65.4 Gy. In 35 patients, chemotherapy was given as part of their initial treatment. The 1- and 2-year survivals for GBM patients were 40 and 14 percent, respectively. Survival figures for AA patients were 76 and 52 percent at 1 and 2 years, respectively. The progression-free rate at 1 year was 13 percent in GBM and 29 percent in AA patients. 34 of 48 patients who received limited-volume irradiation had evidence of progression on postirradiation CT scans. 6 patients (3 GBM, 3 AA) had evidence of a new intracranial metastatic site on CT scan. In 3 patients the metastasis was within the previously irradiated volume, and in 3 other patients, it was outside this volume. All 6 had evidence of progression of their primary tumor at the original location on CT scan prior to the discovery of the metastatic site. 21 patients (15 GBM, 6 AA) had at least 1 postirradiation reoperation for a recurrent mass. 19 patients had recurrent tumors in the primary site, and 2 patients had necrosis but no tumor. Patients who received limited-volume irradiation for high-grade astrocytomas achieved the same survival results as patients treated previously with whole brain irradiation. New intra-cranial metastases did not influence the outcome, since these were always antedated by tumor progression at the primary site. (author). 16 refs.; 8 figs.; 2 tabs.

  17. Hypoxic regulation of the expression of genes encoded estrogen related proteins in U87 glioma cells: eff ect of IRE1 inhibition.

    Science.gov (United States)

    Minchenko, D O; Riabovol, O O; Ratushna, O O; Minchenko, O H

    2017-01-01

    The aim of the present study was to examine the effect of inhibition of endoplasmic reticulum stress signaling, mediated by IRE1 (inositol requiring enzyme 1), which is a central mediator of the unfolded protein response on the expression of genes encoded estrogen related proteins (NRIP1/RIP140, TRIM16/EBBP, ESRRA/NR3B1, FAM162A/E2IG5, PGRMC2/PMBP, and SLC39A6/LIV-1) and their hypoxic regulation in U87 glioma cells for evaluation of their possible significance in the control of glioma cells proliferation. The expression of NRIP1, EBBP, ESRRA, E2IG5, PGRMC2, and SLC39A6 genes in U87 glioma cells, transfected by empty vector pcDNA3.1 (control) and cells without IRE1 signaling enzyme function (transfected by dnIRE1) upon hypoxia, was studied by a quantitative polymerase chain reaction. Inhibition of both enzymatic activities (kinase and endoribonuclease) of IRE1 signaling enzyme function up-regulates the expression of EBBP, E2IG5, PGRMC2, and SLC39A6 genes is in U87 glioma cells in comparison with the control glioma cells, with more significant changes for E2IG5 and PGRMC2 genes. At the same time, the expression of NRIP1 and ESRRA genes is strongly down-regulated in glioma cells upon inhibition of IRE1. We also showed that hypoxia increases the expression of E2IG5, PGRMC2, and EBBP genes and decreases NRIP1 and ESRRA genes expression in control glioma cells. Furthermore, the inhibition of IRE1 in U87 glioma cells decreases the eff ect of hypoxia on the expression of E2IG5 and PGRMC2 genes, eliminates hypoxic regulation of NRIP1 gene, and enhances the sensitivity of ESRRA gene to hypoxic condition. Furthermore, the expression of SLC39A6 gene is resistant to hypoxia in both the glioma cells with and without IRE1 signaling enzyme function. Results of this investigation demonstrate that inhibition of IRE1 signaling enzyme function affects the expression of NRIP1, EBBP, ESRRA, E2IG5, PGRMC2, and SLC39A6 genes in U87 glioma cells in gene specific manner and these changes

  18. Development and Transition of the Radiation, Interplanetary Shocks, and Coronal Sources (RISCS) Toolset

    Science.gov (United States)

    Spann, James F.; Zank, G.

    2014-01-01

    We outline a plan to develop and transition a physics based predictive toolset called The Radiation, Interplanetary Shocks, and Coronal Sources (RISCS) to describe the interplanetary energetic particle and radiation environment throughout the inner heliosphere, including at the Earth. To forecast and "nowcast" the radiation environment requires the fusing of three components: 1) the ability to provide probabilities for incipient solar activity; 2) the use of these probabilities and daily coronal and solar wind observations to model the 3D spatial and temporal heliosphere, including magnetic field structure and transients, within 10 Astronomical Units; and 3) the ability to model the acceleration and transport of energetic particles based on current and anticipated coronal and heliospheric conditions. We describe how to address 1) - 3) based on our existing, well developed, and validated codes and models. The goal of RISCS toolset is to provide an operational forecast and "nowcast" capability that will a) predict solar energetic particle (SEP) intensities; b) spectra for protons and heavy ions; c) predict maximum energies and their duration; d) SEP composition; e) cosmic ray intensities, and f) plasma parameters, including shock arrival times, strength and obliquity at any given heliospheric location and time. The toolset would have a 72 hour predicative capability, with associated probabilistic bounds, that would be updated hourly thereafter to improve the predicted event(s) and reduce the associated probability bounds. The RISCS toolset would be highly adaptable and portable, capable of running on a variety of platforms to accommodate various operational needs and requirements. The described transition plan is based on a well established approach developed in the Earth Science discipline that ensures that the customer has a tool that meets their needs

  19. Cadherin complexes recruit mRNAs and RISC to regulate epithelial cell signaling.

    Science.gov (United States)

    Kourtidis, Antonis; Necela, Brian; Lin, Wan-Hsin; Lu, Ruifeng; Feathers, Ryan W; Asmann, Yan W; Thompson, E Aubrey; Anastasiadis, Panos Z

    2017-10-02

    Cumulative evidence demonstrates that most RNAs exhibit specific subcellular distribution. However, the mechanisms regulating this phenomenon and its functional consequences are still under investigation. Here, we reveal that cadherin complexes at the apical zonula adherens (ZA) of epithelial adherens junctions recruit the core components of the RNA-induced silencing complex (RISC) Ago2, GW182, and PABPC1, as well as a set of 522 messenger RNAs (mRNAs) and 28 mature microRNAs (miRNAs or miRs), via PLEKHA7. Top canonical pathways represented by these mRNAs include Wnt/β-catenin, TGF-β, and stem cell signaling. We specifically demonstrate the presence and silencing of MYC, JUN, and SOX2 mRNAs by miR-24 and miR-200c at the ZA. PLEKHA7 knockdown dissociates RISC from the ZA, decreases loading of the ZA-associated mRNAs and miRNAs to Ago2, and results in a corresponding increase of MYC, JUN, and SOX2 protein expression. The present work reveals a mechanism that directly links junction integrity to the silencing of a set of mRNAs that critically affect epithelial homeostasis. © 2017 Kourtidis et al.

  20. Depletion of key protein components of the RISC pathway impairs pre-ribosomal RNA processing.

    Science.gov (United States)

    Liang, Xue-Hai; Crooke, Stanley T

    2011-06-01

    Little is known about whether components of the RNA-induced silencing complex (RISC) mediate the biogenesis of RNAs other than miRNA. Here, we show that depletion of key proteins of the RISC pathway by antisense oligonucleotides significantly impairs pre-rRNA processing in human cells. In cells depleted of Drosha or Dicer, different precursors to 5.8S rRNA strongly accumulated, without affecting normal endonucleolytic cleavages. Moderate yet distinct processing defects were also observed in Ago2-depleted cells. Physical links between pre-rRNA and these proteins were identified by co-immunoprecipitation analyses. Interestingly, simultaneous depletion of Dicer and Drosha led to a different processing defect, causing slower production of 28S rRNA and its precursor. Both Dicer and Ago2 were detected in the nuclear fraction, and reduction of Dicer altered the structure of the nucleolus, where pre-rRNA processing occurs. Together, these results suggest that Drosha and Dicer are implicated in rRNA biogenesis.

  1. Promoter hypermethylation of mismatch repair gene hMLH1 predicts the clinical response of malignant astrocytomas to nitrosourea.

    Science.gov (United States)

    Fukushima, Takao; Katayama, Yoichi; Watanabe, Takao; Yoshino, Atsuo; Ogino, Akiyoshi; Ohta, Takashi; Komine, Chiaki

    2005-02-15

    In certain types of human cancers, transcriptional inactivation of hMLH1 by promoter hypermethylation plays a causal role in the loss of mismatch repair functions that modulate cytotoxic pathways in response to DNA-damaging agents. The aim of the present study was to investigate the role of promoter methylation of the hMLH1 gene in malignant astrocytomas. We examined the hMLH1 promoter methylation in a homogeneous cohort of patients with 41 malignant astrocytomas treated by 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-2(2-chloroethyl)-3-nitrosourea chemotherapy in combination with radiation and interferon therapy, and assessed the correlation of such methylation with clinical outcome. hMLH1 promoter methylation was found in 6 (15%) of the 41 newly diagnosed malignant astrocytomas. Hypermethylation of the hMLH1 promoter corresponded closely with a loss of immunohistochemical staining for hMLH1 protein (P = 0.0013). Patients with hMLH1-methylated tumors displayed a greater chance of responding to adjuvant therapy as compared with those with hMLH1-unmethylated tumors (P = 0.0150). The presence of hMLH1 hypermethylation was significantly associated with a longer progression-free survival on both univariate analysis (P = 0.0340) and multivariate analysis (P = 0.0161). The present study identified hMLH1 methylation status as a predictor of the clinical response of malignant astrocytomas to chloroethylnitrosourea-based adjuvant therapy. The findings obtained suggest that determination of the methylation status of hMLH1 could provide a potential basis for designing rational chemotherapeutic strategies, as well as for predicting prognosis.

  2. A Real-Time Image Acquisition And Processing System For A RISC-Based Microcomputer

    Science.gov (United States)

    Luckman, Adrian J.; Allinson, Nigel M.

    1989-03-01

    A low cost image acquisition and processing system has been developed for the Acorn Archimedes microcomputer. Using a Reduced Instruction Set Computer (RISC) architecture, the ARM (Acorn Risc Machine) processor provides instruction speeds suitable for image processing applications. The associated improvement in data transfer rate has allowed real-time video image acquisition without the need for frame-store memory external to the microcomputer. The system is comprised of real-time video digitising hardware which interfaces directly to the Archimedes memory, and software to provide an integrated image acquisition and processing environment. The hardware can digitise a video signal at up to 640 samples per video line with programmable parameters such as sampling rate and gain. Software support includes a work environment for image capture and processing with pixel, neighbourhood and global operators. A friendly user interface is provided with the help of the Archimedes Operating System WIMP (Windows, Icons, Mouse and Pointer) Manager. Windows provide a convenient way of handling images on the screen and program control is directed mostly by pop-up menus.

  3. Statistical Use of Argonaute Expression and RISC Assembly in microRNA Target Identification

    Science.gov (United States)

    Stanhope, Stephen A.; Sengupta, Srikumar; den Boon, Johan; Ahlquist, Paul; Newton, Michael A.

    2009-01-01

    MicroRNAs (miRNAs) posttranscriptionally regulate targeted messenger RNAs (mRNAs) by inducing cleavage or otherwise repressing their translation. We address the problem of detecting m/miRNA targeting relationships in homo sapiens from microarray data by developing statistical models that are motivated by the biological mechanisms used by miRNAs. The focus of our modeling is the construction, activity, and mediation of RNA-induced silencing complexes (RISCs) competent for targeted mRNA cleavage. We demonstrate that regression models accommodating RISC abundance and controlling for other mediating factors fit the expression profiles of known target pairs substantially better than models based on m/miRNA expressions alone, and lead to verifications of computational target pair predictions that are more sensitive than those based on marginal expression levels. Because our models are fully independent of exogenous results from sequence-based computational methods, they are appropriate for use as either a primary or secondary source of information regarding m/miRNA target pair relationships, especially in conjunction with high-throughput expression studies. PMID:19779550

  4. Radical proposal for the treatment of malignant astrocytoma

    International Nuclear Information System (INIS)

    Karlsson, U.; Black, P.; Nair, S.; Yablon, J.S.; Brady, L.W.

    1991-01-01

    The traditional treatment for anaplastic astrocytoma (AAF) and glioblastoma multiforme (GBM) leads to local relapse. The recurring element is assumed to be previously radioresistant, reorganizing hypoxic cells that require up to three times the traditional photon irradiation dose for inactivation. We are proposing to coagulate the original lesion with high-dose precision brachytherapy, immediately followed by resection to save the patient from secondary effects of the necrotic region. The treatment then continues with adjuvant external beam radiation therapy to the local surrounding brain and concomitant chemotherapy. The approach inverts the traditional regimen. It has the virtue of being precise, avoiding secondary effects of the necrotic tumor, and satisfying accepted radiobiological principles

  5. Optic nerve pilomyxoid astrocytoma in a patient with Noonan syndrome.

    Science.gov (United States)

    Nair, Sushmita; Fort, John A; Yachnis, Anthony T; Williams, Charles A

    2015-06-01

    Noonan syndrome (NS; MIM 163950) is an autosomal dominant syndrome which is clinically diagnosed by the distinct facial features, short stature, cardiac anomalies and developmental delay. About 50% of cases are associated with gain of function mutations in PTPN11 gene which leads to activation of the RAS/mitogen-activated protein kinase signaling pathway. This is known to have a role in tumorigenesis. Despite this, only limited reports of solid tumors (Fryssira H, Leventopoulos G, Psoni S, et al. Tumor development in three patients with Noonan syndrome. Eur J Pediatr 2008;167:1025-1031; Schuettpelz LG, McDonald S, Whitesell K et al. Pilocytic astrocytoma in a child with Noonan syndrome. Pediatr Blood Cancer 2009;53:1147-1149; Sherman CB, Ali-Nazir A, Gonzales-Gomez I, et al. Primary mixed glioneuronal tumor of the central nervous system in a patient with Noonan syndrome. J Pediatr Hematol Oncol 2009;31:61-64; Sanford RA, Bowman R, Tomita T, et al. A 16 year old male with Noonan's syndrome develops progressive scoliosis and deteriorating gait. Pediatr Neurosurg 1999;30:47-52) and no prior reports of optic gliomas have been described in patients with NS. We present here a patient with NS with a PTPN11 mutation and an optic pathway pilomyxoid astrocytoma. © 2015 Wiley Periodicals, Inc.

  6. High dose rate brachytherapy in treatment of high grade astrocytomas

    International Nuclear Information System (INIS)

    Garcia-Alejo, R.; Delgado, J.M.; Cerro, E. del; Torres, J.J.; Martinez, R.

    1996-01-01

    From May 1994 to June 1995, 18 patients with high grade astrocytomas were entered prospectively on a selective protocol combining surgery, external beam radiotherapy, stereotactic interstitial implantation with HDR Iridium 192 and chemotherapy. Only those patients with tumor size 100cc or less average dimension, high grade astrocytoma, Karnofsky 70 or greater, unilateral, circumscribed, unifocal, tumor stable or responding to external radiation and supratentorial were included in the study. Ages ranged from 16 to 69 years. There were 13 males and 5 females. Surgery consisted of biopsy only in 3 patients, subtotal resection in 11, and gross total resection in 4 patients. Focal external beam radiation portals included the contrast enhancing mass on CT scan plus a 3 cm margin. The protocol called for minimum tumor dose of 60 Gy to be given in 2 Gy daily fractions. An interstitial brachytherapy boost was to be performed two weeks after the conclusion of external beam radiation. The dose was 30 Gy in 4 fractions. The authors analyze on basis on their personal experience, the possibilities and the limits offered by this therapeutic procedure in neuro-oncology. Using stereotactic techniques, interstitial brachytherapy of brain tumors was technically possible with negligible acute morbidity and mortality, and appeared to be effective and may provide for an increase in tumor control in selected cases

  7. MR Findings of Desmoplastic Cerebral Astrocytoma of Infancy. A case report

    International Nuclear Information System (INIS)

    Kim, J.H.; Kim, I.O.; Kim, W.S.; Kim, K.H.; Park, C. M.; Yeon, K.M.

    2003-01-01

    Desmoplastic cerebral astrocytoma of infancy (DCAI) presents as a large supratentorial mass consisting of a central cystic component and an enhancing solid component associated with peripheral dural attachment. We report the unusual MR findings of a DCAI that differed from previously reported cases in terms of the presence of calcification, which is not considered a feature of this tumor, and the absence of an enhancing peripheral dural component

  8. An Efficient Power Estimation Methodology for Complex RISC Processor-based Platforms

    OpenAIRE

    Rethinagiri , Santhosh Kumar; Ben Atitallah , Rabie; Dekeyser , Jean-Luc; Niar , Smail; Senn , Eric

    2012-01-01

    International audience; In this contribution, we propose an efficient power estima- tion methodology for complex RISC processor-based plat- forms. In this methodology, the Functional Level Power Analysis (FLPA) is used to set up generic power models for the different parts of the system. Then, a simulation framework based on virtual platform is developed to evalu- ate accurately the activities used in the related power mod- els. The combination of the two parts above leads to a het- erogeneou...

  9. Benchmark Tests on the New IBM RISC System/6000 590 Workstation

    Directory of Open Access Journals (Sweden)

    Harvey J. Wasserman

    1995-01-01

    Full Text Available The results of benchmark tests on the superscalar IBM RISC System/6000 Model 590 are presented. A set of well-characterized Fortran benchmarks spanning a range of computational characteristics was used for the study. The data from the 590 system are compared with those from a single-processor CRAY C90 system as well as with other microprocessor-based systems, such as the Digital Equipment Corporation AXP 3000/500X and the Hewlett-Packard HP/735.

  10. Preliminary individualized chemotherapy for malignant astrocytomas based on O6-methylguanine-deoxyribonucleic acid methyltransferase methylation analysis.

    Science.gov (United States)

    Watanabe, Takao; Katayama, Yoichi; Ogino, Akiyoshi; Ohta, Takashi; Yoshino, Atsuo; Fukushima, Takao

    2006-08-01

    O(6)-methylguanine-deoxyribonucleic acid methyltransferase gene (MGMT) methylation is apparently correlated with responsiveness to nitrosourea chemotherapy, suggesting this alkylating agent should be effective against MGMT-methylated tumors. MGMT appears not to be linked to platinum resistance, so platinum chemotherapy should be used for MGMT-unmethylated tumors. This study was a preliminary trial of individualized chemotherapy based on MGMT methylation status in a total of 20 patients with newly diagnosed malignant astrocytomas (9 anaplastic astrocytomas and 11 glioblastomas multiforme). The procarbazine, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-2(2-chloroethyl)-3-nitrosourea, and vincristine (PAV) regimen was administered to seven patients with MGMT-methylated tumors, and the carboplatin and etoposide (CE) regimen was administered to 13 patients with MGMT-unmethylated tumors. Objective response to the PAV therapy was noted in all three patients with measurable residual tumor (2 complete responses and 1 partial response). Five of the seven patients continued to be disease-free after initiation of the PAV therapy. Objective response to the CE therapy was seen in only one of seven patients with measurable residual tumor (1 partial response). Three of the 13 patients were free from progression, whereas the remaining 10 patients showed early progression. The PAV regimen is effective against MGMT-methylated malignant astrocytomas, but the CE regimen is not useful at the given dose and schedule in MGMT-unmethylated tumors.

  11. Surgical Management of Pilocytic Astrocytoma of the Optic Nerve: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Ifeoluwa Apanisile

    2017-01-01

    Full Text Available Optic nerve astrocytomas (ONAs are frequent types of optic nerve gliomas (ONGs, which can affect the visual pathway. An 18-year-old male patient was admitted to our department with right-sided intraorbital/retrobulbar swelling, which progressively grew over several months. Clinical examination showed right-sided diplopia, mydriasis, low visual acuity (0.4, exophthalmus (3 cm, epiphora, and severe retrobulbar pain. There was a family history of high-grade (IV astrocytomas in which two of the family members died due to the disease. Preoperative MRI scan revealed a soft tissue mass around the retrobulbar area of the right eye with intact orbital bony walls. Surgery was performed whereby it was dissected freely from the muscles and was separated from the optic nerve and the globe. Histopathologic analysis confirmed a benign astrocytoma. The follow-up examination revealed no recurrent or residual tumor. A systemic review of the literature indicates that early diagnosis and experienced multidisciplinary management are required in case of unilateral, resectable forms of ONAs with no distant metastasis, in order to provide a long-time survival of patients. Surgical intervention of unilateral ONAs is a relatively safe procedure, allowing complete or partial tumor removal with minimal morbidity and low recurrence rate.

  12. Sensing miRNA: Signal Amplification by Cognate RISC for Intracellular Detection of miRNA in Live Cells.

    Science.gov (United States)

    Kavishwar, Amol; Medarova, Zdravka

    2016-01-01

    The ability to detect miRNA expression in live cells would leave these cells available for further manipulation or culture. Here, we describe the design of a miRNA sensor oligonucleotide whose sequence mimics the target mRNA. The sensor has a fluorescent label on one end of the oligo and a quencher on the other. When inside the cell, the sensor is recognized by its cognate miRNA-RISC and gets cleaved, setting the fluorophore free from its quencher. This results in fluorescence "turn on." Since cleavage by the RISC complex is an enzymatic process, the described approach has a very high level of sensitivity (nM). The rate of nonspecific cleavage of the sensor is very slow permitting the collection of meaningful signal over a long period of time.

  13. Supratentorial juvenile pilocytic astrocytoma in a young adult with Silver-Russell syndrome.

    LENUS (Irish Health Repository)

    Fenton, E

    2008-12-01

    Silver-Russell syndrome is a rare genetically heterogeneous disorder in which patients demonstrate intrauterine and postnatal growth retardation, triangular facies, excessive sweating during early childhood, late closure of the anterior fontanelle and skeletal asymmetry. An association with malignancy exists and only one previous intracranial tumour has been reported, a craniopharyngioma. We report the first case of Silver-Russell syndrome associated with a supratentorial juvenile pilocytic astrocytoma.

  14. Silibinin induces apoptosis via calpain-dependent AIF nuclear translocation in U87MG human glioma cell death

    Directory of Open Access Journals (Sweden)

    Kim Yong K

    2011-04-01

    Full Text Available Abstract Background Silibinin, a natural polyphenolic flavonoid, has been reported to induce cell death in various cancer cell types. However, the molecular mechanism is not clearly defined. Our previous study showed that silibinin induces glioma cell death and its effect was effectively prevented by calpain inhibitor. The present study was therefore undertaken to examine the role of calpain in the silibinin-induced glioma cell death. Methods U87MG cells were grown on well tissue culture plates and cell viability was measured by MTT assay. ROS generation and △ψm were estimated using the fluorescence dyes. PKC activation and Bax expression were measured by Western blot analysis. AIF nuclear translocation was determined by Western blot and immunocytochemistry. Results Silibinin induced activation of calpain, which was blocked by EGTA and the calpain inhibitor Z-Leu-Leu-CHO. Silibinin caused ROS generation and its effect was inhibited by calpain inhibitor, the general PKC inhibitor GF 109203X, the specific PKCδ inhibitor rottlerin, and catalase. Silibinin-induce cell death was blocked by calpain inhibitor and PKC inhibitors. Silibinin-induced PKCδ activation and disruption of △ψm were prevented by the calpain inhibitor. Silibinin induced AIF nuclear translocation and its effect was prevented by calpain inhibitor. Transfection of vector expressing microRNA of AIF prevented the silibinin-induced cell death. Conclusions Silibinin induces apoptotic cell death through a calpain-dependent mechanism involving PKC, ROS, and AIF nuclear translocation in U87MG human glioma cells.

  15. Tumour vasculature and angiogenic profile of paediatric pilocytic astrocytoma; is it much different from glioblastoma?

    NARCIS (Netherlands)

    Sie, M.; de Bont, E. S. J. M.; Scherpen, F. J. G.; Hoving, E. W.; den Dunnen, W. F. A.

    2010-01-01

    Aims: Pilocytic astrocytomas are the most frequent brain tumours in children. Because of their high vascularity, this study aimed to obtain insights into potential angiogenic related therapeutic targets in these tumours by characterization of the vasculature and the angiogenic profile. In this study

  16. Introducing RISC: A New Video Inventory for Testing Social Perception.

    Science.gov (United States)

    Rothermich, Kathrin; Pell, Marc D

    2015-01-01

    Indirect forms of speech, such as sarcasm, jocularity (joking), and 'white lies' told to spare another's feelings, occur frequently in daily life and are a problem for many clinical populations. During social interactions, information about the literal or nonliteral meaning of a speaker unfolds simultaneously in several communication channels (e.g., linguistic, facial, vocal, and body cues); however, to date many studies have employed uni-modal stimuli, for example focusing only on the visual modality, limiting the generalizability of these results to everyday communication. Much of this research also neglects key factors for interpreting speaker intentions, such as verbal context and the relationship of social partners. Relational Inference in Social Communication (RISC) is a newly developed (English-language) database composed of short video vignettes depicting sincere, jocular, sarcastic, and white lie social exchanges between two people. Stimuli carefully manipulated the social relationship between communication partners (e.g., boss/employee, couple) and the availability of contextual cues (e.g. preceding conversations, physical objects) while controlling for major differences in the linguistic content of matched items. Here, we present initial perceptual validation data (N = 31) on a corpus of 920 items. Overall accuracy for identifying speaker intentions was above 80% correct and our results show that both relationship type and verbal context influence the categorization of literal and nonliteral interactions, underscoring the importance of these factors in research on speaker intentions. We believe that RISC will prove highly constructive as a tool in future research on social cognition, inter-personal communication, and the interpretation of speaker intentions in both healthy adults and clinical populations.

  17. Pilocytic astrocytoma: a retrospective review

    International Nuclear Information System (INIS)

    Wen, B.-C.; Mayr, Nina A.; Hitchon, Patrick W.; Kao, S.; Hussey, David H.

    1996-01-01

    Purpose: The principle objective of this study is to determine the role of radiation therapy in the management of pilocytic astrocytoma. The specific aims are to assess the results of surgical resection +/- radiation therapy, the dose-response relationships for local tumor control, and the prognostic indicators. Materials and methods: Between Jan. 1970 and Dec. 1995, 60 patients with pilocytic astrocytomas (27 cerebellum, 23 hypothalmus/brain stem, 4 temporal, 3 frontal, and 3 occipital) were seen. All pathologic slides were reviewed and confirmed. Of these, 30 patients had surgery only (8 subtotal resections and 22 total resections), 8 had biopsy followed by radiotherapy (6) or chemotherapy (2), 21 had surgery and postoperative radiotherapy (20 subtotal resections and 1 total resection) and 1 was observed only. The radiation dose was 40.6 Gy/31fr/44ds to 60.2 Gy/35fr/49ds (mean = 52.1 Gy). Results: The overall 5- and 10-year actuarial survival rate was 93% and 93%, and the relapse-free survival rate was 86% and 80%, respectively. Eight patients developed local recurrence and one had leptomeningeal spread. Two patients receiving chemotherapy (vincristine + carboplatin) had persistent but stable disease. The one patient who was observed eventually required surgical resection 25 months later. Subtotal resection without RT: The local recurrence rate was 38% ((3(8))) if no RT was given after subtotal resection. Only 2 of the 3 recurrences were salvaged. All 22 patients who had tumor totally resected had local tumor control. Subtotal resection/biopsy only plus RT: Radiation therapy was effective in controlling the gross disease in 75% ((15(20))) of patients with subtotal resection, and 100% ((6(6))) of patients with biopsy only. In 14 patients receiving a tumor dose ≥ 51 Gy, 13 (93%) had local control, in comparison, to (11(15)) (73%) receiving a tumor dose <51 Gy had tumor control. Location of tumor: Sixty-three percent ((17(27))) of patients with tumor in cerebellum

  18. Development of the Respiratory Index of Severity in Children (RISC score among young children with respiratory infections in South Africa.

    Directory of Open Access Journals (Sweden)

    Carrie Reed

    Full Text Available OBJECTIVE: Pneumonia is a leading cause of death in children worldwide. A simple clinical score predicting the probability of death in a young child with lower respiratory tract infection (LRTI could aid clinicians in case management and provide a standardized severity measure during epidemiologic studies. METHODS: We analyzed 4,148 LRTI hospitalizations in children <24 months enrolled in a pneumococcal conjugate vaccine trial in South Africa from 1998-2001, to develop the Respiratory Index of Severity in Children (RISC. Using clinical data at admission, a multivariable logistic regression model for mortality was developed and statistically evaluated using bootstrap resampling techniques. Points were assigned to risk factors based on their coefficients in the multivariable model. A child's RISC score is the sum of points for each risk factor present. Separate models were developed for HIV-infected and non-infected children. RESULTS: Significant risk factors for HIV-infected and non-infected children included low oxygen saturation, chest indrawing, wheezing, and refusal to feed. The models also included age and HIV clinical classification (for HIV-infected children or weight-for-age (for non-infected children. RISC scores ranged up to 7 points for HIV-infected or 6 points for non-infected children and correlated with probability of death (0-47%, HIV-infected; 0-14%, non-infected. Final models showed good discrimination (area under the ROC curve and calibration (goodness-of-fit. CONCLUSION: The RISC score incorporates a simple set of risk factors that accurately discriminate between young children based on their risk of death from LRTI, and may provide an objective means to quantify severity based on the risk of mortality.

  19. Malignant Trigeminal Nerve Sheath Tumor and Anaplastic Astrocytoma Collision Tumor with High Proliferative Activity and Tumor Suppressor P53 Expression

    Directory of Open Access Journals (Sweden)

    Maher Kurdi

    2014-01-01

    Full Text Available Background. The synchronous development of two primary brain tumors of distinct cell of origin in close proximity or in contact with each other is extremely rare. We present the first case of collision tumor with two histological distinct tumors. Case Presentation. A 54-year-old woman presented with progressive atypical left facial pain and numbness for 8 months. MRI of the brain showed left middle cranial fossa heterogeneous mass extending into the infratemporal fossa. At surgery, a distinct but intermingled intra- and extradural tumor was demonstrated which was completely removed through left orbitozygomatic-temporal craniotomy. Histopathological examination showed that the tumor had two distinct components: malignant nerve sheath tumor of the trigeminal nerve and temporal lobe anaplastic astrocytoma. Proliferative activity and expressed tumor protein 53 (TP53 gene mutations were demonstrated in both tumors. Conclusions. We describe the first case of malignant trigeminal nerve sheath tumor (MTNST and anaplastic astrocytoma in collision and discuss the possible hypothesis of this rare occurrence. We propose that MTNST, with TP53 mutation, have participated in the formation of anaplastic astrocytoma, or vice versa.

  20. High concentration of Daunorubicin and Daunorubicinol in human malignant astrocytomas after systemic administration of liposomal Daunorubicin

    NARCIS (Netherlands)

    Albrecht, K. W.; de Witt Hamer, P. C.; Leenstra, S.; Bakker, P. J.; Beijnen, J. H.; Troost, D.; Kaaijk, P.; Bosch, A. D.

    2001-01-01

    The value of chemotherapy in patients with malignant astrocytoma remains controversial. In our laboratories in vitro experiments with organotypic spheroid cultures showed superior effectiveness of anthracyclines. Systemic administration did not provide in therapeutic concentrations so far. Because

  1. RISC-type microprocessors may revolutionize aerospace simulation

    Science.gov (United States)

    Jackson, Albert S.

    The author explores the application of RISC (reduced instruction set computer) processors in massively parallel computer (MPC) designs for aerospace simulation. The MPC approach is shown to be well adapted to the needs of aerospace simulation. It is shown that any of the three common types of interconnection schemes used with MPCs are effective for general-purpose simulation, although the bus-or switch-oriented machines are somewhat easier to use. For partial differential equation models, the hypercube approach at first glance appears more efficient because the nearest-neighbor connections required for three-dimensional models are hardwired in a hypercube machine. However, the data broadcast ability of a bus system, combined with the fact that data can be transmitted over a bus as soon as it has been updated, makes the bus approach very competitive with the hypercube approach even for these types of models.

  2. RISC-RAD. A European integrated approach to the problem of low doses

    International Nuclear Information System (INIS)

    Meunier, A.; Sabatier, L.; Atkinson, M.; Paretzke, H.; Bouffler, S.; Mullenders, L.

    2007-01-01

    Complete text of publication follows. Funded by the European Commission in the framework of a dedicated programme supporting research in the Nuclear sector (FP6 Euratom), the project RISC-RAD undertakes experimental and modelling studies ultimately to improve low dose radiation cancer risk assessment by exploring and providing evidence for the most appropriate radiation cancer risk projection and interpolation models. It started on 1st January 2004 and is running until 31 st October 2008. It mobilizes a consortium of 31 partners and is coordinated by Dr. Laure Sabatier from the French atomic energy commission. Indeed the project represents an unprecedented attempt to integrate horizontally the research on the effects of low doses of IR at the European level. A multipartner project supporting objective-driven research, RISC-RAD aims at contributing to bridge the remaining gap of scientific knowledge about effects of lows doses of ionizing radiation. It spans a large part of the research spectrum, including many topics addressed during the LOWRAD2007 conference. This presentation intends to give an account of the integrative aspects of the project, insights on the innovative solutions found to approach a complex and controversial scientific topic like the biological effects of low doses of ionizing radiation, and links with some areas of social studies on science.The concept of 'integration' implies the development of a new kind of activity in the research field, which crosses its traditional boundaries : controversies of several kinds must temporarily be overcome within the project management board in order to define and follow a common strategy. Among them, how to reconcile the creative part of fundamental research with the compliance to strict project planning rules has come up as a debate which questions the best way a significant collective and coordinated action can address the issue of the low dose cancer risk assessment on the long term. The knowledge and

  3. Prognostic significance of multiple kallikreins in high-grade astrocytoma

    International Nuclear Information System (INIS)

    Drucker, Kristen L.; Gianinni, Caterina; Decker, Paul A.; Diamandis, Eleftherios P.; Scarisbrick, Isobel A.

    2015-01-01

    Kallikreins have clinical value as prognostic markers in a subset of malignancies examined to date, including kallikrein 3 (prostate specific antigen) in prostate cancer. We previously demonstrated that kallikrein 6 is expressed at higher levels in grade IV compared to grade III astrocytoma and is associated with reduced survival of GBM patients. In this study we determined KLK1, KLK6, KLK7, KLK8, KLK9 and KLK10 protein expression in two independent tissue microarrays containing 60 grade IV and 8 grade III astrocytoma samples. Scores for staining intensity, percent of tumor stained and immunoreactivity scores (IR, product of intensity and percent) were determined and analyzed for correlation with patient survival. Grade IV glioma was associated with higher levels of kallikrein-immunostaining compared to grade III specimens. Univariable Cox proportional hazards regression analysis demonstrated that elevated KLK6- or KLK7-IR was associated with poor patient prognosis. In addition, an increased percent of tumor immunoreactive for KLK6 or KLK9 was associated with decreased survival in grade IV patients. Kaplan-Meier survival analysis indicated that patients with KLK6-IR < 10, KLK6 percent tumor core stained < 3, or KLK7-IR < 9 had a significantly improved survival. Multivariable analysis indicated that the significance of these parameters was maintained even after adjusting for gender and performance score. These data suggest that elevations in glioblastoma KLK6, KLK7 and KLK9 protein have utility as prognostic markers of patient survival. The online version of this article (doi:10.1186/s12885-015-1566-5) contains supplementary material, which is available to authorized users

  4. National Radiological Protection Board accounts 1986-87

    International Nuclear Information System (INIS)

    1987-05-01

    The 1986-87 accounts of the Radiological Protection Board are presented in accordance with the Radiological Protection Act 1970. The report of the Comptroller and Auditor General is also given. (U.K.)

  5. National Radiological Protection Board accounts 1986-87

    Energy Technology Data Exchange (ETDEWEB)

    1987-01-01

    The 1986-87 accounts of the Radiological Protection Board are presented in accordance with the Radiological Protection Act 1970. The report of the Comptroller and Auditor General is also given. (U.K.).

  6. Overexpression of c-erbB2 is a negative prognostic factor in anaplastic astrocytomas

    Directory of Open Access Journals (Sweden)

    Gulati Michel

    2010-03-01

    Full Text Available Abstract The epidermal growth factor receptor (EGFR family, consisting of four tyrosine kinase receptors, c-erbB1-4, seems to be influential in gliomagenesis. The aim of this study was to investigate EGFR gene amplification and expression of c-erbB1-4 receptor proteins in human anaplastic astrocytomas. Formalin-fixed and paraffin-embedded sections from 31 cases were investigated by standard immunohistochemical procedures for expression of c-erbB1-4 receptor proteins using commercial antibodies. EGFR gene amplification was studied by fluorescence in situ hybridization using paraffin-embedded tissues. Two monoclonal antibodies, NCL-EGFR-384 and NCL-EGFR, were used for EGFR detection and they displayed positive immunoreactivity in 97% and 71%, respectively. For c-erbB2 detection three monoclonal antibodies, CB11, 3B5, and 5A2, were applied and they displayed positive immunoreactivity in 45%, 100%, and 52%, respectively. Positive immunostaining for c-erbB3 and c-erbB4 was encountered in 97% and 74%, respectively. The EGFR gene was amplified in 9 out of 31 tumors (29%. After adjusting for age, Karnofsky performance status, and extent of surgical resection, Cox multiple regression analysis with overall survival as the dependent variable revealed that c-erbB2 overexpression detected by the monoclonal antibody clone CB11 was a statistically significant poor prognostic factor (P = 0.004. This study shows the convenience and feasibility of immunohistochemistry when determining the expression of receptor proteins in tissue sections of human astrocytomas. The synchronous overexpression of c-erbB1-4 proteins in anaplastic astrocytomas supports their role in the pathogenesis of these tumors. Further, c-erbB2 overexpression seems to predict aggressive behaviour.

  7. Viral RNAi suppressor reversibly binds siRNA to outcompete Dicer and RISC via multiple turnover.

    Science.gov (United States)

    Rawlings, Renata A; Krishnan, Vishalakshi; Walter, Nils G

    2011-04-29

    RNA interference is a conserved gene regulatory mechanism employed by most eukaryotes as a key component of their innate immune response to viruses and retrotransposons. During viral infection, the RNase-III-type endonuclease Dicer cleaves viral double-stranded RNA into small interfering RNAs (siRNAs) 21-24 nucleotides in length and helps load them into the RNA-induced silencing complex (RISC) to guide the cleavage of complementary viral RNA. As a countermeasure, many viruses have evolved viral RNA silencing suppressors (RSS) that tightly, and presumably quantitatively, bind siRNAs to thwart RNA-interference-mediated degradation. Viral RSS proteins also act across kingdoms as potential immunosuppressors in gene therapeutic applications. Here we report fluorescence quenching and electrophoretic mobility shift assays that probe siRNA binding by the dimeric RSS p19 from Carnation Italian Ringspot Virus, as well as by human Dicer and RISC assembly complexes. We find that the siRNA:p19 interaction is readily reversible, characterized by rapid binding [(1.69 ± 0.07) × 10(8) M(-)(1) s(-1)] and marked dissociation (k(off)=0.062 ± 0.002 s(-1)). We also observe that p19 efficiently competes with recombinant Dicer and inhibits the formation of RISC-related assembly complexes found in human cell extract. Computational modeling based on these results provides evidence for the transient formation of a ternary complex between siRNA, human Dicer, and p19. An expanded model of RNA silencing indicates that multiple turnover by reversible binding of siRNAs potentiates the efficiency of the suppressor protein. Our predictive model is expected to be applicable to the dosing of p19 as a silencing suppressor in viral gene therapy. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Viral RNAi suppressor reversibly binds siRNA to outcompete Dicer and RISC via multiple-turnover

    Science.gov (United States)

    Rawlings, Renata A.; Krishnan, Vishalakshi; Walter, Nils G.

    2011-01-01

    RNA interference (RNAi) is a conserved gene regulatory mechanism employed by most eukaryotes as a key component of their innate immune response against viruses and retrotransposons. During viral infection, the RNase III-type endonuclease Dicer cleaves viral double-stranded RNA into small interfering RNAs (siRNAs), 21–24 nucleotides in length, and helps load them into the RNA-induced silencing complex (RISC) to guide cleavage of complementary viral RNA. As a countermeasure, many viruses have evolved viral RNA silencing suppressor (RSS) proteins that tightly, and presumably quantitatively, bind siRNAs to thwart RNAi-mediated degradation. Viral RSS proteins also act across kingdoms as potential immunosuppressors in gene therapeutic applications. Here we report fluorescence quenching and electrophoretic mobility shift assays that probe siRNA binding by the dimeric RSS p19 from Carnation Italian Ringspot Virus (CIRV), as well as by human Dicer and RISC assembly complexes. We find that the siRNA:p19 interaction is readily reversible, characterized by rapid binding ((1.69 ± 0.07)×108 M−1s−1) and marked dissociation (koff = 0.062 ± 0.002 s−1). We also observe that p19 efficiently competes with recombinant Dicer and inhibits formation of RISC-related assembly complexes found in human cell extract. Computational modeling based on these results provides evidence for the transient formation of a ternary complex between siRNA, human Dicer, and p19. An expanded model of RNA silencing indicates that multiple-turnover by reversible binding of siRNAs potentiates the efficiency of the suppressor protein. Our predictive model is expected to be applicable to the dosing of p19 as a silencing suppressor in viral gene therapy. PMID:21354178

  9. Annual report 1986-87

    International Nuclear Information System (INIS)

    1988-01-01

    The paper presents the annual report 1986-87 of the Universities Research Reactor, United Kingdom. The reactor and associated laboratories were well utilised during the year. The demand for radioactive isotopes has increased over previous years, with 5592 samples irradiated in the 12 month period. The contents of the report contains a description of: the research programme, activation analysis service, teaching programme, and reactor operation and safety arrangements. (U.K.)

  10. Microbial Disruption of Autophagy Alters Expression of the RISC Component AGO2, a Critical Regulator of the miRNA Silencing Pathway.

    Science.gov (United States)

    Sibony, Michal; Abdullah, Majd; Greenfield, Laura; Raju, Deepa; Wu, Ted; Rodrigues, David M; Galindo-Mata, Esther; Mascarenhas, Heidi; Philpott, Dana J; Silverberg, Mark S; Jones, Nicola L

    2015-12-01

    Autophagy is implicated in Crohn's disease (CD) pathogenesis. Recent evidence suggests autophagy regulates the microRNA (miRNA)-induced silencing complex (miRISC). Therefore, autophagy may play a novel role in CD by regulating expression of miRISC, thereby altering miRNA silencing. As microbes associated with CD can alter autophagy, we hypothesized that microbial disruption of autophagy affects the critical miRISC component AGO2. AGO2 expression was assessed in epithelial and immune cells, and intestinal organoids with disrupted autophagy. Microarray technology was used to determine the expression of downstream miRNAs in cells with defective autophagy. Increased AGO2 was detected in autophagy-deficient ATG5-/- and ATG16-/- mouse embryonic fibroblast cells (MEFs) in comparison with wild-type MEFs. Chemical agents and VacA toxin, which disrupt autophagy, increased AGO2 expression in MEFs, epithelial cells lines, and human monocytes, respectively. Increased AGO2 was also detected in ATG7-/- intestinal organoids, in comparison with wild-type organoids. Five miRNAs were differentially expressed in autophagy-deficient MEFs. Pathway enrichment analysis of the differentially expressed miRNAs implicated signaling pathways previously associated with CD. Taken together, our results suggest that autophagy is involved in the regulation of the critical miRISC component AGO2 in epithelial and immune cells and primary intestinal epithelial cells. We propose a mechanism by which autophagy alters miRNA expression, which likely impacts the regulation of CD-associated pathways. Furthermore, as enteric microbial products can manipulate autophagy and AGO2, our findings suggest a novel mechanism by which enteric microbes could influence miRNA to promote disease.

  11. Introducing RISC: A New Video Inventory for Testing Social Perception.

    Directory of Open Access Journals (Sweden)

    Kathrin Rothermich

    Full Text Available Indirect forms of speech, such as sarcasm, jocularity (joking, and 'white lies' told to spare another's feelings, occur frequently in daily life and are a problem for many clinical populations. During social interactions, information about the literal or nonliteral meaning of a speaker unfolds simultaneously in several communication channels (e.g., linguistic, facial, vocal, and body cues; however, to date many studies have employed uni-modal stimuli, for example focusing only on the visual modality, limiting the generalizability of these results to everyday communication. Much of this research also neglects key factors for interpreting speaker intentions, such as verbal context and the relationship of social partners. Relational Inference in Social Communication (RISC is a newly developed (English-language database composed of short video vignettes depicting sincere, jocular, sarcastic, and white lie social exchanges between two people. Stimuli carefully manipulated the social relationship between communication partners (e.g., boss/employee, couple and the availability of contextual cues (e.g. preceding conversations, physical objects while controlling for major differences in the linguistic content of matched items. Here, we present initial perceptual validation data (N = 31 on a corpus of 920 items. Overall accuracy for identifying speaker intentions was above 80% correct and our results show that both relationship type and verbal context influence the categorization of literal and nonliteral interactions, underscoring the importance of these factors in research on speaker intentions. We believe that RISC will prove highly constructive as a tool in future research on social cognition, inter-personal communication, and the interpretation of speaker intentions in both healthy adults and clinical populations.

  12. [The heterogeneity of blood flow on magnetic resonance imaging: a biomarker for grading cerebral astrocytomas].

    Science.gov (United States)

    Revert Ventura, A J; Sanz Requena, R; Martí-Bonmatí, L; Pallardó, Y; Jornet, J; Gaspar, C

    2014-01-01

    To study whether the histograms of quantitative parameters of perfusion in MRI obtained from tumor volume and peritumor volume make it possible to grade astrocytomas in vivo. We included 61 patients with histological diagnoses of grade II, III, or IV astrocytomas who underwent T2*-weighted perfusion MRI after intravenous contrast agent injection. We manually selected the tumor volume and peritumor volume and quantified the following perfusion parameters on a voxel-by-voxel basis: blood volume (BV), blood flow (BF), mean transit time (TTM), transfer constant (K(trans)), washout coefficient, interstitial volume, and vascular volume. For each volume, we obtained the corresponding histogram with its mean, standard deviation, and kurtosis (using the standard deviation and kurtosis as measures of heterogeneity) and we compared the differences in each parameter between different grades of tumor. We also calculated the mean and standard deviation of the highest 10% of values. Finally, we performed a multiparametric discriminant analysis to improve the classification. For tumor volume, we found statistically significant differences among the three grades of tumor for the means and standard deviations of BV, BF, and K(trans), both for the entire distribution and for the highest 10% of values. For the peritumor volume, we found no significant differences for any parameters. The discriminant analysis improved the classification slightly. The quantification of the volume parameters of the entire region of the tumor with BV, BF, and K(trans) is useful for grading astrocytomas. The heterogeneity represented by the standard deviation of BF is the most reliable diagnostic parameter for distinguishing between low grade and high grade lesions. Copyright © 2011 SERAM. Published by Elsevier Espana. All rights reserved.

  13. A Sensitive and Specific Diagnostic Panel to Distinguish Diffuse Astrocytoma from Astrocytosis: Chromosome 7 Gain with Mutant Isocitrate Dehydrogenase 1 and p53

    Science.gov (United States)

    Camelo-Piragua, Sandra; Jansen, Michael; Ganguly, Aniruddha; Kim, J. ChulMin; Cosper, Arjola K.; Dias-Santagata, Dora; Nutt, Catherine L.; Iafrate, A. John; Louis, David N.

    2011-01-01

    One of the major challenges of surgical neuropathology is the distinction of diffuse astrocytoma (World Health Organization [WHO] grade II) from astrocytosis. The most commonly used ancillary tool to solve this problem is p53 immunohistochemistry (IHC), but this is neither sensitive nor specific. Isocitrate dehydrogenase 1 (IDH1) mutations are common in lower grade gliomas, with most causing a specific amino acid change (R132H) that can be detected with a monoclonal antibody. IDH2 mutations are rare, but also occur in gliomas. In addition, gains of chromosome 7 are common in gliomas. In this study we assessed the status of p53, IDH1/2 and chromosome 7 to determine the most useful panel to distinguish astrocytoma from astrocytosis. We studied biopsy specimens from 21 WHO grade II diffuse astrocytomas and 20 reactive conditions. The single most sensitive test to identify astrocytoma is fluorescence in situ hybridization (FISH) for chromosome 7 gain (76.2%). The combination of p53 and mutant IDH1 IHC provides a higher sensitivity (71.4%) than either test alone (47.8%); this combination offers a practical initial approach for the surgical pathologist. The best overall sensitivity (95%) is achieved when FISH for chromosome 7 gain is added to the p53-mutant IDH1 IHC panel. PMID:21343879

  14. Pre-surgical integration of FMRI and DTI of the sensorimotor system in transcortical resection of a high-grade insular astrocytoma

    Directory of Open Access Journals (Sweden)

    Chelsea eEkstrand

    2016-03-01

    Full Text Available Herein we report on a patient with a WHO Grade III astrocytoma in the right insular region in close proximity to the internal capsule who underwent a right frontotemporal craniotomy. Total gross resection of insular gliomas remains surgically challenging based on the possibility of damage to the corticospinal tracts. However, maximizing the extent of resection has been shown to decrease future adverse outcomes. Thus, the goal of such surgeries should focus on maximizing extent of resection while minimizing possible adverse outcomes. In this case, pre-surgical planning included integration of functional magnetic resonance imaging (fMRI and diffusion tensor imaging (DTI, to localize motor and sensory pathways. Novel fMRI tasks were individually developed for the patient to maximize both somatosensory and motor activation simultaneously in areas in close proximity to the tumor. Information obtained was used to optimize resection trajectory and extent, facilitating gross total resection of the astrocytoma. Across all three motor-sensory tasks administered, fMRI revealed an area of interest just superior and lateral to the astrocytoma. Further, DTI analyses showed displacement of the corona radiata around the superior dorsal surface of the astrocytoma, extending in the direction of the activation found using fMRI. Taking into account these results, a transcortical superior temporal gyrus surgical approach was chosen in order to avoid the area of interest identified by fMRI and DTI. Total gross resection was achieved and minor post-surgical motor and sensory deficits were temporary. This case highlights the utility of comprehensive pre-surgical planning, including fMRI and DTI, to maximize surgical outcomes on a case-by-case basis.

  15. Apoptosis and telomeres shortening related to HIV-1 induced oxidative stress in an astrocytoma cell line

    Directory of Open Access Journals (Sweden)

    Mollace Vincenzo

    2009-05-01

    Full Text Available Abstract Background Oxidative stress plays a key role in the neuropathogenesis of Human Immunodeficiency Virus-1 (HIV-1 infection causing apoptosis of astroglia cells and neurons. Recent data have shown that oxidative stress is also responsible for the acceleration of human fibroblast telomere shortening in vitro. In the present study we analyzed the potential relations occurring between free radicals formation and telomere length during HIV-1 mediated astroglial death. Results To this end, U373 human astrocytoma cells have been directly exposed to X4-using HIV-1IIIB strain, for 1, 3 or 5 days and treated (where requested with N-acetylcysteine (NAC, a cysteine donor involved in the synthesis of glutathione (GSH, a cellular antioxidant and apoptosis has been evaluated by FACS analysis. Quantitative-FISH (Q-FISH has been employed for studying the telomere length while intracellular reduced/oxidized glutathione (GSH/GSSG ratio has been determined by High-Performance Liquid Chromatography (HPLC. Incubation of U373 with HIV-1IIIB led to significant induction of cellular apoptosis that was reduced in the presence of 1 mM NAC. Moreover, NAC improved the GSH/GSSG, a sensitive indicator of oxidative stress, that significantly decreased after HIV-1IIIB exposure in U373. Analysis of telomere length in HIV-1 exposed U373 showed a statistically significant telomere shortening, that was completely reverted in NAC-treated U373. Conclusion Our results support the role of HIV-1-mediated oxidative stress in astrocytic death and the importance of antioxidant compounds in preventing these cellular damages. Moreover, these data indicate that the telomere structure, target for oxidative damage, could be the key sensor of cell apoptosis induced by oxidative stress after HIV infection.

  16. A novel rotometer based on a RISC microcontroller.

    Science.gov (United States)

    Heredia-López, F J; Bata-García, J L; Alvarez-Cervera, F J; Góngora-Alfaro, J L

    2002-08-01

    A new, low-cost rotometer, based on a reduced instruction set computer (RISC) microcontroller, is presented. Like earlier devices, it counts the number and direction of full turns for predetermined time periods during the evaluation of turning behavior induced by drug administration in rats. The present stand-alone system includes a nonvolatile memory for long-term data storage and a serial port for data transmission. It also contains a display for monitoring the experiments and has battery backup to avoid interruptions owing to power failures. A high correlation was found (r > .988, p < 2 x 10(-14)) between the counts of the rotometer and those of two trained observers. The system reflects quantitative differences in turning behavior owing to pharmacological manipulations. It provides the most common counting parameters and is inexpensive, flexible, highly reliable, and completely portable (weight including batteries, 159 g).

  17. Functional analysis of neuronal microRNAs in Caenorhabditis elegans dauer formation by combinational genetics and Neuronal miRISC immunoprecipitation.

    Directory of Open Access Journals (Sweden)

    Minh T Than

    2013-06-01

    Full Text Available Identifying the physiological functions of microRNAs (miRNAs is often challenging because miRNAs commonly impact gene expression under specific physiological conditions through complex miRNA::mRNA interaction networks and in coordination with other means of gene regulation, such as transcriptional regulation and protein degradation. Such complexity creates difficulties in dissecting miRNA functions through traditional genetic methods using individual miRNA mutations. To investigate the physiological functions of miRNAs in neurons, we combined a genetic "enhancer" approach complemented by biochemical analysis of neuronal miRNA-induced silencing complexes (miRISCs in C. elegans. Total miRNA function can be compromised by mutating one of the two GW182 proteins (AIN-1, an important component of miRISC. We found that combining an ain-1 mutation with a mutation in unc-3, a neuronal transcription factor, resulted in an inappropriate entrance into the stress-induced, alternative larval stage known as dauer, indicating a role of miRNAs in preventing aberrant dauer formation. Analysis of this genetic interaction suggests that neuronal miRNAs perform such a role partly by regulating endogenous cyclic guanosine monophosphate (cGMP signaling, potentially influencing two other dauer-regulating pathways. Through tissue-specific immunoprecipitations of miRISC, we identified miRNAs and their likely target mRNAs within neuronal tissue. We verified the biological relevance of several of these miRNAs and found that many miRNAs likely regulate dauer formation through multiple dauer-related targets. Further analysis of target mRNAs suggests potential miRNA involvement in various neuronal processes, but the importance of these miRNA::mRNA interactions remains unclear. Finally, we found that neuronal genes may be more highly regulated by miRNAs than intestinal genes. Overall, our study identifies miRNAs and their targets, and a physiological function of these miRNAs in

  18. FGFR1 tyrosine kinase domain duplication in pilocytic astrocytoma with anaplasia.

    Science.gov (United States)

    Ballester, Leomar Y; Penas-Prado, Marta; Leeds, Norman E; Huse, Jason T; Fuller, Gregory N

    2018-04-01

    We report the case of a 27-yr-old male with visual field loss who had a 4.9-cm complex cystic mass in the right occipital lobe. Histologic examination showed pilocytic astrocytoma (PA) with anaplasia, and molecular characterization revealed FGFR1 duplication with additional variants of unknown significance in several genes ( ARID1A, ARID1B, CHEK2, EPHA5, and MLL2 ). This is one of only a very few reported cases of anaplastic PA with characterization of molecular alterations. © 2018 Ballester et al.; Published by Cold Spring Harbor Laboratory Press.

  19. High epiregulin expression in human U87 glioma cells relies on IRE1α and promotes autocrine growth through EGF receptor

    International Nuclear Information System (INIS)

    Auf, Gregor; Vajkoczy, Peter; Seno, Masaharu; Bikfalvi, Andreas; Minchenko, Dmitri; Minchenko, Oleksandr; Moenner, Michel; Jabouille, Arnaud; Delugin, Maylis; Guérit, Sylvaine; Pineau, Raphael; North, Sophie; Platonova, Natalia; Maitre, Marlène; Favereaux, Alexandre

    2013-01-01

    Epidermal growth factor (EGF) receptors contribute to the development of malignant glioma. Here we considered the possible implication of the EGFR ligand epiregulin (EREG) in glioma development in relation to the activity of the unfolded protein response (UPR) sensor IRE1α. We also examined EREG status in several glioblastoma cell lines and in malignant glioma. Expression and biological properties of EREG were analyzed in human glioma cells in vitro and in human tumor xenografts with regard to the presence of ErbB proteins and to the blockade of IRE1α. Inactivation of IRE1α was achieved by using either the dominant-negative strategy or siRNA-mediated knockdown. EREG was secreted in high amounts by U87 cells, which also expressed its cognate EGF receptor (ErbB1). A stimulatory autocrine loop mediated by EREG was evidenced by the decrease in cell proliferation using specific blocking antibodies directed against either ErbB1 (cetuximab) or EREG itself. In comparison, anti-ErbB2 antibodies (trastuzumab) had no significant effect. Inhibition of IRE1α dramatically reduced EREG expression both in cell culture and in human xenograft tumor models. The high-expression rate of EREG in U87 cells was therefore linked to IRE1α, although being modestly affected by chemical inducers of the endoplasmic reticulum stress. In addition, IRE1-mediated production of EREG did not depend on IRE1 RNase domain, as neither the selective dominant-negative invalidation of the RNase activity (IRE1 kinase active) nor the siRNA-mediated knockdown of XBP1 had significant effect on EREG expression. Finally, chemical inhibition of c-Jun N-terminal kinases (JNK) using the SP600125 compound reduced the ability of cells to express EREG, demonstrating a link between the growth factor production and JNK activation under the dependence of IRE1α. EREG may contribute to glioma progression under the control of IRE1α, as exemplified here by the autocrine proliferation loop mediated in U87 cells by the

  20. Context Switching with Multiple Register Windows: A RISC Performance Study

    Science.gov (United States)

    Konsek, Marion B.; Reed, Daniel A.; Watcharawittayakul, Wittaya

    1987-01-01

    Although previous studies have shown that a large file of overlapping register windows can greatly reduce procedure call/return overhead, the effects of register windows in a multiprogramming environment are poorly understood. This paper investigates the performance of multiprogrammed, reduced instruction set computers (RISCs) as a function of window management strategy. Using an analytic model that reflects context switch and procedure call overheads, we analyze the performance of simple, linearly self-recursive programs. For more complex programs, we present the results of a simulation study. These studies show that a simple strategy that saves all windows prior to a context switch, but restores only a single window following a context switch, performs near optimally.

  1. Dendrosomal curcumin nanoformulation downregulates pluripotency genes via miR-145 activation in U87MG glioblastoma cells

    Directory of Open Access Journals (Sweden)

    Tahmasebi Mirgani M

    2014-01-01

    Full Text Available Maryam Tahmasebi Mirgani,1 Benedetta Isacchi,2 Majid Sadeghizadeh,1,* Fabio Marra,3 Anna Rita Bilia,2,* Seyed Javad Mowla,1 Farhood Najafi,4 Esmael Babaei51Department of Genetics, Tarbiat Modares University, Tehran, Iran; 2Department of Chemistry, University of Florence, Sesto Fiorentino, Italy; 3Department of Experimental and Clinical Medicine, University of Florence, Italy; 4Department of Resin and Additives, Institute for Color Science and Technology, Tehran, Iran; 5Department of Biology, University of Tabriz, Tabriz, Iran*These authors contributed equally to this workAbstract: Glioblastoma is an invasive tumor of the central nervous system. Tumor recurrence resulting from ineffective current treatments, mainly due to the blood–brain barrier, highlights the need for innovative therapeutic alternatives. The recent availability of nanotechnology represents a novel targeted strategy in cancer therapy. Natural products have received considerable attention for cancer therapy because of general lower side effects. Curcumin is a new candidate for anticancer treatment, but its low bioavailability and water solubility represent the main disadvantages of its use. Here, curcumin was efficiently encapsulated in a nontoxic nanocarrier, termed dendrosome, to overcome these problems. Dendrosomal curcumin was prepared as 142 nm spherical structures with constant physical and chemical stability. The inhibitory role of dendrosomal curcumin on the proliferation of U87MG cells, a cellular model of glioblastoma, was evaluated by considering master genes of pluripotency and regulatory miRNA (microribonucleic acid. Methylthiazol tetrazolium assay and flow cytometry were used to detect the antiproliferative effects of dendrosomal curcumin. Annexin-V-FLUOS and caspase assay were used to quantify apoptosis. Real-time polymerase chain reaction was used to analyze the expression of OCT4 (octamer binding protein 4 gene variants (OCT4A, OCT4B, and OCT4B1, SOX-2 (SRY

  2. Sustained response to weekly vinblastine in 2 children with pilomyxoid astrocytoma associated with diencephalic syndrome.

    Science.gov (United States)

    Singh, Gurpreet; Wei, Xing Chang; Hader, Walter; Chan, Jennifer A; Bouffet, Eric; Lafay-Cousin, Lucie

    2013-03-01

    Diencephalic syndrome (DS) related to hypothalamic/chiasmatic region tumor has mainly been reported with low-grade glioma. We described 2 young children with DS related to pilomyxoid astrocytoma. Despite the recognized more agressive clinical behavior of this histologic subtype, we report successful resolution of DS and sustained tumor response with prolonged use of single-agent vinblastine.

  3. Cloning of a novel transcription factor-like gene amplified in human glioma including astrocytoma grade I

    NARCIS (Netherlands)

    Fischer, U.; Heckel, D.; Michel, A.; Janka, M.; Hulsebos, T.; Meese, E.

    1997-01-01

    Gene amplification, which is generally considered to occur late in tumor development, is a common feature of high grade glioma. Up until now, there have been no reports on amplification in astrocytoma grade I. In this study, we report cloning and sequencing of a cDNA termed glioma-amplified sequence

  4. Pediatric spinal cord astrocytomas: a retrospective study of 348 patients from the SEER database.

    Science.gov (United States)

    Luksik, Andrew S; Garzon-Muvdi, Tomas; Yang, Wuyang; Huang, Judy; Jallo, George I

    2017-06-01

    OBJECTIVE Intramedullary spinal cord tumors comprise 1%-10% of all childhood central nervous system neoplasms, with astrocytomas representing the most common subtype. Due to their rarity and poor prognosis, large population-based studies are needed to assess the epidemiology and survival risk factors associated with these tumors in the hope of improving outcome. The authors undertook this retrospective study to explore factors that may influence survival in pediatric patients with spinal cord astrocytomas. METHODS Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, a prospective cancer registry, the authors retrospectively assessed survival in histologically confirmed, primary spinal cord astrocytomas in patients 21 years of age and younger. Survival was described with Kaplan-Meyer curves, and a multivariate regression analysis was used to assess the association of several variables with survival while controlling for confounding variables. RESULTS This analysis of 348 cases showed that age (hazard ratio [HR] 1.05, 95% CI 1.01-1.09, p = 0.017), nonwhite race (HR 1.74, 95% CI 1.11-2.74, p = 0.014), high-grade tumor status (HR 14.67, 95% CI 6.69-32.14, p < 0.001), distant or invasive extension of the tumor (HR 2.37, 95% CI 1.02-5.49, p = 0.046), and radiation therapy (HR 3.74, 95% CI 2.18-6.41, p < 0.001) were associated with decreased survival. Partial resection (HR 0.37, 95% CI 0.16-0.83, p = 0.017) and gross-total resection (HR 0.39, 95% CI 0.16-0.95, p = 0.039) were associated with improved survival. CONCLUSIONS Younger age appears to be protective, while high-grade tumors have a much worse prognosis. Early diagnosis and access to surgery appears necessary for improving outcomes, while radiation therapy has an unclear role. There is still much to learn about this disease in the hope of curing children with the misfortune of having one of these rare tumors.

  5. RNAi and retroviruses: are they in RISC?

    Science.gov (United States)

    Vasselon, Thierry; Bouttier, Manuella; Saumet, Anne; Lecellier, Charles-Henri

    2013-02-01

    RNA interference (RNAi) is a potent cellular system against viruses in various organisms. Although common traits are observed in plants, insects, and nematodes, the situation observed in mammals appears more complex. In mammalian somatic cells, RNAi is implicated in endonucleolytic cleavage mediated by artificially delivered small interfering RNAs (siRNAs) as well as in translation repression mediated by microRNAs (miRNAs). Because siRNAs and miRNAs recognize viral mRNAs, RNAi inherently limits virus production and participates in antiviral defense. However, several observations made in the cases of hepatitis C virus and retroviruses (including the human immunodeficiency virus and the primate foamy virus) bring evidence that this relationship is much more complex and that certain components of the RNAi effector complex [called the RNA-induced silencing complex (RISC)], such as AGO2, are also required for viral replication. Here, we summarize recent discoveries that have revealed this dual implication in virus biology. We further discuss their potential implications for the functions of RNAi-related proteins, with special emphasis on retrotransposition and genome stability.

  6. Reliability and validity of the Spanish version of the 10-item Connor-Davidson Resilience Scale (10-item CD-RISC in young adults

    Directory of Open Access Journals (Sweden)

    García-Campayo Javier

    2011-08-01

    Full Text Available Abstract Background The 10-item Connor-Davidson Resilience Scale (10-item CD-RISC is an instrument for measuring resilience that has shown good psychometric properties in its original version in English. The aim of this study was to evaluate the validity and reliability of the Spanish version of the 10-item CD-RISC in young adults and to verify whether it is structured in a single dimension as in the original English version. Findings Cross-sectional observational study including 681 university students ranging in age from 18 to 30 years. The number of latent factors in the 10 items of the scale was analyzed by exploratory factor analysis. Confirmatory factor analysis was used to verify whether a single factor underlies the 10 items of the scale as in the original version in English. The convergent validity was analyzed by testing whether the mean of the scores of the mental component of SF-12 (MCS and the quality of sleep as measured with the Pittsburgh Sleep Index (PSQI were higher in subjects with better levels of resilience. The internal consistency of the 10-item CD-RISC was estimated using the Cronbach α test and test-retest reliability was estimated with the intraclass correlation coefficient. The Cronbach α coefficient was 0.85 and the test-retest intraclass correlation coefficient was 0.71. The mean MCS score and the level of quality of sleep in both men and women were significantly worse in subjects with lower resilience scores. Conclusions The Spanish version of the 10-item CD-RISC showed good psychometric properties in young adults and thus can be used as a reliable and valid instrument for measuring resilience. Our study confirmed that a single factor underlies the resilience construct, as was the case of the original scale in English.

  7. Protective Effects of Mouse Bone Marrow Mesenchymal Stem Cell Soup on Staurosporine Induced Cell Death in PC12 and U87 Cell Lines

    Directory of Open Access Journals (Sweden)

    Hossein Zhaleh

    2016-11-01

    Full Text Available Mouse bone marrow mesenchymal stem cells (mBMSCs soup is promising tool for the treatment of neurodegenerative diseases. mBMSCs soup is easily obtained and is capable of transplantation without rejection. We investigated the effects of mBMSC soup on staurosporine-induced cell death in PC12 and U87 cells lines. The percentage of cell viability, cell death, NO concentration, total neurite length (TNL and fraction of cell differentiation (f% were assessed. Viability assay showed that mBM soup (24 and 48h in time dependent were increased cell viability (p<0.05 and also cell death assay showed that cell death in time dependent were decreased, respectively (p<0.05. TNL and fraction of cell differentiation significantly were increased compared with treatment1 (p<0.05. Our data showed that mBM Soup protects cells, increases cell viability, suppresses cell death and improvement the neurite elongation. We concluded that Mouse bone marrow mesenchymal stem cell soup plays an important protective role in staurosporine-induced cell death in PC12 and U87 cell lines.

  8. Impaired RNA splicing of 5'-regulatory sequences of the astroglial glutamate transporter EAAT2 in human astrocytoma

    NARCIS (Netherlands)

    Münch, C.; Penndorf, A.; Schwalenstöcker, B.; Troost, D.; Ludolph, A. C.; Ince, P.; Meyer, T.

    2001-01-01

    A loss of the glutamate transporter EAAT2 has been reported in the neoplastic transformation of astrocytic cells and astrocytoma. The RNA expression of EAAT2 and five 5'-regulatory splice variants was investigated to identify alterations of the post-transcriptional EAAT2 gene regulation in human

  9. Protein kinase D2 regulates migration and invasion of U87MG glioblastoma cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Bernhart, Eva; Damm, Sabine; Wintersperger, Andrea [Institute of Molecular Biology and Biochemistry, Medical University of Graz, Graz (Austria); DeVaney, Trevor [Institute of Biophysics, Medical University of Graz (Austria); Zimmer, Andreas [Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Karl-Franzens University, Graz (Austria); Raynham, Tony; Ireson, Christopher [Cancer Research Technology Ltd, London (United Kingdom); Sattler, Wolfgang, E-mail: wolfgang.sattler@medunigraz.at [Institute of Molecular Biology and Biochemistry, Medical University of Graz, Graz (Austria)

    2013-08-01

    Glioblastoma multiforme (GBM) is the most common malignant brain tumor, which, despite combined modality treatment, reoccurs and is invariably fatal for affected patients. Recently, a member of the serine/threonine protein kinase D (PRKD) family, PRKD2, was shown to be a potent mediator of glioblastoma growth. Here we studied the role of PRKD2 in U87MG glioblastoma cell migration and invasion in response to sphingosine-1-phosphate (S1P), an activator of PRKD2 and a GBM mitogen. Time-lapse microscopy demonstrated that random cell migration was significantly diminished in response to PRKD2 silencing. The pharmacological PRKD family inhibitor CRT0066101 decreased chemotactic migration and invasion across uncoated or matrigel-coated Transwell inserts. Silencing of PRKD2 attenuated migration and invasion of U87MG cells even more effectively. In terms of downstream signaling, CRT0066101 prevented PRKD2 autophosphorylation and inhibited p44/42 MAPK and to a smaller extent p54/46 JNK and p38 MAPK activation. PRKD2 silencing impaired activation of p44/42 MAPK and p54/46 JNK, downregulated nuclear c-Jun protein levels and decreased c-Jun{sup S73} phosphorylation without affecting the NFκB pathway. Finally, qPCR array analyses revealed that silencing of PRKD2 downregulates mRNA levels of integrin alpha-2 and -4 (ITGA2 and -4), plasminogen activator urokinase (PLAU), plasminogen activator urokinase receptor (PLAUR), and matrix metallopeptidase 1 (MMP1). Findings of the present study identify PRKD2 as a potential target to interfere with glioblastoma cell migration and invasion, two major determinants contributing to recurrence of glioblastoma after multimodality treatment. Highlights: • Sphingosine-1-phosphate induces glioma cell migration and invasion. • Part of the effects is mediated by protein kinase D2 (PRKD2) activation. • Inactivation of PRKD2 attenuates glioblastoma cell migration and invasion. • Both, RNAi and pharmacological inhibition of PRKD2 inhibits MAPK

  10. Protein kinase D2 regulates migration and invasion of U87MG glioblastoma cells in vitro

    International Nuclear Information System (INIS)

    Bernhart, Eva; Damm, Sabine; Wintersperger, Andrea; DeVaney, Trevor; Zimmer, Andreas; Raynham, Tony; Ireson, Christopher; Sattler, Wolfgang

    2013-01-01

    Glioblastoma multiforme (GBM) is the most common malignant brain tumor, which, despite combined modality treatment, reoccurs and is invariably fatal for affected patients. Recently, a member of the serine/threonine protein kinase D (PRKD) family, PRKD2, was shown to be a potent mediator of glioblastoma growth. Here we studied the role of PRKD2 in U87MG glioblastoma cell migration and invasion in response to sphingosine-1-phosphate (S1P), an activator of PRKD2 and a GBM mitogen. Time-lapse microscopy demonstrated that random cell migration was significantly diminished in response to PRKD2 silencing. The pharmacological PRKD family inhibitor CRT0066101 decreased chemotactic migration and invasion across uncoated or matrigel-coated Transwell inserts. Silencing of PRKD2 attenuated migration and invasion of U87MG cells even more effectively. In terms of downstream signaling, CRT0066101 prevented PRKD2 autophosphorylation and inhibited p44/42 MAPK and to a smaller extent p54/46 JNK and p38 MAPK activation. PRKD2 silencing impaired activation of p44/42 MAPK and p54/46 JNK, downregulated nuclear c-Jun protein levels and decreased c-Jun S73 phosphorylation without affecting the NFκB pathway. Finally, qPCR array analyses revealed that silencing of PRKD2 downregulates mRNA levels of integrin alpha-2 and -4 (ITGA2 and -4), plasminogen activator urokinase (PLAU), plasminogen activator urokinase receptor (PLAUR), and matrix metallopeptidase 1 (MMP1). Findings of the present study identify PRKD2 as a potential target to interfere with glioblastoma cell migration and invasion, two major determinants contributing to recurrence of glioblastoma after multimodality treatment. Highlights: • Sphingosine-1-phosphate induces glioma cell migration and invasion. • Part of the effects is mediated by protein kinase D2 (PRKD2) activation. • Inactivation of PRKD2 attenuates glioblastoma cell migration and invasion. • Both, RNAi and pharmacological inhibition of PRKD2 inhibits MAPK

  11. Analysis of difference of association between polymorphisms in the XRCC5, RPA3 and RTEL1 genes and glioma, astrocytoma and glioblastoma.

    Science.gov (United States)

    Jin, Tianbo; Wang, Yuan; Li, Gang; Du, Shuli; Yang, Hua; Geng, Tingting; Hou, Peng; Gong, Yongkuan

    2015-01-01

    Gliomas are the most common aggressive brain tumors and have many complex pathological types. Previous reports have discovered that genetic mutations are associated with the risk of glioma. However, it is unclear whether uniform genetic mutations exist difference between glioma and its two pathological types in the Han Chinese population. We evaluated 20 SNPs of 703 glioma cases (338 astrocytoma cases, 122 glioblastoma cases) and 635 controls in a Han Chinese population using χ(2) test and genetic model analysis. In three case-control studies, we found rs9288516 in XRCC5 gene showed a decreased risk of glioma (OR, 0.85; 95% CI, 0.73-0.99; P = 0.042) and glioblastoma (OR, 0.70; 95% CI, 0.52-0.92; P = 0.001) in the allele model. We identified rs414805 in RPA3 gene showed an increased risk of glioblastoma in allele model (OR, 1.38; 95% CI, 1.00-1.89; P = 0.047) and dominant model (OR, 1.57; 95% CI, 1.05-2.35; P = 0.027), analysis respectively. Meanwhile, rs2297440 in RTEL1 gene showed an increased risk of glioma (OR, 1.30; 95% CI, 1.10-1.54; P = 0.002) and astrocytoma (OR, 1.26; 95% CI, 1.02-1.54; P = 0.029) in the allele model. In addition, we also observed a haplotype of "GCT" in the RTEL1 gene with an increased risk of astrocytoma (P = 0.005). Polymorphisms in the XRCC5, RPA3 and RTEL1 genes, combinating with previous reaserches, are associated with glioma developing. However, those genes mutations may play different roles in the glioma, astrocytoma and glioblastoma, respectively.

  12. Dipeptidyl peptidase IV in two human glioma cell lines

    Directory of Open Access Journals (Sweden)

    A Sedo

    2009-12-01

    Full Text Available There is growing evidence that dipeptidyl peptidase IV [DPP-IV, EC 3.4.14.5] takes part in the metabolism of biologically active peptides participating in the regulation of growth and transformation of glial cells. However, the knowledge on the DPP-IV expression in human glial and glioma cells is still very limited. In this study, using histochemical and biochemical techniques, the DPP-IV activity was demonstrated in two commercially available human glioma cell lines of different transformation degree, as represented by U373 astrocytoma (Grade III and U87 glioblastoma multiforme (Grade IV lines. Higher total activity of the enzyme, as well as its preferential localisation in the plasma membrane, was observed in U87 cells. Compared to U373 population, U87 cells were morphologically more pleiomorphic, they were cycling at lower rate and expressing less Glial Fibrillary Acidic Protein. The data revealed positive correlation between the degree of transformation of cells and activity of DPP-IV. Great difference in expression of this enzyme, together with the phenotypic differences of cells, makes these lines a suitable standard model for further 57 studies of function of this enzyme in human glioma cells.

  13. Validity and reliability of the Spanish version of the 10-item CD-RISC in patients with fibromyalgia

    Science.gov (United States)

    2014-01-01

    Background No resilience scale has been validated in Spanish patients with fibromyalgia. The aim of this study was to evaluate the validity and reliability of the 10-item CD-RISC in a sample of Spanish patients with fibromyalgia. Methods Design: Observational prospective multicenter study. Sample: Patients with diagnoses of fibromyalgia recruited from primary care settings (N = 208). Instruments: In addition to sociodemographic data, the following questionnaires were administered: Pain Visual Analogue Scale (PVAS), the 10-item Connor-Davidson Resilience scale (10-item CD-RISC), the Fibromyalgia Impact Questionnaire (FIQ), the Hospital Anxiety and Depression Scale (HADS), the Pain Catastrophizing Scale (PCS), the Chronic Pain Acceptance Questionnaire (CPAQ), and the Mindful Attention Awareness Scale (MAAS). Results Regarding construct validity, the factor solution in the Principal Component Analysis (PCA) was considered adequate, so the KMO test had a value of 0.91, and the Barlett’s test of sphericity was significant (χ2 = 852.8; gl = 45; p fibromyalgia, acceptable psychometric properties, with a high level of reliability and validity. PMID:24484847

  14. Study of risc factors affecting the number of mental disorders and nervous system diseases for people who participated in liquidation of consequences of ChNPP accident

    International Nuclear Information System (INIS)

    Ivanov, V.K.; Chekin, S.Yu.; Mikhal'skij, A.I.; Petrovskij, A.M.

    1992-01-01

    Interrelation of disease incidence for liquidators and factors affecting it has been studied. The diseases (mental disorders and nervous system diseases) have been taken into account provided more than 10% of people have suffered of the above diseases. Date of getting into the accident zone; duration of work within the zone; the radiation dose accumulated were considered to be risc factors. Getting into the accident zone and duration of work within the zone of accident have been though to be the main risc factors. 3 figs.; 2 tabs

  15. Quality of life and neuropsychological evaluation for patients with malignant astrocytomas: RTOG 91-14

    International Nuclear Information System (INIS)

    Choucair, Ali K.; Scott, Charles; Urtasun, Raul; Nelson, Diana; Mousas, Benjamin; Curran, Walter

    1997-01-01

    Abstract: With increasingly aggressive neurosurgical and radiation therapy modalities (gamma knife, external beam stereotactic radiation and interstitial brachytherapy with or without hyperthermia) offered to patients with malignant astrocytomas (MA), increasing national demand for medical outcome studies and rising health care costs amidst public, business, and governmental debate to cut spending, we as physicians are obligated to continue our research to find effective treatments for malignant astrocytoma (MA) and a cost-effective means to study their impact upon the patient's quality of life (QOL). Purpose: We report data that was collected within the Radiation Therapy Oncology Group (RTOG) on 126 patients with MA who were enrolled in RTOG 91-14. This study was undertaken to prospectively test the feasibility of performing quality of life (QOL) and neuropsychological evaluation (NPE) and collecting this data within the RTOG. Results: The NPE and QOL parameters that were used in this study are cost effective. They are not only much cheaper than formal cognitive and memory testing, but also provide additional information regarding the patients' day to day functional abilities that are not provided by the current routinely used means, such as KPS. The Mini-Mental Status Exam (MMSE) provides greater sensitivity to patients' differences in neurological status and may be preferable to NFS as an eligibility criteria

  16. Transmissió vertical del virus de l'hepatitis C. Factors de risc, història natural dels nens infectats i evolució a llarg termini

    OpenAIRE

    Viñolas Tolosa, Maria

    2016-01-01

    Introducció: La TV del VHC succeeix en el 5-15% dels casos i depèn de factors de risc materns, obstètrics i neonatals. Fins el moment existeix poca informació sobre l’evolució dels nens infectats més enllà dels 2 o 3 primers anys de vida. L’objectiu del present estudi es determinar la taxa de TV, els factors de risc i l’evolució a llarg termini dels nens infectats. Pacients i mètodes: Estudi prospectiu de cohorts de 120 gestants infectades per VHC i els seus fills nascuts a l’Hospital del ...

  17. Pion radiation for high grade astrocytoma: results of a randomized study

    International Nuclear Information System (INIS)

    Pickles, Tom; Goodman, George B.; Rheaume, Dorianne E.; Duncan, Graeme G.; Fryer, Chris J.; Bhimji, Shamim; Ludgate, Charles; Syndikus, Isabel; Graham, Peter; Dimitrov, Mario; Bowen, Julie

    1997-01-01

    Purpose: This study attempted to compare within a randomized study the outcome of pion radiation therapy vs. conventional photon irradiation for the treatment of high-grade astrocytomas. Methods and Materials: Eighty-four patients were randomized to pion therapy (33-34.5 Gyπ), or conventional photon irradiation (60 Gy). Entry criteria included astrocytoma (modified Kernohan high Grade 3 or Grade 4), age 18-70, Karnofsky performance status (KPS) ≥50, ability to start irradiation within 30 days of surgery, unifocal tumor, and treatment volume < 850 cc. The high-dose volume in both arms was computed tomography enhancement plus a 2-cm margin. The study was designed with the power to detect a twofold difference between arms. Results: Eighty-one eligible patients were equally balanced for all known prognostic variables. Pion patients started radiation 7 days earlier on average than photon patients, but other treatment-related variables did not differ. There were no significant differences for either early or late radiation toxicity between treatment arms. Actuarial survival analysis shows no differences in terms of time to local recurrence or overall survival where median survival was 10 months in both arms (p = 0.22). The physician-assessed KPS and patient-assessed quality of life (QOL) measurements were generally maintained within 10 percentage points until shortly before tumor recurrence. There was no apparent difference in the serial KPS or QOL scores between treatment arms. Conclusion: In contrast to high linear energy transfer (LET) therapy for central nervous system tumors, such as neutron or neon therapy, the safety of pion therapy, which is of intermediate LET, has been reaffirmed. However, this study has demonstrated no therapeutic gain for pion therapy of glioblastoma

  18. Balanç benefici/risc del contingut en polifenols i alcohol del vi: bases científiques dels efectes del consum moderat de vi sobre el sistema cardiovascular

    OpenAIRE

    Chiva Blanch, Gemma

    2013-01-01

    [cat] L'objectiu d'aquesta tesi doctoral és avaluar els efectes de les fraccions del vi (alcohòlica i no alcohòlica -principalment polifenols-) sobre els principals factors de risc cardiovascular en 67 homes amb un elevat risc de patir malalties cardiovasculars. Es va realitzar un assaig clínic, aleatoritzat i creuat en el qual tots els participants van rebre en un ordre aleatori les tres intervencions: 30 gr d'alcohol / dia en forma de vi negre, la mateixa quantitat de polifenols en forma de...

  19. The role of radiotherapy in the management of supratentorial low grade astrocytoma

    International Nuclear Information System (INIS)

    Song, M. H.; Chang, H. S.; Lee, K. J.

    1997-01-01

    To evaluate the role of radiotherapy in the management of incompletely resected supratentorial low grade astrocytoma with the analysis of the survival, the pattern of failure, and the prognostic variables affecting survival. Between January 1990 and December 1995, fifty-one patients with supratentorial low grade astrocytoma received radiotherapy after subtotal resection (16 patients) or stereotactic biopsy(35 patients)at Asan Medical Center. External radiotherapy was done by conventional fractionation with the total dose of 4820cGy to 6000cGy(median 5580cGy) and partial brain volume. The follow-up was done from 6 to 79 months(median 48 months). Overall actuarial survival rate at 2 and 5 years were 83.4% and 54.8T, respectively. Progression free survival at 2 and 5 years were 67.4% and 48.7%, respectively. The significant prognostic factors affecting overall survival rate were the performance status, T stage, histologic subtype, radiation field and radiation response. The major pattern of failure was local failure, such as progressive disease and primary site recurrence in 23 patients (45.1%). Progression free survivors excluding 2 patients were physically and intellectually intact without major neurologic deficit. Although the follow-up period of this study was relatively short, overall actuarial and progression free survival rate were encouraging. Patients with good performance status, lower T stage, pilocytic subtype, patients treated with small radiation field and radiation responder showed better survival. As the local failure was the major pattern of failure, the various efforts to decrease the local failure is necessary. (author)

  20. External Beam Radiotherapy in the Management of Low Grade Astrocytoma of the Brain

    International Nuclear Information System (INIS)

    Jeon, Ha Jung

    2009-01-01

    This study was designed to evaluate the effectiveness of postoperative radiotherapy for patients with low-grade astrocytomas and to define an optimal radiotherapeutic regimen and prognostic factors. A total of 69 patients with low-grade astrocytomas underwent surgery and postoperative radiotherapy immediately following surgery at our institution between October 1989 and September 2006. The median patient age was 36 years. Forty-one patients were 40 years or younger and 28 patients were 41 years or older. Fourteen patients underwent a biopsy alone and the remaining 55 patients underwent a subtotal resection. Thirty-nine patients had a Karnofsky performance status of less than 80% and 30 patients had a Karnofsky performance status greater than 80%. Two patients were treated with whole brain irradiation followed by a coned down boost field to the localized area. The remaining 67 patients were treated with a localized field with an appropriate margin. Most of the patients received a dose of 50∼55 Gy and majority of the patients were treated with a dose of 54 Gy. The overall 5-year and 7-year survival rates for all of the 69 patients were 49% and 44%, respectively. Corresponding disease free survival rates were 45% and 40%, respectively. Patients who underwent a subtotal resection showed better survival than patients who underwent a biopsy alone. The overall 5-year survival rates for patients who underwent a subtotal resection and patients who underwent a biopsy alone were 57% and 38%, respectively (p<0.05). Forty-one patients who were 40 years or younger showed a better overall 5-year survival rate as compared with 28 patients who were 41 years or older (56% versus 40%, p<0.05). The overall 5-year survival rates for 30 patients with a Karnofsky performance status greater than 80% and 39 patients with a Karnofsky performance status less than 80% were 51% and 47%, respectively. This finding was not statistically significant. Although one patient was not able to

  1. Steric restrictions of RISC in RNA interference identified with size-expanded RNA nucleobases.

    Science.gov (United States)

    Hernández, Armando R; Peterson, Larryn W; Kool, Eric T

    2012-08-17

    Understanding the interactions between small interfering RNAs (siRNAs) and the RNA-induced silencing complex (RISC), the key protein complex of RNA interference (RNAi), is of great importance to the development of siRNAs with improved biological and potentially therapeutic function. Although various chemically modified siRNAs have been reported, relatively few studies with modified nucleobases exist. Here we describe the synthesis and hybridization properties of siRNAs bearing size-expanded RNA (xRNA) nucleobases and their use as a novel and systematic set of steric probes in RNAi. xRNA nucleobases are expanded by 2.4 Å using benzo-homologation and retain canonical Watson-Crick base-pairing groups. Our data show that the modified siRNA duplexes display small changes in melting temperature (+1.4 to -5.0 °C); substitutions near the center are somewhat destabilizing to the RNA duplex, while substitutions near the ends are stabilizing. RNAi studies in a dual-reporter luciferase assay in HeLa cells revealed that xRNA nucleobases in the antisense strand reduce activity at some central positions near the seed region but are generally well tolerated near the ends. Most importantly, we observed that xRNA substitutions near the 3'-end increased activity over that of wild-type siRNAs. The data are analyzed in terms of site-dependent steric effects in RISC. Circular dichroism experiments show that single xRNA substitutions do not significantly distort the native A-form helical structure of the siRNA duplex, and serum stability studies demonstrated that xRNA substitutions protect siRNAs against nuclease degradation.

  2. Wig1 prevents cellular senescence by regulating p21 mRNA decay through control of RISC recruitment.

    Science.gov (United States)

    Kim, Bong Cho; Lee, Hyung Chul; Lee, Je-Jung; Choi, Chang-Min; Kim, Dong-Kwan; Lee, Jae Cheol; Ko, Young-Gyu; Lee, Jae-Seon

    2012-11-14

    Premature senescence, a key strategy used to suppress carcinogenesis, can be driven by p53/p21 proteins in response to various stresses. Here, we demonstrate that Wig1 plays a critical role in this process through regulation of p21 mRNA stability. Wig1 controls the association of Argonaute2 (Ago2), a central component of the RNA-induced silencing complex (RISC), with target p21 mRNA via binding of the stem-loop structure near the microRNA (miRNA) target site. Depletion of Wig1 prohibited miRNA-mediated p21 mRNA decay and resulted in premature senescence. Wig1 plays an essential role in cell proliferation, as demonstrated in tumour xenografts in mice, and Wig1 and p21 mRNA levels are inversely correlated in human normal and cancer tissues. Together, our data indicate a novel role of Wig1 in RISC target accessibility, which is a key step in RNA-mediated gene silencing. In addition, these findings indicate that fine-tuning of p21 levels by Wig1 is essential for the prevention of cellular senescence.

  3. Classification of astrocyto-mas and meningiomas using statistical discriminant analysis on MRI data

    International Nuclear Information System (INIS)

    Siromoney, Anna; Prasad, G.N.S.; Raghuram, Lakshminarayan; Korah, Ipeson; Siromoney, Arul; Chandrasekaran, R.

    2001-01-01

    The objective of this study was to investigate the usefulness of Multivariate Discriminant Analysis for classifying two groups of primary brain tumours, astrocytomas and meningiomas, from Magnetic Resonance Images. Discriminant analysis is a multivariate technique concerned with separating distinct sets of objects and with allocating new objects to previously defined groups. Allocation or classification rules are usually developed from learning examples in a supervised learning environment. Data from signal intensity measurements in the multiple scan performed on each patient in routine clinical scanning was analysed using Fisher's Classification, which is one method of discriminant analysis

  4. Regulation of sonic hedgehog-GLI1 downstream target genes PTCH1, Cyclin D2, Plakoglobin, PAX6 and NKX2.2 and their epigenetic status in medulloblastoma and astrocytoma

    International Nuclear Information System (INIS)

    Shahi, Mehdi H; Afzal, Mohammad; Sinha, Subrata; Eberhart, Charles G; Rey, Juan A; Fan, Xing; Castresana, Javier S

    2010-01-01

    The Sonic hedgehog (Shh) signaling pathway is critical for cell growth and differentiation. Impairment of this pathway can result in both birth defects and cancer. Despite its importance in cancer development, the Shh pathway has not been thoroughly investigated in tumorigenesis of brain tumors. In this study, we sought to understand the regulatory roles of GLI1, the immediate downstream activator of the Shh signaling pathway on its downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6 in medulloblastoma and astrocytic tumors. We silenced GLI1 expression in medulloblastoma and astrocytic cell lines by transfection of siRNA against GLI1. Subsequently, we performed RT-PCR and quantitative real time RT-PCR (qRT-PCR) to assay the expression of downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6. We also attempted to correlate the pattern of expression of GLI1 and its regulated genes in 14 cell lines and 41 primary medulloblastoma and astrocytoma tumor samples. We also assessed the methylation status of the Cyclin D2 and PTCH1 promoters in these 14 cell lines and 58 primary tumor samples. Silencing expression of GLI1 resulted up-regulation of all target genes in the medulloblastoma cell line, while only PTCH1 was up-regulated in astrocytoma. We also observed methylation of the cyclin D2 promoter in a significant number of astrocytoma cell lines (63%) and primary astrocytoma tumor samples (32%), but not at all in any medulloblastoma samples. PTCH1 promoter methylation was less frequently observed than Cyclin D2 promoter methylation in astrocytomas, and not at all in medulloblastomas. Our results demonstrate different regulatory mechanisms of Shh-GLI1 signaling. These differences vary according to the downstream target gene affected, the origin of the tissue, as well as epigenetic regulation of some of these genes

  5. Value of 18F-3,4-dihydroxyphenylalanine PET/MR image fusion in pediatric supratentorial infiltrative astrocytomas: a prospective pilot study.

    Science.gov (United States)

    Morana, Giovanni; Piccardo, Arnoldo; Milanaccio, Claudia; Puntoni, Matteo; Nozza, Paolo; Cama, Armando; Zefiro, Daniele; Cabria, Massimo; Rossi, Andrea; Garrè, Maria Luisa

    2014-05-01

    Infiltrative astrocytomas (IAs) represent a group of astrocytic gliomas ranging from low-grade to highly malignant, characterized by diffuse invasion of the brain parenchyma. When compared with their adult counterpart, pediatric IAs may be considered biologically distinct entities; nevertheless, similarly to those in adults they represent a complex oncologic challenge. The aim of this study was to investigate the diagnostic role, clinical contribution, and prognostic value of fused (18)F-3,4-dihydroxyphenylalanine ((18)F-DOPA) PET/MR images in pediatric supratentorial IAs. Pediatric patients with supratentorial IAs involving at least 2 cerebral lobes, either newly diagnosed or with suspected disease progression, prospectively underwent (18)F-DOPA PET and conventional MR imaging, performed within 10 d of each other. (18)F-DOPA PET data were interpreted qualitatively and semiquantitatively, fusing images with MR images. PET scans were classified as positive if tumors identified on MR imaging exhibited tracer uptake above the level of the corresponding contralateral normal brain. Maximum standardized uptake values, tumor-to-normal contralateral tissue ratios, and tumor-to-normal striatum ratios were calculated for all tumors. Correlations between the degree and extent of (18)F-DOPA uptake, MR imaging tumor characteristics, and histologic results were investigated. The contribution of (18)F-DOPA PET/MR image fusion was considered relevant if it enabled one to select the most appropriate biopsy site, discriminate between disease progression and treatment-related changes, or influence treatment strategy. The patient's outcome was finally correlated with (18)F-DOPA uptake. Thirteen patients (8 boys and 5 girls) were included (5 diffuse astrocytomas, 2 anaplastic astrocytomas, 5 gliomatosis cerebri, and 1 glioblastoma multiforme). The (18)F-DOPA uptake pattern was heterogeneous in all positive scans (9/13), revealing metabolic heterogeneities within each tumor. Significant

  6. RISC-KIT: Resilience-increasing Strategies for Coasts

    Directory of Open Access Journals (Sweden)

    van Dongeren Ap

    2016-01-01

    Full Text Available High-impact storm events have demonstrated the vulnerability of coastal zones in Europe and beyond. These impacts are likely to increase due to predicted climate change and ongoing coastal development. In order to reduce impacts, disaster risk reduction (DRR measures need to be taken, which prevent or mitigate the effects of storm events. To drive the DRR agenda, the UNISDR formulated the Sendai Framework for Action, and the EU has issued the Floods Directive. However, neither is specific about the methods to be used to develop actionable DRR measures in the coastal zone. Therefore, there is a need to develop methods, tools and approaches which make it possible to: identify and prioritize the coastal zones which are most at risk through a Coastal Risk Assessment Framework, and to evaluate the effectiveness of DRR options for these coastal areas, using an Early Warning/Decision Support System, which can be used both in the planning and event-phase. This paper gives an overview of the products and results obtained in the FP7-funded project RISC-KIT, which aims to develop and apply a set of tools with which highly-vulnerable coastal areas (so-called “hotspots” can be identified.

  7. A dangerous liaison: Leptin and sPLA2-IIA join forces to induce proliferation and migration of astrocytoma cells.

    Directory of Open Access Journals (Sweden)

    Rubén Martín

    Full Text Available Glioblastoma, the most aggressive type of primary brain tumour, shows worse prognosis linked to diabetes or obesity persistence. These pathologies are chronic inflammatory conditions characterized by altered profiles of inflammatory mediators, including leptin and secreted phospholipase A2-IIA (sPLA2-IIA. Both proteins, in turn, display diverse pro-cancer properties in different cell types, including astrocytes. Herein, to understand the underlying relationship between obesity and brain tumors, we investigated the effect of leptin, alone or in combination with sPLA2-IIA on astrocytoma cell functions. sPLA2-IIA induced up-regulation of leptin receptors in 1321N1 human astrocytoma cells. Leptin, as well as sPLA2-IIA, increased growth and migration in these cells, through activation/phosphorylation of key proteins of survival cascades. Leptin, at concentrations with minimal or no activating effects on astrocytoma cells, enhanced growth and migration promoted by low doses of sPLA2-IIA. sPLA2-IIA alone induced a transient phosphorylation pattern in the Src/ERK/Akt/mTOR/p70S6K/rS6 pathway through EGFR transactivation, and co-addition of leptin resulted in a sustained phosphorylation of these signaling regulators. Mechanistically, EGFR transactivation and tyrosine- and serine/threonine-protein phosphatases revealed a key role in this leptin-sPLA2-IIA cross-talk. This cooperative partnership between both proteins was also found in primary astrocytes. These findings thus indicate that the adipokine leptin, by increasing the susceptibility of cells to inflammatory mediators, could contribute to worsen the prognosis of tumoral and neurodegenerative processes, being a potential mediator of some obesity-related medical complications.

  8. Estimation of radiotherapy and MCNU versus radiotherapy and MCNU plus interferon-[beta] for the treatment of anaplastic astrocytoma

    Energy Technology Data Exchange (ETDEWEB)

    Kiya, Katsuzo; Uozumi, Tohru; Kurisu, Kaoru; Ogasawara, Hidenori; Sugiyama, Kazuhiko; Maeda, Hitoshi; Harada, Kunyu (Hiroshima Univ. (Japan). School of Medicine)

    1993-02-01

    The efficacy of radiotherapy and MCNU (MR) was estimated in comparison with radiotherapy and MCNU plus interferon-[beta] (IMR) in 25 patients with anaplastic astrocytoma. The MR group received irradiation with 50[approx]60 Gy and intravenous administration of 2 mg/kg of MCNU on the initial day of irradiation and following every 6[approx]8 weeks interval. The IMR group also received the same regimen in addition to intravenous infusion of 2 x 10[sup 6] IU/m[sup 2] of interferon-[beta] for 5 serial days every eight weeks and following once every two weeks. There were no significant differences between the two groups in terms of background. The response rates of MR and IMR group were 38.5% and 66.7%, respectively. The times to tumor progression (TTP) in the two groups were 11.9[+-]5.8 months and 13.6[+-]7.7 months, respectively. Thus, IMR therapy seems to be more efficacious for patients with anaplastic astrocytoma than MR therapy, but further trials are necessary. (author).

  9. An acid phosphatase in the plasma membranes of human astrocytoma showing marked specificity toward phosphotyrosine protein.

    OpenAIRE

    Leis, J F; Kaplan, N O

    1982-01-01

    The plasma membrane from the human tumor astrocytoma contains an active acid phosphatase activity based on hydrolysis of p-nitrophenyl phosphate. Other acid phosphatase substrates--beta-glycerophosphate, O-phosphorylcholine, and 5'-AMP--are not hydrolyzed significantly. The phosphatase activity is tartrate insensitive and is stimulated by Triton X-100 and EDTA. Of the three known phosphoamino acids, only free O-phosphotyrosine is hydrolyzed by the membrane phosphatase activity. Other acid pho...

  10. A RISC multiprocessor event trigger for the data acquisition system of the H1 experiment at HERA

    International Nuclear Information System (INIS)

    Campbell, A.J.

    1992-01-01

    In late 1991 HERA will collide for the first time stored beams of electrons and protons. This paper describes the multiple RISC processor system for online event filtering and reconstruction installed within the data acquisition system of the H1 experiment. Data is processed at a continuous average rate of ∼6 Mbytes/s in parallel by ∼20 R3000 VMEbus based monoboard computers providing some 400 MIPS computing power

  11. CD133 positive U87 glioma stem cell radiosensitivity and DNA double-strand break repair

    International Nuclear Information System (INIS)

    Li Ping; Zong Tianzhou; Ji Xiaoqin; Lu Xueguan

    2013-01-01

    Objective: To explore the radiosensitivity and DNA double-strand break repair of CD133 + U87 glioma stem cell. Methods: CD133 + and CD133 - cells were isolated from glioma U87 cell lines by flow cytometry sorter system. After irradiated vertically by 4 Gy X-rays, the radiosensitivity of cells was determined by clonogenic assay. The radiation-induced DNA double-strand break repair of CD133 + and CD133 - cells was determined by the neutral comet assay,and the expression of phosphorylated histone H2AX (γ-H2AX) and Rad51 foci were measured by immunofluorescence. Results: The clone forming rate of CD133 + cells was higher than CD133 - cells (t=3.66, P<0.01) with no radiation. The clone forming rate of CD133 + cells irradiated by 4 Gy X-rays has no significant changes compared to that of the non-irradiation cells (t=0.71, P>0.05), but for CD133 - cells, it decreased compared to non-irradiation cells (t=2.91, P<0.05). The tailmoment between CD133 + cells and CD133 - cells had no difference at 0.5 h after irradiation (t=1.44, P>0.05); the tailmoment of CD133 + cells was lower than CD133 - cells at 6 and 24 h after irradiation,respectively (t=5.31 and 8.09, P<0.01). There was no significant difference in the expression of γ-H2AX foci between CD133 + and CD133 - cells at 0.5 and 6 h after irradiation (t=0.12 and 0.99, P>0.05), γ-H2AX foci of CD133 + cells was significantly decreased compared to CD133 - cells at 24 h after irradiation (t=4.99, P<0.01). For Rad 51 foci, there was no difference between CD133 + and CD133 - cells at 0.5 h after irradiation (t=1.12, P>0.05). The expression of Rad 51 foci of CD133 - cells was decreased compared to that of CD133 + cells at 6 and 24 h after irradiation,respectively (t=22.88 and 12.43, P<0.01). And the expression of Rad51 foci of CD133 + cells had no significant changes at 6-24 h after irradiation. Conclusions: Glioma stem cells is more radioresistive than glioma non-stem cells. The probable mechanism is that the DNA double

  12. Efficient Ada multitasking on a RISC register window architecture

    Science.gov (United States)

    Kearns, J. P.; Quammen, D.

    1987-01-01

    This work addresses the problem of reducing context switch overhead on a processor which supports a large register file - a register file much like that which is part of the Berkeley RISC processors and several other emerging architectures (which are not necessarily reduced instruction set machines in the purest sense). Such a reduction in overhead is particularly desirable in a real-time embedded application, in which task-to-task context switch overhead may result in failure to meet crucial deadlines. A storage management technique by which a context switch may be implemented as cheaply as a procedure call is presented. The essence of this technique is the avoidance of the save/restore of registers on the context switch. This is achieved through analysis of the static source text of an Ada tasking program. Information gained during that analysis directs the optimized storage management strategy for that program at run time. A formal verification of the technique in terms of an operational control model and an evaluation of the technique's performance via simulations driven by synthetic Ada program traces are presented.

  13. Regulation of sonic hedgehog-GLI1 downstream target genes PTCH1, Cyclin D2, Plakoglobin, PAX6 and NKX2.2 and their epigenetic status in medulloblastoma and astrocytoma

    Directory of Open Access Journals (Sweden)

    Eberhart Charles G

    2010-11-01

    Full Text Available Abstract Background The Sonic hedgehog (Shh signaling pathway is critical for cell growth and differentiation. Impairment of this pathway can result in both birth defects and cancer. Despite its importance in cancer development, the Shh pathway has not been thoroughly investigated in tumorigenesis of brain tumors. In this study, we sought to understand the regulatory roles of GLI1, the immediate downstream activator of the Shh signaling pathway on its downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6 in medulloblastoma and astrocytic tumors. Methods We silenced GLI1 expression in medulloblastoma and astrocytic cell lines by transfection of siRNA against GLI1. Subsequently, we performed RT-PCR and quantitative real time RT-PCR (qRT-PCR to assay the expression of downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6. We also attempted to correlate the pattern of expression of GLI1 and its regulated genes in 14 cell lines and 41 primary medulloblastoma and astrocytoma tumor samples. We also assessed the methylation status of the Cyclin D2 and PTCH1 promoters in these 14 cell lines and 58 primary tumor samples. Results Silencing expression of GLI1 resulted up-regulation of all target genes in the medulloblastoma cell line, while only PTCH1 was up-regulated in astrocytoma. We also observed methylation of the cyclin D2 promoter in a significant number of astrocytoma cell lines (63% and primary astrocytoma tumor samples (32%, but not at all in any medulloblastoma samples. PTCH1 promoter methylation was less frequently observed than Cyclin D2 promoter methylation in astrocytomas, and not at all in medulloblastomas. Conclusions Our results demonstrate different regulatory mechanisms of Shh-GLI1 signaling. These differences vary according to the downstream target gene affected, the origin of the tissue, as well as epigenetic regulation of some of these genes.

  14. Application of specialized RISC processor for realization of algorithms for track signal filtration on data read from CCD

    International Nuclear Information System (INIS)

    Ban, Ya.; Kotov, V.M.; Kharcharufkova, K.

    1987-01-01

    Algorithms for track signal filtration from bubble and streamer spark chambers read by CCD matrix with elements of 256x288 dimensions are described. The microprogrammed RISC processor is used for preliminary processing and filtration of data obtained. It makes possible to recognize and filter track elements in the zone of 0.25 mm 2 square during 0.17-0.20 s, that maintains it in real time operation

  15. A RISC multiprocessor event trigger for the data acquisition system of the H1 experiment at HERA

    International Nuclear Information System (INIS)

    Campbell, A.J.

    1991-09-01

    In late 1991 HERA will for the first time collide stored beams of electrons and protons. This paper describes the multiple (RISC) modern reduced instruction set processor system for online event filtering and reconstruction installed within the data acquisition system of the H1 experiment. Data is processed at a continuous average rate of ∼ 6 Mbytes/s in parallel by ∼ 20 R3000 VMEbus based monoboard computers providing some 400 mips computing power. (author)

  16. An acid phosphatase in the plasma membranes of human astrocytoma showing marked specificity toward phosphotyrosine protein.

    Science.gov (United States)

    Leis, J F; Kaplan, N O

    1982-11-01

    The plasma membrane from the human tumor astrocytoma contains an active acid phosphatase activity based on hydrolysis of p-nitrophenyl phosphate. Other acid phosphatase substrates--beta-glycerophosphate, O-phosphorylcholine, and 5'-AMP--are not hydrolyzed significantly. The phosphatase activity is tartrate insensitive and is stimulated by Triton X-100 and EDTA. Of the three known phosphoamino acids, only free O-phosphotyrosine is hydrolyzed by the membrane phosphatase activity. Other acid phosphatases tested from potato, wheat germ, milk, and bovine prostate did not show this degree of specificity. The plasma membrane activity also dephosphorylated phosphotyrosine histone at a much greater rate than did the other acid phosphatases. pH profiles for free O-phosphotyrosine and phosphotyrosine histone showed a shift toward physiological pH, indicating possible physiological significance. Phosphotyrosine histone dephosphorylation activity was nearly 10 times greater than that seen for phosphoserine histone dephosphorylation, and Km values were much lower for phosphotyrosine histone dephosphorylation (0.5 microM vs. 10 microM). Fluoride and zinc significantly inhibited phosphoserine histone dephosphorylation. Vanadate, on the other hand, was a potent inhibitor of phosphotyrosine histone dephosphorylation (50% inhibition at 0.5 microM) but not of phosphoserine histone. ATP stimulated phosphotyrosine histone dephosphorylation (160-250%) but inhibited phosphoserine histone dephosphorylation (95%). These results suggest the existence of a highly specific phosphotyrosine protein phosphatase activity associated with the plasma membrane of human astrocytoma.

  17. Reliability and validity of the Khmer version of the 10-item Connor-Davidson Resilience Scale (Kh-CD-RISC10) in Cambodian adolescents.

    Science.gov (United States)

    Duong, Chanmettachampavieng; Hurst, Cameron P

    2016-06-08

    Resilience has been characterized as a defensive factor against the refinement of mental health problems. This study adapted the Connor-Davidson Resilience Scale (Kh-CD-RISC10) for use in Khmer adolescents and subsequently investigates its psychometric properties. Using stratified random sampling, this cross-sectional study sampled Cambodian adolescents from high schools selected randomly within three provinces (Phnom Penh, Battambang and Mondulkiri)-location (rural, urban) combinations. Parallel analysis was used to identify the number of component(s), and the structure of the single factor was subsequently explored using principal axis factoring. A confirmatory factor analysis was then performed to establish the fit of the Kh-CD-RISC10 to another sample. To assess convergent validity, the factor scores of the Khmer version of Connor-Davidson Resilience Scale were categorized into three levels, and then the general negative affectivity (GNA) and physiological hyperarousal (PH) scales (derived from the DASS 21) were compared among the three resilience groups. Of the 798 participants who responded (responded rate = 82.26 %), 440 (41.23 %) were female and the age ranged from 14 to 24 years old (mean = 17.36, SD = 1.325). The internal consistency of the Khmer 10-item CD-RISC was also shown to be high in Cambodian adolescents (Cronbach's alpha = 0. 82). Confirmatory factor analysis revealed the single factor model fit data adequately (χ(2) = 100.103, df = 35, p scale of this population, and can be used to assess the resilience comparing to the level of PTSD symptoms in general Khmer adolescent.

  18. Subventricular zone predicts high velocity of tumor expansion and poor clinical outcome in patients with low grade astrocytoma.

    Science.gov (United States)

    Wen, Bing; Fu, Feixian; Hu, Liangbo; Cai, Qiuyi; Xie, Junshi

    2018-05-01

    The aim of this study is to clarify the association between subventricular zone (SVZ) involvement and velocity of diametric expansion(VDE) in patients with low-grade astrocytoma and also assessed the clinical outcome of those patients. A total of 168 adult patients with newly diagnosed supratentorial low-grade astrocytoma were studied retrospectively. There were 73 patients had SVZ involvement. Patients with SVZ involvement(7.16 ± 6.53 mm/y) had a higher VDE than patients without SVZ involvement(4.38 ± 5.35 mm/y). VDE was modeled as a categorical variable(<4, ≥4 and, <8, ≥8 and, <12, ≥12 mm/y). Logistic regression showed that SVZ involvement was associated with high VDE after adjusting by confounding variables. On the univariate analysis, the results showed that tumor involved with SVZ, VDE ≥ 4 mm/y, VDE ≥ 8 mm/y, and VDE ≥ 8 mm/y were significant predictors of a shorter OS, progression-free survival (PFS) and malignant progression-free survival (MFS)(all p <0.05). The categorical variables of VDE (<4 mm/y, ≥4 mm/y and, <8 mm/y, ≥8 mm/y and, <12 mm/y, ≥12 mm/y) were adjusted by confounding variables in multivariate analysis, respectively. The results indicated that VDE ≥ 8 mm/y, VDE ≥ 12 mm/y were worse prognostic factors for OS, while VDE ≥ 4 mm/y, VDE ≥ 8 mm/y and VDE ≥ 12 mm/y were related to shorter PFS and MFS. In addition, SVZ involvement was prognostic factors in predicting OS and PFS except MFS. Our results demonstrated that SVZ involvement predicted high VDE and worse clinical outcome, and high VDE was associated with poor prognosis in patients with low-grade astrocytoma. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Depressive symptoms, insulin sensitivity and insulin secretion in the RISC cohort study

    DEFF Research Database (Denmark)

    Bot, M; Pouwer, F; De Jonge, P

    2013-01-01

    Sensitivity and Cardiovascular Disease Risk (RISC) study. Presence of significant depressive symptoms was defined as a Center for Epidemiologic Studies Depression Scale (CES-D) score ≥ 16. Standard oral glucose tolerance tests were performed. Insulin sensitivity was assessed with the oral glucose insulin......AIM: This study explored the association of depressive symptoms with indices of insulin sensitivity and insulin secretion in a cohort of non-diabetic men and women aged 30 to 64 years. METHODS: The study population was derived from the 3-year follow-up of the Relationship between Insulin...... sensitivity (OGIS) index. Insulin secretion was estimated using three model-based parameters of insulin secretion (beta-cell glucose sensitivity, the potentiation factor ratio, and beta-cell rate sensitivity). RESULTS: A total of 162 out of 1027 participants (16%) had significant depressive symptoms. Having...

  20. Sulforaphane inhibits invasion via activating ERK1/2 signaling in human glioblastoma U87MG and U373MG cells.

    Directory of Open Access Journals (Sweden)

    Chunliu Li

    Full Text Available Glioblastoma has highly invasive potential, which might result in poor prognosis and therapeutic failure. Hence, the key we study is to find effective therapies to repress migration and invasion. Sulforaphane (SFN was demonstrated to inhibit cell growth in a variety of tumors. Here, we will further investigate whether SFN inhibits migration and invasion and find the possible mechanisms in human glioblastoma U87MG and U373MG cells.First, the optimal time and dose of SFN for migration and invasion study were determined via cell viability and cell morphological assay. Further, scratch assay and transwell invasion assay were employed to investigate the effect of SFN on migration and invasion. Meanwhile, Western blots were used to detect the molecular linkage among invasion related proteins phosphorylated ERK1/2, matrix metalloproteinase-2 (MMP-2 and CD44v6. Furthermore, Gelatin zymography was performed to detect the inhibition of MMP-2 activation. In addition, ERK1/2 blocker PD98059 (25 µM was integrated to find the link between activated ERK1/2 and invasion, MMP-2 and CD44v6.The results showed that SFN (20 µM remarkably reduced the formation of cell pseudopodia, indicating that SFN might inhibit cell motility. As expected, scratch assay and transwell invasion assay showed that SFN inhibited glioblastoma cell migration and invasion. Western blot and Gelatin zymography showed that SFN phosphorylated ERK1/2 in a sustained way, which contributed to the downregulated MMP-2 expression and activity, and the upregulated CD44v6 expression. These molecular interactions resulted in the inhibition of cell invasion.SFN inhibited migration and invasion processes. Furthermore, SFN inhibited invasion via activating ERK1/2 in a sustained way. The accumulated ERK1/2 activation downregulated MMP-2 expression and decreased its activity and upregulated CD44v6. SFN might be a potential therapeutic agent by activating ERK1/2 signaling against human glioblastoma.

  1. AUTOCOUNTER, an ImageJ JavaScript to analyze LC3B-GFP expression dynamics in autophagy-induced astrocytoma cells.

    Science.gov (United States)

    Fassina, L; Magenes, G; Inzaghi, A; Palumbo, S; Allavena, G; Miracco, C; Pirtoli, L; Biggiogera, M; Comincini, S

    2012-10-11

    An ImageJ JavaScript, AUTOCOUNTER, was specifically developed to monitor and measure LC3B-GFP expression in living human astrocytoma cells, namely T98G and U373-MG. Discrete intracellular GFP fluorescent spots derived from transduction of a Baculovirus replication-defective vector (BacMam LC3B-GFP), followed by microscope examinations at different times. After viral transgene expression, autophagy was induced by Rapamycin administration and assayed in ph-p70S6K/p70S6K and LC3B immunoblotting expression as well as by electron microscopy examinations. A mutated transgene, defective in LC3B lipidation, was employed as a negative control to further exclude fluorescent dots derived from protein intracellular aggregation. The ImageJ JavaScript was then employed to evaluate and score the dynamics changes of the number and area of LC3B-GFP puncta per cell in time course assays and in complex microscope examinations. In conclusion, AUTOCOUNTER enabled to quantify LC3B-GFP expression and to monitor dynamics changes in number and shapes of autophagosomal-like vesicles: it might therefore represent a suitable algorithmic tool for in vitro autophagy modulation studies.

  2. Screening for markers of frailty and perceived risk of adverse outcomes using the Risk Instrument for Screening in the Community (RISC).

    LENUS (Irish Health Repository)

    O Caoimh, Rónán

    2014-09-19

    Functional decline and frailty are common in community dwelling older adults, increasing the risk of adverse outcomes. Given this, we investigated the prevalence of frailty-associated risk factors and their distribution according to the severity of perceived risk in a cohort of community dwelling older adults, using the Risk Instrument for Screening in the Community (RISC).

  3. Geometrical study of astrocytomas through fractals and scaling analysis

    International Nuclear Information System (INIS)

    Torres H, F.; Baena N, R.; Vergara V, J.; Guerrero M, M.

    2017-10-01

    The tumor growth is a complex process characterized by the proliferation of uncontrollable cells which invade neighbor tissues. The understanding process of this type of phenomena is very relevant in order to establish diagnosis and proper therapy strategies and to start the valorization of its complexity with proper descriptors produced by the scaling analysis, which define the tumor growth geometry. In this work, obtained results through the scaling analysis for pilocytic astrocytomas, anaplastic and diffuse, are shown, which tumors of primary origin are. On them, it is calculated the fractal dimension and critic exponents of local roughness to characterize in vivo three-dimensional tumor growth. The acquisition of the images for this type of injuries was carried out according to the standard protocol used for brain radiotherapy and radiosurgery, i.e., axial, coronal and sagittal magnetic resonance T1 weighted images and comprising the brain volume for image registration. Image segmentation was performed by the application the K-means procedure upon contrasted images. The results show significant variations of the parameters depending on the tumor stage and its histological origin. (Author)

  4. A case of paraventricular anaplastic astrocytoma following radiation therapy for craniopharyngioma

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, Hiroaki; Fujiwara, Kazunori; Kobayashi, Shin-ichi; Kitahara, Masakazu (Ishinomaki Red Cross Hospital, Miyagi (Japan))

    1994-04-01

    A 20-year-old man received 60 Gy of radiation therapy after partial removal of craniopharyngioma. The patient had been well and follow-up CT scans did not show any aggravation for 16 years. Since his activity gradually diminished, he underwent an MRI at the age of 36 which revealed and abnormal mass on the corpus callosum. The mass lesion progressively enlarged thereafter, and was diagnosed as anaplastic astrocytoma by a stereotactic biopsy. He was treated with interferon, however, died at the age of 37. Review of the literature disclosed 19 other cases of glioma following radiation therapy for sellar/parasellar tumors. Characteristic features of these cases included (1) lowness of age compared to common glioma cases, (2) tendency to be malignant, (3) tendency to occur in areas where significant doses of radiation had been received previously. (author).

  5. Low cost RISC implementation of intelligent ultra fast charger for Ni-Cd battery

    International Nuclear Information System (INIS)

    Petchjatuporn, Panom; Sirisuk, Phaophak; Khaehintung, Noppadol; Sunat, Khamron; Wicheanchote, Phinyo; Kiranon, Wiwat

    2008-01-01

    This paper presents a low cost reduced instruction set computer (RISC) implementation of an intelligent ultra fast charger for a nickel-cadmium (Ni-Cd) battery. The charger employs a genetic algorithm (GA) trained generalized regression neural network (GRNN) as a key to ultra fast charging while avoiding battery damage. The tradeoff between mean square error (MSE) and the computational burden of the GRNN is addressed. Besides, an efficient technique is proposed for estimation of a radial basis function (RBF) in the GRNN. Hardware realization based upon the techniques is discussed. Experimental results with commercial Ni-Cd batteries reveal that while the proposed charger significantly reduces the charging time, it scarcely deteriorates the battery energy storage capability when compared with the conventional charger

  6. Low cost RISC implementation of intelligent ultra fast charger for Ni-Cd battery

    Energy Technology Data Exchange (ETDEWEB)

    Petchjatuporn, Panom; Khaehintung, Noppadol [Department of Control and Instrumentation Engineering, Faculty of Engineering, Mahanakorn University of Technology, Bangkok 10530 (Thailand); Sirisuk, Phaophak; Sunat, Khamron [Department of Computer Engineering, Faculty of Engineering, Mahanakorn University of Technology, Bangkok 10530 (Thailand); Wicheanchote, Phinyo [Test Engineering Department, Sanmina-SCI Systems Co. Ltd. (Thailand); Kiranon, Wiwat [Department of Telecommunication Engineering, Faculty of Engineering, King Mongkut' s Institue of Technology, Ladkrabang, Bangkok 10520 (Thailand)

    2008-02-15

    This paper presents a low cost reduced instruction set computer (RISC) implementation of an intelligent ultra fast charger for a nickel-cadmium (Ni-Cd) battery. The charger employs a genetic algorithm (GA) trained generalized regression neural network (GRNN) as a key to ultra fast charging while avoiding battery damage. The tradeoff between mean square error (MSE) and the computational burden of the GRNN is addressed. Besides, an efficient technique is proposed for estimation of a radial basis function (RBF) in the GRNN. Hardware realization based upon the techniques is discussed. Experimental results with commercial Ni-Cd batteries reveal that while the proposed charger significantly reduces the charging time, it scarcely deteriorates the battery energy storage capability when compared with the conventional charger. (author)

  7. Astrocytoma in the medulla oblongata diagnosed by magnetic resonance imaging

    International Nuclear Information System (INIS)

    Suga, Toshihiro; Takahashi, Shin-ichiro; Sonobe, Makoto; Koshu, Keiji; Hirota, Shigeru; Kawakami, Hiroshi; Fujii, Kyoichi; Namiki, Tsuneo.

    1987-01-01

    A 22-year-old male was admitted to Mito National Hospital with complaints of persistent, progressive dysphagia, hoarseness, and numbness over his entire body. Neurological examination showed bilateral 7th, 9th, and 10th nerve paralysis, tetraparesis, sensory disturbance of the whole body, and hyper-reflexia of all extremities. Pale, low-density areas in the medulla oblongata and upper cervical spinal cord were detected by conventional computed tomography. Magnetic resonance imaging (MRI) disclosed low-signal masses involving those areas and in the lower cervical cord. Suboccipital craniotomy exposed a solid, firm, well demarcated intramedullary tumor in the medulla oblongata. The tumor was removed en bloc and was histologically diagnosed as a pilocytic astrocytoma. The postoperative course was uneventful and the patient's symptoms improved dramatically. Postoperative MRI revealed no residual tumor in the medulla oblongata or upper cervical cord. This case illustrates the value of preoperative MRI, which precisely delineates the location and extent of the tumor and greatly facilitates direct surgery of the medulla oblongata. (author)

  8. Fast neutron boost for the treatment of grade IV astrocytomas

    International Nuclear Information System (INIS)

    Breteau, N.; Destembert, B.; Favre, A.; Pheline, C.; Schlienger, M.

    1989-01-01

    A previous study, on grade IV astrocytomas, compared a combination of photons and fast neutron boost to photons only, both treatments being delivered following a concentrated irradiation schedule. A slight improvement in survival was observed after neutron boost for non operated patients, but not for operated patients. Since death was always related to local recurrence and since no complication occurred after neutron boost, the neutron dose was increased from 6 to 7 Gy in January 1985. No improvement in survival was observed for patients treated with neutron boost after complete resection. After subtotal resection, the group that was treated with the higher neutron boost (7 Gy) showed a significant benefit in survival at twelve months. When patients had only a biopsy before irradiation, there was a benefit in survival after neutron boost, but no additional benefit was gained when the size of the neutron boost was increased from 6 to 7 Gy. (orig.) [de

  9. A viral suppressor of RNA silencing inhibits ARGONAUTE 1 function by precluding target RNA binding to pre-assembled RISC.

    Science.gov (United States)

    Kenesi, Erzsébet; Carbonell, Alberto; Lózsa, Rita; Vértessy, Beáta; Lakatos, Lóránt

    2017-07-27

    In most eukaryotes, RNA silencing is an adaptive immune system regulating key biological processes including antiviral defense. To evade this response, viruses of plants, worms and insects have evolved viral suppressors of RNA silencing proteins (VSRs). Various VSRs, such as P1 from Sweet potato mild mottle virus (SPMMV), inhibit the activity of RNA-induced silencing complexes (RISCs) including an ARGONAUTE (AGO) protein loaded with a small RNA. However, the specific mechanisms explaining this class of inhibition are unknown. Here, we show that SPMMV P1 interacts with AGO1 and AGO2 from Arabidopsis thaliana, but solely interferes with AGO1 function. Moreover, a mutational analysis of a newly identified zinc finger domain in P1 revealed that this domain could represent an effector domain as it is required for P1 suppressor activity but not for AGO1 binding. Finally, a comparative analysis of the target RNA binding capacity of AGO1 in the presence of wild-type or suppressor-defective P1 forms revealed that P1 blocks target RNA binding to AGO1. Our results describe the negative regulation of RISC, the small RNA containing molecular machine. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Optimal gadolinium dose level for magnetic resonance imaging (MRI) contrast enhancement of U87-derived tumors in athymic nude rats for the assessment of photodynamic therapy

    Science.gov (United States)

    Cross, Nathan; Varghai, Davood; Flask, Chris A.; Feyes, Denise K.; Oleinick, Nancy L.; Dean, David

    2009-02-01

    This study aims to determine the effect of varying gadopentetate dimeglumine (Gd-DTPA) dose on Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) tracking of brain tumor photodynamic therapy (PDT) outcome. Methods: We injected 2.5 x 105 U87 cells (derived from human malignant glioma) into the brains of six athymic nude rats. After 9, 12, and 13 days DCE-MRI images were acquired on a 9.4 T micro-MRI scanner before and after administration of 100, 150, or 200 μL of Gd-DTPA. Results: Tumor region normalized DCE-MRI scan enhancement at peak was: 1.217 over baseline (0.018 Standard Error [SE]) at the 100 μL dose, 1.339 (0.013 SE) at the 150 μL dose, and 1.287 (0.014 SE) at the 200 μL dose. DCE-MRI peak tumor enhancement at the 150 μL dose was significantly greater than both the 100 μL dose (p DTPA dose provided the greatest T1 weighted contrast enhancement, while minimizing negative T2* effects, in DCE-MRI scans of U87-derived tumors. Maximizing Gd-DTPA enhancement in DCE-MRI scans may assist development of a clinically robust (i.e., unambiguous) technique for PDT outcome assessment.

  11. Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) for the assessment of Pc 4-sensitized photodynamic therapy of a U87-derived glioma model in the athymic nude rat

    Science.gov (United States)

    Anka, Ali; Thompson, Paul; Mott, Eric; Sharma, Rahul; Zhang, Ruozhen; Cross, Nathan; Sun, Jiayang; Flask, Chris A.; Oleinick, Nancy L.; Dean, David

    2010-02-01

    Introduction: Dynamic Contrast-Enhanced-Magnetic Resonance Imaging (DCE-MRI) may provide a means of tracking the outcome of Pc 4-sensitized photodynamic therapy (PDT) in deeply placed lesions (e.g., brain tumors). We previously determined that 150 μL of gadolinium (Gd-DTPA) produces optimal enhancement of U87-derived intracerebral tumors in an athymic nude rat glioma model. We wish to determine how consistently DCE-MRI enhancement will detect an increase in Gd-enhancement of these tumors following Pc 4-PDT. Methods: We injected 2.5 x 105 U87 cells into the brains of 6 athymic nude rats. After 7-8 days pre-Pc 4 PDT peri-tumor DCE-MRI images were acquired on a 7.0T microMRI scanner before and after administration of 150 μL Gd. DCE-MRI scans were repeated on Days 11, 12, and 13 following Pc 4-PDT (Day 8 or 9). Results: Useful DCE-MRI data were obtained for these animals before and after Pc 4- PDT. In the pre-Pc 4-PDT DCE-MRI scans an average normalized peak Gd enhancement was observed in tumor tissue that was 1.297 times greater than baseline (0.035 Standard Error [SE]). The average normalized peak Gd enhancement in the tumor tissue in the scan following PDT (Day 11) was 1.537 times greater than baseline (0.036 SE), a statistically significant increase in enhancement (p = 0.00584) over the pre-PDT level. Discussion: A 150 μL Gd dose appears to provide an unambiguous increase in signal indicating Pc 4-PDT-induced necrosis of the U87-derived tumor. Our DCEMRI protocol may allow the development of a clinically robust, unambiguous, non-invasive technique for the assessment of PDT outcome.

  12. High resolution 2-D imaging polarimetry of the jet of M87, in the light of U, B and V

    Energy Technology Data Exchange (ETDEWEB)

    Visvanathan, N; Pickles, A J [Australian National Univ., Canberra. Mount Stromlo and Siding Spring Observatories

    1981-01-01

    Polarisation maps to a resolution of 1 arcsec in the jet of M87 are presented. The results show that small-scale structure exists in the magnetic field down to at least this resolution, as evidenced by the fact that the 1 arcsec resolution percentage polarisations are approximately 80% higher than those obtained at a lower resolution, 2 arcsec. The sudden change of position angles of the electric vector near knot B supports shock models of the jet. The jet is significantly broader in the light of U than in B or V. The continuous energy distribution in UBV can be described as a power law spectrum, with a slope of -1.7 +- 0.3 which indicates a turnover in the synchrotron spectrum in the vicinity of V.

  13. Middle Temporal Gyrus Versus Inferior Temporal Gyrus Transcortical Approaches to High-Grade Astrocytomas in the Mediobasal Temporal Lobe: A Comparison of Outcomes, Functional Restoration, and Surgical Considerations.

    Science.gov (United States)

    Quinones-Hinojosa, Alfredo; Raza, Shaan M; Ahmed, Ishrat; Rincon-Torroella, Jordina; Chaichana, Kaisorn; Olivi, Alessandro

    2017-01-01

    High-grade astrocytomas of the mesial temporal lobe may pose surgical challenges. Several approaches (trans-sylvian, subtemporal, and transcortical) have been designed to circumnavigate the critical neurovascular structures and white fiber tracts that surround this area. Considering the paucity of literature on the transcortical approach for these lesions, we describe our institutional experience with transcortical approaches to Grade III/IV astrocytomas in the mesial temporal lobe. Between 1999 and 2009, 23 patients underwent surgery at the Johns Hopkins Medical Institutions for Grade III/IV astrocytomas involving the mesial temporal lobe (without involvement of the temporal neocortex). Clinical notes, operative records, and imaging were reviewed. Thirteen patients had tumors in the dominant hemisphere. All patients underwent surgery via a transcortical approach (14 via the inferior temporal gyrus and 9 via the middle temporal gyrus). Gross total resection was obtained in 92 % of the cohort. Neurological outcomes were: clinically significant stroke (2 patients), new visual deficits (2 patients), new speech deficit (1 patient); seizure control (53 %). In comparison to reported results in the literature for the transylvian and subtemporal approaches, the transcortical approach may provide the access necessary for a gross total resection with minimal neurological consequences. In our series of patients, there was no statistically significant difference in outcomes between the middle temporal gyrus versus the inferior temporal gyrus trajectories.

  14. INS3D - NUMERICAL SOLUTION OF THE INCOMPRESSIBLE NAVIER-STOKES EQUATIONS IN THREE-DIMENSIONAL GENERALIZED CURVILINEAR COORDINATES (DEC RISC ULTRIX VERSION)

    Science.gov (United States)

    Biyabani, S. R.

    1994-01-01

    -field boundaries. Three machine versions of INS3D are available. INS3D for the CRAY is written in CRAY FORTRAN for execution on a CRAY X-MP under COS, INS3D for the IBM is written in FORTRAN 77 for execution on an IBM 3090 under the VM or MVS operating system, and INS3D for DEC RISC-based systems is written in RISC FORTRAN for execution on a DEC workstation running RISC ULTRIX 3.1 or later. The CRAY version has a central memory requirement of 730279 words. The central memory requirement for the IBM is 150Mb. The memory requirement for the DEC RISC ULTRIX version is 3Mb of main memory. INS3D was developed in 1987. The port to the IBM was done in 1990. The port to the DECstation 3100 was done in 1991. CRAY is a registered trademark of Cray Research Inc. IBM is a registered trademark of International Business Machines. DEC, DECstation, and ULTRIX are trademarks of the Digital Equipment Corporation.

  15. Neuronavigation-guided intubated wake-up craniotomy for a patient with a brain astrocytoma

    Directory of Open Access Journals (Sweden)

    Wen-Kuei Fang

    2013-08-01

    Full Text Available Computer-assisted neuronavigation (an image-guided technique that facilitates brain tumor surgery reduces the risk of neurological morbidity. Postoperative neurological dysfunction is also minimized by performing intraoperative neurological testing during awake craniotomy with proper surgical resection of a brain tumor. However, when the patient's airway is not secured, an awake craniotomy can be hazardous if emergent intubation is necessary. The present report describes a young man with a brain tumor who underwent neuronavigation-guided wake-up craniotomy and surgical resection of an astrocytoma. The patient was intubated throughout the course of the procedure, during which modified intraoperative neurological tests were performed for cortical mapping. The patient recovered well after the operation and without any neurological deficits.

  16. High accuracy of arterial spin labeling perfusion imaging in differentiation of pilomyxoid from pilocytic astrocytoma

    Energy Technology Data Exchange (ETDEWEB)

    Nabavizadeh, S.A.; Assadsangabi, R.; Hajmomenian, M.; Vossough, A. [Perelman School of Medicine of the University of Pennsylvania, Department of Radiology, Children' s Hospital of Philadelphia, Philadelphia, PA (United States); Santi, M. [Perelman School of Medicine of the University of Pennsylvania, Department of Pathology, Children' s Hospital of Philadelphia, Philadelphia, PA (United States)

    2015-05-01

    Pilomyxoid astrocytoma (PMA) is a relatively new tumor entity which has been added to the 2007 WHO Classification of tumors of the central nervous system. The goal of this study is to utilize arterial spin labeling (ASL) perfusion imaging to differentiate PMA from pilocytic astrocytoma (PA). Pulsed ASL and conventional MRI sequences of patients with PMA and PA in the past 5 years were retrospectively evaluated. Patients with history of radiation or treatment with anti-angiogenic drugs were excluded. A total of 24 patients (9 PMA, 15 PA) were included. There were statistically significant differences between PMA and PA in mean tumor/gray matter (GM) cerebral blood flow (CBF) ratios (1.3 vs 0.4, p < 0.001) and maximum tumor/GM CBF ratio (2.3 vs 1, p < 0.001). Area under the receiver operating characteristic (ROC) curves for differentiation of PMA from PA was 0.91 using mean tumor CBF, 0.95 using mean tumor/GM CBF ratios, and 0.89 using maximum tumor/GM CBF. Using a threshold value of 0.91, the mean tumor/GM CBF ratio was able to diagnose PMA with 77 % sensitivity, 100 % specificity, and a threshold value of 0.7, provided 88 % sensitivity and 86 % specificity. There was no statistically significant difference between the two tumors in enhancement pattern (p = 0.33), internal architecture (p = 0.15), or apparent diffusion coefficient (ADC) values (p = 0.07). ASL imaging has high accuracy in differentiating PMA from PA. The result of this study may have important applications in prognostication and treatment planning especially in patients with less accessible tumors such as hypothalamic-chiasmatic gliomas. (orig.)

  17. Using a Cray Y-MP as an array processor for a RISC Workstation

    Science.gov (United States)

    Lamaster, Hugh; Rogallo, Sarah J.

    1992-01-01

    As microprocessors increase in power, the economics of centralized computing has changed dramatically. At the beginning of the 1980's, mainframes and super computers were often considered to be cost-effective machines for scalar computing. Today, microprocessor-based RISC (reduced-instruction-set computer) systems have displaced many uses of mainframes and supercomputers. Supercomputers are still cost competitive when processing jobs that require both large memory size and high memory bandwidth. One such application is array processing. Certain numerical operations are appropriate to use in a Remote Procedure Call (RPC)-based environment. Matrix multiplication is an example of an operation that can have a sufficient number of arithmetic operations to amortize the cost of an RPC call. An experiment which demonstrates that matrix multiplication can be executed remotely on a large system to speed the execution over that experienced on a workstation is described.

  18. MICROPROCESADOR DIDÁCTICO DE ARQUITECTURA RISC IMPLEMENTADO EN UN FPGA

    Directory of Open Access Journals (Sweden)

    Víctor H. García Ortega

    2009-01-01

    Full Text Available En este trabajo se presenta el diseño e implementación de un microprocesador de 16 bits de arquitectura RISC tipo MIPS. Las características principales que presenta el microprocesador son: una arquitectura Harvard con una memoria de programa de 64K x 25 bits y una memoria de datos de 64k x 16 bits, una pila de ocho niveles implementada en hardware y la Unidad Lógica-Aritmética (ALU con esquema de acarreo anticipado por propagación y generación para el aumento de velocidad en la ejecución de las operaciones aritméticas. La unidad de control decodifica y maneja las señales de control del microprocesador para ejecutar las instrucciones en un solo ciclo de reloj. La implementación se realizó en un dispositivo lógico programable del tipo FPGA (Field Programmable Gate Array de la familia Spartan-3A de Xilinx. El diseño de cada elemento del microprocesador se desarrolló con el lenguaje de descripción de hardware VHDL.

  19. Multi-bits error detection and fast recovery in RISC cores

    International Nuclear Information System (INIS)

    Wang Jing; Yang Xing; Zhang Weigong; Shen Jiao; Qiu Keni; Zhao Yuanfu

    2015-01-01

    The particles-induced soft errors are a major threat to the reliability of microprocessors. Even worse, multi-bits upsets (MBUs) are ever-increased due to the rapidly shrinking feature size of the IC on a chip. Several architecture-level mechanisms have been proposed to protect microprocessors from soft errors, such as dual and triple modular redundancies (DMR and TMR). However, most of them are inefficient to combat the growing multi-bits errors or cannot well balance the critical paths delay, area and power penalty. This paper proposes a novel architecture, self-recovery dual-pipeline (SRDP), to effectively provide soft error detection and recovery with low cost for general RISC structures. We focus on the following three aspects. First, an advanced DMR pipeline is devised to detect soft error, especially MBU. Second, SEU/MBU errors can be located by enhancing self-checking logic into pipelines stage registers. Third, a recovery scheme is proposed with a recovery cost of 1 or 5 clock cycles. Our evaluation of a prototype implementation exhibits that the SRDP can successfully detect particle-induced soft errors up to 100% and recovery is nearly 95%, the other 5% will inter a specific trap. (paper)

  20. Multi-bits error detection and fast recovery in RISC cores

    Science.gov (United States)

    Jing, Wang; Xing, Yang; Yuanfu, Zhao; Weigong, Zhang; Jiao, Shen; Keni, Qiu

    2015-11-01

    The particles-induced soft errors are a major threat to the reliability of microprocessors. Even worse, multi-bits upsets (MBUs) are ever-increased due to the rapidly shrinking feature size of the IC on a chip. Several architecture-level mechanisms have been proposed to protect microprocessors from soft errors, such as dual and triple modular redundancies (DMR and TMR). However, most of them are inefficient to combat the growing multi-bits errors or cannot well balance the critical paths delay, area and power penalty. This paper proposes a novel architecture, self-recovery dual-pipeline (SRDP), to effectively provide soft error detection and recovery with low cost for general RISC structures. We focus on the following three aspects. First, an advanced DMR pipeline is devised to detect soft error, especially MBU. Second, SEU/MBU errors can be located by enhancing self-checking logic into pipelines stage registers. Third, a recovery scheme is proposed with a recovery cost of 1 or 5 clock cycles. Our evaluation of a prototype implementation exhibits that the SRDP can successfully detect particle-induced soft errors up to 100% and recovery is nearly 95%, the other 5% will inter a specific trap.

  1. Photoassociation spectroscopy of 87Rb2 (5s1/2+5p1/2)0u+ long-range molecular states: Coupling with the (5s1/2+5p3/2)0u+ series analyzed using the Lu-Fano approach

    International Nuclear Information System (INIS)

    Jelassi, H.; Viaris de Lesegno, B.; Pruvost, L.

    2006-01-01

    We report on photoassociation of cold 87 Rb atoms providing the spectroscopy of (5s 1/2 +5p 1/2 )0 u + long-range molecular states, in the energy range of [-12.5, -0.7 cm -1 ] below the dissociation limit. A Lu-Fano approach coupled to the LeRoy-Bernstein formula is used to analyze the data. The Lu-Fano graph exhibits the coupling of the molecular series with the (5s 1/2 +5p 3/2 )0 u + one, which is due to spin effects in the molecule. A two-channel model involving an improved LeRoy-Bernstein formula allows us to characterize the molecular series, to localize (5s 1/2 +5p 3/2 )0 u + levels, to evaluate the coupling, and to predict the energy and width of the first predissociated level of (5s 1/2 +5p 3/2 )0 u + series. An experimental spectrum confirms the prediction

  2. G Protein-Coupled Receptor 87 (GPR87 Promotes Cell Proliferation in Human Bladder Cancer Cells

    Directory of Open Access Journals (Sweden)

    Xia Zhang

    2015-10-01

    Full Text Available G protein-coupled receptor 87 (GPR87 is a newly deorphanized member of the cell surface molecule G protein-coupled receptor family. GPR signaling was shown to play a role in promotion of cell growth and survival, metastasis, and drug resistance. The overexpression of GPR87 has also been reported in many malignant tumors including bladder cancer. The aim of the present study is to examine the effect of silencing GPR87 expression with a replication-deficient recombinant adenoviral vector expressing short hairpin RNA targeting GPR87 (Ad-shGPR87 and to explore the underlying molecular mechanisms in bladder cancer cells. Six GPR87-expressing human bladder cancer cells, HT1197, HT1376, J82, RT112, TCCSUP and UMUC3, were used. Infection with Ad-shGPR87 effectively downregulated the GPR87 expression, and significantly reduced the percentage of viable cells in 4 of 6 cell lines as detected by an MTT assay. Significant inhibition on cell proliferation with Ad-shGPR87 was observed in the wild-type p53 bladder cancer cell lines (HT1197, RT112, TCCSUP and UMUC3, but not in the mutant p53 cells (HT1376 and J82. As represented by a wild-type p53 RT112 cell, Ad-shGPR87 infection significantly enhanced p53 and p21 expression and caused caspase-dependent apoptosis. Furthermore, the treatment with Ad-shGPR87 exerted a significant antitumor effect against the GPR87-expressing RT112 xenografts. GPR87 appeared to be a promising target for gene therapy, and Ad-shGPR87 had strong antitumor effects, specifically anti-proliferative and pro-apoptotic effects, against GPR87-expressing human bladder cancer cells.

  3. Phytometabolite Dehydroleucodine Induces Cell Cycle Arrest, Apoptosis, and DNA Damage in Human Astrocytoma Cells through p73/p53 Regulation.

    Science.gov (United States)

    Bailon-Moscoso, Natalia; González-Arévalo, Gabriela; Velásquez-Rojas, Gabriela; Malagon, Omar; Vidari, Giovanni; Zentella-Dehesa, Alejandro; Ratovitski, Edward A; Ostrosky-Wegman, Patricia

    2015-01-01

    Accumulating evidence supports the idea that secondary metabolites obtained from medicinal plants (phytometabolites) may be important contributors in the development of new chemotherapeutic agents to reduce the occurrence or recurrence of cancer. Our study focused on Dehydroleucodine (DhL), a sesquiterpene found in the provinces of Loja and Zamora-Chinchipe. In this study, we showed that DhL displayed cytostatic and cytotoxic activities on the human cerebral astrocytoma D384 cell line. With lactone isolated from Gynoxys verrucosa Wedd, a medicinal plant from Ecuador, we found that DhL induced cell death in D384 cells by triggering cell cycle arrest and inducing apoptosis and DNA damage. We further found that the cell death resulted in the increased expression of CDKN1A and BAX proteins. A marked induction of the levels of total TP73 and phosphorylated TP53, TP73, and γ-H2AX proteins was observed in D384 cells exposed to DhL, but no increase in total TP53 levels was detected. Overall these studies demonstrated the marked effect of DhL on the diminished survival of human astrocytoma cells through the induced expression of TP73 and phosphorylation of TP73 and TP53, suggesting their key roles in the tumor cell response to DhL treatment.

  4. CREATING THE KULTUK POLYGON FOR EARTHQUAKE PREDICTION: VARIATIONS OF (234U/238U AND 87SR/86SR IN GROUNDWATER FROM ACTIVE FAULTS AT THE WESTERN SHORE OF LAKE BAIKAL

    Directory of Open Access Journals (Sweden)

    S. V. Rasskazov

    2015-01-01

    .5 mkg/l concentrations of uranium (components from the Medlyanka river and Kultuchnaya river, respectively. The U abundances reflect relatively reduced conditions in group 1 and more oxidized in group 2. The higher (234U/238U in the surface water with intermediate concentrations of uranium (0.009–0.500 mkg/l may indicate the admixture of a groundwater component (Fig. 3. Figure 4 shows relations between surface water and groundwater components in the Kultuk polygon in terms of U content. In Figure 5, the field of data points of U and Sr isotope ratios in groundwater from the Kultuk polygon is contoured by curved lines that meet with each other at compositions corresponding to the end members E (87Sr/86Sr=0.7205, 234U/238U=1.0 and NE (87Sr/86Sr=0.70534, 234U/238U=3.3. Uranium ratios of the former and the latter components show equilibrium and the most nonequilibrium compositions, respectively. The field is characteristic of water samples from the rocks of the southern suture zone of the Siberian craton. Shift of the data points of water from stations 26 and 1310 to the right of this data field (i.e. with relative increasing 87Sr/86Sr is due to lateral transition from the rocks of the suture zone to the Archean rocks of the Sharyzhalgai block (Fig. 6. The isotope systematics of uranium and strontium in the strongly nonequilibrium uranium segment is supplemented by the systematics of uranium in (234U/238U vs. 1/U diagram (Fig. 7. The U composition in water from station 40 reflects a combination of processes that take place at station 27 (i.e. in the central part of the deformation system and at station 38 (i.e. at its periphery. Approximately equal contents of uranium at the three above‐mentioned stations may reflect similar oxidization levels of the medium. In the Southern Baikal basin, the Irkutsk Seismic Station recorded an earthquake of class 11.2 on 08 January 2013 [Map…, 2013]. The earthquake epicentre was located near Listvyanka settlement (51.85° N, 105°16

  5. Globular clusters as a source of X-ray emission from the neighbourhood of M87

    International Nuclear Information System (INIS)

    Fabian, A.C.; Pringle, J.E.; Rees, M.J.

    1976-01-01

    It is stated that the X-ray emission from globular clusters may be attributable to accretion on to compact objects, the accreting material being supplied from binary companions, or gas trapped in the potential well of the cluster. Counts of objects in the vicinity of the M87 have revealed that it has an extensive halo of globular clusters, the number of which may exceed 10,000 within a radius of 23 arc min. Most of these clusters may be explicable as a population effect, and the similarity of their optical properties to those of cluster in our own Galaxy suggests that they may also contain X-ray sources. The brighter globular clusters in M87 may, however, be substantially more X-ray luminous, and there may be proportionally more gas available in globular clusters in M87 compared with our Galaxy. The average X-ray luminosity of individual globular clusters may be of the order of 10 38 erg/sec., which raises the possibility that the integrated globular cluster emission may account for a substantial fraction of the X-ray emission observed from the region of M87. In support of this it is noted that the extended X-ray emission from the Virgo cluster is centered on M87, which lies approximately 45 arc min from the cluster centroid, and it is expected that the general X-ray emission from the globular cluster will appear to be smoothly and symmetrically distributed about M87 at moderate spatial resolution. A similar situation may apply to the elliptical galaxy NGC 3311 in Abell 1060 which, as a cluster, has been suggested as the identification for the X-ray source 3 U 1044-40, and it seems possible that that galaxy is surrounded by a similar globular cluster population to that of M87. (U.K.)

  6. Quercetin-induced downregulation of phospholipase D1 inhibits proliferation and invasion in U87 glioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Park, Mi Hee [Department of Molecular Biology, College of Natural Science, Pusan National University, 30 Jangjeon dong, Geumjeong gu, Busan 609-735 (Korea, Republic of); Min, Do Sik, E-mail: minds@pusan.ac.kr [Department of Molecular Biology, College of Natural Science, Pusan National University, 30 Jangjeon dong, Geumjeong gu, Busan 609-735 (Korea, Republic of)

    2011-09-09

    Highlights: {yields} Quercetin, a bioactive flavonoid, suppresses expression and enzymatic activity of phospholipase D1. {yields} Quercetin abolishes NFkB-induced phospholipase D1 expression via inhibition of NFkB transactivation. {yields} Quercetin-induced suppression of phospholipase D1 inhibits invasion and proliferation of human glioma cells. -- Abstract: Phospholipase D (PLD) has been recognized as a regulator of cell proliferation and tumorigenesis, but little is known about the molecules regulating PLD expression. Thus, the identification of small molecules inhibiting PLD expression would be an important advance in PLD-mediated physiology. Quercetin, a ubiquitous bioactive flavonoid, is known to inhibit proliferation and induce apoptosis in a variety of cancer cells. In the present study, we examined the effect of quercetin on the expression of PLD in U87 glioma cells. Quercetin significantly suppressed the expression of PLD1 at the transcriptional level. Moreover, quercetin abolished the protein expression of PLD1 in a time and dose-dependent manner, as well as inhibited PLD activity. Quercetin suppressed NF{kappa}B-induced PLD1 expression via inhibition of NFkB transactivation. Furthermore, quercetin inhibited activation and invasion of metalloproteinase-2 (MMP-2), a key modulator of glioma cell invasion, induced by phosphatidic acid (PA), a product of PLD activity. Taken together these data demonstrate that quercetin abolishes PLD1 expression and subsequently inhibits invasion and proliferation of glioma cells.

  7. Approach to the irradiation of extensive cervical and upper thoracic spinal astrocytoma

    International Nuclear Information System (INIS)

    Dvorak, E.

    1981-01-01

    Intramedullary spinal cord tumors are relatively rare, especially to the extent presented in this report. A 31-year-old woman had been diagnosed as having an inoperable astrocytoma, grade I-II, involving the entire cervical spinal cord and two upper thoracic segments. After decompressive laminectomy, she was referred for a radical course of radiation therapy. An irradiation technique was devised which allowed treatment of a single cylindrical volume of tissue encompassing the known tumor. Field fractionation with undesirable gaps and/or excessive dose to overlying normal structures was avoided. To the cervical spinal cord she received 5590 cGy in 29 fractions over 42 days. By this schedule she received at the same time 4820 cGy to the medulla oblongata and 4880 cGy to the upper thoracic cord. Partial neurological improvement occurred at the end of the treatment. The treatment approach is discussed in the background of the literature data. (orig.) [de

  8. Genomic Deletions Correlate with Underexpression of Novel Candidate Genes at Six Loci in Pediatric Pilocytic Astrocytoma

    Directory of Open Access Journals (Sweden)

    Nicola Potter

    2008-08-01

    Full Text Available The molecular pathogenesis of pediatric pilocytic astrocytoma (PA is not well defined. Previous cytogenetic and molecular studies have not identified nonrandom genetic aberrations. To correlate differential gene expression and genomic copy number aberrations (CNAs in PA, we have used Affymetrix GeneChip HG_U133A to generate gene expression profiles of 19 pediatric patients and the SpectralChip 2600 to investigate CNAs in 11 of these tumors. Hierarchical clustering according to expression profile similarity grouped tumors and controls separately. We identified 1844 genes that showed significant differential expression between tumor and normal controls, with a large number clearly influencing phosphatidylinositol and mitogen-activated protein kinase signaling in PA. Most CNAs identified in this study were single-clone alterations. However, a small region of loss involving up to seven adjacent clones at 7q11.23 was observed in seven tumors and correlated with the underexpression of BCL7B. Loss of four individual clones was also associated with reduced gene expression including SH3GL2 at 9p21.2-p23, BCL7A (which shares 90% sequence homology with BCL7B at 12q24.33, DRD1IP at 10q26.3, and TUBG2 and CNTNAP1 at 17q21.31. Moreover, the down-regulation of FOXG1B at 14q12 correlated with loss within the gene promoter region in most tumors. This is the first study to correlate differential gene expression with CNAs in PA.

  9. The Effect of Sodium Valproate on the Glioblastoma U87 Cell Line Tumor Development on the Chicken Embryo Chorioallantoic Membrane and on EZH2 and p53 Expression

    Directory of Open Access Journals (Sweden)

    Dovilė Kavaliauskaitė

    2017-01-01

    Full Text Available Literature data support evidences that glioblastoma (GBM patients experience prolonged survival due to sodium valproate (NaVP treatment. The study assessed the human GBM cell U87 xenograft studied in the chicken embryo chorioallantoic membrane (CAM model evaluating NaVP effect on tumor. Three groups of tumors (each n = 10 were studied: nontreated, treated with 4 mM, and treated with 8 mM of NaVP. The majority of tumors without NaVP treatment during tumor growth destroyed the chorionic epithelium, invaded the mesenchyme, and induced angiogenesis. Incidence of tumor formation on CAM without invasion into the mesenchyme was higher when U87 cells were treated with NaVP; the effect significantly increased with NaVP concentration. Treatment with 8 mM of NaVP did not show clear dynamics of tumor growth during 5 days; at the same time, the angiogenesis failed. With a strong staining of EZH2, p53 in tumors without NaVP treatment was found, and NaVP significantly decreased the expression of EZH2- and p53-positive cells; the effect was significantly higher at its 8 mM concentration. NaVP has a function in blocking the growth, invasion, and angiogenesis of tumor in the CAM model; tumor growth interferes with EZH2 and p53 molecular pathways, supporting the NaVP potential in GBM therapy.

  10. SKI2 mediates degradation of RISC 5'-cleavage fragments and prevents secondary siRNA production from miRNA targets in Arabidopsis.

    Science.gov (United States)

    Branscheid, Anja; Marchais, Antonin; Schott, Gregory; Lange, Heike; Gagliardi, Dominique; Andersen, Stig Uggerhøj; Voinnet, Olivier; Brodersen, Peter

    2015-12-15

    Small regulatory RNAs are fundamental in eukaryotic and prokaryotic gene regulation. In plants, an important element of post-transcriptional control is effected by 20-24 nt microRNAs (miRNAs) and short interfering RNAs (siRNAs) bound to the ARGONAUTE1 (AGO1) protein in an RNA induced silencing complex (RISC). AGO1 may cleave target mRNAs with small RNA complementarity, but the fate of the resulting cleavage fragments remains incompletely understood. Here, we show that SKI2, SKI3 and SKI8, subunits of a cytoplasmic cofactor of the RNA exosome, are required for degradation of RISC 5', but not 3'-cleavage fragments in Arabidopsis. In the absence of SKI2 activity, many miRNA targets produce siRNAs via the RNA-dependent RNA polymerase 6 (RDR6) pathway. These siRNAs are low-abundant, and map close to the cleavage site. In most cases, siRNAs were produced 5' to the cleavage site, but several examples of 3'-spreading were also identified. These observations suggest that siRNAs do not simply derive from RDR6 action on stable 5'-cleavage fragments and hence that SKI2 has a direct role in limiting secondary siRNA production in addition to its function in mediating degradation of 5'-cleavage fragments. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC

    Directory of Open Access Journals (Sweden)

    Hanane Ennajdaoui

    2016-05-01

    Full Text Available Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3 expression correlates with malignancy, but its role(s in pathogenesis remains enigmatic. We interrogated the IGF2BP3-RNA interaction network in pancreatic ductal adenocarcinoma (PDAC cells. Using a combination of genome-wide approaches, we have identified 164 direct mRNA targets of IGF2BP3. These transcripts encode proteins enriched for functions such as cell migration, proliferation, and adhesion. Loss of IGF2BP3 reduced PDAC cell invasiveness and remodeled focal adhesion junctions. Individual nucleotide resolution crosslinking immunoprecipitation (iCLIP revealed significant overlap of IGF2BP3 and microRNA (miRNA binding sites. IGF2BP3 promotes association of the RNA-induced silencing complex (RISC with specific transcripts. Our results show that IGF2BP3 influences a malignancy-associated RNA regulon by modulating miRNA-mRNA interactions.

  12. IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC.

    Science.gov (United States)

    Ennajdaoui, Hanane; Howard, Jonathan M; Sterne-Weiler, Timothy; Jahanbani, Fereshteh; Coyne, Doyle J; Uren, Philip J; Dargyte, Marija; Katzman, Sol; Draper, Jolene M; Wallace, Andrew; Cazarez, Oscar; Burns, Suzanne C; Qiao, Mei; Hinck, Lindsay; Smith, Andrew D; Toloue, Masoud M; Blencowe, Benjamin J; Penalva, Luiz O F; Sanford, Jeremy R

    2016-05-31

    Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) expression correlates with malignancy, but its role(s) in pathogenesis remains enigmatic. We interrogated the IGF2BP3-RNA interaction network in pancreatic ductal adenocarcinoma (PDAC) cells. Using a combination of genome-wide approaches, we have identified 164 direct mRNA targets of IGF2BP3. These transcripts encode proteins enriched for functions such as cell migration, proliferation, and adhesion. Loss of IGF2BP3 reduced PDAC cell invasiveness and remodeled focal adhesion junctions. Individual nucleotide resolution crosslinking immunoprecipitation (iCLIP) revealed significant overlap of IGF2BP3 and microRNA (miRNA) binding sites. IGF2BP3 promotes association of the RNA-induced silencing complex (RISC) with specific transcripts. Our results show that IGF2BP3 influences a malignancy-associated RNA regulon by modulating miRNA-mRNA interactions. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  13. Phytometabolite Dehydroleucodine Induces Cell Cycle Arrest, Apoptosis, and DNA Damage in Human Astrocytoma Cells through p73/p53 Regulation.

    Directory of Open Access Journals (Sweden)

    Natalia Bailon-Moscoso

    Full Text Available Accumulating evidence supports the idea that secondary metabolites obtained from medicinal plants (phytometabolites may be important contributors in the development of new chemotherapeutic agents to reduce the occurrence or recurrence of cancer. Our study focused on Dehydroleucodine (DhL, a sesquiterpene found in the provinces of Loja and Zamora-Chinchipe. In this study, we showed that DhL displayed cytostatic and cytotoxic activities on the human cerebral astrocytoma D384 cell line. With lactone isolated from Gynoxys verrucosa Wedd, a medicinal plant from Ecuador, we found that DhL induced cell death in D384 cells by triggering cell cycle arrest and inducing apoptosis and DNA damage. We further found that the cell death resulted in the increased expression of CDKN1A and BAX proteins. A marked induction of the levels of total TP73 and phosphorylated TP53, TP73, and γ-H2AX proteins was observed in D384 cells exposed to DhL, but no increase in total TP53 levels was detected. Overall these studies demonstrated the marked effect of DhL on the diminished survival of human astrocytoma cells through the induced expression of TP73 and phosphorylation of TP73 and TP53, suggesting their key roles in the tumor cell response to DhL treatment.

  14. Spatial Substructure in the M87 Globular Cluster System

    Science.gov (United States)

    Feng, Yuting; Zhang, Yunhao; Guhathakurta, Puragra; Peng, Eric; Lim, Sungsoon

    2018-01-01

    Based on the observation of Next Generation Virgo Cluster Survey (NGVS) project, we obtained the u,g,r,i,z and Ks band photometric information of all the objects in the 2 degree × 2 degree area (Pilot Region) around M87, the major subcluster of Virgo. By adapting an Extreme Deconvolution method, which classifies objects into Globular Clusters (GCs), galaxies and foreground stars with their color and morphology data, we got a purer-than-ever GC distribution map with a depth to gmag=25 in Pilot Region. After masking galaxy GCs, smoothing with a 10arcmin Gaussian kernel and performing a flat field correction, we show the GC density map of M87, and got a good sersic fitting of GC radial distribution with a sersic index~2.2 in the central ellipse part (45arcmin semi major axis area of M87). We quantitatively compared our GC sample with a substructure-free mock data set, which was generated from the smoothed density map as well as the sersic fitting, by calculating the 2 point correlation function (TPCF) value in different parts of the map. After separately performing such comparison with mocks based on different galaxy masking radii which vary from 4 times g band effective radius to 10, we found signals of remarkable spatial enhancement in certain directions in the central ellipse of M87, as well as halo substructures shown as lumpiness and holes in the outer region. We present the estimated scales of these substructures from the TPCF results, and, managed to locate them with a statistical analysis of the pixelized GC map. Apart from all results listed above, we discuss the constant, extra-galactic substructure signal at a scale of ~3kpc, which does not diminish with masking sizes, as the evidence of merging and accretion history of M87.

  15. Effect of chemoradiotherapy using ACNU, vincristine, and nicardipine with high-dose irradiation on malignant astrocytomas

    Energy Technology Data Exchange (ETDEWEB)

    Genka, Shigeru; Shitara, Nobuyuki; Nakamura, Hirohiko; Takakura, Kintomo [Tokyo Univ. (Japan). Hospital

    1993-05-01

    Fifty-two patients with malignant astrocytoma were treated with cellular synchronization radiation therapy at the University of Tokyo Hospital between 1977 and 1989. Twenty-five patients (Group 1) received 1 - (4-amino-2-methyl-5-pyrimidinyl)methyl - 3 - (2-chloroethyl) - 3 - nitrosourea hydrochloride (ACNU), vincristine, and 60 Gy of irradiation, and 27 patients (Group 2) ACNU, vincristine, the Ca-channel blocker nicardipine, and 72 Gy of irradiation. Median survival times for Groups 1 and 2 were 15 and 30 months, respectively. Although there was no significant difference, Group 2 achieved longer survival with 1-, 2-, and 3-year survival rates of 85.2, 65.8, and 46.9% compared to rates of 66.7, 40.0, and 26.7%, respectively, for Group 1. (author).

  16. Effect of chemoradiotherapy using ACNU, vincristine, and nicardipine with high-dose irradiation on malignant astrocytomas

    International Nuclear Information System (INIS)

    Genka, Shigeru; Shitara, Nobuyuki; Nakamura, Hirohiko; Takakura, Kintomo

    1993-01-01

    Fifty-two patients with malignant astrocytoma were treated with cellular synchronization radiation therapy at the University of Tokyo Hospital between 1977 and 1989. Twenty-five patients (Group 1) received 1 - (4-amino-2-methyl-5-pyrimidinyl)methyl - 3 - (2-chloroethyl) - 3 - nitrosourea hydrochloride (ACNU), vincristine, and 60 Gy of irradiation, and 27 patients (Group 2) ACNU, vincristine, the Ca-channel blocker nicardipine, and 72 Gy of irradiation. Median survival times for Groups 1 and 2 were 15 and 30 months, respectively. Although there was no significant difference, Group 2 achieved longer survival with 1-, 2-, and 3-year survival rates of 85.2, 65.8, and 46.9% compared to rates of 66.7, 40.0, and 26.7%, respectively, for Group 1. (author)

  17. PHAKOMATOSIS : INTRESTING CASES OF TUBEROUS SCLEROSIS WITH RETINAL ASTROCYTOMA

    Directory of Open Access Journals (Sweden)

    Srinivasa Rao

    2015-05-01

    Full Text Available NTRODUCTION: Tuberous sclerosis complex (TSC or Morbus Bourneville - Pringle disease is an autosomal dominant phakomatosis, first described by Desiree - Magloire Bourneville in 1880. Tuberous sclerosis is a genetic disorder characterized by the growth of numerous benign tumours in many parts of the body caused by mutations on either of two genes, TSC1 and TSC2. This rare genetic disorder is usually associated with a triad of seizures, mental retardation and cutaneous lesions. Approximately one half of all patients affected by TS develop at least one retinal astrocytoma in one eye. PRESENTATION OF CASES: In the department of ophthalmology, G.S.L M edical C ollege, Rajahmundry, we came across 3 cases of tuberous sclerosis involving multi organ systems. Out of 3 cases, 2 cases were reported to be familial and 1case is sporadic, with a history of epilepsy with angiofibromatosis lesions over the face, multiple ash - leaf lesions over the abdomen, renal angiomyolipomas, multiple subependymal nodules in brain and retinal astrocytic hamartomas in the retina. CONCLUSION: It is important to be cognizant of the likely presence of systemic and ocular pathology in a child with mental retardation and skin lesions. Identification of retinal phakomatosis during ocular evaluation in any suspected case of Tuberous sclerosis can aid in the establishment of the diagnosis of the disease

  18. Shifting Patterns of BMI and Skinfold Fatness among US Children: 1985/87 vs. 2012

    Directory of Open Access Journals (Sweden)

    Yan Yang

    2016-12-01

    Full Text Available Background: Childhood obesity has been recognized as a major public health concern. The purpose of this study was to determine specific shifting patterns of BMI and skinfold fatness across different age and sex groups between 1985/87 and 2012. Methods: The data of 9,366 children aged 8-15 years from two nationally representative surveys, i.e., 1985/87 National Children and Youth Fitness Study I & II and 2012 National Health and Nutrition Examination Survey National Youth Fitness Survey, were analyzed. Specifically, changes of BMI-based obesity prevalence and shifting patterns of BMI, height, weight, skinfold body fat percentage (skinfold-fat%, subscapular skinfold, and triceps skinfold from 1985/87 to 2012 were estimated by age and sex using the 1985/87 quartiles as the baseline. Results: Significantly increased obesity prevalence were reconfirmed for both boys (12.12%, P <.001 and girls (3.53%, P <.001 from 1985/87 to 2012. Except for height, all other measures in 2012 experienced an unbalanced shifting pattern, mainly from other quartiles into the 4th quartile of 1985/87. Conclusion: The shifting of both boys’ and girls’ BMI and skinfold-fat% were all concentrated in the 4th quartile of 1985/87, indicating not only that there was a significant increase in BMI and skinfold-fat% in the U.S. children from 1985/87 to 2012, but also into the overweight and obese subgroups, which serves as a serious warning for childhood obesity epidemic and public health.

  19. Perfluorocarbon-Loaded Lipid Nanocapsules to Assess the Dependence of U87-Human Glioblastoma Tumor pO2 on In Vitro Expansion Conditions.

    Science.gov (United States)

    Lemaire, Laurent; Nel, Janske; Franconi, Florence; Bastiat, Guillaume; Saulnier, Patrick

    2016-01-01

    Growing tumor cell lines, such as U87-MG glioma cells, under mild hypoxia (3% O2) leads to a ca. 40% reduction in growth rate once implanted in the brain of nude mice, as compared to normoxia (21% O2) grown cells, wherein the former over-express HIF-1 and VEGF-A. Despite developing differently, the tumors have similar: blood perfusion, oxygen consumption, and vascular surface area parameters, whereas the number of blood vessels is nearly doubled in the tumor arising from normoxia cultured cells. Interestingly, tumor oxygen tension, measured using 19F-oximetry, showed that the normoxia grown cells led to tumors characterized by mild hypoxic environment (approximately 4%) conditions, whilst the hypoxia grown cells led to tumors characterized by physioxic environment (approximately 6%) conditions. This reversal in oxygen concentration may be responsible for the apparent paradoxical growth profiles.

  20. SKI2 mediates degradation of RISC 5′-cleavage fragments and prevents secondary siRNA production from miRNA targets in Arabidopsis

    Science.gov (United States)

    Branscheid, Anja; Marchais, Antonin; Schott, Gregory; Lange, Heike; Gagliardi, Dominique; Andersen, Stig Uggerhøj; Voinnet, Olivier; Brodersen, Peter

    2015-01-01

    Small regulatory RNAs are fundamental in eukaryotic and prokaryotic gene regulation. In plants, an important element of post-transcriptional control is effected by 20–24 nt microRNAs (miRNAs) and short interfering RNAs (siRNAs) bound to the ARGONAUTE1 (AGO1) protein in an RNA induced silencing complex (RISC). AGO1 may cleave target mRNAs with small RNA complementarity, but the fate of the resulting cleavage fragments remains incompletely understood. Here, we show that SKI2, SKI3 and SKI8, subunits of a cytoplasmic cofactor of the RNA exosome, are required for degradation of RISC 5′, but not 3′-cleavage fragments in Arabidopsis. In the absence of SKI2 activity, many miRNA targets produce siRNAs via the RNA-dependent RNA polymerase 6 (RDR6) pathway. These siRNAs are low-abundant, and map close to the cleavage site. In most cases, siRNAs were produced 5′ to the cleavage site, but several examples of 3′-spreading were also identified. These observations suggest that siRNAs do not simply derive from RDR6 action on stable 5′-cleavage fragments and hence that SKI2 has a direct role in limiting secondary siRNA production in addition to its function in mediating degradation of 5′-cleavage fragments. PMID:26464441

  1. 40 CFR 763.87 - Analysis.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Analysis. 763.87 Section 763.87... Asbestos-Containing Materials in Schools § 763.87 Analysis. (a) Local education agencies shall have bulk samples, collected under § 763.86 and submitted for analysis, analyzed for asbestos using laboratories...

  2. Low-grade astrocytoma: surgical outcomes in eloquent versus non-eloquent brain areas

    Directory of Open Access Journals (Sweden)

    André de Macedo Bianco

    2013-01-01

    Full Text Available A retrospective study of 81 patients with low-grade astrocytoma (LGA comparing the efficacy of aggressive versus less aggressive surgery in eloquent and non-eloquent brain areas was conducted. Extent of surgical resection was analyzed to assess overall survival (OS and progression- free survival (PFS. Degree of tumor resection was classified as gross total resection (GTR, subtotal resection (STR or biopsy. GTR, STR and biopsy in patients with tumors in non-eloquent areas were performed in 31, 48 and 21% subjects, whereas in patients with tumors in eloquent areas resections were 22.5, 35 and 42.5%. Overall survival was 4.7 and 1.9 years in patients with tumors in non-eloquent brain areas submitted to GTR/STR and biopsy (p=0.013, whereas overall survival among patients with tumors in eloquent area was 4.5 and 2.1 years (p=0.33. Improved outcome for adult patients with LGA is predicted by more aggressive surgery in both eloquent and non-eloquent brain areas.

  3. 22 CFR 8.7 - Security.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Security. 8.7 Section 8.7 Foreign Relations DEPARTMENT OF STATE GENERAL ADVISORY COMMITTEE MANAGEMENT § 8.7 Security. (a) All officers and members of a committee must have a security clearance for the subject matter level of security at which the committee...

  4. 33 CFR 8.7 - Information.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Information. 8.7 Section 8.7... GUARD RESERVE § 8.7 Information. (a) Information concerning the Coast Guard Reserve may be obtained from Commandant (CG-13), 2100 2nd St. SW., Stop 7801, Washington, DC 20593-7801. (b) Information and requirements...

  5. ARC2D - EFFICIENT SOLUTION METHODS FOR THE NAVIER-STOKES EQUATIONS (DEC RISC ULTRIX VERSION)

    Science.gov (United States)

    Biyabani, S. R.

    1994-01-01

    computers to emulate Cray system time calls, which should be easy to modify for other machines as well. The standard distribution media for this version is a 9-track 1600 BPI ASCII Card Image format magnetic tape. The Cray version was developed in 1987. The IBM ES/3090 version is an IBM port of the Cray version. It is written in IBM VS FORTRAN and has the capability of executing in both vector and parallel modes on the MVS/XA operating system and in vector mode on the VM/XA operating system. Various options of the IBM VS FORTRAN compiler provide new features for the ES/3090 version, including 64-bit arithmetic and up to 2 GB of virtual addressability. The IBM ES/3090 version is available only as a 9-track, 1600 BPI IBM IEBCOPY format magnetic tape. The IBM ES/3090 version was developed in 1989. The DEC RISC ULTRIX version is a DEC port of the Cray version. It is written in FORTRAN 77 for RISC-based Digital Equipment platforms. The memory requirement is approximately 7Mb of main memory. It is available in UNIX tar format on TK50 tape cartridge. The port to DEC RISC ULTRIX was done in 1990. COS and UNICOS are trademarks and Cray is a registered trademark of Cray Research, Inc. IBM, ES/3090, VS FORTRAN, MVS/XA, and VM/XA are registered trademarks of International Business Machines. DEC and ULTRIX are registered trademarks of Digital Equipment Corporation.

  6. Low dose radiation effects: an integrative european approach (Risc-Rad Project) coordinated by the Cea

    International Nuclear Information System (INIS)

    Sabatier, L.

    2006-01-01

    RISC-RAD (Radiosensitivity of Individuals and Susceptibility to Cancer induced by ionizing Radiations) is an Integrated Project funded by the European Commission under 6. Framework Programme / EURATOM. RISC-RAD started on 1. January 2004 for a duration of four years. Coordinated by Cea (Dr Laure Sabatier), it involves 11 European countries (Austria, Denmark, Finland, France, Germany, Ireland, Italy, the Netherlands, Spain, Sweden and the United Kingdom) and 29 research institutions. Objectives: Exposures to low and protracted doses of ionizing radiation are very frequent in normal living environment, at work places, in industry and in medicine. Effects of these exposures on human health cannot be reliably assessed by epidemiological methods, nor is thoroughly understood by biologists. RISC-RAD project proposes to help bridging the gap of scientific knowledge about these effects. To achieve this goal, a necessary key step is to understand the basic mechanisms by which radiation induces cancer. Studying this multistage process in an integrated way, the project offers a new biological approach characterised by and clear-cut and objective-driven scientific policy: the project is focused on the effects of low doses (less than 100 mSv) and protracted doses of radiation. It aims at identifying new parameters that take into account the differences in radiation responses between individuals. A group of modelers works closely with the experimental teams in order to better quantify the risks associated with low and protracted doses. Research work is divided into five work packages interacting closely with each other. WP1 is dedicated to DNA damage. Ionizing Radiation (IR) produce a broad spectrum of base modifications and DNA strand breaks of different kinds, among which double-strand breaks and 'clustered damage' which is thought to be a major feature in biological effectiveness of IR. The aim of Work Package 1 is to improve understanding of the initial DNA damage induced by

  7. Combinatorial delivery of small interfering RNAs reduces RNAi efficacy by selective incorporation into RISC

    Science.gov (United States)

    Castanotto, Daniela; Sakurai, Kumi; Lingeman, Robert; Li, Haitang; Shively, Louise; Aagaard, Lars; Soifer, Harris; Gatignol, Anne; Riggs, Arthur; Rossi, John J.

    2007-01-01

    Despite the great potential of RNAi, ectopic expression of shRNA or siRNAs holds the inherent risk of competition for critical RNAi components, thus altering the regulatory functions of some cellular microRNAs. In addition, specific siRNA sequences can potentially hinder incorporation of other siRNAs when used in a combinatorial approach. We show that both synthetic siRNAs and expressed shRNAs compete against each other and with the endogenous microRNAs for transport and for incorporation into the RNA induced silencing complex (RISC). The same siRNA sequences do not display competition when expressed from a microRNA backbone. We also show that TAR RNA binding protein (TRBP) is one of the sensors for selection and incorporation of the guide sequence of interfering RNAs. These findings reveal that combinatorial siRNA approaches can be problematic and have important implications for the methodology of expression and use of therapeutic interfering RNAs. PMID:17660190

  8. Imaging findings of anaplastic astrocytoma in a child with maple syrup urine disease: a case report.

    Science.gov (United States)

    Aw-Zoretic, Jessie; Wadhwani, Nitin R; Lulla, Rishi R; Rishi, Lulla R; Ryan, Maura E

    2015-09-01

    Maple syrup urine disease (MSUD) is an inborn error of branched-chain amino acid metabolism, which usually presents in childhood with encephalopathy due to cerebral edema and dysmyelination. Even with treatment, metabolic stressors may precipitate later episodes of acute decompensation. Changes related to cerebral and white matter edema have been described by magnetic resonance imaging (MRI), and imaging can aid in both initial diagnosis and evaluation of decompensation. To date, there are no published known reports of cancer in patients with MSUD. Here, we present the first case report of an anaplastic astrocytoma in a teenager with MSUD, with a discussion of imaging findings and the use of magnetic resonance spectroscopy (MRS) to help distinguish between tumor and metabolic changes.

  9. Capturing microRNA targets using an RNA-induced silencing complex (RISC)-trap approach.

    Science.gov (United States)

    Cambronne, Xiaolu A; Shen, Rongkun; Auer, Paul L; Goodman, Richard H

    2012-12-11

    Identifying targets is critical for understanding the biological effects of microRNA (miRNA) expression. The challenge lies in characterizing the cohort of targets for a specific miRNA, especially when targets are being actively down-regulated in miRNA- RNA-induced silencing complex (RISC)-messengerRNA (mRNA) complexes. We have developed a robust and versatile strategy called RISCtrap to stabilize and purify targets from this transient interaction. Its utility was demonstrated by determining specific high-confidence target datasets for miR-124, miR-132, and miR-181 that contained known and previously unknown transcripts. Two previously unknown miR-132 targets identified with RISCtrap, adaptor protein CT10 regulator of kinase 1 (CRK1) and tight junction-associated protein 1 (TJAP1), were shown to be endogenously regulated by miR-132 in adult mouse forebrain. The datasets, moreover, differed in the number of targets and in the types and frequency of microRNA recognition element (MRE) motifs, thus revealing a previously underappreciated level of specificity in the target sets regulated by individual miRNAs.

  10. Stereotactic Radiosurgery for Recurrent or Unresectable Pilocytic Astrocytoma

    Energy Technology Data Exchange (ETDEWEB)

    Hallemeier, Christopher L. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States); Pollock, Bruce E. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States); Department of Neurological Surgery, Mayo Clinic, Rochester, MN (United States); Schomberg, Paula J. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States); Link, Michael J. [Department of Neurological Surgery, Mayo Clinic, Rochester, MN (United States); Brown, Paul D. [Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); Stafford, Scott L., E-mail: Stafford.scott@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States)

    2012-05-01

    Purpose: To report the outcomes in patients with recurrent or unresectable pilocytic astrocytoma (PA) treated with Gamma Knife stereotactic radiosurgery (SRS). Methods and Materials: Retrospective review of 18 patients (20 lesions) with biopsy-confirmed PA having SRS at our institution from 1992 through 2005. Results: The median patient age at SRS was 23 years (range, 4-56). Thirteen patients (72%) had undergone one or more previous surgical resections, and 10 (56%) had previously received external-beam radiation therapy (EBRT). The median SRS treatment volume was 9.1 cm{sup 3} (range, 0.7-26.7). The median tumor margin dose was 15 Gy (range, 12-20). The median follow-up was 8.0 years (range, 0.5-15). Overall survival at 1, 5, and 10 years after SRS was 94%, 71%, and 71%, respectively. Tumor progression (local solid progression, n = 4; local solid progression + distant, n = 1; distant, n = 2; cyst development/progression, n = 4) was noted in 11 patients (61%). Progression-free survival at 1, 5, and 10 years was 65%, 41%, and 17%, respectively. Prior EBRT was associated with inferior overall survival (5-year risk, 100% vs. 50%, p = 0.03) and progression-free survival (5-year risk, 71% vs. 20%, p = 0.008). Nine of 11 patients with tumor-related symptoms improved after SRS. Symptomatic edema after SRS occurred in 8 patients (44%), which resolved with short-term corticosteroid therapy in the majority of those without early disease progression. Conclusions: SRS has low permanent radiation-related morbidity and durable local tumor control, making it a meaningful treatment option for patients with recurrent or unresectable PA in whom surgery and/or EBRT has failed.

  11. Stereotactic Radiosurgery for Recurrent or Unresectable Pilocytic Astrocytoma

    International Nuclear Information System (INIS)

    Hallemeier, Christopher L.; Pollock, Bruce E.; Schomberg, Paula J.; Link, Michael J.; Brown, Paul D.; Stafford, Scott L.

    2012-01-01

    Purpose: To report the outcomes in patients with recurrent or unresectable pilocytic astrocytoma (PA) treated with Gamma Knife stereotactic radiosurgery (SRS). Methods and Materials: Retrospective review of 18 patients (20 lesions) with biopsy-confirmed PA having SRS at our institution from 1992 through 2005. Results: The median patient age at SRS was 23 years (range, 4–56). Thirteen patients (72%) had undergone one or more previous surgical resections, and 10 (56%) had previously received external-beam radiation therapy (EBRT). The median SRS treatment volume was 9.1 cm 3 (range, 0.7–26.7). The median tumor margin dose was 15 Gy (range, 12–20). The median follow-up was 8.0 years (range, 0.5–15). Overall survival at 1, 5, and 10 years after SRS was 94%, 71%, and 71%, respectively. Tumor progression (local solid progression, n = 4; local solid progression + distant, n = 1; distant, n = 2; cyst development/progression, n = 4) was noted in 11 patients (61%). Progression-free survival at 1, 5, and 10 years was 65%, 41%, and 17%, respectively. Prior EBRT was associated with inferior overall survival (5-year risk, 100% vs. 50%, p = 0.03) and progression-free survival (5-year risk, 71% vs. 20%, p = 0.008). Nine of 11 patients with tumor-related symptoms improved after SRS. Symptomatic edema after SRS occurred in 8 patients (44%), which resolved with short-term corticosteroid therapy in the majority of those without early disease progression. Conclusions: SRS has low permanent radiation-related morbidity and durable local tumor control, making it a meaningful treatment option for patients with recurrent or unresectable PA in whom surgery and/or EBRT has failed.

  12. Everolimus Alleviates Obstructive Hydrocephalus due to Subependymal Giant Cell Astrocytomas.

    Science.gov (United States)

    Moavero, Romina; Carai, Andrea; Mastronuzzi, Angela; Marciano, Sara; Graziola, Federica; Vigevano, Federico; Curatolo, Paolo

    2017-03-01

    Subependymal giant cell astrocytomas (SEGAs) are low-grade tumors affecting up to 20% of patients with tuberous sclerosis complex (TSC). Early neurosurgical resection has been the only standard treatment until few years ago when a better understanding of the molecular pathogenesis of TSC led to the use of mammalian target of rapamycin (mTOR) inhibitors. Surgical resection of SEGAs is still considered as the first line treatment in individuals with symptomatic hydrocephalus and intratumoral hemorrhage. We describe four patients with symptomatic or asymptomatic hydrocephalus who were successfully treated with the mTOR inhibitor everolimus. We collected the clinical data of four consecutive patients presenting with symptomatic or asymptomatic hydrocephalus due to a growth of subependymal giant cell atrocytomas and who could not undergo surgery for different reasons. All patients experienced a clinically significant response to everolimus and an early shrinkage of the SEGA with improvement in ventricular dilatation. Everolimus was well tolerated by all individuals. Our clinical series demonstrate a possible expanding indication for mTOR inhibition in TSC, which can be considered in patients with asymptomatic hydrocephalus or even when the symptoms already appeared. It offers a significant therapeutic alternative to individuals that once would have undergone immediate surgery. Everolimus might also allow postponement of a neurosurgical resection, making it elective with an overall lower risk. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Equilibrium electrode U(4)-U and redox U(4)-U(3) potentials in molten alkali metal chlorides medium

    Energy Technology Data Exchange (ETDEWEB)

    Smirnov, M V; Kudyakov, V Ya; Komarov, V E; Salyulev, A B [AN SSSR, Sverdlovsk. Inst. Ehlektrokhimii

    1979-02-01

    Conditional standard electrode potentials of uranium are determined for diluted solutions of its tetrachloride in alkali metal chloride melts (LiCl, NaCl, NaCl-KCl, KCl, RbCl and CsCl) when using U(4) ion activity coefficient values experimentally found by the tensimetric method. These potentials shift to the electronegative side at the temperature decrease and alkali cation radius increase rsub(Msup(+)) according to the empiric ratio E*U(4)-U= -3.06+6.87x10/sup -4/ T-(1.67-10/sup -4/T-0.44) 1/rsub(Msup(+)) +-0.01. The temperature dependences of formal conditional redox potentials of the U(4)-U(3) system for above melted chlorides are estimated. The E*U(4)-U(3) value also becomes more electronegative in the series LiCl, NaCl, NaCl-KCl, KCl, RbCl and CsCl. This alternation is satisfactorily described by the empiric expression E*U(4)-U(3)= -1.74+1.74x10/sup -4/T-(0.71x10/sup -4/T-0.20) 1rsub(Msup(+)) +-0.05. The calculated values Eu*(4)-U(3) are compared with those directly measured for the NaCl-KCl equimolar mixture and 3LiCl-2KCl eutectic mixture. A satisfactory confirmity has been observed.

  14. Equilibrium electrode U(4)-U and redox U(4)-U(3) potentials in molten alkali metal chlorides medium

    International Nuclear Information System (INIS)

    Smirnov, M.V.; Kudyakov, V.Ya.; Komarov, V.E.; Salyulev, A.B.

    1979-01-01

    Conditional standard electrode potentials of uranium are determined for diluted solutions of its tetrachloride in alkali metal chloride melts (LiCl, NaCl, NaCl-KCl, KCl, RbCl and CsCl) when using U(4) ion activity coefficient values experimentally found by the tensimetric method. These potentials shift to the electronegative side at the temperature decrease and alkali cation radius increase rsub(Msup(+)) according to the empiric ratio E*U(4)-U= -3.06+6.87x10 -4 T-(1.67-10 -4 T-0.44) 1/rsub(Msup(+)) +-0.01. The temperature dependences of formal conditional redox potentials of the U(4)-U(3) system for above melted chlorides are estimated. The E*U(4)-U(3) value also becomes more electronegative in the series LiCl, NaCl, NaCl-KCl, KCl, RbCl and CsCl. This alternation is satisfactorily described by the empiric expression E*U(4)-U(3)= -1.74+1.74x10 -4 T-(0.71x10 -4 T-0.20) 1rsub(Msup(+)) +-0.05. The calculated values Eu*(4)-U(3) are compared with those directly measured for the NaCl-KCl equimolar mixture and 3LiCl-2KCl eutectic mixture. A satisfactory confirmity has been observed

  15. Guanine nucleotide-dependent, pertussis toxin-insensitive, stimulation of inositol phosphate formation by carbachol in a membrane preparation from astrocytoma cells

    International Nuclear Information System (INIS)

    Hepler, J.R.; Harden, T.K.

    1986-01-01

    Formation of the inositol phosphates (InsP), InsP 3 , InsP 2 , and InsP 1 was increased in a concentration dependent manner (K/sub 0.5/ ∼ 5 μM) by GTPΣS in washed membranes prepared from 3 H-inositol-prelabelled 1321N1 human astrocytoma cells. Both GTPγS and GppNHp stimulated InsP formation by 2-3 fold over control; GTP and GDP were much less efficacious and GMP had no effect. Although the muscarinic cholinergic receptor agonist carbachol had no effect in the absence of guanine nucleotide, in the presence of 10 μM GTPγS, carbachol stimulated (K/sub 0.5/ ∼ 10 μ M) the formation of InsP above the level achieved with GTPγS alone. The effect of carbachol was completely blocked by atropine. The order of potency for a series of nucleotides for stimulation of InsP formation in the presence of 500 μM carbachol was GTPγS > GppNHp > GTP = GDP. Pertussis toxin, at concentrations that fully ADP-ribosylate and functionally inactivate G/sub i/, had no effect on InsP formation in the presence of GTPγS or GTPγS plus carbachol. Histamine and bradykinin also stimulated InsP formation in the presence of GTPγS in washed membranes from 1321N1 cells. These data are consistent with the idea that a guanine nucleotide regulatory protein that is not G/sub i/ is involved in receptor-mediated stimulation of InsP formation in 1321N1 human astrocytoma cells

  16. Arginylglycylaspartic Acid-Surface-Functionalized Doxorubicin-Loaded Lipid-Core Nanocapsules as a Strategy to Target Alpha(V) Beta(3) Integrin Expressed on Tumor Cells

    Science.gov (United States)

    Antonow, Michelli B.; Franco, Camila; Prado, Willian; Beckenkamp, Aline; Silveira, Gustavo P.; Buffon, Andréia; Guterres, Sílvia S.

    2017-01-01

    Doxorubicin (Dox) clinical use is limited by dose-related cardiomyopathy, becoming more prevalent with increasing cumulative doses. Previously, we developed Dox-loaded lipid-core nanocapsules (Dox-LNC) and, in this study, we hypothesized that self-assembling and interfacial reactions could be used to obtain arginylglycylaspartic acid (RGD)-surface-functionalized-Dox-LNC, which could target tumoral cells overexpressing αvβ3 integrin. Human breast adenocarcinoma cell line (MCF-7) and human glioblastoma astrocytoma (U87MG) expressing different levels of αvβ3 integrin were studied. RGD-functionalized Dox-LNC were prepared with Dox at 100 and 500 mg·mL−1 (RGD-MCMN (Dox100) and RGD-MCMN (Dox500)). Blank formulation (RGD-MCMN) had z-average diameter of 162 ± 6 nm, polydispersity index of 0.11 ± 0.04, zeta potential of +13.2 ± 1.9 mV and (6.2 ± 1.1) × 1011 particles mL−1, while RGD-MCMN (Dox100) and RGD-MCMN (Dox500) showed respectively 146 ± 20 and 215 ± 25 nm, 0.10 ± 0.01 and 0.09 ± 0.03, +13.8 ± 2.3 and +16.4 ± 1.5 mV and (6.9 ± 0.6) × 1011 and (6.1 ± 1.0) × 1011 particles mL−1. RGD complexation was 7.73 × 104 molecules per nanocapsule and Dox loading were 1.51 × 104 and 7.64 × 104 molecules per nanocapsule, respectively. RGD-functionalized nanocapsules had an improved uptake capacity by U87MG cells. Pareto chart showed that the cell viability was mainly affected by the Dox concentration and the period of treatment in both MCF-7 and U87MG. The influence of RGD-functionalization on cell viability was a determinant factor exclusively to U87MG. PMID:29271920

  17. Anaplastic astrocytoma 14 years after radiotherapy for pituitary adenoma

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, Masaru; Misumi, Syuuzou; Kurosaki, Syuuhei; Shibasaki, Takashi; Ohye, Chihiro (Gunma Univ., Maebashi (Japan). School of Medicine)

    1992-04-01

    A case of anaplastic astrocytoma following radiotherapy for growth hormone secreting pituitary adenoma is presented with a review of the literature. A 43 year old female was admitted with signs of acromegaly and hypertension. An eosinophilic pituitary adenoma was subtotally removed by transsphenoidal approach, followed by 60 Gy irradiation using a 2x2 cm lateral field. Fourteen years later at the age of 57, she suffered from headache, recent-memory disturbance and uncinate fits. CT scan and MRI disclosed ring-like enhanced mass lesion in the left temporal lobe, corresponding to the previous irradiated field. {sup 18}F-FDG PET showed hypermetabolism at the lesion. Left frontotemporal craniotomy was performed, and a reddish gray gelatinous tumor containing necrotic center and cyst was partially removed. Histologically, the tumor consisted of hypercellular astrocytic cells with perivascular pseudorosette. Coagulation necrosis at the center of the tumor, and hyalinosis and fibrosis of the blood vessels in and around the tumor, which might have been caused by the antecedent radiotherapy, were recognized. Postoperative radiotherapy and chemotherapy, were given, however, she expired 13 months after the operation. Seven cases, including ours, of malignant glioma following radiotherapy for pituitary adenoma were reported in the literature. A total dose of irradiation varies from 45 to 95 Gy with a mean of 50 Gy. The period of latency before tumor occurrence ranges from 5 to 22 years with a mean of 10 years. The differentiation of radiation-induced gliomas from radionecrosis of the brain is also discussed. (author).

  18. Anaplastic astrocytoma 14 years after radiotherapy for pituitary adenoma

    International Nuclear Information System (INIS)

    Tamura, Masaru; Misumi, Syuuzou; Kurosaki, Syuuhei; Shibasaki, Takashi; Ohye, Chihiro

    1992-01-01

    A case of anaplastic astrocytoma following radiotherapy for growth hormone secreting pituitary adenoma is presented with a review of the literature. A 43 year old female was admitted with signs of acromegaly and hypertension. An eosinophilic pituitary adenoma was subtotally removed by transsphenoidal approach, followed by 60 Gy irradiation using a 2x2 cm lateral field. Fourteen years later at the age of 57, she suffered from headache, recent-memory disturbance and uncinate fits. CT scan and MRI disclosed ring-like enhanced mass lesion in the left temporal lobe, corresponding to the previous irradiated field. 18 F-FDG PET showed hypermetabolism at the lesion. Left frontotemporal craniotomy was performed, and a reddish gray gelatinous tumor containing necrotic center and cyst was partially removed. Histologically, the tumor consisted of hypercellular astrocytic cells with perivascular pseudorosette. Coagulation necrosis at the center of the tumor, and hyalinosis and fibrosis of the blood vessels in and around the tumor, which might have been caused by the antecedent radiotherapy, were recognized. Postoperative radiotherapy and chemotherapy, were given, however, she expired 13 months after the operation. Seven cases, including ours, of malignant glioma following radiotherapy for pituitary adenoma were reported in the literature. A total dose of irradiation varies from 45 to 95 Gy with a mean of 50 Gy. The period of latency before tumor occurrence ranges from 5 to 22 years with a mean of 10 years. The differentiation of radiation-induced gliomas from radionecrosis of the brain is also discussed. (author)

  19. 40 CFR 87.6 - Aircraft safety.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Aircraft safety. 87.6 Section 87.6... POLLUTION FROM AIRCRAFT AND AIRCRAFT ENGINES General Provisions § 87.6 Aircraft safety. The provisions of... met within the specified time without creating a safety hazard. ...

  20. A case of late presentation of precocious puberty due to pituitary astrocytoma

    Directory of Open Access Journals (Sweden)

    Fahimeh Soheilipour

    2015-08-01

    Full Text Available The importance of assessing precocious puberty, especially in boys, is not only due to the great complications it has for the affected patients, but also to the fatal underlying diseases. Therefore, children with central precocious puberty should first undergo neuroimaging. In this case study, we present a 9.5-year-old boy who was referred to Rasoul-e-Akram Medical Center with increased intracranial pressure, nausea/vomiting, and severe headache having begun three months earlier. The development of secondary sexual changes had started two years earlier, and had been neglected. His testes, penis, and pubic hair were at the fourth Tanner stage. He had elevated luteinizing and follicle stimulating hormones. Microscopic evaluation confirmed low-grade pilocytic astrocytoma WHO grade 1. Emergency brain surgery was conducted in which the brain was decompressed, and chemotherapy was started postoperatively. Two years after the surgery, he remains under chemotherapy, with obvious sexual maturation and a height of 154 cm. Training families and medical staff efficiently can help prevent the late diagnosis and treatment of precocious puberty and, as a result, help patients in their social life.

  1. 50 CFR 216.87 - Wildlife research.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Wildlife research. 216.87 Section 216.87 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION... Pribilof Islands Administration § 216.87 Wildlife research. (a) Wildlife research, other than research on...

  2. 7 CFR 3.87 - Agency regulations.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Agency regulations. 3.87 Section 3.87 Agriculture Office of the Secretary of Agriculture DEBT MANAGEMENT Federal Salary Offset § 3.87 Agency regulations. USDA agencies may issue regulations or policies not inconsistent with OPM regulations (5 CFR part 550...

  3. 12 CFR 34.87 - Accounting treatment.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Accounting treatment. 34.87 Section 34.87 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY REAL ESTATE LENDING AND APPRAISALS Other Real Estate Owned § 34.87 Accounting treatment. A national bank shall account for OREO, and sales...

  4. 7 CFR 983.87 - Effective time.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Effective time. 983.87 Section 983.87 Agriculture..., ARIZONA, AND NEW MEXICO Miscellaneous Provisions § 983.87 Effective time. The provisions of this part, as well as any amendments, shall become effective at such time as the Secretary may declare, and shall...

  5. Expression levels of the microRNA maturing microprocessor complex component DGCR8 and the RNA-induced silencing complex (RISC) components argonaute-1, argonaute-2, PACT, TARBP1, and TARBP2 in epithelial skin cancer.

    Science.gov (United States)

    Sand, Michael; Skrygan, Marina; Georgas, Dimitrios; Arenz, Christoph; Gambichler, Thilo; Sand, Daniel; Altmeyer, Peter; Bechara, Falk G

    2012-11-01

    The microprocessor complex mediates intranuclear biogenesis of precursor microRNAs from the primary microRNA transcript. Extranuclear, mature microRNAs are incorporated into the RNA-induced silencing complex (RISC) before interaction with complementary target mRNA leads to transcriptional repression or cleavage. In this study, we investigated the expression profiles of the microprocessor complex subunit DiGeorge syndrome critical region gene 8 (DGCR8) and the RISC components argonaute-1 (AGO1), argonaute-2 (AGO2), as well as double-stranded RNA-binding proteins PACT, TARBP1, and TARBP2 in epithelial skin cancer and its premalignant stage. Patients with premalignant actinic keratoses (AK, n = 6), basal cell carcinomas (BCC, n = 15), and squamous cell carcinomas (SCC, n = 7) were included in the study. Punch biopsies were harvested from the center of the tumors (lesional), from healthy skin sites (intraindividual controls), and from healthy skin sites in a healthy control group (n = 16; interindividual control). The DGCR8, AGO1, AGO2, PACT, TARBP1, and TARBP2 mRNA expression levels were detected by quantitative real-time reverse transcriptase polymerase chain reaction. The DGCR8, AGO1, AGO2, PACT, and TARBP1 expression levels were significantly higher in the AK, BCC, and SCC groups than the healthy controls (P  0.05). This study indicates that major components of the miRNA pathway, such as the microprocessor complex and RISC, are dysregulated in epithelial skin cancer. Copyright © 2011 Wiley Periodicals, Inc.

  6. 14 CFR 33.87 - Endurance test.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Endurance test. 33.87 Section 33.87... STANDARDS: AIRCRAFT ENGINES Block Tests; Turbine Aircraft Engines § 33.87 Endurance test. (a) General. Each engine must be subjected to an endurance test that includes a total of at least 150 hours of operation...

  7. 21 CFR 1250.87 - Wash water.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Wash water. 1250.87 Section 1250.87 Food and Drugs... Sanitation Facilities and Conditions on Vessels § 1250.87 Wash water. Where systems installed on vessels for wash water, as defined in § 1250.3(n), do not comply with the requirements of a potable water system...

  8. Validation of a model to investigate the effects of modifying cardiovascular disease (CVD) risk factors on the burden of CVD: the rotterdam ischemic heart disease and stroke computer simulation (RISC) model.

    Science.gov (United States)

    van Kempen, Bob J H; Ferket, Bart S; Hofman, Albert; Steyerberg, Ewout W; Colkesen, Ersen B; Boekholdt, S Matthijs; Wareham, Nicholas J; Khaw, Kay-Tee; Hunink, M G Myriam

    2012-12-06

    We developed a Monte Carlo Markov model designed to investigate the effects of modifying cardiovascular disease (CVD) risk factors on the burden of CVD. Internal, predictive, and external validity of the model have not yet been established. The Rotterdam Ischemic Heart Disease and Stroke Computer Simulation (RISC) model was developed using data covering 5 years of follow-up from the Rotterdam Study. To prove 1) internal and 2) predictive validity, the incidences of coronary heart disease (CHD), stroke, CVD death, and non-CVD death simulated by the model over a 13-year period were compared with those recorded for 3,478 participants in the Rotterdam Study with at least 13 years of follow-up. 3) External validity was verified using 10 years of follow-up data from the European Prospective Investigation of Cancer (EPIC)-Norfolk study of 25,492 participants, for whom CVD and non-CVD mortality was compared. At year 5, the observed incidences (with simulated incidences in brackets) of CHD, stroke, and CVD and non-CVD mortality for the 3,478 Rotterdam Study participants were 5.30% (4.68%), 3.60% (3.23%), 4.70% (4.80%), and 7.50% (7.96%), respectively. At year 13, these percentages were 10.60% (10.91%), 9.90% (9.13%), 14.20% (15.12%), and 24.30% (23.42%). After recalibrating the model for the EPIC-Norfolk population, the 10-year observed (simulated) incidences of CVD and non-CVD mortality were 3.70% (4.95%) and 6.50% (6.29%). All observed incidences fell well within the 95% credibility intervals of the simulated incidences. We have confirmed the internal, predictive, and external validity of the RISC model. These findings provide a basis for analyzing the effects of modifying cardiovascular disease risk factors on the burden of CVD with the RISC model.

  9. Validation of a model to investigate the effects of modifying cardiovascular disease (CVD risk factors on the burden of CVD: the rotterdam ischemic heart disease and stroke computer simulation (RISC model

    Directory of Open Access Journals (Sweden)

    van Kempen Bob JH

    2012-12-01

    Full Text Available Abstract Background We developed a Monte Carlo Markov model designed to investigate the effects of modifying cardiovascular disease (CVD risk factors on the burden of CVD. Internal, predictive, and external validity of the model have not yet been established. Methods The Rotterdam Ischemic Heart Disease and Stroke Computer Simulation (RISC model was developed using data covering 5 years of follow-up from the Rotterdam Study. To prove 1 internal and 2 predictive validity, the incidences of coronary heart disease (CHD, stroke, CVD death, and non-CVD death simulated by the model over a 13-year period were compared with those recorded for 3,478 participants in the Rotterdam Study with at least 13 years of follow-up. 3 External validity was verified using 10 years of follow-up data from the European Prospective Investigation of Cancer (EPIC-Norfolk study of 25,492 participants, for whom CVD and non-CVD mortality was compared. Results At year 5, the observed incidences (with simulated incidences in brackets of CHD, stroke, and CVD and non-CVD mortality for the 3,478 Rotterdam Study participants were 5.30% (4.68%, 3.60% (3.23%, 4.70% (4.80%, and 7.50% (7.96%, respectively. At year 13, these percentages were 10.60% (10.91%, 9.90% (9.13%, 14.20% (15.12%, and 24.30% (23.42%. After recalibrating the model for the EPIC-Norfolk population, the 10-year observed (simulated incidences of CVD and non-CVD mortality were 3.70% (4.95% and 6.50% (6.29%. All observed incidences fell well within the 95% credibility intervals of the simulated incidences. Conclusions We have confirmed the internal, predictive, and external validity of the RISC model. These findings provide a basis for analyzing the effects of modifying cardiovascular disease risk factors on the burden of CVD with the RISC model.

  10. 40 CFR 87.60 - Introduction.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Introduction. 87.60 Section 87.60 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF AIR... power auxiliary gearbox-mounted components required to drive aircraft systems is not permitted. (e...

  11. 40 CFR 87.80 - Introduction.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Introduction. 87.80 Section 87.80 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF AIR... various operating points representative of engine usage in aircraft. Other smoke measurement systems may...

  12. 40 CFR 87.1 - Definitions.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Definitions. 87.1 Section 87.1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF AIR... commercial aircraft engine. Emission measurement system means all of the equipment necessary to transport and...

  13. 29 CFR 1960.87 - Objectives.

    Science.gov (United States)

    2010-07-01

    ... relationship with local community leaders by informing them of the existing functions and objectives of the... 29 Labor 9 2010-07-01 2010-07-01 false Objectives. 1960.87 Section 1960.87 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED...

  14. Visualisation of an nsPEF induced calcium wave using the genetically encoded calcium indicator GCaMP in U87 human glioblastoma cells.

    Science.gov (United States)

    Carr, Lynn; Bardet, Sylvia M; Arnaud-Cormos, Delia; Leveque, Philippe; O'Connor, Rodney P

    2018-02-01

    Cytosolic, synthetic chemical calcium indicators are typically used to visualise the rapid increase in intracellular calcium ion concentration that follows nanosecond pulsed electric field (nsPEF) application. This study looks at the application of genetically encoded calcium indicators (GECIs) to investigate the spatiotemporal nature of nsPEF-induced calcium signals using fluorescent live cell imaging. Calcium responses to 44kV/cm, 10ns pulses were observed in U87-MG cells expressing either a plasma membrane targeted GECI (GCaMP5-G), or one cytosolically expressed (GCaMP6-S), and compared to the response of cells loaded with cytosolic or plasma membrane targeted chemical calcium indicators. Application of 100 pulses, to cells containing plasma membrane targeted indicators, revealed a wave of calcium across the cell initiating at the cathode side. A similar spatial wave was not observed with cytosolic indicators with mobile calcium buffering properties. The speed of the wave was related to pulse application frequency and it was not propagated by calcium induced calcium release. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Rapid emergence and mechanisms of resistance by U87 glioblastoma cells to doxorubicin in an in vitro tumor microfluidic ecology

    Science.gov (United States)

    Austin, Robert; Lee, Sanghyuk; Park, Sungsu

    We have developed a microfluidic device consisting of approximately 500 hexagonal micro-compartments which provides a complex ecology with wide ranges of drug and nutrient gradients and local populations. This ecology of a fragmented metapopulation induced the drug resistance in stage IV U87 glioblastoma cells to doxorubicin in seven days. Exome and transcriptome sequencing of the resistant cells identified mutations and differentially expressed genes. Gene ontology and pathway analyses of the genes identified showed that they were functionally relevant with the established mechanisms of doxorubicin action. Functional experiments support the in silico analyses and together demonstrate the effects of these genetic changes. Our findings suggest that given the rapid evolution of resistance and the focused response, this technology could act as a rapid screening modality for genetic aberrations leading to resistance to chemotherapy as well as counter-selection of drugs unlikely to be successful ultimately. Technology Innovation Program of the Ministry of Trade, Industry and Energy, Republic of Korea (10050154 to S.L. and S.P.), the National Research Foundation of Korea (NRF-2014M3C9A3065221 to S.L., NRF-2015K1A4A3047851 to J.K. and S.L.) funded by the Minis.

  16. Proposed tandem mirror research program for FY87 presented to the MFAC subcommittee on mirror research, July 8-9, 1986

    International Nuclear Information System (INIS)

    Baldwin, D.E.; Correll, D.L.; Fowler, T.K.; Grubb, D.P.; Hershkowitz, N.; Porter, G.D.; Post, R.S.; Simonen, T.C.

    1986-01-01

    We have reexamined the goal of approx.10 13 cm -3 central-cell density with end-plugging and reconfirmed its importance as a test of thermal barrier end-plugging performance in either Tara or TMX-U. We conclude that, when all factors are considered including the impact on other programs interlinked with LLNL in the present OFE budget, the lowest cost approach to have a fair chance to meet this goal is to extend Tara operation for the full FY87. Continuation of TMX-U operation in FY87, in addition to the full year of Tara operation, would greatly improve the chance of success. Continuation of the mirror program into FY88 and beyond would be based on an experimental program in TMX-U and Tara at a minimum budget level of $25M/y, with restart of MFTF-B requiring an increase in the national fusion budget. The experimental program to be investigated by TMX-U and Tara would include improvement in the mgnetic geometry (stability, beta limits, and transport), continued plug studies (longer pulse length, impurities, drift pumping, and ECH efficiency), and transport studies (chi/sub e/, fueling, and halo formation)

  17. U.S. Army War College Library Communicative Skills: A Selected Bibliography.

    Science.gov (United States)

    1987-10-01

    D-Ai87 489 US ARMY MAR COLLEGE LIBRARY COMMUNICATIVE SKILLS: A i/l SELECTED BIBLIOGRAPHY(U) ARMY WAR COIL CARLISLE BARRACKS PA OCT 87 UNCLASSIFIED F...PERIOD COVERED U.S. Army War College Library Bibliography Communicative Skills A Seecte Bibiogrphy6. PERFORMING ORG. REPORT NUMBER 7. AUTHOR(&) S...BIBLIOGRAPHY as an invitation for you to enjoy the wealth of materials readily available in our library that will help you improve your communicative skills. It

  18. Characterization of TEM1/endosialin in human and murine brain tumors

    International Nuclear Information System (INIS)

    Carson-Walter, Eleanor B; Walter, Kevin A; Winans, Bethany N; Whiteman, Melissa C; Liu, Yang; Jarvela, Sally; Haapasalo, Hannu; Tyler, Betty M; Huso, David L; Johnson, Mahlon D

    2009-01-01

    TEM1/endosialin is an emerging microvascular marker of tumor angiogenesis. We characterized the expression pattern of TEM1/endosialin in astrocytic and metastatic brain tumors and investigated its role as a therapeutic target in human endothelial cells and mouse xenograft models. In situ hybridization (ISH), immunohistochemistry (IH) and immunofluorescence (IF) were used to localize TEM1/endosialin expression in grade II-IV astrocytomas and metastatic brain tumors on tissue microarrays. Changes in TEM1/endosialin expression in response to pro-angiogenic conditions were assessed in human endothelial cells grown in vitro. Intracranial U87MG glioblastoma (GBM) xenografts were analyzed in nude TEM1/endosialin knockout (KO) and wildtype (WT) mice. TEM1/endosialin was upregulated in primary and metastatic human brain tumors, where it localized primarily to the tumor vasculature and a subset of tumor stromal cells. Analysis of 275 arrayed grade II-IV astrocytomas demonstrated TEM1/endosialin expression in 79% of tumors. Robust TEM1/endosialin expression occurred in 31% of glioblastomas (grade IV astroctyomas). TEM1/endosialin expression was inversely correlated with patient age. TEM1/endosialin showed limited co-localization with CD31, αSMA and fibronectin in clinical specimens. In vitro, TEM1/endosialin was upregulated in human endothelial cells cultured in matrigel. Vascular Tem1/endosialin was induced in intracranial U87MG GBM xenografts grown in mice. Tem1/endosialin KO vs WT mice demonstrated equivalent survival and tumor growth when implanted with intracranial GBM xenografts, although Tem1/endosialin KO tumors were significantly more vascular than the WT counterparts. TEM1/endosialin was induced in the vasculature of high-grade brain tumors where its expression was inversely correlated with patient age. Although lack of TEM1/endosialin did not suppress growth of intracranial GBM xenografts, it did increase tumor vascularity. The cellular localization of TEM1

  19. Prognostic factors and survival in primary malignant astrocytomas of the spinal cord: a population-based analysis from 1973 to 2007.

    Science.gov (United States)

    Adams, Hadie; Avendaño, Javier; Raza, Shaan M; Gokaslan, Ziya L; Jallo, George I; Quiñones-Hinojosa, Alfredo

    2012-05-20

    Observational cross-sectional study. Using data from the population-based cancer registries of the Surveillance, Epidemiology and End Results (SEER) program, we analyzed demographic features, tumor and treatment characteristics, as well as survival rates in patients with primary malignant astrocytomas of the spinal cord (PMASC). PMASC is a rare neoplasm and is considered to carry the same dismal outcome as their cerebral counterparts. Our current knowledge is incomplete, and understanding the epidemiology, diagnosis, and optimal treatment still poses challenges. The SEER data from 1973 to 2007 were reviewed for pathologically confirmed primary anaplastic astrocytomas (AA) and glioblastomas of the spinal cord (C72.0). We compared the clinical features and outcomes of the cohort in uni- and multivariate fashion. Survival was calculated and compared using Kaplan-Meier curves and log-rank analysis. Our search criteria retrieved 135 patients diagnosed with PMASC. The median survival for PMASC was 13 months with 1-, 2-, and 5-year survival rates of 51.8%, 32.2%, and 18.7%. Patient diagnosed with AA had a median survival time of 17 months versus 10 months in patients diagnosed with glioblastomas. Adult patients observed markedly prolonged survival compared with the pediatric group, with a 16-month versus 9-month median survival, respectively. Multivariate analysis revealed age at diagnosis, pediatric and adult age groups, sex, tumor histology, and extent of resection as significant predictors of survival. Interestingly, outcomes did not significantly change throughout the last decades or by receiving radiotherapy. Outcome for patients diagnosed with PMASC remains poor and presents an ongoing challenge for professionals in the field of neurospinal medicine and surgery. In our analyses of AA, adult patients, males, and patients undergoing radical resections were associated with increased survival. However, incidence of these lesions is low; hence, building strong

  20. 49 CFR 38.87 - Public information system.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Public information system. 38.87 Section 38.87... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Light Rail Vehicles and Systems § 38.87 Public information system. (a... information. Alternative systems or devices which provide equivalent access are also permitted. (b) [Reserved] ...

  1. Precision spectroscopy with ultracold 87Rb2 triplet molecules

    International Nuclear Information System (INIS)

    Strauss, Christoph

    2011-01-01

    In this thesis I report precision spectroscopy with ultracold 87 Rb 2 triplet molecules where we use lasers to couple the states in different molecular potentials. We study in detail states of the a 3 sum + u and (1) 3 sum + g potentials. These states are of great importance for transferring weakly bound molecules to the ro-vibrational triplet ground state via states of the excited potential. As most experiments start from molecules in their X 1 sum + g ground state, the triplet states were hard to access via dipole transitions and remained largely unexplored. The measurements presented in this thesis are the first detailed study of diatomic 87 Rb 2 molecules in these states. Our experiments start with an ultracold cloud of 87 Rb atoms. We then load this cloud into an optical lattice where we use a magnetic Feshbach resonance at 1007.4 G to perform a Feshbach association. After we have removed all unbound atoms, we end up with a pure sample of weakly bound Feshbach molecules inside the optical lattice. The optical lattice prevents these molecules from colliding with each other which results in molecular lifetimes on the order of a few hundred milliseconds. In the first set of experiments, we use a laser coupling the Feshbach state to the excited (1) 3 sum + g triplet state to map out its low-lying vibrational (v = 0.. 15), rotational, hyperfine, and Zeeman structure. The experimental results are in good agreement with calculations done by Marius Lysebo and Prof. Leif Veseth. We then map out in detail the vibrational, rotational, hyperfine, and Zeeman structure of the a 3 sum + u triplet ground state using dark state spectroscopy with levels in the (1) 3 sum + g potential as an intermediate state. In this scheme we are able to access molecules in triplet states because our Feshbach state has strong triplet character. Interestingly, it happens that some deeply bound states which belong to the X 1 sum + g potential are close to levels in the a 3 sum + u potential. In

  2. 7 CFR 301.87-2 - Regulated articles.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Regulated articles. 301.87-2 Section 301.87-2... Regulations § 301.87-2 Regulated articles. (a) Sugarcane plants, whole or in part, including true seed and...) Any other product, article, or means of conveyance, of any character whatsoever, not covered by...

  3. 47 CFR 87.131 - Power and emissions.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Power and emissions. 87.131 Section 87.131... Technical Requirements § 87.131 Power and emissions. The following table lists authorized emissions and... Authorized emission(s) 9 Maximum power 1 Aeronautical advisory VHF A3E 10 watts. 10 Aeronautical multicom VHF...

  4. 47 CFR 87.137 - Types of emission.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Types of emission. 87.137 Section 87.137... Technical Requirements § 87.137 Types of emission. (a) The assignable emissions, corresponding emission..., and X” may also be used in place of the letter “P” for pulsed radars. 14 Authorized for use at...

  5. 29 CFR 1918.87 - Ship's cargo elevators.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Ship's cargo elevators. 1918.87 Section 1918.87 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR LONGSHORING Handling Cargo § 1918.87 Ship's cargo elevators. (a) Safe working load. The safe workin...

  6. 14 CFR 27.87 - Height-speed envelope.

    Science.gov (United States)

    2010-01-01

    ... applicable power failure condition in paragraph (b) of this section, a limiting height-speed envelope must be... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Height-speed envelope. 27.87 Section 27.87... STANDARDS: NORMAL CATEGORY ROTORCRAFT Flight Performance § 27.87 Height-speed envelope. (a) If there is any...

  7. Nanosecond pulsed electric fields depolarize transmembrane potential via voltage-gated K+, Ca2+ and TRPM8 channels in U87 glioblastoma cells.

    Science.gov (United States)

    Burke, Ryan C; Bardet, Sylvia M; Carr, Lynn; Romanenko, Sergii; Arnaud-Cormos, Delia; Leveque, Philippe; O'Connor, Rodney P

    2017-10-01

    Nanosecond pulsed electric fields (nsPEFs) have a variety of applications in the biomedical and biotechnology industries. Cancer treatment has been at the forefront of investigations thus far as nsPEFs permeabilize cellular and intracellular membranes leading to apoptosis and necrosis. nsPEFs may also influence ion channel gating and have the potential to modulate cell physiology without poration of the membrane. This phenomenon was explored using live cell imaging and a sensitive fluorescent probe of transmembrane voltage in the human glioblastoma cell line, U87 MG, known to express a number of voltage-gated ion channels. The specific ion channels involved in the nsPEF response were screened using a membrane potential imaging approach and a combination of pharmacological antagonists and ion substitutions. It was found that a single 10ns pulsed electric field of 34kV/cm depolarizes the transmembrane potential of cells by acting on specific voltage-sensitive ion channels; namely the voltage and Ca2 + gated BK potassium channel, L- and T-type calcium channels, and the TRPM8 transient receptor potential channel. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. 21 CFR 20.87 - Disclosure to Congress.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Disclosure to Congress. 20.87 Section 20.87 Food... INFORMATION Limitations on Exemptions § 20.87 Disclosure to Congress. (a) All records of the Food and Drug Administration shall be disclosed to Congress upon an authorized request. (b) An authorized request for Food and...

  9. Synaptotagmin 11 interacts with components of the RNA-induced silencing complex RISC in clonal pancreatic β-cells.

    Science.gov (United States)

    Milochau, Alexandra; Lagrée, Valérie; Benassy, Marie-Noëlle; Chaignepain, Stéphane; Papin, Julien; Garcia-Arcos, Itsaso; Lajoix, Anne; Monterrat, Carole; Coudert, Laetitia; Schmitter, Jean-Marie; Ochoa, Begoña; Lang, Jochen

    2014-06-27

    Synaptotagmins are two C2 domain-containing transmembrane proteins. The function of calcium-sensitive members in the regulation of post-Golgi traffic has been well established whereas little is known about the calcium-insensitive isoforms constituting half of the protein family. Novel binding partners of synaptotagmin 11 were identified in β-cells. A number of them had been assigned previously to ER/Golgi derived-vesicles or linked to RNA synthesis, translation and processing. Whereas the C2A domain interacted with the Q-SNARE Vti1a, the C2B domain of syt11 interacted with the SND1, Ago2 and FMRP, components of the RNA-induced silencing complex (RISC). Binding to SND was direct via its N-terminal tandem repeats. Our data indicate that syt11 may provide a link between gene regulation by microRNAs and membrane traffic. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  10. 87Rb-87Sr chronology of H chondrites: constraint and speculations on the early evolution of their parent body

    International Nuclear Information System (INIS)

    Minster, J.-F.; Allegre, C.J.

    1979-01-01

    A precise 87 Rb- 87 Sr whole-rock isochron for H chrondrites and an internal isochron for Tieschitz (H3) have been determined. The age and 87 Sr/ 86 Sr initial ratio of the whole rocks are 4.25 +- 0.05 b.y. and 0.69876 +- 0.00040 (lambda( 87 Rb) = 1.42 X 10 -11 yr -1 ). For Tieschitz, whereas handipicked separates plot on a well-defined line, heavy liquid separates scatter in the 87 Rb/ 86 Sr vs. 87 Sr/ 86 Sr diagram. Leaching experiments by heavy liquids indicate that they might have a sizeable effect on Tieschitz minerals. The age and 87 Sr/ 86 Sr initial ratio as determined by handpicked separates are 4.53 +- 0.06 b.y. and 0.69880 +- 0.00020, indistinguishable from the whole-rock isochron. These results are interpreted as 'primitive isochrons' dating the condensation of chondrites from the solar nebula. The best value of this event is given by joining both isochrons together at 4.518 +- 0.026 b.y. and 87 Sr/ 86 Sr = 0.69881 +- 0.00016. The near identity of this initial ratio with the one of Allende white inclusions argues in favor of a sharp isochronism of condensation from a 87 Sr/ 86 Sr homogeneous nebula. Data from Guarena and Richardton are interpreted as secondary internal isochrons, 100 m.y. after the condensation of the whole rocks. The data are then used to constrain a thermal evolution model of the H chondrite parent body. This body might have a 150-175 km radius, and might have been heated by 26 Al. An 26 Al/ 27 Al ratio of 4-6 X 10 -6 is enough for heating such a body. Further tests for this model are proposed. (Auth.)

  11. Direct measurement of the half-life of Rb{sup 87}; Mesure directe de la periode du rubidium-87; Pryamoe izmerenie poluraspada rubidiya-87; Medicion directa del periodo del {sup 87}Rb

    Energy Technology Data Exchange (ETDEWEB)

    McNair, A; Wilson, H W [United Kingdom Atomic Energy Authority, Aldermaston, Berks. (United Kingdom)

    1962-01-15

    The half-life of Rb{sup 87} has been measured directly by determining the specific activity by a counting method. The half-lives previously obtained lie in the range 4 - 6 x 10{sup 10} years, a value of 5 x 10{sup 10} years being taken usually. Direct counting is rather difficult because of the presence of a large number of very-low-energy electrons in the Rb{sup 87} spectrum. However, it is clearly very desirable to obtain a precise value by the counting method and this the authors have tried to do. In these measurements special attention must be paid to the reduction of thickness of source and of source backing. To increase the accuracy of the measurements, the following methods were used. The source thickness was reduced by use of (i) a 4-{pi} proportional counter of large source area (up to 100 cm{sup 2}), (ii) anti-coincidence operation to reduce background, and (iii) enriched Rb{sup 87} which permits a four-fold reduction in source thickness for a given activity. By these methods, sources down to 5 {mu}g/cm{sup 2} have been measured. Also the relationship between half-life and source thickness was examined so that correction could be made for the very small absorption which remained. The effect of source backing thickness is not so great and can be calculated from (i) the difference in count-rates on either side of the thin supports used and (ii) a study of dependence of half-life on source support thickness. These experiments give a value of about 5.25 x 10{sup 10} years for the half-life. (author) [French] On a mesure la periode du Tubidium-87 directement, en determinant l'activite specifique par comptage. Les periodes obtenues anterieurement se situent entre 4 et 6 {center_dot} 10{sup 10} ans; la valeur habituellement adoptee est de 5 {center_dot} 10{sup 10} ans. Le comptage direct est d'un emploi assez difficile par suite de la presence d'un grand nombre d'electrons de tres faible energie dans le spectre du rubidium-87. Il n'en serait pas moins tres utile

  12. Poly (ɛ-caprolactone) nanoparticles of carboplatin: Preparation, characterization and in vitro cytotoxicity evaluation in U-87 MG cell lines.

    Science.gov (United States)

    Karanam, Vamshikrishna; Marslin, Gregory; Krishnamoorthy, Balakumar; Chellan, Vijayaraghavan; Siram, Karthik; Natarajan, Tamilselvan; Bhaskar, Balaji; Franklin, Gregory

    2015-06-01

    Carboplatin is a platinum based drug used in the treatment of several malignancies. Due to poor cellular uptake, generally, a larger dose of drug is administered to achieve therapeutic levels, causing harmful side-effects such as hematologic toxicity. In order to enhance the cellular uptake of carboplatin, we have developed carboplatin loaded nanoparticles using the biodegradable polymer poly (ɛ-caprolactone) (PCL). Nanoparticles ranging from the size of 23.77±1.37 to 96.73±2.79 nm with positive zeta potential and moderate entrapment efficiency (54.21±0.98%) were obtained. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) confirmed the spherical morphology and smooth surface of all nanoformulations. The concentrations of PCL and the stabilizer (DMAB) are found to play a role in determining the size and the entrapment efficiency of the nanoparticles. Drug release from nanoparticles followed a biphasic pattern with an initial burst release followed by a sustained release for 10h. Results of in vitro cellular uptake and cytotoxicity studies revealed that carboplatin in the form of PCL-nanoparticles were efficiently up taken and displayed profound cytotoxicity to U-87 MG (human glioma) cells than the free drug. Importantly, unlike the free carboplatin, carboplatin in the form of PCL nanoparticles did not present any haemolytic activity in rat erythrocytes, a major side effect of this chemotherapeutic drug. This suggests that poly (ɛ-caprolactone) nanoencapsulation of carboplatin might be an efficient approach to treat cancer, while reducing carboplatin induced haemolysis. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. NONLINEAR COLOR-METALLICITY RELATIONS OF GLOBULAR CLUSTERS. II. A TEST ON THE NONLINEARITY SCENARIO FOR COLOR BIMODALITY USING THE u-BAND COLORS: THE CASE OF M87 (NGC 4486)

    International Nuclear Information System (INIS)

    Yoon, Suk-Jin; Lee, Sang-Yoon; Kim, Hak-Sub; Cho, Jaeil; Chung, Chul; Sohn, Sangmo T.; Blakeslee, John P.

    2011-01-01

    The optical color distributions of globular clusters (GCs) in most large elliptical galaxies are bimodal. Based on the assumed linear relationship between GC colors and their metallicities, the bimodality has been taken as evidence of two GC subsystems with different metallicities in each galaxy and has led to a number of theories in the context of galaxy formation. More recent observations and modeling of GCs, however, suggests that the color-metallicity relations (CMRs) are inflected, and thus colors likely trace metallicities in a nonlinear manner. The nonlinearity could produce bimodal color distributions from a broad underlying metallicity spread, even if it is unimodal. Despite the far-reaching implications, whether CMRs are nonlinear and whether the nonlinearity indeed causes the color bimodality are still open questions. Given that the spectroscopic refinement of CMRs is still very challenging, we here propose a new photometric technique to probe the possible nonlinear nature of CMRs. In essence, a color distribution of GCs is a 'projected' distribution of their metallicities. Since the form of CMRs hinges on which color is used, the shape of color distributions varies depending significantly on the colors. Among other optical colors, the u-band related colors (e.g., u – g and u – z) are theoretically predicted to exhibit significantly less inflected CMRs than other preferred CMRs (e.g., for g – z). As a case study, we performed the Hubble Space Telescope (HST)/WFPC2 archival u-band photometry for the M87 (NGC 4486) GC system with confirmed color bimodality. We show that the u-band color distributions are significantly different from that of g – z and consistent with our model predictions. With more u-band measurements, this method will support or rule out the nonlinear CMR scenario for the origin of GC color bimodality with high confidence. The HST/WFC3 observations in F336W for nearby large elliptical galaxies are highly anticipated in this regard.

  14. Spontaneous regression of residual low-grade cerebellar pilocytic astrocytomas in children

    International Nuclear Information System (INIS)

    Gunny, Roxana S.; Saunders, Dawn E.; Hayward, Richard D.; Phipps, Kim P.; Harding, Brian N.

    2005-01-01

    Cerebellar low-grade astrocytomas (CLGAs) of childhood are benign tumours and are usually curable by surgical resection alone or combined with adjuvant radiotherapy. To undertake a retrospective study of our children with CLGA to determine the optimum schedule for surveillance imaging following initial surgery. In this report we describe the phenomenon of spontaneous regression of residual tumour and discuss its prognostic significance regarding future imaging. A retrospective review was conducted of children treated for histologically proven CLGA at Great Ormond Street Hospital from 1988 to 1998. Of 83 children with CLGA identified, 13 (15.7%) had incomplete resections. Two children with large residual tumours associated with persistent symptoms underwent additional treatment. Eleven children were followed by surveillance imaging alone for a mean of 6.83 years (range 2-13.25 years). Spontaneous tumour regression was seen in 5 (45.5%) of the 11 children. There were no differences in age, gender, symptomatology, histological grade or Ki-67 fractions between those with spontaneous tumour regression and those with progression. There was a non-significant trend that larger volume residual tumours progressed. Residual tumour followed by surveillance imaging may either regress or progress. For children with residual disease we recommend surveillance imaging every 6 months for the first 2 years, every year for years 3, 4 and 5, then every second year if residual tumour is still present 5 years after initial surgery. This would detect not only progressive or recurrent disease, but also spontaneous regression which can occur later than disease progression. (orig.)

  15. Reimiep 87. An interlaboratory U-235 enrichment determination by gamma measurement on solid UF6 sample

    International Nuclear Information System (INIS)

    Aparo, M.; Cresti, P.

    1988-01-01

    Gamma spectroscopy technique, based on the measurement of U 235 186 KeV flux, is now currently used for the determination of Uranium enrichment in different material of nuclear fuel cycle, namely: Uranium metallic, UO 2 pellets, UF 6 liquid or solid. The present paper describes the use of such a technique and the obtained results in determining the U 235 /U atomic isotopic abundance on a certified UF 6 solid sample. The measurements have been carried out in the frame work of the partecipation to the ''UF 6 Interlaboratory Measurements Evaluation Programme'' organized by CBNM/Geel with the support of the ESARDA (European Safeguards Research and Development Association)

  16. 40 CFR 86.1106-87 - Production compliance auditing.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 19 2010-07-01 2010-07-01 false Production compliance auditing. 86.1106-87 Section 86.1106-87 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Light-Duty Trucks § 86.1106-87 Production compliance auditing. For a model year in which upper limits...

  17. 25 CFR 87.9 - Programming aspects of plans.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Programming aspects of plans. 87.9 Section 87.9 Indians... JUDGMENT FUNDS § 87.9 Programming aspects of plans. In assessing any tribal programming proposal the... such reservation residents; the nature of recent programming affecting the subject tribe or group and...

  18. Empirical model of the M 87 jet

    International Nuclear Information System (INIS)

    Shklovskij, I.S.

    1984-01-01

    The nature of the M87 jet is discussed. Recent observations of the M87 jet in radio, optical and X-ray regions, carried out with a sufficiently high resolving power, have revealed an identity of the brightness distribution at all frequencies. This points to a decisive role of the regular magnetic field variations along the jet for its overall structure. The bright knots of the jet are in the places where the field is enhanced. In the same places, a small fraction of relativistic electrons acquires large pitch-angles due to the interaction with plasma waves, leading to the synchrotron emission of the knots. The velocity of the plasma ejected from the nucleus of M87 should be 0.1 c. Thus, the M87 jet is one-sided

  19. 48 CFR 1352.271-87 - Changes-ship repair.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Changes-ship repair. 1352.271-87 Section 1352.271-87 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 1352.271-87 Changes—ship repair. As prescribed in 48 CFR 1371.118,...

  20. Cytotoxicity Effects of Different Surfactant Molecules Conjugated to Carbon Nanotubes on Human Astrocytoma Cells

    Science.gov (United States)

    Dong, Lifeng; Witkowski, Colette M.; Craig, Michael M.; Greenwade, Molly M.; Joseph, Katherine L.

    2009-12-01

    Phase contrast and epifluorescence microscopy were utilized to monitor morphological changes in human astrocytoma cells during a time-course exposure to single-walled carbon nanotube (SWCNT) conjugates with different surfactants and to investigate sub-cellular distribution of the nanotube conjugates, respectively. Experimental results demonstrate that cytotoxicity of the nanotube/surfactant conjugates is related to the toxicity of surfactant molecules attached on the nanotube surfaces. Both sodium dodecyl sulfate (SDS) and sodium dodecylbenzene sulfonate (SDBS) are toxic to cells. Exposure to CNT/SDS conjugates (0.5 mg/mL) for less than 5 min caused changes in cell morphology resulting in a distinctly spherical shape compared to untreated cells. In contrast, sodium cholate (SC) and CNT/SC did not affect cell morphology, proliferation, or growth. These data indicate that SC is an environmentally friendly surfactant for the purification and dispersion of SWCNTs. Epifluorescence microscopy analysis of CNT/DNA conjugates revealed distribution in the cytoplasm of cells and did not show adverse effects on cell morphology, proliferation, or viability during a 72-h incubation. These observations suggest that the SWCNTs could be used as non-viral vectors for diagnostic and therapeutic molecules across the blood-brain barrier to the brain and the central nervous system.

  1. TREATMENT OF PROGRESSION OF DIFFUSE ASTROCYTOMA BY HERBAL MEDICINE: CASE REPORT.

    Science.gov (United States)

    Trogrlić, Ivo; Trogrlić, Dragan; Trogrlić, Zoran

    2016-01-01

    The paper presents the results of the use of phytotherapy in a 33-year-old woman who, after finishing the oncological treatment of diffuse astrocytoma, had tumour progression. Phytotherapy was introduced after the tumour had progressed. It consisted of 4 types of herbal medicine which the subject was taking in form of tea once a day at regular intervals. The patient started phytotherapy along with temozolomide, which was the only oncological treatment she was under after the tumour had progressed. Following the finished chemotherapy, the patient continued the treatment with herbal medicine only. She regularly took phytotherapy without interruption and to the fullest extent for 30 months, and the results of treatment were monitored by periodic scanning using nuclear magnetic resonance technique. The control scanning that was conducted after the end of combined treatment with temozolomide and phytotherapy showed tumour regression. The patient continued with phytotherapy after finishing chemotherapy and, during the following 24 months, it was the sole treatment option. In that period, the regression of the tumour continued, until a control examination 30 months after the introduction of phytotherapy showed no clinical and radiological signs of tumour. The results presented in this research paper clearly indicate the potential of phytotherapy in the treatment of some types of brain tumours. A complete regression of tumour following the treatment with nothing but herbal medicine offers support for such claim. Future research should demonstrate the effectiveness of phytotherapy, as a supplementary form of brain tumour treatment, and the results of this research should be compared with the existing information on the effectiveness of the protocols currently used in the treatment of these types of tumour.

  2. Evaluation of amentoflavone isolated from Cnestis ferruginea Vahl ex DC (Connaraceae) on production of inflammatory mediators in LPS stimulated rat astrocytoma cell line (C6) and THP-1 cells.

    Science.gov (United States)

    Ishola, I O; Chaturvedi, J P; Rai, S; Rajasekar, N; Adeyemi, O O; Shukla, R; Narender, T

    2013-03-27

    Cnestisferruginea (CF) Vahl ex DC (Connaraceae) is a shrub widely used in traditional African medicine for the treatment of various psychiatric illness and inflammatory conditions. This study was carried out to investigate the effect of amentoflavone isolated from methanolic root extract of CF on lipopolysaccharide (LPS)-induced neuroinflammatory cascade of events associated to the oxidative and nitrative stress, and TNF-α production in rat astrocytoma cell line (C6) and human monocytic leukemia cell line (THP-1), respectively. Rat astrocytoma cells (C6) were stimulated with LPS (10μg/ml) alone and in the presence of different concentrations of amentoflavone (0.1-3μg/ml) for 24h incubation period. Nitrite release, reactive oxygen species (ROS), malondialdehyde (MDA) and reduced-glutathione (GSH) in C6 cells were estimated; while the TNF-α level was estimated in THP-1 cell lysate. In vivo analgesic activity was evaluated using mouse writhing and hot plate tests while the anti-inflammatory effect was investigated using carrageenan-induced oedema test. LPS (10μg/ml) significantly (PTHP-1 cells. Amentoflavone (6.25-50mg/kg) significantly (Ptest. It produced time course significant (P<0.05) decrease in oedema formation in rodents. Findings in this study demonstrate the anti-neuroinflammatory and antinoceptive effects of amentoflavone which may suggest its beneficial roles in neuroinflammation associated disorders. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  3. Autophagy protein p62/SQSTM1 is involved in HAMLET-induced cell death by modulating apotosis in U87MG cells.

    Science.gov (United States)

    Zhang, Y-B; Gong, J-L; Xing, T-Y; Zheng, S-P; Ding, W

    2013-03-21

    HAMLET is a complex of oleic acids and decalcified α-lactalbumin that was discovered to selectively kill tumor cells both in vitro and in vivo. Autophagy is an important cellular process involved in drug-induced cell death of glioma cells. We treated U87MG human glioma cells with HAMLET and found that the cell viability was significantly decreased and accompanied with the activation of autophagy. Interestingly, we observed an increase in p62/SQSTM1, an important substrate of autophagosome enzymes, at the protein level upon HAMLET treatment for short periods. To better understand the functionality of autophagy and p62/SQSTM1 in HAMLET-induced cell death, we modulated the level of autophagy or p62/SQSTM1 with biochemical or genetic methods. The results showed that inhibition of autophagy aggravated HAMLET-induced cell death, whereas activation of authophagy attenuated this process. Meanwhile, we found that overexpression of wild-type p62/SQSTM1 was able to activate caspase-8, and then promote HAMLET-induced apoptosis, whereas knockdown of p62/SQSTM1 manifested the opposite effect. We further demonstrated that the function of p62/SQSTM1 following HAMLET treatment required its C-terminus UBA domain. Our results indicated that in addition to being a marker of autophagy activation in HAMLET-treated glioma cells, p62/SQSTM1 could also function as an important mediator for the activation of caspase-8-dependent cell death.

  4. 14 CFR 29.87 - Height-velocity envelope.

    Science.gov (United States)

    2010-01-01

    ... Category A engine isolation requirements, the height-velocity envelope for complete power failure must be... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Height-velocity envelope. 29.87 Section 29... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Flight Performance § 29.87 Height-velocity envelope. (a...

  5. 48 CFR 552.211-87 - Export packing.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Export packing. 552.211-87... FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 552.211-87 Export packing. As prescribed in 511.204(b)(7), insert the following clause: Export Packing (JAN 2010) (a...

  6. Exposure to titanium dioxide and other metallic oxide nanoparticles induces cytotoxicity on human neural cells and fibroblasts

    Directory of Open Access Journals (Sweden)

    James C K Lai

    2008-12-01

    Full Text Available James C K Lai1, Maria B Lai1, Sirisha Jandhyam1, Vikas V Dukhande1, Alok Bhushan1, Christopher K Daniels1, Solomon W Leung21Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, and Biomedical Research Institute; 2Department of Civil and Environmental Engineering, College of Engineering and Biomedical Research Institute, Idaho State University, Pocatello, ID, USAAbstract: The use of titanium dioxide (TiO2 in various industrial applications (eg, production of paper, plastics, cosmetics, and paints has been expanding thereby increasing the occupational and other environmental exposure of these nanoparticles to humans and other species. However, the health effects of exposure to TiO2 nanoparticles have not been systematically assessed even though recent studies suggest that such exposure induces inflammatory responses in lung tissue and cells. Because the effects of such nanoparticles on human neural cells are unknown, we have determined the putative cytotoxic effects of these nanoparticles on human astrocytes-like astrocytoma U87 cells and compared their effects on normal human fibroblasts. We found that TiO2 micro- and nanoparticles induced cell death on both human cell types in a concentration-related manner. We further noted that zinc oxide (ZnO nanoparticles were the most effective, TiO2 nanoparticles the second most effective, and magnesium oxide (MgO nanoparticles the least effective in inducing cell death in U87 cells. The cell death mechanisms underlying the effects of TiO2 micro- and nanoparticles on U87 cells include apoptosis, necrosis, and possibly apoptosis-like and necrosis-like cell death types. Thus, our findings may have toxicological and other pathophysiological implications on exposure of humans and other mammalian species to metallic oxide nanoparticles.Keywords: cytotoxicity of titanium dioxide micro- and nanoparticles, cytotoxicity of zinc oxide and magnesium oxide nanoparticles, human neural cells

  7. Dicty_cDB: Contig-U12802-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available cobacter cetorum strain MIT-0... 38 0.23 AF237484_1( AF237484 |pid:none) Dirofilaria immitis intermed...87 ( O97594 ) RecName: Full=Structural maintenance of chromosomes pro... 36 0.87 U00680_1( U00680 |pid:none) Brugia malayi intermed...1305( CP000879 |pid:none) Petrotoga mobilis SJ95, complet... 38 0.30 (Q9BZF9) RecName: Full=Uveal autoantigen with coiled...ns BAC clone RP11-764E7 from 2, complet... 34 0.79 6 ( FK620261 ) 454GmaGlobSeed354893 Soybean Seed...ditis elegans clone Y71H2X, *** SEQUENCI... 38 4.5 7 ( AC146972 ) Medicago truncatula clone mth2-128d9, compl

  8. Surgical resection of grade II astrocytomas in the superior frontal gyrus.

    Science.gov (United States)

    Peraud, Aurelia; Meschede, Magnus; Eisner, Wilhelm; Ilmberger, Josef; Reulen, Hans-Jürgen

    2002-05-01

    Surgery in the superior frontal gyrus partially involving the supplementary motor area (SMA) may be followed by contralateral transient weakness and aphasia initially indistinguishable from damage to the primary motor cortex. However, recovery is different, and SMA deficits may resolve completely within days to weeks. No study has assessed the distinct postoperative deficits after tumor resection in the SMA on a homogeneous patient group. Twenty-four patients with World Health Organization Grade II astrocytomas in the superior frontal gyrus consecutively treated by surgery were studied. Degree and duration of postoperative deficits were evaluated according to tumor location and boundaries via magnetic resonance imaging scans, intraoperative neuromonitoring results, and extent of tumor resection. Postoperatively, motor deficits were evident in 21 of 24 and speech deficits in 9 of 12 patients. Motor function quickly recovered in 11 and speech function in 3 patients. None of the 12 patients in whom the posterior tumor resection line was at a distance of more than 0.5 cm from the precentral sulcus experienced persistent motor deficits. Eight of these patients developed typical SMA syndrome with transient initiation difficulties. Seven of 12 patients in whom the tumor extended to the precentral sulcus still had motor deficits at the 12-month follow-up assessment. Surgery for Grade II gliomas in the superior frontal gyrus is more likely to result in permanent morbidity when the resection is performed at a distance of less than 0.5 cm from the precentral gyrus or positive stimulation points. Therefore, cortical mapping of motor and speech function, in critical cases under local anesthesia with the patient as his or her own monitor, is recommended; resection should be tailored to obtain good functional outcome and maintain quality of life.

  9. Malignant astrocytoma: hyperfractionated and standard radiotherapy with chemotherapy in a randomized prospective clinical trial

    International Nuclear Information System (INIS)

    Payne, D.G.; Simpson, W.J.; Keen, C.; Platts, M.E.

    1982-01-01

    A prospective randomized trial of 157 patients with malignant astrocytomas (Grade III or IV) was carried out at a single institution. The minimization technique ensured balanced distribution of prognostic factors between the treatment groups. All received oral lomustine (CCNU, 80 mg/m 2 ) six weekly and hydroxyurea (HU, 3.5 gm/m 2 over 5 days) three weekly, for one year or until recurrence, with doses adjusted for myelosuppression. Patients were randomized to daily (5000 rad in 25 fractions (fr) in 5 weeks) or Q3h (every 3 hours) Cobalt 60 irradiation (3600-4000 rad in 36-40 fr of 100 rad each, given 4 fr per day at 3-hour intervals over two weeks). Steroid therapy (up to 16 mg day dexamethasone) was permitted. Complications were moderate and equivalent in the two groups. No significant survival or toxicity differences were seen between the two groups. Age, initial performance status, and extent of surgical resection were found to be significant (P<0.01) prognostic factors for survival. Median survival of the whole group was 48 weeks with a minimum follow-up of one year. There was no advantage to large radiation fields. The hyperfractionation and daily regimes had similar efficacy and toxicity. Hyperfractionation with chemotherapy offers a useful alternative approach in the management of this disease

  10. Effectiveness of interferon-beta and temozolomide combination therapy against temozolomide-refractory recurrent anaplastic astrocytoma

    Directory of Open Access Journals (Sweden)

    Arai Hajime

    2007-08-01

    Full Text Available Abstract Background Malignant gliomas recur even after extensive surgery and chemo-radiotherapy. Although a relatively novel chemotherapeutic agent, temozolomide (TMZ, has demonstrated promising activity against recurrent glioma, the effects last only a few months and drug resistance develops thereafter in most cases. Induction of O6-methylguanine-DNA methyltransferase (MGMT in tumors is considered to be responsible for resistance to TMZ. Interferon-beta has been reported to suppress MGMT in an experimental glioma model. Here we report a patient with TMZ-refractory anaplastic astrocytoma (AA who was treated successfully with a combination of interferon-beta and TMZ. Case presentation A patient with recurrent AA after radiation-chemotherapy and stereotactic radiotherapy was treated with TMZ. After 6 cycles, the tumor became refractory to TMZ, and the patient was treated with interferon-beta at 3 × 106 international units/body, followed by 5 consecutive days of 200 mg/m2 TMZ in cycles of 28 days. After the second cycle the tumor decreased in size by 50% (PR. The tumor showed further shrinkage after 8 months and the patient's KPS improved from 70% to 100%. The immunohistochemical study of the initial tumor specimen confirmed positive MGMT protein expression. Conclusion It is considered that interferon-beta pre-administration increased the TMZ sensitivity of the glioma, which had been refractory to TMZ monotherapy.

  11. The Characteristics of Astrocytomas and Oligodendrogliomas Are Caused by Two Distinct and Interchangeable Signaling Formats

    Directory of Open Access Journals (Sweden)

    Chengkai Dai

    2005-04-01

    Full Text Available Chronic platelet-derived growth factor (PDGF signaling in glial progenitors leads to the formation of oligodendrogliomas in mice, whereas chronic combined Ras and Akt signaling leads to astrocytomas. Different histologies of these tumors imply that the pathways activated by these two oncogenic stimulations are different, and that the apparent lineage of the tumor cells may result from specific signaling activity. Therefore, we have investigated the signaling effects of PDGF in culture and in gliomas in vivo. In culture, PDGF transiently activates ERK1/2 and Akt, and subsequently elevates p21 and PCNA expression similar to chronic PDGF autocrine signaling in cultured astrocytes and PDGF-induced oligodendrogliomas in vivo. Culture experiments show that autocrine PDGF stimulation, and combined active Ras and Akt generate signaling patterns that are in some ways mutually exclusive. Furthermore, forced Akt activity in the context of chronic PDGF stimulation results in cells with an astrocytic differentiation pattern both in culture and in vivo. These data imply that these two interconvertible signaling motifs are distinct in mice and lead to gliomas resembling the two major glioma histologies found in humans. The ability of signaling activity to convert tumor cells from one lineage to another presents a mechanism for the development of tumors apparently comprised of cells from multiple lineages.

  12. STAT6 expression in glioblastoma promotes invasive growth

    International Nuclear Information System (INIS)

    Merk, Barbara C; Owens, Jennifer L; Lopes, Maria-Beatriz S; Silva, Corinne M; Hussaini, Isa M

    2011-01-01

    Glioblastoma (GBM) is a highly aggressive malignant primary brain tumor, characterized by rapid growth, diffuse infiltration of cells into both adjacent and remote brain regions, and a generalized resistance to currently available treatment modalities. Recent reports in the literature suggest that Signal Transducers and Activators of Transcription (STATs) play important roles in the regulation of GBM pathophysiology. STAT6 protein expression was analyzed by Western blotting in GBM cell lines and by immunohistochemistry in a tissue microarray (TMA) of glioma patient tissues. We utilized shRNA against STAT6 to investigate the effects of prolonged STAT6 depletion on the growth and invasion of two STAT6-positive GBM cell lines. Cell proliferation was assessed by measuring 3 H-Thymidine uptake over time. Invasion was measured using an in vitro transwell assay in which cells invade through a type IV collagen matrix toward a chemoattractant (Fetal Bovine Serum). Cells were then stained and counted. Kaplan-Meyer survival curves were generated to show the correlation between STAT6 gene expression and patient survival in 343 glioma patients and in a subset of patients with only GBM. Gene expression microarray and clinical data were acquired from the Rembrandt [1] public data depository (https://caintegrator.nci.nih.gov/rembrandt/). Lastly, a genome-wide expression microarray analysis was performed to compare gene expression in wild-type GBM cells to expression in stable STAT6 knockdown clones. STAT6 was expressed in 2 GBM cell lines, U-1242MG and U-87MG, and in normal astrocytes (NHA) but not in the U-251MG GBM cell line. In our TMA study, STAT6 immunostaining was visible in the majority of astrocytomas of all grades (I-IV) but not in normal brain tissue. In positive cells, STAT6 was localized exclusively in the nuclei over 95% of the time. STAT6-deficient GBM cells showed a reduction in 3 H-Thymidine uptake compared to the wild-type. There was some variation among the

  13. Detection of the argonaute protein Ago2 and microRNAs in the RNA induced silencing complex (RISC) using a monoclonal antibody.

    Science.gov (United States)

    Ikeda, Keigo; Satoh, Minoru; Pauley, Kaleb M; Fritzler, Marvin J; Reeves, Westley H; Chan, Edward K L

    2006-12-20

    MicroRNAs (miRNAs) are short RNA molecules responsible for post-transcriptional gene silencing by the degradation or translational inhibition of their target messenger RNAs (mRNAs). This process of gene silencing, known as RNA interference (RNAi), is mediated by highly conserved Argonaute (Ago) proteins which are the key components of the RNA induced silencing complex (RISC). In humans, Ago2 is responsible for the endonuclease cleavage of targeted mRNA and it interacts with the mRNA-binding protein GW182, which is a marker for cytoplasmic foci referred to as GW bodies (GWBs). We demonstrated that the anti-Ago2 monoclonal antibody 4F9 recognized GWBs in a cell cycle dependent manner and was capable of capturing miRNAs associated with Ago2. Since Ago2 protein is the effector protein of RNAi, anti-Ago2 monoclonal antibody may be useful in capturing functional miRNAs.

  14. Precision spectroscopy with ultracold {sup 87}Rb{sub 2} triplet molecules

    Energy Technology Data Exchange (ETDEWEB)

    Strauss, Christoph

    2011-10-19

    In this thesis I report precision spectroscopy with ultracold {sup 87}Rb{sub 2} triplet molecules where we use lasers to couple the states in different molecular potentials. We study in detail states of the a {sup 3} sum {sup +}{sub u} and (1) {sup 3} sum {sup +}{sub g} potentials. These states are of great importance for transferring weakly bound molecules to the ro-vibrational triplet ground state via states of the excited potential. As most experiments start from molecules in their X {sup 1} sum {sup +}{sub g} ground state, the triplet states were hard to access via dipole transitions and remained largely unexplored. The measurements presented in this thesis are the first detailed study of diatomic {sup 87}Rb{sub 2} molecules in these states. Our experiments start with an ultracold cloud of {sup 87}Rb atoms. We then load this cloud into an optical lattice where we use a magnetic Feshbach resonance at 1007.4 G to perform a Feshbach association. After we have removed all unbound atoms, we end up with a pure sample of weakly bound Feshbach molecules inside the optical lattice. The optical lattice prevents these molecules from colliding with each other which results in molecular lifetimes on the order of a few hundred milliseconds. In the first set of experiments, we use a laser coupling the Feshbach state to the excited (1) {sup 3} sum {sup +}{sub g} triplet state to map out its low-lying vibrational (v = 0.. 15), rotational, hyperfine, and Zeeman structure. The experimental results are in good agreement with calculations done by Marius Lysebo and Prof. Leif Veseth. We then map out in detail the vibrational, rotational, hyperfine, and Zeeman structure of the a {sup 3} sum {sup +}{sub u} triplet ground state using dark state spectroscopy with levels in the (1) {sup 3} sum {sup +}{sub g} potential as an intermediate state. In this scheme we are able to access molecules in triplet states because our Feshbach state has strong triplet character. Interestingly, it

  15. Precision spectroscopy with ultracold {sup 87}Rb{sub 2} triplet molecules

    Energy Technology Data Exchange (ETDEWEB)

    Strauss, Christoph

    2011-10-19

    In this thesis I report precision spectroscopy with ultracold {sup 87}Rb{sub 2} triplet molecules where we use lasers to couple the states in different molecular potentials. We study in detail states of the a {sup 3} sum {sup +}{sub u} and (1) {sup 3} sum {sup +}{sub g} potentials. These states are of great importance for transferring weakly bound molecules to the ro-vibrational triplet ground state via states of the excited potential. As most experiments start from molecules in their X {sup 1} sum {sup +}{sub g} ground state, the triplet states were hard to access via dipole transitions and remained largely unexplored. The measurements presented in this thesis are the first detailed study of diatomic {sup 87}Rb{sub 2} molecules in these states. Our experiments start with an ultracold cloud of {sup 87}Rb atoms. We then load this cloud into an optical lattice where we use a magnetic Feshbach resonance at 1007.4 G to perform a Feshbach association. After we have removed all unbound atoms, we end up with a pure sample of weakly bound Feshbach molecules inside the optical lattice. The optical lattice prevents these molecules from colliding with each other which results in molecular lifetimes on the order of a few hundred milliseconds. In the first set of experiments, we use a laser coupling the Feshbach state to the excited (1) {sup 3} sum {sup +}{sub g} triplet state to map out its low-lying vibrational (v = 0.. 15), rotational, hyperfine, and Zeeman structure. The experimental results are in good agreement with calculations done by Marius Lysebo and Prof. Leif Veseth. We then map out in detail the vibrational, rotational, hyperfine, and Zeeman structure of the a {sup 3} sum {sup +}{sub u} triplet ground state using dark state spectroscopy with levels in the (1) {sup 3} sum {sup +}{sub g} potential as an intermediate state. In this scheme we are able to access molecules in triplet states because our Feshbach state has strong triplet character. Interestingly, it

  16. Expression and Role of GPR87 in Urothelial Carcinoma of the Bladder

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Kakehi

    2013-06-01

    Full Text Available The orphan GPR87 has recently been matched with its ligand LPA, which is a lipid mediator with multiple physiological functions, including cancer cell proliferation. This study aimed to clarify the role of GPR87 in urothelial carcinoma of the bladder. GPR87 expression was assessed in seven human bladder cancer cell lines. A replication-deficient recombinant adenoviral vector expressing shRNA targeting GPR87 (Ad-shGPR87, was constructed. Gene silencing was carried out using Ad-shGPR87. Immunohistochemical analysis was performed for transurethral resection of bladder tumor samples from 71 patients with non-muscle-invasive bladder cancer. We observed GPR87 expression in five of the seven cell lines, and silencing GPR87 gene expression significantly reduced cell viability. GPR87 expression was positive in 38 (54% of 71 tumors. Ki-67 index was associated with positive GPR87 staining status (p < 0.0001. Patients with GPR87-positive tumors had shorter intravesical recurrence-free survival than those with GPR87-negative tumors (p = 0.010. Multivariate analysis revealed that GPR87 staining status was an independent prognostic parameter for intravesical recurrence (p = 0.041. Progression from non-muscle-invasive to muscle-invasive tumor was more frequently observed in patients with GPR87-positive tumors, although this trend did not reach statistical significance (p = 0.056. These results warrant further prospective studies to clarify the role of GPR87 expression in intravesical recurrence and progression in bladder cancer.

  17. Exophytic pilocytic astrocytoma of the brain stem in an adult with encasement of the caudal cranial nerve complex (IX-XII): presurgical anatomical neuroimaging using MRI

    Energy Technology Data Exchange (ETDEWEB)

    Yousry, Indra; Yousry, Tarek A. [Department of Neuroradiology, Klinikum Grosshadern, Ludwig-Maximilians University, Marchioninistr. 15, 81377, Munich (Germany); Muacevic, Alexander; Olteanu-Nerbe, Vlad [Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians University, Munich (Germany); Naidich, Thomas P. [Department of Radiology, Section of Neuroradiology, Mount Sinai Hospital, New York (United States)

    2004-07-01

    We describe a rare case of adult pilocytic astrocytoma in which exophytic growth from the brain stem presented as a right cerebellopontine angle mass. An initial MRI examination using T2- and T1-weighted images without and with contrast suggested the diagnosis of schwannoma. Subsequent use of 3D CISS (three-dimensional constructive interference in steady state) and T1-weighted contrast-enhanced 3D MP-RAGE (three-dimensional magnetization prepared rapid acquisition gradient echo) sequences led to the diagnosis of an exophytic brain stem tumor, documented the precise relationships of the tumor to cranial nerve VIII, revealed encasement of cranial nerves IX-XII (later confirmed intraoperatively), and provided the proper basis for planning surgical management. (orig.)

  18. Exophytic pilocytic astrocytoma of the brain stem in an adult with encasement of the caudal cranial nerve complex (IX-XII): presurgical anatomical neuroimaging using MRI

    International Nuclear Information System (INIS)

    Yousry, Indra; Yousry, Tarek A.; Muacevic, Alexander; Olteanu-Nerbe, Vlad; Naidich, Thomas P.

    2004-01-01

    We describe a rare case of adult pilocytic astrocytoma in which exophytic growth from the brain stem presented as a right cerebellopontine angle mass. An initial MRI examination using T2- and T1-weighted images without and with contrast suggested the diagnosis of schwannoma. Subsequent use of 3D CISS (three-dimensional constructive interference in steady state) and T1-weighted contrast-enhanced 3D MP-RAGE (three-dimensional magnetization prepared rapid acquisition gradient echo) sequences led to the diagnosis of an exophytic brain stem tumor, documented the precise relationships of the tumor to cranial nerve VIII, revealed encasement of cranial nerves IX-XII (later confirmed intraoperatively), and provided the proper basis for planning surgical management. (orig.)

  19. Efficacy of 68Ga-DOTATOC Positron Emission Tomography (PET) CT in Children and Young Adults With Brain Tumors

    Science.gov (United States)

    2017-04-27

    Acoustic Schwannoma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Supratentorial Ependymoma; Meningeal Melanocytoma; Newly Diagnosed Childhood Ependymoma; Recurrent Adult Brain Tumor; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Diffuse Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Fibrillary Astrocytoma; Recurrent Childhood Gemistocytic Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood

  20. Rapid increase in cystic volume of an anaplastic astrocytoma misdiagnosed as neurocysticercosis: A case report

    Science.gov (United States)

    Li, Hong-Jiang; Han, Hong-Xiu; Feng, Dong-Fu

    2016-01-01

    Reports describing a rapid increase in the cystic volume of anaplastic astrocytoma (AA) in a short time frame are rare. The present study reports the case of a 68-year-old male who was admitted to the No. 9 People's Hospital, Shanghai Jiaotong University School of Medicine (Shanghai, China), with a small cystic brain lesion and positive immunological testing for cysticercosis. Head magnetic resonance imaging (MRI) showed a cystic lesion, 6 mm in diameter, in the left frontal lobe. Neurocysticercosis was suspected and the patient was treated with a clinical trial of albendazole and steroids. A period of 25 days later, the patient's condition had deteriorated, and MRI revealed a cystic lesion in the left frontal lobe; thereafter, the cystic lesion was removed and a diagnosis of AA was established. The tumor was soft, ivory white and gelatinous due to myxoid degeneration. In this case, tumor-related angiogenesis and microvascular extravasation (blood-brain barrier disruption) may have been the main cause of the rapid increase in the cystic volume in such a short time frame. The similarity of the glioma and cysticercus antigens may have been the cause of the positive reactions in the cystic fluid. The present study reports the rare occurrence of a rapid increase of cystic volume and potential diagnostic difficulties. PMID:27698865

  1. Non-targeted effects of ionising radiation. Proceedings of the RISC-RAD specialised training course

    International Nuclear Information System (INIS)

    Belyakov, O.V.

    2008-12-01

    The training course 'Non-targeted effects of ionising radiation' took place at the STUK, Radiation and Nuclear Safety Authority, Helsinki, Finland 14-16 February 2005. Proceeding of this course is collected in this volume. The idea of the course was to convene a number of scientists leading in the area of non-targeted effects of ionising radiation with the aim to outline their visions for the role of these effects and outline the future directions of radiation research on the basis of their expertise. The course was supported by the RISC-RAD IP FI6R-CT-2003-508842, Euratom specific programme for research and training on nuclear energy, 6th FP of the EC. The main objectives of the training course were: (1) to clarify the mechanisms of non-targeted effects, in particular, bystander effects, genomic instability and adaptive response; (2) to look if and how non-targeted effects modulate the cancer risk in the low dose region, and whether they relate to protective or harmful functions; (3) to clarify if ionising radiation can cause non-cancer diseases or beneficial effects at low and intermediate doses; (4) address the issue of individual susceptibility and other factors modifying non-targeted responses; (5) attempt to assess the relevance of non-targeted effects for radiation protection and to set the scientific basis for a modern, more realistic, radiation safety system; (6) and finally to contribute to the conceptualisation of a new paradigm in radiation biology that would cover both the classical direct (DNA-targeted) and non-targeted (indirect) effects

  2. 40 CFR 68.87 - Contractors.

    Science.gov (United States)

    2010-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Program 3 Prevention Program § 68.87 Contractors. (a) Application. This... specialty work on or adjacent to a covered process. It does not apply to contractors providing incidental...

  3. Radiotherapy in pediatric pilocytic astrocytomas. A subgroup analysis within the prospective multicenter study HIT-LGG 1996 by the German Society of Pediatric Oncology and Hematology (GPOH)

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, K. [Leipzig Univ. (Germany). Dept. of Radiotherapy and Radiation Oncology; Gnekow, A.; Falkenstein, F. [General Hospital of Augsburg (Germany). Hospital for Children and Adolescents] [and others

    2013-08-15

    Purpose: We evaluated clinical outcomes in the subset of patients who underwent radiotherapy (RT) due to progressive pilocytic astrocytoma within the Multicenter Treatment Study for Children and Adolescents with a Low Grade Glioma HIT-LGG 1996. Patients and methods: Eligibility criteria were fulfilled by 117 patients. Most tumors (65 %) were located in the supratentorial midline, followed by the posterior fossa (26.5 %) and the cerebral hemispheres (8.5 %). Median age at the start of RT was 9.2 years (range 0.7-17.4 years). In 75 cases, external fractionated radiotherapy (EFRT) was administered either as first-line nonsurgical treatment (n = 58) or after progression following primary chemotherapy (n = 17). The median normalized total dose was 54 Gy. Stereotactic brachytherapy (SBT) was used in 42 selected cases. Results: During a median follow-up period of 8.4 years, 4 patients (3.4 %) died and 33 (27.4 %) experienced disease progression. The 10-year overall (OS) and progression-free survival (PFS) rates were 97 and 70 %, respectively. No impact of the RT technique applied (EFRT versus SBT) on progression was observed. The 5-year PFS was 76 {+-} 5 % after EFRT and 65 {+-} 8 % after SBT. Disease progression after EFRT was not influenced by gender, neurofibromatosis type 1 (NF1) status, tumor location (hemispheres versus supratentorial midline versus posterior fossa), age or prior chemotherapy. Normalized total EFRT doses of more than 50.4 Gy did not improve PFS rates. Conclusion: EFRT plays an integral role in the treatment of pediatric pilocytic astrocytoma and is characterized by excellent tumor control. A reduction of the normalized total dose from 54 to 50.4 Gy appears to be feasible without jeopardizing tumor control. SBT is an effective treatment alternative. (orig.)

  4. Orphan Strontium-87 in Abyssal Peridotites: Daddy Was a Granite

    Science.gov (United States)

    Snow, Jonathan E.; Hart, Stanley R.; Dick, Henry J. B.

    1993-12-01

    The 87Sr/86Sr ratios in some bulk abyssal and alpine peridotites are too high to be binary mixtures of depleted mantle and seawater components. The apparent excess, or "orphan," 87Sr appears to be separated from its radioactive parent. Such observations were widely held to be analytical artifacts. Study of several occurrences of orphan 87Sr shows that the orphan component in abyssal peridotite is located in the alteration products of olivine and enstatite in the peridotite. The orphan 87Sr is most likely introduced by infiltration of low-temperature (<200^circC) seawater bearing suspended detrital particulates. These particulates include grains of detrital clay that are partly derived from continental (that is, granitic) sources and thus are highly radiogenic. Orphan 87Sr and other radiogenic isotopes may provide a tracer for low-temperature seawater penetrating into the oceanic crust.

  5. Economic Impact of Hunting Expenditures on Southern U.S.

    OpenAIRE

    Poudel, Jagdish; Munn, Ian A.; Henderson, James E.

    2013-01-01

    Hunting, fishing and wildlife-associated recreation expenditures have played an important role in the U.S economy and help promote conservation and environmental goals. The 2006 U.S Fish and Wildlife Service (USFWS) survey reported 87.5 million people aged 16 and above participated in wildlife-associated recreation activities, spending $122.4 billion on trips and equipment. This spending is a 13 percent increase since 2001. The recently released 2011 National Survey of Fishing, Hunting and Wi...

  6. 40 CFR 81.87 - Metropolitan Boise Intrastate Air Quality Control Region.

    Science.gov (United States)

    2010-07-01

    ... Quality Control Region. 81.87 Section 81.87 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Air Quality Control Regions § 81.87 Metropolitan Boise Intrastate Air Quality Control Region. The Metropolitan Boise Intrastate Air Quality Control Region (Idaho) consists of the territorial area encompassed...

  7. How do environmental and behavioral factors impact ultraviolet radiation effects on health: the RISC-UV Project

    Science.gov (United States)

    Correa, M. P.; Godin-Beekmann, S.; Haeffelin, M.; Saiag, P.; Mahe, E.; Brogniez, C.; Dupont, J. C.; Pazmiño, A.; Auriol, F.; Bonnel, B.

    2009-04-01

    Introduction: RISC-UV is a research project on "Impact of climate change on ultraviolet radiation and risks for health", a research project in which physicists, meteorologists and physicians work together to assess the relative role played by environmental and behavioral factors in the UV-related diseases as skin cancer and vitamin D deficiency. Environmental factors are related to the role played by the alteration in intensity of UV radiation at the Earth's surface resulting from variation in several factors affected by climate change and human activities: stratospheric ozone, cloud cover, aerosols and the reflectivity of the surface. On the other hand, behavioral factors are related to the sun over/underexposure and the correct use of sun-protection (hats, caps, sunglasses, sunscreen lotion, etc.). RISC-UV is organized around three main areas: 1) Organization of a workshop, scheduled for January 2009, which aims to describe the state of the art in the subject within each community and define the requirements of pathologists for epidemiological studies; 2) A pilot study intended to evaluate the consistency between UV measurements delivered simultaneously by satellite-based instruments, ground instruments, radiometers and individual dosimeters. This study is based on measurements campaigns and an analysis of the long-term consistency of data series relating to UV radiation and associated parameters; and 3) Analysis of the weights of medical, behavioral and environmental parameters involved in skin carcinogenesis. A detailed description of these areas can be found in http://www.gisclimat.fr/Doc/GB/D_projects/RISC-UV_GB.html. This presentation focuses on the first results of the UV experimental measurements performed between September 8th and October 8th 2008 in Palaiseau, France (48.7˚ N; 2.2˚ E; 170m - Haeffelin et al., 2005). A second campaign is foreseen for the spring of 2009. The purpose of these campaigns is to obtain, analyze and quantitatively link the

  8. Imaging of 99Tcm-labeled new cyclic RGDfK Dimer in nude mice bearing U87MG human glioma xenografts

    International Nuclear Information System (INIS)

    Jin Xiao'an; Shi Jiyun; Liu Yan; Zhu Zhaohui; Jia Bing; Liu Zhaofei; Shi Ximin; Wang Fan; Li Fang

    2010-01-01

    Objective: (1) To evaluate the effect of insertion of two 15-amino-4, 7, 10, 13-tetraoxapentadecanoic (2 PEG 4 ) linkers into cyclic Arg-Gly-Asp (RGD) Dimer E [c(RGDfK)] 2 on receptor binding in vitro, (2) to assess its biodistribution in vivo and (3) to investigate the value of 99 Tc m labeled 2PEG 4 -Dimer for integrin α v β 3 -positive tumors imaging. Methods: The expression of U87 human glioma cells and integrin α v β 3 was determined by immunofluorescence staining. The half-inhibition concentrations (IC 50 ) for 125 I-cyclo (Arg-Gly-Asp-D-Tyr-Lys) (c(RGDyK)) of c (RGDyK), hydrazinonictinamide (HYNIC)-Dimer and HYNIC-2PEG 4 -Dimer binding to integrin α v β 3 were measured. 99 Tc m -HYNIC-Dimer and 99 Tc m -HYNIC-2PEG 4 -Dimer were synthesized using non-SnCl 2 formulation. Biodistribution and imaging studies were performed in nude mice bearing human glioma xenografts. The unpaired t test was used for statistical analysis. Results: The labeling yield of the two radiotracers was more than 95%, and the radiochemical purity was more than 99% through Sep-Pek C18 cartridge. HYNIC-2PEG 4 -Dimer had significantly higher binding affinity of integrin α v β 3 than c(RGDyK) and HYNIC-Dimer (IC 50 =0.8 nmol/L, 27 nmol/L and 2.4 nmol/L, respectively). Biodistribution study showed that 99 Tc m -HYNIC-2PEG 4 -Dimer was mainly excreted via the kidney. The tumor uptake of 99 Tc m -HYNIC-2PEG 4 -Dimer was higher than that of 99 Tc m -HYNIC-Dimer at 2 h post injection ((5.71±0.96) and (2.10±0.50) % ID/g, t =4.80, P 99 Tc m -HYNIC-2PEG 4 -Dimer is a promising radiotracer for integrin α v β 3 -positive tumor imaging. (authors)

  9. 9 CFR 3.87 - Primary enclosures used to transport nonhuman primates.

    Science.gov (United States)

    2010-01-01

    ... nonhuman primates. 3.87 Section 3.87 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE..., and Transportation of Nonhuman Primates 2 Transportation Standards § 3.87 Primary enclosures used to transport nonhuman primates. Any person subject to the Animal Welfare regulations (9 CFR parts 1, 2, and 3...

  10. THE NEXT GENERATION VIRGO CLUSTER SURVEY. X. PROPERTIES OF ULTRA-COMPACT DWARFS IN THE M87, M49, AND M60 REGIONS

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Chengze [Center for Astronomy and Astrophysics, Department of Physics and Astronomy, Shanghai Jiao Tong University, Shanghai 200240 (China); Peng, Eric W.; Zhang, Hong-Xin [Department of Astronomy, Peking University, Beijing 100871 (China); Côté, Patrick; Ferrarese, Laura; Gwyn, Stephen; Blakeslee, John P. [Herzberg Institute of Astrophysics, National Research Council of Canada, Victoria, BC V9E 2E7 (Canada); Jordán, Andrés; Muñoz, Roberto P.; Puzia, Thomas H. [Instituto de Astrofísica, Facultad de Física, Pontificia Universidad Católica de Chile, Av. Vicuña Mackenna 4860, 7820436 Macul, Santiago (Chile); Mihos, J. Christopher [Department of Astronomy, Case Western Reserve University, Cleveland, OH (United States); Lançon, Ariane [Observatoire Astronomique de Strasbourg, Université de Strasbourg and CNRS, UMR 7550, 11 rue de l’Université, F-67000 Strasbourg (France); Cuillandre, Jean-Charles [CEA/IRFU/SAp, Laboratoire AIM Paris-Saclay, CNRS/INSU, Université Paris Diderot, Observatoire de Paris, PSL Research University, F-91191 Gif-sur-Yvette Cedex (France); Boselli, Alessandro [Aix-Marseille Université, CNRS, LAM (Laboratoire d’Astrophysique de Marseille) UMR 7326, F-13388, Marseille (France); Durrell, Patrick R., E-mail: czliu@sjtu.edu.cn, E-mail: peng@pku.edu.cn [Department of Physics and Astronomy, Youngstown State University, One University Plaza, Youngstown, OH 44555 (United States); and others

    2015-10-10

    We use imaging from the Next Generation Virgo cluster Survey (NGVS) to present a comparative study of ultra-compact dwarf (UCD) galaxies associated with three prominent Virgo sub-clusters: those centered on the massive red-sequence galaxies M87, M49, and M60. We show how UCDs can be selected with high completeness using a combination of half-light radius and location in color–color diagrams (u*iK{sub s} or u*gz). Although the central galaxies in each of these sub-clusters have nearly identical luminosities and stellar masses, we find large differences in the sizes of their UCD populations, with M87 containing ∼3.5 and 7.8 times more UCDs than M49 and M60, respectively. The relative abundance of UCDs in the three regions scales in proportion to sub-cluster mass, as traced by X-ray gas mass, total gravitating mass, number of globular clusters (GCs), and number of nearby galaxies. We find that the UCDs are predominantly blue in color, with ∼85% of the UCDs having colors similar to blue GCs and stellar nuclei of dwarf galaxies. We present evidence that UCDs surrounding M87 and M49 may follow a morphological sequence ordered by the prominence of their outer, low surface brightness envelope, ultimately merging with the sequence of nucleated low-mass galaxies, and that envelope prominence correlates with distance from either galaxy. Our analysis provides evidence that tidal stripping of nucleated galaxies is an important process in the formation of UCDs.

  11. Substance P induces rapid and transient membrane blebbing in U373MG cells in a p21-activated kinase-dependent manner.

    Directory of Open Access Journals (Sweden)

    John Meshki

    Full Text Available U373MG astrocytoma cells endogenously express the full-length neurokinin 1 receptor (NK1R. Substance P (SP, the natural ligand for NK1R, triggers rapid and transient membrane blebbing and we report that these morphological changes have different dynamics and intracellular signaling as compared to the changes that we have previously described in HEK293-NK1R cells. In both cell lines, the SP-induced morphological changes are Gq-independent, and they require the Rho, Rho-associated coiled-coil kinase (ROCK signaling pathway. Using confocal microscopy we have demonstrated that tubulin is phosphorylated subsequent to cell stimulation with SP and that tubulin accumulates inside the blebs. Colchicine, a tubulin polymerization inhibitor, blocked SP-induced blebbing in U373MG but not in HEK293-NK1R cells. Although p21-activated kinase (PAK is expressed in both cell lines, SP induced rapid phosphorylation of PAK in U373MG, but failed to phosphorylate PAK in HEK293-NK1R cells. The cell-permeable Rho inhibitor C3 transferase inhibited SP-induced PAK phosphorylation, but the ROCK inhibitor Y27632 had no effect on PAK phosphorylation, suggesting that Rho activates PAK in a ROCK-independent manner. Our study demonstrates that SP triggers rapid changes in cell morphology mediated by distinct intracellular signaling mechanisms in U373MG versus HEK293-NK1R cells.

  12. Comparative non-cholinergic neurotoxic effects of paraoxon and diisopropyl fluorophosphate (DFP) on human neuroblastoma and astrocytoma cell lines

    International Nuclear Information System (INIS)

    Qian Yongchang; Venkatraj, Jijayanagaram; Barhoumi, Rola; Pal, Ranadip; Datta, Aniruddha; Wild, James R.; Tiffany-Castiglioni, Evelyn

    2007-01-01

    The objective of this study was to evaluate the comparative non-cholinergic neurotoxic effects of paraoxon, which is acutely neurotoxic, and diisopropyl fluorophosphate (DFP), which induces OPIDN, in the human neuroblastoma SY5Y and the human astrocytoma cell line CCF-STTG1. SY5Y cells have been studied extensively as a model for OP-induced neurotoxicity, but CCF cells have not previously been studied. We conducted a preliminary human gene array assay of OP-treated SY5Y cells in order to assess at the gene level whether these cells can distinguish between OP compounds that do and do not cause OPIDN. Paraoxon and DFP induced dramatically different profiles of gene expression. Two genes were upregulated and 13 downregulated by at least 2-fold in paraoxon-treated cells. In contrast, one gene was upregulated by DFP and none was downregulated at the 2-fold threshold. This finding is consistent with current and previous observations that SY5Y cells can distinguish between OPs that do or do not induce OPIDN. We also examined gene array results for possible novel target proteins or metabolic pathways for OP neurotoxicity. Protein levels of glucose regulated protein 78 (GRP78) revealed that paraoxon exposure at 3 μM for 24 h significantly reduced GRP78 levels by 30% in neuroblastoma cells, whereas DFP treatment had no effect. In comparison with SY5Y neuroblastoma cells, paraoxon and DFP (3 μM for 24 h) each significantly increased GRP78 levels by 23-24% in CCF astrocytoma cells. As we have previously evaluated intracellular changes in Ca 2+ levels in SY5Y cells, we investigated the effects of paraoxon and DFP on cellular Ca 2+ homeostasis in CCF by studying cytosolic and mitochondrial basal calcium levels. A significant decrease in the ratio of mitochondrial to cytosolic Ca 2+ fluorescence was detected in CCF cultures treated for either 1 or 3 days with 1, 3, 10, or 30 μM paraoxon. In contrast, treatment with DFP for 1 day had no significant effect on the ratio of

  13. Dicty_cDB: Contig-U16215-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 90 |pid:none) Maxillaria adendrobium voucher JBL... 34 9.8 EU123651_1( EU123651 |... |pid:none) Dichaea poicillantha voucher M. Bl... 34 9.8 EU214391_1( EU214391 |pid:none) Maxillaria adendrobium...87 |pid:none) Maxillaria adendrobium voucher JBL... 34 9.8 EU214423_1( EU214423 |pid:none) Pescatoria cerina... 34 9.8 EU214389_1( EU214389 |pid:none) Maxillaria adendrobium voucher JBL... 34 9.8 >U77053_1( U77053 |pid:

  14. 33 CFR 110.87 - Henderson Harbor, N.Y.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Henderson Harbor, N.Y. 110.87... ANCHORAGE REGULATIONS Special Anchorage Areas § 110.87 Henderson Harbor, N.Y. (a) Area A. The area in the... latitude 43°51′08.8″ N, longitude 76°12′08.9″ W, thence to latitude 43°51′09.0″ N, longitude 76°12′19.0″ W...

  15. Rapid and specific purification of Argonaute-small RNA complexes from crude cell lysates.

    Science.gov (United States)

    Flores-Jasso, C Fabián; Salomon, William E; Zamore, Phillip D

    2013-02-01

    Small interfering RNAs (siRNAs) direct Argonaute proteins, the core components of the RNA-induced silencing complex (RISC), to cleave complementary target RNAs. Here, we describe a method to purify active RISC containing a single, unique small RNA guide sequence. We begin by capturing RISC using a complementary 2'-O-methyl oligonucleotide tethered to beads. Unlike other methods that capture RISC but do not allow its recovery, our strategy purifies active, soluble RISC in good yield. The method takes advantage of the finding that RISC partially paired to a target through its siRNA guide dissociates more than 300 times faster than a fully paired siRNA in RISC. We use this strategy to purify fly Ago1- and Ago2-RISC, as well as mouse AGO2-RISC. The method can discriminate among RISCs programmed with different guide strands, making it possible to deplete and recover specific RISC populations. Endogenous microRNA:Argonaute complexes can also be purified from cell lysates. Our method scales readily and takes less than a day to complete.

  16. Study of Remote Globular Cluster Satellites of M87

    Science.gov (United States)

    Sahai, Arushi; Shao, Andrew; Toloba, Elisa; Guhathakurta, Puragra; Peng, Eric W.; Zhang, Hao

    2017-01-01

    We present a sample of “orphan” globular clusters (GCs) with previously unknown parent galaxies, which we determine to be remote satellites of M87, a massive elliptical galaxy at the center of the Virgo Cluster of Galaxies. Because GCs were formed in the early universe along with their original parent galaxies, which were cannibalized by massive galaxies such as M87, they share similar age and chemical properties. In this study, we first confirm that M87 is the adoptive parent galaxy of our orphan GCs using photometric and spectroscopic data to analyze spatial and velocity distributions. Next, we increase the signal-to-noise ratio of our samples’ spectra through a process known as coaddition. We utilize spectroscopic absorption lines to determine the age and metallicity of our orphan GCs through comparison to stellar population synthesis models, which we then relate to the GCs’ original parent galaxies using a mass-metallicity relation. Our finding that remote GCs of M87 likely developed in galaxies with ~1010 solar masses implies that M87’s outer halo is formed of relatively massive galaxies, serving as important parameters for developing theories about the formation and evolution of massive galaxies.This research was funded in part by NASA/STScI and the National Science Foundation. Most of this work was carried out by high school students working under the auspices of the Science Internship Program at UC Santa Cruz.

  17. Long-term results of postoperative radiotherapy in adult patients with incompletely excised infratentorial low grade astrocytoma

    International Nuclear Information System (INIS)

    Pluta, E.; Glinski, B.; Szpytma, T.; Nowak-Sadzikowska, J.

    2002-01-01

    lnfratentorial low grade astrocytoma (ILGA) occurs rarely in adult patients and accounts for about 3% of all intracranial tumors.The basic method of treatment for ILGA is surgery. Complete resection results in high local control rate and the role of postoperative irradiation in management of partially resected tumors is not clearly determined. The aim of this study was to evaluate the efficacy of postoperative irradiation in adult patients with incompletely excised ILGA. Between 1975 and 1995, thirty one adult patients with incompletely excised ILGA received postoperative irradiation with curative intent. All patients were treated with megavoltage gamma rays ( 60C o). The total dose ranged from 50 to 60 Gy (mean; 54 Gy) and was delivered with daily fraction of 1.8-2 Gy. The treatment volume covered the tumor being area with a margin of 1-2 cm. Tolerance to treatment has been found to be good in 30 patients (97%). The overall 15-year actuarial survival rate was 62% in the entire group. Young patients, up to twenty years of age achieved a 15-year overall actuarial survival rate of 85%, older patients - 46%. This difference was statistically significant (p =0. 0205). Conventionally fractionated postoperative radiotherapy with doses of 50 to 60 Gy may improve long term results of adult patients with ILGA after uncomplete resection. Age is a significant prognostic factor - young patients, up to twenty years of age, show best survival. (author)

  18. 47 CFR 87.151 - Special requirements for differential GPS receivers.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Special requirements for differential GPS receivers. 87.151 Section 87.151 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND... differential GPS receivers. (a) The receiver shall achieve a message failure rate less than or equal to one...

  19. Signaling via G proteins mediates tumorigenic effects of GPR87

    DEFF Research Database (Denmark)

    Arfelt, Kristine Niss; Fares, Suzan; Sparre-Ulrich, Alexander H.

    2017-01-01

    G protein-coupled receptors (GPCRs) constitute a large protein family of seven transmembrane (7TM) spanning proteins that regulate multiple physiological functions. GPR87 is overexpressed in several cancers and plays a role in tumor cell survival. Here, the basal activity of GPR87 was investigated...

  20. China's Biotech Policies and Their Impacts on U.S. Agricultural Exports to China

    OpenAIRE

    Song, Baohui; Marchant, Mary A.

    2006-01-01

    China is a key player in global agricultural markets, and the number one importer of U.S. soybeans and cotton, whereby soybeans and cotton are two of the main biotech commodities commercialized in the United States. As of 2005, 87% of soybeans and 79% of cotton planted in the U.S. were biotech. Thus, changes in China's biotech policies may have a significant impact on U.S. biotech commodity exports to China. An understanding of the evolution of China's biotech regulations and factors that may...

  1. Properties of myelin altered peptide ligand cyclo(87-99)(Ala91,Ala96)MBP87-99 render it a promising drug lead for immunotherapy of multiple sclerosis.

    Science.gov (United States)

    Deraos, George; Rodi, Maria; Kalbacher, Hubert; Chatzantoni, Kokona; Karagiannis, Fotios; Synodinos, Loukas; Plotas, Panayiotis; Papalois, Apostolos; Dimisianos, Nikolaos; Papathanasopoulos, Panagiotis; Gatos, Dimitrios; Tselios, Theodore; Apostolopoulos, Vasso; Mouzaki, Athanasia; Matsoukas, John

    2015-08-28

    Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system, and it has been established that autoreactive T helper (Th) cells play a crucial role in its pathogenesis. Myelin basic protein (MBP) epitopes are major autoantigens in MS, and the sequence MBP87-99 is an immunodominant epitope. We have previously reported that MBP87-99 peptides with modifications at principal T-cell receptor (TCR) contact sites suppressed the induction of EAE symptoms in rats and SJL/J mice, diverted the immune response from Th1 to Th2 and generated antibodies that did not cross react with the native MBP protein. In this study, the linear and cyclic analogs of the MBP87-99 epitope, namely linear (Ala91,Ala96)MBP87-99 (P2) and cyclo(87-99)(Ala91,Ala96)MBP87-99 (P3), were evaluated for their binding to HLA-DR4, stability to lysosomal enzymes, their effect on cytokine secretion by peripheral blood mononuclear cells (PBMC) derived from MS patients or healthy subjects (controls), and their effect in rat EAE. P1 peptide (wild-type, MBP87-99) was used as control. P2 and P3 did not alter significantly the cytokine secretion by control PBMC, in contrast to P1 that induced moderate IL-10 production. In MS PBMC, P2 and P3 induced the production of IL-2 and IFN-γ, with a simultaneous decrease of IL-10, whereas P1 caused a reduction of IL-10 secretion only. The cellular response to P3 indicated that cyclization did not affect the critical TCR contact sites in MS PBMC. Interestingly, the cyclic P3 analog was found to be a stronger binder to HLA-DR4 compared to linear P2. Moreover, cyclic P3 was more stable to proteolysis compared to linear P2. Finally, both P2 and P3 suppressed EAE induced by an encephalitogenic guinea pig MBP74-85 epitope in Lewis rats whereas P1 failed to do so. In conclusion, cyclization of myelin altered peptide ligand (Ala91,Ala96)MBP87-99 improved binding affinity to HLA-DR4, resistance to proteolysis and antigen-specific immunomodulation

  2. Mitochondrial BK Channel Openers CGS7181 and CGS7184 Exhibit Cytotoxic Properties

    Directory of Open Access Journals (Sweden)

    Bartłomiej Augustynek

    2018-01-01

    Full Text Available Potassium channel openers (KCOs have been shown to play a role in cytoprotection through the activation of mitochondrial potassium channels. Recently, in several reports, a number of data has been described as off-target actions for KCOs. In the present study, we investigated the effects of BKCa channel openers CGS7181, CGS7184, NS1619, and NS004 in neuronal cells. For the purpose of this research, we used a rat brain, the mouse hippocampal HT22 cells, and the human astrocytoma U-87 MG cell line. We showed that CGS7184 activated the mitochondrial BKCa (mitoBKCa channel in single-channel recordings performed on astrocytoma mitoplasts. Moreover, when applied to the rat brain homogenate or isolated rat brain mitochondria, CGS7184 increased the oxygen consumption rate, and can thus be considered a potentially cytoprotective agent. However, experiments on intact neuronal HT22 cells revealed that both CGS7181 and CGS7184 induced HT22 cell death in a concentration- and time-dependent manner. By contrast, we did not observe cell death when NS1619 or NS004 was applied. CGS7184 toxicity was not abolished by BKCa channel inhibitors, suggesting that the observed effects were independent of a BKCa-type channel activity. CGS7184 treatment resulted in an increase of cytoplasmic Ca2+ concentration that likely involved efflux from internal calcium stores and the activation of calpains (calcium-dependent proteases. The cytotoxic effect of the channel opener was partially reversed by a calpain inhibitor. Our data show that KCOs under study not only activate mitoBKCa channels from brain tissue, but also induce cell death when used in cellular models.

  3. 7 CFR 8.7 - Continued use.

    Science.gov (United States)

    2010-01-01

    ... the Secretary of Agriculture 4-H CLUB NAME AND EMBLEM § 8.7 Continued use. (a) The Cooperative... use the 4-H Club Name or Emblem: (1) For their own educational or informational purposes according to... materials bearing the 4-H Club Name or Emblem. (4) Any proposal for distribution on an interstate, regional...

  4. A population-based case-control study of mesothelioma deaths among U.S. railroad workers.

    Science.gov (United States)

    Schenker, M B; Garshick, E; Muñoz, A; Woskie, S R; Speizer, F E

    1986-09-01

    We have completed a case-control analysis of mesothelioma deaths among current and retired U.S. railroad employees. Cause-specific death certificates were obtained for 87% of 15,059 deaths reported by the railroad retirement board, and 20 mesotheliomas were identified according to death certificate diagnosis. A 10:1 matched analysis with railroad workers dying of nonmalignant, nonaccidental causes yielded a very strong association with prior railroad work in jobs with potential asbestos exposure (odds ratio = 7.2, 95% lower confidence limit = 3.3). Consideration of railroad occupations with regular asbestos exposures (e.g., skilled trades, steam locomotive repair) yielded an odds ratio of 21.4 (95% lower confidence limit = 8.7), but the occupations with potential intermittent exposure (e.g., engineers, firemen, carmen) yielded a nonsignificant odds ratio of 2.3 (95% lower confidence limit = 0.5). Applying mesothelioma mortality rates from this study to the population of U.S. railroad workers at risk yields an estimate of 416 cases of mesothelioma occurring among U.S. railroad workers between 1981 and 2000.

  5. Cloning and characterization of human RTVP-1b, a novel splice variant of RTVP-1 in glioma cells

    International Nuclear Information System (INIS)

    Xiang Cunli; Sarid, Ronit; Cazacu, Simona; Finniss, Susan; Lee, Hae-Kyung; Ziv-Av, Amotz; Mikkelsen, Tom; Brodie, Chaya

    2007-01-01

    Here, we report the cloning and characterization of RTVP-1b, a novel splice variant of human RTVP-1, which was isolated from the U87 glioma cell line. Sequence analysis revealed that RTVP-1b contains an additional 71 base exon between exons 2 and 3 that is missing in RTVP-1, leading to a frame-shift and a different putative protein. The deduced protein was 237 amino acids in length, sharing the N-terminal 141 amino acids with RTVP-1. RT-PCR analysis demonstrated that RTVP-1b was expressed in a wide range of tissues and that its expression was different from that of RTVP-1. In contrast, RTVP-1 and RTVP-1b showed similar patterns of expression in astrocytic tumors; highly expressed in glioblastomas as compared to normal brains, low-grade astrocytomas and anaplastic oligodendrogliomas. Overexpression of RTVP-1b increased glioma cell proliferation but did not affect cell migration. Our results suggest that RTVP-1b represents a potential prognostic marker and therapeutic target in gliomas

  6. 40 CFR 86.1105-87 - Emission standards for which nonconformance penalties are available.

    Science.gov (United States)

    2010-07-01

    ... development component of the NCP in accordance with § 86.1113-87(h): 0.12. (ii) For petroleum-fueled medium... 40 Protection of Environment 19 2010-07-01 2010-07-01 false Emission standards for which nonconformance penalties are available. 86.1105-87 Section 86.1105-87 Protection of Environment ENVIRONMENTAL...

  7. The nuclear receptor ERβ engages AGO2 in regulation of gene transcription, RNA splicing and RISC loading.

    Science.gov (United States)

    Tarallo, Roberta; Giurato, Giorgio; Bruno, Giuseppina; Ravo, Maria; Rizzo, Francesca; Salvati, Annamaria; Ricciardi, Luca; Marchese, Giovanna; Cordella, Angela; Rocco, Teresa; Gigantino, Valerio; Pierri, Biancamaria; Cimmino, Giovanni; Milanesi, Luciano; Ambrosino, Concetta; Nyman, Tuula A; Nassa, Giovanni; Weisz, Alessandro

    2017-10-06

    The RNA-binding protein Argonaute 2 (AGO2) is a key effector of RNA-silencing pathways It exerts a pivotal role in microRNA maturation and activity and can modulate chromatin remodeling, transcriptional gene regulation and RNA splicing. Estrogen receptor beta (ERβ) is endowed with oncosuppressive activities, antagonizing hormone-induced carcinogenesis and inhibiting growth and oncogenic functions in luminal-like breast cancers (BCs), where its expression correlates with a better prognosis of the disease. Applying interaction proteomics coupled to mass spectrometry to characterize nuclear factors cooperating with ERβ in gene regulation, we identify AGO2 as a novel partner of ERβ in human BC cells. ERβ-AGO2 association was confirmed in vitro and in vivo in both the nucleus and cytoplasm and is shown to be RNA-mediated. ChIP-Seq demonstrates AGO2 association with a large number of ERβ binding sites, and total and nascent RNA-Seq in ERβ + vs ERβ - cells, and before and after AGO2 knock-down in ERβ + cells, reveals a widespread involvement of this factor in ERβ-mediated regulation of gene transcription rate and RNA splicing. Moreover, isolation and sequencing by RIP-Seq of ERβ-associated long and small RNAs in the cytoplasm suggests involvement of the nuclear receptor in RISC loading, indicating that it may also be able to directly control mRNA translation efficiency and stability. These results demonstrate that AGO2 can act as a pleiotropic functional partner of ERβ, indicating that both factors are endowed with multiple roles in the control of key cellular functions.

  8. 27 CFR 479.87 - Cancellation of stamp.

    Science.gov (United States)

    2010-04-01

    ... OTHER FIREARMS Transfer Tax Application and Order for Transfer of Firearm § 479.87 Cancellation of stamp. The method of cancellation of the stamp required by this subpart as prescribed in § 479.67 shall be used. Exemptions Relating to Transfers of Firearms ...

  9. Use of EF5 to Measure the Oxygen Level in Tumor Cells of Patients Undergoing Surgery or Biopsy for Newly Diagnosed Supratentorial Malignant Glioma

    Science.gov (United States)

    2013-01-15

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymoma

  10. Adenosine Receptors Differentially Regulate the Expression of Regulators of G-Protein Signalling (RGS 2, 3 and 4 in Astrocyte-Like Cells.

    Directory of Open Access Journals (Sweden)

    Till Nicolas Eusemann

    Full Text Available The "regulators of g-protein signalling" (RGS comprise a large family of proteins that limit by virtue of their GTPase accelerating protein domain the signal transduction of G-protein coupled receptors. RGS proteins have been implicated in various neuropsychiatric diseases such as schizophrenia, drug abuse, depression and anxiety and aggressive behaviour. Since conditions associated with a large increase of adenosine in the brain such as seizures or ischemia were reported to modify the expression of some RGS proteins we hypothesized that adenosine might regulate RGS expression in neural cells. We measured the expression of RGS-2,-3, and -4 in both transformed glia cells (human U373 MG astrocytoma cells and in primary rat astrocyte cultures stimulated with adenosine agonists. Expression of RGS-2 mRNA as well as RGS2 protein was increased up to 30-fold by adenosine agonists in astrocytes. The order of potency of agonists and the blockade by the adenosine A2B-antagonist MRS1706 indicated that this effect was largely mediated by adenosine A2B receptors. However, a smaller effect was observed due to activation of adenosine A2A receptors. In astrocytoma cells adenosine agonists elicited an increase in RGS-2 expression solely mediated by A2B receptors. Expression of RGS-3 was inhibited by adenosine agonists in both astrocytoma cells and astrocytes. However while this effect was mediated by A2B receptors in astrocytoma cells it was mediated by A2A receptors in astrocytes as assessed by the order of potency of agonists and selective blockade by the specific antagonists MRS1706 and ZM241385 respectively. RGS-4 expression was inhibited in astrocytoma cells but enhanced in astrocytes by adenosine agonists.

  11. A Chance in Hell: Evaluating the Efficacy of U.S. Military Health Systems in Foreign Disaster Relief

    Science.gov (United States)

    2013-12-10

    brochures /Somalia/Somalia.htm (downloaded 10 October, 2008), 8-10. 86Ibid., 9-10. 87U.S. Department of the Army, United States Forces After Action Review...Modeling, and Prediction, College Park, MD, April 3-5, 2012). 232U.S. Department of the Air Force, Air Mobility Planning Factors, Air Force Pamphlet 10...U.S. Department of the Air Force. Air Mobility Planning Factors. Air Force Pamphlet 10-1403. Washington D.C.: Government Printing Office (2003

  12. 36 CFR 1192.87 - Public information system.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Public information system... Light Rail Vehicles and Systems § 1192.87 Public information system. (a) Each vehicle shall be equipped with an interior public address system permitting transportation system personnel, or recorded or...

  13. 25 CFR 87.12 - Insuring the proper performance of approved plans.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Insuring the proper performance of approved plans. 87.12... DISTRIBUTION OF INDIAN JUDGMENT FUNDS § 87.12 Insuring the proper performance of approved plans. A timetable... regarding the maintenance of the timetable, a full accounting of any per capita distribution, and the...

  14. STS-87 Mission Specialist Winston E. Scott suits up

    Science.gov (United States)

    1997-01-01

    STS-87 Mission Specialist Winston Scott dons his launch and entry suit with the assistance of a suit technician in the Operations and Checkout Building. This is Scotts second space flight. He and the five other crew members will depart shortly for Launch Pad 39B, where the Space Shuttle Columbia awaits liftoff on a 16-day mission to perform microgravity and solar research. Scott is scheduled to perform an extravehicular activity spacewalk with Mission Specialist Takao Doi, Ph.D., of the National Space Development Agency of Japan, during STS-87. He also performed a spacewalk on STS-72.

  15. Effective Anti-miRNA Oligonucleotides Show High Releasing Rate of MicroRNA from RNA-Induced Silencing Complex.

    Science.gov (United States)

    Ariyoshi, Jumpei; Matsuyama, Yohei; Kobori, Akio; Murakami, Akira; Sugiyama, Hiroshi; Yamayoshi, Asako

    2017-10-01

    MicroRNAs (miRNAs) regulate gene expression by forming RNA-induced silencing complexes (RISCs) and have been considered as promising therapeutic targets. MiRNA is an essential component of RISC for the modulation of gene expression. Therefore, the release of miRNA from RISC is considered as an effective method for the inhibition of miRNA functions. In our previous study, we reported that anti-miRNA oligonucleotides (AMOs), which are composed of the 2'-O-methyl (2'-OMe) RNA, could induce the release of miRNA from RISC. However, the mechanisms underlying the miRNA-releasing effects of chemically modified AMOs, which are conventionally used as anti-cancer drugs, are still unclear. In this study, we investigated the relationship between the miRNA releasing rate from RISC and the inhibitory effect on RISC activity (IC 50 ) using conventional chemically modified AMOs. We demonstrated that the miRNA-releasing effects of AMOs are directly proportional to the IC 50 values, and AMOs, which have an ability to promote the release of miRNA from RISC, can effectively inhibit RISC activity in living cells.

  16. The Ongoing Growth of the M87 Halo through Accretion Events

    Directory of Open Access Journals (Sweden)

    Alessia Longobardi

    2015-12-01

    Full Text Available Planetary nebulas (PNs offer a unique tool to investigate the outer regions of massive galaxies because their strong [OIII]λ5007Å emission line makes them detectable out to several effective radii from the galaxy’s centre. We use a deep and extended spectroscopic survey of PNs (∼300 objects to study the spatial distribution, the kinematics and the stellar populations in the extended outer halo of the bright elliptical galaxy M87 (NGC 4486 in the Virgo cluster. We show that in the Virgo core, M87 stellar halo and the intracluster light are two distinct dynamical components, with different velocity distributions. Moreover the synergy of the PN kinematical information and the deep V/B-band photometry revealed an ongoing accretion event in the outer regions of M87. This satellite accretion represents a non-negligible perturbation of the halo properties: beyond 60 kpc the M87 halo is still growing with 60% of its light being added by the accretion event at the distance where it is detected.

  17. Geochemical and multi-isotopic (87Sr/86Sr, 143Nd/144Nd, 238U/235U) perspectives of sediment sources, depositional conditions, and diagenesis of the Marcellus Shale, Appalachian Basin, USA

    Science.gov (United States)

    Phan, Thai T.; Gardiner, James B.; Capo, Rosemary C.; Stewart, Brian W.

    2018-02-01

    We investigate sediment sources, depositional conditions and diagenetic processes affecting the Middle Devonian Marcellus Shale in the Appalachian Basin, eastern USA, a major target of natural gas exploration. Multiple proxies, including trace metal contents, rare earth elements (REE), the Sm-Nd and Rb-Sr isotope systems, and U isotopes were applied to whole rock digestions and sequentially extracted fractions of the Marcellus shale and adjacent units from two locations in the Appalachian Basin. The narrow range of εNd values (from -7.8 to -6.4 at 390 Ma) is consistent with derivation of the clastic sedimentary component of the Marcellus Shale from a well-mixed source of fluvial and eolian material of the Grenville orogenic belt, and indicate minimal post-depositional alteration of the Sm-Nd system. While silicate minerals host >80% of the REE in the shale, data from sequentially extracted fractions reflect post-depositional modifications at the mineralogical scale, which is not observed in whole rock REE patterns. Limestone units thought to have formed under open ocean (oxic) conditions have δ238U values and REE patterns consistent with modern seawater. The δ238U values in whole rock shale and authigenic phases are greater than those of modern seawater and the upper crust. The δ238U values of reduced phases (the oxidizable fraction consisting of organics and sulfide minerals) are ∼0.6‰ greater than that of modern seawater. Bulk shale and carbonate cement extracted from the shale have similar δ238U values, and are greater than δ238U values of adjacent limestone units. We suggest these trends are due to the accumulation of chemically and, more likely, biologically reduced U from anoxic to euxinic bottom water as well as the influence of diagenetic reactions between pore fluids and surrounding sediment and organic matter during diagenesis and catagenesis.

  18. Palbociclib Isethionate in Treating Younger Patients With Recurrent, Progressive, or Refractory Central Nervous System Tumors

    Science.gov (United States)

    2017-09-27

    Childhood Choroid Plexus Tumor; Childhood Ependymoblastoma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor

  19. Sr isotopes and U series radionuclides in the Sangemini area (Central Italy: Hydrogeology implications

    Directory of Open Access Journals (Sweden)

    Maurizio Barbieri

    2014-06-01

    Full Text Available The strontium isotopic ratio (expressed as 87Sr/86Sr of groundwater represents a useful method for studying and understanding the groundwater circulations, also, the U and Ra isotopic compositions can vary as function of the groundwater residence time. This paper reports an evaluation of the probable recharge area of the Sangemini mineral water springs (Terni-Umbria Central Italy and an estimate of the residence time of the aquifer by coupling Sr and U series isotopic systematics. For this study have been analyzed four water sample for the isotope ratio of 87Sr/86Sr, and eleven samples, shallow waters and groundwaters, for U and Ra, furthermore were determined the values of isotopic ratio for sample of typical rocks of the area. The results of this study allow to identify: a recharge area in a restricted sector of the Meso-Cenozoic carbonates a longer and more effective water/rock interaction in the Quaternary series. U and Ra recoil models allow to estimate a groundwater residence time of about 350 years and a total water volume whose value (64*106 m3 agrees with the limited extension of the aquifer. The extension of the aquifer was constrained by comparing Sr isotopic composition of waters and local geological formations. Groundwaters seem mainly to circulate in clayey sandy Quaternary series characterized by low redox conditions.

  20. The corrosion protection of 2219-T87 aluminum by anodizing

    Science.gov (United States)

    Danford, M. D.

    1991-01-01

    Various types of anodizing coatings were studied for 2219-T87 aluminum. These include both type II and type III anodized coats which were water sealed and a newly developed and proprietary Magnaplate HCR (TM) coat. Results indicate that type II anodizing is not much superior to type II anodizing as far as corrosion protection for 2219-T87 aluminum is concerned. Magnaplate HCR (TM) coatings should provide superior corrosion protection over an extended period of time using a coating thickness of 51 microns (2.0 mils).

  1. Double-strand break induction and DNA damage response after {sup 12}C ion and photon radiation in U87 glioblastoma cells; Doppelstrangbruch-Induktion und DNA-Schadensantwort nach {sup 12}C-Ionen- und Photonenstrahlung in U87 Glioblastomzellen

    Energy Technology Data Exchange (ETDEWEB)

    Lopez Perez, Ramon

    2015-04-22

    Heavy ion radiation has greater biological effectiveness than the same physical dose of photon radiation. In this work the underlying reasons in the DNA damage response were analyzed in U87 glioblastoma cells. DNA double-strand breaks (DSBs) are the decicive lesions for the effectiveness of ionizing radiation. Their induction and repair was measured in the context of the cell cycle based on the DSB marker γH2AX (the phosphorylated form of the histone variant H2AX). Further, radiation-specific differences in choice of the DSB repair pathway was analyzed, as well as the consequences of repair failure. The results showed that in contrast to photons, {sup 12}C ion radiation produces more severe DSBs that are repaired delayed and with slower kinetics. Accordingly, stronger and longer lasting cell cycle delays, predominantly at the G2/M border, and a higher rate of apoptosis was detected for {sup 12}C ion radiation. Autophagy, an alternative mechanism of programmed cell death, was not relevant for neither of the two types of radiation. The effect of {sup 12}C ion radiation was less dependent on the cell cycle stage than for photon radiation. This became particularly evident in the DSB repair velocities during S- and G2-phase. After {sup 12}C ion radiation, cells were more dependent on homologous recombination repair (HRR) compared to photon radiation. The reason therefore that in contrast to photons, {sup 12}C ion radiation induced graver DSBs that were repaired slower and more dependent on HRR, was most probably enhanced clustering of DSBs due to the higher ionization density of {sup 12}C ion radiation. Microscopic inspection of immunofluorently stained γH2AX revealed that {sup 12}C ion radiation induced bigger DSB repair foci containing more γH2AX molecules (higher fluorescence intensity), although their initial number was smaller. Besides the foci, a weaker pan-nuclear γH2AX staining was observed that increased in a dose-dependent manner and was more pronounced

  2. 40 CFR 86.1114-87 - Suspension and voiding of certificates of conformity.

    Science.gov (United States)

    2010-07-01

    ... of conformity. 86.1114-87 Section 86.1114-87 Protection of Environment ENVIRONMENTAL PROTECTION... conformity. (a) The certificate of conformity is suspended with respect to any engine or vehicle failing... certificate of conformity if the manufacturer, after electing to conduct a PCA, fails to adhere to the...

  3. XMM-Newton high-resolution spectroscopy reveals the chemical evolution of M 87

    NARCIS (Netherlands)

    Werner, N.; Boehringer, H.; Kaastra, J.S.; de Plaa, J.; Simionescu, D.; Vink, J.

    2006-01-01

    We present a study of chemical abundances in the giant elliptical galaxy M 87 using high-resolution spectra obtained with the Reflection Grating Spectrometers during two deep XMM-Newton observations. While we confirm the two-temperature structure of the inter-stellar medium (ISM) in M 87, we also

  4. Enhanced effect of folated pluronic F87-PLA/TPGS mixed micelles on targeted delivery of paclitaxel.

    Science.gov (United States)

    Xiong, Xiang Yuan; Pan, Xiaoqian; Tao, Long; Cheng, Feng; Li, Zi Ling; Gong, Yan Chun; Li, Yu Ping

    2017-10-01

    Targeted drug delivery systems have great potential to overcome the side effect and improve the bioavailability of conventional anticancer drugs. In order to further improve the antitumor efficacy of paclitaxel (PTX) loaded in folated Pluronic F87/poly(lactic acid) (FA-F87-PLA) micelles, D-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS or Vitamin E TPGS) were added into FA-F87-PLA to form FA-F87-PLA/TPGS mixed micelles. The LE of PTX-loaded mixed micelles (13.5%) was highest in the mass ratio 5 to 3 of FA-F87-PLA to TPGS. The in vitro cytotoxicity assays indicated that the IC50 values for free PTX injections, PTX-loaded FA-F87-PLA micelles and PTX-loaded FA-F87-PLA/TPGS mixed micelles after 72h of incubation were 1.52, 0.42 and 0.037mg/L, respectively. The quantitative cellular uptake of coumarin 6-loaded FA-F87-PLA/TPGS and FA-F87-PLA micelles showed that the cellular uptake efficiency of mixed micelles was higher for 2 and 4h incubation, respectively. In vivo pharmacokinetic studies found that the AUC of PTX-loaded FA-F87-PLA/TPGS mixed micelles is almost 1.4 times of that of PTX-loaded FA-F87-PLA micelles. The decreased particle size and inhibition of P-glycoprotein effect induced by the addition of TPGS could result in enhancing the cellular uptake and improving the antitumor efficiency of PTX-loaded FA-F87-PLA/TPGS mixed micelles. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Evidence for core-coupled states in 87Y from a 89Y(p, t)87Y and 88Sr(p, t)86Sr comparison

    International Nuclear Information System (INIS)

    Oelrich, I.C.; Krien, K.; DelVecchio, R.M.; Naumann, R.A.

    1976-01-01

    The 89 Y(p, t) 87 Y and 88 Sr(p, t) 86 Sr reactions were studied at 42 MeV proton energy, using a quadrupole-dipole-dipole-dipole spectograph. Comparison of excitation energies, (p, t) cross section strengths and angular distribution shapes indicates that basis features of the core-coupling model apply to these nuclei. However, mixing of single particle states with the core-coupled states is evident. The (p, t) cross-section strength summed over the 87 Y multiplet is found with few exceptions to be nearly a constant multiple of the (p, t) strength of the associated 86 Sr state

  6. Superconductivity in the U(Th)-Y-Ba-Cu-O systems

    International Nuclear Information System (INIS)

    Qin Qizong; He Adi; Jia Weijie; Ma Lidun; Cheng Huansheng; Hua Zhongyi

    1989-01-01

    High T c superconductivity has been observed both resistively and magnetically in the new U(Th)-Y-Ba-Cu-O systems. The zero resistance temperature of the three samples with nominal composition of U 0.1 Y 1.1 Ba 0.8 Cu O 4-z , U 0.15 Y 1.05 Ba 0.8 Cu 4-z and Th 0.3 Y 0.8 Ba 0.8 Cu 4-z is 87K, 79K and 74K, respectively. The result of ac magnetic susceptibility measurement implies that the superconducting state is realized in the U-doped samples below 90K. The stoichimetry of the U-Y-Ba-Cu O superconductors has the aid of Rutherford backscattering and nuclear reaction 16 O(d, p) 17 O. The analytical results show that the 'real composition' of somples may be different from that of the nomial composition. The X ray diffraction analysis of the U-Y-Ba-Cu-O system shows that none of the peaks can be fitted to the uranium oxides and the other raw materiale structure, and its pattern may be attributed to new multiple phases with structure different from the known singlephase superconducting oxides

  7. 68Ga-labeling and in vivo evaluation of a uPAR binding DOTA- and NODAGA-conjugated peptide for PET imaging of invasive cancers

    DEFF Research Database (Denmark)

    Persson, Morten; Madsen, Jacob; Østergaard, Søren

    2012-01-01

    , uPAR binding affinity and cell uptake were determined. To characterize the in vivo properties, dynamic microPET imaging was carried out in nude mice bearing human glioma U87MG tumor xenograft. RESULTS: In vitro experiments revealed uPAR binding affinities in the lower nM range for both conjugated......-AE105-NH(2) was observed. Good stability in phosphate-buffered saline and mouse plasma was observed. High cell uptake was found for both tracers in U87MG tumor cells. Dynamic microPET imaging demonstrated good tumor-to-background ratio for both tracers. Tumor uptake was 2.1% ID/g and 1.3% ID/g 30 min...... positron emission tomography (PET) in human cancer xenograft mice models. Here we introduce (68)Ga-DOTA-AE105-NH(2) and (68)Ga-NODAGA-AE105-NH(2) and evaluate their imaging properties using small-animal PET. METHODS: Synthesis of DOTA-AE105-NH(2) and NODAGA-AE105-NH(2) was based on solid-phase peptide...

  8. The effect of everolimus on renal angiomyolipoma in pediatric patients with tuberous sclerosis being treated for subependymal giant cell astrocytoma.

    Science.gov (United States)

    Bissler, John J; Franz, David N; Frost, Michael D; Belousova, Elena; Bebin, E Martina; Sparagana, Steven; Berkowitz, Noah; Ridolfi, Antonia; Kingswood, J Christopher

    2018-01-01

    Patients with tuberous sclerosis complex (TSC) often have multiple TSC-associated hamartomas, particularly in the brain and kidney. This was a post hoc analysis of pediatric patients being treated for subependymal giant cell astrocytomas (SEGAs) during the phase 3, randomized, double-blind, placebo-controlled EXIST-1 trial. Patients were initially randomly assigned to receive everolimus 4.5 mg/m 2 /day (target blood trough 5-15 mg/dl) or placebo and could continue in an open-label extension phase. Angiomyolipoma response rates were analyzed in patients aged 20% increase in kidney volume from nadir, and angiomyolipoma-related bleeding ≥ grade 2. Tolerability was also assessed. Overall, this analysis included 33 patients. Renal angiomyolipoma response was achieved by 75.8% of patients (95% confidence interval, 57.7-88.9%), with sustained mean reductions in renal angiomyolipoma volume over nearly 4 years of treatment. In addition, most (≥80%) achieved clinically relevant reductions in angiomyolipoma volume (≥50%), beginning at week 24 and continuing for the remainder of the study. Everolimus was generally well tolerated in this subgroup, with most adverse events being grade 1 or 2 in severity. Although everolimus is currently not indicated for this use, this analysis from EXIST-1 demonstrates its long-term efficacy and safety for the treatment of renal angiomyolipoma in pediatric patients undergoing treatment for TSC-associated SEGA.

  9. Differentiation of hemangioblastomas from pilocytic astrocytomas using 3-T magnetic resonance perfusion-weighted imaging and MR spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    She, D.J.; Xing, Z.; Zeng, Z.; Cao, D.R. [First Affiliated Hospital of Fujian Medical University, Department of Radiology, Fuzhou, Fujian (China); Shang, X.Y. [University of California, San Diego, Department of Medicine and the Moores UCSD Cancer Center, La Jolla, CA (United States)

    2015-03-01

    Hemangioblastomas and pilocytic astrocytomas (PAs) present similar imaging features on conventional MR imaging, making differential diagnosis a challenge. The purpose of this study was to evaluate the usefulness of dynamic susceptibility-weighted contrast-enhanced perfusion-weighted imaging (DSC-PWI) and proton MR spectroscopic imaging in the differentiation of hemangioblastomas and PAs. A 3.0-T MR imaging unit was used to perform DSC-PWI and conventional MR imaging on 14 patients with hemangioblastomas and 22 patients with PAs. Four patients with hemangioblastomas and 10 PA patients also underwent proton MR spectroscopy. Parameters of relative peak height (rPH) and relative percentage of signal intensity recovery (rPSR) were acquired by DSC-PWI and variables of N-acetylaspasrtate (NAA)/creatine (Cr), choline (Cho)/Cr, and lactate-lipid (Lac-Lip)/Cr by MR spectroscopy. The sensitivity, specificity, and the area under the receiver operating characteristic curve of all analyzed parameters at respective cutoff values were determined. Higher rPH but lower rPSR values were detected in hemangioblastomas compared to PAs. The NAA/Cr ratio was significantly lower in hemangioblastomas compared with PAs. The threshold values ≥3.2 for rPH provide sensitivity, specificity, positive predictive values, and negative predictive values of 85.7, 95.5, 92.3, and 91.3 %, respectively, for differentiating hemangioblastomas from PAs. The optimal threshold values were ≤0.9 for rPSR and ≤1.5 for NAA/Cr ratios in tumor. Significantly higher rPH and lower NAA/Cr were seen in patients with hemangioblastomas when compared with PA patients, suggesting that DSC-PWI and proton MR spectroscopy are helpful in the characterization and differentiation of these two types of tumors. (orig.)

  10. The extrinsic and intrinsic apoptotic pathways are involved in manganese toxicity in rat astrocytoma C6 cells.

    Science.gov (United States)

    Alaimo, Agustina; Gorojod, Roxana M; Kotler, Mónica L

    2011-08-01

    Manganese (Mn) is a trace element known to be essential for maintaining the proper function and regulation of many biochemical and cellular reactions. However, chronic exposure to high levels of Mn in occupational or environmental settings can lead to its accumulation in the brain resulting in a degenerative brain disorder referred to as Manganism. Astrocytes are the main Mn store in the central nervous system and several lines of evidence implicate these cells as major players in the role of Manganism development. In the present study, we employed rat astrocytoma C6 cells as a sensitive experimental model for investigating molecular mechanisms involved in Mn neurotoxicity. Our results show that C6 cells undergo reactive oxygen species-mediated apoptotic cell death involving caspase-8 and mitochondrial-mediated pathways in response to Mn. Exposed cells exhibit typical apoptotic features, such as chromatin condensation, cell shrinkage, membrane blebbing, caspase-3 activation and caspase-specific cleavage of the endogenous substrate poly (ADP-ribose) polymerase. Participation of the caspase-8 dependent pathway was assessed by increased levels of FasL, caspase-8 activation and Bid cleavage. The involvement of the mitochondrial pathway was demonstrated by the disruption of the mitochondrial membrane potential, the opening of the mitochondrial permeability transition pore, cytochrome c release, caspase-9 activation and the increased mitochondrial levels of the pro-apoptotic Bcl-2 family proteins. In addition, our data also shows for the first time that mitochondrial fragmentation plays a relevant role in Mn-induced apoptosis. Taking together, these findings contribute to a deeper elucidation of the molecular signaling mechanisms underlying Mn-induced apoptosis. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Human Rhinovirus 87 and Enterovirus 68 Represent a Unique Serotype with Rhinovirus and Enterovirus Features

    Science.gov (United States)

    Blomqvist, Soile; Savolainen, Carita; Råman, Laura; Roivainen, Merja; Hovi, Tapani

    2002-01-01

    It has recently been reported that all but one of the 102 known serotypes of the genus Rhinovirus segregate into two genetic clusters (C. Savolainen, S. Blomqvist, M. N. Mulders, and T. Hovi, J. Gen. Virol. 83:333-340, 2002). The only exception is human rhinovirus 87 (HRV87). Here we demonstrate that HRV87 is genetically and antigenically highly similar to enterovirus 68 (EV68) and is related to EV70, the other member of human enterovirus group D. The partial nucleotide sequences of the 5′ untranslated region, capsid regions VP4/VP2 and VP1, and the 3D RNA polymerase gene of the HRV87 prototype strain F02-3607 Corn showed 97.3, 97.8, 95.2, and 95.9% identity to the corresponding regions of EV68 prototype strain Fermon. The amino acid identities were 100 and 98.1% for the products of the two capsid regions and 97.9% for 3D RNA polymerase. Antigenic cross-reaction between HRV87 and EV68 was indicated by microneutralization with monotypic antisera. Phylogenetic analysis showed definite clustering of HRV87 and EV68 with EV70 for all sequences examined. Both HRV87 and EV68 were shown to be acid sensitive by two different assays, while EV70 was acid resistant, which is typical of enteroviruses. The cytopathic effect induced by HRV87 or EV68 was inhibited by monoclonal antibodies to the decay-accelerating factor known to be the receptor of EV70. We conclude that HRV87 and EV68 are strains of the same picornavirus serotype presenting features of both rhinoviruses and enteroviruses. PMID:12409401

  12. Mapping the topographic epitope landscape on the urokinase plasminogen activator receptor (uPAR) by surface plasmon resonance and X-ray crystallography

    DEFF Research Database (Denmark)

    Zhao, Baoyu; Gandhi, Sonu; Yuan, Cai

    2015-01-01

    The urokinase-type plasminogen activator receptor (uPAR or CD87) is a glycolipid-anchored membrane protein often expressed in the microenvironment of invasive solid cancers and high levels are generally associated with poor patient prognosis (Kriegbaum et al., 2011 [1]). uPAR is organized as a dy...... of these mAbs by X-ray crystallography alone and in complex with uPAR [deposited in the PDB database as 4QTH and 4QTI, respectively]....

  13. 47 CFR 87.145 - Acceptability of transmitters for licensing.

    Science.gov (United States)

    2010-10-01

    ...., SW., Washington, DC 20591. (c) The equipment listed below is exempted from certification. The... § 87.147(e). (4) Signal generators when used as radionavigation land test stations (MTF). (d) Aircraft...

  14. Post-treatment changes of tumour perfusion parameters can help to predict survival in patients with high-grade astrocytoma

    Energy Technology Data Exchange (ETDEWEB)

    Sanz-Requena, Roberto; Marti-Bonmati, Luis [Hospital Quironsalud Valencia, Radiology Department, Valencia (Spain); Hospital Universitari i Politecnic La Fe, Grupo de Investigacion Biomedica en Imagen, Valencia (Spain); Revert-Ventura, Antonio J.; Salame-Gamarra, Fares [Hospital de Manises, Radiology Department, Manises (Spain); Garcia-Marti, Gracian [Hospital Quironsalud Valencia, Radiology Department, Valencia (Spain); Hospital Universitari i Politecnic La Fe, Grupo de Investigacion Biomedica en Imagen, Valencia (Spain); CIBER-SAM, Instituto de Salud Carlos III, Madrid (Spain); Perez-Girbes, Alexandre [Hospital Universitari i Politecnic La Fe, Grupo de Investigacion Biomedica en Imagen, Valencia (Spain); Molla-Olmos, Enrique [Hospital La Ribera, Radiology Department, Alzira (Spain)

    2017-08-15

    Vascular characteristics of tumour and peritumoral volumes of high-grade gliomas change with treatment. This work evaluates the variations of T2*-weighted perfusion parameters as overall survival (OS) predictors. Forty-five patients with histologically confirmed high-grade astrocytoma (8 grade III and 37 grade IV) were included. All patients underwent pre- and post-treatment T2*-weighted contrast-enhanced magnetic resonance (MR) imaging. Tumour, peritumoral and control volumes were segmented. Relative variations of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), K{sup trans-T2*}, k{sub ep-T2*}, v{sub e-T2*} and v{sub p-T2*} were calculated. Differences regarding tumour grade and surgical resection extension were evaluated with ANOVA tests. For each parameter, two groups were defined by non-supervised clusterisation. Survival analysis were performed on these groups. For the tumour region, the 90th percentile increase or stagnation of CBV was associated with shorter survival, while a decrease related to longer survival (393 ± 189 vs 594 ± 294 days; log-rank p = 0.019; Cox hazard-ratio, 2.31; 95% confidence interval [CI], 1.12-4.74). K{sup trans-T2*} showed similar results (414 ± 177 vs 553 ± 312 days; log-rank p = 0.037; hazard-ratio, 2.19; 95% CI, 1.03-4.65). The peritumoral area values showed no relationship with OS. Post-treatment variations of the highest CBV and K{sup trans-T2*} values in the tumour volume are predictive factors of OS in patients with high-grade gliomas. (orig.)

  15. The Observational and Theoretical Tidal Radii of Globular Clusters in M87

    Science.gov (United States)

    Webb, Jeremy J.; Sills, Alison; Harris, William E.

    2012-02-01

    Globular clusters have linear sizes (tidal radii) which theory tells us are determined by their masses and by the gravitational potential of their host galaxy. To explore the relationship between observed and expected radii, we utilize the globular cluster population of the Virgo giant M87. Unusually deep, high signal-to-noise images of M87 are used to measure the effective and limiting radii of approximately 2000 globular clusters. To compare with these observations, we simulate a globular cluster population that has the same characteristics as the observed M87 cluster population. Placing these simulated clusters in the well-studied tidal field of M87, the orbit of each cluster is solved and the theoretical tidal radius of each cluster is determined. We compare the predicted relationship between cluster size and projected galactocentric distance to observations. We find that for an isotropic distribution of cluster velocities, theoretical tidal radii are approximately equal to observed limiting radii for R gc < 10 kpc. However, the isotropic simulation predicts a steep increase in cluster size at larger radii, which is not observed in large galaxies beyond the Milky Way. To minimize the discrepancy between theory and observations, we explore the effects of orbital anisotropy on cluster sizes, and suggest a possible orbital anisotropy profile for M87 which yields a better match between theory and observations. Finally, we suggest future studies which will establish a stronger link between theoretical tidal radii and observed radii.

  16. THE OBSERVATIONAL AND THEORETICAL TIDAL RADII OF GLOBULAR CLUSTERS IN M87

    International Nuclear Information System (INIS)

    Webb, Jeremy J.; Sills, Alison; Harris, William E.

    2012-01-01

    Globular clusters have linear sizes (tidal radii) which theory tells us are determined by their masses and by the gravitational potential of their host galaxy. To explore the relationship between observed and expected radii, we utilize the globular cluster population of the Virgo giant M87. Unusually deep, high signal-to-noise images of M87 are used to measure the effective and limiting radii of approximately 2000 globular clusters. To compare with these observations, we simulate a globular cluster population that has the same characteristics as the observed M87 cluster population. Placing these simulated clusters in the well-studied tidal field of M87, the orbit of each cluster is solved and the theoretical tidal radius of each cluster is determined. We compare the predicted relationship between cluster size and projected galactocentric distance to observations. We find that for an isotropic distribution of cluster velocities, theoretical tidal radii are approximately equal to observed limiting radii for R gc < 10 kpc. However, the isotropic simulation predicts a steep increase in cluster size at larger radii, which is not observed in large galaxies beyond the Milky Way. To minimize the discrepancy between theory and observations, we explore the effects of orbital anisotropy on cluster sizes, and suggest a possible orbital anisotropy profile for M87 which yields a better match between theory and observations. Finally, we suggest future studies which will establish a stronger link between theoretical tidal radii and observed radii.

  17. 40 CFR 600.006-87 - Data and information requirements for fuel economy vehicles.

    Science.gov (United States)

    2010-07-01

    ..., motor controller, battery configuration, or other components performed within 2,000 miles prior to fuel... fuel economy vehicles. 600.006-87 Section 600.006-87 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY AND CARBON-RELATED EXHAUST EMISSIONS OF MOTOR VEHICLES Fuel...

  18. Analysis of Defenses Against Code Reuse Attacks on Modern and New Architectures

    Science.gov (United States)

    2015-09-01

    Hardware Architecture 55 5.1 Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 5.2 RISC -V Extensions...56 5.3 RISC -V Tag Policies . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 5.3.1 Basic Return Pointer Policy...60 5.4 RISC -V Policy Test Framework . . . . . . . . . . . . . . . . . . . . . 60 6 Compiler Support 63 6.1 LLVM

  19. 10 CFR 50.69 - Risk-informed categorization and treatment of structures, systems and components for nuclear...

    Science.gov (United States)

    2010-01-01

    ..., systems and components for nuclear power reactors. (a) Definitions. Risk-Informed Safety Class (RISC)-1... functions. Risk-Informed Safety Class (RISC)-2 structures, systems and components (SSCs) means nonsafety-related SSCs that perform safety significant functions. Risk-Informed Safety Class (RISC)-3 structures...

  20. On-farm animal welfare assessment in dairy cattle: improved lameness detection

    OpenAIRE

    Chapinal Gomez, Nuria

    2013-01-01

    Estudi realitzat a partir d’una estada a la University of British Columbia, Canada, entre 2010 i 2012. Primerament es va desenvolupar una escala per mesurar coixeses (amb valors de l’1 al 5). Aquesta escala es va utilitzar per estudiar l’associació entre factors de risc a nivell de granja (disseny de le instal.lacions i maneig) i la prevalencia de coixeses a Nord America. Les dades es van recollir en un total de 40 granges al Nord Est dels E.E.U.U (NE) i 39 a California (CA) . Totes les vaque...

  1. Adult Diffuse Astrocytoma in the Medulla Oblongata: Molecular Biological Analyses Including H3F3A Mutation of Histone H3.3.

    Science.gov (United States)

    Uekawa, Ken; Nakamura, Hideo; Shinojima, Naoki; Takezaki, Tatsuya; Yano, Shigetoshi; Kuratsu, Jun-Ichi

    2016-04-01

    Unlike in children, brain stem gliomas in adult are rare and still poorly understood. In addition, most adult brain stem gliomas result predominantly in the pons and are less often found in the medulla oblongata. Here, we report a case of an adult glioma in the medulla oblongata and its molecular biological features. A 46-year-old male presented with gait disturbance, paresthesia, and dysphagia. Magnetic resonance imaging (MRI) showed a diffuse hyper-intensive lesion in the medulla oblongata on a T 2 -weighted image without gadolinium contrast enhancement. We performed an open biopsy and the lesion was pathologically diagnosed as a diffuse astrocytoma. Molecular biological analyses revealed the absence of histone H3.3 mutation (H3F3A K27M), and presence of methylation of O-6-methylguanine-DNA methyltransferase (MGMT) promoter and a mutation in isocitrate dehydrogenase 1 (IDH-1). The patient received local radiotherapy and temozolomide chemotherapy. The patient's symptoms were ameliorated, and MRI showed no tumor growth at 6 months after the initial treatment. Biopsy for brain stem lesions is generally thought to have risk of complications, but if performed minimally, it is useful to diagnose and determine treatment strategy. Obtaining patient characteristics and molecular biological features will provide insight towards therapeutic treatment for adult brain stem gliomas.

  2. Canadian gas exports to U.S. set fourth consecutive record

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    Canadian natural gas exports in 1991 set a record for the fourth year in a row, Canadian Enerdata Ltd. reports. The Markham, Ont., consulting firm the shipments of gas to the U.S., Canada's only export customer for that fuel, jumped 16.8% in 1991 to 1.679 tcf. That volume replaced the previous record of 1.437 tcf exported just 1 year earlier. Enerdata figures show the 1991 export performance increased Canada's share of the U.S. gas market to a record high of 8.7%, up from 7.7% in 1990, 7.1% in 1989, 7.0% in 1988, 5.9% in 1987, and, only 4.6% in 1986. This paper reports that the performance positions Canadian exporters well for larger increases in volume and price as the U.S. gas market tightens and Canadian gas export capacity is increased in the mid-1990s

  3. First results of the radiological surveillance of RIT trial for high grade astrocytomas in Cuba

    Energy Technology Data Exchange (ETDEWEB)

    Amador Balbona, Z.H.; Pardo Ayra, F.E.; Torres Berdeguez, M.B. [Isotope Centre, Havana (Cuba). Radiation Protection Dept.

    2004-07-01

    The first phase of the clinical trial using the humanized monoclonal antibody h-R3 labeled with {sup 188} Re, for radioimmunotherapy (RIT) of brain tumors began in the Republic of Cuba in 2002. This monoclonal antibody was obtained in the country and it is required to evaluate its toxicity, biodistribution and internal radiation dosimetry. Five groups of three patients of each one with an administered activity from 0.37 GBq to 1.1 GBq, are considered. The aim of this work is to assess workers doses and public doses for this research and to compare projected doses with the first results related to the radiological surveillance. The contribution to the total effective dose and equivalent dose in extremities are calculated with the code Microshield version 4.0 by each activity level, operation and total quantity of patients. We take into account radioactive decay of {sup 188} Re and consider that only a person made all of the operations during this study. It is demonstrated that individual doses are acceptable and lower than world average effective annual dose of natural radiation background (2.4 mSv), because for the operations of more risk are used individual protection means. Nevertheless, it is identified that nurses are the most exposed. The projected maximum equivalent dose to hands is about 4 mSv and it belongs to the neurosurgeon. Radiological surveillance is performed to verify our calculations. Five workers and public (four individuals) are monitoring for each patient with direct reading dosimeters DOSICARD and TLD for extremities. For the first seven patients results are obtained. The conservative assumptions in the dose assessment and the compliance with established safety procedures determine that the registered doses are lower than those were projected. RIT with 188 Re for high-grade astrocytomas is a safety practice from radiation protection point of view. There is not a reference of a similar study in Latin America. (author)

  4. First results of the radiological surveillance of RIT trial for high grade astrocytomas in Cuba

    International Nuclear Information System (INIS)

    Amador Balbona, Z.H.; Pardo Ayra, F.E.; Torres Berdeguez, M.B.

    2004-01-01

    The first phase of the clinical trial using the humanized monoclonal antibody h-R3 labeled with 188 Re, for radioimmunotherapy (RIT) of brain tumors began in the Republic of Cuba in 2002. This monoclonal antibody was obtained in the country and it is required to evaluate its toxicity, biodistribution and internal radiation dosimetry. Five groups of three patients of each one with an administered activity from 0.37 GBq to 1.1 GBq, are considered. The aim of this work is to assess workers doses and public doses for this research and to compare projected doses with the first results related to the radiological surveillance. The contribution to the total effective dose and equivalent dose in extremities are calculated with the code Microshield version 4.0 by each activity level, operation and total quantity of patients. We take into account radioactive decay of 188 Re and consider that only a person made all of the operations during this study. It is demonstrated that individual doses are acceptable and lower than world average effective annual dose of natural radiation background (2.4 mSv), because for the operations of more risk are used individual protection means. Nevertheless, it is identified that nurses are the most exposed. The projected maximum equivalent dose to hands is about 4 mSv and it belongs to the neurosurgeon. Radiological surveillance is performed to verify our calculations. Five workers and public (four individuals) are monitoring for each patient with direct reading dosimeters DOSICARD and TLD for extremities. For the first seven patients results are obtained. The conservative assumptions in the dose assessment and the compliance with established safety procedures determine that the registered doses are lower than those were projected. RIT with 188 Re for high-grade astrocytomas is a safety practice from radiation protection point of view. There is not a reference of a similar study in Latin America. (author)

  5. 24 CFR 87.205 - Professional and technical services.

    Science.gov (United States)

    2010-04-01

    ... professional or technical discipline. For example, drafting of a legal document accompanying a bid or proposal... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Professional and technical services... and technical services. (a) The prohibition on the use of appropriated funds, in § 87.100 (a), does...

  6. Tipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma

    Science.gov (United States)

    2013-10-07

    Childhood High-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  7. Measurement of K-electron capture probability in the decay of 87Y

    International Nuclear Information System (INIS)

    Prasad, N.V.S.V.; Murty, G.S.K.; Rao, M.V.S.C.; Sastry, D.L.

    1993-01-01

    The K-electron capture probability for the 1/2 - to 3/2 - transition in the decay of 87 Y to the 873.0 keV level in the daughter 87 Sr was measured for the first time using an x-γ summing method. The experimental P K value was found to be 0.911 ± 0.047, in agreement with the theoretical value of 0.878. (author)

  8. The 5'-end heterogeneity of adenovirus virus-associated RNAI contributes to the asymmetric guide strand incorporation into the RNA-induced silencing complex.

    Science.gov (United States)

    Xu, Ning; Gkountela, Sofia; Saeed, Khalid; Akusjärvi, Göran

    2009-11-01

    Human Adenovirus type 5 encodes two short RNA polymerase III transcripts, the virus-associated (VA) RNAI and VA RNAII, which can adopt stable hairpin structures that resemble micro-RNA precursors. The terminal stems of the VA RNAs are processed into small RNAs (mivaRNAs) that are incorporated into RISC. It has been reported that VA RNAI has two transcription initiation sites, which produce two VA RNAI species; a major species, VA RNAI(G), which accounts for 75% of the VA RNAI pool, and a minor species, VA RNAI(A), which initiates transcription three nucleotides upstream compared to VA RNAI(G). We show that this 5'-heterogeneity results in a dramatic difference in RISC assembly. Thus, both VA RNAI(G) and VA RNAI(A) are processed by Dicer at the same position in the terminal stem generating the same 3'-strand mivaRNA. This mivaRNA is incorporated into RISC with 200-fold higher efficiency compared to the 5'-strand of mivaRNAI. Of the small number of 5'-strands used in RISC assembly only VA RNAI(A) generated active RISC complexes. We also show that the 3'-strand of mivaRNAI, although being the preferred substrate for RISC assembly, generates unstable RISC complexes with a low in vitro cleavage activity, only around 2% compared to RISC assembled on the VA RNAI(A) 5'-strand.

  9. ISSN 2073-9990 East Cent. Afr. J. surg

    African Journals Online (AJOL)

    Hp 630 Dual Core

    Key words: -Pilocytic astrocytoma • pilomyxoid astrocytoma • diagnosis • cerebellar ... of cerebellar Pilocytic astrocytoma, he was operated on 07/05/2015 midline .... initial therapy in the treatment of PMAs.16Whereas the literature is replete ...

  10. M 87 at metre wavelengths: the LOFAR picture

    NARCIS (Netherlands)

    de Gasperin, F.; et al., [Unknown; Alexov, A.; Hessels, J.; Swinbank, J.; van Leeuwen, J.; Wise, M.

    2012-01-01

    Context.M 87 is a giant elliptical galaxy located in the centre of the Virgo cluster, which harbours a supermassive black hole of mass 6.4 × 109 M⊙, whose activity is responsible for the extended (80 kpc) radio lobes that surround the galaxy. The energy generated by matter falling onto the central

  11. M87 at metre wavelengths: the LOFAR picture

    NARCIS (Netherlands)

    de Gasperin, F.; Orrú, E.; Murgia, M.; Merloni, A.; Falcke, H.; Beck, R.; Beswick, R.; Birzan, L.; Bonafede, A.; Brüggen, M.; Brunetti, G.; Chyzy, K.; Conway, J.; Croston, J.H.; Ensslin, T.; Ferrari, C.; Heald, G.; Heidenreich, S.; Jackson, N.; Macario, G.; McKean, J.; Miley, G.; Morganti, R.; Offringa, A.; Pizzo, R.; Rafferty, D.; Röttgering, H.; Shulevski, A.; Steinmetz, M.; Tasse, C.; van der Tol, S.; van Driel, W.; van Weeren, R.J.; van Zwieten, J.E.; Alexov, A.; Anderson, J.; Asgekar, A.; Avruch, M.; Bell, M.; Bell, M.R.; Bentum, M.J.; Bernardi, G.; Best, P.; Breitling, F.; Broderick, J.W.; Butcher, A.; Ciardi, B.; Dettmar, R.J.; Eislöffel, J.; Frieswijk, W.; Gankema, H.; Garrett, M.; Gerbers, M.; Griessmeier, J.M.; Gunst, A.W.; Hassall, T.E.; Hessels, J.; Hoeft, M.; Horneffer, A.; Karastergiou, A.; Köhler, J.; Koopman, Y.; Kuniyoshi, M.; Kuper, G.; Maat, P.; Mann, G.; Mevius, M.; Mulcahy, D.D.; Munk, H.; Nijboer, R.; Noordam, J.; Paas, H.; Pandey, M.; Pandey, V.N.; Polatidis, A.; Reich, W.; Schoenmakers, A.P.; Sluman, J.; Smirnov, O.; Sobey, C.; Stappers, B.; Swinbank, J.; Tagger, M.; Tang, Y.; van Bemmel, I.; van Cappellen, W.; van Duin, A.P.; van Haarlem, M.; van Leeuwen, J.; Vermeulen, R.; Vocks, C.; White, S.; Wise, M.; Wucknitz, O.; Zarka, P.

    2012-01-01

    Context: M 87 is a giant elliptical galaxy located in the centre of the Virgo cluster, which harbours a supermassive black hole of mass 6.4 × 109 M⊙, whose activity is responsible for the extended (80 kpc) radio lobes that surround the galaxy. The energy generated by matter falling onto the central

  12. A Pilot Study on Applying Option 2 to Two Systems in the UCN 3, 4 - HPSI, ESWS

    International Nuclear Information System (INIS)

    Kim, Kil Yoo; Kang, D. I.; Hwang, M J.; Yang, J. E.

    2005-04-01

    This report describes the Option 2 method applied to high pressure safety injection system(HPSI) and essential service water system(ESW) UCN 3,4 based on the U.S NEI 00-04 Option 2 methodology. Thus, in the Option 2 applications under the 10 CFR 50.69 requirement, the special treatment requirements for 'RISC-3' SSCs could be relaxed, while the regulartory requirements for 'RISC-2' SSCs will be enhanced. The results of Option 2 applications for the two systems of UCN 3,4 show that 161 out of 277 safety related SSCs can be treated with relaxed requirements in the HPSI, while 20 non-safety related SSCs should be treated with special treatment requirements. Also, in the ESW, special treatment requirements for the 121 out of 238 safety related SSCs can be relaxed, and new special treatments are required for 4 non-safety related SSCs

  13. Modeling Polarized Emission from Black Hole Jets: Application to M87 Core Jet

    Directory of Open Access Journals (Sweden)

    Monika Mościbrodzka

    2017-09-01

    Full Text Available We combine three-dimensional general-relativistic numerical models of hot, magnetized Advection Dominated Accretion Flows around a supermassive black hole and the corresponding outflows from them with a general relativistic polarized radiative transfer model to produce synthetic radio images and spectra of jet outflows. We apply the model to the underluminous core of M87 galaxy. The assumptions and results of the calculations are discussed in context of millimeter observations of the M87 jet launching zone. Our ab initio polarized emission and rotation measure models allow us to address the constrains on the mass accretion rate onto the M87 supermassive black hole.

  14. JAK/STAT-1 Signaling Is Required for Reserve Intestinal Stem Cell Activation during Intestinal Regeneration Following Acute Inflammation

    Directory of Open Access Journals (Sweden)

    Camilla A. Richmond

    2018-01-01

    Full Text Available The intestinal epithelium serves as an essential barrier to the outside world and is maintained by functionally distinct populations of rapidly cycling intestinal stem cells (CBC ISCs and slowly cycling, reserve ISCs (r-ISCs. Because disruptions in the epithelial barrier can result from pathological activation of the immune system, we sought to investigate the impact of inflammation on ISC behavior during the regenerative response. In a murine model of αCD3 antibody-induced small-intestinal inflammation, r-ISCs proved highly resistant to injury, while CBC ISCs underwent apoptosis. Moreover, r-ISCs were induced to proliferate and functionally contribute to intestinal regeneration. Further analysis revealed that the inflammatory cytokines interferon gamma and tumor necrosis factor alpha led to r-ISC activation in enteroid culture, which could be blocked by the JAK/STAT inhibitor, tofacitinib. These results highlight an important role for r-ISCs in response to acute intestinal inflammation and show that JAK/STAT-1 signaling is required for the r-ISC regenerative response.

  15. M 87 at metre wavelengths : The LOFAR picture

    NARCIS (Netherlands)

    de Gasperin, F.; Orru, E.; Murgia, M.; Merloni, A.; Falcke, H.; Beck, R.; Beswick, R.; Birzan, L.; Bonafede, A.; Brueggen, M.; Brunetti, G.; Chyzy, K.; Conway, J.; Croston, J. H.; Ensslin, T.; Ferrari, C.; Heald, G.; Heidenreich, S.; Jackson, N.; Macario, G.; McKean, J.; Miley, G.; Morganti, R.; Offringa, A.; Pizzo, R.; Rafferty, D.; Rottgering, H.; Shulevski, A.; Steinmetz, M.; Tasse, C.; van der Tol, S.; van Driel, W.; van Weeren, R. J.; van Zwieten, J. E.; Alexov, A.; Anderson, J.; Asgekar, A.; Avruch, M.; Bell, M.; Bell, M. R.; Bentum, M.; Bernardi, G.; Best, P.; Breitling, F.; Broderick, J. W.; Butcher, A.; Ciardi, B.; Dettmar, R. J.; Eisloeffel, J.; Frieswijk, W.; Gankema, H.; Garrett, M.; Gerbers, M.; Griessmeier, J. M.; Gunst, A. W.; Hassall, T. E.; Hessels, J.; Hoeft, M.; Horneffer, A.; Karastergiou, A.; Koehler, J.; Koopman, Y.; Kuniyoshi, M.; Kuper, G.; Maat, P.; Mann, G.; Mevius, M.; Mulcahy, D. D.; Munk, H.; Nijboer, R.; Noordam, J.; Paas, Harm; Pandey, M.; Pandey, V. N.; Polatidis, A.; Reich, W.; Schoenmakers, A. P.; Sluman, J.; Smirnov, O.; Sobey, C.; Stappers, B.; Swinbank, J.; Tagger, M.; Tang, Y.; van Bemmel, I.; van Cappellen, W.; van Duin, A. P.; van Haarlem, M.; van Leeuwen, J.; Vermeulen, R.; Vocks, C.; White, S.; Wise, M.; Wucknitz, O.; Zarka, P.

    2012-01-01

    Context. M87 is a giant elliptical galaxy located in the centre of the Virgo cluster, which harbours a supermassive black hole of mass 6.4x10(9) M-circle dot, whose activity is responsible for the extended (80 kpc) radio lobes that surround the galaxy. The energy generated by matter falling onto the

  16. Double uterus with obstructed hemivagina and ipsilateral renal agenesis: pelvic anatomic variants in 87 cases.

    Science.gov (United States)

    Fedele, L; Motta, F; Frontino, G; Restelli, E; Bianchi, S

    2013-06-01

    What are the anatomic variants (and their frequencies) of double uterus, obstructed hemivagina and ipsilateral renal agenesis? Most cases examined (72.4%) were of the classic anatomic variant of the Herlyn-Werner-Wunderlich syndrome (with didelphys uterus, obstructed hemivagina and ipsilateral renal agenesis) but the 27.6% of cases are of a rare variant of the syndrome (with uterus septum or cervical agenesis), showing relevant clinical and surgical implications. The extreme variability of anatomic structures involved in this syndrome (both uterus, cervico-vaginal and renal anomalies) is well known, even if a complete and uniform analysis of all its heterogeneous presentations in a large series is lacking. This is a retrospective study with 87 patients referred to our third level referral center between 1981 and 2011. We analyzed the laparoscopic and chart records of 87 women, who referred to our institute with double uterus, unilateral cervico-vaginal obstruction and ipsilateral renal anomalies. Sixty-three of 87 patients had the more classic variant of didelphys uterus with obstructed hemivagina; 10/87 patients had septate bicollis uterus with obstructed hemivagina; 9/87 patients had bicornuate bicollis uterus with obstructed hemivagina; 4/87 patients had didelphys uterus with unilateral cervical atresia; 1/87 patients had bicornuate uterus with one septate cervix and unilateral obstructed hemivagina. This is a retrospective study with a long enrolling period (30 years). New insights in the anatomic variants of this rare syndrome with their relevant surgical implications.

  17. 75 FR 53195 - Security Zone; U.S. Coast Guard BSU Seattle, Pier 36, Seattle, WA

    Science.gov (United States)

    2010-08-31

    ... its effects on them and participate in the rulemaking process. Small businesses may send comments on... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 165 [Docket No. USCG-2010-0021] RIN 1625-AA87 Security Zone; U.S. Coast Guard BSU Seattle, Pier 36, Seattle, WA AGENCY: Coast Guard, DHS. ACTION...

  18. Identifying hotspots of coastal risk and evaluating DRR measures: results from the RISC-KIT project.

    Science.gov (United States)

    Van Dongeren, A.; Ciavola, P.; Viavattene, C.; Dekleermaeker, S.; Martinez, G.; Ferreira, O.; Costa, C.

    2016-02-01

    High-impact storm events have demonstrated the vulnerability of coastal zones in Europe and beyond. These impacts are likely to increase due to predicted climate change and ongoing coastal development. In order to reduce impacts, disaster risk reduction (DRR) measures need to be taken, which prevent or mitigate the effects of storm events. To drive the DRR agenda, the UNISDR formulated the Sendai Framework for Action, and the EU has issued the Floods Directive. However, neither is specific about the methods to be used to develop actionable DRR measures in the coastal zone. Therefore, there is a need to develop methods, tools and approaches which make it possible to: identify and prioritize the coastal zones which are most at risk through a Coastal Risk Assessment Framework, evaluate the effectiveness of DRR options for these coastal areas, using an Early Warning/Decision Support System, which can be used both in the planning and event-phase. This paper gives an overview of the products and results obtained in the FP7-funded project RISC-KIT, which aims to develop and apply a set of tools with which highly-vulnerable coastal areas (so-called "hotspots") can be identified. The identification is done using the Coastal Risk Assessment Framework, or CRAF, which computes the intensity from multi-hazards, the exposure and the vulnerability, all components of risk, including network and cascading effects. Based on this analysis hot spots of risk which warrant coastal protection investments are selected. For these hotspot areas, high-resolution Early Warning and Decision Support Tools are developed with which it is possible to compute in detail the effectiveness of Disaster Risk Reduction measures in storm event scenarios, which helps decide which measures to implement in the planning phase. The same systems, but now driven with real time data, can also be used for early warning systems. All tools are tested on eleven case study areas, at least one on each EU Regional Sea

  19. Infections in British clinical laboratories, 1986-87.

    OpenAIRE

    Grist, N R; Emslie, J A

    1989-01-01

    During 1986-87 this continuing survey showed 15 specific infections in the staff of 235 laboratories, representing 28,524 person years of exposure. The community was the probable source of four of the five cases of tuberculosis and one of the five cases of salmonellosis. Occupational exposure was the probable cause of four infections by Shigella flexneri, three by Salmonella typhimurium, and one by S typhi, all affecting medical laboratory scientific officers (MLSOs) in microbiology. Occupati...

  20. Tumor grading of adult astrocytic glioma on MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Kee Hyun; Choi, Choong Gon; Han, Moon Hee; Lee, Seon Kyu [Seoul National University College of Medicine, Seoul (Korea, Republic of); Suh, Jung Ho [Yonsei University College of Medicine, Seoul (Korea, Republic of); Lee, Ho Kyu; Suh, Dae Chul [Ulsan University College of Medicine, Seoul (Korea, Republic of); Choi, Kyu Ho [Catholic University College of Medicine, Seoul (Korea, Republic of); Byun, Hong Sik [Korea Cancer Center Hospital, Seoul (Korea, Republic of); Choi, Woo Suk [Kyung Hee University College of Medicine, Seoul (Korea, Republic of)

    1994-09-15

    The purpose of this study is to determine predictive MR features for grading of astrocytic gliomas and to evaluate the accuracy of MR grading in these tumors. We retrospectively reviewed 135 cases of supratentorial astrocytic gliomas in adult (age > 15 years), all of which were proved by open biopsy. Two observers analysed MR images independently with criteria of margin, edema, mass effect, signal heterogeneity, necrosis, cyst formation, hemorrhage, tumor vascularity, enhancement degree, and enhancement size. The patterns of enhancement were categorized into no, homogeneous, heterogeneous, thin smooth rim, thin irregular rim, and thick irregular rim enhancement patterns. Observers finally diagnosed each case as one of low-grade astrocytoma, anaplastic astrocytoma or glioblastoma multiforme. Statistically significant MR features for grading of these tumors were revealed as necrosis (p < 0.001), edema (0.008), and signal heterogeneity (p < 0.025). When compared with histopathologic grading, MR graded correctly 76%- 77% of cases in two tired system(low-grade astrocytoma versus high-grade astrocytoma), but only 67%-69% of cases in three tiered system(low-grade astrocytoma, anaplastic astrocytoma, glioblastoma multiforme). No contrast enhancement was seen in 45% and 23% of low-grade astrocytoma and anaplastic astrocytoma respectively. Glioblastoma multiforme frequently showed thick irregular rim enhancement (57%), but no enhancement at all in 8%. We have concluded that necrosis and edema are significant predictive MR features for grading of supratentorial astrocytic gliomas in adult, and MR was correct in 76%-77% of cases for predicting pathologic grading astrocytomas in two tiered system.