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Sample records for active demethylation represent

  1. Active DNA demethylation by oxidation and repair

    Institute of Scientific and Technical Information of China (English)

    Zhizhong Gong; Jian-Kang Zhu

    2011-01-01

    DNA methylation and demethylation are increasingly recognized as important epigenetic factors in both plants and animals.DNA methylation,which is catalyzed by DNA methyltransferases (DNMTs),is a relatively stable and heritable modification that controls gene expression,cellular differentiation,genomic imprinting,paramutation,transposon movement,X-inactivation,and embryogenesis [1].The methylation of cytosine to 5-methylcytosine (5mC) is an important example of DNA modification in animals and plants.This highlight concerns DNA demethylation mechanisms in mammals and whether they are similar to that in plants.

  2. Active DNA demethylation by DNA repair: Facts and uncertainties.

    Science.gov (United States)

    Schuermann, David; Weber, Alain R; Schär, Primo

    2016-08-01

    Pathways that control and modulate DNA methylation patterning in mammalian cells were poorly understood for a long time, although their importance in establishing and maintaining cell type-specific gene expression was well recognized. The discovery of proteins capable of converting 5-methylcytosine (5mC) to putative substrates for DNA repair introduced a novel and exciting conceptual framework for the investigation and ultimate discovery of molecular mechanisms of DNA demethylation. Against the prevailing notion that DNA methylation is a static epigenetic mark, it turned out to be dynamic and distinct mechanisms appear to have evolved to effect global and locus-specific DNA demethylation. There is compelling evidence that DNA repair, in particular base excision repair, contributes significantly to the turnover of 5mC in cells. By actively demethylating DNA, DNA repair supports the developmental establishment as well as the maintenance of DNA methylation landscapes and gene expression patterns. Yet, while the biochemical pathways are relatively well-established and reviewed, the biological context, function and regulation of DNA repair-mediated active DNA demethylation remains uncertain. In this review, we will thus summarize and critically discuss the evidence that associates active DNA demethylation by DNA repair with specific functional contexts including the DNA methylation erasure in the early embryo, the control of pluripotency and cellular differentiation, the maintenance of cell identity, and the nuclear reprogramming. PMID:27247237

  3. The Emerging Nexus of Active DNA Demethylation and Mitochondrial Oxidative Metabolism in Post-Mitotic Neurons

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    Huan Meng

    2014-12-01

    Full Text Available The variable patterns of DNA methylation in mammals have been linked to a number of physiological processes, including normal embryonic development and disease pathogenesis. Active removal of DNA methylation, which potentially regulates neuronal gene expression both globally and gene specifically, has been recently implicated in neuronal plasticity, learning and memory processes. Model pathways of active DNA demethylation involve ten-eleven translocation (TET methylcytosine dioxygenases that are dependent on oxidative metabolites. In addition, reactive oxygen species (ROS and oxidizing agents generate oxidative modifications of DNA bases that can be removed by base excision repair proteins. These potentially link the two processes of active DNA demethylation and mitochondrial oxidative metabolism in post-mitotic neurons. We review the current biochemical understanding of the DNA demethylation process and discuss its potential interaction with oxidative metabolism. We then summarise the emerging roles of both processes and their interaction in neural plasticity and memory formation and the pathophysiology of neurodegeneration. Finally, possible therapeutic approaches for neurodegenerative diseases are proposed, including reprogramming therapy by global DNA demethylation and mitohormesis therapy for locus-specific DNA demethylation in post-mitotic neurons.

  4. MAGEB2 is activated by promoter demethylation in head and neck squamous cell carcinoma.

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    Kavita M Pattani

    Full Text Available PURPOSE: Although promoter hypermethylation has been an accepted means of tumor suppressor gene inactivation, activation of otherwise normally repressed proto-oncogenes by promoter demethylation has been infrequently documented. EXPERIMENTAL DESIGN: In this study we performed an integrative, whole-genome analysis for discovery of epigenetically activated proto-oncogenes in head and neck cancer tumors. We used the 47K GeneChip U133 Plus 2.0 Affymetrix expression microarray platform to obtain re-expression data from 5-aza treated normal cell line and expression data from primary head and neck squamous cell carcinoma (HNSCC tumor tissues and normal mucosa tissues. We then investigated candidate genes by screening promoter regions for CpG islands and bisulfite sequencing followed by QUMSP and RT PCR for the best candidate genes. Finally, functional studies were performed on the top candidate gene. RESULTS: From the top 178 screened candidates 96 had CpG islands in their promoter region. Seven candidate genes showed promoter region methylation in normal mucosa samples and promoter demethylation in a small cohort of primary HNSCC tissues. We then studied the demethylation of the top 3 candidate genes in an expanded cohort of 76 HNSCC tissue samples and 17 normal mucosa samples. We identified MAGEB2 as having significant promoter demethylation in primary head and neck squamous cell carcinoma tissues. We then found significantly higher expression of MAGEB2 in tumors in a separate cohort of 73 primary HNSCC tissues and 31 normal tissues. Finally, we found that MAGEB2 has growth promoting effects on minimally transformed oral keratinocyte cell lines but not a definite effect on HNSCC cell lines. CONCLUSION: In conclusion, we identified MAGEB2 as activated by promoter demethylation in HNSCCand demonstrates growth promoting effects in a minimally transformed oral keratinocyte cell line. More studies are needed to evaluate MAGBE2's exact role in HNSCC.

  5. Targeted DNA demethylation and activation of endogenous genes using programmable TALE-TET1 fusion proteins.

    Science.gov (United States)

    Maeder, Morgan L; Angstman, James F; Richardson, Marcy E; Linder, Samantha J; Cascio, Vincent M; Tsai, Shengdar Q; Ho, Quan H; Sander, Jeffry D; Reyon, Deepak; Bernstein, Bradley E; Costello, Joseph F; Wilkinson, Miles F; Joung, J Keith

    2013-12-01

    Genome-wide studies have defined cell type-specific patterns of DNA methylation that are important for regulating gene expression in both normal development and disease. However, determining the functional significance of specific methylation events remains challenging, owing to the lack of methods for removing such modifications in a targeted manner. Here we describe an approach for efficient targeted demethylation of specific CpGs in human cells using fusions of engineered transcription activator-like effector (TALE) repeat arrays and the TET1 hydroxylase catalytic domain. Using these TALE-TET1 fusions, we demonstrate that modification of critical methylated promoter CpG positions can lead to substantial increases in the expression of endogenous human genes. Our results delineate a strategy for understanding the functional significance of specific CpG methylation marks in the context of endogenous gene loci and validate programmable DNA demethylation reagents with potential utility for research and therapeutic applications.

  6. Coordinated activation of candidate proto-oncogenes and cancer testes antigens via promoter demethylation in head and neck cancer and lung cancer.

    Directory of Open Access Journals (Sweden)

    Ian M Smith

    Full Text Available BACKGROUND: Epigenetic alterations have been implicated in the pathogenesis of solid tumors, however, proto-oncogenes activated by promoter demethylation have been sporadically reported. We used an integrative method to analyze expression in primary head and neck squamous cell carcinoma (HNSCC and pharmacologically demethylated cell lines to identify aberrantly demethylated and expressed candidate proto-oncogenes and cancer testes antigens in HNSCC. METHODOLOGY/PRINCIPAL FINDINGS: We noted coordinated promoter demethylation and simultaneous transcriptional upregulation of proto-oncogene candidates with promoter homology, and phylogenetic footprinting of these promoters demonstrated potential recognition sites for the transcription factor BORIS. Aberrant BORIS expression correlated with upregulation of candidate proto-oncogenes in multiple human malignancies including primary non-small cell lung cancers and HNSCC, induced coordinated proto-oncogene specific promoter demethylation and expression in non-tumorigenic cells, and transformed NIH3T3 cells. CONCLUSIONS/SIGNIFICANCE: Coordinated, epigenetic unmasking of multiple genes with growth promoting activity occurs in aerodigestive cancers, and BORIS is implicated in the coordinated promoter demethylation and reactivation of epigenetically silenced genes in human cancers.

  7. Hepatitis B virus X protein induces EpCAM expression via active DNA demethylation directed by RelA in complex with EZH2 and TET2.

    Science.gov (United States)

    Fan, H; Zhang, H; Pascuzzi, P E; Andrisani, O

    2016-02-11

    Chronic hepatitis B virus (HBV) infection is a major risk factor for developing hepatocellular carcinoma (HCC), and HBV X protein (HBx) acts as cofactor in hepatocarcinogenesis. In liver tumors from animals modeling HBx- and HBV-mediated hepatocarcinogenesis, downregulation of chromatin regulating proteins SUZ12 and ZNF198 induces expression of several genes, including epithelial cell adhesion molecule (EpCAM). EpCAM upregulation occurs in HBV-mediated HCCs and hepatic cancer stem cells, by a mechanism not understood. Herein we demonstrate HBx induces EpCAM expression via active DNA demethylation. In hepatocytes, EpCAM is silenced by polycomb repressive complex 2 (PRC2) and ZNF198/LSD1/Co-REST/HDAC1 chromatin-modifying complexes. Cells with stable knockdown of SUZ12, an essential PRC2 subunit, upon HBx expression demethylate a CpG dinucleotide located adjacent to NF-κB/RelA half-site. This NF-κB/RelA site is in a CpG island downstream from EpCAM transcriptional start site (TSS). Chromatin immunoprecipitation (ChIP) assays demonstrate HBx-dependent RelA occupancy of NF-κB half-site, whereas RelA knockdown suppresses CpG demethylation and EpCAM expression. Tumor necrosis factor-α activates RelA, propagating demethylation to nearby CpG sites, shown by sodium bisulfite sequencing. RelA-dependent demethylation occurring upon HBx expression requires methyltrasferase EZH2, TET2 a key factor in cytosine demethylation and inactive DNMT3L, shown by knockdown assays and sodium bisulfite sequencing. Co-immunoprecipitations and sequential ChIP assays demonstrate that RelA in the presence of HBx forms a complex with EZH2, TET2 and DNMT3L, although the role of DNMT3L remains to be understood. Interestingly, the human EpCAM gene also has a CpG island downstream from its TSS, and a NF-κB-binding site flanked by CpGs. HepG2 cells derived from human HCC exhibit demethylation of these NF-κB-flanking CpG sites, and HBV replication propagates demethylation to nearby CpG sites. DLK

  8. Evidence that active demethylation mechanisms maintain the genome of carcinoma in situ cells hypomethylated in the adult testis

    DEFF Research Database (Denmark)

    Kristensen, D G; Nielsen, J E; Jørgensen, Anne;

    2014-01-01

    absent. Both maintenance and de novo methyltransferases were detected in CIS cells.Conclusion:The data are consistent with the presence of an active DNA de-methylation pathway in CIS cells. The hypomethylated genome of CIS cells may contribute to phenotypic plasticity and invasive capabilities......Background:Developmental arrest of fetal germ cells may lead to neoplastic transformation and formation of germ cell tumours via carcinoma in situ (CIS) cells. Normal fetal germ cell development requires complete erasure and re-establishment of DNA methylation. In contrast to normal spermatogonia......, the genome of CIS cells remains unmethylated in the adult testis. We here investigated the possible active and passive pathways that can sustain the CIS genome hypomethylated in the adult testis.Methods:The levels of 5-methyl-cytosine (5mC) and 5-hydroxy-methyl-cytosine (5hmC) in DNA from micro-dissected CIS...

  9. MERVL/Zscan4 Network Activation Results in Transient Genome-wide DNA Demethylation of mESCs.

    Science.gov (United States)

    Eckersley-Maslin, Mélanie A; Svensson, Valentine; Krueger, Christel; Stubbs, Thomas M; Giehr, Pascal; Krueger, Felix; Miragaia, Ricardo J; Kyriakopoulos, Charalampos; Berrens, Rebecca V; Milagre, Inês; Walter, Jörn; Teichmann, Sarah A; Reik, Wolf

    2016-09-27

    Mouse embryonic stem cells are dynamic and heterogeneous. For example, rare cells cycle through a state characterized by decondensed chromatin and expression of transcripts, including the Zscan4 cluster and MERVL endogenous retrovirus, which are usually restricted to preimplantation embryos. Here, we further characterize the dynamics and consequences of this transient cell state. Single-cell transcriptomics identified the earliest upregulated transcripts as cells enter the MERVL/Zscan4 state. The MERVL/Zscan4 transcriptional network was also upregulated during induced pluripotent stem cell reprogramming. Genome-wide DNA methylation and chromatin analyses revealed global DNA hypomethylation accompanying increased chromatin accessibility. This transient DNA demethylation was driven by a loss of DNA methyltransferase proteins in the cells and occurred genome-wide. While methylation levels were restored once cells exit this state, genomic imprints remained hypomethylated, demonstrating a potential global and enduring influence of endogenous retroviral activation on the epigenome. PMID:27681430

  10. Fluconazole Binding and Sterol Demethylation in Three CYP51 Isoforms Indicate Differences in Active Site Topology

    Energy Technology Data Exchange (ETDEWEB)

    Bellamine, A.; Lepesheva, Galina I.; Waterman, Mike (Vanderbilt)

    2010-11-16

    14{alpha}-Demethylase (CYP51) is a key enzyme in all sterol biosynthetic pathways (animals, fungi, plants, protists, and some bacteria), catalyzing the removal of the C-14 methyl group following cyclization of squalene. Based on mutations found in CYP51 genes from Candida albicans azole-resistant isolates obtained after fluconazole treatment of fungal infections, and using site-directed mutagenesis, we have found that fluconazole binding and substrate metabolism vary among three different CYP51 isoforms: human, fungal, and mycobacterial. In C. albicans, the Y132H mutant from isolates shows no effect on fluconazole binding, whereas the F145L mutant results in a 5-fold increase in its IC{sub 50} for fluconazole, suggesting that F145 (conserved only in fungal 14{alpha}-demethylases) interacts with this azole. In C. albicans, F145L accounts, in part, for the difference in fluconazole sensitivity reported between mammals and fungi, providing a basis for treatment of fungal infections. The C. albicans Y132H and human Y145H CYP51 mutants show essentially no effect on substrate metabolism, but the Mycobacterium tuberculosis F89H CYP51 mutant loses both its substrate binding and metabolism. Because these three residues align in the three isoforms, the results indicate that their active sites contain important structural differences, and further emphasize that fluconazole and substrate binding are uncoupled properties.

  11. Azacytidine and decitabine induce gene-specific and non-random DNA demethylation in human cancer cell lines.

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    Sabine Hagemann

    Full Text Available The DNA methyltransferase inhibitors azacytidine and decitabine represent archetypal drugs for epigenetic cancer therapy. To characterize the demethylating activity of azacytidine and decitabine we treated colon cancer and leukemic cells with both drugs and used array-based DNA methylation analysis of more than 14,000 gene promoters. Additionally, drug-induced demethylation was compared to methylation patterns of isogenic colon cancer cells lacking both DNA methyltransferase 1 (DNMT1 and DNMT3B. We show that drug-induced demethylation patterns are highly specific, non-random and reproducible, indicating targeted remethylation of specific loci after replication. Correspondingly, we found that CG dinucleotides within CG islands became preferentially remethylated, indicating a role for DNA sequence context. We also identified a subset of genes that were never demethylated by drug treatment, either in colon cancer or in leukemic cell lines. These demethylation-resistant genes were enriched for Polycomb Repressive Complex 2 components in embryonic stem cells and for transcription factor binding motifs not present in demethylated genes. Our results provide detailed insights into the DNA methylation patterns induced by azacytidine and decitabine and suggest the involvement of complex regulatory mechanisms in drug-induced DNA demethylation.

  12. OGG1 is essential in oxidative stress induced DNA demethylation.

    Science.gov (United States)

    Zhou, Xiaolong; Zhuang, Ziheng; Wang, Wentao; He, Lingfeng; Wu, Huan; Cao, Yan; Pan, Feiyan; Zhao, Jing; Hu, Zhigang; Sekhar, Chandra; Guo, Zhigang

    2016-09-01

    DNA demethylation is an essential cellular activity to regulate gene expression; however, the mechanism that triggers DNA demethylation remains unknown. Furthermore, DNA demethylation was recently demonstrated to be induced by oxidative stress without a clear molecular mechanism. In this manuscript, we demonstrated that 8-oxoguanine DNA glycosylase-1 (OGG1) is the essential protein involved in oxidative stress-induced DNA demethylation. Oxidative stress induced the formation of 8-oxoguanine (8-oxoG). We found that OGG1, the 8-oxoG binding protein, promotes DNA demethylation by interacting and recruiting TET1 to the 8-oxoG lesion. Downregulation of OGG1 makes cells resistant to oxidative stress-induced DNA demethylation, while over-expression of OGG1 renders cells susceptible to DNA demethylation by oxidative stress. These data not only illustrate the importance of base excision repair (BER) in DNA demethylation but also reveal how the DNA demethylation signal is transferred to downstream DNA demethylation enzymes. PMID:27251462

  13. Transcriptional activation of the Epstein-Barr virus latency C promoter after 5-azacytidine treatment: evidence that demethylation at a single CpG site is crucial.

    Science.gov (United States)

    Robertson, K D; Hayward, S D; Ling, P D; Samid, D; Ambinder, R F

    1995-01-01

    The Epstein-Barr Virus (EBV) latency C promoter (Cp) is the origin of transcripts for six viral proteins. The promoter is active in lymphoblastoid B-cell lines but silent in many EBV-associated tumors and tumor cell lines. In these latter cell lines, the viral episome is hypermethylated in the vicinity of this promoter. We show that in such a cell line (Rael, a Burkitt's lymphoma line), 5-azacytidine inhibits DNA methyltransferase, brings about demethylation of EBV genomes, activates Cp transcription, and induces the expression of EBNA-2. Investigation of the phenomenon demonstrates the importance of the methylation status of a particular CpG site for the regulation of the Cp: (i) genomic sequencing shows that this site is methylated when the Cp is inactive and is not methylated when the promoter is active; (ii) methylation or transition mutation at this site abolishes complex formation with a cellular binding activity (CBF2) as determined by electrophoretic mobility shift analyses, competition binding analyses, and DNase I footprinting; and (iii) a single C --> T transition mutation at this site is associated with a marked reduction (> 50-fold) of transcriptional activity in a reporter plasmid. Thus, the CBF2 binding activity is shown to be methylation sensitive and crucial to EBNA-2-mediated activation of the Cp. PMID:7565767

  14. Interactions between CYP2C9 and CYP2C19 in reconstituted binary systems influence their catalytic activity: possible rationale for the inability of CYP2C19 to catalyze methoxychlor demethylation in human liver microsomes.

    Science.gov (United States)

    Hazai, Eszter; Kupfer, David

    2005-01-01

    Previous studies in our laboratory showed that among cDNA-expressed human cytochrome P450 (P450) supersomes, CYP2C19 was the most active in methoxychlor-O-demethylation. However, based on the lack of inhibition of methoxychlor-O-demethylation by monoclonal anti-CYP2C19 antibodies in human liver microsomes (HLM), CYP2C19 did not seem to catalyze that reaction in HLM. By contrast, CYP2C9, much less active than CYP2C19 in supersomes, was the most active in HLM. The current study examines whether the lack of methoxychlor-O-demethylation by CYP2C19 in HLM was due to CYP2C19 exhibiting inferior competition for the NADPH-cytochrome P450 reductase (CPR) versus CYP2C9 and explores the interactions between CYP2C9 and CYP2C19 in a singular and binary complex of a reconstituted system. When reconstituted with CPR, cytochrome b(5), and lipid, purified CYP2C19 and CYP2C9 catalyzed methoxychlor-O-demethylation. However, whereas equimolar CPR to CYP2C9 supported maximal rates of methoxychlor demethylation and diclofenac hydroxylation, the rate of methoxychlor demethylation by CYP2C19 was not fully saturated, even with a 9-fold molar excess of CPR over CYP2C19. This behavior of CYP2C19 was also observed with S-mephenytoin as the substrate. When a binary reconstitution system was prepared by mixing CYP2C9 and CYP2C19 enzymes, methoxychlor-O-demethylation and S-mephenytoin hydroxylation by CYP2C19 were dramatically inhibited. Inhibition depended on the amount of CPR and substrate used. By contrast, in the incubation containing CYP2C9, diclofenac hydroxylation was activated by the presence of CYP2C19. These results show that interactions among P450 enzymes can modulate their catalytic rates, which depend on the substrate undergoing metabolism.

  15. Activation of HIV transcription by the viral Tat protein requires a demethylation step mediated by lysine-specific demethylase 1 (LSD1/KDM1.

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    Naoki Sakane

    2011-08-01

    Full Text Available The essential transactivator function of the HIV Tat protein is regulated by multiple posttranslational modifications. Although individual modifications are well characterized, their crosstalk and dynamics of occurrence during the HIV transcription cycle remain unclear.We examine interactions between two critical modifications within the RNA-binding domain of Tat: monomethylation of lysine 51 (K51 mediated by Set7/9/KMT7, an early event in the Tat transactivation cycle that strengthens the interaction of Tat with TAR RNA, and acetylation of lysine 50 (K50 mediated by p300/KAT3B, a later process that dissociates the complex formed by Tat, TAR RNA and the cyclin T1 subunit of the positive transcription elongation factor b (P-TEFb. We find K51 monomethylation inhibited in synthetic Tat peptides carrying an acetyl group at K50 while acetylation can occur in methylated peptides, albeit at a reduced rate. To examine whether Tat is subject to sequential monomethylation and acetylation in cells, we performed mass spectrometry on immunoprecipitated Tat proteins and generated new modification-specific Tat antibodies against monomethylated/acetylated Tat. No bimodified Tat protein was detected in cells pointing to a demethylation step during the Tat transactivation cycle. We identify lysine-specific demethylase 1 (LSD1/KDM1 as a Tat K51-specific demethylase, which is required for the activation of HIV transcription in latently infected T cells. LSD1/KDM1 and its cofactor CoREST associates with the HIV promoter in vivo and activate Tat transcriptional activity in a K51-dependent manner. In addition, small hairpin RNAs directed against LSD1/KDM1 or inhibition of its activity with the monoamine oxidase inhibitor phenelzine suppresses the activation of HIV transcription in latently infected T cells.Our data support the model that a LSD1/KDM1/CoREST complex, normally known as a transcriptional suppressor, acts as a novel activator of HIV transcription through

  16. DNA demethylation in the PTEN gene promoter induced by 5-azacytidine activates PTEN expression in the MG-63 human osteosarcoma cell line.

    Science.gov (United States)

    Song, Deye; Ni, Jiangdong; Xie, Hongming; Ding, Muliang; Wang, Jun

    2014-05-01

    This study used the MG-63 osteosarcoma cell line to investigate the demethylation of the phosphate and tension homolog (PTEN) gene promoter and the change in PTEN gene expression levels, which are caused by the methylation inhibitor 5-azacytidine (5-Zac), and the association between the two. Different concentrations of 5-Zac (0, 5 and 10 μmol/l) were added into the MG-63 cell culture medium and the cells were cultured for 72 h. The following techniques were performed on the cells: Western blot analysis to detect the PTEN protein; reverse transcription-polymerase chain reaction (PCR) to detect the mRNA transcription levels of the PTEN gene; flow cytometry to detect the cell apoptotic rate; and sodium bisulfate to deal with the DNA of each group. The genes of the PTEN promoter and the transcription factors specificity protein 1 (Sp1) and Myc were PCR amplified and transformed into Escherichia coli, then a number of clones were selected for sequencing and the methylation status of the amplified PTEN promoter fragment was detected. Following culture of the MG-63 cells with 5-Zac at concentrations of 0, 5 and 10 μmol/l for 72 h, the expression levels of PTEN protein in each group were gradually increased, presenting a concentration-dependent effect: Group 0 μmol/l compared with groups 5 and 10 μmol/l, P<0.05; and group 5 μmol/l compared with group 10 μmol/l, P=0.007. The mRNA expression levels of the PTEN gene significantly increased. The apoptotic rates of groups 0, 5 and 10 μmol/l were 0.69±0.42, 2.50±0.30 and 6.59±0.62%, and significant differences (P<0.01) were observed between every two groups. The bisulfate DNA sequencing results of three groups showed that, following the treatment with 5-Zac, the binding of the CG site to transcription factors was affected by demethylation. The average rate of demethylation indicated a statistical difference among the three groups. In conclusion, the methylation inhibitor 5-Zac leads to a significant increase in the

  17. DNA demethylation in the PTEN gene promoter induced by 5-azacytidine activates PTEN expression in the MG-63 human osteosarcoma cell line

    Science.gov (United States)

    SONG, DEYE; NI, JIANGDONG; XIE, HONGMING; DING, MULIANG; WANG, JUN

    2014-01-01

    This study used the MG-63 osteosarcoma cell line to investigate the demethylation of the phosphate and tension homolog (PTEN) gene promoter and the change in PTEN gene expression levels, which are caused by the methylation inhibitor 5-azacytidine (5-Zac), and the association between the two. Different concentrations of 5-Zac (0, 5 and 10 μmol/l) were added into the MG-63 cell culture medium and the cells were cultured for 72 h. The following techniques were performed on the cells: Western blot analysis to detect the PTEN protein; reverse transcription-polymerase chain reaction (PCR) to detect the mRNA transcription levels of the PTEN gene; flow cytometry to detect the cell apoptotic rate; and sodium bisulfate to deal with the DNA of each group. The genes of the PTEN promoter and the transcription factors specificity protein 1 (Sp1) and Myc were PCR amplified and transformed into Escherichia coli, then a number of clones were selected for sequencing and the methylation status of the amplified PTEN promoter fragment was detected. Following culture of the MG-63 cells with 5-Zac at concentrations of 0, 5 and 10 μmol/l for 72 h, the expression levels of PTEN protein in each group were gradually increased, presenting a concentration-dependent effect: Group 0 μmol/l compared with groups 5 and 10 μmol/l, P<0.05; and group 5 μmol/l compared with group 10 μmol/l, P=0.007. The mRNA expression levels of the PTEN gene significantly increased. The apoptotic rates of groups 0, 5 and 10 μmol/l were 0.69±0.42, 2.50±0.30 and 6.59±0.62%, and significant differences (P<0.01) were observed between every two groups. The bisulfate DNA sequencing results of three groups showed that, following the treatment with 5-Zac, the binding of the CG site to transcription factors was affected by demethylation. The average rate of demethylation indicated a statistical difference among the three groups. In conclusion, the methylation inhibitor 5-Zac leads to a significant increase in the

  18. Process for demethylating dimethylsulfonium compounds

    NARCIS (Netherlands)

    Hansen, Theo; van der Maarel, Marc

    1998-01-01

    PCT No. PCT/EP94/01640 Sec. 371 Date Nov. 14, 1995 Sec. 102(e) Date Nov. 14, 1995 PCT Filed May 16, 1994 PCT Pub. No. WO94/26918 PCT Pub. Date Nov. 24, 1994Process for preparing S-methylmercapto and mercapto compounds comprising the step of demethylating a dimethylsulfonium compound of formula I to

  19. Non-small-cell lung cancer-induced immunosuppression by increased human regulatory T cells via Foxp3 promoter demethylation.

    Science.gov (United States)

    Ke, Xing; Zhang, Shuping; Xu, Jian; Liu, Genyan; Zhang, Lixia; Xie, Erfu; Gao, Li; Li, Daqian; Sun, Ruihong; Wang, Fang; Pan, Shiyang

    2016-05-01

    Patients with non-small-cell lung cancer (NSCLC) have immune defects that are poorly understood. Forkhead box protein P3 (Foxp3) is crucial for immunosuppression by CD4(+) regulatory T cells (Tregs). It is not well known how NSCLC induces Foxp3 expression and causes immunosuppression in tumor-bearing patients. Our study found a higher percentage of CD4(+) Tregs in the peripheral blood of NSCLC compared with healthy donors. NSCLC patients showed demethylation of eight CpG sites within the Foxp3 promoter with methylation ratios negatively correlated with CD4(+)CD25(+)Foxp3(+) T levels. Foxp3 expression in CD4(+) Tregs was directly regulated by Foxp3 promoter demethylation and was involved in immunosuppression by NSCLC. To verify the effect of tumor cells on the phenotype and function of CD4(+) Tregs, we established a coculture system using NSCLC cell line and healthy CD4(+) T cells and showed that SPC-A1 induced IL-10 and TGF-β1 secretion by affecting the function of CD4(+) Tregs. The activity of DNA methyltransferases from CD4(+) T was decreased during this process. Furthermore, eight CpG sites within the Foxp3 promoter also appeared to have undergone demethylation. Foxp3 is highly expressed in CD4(+) T cells, and this may be caused by gene promoter demethylation. These induced Tregs are highly immunosuppressive and dramatically inhibit the proliferative activity of naïve CD4(+) T cells. Our study provides one possible mechanism describing Foxp3 promoter demethylation changes by which NSCLC down-regulates immune responses and contributes to tumor progression. Foxp3 represents an important target for NSCLC anti-tumor immunotherapy.

  20. Identification of Three New N-Demethylated and O-Demethyled Bisbenzylisoquinoline Alkaloid Metabolites of Isoliensinine from Dog Hepatic Microsomes

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    Su Zeng

    2012-10-01

    Full Text Available Isoliensinine, a natural phenolic bisbenzyltetrahydroisoquinoline alkaloid, has received considerable attention for its potential biological effects such as antioxidant and anti-HIV activities. From the dog hepatic microsomes of isoliensinine, three new N-demethylated and O-demethylated metabolites, 2-N-desmethyl-isoliensinine (M1, 2'-N-desmethylisoliensinine (M2, and 2'-N-6-O-didesmethylisoliensinine (M3, were identified by high-performance liquid chromatography and data-dependent electrospray ionization tandem mass spectrometry. Possible metabolic pathways for isoliensinine have been proposed. The result should prove very helpful for evaluation of the drug-like properties of isoliensinine and other bisbenzylisoquinoline alkaloids.

  1. Recent activities of the Seismology Division Early Career Representative(s)

    Science.gov (United States)

    Agius, Matthew; Van Noten, Koen; Ermert, Laura; Mai, P. Martin; Krawczyk, CharLotte

    2016-04-01

    The European Geosciences Union is a bottom-up-organisation, in which its members are represented by their respective scientific divisions, committees and council. In recent years, EGU has embarked on a mission to reach out for its numerous 'younger' members by giving awards to outstanding young scientists and the setting up of Early Career Scientists (ECS) representatives. The division representative's role is to engage in discussions that concern students and early career scientists. Several meetings between all the division representatives are held throughout the year to discuss ideas and Union-wide issues. One important impact ECS representatives have had on EGU is the increased number of short courses and workshops run by ECS during the annual General Assembly. Another important contribution of ECS representatives was redefining 'Young Scientist' to 'Early Career Scientist', which avoids discrimination due to age. Since 2014, the Seismology Division has its own ECS representative. In an effort to more effectively reach out for young seismologists, a blog and a social media page dedicated to seismology have been set up online. With this dedicated blog, we'd like to give more depth to the average browsing experience by enabling young researchers to explore various seismology topics in one place while making the field more exciting and accessible to the broader community. These pages are used to promote the latest research especially of young seismologists and to share interesting seismo-news. Over the months the pages proved to be popular, with hundreds of views every week and an increased number of followers. An online survey was conducted to learn more about the activities and needs of early career seismologists. We present the results from this survey, and the work that has been carried out over the last two years, including detail of what has been achieved so far, and what we would like the ECS representation for Seismology to achieve. Young seismologists are

  2. Dynamic and selective HERV RNA expression in neuroblastoma cells subjected to variation in oxygen tension and demethylation.

    Science.gov (United States)

    Hu, Lijuan; Uzhameckis, Dmitrijs; Hedborg, Fredrik; Blomberg, Jonas

    2016-01-01

    We studied HERV expression in cell lines after hypoxia, mitogenic stimulation, and demethylation, to better understand if hypoxia may play a role in ERV activation also within the nervous system, as represented by neuroblastoma cell lines. The level of RNA of four human ERV groups (HERVs) (HERVE, I/T, H, and W), and three housekeeping genes, of different cell lines including A549, COS-1, Namalwa, RD-L and Vero-E6, as well as human neuroblastoma cell lines SH-SY5Y, SK-N-DZ, and SK-N-AS were studied using reverse transcription and real-time quantitative PCR (QPCR). During the course of recovery from hypoxia a pronounced and selective activation of RNA expression of HERVW-like sequences, but not of HERVE, I/T, H, and three housekeeping genes, was found in the neuroblastoma cell lines, most pronounced in SK-N-DZ. In the SK-N-DZ cell line, we also tested the expression of HERVs after chemical treatments. HERVW-like sequences were selectively upregulated by 5-azacytidine, a demethylating agent. Some HERVW loci seem especially responsive to hypoxia and demethylation. HERV expression in neuroblastoma cells is selectively and profoundly influenced by some physiological and chemical stimuli.

  3. Representing cognitive activities and errors in HRA trees

    International Nuclear Information System (INIS)

    A graphic representation method is presented herein for adapting an existing technology--human reliability analysis (HRA) event trees, used to support event sequence logic structures and calculations--to include a representation of the underlying cognitive activity and corresponding errors associated with human performance. The analyst is presented with three potential means of representing human activity: the NUREG/CR-1278 HRA event tree approach; the skill-, rule- and knowledge-based paradigm; and the slips, lapses, and mistakes paradigm. The above approaches for representing human activity are integrated in order to produce an enriched HRA event tree -- the cognitive event tree system (COGENT)-- which, in turn, can be used to increase the analyst's understanding of the basic behavioral mechanisms underlying human error and the representation of that error in probabilistic risk assessment. Issues pertaining to the implementation of COGENT are also discussed

  4. Ligand Binding Affinities of Arctigenin and Its Demethylated Metabolites to Estrogen Receptor Alpha

    OpenAIRE

    Masao Hattori; Jong-Hyun Lee; Jong-Sik Jin

    2013-01-01

    Phytoestrogens are defined as plant-derived compounds with estrogen-like activities according to their chemical structures and activities. Plant lignans are generally categorized as phytoestrogens. It was reported that (−)-arctigenin, the aglycone of arctiin, was demethylated to (−)-dihydroxyenterolactone (DHENL) by Eubacterium (E.) sp. ARC-2. Through stepwise demethylation, E. sp. ARC-2 produced six intermediates, three mono-desmethylarctigenins and three di-desmethylarct...

  5. Simultaneous quantification of phencynonate and its active metabolite N-demethyl phencynonate in human plasma using liquid chromatography and isotope-dilution mass spectrometry.

    Science.gov (United States)

    Chen, Zhengang; Xie, Hui; Liu, Jinbo; Wang, Guangshun

    2015-09-01

    A sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously quantify phencynonate (PCN) and its major metabolite N-demethyl phencynonate (DM-PCN) in human plasma. Following one-step liquid-liquid extraction, the analytes were separated on a reversed-phase C18 column. Methanol and 0.02% formic acid in 10 mM ammonium acetate (62:38, v/v) was used as isocratic mobile phase at a flow-rate of 0.3 mL/min. An API 5000 tandem mass spectrometer equipped with a Turbo IonSpray ionization source was used as the detector and was operated in the positive ion mode. Multiple reaction monitoring using the transition of m/z 358.4 → m/z 156.2, m/z 344.4 → m/z 142.2, and m/z 361.3 → m/z 159.2 was performed to quantify PCN, DM-PCN, and the internal standard (D3 -PCN), respectively. This approach showed a lower limit of quantification of 10 pg/mL and 25 pg/mL for PCN and DM-PCN in plasma, respectively. This sensitivity was at least 50-fold superior to previously reported ones and thus enabled the approach well applicable to low-dose pharmacokinetic studies. The intra- and inter-day precisions were less than 14.2 % at each QC level for both PCN and DM-PCN. The inter-day relative errors ranged from -1.9% to -4.9% for PCN, and from 0.6% to 6.4% for DM-PCN. As a proof of principle, the validated method was successfully applied to simultaneous quantification of circulating PCN and DM-PCN in healthy subjects after a single oral administration of 2 mg phencynonate hydrochloride pellet.

  6. Demethylating agent, 5-azacytidine, reverses differentiation of embryonic stem cells

    International Nuclear Information System (INIS)

    The de novo methylation activity is essential for embryonic development as well as embryonic stem (ES) cell differentiation, where the intensive and extensive DNA methylation was detected. In this study, we investigated the effects of a demethylating agent, 5-azacytidine (5-AzaC), on differentiated ES cells in order to study the possibility of reversing the differentiation process. We first induced differentiation of ES cells by forming embryoid bodies, and then the cells were treated with 5-AzaC. The cells showed some undifferentiated features such as stem cell-like morphology with unclear cell-to-cell boundary and proliferative responsiveness to LIF. Moreover, 5-AzaC increased the expressions of ES specific markers, SSEA-1, and alkaline phosphatase activity as well as ES specific genes, Oct4, Nanog, and Sox2. We also found that 5-AzaC demethylated the promoter region of H19 gene, a typical methylated gene during embryonic differentiation. These results indicate that 5-AzaC reverses differentiation state of ES cells through its DNA demethylating activity to differentiation related genes

  7. Oncogenic Myc Induces Expression of Glutamine Synthetase through Promoter Demethylation.

    Science.gov (United States)

    Bott, Alex J; Peng, I-Chen; Fan, Yongjun; Faubert, Brandon; Zhao, Lu; Li, Jinyu; Neidler, Sarah; Sun, Yu; Jaber, Nadia; Krokowski, Dawid; Lu, Wenyun; Pan, Ji-An; Powers, Scott; Rabinowitz, Joshua; Hatzoglou, Maria; Murphy, Daniel J; Jones, Russell; Wu, Song; Girnun, Geoffrey; Zong, Wei-Xing

    2015-12-01

    c-Myc is known to promote glutamine usage by upregulating glutaminase (GLS), which converts glutamine to glutamate that is catabolized in the TCA cycle. Here we report that in a number of human and murine cells and cancers, Myc induces elevated expression of glutamate-ammonia ligase (GLUL), also termed glutamine synthetase (GS), which catalyzes the de novo synthesis of glutamine from glutamate and ammonia. This is through upregulation of a Myc transcriptional target thymine DNA glycosylase (TDG), which promotes active demethylation of the GS promoter and its increased expression. Elevated expression of GS promotes cell survival under glutamine limitation, while silencing of GS decreases cell proliferation and xenograft tumor growth. Upon GS overexpression, increased glutamine enhances nucleotide synthesis and amino acid transport. These results demonstrate an unexpected role of Myc in inducing glutamine synthesis and suggest a molecular connection between DNA demethylation and glutamine metabolism in Myc-driven cancers.

  8. Engineering activities on the ITER representative diagnostic equatorial port plug

    International Nuclear Information System (INIS)

    Most of ITER diagnostic systems are integrated in port plugs, which are water cooled stainless steel structures inserted into the vacuum vessel ports. The port plug must provide basic functions such as neutron and gamma shielding, supporting the first wall armour (BSM), closing the vacuum vessel ports, while supporting the diagnostic equipments. ITER diagnostic port plug must resist a severe environment like high temperature due to neutron interaction with the structures and high electromechanical loading during disruptions events. CEA has contributed to the design and integration tasks in the frame of the representative equatorial port plug EQ no. 01, in particular on the engineering, structural and thermal finite element analysis. These detailed analyses have highlighted some design issues which were worked out through different solutions. This paper contains a description of the engineering activities performed such as: -The static mechanical calculations of the top plate closure system under disruption load. -The static mechanical calculations of the BSM attachment to the port plug. These two first studies led to design changes proposals which significantly improved the behaviour of the structures but also showed that the safety margin with respect to design limits is quite low. -The design of a Diagnostic Shield Module (DSM) integrated inside the port plug and a proposition of attachment scheme, with respect to disruption loads. The manufacturing of the DSM has been taken into account, as well as diagnostic integration inside the structure and maintenance aspects. -The thermal assessment of the port plug under neutronic load during normal operation, with the optimization of the cooling system. The maximum temperature calculated in normal operation has been reduced from 900 deg. C to less than 400 deg. C in the front plate; and the cooling arrangement at the back of the port plug has been simplified without important temperature increase.

  9. Tetrahydrofolate serves as a methyl acceptor in the demethylation of dimethylsulfoniopropionate in cell extracts of sulfate-reducing bacteria

    NARCIS (Netherlands)

    Jansen, M; Hansen, T.A.

    1998-01-01

    Tetrahydrofolate was shown to function as a methyl acceptor in the anaerobic demethylation of dimethylsulfoniopropionate to methylthiopropionate in cell extracts of the sulfate-reducing bacterium strain WN. Dimethylsulfoniopropionate-dependent activities were 0.56 mu mol methyltetrahydrofolate min(-

  10. Ligand binding affinities of arctigenin and its demethylated metabolites to estrogen receptor alpha.

    Science.gov (United States)

    Jin, Jong-Sik; Lee, Jong-Hyun; Hattori, Masao

    2013-01-01

    Phytoestrogens are defined as plant-derived compounds with estrogen-like activities according to their chemical structures and activities. Plant lignans are generally categorized as phytoestrogens. It was reported that (-)-arctigenin, the aglycone of arctiin, was demethylated to (-)-dihydroxyenterolactone (DHENL) by Eubacterium (E.) sp. ARC-2. Through stepwise demethylation, E. sp. ARC-2 produced six intermediates, three mono-desmethylarctigenins and three di-desmethylarctigenins. In the present study, ligand binding affinities of (-)-arctigenin and its seven metabolites, including DHENL, were investigated for an estrogen receptor alpha, and found that demethylated metabolites had stronger binding affinities than (-)-arctigenin using a ligand binding screen assay method. The IC(50) value of (2R,3R)-2-(4-hydroxy-3-methoxybenzyl)-3-(3,4-dihydroxybenzyl)-butyrolactone was 7.9 × 10⁻⁴ M. PMID:23325100

  11. Ligand Binding Affinities of Arctigenin and Its Demethylated Metabolites to Estrogen Receptor Alpha

    Directory of Open Access Journals (Sweden)

    Masao Hattori

    2013-01-01

    Full Text Available Phytoestrogens are defined as plant-derived compounds with estrogen-like activities according to their chemical structures and activities. Plant lignans are generally categorized as phytoestrogens. It was reported that (−-arctigenin, the aglycone of arctiin, was demethylated to (−-dihydroxyenterolactone (DHENL by Eubacterium (E. sp. ARC-2. Through stepwise demethylation, E. sp. ARC-2 produced six intermediates, three mono-desmethylarctigenins and three di-desmethylarctigenins. In the present study, ligand binding affinities of (−-arctigenin and its seven metabolites, including DHENL, were investigated for an estrogen receptor alpha, and found that demethylated metabolites had stronger binding affinities than (−-arctigenin using a ligand binding screen assay method. The IC50 value of (2R,3R-2-(4-hydroxy-3-methoxybenzyl-3-(3,4-dihydroxybenzyl-butyrolactone was 7.9 × 10−4 M.

  12. Demethylating Agents in the Treatment of Cancer

    Directory of Open Access Journals (Sweden)

    Paul M. Howell, Jr.

    2010-07-01

    Full Text Available Gene silencing resulting from aberrant DNA methylation can lead to tumorigenesis. Therefore, drugs that inhibit or interfere with DNA methylation have been used to reactivate and induce silenced gene re-expression in malignancies. Two demethylating agents, azacitidine and decitabine, are approved for the treatment of myelodysplastic syndromes (MDS by the U.S. Food and Drug Administration (FDA, and are now considered the standard of care in MDS. In this review, we discuss clinical data, including clinical benefits and toxicities, which led to the approval of azacitidine and decitabine. We also summarize findings from clinical trials that used these two demethylating agents in the treatment of solid tumors. Lastly, we discuss some limitations in the use of azacitidine and decitabine in cancer therapy.

  13. RNA-directed DNA methylation and demethylation in plants

    Institute of Scientific and Technical Information of China (English)

    CHINNUSAMY; Viswanathan

    2009-01-01

    RNA-directed DNA methylation (RdDM) is a nuclear process in which small interfering RNAs (siRNAs) direct the cytosine methylation of DNA sequences that are complementary to the siRNAs. In plants, double stranded-RNAs (dsRNAs) generated by RNA-dependent RNA polymerase 2 (RDR2) serve as precursors for Dicer-like 3 dependent biogenesis of 24-nt siRNAs. Plant specific RNA polymerase IV (Pol IV) is presumed to generate the initial RNA transcripts that are substrates for RDR2. siRNAs are loaded onto an argonaute4-containing RISC (RNA-induced silencing complex) that targets the de novo DNA methyltransferase DRM2 to RdDM target loci. Nascent RNA transcripts from the target loci are generated by another plant-specific RNA polymerase, Pol V, and these transcripts help recruit com- plementary siRNAs and the associated RdDM effector complex to the target loci in a transcrip- tion-coupled DNA methylation process. Small RNA binding proteins such as ROS3 may direct tar- get-specific DNA demethylation by the ROS1 family of DNA demethylases. Chromatin remodeling en- zymes and histone modifying enzymes also participate in DNA methylation and possibly demethylation. One of the well studied functions of RdDM is transposon silencing and genome stability. In addition, RdDM is important for paramutation, imprinting, gene regulation, and plant development. Lo- cus-specific DNA methylation and demethylation, and transposon activation under abiotic stresses suggest that RdDM is also important in stress responses of plants. Further studies will help illuminate the functions of RdDM in the dynamic control of epigenomes during development and environmental stress responses.

  14. Mining and representing recommendations in actively evolving recommender systems

    DEFF Research Database (Denmark)

    Assent, Ira

    2010-01-01

    Recommender systems provide an automatic means of filtering out interesting items, usually based on past similarity of user ratings. In previous work, we have suggested a model that allows users to actively build a recommender network. Users express trust, obtain transparency, and grow (anonymous......) recommender connections. In this work, we propose mining such active systems to generate easily understandable representations of the recommender network. Users may review these representations to provide active feedback. This approach further enhances the quality of recommendations, especially as topics of...

  15. Epigenetic targets and drug discovery Part 2: Histone demethylation and DNA methylation.

    Science.gov (United States)

    Liu, Ke; Liu, Yanli; Lau, Johnathan L; Min, Jinrong

    2015-07-01

    Chromatin structure is dynamically modulated by various chromatin modifications, such as histone/DNA methylation and demethylation. We have reviewed histone methyltransferases and methyllysine binders in terms of small molecule screening and drug discovery in the first part of this review series. In this part, we will summarize recent progress in chemical probe and drug discovery of histone demethylases and DNA methyltransferases. Histone demethylation and DNA methylation have attracted a lot of attention regarding their biology and disease implications. Correspondingly, many small molecule compounds have been designed to modulate the activity of histone demethylases and DNA methyltransferases, and some of them have been developed into therapeutic drugs or put into clinical trials.

  16. Targeting protein lysine methylation and demethylation in cancers

    Institute of Scientific and Technical Information of China (English)

    Yunlong He; Ilia Korboukh; Jian Jin; Jing Huang

    2012-01-01

    During the last decade,we saw an explosion of studies investigating the role of lysine methylation/demethylation of histones and non-histone proteins,such as p53,NF-kappaB,and E2F1.These ‘Ying-Yang' post-translational modifications are important to fine-tuning the activity of these proteins. Lysine methylation and demethylation are catalyzed by protein lysine methyltransferases (PKMTs) and protein lysine demethylases (PKDMs).PKMTs,PKDMs,and their substrates have been shown to play important roles in cancers.Although the underlying mechanisms of tumorigenesis are still largely unknown,growing evidence is starting to link aberrant regulation of methylation to tumorigenesis.This review focuses on summarizing the recent progress in understanding of the function of protein lysine methylation,and in the discovery of small molecule inhibitors for PKMTs and PKDMs.We also discuss the potential and the caveats of targeting protein lysine methylation for the treatment of cancer.

  17. Virion protein 16 induces demethylation of DNA integrated within chromatin in a novel mammalian cell model

    Institute of Scientific and Technical Information of China (English)

    Lu Yang; Huijun Wang; Xin Luo; Pengliang Mao; Weidong Tian; Yujiang Shi; Guoying Huang; Jin Zhang; Duan Ma

    2012-01-01

    DNA methylation and demethylation play important roles in mediating epigenetic regulation.So far,the mechanism of DNA demethylation remains elusive and controversial.Here,we constructed a plasmid,named with pCBS-luc,that contained an artificial CpG island,eight Gal4 DNA-binding domain binding site,an SV40 promoter,and a firefly luciferase reporter gene.The linearized pCBS-luc plasmid was methylated in vitro by DNA methyltransferase, and transfected into the HEK293 cells.The stable HEK293 transfectants with methylated pCBS-luc (me-pCBS-luc) were selected and obtained.The methylation status of the selected stable cell lines were confirmed by bisulfite sequencing polymerase chain reaction amplification.The methylation status could be maintained even after 15 passages.The virion protein 16 (VP16) was reported to enhance DNA demethylation around its binding sites of the promoter region in Xenopus fertilized eggs.Using our me-pCBS-luc model,we found that VP16 also had the ability to activate the expression of methylated luciferase reporter gene and induce DNA demethylation in chromatin DNA in mammalian cells.Altogether,we constructed a cell model stably integrated with the me-pCBS-luc reporter plasmid,and in this model we found that VP16 could lead to DNA demethylation.We believe that this cell model will have many potential applications in the future research on DNA demethylation and dynamic process of chromatin modification.

  18. Production of Hydrolysable Tannin-Like Structures During the Microbial Demethylation of lignin: An Assessment Using13C-Labeled Tetramethylammonium Hydroxide Thermochemolysis.

    Science.gov (United States)

    Filley, T.; Blanchette, R.; Nierop, K.; Gamblin, D.

    2003-12-01

    Phenolic compounds in soils are important mediators of microbial activity, metal mobility, soil redox, and soil organic matter building processes. Direct tannin input and the microbial decomposition of lignin in litter and soil are important contributors to this pool of phenols. The ability to accurately assess the relative differences in lignin decay (which are initiated by demethylation and side chain oxidation) among synapyl, coniferyl, and p-coumaryl components of detrital lignin requires the ability to determine microbial demethylation within the complex soil residues. Differentiating between hydrolysable tannins and contributions from advanced lignin decay can be problematic for many of the most common molecular techniques such as alkaline CuO oxidation, pyrolysis GC, and tetramethylammonium hydroxide thermochemolysis because of either the masking effects of derivatizing agents, oxidative damage to ortho-phenols or low volatility of lignin monomers. In this study we investigate lignin demethylation and polyhydroxyl-aromatic production in BC and C horizons of sandy forest soils dominated by oak, the A horizon from a red spruce forest, and controlled microbial inoculation studies of woody tissue using in-line 13C-labeled tetramethylammonium hydroxide thermochemolysis. Both white-rot and brown-rot decay resulted in syringyl demethylation, with the latter exhibiting more aggressive demethylation chemistry, while coniferyl monomer demethylation was essentially restricted to brown-rot decay. In a typical brown-rot sequence demethylation of syringyl components occurs more rapidly than coniferyl units within the same tissue and lower molecular weight fragments are likewise more demethylated than lignin monomers containing the full glycerol side chain. Demethylation of both methoxyl groups in the syringyl monomer is evident in soil horizons as well as laboratory inoculations. The latter may suggest demethylation after lignin depolymerization. Low molecular weight

  19. Global DNA hypermethylation-associated cancer chemotherapy resistance and its reversion with the demethylating agent hydralazine

    Directory of Open Access Journals (Sweden)

    Benitez-Bribiesca Luis

    2006-08-01

    Full Text Available Abstract Background The development of resistance to cytotoxic chemotherapy continues to be a major obstacle for successful anticancer therapy. It has been shown that cells exposed to toxic concentrations of commonly used cancer chemotherapy agents develop DNA hypermetylation. Hence, demethylating agents could play a role in overcoming drug resistance. Methods MCF-7 cells were rendered adriamycin-resistant by weekly treatment with adriamycin. Wild-type and the resulting MCF-7/Adr cells were analyzed for global DNA methylation. DNA methyltransferase activity and DNA methyltransferase (dnmt gene expression were also determined. MCF-7/Adr cells were then subjected to antisense targeting of dnmt1, -3a, and -b genes and to treatment with the DNA methylation inhibitor hydralazine to investigate whether DNA demethylation restores sensitivity to adriamycin. Results MCF-7/Adr cells exhibited the multi-drug resistant phenotype as demonstrated by adriamycin resistance, mdr1 gene over-expression, decreased intracellular accumulation of adriamycin, and cross-resistance to paclitaxel. The mdr phenotype was accompanied by global DNA hypermetylation, over-expression of dnmt genes, and increased DNA methyltransferase activity as compared with wild-type MCF-7 cells. DNA demethylation through antisense targeting of dnmts or hydralazine restored adriamycin sensitivity of MCF-7/Adr cells to a greater extent than verapamil, a known inhibitor of mdr protein, suggesting that DNA demethylation interferes with the epigenetic reprogramming that participates in the drug-resistant phenotype. Conclusion We provide evidence that DNA hypermethylation is at least partly responsible for development of the multidrug-resistant phenotype in the MCF-7/Adr model and that hydralazine, a known DNA demethylating agent, can revert the resistant phenotype.

  20. RNA-directed DNA methylation and demethylation in plants

    Institute of Scientific and Technical Information of China (English)

    CHINNUSAMY Viswanathan; ZHU Jian-Kang

    2009-01-01

    A-dlrected DNA methylation (RdDM) Is a nuclear process in which small Interfering RNAs (siRNAs)direct the cytosine methylation of DNA sequences that are complementary to the siRNAs. In plants,double stranded-RNAs (dsRNAs) generated by RNA-dependent RNA polymerase 2 (RDR2) serve as precursors for Dicer-like 3 dependent biogenesis of 24-nt siRNAs. Plant specific RNA polymerase IV (Pol IV) is presumed to generate the initial RNA transcripts that are substrates for RDR2. siRNAs are loaded onto an argonaute4-containlng RlSC (RNA-induced silencing complex) that targets the de novo DNA methyltransferase DRM2 to RdDM target locl. Nascent RNA transcripts from the target loci are generated by another plant-specific RNA polymerase, Pol V, and these transcripts help recruit com-plementary siRNAs and the associated RdDM effector complex to the target loci in a transcrip-tion-coupled DNA methylation process. Small RNA binding proteins such as ROS3 may direct tar-get-specific DNA demethyiation by the ROS1 family of DNA demethylases. Chromatin remodeling en-zymes and histone modifying enzymes also participate in DNA methylation and possibly demethylation.One of the well studied functions of RdOM is transposon silencing and genome stability. In addition,RdDM is important for paramutation, imprinting, gene regulation, and plant development. Locus-specific DNA methylation and demethylation, and transposon activation under abiotic stresses suggest that RdDM is also important in stress responses of plants. Further studies will help illuminate the functions of RdDM in the dynamic control of epigenomes during development and environmental stress responses.

  1. Demethylation and cleavage of dimethylsulfoniopropionate in marine intertidal sediments

    Science.gov (United States)

    Visscher, P.T.; Kiene, R.P.; Taylor, B.F.

    1994-01-01

    Demethylation and cleavage of dimethylsulfoniopropionate (DMSP) was measured in three different types of,intertidal marine sediments: a cyanobacterial mat, a diatom-covered tidal flat and a carbonate sediment. Consumption rates of added DMSP were highest in cyanobacterial mat slurries (59 ?? mol DMSP l-1 slurry h-1) and lower in slurries from a diatom mat and a carbonate tidal sediment (24 and 9 ??mol DMSP l-1 h-1, respectively). Dimethyl sulfide (DMS) and 3-mercaptopropionate (MPA) were produced simultaneously during DMSP consumption, indicating that cleavage and demethylation occurred at the same time. Viable counts of DMSP-utilizing bacteria revealed a population of 2 x 107 cells cm-3 sediment (90% of these cleaved DMSP to DMS, 10% demethylated DMSP to MPA) in the cyanobacterial mat, 7 x 105 cells cm-3 in the diatom mat (23% cleavers, 77% demethylators), and 9 x 104 cells cm-3 (20% cleavers and 80% demethylators) in the carbonate sediment. In slurries of the diatom mat, the rate of MPA production from added 3-methiolpropionate (MMPA) was 50% of the rate of MPA formation from DMSP. The presence of a large population of demethylating bacteria and the production of MPA from DMSP suggest that the demethylation pathway, in addition to cleavage, contributes significantly to DMSP consumption in coastal sediments.

  2. Dietary compound isoliquiritigenin prevents mammary carcinogenesis by inhibiting breast cancer stem cells through WIF1 demethylation

    OpenAIRE

    Wang, Neng; Wang, Zhiyu; Wang, Yu; Xie, Xiaoming; Shen, Jiangang; Peng, Cheng; You, Jieshu; Peng, Fu; Tang, Hailin; Guan, Xinyuan; Chen, Jianping

    2015-01-01

    Breast cancer stem cells (CSCs) are considered as the root of mammary tumorigenesis. Previous studies have demonstrated that ISL efficiently limited the activities of breast CSCs. However, the cancer prevention activities of ISL and its precise molecular mechanisms remain largely unknown. Here, we report a novel function of ISL as a natural demethylation agent targeting WIF1 to prevent breast cancer. ISL administration suppressed in vivo breast cancer initiation and progression, accompanied b...

  3. Promoter demethylation of Keap1 gene in human diabetic cataractous lenses

    Energy Technology Data Exchange (ETDEWEB)

    Palsamy, Periyasamy [Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE (United States); Ayaki, Masahiko [Shizuoka National Hospital, Saitama (Japan); Elanchezhian, Rajan [Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE (United States); Shinohara, Toshimichi, E-mail: tshinohara@unmc.edu [Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE (United States)

    2012-07-06

    Highlights: Black-Right-Pointing-Pointer We found significant Keap1 promoter demethylation in diabetic cataractous lenses. Black-Right-Pointing-Pointer Demethylation of Keap1 gene upregulated the expression of Keap1 mRNA and protein. Black-Right-Pointing-Pointer Elevated levels of Keap1 are known to decrease the levels of Nrf2. Black-Right-Pointing-Pointer Thereby, the levels of antioxidant enzymes are suppressed by decreased Nrf2 level. -- Abstract: Age-related cataracts (ARCs) are the major cause of visual impairments worldwide, and diabetic adults tend to have an earlier onset of ARCs. Although age is the strongest risk factor for cataracts, little is known how age plays a role in the development of ARCs. It is known that oxidative stress in the lens increases with age and more so in the lenses of diabetics. One of the central adaptive responses against the oxidative stresses is the activation of the nuclear transcriptional factor, NF-E2-related factor 2 (Nrf2), which then activates more than 20 different antioxidative enzymes. Kelch-like ECH associated protein 1 (Keap1) targets and binds to Nrf2 for proteosomal degradation. We hypothesized that hyperglycemia will lead to a dysfunction of the Nrf2-dependent antioxidative protection in the lens of diabetics. We studied the methylation status of the CpG islands in 15 clear and 21 diabetic cataractous lenses. Our results showed significant levels of demethylated DNA in the Keap1 promoter in the cataractous lenses from diabetic patients. In contrast, highly methylated DNA was found in the clear lens and tumorized human lens epithelial cell (HLEC) lines (SRA01/04). HLECs treated with a demethylation agent, 5-aza-2 Prime deoxycytidine (5-Aza), had a 10-fold higher levels of Keap1 mRNA, 3-fold increased levels of Keap1 protein, produced higher levels of ROS, and increased cell death. Our results indicated that demethylation of the CpG islands in the Keap1 promoter will activate the expression of Keap1 protein, which

  4. A New Synthetic Route to Dihydrobenzopyran Via Tandem Demethylation Cyclisation

    OpenAIRE

    Shanmugam, G; S. Shanmuga Sundara Raj; Thirumurugan, R.; N. D. Pradeep Singh; Viswanathan Kasinath; Geetha Gopalakrishnan

    2000-01-01

    A tandem demethylation-cyclisation reaction resulting in the formation of pyran rings using AlCl3/EtSH reagent under mild reaction conditions is reported. X-ray diffraction studies on the intermediate support the suggested mechanism.

  5. Regioselective demethylation of quinoline derivatives. A DFT rationalization

    Science.gov (United States)

    Belferdi, Fatiha; Merabet, Naima; Belkhiri, Lotfi; Douara, Bachir

    2016-08-01

    Demethylation of compound 2,7-dimethoxyquinoline-3-carbaldehyde 1, is carried out using BBr3. However, all attempts led, either to the starting material or to the regioselective demethylation at position 2 affording the product 4a. The nature (donor or acceptor) and the position of the R (CHO or CN) group is likely to play a role in the preventing the demethylation at position 7. To address this phenomena, the demethylation of 2-chloro-7-methoxyquinoline-3-carbaldehyde 2 and 2,7-dimethoxyquinoline-3-carbaldehyde 3 has been carried out. To support the results obtained, theoretical computations at DFT level (vide infra) have been carried out upon compound 1. The exploration of how the gas-phase demethylation process on Quinoline can be affected at a position 7 center by stepwise substation effects using different electro-donor and attractor groups, show that demethylation process seems to be more favorable when substituent is an electro-donor. This is sustained by bond energy and thermodynamic analyses (vide infra).

  6. Simulated vibrational spectra of aflatoxins and their demethylated products and the estimation of the energies of the demethylation reactions

    Science.gov (United States)

    Billes, Ferenc; Móricz, Ágnes M.; Tyihák, Ernő; Mikosch, Hans

    2006-06-01

    The structure of four natural mycotoxins, the aflatoxin B 1, B 2, G 1 and G 2 and their demethylated products were optimized with quantum chemical method. The energies and the thermodynamic functions of the molecules were calculated and applied to calculation of the reaction energies of the demethylations. Further results of the calculations are the vibrational force constants, the infrared spectra of the molecules and the assignments of the spectral bands.

  7. Demethylation of arsenic limits its volatilization in fungi

    International Nuclear Information System (INIS)

    Arsenic (As) biomethylation is increasingly being regarded as a promising method to volatize As from the environment; however, the As volatilization efficiency of most microorganisms is low. Here, the speciation transformation of dimethylarsinic acid (DMA) as an important methylation intermediate in the cells of Fusarium oxysporum CZ-8F1, Penicillium janthinellum SM-12F4, and Trichoderma asperellum SM-12F1 were investigated. These fungal strains have been certified to volatilize As from As-loaded environment. In situ X-ray absorption near edge structure (XANES) indicated that demethylation of DMA with methylarsonic acid (MMA), arsenate [As(V)], and arsenite [As(III)] as intermediates or products occurred in fungal cells after exposure to DMA for 15 days. 36.7–55.7% of the original DMA could lose one or two methyl groups and be changed into MMA or inorganic As. Chromatographic separation of the cell lysates also supported these findings. Thus it comes that demethylation might be a remarkable internal factor limiting As volatilization efficiency. - Highlights: • XAS and chromatographic separation were used to study the speciation change of DMA. • DMA demethylation with MMA, As(V), and As(III) as products occurred in fungal cells. • Demethylation might be responsible for the limited volatilization efficiency of As. - Demethylation might be responsible for the limited methylation efficiency of As

  8. Enantioselective accumulation of (--)-pinoresinol through O-demethylation of (+/-)-eudesmin by Aspergillus niger.

    Science.gov (United States)

    Kasahara, H; Miyazawa, M; Kameoka, H

    1997-04-01

    Microbial transformation of (+/-)-eudesmin by Aspergillus niger was investigated. Enantioselective accumulation of (--)-pinoresinol was shown through O-demethylation of (+/-)-eudesmin. This fungus O- demethylated both enantiomers of eudesmin, but the conversion rates for each enantiomer were clearly different.

  9. Process for demethylating S-methyl-mercapto compounds

    NARCIS (Netherlands)

    Hansen, Theo; Jansen, Michael; van der Maarel, Marc

    1998-01-01

    PCT No. PCT/EP95/02883 Sec. 371 Date Jan. 8, 1997 Sec. 102(e) Date Jan. 8, 1997 PCT Filed Jul. 19, 1995 PCT Pub. No. WO96/03518 PCT Pub. Date Feb. 8, 1996The invention concerns a process for preparing mercapto compounds comprising the step of demethylating an S-methyl-mercapto compound of Formula I

  10. A New Synthetic Route to Dihydrobenzopyran Via Tandem Demethylation Cyclisation

    Directory of Open Access Journals (Sweden)

    G. Shanmugam

    2000-06-01

    Full Text Available A tandem demethylation-cyclisation reaction resulting in the formation of pyran rings using AlCl3/EtSH reagent under mild reaction conditions is reported. X-ray diffraction studies on the intermediate support the suggested mechanism.

  11. Anaerobic Mercury Methylation and Demethylation by Geobacter bemidjiensis Bem.

    Science.gov (United States)

    Lu, Xia; Liu, Yurong; Johs, Alexander; Zhao, Linduo; Wang, Tieshan; Yang, Ziming; Lin, Hui; Elias, Dwayne A; Pierce, Eric M; Liang, Liyuan; Barkay, Tamar; Gu, Baohua

    2016-04-19

    Microbial methylation and demethylation are two competing processes controlling the net production and bioaccumulation of neurotoxic methylmercury (MeHg) in natural ecosystems. Although mercury (Hg) methylation by anaerobic microorganisms and demethylation by aerobic Hg-resistant bacteria have both been extensively studied, little attention has been given to MeHg degradation by anaerobic bacteria, particularly the iron-reducing bacterium Geobacter bemidjiensis Bem. Here we report, for the first time, that the strain G. bemidjiensis Bem can mediate a suite of Hg transformations, including Hg(II) reduction, Hg(0) oxidation, MeHg production and degradation under anoxic conditions. Results suggest that G. bemidjiensis utilizes a reductive demethylation pathway to degrade MeHg, with elemental Hg(0) as the major reaction product, possibly due to the presence of genes encoding homologues of an organomercurial lyase (MerB) and a mercuric reductase (MerA). In addition, the cells can strongly sorb Hg(II) and MeHg, reduce or oxidize Hg, resulting in both time and concentration-dependent Hg species transformations. Moderate concentrations (10-500 μM) of Hg-binding ligands such as cysteine enhance Hg(II) methylation but inhibit MeHg degradation. These findings indicate a cycle of Hg methylation and demethylation among anaerobic bacteria, thereby influencing net MeHg production in anoxic water and sediments. PMID:27019098

  12. Does Improving Exercise Capacity and Daily Activity Represent the Holistic Perspective of a New COPD Approach?

    Science.gov (United States)

    Di Marco, Fabiano; Santus, Pierachille; Sotgiu, Giovanni; Blasi, Francesco; Centanni, Stefano

    2015-01-01

    In COPD patients a reduced daily activity has been well documented, resulting from both respiratory and non-respiratory manifestations of the disease. An evaluation by multisensory armband has confirmed that daily physical activity is mainly associated with dynamic hyperinflation, regardless of COPD severity. This aspect is crucial, since exercise capacity is closely correlated to life expectancy. Notwithstanding the causal key role of lung impairment in the patient's symptoms, some authors have suggested that other factors, such as systemic inflammation and co-morbidities, have an important role, particularly as mortality risk factors. Many studies suggest the efficacy of bronchodilators and rehabilitation in improving exercise capacity, and, speaking in terms of daily life, in increasing the number of days in which patients are able to perform their usual activities. On this evidence, the first aim in the management of COPD should be to improve exercise capacity and daily activity since these outcomes have direct effects on patients' quality of life, co-morbidities (heart and metabolic diseases), and prognosis. Thus, improving physical activity represents a modern approach aimed at dealing with both pulmonary and systemic manifestations of the disease. It is however worth of notice to remember that in patients affected by COPD the relationship between the improvement of "potential" exercise capacity and daily physical activity has been found to be only moderate to weak. Obtaining a significant behavior modification with regard to daily physical activity, together with the optimization of therapy thus represents currently the true challenge. PMID:26457460

  13. Involvement of mitochondria and caspase pathways in N-demethyl-clarithromycin-induced apoptosis in human cervical cancer HeLa cell

    Institute of Scientific and Technical Information of China (English)

    Ai-min QIAO; Takashi IKEJIMA; Shini-chi TASHIRO; Satoshi ONODERA; Wei-ge ZHANG; Ying-liang WU

    2006-01-01

    Aim: To study the mechanisms by which N-demethyl-clarithromycin (NDC) induces human cervical cancer HeLa cell apoptosis in vitro. Methods: The viability of N-demethyl-clarithromycin-induced HeLa cells was measured by MTT assay. Apoptotic cells with condensed nuclei were visualized by phase contrast microscopy. Nucleosomal DNA fragmentation was assayed by agarose gel electrophoresis. Measurement of mitochondrial transmembrane potential was analyzed by a FACScan flowcytometer. Caspase-3, poly-(ADP-ribose) polymerase (PARP), caspase-activated DNase (ICAD), Bcl-2, Bax, p53, and SIRT1 protein expression and the release of cytochrome c were detected by Western blot analysis. Results: N-demethyl-clarithromycin, an anti-inflammatory substance, inhibited HeLa cell growth in a dose- and time-dependent manner.N-demethyl-clarithromycin induced HeLa cell death through the apoptotic pathways. The pan-caspase inhibitor (z-VAD-fmk), caspase-3 inhibitor (z-DEVD-fmk) and the caspase-9 inhibitor (z-LEHD-fmk) partially enhanced cell viability induced by N-demethyl-clarithromycin, but the caspase-8 inhibitor (z-IETD-fmk) had almost no effect. Caspase-3 was activated then followed by the degradation of caspase-3 substrates, the inhibitor of ICAD and PARP. Simultaneously, mitochondrial transmembrane potential was markedly reduced and the release of cytochrome c in the cytosol was increased.N-demethyl-clarithromycin upregulated the expression ratio of mitochondrial Bax/Bcl-2, and significantly increased the expression of the p53 protein. It also downregulated anti-apoptotic protein SIRT1 expression. Conclusion: N-demethyl-clarithromycin induced apoptosis in HeLa cells via the mitochondrial pathway.

  14. Norcantharidin blocks Wnt/β-catenin signaling via promoter demethylation of WIF-1 in glioma.

    Science.gov (United States)

    Xie, Dajiang; Xie, Jixi; Wan, Yingfeng; Ma, Li; Qi, Xuchen; Wang, Kun; Yang, Shuxu

    2016-04-01

    Glioma is one of the most common primary intracranial tumors, and the prognosis is poor even though much treatment management is employed. Wnt/β-catenin signaling has been reported to be associated with glioma. Norcantharidin (NCTD) is the demethylated analog of cantharidin isolated from blister beetles, and it is reported to possess anticancer activity but less nephrotoxicity than cantharidin. Accordingly, we aimed to investigate NCTD as an anti-neoplastic drug that inhibits the Wnt/β‑catenin pathway via promoter demethylation of Wnt inhibitory factor-1 (WIF-1) in glioma growth in vitro. In the present study, we report that NCTD inhibited cell proliferation, induced apoptosis and cell cycle arrest, and suppressed cell migration and invasion in vitro. Moreover, we observed that the expression levels of WIF-1 mRNA and protein in the NCTD-treated cells were increased significantly compared with these levels in the negative control (NC) cells. Promoter demethylation was observed in the NCTD‑treated cells. In contrast, aberrant methylation was observed in the NC cells. Additionally, more investigation revealed that NCTD suppressed activity of Wnt/β-catenin signaling and transcription of β-catenin/TCF-4. Furthermore, the expression of apoptosis-related proteins Bcl-2 and cleaved caspase-3 indicated significant cell apoptosis. We provide initial evidence that NCTD reactivates WIF-1 from a methylation state, and downregulates canonical Wnt/β-catenin signaling. Our findings revealed that NCTD is effective for glioma in vitro and may be a new therapeutic option in vivo. PMID:26781164

  15. A suite of methods for representing activity space in a healthcare accessibility study

    Directory of Open Access Journals (Sweden)

    Gesler Wilbert M

    2005-10-01

    Full Text Available Abstract Background "Activity space" has been used to examine how people's habitual movements interact with their environment, and can be used to examine accessibility to healthcare opportunities. Traditionally, the standard deviational ellipse (SDE, a Euclidean measure, has been used to represent activity space. We describe the construction and application of the SDE at one and two standard deviations, and three additional network-based measures of activity space using common tools in GIS: the road network buffer (RNB, the 30-minute standard travel time polygon (STT, and the relative travel time polygon (RTT. We compare the theoretical and methodological assumptions of each measure, and evaluate the measures by examining access to primary care services, using data from western North Carolina. Results Individual accessibility is defined as the availability of healthcare opportunities within that individual's activity space. Access is influenced by the shape and area of an individual's activity space, the spatial distribution of opportunities, and by the spatial structures that constrain and direct movement through space; the shape and area of the activity space is partly a product of how it is conceptualized and measured. Network-derived measures improve upon the SDE by incorporating the spatial structures (roads that channel movement. The area of the STT is primarily influenced by the location of a respondent's residence within the road network hierarchy, with residents living near primary roads having the largest activity spaces. The RNB was most descriptive of actual opportunities and can be used to examine bypassing. The area of the RTT had the strongest correlation with a healthcare destination being located inside the activity space. Conclusion The availability of geospatial technologies and data create multiple options for representing and operationalizing the construct of activity space. Each approach has its strengths and limitations

  16. The p16-specific reactivation and inhibition of cell migration through demethylation of CpG islands by engineered transcription factors.

    Science.gov (United States)

    Zhang, Baozhen; Xiang, Shengyan; Zhong, Qiming; Yin, Yanru; Gu, Liankun; Deng, Dajun

    2012-10-01

    Methylation of CpG islands inactivates transcription of tumor suppressor genes including p16 (CDKN2A). Inhibitors of DNA methylation and histone deacylation are recognized as useful cancer therapeutic chemicals through reactivation of the expression of methylated genes. However, these inhibitors are not target gene-specific, so that they lead to serious side effects as regular cytotoxic chemotherapy agents. To explore the feasibility of methylated gene-specific reactivation by artificial transcription factors, we engineered a set of Sp1-like seven-finger zinc-finger proteins (7ZFPs) targeted to a 21-bp sequence of the p16 promoter and found that these 7ZFPs could bind specifically to the target p16 promoter probe. Then the p16-specific artificial transcription factors (p16ATFs) were made from these 7ZFPs and the transcription activator VP64. Results showed that transient transfection of some p16ATFs selectively up-regulated the endogenous p16 expression in the p16-active 293T cells. Moreover, the transient transfection of the representative p16ATF-6I specifically reactivated p16 expression in the p16-methylated H1299 and AGS cells pretreated with a nontoxic amount of 5'-aza-deoxycytidine (20 and 80 nM, respectively). In addition, stable transfection of the p16ATF induced demethylation of p16 CpG island and trimethylation of histone H3K4, and inhibited recruitment of DNA methyltransferase 1 and trimethylation of H3K9 and H3K27 in the p16 promoter in H1299 cells without 5'-aza-deoxycytidine pretreatment. Notably, inhibition of cell migration and invasion was observed in these p16-reactivated cells induced by transient and stable p16ATF transfection. These results demonstrate that p16ATF not only specifically reactivates p16 expression through demethylation of CpG islands, but also restores methylated p16 function. PMID:22738793

  17. Quantification for total demethylation potential of environmental samples utilizing the EGFP reporter gene.

    Science.gov (United States)

    Qian, Yan; Wang, Xiao-li; Lv, Zhan-lu; Tysklind, Mats; Guo, Chen; Liang, Bao; Wu, Jia-bing; Yang, Yong-jian; Yang, Yi-shu; Wang, Fei-fei; Duan, Xiao-li; Ma, Jin; Wei, Yong-jie; Wang, Chun-hui; Yang, Li-xin; Zhang, Jin-liang; Shi, Xiao-ming; Wang, Xian-liang

    2016-04-01

    The demethylation potential of pollutants is arguably an innate component of their toxicity in environmental samples. A method was developed for determining the total demethylation potential of food samples (TDQ). The demethylation epigenetic toxicity was determined using the Hep G2 cell line transfected with pEGFP-C3 plasmids containing a methylated promoter of the EGFP reporter gene. The total demethylation potential of the sample extracts (the 5-AZA-CdR demethylation toxic equivalency) can be quantified within one week by using a standard curve of the 5-AZA-CdR demethylation agent. To explore the applicability of TDQ for environmental samples, 17 groundwater samples were collected from heavy polluted Kuihe river and the total demethylation potentials of the sample extracts were measured successfully. Meaningful demethylation toxic equivalencies ranging from 0.00050 to 0.01747μM were found in all groundwater sample extracts. Among 19 kinds of inorganic substance, As and Cd played important roles for individual contribution to the total demethylation epigenetic toxicity. The TDQ assay is reliable and fast for quantifying the DNA demethylation potential of environmental sample extracts, which may improve epigenetic toxicity evaluations for human risk assessment, and the consistent consuming of groundwater alongside the Kuihe river pose unexpected epigenetic health risk to the local residents. PMID:26774982

  18. Long-term stability of demethylation after transient exposure to 5-aza-2'-deoxycytidine correlates with sustained RNA polymerase II occupancy.

    Science.gov (United States)

    Kagey, Jacob D; Kapoor-Vazirani, Priya; McCabe, Michael T; Powell, Doris R; Vertino, Paula M

    2010-07-01

    DNA methyltransferase inhibitors are currently the standard of care for myelodysplastic syndrome and are in clinical trials for leukemias and solid tumors. However, the molecular basis underlying their activity remains poorly understood. Here, we studied the induction and long-term stability of gene reactivation at three methylated tumor suppressor loci in response to the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-azaCdR) in human breast cancer cells. At the TMS1/ASC locus, treatment with 5-azaCdR resulted in partial DNA demethylation, the reengagement of RNA polymerase II (Pol II), and a shift from a repressive chromatin profile marked with H3K9me2 and H4K20me3 to an active profile enriched in H3ac and H3K4me2. Using a single-molecule approach coupling chromatin immunoprecipitation with bisulfite sequencing, we show that H3ac, H3K4me2, and Pol II selectively associated with the demethylated alleles, whereas H3K9me2 preferentially marked alleles resistant to demethylation. H4K20me3 was unaffected by DNA demethylation and associated with both unmethylated and methylated alleles. After drug removal, TMS1 underwent partial remethylation, yet a subset of alleles remained stably demethylated for over 3 months. These alleles remained selectively associated with H3K4me2, H3ac, and Pol II and correlated with a sustained low level of gene expression. TMS1 alleles reacquired H3K9me2 over time, and those alleles that became remethylated retained H3ac. In contrast, CDH1 and ESR1 were remethylated and completely silenced within approximately 1 week of drug removal, and failed to maintain stably unmethylated alleles. Our data suggest that the ability to maintain Pol II occupancy is a critical factor in the long-term stability of drug-induced CpG island demethylation. PMID:20587535

  19. Long-term stability of demethylation after transient exposure to 5-aza-2′-deoxycytidine correlates with sustained RNA polymerase II occupancy*

    Science.gov (United States)

    Kagey, Jacob D.; Kapoor-Vazirani, Priya; McCabe, Michael T.; Powell, Doris R.; Vertino, Paula M.

    2010-01-01

    DNA methyltransferase (DNMT) inhibitors are currently the standard of care for myelodysplastic syndrome and are in clinical trials for leukemias and solid tumors. However, the molecular basis underlying their activity remains poorly understood. Here we studied the induction and long-term stability of gene reactivation at three methylated tumor suppressor loci in response to the DNMT inhibitor 5-aza-2′-deoxycytidine (5-azaCdR)in human breast cancer cells. At the TMS/ASC locus, treatment with 5-azaCdR resulted in partial DNA demethylation, the re-engagement of RNA polymerase II (Pol II), and a shift from a repressive chromatin profile marked with H3K9me2 and H4K20me3 to an active profile enriched in H3ac and H3K4me2. Using a single molecule approach coupling chromatin immunoprecipitation with bisulfite sequencing, we show that H3ac, H3K4me2, and Pol II selectively associated with the demethylated alleles, whereas H3K9me2 preferentially marked alleles resistant to demethylation. H4K20me3 was unaffected by DNA demethylation and associated with unmethylated and methylated alleles. After drug removal, TMS1 underwent partial remethylation yet a subset of alleles remained stably demethylated for over three months. These alleles remained selectively associated with H3K4me2, H3ac, and Pol II and correlated with a sustained low level of gene expression. TMS1 alleles reacquire H3K9me2over time and those alleles that became remethylated retained H3ac. In contrast, CDH1and ESR1 were remethylated and completely silenced within ~1 week of drug removal, and failed to maintain stably unmethylated alleles. Our data suggest that the ability to maintain Pol II occupancy is a critical factor in the long-term stability of drug-induced CpG island demethylation. PMID:20587535

  20. CYP2C subfamily, primarily CYP2C9, catalyses the enantioselective demethylation of the endocrine disruptor pesticide methoxychlor in human liver microsomes: use of inhibitory monoclonal antibodies in P450 identification.

    Science.gov (United States)

    Hu, Y; Krausz, K; Gelboin, H V; Kupfer, D

    2004-02-01

    1. The endocrine disruptor pesticide methoxychlor undergoes O-demethylation by mammalian liver microsomes forming chiral mono-phenolic (1,1,1-trichloro-2-(4-hydroxyphenyl)-2-(4-methoxyphenyl)ethane, i.e. mono-OH-M) and achiral bis-phenolic oestrogenic metabolites. Human liver microsomes (HLM) generated primarily the S-mono-OH-M. 2. Inhibitory monoclonal antibodies (MAb) identified those P450s catalysing the enantioselective O-demethylation of methoxychlor. In HLM, O-demethylation was inhibited by MAb anti-2C9 (30-40%), diminishing the per cent of S-mono-OH-M from about 80 to 55-60%. MAb anti-CYP1A2, 2A6, 2B6, 2C8, 2C19, 2D6 and 3A4 did not affect the demethylation rate in HLM. Nevertheless, MAb anti-CYP1A2 decreased the formation of R-mono-OH-M from 21-23 to 10-17%, indicating that CYP1A2 exhibits a role in generating the R-enantiomer. 3. Among cDNA-expressed human P450s (supersomes), CYP2C19 was the most active in demethylation, but in HLM, CYP2C19 appeared inactive (no inhibition by MAb anti-CYP2C19). There was a substantial difference in the per cent inhibition of demethylation by MAb anti-CYP2C9 and anti-rat CYP2C (MAb inhibiting all human CYP2C forms) and in altering the enantioselectivity, suggesting that demethylation by combined CYP2C8, 2C18 and 2C19 was significant (20-30%). 4. Polymorphism of methoxychlor demethylation was examined with supersomes and HLM-expressing CYP2C9 allelic variants. CYP2C9*1 and 2C9*2 were highly active; however, CYP2C9*3 appeared inactive.

  1. Mitochondrial DNA copy number is regulated by DNA methylation and demethylation of POLGA in stem and cancer cells and their differentiated progeny.

    Science.gov (United States)

    Lee, W; Johnson, J; Gough, D J; Donoghue, J; Cagnone, G L M; Vaghjiani, V; Brown, K A; Johns, T G; St John, J C

    2015-02-26

    Mitochondrial DNA (mtDNA) copy number is strictly regulated during differentiation so that cells with a high requirement for ATP generated through oxidative phosphorylation have high mtDNA copy number, whereas those with a low requirement have few copies. Using immunoprecipitation of DNA methylation on 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), which distinguish between de novo DNA methylation and demethylation, respectively, we set out to determine whether DNA methylation at exon 2 of the human mtDNA-specific polymerase (DNA polymerase gamma A (POLGA)) regulates cell-specific mtDNA copy number in highly proliferative and terminally differentiated cells. Highly proliferative cancer and pluripotent and multipotent cells possessed low mtDNA copy number and were highly methylated at exon 2 of POLGA in contrast to post-mitotic cells. Unlike neural stem cells, cancer cells were unable to differentiate and remained extensively DNA methylated at exon 2 of POLGA. However, mtDNA depletion of cancer cells reduced DNA methylation at exon 2 of POLGA as they replenished mtDNA to form tumours in mice. Glioblastoma cells treated with the DNA demethylation agent 5-azacytidine over 28 days of astrocyte-induced differentiation demethylated exon 2 of POLGA leading to increased mtDNA copy number and expression of the astrocyte endpoint marker glial fibrillary acidic protein (GFAP). However, the demethylation agent vitamin C (VitC) was unable to sustain increased mtDNA copy number and differentiation, as was the case when VitC was withdrawn after short-term treatment. These data demonstrate that DNA demethylation of POLGA is an essential regulator of mtDNA copy number and cellular fate and that cancer cells are only able to modulate DNA methylation of POLGA and mtDNA copy number in the presence of a DNA demethylation agent that inhibits de novo methyltransferase 1 activity.

  2. Redistribution of demethylated RNA helicase A during foot-and-mouth disease virus infection: Role of Jumonji C-domain containing protein 6 in RHA demethylation

    International Nuclear Information System (INIS)

    Previously, RNA helicase A (RHA) re-localization from the nucleus to the cytoplasm in foot-and-mouth disease virus (FMDV) infected cells was shown to coincide with loss of RHA methylated arginine residues at its C-terminus. The potential interaction between RHA and Jumonji C-domain (JmjC) protein 6 (JMJD6) arginine demethylase in infected cells was investigated. Treatment with N-oxalylglycine (NOG) inhibitor of JmjC demethylases prevented FMDV-induced RHA demethylation and re-localization, and also decreased viral protein synthesis and virus titers. Physical interaction between JMJD6 and RHA was demonstrated via reciprocal co-immunoprecipitation, where RHA preferentially bound JMJD6 monomers. Nuclear efflux of demethylated RHA (DM-RHA) coincided with nuclear influx of JMJD6, which was not observed using another picornavirus. A modified biochemical assay demonstrated JMJD6 induced dose-dependent demethylation of RHA and two RHA-derived isoforms, which could be inhibited by NOG. We propose a role for JMJD6 in RHA demethylation stimulated by FMDV, that appears to facilitate virus replication. - Highlights: • We examined the role of JMJD6 in FMDV-induced RHA demethylation process. • Using an arginine demethylation assay showed that JMJD6 is involved in RHA demethylation. • A demethylases inhibitor reduced cytoplasmic accumulation of RHA and FMDV titers

  3. Redistribution of demethylated RNA helicase A during foot-and-mouth disease virus infection: Role of Jumonji C-domain containing protein 6 in RHA demethylation

    Energy Technology Data Exchange (ETDEWEB)

    Lawrence, Paul; Conderino, Joseph S.; Rieder, Elizabeth, E-mail: elizabeth.rieder@ars.usda.gov

    2014-03-15

    Previously, RNA helicase A (RHA) re-localization from the nucleus to the cytoplasm in foot-and-mouth disease virus (FMDV) infected cells was shown to coincide with loss of RHA methylated arginine residues at its C-terminus. The potential interaction between RHA and Jumonji C-domain (JmjC) protein 6 (JMJD6) arginine demethylase in infected cells was investigated. Treatment with N-oxalylglycine (NOG) inhibitor of JmjC demethylases prevented FMDV-induced RHA demethylation and re-localization, and also decreased viral protein synthesis and virus titers. Physical interaction between JMJD6 and RHA was demonstrated via reciprocal co-immunoprecipitation, where RHA preferentially bound JMJD6 monomers. Nuclear efflux of demethylated RHA (DM-RHA) coincided with nuclear influx of JMJD6, which was not observed using another picornavirus. A modified biochemical assay demonstrated JMJD6 induced dose-dependent demethylation of RHA and two RHA-derived isoforms, which could be inhibited by NOG. We propose a role for JMJD6 in RHA demethylation stimulated by FMDV, that appears to facilitate virus replication. - Highlights: • We examined the role of JMJD6 in FMDV-induced RHA demethylation process. • Using an arginine demethylation assay showed that JMJD6 is involved in RHA demethylation. • A demethylases inhibitor reduced cytoplasmic accumulation of RHA and FMDV titers.

  4. Color harmony represented by activity in the medial orbitofrontal cortex and amygdala

    Directory of Open Access Journals (Sweden)

    Takashi eIkeda

    2015-07-01

    Full Text Available Observing paired colors with a different hue (in terms of chroma and lightness engenders pleasantness from such harmonious combinations; however, negative reactions can emerge from disharmonious combinations. Currently, neural mechanisms underlying the aesthetic and emotional aspects of color perception remain unknown. The current study reports evidence regarding the neural correlates of color harmony and disharmony. Functional magnetic resonance imaging was used to assess brain regions activated by harmonious or disharmonious color combinations in comparison to other stimuli. Results showed that the left medial orbitofrontal cortex and left amygdala were activated when participants observed harmonious and disharmonious stimuli, respectively. Taken together, these findings suggest that color disharmony may depend on stimulus properties and more automatic neural processes mediated by the amygdala, whereas color harmony is harder to discriminate based on color characteristics and is reflected by the aesthetic value represented in the medial orbitofrontal cortex. This study has a limitation that we could not exclude the effect of preference for color combination, which has a strong positive correlation with color harmony.

  5. Using McDaniel's model to represent non-Rayleigh active sonar reverberation

    Science.gov (United States)

    Gu, Ming

    Reverberation in active sonar systems has often been observed to follow non-Rayleigh distributions. Current statistical models tend to be either too restrictive, leading to significant mismatch error, or too general, leading to large estimation error. McDaniel's model has shown promise as having reasonably tight representation in terms of skewness and kurtosis for reverberation from a variety of sonar systems. This dissertation intensively explores capability and effectiveness of the generalized McDaniel's model in representing non-Rayleigh reverberation when minimal data are available. Three major topics are covered in this dissertation. First, derivation and computation of the cumulative distribution function of McDaniel's model is addressed. Two approaches, one based on direct integration and the other via characteristic function inversion, are both shown to achieve adequate precision with the former leading to a closed-form solution and the latter requiring significantly less computational effort. Second, parameter estimators using both method of moments (MM) and maximum likelihood (ML) algorithms are developed. The MM estimator has the advantage of a simple and rapid implementation, but the disadvantage of a non- zero probability of a solution not existing. Bootstrap/pruning techniques are proposed to partially deal with the failure of this method. The ML estimator will always provide a solution; however, it requires multivariate optimization. The expectation-maximization (EM) algorithm iteration is also derived for obtaining the ML estimates and compared with the simplex method and quasi-Newton multivariate optimization routines. Furthermore, the ability of various statistical models to represent the probability of false alarm is evaluated as a function of sample size. It is demonstrated that when minimal data are available, McDaniel's model can more accurately represent non-Rayleigh reverberation than the K or Rayleigh mixture models. Third, detection

  6. DNA去甲基化机制的研究进展%Progress in Study on Mechanism of DNA Demethylation

    Institute of Scientific and Technical Information of China (English)

    曹领改; 张旸; 蓝兴国; 李玉花

    2012-01-01

    As a significant epigenetic modification, DNA methylation plays a critical role in regulating gene expression and maintaining genomic stability in mammals and flowering plants. DNA methylation level and pattern of change will lead to abnormal phenotype or even death. The level and pattern of 5-Mc are determined by both DNA methylation and demethylation processes. Demethylation of DNA can be passive and active. The formation of DNA methylation pattern depends on the active demethylation. Five potential mechanisms of DNA active demethylation are reviewed in this paper: base excision repair involved with DNA glycosylases, base excision repair involved with enzymatic deamination, nucleotide excision repair, oxidative demethylation and hydrolysis.%DNA甲基化作为动植物体内一种重要的表观遗传修饰形式,在调控基因表达、维持基因组的稳定性等方面发挥重要的生物学作用.固有DNA甲基化水平和模式的变化会导致生物的表型异常甚至死亡.而5-甲基胞嘧啶的水平和模式是由DNA甲基化和去甲基化共同决定的.DNA去甲基化可以分为主动去甲基化与被动去甲基化,而基因组甲基化模式的形成主要依赖于主动去甲基化.本文综述了生物体内DNA主动去甲基化五种潜在机制:DNA转葡糖基酶参与的碱基切除修复途径、脱氨酶参与的碱基切除修复途径、核苷酸切除修复途径、氧化作用去甲基化与水解作用去甲基化.

  7. Design and synthesis of novel 4'-demethyl-4-deoxypodophyllotoxin derivatives as potential anticancer agents.

    Science.gov (United States)

    Zhu, Xiong; Fu, Junjie; Tang, Yan; Gao, Yuan; Zhang, Shijin; Guo, Qinglong

    2016-02-15

    A group of podophyllotoxin (PPT) derivatives (7a-j) were synthesized by conjugating aryloxyacetanilide moieties to the 4'-hydroxyl of 4'-demethyl-4-deoxypodophyllotoxin (DDPT), and their anticancer activity was evaluated. It was found that the most potent compound 7d inhibited the proliferation of three cancer cell lines with sub to low micromolar IC50 values. Furthermore, it was demonstrated that 7d induced cell cycle arrest in G2/M phase in MGC-803 cells, and regulated the expression of cell cycle check point proteins, such as cyclin A, cyclin B, CDK1, cdc25c, and p21. Finally, 4 mg/kg of 7d reduced the weights and volumes of HepG2 xenografts in mice. Our findings suggest that 7d might be a potential anticancer agent. PMID:26804229

  8. Suppression of gluconeogenic gene expression by LSD1-mediated histone demethylation.

    Directory of Open Access Journals (Sweden)

    Dongning Pan

    Full Text Available Aberrant gluconeogenic gene expression is associated with diabetes, glycogen storage disease, and liver cancer. However, little is known how these genes are regulated at the chromatin level. In this study, we investigated in HepG2 cells whether histone demethylation is a potential mechanism. We found that knockdown or pharmacological inhibition of histone demethylase LSD1 causes remarkable transcription activation of two gluconeogenic genes, FBP1 and G6Pase, and consequently leads to increased de novo glucose synthesis and decreased intracellular glycogen content. Mechanistically, LSD1 occupies the promoters of FBP1 and G6Pase, and modulates their H3K4 dimethylation levels. Thus, our work identifies an epigenetic pathway directly governing gluconeogenic gene expression, which might have important implications in metabolic physiology and diseases.

  9. A probabilistic generative model for quantification of DNA modifications enables analysis of demethylation pathways.

    Science.gov (United States)

    Äijö, Tarmo; Huang, Yun; Mannerström, Henrik; Chavez, Lukas; Tsagaratou, Ageliki; Rao, Anjana; Lähdesmäki, Harri

    2016-03-14

    We present a generative model, Lux, to quantify DNA methylation modifications from any combination of bisulfite sequencing approaches, including reduced, oxidative, TET-assisted, chemical-modification assisted, and methylase-assisted bisulfite sequencing data. Lux models all cytosine modifications (C, 5mC, 5hmC, 5fC, and 5caC) simultaneously together with experimental parameters, including bisulfite conversion and oxidation efficiencies, as well as various chemical labeling and protection steps. We show that Lux improves the quantification and comparison of cytosine modification levels and that Lux can process any oxidized methylcytosine sequencing data sets to quantify all cytosine modifications. Analysis of targeted data from Tet2-knockdown embryonic stem cells and T cells during development demonstrates DNA modification quantification at unprecedented detail, quantifies active demethylation pathways and reveals 5hmC localization in putative regulatory regions.

  10. The Cell Cycle: An Activity Using Paper Plates to Represent Time Spent in Phases of the Cell Cycle

    Science.gov (United States)

    Scherer, Yvette D.

    2014-01-01

    In this activity, students are given the opportunity to combine skills in math and geometry for a biology lesson in the cell cycle. Students utilize the data they collect and analyze from an online onion-root-tip activity to create a paper-plate time clock representing a 24-hour cell cycle. By dividing the paper plate into appropriate phases of…

  11. Activity Profiles and Physiological Responses of Representative Tag Football Players in Relation to Playing Position and Physical Fitness

    OpenAIRE

    Luke W Hogarth; Burkett, Brendan J; McKean, Mark R.

    2015-01-01

    This study determined the physical fitness, match-activity profiles and physiological responses of representative tag football players and examined the relationship between physical fitness and the match-activity profile. Microtechnology devices and heart rate (HR) chest straps were used to determine the match-activity profiles of sixteen tag football players for five matches during the 2014 Australian National Championships. The relationships between lower body muscular power, straight line ...

  12. Fire activity and severity in the western US vary along proxy gradients representing fuel amount and fuel moisture.

    Directory of Open Access Journals (Sweden)

    Sean A Parks

    Full Text Available Numerous theoretical and empirical studies have shown that wildfire activity (e.g., area burned at regional to global scales may be limited at the extremes of environmental gradients such as productivity or moisture. Fire activity, however, represents only one component of the fire regime, and no studies to date have characterized fire severity along such gradients. Given the importance of fire severity in dictating ecological response to fire, this is a considerable knowledge gap. For the western US, we quantify relationships between climate and the fire regime by empirically describing both fire activity and severity along two climatic water balance gradients, actual evapotranspiration (AET and water deficit (WD, that can be considered proxies for fuel amount and fuel moisture, respectively. We also concurrently summarize fire activity and severity among ecoregions, providing an empirically based description of the geographic distribution of fire regimes. Our results show that fire activity in the western US increases with fuel amount (represented by AET but has a unimodal (i.e., humped relationship with fuel moisture (represented by WD; fire severity increases with fuel amount and fuel moisture. The explicit links between fire regime components and physical environmental gradients suggest that multivariable statistical models can be generated to produce an empirically based fire regime map for the western US. Such models will potentially enable researchers to anticipate climate-mediated changes in fire recurrence and its impacts based on gridded spatial data representing future climate scenarios.

  13. Association Between User-Generated Commuting Data and Population-Representative Active Commuting Surveillance Data - Four Cities, 2014-2015.

    Science.gov (United States)

    Whitfield, Geoffrey P; Ussery, Emily N; Riordan, Brian; Wendel, Arthur M

    2016-01-01

    Creating environments that support all types of physical activity, including active transportation, is a public health priority (1). Public health surveillance that identifies the locations where community members walk and bicycle (i.e., engage in active transportation) can inform such efforts. Traditional population-representative active transportation surveillance incurs a considerable time lag between data collection and dissemination, and often lacks geographic specificity (2). Conversely, user-generated active transportation data from Global Positioning System (GPS)-based activity tracking devices and mobile applications can provide near real-time information, but might be subject to self-selection bias among users. CDC analyzed the association between GPS-based commuting data from a company that allows tracking of activity with a mobile application (Strava, Inc., San Francisco, California) and population-representative commuting data from the U.S. Census Bureau's American Community Survey (ACS) (3) for four U.S. cities. The level of analysis was the Census block group. The number of GPS-tracked commuters in Strava was associated with the number of ACS active commuters (Spearman's rho = 0.60), suggesting block groups were ranked similarly based on these distinct but related measurements. The correlation was higher in high population density areas. User-generated active transportation data might complement traditional surveillance systems by providing near real-time, location-specific information on where active transportation occurs. PMID:27632357

  14. Distance to green space and physical activity: a danish national representative survey

    DEFF Research Database (Denmark)

    Toftager, Mette; Ekholm, Ola; Schipperijn, Jasper;

    2011-01-01

    This study examines the relationship between distance to green space and the level of physical activity among the population of Denmark. In addition, the relationship between distance to green space and obesity is investigated.......This study examines the relationship between distance to green space and the level of physical activity among the population of Denmark. In addition, the relationship between distance to green space and obesity is investigated....

  15. Method for recovering and using lignin in adhesive resins by extracting demethylated lignin

    Science.gov (United States)

    Schroeder, Herbert A.

    1991-01-01

    Lignin, or a lignin derived material, which has been significantly demethylated (e.g., the demethylated lignin found in the raffinate produced as a by-product of dimethyl sulfide production which can be carried out using the spent liquor from wood pulping operations) can be isolated by a process wherein an organic solvent is added to a lignin-containing aqueous solution. The organic solvent is typically a polar, and at least a partially water-immiscible substance such as, for example, ethyl acetate. The resulting lignin-containing aqueous solution/organic solvent mixture is acidified to produce a water layer which is discarded and an organic solvent layer which contains the demethylated lignin. Upon its recovery, the demethylated lignin is preferably dried and stored until it is used (along with an alkali, an aldehyde and an adhesive filler) in compounding an adhesive of the type generally used in the manufacture of plywood.

  16. Decreased electrophysiological activity represents the conscious state of emptiness in meditation.

    Science.gov (United States)

    Hinterberger, Thilo; Schmidt, Stephanie; Kamei, Tsutomu; Walach, Harald

    2014-01-01

    Many neuroscientific theories explain consciousness with higher order information processing corresponding to an activation of specific brain areas and processes. In contrast, most forms of meditation ask for a down-regulation of certain mental processing activities while remaining fully conscious. To identify the physiological properties of conscious states with decreased mental and cognitive processing, the electrical brain activity (64 channels of EEG) of 50 participants of various meditation proficiencies was measured during distinct and idiosyncratic meditative tasks. The tasks comprised a wakeful "thoughtless emptiness (TE)," a "focused attention," and an "open monitoring" task asking for mindful presence in the moment and in the environment without attachment to distracting thoughts. Our analysis mainly focused on 30 highly experienced meditators with at least 5 years and 1000 h of meditation experience. Spectral EEG power comparisons of the TE state with the resting state or other forms of meditation showed decreased activities in specific frequency bands. In contrast to a focused attention task the TE task showed significant central and parietal gamma decreases (p meditation practice did not present those differences significantly. Our findings indicate that a conscious state of TE reached by experienced meditators is characterized by reduced high-frequency brain processing with simultaneous reduction of the low frequencies. This suggests that such a state of meditative conscious awareness might be different from higher cognitive and mentally focused states but also from states of sleep and drowsiness.

  17. Decreased Electrophysiological Activity Represents the Conscious State of Emptiness in Meditation

    Directory of Open Access Journals (Sweden)

    Thilo eHinterberger

    2014-02-01

    Full Text Available Many neuroscientific theories explain consciousness with higher order information processing corresponding to an activation of specific brain areas and processes. In contrast, most forms of meditation ask for a down-regulation of certain mental processing activities while remaining fully conscious. To identify the physiological properties of conscious states with decreased mental and cognitive processing, the electrical brain activity (64 channels of EEG of 50 participants of various meditation proficiencies was measured during distinct and idiosyncratic meditative tasks. The tasks comprised a wakeful ‘thoughtless emptiness (TE’, a ‘focused attention’, and an ‘open monitoring’ task asking for mindful presence in the moment and in the environment without attachment to distracting thoughts. Our analysis mainly focused on 30 highly experienced meditators with at least 5 years and 1000 hours of meditation experience.Spectral EEG power comparisons of the TE state with the resting state or other forms of meditation showed decreased activities in specific frequency bands. In contrast to a focused attention task the TE task showed significant central and parietal gamma decreases (pOur findings indicate that a conscious state of thoughtless emptiness reached by experienced meditators is characterized by reduced high-frequency brain processing with simultaneous reduction of the low frequencies. This suggests that such a state of meditative conscious awareness might be different from higher cognitive and mentally focused states but also from states of sleep and drowsiness.

  18. Extracurricular Activities and Bullying Perpetration: Results from a Nationally Representative Sample

    Science.gov (United States)

    Riese, Alison; Gjelsvik, Annie; Ranney, Megan L.

    2015-01-01

    Background: Bullying is a widespread problem for school-aged children and adolescents. Interventions to reduce bullying are not well disseminated. Extracurricular involvement is, however, common. This study aims to examine the relationship between parent-reported participation in extracurricular activities and bullying perpetration. Methods: Using…

  19. Norcantharidin inhibits Wnt signal pathway via promoter demethylation of WIF-1 in human non-small cell lung cancer.

    Science.gov (United States)

    Xie, Junran; Zhang, Yaping; Hu, Xuming; Lv, Ran; Xiao, Dongju; Jiang, Li; Bao, Qi

    2015-05-01

    Wingless-type (Wnt) family of secreted glycoproteins is a group of signal molecules implicated in oncogenesis. Abnormal activation of Wnt signal pathway is associated with a variety of human cancers, including non-small cell lung cancer (NSCLC). Wnt antagonists, such as the secreted frizzled-related protein (SFRP) family, Wnt inhibitory factor-1 (WIF-1) and cerberus, inhibit Wnt signal pathway by directly binding to Wnt molecules. Norcantharidin (NCTD) is known to possess anticancer activity but less nephrotoxicity than cantharidin. In this study, we found that NCTD inhibited cell proliferation, induced apoptosis, arrested cell cycle and suppressed cell invasion/migration in vitro. Additionally, Wnt signal pathway transcription was also suppressed. NCTD treatment blocked cytoplasmic translocation of beta-catenin into the nucleus. Alterations of apoptosis-related proteins, such as Bax, cleaved caspase-3 (pro-apoptotic) and Bcl-2 (anti-apoptotic), had been detected. Furthermore, the expression levels of WIF-1 and SFRP1 were significantly increased in NCTD-treated groups compared with negative control (NC) groups. Abnormal methylation was observed in NC groups, while NCTD treatment promoted WIF-1 demethylation. The present study revealed that NCTD activated WIF-1 via promoter demethylation, inhibiting the canonical Wnt signal pathway in NSCLC, which may present a new therapeutic target in vivo. PMID:25814287

  20. Arsenic Demethylation by a C·As Lyase in Cyanobacterium Nostoc sp. PCC 7120.

    Science.gov (United States)

    Yan, Yu; Ye, Jun; Xue, Xi-Mei; Zhu, Yong-Guan

    2015-12-15

    Arsenic, a ubiquitous toxic substance, exists mainly as inorganic forms in the environment. It is perceived that organoarsenicals can be demethylated and degraded into inorganic arsenic by microorganisms. Few studies have focused on the mechanism of arsenic demethylation in bacteria. Here, we investigated arsenic demethylation in a typical freshwater cyanobacterium Nostoc sp. PCC 7120. This bacterium was able to demethylate monomethylarsenite [MAs(III)] rapidly to arsenite [As(III)] and also had the ability to demethylate monomethylarsenate [MAs(V)] to As(III). The NsarsI encoding a C·As lyase responsible for MAs(III) demethylation was cloned from Nostoc sp. PCC 7120 and heterologously expressed in an As-hypersensitive strain Escherichia coli AW3110 (ΔarsRBC). Expression of NsarsI was shown to confer MAs(III) resistance through arsenic demethylation. The purified NsArsI was further identified and functionally characterized in vitro. NsArsI existed mainly as the trimeric state, and the kinetic data were well-fit to the Hill equation with K0.5 = 7.55 ± 0.33 μM for MAs(III), Vmax = 0.79 ± 0.02 μM min(-1), and h = 2.7. Both of the NsArsI truncated derivatives lacking the C-terminal 10 residues (ArsI10) or 23 residues (ArsI23) had a reduced ability of MAs(III) demethylation. These results provide new insights for understanding the important role of cyanobacteria in arsenic biogeochemical cycling in the environment.

  1. DNA demethylation induced by 5-azacytidine does not affect fragile X expression.

    OpenAIRE

    Glover, T W; Coyle-Morris, J; Pearce-Birge, L; Berger, C; Gemmill, R M

    1986-01-01

    Experiments were performed to determine the role of DNA demethylation in fragile X expression. Fragile X positive lymphoblastoid cells were treated with 5-azacytidine and harvested for analysis of fragile X expression both directly following treatment and after a recovery period in the absence of the drug. The effectiveness of 5-azacytidine treatment in inducing DNA demethylation was concurrently monitored by analysis of methylation changes at random autosomal loci in isolated DNA from treate...

  2. BOLD data representing activation and connectivity for rare no-go versus frequent go cues.

    Science.gov (United States)

    Meffert, Harma; Hwang, Soonjo; Nolan, Zachary T; Chen, Gang; Blair, James R

    2016-06-01

    The neural circuitry underlying response control is often studied using go/no-go tasks, in which participants are required to respond as fast as possible to go cues and withhold from responding to no-go stimuli. In the current task, response control was studied using a fully counterbalanced design in which blocks with a low frequency of no-go cues (75% go, 25% no-go) were alternated with blocks with a low frequency of go cues (25% go, 75% no-go); see also "Segregating attention from response control when performing a motor inhibition task: Segregating attention from response control" [1]. We applied a whole brain corrected, paired t-test to the data assessing for regions differentially activated by low frequency no-go cues relative to high frequency go cues. In addition, we conducted a generalized psychophysiological interaction analysis on the data using a right inferior frontal gyrus seed region. This region was identified through the BOLD response t-test and was chosen because right inferior gyrus is highly implicated in response inhibition. PMID:26955650

  3. Association of Dietary Behaviors with Physical Activity in a Nationally Representative Sample of Children and Adolescents: the CASPIAN- IV Study

    OpenAIRE

    Saeid Safiri; Roya Kelishadi; Mostafa Qorbani; Razieh Lotfi; Shirin Djalalinia; Delara Salehifar; Mohammad Esmaeil Motlagh; Gelayol Ardalan; Morteza Mansourian; Hamid Asayesh; Ramin Heshmat

    2016-01-01

    Background: Nutritional health and adequate physical activity (PA), especially in childhood and grow periods, have a substantial role in health. This study assessed the association of dietary behaviors (main courses and snacks intake) with PA in children and adolescents. Materials and Methods: Using multistage random cluster sampling method, a representative sample of 14,880 school students were selected from urban and rural areas of 30 provinces of Iran. Through a validated questionnaire, da...

  4. Redistribution of demethylated RNA helicase A during foot-and-mouth disease virus infection: role of jumonji C-domain containing protein 6 in RHA demethylation

    Science.gov (United States)

    We previously reported that RNA Helicase A (RHA) re-localized from the nucleus to the cytoplasm in foot-and-mouth disease virus (FMDV) infected cells, coincident with a reduction in methylation of arginine residues in the RHA C-terminus. To further define the mechanism of RHA demethylation in FMDV-...

  5. Activity Profiles and Physiological Responses of Representative Tag Football Players in Relation to Playing Position and Physical Fitness.

    Directory of Open Access Journals (Sweden)

    Luke W Hogarth

    Full Text Available This study determined the physical fitness, match-activity profiles and physiological responses of representative tag football players and examined the relationship between physical fitness and the match-activity profile. Microtechnology devices and heart rate (HR chest straps were used to determine the match-activity profiles of sixteen tag football players for five matches during the 2014 Australian National Championships. The relationships between lower body muscular power, straight line running speed and Yo-Yo intermittent recovery test level 2 (Yo-Yo IR2 and the match-activity profile were examined using Pearson's correlation coefficients. Outside players had greater lower body muscular power (ES = 0.98 and straight line running speed (ES = 1.03-1.18 than inside players, and also covered greater very high-speed running (VHSR distance/min (ES = 0.67 and reached higher peak running speeds (ES = 0.95 during matches. Inside and outside players performed a similar number of repeated high-intensity effort (RHIE bouts and reported similar mean and maximum efforts per RHIE bout. However, there were differences between playing positions for mean and maximal RHIE effort durations (ES = 0.69-1.15 and mean RHIE bout recovery (ES = 0.56. Inside and outside players also reported small to moderate differences (ES = 0.43-0.80 for times spent in each HR zone. There were a number of moderate to very large correlations between physical fitness measures and match-activity profile variables. This study found lower body muscular power, straight line running speed and Yo-Yo IR2 to be related to the match-activities of representative tag football players, although differences between inside and outside players suggest that athlete testing and training practices should be modified for different playing positions.

  6. Epigenetic DNA Demethylation Causes Inner Ear Stem Cell Differentiation into Hair Cell-Like Cells

    Science.gov (United States)

    Zhou, Yang; Hu, Zhengqing

    2016-01-01

    The DNA methyltransferase (DNMT) inhibitor 5-azacytidine (5-aza) causes genomic demethylation to regulate gene expression. However, it remains unclear whether 5-aza affects gene expression and cell fate determination of stem cells. In this study, 5-aza was applied to mouse utricle sensory epithelia-derived progenitor cells (MUCs) to investigate whether 5-aza stimulated MUCs to become sensory hair cells. After treatment, MUCs increased expression of hair cell genes and proteins. The DNA methylation level (indicated by percentage of 5-methylcytosine) showed a 28.57% decrease after treatment, which causes significantly repressed DNMT1 protein expression and DNMT activity. Additionally, FM1-43 permeation assays indicated that the permeability of 5-aza-treated MUCs was similar to that of sensory hair cells, which may result from mechanotransduction channels. This study not only demonstrates a possible epigenetic approach to induce tissue specific stem/progenitor cells to become sensory hair cell-like cells, but also provides a cell model to epigenetically modulate stem cell fate determination. PMID:27536218

  7. Re-expression of RASSF1A by 5-Aza-CdR Induced Demethylation of the Promoter Region in Human Biliary Tract Carcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    ZUO Shi; CHEN Yongjun; XU Lining; TANG Qibin; ZOU Shengquan

    2007-01-01

    Hypermethylation of the promoter region is an important mean for the transcriptional repression of a number of cancer-associated genes, and over-expression and/or increased activity of DNA methyltransferase are considered to be the main cause of promoter hypermethylation. In order to further explore the epigenetic mechanism of tumor suppressor gene RASSF1A inactivation,5-aza-2'-deoxycytidine (5-Aza-CdR), a DNA methyltransferase inhibitor, was used to treat the human biliary tract carcinoma cell line QBC-939 at the concentration of 5 μmol/L for 24 h in this study. After the chemical intervention with 5-Aza-CdR, the methylation status in the promoter region of RASSF1A gene was detected by methylation specific PCR (MS-PCR), and the expression alteration of RASSF1A mRNA and protein were observed by RT-PCR and Western Blot respectively. Following the treatment with 5-Aza-CdR, methylaiton status in the promoter region of RASSF1A gene was reversed from methylation to unmethylation. A 280 bp DNA band which represented RASS1FA expression at transcriptional level and a 40 kDa (1kDa=0.9921 ku) protein band which represented RASSF1A expression at protein level were detected by RT-PCR and Western Blot respectively in the experimental group cells and there were no corresponding bands in the control group cells. The experimental results suggest that 5-Aza-CdR can induce demethylation in the promoter region of RASSF1A. It can also reverse epigenetic transcriptional silencing caused by DNA methylation and induce the re-expression of RASSF1A in QBC-939. This study also suggest that the mechanism of RASSF1A inactivation is very closely related to the methylation of the promoter region, which may provide a new epigenetic understanding for tumor related gene inactivation and the pathogenesis of biliary tract carcinoma.

  8. Mbd2 Promotes Foxp3 Demethylation and T-Regulatory-Cell Function

    OpenAIRE

    Wang, Liqing; Liu, Yujie; Han, Rongxiang; Ulf H Beier; Thomas, Rajan M.; Wells, Andrew D.; Hancock, Wayne W.

    2013-01-01

    Use of Foxp3-positive (Foxp3+) T-regulatory (Treg) cells as potential cellular therapy in patients with autoimmunity, or post-stem cell or -organ transplantation, requires a sound understanding of the transcriptional regulation of Foxp3. Conserved CpG dinucleotides in the Treg-specific demethylation region (TSDR) upstream of Foxp3 are demethylated only in stable, thymus-derived Foxp3+ Treg cells. Since methyl-binding domain (Mbd) proteins recruit histone-modifying and chromatin-remodeling com...

  9. Demethylating agent decitabine induces autologous cancer testis antigen specific cytotoxic T lymphocytes in vivo

    Institute of Scientific and Technical Information of China (English)

    ZHOU Ji-hao; YAO Yu-shi; WANG Li-xin; WANG Jia; LI Yong-hui; JIANG Meng-meng; ZHOU Min-hang

    2013-01-01

    Background Cancer testis antigens (CTAs) are a novel group of tumor associated antigens.Demethylating agent decitabine was reported to be able to up-regulate CTAs through its hypomethylation mechanism,thus enhance the immunogenicity of leukemia cells.However,few researches have ever focused on the questions that whether this immunostimulatory effect of decitabine could induce autologous CTA specific cytotoxic T lymphocytes (CTLs) in vivo,and if so,whether this effect contributes to disease control.In this study,we aimed to show that decitabine could induce specific autologous CTLs against some mouse CTAs in leukemia cells in vitro and in vivo.Methods Several mouse CTAs were screened by RT-PCR.CTL specific to one of the CTAs named P1A was detected and sorted by P1A specific dimer by flow cytometry.The activity of specific CTLs was measured by real time RT-PCR.Results We firstly screened expression of some CTAs in mouse leukemia cells before and after decitabine treatment and found that decitabine treatment did up-regulate expression of many CTAs.Then we measured the CTLs' activity specific to a mouse CTA P1A in vivo and showed that this activity increased after decitabine treatment.Finally,we sorted these in vivo induced P1A specific CTLs by flow cytometry and demonstrated their cytotoxicity against decitabine treated leukemia cells.Conclusions Our study showed the autologous immune response induced by decitabine in vivo.And more importantly,we firstly proved that this response may contribute to disease control.We believe that this immunostimulatory effect is another anti-cancer mechanism of decitabine,and this special effect would inspire new applications of decitabine in the field of leukemia treatment in the future.

  10. Base-oxidant promoted metal-free N-demethylation of arylamines

    Indian Academy of Sciences (India)

    VINAYAK BOTLA; CHIRANJEEVI BARREDDI; RAMANA V DAGGUPATI; CHANDRASEKHARAM MALAPAKA

    2016-09-01

    A metal-free oxidative N-demethylation of arylamines with triethylamine as a base and tert-butyl hydroperoxide (TBHP) as oxidant is reported in this paper. The reaction is general, practical, inexpensive, non-toxic, and the method followed is environmentally benign, with moderate to good yields.

  11. Biochemical mechanisms involved in selective fungitoxicity of fungicides which inhibit sterol 14_-demethylation.

    NARCIS (Netherlands)

    Kapteyn, J.C.

    1993-01-01

    Sterol demethylation inhibitors (DMIs) are antifungal agents which inhibit the biosynthesis of ergosterol by binding to cytochrome-P450-dependent sterol 14ce-demethylase (P450 14DM ). These compounds significantly differ in both toxicity and selectivity. This thesis

  12. Testosterone Depletion Induces Demethylation of Murine Reelin Promoter CpG Dinucleotides: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Victor Augusto Moraes da Silva

    2015-01-01

    Full Text Available Schizophrenia (SZ is a debilitating mental disorder characterized by psychotic events, abnormal social behavior, false beliefs, and auditory hallucinations. Hypermethylation of the promoter region of reelin (RELN, a gene involved in regulation of neuronal positioning during telencephalic development, is strongly associated with low protein expression in several cortical structures and promoter hypermethylation in brain from postmortem SZ subjects. Recent experimental data suggests that testosterone is able to promote RELN demethylation, although no direct evidence of hormonal influence on reelin promoter methylation was obtained. We investigated if reduced levels of plasma testosterone in adult male mice lead to Reln promoter demethylation. Animals were administered with flutamide, an antiandrogenic compound, and reelin promoter methylation was assessed using methylationspecific PCR using bisulfite DNA from cerebellum. We found that flutamide was able to significantly lower plasma testosterone when compared to control mice, and treatment did not influence animal survival and body weight. We also show that low plasma testosterone was associated with demethylation of a cytosine residue located at −860 in reelin promoter region. These preliminary data suggest that androgenic hormones can influence cerebral reelin demethylation. To our knowledge, this is the first experimental approach directly linking testosterone depletion and RELN promoter methylation.

  13. Testosterone Depletion Induces Demethylation of Murine Reelin Promoter CpG Dinucleotides: A Preliminary Study.

    Science.gov (United States)

    da Silva, Victor Augusto Moraes; Dantas, Marília de Souza; Silva, Leonardo Agostinho de Castro; Carneiro, Juliana Garcia; Schamber-Reis, Bruno Luiz Fonseca

    2015-01-01

    Schizophrenia (SZ) is a debilitating mental disorder characterized by psychotic events, abnormal social behavior, false beliefs, and auditory hallucinations. Hypermethylation of the promoter region of reelin (RELN), a gene involved in regulation of neuronal positioning during telencephalic development, is strongly associated with low protein expression in several cortical structures and promoter hypermethylation in brain from postmortem SZ subjects. Recent experimental data suggests that testosterone is able to promote RELN demethylation, although no direct evidence of hormonal influence on reelin promoter methylation was obtained. We investigated if reduced levels of plasma testosterone in adult male mice lead to Reln promoter demethylation. Animals were administered with flutamide, an antiandrogenic compound, and reelin promoter methylation was assessed using methylationspecific PCR using bisulfite DNA from cerebellum. We found that flutamide was able to significantly lower plasma testosterone when compared to control mice, and treatment did not influence animal survival and body weight. We also show that low plasma testosterone was associated with demethylation of a cytosine residue located at -860 in reelin promoter region. These preliminary data suggest that androgenic hormones can influence cerebral reelin demethylation. To our knowledge, this is the first experimental approach directly linking testosterone depletion and RELN promoter methylation. PMID:26526966

  14. Anti-HIV activities of HIV-1 reverse transcriptase inhibitor racemic 11-demethyl-calanolide A%HIV-1逆转录酶抑制剂消旋11-去甲胡桐素A的抗HIV-1活性研究

    Institute of Scientific and Technical Information of China (English)

    彭宗根; 陈鸿珊; 王琳; 刘刚

    2008-01-01

    本文比较研究消旋11*去甲胡桐素A[(±)-11-demethyl-calauolide A]和其母体消旋胡桐素A[(±)-calanolide A]在体外、细胞培养内和小鼠体内给药后血清的抗HIV+1(human immunodeficiency virus type 1)活性.二者在体外对HIV-1逆转录酶(reverse transcriptase,RT)的半数抑制浓度(IC50)分别为(3.028±2.514)μmol·L-1和(3.965±5.235)μmol·L-1.在HIV-1感染的MT-4细胞培养内抑制HIV-1细胞病变的IC50和选择指数分别为(1.081±0.337)μmol·L-1和26及(1.297±0.076)μmol·L-1和21.腹腔注射小鼠1次(100 mg·L-1)后30 min和60 min的血清对HIV-1 RT的抑制率前者分别为(42.7±1.5)%和(32.2±6.1)%,后者分别为(40.7±6.3)%和(29.2±6.7)%,说明消旋11-去甲胡桐素A为新非核苷类HIV-1逆转录酶抑制剂,比其母体消旋胡桐素A的抗HIV-1活性略高,值得进一步研究.

  15. Lignin demethylation and polysaccharide decomposition in spruce sapwood degraded by brown rot fungi

    Energy Technology Data Exchange (ETDEWEB)

    Filley, T.R.; Cody, G.D.; Noser, C. [Carnegie Inst. of Washington, DC (United States). Geophysical Lab.; Goodell, B. [University of Maine, Orono, ME (United States). Dept. of Wood Science; Jellison, J.; Ostrofsky, A. [University of Maine, Orono, ME (United States). Dept. of Biological Sciences

    2002-07-01

    The organic residues produced in the brown-rot (BR) of wood by many basidiomycetes fungi are ubiquitous on most coniferous forest floors. This degraded wood tissue is characterized by low levels of polysaccharides and a high proportion of demethylated lignin with minor glycerol side chain oxidation. Because of the selective enrichment in an aromatic dihydroxy-rich lignin residue, the chemical and biological reactivity of BR degraded wood will be distinctly different from white rot, the other primary class of fungal wood decay, which typically produces oxidized, lignin-depleted residues. The biochemical mechanism by which BR fungi perform this distinctive degradative chemistry is only starting to become known, and molecular studies which examine the chemical changes imparted to lignin over the long-term decay process are lacking. Using {sup 13}C-labeled tetramethylammonium hydroxide thermochemolysis ({sup 13}C -TMAH) and solid state {sup 13}C NMR, we investigated the relationship between lignin oxidation/demethylation and polysaccharide metabolism in a 32-week time series study of spruce sapwood inoculated with either of two BR fungi (Postia placenta and Gloeophyllum trabeum). Our findings demonstrate a close relationship between lignin demethylation and polysaccharide loss and suggest demethylation may play a mechanistic role in polysaccharide loss, possibly by assisting in Fenton reactions where catechol/quinone oxidation and cycling aids in iron reduction. The residue remaining after 16 weeks of decay is devoid of polysaccharides, in contrast to the 68% polysaccharide carbon present in the initial spruce, and exhibits an increased aromatic dihydroxy content (resulting from demethylation of the 3-methoxyl carbon) of up to 22% of the lignin, as determined by {sup 13}C-TMAH thermochemolysis. In a typical soil or porewater environment these chemical changes would make BR residues highly reactive toward redox sensitive polyvalent metals (e.g. ferric iron) and likely

  16. Representing dispositions

    Directory of Open Access Journals (Sweden)

    Röhl Johannes

    2011-08-01

    Full Text Available Abstract Dispositions and tendencies feature significantly in the biomedical domain and therefore in representations of knowledge of that domain. They are not only important for specific applications like an infectious disease ontology, but also as part of a general strategy for modelling knowledge about molecular interactions. But the task of representing dispositions in some formal ontological systems is fraught with several problems, which are partly due to the fact that Description Logics can only deal well with binary relations. The paper will discuss some of the results of the philosophical debate about dispositions, in order to see whether the formal relations needed to represent dispositions can be broken down to binary relations. Finally, we will discuss problems arising from the possibility of the absence of realizations, of multi-track or multi-trigger dispositions and offer suggestions on how to deal with them.

  17. Association of Dietary Behaviors with Physical Activity in a Nationally Representative Sample of Children and Adolescents: the CASPIAN- IV Study

    Directory of Open Access Journals (Sweden)

    Saeid Safiri

    2016-03-01

    Full Text Available Background: Nutritional health and adequate physical activity (PA, especially in childhood and grow periods, have a substantial role in health. This study assessed the association of dietary behaviors (main courses and snacks intake with PA in children and adolescents. Materials and Methods: Using multistage random cluster sampling method, a representative sample of 14,880 school students were selected from urban and rural areas of 30 provinces of Iran. Through a validated questionnaire, daily consumption of main course ( breakfast, lunch, and dinner as well as daily consumption of different snacks and health foods ( fast foods, milk, vegetables, dry fruits, fresh fruits, sweetened beverages, salty snacks and sweets were recorded for every participants. Information of past week weekly frequency of leisure time PA was collected. Results: Overall, 13,486 out of 14,880 students (response rate: 90.6% participated in this survey. Participants consisted of 6,640 (49.2% girls and 75.6% urban residents; their mean and standard deviation (SD age was 12.47 (3.36 years. Daily consumption of fresh fruits (odds ratio [OR]: 1.35, 95%confidence interval [CI]: 1.20-1.52, dried fruits (OR: 1.21; 95%CI: 1.06-1.40, vegetable (OR: 1.39; 95% CI: 1.24-1.56, and milk (OR: 1.35; 95% CI: 1.21-1.52 increased the odds of high PA compare to low PA in adjusted model.  Skipping the breakfast, lunch and dinner decreased the odds of moderate and high PA compare to low PA (P

  18. Lipoxygenase—mediated N—demethylation of imipramine and related tricyclic antidepressants

    Institute of Scientific and Technical Information of China (English)

    HuJA; SajaM

    2002-01-01

    The ability of soybean lipoxygenase to mediate the N-demethylation of imipramine and related drugs in the presence of hydrogen peroxide was examined.Under optimal assay conditions,Vmax values of 14 to 18 mol formaldehyde·min-1·mol-1 enzyme were observed.An inhibition of formaldehyde and desipramine formation by nordihydroguaiaretic acid confirmed the lipoxygenase involvement.The blockade of the reaction by glutathione,dithiothreitol butylated hydroxyanisole (BHA) and butylated hydroxytoluene(BHT) indicated the generation of a free radical intermediate from imipramine.Desipramine,trimipramine,clomipramine,and diltiazem,but not amitriptyline and doxepin,were also oxidized,albeit at a lower rate.Collectively,the evidence gathered in this study suggests,for the first time,that tricyclic antidepressant drugs may undergo lipoxygenase-catalyzed N-demethylation.

  19. Characterizing resistance of Erysiphe necator to fungicides belonging to the quinone outside inhibitors and demethylation inhibitors

    OpenAIRE

    Rallos, Lynn Esther Espada

    2013-01-01

    Practical resistance of Erysiphe necator to quinone outside inhibitors (QoIs) is now widespread, and resistance to demethylation inhibitors (DMIs) has also developed.  The goal of this research was to characterize fungicide resistance by elucidating resistance mechanisms and determining its stability.  QoI resistance persisted for several years in a field population after QoI application ended.  Resistant isolates were highly competitive in mixed populations in competition assays under labora...

  20. Demethylation of the human eotaxin-3 gene promoter leads to the elevated expression of eotaxin-3

    OpenAIRE

    Lim, Eunjin; Rothenberg, Marc E.

    2013-01-01

    DNA demethylation has been primarily studied in the context of development biology, cell fate, and cancer, with less attention on inflammation. Herein, we investigate the association between DNA methylation and production of the chemoattractant cytokine eotaxin-3 in the tissue of patients with allergic disease. Regions of the human eotaxin-3 promoter were found to be hypomethylated in primary epithelial cells obtained from allergic tissue compared with normal control tissue (CTL). The demethy...

  1. Global identification of genes regulated by estrogen signaling and demethylation in MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Putnik, Milica, E-mail: milica.putnik@ki.se [Department of Biosciences and Nutrition, Novum, Karolinska Institutet, Huddinge S-14183 (Sweden); Zhao, Chunyan, E-mail: chunyan.zhao@ki.se [Department of Biosciences and Nutrition, Novum, Karolinska Institutet, Huddinge S-14183 (Sweden); Gustafsson, Jan-Ake, E-mail: jan-ake.gustafsson@ki.se [Department of Biosciences and Nutrition, Novum, Karolinska Institutet, Huddinge S-14183 (Sweden); Department of Biology and Biochemistry, Science and Engineering Research Center Bldg, University of Houston, Houston, TX 77204-5056 (United States); Dahlman-Wright, Karin, E-mail: karin.dahlman-wright@ki.se [Department of Biosciences and Nutrition, Novum, Karolinska Institutet, Huddinge S-14183 (Sweden)

    2012-09-14

    Highlights: Black-Right-Pointing-Pointer Estrogen signaling and demethylation can both control gene expression in breast cancers. Black-Right-Pointing-Pointer Cross-talk between these mechanisms is investigated in human MCF-7 breast cancer cells. Black-Right-Pointing-Pointer 137 genes are influenced by both 17{beta}-estradiol and demethylating agent 5-aza-2 Prime -deoxycytidine. Black-Right-Pointing-Pointer A set of genes is identified as targets of both estrogen signaling and demethylation. Black-Right-Pointing-Pointer There is no direct molecular interplay of mediators of estrogen and epigenetic signaling. -- Abstract: Estrogen signaling and epigenetic modifications, in particular DNA methylation, are involved in regulation of gene expression in breast cancers. Here we investigated a potential regulatory cross-talk between these two pathways by identifying their common target genes and exploring underlying molecular mechanisms in human MCF-7 breast cancer cells. Gene expression profiling revealed that the expression of approximately 140 genes was influenced by both 17{beta}-estradiol (E2) and a demethylating agent 5-aza-2 Prime -deoxycytidine (DAC). Gene ontology (GO) analysis suggests that these genes are involved in intracellular signaling cascades, regulation of cell proliferation and apoptosis. Based on previously reported association with breast cancer, estrogen signaling and/or DNA methylation, CpG island prediction and GO analysis, we selected six genes (BTG3, FHL2, PMAIP1, BTG2, CDKN1A and TGFB2) for further analysis. Tamoxifen reverses the effect of E2 on the expression of all selected genes, suggesting that they are direct targets of estrogen receptor. Furthermore, DAC treatment reactivates the expression of all selected genes in a dose-dependent manner. Promoter CpG island methylation status analysis revealed that only the promoters of BTG3 and FHL2 genes are methylated, with DAC inducing demethylation, suggesting DNA methylation directs repression of

  2. Regeneration and DNA demethylation do not trigger PDX-1 expression in rat hepatocytes

    Institute of Scientific and Technical Information of China (English)

    Rudolf; T; Pillich; Gianfranco; Scarsella; Gianfranco; Risuleo

    2010-01-01

    AIM:To explore the possibility that PDX-1 gene is reactivated as a consequence of molecular events that occur during liver regeneration. METHODS:Rat hepatocytes were maintained in DMEM- F12,10%fetal bovine serum(FBS),penicillin/streptomycin and geneticin when applicable.Rat insulinoma RIN 1046-38 cells were maintained in M-199-10%FBS and penicillin/streptomycin.The final concentration of glucose was 11.1 mmol/L.During regeneration,lateral and medial liver lobes of adult male Wistar rats were surgically removed,with up 70%loss of liver mass.In methylation experiments,5-aza-deoxycytidine(5-aza-dC)was used.Primer3 software was used for poly- merase chain reaction(PCR).Quantitative real time PCR (qRT-PCR)was performed using SYBR Green technol- ogy;primers were designed by Beacon Designer 6 software.Western blotting and SDS-PAGE were performed according to standard procedures.Antibodies were purchased from commercial suppliers.RESULTS:We explored the possibility that liver regeneration could trigger PDX-1 expression,and hence insulin production.Twenty-four hours after surgical liver removal,regeneration was active as demonstrated by the increased proliferating cell nuclear antigen;however, all the other checked genes(involved in insulin gene expression):PC-1,Ngn3,NeuroD1,Btc,PDX-1 and Ins-1, were not related to the molecular events caused by this process.The only marker detected in regenerating liver was E47:a transcription factor of the the basic helixloop-helix family known to be expressed ubiquitously in mammalian cells.In the rat pancreas,almost all of the tested genes were expressed as shown by RT-PCR, except for Ngn3,which was silenced 2 d after birth. Therefore,the molecular events in liver regeneration are not sufficient to promote PDX-1 expression.DNA methylation is a known mechanism to achieve stable re- pression of gene expression in mammals:Hxk 2 gene is silenced through this mechanism in normal hepatocytes. The administration of 5-aza-dC to cultured cells

  3. A 5-methylcytosine DNA glycosylase/lyase demethylates the retrotransposon Tos17 and promotes its transposition in rice

    KAUST Repository

    La, Honggui

    2011-09-06

    DNA 5-methylcytosine (5-meC) is an important epigenetic mark for transcriptional gene silencing in many eukaryotes. In Arabidopsis, 5-meC DNA glycosylase/lyases actively remove 5-meC to counter-act transcriptional gene silencing in a locus-specific manner, and have been suggested to maintain the expression of transposons. However, it is unclear whether plant DNA demethylases can promote the transposition of transposons. Here we report the functional characterization of the DNA glycosylase/lyase DNG701 in rice. DNG701 encodes a large (1,812 amino acid residues) DNA glycosylase domain protein. Recombinant DNG701 protein showed 5-meC DNA glycosylase and lyase activities in vitro. Knockout or knockdown of DNG701 in rice plants led to DNA hypermethylation and reduced expression of the retrotransposon Tos17. Tos17 showed less transposition in calli derived from dng701 knockout mutant seeds compared with that in wild-type calli. Overexpression of DNG701 in both rice calli and transgenic plants substantially reduced DNA methylation levels of Tos17 and enhanced its expression. The overexpression also led to more frequent transposition of Tos17 in calli. Our results demonstrate that rice DNG701 is a 5-meC DNA glycosylase/lyase responsible for the demethylation of Tos17 and this DNA demethylase plays a critical role in promoting Tos17 transposition in rice calli.

  4. Demethylation profile of the TNF-α promoter gene is associated with high expression of this cytokine in Dengue virus patients.

    Science.gov (United States)

    Gomes, Alessandra Vilas Boas Terra; de Souza Morais, Stella Maria; Menezes-Filho, Sergio Luiz; de Almeida, Luiz Gustavo Nogueira; Rocha, Raissa Prado; Ferreira, Jaqueline Maria Siqueira; Dos Santos, Luciana Lara; Malaquias, Luiz Cosme Cotta; Coelho, Luiz Felipe Leomil

    2016-08-01

    Dengue is the most prevalent arthropod-borne viral illness in humans. The overexpression of cytokines by Dengue virus (DENV) infected cells is associated with the most severe forms of the disease. Unmethylated CpG islands are related to a transcriptionally active structure, whereas methylated DNA recruits methyl-binding proteins that inhibit gene expression. Several studies have described the importance of epigenetic events in the regulation and expression of many cytokines. The purpose of the present study was to evaluate the methylation status of the IFN-γ and TNF-α promoters in DNA extracted from dengue infected patients using methylation-specific polymerase chain reaction. A high frequency of demethylation was observed in the TNF-α promoter of DENV infected patients when compared to non-infected controls. The patients with an unmethylated profile showed higher expression of TNF-α mRNA than patients with the methylated status. No difference was found in the methylation frequency between the two analyzed groups regarding the IFN-γ promoter or in the expression of IFN-γ transcripts. The present study provides the first association of TNF-α promoter demethylation in DENV infected individuals and demonstrates a correlation between the methylation status of the region analyzed and the expression of TNF-α transcripts in DENV infected patients. J. Med. Virol. 88:1297-1302, 2016. © 2016 Wiley Periodicals, Inc. PMID:26792115

  5. Decaffeination and measurement of caffeine content by addicted Escherichia coli with a refactored N-demethylation operon from Pseudomonas putida CBB5.

    Science.gov (United States)

    Quandt, Erik M; Hammerling, Michael J; Summers, Ryan M; Otoupal, Peter B; Slater, Ben; Alnahhas, Razan N; Dasgupta, Aurko; Bachman, James L; Subramanian, Mani V; Barrick, Jeffrey E

    2013-06-21

    The widespread use of caffeine (1,3,7-trimethylxanthine) and other methylxanthines in beverages and pharmaceuticals has led to significant environmental pollution. We have developed a portable caffeine degradation operon by refactoring the alkylxanthine degradation (Alx) gene cluster from Pseudomonas putida CBB5 to function in Escherichia coli. In the process, we discovered that adding a glutathione S-transferase from Janthinobacterium sp. Marseille was necessary to achieve N 7 -demethylation activity. E. coli cells with the synthetic operon degrade caffeine to the guanine precursor, xanthine. Cells deficient in de novo guanine biosynthesis that contain the refactored operon are ″addicted″ to caffeine: their growth density is limited by the availability of caffeine or other xanthines. We show that the addicted strain can be used as a biosensor to measure the caffeine content of common beverages. The synthetic N-demethylation operon could be useful for reclaiming nutrient-rich byproducts of coffee bean processing and for the cost-effective bioproduction of methylxanthine drugs.

  6. Representing active travel: a formative evaluation of a computer visualisation tool demonstrating a new walking and cycling route

    OpenAIRE

    Bill, Emma; Baker, Graham; Ferguson, Neil S.; Drinkwater, David; Mutrie, Nanette

    2015-01-01

    Transport and public health researchers have a shared interest in the promotionof active travel. Walking and cycling are activities that may help to achieve healthbenefits while also contributing to wider sustainability goals, such as a reduction in carbon emissions from transport, improvements in air quality, and reduced congestion. A variety of interventions have been used to promote travel behaviour change, for example, infrastructure change and personalised travel planning. Some researche...

  7. GC-MS-olfactometric characterization of the most aroma-active components in a representative aromatic extract from Iranian saffron (Crocus sativus L.).

    Science.gov (United States)

    Amanpour, Asghar; Sonmezdag, A Salih; Kelebek, Hasim; Selli, Serkan

    2015-09-01

    Aroma and aroma-active compounds of Iranian saffron (Crocus sativus L.) were analyzed by gas chromatography-mass spectrometry-olfactometry. The saffron aromatic extracts were obtained by four different extraction techniques including solvent-assisted flavour evaporation (SAFE), liquid-liquid extraction (LLE), solid phase extraction (SPE), and simultaneous distillation extraction (SDE) and compared to achieve a representative aromatic extract from saffron. According to sensory analysis, the aromatic extract obtained by SAFE was the most representative of saffron odour. A total of 28 aroma compounds were identified in saffron. Ketones were quantitatively the most dominant volatiles in saffron, followed by aldehydes and acids. Aroma extract dilution analysis (AEDA) was used for the determination of aroma-active compounds of saffron. A total of nine aroma-active compounds were detected in the aromatic extract. On the basis of the flavour dilution (FD) factor, the most powerful aroma active compounds were safranal (FD = 512), 4-ketoisophorone (FD = 256) and dihydrooxophorone (FD = 128).

  8. Local chromatin microenvironment determines DNMT activity : from DNA methyltransferase to DNA demethylase or DNA dehydroxymethylase

    NARCIS (Netherlands)

    van der Wijst, Monique G. P.; Venkiteswaran, Muralidhar; Chen, Hui; Xu, Guo-Liang; Plosch, Torsten; Rots, Marianne G.

    2015-01-01

    Insights on active DNA demethylation disproved the original assumption that DNA methylation is a stable epigenetic modification. Interestingly, mammalian DNA methyltransferases 3A and 3B (DNMT-3A and -3B) have also been reported to induce active DNA demethylation, in addition to their well-known fun

  9. Pharmacodynamic modelling of in vitro activity of tetracycline against a representative, naturally occurring population of porcine Escherichia coli

    DEFF Research Database (Denmark)

    Ahmad, Amais; Zachariasen, Camilla; Christiansen, Lasse Engbo;

    2015-01-01

    text] between susceptible and resistant strains in the absence of a drug was not different. EC 50 increased linearly with MIC on a log-log scale, and γ was different between susceptible and resistant strains. The in vitro model parameters described the inhibition effect of tetracycline on E. coli when...... of Escherichia coli representative of those found in the Danish pig population, we compared the growth of 50 randomly selected strains. The observed net growth rates were used to describe the in vitro pharmacodynamic relationship between drug concentration and net growth rate based on E max model with three...... parameters: maximum net growth rate (α max ); concentration for a half-maximal response (E max ); and the Hill coefficient (γ). The net growth rate in the absence of antibiotic did not differ between susceptible and resistant isolates (P = 0.97). The net growth rate decreased with increasing tetracycline...

  10. Inhibition of H3K4me2 Demethylation Protects Auditory Hair Cells from Neomycin-Induced Apoptosis.

    Science.gov (United States)

    He, Yingzi; Yu, Huiqian; Cai, Chengfu; Sun, Shan; Chai, Renjie; Li, Huawei

    2015-08-01

    Aminoglycoside-induced hair cell loss is a major cause of hearing impairment in children and deserves more attention in medical research. Epigenetic mechanisms have been shown to protect hair cells from ototoxic drugs. In this study, we focused on the role of dimethylated histone H3K4 (H3K4me2) in hair cell survival. To investigate the effects of lysine-specific demethylase 1 (LSD1)--the histone demethylase primarily responsible for demethylating H3K4me2--on neomycin-induced hair cell loss, isolated cochleae were pretreated with LSD1 inhibitors followed by neomycin exposure. There was a severe loss of hair cells in the organ of Corti after neomycin exposure, and inhibition of LSD1 significantly protected against neomycin-induced hair cell loss. H3K4me2 expression in the nuclei of hair cells decreased after exposure to neomycin, and blocking the decreased expression of H3K4me2 with LSD1 inhibitors prevented hair cell loss. Local delivery of these inhibitors in vivo also protected hair cells from neomycin-induced ototoxicity and maintained the hearing threshold in mice as determined by auditory brain stem response. This inhibition of neomycin-induced apoptosis occurs via reduced caspase-3 activation. Together, our findings demonstrate the protective role for H3K4me2 against neomycin-induced hair cell loss and hearing loss.

  11. Validation of 13CO2 breath analysis as a measurement of demethylation of stable isotope labeled aminopyrine in man

    International Nuclear Information System (INIS)

    Interval sampling of expired breath as a simple, non-invasive assessment of the effect of liver disease upon hepatic microsomal drug metabolism, has been demonstrated with [14C] dimethylaminoantipyrine (aminopyrine). In order to eliminate radiation risk the authors have validated the use of aminopyrine labeled with the stable, non-radioactive isotope 13C. Simultaneous oral administration of both [14C]- and [13C] aminopyrine to five adult subjects without liver disease as well as five patients with known liver disease, resulted in the excretion of label at nearly identical rates in both individual time collections (r=0.94) as well as cumulative excretion for three hours (r=0.97). An oral dose of 2-mg/kg of [13C) aminopyrine resulted in rates of production of 13CO2 significantly greater than baseline variations in 13CO2 production in the fasting, resting subject. Measurements of a single peak value at one half hour correlated closely with the determination of cumulative appearance over three hours (r=0.96). A consistent reproducible increase in the peak production of 13CO2 was observed when five patients received phenobarbital. Stable isotope labeled aminopyrine may be used to detect the effects of disease and treatment upon hepatic N-demethylation activity in human subjects without incurring any risk from radiation. Furthermore, the availability of another isotopic carbon label should make possible the study of direct drug-drug interaction utilizing CO2 analysis. (Auth.)

  12. Activity in neurons of a putative protocerebral circuit representing information about a ten component plant odour blend in Heliothis virescens.

    Directory of Open Access Journals (Sweden)

    Bjarte Bye Løfaldli

    2012-09-01

    Full Text Available The olfactory pathway in the insect brain is anatomically well described from the antennal lobe to the mushroom bodies and the lateral protocerebrum in several species. Less is known about the further connections of the olfactory network in protocerebrum and how information about relevant plant odorants and mixtures are represented in this network, resulting in output information mediated by descending neurons. In the present study we have recorded intracellularly followed by dye injections from neurons in the lateral- and superior protocerebrum of the moth, Heliothis virescens. As relevant stimuli, we have used selected primary plant odorants and mixtures of them. The results provide the morphology and physiological responses of neurons involved in a putative circuit connecting the mushroom body lobes, the superior and the lateral protocerebrum, as well as input to superior and lateral protocerebrum by one multiglomerular antennal lobe neuron and output from the lateral protocerebrum by one descending neuron. All neurons responded to one particular mixture of ten primary plant odorants, some of them also to single odorants of the mixture. Altogether, the physiological data indicate integration in protocerebral neurons of information from several of the receptor neuron types functionally described in this species.

  13. Evaluation of Antioxidant Activity, Polyphenolic Compounds, Amino Acids and Mineral Elements of Representative Genotypes of Lonicera edulis

    Directory of Open Access Journals (Sweden)

    Jiri Sochor

    2014-05-01

    Full Text Available The aim of this study was to evaluate the bioactive substances in 19 berry cultivars of edible honeysuckle (Lonicera edulis. A statistical evaluation was used to determine the relationship between the content of selected bioactive substances and individual cultivars. Regarding mineral elements, the content of sodium was measured using potentiometry and spectrophotometry. The content of selected polyphenolic compounds with high antioxidant activity was determined by a HPLC–UV/ED method. The total amount of polyphenols was determined by the Folin-Ciocalteu method. The antioxidant activity was determined using five methods (DPPH, FRAP, ABTS, FR and DMPD that differ in their principles. The content of 13 amino acids was determined by ion-exchange chromatography. The experimental results obtained for the different cultivars were evaluated and compared by statistical and bioinformatic methods. A unique feature of this study lies in the exhaustive analysis of the chosen parameters (amino acids, mineral elements, polyphenolic compounds and antioxidant activity during one growing season.

  14. Perceptions and Attitudes of Egyptian Health Professionals and Policy-Makers towards Pharmaceutical Sales Representatives and Other Promotional Activities.

    Directory of Open Access Journals (Sweden)

    Susan Kamal

    Full Text Available Pharmaceutical promotion activities in low and middle-income countries are often neither regulated nor monitored. While Egypt has the highest population and per capita use of medicines in the Arab world, we know very little about pharmaceutical companies promotional activities in the country.To explore and analyze the perceptions of physicians towards promotional and marketing activities of pharmaceutical companies among physicians and pharmacists in Egypt.Perspectives of different healthcare system stakeholders were explored through semi-structured, in-depth interviews conducted in 2014 in Cairo, Egypt. Interviewees were chosen via purposive sampling and snowball technique. Each interview was recorded and transcribed. Then qualitative, thematic analysis was conducted with the help of NVIVO software.The majority of physicians and pharmacists acknowledged exposure to pharmaceutical promotion. It was commonly believed that interaction with the pharmaceutical industry is necessary and both associated risks and benefits were acknowledged. The interviewed physicians considered themselves competent enough to minimize risks and maximize benefits to their prescribing habits. Views diverged on the extent and magnitude of the risks and benefits of pharmaceutical promotion, especially in regard to the influence on patients' health.Pharmaceutical promotion in Egypt is intensely directed at prescribers and dispensers. Physicians, pharmacists and policymakers expressed little skepticism to the influence of promotion towards their individual prescribing. Raising awareness of the pitfalls of pharmaceutical promotion is necessary, especially among the less experienced physicians.

  15. Continuous Zebularine Treatment Effectively Sustains Demethylation in Human Bladder Cancer Cells

    Science.gov (United States)

    Cheng, Jonathan C.; Weisenberger, Daniel J.; Gonzales, Felicidad A.; Liang, Gangning; Xu, Guo-Liang; Hu, Ye-Guang; Marquez, Victor E.; Jones, Peter A.

    2004-01-01

    During tumorigenesis, tumor suppressor and cancer-related genes are commonly silenced by aberrant DNA methylation in their promoter regions. Recently, we reported that zebularine [1-(β-d-ribofuranosyl)-1,2-dihydropyrimidin-2-one] acts as an inhibitor of DNA methylation and exhibits chemical stability and minimal cytotoxicity both in vitro and in vivo. Here we show that continuous application of zebularine to T24 cells induces and maintains p16 gene expression and sustains demethylation of the 5′ region for over 40 days, preventing remethylation. In addition, continuous zebularine treatment effectively and globally demethylated various hypermethylated regions, especially CpG-poor regions. The drug caused a complete depletion of extractable DNA methyltransferase 1 (DNMT1) and partial depletion of DNMT3a and DNMT3b3. Last, sequential treatment with 5-aza-2′-deoxycytidine followed by zebularine hindered the remethylation of the p16 5′ region and gene resilencing, suggesting the possible combination use of both drugs as a potential anticancer regimen. PMID:14729971

  16. DNA demethylation upregulated Nrf2 expression in Alzheimer's disease cellular model

    Directory of Open Access Journals (Sweden)

    Huimin eCao

    2016-01-01

    Full Text Available Nuclear factor erythroid 2-related factor 2 (Nrf2 is an important transcription factor in the defense against oxidative stress. Cumulative evidence has shown that oxidative stress plays a key role in the pathogenesis of Alzheimer's disease (AD. Previous animal and clinical studies had observed decreased expression of Nrf2 in AD. However, the underlying regulation mechanisms of Nrf2 in AD remain unclear. Here, we used the DNA methyltransferases (Dnmts inhibitor 5-aza-2′-deoxycytidine (5-Aza to test whether Nrf2 expression was regulated by methylation in N2a cells characterizing by expressing human Swedish mutant amyloid precursor protein (N2a/APPswe. We found 5-Aza treatment increased Nrf2 at both mRNA and protein levels via down-regulating the expression of Dnmts and DNA demethylation. In addition, 5-Aza mediated upregulation of Nrf2 expression was concomitant with increased nuclear translocation of Nrf2 and higher expression of Nrf2 downstream target gene NAD(PH:quinone oxidoreductas (NQO1. Our study showed that DNA demethylation promoted the Nrf2 cell signaling pathway, which may enhance the antioxidant system against AD development.

  17. The Fundamental Plane of Black Hole Activity Represented in Terms of Dimensionless Beam Power and Bolometric Luminosity

    OpenAIRE

    Daly, Ruth A.; Stout, Douglas A.; Mysliwiec, Jeremy N.

    2016-01-01

    The fundamental plane of black hole activity indicates a relationship between compact radio emission, X-ray luminosity, and black hole mass of black hole systems. The compact radio source is likely a tracer of jet power and the X-ray luminosity is likely a tracer of the bolometric luminosity of an accretion disk. To study the relationship between beam power, $L_j$, accretion disk bolometric luminosity, $L_{bol}$, and black hole mass or Eddington luminosity, $L_{EDD}$, for sources with various...

  18. Photography by Cameras Integrated in Smartphones as a Tool for Analytical Chemistry Represented by an Butyrylcholinesterase Activity Assay.

    Science.gov (United States)

    Pohanka, Miroslav

    2015-06-11

    Smartphones are popular devices frequently equipped with sensitive sensors and great computational ability. Despite the widespread availability of smartphones, practical uses in analytical chemistry are limited, though some papers have proposed promising applications. In the present paper, a smartphone is used as a tool for the determination of cholinesterasemia i.e., the determination of a biochemical marker butyrylcholinesterase (BChE). The work should demonstrate suitability of a smartphone-integrated camera for analytical purposes. Paper strips soaked with indoxylacetate were used for the determination of BChE activity, while the standard Ellman's assay was used as a reference measurement. In the smartphone-based assay, BChE converted indoxylacetate to indigo blue and coloration was photographed using the phone's integrated camera. A RGB color model was analyzed and color values for the individual color channels were determined. The assay was verified using plasma samples and samples containing pure BChE, and validated using Ellmans's assay. The smartphone assay was proved to be reliable and applicable for routine diagnoses where BChE serves as a marker (liver function tests; some poisonings, etc.). It can be concluded that the assay is expected to be of practical applicability because of the results' relevance.

  19. The Fundamental Plane of Black Hole Activity Represented in Terms of Dimensionless Beam Power and Bolometric Luminosity

    CERN Document Server

    Daly, Ruth A; Mysliwiec, Jeremy N

    2016-01-01

    The fundamental plane of black hole activity indicates a relationship between compact radio emission, X-ray luminosity, and black hole mass of black hole systems. The compact radio source is likely a tracer of jet power and the X-ray luminosity is likely a tracer of the bolometric luminosity of an accretion disk. To study the relationship between beam power, $L_j$, accretion disk bolometric luminosity, $L_{bol}$, and black hole mass or Eddington luminosity, $L_{EDD}$, for sources with various tracers of beam power and disk luminosity, it is shown that fundamental plane parameters allow the plane to be recast in the form $\\rm{log} (L_j/L_{EDD}) = A ~\\rm{log}(L_{bol}/L_{EDD}) +B$, where $A$ can be expressed in terms of best fit fundamental plane parameters. Consistent values of $A$ are obtained for nine samples of sources. Samples of LINERS, AGN, and GBH that lie on the fundamental plane are converted to dimensionless luminosities and studied, and a sample of powerful radio sources is included. The different ca...

  20. Survey by senior NRC management to obtain veiwpoints on the safety impact of regulatory activities from representative utilities operating and constructing nuclear power plants

    International Nuclear Information System (INIS)

    A survey of licensee staff members representing the several organizational elements in different licensee corporate and plant staffs was conducted by senior NRC management to obtain licensee views on the potential safety consequences and impact of NRC regulatory activities. The comments received addressed the full scope of NRC activities and the negative impact of agency actions on licensee resources, staff performance, planning and scheduling, and organizational effectiveness. The findings of the survey is that the pace and nature of regulatory actions have created a potential safety problem which deserves further evaluation by the agency

  1. 5-azacytidine improves the osteogenic differentiation potential of aged human adipose-derived mesenchymal stem cells by DNA demethylation.

    Science.gov (United States)

    Yan, Xueying; Ehnert, Sabrina; Culmes, Mihaela; Bachmann, Anastasia; Seeliger, Claudine; Schyschka, Lilianna; Wang, Zhiyong; Rahmanian-Schwarz, Afshin; Stöckle, Ulrich; De Sousa, Paul A; Pelisek, Jaroslav; Nussler, Andreas K

    2014-01-01

    The therapeutic value of adipose-derived mesenchymal stem cells (Ad-MSCs) for bone regeneration is critically discussed. A possible reason for reduced osteogenic potential may be an age-related deterioration of the Ad-MSCs. In long term in vitro culture, epigenomic changes in DNA methylation are known to cause gene silencing, affecting stem cell growth as well as the differentiation potential. In this study, we observed an age-related decline in proliferation of primary human Ad-MSCs. Decreased Nanog, Oct4 and Lin28A and increased Sox2 gene-expression was accompanied by an impaired osteogenic differentiation potential of Ad-MSCs isolated from old donors (>60 a) as compared to Ad-MSCs isolated from younger donors (<45 a). 5-hydroxymethylcytosine (5 hmC) and 5-methylcytonsine (5 mC) distribution as well as TET gene expression were evaluated to assess the evidence of active DNA demethylation. We observed a decrease of 5 hmC in Ad-MSCs from older donors. Incubation of these cells with 5-Azacytidine induced proliferation and improved the osteogenic differentiation potential in these cells. The increase in AP activity and matrix mineralization was associated with an increased presence of 5 hmC as well as with an increased TET2 and TET3 gene expression. Our data show, for the first time, a decrease of DNA hydroxymethylation in Ad-MSCs which correlates with donor-age and that treatment with 5-Azacytidine provides an approach which could be used to rejuvenate Ad-MSCs from aged donors. PMID:24603866

  2. 5-azacytidine improves the osteogenic differentiation potential of aged human adipose-derived mesenchymal stem cells by DNA demethylation.

    Directory of Open Access Journals (Sweden)

    Xueying Yan

    Full Text Available The therapeutic value of adipose-derived mesenchymal stem cells (Ad-MSCs for bone regeneration is critically discussed. A possible reason for reduced osteogenic potential may be an age-related deterioration of the Ad-MSCs. In long term in vitro culture, epigenomic changes in DNA methylation are known to cause gene silencing, affecting stem cell growth as well as the differentiation potential. In this study, we observed an age-related decline in proliferation of primary human Ad-MSCs. Decreased Nanog, Oct4 and Lin28A and increased Sox2 gene-expression was accompanied by an impaired osteogenic differentiation potential of Ad-MSCs isolated from old donors (>60 a as compared to Ad-MSCs isolated from younger donors (<45 a. 5-hydroxymethylcytosine (5 hmC and 5-methylcytonsine (5 mC distribution as well as TET gene expression were evaluated to assess the evidence of active DNA demethylation. We observed a decrease of 5 hmC in Ad-MSCs from older donors. Incubation of these cells with 5-Azacytidine induced proliferation and improved the osteogenic differentiation potential in these cells. The increase in AP activity and matrix mineralization was associated with an increased presence of 5 hmC as well as with an increased TET2 and TET3 gene expression. Our data show, for the first time, a decrease of DNA hydroxymethylation in Ad-MSCs which correlates with donor-age and that treatment with 5-Azacytidine provides an approach which could be used to rejuvenate Ad-MSCs from aged donors.

  3. 5-Azacytidine Improves the Osteogenic Differentiation Potential of Aged Human Adipose-Derived Mesenchymal Stem Cells by DNA Demethylation

    Science.gov (United States)

    Culmes, Mihaela; Bachmann, Anastasia; Seeliger, Claudine; Schyschka, Lilianna; Wang, Zhiyong; Rahmanian-Schwarz, Afshin; Stöckle, Ulrich; De Sousa, Paul A.; Pelisek, Jaroslav; Nussler, Andreas K.

    2014-01-01

    The therapeutic value of adipose-derived mesenchymal stem cells (Ad-MSCs) for bone regeneration is critically discussed. A possible reason for reduced osteogenic potential may be an age-related deterioration of the Ad-MSCs. In long term in vitro culture, epigenomic changes in DNA methylation are known to cause gene silencing, affecting stem cell growth as well as the differentiation potential. In this study, we observed an age-related decline in proliferation of primary human Ad-MSCs. Decreased Nanog, Oct4 and Lin28A and increased Sox2 gene-expression was accompanied by an impaired osteogenic differentiation potential of Ad-MSCs isolated from old donors (>60 a) as compared to Ad-MSCs isolated from younger donors (<45 a). 5-hydroxymethylcytosine (5 hmC) and 5-methylcytonsine (5 mC) distribution as well as TET gene expression were evaluated to assess the evidence of active DNA demethylation. We observed a decrease of 5 hmC in Ad-MSCs from older donors. Incubation of these cells with 5-Azacytidine induced proliferation and improved the osteogenic differentiation potential in these cells. The increase in AP activity and matrix mineralization was associated with an increased presence of 5 hmC as well as with an increased TET2 and TET3 gene expression. Our data show, for the first time, a decrease of DNA hydroxymethylation in Ad-MSCs which correlates with donor-age and that treatment with 5-Azacytidine provides an approach which could be used to rejuvenate Ad-MSCs from aged donors. PMID:24603866

  4. Simultaneous determination of levophencynonate and its metabolite demethyl levophencynonate in human plasma by liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Li, Bo; Qi, Wenyuan; Shi, Aixin; Hu, Xin; Cheng, Gang

    2016-08-01

    A sensitive and convenient high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed to determine levophencynonate and demethyl levophencynonate levels in human plasma simultaneously. Chromatographic separation was achieved on a SHIMADZU Shim-Pack XR C8 column and mass spectrometric analysis was performed by an API5000 mass spectrometer coupled with an electro-spray ionization (ESI) source in the positive ion mode. The MRM transitions of m/z 358.4→156.4 and 344.5→144.2 were used to quantify levophencynonate and demethyl levophencynonate, respectively. This analytical method was fully validated with specificity, linearity, lower limit of quantitation (LLOQ), accuracy, precision, stability, matrix effect and recovery. The linearity of this method were developed to be within the concentration ranges of 10-4000pg/mL for levophencynonate and 25-8000pg/mL for demethyl levophencynonate in human plasma. This method was used in a clinical study which was administrated with single oral dose for Chinese healthy subjects to investigate the pharmacokinetics of levophencynonate and demethyl levophencynonate. PMID:27304783

  5. Sensitivity of Mycosphaerella graminicola isolates to demethylation-inhibiting (DMI) fungicides

    DEFF Research Database (Denmark)

    Ronis, Antanas; Jørgensen, Lise Nistrup; Semaskiene, Roma;

    2014-01-01

    collected from different locations of Lithuania were tested in vitro for sensitivity to demethylation-inhibiting (DMI) fungicides epoxiconazole, cyproconazole and prothioconazole. Fungicide concentrations were chosen from the proposed Fungicide Resistance Action Committee (FRAC) methods. Microtitre plates......Mycosphaerella graminicola (Fuckel) J. Schröt. (anamorph Zymoseptoria tritici (Desm.) Quaedvlieg & Crous) causes Septoria leaf blotch disease of wheat. The disease can be responsible for yield losses of 30–50% and, when severe, requires management with a fungicide. Single picnidia isolates...... that fungicides epoxiconazole and prothioconazole significantly reduced the area under the disease progress curve (AUDPC) values of Septoria leaf blotch compared with untreated plots in winter wheat. In most cases, a single fungicide application significantly increased grain yield and a thousand grain weight...

  6. Role of U.S. Nuclear Regulatory Commission's On-Site Representatives in pre-licensing activities for a high-level radioactive waste repository

    International Nuclear Information System (INIS)

    Under the Nuclear Waste Policy Act, the US Department of Energy and the US Nuclear Regulatory Commission are required to consult with each other prior to DOE's submittal of a license application to construct a high-level radioactive waste repository. DOE entered into an agreement which, in part, enabled NRC On-Site Representatives to be stationed at a high-level waste candidate site open-quotes principally to serve as a point of prompt informational exchange and consultation and to preliminary identify concerns about such investigations relating to potential licensing issues.close quotes On-Site Representatives' direct observation of site characterization activities including construction of an underground studies facility (at Yucca Mountain, NV candidate site) provides NRC staff opportunities to help ensure that DOE will develop data which are appropriate to determine if the site will safely isolate waste and which will be defensible in a License Application. The On-Site Representatives, through supervision and input from the Division of High-Level Waste Management, may consult with the DOE site project office and its contractor staff on items pertaining to management and program controls necessary to satisfy NRC licensing needs, such as demonstrated application of procedural controls and technical data that will support a License Application. The On-Site Representatives interact with DOE through consultations with project staff, quality assurance workshops, observations of reviews of computer software and Q-List considerations, responses to audit and surveillance observations and day-to-day contact with DOE site management, QA staff, and technical investigators

  7. The applicability of activities in kinetic expressions: A more fundamental approach to represent the kinetics of the system CO2–OH-salt in terms of activities

    NARCIS (Netherlands)

    Haubrock, J.; Hogendoorn, J.A.; Versteeg, G.F.

    2007-01-01

    The applicability of utilizing activities instead of concentrations in kinetic expressions has been investigated using the reaction of CO2 in sodium hydroxide solutions also containing different neutral salts (LiCl, KCl and NaCl) as model system. For hydroxide systems it is known that when the react

  8. Genome-wide studies of histone demethylation catalysed by the fission yeast homologues of mammalian LSD1.

    Directory of Open Access Journals (Sweden)

    Michael Opel

    Full Text Available In order to gain a more global view of the activity of histone demethylases, we report here genome-wide studies of the fission yeast SWIRM and polyamine oxidase (PAO domain homologues of mammalian LSD1. Consistent with previous work we find that the two S. pombe proteins, which we name Swm1 and Swm2 (after SWIRM1 and SWIRM2, associate together in a complex. However, we find that this complex specifically demethylates lysine 9 in histone H3 (H3K9 and both up- and down-regulates expression of different groups of genes. Using chromatin-immunoprecipitation, to isolate fragments of chromatin containing either H3K4me2 or H3K9me2, and DNA microarray analysis (ChIP-chip, we have studied genome-wide changes in patterns of histone methylation, and their correlation with gene expression, upon deletion of the swm1(+ gene. Using hyper-geometric probability comparisons we uncover genetic links between lysine-specific demethylases, the histone deacetylase Clr6, and the chromatin remodeller Hrp1. The data presented here demonstrate that in fission yeast the SWIRM/PAO domain proteins Swm1 and Swm2 are associated in complexes that can remove methyl groups from lysine 9 methylated histone H3. In vitro, we show that bacterially expressed Swm1 also possesses lysine 9 demethylase activity. In vivo, loss of Swm1 increases the global levels of both H3K9me2 and H3K4me2. A significant accumulation of H3K4me2 is observed at genes that are up-regulated in a swm1 deletion strain. In addition, H3K9me2 accumulates at some genes known to be direct Swm1/2 targets that are down-regulated in the swm1Delta strain. The in vivo data indicate that Swm1 acts in concert with the HDAC Clr6 and the chromatin remodeller Hrp1 to repress gene expression. In addition, our in vitro analyses suggest that the H3K9 demethylase activity requires an unidentified post-translational modification to allow it to act. Thus, our results highlight complex interactions between histone demethylase

  9. Linking active DNA demethylation by Thymine DNA Glycosylase with epigenetic regulation of gene expression

    OpenAIRE

    Wirz, Annika

    2014-01-01

    The correct regulation of epigenetic modifications is crucial for cell plasticity and the establishment of cell identity. The underlying molecular mechanisms are not clear, but a role for DNA repair proteins has been implicated in this context, the investigation of which was the overall aim of my PhD thesis. The Thymine DNA Glycosylase (TDG) was described to excise the deamination products of cytosine (C) and 5-methylcytosine (5-mC), thereby initiating base excision repair (BER; Nedderman...

  10. Active play and screen time in US children aged 4 to 11 years in relation to sociodemographic and weight status characteristics: a nationally representative cross-sectional analysis

    Directory of Open Access Journals (Sweden)

    Must Aviva

    2008-10-01

    Full Text Available Abstract Background The high prevalence of childhood obesity underscores the importance of monitoring population trends in children's activity and screen time, and describing associations with child age, gender, race/ethnicity, and weight status. Our objective was to estimate the proportion of young children in the US who have low levels of active play or high levels of screen time, or who have both these behaviors, and to describe associations with age, gender, race/ethnicity, and weight status. Methods We analyzed data collected during the National Health and Nutrition Examination Surveys 2001–2004, a US nationally representative cross-sectional study. We studied 2964 children aged 4.00 to 11.99 years. Our main outcomes were reported weekly times that the child played or exercised hard enough to sweat or breathe hard (active play, daily hours the child watched television/videos, used computers, or played computer games (screen time, and the combination of low active play and high screen time. Low active play was defined as active play 6 times or less per week. High screen time was defined as more than 2 hours per day. We accounted for the complex survey design in analyses and report proportions and 95% confidence intervals. We used Wald Chi-square to test for differences between proportions. To identify factors associated with low active play and high screen time, we used multivariate logistic regression. Results Of US children aged 4 to 11 years, 37.3% (95% confidence interval, 34.1% to 40.4% had low levels of active play, 65.0% (95% CI, 61.4% to 68.5% had high screen time, and 26.3% (95% CI, 23.8% to 28.9% had both these behaviors. Characteristics associated with a higher probability of simultaneously having low active play and high screen time were older age, female gender, non-Hispanic black race/ethnicity, and having a BMI-for-age ≥95th percentile of the CDC growth reference. Conclusion Many young children in the US are reported to

  11. Testing Theory of Planned Behavior and Neo-Socioanalytic Theory models of trait activity, industriousness, exercise social cognitions, exercise intentions, and physical activity in a representative U.S. sample

    OpenAIRE

    Phuong Thi Vo; Tim eBogg

    2015-01-01

    Prior research identified assorted relations between trait and social cognition models of personality and engagement in physical activity. Using a representative U.S. sample (N = 957), the goal of the present study was to test two alternative structural models of the relationships among the extraversion-related facet of activity, the conscientiousness-related facet of industriousness, social cognitions from the Theory of Planned Behavior (perceived behavioral control, affective attitudes, sub...

  12. Mescaline-induced changes of brain-cortex ribosomes. Mescaline demethylase activity of brain-cortex soluble supernatant.

    Science.gov (United States)

    Datta, R K; Ghosh, J J

    1977-02-01

    Brain-cortex slices demethylate mescaline and p-methoxyacetanilide, a reference O-demethylating substrate, though the rate of demethylation of mescaline is about one third that of the reference substrate. The demethylase activity is localized mostly in the soluble supernatant (105 000 x g). It is purified 47-fold with respect to the demethylation of mescaline by ammonium sulfate precipitation and DEAE cellulose chromatography. The partially purified demethylase, which is stable for 3-5 days at -5 degrees C in the presence of dithiothreitol and glutathione and is inhibited by p-chloromercuribenzoate, has maximal activity at pH between 7.2 and 8.0. It demethylates mescaline into 3,4-dimethoxy-5-hydroxyphenethylamine and 3,5-dimethoxy-4-hydroxyphenethylamine and some unidentified derivatives.

  13. A NEW MODEL AND IMPROVED CABLE FUNCTION FOR REPRESENTING THE ACTIVATING PERIPHERAL NERVES BY A TRANSVERSE ELECTRIC FIELD DURING MAGNETIC STIMULATION

    Institute of Scientific and Technical Information of China (English)

    Yu Hui; Zheng Chongxun; Wang Haiyan; Wang Yi

    2005-01-01

    Objective Previous studies of peripheral nerves activation during magnetic stimulation have focused almost exclusively on the cause of high external parallel electric field along the nerves, whereas the effect of the transverse component has been ignored. In the present paper, the classical cable function is modified to represent the excitation of peripheral nerves stimulated by a transverse electric field during magnetic stimulation. Methods Responses of the Ranvier nodes to a transverse-field are thoroughly investigated by mathematic simulation. Results The simulation demonstrates that the excitation results from the net inward current driven by an external field. Based on a two-stage process, a novel model is introduced to describe peripheral nerves stimulated by a transverse-field. Based on the new model, the classical cable function is modified. Conclusion Using this modified cable equation, the excitation threshold of peripheral nerves in a transverse field during MS is obtained. The modified cable equation can be used to represent the response of peripheral nerves by an arbitrary electric field.

  14. Germicidal activities of representatives of five different teat dip classes against three bovine mycoplasma species using a modified excised teat model.

    Science.gov (United States)

    Boddie, R L; Owens, W E; Ray, C H; Nickerson, S C; Boddie, N T

    2002-08-01

    Six representative teat dips from five different teat dip classes were tested for germicidal activity against challenge exposure to Mycoplasma bovis, Mycoplasma californicum, and Mycoplasma bovigenitalium using a modified excised teat model. All teat dip formulations tested were efficacious against all of the Mycoplasma species, providing bacterial logarithmic reductions above 4. The germicides performed best against M. bovigenitalium with an average log reduction (LR) of 6.29. Average LR were 5.41 and 5.70 against M. bovis and M. californicum, respectively. The iodine and chlorhexidine products performed best against M. bovis and M. californicum, respectively, with complete kill of all organisms. The chlorhexidine and the barrier chlorine product also had complete kill of M. bovigenitalium organisms. PMID:12214982

  15. O-Demethylation and successive oxidative dechlorination of methoxychlor by Bradyrhizobium sp. strain 17-4, isolated from river sediment.

    Science.gov (United States)

    Satsuma, Koji; Masuda, Minoru; Sato, Kiyoshi

    2012-08-01

    O-Demethylation of insecticide methoxychlor is well known as a phase I metabolic reaction in various eukaryotic organisms. Regarding prokaryotic organisms, however, no individual species involved in such reaction have been specified and characterized so far. Here we successfully isolated a bacterium that mediates oxidative transformation of methoxychlor, including O-demethylation and dechlorination, from river sediment. The isolate was found to be closely related to Bradyrhizobium elkanii at the 16S rRNA gene sequence level (100% identical). However, based on some differences in the physiological properties of this bacterium, we determined that it was actually a different species, Bradyrhizobium sp. strain 17-4. The isolate mediated O-demethylation of methoxychlor to yield a monophenolic derivative [Mono-OH; 1,1,1-trichloro-2-(4-hydroxyphenyl)-2-(4-methoxyphenyl)ethane] as the primary degradation product. The chiral high-performance liquid chromatography (HPLC) analysis revealed that the isolate possesses high enantioselectivity favoring the formation of (S)-Mono-OH (nearly 100%). Accompanied by the sequential O-demethylation to form the bis-phenolic derivative Bis-OH [1,1,1-trichloro-2,2-bis(4-hydroxyphenyl)ethane], oxidative dechlorination of the side chain proceeded, and monophenolic carboxylic acid accumulated, followed by the formation of multiple unidentified polar degradation products. The breakdown proceeded more rapidly when reductively dechlorinated (dichloro-form) methoxychlor was applied as the initial substrate. The resultant carboxylic acids and polar degradation products are likely further biodegraded by ubiquitous bacteria. The isolate possibly plays an important role for complete degradation (mineralization) of methoxychlor by providing the readily biodegradable substrates.

  16. Site-specific demethylation and normal chromatin structure of the human dihydrofolate reductase gene promoter after transfection into CHO cells.

    OpenAIRE

    Shimada, T.; Inokuchi, K; Nienhuis, A W

    1987-01-01

    The effect of in vitro methylation on the function and chromatin structure of the human dihydrofolate reductase (DHFR) promoter linked to the DHFR coding sequences (minigene) was studied after DNA-mediated gene transfer into DHFR- CHO cells. Methylation of HhaI sites reduced the transforming frequency to about 10% of control, whereas methylation of HpaII sites had a less significant effect. The integrated genes were demethylated at specific sites in the promoter sequence, namely, HpaII sites ...

  17. Determination of parameters influencing methylation and demethylation in tropical lakes in Brazil and Nicaragua

    International Nuclear Information System (INIS)

    Increased awareness about the toxicity of mercury (Hg) has during the latest decades resulted in reduced Hg use in industrialised countries. Developing countries, on the contrary, have largely increased their anthropogenic Hg emissions caused by its use in gold mining, transfer of Hg emitting factories from developed countries, and increased burning of coal without appropriate flue gas cleaning. These increased emissions occur mainly in the tropics, where the fate of Hg is not well documented. The aim of the present study is to increase the knowledge about Hg levels and transformations in two tropical areas affected by anthropogenic Hg emissions - the Pantanal wetland in Brazil, housing gold miners using the amalgamation method, and Lake Xolotilan (Managua) in Nicaragua, where a chlor-alkali plant relocated from the USA has emitted much Hg. Actual Hg content in water, biota, and sediment will be determined by atomic fluorescence spectrophotometry and atomic absorption spectrophotometry. Mercury inethylation capacity in sediments and selected biota will be determined with in-situ incubations with 203Hg and subsequent radiological measurements. Factors affecting the methylation and demethylation rates will be identified by varying environmental conditions such as pH, redox potential, conductivity, light, temperature, geochemical factors and population of bacteria. Sediment turnover will be studied by determining fallout cesium (137Cs) in sediment profiles. The study is expected to increase the knowledge about Hg-transformations in the tropics and point out proper measures to reduce health hazards due to Hg-exposure. (author)

  18. Prevention of Helicobacter pylori-induced gastric cancers in gerbils by a DNA demethylating agent.

    Science.gov (United States)

    Niwa, Tohru; Toyoda, Takeshi; Tsukamoto, Tetsuya; Mori, Akiko; Tatematsu, Masae; Ushijima, Toshikazu

    2013-04-01

    Suppression of aberrant DNA methylation is a novel approach to cancer prevention, but, so far, the efficacy of the strategy has not been evaluated in cancers associated with chronic inflammation. Gastric cancers induced by Helicobacter pylori infection are known to involve aberrant DNA methylation and associated with severe chronic inflammation in their early stages. Here, we aimed to clarify whether suppression of aberrant DNA methylation can prevent H. pylori-induced gastric cancers using a Mongolian gerbil model. Administration of a DNA demethylating agent, 5-aza-2'-deoxycytidine (5-aza-dC), to gerbils (0.125 mg/kg for 50-55 weeks) decreased the incidence of gastric cancers induced by H. pylori infection and N-methyl-N-nitrosourea (MNU) treatment from 55.2% to 23.3% (P testicular atrophy. These results showed that 5-aza-dC treatment can prevent H. pylori-induced gastric cancers and suggested that removal of induced DNA methylation and/or suppression of DNA methylation induction can become a target for prevention of chronic inflammation-associated cancers. PMID:23559452

  19. Approach for selective separation of thiophenic and sulfidic sulfur compounds from petroleum by methylation/demethylation.

    Science.gov (United States)

    Wang, Meng; Zhao, Suoqi; Chung, Keng H; Xu, Chunming; Shi, Quan

    2015-01-20

    Detailed characterization of petroleum derived sulfur compounds has been challenging, due to the complex composition of the hydrocarbon matrix. A novel method was developed for selective separation of thiophenic and sulfidic compounds from petroleum. Sulfur compounds were methylated to sulfonium salts by AgBF4 and CH3I, then the polar salts were separated by precipitation from petroleum matrix. The thiophenic and sulfidic sulfonium salts were sequentially demethylated with 7-azaindole and 4-dimethylaminopyridine, obtaining original thiophenic and sulfidic compounds, respectively. The method was validated by model compounds, and applied to a diesel and a vacuum distillation petroleum fraction. Sulfur fractions were characterized by gas chromatography (GC) coupled with a sulfur chemiluminescence detector (SCD) and quadrupole mass spectrometry (MS), and high resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). The technique was effective to selectively obtain high-purity thiophenic and sulfidic compounds and showed rare discrimination among sulfur compounds with ranging molecular weights and degrees of unsaturation. The method would facilitate multifaceted detailed characterization of sulfur compounds in an organic complex matrix. PMID:25519193

  20. Suppression of TET1-Dependent DNA Demethylation Is Essential for KRAS-Mediated Transformation

    Directory of Open Access Journals (Sweden)

    Bo-Kuan Wu

    2014-12-01

    Full Text Available Hypermethylation-mediated tumor suppressor gene (TSG silencing is a central epigenetic alteration in RAS-dependent tumorigenesis. Ten-eleven translocation (TET enzymes can depress DNA methylation by hydroxylation of 5-methylcytosine (5mC bases to 5-hydroxymethylcytosine (5hmC. Here, we report that suppression of TET1 is required for KRAS-induced DNA hypermethylation and cellular transformation. In distinct nonmalignant cell lines, oncogenic KRAS promotes transformation by inhibiting TET1 expression via the ERK-signaling pathway. This reduces chromatin occupancy of TET1 at TSG promoters, lowers levels of 5hmC, and increases levels of 5mC and 5mC-dependent transcriptional silencing. Restoration of TET1 expression by ERK pathway inhibition or ectopic TET1 reintroduction in KRAS-transformed cells reactivates TSGs and inhibits colony formation. KRAS knockdown increases TET1 expression and diminishes colony-forming ability, whereas KRAS/TET1 double knockdown bypasses the KRAS dependence of KRAS-addicted cancer cells. Thus, suppression of TET1-dependent DNA demethylation is critical for KRAS-mediated transformation.

  1. Demethylation of FANCF gene may be a potential treatment through inhibiting the proliferation of cervical cancer

    Institute of Scientific and Technical Information of China (English)

    Min Li; Chanyu Zhang

    2013-01-01

    Objective: The aim of the study was to explore the effect of demethylating agent 5-Aza-2'-deoxycytidine (5-ADC) on expression of Fanconi anemia complementation group F (FANCF) gene and the proliferation of cervical cancer cells, to observe cell's sensitivity to chemotherapeutic drug taxol, and to explore the antitumor effect of 5-ADC as well as the new treatment of cervical cancer. Methods: Cervical cancer cell lines SiHa (FANCF gene full-methylated) and Hela (unmethylated) were treated with 5-ADC. We used the methylation-specific PCR (MSP), reverse transcription-polymerase chain reaction (RT-PCR) and Western blot to detect the FANCF methylation, mRNA and protein respectively. The 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the proliferation of cells. The cytotoxicity of taxol was measured by flow cytometer. The nude mice bearing SiHa was used to observe the effect of 5-ADC in vivo. Results: Inhibition of DNA promoter methylation by 5-ADC reactivated the expression of FANCF mRNA and protein in SiHa cells, consistent with decreased growth speed and increased taxol resistance. These results were proven in experiments in vivo. Conclusion: The 5-ADC probably become a potential treatment drug through inhibiting the proliferation of cervical cancer cells in taxol-resistant patients.

  2. PM6 study of free radical scavenging mechanisms of flavonoids: why does O-H bond dissociation enthalpy effectively represent free radical scavenging activity?

    Science.gov (United States)

    Amić, Dragan; Stepanić, Višnja; Lučić, Bono; Marković, Zoran; Dimitrić Marković, Jasmina M

    2013-06-01

    It is well known that the bond dissociation enthalpy (BDE) of the O-H group is related to the hydrogen atom transfer (HAT) mechanism of free radical scavenging that is preferred in gas-phase and non-polar solvents. The present work shows that the BDE may also be related to radical scavenging processes taking place in polar solvents, i.e., single electron transfer followed by proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET). This is so because the total energy requirements related to the SET-PT [sum of the ionization potential (IP) and proton dissociation enthalpy (PDE)] and the SPLET [sum of the proton affinity (PA) and electron transfer enthalpy (ETE)] are perfectly correlated with the BDE. This could explain why the published data for polyphenolic antioxidant activity measured by various assays are better correlated with the BDE than with other reaction enthalpies involved in radical scavenging mechanisms, i.e., the IP, PDE, PA and ETE. The BDE is fairly well able to rank flavonoids as antioxidants in any medium, but to conclude which radical scavenging mechanism represents the most probable reaction pathway from the thermodynamic point of view, the IP and PA (ETE) should also be considered. This is exemplified in the case of the radical scavenging activity of 25 flavonoids.

  3. Nodulation of legumes, nitrogenase activity of roots and occurrence of nitrogen-fixing Azospirillum spp. In representative soils of central Amazonia

    Energy Technology Data Exchange (ETDEWEB)

    Sylvester-Bradley, R.; De Oliverira, L.A.; De Podesta Filho, J.A.; St. John, T.V.

    1980-12-01

    Leguminosae do not predominate in the Brazilian Amazon rain forest, although they are among the five best represented families. Plant roots from various soils were examined for the presence of nodules, acetylene-reducing activity and N/sub 2/-fixing Azospirillum spp. Abundant nodulation was found in black earth (''terra preta dos indios'') and in one case on sandy soil under campinarana vegetation along a tributary of the upper Rio Negro. In sandy latosol some nodules occurred in secondary forest and fewer in primary forest. Legumes in disturbed clayey or sandy latosol showed more frequent nodulation. Primary forest on alluvial (''varzea'') soil, and in Bahia coastal rain forest on sandy latosol and Erythrina glauca used for shading cacao plantations were abundantly nodulated. Acetylene reduction assays showed no, or very little, nitrogenase activity of roots from primary or secondary forest on clayey latosol near Manaus. Nodulated roots from secondary forest on sandy latosol showed acetylene-reducing activity. High rates of acetylene reduction were observed in nodulated roots of primary forest on alluvial ''varzea'' soil. Root samples showed ethylene absorption in controls without acetylene which might interfere with the results of acetylene reduction tests. The incidence of Azospirillum was also higher in black earth than the other soils examined, and in soils with higher pH. The hypothesis that Azospirillum is associated with Trema micantha roots was refuted. Roots and soils collected under cultivated grasses showed a higher incidence of Azospirillum when fertilized with phosphorus and lime. Results indicate that nitrogen fixation did occur in association with roots in some soils, but not with roots of primary or secondary forest on clayey latosol in the vicinity of Manaus, which is the most common soil in Central Amazonia. The possible reasons for this are discussed.

  4. Using Satellite Data to Represent Tropical Instability Waves (TIWs-Induced Wind for Ocean Modeling: A Negative Feedback onto TIW Activity in the Pacific

    Directory of Open Access Journals (Sweden)

    Jinzhong Min

    2013-05-01

    Full Text Available Recent satellite data and modeling studies indicate a pronounced role Tropical Instability Waves (TIW-induced wind feedback plays in the tropical Pacific climate system. Previously, remotely sensed data were used to derive a diagnostic model for TIW-induced wind stress perturbations (τTIW, which was embedded into an ocean general circulation model (OGCM to take into account TIW-induced ocean-atmosphere coupling in the tropical Pacific. While the previous paper by Zhang (2013 is concerned with the effect on the mean ocean state, the present paper is devoted to using the embedded system to examine the effects on TIW activity in the ocean, with τTIW being interactively determined from TIW-scale sea surface temperature (SSTTIW fields generated in the OGCM, written as τTIW = αTIW·F(SSTTIW, where αTIW is a scalar parameter introduced to represent the τTIW forcing intensity. Sensitivity experiments with varying αTIW (representing TIW-scale wind feedback strength are performed to illustrate a negative feedback induced by TIW-scale air-sea coupling and its relationship with TIW variability in the ocean. Consistent with previous modeling studies, TIW wind feedback tends to have a damping effect on TIWs in the ocean, with a general inverse relationship between the τTIW intensity and TIWs. It is further shown that TIW-scale coupling does not vary linearly with αTIW: the coupling increases linearly with intensifying τTIW forcing at low values of αTIW (in a weak τTIW forcing regime; it becomes saturated at a certain value of αTIW; it decreases when αTIW goes above a threshold value as the τTIW forcing increases further. This work presents a clear demonstration of using satellite data to effectively represent TIW-scale wind feedback and its multi-scale interactions with large-scale ocean processes in the tropical Pacific.

  5. Suppression of Wnt signaling by the miR-29 family is mediated by demethylation of WIF-1 in non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Highlights: •Dnmt3A and Dnmt3B are involved in the down-regulation of WIF-1 expression in non-small-cell lung cancer. •MiR-29 family members could restore WIF-1 expression through demethylation. •MiR-29s suppress Wnt/β-catenin signaling pathway and inhibit tumor growth. •The expression of miR-29a and miR-29b could be regulated partially in a positive feedback loop. -- Abstract: Wnt inhibitory factor-1 (WIF-1) silencing induced by promoter hypermethylation is a common mechanism of aberrant activation of the Wnt signaling pathway in non-small-cell lung cancer (NSCLC). However, the activity of regulators associated with the methylation of the WIF-1 gene remains unclear. Here, we investigated the role of three DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) in the expression of WIF-1. The three DNMTs were up-regulated in NSCLC tumor tissues and suppression of DNMT3A and DNMT3B restored the expression of WIF-1 in NSCLC cells. The miR-29 family (miR-29a, -29b, and -29c), which negatively regulates DNMT3A and DNMT3B, was examined in association with the Wnt/β-catenin signaling pathway. A positive correlation between the expression of WIF-1 and that of MiR-29s was observed in NSCLC tissues. Methylation-specific PCR and Western blotting indicated that miR-29s positively regulate WIF-1 expression by inhibiting the methylation of its promoter. Furthermore, miR-29 overexpression downregulated β-catenin expression, inhibited cell proliferation and induced apoptosis. The expression of miR-29a and miR-29b was partially regulated by DNMT3A and DNMT3B in a positive feedback loop. Taken together, our findings show that miR-29s suppress the Wnt signaling pathway through demethylation of WIF-1 in NSCLC

  6. Suppression of Wnt signaling by the miR-29 family is mediated by demethylation of WIF-1 in non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Min [Department of Respiratory Medicine, Shanghai Tenth People’s Hospital, Tongji University, Shanghai 200072 (China); Wu, Junjie, E-mail: wujunjiesh@126.com [Department of Pneumology, Changhai Hospital of Shanghai, Second Military Medical University, Shanghai 200433 (China); State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200433 (China); Cai, Yong, E-mail: dryongcai@126.com [Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433 (China)

    2013-09-06

    Highlights: •Dnmt3A and Dnmt3B are involved in the down-regulation of WIF-1 expression in non-small-cell lung cancer. •MiR-29 family members could restore WIF-1 expression through demethylation. •MiR-29s suppress Wnt/β-catenin signaling pathway and inhibit tumor growth. •The expression of miR-29a and miR-29b could be regulated partially in a positive feedback loop. -- Abstract: Wnt inhibitory factor-1 (WIF-1) silencing induced by promoter hypermethylation is a common mechanism of aberrant activation of the Wnt signaling pathway in non-small-cell lung cancer (NSCLC). However, the activity of regulators associated with the methylation of the WIF-1 gene remains unclear. Here, we investigated the role of three DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) in the expression of WIF-1. The three DNMTs were up-regulated in NSCLC tumor tissues and suppression of DNMT3A and DNMT3B restored the expression of WIF-1 in NSCLC cells. The miR-29 family (miR-29a, -29b, and -29c), which negatively regulates DNMT3A and DNMT3B, was examined in association with the Wnt/β-catenin signaling pathway. A positive correlation between the expression of WIF-1 and that of MiR-29s was observed in NSCLC tissues. Methylation-specific PCR and Western blotting indicated that miR-29s positively regulate WIF-1 expression by inhibiting the methylation of its promoter. Furthermore, miR-29 overexpression downregulated β-catenin expression, inhibited cell proliferation and induced apoptosis. The expression of miR-29a and miR-29b was partially regulated by DNMT3A and DNMT3B in a positive feedback loop. Taken together, our findings show that miR-29s suppress the Wnt signaling pathway through demethylation of WIF-1 in NSCLC.

  7. Demethylation of Circulating Estrogen Receptor Alpha Gene in Cerebral Ischemic Stroke.

    Directory of Open Access Journals (Sweden)

    Hsiu-Fen Lin

    Full Text Available Estrogen is involved in neuron plasticity and can promote neuronal survival in stroke. Its actions are mostly exerted via estrogen receptor alpha (ERα. Previous animal studies have shown that ERα is upregulated by DNA demethylation following ischemic injury. This study investigated the methylation levels in the ERα promoter in the peripheral blood of ischemic stroke patients.The study included 201 ischemic stroke patients, and 217 age- and sex-comparable healthy controls. The quantitative methylation level in the 14 CpG sites of the ERα promoter was measured by pyrosequencing in each participant. Multivariate regression model was used to adjust for stroke traditional risk factors. Stroke subtypes and sex-specific analysis were also conducted.The results demonstrated that the stroke cases had a lower ERα methylation level than controls in all 14 CpG sites, and site 13 and site 14 had significant adjusted p-values of 0.035 and 0.026, respectively. Stroke subtypes analysis showed that large-artery atherosclerosis and cardio-embolic subtypes had significantly lower methylation levels than the healthy controls at CpG site 5, site 9, site 12, site 13 and site 14 with adjusted p = 0.039, 0.009, 0.025, 0.046 and 0.027 respectively. However, the methylation level for the patients with small vessel subtype was not significant. We combined the methylation data from the above five sites for further sex-specific analysis. The results showed that the significant association only existed in women (adjusted p = 0.011, but not in men (adjusted p = 0.300.Female stroke cases have lower ERα methylation levels than those in the controls, especially in large-artery and cardio-embolic stroke subtypes. The study implies that women suffering from ischemic stroke of specific subtype may undergo different protective mechanisms to reduce the brain injury.

  8. [Nutrition, physical activity and substance use in children and adolescents : Representative results of the federal state module Thuringia in KiGGS wave 1].

    Science.gov (United States)

    Krause, Laura; Anding, Christine; Kamtsiuris, Panagiotis

    2016-08-01

    The term health behaviour combines both health-promoting and health-risk components. In this study, the health behaviour of children and adolescents in Thuringia is analysed. The database was a representative subsample of the federal state module Thuringia, which was conducted by the Robert Koch Institute as part of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) wave 1 (2010-2012; n = 4,096; 3-17 years). Health behaviour was described based on nine indicators: fruit and vegetable consumption, soft drink consumption, breakfast at home, physical activity, sport, swimming ability, alcohol consumption, smoking and water pipe consumption (shisha smoking). Prevalence and mean values with 95 % confidence intervals were reported, and based on logistic or linear regression, the significance of the group differences was examined. The results show that 43.4 % of children and adolescents in Thuringia ate fruits and vegetables daily, 44.5 % consumed soft drinks less than once a week, and 67.9 % had breakfast at home every weekday. In addition, 31.0 % of children and adolescents in Thuringia were physically active at least 60 min a day, 69.8 % did sports for at least 2 h a week, and 81.5 % can swim. Additionally, 15.9 % of adolescents in Thuringia had hazardous alcohol consumption, 14.4 % currently smoked, and 20.0 % smoked a water pipe. Differences existed with regard to gender, age, socio-economic status (SES) of the family and residence (urban/rural). In summary, many of the children and adolescents in Thuringia demonstrate relatively positive health behaviour. However, the results also indicate groups at higher risk of unhealthy behaviour, such as children and adolescents from families with low SES. PMID:27351434

  9. 5-Azacytidine-induced reactivation of the human X chromosome-linked PGK1 gene is associated with a large region of cytosine demethylation in the 5 prime CpG island

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, R.S.; Gartler, S.M. (Univ. of Washington, Seattle (USA))

    1990-06-01

    Hamster-human cell hybrids containing an inactive human X chromosome were treated with 5-azacytidine and derived clones were examined for phosphoglycerate kinase activity and cytosine methylation in the human PGK1 (X chromosome-linked phosphoglycerate kinase) gene. Comparisons between expressing and nonexpressing clones indicated that demethylation of several methylation-sensitive restriction sites outside of the 5{prime} CpG island were unnecessary for expression. High-resolution polyacrylamide gel analysis of 25 Hpa II, Hha I, and Tha I sites revealed that all clones expressing PGK1 were unmethylated in a large region of the CpG island that includes the transcription start site and 400 base pairs upstream. Many nonexpressing clones had discontinuous patterns of demethylation. Remethylation was often observed in subclones of nonexpressing hybrids. These data suggest that a specific zone of methylation-free DNA within the PGK1 promoter is required for transcription. In addition, the presence of neighboring methylcytosines appears to decrease the heritable stability of unmethylated CpGs in this region.

  10. 5-Azacytidine-induced reactivation of the human X chromosome-linked PGK1 gene is associated with a large region of cytosine demethylation in the 5' CpG island.

    Science.gov (United States)

    Hansen, R S; Gartler, S M

    1990-01-01

    Hamster-human cell hybrids containing an inactive human X chromosome were treated with 5-azacytidine and derived clones were examined for phosphoglycerate kinase activity and cytosine methylation in the human PGK1 (X chromosome-linked phosphoglycerate kinase) gene. Comparisons between expressing and nonexpressing clones indicated that demethylation of several methylation-sensitive restriction sites outside of the 5' CpG island were unnecessary for expression. High-resolution polyacrylamide gel analysis of 25 Hpa II, Hha I, and Tha I sites revealed that all clones expressing PGK1 were unmethylated in a large region of the CpG island that includes the transcription start site and 400 base pairs upstream. Many nonexpressing clones had discontinuous patterns of demethylation. Remethylation was often observed in subclones of nonexpressing hybrids. These data suggest that a specific zone of methylation-free DNA within the PGK1 promoter is required for transcription. In addition, the presence of neighboring methylcytosines appears to decrease the heritable stability of unmethylated CpGs in this region. Images PMID:1693431

  11. The Akt/mTOR/p70S6K pathway is activated in IgA nephropathy and rapamycin may represent a viable treatment option.

    Science.gov (United States)

    Tian, Jihua; Wang, Yanhong; Guo, Haixiu; Li, Rongshan

    2015-12-01

    IgA nephropathy (IgAN) is one of the most frequent forms of glomerulonephritis, and 20 to 40% of patients progress to end-stage renal disease (ESRD) within 20 years of disease onset. However, little is known about the molecular pathways involved in the altered physiology of mesangial cells during IgAN progression. This study was designed to explore the role of mTOR signaling and the potential of targeted rapamycin therapy in a rat model of IgAN. After establishing an IgA nephropathy model, the rats were randomly divided into four groups: control, control+rapamycin, IgAN and IgA+rapamycin. Western blotting and immunohistochemistry were performed to determine phospho-Akt, p70S6K and S6 protein levels. Coomassie Brilliant Blue was utilized to measure 24-h urinary protein levels. The biochemical parameters of the rats were analyzed with an autoanalyzer. To evaluate IgA deposition in the glomeruli, FITC-conjugated goat anti-rat IgA antibody was used for direct immunofluorescence. Cellular proliferation and the mesangial matrix in glomeruli were assayed via histological and morphometric procedures. Our results showed that p70S6K, S6 and Akt phosphorylation were significantly upregulated in IgAN rats, and rapamycin effectively inhibited p70S6K and S6 phosphorylation. A low dose of the mTOR inhibitor rapamycin reduced proteinuria, inhibited IgA deposition, and protected kidney function in an IgAN rat model. Low-dose rapamycin treatment corresponded to significantly lower cellular proliferation rates and a decreased mesangial matrix in the glomeruli. In conclusion, the Akt/mTOR/p70S6K pathway was activated in IgAN, and our findings suggested that rapamycin may represent a viable option for the treatment of IgAN. PMID:26297427

  12. PSEN1 promoter demethylation in hyperhomocysteinemic TgCRND8 mice is the culprit, not the consequence.

    Science.gov (United States)

    Fuso, Andrea; Cavallaro, Rosaria A; Cavallaroa, Rosaria A; Nicolia, Vincenzina; Scarpa, Sigfrido

    2012-06-01

    In recent years, in parallel with the growing awareness of the multifactorial nature of Late Onset Alzheimer's Disease, the possibility that epigenetic mechanisms could be involved in the onset and/or progression of the pathology assumed an increasingly intriguing and leading role in Alzheimer's research. Today, many scientific reports indicate the existence of an epigenetic drift during ageing, in particular in Alzheimer's subjects. At the same time, experimental evidences are provided with the aim to demonstrate the causative or consequential role of epigenetic mechanisms. Our research group was involved in the last ten years in studying DNA methylation, the main epigenetic modification, in relationship to altered one-carbon metabolism (namely high homocysteine and low B vitamins levels), in Alzheimer's experimental models. Our previous findings about the demethylation of Presenilin1 gene promoter in nutritionally-induced hyperhomocysteinemia in a transgenic mouse model clearly demonstrated that Presenilin1 is regulated by DNA methylation. One of the open questions raised by our studies was if the observed demethylation was solely due to the induced imbalance of one-carbon metabolism or could be a response to the massive deposition of amyloid plaques in transgenic mice. Here we analyzed old (10 months) mice under standard diet in order to evidence possible changes in Presenilin1 promoter methylation in transgenic (TgCRND8 mice, carrying a double-mutated human APP transgene) vs. wt mice (129Sv) after prolonged exposure to amyloid. We found no differences in Presenilin1 methylation despite a slight increase in gene expression; these results suggest that amyloid production is not responsible for Presenilin1 demethylation in TgCRND8 mice brain. PMID:22272624

  13. Relationship of the demethylation of the DNA with the induction of the sister chromatid exchanges (SCE) In vivo

    International Nuclear Information System (INIS)

    The methylation of the DNA is an epigenetic modification that has an important paper in the regulation of the functionality of the genome of the organisms. It can be altered by demethylation processes, either natural or experimentally induced. The 5-azacytidine (Aza) is a compound that causes the demethylation of the DNA (dm-DNA), inducing with it, expression genic and increase in the frequency of the Sister Chromatid Exchange (SCE). The SCE is a genotoxicity indicator, caused by diverse mutagens and carcinogen. Since the biological meaning and the formation mechanism of this phenomenon has not been totally illustrious, the exploration of the relation between the dm-DNA and the induction of SCE, it could offer new knowledge to explain those queries. The purpose of this work was to study in cells of the mouse bone marrow In vivo, the effect of the Aza on the induction of SCE, based on two aspects: 1) dose answer and 2) the effectiveness of multiple exhibition. To six groups of three to five animals, they are administered Aza to dose of 5, 10, 15 or 20 mg/Kg of weight; in sharp or multiple form, previously to the bromodeoxyuridine supply and 24 h was sacrificed after this; 2 h after an injection with colchicine. Preparations of those metaphases were made, those which were dyed by means of a technique of fluorescence more Giemsa. It was observed that to sharp low dose, the Aza produced an increment in the frequency of SCE that although small it was proportional and statistically significant. To sharp and multiple high doses, the Aza doesn't cause additional increments of SCE, but if toxicity at cellular level and of individuals. It is concluded that a relationship exists between the dm-DNA and the induction of SCE. It is suggested that the total demethylation of the DNA causes 2 SCE/Cell in cells of the mouse bone marrow, or that the cytotoxicity prevents to evidence a bigger induction. (Author)

  14. 牛蒡苷元的脱甲基化研究%Study of Demethylation of ( - )-Arctigenin

    Institute of Scientific and Technical Information of China (English)

    李馥睿; 窦德强; 陈桂荣; 康廷国; 李洪福

    2011-01-01

    Objective: To synthesize demethylic derivatives of ( - )-arctigenin and look for a feasible method of demethylation.Methods: Starting with ( - )-arctigenin, two target products were synthesized with aluminum chloride and hydrobromic acid.Results: Compound 2 was obtained through hydrobromic acid-acetic acid demethylic system.This washigh-yield method which could be operated easily.Conclusion: The optimum technological condition was investigated, refluxing at 110 ℃ for 8h.The yield reached 87%.The structures of the products were determined by 13C-NMR and 1 H-NMR.%目的:以活性天然产物牛蒡苷元为原料,合成其脱甲基衍生物,寻找适宜的脱甲基化方法.方法:以牛蒡苷元为底物,分别以无水氯化铝或氢溴酸为脱甲基试剂进行反应,比较两者脱甲基能力,并制备了目标产物.结果:合成了两个牛蒡苷元脱甲基衍生物,其中化合物2是首次利用氢溴酸-冰醋酸系统进行脱甲基反应而制备得到,采用氢溴酸-冰醋酸系统进行脱甲基反应,收率较高,操作简单.结论:牛蒡苷元脱甲基化最佳工艺条件为:以牛蒡苷元为原料,氢溴酸作为脱甲基试剂,在110℃条件下反应8h,收率87%,并通过核磁共振碳谱和氢谱对目标产物进行了结构确证.

  15. Global demethylation of rat chondrosarcoma cells after treatment with 5-aza-2'-deoxycytidine results in increased tumorigenicity.

    Directory of Open Access Journals (Sweden)

    Christopher A Hamm

    Full Text Available Abnormal patterns of DNA methylation are observed in several types of human cancer. While localized DNA methylation of CpG islands has been associated with gene silencing, the effect that genome-wide loss of methylation has on tumorigenesis is not completely known. To examine its effect on tumorigenesis, we induced DNA demethylation in a rat model of human chondrosarcoma using 5-aza-2-deoxycytidine. Rat specific pyrosequencing assays were utilized to assess the methylation levels in both LINEs and satellite DNA sequences following 5-aza-2-deoxycytidine treatment. Loss of DNA methylation was accompanied by an increase in invasiveness of the rat chondrosarcoma cells, in vitro, as well as by an increase in tumor growth in vivo. Subsequent microarray analysis provided insight into the gene expression changes that result from 5-aza-2-deoxycytidine induced DNA demethylation. In particular, two genes that may function in tumorigenesis, sox-2 and midkine, were expressed at low levels in control cells but upon 5-aza-2-deoxycytidine treatment these genes became overexpressed. Promoter region DNA analysis revealed that these genes were methylated in control cells but became demethylated following 5-aza-2-deoxycytidine treatment. Following withdrawal of 5-aza-2-deoxycytidine, the rat chondrosarcoma cells reestablished global DNA methylation levels that were comparable to that of control cells. Concurrently, invasiveness of the rat chondrosarcoma cells, in vitro, decreased to a level indistinguishable to that of control cells. Taken together these experiments demonstrate that global DNA hypomethylation induced by 5-aza-2-deoxycytidine may promote specific aspects of tumorigenesis in rat chondrosarcoma cells.

  16. Representative of the municipality

    International Nuclear Information System (INIS)

    Full text of publication follows. The decommissioning of the Vandellos-I nuclear power plant was a big challenge for the host community of Vandellos i l'Hospitalet de l'Infant and the close-by region. Closing down of the facility resulted in a rise of unemployment and a decrease of municipal income. The public was concerned with three issues: safety, transparency and information about the decommissioning, and economic future. Therefore, from the very beginning, municipal governments entered into negotiations with ENRESA on socio-economic benefits, including local employment in dismantling activities, and other types of financial and non-financial compensation. The ADE business association, i.e. a network of business organisations was created that guided the allotment of work to local firms. To satisfy public demand, local municipalities focused on the triad of safety, dialogue and local development, considered the three 'pillars of trust'. A Municipal Monitoring Commission was created, made up of representatives of affected municipalities, the regional government, the ADE business association, trade unions, the local university, the NPP management and ENRESA to monitor the dismantling process and regularly inform the local public. Items that were handled by this Commission included: - Work process monitoring. - Workers. - Materials Control. - Conventional and radioactive or contaminated waste management. - Emanation waste management (liquid and gas) - Safety (training and accidents). - Surveillance (radiological and environmental: dust, noise). - Effects. - Fulfillment of agreed conditions. A number of communication tools and channels were used, e.g., public information meetings, an information centre, the municipal magazine, the municipal radio station, and meetings with representatives of the local press. Particularly innovative was the idea to ask academics from the University of Tarragona to help with 'translating' technical information into language that could

  17. Human in vitro induced T regulatory cells and memory T cells share common demethylation of specific FOXP3 promoter region

    OpenAIRE

    Bégin, Philippe; Schulze, Janika; Baron, Udo; Olek, Sven; Rebecca N Bauer; Passerini, Laura; Baccheta, Rosa; Nadeau, Kari C.

    2015-01-01

    Background The FOXP3 gene is the master regulator for T regulatory cells and is under tight DNA methylation control at the Treg specific demethylated region (TSDR) in its first intron. This said, methylation of its promoter region, the significance of which is unknown, has also been associated with various immune-related disease states such as asthma, food allergy, auto-immunity and cancer. Here, we used induced T regulatory cells (iTreg) as a target cell population to identify candidate hypo...

  18. Synergism between demethylation inhibitor fungicides or gibberellin inhibitor plant growth regulators and bifenthrin in a pyrethroid-resistant population of Listronotus maculicollis (Coleoptera: Curculionidae).

    Science.gov (United States)

    Ramoutar, D; Cowles, R S; Requintina, E; Alm, S R

    2010-10-01

    In 2007-2008, the "annual bluegrass weevil," Listronotus maculicollis Kirby (Coleoptera: Curculionidae), a serious pest of Poa annua L. (Poales: Poaceae) on U.S. golf courses, was shown to be resistant to two pyrethroids, bifenthrin and lambda-cyhalothrin. In 2008, we showed that bifenthrin resistance was principally mediated by oxidase detoxification (cytochrome P450 [P450]). P450s can be inhibited by demethylation inhibitor fungicides and gibberellin inhibitor plant growth regulators, both of which are commonly used on golf courses. We tested these compounds for synergistic activity with bifenthin against a pyrethroid-resistant population of L. maculicollis. The LD50 value for bifenthrin was significantly reduced from 87 ng per insect (without synergists) to 9.6-40 ng per insect after exposure to the fungicides fenarimol, fenpropimorph, prochloraz, propiconazole, and pyrifenox and the plant growth regulators flurprimidol, paclobutrazol, and trinexapac-ethyl. Simulated field exposure with formulated products registered for use on turf revealed enhanced mortality when adult weevils were exposed to bifenthrin (25% mortality, presented alone) combined with field dosages of propiconizole, fenarimol, flurprimidol, or trinexapac-ethyl (range, 49-70% mortality).

  19. Breath analysis of 13CO2 following N-demethylation of 13C-aminopyrine: a measure of liver microsomal function

    International Nuclear Information System (INIS)

    The hepatic microsomal mixed function oxidase enzyme activity has been measured by N-demethylation of 4-dimethyl-14C-aminopyrine (DAP). Analysis of 14CO2 in expired breath has recently been validated in the rat and man as a measure of this function. In the present study we examine the use of DAP labeled with the stable isotope carbon-13, in order to permit broader clinical application of this test by avoiding radiation exposure. Two mg/kg of 86% enriched 13C-DAP were given orally to 4 normal subjects and 5 patients with cholestatic liver disease. All subjects were fasted overnight and studied at rest. Breath samples were collected at 1/2 hour intervals for 3 hours. In all samples the excess of 13CO2 was significantly greater than the variation in baseline after ingestion of unlabeled DAP. In normal subjects the peak production of 13CO2 occurred in the first 1/2 hour sample. Unlabeled DAP (8 mg/kg) clearance from serum correlated with excess 13CO2 production measured in exhaled breath confirming the 14CO2 results. When phenobarbital (180 mg/day) was administered, an increase in exhaled 13CO2 was observed. Measurement of 13CO2 in breath following DAP provides a reproducible clinical measure of microsomal function and drug induction. The use of stable carbon-13 labeled DAP permits measurement of liver microsomal function in patients who cannot receive radioactive labeled DAP

  20. Role of heme oxygenase-1 in demethylating effects on SKM-1 cells induced by decitabine.

    Science.gov (United States)

    Gao, R; Ma, D; Wang, P; Sun, J; Wang, J S; Fang, Q

    2015-12-22

    We evaluated the influence of heme oxygenase-1 (HO-1) gene inhibition in myelodysplastic syndrome (MDS) cell line SKM-1 on enhancement of the demethylating effects of decitabine on p15, and explored the possible mechanism. DNMT1 gene expression in SKM-1 cells was silenced by being transfected by a constructed siRNA with liposomes. The proliferation inhibition rates after drug treatment were detected by cell counting kit-8 assay. The apoptotic rates were detected by Annexin V/PI assay with flow cytometry. The expressions of p16, p15, TP73, CDH1, ESR1, and PDLIM4 mRNAs were detected by real-time PCR, and those of HO-1, DNMT1, DNMT3A, DNMT3B, HDAC, and p15 proteins were measured by western blot. The degree of methylation of the p15 gene was analyzed by using methylation-specific PCR (MSP). CCK-8 assay showed that after HO-1 gene expression was inhibited; the proliferation rate of SKM-1 cells treated by decitabine (70.91 ± 0.05%) was significantly higher than that of the control group (53.67 ± 0.05%). Flow cytometry showed that the apoptotic rate of SKM- 1 cells treated by decitabine in combination with HO-1 expression inhibition (44.25 ± 0.05%) exceeded that of the cells treated by this drug alone (37.70 ± 0.05%). MSP showed that inhibiting HO-1 expression significantly increased the degree of methylation of the p15 gene. As suggested by western blot, the degree of methylation of the p15 protein was changed after decitabine treatment when the expression of the HO-1 protein was changed, being associated with the affected DNMT1 expression. Inhibited HO-1 expression attenuated the hypermethylation of CDKN2B by suppressing DNMT1, which was conducive to treatment by cooperating with decitabine. In conclusion, the findings of this study provide valuable experimental evidence for targeted MDS therapy, and a theoretical basis for further studies.

  1. Testing Theory of Planned Behavior and Neo-Socioanalytic Theory models of trait activity, industriousness, exercise social cognitions, exercise intentions, and physical activity in a representative U.S. sample.

    Science.gov (United States)

    Vo, Phuong T; Bogg, Tim

    2015-01-01

    Prior research identified assorted relations between trait and social cognition models of personality and engagement in physical activity. Using a representative U.S. sample (N = 957), the goal of the present study was to test two alternative structural models of the relationships among the extraversion-related facet of activity, the conscientiousness-related facet of industriousness, social cognitions from the Theory of Planned Behavior (perceived behavioral control, affective attitudes, subjective norms, intentions), Social Cognitive Theory (self-efficacy, outcome expectancies), and the Transtheoretical Model (behavioral processes of change), and engagement in physical activity. Path analyses with bootstrapping procedures were used to model direct and indirect effects of trait and social cognition constructs on physical activity through two distinct frameworks - the Theory of Planned Behavior and Neo-Socioanalytic Theory. While both models showed good internal fit, comparative model information criteria showed the Theory-of-Planned-Behavior-informed model provided a better fit. In the model, social cognitions fully mediated the relationships from the activity facet and industriousness to intentions for and engagement in physical activity, such that the relationships were primarily maintained by positive affective evaluations, positive expected outcomes, and confidence in overcoming barriers related to physical activity engagement. The resultant model - termed the Disposition-Belief-Motivation model- is proposed as a useful framework for organizing and integrating personality trait facets and social cognitions from various theoretical perspectives to investigate the expression of health-related behaviors, such as physical activity. Moreover, the results are discussed in terms of extending the application of the Disposition-Belief-Motivation model to longitudinal and intervention designs for physical activity engagement. PMID:26300811

  2. Testing Theory of Planned Behavior and Neo-Socioanalytic Theory models of trait activity, industriousness, exercise social cognitions, exercise intentions, and physical activity in a representative U.S. sample.

    Science.gov (United States)

    Vo, Phuong T; Bogg, Tim

    2015-01-01

    Prior research identified assorted relations between trait and social cognition models of personality and engagement in physical activity. Using a representative U.S. sample (N = 957), the goal of the present study was to test two alternative structural models of the relationships among the extraversion-related facet of activity, the conscientiousness-related facet of industriousness, social cognitions from the Theory of Planned Behavior (perceived behavioral control, affective attitudes, subjective norms, intentions), Social Cognitive Theory (self-efficacy, outcome expectancies), and the Transtheoretical Model (behavioral processes of change), and engagement in physical activity. Path analyses with bootstrapping procedures were used to model direct and indirect effects of trait and social cognition constructs on physical activity through two distinct frameworks - the Theory of Planned Behavior and Neo-Socioanalytic Theory. While both models showed good internal fit, comparative model information criteria showed the Theory-of-Planned-Behavior-informed model provided a better fit. In the model, social cognitions fully mediated the relationships from the activity facet and industriousness to intentions for and engagement in physical activity, such that the relationships were primarily maintained by positive affective evaluations, positive expected outcomes, and confidence in overcoming barriers related to physical activity engagement. The resultant model - termed the Disposition-Belief-Motivation model- is proposed as a useful framework for organizing and integrating personality trait facets and social cognitions from various theoretical perspectives to investigate the expression of health-related behaviors, such as physical activity. Moreover, the results are discussed in terms of extending the application of the Disposition-Belief-Motivation model to longitudinal and intervention designs for physical activity engagement.

  3. Testing Theory of Planned Behavior and Neo-Socioanalytic Theory models of trait activity, industriousness, exercise social cognitions, exercise intentions, and physical activity in a representative U.S. sample

    Directory of Open Access Journals (Sweden)

    Phuong Thi Vo

    2015-08-01

    Full Text Available Prior research identified assorted relations between trait and social cognition models of personality and engagement in physical activity. Using a representative U.S. sample (N = 957, the goal of the present study was to test two alternative structural models of the relationships among the extraversion-related facet of activity, the conscientiousness-related facet of industriousness, social cognitions from the Theory of Planned Behavior (perceived behavioral control, affective attitudes, subjective norms, intentions, Social Cognitive Theory (self-efficacy, outcome expectancies, and the Transtheoretical Model (behavioral processes of change, and engagement in physical activity. Path analyses with bootstrapping procedures were used to model direct and indirect effects of trait and social cognition constructs on physical activity through two distinct frameworks – the Theory of Planned Behavior and Neo-Socioanalytic Theory. While both models showed good internal fit, comparative model information criteria showed the Theory-of-Planned-Behavior-informed model provided a better fit. In the model, social cognitions fully mediated the relationships from the activity facet and industriousness to intentions for and engagement in physical activity, such that the relationships were primarily maintained by positive affective evaluations, positive expected outcomes, and confidence in overcoming barriers related to physical activity engagement. The resultant model – termed the Disposition-Belief-Motivation model – is proposed as a useful framework for organizing and integrating personality trait facets and social cognitions from various theoretical perspectives to investigate the expression of health-related behaviors, such as physical activity. Moreover, the results are discussed in terms of extending the application of the Disposition-Belief-Motivation model to longitudinal and intervention designs for physical activity engagement.

  4. A novel diterpene skeleton: identification of a highly aromatic, cytotoxic and antioxidant 5-methyl-10-demethyl-abietane-type diterpene from Premna serratifolia.

    Science.gov (United States)

    Habtemariam, Solomon; Varghese, George K

    2015-01-01

    Premna serratifolia Linn. (syn: . P. corymbosa (Burm. f.) Merr., P. integrifolia L. and P. obtusifolia R. Br.) is a member of the Verbenaceae family that is extensively used in the Ayurvedic system of medicine in India. As part of our continuous pharmacological and phytochemical studies on medicinal plants, we have screened the methanolic extracts of leaves, root bark (RB) and root wood of P. serratifolia for cytotoxic activity against two cancer cell lines: SHSY-5Y neuroblastoma and B16 melanoma cells. The RB extract that showed promising activity was fractionated using solvents of increasing polarity followed by a combination of Sephadex LH-20 column and Combiflash chromatography as well as HPLC to afford the active principle. Comprehensive spectroscopic analysis including 1D and 2D NMR (COSY, HMQC, HMBC, NOESY) and MS analysis revealed the identity of the isolated compound as 11,12,16-trihydroxy-2-oxo-5-methyl-10-demethyl-abieta-1[10],6,8,11,13-pentene that appears to be a novel compound based on a new diterpene skeleton. The cytotoxic activity of the isolated compound was 21 and 23 times higher than the crude extract against the SHSY-5Y and B16 cells, respectively. The novel compound also possesses in vitro antioxidant effects as evidenced by the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging effect where an IC50 value of 20.4 ± 1.3 μM was obtained. In comparison, the positive control, caffeic acid, showed an IC50 value of 14.4 ± 1.6 μM. PMID:25250850

  5. [Methylation of FHIT gene promoter region in DNA from plasma of patients with myelodysplastic syndromes and demethylating effect of decitabine].

    Science.gov (United States)

    Deng, Yin-Fen; Zhang, Lei; Zhang, Xiu-Qun; Hu, Ming-Qiu; Dai, Dan; Zhang, Xue-Zhong; Xu, Yan-Li

    2012-10-01

    This study was aimed to detect the methylation status of FHIT gene promoter region in the DNA from plasma of patients with myelodysplastic syndrome (MDS), and to investigate the demethylating effect of decitabine. Methylation-specific PCR method was used to detect the methylation status of FHIT gene promoter region in the DNA from plasma of 4 patients with MDS before and after treatment with decitabine plus semis CAG therapy (among them, 1 case of newly diagnosed MDS, 3 cases progressed into acute leukemia). The results indicated that 3 cases were found to have an increased methylation in the promoter region. After treatment with decitabine plus semis CAG, increased methylation was reversed in 2 cases. In 4 cases, 2 cases displayed clinical response. It is concluded that FHIT gene hypermethylation is associated with MDS pathogenesis. Decitabine has demethylating effect on the FHIT gene hypermethylation of plasma from MDS patients. Detecting the methylation status of FHIT gene in DNA from plasma may play a role in MDS auxiliary diagnosis or prognosis.

  6. IFNγ+ Treg in-vivo and in-vitro represent both activated nTreg and peripherally induced aTreg and remain phenotypically stable in-vitro after removal of the stimulus

    OpenAIRE

    Daniel, Volker; Trojan, Karina; Adamek, Martina; Opelz, Gerhard

    2015-01-01

    Background: IFNγ-producing CD4+CD25+Foxp3+CD127- Treg represent the first line of Treg during an immune response. In the present study we determined whether IFNγ+ Treg in-vivo and in-vitro are Helios-positive representing activated natural (nTreg) or Helios-negative representing adaptive Treg (aTreg) and whether they originate from CD4+CD25+ and/or CD4+CD25- PBL. Furtheron, we investigated whether they are inducible by recombinant IFNγ (rIFNγ) as a single stimulus, decrease in-vitro after eli...

  7. The representative animal

    OpenAIRE

    Harrison, J. M.

    1994-01-01

    The anthropocentric approach to the study of animal behavior uses representative nonhuman animals to understand human behavior. This approach raises problems concerning the comparison of the behavior of two different species. The datum of behavior analysis is the behavior of humans and representative animal phenotypes. The behavioral phenotype is the product of the ontogeny and phylogeny of each species, and this requires that contributions of genotype as well as behavioral history to experim...

  8. Suppression of Wnt signaling by the miR-29 family is mediated by demethylation of WIF-1 in non-small-cell lung cancer.

    Science.gov (United States)

    Tan, Min; Wu, Junjie; Cai, Yong

    2013-09-01

    Wnt inhibitory factor-1 (WIF-1) silencing induced by promoter hypermethylation is a common mechanism of aberrant activation of the Wnt signaling pathway in non-small-cell lung cancer (NSCLC). However, the activity of regulators associated with the methylation of the WIF-1 gene remains unclear. Here, we investigated the role of three DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) in the expression of WIF-1. The three DNMTs were up-regulated in NSCLC tumor tissues and suppression of DNMT3A and DNMT3B restored the expression of WIF-1 in NSCLC cells. The miR-29 family (miR-29a, -29b, and -29c), which negatively regulates DNMT3A and DNMT3B, was examined in association with the Wnt/β-catenin signaling pathway. A positive correlation between the expression of WIF-1 and that of MiR-29s was observed in NSCLC tissues. Methylation-specific PCR and Western blotting indicated that miR-29s positively regulate WIF-1 expression by inhibiting the methylation of its promoter. Furthermore, miR-29 overexpression downregulated β-catenin expression, inhibited cell proliferation and induced apoptosis. The expression of miR-29a and miR-29b was partially regulated by DNMT3A and DNMT3B in a positive feedback loop. Taken together, our findings show that miR-29s suppress the Wnt signaling pathway through demethylation of WIF-1 in NSCLC. PMID:23939044

  9. Mild Glucose Starvation Induces KDM2A-Mediated H3K36me2 Demethylation through AMPK To Reduce rRNA Transcription and Cell Proliferation.

    Science.gov (United States)

    Tanaka, Yuji; Yano, Hirohisa; Ogasawara, Sachiko; Yoshioka, Sho-Ichi; Imamura, Hiromi; Okamoto, Kengo; Tsuneoka, Makoto

    2015-12-01

    Environmental conditions control rRNA transcription. Previously, we found that serum and glucose deprivation induces KDM2A-mediated H3K36me2 demethylation in the rRNA gene (rDNA) promoter and reduces rRNA transcription in the human breast cancer cell line MCF-7. However, the molecular mechanism and biological significance are still unclear. In the present study, we found that glucose starvation alone induced the KDM2A-dependent reduction of rRNA transcription. The treatment of cells with 2-deoxy-d-glucose, an inhibitor of glycolysis, reduced rRNA transcription and H3K36me2 in the rDNA promoter, both of which were completely dependent on KDM2A in low concentrations of 2-deoxy-d-glucose, that is, mild starvation conditions. The mild starvation induced these KDM2A activities through AMP-activated kinase (AMPK) but did not affect another AMPK effector of rRNA transcription, TIF-IA. In the triple-negative breast cancer cell line MDA-MB-231, the mild starvation also reduced rRNA transcription in a KDM2A-dependent manner. We detected KDM2A in breast cancer tissues irrespective of their estrogen receptor, progesterone receptor, and HER2 status, including triple-negative cancer tissues. In both MCF-7 and MDA-MB-231 cells, mild starvation reduced cell proliferation, and KDM2A knockdown suppressed the reduction of cell proliferation. These results suggest that under mild glucose starvation AMPK induces KDM2A-dependent reduction of rRNA transcription to control cell proliferation.

  10. Comparative in vitro metabolism of methoxychlor in male and female rats: metabolism of demethylated methoxychlor metabolites by precision-cut rat liver slices.

    Science.gov (United States)

    Ohyama, K; Maki, S; Sato, K; Kato, Y

    2005-07-01

    The in vitro metabolism of demethylated methoxychlor (MXC) metabolites, mono-OH-MXC (including (R)- and (S)-isomers) and bis-OH-MXC (mono- and bis-demethylated MXC, respectively), was conducted using precision-cut liver slices to understand the sex-dependent metabolism of MXC in rats. In the study with bis-OH-MXC, the substrate underwent extensive conjugation producing its glucuronide and glucuronide/sulphate diconjugate, and no significant sex differences were found. On the contrary, the metabolism of mono-OH-MXC appeared to exhibit the sex differences in the metabolic profiles. The bis-OH-MXC glucuronide and glucuronide/sulphate diconjugate were major metabolites in male rat, whereas the mono- and bis-OH-MXC glucuronides predominated in the female. The per cent distribution of the demethylated products (sum of bis-OH-MXC derivatives) was approximately 90% for the male (for both isomers) and 81 (R-) to 56% (S-) for the female. The metabolic profiles in (S)-mono-OH-MXC, which is the predominant enantiomer preferentially produced in MXC metabolism in rats, showed a similar pattern to that of MXC compared with the (R)-isomer. The results indicate that the sex differences in oxidative demethylation of the intermediate, (S)-mono-OH-MXC, could be one of the probable reasons for the sex-dependent metabolism of MXC in rats, and the stereo-structural preference of the contributing demethylase enzymes appear to be involved.

  11. Representing properties locally.

    Science.gov (United States)

    Solomon, K O; Barsalou, L W

    2001-09-01

    Theories of knowledge such as feature lists, semantic networks, and localist neural nets typically use a single global symbol to represent a property that occurs in multiple concepts. Thus, a global symbol represents mane across HORSE, PONY, and LION. Alternatively, perceptual theories of knowledge, as well as distributed representational systems, assume that properties take different local forms in different concepts. Thus, different local forms of mane exist for HORSE, PONY, and LION, each capturing the specific form that mane takes in its respective concept. Three experiments used the property verification task to assess whether properties are represented globally or locally (e.g., Does a PONY have mane?). If a single global form represents a property, then verifying it in any concept should increase its accessibility and speed its verification later in any other concept. Verifying mane for PONY should benefit as much from having verified mane for LION earlier as from verifying mane for HORSE. If properties are represented locally, however, verifying a property should only benefit from verifying a similar form earlier. Verifying mane for PONY should only benefit from verifying mane for HORSE, not from verifying mane for LION. Findings from three experiments strongly supported local property representation and ruled out the interpretation that object similarity was responsible (e.g., the greater overall similarity between HORSE and PONY than between LION and PONY). The findings further suggest that property representation and verification are complicated phenomena, grounded in sensory-motor simulations.

  12. Induced Pib Expression and Resistance to Magnaporthe grisea are Compromised by Cytosine Demethylation at Critical Promoter Regions in Rice

    Institute of Scientific and Technical Information of China (English)

    Yuan Li; Qiong Xia; Hongping Kou; Dan Wang; Xiuyun Lin; Ying Wu; Chunming Xu; Shaochen Xing

    2011-01-01

    Pib is a well-characterized rice blast-resistance gene belonging to the nucleotide binding site (NBS) and leucine-rich repeat (LRR) superfamily.Expression of Pib was low under non-challenged conditions,but strongly induced by the blast-causing fungal pathogen Magnaporthe grisea,thereby conferring resistance to the pathogen.It is generally established that cytosine methylation of the promoter-region often plays a repressive role in modulating expression of the gene in question.We report here that two critical regions of the Pib promoter were heavily CG cytosine-methylated in both cultivars studied.Surprisingly,induced expression of Pib by M.grisea infection did not entail its promoter demethylation,and partial demethylation by 5-azacytidine-treatment actually reduced Pib expression relative to wildtype plants.Accordingly,the blast disease-resistance was compromised in the 5’-azaC-treated plants relative to wild-type.In contrast,the disease susceptibility was not affected by the 5’-azaC treatment in another two rice cultivars that did not contain the Pib gene,ruling out effects of other R genes and non-specific genotoxic effects by the drug-treatment as a cause for the compromised Pib-conditioned blast-resistance.Taken together,our results suggest that promoter DNA methylation plays a novel enhancing role in conditioning high-level of induced expression of the Pib gene in times of M.grisea infection,and its conferred resistance to the pathogen.

  13. DNA methylation and demethylation:current status and future per-spective%DNA甲基化和去甲基化的研究现状及思考

    Institute of Scientific and Technical Information of China (English)

    邓大君

    2014-01-01

    DNA methylation plays important roles in cell differentiation, embryonic development, host adaptations to environmental factors, and pathogenesis through regulation of gene transcription and imprinting, X-inactivation, and de-fense of foreign genetic material invasion, is currently one of the hottest research fields on epigenetics. In the past few years, a number of important findings on DNA methylation have been achieved. These findings include discovery of TETs-catalyzed cytosine hydroxymethylation and its functions in the early embryonic development; the relationship be-tween active and passive DNA demethylation;establishment and maintenance of DNA methylation patterns and their asso-ciations with histone modifications, chromatin configuration, polycomb group proteins and non-coding RNA bindings. DNA methylation has become a new potential biomarker and therapy target.%DNA甲基化通过调节基因转录、印记、X染色体灭活和防御外源性遗传物质入侵等,在细胞分化、胚胎发育、环境适应和疾病发生发展上发挥重要作用,是当前表观遗传学研究的热点领域之一。文章介绍了在过去几年中TET介导的DNA羟甲基化及其在早期胚胎发育中的作用, DNA主动去甲基化及其与被动去甲基化的关系, DNA甲基化建立及其与组蛋白修饰、染色质构象、多梳蛋白和非编码RNA结合等关系方面的重要研究进展和存在的问题以及DNA甲基化的转化应用前景。

  14. Representing distance, consuming distance

    DEFF Research Database (Denmark)

    Larsen, Gunvor Riber

    Title: Representing Distance, Consuming Distance Abstract: Distance is a condition for corporeal and virtual mobilities, for desired and actual travel, but yet it has received relatively little attention as a theoretical entity in its own right. Understandings of and assumptions about distance...

  15. Lactococcus lactis TrxD represents a subgroup of thioredoxins prevalent in Gram-positive bacteria containing WCXDC active site motifs

    DEFF Research Database (Denmark)

    Björnberg, Olof; Efler, Petr; Epie, Denis Ebong;

    2014-01-01

    Three protein disulfide reductases of the thioredoxin superfamily from the industrially important Gram-positive Lactococcus lactis (LlTrxA, LlTrxD and LlNrdH) are compared to the "classical" thioredoxin from Escherichia coil (EcTrx1). LlTrxA resembles EcTrx1 with a WCGPC active site motif and oth...

  16. Using Graph Components Derived from an Associative Concept Dictionary to Predict fMRI Neural Activation Patterns that Represent the Meaning of Nouns.

    Science.gov (United States)

    Akama, Hiroyuki; Miyake, Maki; Jung, Jaeyoung; Murphy, Brian

    2015-01-01

    In this study, we introduce an original distance definition for graphs, called the Markov-inverse-F measure (MiF). This measure enables the integration of classical graph theory indices with new knowledge pertaining to structural feature extraction from semantic networks. MiF improves the conventional Jaccard and/or Simpson indices, and reconciles both the geodesic information (random walk) and co-occurrence adjustment (degree balance and distribution). We measure the effectiveness of graph-based coefficients through the application of linguistic graph information for a neural activity recorded during conceptual processing in the human brain. Specifically, the MiF distance is computed between each of the nouns used in a previous neural experiment and each of the in-between words in a subgraph derived from the Edinburgh Word Association Thesaurus of English. From the MiF-based information matrix, a machine learning model can accurately obtain a scalar parameter that specifies the degree to which each voxel in (the MRI image of) the brain is activated by each word or each principal component of the intermediate semantic features. Furthermore, correlating the voxel information with the MiF-based principal components, a new computational neurolinguistics model with a network connectivity paradigm is created. This allows two dimensions of context space to be incorporated with both semantic and neural distributional representations. PMID:25928363

  17. Using Graph Components Derived from an Associative Concept Dictionary to Predict fMRI Neural Activation Patterns that Represent the Meaning of Nouns.

    Directory of Open Access Journals (Sweden)

    Hiroyuki Akama

    Full Text Available In this study, we introduce an original distance definition for graphs, called the Markov-inverse-F measure (MiF. This measure enables the integration of classical graph theory indices with new knowledge pertaining to structural feature extraction from semantic networks. MiF improves the conventional Jaccard and/or Simpson indices, and reconciles both the geodesic information (random walk and co-occurrence adjustment (degree balance and distribution. We measure the effectiveness of graph-based coefficients through the application of linguistic graph information for a neural activity recorded during conceptual processing in the human brain. Specifically, the MiF distance is computed between each of the nouns used in a previous neural experiment and each of the in-between words in a subgraph derived from the Edinburgh Word Association Thesaurus of English. From the MiF-based information matrix, a machine learning model can accurately obtain a scalar parameter that specifies the degree to which each voxel in (the MRI image of the brain is activated by each word or each principal component of the intermediate semantic features. Furthermore, correlating the voxel information with the MiF-based principal components, a new computational neurolinguistics model with a network connectivity paradigm is created. This allows two dimensions of context space to be incorporated with both semantic and neural distributional representations.

  18. OSMOSE experiment representativity studies.

    Energy Technology Data Exchange (ETDEWEB)

    Aliberti, G.; Klann, R.; Nuclear Engineering Division

    2007-10-10

    The OSMOSE program aims at improving the neutronic predictions of advanced nuclear fuels through measurements in the MINERVE facility at the CEA-Cadarache (France) on samples containing the following separated actinides: Th-232, U-233, U-234, U-235, U-236, U-238, Np-237, Pu-238, Pu-239, Pu-240, Pu-241, Pu-242, Am-241, Am-243, Cm-244 and Cm-245. The goal of the experimental measurements is to produce a database of reactivity-worth measurements in different neutron spectra for the separated heavy nuclides. This database can then be used as a benchmark for integral reactivity-worth measurements to verify and validate reactor analysis codes and integral cross-section values for the isotopes tested. In particular, the OSMOSE experimental program will produce very accurate sample reactivity-worth measurements for a series of actinides in various spectra, from very thermalized to very fast. The objective of the analytical program is to make use of the experimental data to establish deficiencies in the basic nuclear data libraries, identify their origins, and provide guidelines for nuclear data improvements in coordination with international programs. To achieve the proposed goals, seven different neutron spectra can be created in the MINERVE facility: UO2 dissolved in water (representative of over-moderated LWR systems), UO2 matrix in water (representative of LWRs), a mixed oxide fuel matrix, two thermal spectra containing large epithermal components (representative of under-moderated reactors), a moderated fast spectrum (representative of fast reactors which have some slowing down in moderators such as lead-bismuth or sodium), and a very hard spectrum (representative of fast reactors with little moderation from reactor coolant). The different spectra are achieved by changing the experimental lattice within the MINERVE reactor. The experimental lattice is the replaceable central part of MINERVE, which establishes the spectrum at the sample location. This configuration

  19. Enantioselective recognition of mono-demethylated methoxychlor metabolites by the estrogen receptor.

    Science.gov (United States)

    Miyashita, Masahiro; Shimada, Takahiro; Nakagami, Shizuka; Kurihara, Norio; Miyagawa, Hisashi; Akamatsu, Miki

    2004-02-01

    Metabolites of methoxychlor such as 2-(p-hydroxyphenyl)-2-(p-methoxyphenyl)-1,1,1-trichloroethane (mono-OH-MXC) and 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (bis-OH-MXC), have estrogenic activity. Mono-OH-MXC is a chiral compound in which the carbon atom bridging two benzene rings is the chiral centre. In previous studies the estrogenic activity of racemic mono-OH-MXC has been measured, and the activity of each enantiomer of this compound has not yet been elucidated. In this study, we evaluated the estrogen receptor-binding activity of each enantiomer of mono-OH-MXC to clarify the enantioselective recognition by the estrogen receptor. (S)-mono-OH-MXC showed 3-fold higher binding activity than that of the (R) enantiomer. The activity of bis-OH-MXC was only 1.7-fold higher than that of (S)-mono-OH-MXC. This result suggests that the one hydroxy group and the orientation of the CCl3 group of mono- and bis-OH-MXCs are important for the interaction with the estrogen receptor. The result also points out the estrogenic activity of methoxychlor after metabolic activation in vivo, which predominantly produces the (S)-mono-OH-MXC, may be higher than estimated from the in vitro activity of racemic mixtures.

  20. Comparison of the EPIC Physical Activity Questionnaire with combined heart rate and movement sensing in a nationally representative sample of older British adults.

    Directory of Open Access Journals (Sweden)

    Vanesa España-Romero

    Full Text Available OBJECTIVES: To compare physical activity (PA subcomponents from EPIC Physical Activity Questionnaire (EPAQ2 and combined heart rate and movement sensing in older adults. METHODS: Participants aged 60-64y from the MRC National Survey of Health and Development in Great Britain completed EPAQ2, which assesses self-report PA in 4 domains (leisure time, occupation, transportation and domestic life during the past year and wore a combined sensor for 5 consecutive days. Estimates of PA energy expenditure (PAEE, sedentary behaviour, light (LPA and moderate-to-vigorous PA (MVPA were obtained from EPAQ2 and combined sensing and compared. Complete data were available in 1689 participants (52% women. RESULTS: EPAQ2 estimates of PAEE and MVPA were higher than objective estimates and sedentary time and LPA estimates were lower [bias (95% limits of agreement in men and women were 32.3 (-61.5 to 122.6 and 29.0 (-39.2 to 94.6 kJ/kg/day for PAEE; -4.6 (-10.6 to 1.3 and -6.0 (-10.9 to -1.0 h/day for sedentary time; -171.8 (-454.5 to 110.8 and -60.4 (-367.5 to 246.6 min/day for LPA; 91.1 (-159.5 to 341.8 and 55.4 (-117.2 to 228.0 min/day for MVPA]. There were significant positive correlations between all self-reported and objectively assessed PA subcomponents (rho= 0.12 to 0.36; the strongest were observed for MVPA (rho = 0.30 men; rho = 0.36 women and PAEE (rho = 0.26 men; rho = 0.25 women. CONCLUSION: EPAQ2 produces higher estimates of PAEE and MVPA and lower estimates of sedentary and LPA than objective assessment. However, both methodologies rank individuals similarly, suggesting that EPAQ2 may be used in etiological studies in this population.

  1. Urinary Elimination of Coproporphyrins Is Dependent on ABCC2 Polymorphisms and Represents a Potential Biomarker of MRP2 Activity in Humans

    Science.gov (United States)

    Benz-de Bretagne, Isabelle; Respaud, Renaud; Vourc'h, Patrick; Halimi, Jean-Michel; Caille, Agnès; Hulot, Jean-Sébastien; Andres, Christian R.; Le Guellec, Chantal

    2011-01-01

    MRP2 encoded by ABCC2 gene is involved in the secretion of numerous drugs and endogenous substrates. Patients with Dubin-Johnson syndrome due to mutation in ABCC2 gene have elevated urinary coproporphyrin ratio (UCP I/(I + III)). Here we investigated whether this ratio could serve as a biomarker of MRP2 function. Phenotype-genotype relationships were studied in 74 healthy subjects by measuring individual UCP I/(I + III) ratio obtained on 24-hour urine and by analyzing five common SNPs in ABCC2 gene. The UCP I/(I + III) ratio varied from 14.7% to 46.0% in our population. Subjects with 3972TT genotype had a higher ratio (P = .04) than those carrying the C allele. This higher UCP I/(I + III) ratio was correlated with a higher level of isomer I excretion. This study provides a proof of concept that UCP I/(I + III) ratio can be used as a biomarker of MRP2 function in clinical studies as it provides quantitative information about the in vivo activity of MRP2 in a given patient. PMID:21541183

  2. Urinary Elimination of Coproporphyrins Is Dependent on ABCC2 Polymorphisms and Represents a Potential Biomarker of MRP2 Activity in Humans

    Directory of Open Access Journals (Sweden)

    Isabelle Benz-de Bretagne

    2011-01-01

    Full Text Available MRP2 encoded by ABCC2 gene is involved in the secretion of numerous drugs and endogenous substrates. Patients with Dubin-Johnson syndrome due to mutation in ABCC2 gene have elevated urinary coproporphyrin ratio (UCP I/(I + III. Here we investigated whether this ratio could serve as a biomarker of MRP2 function. Phenotype-genotype relationships were studied in 74 healthy subjects by measuring individual UCP I/(I + III ratio obtained on 24-hour urine and by analyzing five common SNPs in ABCC2 gene. The UCP I/(I + III ratio varied from 14.7% to 46.0% in our population. Subjects with 3972TT genotype had a higher ratio (=.04 than those carrying the C allele. This higher UCP I/(I + III ratio was correlated with a higher level of isomer I excretion. This study provides a proof of concept that UCP I/(I + III ratio can be used as a biomarker of MRP2 function in clinical studies as it provides quantitative information about the in vivo activity of MRP2 in a given patient.

  3. Reductive activation with cysteine represents a chromium(III)-dependent pathway in the induction of genotoxicity by carcinogenic chromium(VI).

    Science.gov (United States)

    Zhitkovich, Anatoly; Quievryn, George; Messer, Joseph; Motylevich, Zhanna

    2002-10-01

    Induction of DNA damage by carcinogenic hexavalent chromium compounds [Cr(VI)] results from its reduction to lower oxidation states. Reductive metabolism of Cr(VI) generates intermediate Cr(V/IV)species, organic radicals, and finally Cr(III), which forms stable complexes with many biological ligands, including DNA. To determine the biological significance of different reaction products, we examined genotoxic responses and the formation of DNA damage during reduction of Cr(VI) by its biological reducer, cysteine. We have found that cysteine-dependent activation of Cr(VI) led to the formation of Cr-DNA and cysteine-Cr-DNA adducts as well as interstrand DNA cross-links. The yield of binary and ternary DNA adducts was relatively constant at different concentrations of Cr(VI) and averaged approximately 54 and 45%, respectively. Interstrand DNA cross-links accounted on average for 1% of adducts, and their yield was even less significant at low Cr(VI) concentrations. Reduction of Cr(VI) in several commonly used buffers did not induce detectable damage to the sugar-phosphate backbone of DNA. Replication of Cr(VI)-modified plasmids in intact human fibroblasts has shown that cysteine-dependent metabolism of Cr(VI) resulted in the formation of mutagenic and replication-blocking DNA lesions. Selective elimination of Cr-DNA adducts from Cr(VI)-treated plasmids abolished all genotoxic responses, indicating that nonoxidative, Cr(III)-dependent reactions were responsible for the induction of both mutagenicity and replication blockage by Cr(VI). The demonstration of the mutagenic potential of Cr-DNA adducts suggests that these lesions can be explored in the development of specific and mechanistically important biomarkers of exposure to toxic forms of Cr.

  4. Representing and Performing Businesses

    DEFF Research Database (Denmark)

    Boll, Karen

    2014-01-01

    This article investigates a segmentation model used by the Danish Tax and Customs Administration to classify businesses’ motivational postures. The article uses two different conceptualisations of performativity to analyse what the model’s segmentations do: Hacking’s notion of making up people...... and MacKenzie’s idea of performativity. Based on these two approaches, the article demonstrates that the segmentation model represents and performs the businesses as it makes up certain new ways to be a business and as the businesses can be seen as moving targets. Inspired by MacKenzie the argument...... around it is in motion and can be shaped, however, it sees itself as stable. This assumption turns out to be problematic as the tax administration questions the model’s ability to produce valid comparisons. The article presents a detailed analysis of the model’s performativity, providing an example...

  5. Paroxetine, a cytochrome P450 2D6 inhibitor, diminishes the stereoselective O-demethylation and reduces the hypoalgesic effect of tramadol

    DEFF Research Database (Denmark)

    Laugesen, S; Enggaard, T P; Pedersen, R S;

    2005-01-01

    OBJECTIVE: Tramadol hydrochloride (INN, tramadol) exerts its antinociceptive action through a monoaminergic effect mediated by the parent compound and an opioid effect mediated mainly by the O-demethylated metabolite (+)-M1. O-demethylation is catalyzed by cytochrome P450 (CYP) 2D6. Paroxetine...... is a very potent inhibitor of CYP2D6. The objective of this study was to investigate the influence of paroxetine pretreatment on the biotransformation and the hypoalgesic effect of tramadol. METHODS: With and without paroxetine pretreatment (20 mg daily for 3 consecutive days), the formation of M1...... and the analgesic effect of 150 mg of tramadol were studied in 16 healthy extensive metabolizers of sparteine in a randomized, double-blind, placebo-controlled, 4-way crossover study by use of experimental pain models. RESULTS: With paroxetine pretreatment, the area under the plasma concentration-time curve (AUC...

  6. Induction of flowering by 5-azacytidine in some plant species: relationship between the stability of photoperiodically induced flowering and flower-inducing effect of DNA demethylation.

    Science.gov (United States)

    Kondo, Hiroshi; Miura, Takashi; Wada, Kaede C; Takeno, Kiyotoshi

    2007-11-01

    The flower-inducing effect of 5-azacytidine, a DNA demethylating reagent, was examined in several plant species with a stable or unstable photoperiodically induced flowering state under non-inductive photoperiodic conditions. The long day plant Silene armeria, whose flowering state is stable and the short day plant Pharbitis nil, whose flowering state is unstable were induced to flower by 5-azacytidine under a non-inductive condition. Thus, the replacement of photoinduction by 5-azacytidine treatment is not specific to Perilla frutescens. On the other hand, 5-azacytidine did not induce flowering in Xanthium strumarium whose flowering state is stable and Lemna paucicostata whose flowering state is unstable. Thus, epigenetics caused by DNA demethylation may be involved in the regulation of photoperiodic flowering irrespective of the stability of the photoperiodically induced flowering state. PMID:18251884

  7. Catalytic Mechanism of the Oxidative Demethylation of 4-(Methoxymethyl)phenol by Vanillyl-Alcohol Oxidase. Evidence for Formation of a p-Quinone Methide Intermediate

    OpenAIRE

    Fraaije, Marco W.; van Berkel, Willem J H

    1997-01-01

    The catalytic mechanism for the oxidative demethylation of 4-(methoxymethyl)phenol by the covalent flavoprotein vanillyl-alcohol oxidase was studied. Using H218O, it was found that the carbonylic oxygen atom from the product 4-hydroxybenzaldehyde originates from a water molecule. Oxidation of vanillyl alcohol did not result in any incorporation of 18O. Enzyme-monitored turnover experiments revealed that for both substrates a process involving flavin reduction is rate determining. During anaer...

  8. Mercury methylation and demethylation by periphyton biofilms and their host in a fluvial wetland of the St. Lawrence River (QC, Canada)

    Energy Technology Data Exchange (ETDEWEB)

    Hamelin, Stéphanie; Planas, Dolors [GRIL, Département de sciences biologiques, Université du Québec à Montréal, C.P. 8888, Succursale Centre-Ville, Montreal, Quebec H3C 3P8 (Canada); Amyot, Marc [GRIL, Département de sciences biologiques, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montréal, Quebec H3C 3J7 (Canada)

    2015-04-15

    Wetlands in large rivers are important sites of production of the neurotoxin methylmercury (MeHg), and the periphyton growing on wetland macrophytes are increasingly recognized as key players in this production and transfer in food webs. Information is lacking about mercury methylation (K{sub m}) and demethylation (K{sub d}) rates in periphytic biofilms from the Northern Hemisphere, as well as about the drivers of net MeHg production, hampering ecosystem modeling of Hg cycling. Mercury methylation and demethylation rates were measured in periphytic biofilms growing on submerged plants in a shallow fluvial lake located in a temperate cold region (St. Lawrence River, Quebec, Canada). Incubations were performed in situ within macrophyte beds using low-level spikes of {sup 199}HgO and Me{sup 200}Hg stable isotopes as tracers. A direct relationship was observed between K{sub m} (0.002 to 0.137 d{sup −1}) and [MeHg] in periphyton. A similar relationship was found between K{sub d} (0.096 to 0.334 d{sup −1}) and [inorganic Hg]. Periphyton of Lake St. Pierre reached high levels of net MeHg production that were two orders of magnitude higher than those found in local sediment. This production varied through the plant growing season and was mainly driven by environmental variables such as depth of growth, available light, dissolved oxygen, temperature, plant community structure, and productivity of the habitat. - Highlights: • Periphyton Hg methylation and demethylation were studied in a large fluvial lake. • Addition of stable Hg isotopes was used to obtain in situ rates for these processes. • Net methylation was higher in periphyton than in local sediments. • Methylation and demethylation rates fluctuated during the summer. • Key drivers of rates were depth, light, temperature, and community structure.

  9. Mercury methylation and demethylation by periphyton biofilms and their host in a fluvial wetland of the St. Lawrence River (QC, Canada)

    International Nuclear Information System (INIS)

    Wetlands in large rivers are important sites of production of the neurotoxin methylmercury (MeHg), and the periphyton growing on wetland macrophytes are increasingly recognized as key players in this production and transfer in food webs. Information is lacking about mercury methylation (Km) and demethylation (Kd) rates in periphytic biofilms from the Northern Hemisphere, as well as about the drivers of net MeHg production, hampering ecosystem modeling of Hg cycling. Mercury methylation and demethylation rates were measured in periphytic biofilms growing on submerged plants in a shallow fluvial lake located in a temperate cold region (St. Lawrence River, Quebec, Canada). Incubations were performed in situ within macrophyte beds using low-level spikes of 199HgO and Me200Hg stable isotopes as tracers. A direct relationship was observed between Km (0.002 to 0.137 d−1) and [MeHg] in periphyton. A similar relationship was found between Kd (0.096 to 0.334 d−1) and [inorganic Hg]. Periphyton of Lake St. Pierre reached high levels of net MeHg production that were two orders of magnitude higher than those found in local sediment. This production varied through the plant growing season and was mainly driven by environmental variables such as depth of growth, available light, dissolved oxygen, temperature, plant community structure, and productivity of the habitat. - Highlights: • Periphyton Hg methylation and demethylation were studied in a large fluvial lake. • Addition of stable Hg isotopes was used to obtain in situ rates for these processes. • Net methylation was higher in periphyton than in local sediments. • Methylation and demethylation rates fluctuated during the summer. • Key drivers of rates were depth, light, temperature, and community structure

  10. Overexpression of ShCYP51B and ShatrD in Sclerotinia homoeocarpa Isolates Exhibiting Practical Field Resistance to a Demethylation Inhibitor Fungicide

    OpenAIRE

    Hulvey, Jon; Popko, James T.; Sang, Hyunkyu; Berg, Andrew; Jung, Geunhwa

    2012-01-01

    We investigated genetic factors that govern the reduced propiconazole sensitivity of Sclerotinia homoeocarpa field isolates collected during a 2-year field efficacy study on dollar spot disease of turf in five New England sites. These isolates displayed a >50-fold range of in vitro sensitivity to a sterol demethylation inhibitor (DMI) fungicide, propiconazole, making them ideal for investigations of genetic mechanisms of reduced DMI sensitivity. The CYP51 gene homolog in S. homoeocarpa (ShCYP...

  11. Novel Substrate Specificity and Temperature-Sensitive Activity of Mycosphaerella graminicola CYP51 Supported by the Native NADPH Cytochrome P450 Reductase

    OpenAIRE

    Price, Claire L.; Warrilow, Andrew G. S.; Parker, Josie E.; Mullins, Jonathan G. L.; Nes, W. David; Kelly, Diane E.; Kelly, Steven L.

    2015-01-01

    Mycosphaerella graminicola (Zymoseptoria tritici) is an ascomycete filamentous fungus that causes Septoria leaf blotch in wheat crops. In Europe the most widely used fungicides for this major disease are demethylation inhibitors (DMIs). Their target is the essential sterol 14α-demethylase (CYP51), which requires cytochrome P450 reductase (CPR) as its redox partner for functional activity. The M. graminicola CPR (MgCPR) is able to catalyze the sterol 14α-demethylation of eburicol and lanostero...

  12. High salt promotes autoimmunity by TET2-induced DNA demethylation and driving the differentiation of Tfh cells.

    Science.gov (United States)

    Wu, Haijing; Huang, Xin; Qiu, Hong; Zhao, Ming; Liao, Wei; Yuan, Shuguang; Xie, Yubing; Dai, Yong; Chang, Christopher; Yoshimura, Akihiko; Lu, Qianjin

    2016-01-01

    Follicular helper T cells (Tfh) have been well documented to play a critical role in autoimmunity, such as systemic lupus erythematosus (SLE), by helping B cells. In this study, high salt (sodium chloride, NaCl), under physiological conditions, was demonstrated to increase the differentiation of Tfh. A high-salt diet markedly increased lupus features in MRL/lpr mice. The mechanism is NaCl-induced DNA demethylation via the recruitment of the hydroxytransferase Ten-Eleven Translocation 2 (TET2). Gene silencing of TET2 obviously diminished NaCl-induced Tfh cell polarization in vitro. In addition, the gene expression of sh2d1a, map3k1, spn and stat5b was enhanced after NaCl treatment, consistent with the findings in lupus CD4(+)T cells. However, only spn was directly regulated by TET2, and spn was not the sole target for NaCl. Our findings not only explain the epigenetic mechanisms of high-salt induced autoimmunity but also provide an attractive molecular target for intervention strategies of patients. PMID:27325182

  13. Epigenetic regulations in the IFNγ signalling pathway: IFNγ-mediated MHC class I upregulation on tumour cells is associated with DNA demethylation of antigen-presenting machinery genes.

    Science.gov (United States)

    Vlková, Veronika; Štěpánek, Ivan; Hrušková, Veronika; Šenigl, Filip; Mayerová, Veronika; Šrámek, Martin; Šímová, Jana; Bieblová, Jana; Indrová, Marie; Hejhal, Tomáš; Dérian, Nicolas; Klatzmann, David; Six, Adrien; Reiniš, Milan

    2014-08-30

    Downregulation of MHC class I expression on tumour cells, a common mechanism by which tumour cells can escape from specific immune responses, can be associated with coordinated silencing of antigen-presenting machinery genes. The expression of these genes can be restored by IFNγ. In this study we documented association of DNA demethylation of selected antigen-presenting machinery genes located in the MHC genomic locus (TAP-1, TAP-2, LMP-2, LMP-7) upon IFNγ treatment with MHC class I upregulation on tumour cells in several MHC class I-deficient murine tumour cell lines (TC-1/A9, TRAMP-C2, MK16 and MC15). Our data also documented higher methylation levels in these genes in TC-1/A9 cells, as compared to their parental MHC class I-positive TC-1 cells. IFNγ-mediated DNA demethylation was relatively fast in comparison with demethylation induced by DNA methyltransferase inhibitor 5-azacytidine, and associated with increased histone H3 acetylation in the promoter regions of APM genes. Comparative transcriptome analysis in distinct MHC class I-deficient cell lines upon their treatment with either IFNγ or epigenetic agents revealed that a set of genes, significantly enriched for the antigen presentation pathway, was regulated in the same manner. Our data demonstrate that IFNγ acts as an epigenetic modifier when upregulating the expression of antigen-presenting machinery genes.

  14. Influence of Decitabine on Demethylation of P15INK4B Gene and the Growth and Apoptosis of Burkitt Lymphoma Raji Cells

    Directory of Open Access Journals (Sweden)

    LIU Qiao

    2014-12-01

    Full Text Available Objective: To explore the methylation status of P15INK4B gene and the biochemical influence of decitabine on the demethylation of P15INK4B gene and the growth and apoptosis of Burkitt lymphoma Raji cells. Methods: Trypan blue was used to test the effects of different concentrations of decitabine on cell growth curve of Burkitt lymphoma Rajj cells. Cell apoptostic rate was detected by flow cytometry (FCM. The expression of P15INK4B gene was detected by reverse transcription-polymerase chain reaction (RT-PCR and the degree of methylation of P15INK4B gene by methylation-specific PCR (MSP. Results: Different concentrations of decitabine had an inhibiting effect on the proliferation of Raji cells, and promote the apoptosis of Raji cells. After 48-h treatment of decitabine, the mRNA expression of P15INK4B gene of Raji cells was up-regulated in a dose-dependent manner by inducing the demethylation of P15INK4B gene. . Conclusion: There exists hypermethylated P15INK4B gene in Burkitt lymphoma Raji cells which makes P15INK4B gene down-regulated. However, decitabine can up-regulate the mRNA expression of P15INK4B gene through inducing the demethylation of P15INK4B gene, thus inhibiting the proliferation of lymphoma Raji cells.

  15. Representative offices of foreign companies in Romania

    OpenAIRE

    Mihail ANTONESCU; Ligia ANTONESCU

    2015-01-01

    In order to promote commercial interests in Romania, foreign companies and economic organizations can establish a representative office in Romania. Representative companies and foreign economic organizations operate in Romania under an authorization procedure established by the Ministry of Economy, Trade and Tourism. These institutions unfold activities on behalf of the companies they represent, often having an intermediary role between foreign companies and partners in Romania.

  16. Determination of total and organic mercury and evaluation of methylation and demethylation processes in sediments of the Rio Grande Reservoir, State of Sao Paulo, Brazil

    International Nuclear Information System (INIS)

    The Rio Grande reservoir is located in the metropolitan area of Sao Paulo and it is a very important water supply for this region. In the present study bottom waters and sediment samples collected in this reservoir, in four sampling points, in four campaigns, from September 2008 to January 2010, were analyzed. Firstly total Hg was determined in sediment and bottom waters by cold vapor atomic absorption technique (CV AAS). Following, the analytical methodology for organic Hg was adapted from literature, where the organomercurial compounds were extracted with dichloromethane in acid medium and subsequent destruction of organic compounds by bromine chloride. The validation of this methodology, in terms of precision and accuracy, was performed by means of IAEA 405 and BCR-CRM 580 reference materials analyses. For methylation and demethylation processes evaluation in this environment, the following physical and chemical parameters were assessed, in situ: pH, water temperature, redox potential (EH), transparency and depth. For the sediment samples, granulometry, total organic carbon, sulphate-reducing bacteria, total N and P, besides the metals Co, Cu, Fe and Mn were evaluated. The selection of these parameters was related to the factors that influence the behavior of MeHg in the sediments and its transition zone. Total Hg ranging from 1.0 to 71.0 mg kg'-1 and organic mercury from -1 in sediments and methylation rates from 0.06 to 1.4% were found, along the reservoir. Different methylation conditions along the reservoir and its influences were also discussed. As supplementary study the concentration of some metals and trace elements in the sediments by neutron activation analysis technique was determined. As, Ba, Br, Co, Cr, Cs, Hf, Fe, Na, Rb, Sb, Sc and Zn and rare earth elements Ce, Eu, La, Lu, Nd, Sm and Yb were determined. The enrichment factor in relation to earth crust values using Sc as normalizer element reached values higher than 2.0 for the elements As, Br, Sb

  17. Silencing HO-1 sensitizes SKM-1 cells to apoptosis induced by low concentration 5-azacytidine through enhancing p16 demethylation.

    Science.gov (United States)

    Wang, Ping; Ma, Dan; Wang, Jishi; Fang, Qin; Gao, Rui; Wu, Weibing; Lu, Tangsheng; Cao, Lu

    2015-03-01

    Heme oxygenase-1 was reported previously as a resistance target on acute myelocytic leukemia (AML). We found that HO-1 was resistant to 5-azacytidine (AZA) treatment of myelodysplastic syndrome (MDS), and explored further the relative mechanisms. Patient bone marrow mononuclear cells (n=48) diagnosed as different levels of MDS were collected. Cell growth was evaluated by MTT assay; cell cycle and apoptosis were detected by flow cytometry; mRNA expression was assessed by real-time PCR, protein expression was analyzed through western blotting. Methylation was assessed by MSP. The survival time, and weight of mice were recorded. HO-1 overexpression was observed in SKM-1 cells after AZA treatment comparing to other cell lines. The HO-1 expression in MDS patients with high-risk was higher than in low-risk patients. After HO-1 was silenced by lentivirus-mediated siRNA, the proliferation of SKM-1 cells was effectively inhibited by low concentration AZA, and the cell cycle was arrested in the G0/G1 phase. Upregulation of p16 and changing of p16-relative cell cycle protein was observed after silencing HO-1 in AZA treated SKM-1 cells. In addition, DNMT1 was downregulated following the decrease of HO-1 expression. In vivo, silencing HO-1 inhibited SKM-1 cell growth induced by AZA in a NOD/SCID mouse model. Silencing HO-1 sensitized SKM-1 cells toward AZA, which may be attributed to the influence of HO-1 on AZA-induced p16 demethylation. HO-1 may be one of the targets that enhance the therapeutic effects of AZA on MDS malignant transformation inspiring new treatment methods for high-risk and very high-risk MDS patients in clinical practice. PMID:25585641

  18. Demethylation of miR-9-3 and miR-193a Genes Suppresses Proliferation and Promotes Apoptosis in Non-Small Cell Lung Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Jinliang Wang

    2013-12-01

    Full Text Available Background: MicroRNAs miR-9-3 and miR-193a have recently been found to be hypermethylated in a variety of non-small cell lung cancer (NSCLC cells and primary human tumors. The objectives of this study were to investigate the role of demethylation of miR-9-3 and miR-193a genes in regulating proliferation and apoptosis in NSCLCs, and to decipher the potential mechanisms underlying the properties. Methods: MTT and population doubling time by flow cytometry were used to assess cell proliferation. Enzyme-Linked Immunosorbent Assay and caspase-3 activity assay were employed to evaluate apoptosis. Real-time RT-PCR and Western blot were used to quantify gene expression at mRNA and protein levels, respectively. Methylation-specific PCR was utilized to assess methylation status. Results: We found that demethylation agent 5-Aza-2'-deoxycytidine (5-AzaC reduced cell numbers and prolonged population doubling time (PDT, and promoted doxorubicin-induced apoptosis in seven NSCLC cell lines with different methylation statuses on miR-9-3 and miR-193a promoter regions: NCI-H1993/NCI-H1915 (miR-9-3+/miR-193a+, NCI-H1975/NCI-H200 (miR-9-3+/miR-193a-, A427/NCI-H2073 (miR-9-3-/miR-193a+, and NCI-H1703 (miR-9-3-/miR-193a-. Treatment with 5-AzaC concomitantly upregulated expression of miR-9-3 and miR-193a, and downregulated their respective target genes NF-κB and Mcl-1. The effects of 5-AzaC were abolished by concomitant knockdown of miR-9-3 and miR-193a using the complex antisense technique, whereas forced ectopic expression of miR-9-3 and miR-193a mimicked the effects of 5-AzaC. We further observed that the strength of proliferation inhibition and apoptosis promotion elicited by 5-AzaC was in the order of NCI-H1993/NCI-H1915 > A427/NCI-H2073 > NCI-H1975/NCI-H200 > NCI-H1703. Conclusions: Methylation-silencing of miR-9-3 and miR-193a may be an important epigenetic mechanisms favoring NSCLC cell growth and survival for carcinogenesis and cancer progression, and

  19. The accumulation of DNA demethylation in Sat α in normal gastric tissues with Helicobacter pylori infection renders susceptibility to gastric cancer in some individuals.

    Science.gov (United States)

    Saito, Masaaki; Suzuki, Koichi; Maeda, Takafumi; Kato, Takaharu; Kamiyama, Hidenori; Koizumi, Kei; Miyaki, Yuichiro; Okada, Shinichiro; Kiyozaki, Hirokazu; Konishi, Fumio

    2012-06-01

    Helicobacter pylori (HP) infection is widely recognized as a risk factor for gastric cancer, but only a minority of infected individuals develop gastric cancer. The aim of this study was to determine whether DNA demethylation in non-cancerous gastric mucosa (NGM) significantly enhances susceptibility to gastric cancer. A total of 165 healthy volunteers, including 83 HP-positive and 82-negative individuals, as well as 83 patients with single and 18 with synchronous double gastric cancer (GC) were enrolled in this study. The relative demethylation levels (RDLs) of repetitive sequences, including Alu, LINE-1 and Sat α, were quantified by real-time methylation-specific polymerase chain reaction. The Alu RDL did not exhibit any differences within each respective group, whereas LINE-1 RDL was significantly elevated in cancer tissues compared with the NGM in the other groups (P<0.001). Our results indicated that a gradual increase in Sat α RDL correlated with HP infection and cancer development. Sat α RDL was significantly elevated in the NGM in HP-positive compared with HP-negative (P<0.001), and significantly elevated in cancer tissues (P<0.001). Although the Sat α RDL of the NGM in the total population increased in an age-dependent manner, it was significantly increased in a fraction of younger GC patients (<45 years) compared with all of the others (45 years or older, P=0.0391). In addition, double GC exhibited a significantly higher Sat α RDL in the NGM compared with single GC (P=0.0014). In these two fractions, Sat α RDL in the NGM exhibited an inverse correlation with age. In conclusion, the present study demonstrated that the accumulation of DNA demethylation in Sat α RDL in the NGM with HP infection potentially renders susceptibility to gastric cancer in a fraction of GC patients younger than 45 years or in patients with multiple cancers. PMID:22426602

  20. Modulation by decitabine of gene expression and growth of osteosarcoma U2OS cells in vitro and in xenografts: Identification of apoptotic genes as targets for demethylation

    Directory of Open Access Journals (Sweden)

    Xue Hui

    2007-09-01

    Full Text Available Abstract Background Methylation-mediated silencing of genes is one epigenetic mechanism implicated in cancer. Studies regarding the role of modulation of gene expression utilizing inhibitors of DNA methylation, such as decitabine, in osteosarcoma (OS have been limited. A biological understanding of the overall effects of decitabine in OS is important because this particular agent is currently undergoing clinical trials. The objective of this study was to measure the response of the OS cell line, U2OS, to decitabine treatment both in vitro and in vivo. Results Microarray expression profiling was used to distinguish decitabine-dependent changes in gene expression in U2OS cells, and to identify responsive loci with demethylated CpG promoter regions. U2OS xenografts were established under the sub-renal capsule of immune-deficient mice to study the effect of decitabine in vivo on tumor growth and differentiation. Reduced nuclear methylation levels could be detected in xenografts derived from treated mice by immunohistochemistry utilizing a 5-methylcytidine antibody. Decitabine treatment reduced tumor xenograft size significantly (p in vitro (p GADD45A, HSPA9B, PAWR, PDCD5, NFKBIA, and TNFAIP3 were also induced to ≥2-fold in vivo. Quantitative methylation pyrosequencing confirmed that the tested pro-apoptotic genes had CpG-island DNA demethylationas a result of U2OS decitabine treatment both in vitro and in xenografts Conclusion These data provide new insights regarding the use of epigenetic modifiers in OS, and have important implications for therapeutic trials involving demethylation drugs. Collectively, these data have provided biological evidence that one mode of action of decitabine may be the induction of apoptosis utilizing promoter-CpG demethylation of specific effectors in cell death pathways in OS.

  1. Representative Ensembles in Statistical Mechanics

    OpenAIRE

    V. I. YUKALOV

    2007-01-01

    The notion of representative statistical ensembles, correctly representing statistical systems, is strictly formulated. This notion allows for a proper description of statistical systems, avoiding inconsistencies in theory. As an illustration, a Bose-condensed system is considered. It is shown that a self-consistent treatment of the latter, using a representative ensemble, always yields a conserving and gapless theory.

  2. A Simple, Rapid and Mild One Pot Synthesis of Benzene Ring Acylated and Demethylated Analogues of Harmine under Solvent-free Conditions

    OpenAIRE

    Siddiqui, Bina S.; Syed Imran Hassan; Farhat Farhat; Syed Nawazish Ali; Sabira Begum

    2008-01-01

    A simple, rapid, solvent-free, room temperature one pot synthesis of benzene ring acylated and demethylated analogues of harmine using acyl halides/acid anhydrides and AlCl3 has been developed. Eight different acyl halides/acid anhydrides were used in the synthesis. The resulting mixture of products was separated by column chromatography to afford 10- and 12-monoacyl analogues, along with 10,12-diacyl-11-hydroxy products. In five cases the corresponding 10-acyl-11-hydroxy analogues were also ...

  3. A Simple, Rapid and Mild One Pot Synthesis of Benzene Ring Acylated and Demethylated Analogues of Harmine under Solvent-free Conditions

    Directory of Open Access Journals (Sweden)

    Bina S. Siddiqui

    2008-08-01

    Full Text Available A simple, rapid, solvent-free, room temperature one pot synthesis of benzene ring acylated and demethylated analogues of harmine using acyl halides/acid anhydrides and AlCl3 has been developed. Eight different acyl halides/acid anhydrides were used in the synthesis. The resulting mixture of products was separated by column chromatography to afford 10- and 12-monoacyl analogues, along with 10,12-diacyl-11-hydroxy products. In five cases the corresponding 10-acyl-11-hydroxy analogues were also obtained. Yields from the eight syntheses (29 products in total were in the 6-34% range and all compounds were fully characterized.

  4. Orchard factors associated with resistance and cross resistance to sterol demethylation inhibitor fungicides in populations of Venturia inaequalis from Pennsylvania.

    Science.gov (United States)

    Pfeufer, Emily E; Ngugi, Henry K

    2012-03-01

    Orchard management practices, such as destroying of overwintered inoculum and limiting the number of fungicide applications, are often recommended as tactics for slowing the development of resistance to sterol demethylation-inhibitor (DMI) fungicides in populations of Venturia inaequalis. However, there is little quantitative evidence relating the use of such practices to levels of resistance in orchards. The aim of this study was to evaluate the sensitivity of V. inaequalis isolates from Pennsylvania to DMI fungicides, and to identify orchard management factors related to the incidence of resistant isolates. In total, 644 single-spore V. inaequalis cultures obtained from 20 apple orchards in 2008 or 2009 were tested for sensitivity to myclobutanil, fenbuconazole, or difenoconazole. Growers provided management history of the sampled plots. Widespread shifts toward resistance to the three fungicides were noted, with mean effective concentration for 50% inhibition (EC(50)) values of 2.136, 0.786, and 0.187 μg/ml for myclobutanil, fenbuconazole, and difenoconazole, respectively. Cross resistance to the three fungicides was documented in high correlation (Spearman's r > 0.6) between mean EC(50) values for 14 orchards. Based on a 0.5-μg/ml threshold, 66 and 26% of isolates were resistant to myclobutanil and fenbuconazole, respectively, and 22% were cross resistant to the two fungicides. A significant between-year shift toward increased resistance was noted in two of three orchards surveyed in both years. Failure to use dormant copper sprays, older trees, larger orchards, orchards with ≤10 cultivars, and application of >4 DMI sprays were positively correlated (0.0001 resistant isolates. Isolates from orchards with >4 DMI sprays were four times as likely to be resistant to fenbuconazole (odds ratio = 4.57; P = 0.015). Isolates from orchards without dormant copper sprays were twice as likely to be cross-shifted toward resistance to all three fungicides (odds ratio = 1

  5. Structure of the first representative of Pfam family PF04016 (DUF364) reveals enolase and Rossmann-like folds that combine to form a unique active site with a possible role in heavy-metal chelation

    International Nuclear Information System (INIS)

    The crystal structure of the first representative of DUF364 family reveals a combination of enolase N-terminal-like and C-terminal Rossmann-like folds. Analysis of the interdomain cleft combined with sequence and genome context conservation among homologs, suggests a unique catalytic site likely involved in the synthesis of a flavin or pterin derivative. The crystal structure of Dhaf4260 from Desulfitobacterium hafniense DCB-2 was determined by single-wavelength anomalous diffraction (SAD) to a resolution of 2.01 Å using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). This protein structure is the first representative of the PF04016 (DUF364) Pfam family and reveals a novel combination of two well known domains (an enolase N-terminal-like fold followed by a Rossmann-like domain). Structural and bioinformatic analyses reveal partial similarities to Rossmann-like methyltransferases, with residues from the enolase-like fold combining to form a unique active site that is likely to be involved in the condensation or hydrolysis of molecules implicated in the synthesis of flavins, pterins or other siderophores. The genome context of Dhaf4260 and homologs additionally supports a role in heavy-metal chelation

  6. The applicability of activities in kinetic expressions : A more fundamental approach to represent the kinetics of the systemCO2–OH−–salt in terms of activities

    NARCIS (Netherlands)

    Haubrock, J.; Hogendoorn, J.A.; Versteeg, G.F.

    2007-01-01

    The applicability of utilizing activities instead of concentrations in kinetic expressions has been investigated using the reaction of CO2 in sodium hydroxide solutions also containing different neutral salts (LiCl, KCl and NaCl) as model system. For hydroxide systems it is known that when the react

  7. Demethylation of Cancer/Testis Antigens and CpG ODN Stimulation Enhance Dendritic Cell and Cytotoxic T Lymphocyte Function in a Mouse Mammary Model

    Directory of Open Access Journals (Sweden)

    Jun-Zhong Sun

    2013-01-01

    Full Text Available Background. Cancer/testis antigens (CTAs are ideal targets for cancer immunotherapy in virtue of their restricted expression profile in normal tissues. However, CTA-targeted immunotherapy has been rather disappointing clinical setting for CTAs are downregulated by cytosine-phosphate-guanosine (CpG methylation in their promoter regions, so that tumor cells have low immunogenicity. Methods. We reinduced mouse CTA P1A through demethylation process and generated P1A-specific cytotoxic lymphocytes (CTLs by immunizing BALB/c (H-2d mice with dendritic cells pulsed with a P1A-specific peptide and CpG oligodeoxynucleotide (ODN immune adjuvant. Results. We found that demethylation and CpG ODN immune adjuvant stimulation facilitated DC maturation and enhanced the allogenic capacity of P1A-specific CTLs against target cells both in vitro and in vivo. Conclusions. Our results suggested that CTA induction and immune adjuvant stimulation is a feasible strategy in cancer immunotherapy.

  8. Analysis of the machinery and intermediates of the 5hmC-mediated DNA demethylation pathway in aging on samples from the MARK-AGE Study

    Science.gov (United States)

    Valentini, Elisabetta; Zampieri, Michele; Malavolta, Marco; Bacalini, Maria Giulia; Calabrese, Roberta; Guastafierro, Tiziana; Reale, Anna; Franceschi, Claudio; Hervonen, Antti; Koller, Bernhard; Bernhardt, Jürgen; Slagboom, P. Eline; Toussaint, Olivier; Sikora, Ewa; Gonos, Efstathios S.; Breusing, Nicolle; Grune, Tilman; Jansen, Eugène; Dollé, Martijn E.T.; Moreno-Villanueva, María; Sindlinger, Thilo; Bürkle, Alexander; Ciccarone, Fabio; Caiafa, Paola

    2016-01-01

    Gradual changes in the DNA methylation landscape occur throughout aging virtually in all human tissues. A widespread reduction of 5-methylcytosine (5mC), associated with highly reproducible site-specific hypermethylation, characterizes the genome in aging. Therefore, an equilibrium seems to exist between general and directional deregulating events concerning DNA methylation controllers, which may underpin the age-related epigenetic changes. In this context, 5mC-hydroxylases (TET enzymes) are new potential players. In fact, TETs catalyze the stepwise oxidation of 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), driving the DNA demethylation process based on thymine DNA glycosylase (TDG)-mediated DNA repair pathway. The present paper reports the expression of DNA hydroxymethylation components, the levels of 5hmC and of its derivatives in peripheral blood mononuclear cells of age-stratified donors recruited in several European countries in the context of the EU Project ‘MARK-AGE’. The results provide evidence for an age-related decline of TET1, TET3 and TDG gene expression along with a decrease of 5hmC and an accumulation of 5caC. These associations were independent of confounding variables, including recruitment center, gender and leukocyte composition. The observed impairment of 5hmC-mediated DNA demethylation pathway in blood cells may lead to aberrant transcriptional programs in the elderly. PMID:27587280

  9. Decitabine-Induced Demethylation of 5′ CpG Island in GADD45A Leads to Apoptosis in Osteosarcoma Cells

    Directory of Open Access Journals (Sweden)

    Khaldoun Al-Romaih

    2008-05-01

    Full Text Available GADD45 genes are epigenetically inactivated in various types of cancer and tumor cell lines. To date, defects of the GADD45 gene family have not been implicated in osteosarcoma (OS oncogenesis, and the role of this pathway in regulating apoptosis in this tumor is unknown. The therapeutic potential of Gadd45 in OS emerged when our previous studies showed that GADD45A was reexpressed by treatment with the demethylation drug decitabine. In this study, we analyze the OS cell lines MG63 and U2OS and show that on treatment with decitabine, a significant loss of DNA methylation of GADD45A was associated with elevated expression and induction of apoptosis. In vivo affects of decitabine treatment in mice showed that untreated control xenografts exhibited low nuclear staining for Gadd45a protein, whereas the nuclei from xenografts in decitabine-treated mice exhibited increased amounts of protein and elevated apoptosis. To show the specificity of this gene for decitabine-induced apoptosis in OS, GADD45A mRNAs were disrupted using short interference RNA, and the ability of the drug to induce apoptosis was reduced. Understanding the role of demethylation of GADD45A in reexpression of this pathway and restoration of apoptotic control is important for understanding OS oncogenesis and for more targeted therapeutic approaches.

  10. Antibacterial and antifungal activity of liriodenine and related oxoaporphine alkaloids.

    Science.gov (United States)

    Hufford, C D; Sharma, A S; Oguntimein, B O

    1980-10-01

    Liriodenine was evaluated for its antibacterial and antifungal activity against several microorganisms. Other related oxoaporphine alkaloids also were evaluated. Attempts to prepare oxoaporphine alkaloids from N-acetylnoraporphines were unsuccessful, but an unexpected phenanthrene alkaloid was obtained. A novel N-demethylation reaction was noted when oxogaucine methiodide and liriodenine methiodide were treated with alumina. PMID:7420287

  11. Representative process sampling - in practice

    DEFF Research Database (Denmark)

    Esbensen, Kim; Friis-Pedersen, Hans Henrik; Julius, Lars Petersen;

    2007-01-01

    Didactic data sets representing a range of real-world processes are used to illustrate "how to do" representative process sampling and process characterisation. The selected process data lead to diverse variogram expressions with different systematics (no range vs. important ranges; trends and...

  12. Genome-wide methylation and expression profiling identifies promoter characteristics affecting demethylation-induced gene up-regulation in melanoma

    Directory of Open Access Journals (Sweden)

    Halaban Ruth

    2010-02-01

    Full Text Available Abstract Background Abberant DNA methylation at CpG dinucleotides represents a common mechanism of transcriptional silencing in cancer. Since CpG methylation is a reversible event, tumor supressor genes that have undergone silencing through this mechanism represent promising targets for epigenetically active anti-cancer therapy. The cytosine analog 5-aza-2'-deoxycytidine (decitabine induces genomic hypomethylation by inhibiting DNA methyltransferase, and is an example of an epigenetic agent that is thought to act by up-regulating silenced genes. Methods It is unclear why decitabine causes some silenced loci to re-express, while others remain inactive. By applying data-mining techniques to large-scale datasets, we attempted to elucidate the qualities of promoter regions that define susceptibility to the drug's action. Our experimental data, derived from melanoma cell strains, consist of genome-wide gene expression data before and after treatment with decitabine, as well as genome-wide data on un-treated promoter methylation status, and validation of specific genes by bisulfite sequencing. Results We show that the combination of promoter CpG content and methylation level informs the ability of decitabine treatment to up-regulate gene expression. Promoters with high methylation levels and intermediate CpG content appear most susceptible to up-regulation by decitabine, whereas few of those highly methylated promoters with high CpG content are up-regulated. For promoters with low methylation levels, those with high CpG content are more likely to be up-regulated, whereas those with low CpG content are underrepresented among up-regulated genes. Conclusions Clinically, elucidating the patterns of action of decitabine could aid in predicting the likelihood of up-regulating epigenetically silenced tumor suppressor genes and others from pathways involved with tumor biology. As a first step toward an eventual translational application, we build a classifier

  13. Agrotourism-Representative Issues And Pro Arguments

    Directory of Open Access Journals (Sweden)

    Ramona Ciolac

    2016-05-01

    Full Text Available Many governments from European Union recognize the fact that agrotourism and rural tourism represents one way that can save the agriculture in that in the coming year’s rural tourism and agrotourism will become representative elements for rural area, the arguments of this representativity being the purpose of this paper. The rural area offers great opportunities for development of agrotourism, practicing of its being necessary in the current period. At the majority of rural settlements, the defining emblematic is multiple: the quality of landscape and warmth of the inhabitants, works of art and popular technique, traditional occupations, costumes, customs, traditions, cuisine, resources, etc. To these is added also the awareness, by small farmers, of the need to diversify agricultural activity, both in and outside the farm, by engaging in other activities, with non-agricultural character, from which agrotourism is one of the most circulated.

  14. Representing Learning With Graphical Models

    Science.gov (United States)

    Buntine, Wray L.; Lum, Henry, Jr. (Technical Monitor)

    1994-01-01

    Probabilistic graphical models are being used widely in artificial intelligence, for instance, in diagnosis and expert systems, as a unified qualitative and quantitative framework for representing and reasoning with probabilities and independencies. Their development and use spans several fields including artificial intelligence, decision theory and statistics, and provides an important bridge between these communities. This paper shows by way of example that these models can be extended to machine learning, neural networks and knowledge discovery by representing the notion of a sample on the graphical model. Not only does this allow a flexible variety of learning problems to be represented, it also provides the means for representing the goal of learning and opens the way for the automatic development of learning algorithms from specifications.

  15. Burnout in Customer Service Representatives

    OpenAIRE

    Tariq Jalees; Javed Zeeshan

    2008-01-01

    The purpose and aim of this research was to (1) identify the factors that contributes towards job burnout in sales service representative (2) What are the relationships of these factors (3) To empirically test the relationships of the determinants relating to burnout in customer service representatives. Based on literature survey six different variables related to burnout were identified. The variables were (1) Emotional exhaustion.(2) Reduced personal accomplishment.(3) Job induced tension.(...

  16. Marc Treib: Representing Landscape Architecture

    DEFF Research Database (Denmark)

    Braae, Ellen Marie

    2008-01-01

    The editor of Representing Landscape Architecture, Marc Treib, argues that there is good reason to evaluate the standard practices of representation that landscape architects have been using for so long. In the rush to the promised land of computer design these practices are now in danger of being...... left by the wayside. The 14 often both fitting and well crafted contributions of this publication offer an approach to how landscape architecture has been and is currently represented; in the design study, in presentation, in criticism, and in the creation of landscape architecture....

  17. Epigenetic reactivation of Nrf2 in murine prostate cancer TRAMP C1 cells by natural phytochemicals Z-ligustilide and Radix angelica sinensis via promoter CpG demethylation.

    Science.gov (United States)

    Su, Zheng-Yuan; Khor, Tin Oo; Shu, Limin; Lee, Jong Hun; Saw, Constance Lay-Lay; Wu, Tien-Yuan; Huang, Ying; Suh, Nanjoo; Yang, Chung S; Conney, Allan H; Wu, Qing; Kong, Ah-Ng Tony

    2013-03-18

    Cancer development has been linked to epigenetic modifications of cancer oncogenes and tumor suppressor genes; in advanced metastatic cancers, severe epigenetic modifications are present. We previously demonstrated that the progression of prostate tumors in TRAMP mice is associated with methylation silencing of the Nrf2 promoter and a reduced level of transcription of Nrf2 and Nrf2 target genes. Radix Angelicae Sinensis (RAS; Danggui) is a medicinal herb and health food supplement that has been widely used in Asia for centuries. Z-Ligustilide (Lig) is one of the bioactive components of RAS. We investigated the potential of Lig and RAS to restore Nrf2 gene expression through epigenetic modification in TRAMP C1 cells. Lig and RAS induced the mRNA and protein expression of endogenous Nrf2 and Nrf2 downstream target genes, such as HO-1, NQO1, and UGT1A1. Bisulfite genomic sequencing revealed that Lig and RAS treatment decreased the level of methylation of the first five CpGs of the Nrf2 promoter. A methylation DNA immunoprecipitation assay demonstrated that Lig and RAS significantly decreased the relative amount of methylated DNA in the Nrf2 gene promoter region. Lig and RAS also inhibited DNA methyltransferase activity in vitro. Collectively, these results suggest that Lig and RAS are able to demethylate the Nrf2 promoter CpGs, resulting in the re-expression of Nrf2 and Nrf2 target genes. Epigenetic modifications of genes, including Nrf2, may therefore contribute to the overall health benefits of RAS, including the anticancer effect of RAS and its bioactive component, Lig.

  18. Modulators of membrane drug transporters potentiate the activity of the DMI fungicide oxpoconazole against Botrytis cinerea

    NARCIS (Netherlands)

    Hayashi, K.; Schoonbeek, H.; Waard, de M.A.

    2003-01-01

    Modulators known to reduce multidrug resistance in tumour cells were tested for their potency to synergize the fungitoxic activity of the fungicide oxpoconazole, a sterol demethylation inhibitor (DMI), against Botrytis cinerea Pers. Chlorpromazine, a phenothiazine compound known as a calmodulin anta

  19. Representing culture in interstellar messages

    Science.gov (United States)

    Vakoch, Douglas A.

    2008-09-01

    As scholars involved with the Search for Extraterrestrial Intelligence (SETI) have contemplated how we might portray humankind in any messages sent to civilizations beyond Earth, one of the challenges they face is adequately representing the diversity of human cultures. For example, in a 2003 workshop in Paris sponsored by the SETI Institute, the International Academy of Astronautics (IAA) SETI Permanent Study Group, the International Society for the Arts, Sciences and Technology (ISAST), and the John Templeton Foundation, a varied group of artists, scientists, and scholars from the humanities considered how to encode notions of altruism in interstellar messages . Though the group represented 10 countries, most were from Europe and North America, leading to the group's recommendation that subsequent discussions on the topic should include more globally representative perspectives. As a result, the IAA Study Group on Interstellar Message Construction and the SETI Institute sponsored a follow-up workshop in Santa Fe, New Mexico, USA in February 2005. The Santa Fe workshop brought together scholars from a range of disciplines including anthropology, archaeology, chemistry, communication science, philosophy, and psychology. Participants included scholars familiar with interstellar message design as well as specialists in cross-cultural research who had participated in the Symposium on Altruism in Cross-cultural Perspective, held just prior to the workshop during the annual conference of the Society for Cross-cultural Research . The workshop included discussion of how cultural understandings of altruism can complement and critique the more biologically based models of altruism proposed for interstellar messages at the 2003 Paris workshop. This paper, written by the chair of both the Paris and Santa Fe workshops, will explore the challenges of communicating concepts of altruism that draw on both biological and cultural models.

  20. Representing objects, relations, and sequences.

    Science.gov (United States)

    Gallant, Stephen I; Okaywe, T Wendy

    2013-08-01

    Vector symbolic architectures (VSAs) are high-dimensional vector representations of objects (e.g., words, image parts), relations (e.g., sentence structures), and sequences for use with machine learning algorithms. They consist of a vector addition operator for representing a collection of unordered objects, a binding operator for associating groups of objects, and a methodology for encoding complex structures. We first develop constraints that machine learning imposes on VSAs; for example, similar structures must be represented by similar vectors. The constraints suggest that current VSAs should represent phrases ("The smart Brazilian girl") by binding sums of terms, in addition to simply binding the terms directly. We show that matrix multiplication can be used as the binding operator for a VSA, and that matrix elements can be chosen at random. A consequence for living systems is that binding is mathematically possible without the need to specify, in advance, precise neuron-to-neuron connection properties for large numbers of synapses. A VSA that incorporates these ideas, Matrix Binding of Additive Terms (MBAT), is described that satisfies all constraints. With respect to machine learning, for some types of problems appropriate VSA representations permit us to prove learnability rather than relying on simulations. We also propose dividing machine (and neural) learning and representation into three stages, with differing roles for learning in each stage. For neural modeling, we give representational reasons for nervous systems to have many recurrent connections, as well as for the importance of phrases in language processing. Sizing simulations and analyses suggest that VSAs in general, and MBAT in particular, are ready for real-world applications. PMID:23607563

  1. The DNA methylation profile of activated human natural killer cells.

    Science.gov (United States)

    Wiencke, John K; Butler, Rondi; Hsuang, George; Eliot, Melissa; Kim, Stephanie; Sepulveda, Manuel A; Siegel, Derick; Houseman, E Andres; Kelsey, Karl T

    2016-05-01

    Natural killer (NK) cells are now recognized to exhibit characteristics akin to cells of the adaptive immune system. The generation of adaptive memory is linked to epigenetic reprogramming including alterations in DNA methylation. The study herein found reproducible genome wide DNA methylation changes associated with human NK cell activation. Activation led predominately to CpG hypomethylation (81% of significant loci). Bioinformatics analysis confirmed that non-coding and gene-associated differentially methylated sites (DMS) are enriched for immune related functions (i.e., immune cell activation). Known DNA methylation-regulated immune loci were also identified in activated NK cells (e.g., TNFA, LTA, IL13, CSF2). Twenty-one loci were designated high priority and further investigated as potential markers of NK activation. BHLHE40 was identified as a viable candidate for which a droplet digital PCR assay for demethylation was developed. The assay revealed high demethylation in activated NK cells and low demethylation in naïve NK, T- and B-cells. We conclude the NK cell methylome is plastic with potential for remodeling. The differentially methylated region signature of activated NKs revealed similarities with T cell activation, but also provided unique biomarker candidates of NK activation, which could be useful in epigenome-wide association studies to interrogate the role of NK subtypes in global methylation changes associated with exposures and/or disease states. PMID:26967308

  2. Semantic Representatives of the Concept

    Directory of Open Access Journals (Sweden)

    Elena N. Tsay

    2013-01-01

    Full Text Available In the article concept as one of the principle notions of cognitive linguistics is investigated. Considering concept as culture phenomenon, having language realization and ethnocultural peculiarities, the description of the concept “happiness” is presented. Lexical and semantic paradigm of the concept of happiness correlates with a great number of lexical and semantic variants. In the work semantic representatives of the concept of happiness, covering supreme spiritual values are revealed and semantic interpretation of their functioning in the Biblical discourse is given.

  3. DNA demethylating agent 5-azacytidine inhibits myeloid-derived suppressor cells induced by tumor growth and cyclophosphamide treatment

    OpenAIRE

    Mikyšková, R; Indrová, M. (Marie); Vlková, V. (Veronika); Bieblová, J. (Jana); Šímová, J; Paračková, Z. (Zuzana); Pajtasz-Piasecka, E.; Rossowska, J.; Reiniš, M

    2014-01-01

    MDSCs represent one of the key players mediating immunosuppression. These cells accumulate in the TME, lymphoid organs, and blood during tumor growth. Their mobilization was also reported after CY therapy. DNMTi 5AC has been intensively studied as an antitumor agent. In this study, we examined, using two different murine tumor models, the modulatory effects of 5AC on TU-MDSCs and CY-MDSCs tumor growth and CY therapy. Indeed, the percentage of MDSCs in the TME and spleens of 5AC-treated mice b...

  4. Danazol Inhibits Cytochrome P450 2J2 Activity in a Substrate-independent Manner.

    Science.gov (United States)

    Lee, Eunyoung; Wu, Zhexue; Shon, Jong Cheol; Liu, Kwang-Hyeon

    2015-08-01

    Cytochrome P450 2J2 (CYP2J2) is an enzyme responsible for the metabolism of endogenous substrates including arachidonic acid, as well as therapeutic drugs such as albendazole, astemizole, ebastine, and terfenadine. Selective inhibitors of CYP2J2 are essential for P450 reaction phenotyping studies. To find representative CYP2J2 index inhibitors, we evaluated the inhibitory potential of danazol, hydroxyebastine, telmisartan, and terfenadone against CYP2J2 activity for four representative CYP2J2 substrates (albendazole, astemizole, ebastine, and terfenadine) using recombinant CYP2J2. Of these four CYP2J2 inhibitors, danazol strongly inhibited CYP2J2-mediated albendazole, astemizole, ebastine, and terfenadine metabolism in a substrate-independent manner, with IC50 values of 0.05, 0.07, 0.18, and 0.34 μM, respectively. Danazol noncompetitively inhibited CYP2J2-mediated astemizole O-demethylation activities with a Ki value of 0.06 μM. Terfenadone strongly inhibited CYP2J2-mediated albendazole, astemizole, and terfenadine metabolism (IC50 20 μM). Taken together, these data suggest that danazol may be used as a CYP2J2 index inhibitor in reaction phenotyping studies. PMID:26048912

  5. Homocysteine harasses the imprinting expression of IGF2 and H19 by demethylation of differentially methylated region between IGF2/H19 genes

    Institute of Scientific and Technical Information of China (English)

    Lijuan Li; Jing Xie; Meng Zhang; Shuren Wang

    2009-01-01

    Homocysteine (Hcy) can induce proliferation of vascular smooth muscle cells (VSMCs), which is a key event in the genesis of the lesions of atherosclerosis. Insulinlike growth factor 2 (IGF2) and 1119 are two important regulating molecules of cell proliferation. The role of Hcy in the proliferation of smooth muscle cell by regulating IGF2 and HI9 has not been shown or analyzed so far. This study aims to investigate the potential impact of Hcy on gene imprinting of IGF2 and 1-119.Cultured human umbilical VSMCs were treated with different concentrations of Hcy. The DNA methylation status of VSMCs was assayed by nested methylationspecific polymerase chain reaction (PCR). The mRNA levels of H19, IGF2, and CCCTC-binding factor (CTCF) were detected by reverse transcription PCR,and the protein expression of IGF2 by Western blotting. The results showed that the Hcy treatment resulted in hypomethylation of the sixth CTCF-binding site upstream of 1119 of VSMCs. The expression of H19 was increased, whereas the IGF2 mRNA and protein were decreased, the CTCF expression increased with the increase in Hcy concentration. These data indicated that Hcy could induce hypomethylation of the sixth CTCF-binding sites upstream of 1119, which is an important regulating area for the imprinting expression of IGF2 and 1119. The increased CTCF expression may be a potential mechanism for the demethylation modification of DNA, which resulted from the Hcy treatment.

  6. Effects of the Demethylating Agent, 5-Azacytidine, on Expression of the Kallikrein-Kinin Genes in Carcinoma Cells of the Lung and Pleura

    Directory of Open Access Journals (Sweden)

    Joshua Wong

    2011-01-01

    Full Text Available Tissue kallikrein (KLK1 and plasma kallikrein (KLKB1 may regulate the growth and proliferation of tumours of the lung and pleura, through the generation of kinin peptides that signal through the kinin B1 (BDKRB1 and B2 (BDKRB2 receptors. The development and progression of cancer results from genetic mutations, as well as epigenetic changes that include methylation of DNA at CpG islands. The aim of this study was to assess whether expression of the kallikrein-kinin genes in lung cancer and mesothelioma cells is regulated by DNA methylation. Quantitative reverse transcriptase-PCR and immunocytochemistry showed differences in the basal expression of the kallikrein-kinin genes and proteins in lung carcinoma and mesothelioma cells, compared with non-malignant lung epithelial and mesothelial cells, respectively. Following treatment with the demethylating agent, 5-azacytidine (5-AZA, KLKB1 mRNA expression was consistently increased in both lung carcinoma and mesothelioma cells, whereas KLK1, BDKRB1 and BDKRB2 mRNA expression was decreased or unchanged. Increased expression of KLKB1 after 5-AZA treatment suggests it may function as a tumour suppressor gene in cancers of the lung and pleura. Studies on DNA methylation of the kallikrein-kinin genes will enhance understanding of their role in carcinogenesis and provide insights into the importance of kallikreins as tumour biomarkers.

  7. Effects of the Demethylating Agent, 5-Azacytidine, on Expression of the Kallikrein-Kinin Genes in Carcinoma Cells of the Lung and Pleura

    Science.gov (United States)

    Wong, Joshua; Sia, Yee Yen; Misso, Neil L.; Aggarwal, Shashi; Ng, Angeline; Bhoola, Kanti D.

    2011-01-01

    Tissue kallikrein (KLK1) and plasma kallikrein (KLKB1) may regulate the growth and proliferation of tumours of the lung and pleura, through the generation of kinin peptides that signal through the kinin B1 (BDKRB1) and B2 (BDKRB2) receptors. The development and progression of cancer results from genetic mutations, as well as epigenetic changes that include methylation of DNA at CpG islands. The aim of this study was to assess whether expression of the kallikrein-kinin genes in lung cancer and mesothelioma cells is regulated by DNA methylation. Quantitative reverse transcriptase-PCR and immunocytochemistry showed differences in the basal expression of the kallikrein-kinin genes and proteins in lung carcinoma and mesothelioma cells, compared with non-malignant lung epithelial and mesothelial cells, respectively. Following treatment with the demethylating agent, 5-azacytidine (5-AZA), KLKB1 mRNA expression was consistently increased in both lung carcinoma and mesothelioma cells, whereas KLK1, BDKRB1 and BDKRB2 mRNA expression was decreased or unchanged. Increased expression of KLKB1 after 5-AZA treatment suggests it may function as a tumour suppressor gene in cancers of the lung and pleura. Studies on DNA methylation of the kallikrein-kinin genes will enhance understanding of their role in carcinogenesis and provide insights into the importance of kallikreins as tumour biomarkers. PMID:21904690

  8. Rescue of Early bace-1 and Global DNA Demethylation by S-Adenosylmethionine Reduces Amyloid Pathology and Improves Cognition in an Alzheimer’s Model

    Science.gov (United States)

    Do Carmo, Sonia; Hanzel, Cecilia E.; Jacobs, Marie L.; Machnes, Ziv; Iulita, M. Florencia; Yang, Jingyun; Yu, Lei; Ducatenzeiler, Adriana; Danik, Marc; Breuillaud, Lionel S.; Bennett, David A.; Szyf, Moshe; Cuello, A. Claudio

    2016-01-01

    General DNA hypomethylation is associated with Alzheimer’s disease (AD), but it is unclear when DNA hypomethylation starts or plays a role in AD pathology or whether DNA re-methylation would rescue early amyloid-related cognitive impairments. In an APP transgenic mouse model of AD-like amyloid pathology we found that early intraneuronal amyloid beta build-up is sufficient to unleash a global and beta-site amyloid precursor protein cleaving enzyme 1 (bace-1) DNA demethylation in AD-vulnerable brain regions. S-adenosylmethionine administration at these early stages abolished this hypomethylation, diminished the amyloid pathology and restored cognitive capabilities. To assess a possible human significance of findings, we examined the methylation at 12 CpGs sites in the bace-1 promoter, using genome-wide DNA methylation data from 740 postmortem human brains. Thus, we found significant associations of bace-1 promoter methylation with β-amyloid load among persons with AD dementia, and PHFtau tangle density. Our results support a plausible causal role for the earliest amyloid beta accumulation to provoke DNA hypomethylation, influencing AD pathological outcomes. PMID:27681803

  9. Determination of the Proportion of Total Soil Extracellular Acid Phosphomonoesterase (E.C. 3.1.3.2 Activity Represented by Roots in the Soil of Different Forest Ecosystems

    Directory of Open Access Journals (Sweden)

    Klement Rejsek

    2012-01-01

    Full Text Available The aim of this study is to present a new method for determining the root-derived extracellular acid phosphomonoesterase (EAPM activity fraction within the total EAPM activity of soil. EAPM activity was determined for roots, organic and mineral soil. Samples were collected using paired PVC cylinders, inserted to a depth of 15 cm, within seven selected forest stands. Root-derived EAPM formed between 4 and18% of the total EAPM activity of soil from forests of differing maturity. A new approach, presented in this work, enables separation of root-derived EAPM activity from total soil EAPM. Separation of root-derived EAPM from soil provides a better understanding of its role in P-cycling in terrestrial ecosystems. The method presented in this work is a first step towards the separation of root- and microbe-derived EAPM in soils, which are thought to possess different kinetic properties and different sensitivity to environmental change.

  10. Want change? Call your representative

    Science.gov (United States)

    Fischhoff, Ilya R.

    2011-07-01

    During my tenure as an AGU Congressional Science Fellow, which began in September 2010 and continues until November 2011, my time has been shared between working with the U.S. House of Representatives Natural Resource Committee Democratic staff and in the office of Rep. Ed Markey (D-Mass., ranking Democrat on the committee). I appreciate getting to work with staff, fellows, and interns who inspire me, make me laugh, and know their issues cold. Much of my work on the committee is related to fish, wildlife, oceans, lands, and water issues and is directly related to my background in ecology and evolutionary biology (I studied zebra ecology and behavior in Kenya). My assignments have included asking the Environmental Protection Agency (EPA) about why it has not changed the allowed usage of certain pesticides that the National Marine Fisheries Service has found to jeopardize the recovery of endangered Pacific salmon; helping to identify research needs and management options to combat the swiftly spreading and catastrophic white nose syndrome in North American bats; and inquiring as to whether a captive-ape welfare bill, if passed without amendment, could thwart development of a vaccine to stop the Ebola virus from continuing to cause mass mortality in endangered wild apes.

  11. [Lactase deficiency among representatives of various nationalities of Siberia].

    Science.gov (United States)

    Zhvavyĭ, N F; Kozlov, A I; Kondik, V M

    1991-01-01

    Some features of lactase tolerance were investigated in representatives of varying groups of indigenous population in Siberia-Mansi, Khanty, Nenets, Buryats. The indirect method was used to evaluate lactase activity. A total of 92 subjects were investigated. It was found that 32% of the representatives of the Urals population group and 53% of Buryats were capable of lactase assimilating. The data obtained correspond to the cultural-genetic hypothesis on the nature of lactase tolerance in the representatives of different ethnic groups.

  12. Stability of XIST repression in relation to genomic imprinting following global genome demethylation in a human cell line

    Energy Technology Data Exchange (ETDEWEB)

    Araújo, E.S.S. de [Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP (Brazil); Centro Internacional de Pesquisa, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Vasques, L.R. [Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP (Brazil); Stabellini, R.; Krepischi, A.C.V. [Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP (Brazil); Centro Internacional de Pesquisa, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Pereira, L.V. [Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP (Brazil)

    2014-10-17

    DNA methylation is essential in X chromosome inactivation and genomic imprinting, maintaining repression of XIST in the active X chromosome and monoallelic repression of imprinted genes. Disruption of the DNA methyltransferase genes DNMT1 and DNMT3B in the HCT116 cell line (DKO cells) leads to global DNA hypomethylation and biallelic expression of the imprinted gene IGF2 but does not lead to reactivation of XIST expression, suggesting that XIST repression is due to a more stable epigenetic mark than imprinting. To test this hypothesis, we induced acute hypomethylation in HCT116 cells by 5-aza-2′-deoxycytidine (5-aza-CdR) treatment (HCT116-5-aza-CdR) and compared that to DKO cells, evaluating DNA methylation by microarray and monitoring the expression of XIST and imprinted genes IGF2, H19, and PEG10. Whereas imprinted genes showed biallelic expression in HCT116-5-aza-CdR and DKO cells, the XIST locus was hypomethylated and weakly expressed only under acute hypomethylation conditions, indicating the importance of XIST repression in the active X to cell survival. Given that DNMT3A is the only active DNMT in DKO cells, it may be responsible for ensuring the repression of XIST in those cells. Taken together, our data suggest that XIST repression is more tightly controlled than genomic imprinting and, at least in part, is due to DNMT3A.

  13. Stability of XIST repression in relation to genomic imprinting following global genome demethylation in a human cell line

    International Nuclear Information System (INIS)

    DNA methylation is essential in X chromosome inactivation and genomic imprinting, maintaining repression of XIST in the active X chromosome and monoallelic repression of imprinted genes. Disruption of the DNA methyltransferase genes DNMT1 and DNMT3B in the HCT116 cell line (DKO cells) leads to global DNA hypomethylation and biallelic expression of the imprinted gene IGF2 but does not lead to reactivation of XIST expression, suggesting that XIST repression is due to a more stable epigenetic mark than imprinting. To test this hypothesis, we induced acute hypomethylation in HCT116 cells by 5-aza-2′-deoxycytidine (5-aza-CdR) treatment (HCT116-5-aza-CdR) and compared that to DKO cells, evaluating DNA methylation by microarray and monitoring the expression of XIST and imprinted genes IGF2, H19, and PEG10. Whereas imprinted genes showed biallelic expression in HCT116-5-aza-CdR and DKO cells, the XIST locus was hypomethylated and weakly expressed only under acute hypomethylation conditions, indicating the importance of XIST repression in the active X to cell survival. Given that DNMT3A is the only active DNMT in DKO cells, it may be responsible for ensuring the repression of XIST in those cells. Taken together, our data suggest that XIST repression is more tightly controlled than genomic imprinting and, at least in part, is due to DNMT3A

  14. DNA demethylating agent 5-azacytidine inhibits myeloid-derived suppressor cells induced by tumor growth and cyclophosphamide treatment.

    Science.gov (United States)

    Mikysková, Romana; Indrová, Marie; Vlková, Veronika; Bieblová, Jana; Símová, Jana; Paracková, Zuzana; Pajtasz-Piasecka, Elzbieta; Rossowska, Joanna; Reinis, Milan

    2014-01-01

    MDSCs represent one of the key players mediating immunosuppression. These cells accumulate in the TME, lymphoid organs, and blood during tumor growth. Their mobilization was also reported after CY therapy. DNMTi 5AC has been intensively studied as an antitumor agent. In this study, we examined, using two different murine tumor models, the modulatory effects of 5AC on TU-MDSCs and CY-MDSCs tumor growth and CY therapy. Indeed, the percentage of MDSCs in the TME and spleens of 5AC-treated mice bearing TRAMP-C2 or TC-1/A9 tumors was found decreased. The changes in the MDSC percentage were accompanied by a decrease in the Arg-1 gene expression, both in the TME and spleens. CY treatment of the tumors resulted in additional MDSC accumulation in the TME and spleens. This accumulation was subsequently inhibited by 5AC treatment. A combination of CY with 5AC led to the highest tumor growth inhibition. Furthermore, in vitro cultivation of spleen MDSCs in the presence of 5AC reduced the percentage of MDSCs. This reduction was associated with an increased percentage of CD11c(+) and CD86(+)/MHCII(+) cells. The observed modulatory effect on MDSCs correlated with a reduction of the Arg-1 gene expression, VEGF production, and loss of suppressive capacity. Similar, albeit weaker effects were observed when MDSCs from the spleens of tumor-bearing animals were cultivated with 5AC. Our findings indicate that beside the direct antitumor effect, 5AC can reduce the percentage of MDSCs accumulating in the TME and spleens during tumor growth and CY chemotherapy, which can be beneficial for the outcome of cancer therapy. PMID:24389335

  15. Overexpression of ShCYP51B and ShatrD in Sclerotinia homoeocarpa isolates exhibiting practical field resistance to a demethylation inhibitor fungicide.

    Science.gov (United States)

    Hulvey, Jon; Popko, James T; Sang, Hyunkyu; Berg, Andrew; Jung, Geunhwa

    2012-09-01

    We investigated genetic factors that govern the reduced propiconazole sensitivity of Sclerotinia homoeocarpa field isolates collected during a 2-year field efficacy study on dollar spot disease of turf in five New England sites. These isolates displayed a >50-fold range of in vitro sensitivity to a sterol demethylation inhibitor (DMI) fungicide, propiconazole, making them ideal for investigations of genetic mechanisms of reduced DMI sensitivity. The CYP51 gene homolog in S. homoeocarpa (ShCYP51B), encoding the enzyme target of DMIs, is likely a minor genetic factor for reduced propiconazole sensitivity, since there were no differences in constitutive relative expression (RE) values and only 2-fold-higher induced RE values for insensitive than for sensitive isolate groups. Next, we mined RNA-Seq transcriptome data for additional genetic factors and found evidence for the overexpression of a homolog of Botrytis cinerea atrD (BcatrD), ShatrD, a known efflux transporter of DMI fungicides. The ShatrD gene showed much higher constitutive and induced RE values for insensitive isolates. Several polymorphisms were found upstream of ShatrD but were not definitively linked to overexpression. The screening of constitutive RE values of ShCYP51B and ShatrD in isolates from two golf courses that exhibited practical field resistance to propiconazole uncovered evidence for significant population-specific overexpression of both genes. However, linear regression demonstrated that the RE of ShatrD displays a more significant relationship with propiconazole sensitivity than that of ShCYP51B. In summary, our results suggest that efflux is a major determinant of the reduced DMI sensitivity of S. homoeocarpa genotypes in New England, which may have implications for the emergence of practical field resistance in this important turfgrass pathogen.

  16. Efecto de actividades turísticas sobre el comportamiento de fauna representativa de las Islas Galápagos, Ecuador Short-term effects of tourism activities on the behavior of representative fauna on the Galapagos Islands, Ecuador

    Directory of Open Access Journals (Sweden)

    Fernanda González-Pérez

    2010-01-01

    Full Text Available Fueron consideradas clave para actividades turísticas en 16 sitios de las Islas Galápagos: la raya sartén marmoleada (Taeniura meyeri, raya águila (Aetobatus narinari, tiburón de aleta blanca (Triaenodon obesus, tortuga verde (Chelonia mydas, cormorán no volador (Phalacrocorax harrisi y lobo marino de Galápagos (Zalophus califórnianus, con el objetivo de analizar reacciones a corto plazo ante actividades de buceo apnea o "snorkeling", buceo autónomo o "scuba", paseos en bote o "panga-ride" y caminatas. Para cada especie se documentó su comportamiento al momento del encuentro con los turistas y su reacción ante dicha situación. El uso del Análisis de Correspondencias reveló que el tipo de reacción de las especies depende significativamente de la actividad turística, a excepción de las rayas sartén marmoleada y águila. Asimismo, los análisis indican que, a nivel de especie, cada actividad turística estuvo asociada significativamente con reacciones animales particulares. Esto sugiere que las especies analizadas son sensibles ante determinadas actividades turísticas, por lo que se deberían implementar recomendaciones de manejo a fin de garantizar la sustentabilidad del ecoturismo.This study focused on the short-term reactions of six key species (Taeniura meyeri, Aetobatus narinari, Triaendon obesus, Chelonia mydas, Phalacrocorax harrisi, and Zalophus califórnianus during tourism activities (SCUBA diving, panga-ride, snorkeling, and hiking at 16 tourist sites on the islands. For each species we recorded its behavior when first encountering tourists and its reaction following this encounter. A Correspondence Analysis revealed that the type of reaction of the species depended significantly on the type of touristic activity, with the exception of the black spotted and eagle rays. Moreover, the analysis showed that, for each species, the different tourist activities were significantly associated with particular animal activities

  17. 10 CFR 63.332 - Representative volume.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Representative volume. 63.332 Section 63.332 Energy... Protection Standards § 63.332 Representative volume. (a) The representative volume is the volume of ground... radionuclides released from the Yucca Mountain disposal system that will be in the representative volume....

  18. Do pharmaceutical representatives misuse their drug samples?

    OpenAIRE

    Tong, K. L.; Lien, C. Y.

    1995-01-01

    OBJECTIVE: To determine the extent to which pharmaceutical representatives misuse their samples. DESIGN: Voluntary questionnaire survey. SETTING: A family practice office. PARTICIPANTS: Pharmaceutical representatives visiting the office during a 3-month period. MAIN OUTCOME MEASURES: Number of surveyed representatives who self-medicated, provided samples of prescription drugs to nonphysicians, or exchanged drugs with other representatives; classes of prescription drugs most commonly used; and...

  19. High-Mannose Specific Lectin and Its Recombinants from a Carrageenophyta Kappaphycus alvarezii Represent a Potent Anti-HIV Activity Through High-Affinity Binding to the Viral Envelope Glycoprotein gp120.

    Science.gov (United States)

    Hirayama, Makoto; Shibata, Hiromi; Imamura, Koji; Sakaguchi, Takemasa; Hori, Kanji

    2016-04-01

    We previously reported that a high-mannose binding lectin KAA-2 from the red alga Kappaphycus alvarezii, which is an economically important species and widely cultivated as a source of carrageenans, had a potent anti-influenza virus activity. In this study, the full-length sequences of two KAA isoforms, KAA-1 and KAA-2, were elucidated by a combination of peptide mapping and cDNA cloning. They consisted of four internal tandem-repeated domains, which are conserved in high-mannose specific lectins from lower organisms, including a cyanobacterium Oscillatoria agardhii and a red alga Eucheuma serra. Using an Escherichia coli expression system, an active recombinant form of KAA-1 (His-tagged rKAA-1) was successfully generated in the yield of 115 mg per a litter of culture. In a detailed oligosaccharide binding analysis by a centrifugal ultrafiltration-HPLC method with 27 pyridylaminated oligosaccharides, His-tagged rKAA-1 and rKAA-1 specifically bound to high-mannose N-glycans with an exposed α1-3 mannose in the D2 arm as the native lectin did. Predicted from oligosaccharide-binding specificity, a surface plasmon resonance analysis revealed that the recombinants exhibit strong interaction with gp120, a heavily glycosylated envelope glycoprotein of HIV with high association constants (1.48-1.61 × 10(9) M(-1)). Native KAAs and the recombinants inhibited the HIV-1 entry at IC50s of low nanomolar levels (7.3-12.9 nM). Thus, the recombinant proteins would be useful as antiviral reagents targeting the viral surface glycoproteins with high-mannose N-glycans, and the cultivated alga K. alvarezii could also be a good source of not only carrageenans but also this functional lectin(s). PMID:26661793

  20. Representing Uncertainty by Probability and Possibility

    DEFF Research Database (Denmark)

    Uncertain parameters in modeling are usually represented by probability distributions reflecting either the objective uncertainty of the parameters or the subjective belief held by the model builder. This approach is particularly suited for representing the statistical nature or variance of uncer......Uncertain parameters in modeling are usually represented by probability distributions reflecting either the objective uncertainty of the parameters or the subjective belief held by the model builder. This approach is particularly suited for representing the statistical nature or variance...

  1. Physical activity and screen-based media use: cross-sectional associations with health-related quality of life and the role of body satisfaction in a representative sample of German adolescents.

    Science.gov (United States)

    Finne, Emily; Bucksch, Jens; Lampert, Thomas; Kolip, Petra

    2013-01-01

    Purpose: Although it is widely accepted that physical activity (PA) positively, and screen-based media use (SBM) negatively, affects well-being, there is a lack of studies relating PA and SBM to health-related quality of life (HRQoL) in adolescents. We examined these associations in German adolescents for different HRQoL subdomains and explored the role of body satisfaction as a possible mediator. Methods: The 11-17-year-old subsample of the German Health Interview and Examination Survey (2003-2006) was analysed (N = 6813; 51.3% male). Cross-sectional associations of self-reported PA frequency and amount of daily SBM with HRQoL subscale scores (according to KINDL-R) were examined by hierarchical linear regression models, adjusting for the clustering of the sample and for a variety of possible confounders. The size and significance of indirect effects via body (dis)satisfaction (BDS) were examined by mediation analyses. Results: Higher PA frequency was significantly associated with higher HRQoL on nearly all subscales and dose-response-relationships were observable. Variations were greatest in terms of social well-being in boys (effect size d = 0.59) and physical well-being in girls (d = 0.43). Higher SBM was related to lower HRQoL on all subscales in girls and on some subscales in boys, with the largest effects for school functioning in both genders (d = 0.31 and 0.37, respectively). The mediated effects for PA and SBM were significant in both genders, but the sizes and the proportions of total effects mediated by body satisfaction were rather small. Conclusions: Higher PA frequency was associated with higher self-reported HRQoL, and higher SBM was associated with lower self-reported HRQoL in both genders, even after adjusting for relevant covariates. The results support the assumption of independent health impacts of both behaviours, although no causal relationship can be confirmed with these cross-sectional data. Mechanisms other than body satisfaction must

  2. Lysine-Specific Demethylase 1 Has Dual Functions as a Major Regulator of Androgen Receptor Transcriptional Activity

    Directory of Open Access Journals (Sweden)

    Changmeng Cai

    2014-12-01

    Full Text Available Lysine-Specific Demethylase 1 (LSD1, KDM1A functions as a transcriptional corepressor through demethylation of histone 3 lysine 4 (H3K4 but has a coactivator function on some genes through mechanisms that are unclear. We show that LSD1, interacting with CoREST, associates with and coactivates androgen receptor (AR on a large fraction of androgen-stimulated genes. A subset of these AR/LSD1-associated enhancer sites have histone 3 threonine 6 phosphorylation (H3T6ph, and these sites are further enriched for androgen-stimulated genes. Significantly, despite its coactivator activity, LSD1 still mediates H3K4me2 demethylation at these androgen-stimulated enhancers. FOXA1 is also associated with LSD1 at AR-regulated enhancer sites, and a FOXA1 interaction with LSD1 enhances binding of both proteins at these sites. These findings show that LSD1 functions broadly as a regulator of AR function, that it maintains a transcriptional repression function at AR-regulated enhancers through H3K4 demethylation, and that it has a distinct AR-linked coactivator function mediated by demethylation of other substrates.

  3. 5 CFR 511.608 - Employee representatives.

    Science.gov (United States)

    2010-01-01

    ... representative would cause a conflict of interest or position; an employee who cannot be released from his or her... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Employee representatives. 511.608 Section... CLASSIFICATION UNDER THE GENERAL SCHEDULE Classification Appeals § 511.608 Employee representatives. An...

  4. Comparing German and Danish employee representatives on European Works Councils

    DEFF Research Database (Denmark)

    Bicknell, Helen; Knudsen, Herman Lyhne

    2006-01-01

    can be observed in the way German and Danish EWC representatives act on and view EWCs? Can differences be explained by cross-national variations in representation structures and associated trade union policies? The article describes the national representation structures in the two countries......This article aims to analyse the links and possible‘fit’ between German and Danish representation structures and trade union policies on the one hand, and the views and activities of European Works Council (EWC) representatives from the two countries on the other. Which similarities or differences......, their linkage to EWCs and trade unions, and identifies the typical profile of German and Danish EWC representatives respectively. Data on how the representatives view the EWC and its activities and the extent to which they have been involved in negotiations with management are presented and analysed...

  5. Mining Representative Subset Based on Fuzzy Clustering

    Institute of Scientific and Technical Information of China (English)

    ZHOU Hongfang; FENG Boqin; L(U) Lintao

    2007-01-01

    Two new concepts-fuzzy mutuality and average fuzzy entropy are presented. Then based on these concepts, a new algorithm-RSMA (representative subset mining algorithm) is proposed, which can abstract representative subset from massive data.To accelerate the speed of producing representative subset, an improved algorithm-ARSMA(accelerated representative subset mining algorithm) is advanced, which adopt combining putting forward with backward strategies. In this way, the performance of the algorithm is improved. Finally we make experiments on real datasets and evaluate the representative subset. The experiment shows that ARSMA algorithm is more excellent than RandomPick algorithm either on effectiveness or efficiency.

  6. EEG microstates during resting represent personality differences.

    Science.gov (United States)

    Schlegel, Felix; Lehmann, Dietrich; Faber, Pascal L; Milz, Patricia; Gianotti, Lorena R R

    2012-01-01

    We investigated the spontaneous brain electric activity of 13 skeptics and 16 believers in paranormal phenomena; they were university students assessed with a self-report scale about paranormal beliefs. 33-channel EEG recordings during no-task resting were processed as sequences of momentary potential distribution maps. Based on the maps at peak times of Global Field Power, the sequences were parsed into segments of quasi-stable potential distribution, the 'microstates'. The microstates were clustered into four classes of map topographies (A-D). Analysis of the microstate parameters time coverage, occurrence frequency and duration as well as the temporal sequence (syntax) of the microstate classes revealed significant differences: Believers had a higher coverage and occurrence of class B, tended to decreased coverage and occurrence of class C, and showed a predominant sequence of microstate concatenations from A to C to B to A that was reversed in skeptics (A to B to C to A). Microstates of different topographies, putative "atoms of thought", are hypothesized to represent different types of information processing.The study demonstrates that personality differences can be detected in resting EEG microstate parameters and microstate syntax. Microstate analysis yielded no conclusive evidence for the hypothesized relation between paranormal belief and schizophrenia. PMID:21644026

  7. Automated extraction of lysergic acid diethylamide (LSD) and N-demethyl-LSD from blood, serum, plasma, and urine samples using the Zymark RapidTrace with LC/MS/MS confirmation.

    Science.gov (United States)

    de Kanel, J; Vickery, W E; Waldner, B; Monahan, R M; Diamond, F X

    1998-05-01

    A forensic procedure for the quantitative confirmation of lysergic acid diethylamide (LSD) and the qualitative confirmation of its metabolite, N-demethyl-LSD, in blood, serum, plasma, and urine samples is presented. The Zymark RapidTrace was used to perform fully automated solid-phase extractions of all specimen types. After extract evaporation, confirmations were performed using liquid chromatography (LC) followed by positive electrospray ionization (ESI+) mass spectrometry/mass spectrometry (MS/MS) without derivatization. Quantitation of LSD was accomplished using LSD-d3 as an internal standard. The limit of quantitation (LOQ) for LSD was 0.05 ng/mL. The limit of detection (LOD) for both LSD and N-demethyl-LSD was 0.025 ng/mL. The recovery of LSD was greater than 95% at levels of 0.1 ng/mL and 2.0 ng/mL. For LSD at 1.0 ng/mL, the within-run and between-run (different day) relative standard deviation (RSD) was 2.2% and 4.4%, respectively.

  8. Think tank (3) - Present activities of other representative organizations

    Science.gov (United States)

    Obara, Michio

    There were some think tank businesses in Japan before the war. South Manchuria Railway Company established its Research Department for the purpose of getting power to control Manchuria as a colony, and got the good results. Think tank business was flourishing three times after the war. This business attracts much attention when the social and economic paradigm is going to change. Among the key large-scale think tanks in Japan, Nomura Research Institute, Ltd. (NRI) was the first to enhance the system functions by the merger, and posted think tank function up in the SI business. Mitsubishi Research Institute, Inc. (MRI) intends to be an orthodox think tank, and established an advanced research institute and the laboratory for R&D. Daiwa Institute of Research, Ltd. (DIR) focuses on economic forecast by using system. Fuji Research Institute, Corp. (FUJI RIC) focuses on survey and policy proposing in macro-economics, and analyzing technology. The Japan Research Institute, Ltd. (JRI) focuses on regional development, and R&D in advanced technology.

  9. [Temporal lobe epilepsy and active neurocysticercosis: two representative case reports].

    Science.gov (United States)

    Ramos-Zúñiga, Rodrigo; Pérez-Gómez, Héctor R; Gaytán-Martínez, Luis A; Vega-Ruiz, Brenda; Soto-Rodríguez, Sofía; Rochín-Mozqueda, Alejandro

    2015-01-01

    Introduccion. Existen pocas evidencias notificadas de casos de epilepsia del lobulo temporal asociadas a cisticercosis activa en su fase quistica. El objetivo es presentar la correlacion entre cisticercosis activa en zonas topograficas asociadas a epilepsia del lobulo temporal, con las manifestaciones neuropsiquiatricas y el patron de crisis parciales secundariamente generalizadas. Casos clinicos. Dos casos de pacientes adultos con manifestaciones neuropsiquiatricas de un año de evolucion, refractarios a tratamiento farmacologico antipsicotico, y en quienes posteriormente aparecen crisis convulsivas parciales secundariamente generalizadas de inicio tardio. Se identifica la presencia de cisticercosis activa en el lobulo temporal en un paciente, y en la insula, en el otro. Buen control clinico posterior al tratamiento con albendazol, pero se mantiene el mismo tratamiento anticonvulsionante para considerar la pertinencia de su retirada farmacologica. Conclusiones. La neurocisticercosis activa puede ser causa de trastornos neuropsiquiatricos adquiridos y de epilepsia del lobulo temporal de inicio tardio cuando su topografia se encuentra en el circuito mesolimbico. El diagnostico etiologico oportuno y el tratamiento apropiado permiten el control adecuado de su sintomatologia y, potencialmente, su curacion definitiva.

  10. Representing Others in a Public Good Game

    Directory of Open Access Journals (Sweden)

    Karen Evelyn Hauge

    2015-09-01

    Full Text Available In many important public good situations the decision-making power and authority is delegated to representatives who make binding decisions on behalf of a larger group. The purpose of this study is to compare contribution decisions made by individuals with contribution decisions made by group representatives. We present the results from a laboratory experiment that compares decisions made by individuals in inter-individual public good games with decisions made by representatives on behalf of their group in inter-group public good games. Our main finding is that contribution behavior differs between individuals and group representatives, but only for women. While men’s choices are equally self-interested as individuals and group representatives, women make less self-interested choices as group representatives.

  11. Representing Quadric Surfaces Using NURBS Surfaces

    Institute of Scientific and Technical Information of China (English)

    秦开怀

    1997-01-01

    A method for representing quadrc surfaces using NURBS is presented.By means of the necessary and sufficient conditons for NURBS curves to precisely represent circular arcs and other conics,quadric surfaces can be represented by NURBS surfaces with fewer control vertices.The method can be used not only for NURBS surface representation of quadric surfaces,but also for rounding polyhedrons.Many examples are given in the paper.

  12. Representing Animal-Others in Educational Research

    Science.gov (United States)

    Kuhl, Gail J.

    2011-01-01

    This paper encourages environmental and humane education scholars to consider the ethical implications of how nonhuman animals are represented in research. I argue that research representations of animals can work to either break down processes of "othering," or reinforce them. I explore various options for representing other animals, including…

  13. Antecedents and Consequences of Sales Representatives' Relationship Termination Competence

    DEFF Research Database (Denmark)

    Geersbro, Jens; Ritter, Thomas

    2013-01-01

    . In addition, termination competence significantly affects the value of customer portfolios. Practical implications: The findings suggest that managers should more actively consider relationship termination as a legitimate option in customer relationship management. In order to increase the value of a firm...... the antecedents and consequences of sales representatives' relationship termination competence. Design/methodology/approach: A model of antecedents of sales representatives' relationship termination competence is developed and tested using a cross-sectional survey of more than 800 sales representatives....... The impact of the constructs "termination acceptance", "definition of non-customer", "termination routines" and "termination incentives" on termination competence are analyzed using PLS. Findings: A sales representative's termination competence is positively influenced by greater clarity and wider...

  14. Union Learning Representatives: Facilitating Professional Development for Scottish Teachers

    Science.gov (United States)

    Alexandrou, Alex; O'Brien, Jim

    2007-01-01

    In the United Kingdom, teachers' professional associations and labor organizations, notably in the form of trade unions have historically been involved in education and training in the workplace. Recently, in the United Kingdom this activity has gained greater credence and importance due to the emergence of trade union learning representatives who…

  15. Regulation of demethylation and re-expression of RASSF1A gene in gastric cancer cell lines by combined treatment of 5-Aza-CdR and NaB

    Institute of Scientific and Technical Information of China (English)

    Wen-Jing Shen; Dong-Qiu Dai; Yue Teng; Hong-Bo Liu

    2008-01-01

    AIM: To investigate the changes of methylation state and expression of RASSF1A gene in human gastric cancer cell lines SGC7901 and BGC823 which were treated in vitro with demethlylating agent 5-Aza-CdR in combination with histone deacetylase inhibitor NaB.METHODS: After SGC7901 and BGC823 cells were treated with 5-Aza-CdR and/or NaB, the methylation state of RASSF1A gene was detected by methylation-specific PCR, and the changes in expression of mRNA and protein level of RASSF1A gene were observed by RT-PCR and Western-blotting before and after drug treatment.RESULTS: Hypermethylation was detected in the promoter region of RASSF1A gene in both SGC7901 and BGC823 cells, and there was no expression of this gene at both mRNA and protein level. After treatment with 5-Aza-CdR, demethylation occurred in the promoter region of RASSF1A gene, which subsequently induced re-expression of this gene. The treatment with NaB alone showed no effect on the methylation state and expression of RASSF1A gene. The combined treatment of 5-Aza-CdR and NaB induced complete demethylation of RASSF1A gene, leading to a significantly higher re-expression of the mRNA and protein of RASSF1A than those treated with 5-Aza-CdR alone (P < 0.05).CONCLUSION: Hypermethylation in the promoter region is related to inactivation of RASSF1A gene in human gastric cancer cell lines SGC7901 and BGC823, while demethlylating agent 5-Aza-CdR can reverse the methylation state of RASSF1A gene and induce itsre-expression. Histone deacetylase inhibitor NaB had a synergistic effect with 5-Aza-CdR in both demethylation and gene transcriptional regulation.(c) 2008 WJG. All rights reserved.

  16. Relationship of the demethylation of the DNA with the induction of the sister chromatid exchanges (SCE) In vivo; Relacion de la desmetilacion del ADN con la induccion de intercambios en las cromatidas hermanas (ICH) In vivo

    Energy Technology Data Exchange (ETDEWEB)

    Toribio E, E

    2005-07-01

    The methylation of the DNA is an epigenetic modification that has an important paper in the regulation of the functionality of the genome of the organisms. It can be altered by demethylation processes, either natural or experimentally induced. The 5-azacytidine (Aza) is a compound that causes the demethylation of the DNA (dm-DNA), inducing with it, expression genic and increase in the frequency of the Sister Chromatid Exchange (SCE). The SCE is a genotoxicity indicator, caused by diverse mutagens and carcinogen. Since the biological meaning and the formation mechanism of this phenomenon has not been totally illustrious, the exploration of the relation between the dm-DNA and the induction of SCE, it could offer new knowledge to explain those queries. The purpose of this work was to study in cells of the mouse bone marrow In vivo, the effect of the Aza on the induction of SCE, based on two aspects: 1) dose answer and 2) the effectiveness of multiple exhibition. To six groups of three to five animals, they are administered Aza to dose of 5, 10, 15 or 20 mg/Kg of weight; in sharp or multiple form, previously to the bromodeoxyuridine supply and 24 h was sacrificed after this; 2 h after an injection with colchicine. Preparations of those metaphases were made, those which were dyed by means of a technique of fluorescence more Giemsa. It was observed that to sharp low dose, the Aza produced an increment in the frequency of SCE that although small it was proportional and statistically significant. To sharp and multiple high doses, the Aza doesn't cause additional increments of SCE, but if toxicity at cellular level and of individuals. It is concluded that a relationship exists between the dm-DNA and the induction of SCE. It is suggested that the total demethylation of the DNA causes 2 SCE/Cell in cells of the mouse bone marrow, or that the cytotoxicity prevents to evidence a bigger induction. (Author)

  17. 7 CFR 1205.20 - Representative period.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Representative period. 1205.20 Section 1205.20 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... period means the 2006 calendar year....

  18. Request by the Resident Representative of Iraq

    International Nuclear Information System (INIS)

    The attached clarification by a spokesman of the Iraqi Ministry of Foreign Affairs is being circulated for the information of Member States pursuant to a request made by the Resident Representative of Iraq

  19. REFractions: The Representing Equivalent Fractions Game

    Science.gov (United States)

    Tucker, Stephen I.

    2014-01-01

    Stephen Tucker presents a fractions game that addresses a range of fraction concepts including equivalence and computation. The REFractions game also improves students' fluency with representing, comparing and adding fractions.

  20. Enhancing policy innovation by redesigning representative democracy

    DEFF Research Database (Denmark)

    Sørensen, Eva

    2016-01-01

    . Two Danish case studies indicate that collaboration between politicians and relevant and affected stakeholders can promote policy innovation, but also that a redesign of representative democracy is needed in order to establish a productive combination of political leadership, competition...

  1. Representative Democracy in Australian Local Government

    OpenAIRE

    Colin Hearfield; Brian Dollery

    2009-01-01

    In an assessment of representative democracy in Australian local government, this paper considers long-run changes in forms of political representation, methods of vote counting, franchise arrangements, numbers of local government bodies and elected representatives, as well as the thorny question of constitutional recognition. This discussion is set against the background of ongoing tensions between the drive for economic efficiency and the maintenance of political legitimacy, along with more...

  2. Do regional climate models represent regional climate?

    Science.gov (United States)

    Maraun, Douglas; Widmann, Martin

    2014-05-01

    When using climate change scenarios - either from global climate models or further downscaled - to assess localised real world impacts, one has to ensure that the local simulation indeed correctly represents the real world local climate. Representativeness has so far mainly been discussed as a scale issue: simulated meteorological variables in general represent grid box averages, whereas real weather is often expressed by means of point values. As a result, in particular simulated extreme values are not directly comparable with observed local extreme values. Here we argue that the issue of representativeness is more general. To illustrate this point, assume the following situations: first, the (GCM or RCM) simulated large scale weather, e.g., the mid-latitude storm track, might be systematically distorted compared to observed weather. If such a distortion at the synoptic scale is strong, the simulated local climate might be completely different from the observed. Second, the orography even of high resolution RCMs is only a coarse model of true orography. In particular in mountain ranges the simulated mesoscale flow might therefore considerably deviate from the observed flow, leading to systematically displaced local weather. In both cases, the simulated local climate does not represent observed local climate. Thus, representativeness also encompasses representing a particular location. We propose to measure this aspect of representativeness for RCMs driven with perfect boundary conditions as the correlation between observations and simulations at the inter-annual scale. In doing so, random variability generated by the RCMs is largely averaged out. As an example, we assess how well KNMIs RACMO2 RCM at 25km horizontal resolution represents winter precipitation in the gridded E-OBS data set over the European domain. At a chosen grid box, RCM precipitation might not be representative of observed precipitation, in particular in the rain shadow of major moutain ranges

  3. Studies of H3K4me3 demethylation by KDM5B/Jarid1B/PLU1 reveals strong substrate recognition in vitro and identifies 2,4-pyridine-dicarboxylic acid as an in vitro and in cell inhibitor

    DEFF Research Database (Denmark)

    Kristensen, Line Hyltoft; Nielsen, Anders Laerke; Helgstrand, Charlotte;

    2012-01-01

    Dynamic methylations and demethylations of histone lysine residues are important for gene regulation and are facilitated by histone methyltransferases and histone demethylases (HDMs). KDM5B/Jarid1B/PLU1 is an H3K4me3/me2 specific lysine demethylase belonging to the family of JmjC domain containin...

  4. Nonequilibrium representative ensembles for isolated quantum systems

    International Nuclear Information System (INIS)

    An isolated quantum system is considered, prepared in a nonequilibrium initial state. In order to uniquely define the system dynamics, one has to construct a representative statistical ensemble. From the principle of least action it follows that the role of the evolution generator is played by a grand Hamiltonian, but not merely by its energy part. A theorem is proved expressing the commutators of field operators with operator products through variational derivatives of these products. A consequence of this theorem is the equivalence of the variational equations for field operators with the Heisenberg equations for the latter. A finite quantum system cannot equilibrate in the strict sense. But it can tend to a quasi-stationary state characterized by ergodic averages and the appropriate representative ensemble depending on initial conditions. Microcanonical ensemble, arising in the eigenstate thermalization, is just a particular case of representative ensembles. Quasi-stationary representative ensembles are defined by the principle of minimal information. The latter also implies the minimization of an effective thermodynamic potential. -- Highlights: → The evolution of a nonequilibrium isolated quantum system is considered. → The grand Hamiltonian is shown to be the evolution generator. → A theorem is proved connecting operator commutators with variational derivatives. → Quasi-stationary states are described by representative ensembles. → These ensembles, generally, depend on initial conditions.

  5. Total Synthesis and Antifungal Activity of Palmarumycin CP17 and Its Methoxy Analogues.

    Science.gov (United States)

    Wang, Ruina; Liu, Guoyue; Yang, Mingyan; Wang, Mingan; Zhou, Ligang

    2016-01-01

    Total synthesis of naturally occurring spirobisnaphthalene palmarumycin CP17 and its methoxy analogues was first achieved through Friedel-Crafts acylation, Wolff-Kishner reduction, intramolecular cyclization, ketalization, benzylic oxidation, and demethylation using the inexpensive and readily available methoxybenzene, 1,2-dimethoxybenzene and 1,4-dimethoxybenzene and 1,8-dihydroxynaphthalene as raw materials. Demethylation with (CH₃)₃SiI at ambient temperature resulted in ring A aromatization and acetal cleavage to give rise to binaphthyl ethers. The antifungal activities of these spirobisnaphthalene derivatives were evaluated, and the results revealed that 5 and 9b exhibit EC50 values of 9.34 µg/mL and 12.35 µg/mL, respectively, against P. piricola. PMID:27164077

  6. Total Synthesis and Antifungal Activity of Palmarumycin CP17 and Its Methoxy Analogues

    Directory of Open Access Journals (Sweden)

    Ruina Wang

    2016-05-01

    Full Text Available Total synthesis of naturally occurring spirobisnaphthalene palmarumycin CP17 and its methoxy analogues was first achieved through Friedel-Crafts acylation, Wolff-Kishner reduction, intramolecular cyclization, ketalization, benzylic oxidation, and demethylation using the inexpensive and readily available methoxybenzene, 1,2-dimethoxybenzene and 1,4-dimethoxybenzene and 1,8-dihydroxynaphthalene as raw materials. Demethylation with (CH33SiI at ambient temperature resulted in ring A aromatization and acetal cleavage to give rise to binaphthyl ethers. The antifungal activities of these spirobisnaphthalene derivatives were evaluated, and the results revealed that 5 and 9b exhibit EC50 values of 9.34 µg/mL and 12.35 µg/mL, respectively, against P. piricola.

  7. Representative Sampling for reliable data analysis

    DEFF Research Database (Denmark)

    Petersen, Lars; Esbensen, Kim Harry

    2005-01-01

    aspects are illustrated with many practical examples of TOS at work in typical scenarios, presented to yield a general overview. TOS provides a full scientific definition of the concept of sampling correctness, an attribute of the sampling process that must never be compromised. For this purpose...... the Fundamental Sampling Principle (FSP) also receives special attention. TOS provides the first complete scientific definition of sampling representativeness. Only correct (unbiased) mass reduction will ensure representative sampling. It is essential to induct scientific and technological professions in the TOS...

  8. Representing Uncertainty on Model Analysis Plots

    CERN Document Server

    Smith, Trevor I

    2016-01-01

    Model analysis provides a mechanism for representing student learning as measured by standard multiple-choice surveys. The model plot contains information regarding both how likely students in a particular class are to choose the correct answer and how likely they are to choose an answer consistent with a well-documented conceptual model. Unfortunately Bao's original presentation of the model plot did not include a way to represent uncertainty in these measurements. I present details of a method to add error bars to model plots by expanding the work of Sommer and Lindell. I also provide a template for generating model plots with error bars.

  9. Effects of 5-azacytidine on natural killer cell activating receptor expression in patients with refractory anemia with excess of blasts

    Directory of Open Access Journals (Sweden)

    Régis T. Costello

    2015-01-01

    Full Text Available Epigenetic drugs modify DNA methylation and are used in refractory anemia with excess of blasts (RAEB. These drugs may reactivate anti-oncogene expression and restore a normal phenotype instead of inducing antitumor toxicity, although they also have immunosuppressive effects on T-lymphocytes [1] In RAEB and acute myeloid leukemia, a defect in natural killer (NK cell cytotoxicity has been shown, which relies on abnormal expression of activating receptors. Previous study has shown that 5-azacytidine impaired mRNA synthesis and induced apoptosis in NK cells [2]. In this study we investigated the effect of the demethylating drug 5-azacytidine (Vidaza® on NK receptors with the hypothesis that demethylation of the promoters of activating NK receptor genes induces gene reactivation and thus may increase their expression.

  10. Effects of 5-azacytidine on natural killer cell activating receptor expression in patients with refractory anemia with excess of blasts

    Science.gov (United States)

    Costello, Régis T.; Leclercq, Amélie; Treut, Thérèse Le; Sanchez, Carole; Mercier, Delphine; Sébahoun, Gérard

    2015-01-01

    Epigenetic drugs modify DNA methylation and are used in refractory anemia with excess of blasts (RAEB). These drugs may reactivate anti-oncogene expression and restore a normal phenotype instead of inducing antitumor toxicity, although they also have immunosuppressive effects on T-lymphocytes [1] In RAEB and acute myeloid leukemia, a defect in natural killer (NK) cell cytotoxicity has been shown, which relies on abnormal expression of activating receptors. Previous study has shown that 5-azacytidine impaired mRNA synthesis and induced apoptosis in NK cells [2]. In this study we investigated the effect of the demethylating drug 5-azacytidine (Vidaza®) on NK receptors with the hypothesis that demethylation of the promoters of activating NK receptor genes induces gene reactivation and thus may increase their expression. PMID:25709892

  11. Effects of 5-azacytidine on natural killer cell activating receptor expression in patients with refractory anemia with excess of blasts.

    Science.gov (United States)

    Costello, Régis T; Leclercq, Amélie; Treut, Thérèse Le; Sanchez, Carole; Mercier, Delphine; Sébahoun, Gérard

    2015-01-01

    Epigenetic drugs modify DNA methylation and are used in refractory anemia with excess of blasts (RAEB). These drugs may reactivate anti-oncogene expression and restore a normal phenotype instead of inducing antitumor toxicity, although they also have immunosuppressive effects on T-lymphocytes [1] In RAEB and acute myeloid leukemia, a defect in natural killer (NK) cell cytotoxicity has been shown, which relies on abnormal expression of activating receptors. Previous study has shown that 5-azacytidine impaired mRNA synthesis and induced apoptosis in NK cells [2]. In this study we investigated the effect of the demethylating drug 5-azacytidine (Vidaza(®)) on NK receptors with the hypothesis that demethylation of the promoters of activating NK receptor genes induces gene reactivation and thus may increase their expression. PMID:25709892

  12. The Role of the Faculty Athletics Representative.

    Science.gov (United States)

    Cooper, Arthur W.

    1992-01-01

    The faculty athletics representative plays an important role in the athletic-academic relationship. This responsibility includes certifying student-athlete eligibility, reporting academic data as required, evaluating athlete-applicant qualifications and abilities, regular evaluation of athlete performance, and participation in evaluation of…

  13. Attributes Heeded When Representing an Osmosis Problem.

    Science.gov (United States)

    Zuckerman, June Trop

    Eighteen high school science students were involved in a study to determine what attributes in the problem statement they need when representing a typical osmosis problem. In order to realize this goal students were asked to solve problems aloud and to explain their answers. Included as a part of the results are the attributes that the students…

  14. Representing Context in Hypermedia Data Models

    DEFF Research Database (Denmark)

    Hansen, Frank Allan

    2005-01-01

    application data can be a challenging task. Thispaper describes how digital context traditionally has beenrepresented in hypermedia data models and how this representationcan scale to also represent physical context. TheHyCon framework and data model, designed for the developmentof mobile context......-aware hypermedia systems, arepresented as concrete examples of a model combining applicationdata, hypermedia structures and context informationin one model....

  15. 28 CFR 104.4 - Personal Representative.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Personal Representative. 104.4 Section 104.4 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) SEPTEMBER 11TH VICTIM COMPENSATION... evidence of a “dispute” pursuant to paragraph (d) of this section. (d) Disputes as to identity. The...

  16. A Framework for Representing Moving Objects

    DEFF Research Database (Denmark)

    Becker, Ludger; Blunck, Henrik; Hinrichs, Klaus;

    2004-01-01

    We present a framework for representing the trajectories of moving objects and the time-varying results of operations on moving objects. This framework supports the realization of discrete data models of moving objects databases, which incorporate representations of moving objects based on non-li...

  17. CYP2C19基因型和CYP2C9对人肝微粒体中氟西汀N-去甲基代谢的影响%Effects of CYP2C19 genotype and CYP2C9 on fluoxetine N-demethylation in human liver microsomes

    Institute of Scientific and Technical Information of China (English)

    刘昭前; 舒焱; 黄松林; 王连生; 何楠; 周宏灏

    2001-01-01

    目的:本实验旨在研究CYP2C19基因型人肝微粒体中氟西汀N-去甲基代谢的酶促动力学特点并鉴定参与此代谢途径的细胞色素P-450酶.方法:测定基因型CYP2C19肝微粒体中去甲氟西汀形成的酶促动力学.鉴定氟西汀N-去甲基酶活性与细胞色素P-450 2C9,2C19,1A2和2D6酶活性的相关性,同时应用各种细胞色素P-450酶的选择性抑制剂和化学探针进行抑制实验,从而确定参与氟西汀N-去甲基代谢的细胞色素P-450酶.结果:去甲氟西汀生成的酶促动力学数据符合单酶模型,并具有Michaelis-Menten动力学特征.当底物浓度为氟西汀25μmol/L和100 μmol/L时,去甲氟西汀(N-FLU)的生成率分别与甲磺丁脲3-羟化酶活性显著相关(r1=0.821,P1=0.001;r2=0.668,P2=0.013),当底物浓度为氟西汀100 μmol/L时,N-FLU的生成率与S-美芬妥因4'-羟化酶活性显著相关(r=0.717,P=0.006).PM肝微粒中磺胺苯吡唑和醋竹桃霉素对氟西汀N-去甲基代谢的抑制作用显著大于EM(73%vs 45%,P<0.01).结论:在生理底物浓度下,CYP2C9是催化人肝微粒体中氟西汀N-去甲基代谢的主要CYP-450酶;而高底物浓度时,以CYP2C19的作用为主.%AIM: The present study was designed to define the kinetic behavior of fluoxetine N-demethylation in human liver microsomes and to identify the isoforms of cytochrome P-450 (CYP) involved in this metabolic pathway. METHODS: The kinetics of the formation of norfluoxetine was determined in human liver microsomes from six genotyped CYP2C19 extensive metabolizers (EM). The correlation studies between the fluoxetine N-demethylase activity and various CYP enzyme activities were performed. Selective inhibitors or chemical probes of various cytochrome P-450 isoforms were also employed. RESULTS: The kinetics of norfluoxetine formation in all liver microsomes were fitted by a singleenzyme Michaelis-Menten equation (mean Km=32 μmol/L±7

  18. Representative parameter of immunostimulatory ginseng polysaccharide to predict radioprotection

    Energy Technology Data Exchange (ETDEWEB)

    Son, Hyeog Jin; Shim, Ji Young; Ahn, Ji Yeon; Yun, Yeon Sook; Song, Jie Young [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2008-09-15

    According to the increase in the use of radiotherapy to cancer patients, many approaches have been tried to develop new agents for the protection of surrounding normal tissues. However, it is still few applied in the clinic as a radioprotector. We aim to find a representative parameter for radioprotection to easily predict the activity of in vivo experiment from the results of in vitro screening. The polysaccharide extracted from Panax ginseng was used in this study because the immunostimulator has been regarded as one of the radioprotective agent category and was already reported having a promising radioprotective activity through the increase of hematopoietic cells and the production of several cytokines. Mitogenic activity, AK cells activity and nitric oxide production were monitored for the in vitro immunological assay, and endogenous Colony-Forming Unit (e-CFU) was measured as in vivo radioprotective parameter. The immunological activity was increased by the galactose contents of ginseng polysaccharide dependently. The result of this study suggests that mitogenic activity of splenocytes demonstrated a good correlation with in vivo radioprotective effect, and may be used as a representative parameter to screen the candidates for radioprotector.

  19. Representing clinical guidelines in UMl: a comparative study.

    Science.gov (United States)

    Hederman, Lucy; Smutek, Daniel; Wade, Vincent; Knape, Thomas

    2002-01-01

    Clinical guidelines can be represented using models, such as GLIF, specifically designed for healthcare guidelines. This paper demonstrates that they can also be modelled using a mainstream business modelling language such as UML. The paper presents a guideline in GLIF and as UML activity diagrams, and then presents a mapping of GLIF primitives to UML. The potential benefits of using a mainstream modelling language are outlined. These include availability of advanced modelling tools, transfer between modelling tools, and automation via business workflow technology.

  20. Strong imploding shock - The representative curve

    Science.gov (United States)

    Mishkin, E. A.; Alejaldre, C.

    1981-02-01

    The representative curve of the ideal gas behind the front of a spherically or cylindrically asymmetric strong imploding shock is derived. The partial differential equations of mass, momentum and energy conservation are reduced to a set of ordinary differential equations by the method of quasi-separation of variables, following which the reduced pressure and density as functions of the radius with respect to the shock front are explicit functions of coordinates defining the phase plane of the self-similar solution. The curve in phase space representing the state of the imploded gas behind the shock front is shown to pass through the point where the reduced pressure is maximum, which is located somewhat behind the shock front and ahead of the tail of the shock.

  1. Data structures and apparatuses for representing knowledge

    Energy Technology Data Exchange (ETDEWEB)

    Hohimer, Ryan E; Thomson, Judi R; Harvey, William J; Paulson, Patrick R; Whiting, Mark A; Tratz, Stephen C; Chappell, Alan R; Butner, Robert S

    2014-02-18

    Data structures and apparatuses to represent knowledge are disclosed. The processes can comprise labeling elements in a knowledge signature according to concepts in an ontology and populating the elements with confidence values. The data structures can comprise knowledge signatures stored on computer-readable media. The knowledge signatures comprise a matrix structure having elements labeled according to concepts in an ontology, wherein the value of the element represents a confidence that the concept is present in an information space. The apparatus can comprise a knowledge representation unit having at least one ontology stored on a computer-readable medium, at least one data-receiving device, and a processor configured to generate knowledge signatures by comparing datasets obtained by the data-receiving devices to the ontologies.

  2. Climate Change and the Representative Agent

    Energy Technology Data Exchange (ETDEWEB)

    Howarth, R.B. [Environmental Studies Program, Dartmouth College, Hanover, New Hampshire 03755 (United States)

    2000-02-01

    The artifice of an infinitely-lived representative agent is commonly invoked to balance the present costs and future benefits of climate stabilization policies. Since actual economies are populated by overlapping generations of finite-lived persons, this approach begs important questions of welfare aggregation. This paper compares the results of representative agent and overlapping generations models that are numerically calibrated based on standard assumptions regarding climate economy interactions. Under two social choice rules - Pareto efficiency and classical utilitarianism - the models generate closely similar simulation results. In the absence of policies to redistribute income between present and future generations, efficient rates of carbon dioxide emissions abatement rise from 15 to 20% between the years 2000 and 2105. Under classical utilitarianism, in contrast, optimal control rates rise from 48 to 79% this same period. 23 refs.

  3. Representing Boolean Functions by Decision Trees

    KAUST Repository

    Chikalov, Igor

    2011-01-01

    A Boolean or discrete function can be represented by a decision tree. A compact form of decision tree named binary decision diagram or branching program is widely known in logic design [2, 40]. This representation is equivalent to other forms, and in some cases it is more compact than values table or even the formula [44]. Representing a function in the form of decision tree allows applying graph algorithms for various transformations [10]. Decision trees and branching programs are used for effective hardware [15] and software [5] implementation of functions. For the implementation to be effective, the function representation should have minimal time and space complexity. The average depth of decision tree characterizes the expected computing time, and the number of nodes in branching program characterizes the number of functional elements required for implementation. Often these two criteria are incompatible, i.e. there is no solution that is optimal on both time and space complexity. © Springer-Verlag Berlin Heidelberg 2011.

  4. Representing exact number visually using mental abacus.

    Science.gov (United States)

    Frank, Michael C; Barner, David

    2012-02-01

    Mental abacus (MA) is a system for performing rapid and precise arithmetic by manipulating a mental representation of an abacus, a physical calculation device. Previous work has speculated that MA is based on visual imagery, suggesting that it might be a method of representing exact number nonlinguistically, but given the limitations on visual working memory, it is unknown how MA structures could be stored. We investigated the structure of the representations underlying MA in a group of children in India. Our results suggest that MA is represented in visual working memory by splitting the abacus into a series of columns, each of which is independently stored as a unit with its own detailed substructure. In addition, we show that the computations of practiced MA users (but not those of control participants) are relatively insensitive to verbal interference, consistent with the hypothesis that MA is a nonlinguistic format for exact numerical computation.

  5. Representing a public that does not exist

    DEFF Research Database (Denmark)

    Korsgaard, Morten Timmermann

    , and the only way of retaining any form of authority (and legitimacy as a teacher) is to remain loyal to the task of presenting this world to the child. This challenge presents itself acutely in the form of a global reform agenda that legitimizes standardisation and accountability while eroding the authority......In her seminal essay ‘The Crisis in Education’ Hannah Arendt presents teachers with the challenge of having to represent a world that is becoming out of joint. This means that the teacher stands as a representative of a world that is becoming increasingly inexplicable and incomprehensible...... and function of the teacher. Confronted by this teachers and educationalists in Denmark have chosen different paths. One current returns to nationalistic and traditional educational ideals and another accepts the global agenda and attempts to find a new form of legitimacy within the ‘what works’ framework...

  6. Representing exact number visually using mental abacus.

    Science.gov (United States)

    Frank, Michael C; Barner, David

    2012-02-01

    Mental abacus (MA) is a system for performing rapid and precise arithmetic by manipulating a mental representation of an abacus, a physical calculation device. Previous work has speculated that MA is based on visual imagery, suggesting that it might be a method of representing exact number nonlinguistically, but given the limitations on visual working memory, it is unknown how MA structures could be stored. We investigated the structure of the representations underlying MA in a group of children in India. Our results suggest that MA is represented in visual working memory by splitting the abacus into a series of columns, each of which is independently stored as a unit with its own detailed substructure. In addition, we show that the computations of practiced MA users (but not those of control participants) are relatively insensitive to verbal interference, consistent with the hypothesis that MA is a nonlinguistic format for exact numerical computation. PMID:21767040

  7. Meeting staff representatives of the European Agencies

    CERN Multimedia

    Staff Association

    2014-01-01

      The AASC (Assembly of Agency Staff Committee) held its 27th Meeting of the specialized European Agencies on 26 and 27 May on the premises of the OHIM (Office for Harmonization in the Internal Market) in Alicante, Spain. Two representatives of the CERN Staff Association, in charge of External Relations, attended as observers. This participation is a useful complement to regular contacts we have with FICSA (Federation of International Civil Servants' Associations), which groups staff associations of the UN Agencies, and the annual CSAIO conferences (Conference of Staff Associations of International Organizations), where each Autumn representatives of international organizations based in Europe meet to discuss themes of common interest to better promote and defend the rights of the international civil servants. All these meetings allow us to remain informed on items that are directly or indirectly related to employment and social conditions of our colleagues in other international and Europ...

  8. Diversity and representativeness: two key factors

    CERN Document Server

    Staff Association

    2013-01-01

    In the past few weeks many of you have filled out the questionnaire for preparing the upcoming Five-yearly review. Similarly, Staff Association members have elected their delegates to the Staff Council for the coming two years. Once again we would like to thank all those who have taken the time and effort to make their voice heard on these two occasions. Elections to the Staff Council Below we publish the new Staff Council with its forty delegates who will represent in 2014 and 2015 all CERN staff in the discussions with Management and Member States in the various bodies and committees. Therefore it is important that the Staff Council represents as far as possible the diversity of the CERN population. By construction, the election process with its electoral colleges and two-step voting procedure guarantees that all Departments, even the small ones, and the various staff categories are correctly represented. Figure 1 shows the participation rate in the elections. The average rate is just above 52 %, with ...

  9. Latency represents sound frequency in mouse IC

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Frequency is one of the fundamental parameters of sound.The frequency of an acoustic stimulus can be represented by a neural response such as spike rate,and/or first spike latency(FSL)of a given neuron.The spike rates/frequency function of most neurons changes with different acoustic ampli-tudes,whereas FSL/frequency function is highly stable.This implies that FSL might represent the fre-quency of a sound stimulus more efficiently than spike rate.This study involved representations of acoustic frequency by spike rate and FSL of central inferior colliculus(IC)neurons responding to free-field pure-tone stimuli.We found that the FSLs of neurons responding to characteristic frequency(CF)of sound stimulus were usually the shortest,regardless of sound intensity,and that spike rates of most neurons showed a variety of function according to sound frequency,especially at high intensities.These results strongly suggest that FSL of auditory IC neurons can represent sound frequency more precisely than spike rate.

  10. Latency represents sound frequency in mouse IC

    Institute of Scientific and Technical Information of China (English)

    QIU Qiang; TANG Jie; YU ZuLin; ZHANG Juan; ZHOU YingJie; XIAO ZhongJu; SHEN JunXian

    2007-01-01

    Frequency is one of the fundamental parameters of sound. The frequency of an acoustic stimulus can be represented by a neural response such as spike rate, and/or first spike latency (FSL) of a given neuron. The spike rates/frequency function of most neurons changes with different acoustic amplitudes, whereas FSL/frequency function is highly stable. This implies that FSL might represent the frequency of a sound stimulus more efficiently than spike rate. This study involved representations of acoustic frequency by spike rate and FSL of central inferior colliculus (IC) neurons responding to free-field pure-tone stimuli. We found that the FSLs of neurons responding to characteristic frequency (CF) of sound stimulus were usually the shortest, regardless of sound intensity, and that spike rates of most neurons showed a variety of function according to sound frequency, especially at high intensities.These results strongly suggest that FSL of auditory IC neurons can represent sound frequency more precisely than spike rate.

  11. Computing ideal class representatives in quaternion algebras

    CERN Document Server

    Pacetti, Ariel

    2010-01-01

    Let $K$ be a number field and $B$ a quaternion algebra over $K$. Let $R' \\subseteq R \\subseteq B$ be Bass orders and suppose that $\\{\\mathfrak{a}_i\\}_{i\\in I}$ is a set of left $R$-ideal representatives. In this article we show how to construct in an effective way a set $\\{\\mathfrak{b}_j\\}_{j\\in J}$ of left $\\tilde{R}$-ideal representatives for an order $\\tilde{R}$ in the same genus as $R'$, such that each $\\mathfrak{b}_j$ is contained in some $\\mathfrak{a}_i$ and, furthermore, $\\mathscr{N}\\mathfrak{b}_j =\\mathscr{N}\\mathfrak{a}_i$. The construction does not use the knowledge of the class number of $R'$, and instead of checking for equivalences many times, it only depends on some knowledge of global units. As an application of the method, we compute the weight $3/2$ modular forms mapping to the elliptic curves of rank $0$ over $\\mathbb{Q}$ whose conductor is a power of $2$. We also give an example of the method for an order $R$ of level $30$ in an algebra over the real quadratic field $\\mathbb{Q}[\\sqrt{5}]$ w...

  12. How Are Feedbacks Represented in Land Models?

    Directory of Open Access Journals (Sweden)

    Yang Chen

    2016-09-01

    Full Text Available Land systems are characterised by many feedbacks that can result in complex system behaviour. We defined feedbacks as the two-way influences between the land use system and a related system (e.g., climate, soils and markets, both of which are encompassed by the land system. Land models that include feedbacks thus probably more accurately mimic how land systems respond to, e.g., policy or climate change. However, representing feedbacks in land models is a challenge. We reviewed articles incorporating feedbacks into land models and analysed each with predefined indicators. We found that (1 most modelled feedbacks couple land use systems with transport, soil and market systems, while only a few include feedbacks between land use and social systems or climate systems; (2 equation-based land use models that follow a top-down approach prevail; and (3 feedbacks’ effects on system behaviour remain relatively unexplored. We recommend that land system modellers (1 consider feedbacks between land use systems and social systems; (2 adopt (bottom-up approaches suited to incorporating spatial heterogeneity and better representing land use decision-making; and (3 pay more attention to nonlinear system behaviour and its implications for land system management and policy.

  13. Picturing and modelling catchments by representative hillslopes

    Science.gov (United States)

    Loritz, Ralf; Hassler, Sibylle; Jackisch, Conrad; Zehe, Erwin

    2016-04-01

    Hydrological modelling studies often start with a qualitative sketch of the hydrological processes of a catchment. These so-called perceptual models are often pictured as hillslopes and are generalizations displaying only the dominant and relevant processes of a catchment or hillslope. The problem with these models is that they are prone to become too much predetermined by the designer's background and experience. Moreover it is difficult to know if that picture is correct and contains enough complexity to represent the system under study. Nevertheless, because of their qualitative form, perceptual models are easy to understand and can be an excellent tool for multidisciplinary exchange between researchers with different backgrounds, helping to identify the dominant structures and processes in a catchment. In our study we explore whether a perceptual model built upon an intensive field campaign may serve as a blueprint for setting up representative hillslopes in a hydrological model to reproduce the functioning of two distinctly different catchments. We use a physically-based 2D hillslope model which has proven capable to be driven by measured soil-hydrological parameters. A key asset of our approach is that the model structure itself remains a picture of the perceptual model, which is benchmarked against a) geo-physical images of the subsurface and b) observed dynamics of discharge, distributed state variables and fluxes (soil moisture, matric potential and sap flow). Within this approach we are able to set up two behavioral model structures which allow the simulation of the most important hydrological fluxes and state variables in good accordance with available observations within the 19.4 km2 large Colpach catchment and the 4.5 km2 large Wollefsbach catchment in Luxembourg without the necessity of calibration. This corroborates, contrary to the widespread opinion, that a) lower mesoscale catchments may be modelled by representative hillslopes and b) physically

  14. Activities.

    Science.gov (United States)

    Moody, Mally

    1992-01-01

    A series of four activities are presented to enhance students' abilities to appreciate and use trigonometry as a tool in problem solving. Activities cover problems applying the law of sines, the law of cosines, and matching equivalent trigonometric expressions. A teacher's guide, worksheets, and answers are provided. (MDH)

  15. Using resource graphs to represent conceptual change

    Directory of Open Access Journals (Sweden)

    Michael C. Wittmann

    2006-08-01

    Full Text Available We introduce resource graphs, a representation of linked ideas used when reasoning about specific contexts in physics. Our model is consistent with previous descriptions of coordination classes and resources. It represents mesoscopic scales that are neither knowledge-in-pieces nor large-scale concepts. We use resource graphs to describe several forms of conceptual change: incremental, cascade, wholesale, and dual construction. For each, we give evidence from the physics education research literature to show examples of each form of conceptual change. Where possible, we compare our representation to models used by other researchers. Building on our representation, we analyze another form of conceptual change, differentiation, and suggest several experimental studies that would help understand the differences between reform-based curricula.

  16. Representing the vacuum polarization on de Sitter

    Energy Technology Data Exchange (ETDEWEB)

    Leonard, Katie E.; Woodard, Richard P. [Department of Physics, University of Florida, Gainesville, Florida 32611 (United States); Prokopec, Tomislav [Institute of Theoretical Physics (ITP) and Spinoza Institute, Utrecht University, Postbus 80195, 3508 TD Utrecht (Netherlands)

    2013-03-15

    Previous studies of the vacuum polarization on de Sitter have demonstrated that there is a simple, noncovariant representation of it in which the physics is transparent. There is also a cumbersome, covariant representation in which the physics is obscure. Despite being unwieldy, the latter form has a powerful appeal for those who are concerned about de Sitter invariance. We show that nothing is lost by employing the simple, noncovariant representation because there is a closed form procedure for converting its structure functions to those of the covariant representation. We also present a vastly improved technique for reading off the noncovariant structure functions from the primitive diagrams. And we discuss the issue of representing the vacuum polarization for a general metric background.

  17. Using resource graphs to represent conceptual change

    CERN Document Server

    Wittmann, M C

    2006-01-01

    We introduce resource graphs, a representation of linked ideas used when reasoning about specific contexts in physics. Our model is consistent with previous descriptions of resources and coordination classes. It can represent mesoscopic scales that are neither knowledge-in-pieces or large-scale concepts. We use resource graphs to describe several forms of conceptual change: incremental, cascade, wholesale, and dual construction. For each, we give evidence from the physics education research literature to show examples of each form of conceptual change. Where possible, we compare our representation to models used by other researchers. Building on our representation, we introduce a new form of conceptual change, differentiation, and suggest several experimental studies that would help understand the differences between reform-based curricula.

  18. STATISTICAL MODELS OF REPRESENTING INTELLECTUAL CAPITAL

    Directory of Open Access Journals (Sweden)

    Andreea Feraru

    2016-07-01

    Full Text Available This article entitled Statistical Models of Representing Intellectual Capital approaches and analyses the concept of intellectual capital, as well as the main models which can support enterprisers/managers in evaluating and quantifying the advantages of intellectual capital. Most authors examine intellectual capital from a static perspective and focus on the development of its various evaluation models. In this chapter we surveyed the classical static models: Sveiby, Edvisson, Balanced Scorecard, as well as the canonical model of intellectual capital. Among the group of static models for evaluating organisational intellectual capital the canonical model stands out. This model enables the structuring of organisational intellectual capital in: human capital, structural capital and relational capital. Although the model is widely spread, it is a static one and can thus create a series of errors in the process of evaluation, because all the three entities mentioned above are not independent from the viewpoint of their contents, as any logic of structuring complex entities requires.

  19. Towards a representative periphytic diatom sample

    Directory of Open Access Journals (Sweden)

    2007-01-01

    Full Text Available The need to acquire a representative periphytic diatom sample for river water quality monitoring has been recognised in the development of existing diatom indices, important in the development and employment of diatom monitoring tools for the Water Framework Directive. In this study, a nested design with replication is employed to investigate the magnitude of variation in diatom biomass, composition and Trophic Diatom Index at varying scales within a small chalk river. The study shows that the use of artificial substrates may not result in diatom communities that are typical of the surrounding natural substrates. Periphytic diatom biomass and composition varies between artificial and natural substrates, riffles and glides and between two stretches of the river channel. The study also highlights the existence of high variation in diatom frustule frequency and biovolume at the individual replicate scale which may have implications for the use of diatoms in routine monitoring.

  20. Probability & Perception: The Representativeness Heuristic in Action

    Science.gov (United States)

    Lu, Yun; Vasko, Francis J.; Drummond, Trevor J.; Vasko, Lisa E.

    2014-01-01

    If the prospective students of probability lack a background in mathematical proofs, hands-on classroom activities may work well to help them to learn to analyze problems correctly. For example, students may physically roll a die twice to count and compare the frequency of the sequences. Tools such as graphing calculators or Microsoft Excel®…

  1. Representative bureaucracy:does female police leadership affect gender-based violence arrests?

    OpenAIRE

    Johnston, K.; Houston, John

    2016-01-01

    Representative bureaucracy theory postulates that passive representation leads to active representation of minority groups. This article investigates the passive representation of female police officers at leadership levels and the active representation of women vis-a-vis gender-based violence arrest rates in the UK. Much of the extant research on representative bureaucracy is located at street level, with evidence showing that discretionary power of minority bureaucrats can lead to active re...

  2. Demethylation of the pesticide methoxychlor in liver and intestine from untreated, methoxychlor-treated, and 3-methylcholanthrene-treated channel catfish (Ictalurus punctatus): evidence for roles of CYP1 and CYP3A family isozymes.

    Science.gov (United States)

    Stuchal, Leah D; Kleinow, Kevin M; Stegeman, John J; James, Margaret O

    2006-06-01

    Exposure to the organochlorine pesticide methoxychlor (MXC) is associated with endocrine disruption in several species through biotransformation to mono-desmethyl-MXC (OH-MXC) and bis-desmethyl-MXC (HPTE), which interact with estrogen receptors. The biotransformation of [14C]methoxychlor was examined in channel catfish (Ictalurus punctatus), a freshwater species found in the southern United States. Hepatic microsomes formed OH-MXC and HPTE, assessed by comigration with authentic standards. The Km for OH-MXC formation by control liver microsomes was 3.8 +/- 1.3 microM (mean +/- S.D., n = 4), and Vmax was 131 +/- 53 pmol/min/mg protein. These values were similar to those of catfish pretreated with 2 mg/kg methoxychlor i.p. for 6 days (Km 3.3 +/- 0.8 microM and Vmax 99 +/- 17 pmol/min/mg) but less (p Methoxychlor pretreatment significantly reduced intestinal metabolite formation from 32 +/- 4 to 15 +/- 6 pmol/min/mg (mean +/- S.D., n = 4), whereas 3-MC treatment significantly increased OH-MXC production to 72 +/- 22 pmol/min/mg. Ketoconazole, clotrimazole, and alpha-naphthoflavone all decreased the production of OH-MXC in liver microsomes, whereas alpha-naphthoflavone stimulated HPTE formation, suggesting that CYP1 and CYP3 family isozymes demethylated methoxychlor. The results suggest that the formation of estrogenic metabolites from methoxychlor would be more rapid in catfish coexposed to CYP1 inducers.

  3. Molecular dynamics analysis reveals structural insights into mechanism of nicotine N-demethylation catalyzed by tobacco cytochrome P450 mono-oxygenase.

    Directory of Open Access Journals (Sweden)

    Shan Wang

    Full Text Available CYP82E4, a cytochrome P450 monooxygenase, has nicotine N-demethylase (NND activity, which mediates the bioconversion of nicotine into nornicotine in senescing tobacco leaves. Nornicotine is a precursor of the carcinogen, tobacco-specific nitrosamine. CYP82E3 is an ortholog of CYP82E4 with 95% sequence identity, but it lacks NND activity. A recent site-directed mutagenesis study revealed that a single amino acid substitution, i.e., cysteine to tryptophan at the 330 position in the middle of protein, restores the NND activity of CYP82E3 entirely. However, the same amino acid change caused the loss of the NND activity of CYP82E4. To determine the mechanism of the functional turnover of the two molecules, four 3D structures, i.e., the two molecules and their corresponding cys-trp mutants were modeled. The resulting structures exhibited that the mutation site is far from the active site, which suggests that no direct interaction occurs between the two sites. Simulation studies in different biological scenarios revealed that the mutation introduces a conformation drift with the largest change at the F-G loop. The dynamics trajectories analysis using principal component analysis and covariance analysis suggests that the single amino acid change causes the opening and closing of the transfer channels of the substrates, products, and water by altering the motion of the F-G and B-C loops. The motion of helix I is also correlated with the motion of both the F-G loop and the B-C loop and; the single amino acid mutation resulted in the curvature of helix I. These results suggest that the single amino acid mutation outside the active site region may have indirectly mediated the flexibility of the F-G and B-C loops through helix I, causing a functional turnover of the P450 monooxygenase.

  4. The Two Sides of the Representative Coin

    Directory of Open Access Journals (Sweden)

    Keith Sutherland

    2011-12-01

    Full Text Available In Federalist 10 James Madison drew a functional distinction between “parties” (advocates for factional interests and “judgment” (decision-making for the public good and warned of the corrupting effect of combining both functions in a “single body of men.” This paper argues that one way of overcoming “Madisonian corruption” would be by restricting political parties to an advocacy role, reserving the judgment function to an allotted (randomly-selected microcosm of the whole citizenry, who would determine the outcome of parliamentary debates by secret ballot—a division of labour suggested by James Fishkin’s experiments in deliberative polling. The paper then defends this radical constitutional proposal against Bernard Manin’s (1997 claim that an allotted microcosm could not possibly fulfil the “consent” requirement of Natural Right theory. Not only does the proposal challenge Manin’s thesis, but a 28th Amendment implementing it would finally reconcile the competing visions that have bedevilled representative democracy since the Constitutional Convention of 1787.

  5. Multicriteria analysis of ontologically represented information

    Science.gov (United States)

    Wasielewska, K.; Ganzha, M.; Paprzycki, M.; Bǎdicǎ, C.; Ivanovic, M.; Lirkov, I.

    2014-11-01

    Our current work concerns the development of a decision support system for the software selection problem. The main idea is to utilize expert knowledge to help the user in selecting the best software / method / computational resource to solve a computational problem. Obviously, this involves multicriterial decision making and the key open question is: which method to choose. The context of the work is provided by the Agents in Grid (AiG) project, where the software selection (and thus multicriterial analysis) is to be realized when all information concerning the problem, the hardware and the software is ontologically represented. Initially, we have considered the Analytical Hierarchy Process (AHP), which is well suited for the hierarchical data structures (e.g., such that have been formulated in terms of ontologies). However, due to its well-known shortcomings, we have decided to extend our search for the multicriterial analysis method best suited for the problem in question. In this paper we report results of our search, which involved: (i) TOPSIS (Technique for Order Preference by Similarity to Ideal Solution), (ii) PROMETHEE, and (iii) GRIP (Generalized Regression with Intensities of Preference). We also briefly argue why other methods have not been considered as valuable candidates.

  6. EEG microstates during resting represent personality differences

    OpenAIRE

    Schlegel, Felix; Lehmann, Dietrich; Faber, Pascal L.; Milz, Patricia; Gianotti, Lorena R R

    2011-01-01

    We investigated the spontaneous brain electric activity of 13 skeptics and 16 believers in paranormal phenomena; they were university students assessed with a self-report scale about paranormal beliefs. 33-channel EEG recordings during no-task resting were processed as sequences of momentary potential distribution maps. Based on the maps at peak times of Global Field Power, the sequences were parsed into segments of quasi-stable potential distribution, the 'microstates'. The microstates were ...

  7. Synergistic re-activation of epigenetically silenced genes by combinatorial inhibition of DNMTs and LSD1 in cancer cells.

    Directory of Open Access Journals (Sweden)

    Han Han

    Full Text Available Epigenetic gene silencing, mediated by aberrant promoter DNA hypermethylation and repressive histone modifications, is a hallmark of cancer. Although heritable, the dynamic nature and potential reversibility through pharmacological interventions make such aberrations attractive targets. Since cancers contain multiple epigenetic abnormalities, combining therapies that target different defects could potentially enhance their individual efficacies. 5-Aza-2'-deoxycytidine (5-Aza-CdR, FDA-approved drug for the treatment of myelodysplastic syndrome, can inhibit DNA methyltransferases (DNMTs upon incorporation into the DNA of dividing cells, resulting in global demethylation. More recently, the first histone demethylase, lysine specific demethylase 1 (LSD1, which demethylates both histone and non-histone substrates, has become a new target for epigenetic therapy. Using, clorgyline, an LSD1 inhibitor (LSD1i to treat cancer cell lines, we show that clorgyline employs two mechanisms of action depending on the cell type: it can either induce global DNA demethylation or inhibit LSD1-driven H3K4me2 and H3K4me1 demethylation to establish an active chromatin configuration. We also investigate the therapeutic efficacy of combining 5-Aza-CdR with clorgyline and determine that this combinatorial treatment has synergistic effects on reactivating aberrantly silenced genes by enriching H3K4me2 and H3K4me1. Many of the reactivated genes are categorized as cancer testis antigens or belong to the interferon-signaling pathway, suggesting potential implications for immunotherapy. Together, our results demonstrate that combinatorial treatment consisting of a DNMT inhibitor (DNMTi and an LSD1i have enhanced therapeutic values and could improve the efficacy of epigenetic therapy.

  8. Application to Representative Structures. Other Representative Structures: Mutsu-Ogawara, Niigata East and West

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Burcharth, Hans F.

    1999-01-01

    Reliability analyses are performed for three Japanese vertical wall breakwaters in this chapter. Only the geotechnical failure modes described in chapter 3 are investigated. For none of the breakwaters detailed data are available for the wave climate and for the soil conditions. Therefore represe...... representative values for those parameters are used and consequently the results should be considered as the result of a parameter study. The following three breakwaters are considered in sections 2, 3 and 4: Mutsu-Ogawara, Niigata East and Niigata West....

  9. N,N-dimethylglycyl-amido derivative of minocycline and 6-demethyl-6-desoxytetracycline, two new glycylcyclines highly effective against tetracycline-resistant gram-positive cocci.

    OpenAIRE

    Goldstein, F W; Kitzis, M D; Acar, J F

    1994-01-01

    The in vitro activities of the N,N-dimethylglycyl-amino derivative of minocycline (DMG-MINO) and 6-dimethyl-6-dexoxytetracycline (DMG-DMDOT), members of a new generation of tetracyclines, were evaluated by an agar dilution method and were compared with those of tetracycline and minocycline against 224 tetracycline-resistant and 73 tetracycline-susceptible recent clinical isolates of gram-positive cocci, including multiple-antibiotic-resistant methicillin-resistant Staphylococcus aureus and pe...

  10. Drug and drug-related supply promotion by pharmaceutical company representatives at VA facilities. Final rule.

    Science.gov (United States)

    2012-03-01

    This final rule amends the Department of Veterans Affairs (VA) regulations regarding access to VA facilities by pharmaceutical company representatives. The purposes of the rule are to reduce or eliminate any potential for disruption in the patient care environment, manage activities and promotions at VA facilities, and provide pharmaceutical company representatives with a consistent standard of permissible business practice at VA facilities. The amendments will facilitate mutually beneficial relationships between VA and pharmaceutical company representatives. PMID:22420057

  11. Representing Identity and Equivalence for Scientific Data

    Science.gov (United States)

    Wickett, K. M.; Sacchi, S.; Dubin, D.; Renear, A. H.

    2012-12-01

    Matters of equivalence and identity are central to the stewardship of scientific data. In order to properly prepare for and manage the curation, preservation and sharing of digitally-encoded data, data stewards must be able to characterize and assess the relationships holding between data-carrying digital resources. However, identity-related questions about resources and their information content may not be straightforward to answer: for example, what exactly does it mean to say that two files contain the same data, but in different formats? Information content is frequently distinguished from particular representations, but there is no adequately developed shared understanding of what this really means and how the relationship between content and its representations hold. The Data Concepts group at the Center for Informatics Research in Science and Scholarship (CIRSS), University of Illinois at Urbana Champaign, is developing a logic-based framework of fundamental concepts related to scientific data to support curation and integration. One project goal is to develop precise accounts of information resources carrying the same data. We present two complementary conceptual models for information representation: the Basic Representation Model (BRM) and the Systematic Assertion Model (SAM). We show how these models provide an analytical account of digitally-encoded scientific data and a precise understanding of identity and equivalence. The Basic Representation Model identifies the core entities and relationships involved in representing information carried by digital objects. In BRM, digital objects are symbol structures that express propositional content, and stand in layered encoding relationships. For example, an RDF description may be serialized as either XML or N3, and those expressions in turn may be encoded as either UTF-8 or UTF-16 sequences. Defining this encoding stack reveals distinctions necessary for a precise account of identity and equivalence

  12. HOW TO REPRESENT THE GENETIC CODE?

    Directory of Open Access Journals (Sweden)

    N.S. Santos-Magalhães

    2004-05-01

    Full Text Available The advent of molecular genetic comprises a true revolution of far-reaching consequences for human-kind, which evolved into a specialized branch of the modern-day Biochemistry. The analysis of specicgenomic information are gaining wide-ranging interest because of their signicance to the early diag-nosis of disease, and the discovery of modern drugs. In order to take advantage of a wide assortmentof signal processing (SP algorithms, the primary step of modern genomic SP involves convertingsymbolic-DNA sequences into complex-valued signals. How to represent the genetic code? Despitebeing extensively known, the DNA mapping into proteins is one of the relevant discoveries of genetics.The genetic code (GC is revisited in this work, addressing other descriptions for it, which can beworthy for genomic SP. Three original representations are discussed. The inner-to-outer map buildson the unbalanced role of nucleotides of a codon. A two-dimensional-Gray genetic representationis oered as a structured map that can help interpreting DNA spectrograms or scalograms. Theseare among the powerful visual tools for genome analysis, which depends on the choice of the geneticmapping. Finally, the world-chart for the GC is investigated. Evoking the cyclic structure of thegenetic mapping, it can be folded joining the left-right borders, and the top-bottom frontiers. As aresult, the GC can be drawn on the surface of a sphere resembling a world-map. Eight parallels oflatitude are required (four in each hemisphere as well as four meridians of longitude associated tofour corresponding anti-meridians. The tropic circles have 11.25o, 33.75o, 56.25o, and 78.5o (Northand South. Starting from an arbitrary Greenwich meridian, the meridians of longitude can be plottedat 22.5o, 67.5o, 112.5o, and 157.5o (East and West. Each triplet is assigned to a single point on thesurface that we named Nirenberg-Kohamas Earth. Despite being valuable, usual representations forthe GC can be

  13. Reactivating aberrantly hypermethylated p15 gene in leukemic T cells by a phenylhexyl isothiocyanate mediated inter-active mechanism on DNA and chromatin

    Directory of Open Access Journals (Sweden)

    Jiang Shaohong

    2010-11-01

    Full Text Available Abstract Background We have previously demonstrated that phenylhexyl isothiocyanate (PHI, a synthetic isothiocyanate, inhibits histone deacetylases and remodels chromatins to induce growth arrest in HL-60 myeloid leukemia cells in a concentration-dependent manner. Methods To investigate the effect of PHI, a novel histone deacetylases inhibitor (HDACi, on demethylation and activation of transcription of p15 in acute lymphoid leukemia cell line Molt-4, and to further decipher the potential mechanism of demethylation, DNA sequencing and modified methylation specific PCR (MSP were used to screen p15-M and p15-U mRNA after Molt-4 cells were treated with PHI, 5-Aza and TSA. DNA methyltransferase 1 (DNMT1, 3A (DNMT3A, 3B (DNMT3B and p15 mRNA were measured by RT-PCR. P15 protein, acetylated histone H3 and histone H4 were detected by Western Blot. Results The gene p15 in Molt-4 cells was hypermethylated and inactive. Hypermethylation of gene p15 was attenuated and p15 gene was activated de novo after 5 days exposure to PHI in a concentration-dependent manner. DNMT1 and DNMT3B were inhibited by PHI (P Conclusion PHI could induce both DNA demethylation and acetylated H3 and H4 accumulation in Molt-4 cells. Hypermethylation of gene p15 was reversed and p15 transcription could be reactivated de novo by PHI.

  14. Actividad física deportiva en una muestra representativa de la población de la Región de Murcia Physical sports activity in a representative sample of the population of Región de Murcia, Spain

    Directory of Open Access Journals (Sweden)

    M.T. Martínez-Ros

    2003-02-01

    the region of Murcia, Spain, and to analyze its association with major demographic and socioeconomic determinants and other cardiovascular risk factors. Methods: Survey of a representative sample of the population aged between 18 and 65 years from Murcia was performed using multistage random sampling with definition of the sample quotas. A total of 3091 individuals were surveyed. The frequency and duration of intense physical sports activity during the two weeks prior to the survey was obtained using a validated questionnaire. Information was also collected on socioeconomic variables, smoking, blood pressure, weight and height and a blood test was performed to determine plasma lipids. Intense or vigorous physical activity (≥ 6 Metabolic Equivalents [MET] was measured in kcal/day and reduced to hours/week to give three categories: no vigorous physical activity, less than 2 hours/week, and 2 hours/week or more. Results: Overall, 17.8% (95% CI: 16.6-19.0 of the adult population of the region of Murcia performed intense physical activity for ≥ 2 hours/week. The figures were twice as high in men (23.1%; 95% CI: 21.0-25.2 than in women (12.5%; 95% CI: 10.9-14.1. In the logistic regression analysis, a higher frequency of intense physical activity was associated with age, level of education and employment situation. In men it was also associated with occupation and residence in urban areas. Conclusions: During the study period, one in five adults in the region of Murcia took intense physical sports activity with a frequency and duration that were compatible with the prevention of episodes of coronary ischemia.

  15. Oxidative spectroelectrochemistry of two representative coumarins

    Energy Technology Data Exchange (ETDEWEB)

    Hu Xinran [Anhui Key Lab of Controllable Chemical Reaction and Material Chemical Engineering, School of Chemical Engineering, Hefei University of Technology, Hefei 230009 (China); He Jianbo, E-mail: jbhe@hfut.edu.c [Anhui Key Lab of Controllable Chemical Reaction and Material Chemical Engineering, School of Chemical Engineering, Hefei University of Technology, Hefei 230009 (China); Center for Analysis and Measurement, Hefei University of Technology, Hefei 230009 (China); Wang Yan; Zhu Yanwu [Anhui Key Lab of Controllable Chemical Reaction and Material Chemical Engineering, School of Chemical Engineering, Hefei University of Technology, Hefei 230009 (China); Tian Jingjing [Center for Analysis and Measurement, Hefei University of Technology, Hefei 230009 (China)

    2011-02-28

    Electrochemical oxidation of two isomeric coumarins, umbelliferone (UF, 7-hydroxycoumarin) and benzotertonic acid (BA, 4-hydroxycoumarin), were comparatively studied in aqueous buffer solutions by cyclic voltammetry, in situ long-path-length thin-layer UV-vis spectroelectrochemistry and ex situ ATR-FTIR spectrometry. Both the coumarins undergo the completely irreversible oxidation but following totally different oxidation mechanisms. The 7-OH but not the 4-OH group can contribute to antioxidative activity of coumarin via an electron transfer mechanism. Electro-oxidation of UF occurs at the 7-OH position and produces an insulating polymer film at the electrode surface, which probably consists of a poly(ethylene oxide) backbone with coumarin side groups. The toxicity-related coumarin 3,4-epoxide is a possible intermediate in the UF oxidation. Electro-oxidation of BA occurs at the C{sub 3}=C{sub 4} double bond, also yielding a non-conductive film at the electrode surface. In this process salicylaldehyde as the possible intermediate undergoes further oxidation to form the poly(aryl ether) film. The knowledge of the mechanisms of UF and BA oxidation should be helpful in understanding the roles and conversion of coumarins in their biological and chemical processes.

  16. Drosophila p53 is required to increase the levels of the dKDM4B demethylase after UV-induced DNA damage to demethylate histone H3 lysine 9.

    Science.gov (United States)

    Palomera-Sanchez, Zoraya; Bucio-Mendez, Alyeri; Valadez-Graham, Viviana; Reynaud, Enrique; Zurita, Mario

    2010-10-01

    Chromatin undergoes a variety of changes in response to UV-induced DNA damage, including histone acetylation. In human and Drosophila cells, this response is affected by mutations in the tumor suppressor p53. In this work, we report that there is a global decrease in trimethylated Lys-9 in histone H3 (H3K9me3) in salivary gland cells in wild type flies in response to UV irradiation. In contrast, flies with mutations in the Dmp53 gene have reduced basal levels of H3K9me3, which are then increased after UV irradiation. The reduction of H3K9me3 in response to DNA damage occurs preferentially in heterochromatin. Our experiments demonstrate that UV irradiation enhances the levels of Lys-9 demethylase (dKDM4B) transcript and protein in wild type flies, but not in Dmp53 mutant flies. Dmp53 binds to a DNA element in the dKdm4B gene as a response to UV irradiation. Furthermore, heterozygous mutants for the dKdm4B gene are more sensitive to UV irradiation; they are deficient in the removal of cyclobutane-pyrimidine dimers, and the decrease of H3K9me3 levels following DNA damage is not observed in dKdm4B mutant flies. We propose that in response to UV irradiation, Dmp53 enhances the expression of the dKDM4B histone demethylase, which demethylates H3K9me3 preferentially in heterochromatin regions. This mechanism appears to be essential for the proper function of the nucleotide excision repair system.

  17. All-trans retinoic acid promotes TGF-β-induced Tregs via histone modification but not DNA demethylation on Foxp3 gene locus.

    Directory of Open Access Journals (Sweden)

    Ling Lu

    Full Text Available BACKGROUND: It has been documented all-trans retinoic acid (atRA promotes the development of TGF-β-induced CD4(+Foxp3(+ regulatory T cells (iTreg that play a vital role in the prevention of autoimmune responses, however, molecular mechanisms involved remain elusive. Our objective, therefore, was to determine how atRA promotes the differentiation of iTregs. METHODOLOGY/PRINCIPAL FINDINGS: Addition of atRA to naïve CD4(+CD25(- cells stimulated with anti-CD3/CD28 antibodies in the presence of TGF-β not only increased Foxp3(+ iTreg differentiation, but maintained Foxp3 expression through apoptosis inhibition. atRA/TGF-β-treated CD4(+ cells developed complete anergy and displayed increased suppressive activity. Infusion of atRA/TGF-β-treated CD4(+ cells resulted in the greater effects on suppressing symptoms and protecting the survival of chronic GVHD mice with typical lupus-like syndromes than did CD4(+ cells treated with TGF-β alone. atRA did not significantly affect the phosphorylation levels of Smad2/3 and still promoted iTreg differentiation in CD4(+ cells isolated from Smad3 KO and Smad2 conditional KO mice. Conversely, atRA markedly increased ERK1/2 activation, and blockade of ERK1/2 signaling completely abolished the enhanced effects of atRA on Foxp3 expression. Moreover, atRA significantly increased histone methylation and acetylation within the promoter and conserved non-coding DNA sequence (CNS elements at the Foxp3 gene locus and the recruitment of phosphor-RNA polymerase II, while DNA methylation in the CNS3 was not significantly altered. CONCLUSIONS/SIGNIFICANCE: We have identified the cellular and molecular mechanism(s by which atRA promotes the development and maintenance of iTregs. These results will help to enhance the quantity and quality of development of iTregs and may provide novel insights into clinical cell therapy for patients with autoimmune diseases and those needing organ transplantation.

  18. Solar Heliospheric and INterplanetary Environment (SHINE) Students - Student Representatives' Perspectives

    Science.gov (United States)

    Pahud, D. M.; Niembro, T.

    2014-12-01

    The SHINE workshop is an annual meeting of solar and heliospheric scientists which, in addition to aiming to improve understanding of solar disturbances and their propagation to, and effect, on the Earth (shinecon.org), is dedicated to actively supporting students. This dedication is substantiated in part through the National Science Foundation (NSF) providing funding for student attendance to the workshop, which enables student participation. Another example of SHINE's commitment to its student members is the incorporation of a Student Day prior to the workshop since 2003, entirely organized and run by two student representatives. While there are variations in format from year to year, Student Day consists of tutorials and research talks exclusively by student volunteers to an audience of only students. The day is intended to provide a low-stress environment for students to learn about the various topics addressed during the workshop, to ask questions freely, and to engage in scientific discussion with other students which hopefully is a catalyst for collaboration. As a result of positive experiences, over the past decade student attendance and participation in the workshop have increased. At the SHINE 2014 workshop, nearly a third of attendees were students. SHINE student visibility has increased over the years, with student posters being advertised at breakfast, inclusion of a student day summary by the student representatives during a plenary session, and continued support from the steering committee. Students are also promoting a broader impact of SHINE sciences via increased social media presence. From a student representative's perspective, SHINE has built and fostered a healthy student community and encourages students to engage in shaping the future of the field.

  19. 48 CFR 1830.7002-3 - Representative investment calculations.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Representative investment... Representative investment calculations. (a) The calculation of the representative investment requires... accounting period, the contractor shall either: (1) Determine a representative investment for the...

  20. Brain mechanisms for representing what another person sees.

    Science.gov (United States)

    Heyda, Ratha D; Green, Steven R; Vander Wyk, Brent C; Morris, James P; Pelphrey, Kevin A

    2010-04-01

    We used functional magnetic resonance imaging (fMRI) and a naturalistic joint attention scenario to evaluate two, alternative hypotheses concerning the social brain. The first, Content Specific Attribution hypothesis, was that core regions previously identified as being involved in social cognition also participate in representing the contents of another mind. The second, Dual Role hypothesis, was that extrastriate, category-specific visual regions respond to a visible stimulus of a specific category and to the same stimulus occluded, but when it appears to be the focus of another person's visual attention. Participants viewed category-specific stimuli (Place and Body images) to localize the extrastriate body area (EBA) and parahippocampal place area (PPA). Then, they observed a computerized character viewing each stimulus category, occluded from the participant's view. In support of the Content Specific Attribution hypothesis, whole-brain analyses revealed that viewing someone else looking at an occluded picture of a body activated brain regions previously associated with components of social cognition more than viewing someone else looking at an occluded picture of a place. Counter to the Dual Role hypothesis, functional region of interest (ROI) analyses revealed that the EBA and PPA were not clearly involved in representing what the character was seeing.

  1. Demethylation of IGFBP5 by Histone Demethylase KDM6B Promotes Mesenchymal Stem Cell-Mediated Periodontal Tissue Regeneration by Enhancing Osteogenic Differentiation and Anti-Inflammation Potentials.

    Science.gov (United States)

    Liu, Dayong; Wang, Yuejun; Jia, Zhi; Wang, Liping; Wang, Jinsong; Yang, Dongmei; Song, Jianqiu; Wang, Songlin; Fan, Zhipeng

    2015-08-01

    Mesenchymal stem cell (MSC)-mediated periodontal tissue regeneration is considered a promising method for periodontitis treatment. The molecular mechanism underlying directed differentiation and anti-inflammatory actions remains unclear, thus limiting potential MSC application. We previously found that insulin-like growth factor binding protein 5 (IGFBP5) is highly expressed in dental tissue-derived MSCs compared with in non-dental tissue-derived MSCs. IGFBP5 is mainly involved in regulating biological activity of insulin-like growth factors, and its functions in human MSCs and tissue regeneration are unclear. In this study, we performed gain- and loss-of-function assays to test whether IGFBP5 could regulate the osteogenic differentiation and anti-inflammatory potential in MSCs. We found that IGFBP5 expression was upregulated upon osteogenic induction, and that IGFBP5 enhanced osteogenic differentiation in MSCs. We further showed that IGFBP5 prompted the anti-inflammation effect of MSCs via negative regulation of NFκB signaling. Depletion of the histone demethylase lysine (K)-specific demethylase 6B (KDM6B) downregulated IGFBP5 expression by increasing histone K27 methylation in the IGFBP5 promoter. Moreover, IGFBP5 expression in periodontal tissues was downregulated in individuals with periodontitis compared with in healthy people, and IGFBP5 enhanced MSC-mediated periodontal tissue regeneration and alleviated local inflammation in a swine model of periodontitis. In conclusion, our present results reveal a new function for IGFBP5, provide insight into the mechanism underlying the directed differentiation and anti-inflammation capacities of MSCs, and identify a potential target mediator for improving tissue regeneration.

  2. [On modern representatives of Wenzhou medicine and their reform thoughts].

    Science.gov (United States)

    Liu, Shi-jue; Chen, Ke-zheng; Yang, Li-ren

    2006-04-01

    Reform thought was the mainstream of thoughts among the modern Wenzhou intellectual communities. It exerted great and profound influences on medical learning and activities, with medical education as the chief reform practice of Wenzhou intellectual communities in the late Qing Dynasty. Liji Hospital and Liji Medical School were the symbols of the reform. Chen Qiu was a thinker and doctor; Xu Dingchao was an officer and doctor; Chen Baoshan was a professionally educated physician; and Xu Yunzhi was a folk doctor inherited the experiences handed down from his family. The four representatives of Wenzhou medicine, though with different social backgrounds, and their purpose of studying medicine and experience of being a doctor different alike, their medical thoughts are naturally different, reflected the overall condition of Wenzhou medicine in the late Qing Dynasty. PMID:17096986

  3. [Dangerous liaisons--physicians and pharmaceutical sales representatives].

    Science.gov (United States)

    Granja, Mónica

    2005-01-01

    Interactions between physicians and detailers (even when legitimate ones) raise scientific and ethical questions. In Portugal little thinking and discussion has been done on the subject and the blames for bribery have monopolized the media. This work intended to review what has been said in medical literature about these interactions. How do physicians see themselves when interacting with pharmaceutical companies and their representatives? Do these companies in fact change their prescriptive behaviour, and, if so, how do they change it? How can physicians interact with detailers and still keep their best practice? A Medline research, from 1966 till 2002, was performed using the key-words as follows. A database similar to Medline but concerning medical journals published in Portugal, Index das Revistas Médicas Portuguesas, was also researched from 1992 to 2002. Pharmaceutical companies are profit bound and they allot promoting activities, and detailing in particular, huge amounts of money. Most physicians hold firmly to the belief that they are able to resist and not be influenced by drug companies promotion activities. Nevertheless, all previous works on literature tell us the opposite. Market research also indicates that detailers effectively promote drug sales. Various works also suggest that the information detailers provide to physicians may be largely incorrect, even comparing it to the written information provided by the pharmaceutical companies they work for. The frequency at which portuguese physicians (especially family physicians) contact with pharmaceutical sales representatives is higher than the frequency reported in countries where the available studies come from (namely, Canada and the United States of America). This may put portuguese physicians at a higher risk, making it imperative that work and wide debate are initiated among the class. PMID:16202335

  4. [Dangerous liaisons--physicians and pharmaceutical sales representatives].

    Science.gov (United States)

    Granja, Mónica

    2005-01-01

    Interactions between physicians and detailers (even when legitimate ones) raise scientific and ethical questions. In Portugal little thinking and discussion has been done on the subject and the blames for bribery have monopolized the media. This work intended to review what has been said in medical literature about these interactions. How do physicians see themselves when interacting with pharmaceutical companies and their representatives? Do these companies in fact change their prescriptive behaviour, and, if so, how do they change it? How can physicians interact with detailers and still keep their best practice? A Medline research, from 1966 till 2002, was performed using the key-words as follows. A database similar to Medline but concerning medical journals published in Portugal, Index das Revistas Médicas Portuguesas, was also researched from 1992 to 2002. Pharmaceutical companies are profit bound and they allot promoting activities, and detailing in particular, huge amounts of money. Most physicians hold firmly to the belief that they are able to resist and not be influenced by drug companies promotion activities. Nevertheless, all previous works on literature tell us the opposite. Market research also indicates that detailers effectively promote drug sales. Various works also suggest that the information detailers provide to physicians may be largely incorrect, even comparing it to the written information provided by the pharmaceutical companies they work for. The frequency at which portuguese physicians (especially family physicians) contact with pharmaceutical sales representatives is higher than the frequency reported in countries where the available studies come from (namely, Canada and the United States of America). This may put portuguese physicians at a higher risk, making it imperative that work and wide debate are initiated among the class.

  5. Statistics On Title II Direct Payments To Claimant Representatives

    Data.gov (United States)

    Social Security Administration — Every person has the right to be represented by an attorney or other representative while pursuing a claim or other rights. This dataset contains data around Title...

  6. Physical modelling of representative particles of electrodeposited copper powders

    Directory of Open Access Journals (Sweden)

    SNEZANA B. KRSTIC

    2006-04-01

    Full Text Available A method for the estimation of the size of the representative particle of a copper powder is given. Cross sections of representative particles of flowing and non-flowing powders estimated by this procedure are also presented.

  7. 5-Azacytidine Promotes an Inhibitory T-Cell Phenotype and Impairs Immune Mediated Antileukemic Activity

    OpenAIRE

    Thomas Stübig; Anita Badbaran; Tim Luetkens; York Hildebrandt; Djordje Atanackovic; Binder, Thomas M. C.; Boris Fehse; Nicolaus Kröger

    2014-01-01

    Demethylating agent, 5-Azacytidine (5-Aza), has been shown to be active in treatment of myeloid malignancies. 5-Aza enhances anticancer immunity, by increasing expression of tumor-associated antigens. However, the impact of 5-Aza immune responses remains poorly understood. Here, T-cell mediated tumor immunity effects of 5-Aza, are investigated in vitro and in vivo. T-cells from healthy donors were treated with 5-Aza and analyzed by qRT-PCR and flow cytometry for changes in gene expression and...

  8. Up-regulation of HLA class-I antigen expression and antigen-specific CTL response in cervical cancer cells by the demethylating agent hydralazine and the histone deacetylase inhibitor valproic acid

    Directory of Open Access Journals (Sweden)

    Lizano-Soberón Marcela

    2006-12-01

    Full Text Available Abstract Background DNA hypermethylation and histone deacetylation are epigenetic events that contribute to the absence or downregulated expression of different components of the tumor recognition complex. These events affect the processing and presentation of antigenic peptides to CTLs by HLA class-I molecules. In this work evaluated the effect of the DNA hypomethylating agent hydralazine and the histone deacetylase inhibitor valproic acid, on the expression of HLA class-I molecules and on the antigen-specific immune recognition of cervical cancer cells. Methods Cell lines C33A (HPV-, CaSki (HPV-16+ and MS751 (HPV-18+ were treated with hydralazine and valproic acid to assess the expression of HLA class-I molecules by flow cytometry and RT-PCR. Promoter methylation of HLA class-I -A, -B and C, was also evaluated by Methylation-Specific PCR. Primary cervical tumors of four HLA-A*0201 allele patients were typed for HPV and their CTL's stimulated in vitro with the T2 cell line previously loaded with 50 μM of the HPV peptides. Cytotoxicity of stimulated CTL's was assayed against Caski and MS751 cells pre-treated with hydralazine and valproic acid. Results Valproic acid and hydralazine/valproic acid up-regulated the constitutive HLA class-I expression as evaluated by flow cytometry and RT-PCR despite constitutive promoter demethylation at these loci. Hydralazine and valproic acid in combination but no IFN-gamma hyperacetylated histone H4 as evaluated by ChiP assay. The antigenic immune recognition of CaSki and MS751 cells by CTLs specific to HPV-16/18 E6 and E7-derived epitopes, was increased by VA and H/VA and the combination of H/VA/IFN-gamma. Conclusion These results support the potential use of hydralazine and valproic acid as an adjuvant for immune intervention in cervical cancer patients whenever clinical protocols based on tumor antigen recognition is desirable, like in those cases where the application of E6 and E7 based therapeutic vaccines

  9. 42 CFR 422.1010 - Authority of representatives.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Authority of representatives. 422.1010 Section 422.1010 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES....1010 Authority of representatives. (a) A representative appointed and qualified in accordance with...

  10. 42 CFR 423.1010 - Authority of representatives.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Authority of representatives. 423.1010 Section 423.1010 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Penalties § 423.1010 Authority of representatives. (a) A representative appointed and qualified...

  11. 40 CFR 197.31 - What is a representative volume?

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false What is a representative volume? 197... a representative volume? (a) It is the volume of ground water that would be withdrawn annually from... Yucca Mountain disposal system that will be in the representative volume. The DOE must then use...

  12. 22 CFR 23.4 - Representative value in exchange.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Representative value in exchange. 23.4 Section 23.4 Foreign Relations DEPARTMENT OF STATE FEES AND FUNDS FINANCE AND ACCOUNTING § 23.4 Representative value in exchange. Representative value in exchange for the collection of a fee means...

  13. 19 CFR 146.2 - Port director as Board representative.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Port director as Board representative. 146.2...; DEPARTMENT OF THE TREASURY (CONTINUED) FOREIGN TRADE ZONES General Provisions § 146.2 Port director as Board representative. The appropriate port director shall be in charge of the zone as the representative of the Board....

  14. Multi-mode entangled states represented as Grassmannian polynomials

    Science.gov (United States)

    Maleki, Y.

    2016-06-01

    We introduce generalized Grassmannian representatives of multi-mode state vectors. By implementing the fundamental properties of Grassmann coherent states, we map the Hilbert space of the finite-dimensional multi-mode states to the space of some Grassmannian polynomial functions. These Grassmannian polynomials form a well-defined space in the framework of Grassmann variables; namely Grassmannian representative space. Therefore, a quantum state can be uniquely defined and determined by an element of Grassmannian representative space. Furthermore, the Grassmannian representatives of some maximally entangled states are considered, and it is shown that there is a tight connection between the entanglement of the states and their Grassmannian representatives.

  15. Multi-mode entangled states represented as Grassmannian polynomials

    Science.gov (United States)

    Maleki, Y.

    2016-09-01

    We introduce generalized Grassmannian representatives of multi-mode state vectors. By implementing the fundamental properties of Grassmann coherent states, we map the Hilbert space of the finite-dimensional multi-mode states to the space of some Grassmannian polynomial functions. These Grassmannian polynomials form a well-defined space in the framework of Grassmann variables; namely Grassmannian representative space. Therefore, a quantum state can be uniquely defined and determined by an element of Grassmannian representative space. Furthermore, the Grassmannian representatives of some maximally entangled states are considered, and it is shown that there is a tight connection between the entanglement of the states and their Grassmannian representatives.

  16. Investigations on Inhibitors of Hedgehog Signal Pathway: A Quantitative Structure-Activity Relationship Study

    Directory of Open Access Journals (Sweden)

    Zhiwei Cao

    2011-05-01

    Full Text Available The hedgehog signal pathway is an essential agent in developmental patterning, wherein the local concentration of the Hedgehog morphogens directs cellular differentiation and expansion. Furthermore, the Hedgehog pathway has been implicated in tumor/stromal interaction and cancer stem cell. Nowadays searching novel inhibitors for Hedgehog Signal Pathway is drawing much more attention by biological, chemical and pharmological scientists. In our study, a solid computational model is proposed which incorporates various statistical analysis methods to perform a Quantitative Structure-Activity Relationship (QSAR study on the inhibitors of Hedgehog signaling. The whole QSAR data contain 93 cyclopamine derivatives as well as their activities against four different cell lines (NCI-H446, BxPC-3, SW1990 and NCI-H157. Our extensive testing indicated that the binary classification model is a better choice for building the QSAR model of inhibitors of Hedgehog signaling compared with other statistical methods and the corresponding in silico analysis provides three possible ways to improve the activity of inhibitors by demethylation, methylation and hydroxylation at specific positions of the compound scaffold respectively. From these, demethylation is the best choice for inhibitor structure modifications. Our investigation also revealed that NCI-H466 served as the best cell line for testing the activities of inhibitors of Hedgehog signal pathway among others.

  17. Representative Delay Measurements (RDM: Facing the Challenge of Modern Networks

    Directory of Open Access Journals (Sweden)

    Joachim Fabini

    2015-02-01

    Full Text Available Network access technologies have evolved significantly in the last years. They deploy novel mechanisms like reactive capacity allocation and time-slotted operation to optimize overall network capacity. From a single node's perspective, such optimizations decrease network determinism and measurement repeatability. Evolving application fields like machine to machine (M2M communications or real-time gaming often have strict real-time requirements to operate correctly. Highly accurate delay measurements are necessary to monitor network compliance with application demands or to detect deviations of normal network behavior, which may be caused by network failures, misconfigurations or attacks. This paper analyzes factors that challenge active delay measurements in modern networks. It introduces the Representative Delay Measurement tool (RDM that addresses these factors and proposes solutions that conform to requirements of the recently published RFC7312. Delay measurement results acquired using RDM in live networks confirm that advanced measurement methods can significantly improve the quality of measurement samples by isolating systematic network behavior. The resulting high-quality samples are one prerequisite for accurate statistics that support proper operation of subsequent algorithms and applications.

  18. 5-氮杂-2′-脱氧胞苷诱导肝癌细胞株SLIT2基因去甲基化的实验研究%5-Aza-CdR induces demethylation of SLIT2 gene in human hepatoma cell lines

    Institute of Scientific and Technical Information of China (English)

    李培坤; 耿小平

    2015-01-01

    Objective To investigate the effect of 5-Aza-CdR on methylation state and transcription of SLIT2 gene in hepatocellular carcinoma cell lines,and to discuss mechanism of SLIT2 gene silencing in 5 human hepatoma cell lines as well as the effect of demethylation agent on its expression.Methods All cell lines of SUN449,BEL-7402,SMMC-7721,Hep3B and HepG2 were cultured in vitro and treated with 10 mmol/L 5-Aza-CdR.The promoter methylation state of SLIT2 gene and the mRNA expression of SLIT2 gene in the 5 hepatoma cell lines before and after 5-Aza-CdR treatment were detected by methylation-specific PCP (MSP)and reverse transcription-PCR (RT-PCR),re-spectively.Results Promoter hypermethylation of SLIT2 gene was detected in all 5 hepatoma cell lines and SLIT2 gene was expressed at a low level before 5-Aza-CdR treatment.After treated with demethylation agent 5-Aza-CdR,the promoter region of SLIT2 gene exhibited dem-ethylation state,and gene expression increased significantly at mRNA level.Conclusion Promoter hypermethylation is a main mechanism of SLIT2 gene silencing in 5 human hepatoma cell lines,and could be reversed by demethylation agent 5-Aza-CdR. carcinoma cell lines,and to discuss mechanism of SLIT2 gene silencing in 5 human hepatoma cell lines as well as the effect of demethylation agent on its expression.Methods All cell lines of SUN449,BEL-7402,SMMC-7721,Hep3B and HepG2 were cultured in vitro and treated with 10 mmol/L 5-Aza-CdR.The promoter methylation state of SLIT2 gene and the mRNA expression of SLIT2 gene in the 5 hepatoma cell lines before and after 5-Aza-CdR treatment were detected by methylation-specific PCP (MSP)and reverse transcription-PCR (RT-PCR),re-spectively.Results Promoter hypermethylation of SLIT2 gene was detected in all 5 hepatoma cell lines and SLIT2 gene was expressed at a low level before 5-Aza-CdR treatment.After treated with demethylation agent 5-Aza-CdR,the promoter region of SLIT2 gene exhibited dem-ethylation state,and gene expression

  19. High School Students' Perception of University Students as STEM Representatives

    DEFF Research Database (Denmark)

    Poulsen, Eva Lykkegaard

    The Danish government has an ambition to recruit more high school students into STEM edu-cations (science, technology, engineering and/or mathematics). The students’ choice of further education is based on the people and jobs they have knowledge of. Therefore, to recruit more students into STEM...... studies, it is important to introduce high school students to good STEM representatives to make possible the development of potential STEM identities. A potential identity within a specific subject area relies on at least a situation bound relation-ship to the subject area or the person representing it....... Some representatives transmit infor-mation and are thereby definers, whereas other representatives illustrates as personal examples and are thereby models. This study focuses on high school students’ views on STEM representatives and the impact these representatives have on the high school students...

  20. High School Students' perception of University Students as STEM representatives

    DEFF Research Database (Denmark)

    Poulsen, Eva Lykkegaard

    2012-01-01

    The Danish government has an ambition to recruit more high school students into STEM educations (science, technology, engineering and/or mathematics). The students’ choice of further education is based on the people and jobs they have knowledge of. Therefore, to recruit more students into STEM...... studies, it is important to introduce high school students to good STEM representatives to make possible the development of potential STEM identities. A potential identity within a specific subject area relies on at least a situation bound relationship to the subject area or the person representing it....... Some representatives transmit information and are thereby definers, whereas other representatives illustrates as personal examples and are thereby models. This study focuses on high school students’ views on STEM representatives and the impact these representatives have on the high school students...

  1. DNA methylation in porcine preimplantation embryos developed in-vivo or produced by in-vitro fertilization, parthenogenetic activation and somatic cell nuclear transfer

    DEFF Research Database (Denmark)

    Deshmukh, Rahul Shahaji; Østrup, Olga; Østrup, Esben;

    2011-01-01

    vitro fertilized (IVF), somatic cell nuclear transfer (SCNT) and parthenogenetically activated (PA) embryos were evaluated for DNA methylation quantification at different developmental stages. Fertilized (IV and IVF) one-cell stages lacked a substantial active demethylation of the paternal genome....... Embryos produced under in vitro conditions had higher levels of DNA methylation than IV. A lineage-specific DNA methylation (hypermethylation of the inner cell mass and hypomethylation of the trophectoderm) was observed in porcine IV late blastocysts, but was absent in PA- and SCNT-derived blastocysts...

  2. 22 CFR 41.25 - NATO representatives, officials, and employees.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false NATO representatives, officials, and employees... UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED Foreign Government Officials § 41.25 NATO representatives, officials, and employees. (a) Classification. An alien shall be classified under the symbol...

  3. 40 CFR 96.82 - NOX authorized account representative.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false NOX authorized account representative... PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS Individual Unit Opt-ins § 96.82 NOX authorized account representative. A unit for which...

  4. 40 CFR 97.82 - NOX authorized account representative.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false NOX authorized account representative... PROGRAMS (CONTINUED) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS Individual Unit Opt-ins. § 97.82 NOX authorized account representative. A unit for which an application for a...

  5. 32 CFR 705.14 - Embarkation of media representatives.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false Embarkation of media representatives. 705.14 Section 705.14 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY UNITED STATES... when they would be available for interviews and photos. (5) Representatives of press associations...

  6. 20 CFR 211.5 - Employee representative compensation.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Employee representative compensation. 211.5... CREDITABLE RAILROAD COMPENSATION § 211.5 Employee representative compensation. All payments made by a railway... office he occupies with such organization are creditable as compensation, including payments made...

  7. 14 CFR 183.31 - Designated manufacturing inspection representatives.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Designated manufacturing inspection representatives. 183.31 Section 183.31 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF...: Privileges § 183.31 Designated manufacturing inspection representatives. A designated...

  8. NLRP3 Activation Was Regulated by DNA Methylation Modification during Mycobacterium tuberculosis Infection

    Science.gov (United States)

    Wei, Meili; Wang, Lu; Wu, Tao; Xi, Jun; Han, Yuze; Yang, Xingxiang; Zhang, Ding; Fang, Qiang

    2016-01-01

    Mycobacterium tuberculosis (Mtb) infection activates the NLRP3 inflammasome in macrophages and dendritic cells. Much attention has been paid to the mechanisms for regulation of NLRP3 against Mtb. However, whether epigenetic mechanisms participated in NLRP3 activation is still little known. Here we showed that NLRP3 activation was regulated by DNA methylation modification. Mtb infection promoted NLRP3 activation and inflammatory cytokines expression. NLRP3 promoter was cloned and subsequently identified by Dual-Luciferase Reporter System. The results showed that NLRP3 promoter activity was decreased after methylation by DNA methylase Sss I in vitro. Meanwhile, DNA methyltransferases inhibitor DAC could upregulate the expression of NLRP3. Furthermore, promoter region of NLRP3 gene was demethylated after Mtb H37Rv strain infection. These data revealed that DNA methylation was involved in NLRP3 inflammasome activation during Mtb infection and provided a new insight into the relationship between host and pathogens. PMID:27366746

  9. Representing clusters using a maximum common edge substructure algorithm applied to reduced graphs and molecular graphs.

    Science.gov (United States)

    Gardiner, Eleanor J; Gillet, Valerie J; Willett, Peter; Cosgrove, David A

    2007-01-01

    Chemical databases are routinely clustered, with the aim of grouping molecules which share similar structural features. Ideally, medicinal chemists are then able to browse a few representatives of the cluster in order to interpret the shared activity of the cluster members. However, when molecules are clustered using fingerprints, it may be difficult to decipher the structural commonalities which are present. Here, we seek to represent a cluster by means of a maximum common substructure based on the shared functionality of the cluster members. Previously, we have used reduced graphs, where each node corresponds to a generalized functional group, as topological molecular descriptors for virtual screening. In this work, we precluster a database using any clustering method. We then represent the molecules in a cluster as reduced graphs. By repeated application of a maximum common edge substructure (MCES) algorithm, we obtain one or more reduced graph cluster representatives. The sparsity of the reduced graphs means that the MCES calculations can be performed in real time. The reduced graph cluster representatives are readily interpretable in terms of functional activity and can be mapped directly back to the molecules to which they correspond, giving the chemist a rapid means of assessing potential activities contained within the cluster. Clusters of interest are then subject to a detailed R-group analysis using the same iterated MCES algorithm applied to the molecular graphs. PMID:17309248

  10. Administrative Circular No. 13 (Rev. 3) - Guarantees for representatives of the personnel

    CERN Multimedia

    2014-01-01

    Administrative Circular No. 13 (Rev. 3) entitled “Guarantees for representatives of the personnel”, approved by the Director-General following discussion at the Standing Concertation Committee meeting of 5 December 2013 and entering into force on 1 January 2014, is available on the intranet site of the Human Resources Department (see here).   This circular is applicable to all members of the personnel. It cancels and replaces Administrative Circular No. 13 (Rev. 2) entitled “Guarantees for members of the personnel holding representative office” of November 1992. The circular was revised in order to adapt the time given to the representatives of the personnel to perform their elective mandate and to ensure more transparency in their activities, by indicating, inter alia, the percentage of time worked in the framework of their mandate, as well as the training, activities and ensuing results. Department Head Office HR Department

  11. Genetic Grouping of Medulloblastomas by Representative Markers in Pathologic Diagnosis1

    OpenAIRE

    Min, Hye Sook; Lee, Ji Yeoun; Kim, Seung-Ki; Park, Sung-Hye

    2013-01-01

    A recent analysis of the genetic features of medulloblastoma (MB) suggested classification into distinct subgroups according to gene expression profiles, including the Wingless signaling pathway-activated group (WNT group), the Sonic Hedgehog signaling pathway-activated group (SHH group), group 3, and group 4. To classify MB according to genetic features in practice, we analyzed 74 MBs using representative markers of each group. Based on immunohistochemistries (IHC), cytogenetic alterations, ...

  12. PENGARUH KOMPETENSI ACCOUNT REPRESENTATIVE DAN INDEPENDENSI ACCOUNT REPRESENTATIVE TERHADAP STRATEGI PENGAMANAN PENERIMAAN PAJAK KANWIL DIREKTORAT JENDERAL PAJAK DIY

    OpenAIRE

    ADIWIJAYA, Y.YUDITYA

    2014-01-01

    Penelitian ini dilakukan dengan tujuan untuk mengkaji dan mengidentifikasi apakah pihak Direktorat Jenderal Pajak, yang dalam hal ini adalah Kanwil Direktorat Jenderal Pajak DIY telah memikirkan aspek kompetensi dan independensi Account Representative dalam rangka memenuhi kebutuhan pelayanan Wajib Pajak agar target penerimaan pajak dapat tercapai. Survei dilakukan pada Account Representative yang berada di wilayah kerja Kanwil Direktorat Jenderal Pajak DIY. Penentuan responden dilakukan d...

  13. Do Perceptions of Hiring Criteria Differ for Sales Managers and Sales Representatives? Implications for Marketing Education

    Science.gov (United States)

    Raymond, Mary Anne; Carlson, Les; Hopkins, Christopher D.

    2006-01-01

    Using both qualitative and quantitative methods, this study explores whether perceptions of critical hiring criteria for entry-level sales positions differ across sales managers and sales representatives. This research also examines which classroom activities and skills these individuals perceive to be most important for strengthening the desired…

  14. Representative Model of the Learning Process in Virtual Spaces Supported by ICT

    Science.gov (United States)

    Capacho, José

    2014-01-01

    This paper shows the results of research activities for building the representative model of the learning process in virtual spaces (e-Learning). The formal basis of the model are supported in the analysis of models of learning assessment in virtual spaces and specifically in Dembo´s teaching learning model, the systemic approach to evaluating…

  15. Anti-tumor effect of 5-aza-2'-deoxycytidine by inhibiting telomerase activity in hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Shuang-Fen Tao; Chang-Song Zhang; Xian-Ling Guo; Yun Xu; Shan-Shan Zhang; Jian-Rui Song; Rong Li

    2012-01-01

    AIM:To investigate the effect of the demethylating reagent 5-aza-2'-deoxycitidine (DAC) on telomerase activity in hepatocellular carcinoma (HCC) cell lines,SMMC-7721 and HepG2.METHODS:The related gene expression in cell lines was examined by real-time reverse transcription-polymerase chain reaction and Western blotting analysis.The telomerase activity was examined by telomeric repeat amplification protocol-enzyme-linked immunosorbent assay and DNA methylation was determined by methylation-specific polymerase chain reaction.RESULTS:The telomerase activity was significantly reduced in both cell lines treated with DAC,accompanied by downregulation of telomerase reverse transcriptase (hTERT).We also observed the effect of DAC on the methylation status of hTERT promoter and the expression of regulatory genes,such as c-myc,p15,p16,p21,E2F1,and WT1.The methylation status of hTERT promoter could be reversed in SMMC-7721 by DAC,but not in HepG2 cells.However,p16 expression could be reactivated by demethylation of its promoter,and c-Myc expression was repressed in both cell lines.Moreover,DAC could enhance the sensitivity to the chemotherapeutic agents,such as cisplatin,by induction of apoptosis of HCC cells.CONCLUSION:The DAC exerts its anti-tumor effects in HCC cells by inhibiting the telomerase activity.

  16. Allegheny County Pennsylvania House of Representatives District Boundaries

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — This dataset demarcates the Pennsylvania House of Representatives district boundaries within Allegheny County. If viewing this description on the Western...

  17. Representative Consumer's Risk Aversion and Efficient Risk-Sharing Rules

    OpenAIRE

    Hara, Chiaki; Huang, James; Kuzmics, Christoph

    2007-01-01

    We study the representative consumer's risk attitude and efficient risk-sharing rules in a singleperiod, single-good economy in which consumers have homogeneous probabilistic beliefs but heterogeneous risk attitudes. We prove that if all consumers have convex absolute risk tolerance, so must the representative consumer. We also identify a relationship between the curvature of an individual consumer's individual risk sharing rule and his absolute cautiousness, the first derivative of absolute ...

  18. Representative Consumer's Risk Aversion and Efficient Risk-Sharing Rules

    OpenAIRE

    Hara, Chiaki; Kuzmics, Christoph

    2004-01-01

    We study the representative consumer's risk attitude and efficient risk-sharing rules in a single-period, single-good economy in which consumers have homogeneous probabilistic beliefs but heterogeneous risk attitudes. We prove that if all consumers have convex absolute risk tolerance, so must the representative consumer. We also identify a relationship between the curvature of an individual consumer's individual risk sharing rule and his absolute cautiousness, the first derivative of absolute...

  19. Lifestyle choices and mental health : a representative population survey

    OpenAIRE

    Velten, Julia; Lavallee, Kristen L; Scholten, Saskia; Meyer, Andrea Hans; Zhang, Xiao-Chi; Schneider, Silvia; Margraf, Jürgen

    2014-01-01

    Background Identifying healthy lifestyle behaviours that promote psychological wellbeing is crucial to preventing mental disorders. The aim of the current study was to evaluate the individual and combined associations between different aspects of everyday life and mental health within a representative community sample in Germany. Method The study was conducted in 2012/2013 and included 7,937 participants representative of the German population. Lifestyle factors were assessed via self-report ...

  20. Estimating PIGLOG Demands Using Representative versus Average Expenditure

    OpenAIRE

    Hahn, William F.; Taha, Fawzi A.; Davis, Christopher G.

    2013-01-01

    Economists often use aggregate time series data to estimate consumer demand functions. Some of the popular applied demand systems have a PIGLOG form. In the most general PIGLOG cases the “average” demand for a good is a function of the representative consumer expenditure not the average consumer expenditure. We would need detailed information on each period’s expenditure distribution to calculate the representative expenditure. This information is generally unavailable, so average expenditure...

  1. Disentangling the representativeness heuristic from the availability heuristic

    OpenAIRE

    Braga, João Pedro Niza

    2015-01-01

    Tese de doutoramento, Psicologia (Cognição Social), Universidade de Lisboa, Faculdade de Psicologia, 2015 Most judgments, predictions and decisions rely on simplifying reasoning heuristics, such as representativeness and availability heuristics. Representativeness heuristic relies on a judgment of similarity between a categorical prototype and a target. Availability heuristic relies on the accessibility of instances. A crucial assumption of Heuristics and Biases research progra...

  2. Work Induced Stress among Medical Representatives in Aurangabad City, Maharashtra

    OpenAIRE

    Sandip B Patil, Jeewan Singh Meena

    2013-01-01

    Introduction: As there is a boom in pharmaceutical industry nowadays, the need for the Medical representatives is also increasing simultaneously. The pressure of achieving targets is resulting into the work induced stress among medical representatives. Objective: To assess the work induced stress and various factors responsible for it and also to evaluate some of the health consequences. Method: To achieve the purpose of work, data was collected using a self-administered questionnaire...

  3. Direct and Representative Democracy - Supplementing, not Excluding Each Other

    DEFF Research Database (Denmark)

    Svensson, Palle

    2007-01-01

      This paper presents and discuses four main arguments for and against direct democracy, popular initiatives and referendums: (1) higher responsiveness versus lesser quality; (2) higher popular responsibility versus weaker representatives; (3) higher popular participation versus deeper conflicts......: and (4) more transparency and enlightened understanding versus less confidentiality. The arguments are discussed in relation to general political goals of good government such as legitimacy, efficiency and stability. The basic thesis of the paper is that direct and representative forms of democracy...

  4. Patient representatives' views on patient information in clinical cancer trials

    DEFF Research Database (Denmark)

    Dellson, Pia; Nilbert, Mef; Carlsson, Christina

    2016-01-01

    of future simplified and more attractive informed consent forms. CONCLUSIONS: The emotional and cognitive responses to written patient information reported by patient representatives provides a basis for revised formats in future trials and add to the body of information that support use of plain language...... responses. Subthemes related to the former included individual preferences and perceptions of effect, while subthemes related to the latter were comprehensibility and layout. Based on these observations the patient representatives provided suggestions for improvement, which largely included development...

  5. Elections for staff representatives – Join, commit and vote!

    CERN Multimedia

    Staff Association

    2015-01-01

    The Staff Council is a statutory body representing collectively in the area of employment conditions all CERN staff members (MPE and MPA), as well as the pensioners, former Cernois. The Staff Council is the supreme representative body of the CERN staff and pensioners, which defines the main lines of the policy of the Staff Association. The Staff Council is composed of staff representatives (45 seats to represent staff members, and 5 for representing fellows and associate members), as well as delegates for pensioners (seven positions), designated by GAC-EPA. Every two years, the Council is renewed through elections. Concerning the 45 delegates representing staff members, all departments have a least two seats allocated, one in career paths AA to D and one in career paths E to H. This guarantees a fair distribution of seats among the various organizational units and career paths. The table below, shows the exact number of delegates per department and career paths. Staff members or fellows who want to participa...

  6. Work Induced Stress among Medical Representatives in Aurangabad City, Maharashtra

    Directory of Open Access Journals (Sweden)

    Sandip B Patil, Jeewan Singh Meena

    2013-01-01

    Full Text Available Introduction: As there is a boom in pharmaceutical industry nowadays, the need for the Medical representatives is also increasing simultaneously. The pressure of achieving targets is resulting into the work induced stress among medical representatives. Objective: To assess the work induced stress and various factors responsible for it and also to evaluate some of the health consequences. Method: To achieve the purpose of work, data was collected using a self-administered questionnaire which was distributed to the medical representatives (n=100 by the principal investigator. The survey was carried in the city of Aurangabad during August to October 2012. Data were entered into SPSS (version 17 & analyzed using descriptive statistics. Result: Almost 66% of medical representatives were under pressure & were having some form of stress. Main reasons found were dissatisfaction with job profile (60%) & working hours (63%, continuous pressure for improved performance (73% and conflicting demands between work & home (78%. Conclusion: There is significant amount of work induced stress among medical representatives. It is creating many health ha-zards. Unless work induced stress among medical representatives is recognized and reduced they will remain on the brim of getting many health consequences.

  7. Identification of objective representative scenarios for hazard assessment

    Science.gov (United States)

    Sandri, Laura; Selva, Jacopo; Costa, Antonio

    2016-04-01

    Assessment of volcanic hazards is typically based on one or a few representative eruptive scenarios, meant as specific combinations of a representative eruptive size, intensity, and vent position, selected with subjective criteria neglecting the full intrinsic natural variability characterizing volcanic processes. In common practice, the size and intensity of such scenarios are taken as representative of wider ranges, here termed "size classes". The approach implicitly or explicitly assumes that the inter-size class variability (among different eruptive size classes) is predominant with respect to the intra-size class variability (i.e., the variability inside each range represented by an eruptive size and intensity), the latter assumed as negligible. So far, no quantitative study has been carried out to verify such an assumption. Here, we first adopt a novel statistical strategy, that accounts for the full natural variability, to quantify the Probabilistic Volcanic Hazard Assessment for tephra fallout in the Campania area. Secondly, we compare the results of the new method with those based on few representative scenarios only. On one hand, such comparison allows for determining when the simplified approach is valid, and quantifying the bias introduced in hazard assessment when the full variability is not accounted for. On the other hand, this novel approach opens the way to an objective a posteriori identification of a limited number of representative scenarios, which are necessary when there is no possibility to explore the full variability, as for example for rapid hazard assessment during emergencies, or for short-term hazard assessment.

  8. Heterogeneous researchers in a two-sector representative consumer economy

    Directory of Open Access Journals (Sweden)

    Orlando Gomes

    2006-06-01

    Full Text Available Research activities have uncertain outcomes. The question asked in this paper is whether or not this uncertainty can be a central piece on the explanation of long run consumption growth paths. More specifically, we inquire how the existence of different research projects, with different degrees of uncertainty, contributes to unpredictable consumption growth paths. The proposed scenario is a two-sector representative consumer model with researchers that invest in different innovation projects. There is heterogeneity in terms of risk associated to research programs (researchers invest in projects with the same expected outcome but different volatility. This difference in volatility, combined with an adaptive learning - bounded rationality rule, implies an aggregate index of technology and a consumption growth rate that do not present a predictable pattern over time.As actividades de investigação produzem resultados incertos. A questão colocada neste artigo é se esta incerteza pode ser uma peça central na explicação das trajectórias de crescimento do consumo no longo prazo. Mais especificamente, pergunta-se como a existência de diferentes projectos de investigação, com diferentes graus de incerteza associados, contribui para trajectórias de crescimento do consumo que não são passíveis de previsão. O cenário proposto é um modelo de consumidor representativo de dois sectores com investigadores que investem em diferentes projectos de inovação. Existe heterogeneidade ao nível do risco associado aos programas de investigação (os investigadores investem em projectos com o mesmo resultado esperado mas diferente volatilidade. A diferença na volatilidade, combinada com uma regra de aprendizagem adaptativa - racionalidade limitada, implica um índice agregado de tecnologia e uma taxa de crescimento do consumo que não apresentam um padrão previsível ao longo do tempo.

  9. The roles of co-chaperone CCRP/DNAJC7 in Cyp2b10 gene activation and steatosis development in mouse livers.

    Directory of Open Access Journals (Sweden)

    Marumi Ohno

    Full Text Available Cytoplasmic constitutive active/androstane receptor (CAR retention protein (CCRP and also known as DNAJC7 is a co-chaperone previously characterized to retain nuclear receptor CAR in the cytoplasm of HepG2 cells. Here we have produced CCRP knockout (KO mice and demonstrated that CCRP regulates CAR at multiple steps in activation of the cytochrome (Cyp 2b10 gene in liver: nuclear accumulation, RNA polymerase II recruitment and epigenetic modifications. Phenobarbital treatment greatly increased nuclear CAR accumulation in the livers of KO males as compared to those of wild type (WT males. Despite this accumulation, phenobarbital-induced activation of the Cyp2b10 gene was significantly attenuated. In ChIP assays, a CAR/retinoid X receptor-α (RXRα heterodimer binding to the Cyp2b10 promoter was already increased before phenobarbital treatment and further pronounced after treatment. However, RNA polymerase II was barely recruited to the promoter even after phenobarbital treatment. Histone H3K27 on the Cyp2b10 promoter was de-methylated only after phenobarbital treatment in WT but was fully de-methylated before treatment in KO males. Thus, CCRP confers phenobarbital-induced de-methylation capability to the promoter as well as the phenobarbital responsiveness of recruiting RNA polymerase II, but is not responsible for the binding between CAR and its cognate sequence, phenobarbital responsive element module. In addition, KO males developed steatotic livers and increased serum levels of total cholesterol and high density lipoprotein in response to fasting. CCRP appears to be involved in various hepatic regulations far beyond CAR-mediated drug metabolism.

  10. 地西他滨对急性白血病患者甲基化凋亡蛋白酶活化因子1基因的去甲基化作用%Demethylation stduy of decitabine in acute leukemia patients with Apaf-1 gene methylated

    Institute of Scientific and Technical Information of China (English)

    郭军; 杨恩芹; 杨晖

    2013-01-01

    Objective To investigate the effectiveness of decitabine demethylation in treatment of acute leukemia.Methods Methylation specific PCR (MSP) was used to detected the methylation status of Apaf-1 gene promoter.10 cases entering the group.MSP was used to detected the 10 cases methylation status of Apaf-1 promoter between pre-and post-treatment of dicitabine.RT-PCR method used was to detect the differential expression levels of Apaf-1 mRNA in acute leukemia bone marrow mononuclear cell between preand post-treatment of decitabine.Results In post-treatment of decitabine,6 cases Apaf-1 gene promoter was demethylated.The loss expression of Apaf-1 mRNA re-expressed in 4 cases.6 cases Apaf-1 mRNA still express deletion.6 cases patients have Apaf-1 mRNA exprssion deletion,However,4 cases Apaf-1 gene was demethylated,2 cases methylated in post-treatment,maybe related to allele deletion or allelic varriants.Conclusion Post treatment of decitabine.Apaf-1 gene promotor was demethylated and repress the expression of Apaf-1 mRNA,play a key role in apoptosis maybe a new method for treatment of acute leukemia.%目的 探讨地西他滨去甲基化作用治疗急性白血病患者的有效性.方法 通过甲基化特异性PCR选取10例凋亡蛋白酶活化因子1(Apaf-1)基因启动子发生甲基化的患者,经地西他滨治疗后,通过甲基化特异性PCR检测患者Apaf-1基因去甲基化状态.通过反转录PCR检测10例患者经地西他滨治疗前后骨髓单个核细胞Apaf-1基因mRNA表达情况.结果 甲基化特异性PCR检测示,10例患者经地西他滨治疗后,6例发生了去甲基化.治疗前10例患者因甲基化Apaf-1 mRNA均表达缺失,经地西他滨治疗后,4例重新表达,6例未表达.治疗后6例Apaf-1 mRNA表达缺失的患者中,4例Apaf-1基因未发生去甲基化,2例发生去甲基化,考虑可能与等位基因缺失或突变有关.结论 地西他滨通过使Apaf-1基因启动子去甲基化恢复抑癌基因的表达,发挥其凋亡中的关键因子作用.

  11. Associated factors of obesity in Spanish representative samples

    Directory of Open Access Journals (Sweden)

    Rosa M. Ortega Anta

    2013-09-01

    Full Text Available Given the dramatic increase in the prevalence of obesity and the serious health and economic consequences, the scientific community, health professionals and health agencies are looking for the best strategies to prevent/ fight this trend. In order to plan the most appropriate intervention measures the first step is to identify the associated factors of obesity. This paper presents the results of research conducted/coordinated by our research team and promoted by the Spanish Food Safety Agency (AESAN, in the last five years. These studies were focussed on representative samples of the Spanish population, paying attention to the condition of overweight/obesity and their associated factors. The first study, FANPE ("Fuentes alimentarias de nutrientes de la población española" (2009, was centered in 418 adults (18-60 years from 15 provinces (30 sampling points. Its aim was to analyze the dietary sources of nutrients, paying particular attention to sodium. This research showed that the risk of overweight/obesity increases with age, in people who have follow weight control diets, in ex-smokers, married people and those who slept less than 8.5 hours per day, while the risk is lower in women, people who make sport and those with an University degree. It was also found that overweight people had higher sodium intake and urine excretion. Therefore, and having in mind that 88.2% of the subjects took more than 2 g/day of sodium (the maximum recommended, it is advised to lower the sodium intake not only from the health point of view but also as a probably strategy against obesity. The study ALADINO (Estudio de Alimentación, Actividad física, Desarrollo Infantil y Obesidad- Study of the Diet, Physical Activity, Child Development and Obesity (2010-2011 was focused on 7659 children (6-9 years from 19 autonomous communities. We founded a higher percentage of overweight/obesity in boys than in girls, and a significant increase in the figures from the age of 7

  12. Associated factors of obesity in Spanish representative samples.

    Science.gov (United States)

    Ortega Anta, Rosa M; López-Solaber, Ana M; Pérez-Farinós, Napoleón

    2013-09-01

    Given the dramatic increase in the prevalence of obesity and the serious health and economic consequences, the scientific community, health professionals and health agencies are looking for the best strategies to prevent/ fight this trend. In order to plan the most appropriate intervention measures the first step is to identify the associated factors of obesity. This paper presents the results of research conducted/coordinated by our research team and promoted by the Spanish Food Safety Agency (AESAN), in the last five years. These studies were focussed on representative samples of the Spanish population, paying attention to the condition of overweight/obesity and their associated factors. The first study, FANPE ("Fuentes alimentarias de nutrientes de la población española") (2009), was centered in 418 adults (18-60 years) from 15 provinces (30 sampling points). Its aim was to analyze the dietary sources of nutrients, paying particular attention to sodium. This research showed that the risk of overweight/obesity increa ses with age, in people who have follow weight control diets, in ex-smokers, married people and those who slept less than 8.5 hours per day, while the risk is lower in women, people who make sport and those with a University degree. It was also found that overweight people had higher sodium intake and urine excretion. Therefore, and having in mind that 88.2% of the subjects took more than 2 g/day of sodium (the maximum recommended), it is advised to lower the sodium intake not only from the health point of view but also as a probably strategy against obesity. The study ALADINO (Estudio de Alimentación, Actividad física, Desarrollo Infantil y Obesidad--Study of the Diet, Physical Activity, Child Development and Obesity) (2010-2011) was focused on 7659 children (6-9 years) from 19 autonomous communities. We founded a higher percentage of overweight/obesity in boys than in girls, and a significant increase in the figures from the age of 7. Being

  13. Associated factors of obesity in Spanish representative samples.

    Science.gov (United States)

    Ortega Anta, Rosa M; López-Solaber, Ana M; Pérez-Farinós, Napoleón

    2013-09-01

    Given the dramatic increase in the prevalence of obesity and the serious health and economic consequences, the scientific community, health professionals and health agencies are looking for the best strategies to prevent/ fight this trend. In order to plan the most appropriate intervention measures the first step is to identify the associated factors of obesity. This paper presents the results of research conducted/coordinated by our research team and promoted by the Spanish Food Safety Agency (AESAN), in the last five years. These studies were focussed on representative samples of the Spanish population, paying attention to the condition of overweight/obesity and their associated factors. The first study, FANPE ("Fuentes alimentarias de nutrientes de la población española") (2009), was centered in 418 adults (18-60 years) from 15 provinces (30 sampling points). Its aim was to analyze the dietary sources of nutrients, paying particular attention to sodium. This research showed that the risk of overweight/obesity increa ses with age, in people who have follow weight control diets, in ex-smokers, married people and those who slept less than 8.5 hours per day, while the risk is lower in women, people who make sport and those with a University degree. It was also found that overweight people had higher sodium intake and urine excretion. Therefore, and having in mind that 88.2% of the subjects took more than 2 g/day of sodium (the maximum recommended), it is advised to lower the sodium intake not only from the health point of view but also as a probably strategy against obesity. The study ALADINO (Estudio de Alimentación, Actividad física, Desarrollo Infantil y Obesidad--Study of the Diet, Physical Activity, Child Development and Obesity) (2010-2011) was focused on 7659 children (6-9 years) from 19 autonomous communities. We founded a higher percentage of overweight/obesity in boys than in girls, and a significant increase in the figures from the age of 7. Being

  14. Selection of Representative Models for Decision Analysis Under Uncertainty

    Science.gov (United States)

    Meira, Luis A. A.; Coelho, Guilherme P.; Santos, Antonio Alberto S.; Schiozer, Denis J.

    2016-03-01

    The decision-making process in oil fields includes a step of risk analysis associated with the uncertainties present in the variables of the problem. Such uncertainties lead to hundreds, even thousands, of possible scenarios that are supposed to be analyzed so an effective production strategy can be selected. Given this high number of scenarios, a technique to reduce this set to a smaller, feasible subset of representative scenarios is imperative. The selected scenarios must be representative of the original set and also free of optimistic and pessimistic bias. This paper is devoted to propose an assisted methodology to identify representative models in oil fields. To do so, first a mathematical function was developed to model the representativeness of a subset of models with respect to the full set that characterizes the problem. Then, an optimization tool was implemented to identify the representative models of any problem, considering not only the cross-plots of the main output variables, but also the risk curves and the probability distribution of the attribute-levels of the problem. The proposed technique was applied to two benchmark cases and the results, evaluated by experts in the field, indicate that the obtained solutions are richer than those identified by previously adopted manual approaches. The program bytecode is available under request.

  15. Representing Topological Relationships Among Heterogeneous Geometry-Collection Features

    Institute of Scientific and Technical Information of China (English)

    Zhi-NongZhong[; NingJing; LuoChen; Qiu-YunWu

    2004-01-01

    Topological relationships between two spatial features represent important knowledge in Geographical Information Systems (GIS). In the last few years, many models that represent topological relationships have been proposed. But these models cannot represent the topological relationships between heterogeneous geometrycollection features, which are composed of different dimensional geometries. In this paper, the formal definition of regular heterogeneous geometrycollection and regularization rules are given. Based on the spatial model, two methods for representing topological relationships between these complex features are proposed. The first method is Dimensionally Extended Nine-Intersection Model Based on Components (DE-9IMBC) that extends Dimensionally Extended Nine-Intersection Model (DE-9IM) and takes into account the topological relationships between components of these complex features. The advantage of DE-9IMBC is that a large number of different topological relationships can be checked. The second method extends the definitions of topological relationships in Open Geodata Interoperability Specification (OpenGIS), and redefines the seven named topological relationships: {Disjoint, Touches, Within, Crosses, Overlaps, Contains and Equal}, to represent the topological relationships between heterogeneous geometrycollection features. It is proven that the seven extended topological relationships are complete and mutually exclusive, and they are suitable for being embedded in spatial query languages.

  16. Representing Topological Relationships Among Heterogeneous Geometry-Collection Features

    Institute of Scientific and Technical Information of China (English)

    Zhi-Nong Zhong; Ning Jing; Luo Chen; Qiu-Yun Wu

    2004-01-01

    Topological relationships between two spatial features represent important knowledge in Geographical Information Systems (GIS). In the last few years, many models that represent topological relationships have been proposed. But these models cannot represent the topological relationships between heterogeneous geometrycollection features, which are composed of different dimensional geometries. In this paper, the formal definition of regular heterogeneous geometrycollection and regularization rules are given. Based on the spatial model, two methods for representing topological relationships between these complex features are proposed. The first method is Dimensionally Extended Nine-Intersection Model Based on Components (DE-9IMBC) that extends Dimensionally Extended Nine-Intersection Model (DE-9IM) and takes into account the topological relationships between components of these complex features. The advantage of DE-9IMBC is that a large number of different topological relationships can be checked. The second method extends the definitions of topological relationships in Open Geodata Interoperability Specification (OpenGIS), and redefines the seven named topological relationships:{Disjoint, Touches, Within, Crosses, Overlaps, Contains and Equal}, to represent the topological relationships between heterogeneous geometrycollection features. It is proven that the seven extended topological relationships are complete and mutually exclusive, and they are suitable for being embedded in spatial query languages.

  17. Automatic selection of representative proteins for bacterial phylogeny

    Directory of Open Access Journals (Sweden)

    Goldberg David

    2005-05-01

    Full Text Available Abstract Background Although there are now about 200 complete bacterial genomes in GenBank, deep bacterial phylogeny remains a difficult problem, due to confounding horizontal gene transfers and other phylogenetic "noise". Previous methods have relied primarily upon biological intuition or manual curation for choosing genomic sequences unlikely to be horizontally transferred, and have given inconsistent phylogenies with poor bootstrap confidence. Results We describe an algorithm that automatically picks "representative" protein families from entire genomes for use as phylogenetic characters. A representative protein family is one that, taken alone, gives an organismal distance matrix in good agreement with a distance matrix computed from all sufficiently conserved proteins. We then use maximum-likelihood methods to compute phylogenetic trees from a concatenation of representative sequences. We validate the use of representative proteins on a number of small phylogenetic questions with accepted answers. We then use our methodology to compute a robust and well-resolved phylogenetic tree for a diverse set of sequenced bacteria. The tree agrees closely with a recently published tree computed using manually curated proteins, and supports two proposed high-level clades: one containing Actinobacteria, Deinococcus, and Cyanobacteria ("Terrabacteria", and another containing Planctomycetes and Chlamydiales. Conclusion Representative proteins provide an effective solution to the problem of selecting phylogenetic characters.

  18. A geographic data model for representing ground water systems.

    Science.gov (United States)

    Strassberg, Gil; Maidment, David R; Jones, Norm L

    2007-01-01

    The Arc Hydro ground water data model is a geographic data model for representing spatial and temporal ground water information within a geographic information system (GIS). The data model is a standardized representation of ground water systems within a spatial database that provides a public domain template for GIS users to store, document, and analyze commonly used spatial and temporal ground water data sets. This paper describes the data model framework, a simplified version of the complete ground water data model that includes two-dimensional and three-dimensional (3D) object classes for representing aquifers, wells, and borehole data, and the 3D geospatial context in which these data exist. The framework data model also includes tabular objects for representing temporal information such as water levels and water quality samples that are related with spatial features. PMID:17600583

  19. Novel, Unifying Mechanism for Mescaline in The Central Nervous System: Electrochemistry, Catechol Redox Metabolite, Receptor, Cell Signaling and Structure Activity Relationships

    Directory of Open Access Journals (Sweden)

    Peter Kovacic

    2009-01-01

    Full Text Available A unifying mechanism for abused drugs has been proposed previously from the standpoint of electron transfer. Mescaline can be accommodated within the theoretical framework based on redox cycling by the catechol metabolite with its quinone counterpart. Electron transfer may play a role in electrical effects involving the nervous system in the brain. This approach is in accord with structure activity relationships involving mescaline, abused drugs, catecholamines and etoposide. Inefficient demethylation is in keeping with the various drug properties, such as requirement for high dosage and slow acting.

  20. Spatio-temporal representativeness of aerosol remote sensing observations

    Science.gov (United States)

    Schutgens, Nick; Gryspeerdt, Edward; Tsyro, Svetlana; Goto, Daisuke; Watson-Parris, Duncan; Weigum, Natalie; Schulz, Michael; Stier, Philip

    2016-04-01

    One characteristic of remote sensing observations is the strong intermittency with which they observe the same scene. Due to unfavourable conditions (due to e.g. low visible light, cloudiness or high surface albedo), sampling constraints (due to e.g. polar orbits) or instrument malfunction or maintenance, gaps in the observing record of hours to months exist. At the same time, satellite L3 products often are spatial aggregates over considerable distances (e.g. 1 by 1 degree). We study the impact of spatio-temporal sampling of observations on their representativeness: i.e. how well can satellite products represent the large scale (~ 100 by 100 km) aerosol field over periods of days, months, or years. This study was conducted by using diverse global and regional aerosol models as a truth and sub-sample them according to actual observations. In this way, we have been able to study the representativeness of different observing systems like MODIS, CALIOP and AERONET. Monthly and yearly averages allow serious sampling errors, that may still be present in multi-year climatologies due to recurring observing patterns. Even daily averages are affected as diurnal cycles can often not be observed. We discuss the implications these representativeness errors have for e.g. model evaluation or the construction of climatologies. We also assess similar representativeness issues in ground site in-situ observations from e.g. EMEP or IMPROVE and show that satellite datasets have distinct advantages due to their better spatial coverage provided temporal sampling is dealt with properly (i.e. through collocation of datasets). Finally, we briefly introduce a software tool (the Community Intercomparison Suite or CIS) that is designed to improve representativeness of datasets in intercomparion studies through aggregation and collocation of data.

  1. Fuel options from microalgae with representative chemical compositions

    Energy Technology Data Exchange (ETDEWEB)

    Feinberg, D. A.

    1984-07-01

    Representative species of microalgae are examined with respect to their reported chemical compositions. Each species is analyzed under a variety of culture conditions, with the objective being to characterize an optimum mixture of fuel products (e.g., methane, ethanol, methylester) which should be produced by the particular species. Historically the emphasis has been on the entire algal cell mass. Using the reported chemical composition for the representative species under specific sets of growth conditions, some conclusions can be drawn about the preferred fuel product conversion routes that could be employed. 10 references, 7 figures, 12 tables.

  2. A geometric language for representing structure in polyphonic music

    DEFF Research Database (Denmark)

    Meredith, David

    2012-01-01

    In 1981, Deutsch and Feroe proposed a formal language for representing melodic pitch structure that employed the powerful concept of hierarchically-related pitch alphabets. However, neither rhythmic structure nor pitch structure in polyphonic music can be adequately represented using this language....... A new language is proposed here that incorporates certain features of Deutsch and Feroe’s model but extends and generalises it to allow for the representation of both rhythm and pitch structure in polyphonic music. The new language adopts a geometric approach in which a passage of polyphonic music...

  3. Closed-set-based Discovery of Representative Association Rules Revisited

    CERN Document Server

    Balcázar, José L

    2010-01-01

    The output of an association rule miner is often huge in practice. This is why several concise lossless representations have been proposed, such as the "essential" or "representative" rules. We revisit the algorithm given by Kryszkiewicz (Int. Symp. Intelligent Data Analysis 2001, Springer-Verlag LNCS 2189, 350-359) for mining representative rules. We show that its output is sometimes incomplete, due to an oversight in its mathematical validation, and we propose an alternative complete generator that works within only slightly larger running times.

  4. Representing adaptive eLearning strategies in IMS Learning Design

    NARCIS (Netherlands)

    Burgos, Daniel; Tattersall, Colin; Koper, Rob

    2006-01-01

    Burgos, D., Tattersall, C., & Koper, E. J. R. (2006). Representing adaptive eLearning strategies in IMS Learning Design. In R. Koper & K. Stefanov (Eds.), Proceedings of the International Workshop in Learning Networks for Lifelong Competence Development (pp. 54-60). March, 30-31, 2006, Sofia, Bulgar

  5. 26 CFR 31.3211-3 - Employee representative supplemental tax.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Employee representative supplemental tax. 31... (CONTINUED) EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE Railroad Retirement Tax Act (Chapter 22, Internal Revenue Code of 1954) Tax on...

  6. 42 CFR 422.672 - Appointment of representatives.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Appointment of representatives. 422.672 Section 422.672 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM MEDICARE ADVANTAGE PROGRAM Medicare Contract Determinations and Appeals §...

  7. 42 CFR 422.674 - Authority of representatives.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Authority of representatives. 422.674 Section 422.674 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM MEDICARE ADVANTAGE PROGRAM Medicare Contract Determinations and Appeals §...

  8. Research Note: Representing Identity and Relationships in Information Systems

    OpenAIRE

    Martin, M.

    2007-01-01

    This research note is concerned with how identity and of relationship are represented in information systems. It presents a real world example of the problems that can arise in the delivery of social care and explores some thoughts about the application of Peirce’s ideas to respond to these issues in the context of case management and record systems.

  9. Party member recruitment and the representativeness of party membership

    DEFF Research Database (Denmark)

    Kosiara-Pedersen, Karina

    Party membership figures are in decline. However, parties are still recruiting party members. Are there any differences in the social and political characteristics of old and new party members? If there is a difference, are new party members more or less representative for party voters than old...

  10. Sexual desire in a nationally representative Danish population

    DEFF Research Database (Denmark)

    Eplov, Lene; Giraldi, Annamaria; Davidsen, Michael;

    2007-01-01

    INTRODUCTION: There are only a few studies on the frequency of sexual desire in the general population, whereas studies investigating the frequency of disordered sexual desire are more common. AIM: The aim of this study was to describe the frequency of sexual desire in a representative sample of ...

  11. 7 CFR 1212.12 - Importer-Handler Representative.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Importer-Handler Representative. 1212.12 Section 1212... PACKERS AND IMPORTERS RESEARCH, PROMOTION, CONSUMER EDUCATION AND INDUSTRY INFORMATION ORDER Honey Packers and Importers Research, Promotion, Consumer Education, and Industry Information Order...

  12. 40 CFR 97.11 - Alternate NOX authorized account representative.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Alternate NOX authorized account... PROGRAMS (CONTINUED) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS NOX Authorized Account Representative for NOX Budget Sources § 97.11 Alternate NOX authorized...

  13. 40 CFR 96.11 - Alternate NOX authorized account representative.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Alternate NOX authorized account... PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS NOX Authorized Account Representative for NOX Budget Sources § 96.11 Alternate...

  14. Exhaustive search for conservation networks of populations representing genetic diversity.

    Science.gov (United States)

    Diniz-Filho, J A F; Diniz, J V B P L; Telles, M P C

    2016-01-01

    Conservation strategies routinely use optimization methods to identify the smallest number of units required to represent a set of features that need to be conserved, including biomes, species, and populations. In this study, we provide R scripts to facilitate exhaustive search for solutions that represent all of the alleles in networks with the smallest possible number of populations. The script also allows other variables to be added to describe the populations, thereby providing the basis for multi-objective optimization and the construction of Pareto curves by averaging the values in the solutions. We applied this algorithm to an empirical dataset that comprised 23 populations of Eugenia dysenterica, which is a tree species with a widespread distribution in the Cerrado biome. We observed that 15 populations would be necessary to represent all 249 alleles based on 11 microsatellite loci, and that the likelihood of representing all of the alleles with random networks is less than 0.0001. We selected the solution (from two with the smallest number of populations) obtained for the populations with a higher level of climatic stability as the best strategy for in situ conservation of genetic diversity of E. dysenterica. The scripts provided in this study are a simple and efficient alternative to more complex optimization methods, especially when the number of populations is relatively small (i.e., <25 populations). PMID:26909939

  15. Using sound to represent spatial data in ArcGIS

    Science.gov (United States)

    Bearman, Nick; Fisher, Peter F.

    2012-09-01

    An extension to ESRI's, ArcGIS was created to allow spatial data to be represented using sound. A number of previous studies have used sound in combination with visual stimuli, but only a limited selection have looked at this with explicit reference to spatial data and none have created an extension for industry standard GIS software. The extension can sonify any raster data layer and represent this using piano notes. The user can choose from a number of different scales of piano notes and decide how the program plays the sound; this flexibility allows the extension to effectively represent a number of different types of data. The extension was evaluated in one-to-one semi-structured interviews with geographical information professionals, who explored aspects of a number of different data sets. Further research is needed to discover the best use of sound in a spatial data context, both in terms of which sounds to use and what data are most effectively represented using those sounds.

  16. Teachers' Voices/Stories: Dilemmas in Representing the Research Data

    Science.gov (United States)

    Naidu, Sham

    2011-01-01

    The article discusses the issue of how to represent teachers' stories and narratives in the arena of performance management. It is argued that at a time when "teachers" voices are being enthusiastically pursued and promoted, teachers' work is being technisized and narrowed" (Goodson, 1998). Arguably, teachers' knowledge regarding their work…

  17. New Strategies for Representing Mental Illness on Canadian Stages

    Science.gov (United States)

    Johnston, Kirsty

    2009-01-01

    Workman Arts, a Toronto-based theatre and visual arts company with a 20-year history, provides a rich site for re-imagining stigmatised representations of mental illness. Writing and performing against a long tradition of representing people with mental illnesses as incoherent speakers and visually different, company members seek to re-imagine…

  18. How Physicians "Learn" from Pharmaceutical Representatives: An Exploration.

    Science.gov (United States)

    Slotnick, H. B.; Kristjanson, Arlinda F.

    1999-01-01

    Interviews with 118 rural and urban physicians revealed their belief that pharmaceutical information provided in response to their questions was more credible than that offered spontaneously by sales representatives. Information must satisfy an existing need and must be verified as a possible solution to practice problems. (SK)

  19. Professional Human Service Occupation Biases Represented in General Psychology Textbooks

    Science.gov (United States)

    Firmin, Michael W.; Johnson, Erica J.; Wikler, Jeremiah

    2009-01-01

    We examined the coverage given by General Psychology textbooks, representing 8 major commercial publishers, regarding the professions of psychology, counseling, marriage & family therapy, and social workers. Of the 24 textbooks assessed, we found substantial bias favoring the coverage of psychology. While 25% of the texts mentioned social workers,…

  20. Identifying and Representing Elements of Local Contexts in Namibia

    DEFF Research Database (Denmark)

    Rodil, Kasper; Løvborg Jensen, Kasper; Rehm, Matthias;

    2013-01-01

    In an attempt to represent local context in a 3D visualisa- tionfor rural elders in Namibia we have foundmajor dierences in thecon- ceptualizationof this context between external and local partners in the co-creation process. Through the evaluation of a mobile context capture tool we found a clear...

  1. Communication received from the Resident Representatives of Argentina and Brazil

    International Nuclear Information System (INIS)

    The document reproduces the communication received by the Director General from the Resident Representatives of Argentina and Brazil to the Agency to inform him about the official inauguration on 9 December 1992 of the headquarters of the Brazilian-Argentine Agency for Accounting and Control of Nuclear Materials (ABACC) in Rio de Janeiro

  2. Reaching a Representative Sample of College Students: A Comparative Analysis

    Science.gov (United States)

    Giovenco, Daniel P.; Gundersen, Daniel A.; Delnevo, Cristine D.

    2016-01-01

    Objective: To explore the feasibility of a random-digit dial (RDD) cellular phone survey in order to reach a national and representative sample of college students. Methods: Demographic distributions from the 2011 National Young Adult Health Survey (NYAHS) were benchmarked against enrollment numbers from the Integrated Postsecondary Education…

  3. Representing and Inferring Visual Perceptual Skills in Dermatological Image Understanding

    Science.gov (United States)

    Li, Rui

    2013-01-01

    Experts have a remarkable capability of locating, perceptually organizing, identifying, and categorizing objects in images specific to their domains of expertise. Eliciting and representing their visual strategies and some aspects of domain knowledge will benefit a wide range of studies and applications. For example, image understanding may be…

  4. Voice of the People: Representative Government in the United States.

    Science.gov (United States)

    Bliss, Pam, Ed.; Heinz, Ann, Ed.; Kaplan, Howard, Ed.; Landman, James, Ed.

    2001-01-01

    This magazine aims to help high school teachers of civics, government, history, law, and law-related education program developers educate students about legal issues. This issue focuses on voting. It contains 11 articles: (1) "The Project of Democracy" (A. Keyssar) demonstrates how the story of the right to vote represents a slow and fitful…

  5. Planning to Move: Effects on Representing the Currently Inhabited Environment.

    Science.gov (United States)

    Wofsey, Elizabeth; And Others

    1979-01-01

    Individuals with articulated plans for moving to a new environment and individuals lacking such plans produced written descriptions and drawings of their currently inhabited environment. Results indicated that individuals with highly articulated plans represented their present environment as reflecting significantly greater self-world distancing…

  6. 22 CFR 41.52 - Information media representative.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Information media representative. 41.52 Section 41.52 Foreign Relations DEPARTMENT OF STATE VISAS VISAS: DOCUMENTATION OF NONIMMIGRANTS UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED Business and Media Visas § 41.52 Information media...

  7. Representing Mental Spaces and Dynamics of Natural Language Semantics

    Directory of Open Access Journals (Sweden)

    Ramin Golshaie

    2011-01-01

    Full Text Available

    Building systems with the robustness of human reasoning capabilities requires inspirations from cognitive science.  The primary objective of this study is to investigate the possibility of representing some basic principles of cognitive semantics’ Mental Spaces Theory such as domain construction, reality status of domains and their elements, and mental attitudes in a knowledge representation framework for the purpose of developing cognitively plausible knowledge representation systems. The model used as the basis of representation is the extended version of conventional semantic networks, namely Multi-Layered Extended Semantic Networks (MultiNet. The data used in this study have been selected from English expressions and have been represented in MWR, MultiNet’s knowledge representation software. Results obtained from analysis of represented data and their comparison to principles of mental spaces theory shows that theoretical constructs of mental spaces theory such as domain construction, reality status of domains and their elements, and mental attitudes can be formally represented in the MultiNet framework.

  8. 20 CFR 410.583 - Responsibility of representative payee.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Responsibility of representative payee. 410.583 Section 410.583 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL COAL MINE HEALTH AND SAFETY ACT OF 1969, TITLE IV-BLACK LUNG BENEFITS (1969- ) Payment of Benefits § 410.583 Responsibility...

  9. 20 CFR 266.7 - Accountability of a representative payee.

    Science.gov (United States)

    2010-04-01

    ... felony or misdemeanor offense under the statutes administered by the Board or by the Social Security... responsibility for the care of the annuitant. If the representative payee does not give the Board the requested... determines that the payee had a good reason for not complying with the Board's request, and the...

  10. Development of Reasoning Associated with Pictographs: Representing, Interpreting, and Predicting.

    Science.gov (United States)

    Watson, Jane M.; Moritz, Jonathan B.

    2001-01-01

    Proposes a developmental model involving four response levels concerning how students arrange pictures to represent data in a pictograph, how they interpret these pictographs, and how they make predictions based on these pictographs. The model is exemplified by responses from three related interview-based studies. Discusses educational…

  11. Learning, Labour and Union Learning Representatives: Promoting Workplace Learning

    Science.gov (United States)

    Ball, Malcolm

    2011-01-01

    The initiative by the Trades Union Congress (TUC) and affiliated trade unions in the UK to appoint trade union learning representatives (ULRs), to promote learning among their members, is a significant development in adult learning. Understandably, the initiative has attracted the attention of academic researchers, but primarily from the…

  12. Representing User Navigation in XML Retrieval with Structural Summaries

    DEFF Research Database (Denmark)

    Ali, M. S.; Consens, Mariano P.; Larsen, Birger

    This poster presents a novel way to represent user navigation in XML retrieval using collection statistics from XML summaries. Currently, developing user navigation models in XML retrieval is costly and the models are specific to collected user assessments. We address this problem by proposing...

  13. 20 CFR 404.1705 - Who may be your representative.

    Science.gov (United States)

    2010-04-01

    ...) Attorney. You may appoint as your representative in dealings with us, any attorney in good standing who— (1) Has the right to practice law before a court of a State, Territory, District, or island possession of the United States, or before the Supreme Court or a lower Federal court of the United States; (2)...

  14. 20 CFR 416.1505 - Who may be your representative.

    Science.gov (United States)

    2010-04-01

    ...) Attorney. You may appoint as your representative in dealings with us any attorney in good standing who— (1) Has the right to practice law before a court of a State, Territory, District, or island possession of the United States, or before the Supreme Court or a lower Federal court of the United States; (2)...

  15. The role of a representative reinsurer in optimal reinsurance

    NARCIS (Netherlands)

    T.J. Boonen; K.S. Tan; S.C. Zhuang

    2016-01-01

    In this paper, we consider a one-period optimal reinsurance design model with nn reinsurers and an insurer. For very general preferences of the insurer and that all reinsurers use a distortion premium principle, we establish the existence of a representative reinsurer and this in turn facilitates so

  16. Representativeness and seasonality of major ion records derived from NEEM firn cores

    Directory of Open Access Journals (Sweden)

    G. Gfeller

    2014-05-01

    Full Text Available The seasonal and annual representativeness of ionic aerosol proxies (among others, calcium, sodium, ammonium and nitrate in various firn cores in the vicinity of the NEEM drill site in north-west Greenland have been assessed. Seasonal representativeness is very high as one core explains more than 60% of the variability within the area. The inter-annual representativeness, however, can be substantially lower (depending on the species making replicate coring indispensable to derive the atmospheric variability of aerosol species. A single core at the NEEM site records only 30% of the inter-annual atmospheric variability in some species, while five replicate cores are already needed to cover approximately 70% of the inter-annual atmospheric variability in all species. The spatial representativeness is very high within 60 cm, rapidly decorrelates within 10 m but does not diminish further within 3 km. We attribute this to wind reworking of the snow pack leading to sastrugi formation. Due to the high resolution and seasonal representativeness of the records we can derive accurate seasonalities of the measured species for modern times as well as for pre-industrial times. Sodium and calcium show similar seasonality (peaking in February and March respectively for modern and pre-industrial times, whereas ammonium and nitrate are influenced by anthropogenic activities. Nitrate and ammonium both peak in May during modern times, whereas during pre-industrial times ammonium peaked during July–August and nitrate during June–July.

  17. Representativeness and seasonality of major ion records derived from NEEM firn cores

    Science.gov (United States)

    Gfeller, G.; Fischer, H.; Bigler, M.; Schüpbach, S.; Leuenberger, D.; Mini, O.

    2014-10-01

    The seasonal and annual representativeness of ionic aerosol proxies (among others, calcium, sodium, ammonium and nitrate) in various firn cores in the vicinity of the NEEM drill site in northwest Greenland have been assessed. Seasonal representativeness is very high as one core explains more than 60% of the variability within the area. The inter-annual representativeness, however, can be substantially lower (depending on the species) making replicate coring indispensable to derive the atmospheric variability of aerosol species. A single core at the NEEM site records only 30% of the inter-annual atmospheric variability in some species, while five replicate cores are already needed to cover approximately 70% of the inter-annual atmospheric variability in all species. The spatial representativeness is very high within 60 cm, rapidly decorrelates within 10 m but does not diminish further within 3 km. We attribute this to wind reworking of the snow pack leading to sastrugi formation. Due to the high resolution and seasonal representativeness of the records we can derive accurate seasonalities of the measured species for modern (AD 1990-2010) times as well as for pre-industrial (AD 1623-1750) times. Sodium and calcium show similar seasonality (peaking in February and March respectively) for modern and pre-industrial times, whereas ammonium and nitrate are influenced by anthropogenic activities. Nitrate and ammonium both peak in May during modern times, whereas during pre-industrial times ammonium peaked during July-August and nitrate during June-July.

  18. Representativeness and seasonality of major ion records derived from NEEM firn cores

    Directory of Open Access Journals (Sweden)

    G. Gfeller

    2014-10-01

    Full Text Available The seasonal and annual representativeness of ionic aerosol proxies (among others, calcium, sodium, ammonium and nitrate in various firn cores in the vicinity of the NEEM drill site in northwest Greenland have been assessed. Seasonal representativeness is very high as one core explains more than 60% of the variability within the area. The inter-annual representativeness, however, can be substantially lower (depending on the species making replicate coring indispensable to derive the atmospheric variability of aerosol species. A single core at the NEEM site records only 30% of the inter-annual atmospheric variability in some species, while five replicate cores are already needed to cover approximately 70% of the inter-annual atmospheric variability in all species. The spatial representativeness is very high within 60 cm, rapidly decorrelates within 10 m but does not diminish further within 3 km. We attribute this to wind reworking of the snow pack leading to sastrugi formation. Due to the high resolution and seasonal representativeness of the records we can derive accurate seasonalities of the measured species for modern (AD 1990–2010 times as well as for pre-industrial (AD 1623–1750 times. Sodium and calcium show similar seasonality (peaking in February and March respectively for modern and pre-industrial times, whereas ammonium and nitrate are influenced by anthropogenic activities. Nitrate and ammonium both peak in May during modern times, whereas during pre-industrial times ammonium peaked during July–August and nitrate during June–July.

  19. Twenty-sixth general conference meeting of representatives of RCA member states. Report

    International Nuclear Information System (INIS)

    The meeting discussed the following issues: RCA Annual Report 1996; Report of the 19th RCA Working Group Meeting, Yangon Myanmar, 10-14 March 1997; RCA in the next 25 years; Development finance and the RCA; locating a senior RCA representative in the region; RCA guidelines and operating rules; TCDC activities; terminal tripartite review meeting on UNDP/RCA/IAEA project; status of new joint UNDP/RCA/IAEA project; options for the new joint project; RCA activities and budget in 1997 and 1998; reformulation and health care project; RCA proposed programme for 1999-2000; country statements; extension of RCA agreement; RCA 25th anniversary; venue and date of the 20th regular meeting of national RCA representatives

  20. Heterogeneous Antibody-Based Activity Assay for Lysine Specific Demethylase 1 (LSD1) on a Histone Peptide Substrate.

    Science.gov (United States)

    Schmitt, Martin L; Ladwein, Kathrin I; Carlino, Luca; Schulz-Fincke, Johannes; Willmann, Dominica; Metzger, Eric; Schilcher, Pierre; Imhof, Axel; Schüle, Roland; Sippl, Wolfgang; Jung, Manfred

    2014-07-01

    Posttranslational modifications of histone tails are very important for epigenetic gene regulation. The lysine-specific demethylase LSD1 (KDM1A/AOF2) demethylates in vitro predominantly mono- and dimethylated lysine 4 on histone 3 (H3K4) and is a promising target for drug discovery. We report a heterogeneous antibody-based assay, using dissociation-enhanced lanthanide fluorescent immunoassay (DELFIA) for the detection of LSD1 activity. We used a biotinylated histone 3 peptide (amino acids 1-21) with monomethylated lysine 4 (H3K4me) as the substrate for the detection of LSD1 activity with antibody-mediated quantitation of the demethylated product. We have successfully used the assay to measure the potency of reference inhibitors. The advantage of the heterogeneous format is shown with cumarin-based LSD1 inhibitor candidates that we have identified using virtual screening. They had shown good potency in an established LSD1 screening assay. The new heterogeneous assay identified them as false positives, which was verified using mass spectrometry. PMID:24687155

  1. Stress enhances the gene expression and enzyme activity of phenylalanine ammonia-lyase and the endogenous content of salicylic acid to induce flowering in pharbitis.

    Science.gov (United States)

    Wada, Kaede C; Mizuuchi, Kaori; Koshio, Aya; Kaneko, Kentaro; Mitsui, Toshiaki; Takeno, Kiyotoshi

    2014-07-01

    The involvement of salicylic acid (SA) in the regulation of stress-induced flowering in the short-day plant pharbitis (also called Japanese morning glory) Ipomoea nil (formerly Pharbitis nil) was studied. Pharbitis cv. Violet was induced to flower when grown in 1/100-strength mineral nutrient solution under non-inductive long-day conditions. All fully expanded true leaves were removed from seedlings, leaving only the cotyledons, and flowering was induced under poor-nutrition stress conditions. This indicates that cotyledons can play a role in the regulation of poor-nutrition stress-induced flowering. The expression of the pharbitis homolog of PHENYLALANINE AMMONIA-LYASE, the enzyme activity of phenylalanine ammonia-lyase (PAL; E.C. 4.3.1.5) and the content of SA in the cotyledons were all up-regulated by the stress treatment. The Violet was also induced to flower by low-temperature stress, DNA demethylation and short-day treatment. Low-temperature stress enhanced PAL activity, whereas non-stress factors such as DNA demethylation and short-day treatment decreased the activity. The PAL enzyme activity was also examined in another cultivar, Tendan, obtaining similar results to Violet. The exogenously applied SA did not induce flowering under non-stress conditions but did promote flowering under weak stress conditions in both cultivars. These results suggest that stress-induced flowering in pharbitis is induced, at least partly, by SA, and the synthesis of SA is promoted by PAL.

  2. Representative Model Of The Learning Process 
In Virtual Spaces Supported By Ict

    OpenAIRE

    CAPACHO, José

    2014-01-01

    This paper shows the results of research activities for building the representative model of the learning process in virtual spaces (e-Learning). The formal basis of the model are supported in the analysis of models of learning assessment in virtual spaces and specifically in Dembo´s teaching learning model, the systemic approach to evaluating virtual learning by Badrul H. Khan, and the Cybernetic model for evaluating virtual learning environments. The e-Learning model is syste...

  3. Representative Model of the Learning Process in Virtual Spaces Supported by ICT

    OpenAIRE

    CAPACHO, José

    2015-01-01

    This paper shows the results of research activities for building the representative model of the learning process in virtual spaces (e-Learning). The formal basis of the model are supported in the analysis of models of learning assessment in virtual spaces and specifically in Dembo´s teaching learning model, the systemic approach to evaluating virtual learning by Badrul H. Khan, and the Cybernetic model for evaluating virtual learning environments. The e-Learning model is systemic and of feed...

  4. Compared Analysis of Representative Learning and Content Management Systems used in Education

    OpenAIRE

    Alina Mihaela ION

    2012-01-01

    Online learning management systems used in universities do not fulfill entirely user requests. In order to optimize the activity of students and professors, an educational platform should provide both features of content learning management and features of content management. In this paper, we selected for analysis the most representative learning management systems (LMS) and content management systems (CMS) on the market. We analyzed both products that require paid license and free products ...

  5. An affordable proxy of representative national survey on radon concentration in dwellings: Design, organisation and preliminary evaluation of representativeness

    International Nuclear Information System (INIS)

    Representative national surveys in dwellings are important to unbiasedly evaluate the exposure of the general population to radon. In Italy, a representative national survey was conducted from 1989 to 1996, which involved about 5600 dwellings in 232 towns. Later on, some Regions carried out more detailed surveys, but a new national survey in dwellings is necessary in order to obtain a more thorough estimate of radon concentration distribution over the Italian territory. The need to make this survey in an affordable way led to implement a new approach based on the collaboration between the Istituto Superiore di Sanità and a national company with workplaces and employees' homes throughout the country. The intent is to carry out a proxy of a population representative survey by measuring radon concentration in the homes of a random sample of the company employees. The realisation of this survey was affordable, thanks to the availability of corporate e-mail for each employee, intranet service, and company internal mail service. A dedicated web procedure and e-questionnaires allowed to automatically manage the contact with employees and to collect their data, which were both cost- and time-saving. Using this e-mail contact approach, 53% of contacted employees consented to participate in the survey. Radon concentration passive measuring devices were distributed to about 7000 dwellings, using about 14000 CR-39 detectors (two measured rooms per dwelling). In order to reduce costs, the devices were exposed for 12 months instead of two consecutive 6-month periods (as with the former national survey). A first checking of the actual representativeness of the sample was done by comparing characteristics of dwellings and occupants in the sample with corresponding data from the latest National Census. This was accomplished thanks to the fact that the questions in the survey questionnaire were tailored to the categories adopted for the Census questionnaire. A preliminary

  6. Impact of pharmaceutical representative visits on GPs' drug preferences

    DEFF Research Database (Denmark)

    Søndergaard, Jens; Vach, Kirstin; Kragstrup, Jakob;

    2009-01-01

    BACKGROUND: Pharmaceutical representative visits are believed to have substantial impact, but the effects on prescribing patterns have not been systematically evaluated. OBJECTIVE: This study investigates how pharmaceutical sales representative visits influenced physicians' company-specific drug...... were (i) company-specific drug preferences measured as the proportion of dispensings of the promoted drug among all dispensings of fixed combinations of inhaled corticosteroid and long-acting beta2-agonists and (ii) the proportion of patients receiving repeated beta2-agonist dispensings who were...... treated with inhaled steroids. RESULTS: The first visit had a statistically significant effect on the GPs' drug preference in favour of the marketed drug [odds ratio (OR), 2.39; 95% confidence interval (CI), 1.72-3.32]. The effect on drug preference increased further after the second visit (OR, 1.51; 95...

  7. Representing Scientific Communities by Data Visualization (1/2)

    CERN Document Server

    CERN. Geneva

    2016-01-01

    These lectures present a research that investigates the representation of communities, and the way to foster their understanding by different audiences. Communities are complex multidimensional entities intrinsically difficult to represent synthetically. The way to represent them is likely to differ depending on the audience considered: governing entities trying to make decision for the future of the community, general public trying to understand the nature of the community and the members of the community themselves. This work considers two types of communities as example: a scientific organization and an arising domain: the EPFL institutional community composed of faculty members and researchers and, at a world wide level, the emerging community of Digital Humanities researchers. For both cases, the research is organised as a process going from graphical research to actual materialization as physical artefacts (posters, maps, etc.), possibly extended using digital devices (augmented reality applications). T...

  8. Processes, data structures, and apparatuses for representing knowledge

    Science.gov (United States)

    Hohimer, Ryan E.; Thomson, Judi R.; Harvey, William J.; Paulson, Patrick R.; Whiting, Mark A.; Tratz, Stephen C.; Chappell, Alan R.; Butner, R. Scott

    2011-09-20

    Processes, data structures, and apparatuses to represent knowledge are disclosed. The processes can comprise labeling elements in a knowledge signature according to concepts in an ontology and populating the elements with confidence values. The data structures can comprise knowledge signatures stored on computer-readable media. The knowledge signatures comprise a matrix structure having elements labeled according to concepts in an ontology, wherein the value of the element represents a confidence that the concept is present in an information space. The apparatus can comprise a knowledge representation unit having at least one ontology stored on a computer-readable medium, at least one data-receiving device, and a processor configured to generate knowledge signatures by comparing datasets obtained by the data-receiving devices to the ontologies.

  9. Chaos control applied to cardiac rhythms represented by ECG signals

    Science.gov (United States)

    Borem Ferreira, Bianca; Amorim Savi, Marcelo; Souza de Paula, Aline

    2014-10-01

    The control of irregular or chaotic heartbeats is a key issue in cardiology. In this regard, chaos control techniques represent a good alternative since they suggest treatments different from those traditionally used. This paper deals with the application of the extended time-delayed feedback control method to stabilize pathological chaotic heart rhythms. Electrocardiogram (ECG) signals are employed to represent the cardiovascular behavior. A mathematical model is employed to generate ECG signals using three modified Van der Pol oscillators connected with time delay couplings. This model provides results that qualitatively capture the general behavior of the heart. Controlled ECG signals show the ability of the strategy either to control or to suppress the chaotic heart dynamics generating less-critical behaviors.

  10. Are there martial art styles that represent natural systems?

    Directory of Open Access Journals (Sweden)

    Joachim T. Haug

    2015-12-01

    Full Text Available For didactics, systematically structured teaching contents are desirable, and natural systems would be most comprehensible. We tested whether serrada-escrima styles (SES, a type of Filipino martial arts, represent a natural system. Natural systems are considered to have an inner coherence. This means that based on some elements of the system the other elements can be predicted, based on knowledge of the characteristics of the elements of the system. SES is a good candidate to test this hypothesis, as it embraces only a relatively small set of techniques. It appears that SES indeed represents a natural, coherent system with 12 elements that can be grouped into three also coherent sets, each with four techniques. One basic pre-assumption is necessary to make SES a natural system; this pre-assumption is derived from knowledge of medieval European sword fighting, more precisely Messerfechten. We furthermore discuss indications for the historic background of SES.

  11. Manikin families representing obese airline passengers in the US.

    Science.gov (United States)

    Park, Hanjun; Park, Woojin; Kim, Yongkang

    2014-01-01

    Aircraft passenger spaces designed without proper anthropometric analyses can create serious problems for obese passengers, including: possible denial of boarding, excessive body pressures and contact stresses, postural fixity and related health hazards, and increased risks of emergency evacuation failure. In order to help address the obese passenger's accommodation issues, this study developed male and female manikin families that represent obese US airline passengers. Anthropometric data of obese individuals obtained from the CAESAR anthropometric database were analyzed through PCA-based factor analyses. For each gender, a 99% enclosure cuboid was constructed, and a small set of manikins was defined on the basis of each enclosure cuboid. Digital human models (articulated human figures) representing the manikins were created using a human CAD software program. The manikin families were utilized to develop design recommendations for selected aircraft seat dimensions. The manikin families presented in this study would greatly facilitate anthropometrically accommodating large airline passengers.

  12. Representing the environment 3.0. Maps, models, networks.

    Directory of Open Access Journals (Sweden)

    Letizia Bollini

    2014-05-01

    Full Text Available Web 3.0 is changing the world we live and perceive the environment anthropomorphized, making a stratifation of levels of experience and mediated by the devices. If the urban landscape is designed, shaped and planned space, there is a social landscape that overwrite the territory of values, representations shared images, narratives of personal and collective history. Mobile technology introduces an additional parameter, a kind of non-place, which allows the coexistence of the here and elsewhere in an sort of digital landscape. The maps, mental models, the system of social networks become, then, the way to present, represented and represent themselves in a kind of ideal coring of the co-presence of levels of physical, cognitive and collective space.

  13. Forms representing forms and linear spaces on hypersurfaces

    CERN Document Server

    Brandes, Julia

    2012-01-01

    A generalisation of Waring's problem, considered first by Arkhipov and Karatsuba, is the question of representing not an integer, but a given polynomial, as a sum of powers of linear polynomials. We investigate a related problem and prove a Hasse principle for the number of identical representations of a set of given forms by homogeneous polynomials of general shape. The result leads to sizeable improvements for estimates of the number of linear spaces on the intersection of hypersurfaces.

  14. Qualitative interviewing of respondents in large representative surveys

    OpenAIRE

    Groh-Samberg, Olaf; Tucci, Ingrid

    2010-01-01

    "Large representative surveys are using mixed methods to an ever-increasing degree. Biomarkers, register data, and experiments, for example, provide different types of data that can be linked with survey data. The use of qualitative interviewing of participants in longitudinal surveys is still rare, however, in the social sciences. Yet qualitative methods have proven just as valuable as quantitative methods in providing insights into social reality by reflecting the multidimensionality of ind...

  15. Representing and Reasoning over Topological Relations in OWL

    OpenAIRE

    Batsakis, Sotiris; Antoniou, Grigoris; Tachmazidis, Ilias

    2014-01-01

    Representing topological information for the Semantic Web often involves qualitative defined natural language terms such as "Into" or "Overlapping". This can be the case when exact coordinates of spatial regions are not available, they are incomplete or unreliable. Topological spatial relations are the most important aspect of spatial representation and reasoning, thus embedding such relations into an ontology along with their semantics as expressed using reasoning rules is an import...

  16. A program for representing and simulating population genetic phenomena

    Directory of Open Access Journals (Sweden)

    Nuin Paulo A.S.

    2000-01-01

    Full Text Available The paper describes a computer program for representing and simulating population genetic phenomena, such as the distribution of gene and genotype frequencies under different mating systems (panmixia, inbreeding and assortative mating systems and under influence of evolution factors (mutation, selection, gene flow and genetic drift. The program was written in Visual Basic (Microsoft, Inc. and is able to run in any IBM-PC compatible computer running Windows 3.1 or later versions.

  17. Representing value judgements in the evaluation options for nuclear waste

    International Nuclear Information System (INIS)

    In this report we show how the concept of Best Practical Environmental Option for nuclear waste management may be articulated using the methods of Multi-attribute Value Analysis. The concept of characteristic weights is introduced to represent differences of opinion on the relative importance of different factors that may reasonably be held, and show how these may be used to summarise information for decision-makers in a concise way. (author)

  18. Representativeness of the European social partner organisations: Footwear industry - Netherlands

    OpenAIRE

    Grünell, M.

    2010-01-01

    The aim of this representativeness study is to identify the respective national and supranational actors (i.e. trade unions and employer organisations) in the field of industrial relations in the footwear industry in the Netherlands. In order to determine their relative importance in the sector’s industrial relations, this study will, in particular, focus on their representational quality as well as on their role in collective bargaining.

  19. Our (represented) World: A Quantum-Like Object

    OpenAIRE

    Lambert-Mogiliansky, Ariane; Dubois, François

    2015-01-01

    It has been suggested that observed cognitive limitations may be an expression of the quantum-like structure of the mind. In this paper we explore some implications of this hypothesis for learning i.e., for the construction of a representation of the world. For a quantum-like individual, there exists a multiplicity of mentally incompatible (Bohr complementary) but equally valid and complete representations (mental pictures) of the world. The process of learning i.e., of constructing a represe...

  20. The impact of rising energy costs on representative farms

    OpenAIRE

    Raulston, J. Marc; Knapek, George M.; Richardson, James W.; Outlaw, Joe L.; Bryant, Henry L.

    2005-01-01

    Recent increases in natural gas and fossil fuel based energy sources have had a negative impact on the financial condition of agricultural producers across the nation. • In addition to higher fuel costs for trucks, equipment, and irrigation motors, the cost of nitrogen fertilizer is closely linked to energy prices and has also increased significantly. • This study quantifies the impacts of these increases on the economic viability of representative farms located throughout the United States f...

  1. Representative landscapes in the forested area of Canada.

    Science.gov (United States)

    Cardille, Jeffrey A; White, Joanne C; Wulder, Mike A; Holland, Tara

    2012-01-01

    Canada is a large nation with forested ecosystems that occupy over 60% of the national land base, and knowledge of the patterns of Canada's land cover is important to proper environmental management of this vast resource. To this end, a circa 2000 Landsat-derived land cover map of the forested ecosystems of Canada has created a new window into understanding the composition and configuration of land cover patterns in forested Canada. Strategies for summarizing such large expanses of land cover are increasingly important, as land managers work to study and preserve distinctive areas, as well as to identify representative examples of current land-cover and land-use assemblages. Meanwhile, the development of extremely efficient clustering algorithms has become increasingly important in the world of computer science, in which billions of pieces of information on the internet are continually sifted for meaning for a vast variety of applications. One recently developed clustering algorithm quickly groups large numbers of items of any type in a given data set while simultaneously selecting a representative-or "exemplar"-from each cluster. In this context, the availability of both advanced data processing methods and a nationally available set of landscape metrics presents an opportunity to identify sets of representative landscapes to better understand landscape pattern, variation, and distribution across the forested area of Canada. In this research, we first identify and provide context for a small, interpretable set of exemplar landscapes that objectively represent land cover in each of Canada's ten forested ecozones. Then, we demonstrate how this approach can be used to identify flagship and satellite long-term study areas inside and outside protected areas in the province of Ontario. These applications aid our understanding of Canada's forest while augmenting its management toolbox, and may signal a broad range of applications for this versatile approach. PMID

  2. BRAIN MECHANISMS FOR REPRESENTING WHAT ANOTHER PERSON SEES

    OpenAIRE

    Heyda, Ratha D.; Green, Steven R.; Vander Wyk, Brent C.; James P Morris; Pelphrey, Kevin A.

    2010-01-01

    We used functional magnetic resonance imaging (fMRI) and a naturalistic joint attention scenario to evaluate two, alternative hypotheses concerning the social brain. The first, Content Specific Attribution hypothesis, was that core regions previously identified as being involved in social cognition also participate in representing the contents of another mind. The second, Dual Role hypothesis, was that extrastriate, category-specific visual regions respond to a visible stimulus of a specific ...

  3. The English Revolution and a Representative and Constitutional Government

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yue

    2014-01-01

    This article gives a brief introduction to the English Revolution and describes a detailed study of influence, as well as the explanation of a representative and constitutional government. The English Revolution which happened in Britain is a histori-cal event of great influence. It abolished the autarchic system of king and began to rule the society by law. We can conclude that it created good political conditions for Britain to become a kingdom of modern civilization.

  4. Representing young people's sexuality in the 'youth' media

    OpenAIRE

    Batchelor, S.A.; Kitzinger, J.; Burtney, E.

    2004-01-01

    This paper reports findings from a content analysis of the main messages about sexuality in media outlets consumed by young people. It examines how sexuality is represented and the level of sexual health information provided in some UK magazines and TV programmes targeted at young people. Our findings show that such outlets included a vast range of useful discussion including information about health concerns and in-depth exploration of issues such as consent and examples of couples exploring...

  5. Representing electrons a biographical approach to theoretical entities

    CERN Document Server

    Arabatzis, Theodore

    2006-01-01

    Both a history and a metahistory, Representing Electrons focuses on the development of various theoretical representations of electrons from the late 1890s to 1925 and the methodological problems associated with writing about unobservable scientific entities. Using the electron-or rather its representation-as a historical actor, Theodore Arabatzis illustrates the emergence and gradual consolidation of its representation in physics, its career throughout old quantum theory, and its appropriation and reinterpretation by chemists. As Arabatzis develops this novel biographical

  6. Does the Poynting vector always represent electromagnetic power flow?

    CERN Document Server

    Wang, Changbiao

    2015-01-01

    Poynting vector as electromagnetic power flow has prevailed over one hundred years in the community. However in this paper, it is shown from Maxwell equations that the Poynting vector may not represent the electromagnetic power flow for a plane wave in a non-dispersive, lossless, non-conducting, anisotropic uniform medium; this important conclusion revises the conventional understanding of Poynting vector. It is also shown that this conclusion is clearly supported by Fermat's principle and special theory of relativity.

  7. Hydraulic behaviour of a representative structural volume for containment buildings

    International Nuclear Information System (INIS)

    This contribution presents a simplified hydro mechanical approach for the study of sensitive structures like containment vessels of nuclear power plants. It is based on the calculation of permeability from two independent preliminary computations (drying and mechanical effects). The resulting distribution of the transfer property is then included in a hydraulic simulation to represent the consequences of a mechanical degradation on a gas pressure gradient simulation. Contrary to fully coupled methods which require a large number of parameters and heavy computational resources, this technique is suitable for large scale structural applications. The method is applied on a FE Representative Structural Volume model of a typical 1300 MWe prestressed containment vessel (PPCV) representative of the Electricite de France French power plants. It incorporates almost all components of the real structure with concrete, vertical and horizontal reinforcement bars, transverse reinforcements and prestressed tendons in both horizontal and vertical directions. The effect of damage localization on the hydraulic regime is investigated and an indicator based on the radial flow is developed to locate the zones where the leakage rate may be critical. (authors)

  8. Reference materials and representative test materials: the nanotechnology case

    Energy Technology Data Exchange (ETDEWEB)

    Roebben, G., E-mail: gert.roebben@ec.europa.eu [Joint Research Centre of the European Commission, Institute for Reference Materials and Measurements (Belgium); Rasmussen, K. [Joint Research Centre of the European Commission, Institute for Health and Consumer Protection (Italy); Kestens, V.; Linsinger, T. P. J. [Joint Research Centre of the European Commission, Institute for Reference Materials and Measurements (Belgium); Rauscher, H. [Joint Research Centre of the European Commission, Institute for Health and Consumer Protection (Italy); Emons, H. [Joint Research Centre of the European Commission, Institute for Reference Materials and Measurements (Belgium); Stamm, H. [Joint Research Centre of the European Commission, Institute for Health and Consumer Protection (Italy)

    2013-03-15

    An increasing number of chemical, physical and biological tests are performed on manufactured nanomaterials for scientific and regulatory purposes. Existing test guidelines and measurement methods are not always directly applicable to or relevant for nanomaterials. Therefore, it is necessary to verify the use of the existing methods with nanomaterials, thereby identifying where modifications are needed, and where new methods need to be developed and validated. Efforts for verification, development and validation of methods as well as quality assurance of (routine) test results significantly benefit from the availability of suitable test and reference materials. This paper provides an overview of the existing types of reference materials and introduces a new class of test materials for which the term 'representative test material' is proposed. The three generic concepts of certified reference material, reference material(non-certified) and representative test material constitute a comprehensive system of benchmarks that can be used by all measurement and testing communities, regardless of their specific discipline. This paper illustrates this system with examples from the field of nanomaterials, including reference materials and representative test materials developed at the European Commission's Joint Research Centre, in particular at the Institute for Reference Materials and Measurements (IRMM), and at the Institute for Health and Consumer Protection (IHCP).

  9. Representativity and reproducibility of DNA malignancy grading in different carcinomas.

    Science.gov (United States)

    Böcking, A; Chatelain, R; Homge, M; Daniel, R; Gillissen, A; Wohltmann, D

    1989-04-01

    The reproducibility of the determination of the "DNA malignancy grade" (DNA-MG) was tested in 56 carcinomas of the colon, breast and lung while its representativity was tested on 195 slides from 65 tumors of the colon, breast and lung. DNA measurements were performed on Feulgen-stained smears with the TAS Plus TV-based image analysis system combined with an automated microscope. The variance of the DNA values of tumor cells around the 2c peak, the "2c deviation index" (2cDI), was taken as a basis for the computation of the DNA-MG, which ranges on a continuous scale from 0.01 to 3.00. The representativity, analyzed by comparison of the DNA-MGs measured in three different areas of the same tumor greater than or equal to 1.5 cm apart from each other, yielded an 81% agreement. No significant differences between DNA-MGs of these areas were found. The intraobserver and interobserver reproducibilities of the DNA grading system, investigated by repeated DNA measurements, were 83.9% and 82.2%, respectively. In comparison, histopathologic grading of the 27 breast cancers studied yielded 65% intraobserver and 57% interobserver reproducibilities and 66% representativity.

  10. Reference materials and representative test materials: the nanotechnology case

    International Nuclear Information System (INIS)

    An increasing number of chemical, physical and biological tests are performed on manufactured nanomaterials for scientific and regulatory purposes. Existing test guidelines and measurement methods are not always directly applicable to or relevant for nanomaterials. Therefore, it is necessary to verify the use of the existing methods with nanomaterials, thereby identifying where modifications are needed, and where new methods need to be developed and validated. Efforts for verification, development and validation of methods as well as quality assurance of (routine) test results significantly benefit from the availability of suitable test and reference materials. This paper provides an overview of the existing types of reference materials and introduces a new class of test materials for which the term ‘representative test material’ is proposed. The three generic concepts of certified reference material, reference material(non-certified) and representative test material constitute a comprehensive system of benchmarks that can be used by all measurement and testing communities, regardless of their specific discipline. This paper illustrates this system with examples from the field of nanomaterials, including reference materials and representative test materials developed at the European Commission’s Joint Research Centre, in particular at the Institute for Reference Materials and Measurements (IRMM), and at the Institute for Health and Consumer Protection (IHCP).

  11. Representing plants as rigid cylinders in experiments and models

    Science.gov (United States)

    Vargas-Luna, Andrés; Crosato, Alessandra; Calvani, Giulio; Uijttewaal, Wim S. J.

    2016-07-01

    Simulating the morphological adaptation of water systems often requires including the effects of plants on water and sediment dynamics. Physical and numerical models need representing vegetation in a schematic easily-quantifiable way despite the variety of sizes, shapes and flexibility of real plants. Common approaches represent plants as rigid cylinders, but the ability of these schematizations to reproduce the effects of vegetation on morphodynamic processes has never been analyzed systematically. This work focuses on the consequences of representing plants as rigid cylinders in laboratory tests and numerical simulations. New experiments show that the flow resistance decreases for increasing element Reynolds numbers for both plants and rigid cylinders. Cylinders on river banks can qualitatively reproduce vegetation effects on channel width and bank-related processes. A comparative review of numerical simulations shows that Baptist's method that sums the contribution of bed shear stress and vegetation drag, underestimates bed erosion within sparse vegetation in real rivers and overestimates the mean flow velocity in laboratory experiments. This is due to assuming uniform flow among plants and to an overestimation of the role of the submergence ratio.

  12. Characterization of the active site properties of CYP4F12.

    Science.gov (United States)

    Eksterowicz, John; Rock, Dan A; Rock, Brooke M; Wienkers, Larry C; Foti, Robert S

    2014-10-01

    Cytochrome P450 4F12 is a drug-metabolizing enzyme that is primarily expressed in the liver, kidney, colon, small intestine, and heart. The properties of CYP4F12 that may impart an increased catalytic selectivity (decreased promiscuity) were explored through in vitro metabolite elucidation, kinetic isotope effect experiments, and computational modeling of the CYP4F12 active site. By using astemizole as a probe substrate for CYP4F12 and CYP3A4, it was observed that although CYP4F12 favored astemizole O-demethylation as the primary route of metabolism, CYP3A4 was capable of metabolizing astemizole at multiple sites on the molecule. Deuteration of astemizole at the site of O-demethylation resulted in an isotope effect of 7.1 as well as an 8.3-fold decrease in the rate of clearance for astemizole by CYP4F12. Conversely, although an isotope effect of 3.8 was observed for the formation of the O-desmethyl metabolite when deuterated astemizole was metabolized by CYP3A4, there was no decrease in the clearance of astemizole. Development of a homology model of CYP4F12 based on the crystal structure of cytochrome P450 BM3 predicted an active site volume for CYP4F12 that was approximately 76% of the active site volume of CYP3A4. As predicted, multiple favorable binding orientations were available for astemizole docked into the active site of CYP3A4, but only a single binding orientation with the site of O-demethylation oriented toward the heme was identified for CYP4F12. Overall, it appears that although CYP4F12 may be capable of binding similar ligands to other cytochrome P450 enzymes such as CYP3A4, the ability to achieve catalytically favorable orientations may be inherently more difficult because of the increased steric constraints of the CYP4F12 active site. PMID:25074871

  13. Selection of representative emerging micropollutants for drinking water treatment studies: a systematic approach.

    Science.gov (United States)

    Jin, Xiaohui; Peldszus, Sigrid

    2012-01-01

    Micropollutants remain of concern in drinking water, and there is a broad interest in the ability of different treatment processes to remove these compounds. To gain a better understanding of treatment effectiveness for structurally diverse compounds and to be cost effective, it is necessary to select a small set of representative micropollutants for experimental studies. Unlike other approaches to-date, in this research micropollutants were systematically selected based solely on their physico-chemical and structural properties that are important in individual water treatment processes. This was accomplished by linking underlying principles of treatment processes such as coagulation/flocculation, oxidation, activated carbon adsorption, and membrane filtration to compound characteristics and corresponding molecular descriptors. A systematic statistical approach not commonly used in water treatment was then applied to a compound pool of 182 micropollutants (identified from the literature) and their relevant calculated molecular descriptors. Principal component analysis (PCA) was used to summarize the information residing in this large dataset. D-optimal onion design was then applied to the PCA results to select structurally representative compounds that could be used in experimental treatment studies. To demonstrate the applicability and flexibility of this selection approach, two sets of 22 representative micropollutants are presented. Compounds in the first set are representative when studying a range of water treatment processes (coagulation/flocculation, oxidation, activated carbon adsorption, and membrane filtration), whereas the second set shows representative compounds for ozonation and advanced oxidation studies. Overall, selected micropollutants in both lists are structurally diverse, have wide-ranging physico-chemical properties and cover a large spectrum of applications. The systematic compound selection approach presented here can also be adjusted to fit

  14. Selection of representative emerging micropollutants for drinking water treatment studies: a systematic approach.

    Science.gov (United States)

    Jin, Xiaohui; Peldszus, Sigrid

    2012-01-01

    Micropollutants remain of concern in drinking water, and there is a broad interest in the ability of different treatment processes to remove these compounds. To gain a better understanding of treatment effectiveness for structurally diverse compounds and to be cost effective, it is necessary to select a small set of representative micropollutants for experimental studies. Unlike other approaches to-date, in this research micropollutants were systematically selected based solely on their physico-chemical and structural properties that are important in individual water treatment processes. This was accomplished by linking underlying principles of treatment processes such as coagulation/flocculation, oxidation, activated carbon adsorption, and membrane filtration to compound characteristics and corresponding molecular descriptors. A systematic statistical approach not commonly used in water treatment was then applied to a compound pool of 182 micropollutants (identified from the literature) and their relevant calculated molecular descriptors. Principal component analysis (PCA) was used to summarize the information residing in this large dataset. D-optimal onion design was then applied to the PCA results to select structurally representative compounds that could be used in experimental treatment studies. To demonstrate the applicability and flexibility of this selection approach, two sets of 22 representative micropollutants are presented. Compounds in the first set are representative when studying a range of water treatment processes (coagulation/flocculation, oxidation, activated carbon adsorption, and membrane filtration), whereas the second set shows representative compounds for ozonation and advanced oxidation studies. Overall, selected micropollutants in both lists are structurally diverse, have wide-ranging physico-chemical properties and cover a large spectrum of applications. The systematic compound selection approach presented here can also be adjusted to fit

  15. Reactivation of a methylation-silenced gene in adenovirus-transformed cells by 5-azacytidine or by E1A trans activation.

    Science.gov (United States)

    Knust, B; Brüggemann, U; Doerfler, W

    1989-01-01

    In the adenovirus type 2 (Ad2)-transformed hamster cell line HE3, the integrated late E2A promoter of Ad2 DNA is inactive, is methylated at all three 5'-CCGG-3' sequences, and can be reactivated by growing the cells in the presence of 50 microM 5-azacytidine (5-azaC). The three 5'-CCGG-3' sequences then become demethylated. Demethylation and reactivation are stable over 30 passages even after the removal of 5-azaC. The dormant late E2A promoter in cell line HE3 can also be reactivated by transfecting the cells with recombinant plasmids that carry the left terminal E1A and part of the E1B region of Ad2 DNA or the E1A 13S cDNA, but not with plasmids containing the E1A 12S cDNA. The E1A 13S cDNA encodes the 289-amino-acid trans-activating protein of Ad2. The E1A-mediated reactivation of the late E2A promoter is not accompanied by its demethylation in both DNA complements. Cell line HE3 produces constitutively E1A-encoded mRNAs and reactivates the methylated late E2A promoter-chloramphenicol acetyltransferase gene construct after transfection into HE3 cells. Constitutive levels of the endogenous E1A gene products in HE3 cells are detectable but, paradoxically, appear insufficient to reactivate the endogenous, chromosomally integrated E2A gene. Images PMID:2473219

  16. Do capture data from mosquito traps represent reality?

    Science.gov (United States)

    Collectively, the effects of mechanical trap style, the method of trap placement in the field, mosquito activity phase, and other biological phenomena are manifest as sample bias that leads to vector detection failure(s) and/or erroneous predictions of mosquito activity. The goal of this research i...

  17. Novel Substrate Specificity and Temperature-Sensitive Activity of Mycosphaerella graminicola CYP51 Supported by the Native NADPH Cytochrome P450 Reductase.

    Science.gov (United States)

    Price, Claire L; Warrilow, Andrew G S; Parker, Josie E; Mullins, Jonathan G L; Nes, W David; Kelly, Diane E; Kelly, Steven L

    2015-05-15

    Mycosphaerella graminicola (Zymoseptoria tritici) is an ascomycete filamentous fungus that causes Septoria leaf blotch in wheat crops. In Europe the most widely used fungicides for this major disease are demethylation inhibitors (DMIs). Their target is the essential sterol 14α-demethylase (CYP51), which requires cytochrome P450 reductase (CPR) as its redox partner for functional activity. The M. graminicola CPR (MgCPR) is able to catalyze the sterol 14α-demethylation of eburicol and lanosterol when partnered with Candida albicans CYP51 (CaCYP51) and that of eburicol only with M. graminicola CYP51 (MgCYP51). The availability of the functional in vivo redox partner enabled the in vitro catalytic activity of MgCYP51 to be demonstrated for the first time. MgCYP51 50% inhibitory concentration (IC50) studies with epoxiconazole, tebuconazole, triadimenol, and prothioconazole-desthio confirmed that MgCYP51 bound these azole inhibitors tightly. The characterization of the MgCPR/MgCYP51 redox pairing has produced a functional method to evaluate the effects of agricultural azole fungicides, has demonstrated eburicol specificity in the activity observed, and supports the conclusion that prothioconazole is a profungicide. PMID:25746994

  18. All Three Endogenous Quinone Species of Escherichia coli Are Involved in Controlling the Activity of the Aerobic/Anaerobic Response Regulator ArcA.

    Science.gov (United States)

    van Beilen, Johan W A; Hellingwerf, Klaas J

    2016-01-01

    The enteron Escherichia coli is equipped with a branched electron transfer chain that mediates chemiosmotic electron transfer, that drives ATP synthesis. The components of this electron transfer chain couple the oxidation of available electron donors from cellular metabolism (e.g., NADH, succinate, lactate, formate, etc.) to the reduction of electron acceptors like oxygen, nitrate, fumarate, di-methyl-sulfoxide, etc. Three different quinones, i.e., ubiquinone, demethyl-menaquinone and menaquinone, couple the transfer of electrons between the dehydrogenases and reductases/oxidases that constitute this electron transfer chain, whereas, the two-component regulation system ArcB/A regulates gene expression, to allow the organism to adapt itself to the ambient conditions of available electron donors and acceptors. Here, we report that E. coli can grow and adjust well to transitions in the availability of oxygen, with any of the three quinones as its single quinone. In all three 'single-quinone' E. coli strains transitions in the activity of ArcB are observed, as evidenced by changes in the level of phosphorylation of the response regulator ArcA, upon depletion/readmission of oxygen. These results lead us to conclude that all quinol species of E. coli can reduce (i.e., activate) the sensor ArcB and all three quinones oxidize (i.e., de-activate) it. These results also confirm our earlier conclusion that demethyl-menaquinone can function in aerobic respiration. PMID:27656164

  19. Metabolite Profile Resulting from the Activation/Inactivation of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 2-Methyltetrahydro-β-carboline by Oxidative Enzymes

    Directory of Open Access Journals (Sweden)

    Tomás Herraiz

    2013-01-01

    Full Text Available Metabolic enzymes are involved in the activation/deactivation of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyiridine (MPTP neurotoxin and its naturally occurring analogs 2-methyltetrahydro-β-carbolines. The metabolic profile and biotransformation of these protoxins by three enzymes, monoamine oxidase (MAO, cytochrome P450, and heme peroxidases (myeloperoxidase and lactoperoxidase, were investigated and compared. The metabolite profile differed among the enzymes investigated. MAO and heme peroxidases activated these substances to toxic pyridinium and β-carbolinium species. MAO catalyzed the oxidation of MPTP to 1-methyl-4-phenyl-2,3-dihydropyridinium cation (MPDP+, whereas heme peroxidases catalyzed the oxidation of MPDP+ to 1-methyl-4-phenylpyridinium (MPP+ and of 2-methyltetrahydro-β-carboline to 2-methyl-3,4-dihydro-β-carbolinium cation (2-Me-3,4-DHβC+. These substances were inactivated by cytochrome P450 2D6 through N-demethylation and aromatic hydroxylation (MPTP and aromatic hydroxylation (2-methyltetrahydro-β-carboline. In conclusion, the toxicological effects of these protoxins might result from a balance between the rate of their activation to toxic products (i.e., N-methylpyridinium-MPP+ and MPDP+- and N-methyl-β-carbolinium—βC+— by MAO and heme peroxidases and the rate of inactivation (i.e., N-demethylation, aromatic hydroxylation by cytochrome P450 2D6.

  20. Defining And Characterizing Sample Representativeness For DWPF Melter Feed Samples

    Energy Technology Data Exchange (ETDEWEB)

    Shine, E. P.; Poirier, M. R.

    2013-10-29

    Representative sampling is important throughout the Defense Waste Processing Facility (DWPF) process, and the demonstrated success of the DWPF process to achieve glass product quality over the past two decades is a direct result of the quality of information obtained from the process. The objective of this report was to present sampling methods that the Savannah River Site (SRS) used to qualify waste being dispositioned at the DWPF. The goal was to emphasize the methodology, not a list of outcomes from those studies. This methodology includes proven methods for taking representative samples, the use of controlled analytical methods, and data interpretation and reporting that considers the uncertainty of all error sources. Numerous sampling studies were conducted during the development of the DWPF process and still continue to be performed in order to evaluate options for process improvement. Study designs were based on use of statistical tools applicable to the determination of uncertainties associated with the data needs. Successful designs are apt to be repeated, so this report chose only to include prototypic case studies that typify the characteristics of frequently used designs. Case studies have been presented for studying in-tank homogeneity, evaluating the suitability of sampler systems, determining factors that affect mixing and sampling, comparing the final waste glass product chemical composition and durability to that of the glass pour stream sample and other samples from process vessels, and assessing the uniformity of the chemical composition in the waste glass product. Many of these studies efficiently addressed more than one of these areas of concern associated with demonstrating sample representativeness and provide examples of statistical tools in use for DWPF. The time when many of these designs were implemented was in an age when the sampling ideas of Pierre Gy were not as widespread as they are today. Nonetheless, the engineers and

  1. Representing and analysing molecular and cellular function using the computer.

    Science.gov (United States)

    van Helden, J; Naim, A; Mancuso, R; Eldridge, M; Wernisch, L; Gilbert, D; Wodak, S J

    2000-01-01

    Determining the biological function of a myriad of genes, and understanding how they interact to yield a living cell, is the major challenge of the post genome-sequencing era. The complexity of biological systems is such that this cannot be envisaged without the help of powerful computer systems capable of representing and analysing the intricate networks of physical and functional interactions between the different cellular components. In this review we try to provide the reader with an appreciation of where we stand in this regard. We discuss some of the inherent problems in describing the different facets of biological function, give an overview of how information on function is currently represented in the major biological databases, and describe different systems for organising and categorising the functions of gene products. In a second part, we present a new general data model, currently under development, which describes information on molecular function and cellular processes in a rigorous manner. The model is capable of representing a large variety of biochemical processes, including metabolic pathways, regulation of gene expression and signal transduction. It also incorporates taxonomies for categorising molecular entities, interactions and processes, and it offers means of viewing the information at different levels of resolution, and dealing with incomplete knowledge. The data model has been implemented in the database on protein function and cellular processes 'aMAZE' (http://www.ebi.ac.uk/research/pfbp/), which presently covers metabolic pathways and their regulation. Several tools for querying, displaying, and performing analyses on such pathways are briefly described in order to illustrate the practical applications enabled by the model.

  2. Distribution of Records Defined on Ordered Words Representing Lattice Paths

    Directory of Open Access Journals (Sweden)

    A. M. Alahmadi

    2011-01-01

    Full Text Available Problem statement: Let the sequence i1,i2,…,in, denoted by Snn be an increasing ordered word of length n taken from the set of the n positive integers S= {1,2,…,n}, m, n ∈N&plus, m≥n.. Approach: That is 1≤i1≤i2≤…≤in≤n. Treating Snn as a sequence of weak records {Lj = ij}, i, j = 1,2,…,n, the distribution of the single weak record as well as the joint distribution of weak records were found before. Results: By defining the notion of strong records on the sequence {Lj = ij}, the distribution of a single strong record was found for m=n. In another aspect, it can be shown that the lattice path in the plane from (0,1 to (m, n , consisting of unit segments up and to the right, can be represented by a sequence i1, i2,…, im where 1≤i1≤i2≤…≤im≤n, m, n ∈N+ m ≥ n. That is, such lattice paths can be represented, in one to one correspondence, by ordered increasing words of length m taken from the set S. Conclusion/Recommendations: In this article, we are going to extend the notion of weak and strong records to these sequences representing lattice paths for m>n and obtain their distributions. This result allows us to study lattice paths via ordered words of non negative integers.

  3. Representative Vector Machines: A Unified Framework for Classical Classifiers.

    Science.gov (United States)

    Gui, Jie; Liu, Tongliang; Tao, Dacheng; Sun, Zhenan; Tan, Tieniu

    2016-08-01

    Classifier design is a fundamental problem in pattern recognition. A variety of pattern classification methods such as the nearest neighbor (NN) classifier, support vector machine (SVM), and sparse representation-based classification (SRC) have been proposed in the literature. These typical and widely used classifiers were originally developed from different theory or application motivations and they are conventionally treated as independent and specific solutions for pattern classification. This paper proposes a novel pattern classification framework, namely, representative vector machines (or RVMs for short). The basic idea of RVMs is to assign the class label of a test example according to its nearest representative vector. The contributions of RVMs are twofold. On one hand, the proposed RVMs establish a unified framework of classical classifiers because NN, SVM, and SRC can be interpreted as the special cases of RVMs with different definitions of representative vectors. Thus, the underlying relationship among a number of classical classifiers is revealed for better understanding of pattern classification. On the other hand, novel and advanced classifiers are inspired in the framework of RVMs. For example, a robust pattern classification method called discriminant vector machine (DVM) is motivated from RVMs. Given a test example, DVM first finds its k -NNs and then performs classification based on the robust M-estimator and manifold regularization. Extensive experimental evaluations on a variety of visual recognition tasks such as face recognition (Yale and face recognition grand challenge databases), object categorization (Caltech-101 dataset), and action recognition (Action Similarity LAbeliNg) demonstrate the advantages of DVM over other classifiers.

  4. Doctors’ opinions of information provided by Libyan pharmaceutical company representatives

    Directory of Open Access Journals (Sweden)

    Mustafa A. Alssageer

    2012-11-01

    Full Text Available Objective: To examine the opinions of Libyan doctors regarding the quality of drug information provided by pharmaceutical company representatives (PCRs during detailing visits. Method: An anonymous survey was conducted among 1,000 doctors from selected institutes in Tripoli, Benghazi and Sebha. Doctors were asked questions regarding the quality of information provided during drug-detailing visits. Results: A questionnaire return rate of 61% (608 returned questionnaires out of 1,000 was achieved. The majority (n=463, 76% of surveyed participants graded the quality of information provided as average. Approximately, 40% of respondents indicated that contraindications, precautions, interactions and adverse effects of products promoted by PCRs were never or rarely mentioned during promotional visits, and 65% of respondents indicated that an alternative drug to the promoted product was never or rarely mentioned by the representatives. More than 50% of respondents (n=310, 51% reported that PCRs were not always able to answer all questions about their products. Only seven respondents (1% believed that PCRs never exaggerated the uniqueness, efficacy or safety of their product. The majority of respondents (n=342, 56% indicated that verbal information was not always consistent with written information provided. Seven per cent of respondents (n=43 admitted that they did not know whether or not the verbal information provided by PCRs was consistent with written information. Conclusion: Doctors believe that the provision of drug information by PCRs in Libya is incomplete and often exaggerated. Pharmaceutical companies should ensure that their representatives are trained to a standard to provide reliable information regarding the products they promote.

  5. Jane Austen and her representative work Pride and Prejudice

    Institute of Scientific and Technical Information of China (English)

    许若冰

    2011-01-01

    Pride and Prejudice is the representative work of Jane Austen in which she narrates a story about love and marriage. Through a female's sight, she portrays different female characters in the story by minute description and humor words. And from heroine Elizabeth. we can learn Jane Austen's thought corning love and marriage. From the story, we can learn living condition for female in that period. And we study what Austin want to state about the relationship for love and marriage.

  6. Structural knowledge techniques for representing, conveying, and acquiring structural knowledge

    CERN Document Server

    Jonassen, David H; Beissner, Katherine; Yacci, Michael

    2013-01-01

    This book introduces the concept of a hypothetical type of knowledge construction -- referred to as structural knowledge -- that goes beyond traditional forms of information recall to provide the bases for knowledge application. Assuming that the validity of the concept is accepted, the volume functions as a handbook for supporting the assessment and use of structural knowledge in learning and instructional settings. It's descriptions are direct and short, and its structure is consistent. Almost all of the chapters describe a technique for representing and assessing structural knowledge acquis

  7. Threat representative droplet generation and surface interaction analysis

    Science.gov (United States)

    Simpson, Steven; Chyba, Thomas H.; Jones, Robert M.; Harper, Gordon; Haslam, Diane

    2011-05-01

    We present our experiments with state-of-the-art equipment to dispense threat-representative (3 - 90 nL) freely falling droplets of viscous chemical material (material can be created on demand and the behavior of the droplet on a surface can be monitored as a function of time. Knowledge of how these droplets behave on surfaces is critical in understanding an entire chemical threat scenario and directly impacts the design, testing, and success of standoff surface chemical sensor technology and modeling efforts alike. We are currently working to address this knowledge gap by recording 'cradle-to-grave' droplet dissemination and surface interaction events.

  8. A Graph Based Interface for Representing Volume Visualization Results

    Science.gov (United States)

    Patten, James M.; Ma, Kwan-Liu

    1998-01-01

    This paper discusses a graph based user interface for representing the results of the volume visualization process. As images are rendered, they are connected to other images in a graph based on their rendering parameters. The user can take advantage of the information in this graph to understand how certain rendering parameter changes affect a dataset, making the visualization process more efficient. Because the graph contains more information than is contained in an unstructured history of images, the image graph is also helpful for collaborative visualization and animation.

  9. Markov LIMID processes for representing and solving renewal problems

    DEFF Research Database (Denmark)

    Jørgensen, Erik; Kristensen, Anders Ringgaard; Nilsson, Dennis

    2014-01-01

    In this paper a new tool for simultaneous optimisation of decisions on multiple time scales is presented. The tool combines the dynamic properties of Markov decision processes with the flexible and compact state space representation of LImited Memory Influence Diagrams (Limids). A temporal version...... to model a Markov Limid Process, where each TemLimid represents a macro action. Algorithms are presented to find optimal plans for a sequence of such macro actions. Use of algorithms is illustrated based on an extended version of an example from pig production originally used to introduce the Limid concept...

  10. The live album or many ways of representing performance

    Directory of Open Access Journals (Sweden)

    Mazzanti Sergio

    2014-01-01

    Full Text Available The analysis of live albums can clarify the dialectic between studio recordings and live performances. After discussing key concepts such as authenticity, space, time and place, and documentation, the author gives a preliminary definition of live albums, combining available descriptions and comparing them with different typologies and functions of these recordings. The article aims to give a new definition of the concept of live albums, gathering their primary elements: “A live album is an officially released extended recording of popular music representing one or more actually occurred public performances”.

  11. FEAT-REP : representing features in CAD/CAM

    OpenAIRE

    Klauck, Christoph; Bernardi, Ansgar; Legleitner, Ralf

    1991-01-01

    When CAD/CAM experts view a workpiece, they perceive it in terms of their own expertise. These terms, called features, which are build upon a syntax (geometry) and a semantic (e.g. skeletal plans in manufacturing or functional relations in design), provide an abstraction mechanism to facilitate the creation, manufacturing and analysis of workpieces. Our goal is to enable experts to represent their own feature-language via a feature-grammar in the computer to build feature-based systems e.g. C...

  12. Quantum turing machine and brain model represented by Fock space

    Science.gov (United States)

    Iriyama, Satoshi; Ohya, Masanori

    2016-05-01

    The adaptive dynamics is known as a new mathematics to treat with a complex phenomena, for example, chaos, quantum algorithm and psychological phenomena. In this paper, we briefly review the notion of the adaptive dynamics, and explain the definition of the generalized Turing machine (GTM) and recognition process represented by the Fock space. Moreover, we show that there exists the quantum channel which is described by the GKSL master equation to achieve the Chaos Amplifier used in [M. Ohya and I. V. Volovich, J. Opt. B 5(6) (2003) 639., M. Ohya and I. V. Volovich, Rep. Math. Phys. 52(1) (2003) 25.

  13. Representing a P-complete problem by small trellis automata

    CERN Document Server

    Okhotin, Alexander

    2009-01-01

    A restricted case of the Circuit Value Problem known as the Sequential NOR Circuit Value Problem was recently used to obtain very succinct examples of conjunctive grammars, Boolean grammars and language equations representing P-complete languages (Okhotin, http://dx.doi.org/10.1007/978-3-540-74593-8_23 "A simple P-complete problem and its representations by language equations", MCU 2007). In this paper, a new encoding of the same problem is proposed, and a trellis automaton (one-way real-time cellular automaton) with 11 states solving this problem is constructed.

  14. Efeito da variação do ph e da temperatura de síntese no desempenho de adesivos à base de creosoto vegetal desmetilado-formaldeído Effect ph variation and synthesis temperature on the performance of thermosetting adhesive formulations based on demethylated wood creosote-formaldehyde

    Directory of Open Access Journals (Sweden)

    Crístian Bacelar Santos

    2003-08-01

    Full Text Available O objetivo deste trabalho foi a produção de adesivos para madeira a partir de creosoto desmetilado. Para isto, foram sintetizadas diferentes formulações de adesivos para madeira a partir de creosoto desmetilado e paraformaldeído, variando-se o pH inicial da formulação (12,00, 12,25, 12,50, 12,75, 13,00, 13,25 e 13,50 e a temperatura de síntese (60 e 70 °C, para possibilitar a verificação dos melhores pHs e da melhor temperatura para elaboração do adesivo. Foi verificado, por meio da avaliação do gel time, que a melhor temperatura de síntese foi 70 °C. Foram realizadas, então, análises por DSC (calorimetria diferencial exploratória, para obtenção dos parâmetros cinéticos e caracterização das formulações adesivas de creosoto desmetilado sintetizadas a 70 °C. Os adesivos foram utilizados para colagem, a quente (160 °C e sob pressão (12 kgf/cm², de lâminas de Araucaria angustifolia. Após a colagem, foram realizados os ensaios de resistência mecânica ao cisalhamento por tração, para condição seca e úmida. Verificou-se que a resistência da linha de cola e a porcentagem de falha na madeira para os adesivos de creosoto desmetilado sintetizados a 70 °C foram inferiores às do adesivo de fenol-formaldeído sintetizado em laboratório, que foi utilizado como padrão.The objective of this work was the production of adhesives based on demethylated creosote for bonding of wood. Different formulations of demethylated wood bcreosote/formaldehyde were evaluated aiming at improving their bonding properties. The initial pH value and the synthesis temperature were varied in order to obtain the best values for producing the adhesives. Thus, seven pH values (12.00, 12.25, 12.50, 12.75, 13.00, 13.25, and 13.50 and two different temperatures (60 °C and 70 °C were applied. It was observed by gel time evaluation that the best synthesis temperature was 70 °C. The kinetic parameters were obtained through DSC analysis

  15. Psychosocial workload and stress in the workers’ representative

    Science.gov (United States)

    2012-01-01

    Background Using a data set of works councils of trade union IG Metal, this paper investigates psychosocial stress and strain on this specific group in comparison to employees working in administration in general (leadership and non-leadership-role) and a national reference value. Methods For assessing psychosocial work factors on works councils within the sector represented by the trade union IG Metal in Germany, a research by using the German standard version of COPSOQ (Copenhagen Psychosocial Questionnaire) was performed. The instrument includes 87 single items forming 25 aspects of strain and stress. Results from the study group of works councils were compared to those from employees working in administration and to the general population mean (COPSOQ database). Statistical analysis included t-tests, analysis of variance and multiple comparisons of means. To be significant in terms of statistics, pmobbing, cognitive stress symptoms and burnout. Unfavourable results were obtained for the aspects: quality of leadership, social support, sense of community and general health. Favourable findings were found on the scales: influence at work, quantity of social relations and the partly positive values for quantitative demands and commitment to the workplace. Conclusion Compared to the reference groups, works council members perceive the psychosocial demands of working life as more exhausting for the majority of aspects. This allows several conclusions. One reason may be the extended tasks employee representatives face, an other may be that the education of most works council members does not seem appropriate to the high demands of their managerial and executive tasks. PMID:23101876

  16. Soil monitoring in Germany. Spatial representativity and methodical comparability

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, W.; Pesch, R.; Schmidt, G. [Inst. fuer Umweltwissenschaften sowie Forschungszentrum fuer Geoinformatik und Fernerkundung der Hochschule Vechta, Vechta (Germany)

    2004-07-01

    Soil monitoring in Germany should register the current soil condition, monitor its changes and provide a forecast for future development. In order to achieve these goals, the long-term soil monitoring sites in Germany (BDF - Bodendauerbeobachtungsflaechen) have been established by the federal states. This has been done according to criteria worked out by soil monitoring experts. In this article a method for the examination of the suitability of Germany's soil monitoring sites for soil conservation and protection purposes, as well as for environmental monitoring and reporting, is introduced. This method includes the landscape representativity of soil monitoring sites as well as the comparability and spatial validity of collected data. Methods. BDF-criteria are operationalized in a three-step procedure: at first, a metadatabase is established containing information that allows the comparison of monitoring sites by means of measuring parameters, methods and quality assurance as well as quality control of measurements. Secondly, the representativity of the BDF-sites for soil types, land use, vegetation, and climate (air temperature, duration of sunlight, precipitation) by means of frequency statistics and neighborhood analysis is quantified. At last, the spatial validity of soil monitoring data is examined through the application of geostatistical methods. Both data and statistical methods are integrated in a geoinformationsystem (GIS). (orig.)

  17. Using Logic Programming to Represent Information Content Inclusion Relations

    Directory of Open Access Journals (Sweden)

    Doug Salt

    2012-02-01

    Full Text Available Datalog is a widely recognised language for a certain class of deductive databases. Information Content Inclusion Relation (IIR formulates a general, information theoretic relationship between: data constructs; between data constructs and real world objects, and between real world objects. IIR is particularly concerned with the information that data carry. It would therefore seem desirable to find out whether IIR and reasoning based on IIR may be implemented by using ‘safe’ Datalog. We present and prove the following theorem:Any database system that can be modelled using IIR can be represented as a ‘safe’ Datalog program.}This paper explores the nature of the relationship between the two frameworks for representing domains of application, in order that such representations of IIR by `safe' Datalog can then be used as a tool for the analysis of any site that can be approached with the notion of information content, and in particular any given database, and hence how a database works may be approached in terms of information content of events.

  18. Reduced-Reference Video Quality Estimation Using Representative Luminance

    Science.gov (United States)

    Yamada, Toru; Miyamoto, Yoshihiro; Serizawa, Masahiro; Nishitani, Takao

    This paper proposes a video-quality estimation method based on a reduced-reference model for realtime quality monitoring in video streaming services. The proposed method chooses representative-luminance values for individual original-video frames at a server side and transmits those values, along with the pixel-position information of the representative-luminance values in each frame. On the basis of this information, peak signal-to-noise ratio (PSNR) values at client sides can be estimated. This enables realtime monitoring of video-quality degradation by transmission errors. Experimental results show that accurate PSNR estimation can be achieved with additional information at a low bit rate. For SDTV video sequences which are encoded at 1 to 5Mbps, accurate PSNR estimation (correlation coefficient of 0.92 to 0.95) is achieved with small amount of additional information of 10 to 50kbps. This enables accurate realtime quality monitoring in video streaming services without average video-quality degradation.

  19. Challenges to Issues of Balance and Representativeness in African Lexicography

    Directory of Open Access Journals (Sweden)

    Thapelo Joseph Otlogetswe

    2011-10-01

    Full Text Available

    Abstract: Modern dictionaries depend on corpora of different sizes and types for frequency listings, concordances and collocations, illustrative sentences and grammatical information. With the help of computer software, retrieving such information has increasingly become relatively easy. However, the quality of retrieved information for lexicographic purposes depends on the information input at the stage of corpus construction. If corpora are not representative of the different language usages of a speech community, they may prove to be unreliable sources of lexicographic information. There are, however, issues in African languages which make many African corpora questionable. These issues include a lack of texts of different genres, the unavailability of balanced and representative written texts, a complete absence of spoken texts as well as literacy problems in African societies. This article therefore explores the different challenges to the construction of reliable corpora in African languages. It argues that African languages face peculiar challenges and corpus research may require a different treatment compared to European and American corpus research. It finally concludes that issues of balance and representativeness appear theoretically impossible when looking at the results of sociolinguistic research on the different existing language varieties which are difficult to represent accurately in a corpus.

    Keywords: AFRICAN LANGUAGES, BALANCE, BANK OF ENGLISH, BORROWING,BRITISH NATIONAL CORPUS, COBUILD, CODE-SWITCHING, COMPUTERS, CORPORA,DIALECT, DICTIONARIES, FREQUENCY, LANGUAGE VARIETY, REPRESENTATIVENESS,SETSWANA, SOCIOLINGUISTICS, SPEECH, TEXT

    Opsomming: Uitdagings betreffende kwessies van balans en verteenwoordigendheidin Afrikaleksikografie. Moderne woordeboeke steun op korpusse vanverskillende groottes en soorte vir frekwensielyste, konkordansies en kollokasies, voorbeeldsinneen taalkundige inligting. Met die hulp van

  20. Methylation of FHIT Gene Promoter Region in DNA from Plasma of Patients with Myelodysplastic Syndomes and Demethylating Effect of Decitabine%骨髓增生异常综合征患者血浆DNA中FHIT基因启动子区甲基化状态及地西他滨的去甲基化作用

    Institute of Scientific and Technical Information of China (English)

    邓银芬; 张磊; 张秀群; 胡明秋; 戴丹; 张学忠; 徐燕丽

    2012-01-01

    This study was aimed to detect the methylation status of FHIT gene promoter region in the DNA from plasma of patients with myelodysplastic syndrome ( MDS) , and to investigate the demethylating effect of decitabine. Methylation-specific PCR method was used to detect the methylation status of FHIT gene promoter region in the DNA from plasma of 4 patients with MDS before and after treatment with decitabine plus semis CAG therapy(among them, 1 case of newly diagnosed MDS, 3 cases progressed into acute leukemia). The results indicated that 3 cases were found to have an increased methylation in the promoter region. After treatment with decitabine plus semis CAG, increased methylation was reversed in 2 cases. In 4 cases, 2 cases displayed clinical response. It is concluded that FHIT gene hypermethylation is associated with MDS pathogenesis. Decitabine has demethylating effect on the FHIT gene hypermethylation of plasma from MDS patients. Detecting the methylation status of FHIT gene in DNA from plasma may play a role in MDS auxiliary diagnosis or prognosis.%本研究旨在检测骨髓增生异常综合征( MDS)患者血浆DNA中FHIT基因启动子区域甲基化状况及地西他滨对其甲基化的影响.采用甲基化特异性聚合酶链反应法检测1例初治的MDS患者、3例MDS转化而来的AML患者在地西他滨序贯半量CAG方案化疗前后血浆DNA中FHIT基因启动子区域CPG岛甲基化情况,并分析其临床疗效.结果表明,3例患者治疗前有FHIT基因甲基化.治疗1个疗程后其中2例患者FHIT基因甲基化得到逆转,4例患者中有2例获得临床缓解,2例无效.结论:MDS的发生可能与FHIT基因甲基化相关,地西他滨对MDS患者血浆DNA中FHIT基因高甲基化具有明显的去甲基化作用.血浆DNA的FHIT基因甲基化检测可能成为MDS辅助诊断和预后判断的分子标记.

  1. Synthesis, Characterization, and Agricultural Biological Activities of 5-Fluoro-2-hydroxy Butyrophenone

    Directory of Open Access Journals (Sweden)

    Fengli Xin

    2013-01-01

    Full Text Available A novel synthetic approach towards 5-fluoro-2-hydroxy butyrophenone is reported. Using 4-fluorophenol as a raw material, the processes of etherification protection, Friedel-Crafts acylation and demethylation provide the target compound under mild conditions. The structure was characterized by the melting point and IR, MS, 1H-NMR, and 13C-NMR spectroscopy. The bioassay results indicate that the target compound exhibits potent antifungal activities against Valsa mali, Coniella dipodiella, and other agricultural plant fungi. The target compound also shows potent herbicidal activities for Lactuca sativa, a dicotyledon, and Echinochloa crus-galli, a monocotyledon. The toxicity regression C50 values of the compound against Valsa mali, Coniothyrium diplodiella, Lactuca sativa seedling, and Echinochloa crusgalli seedling were calculated by SPSS. The Hormesis effect for roots of Echinochloa crusgalli was confirmed.

  2. Health behaviour in children and adolescents with type 1 diabetes compared to a representative reference population.

    Directory of Open Access Journals (Sweden)

    Sebastian Kummer

    Full Text Available OBJECTIVE: We provide a population-based overview of health behaviours of children and adolescents with type 1 diabetes in comparison to the general population, and analyse their relevance for glycaemic control and self-rated health status. METHODS: Data from questionnaires of 11- to 17-year-old children and adolescents with diabetes (n = 629 were compared to a representative sample (n = 6,813. RESULTS: Children and adolescents with type 1 diabetes had a significantly increased odds of infrequent physical activity (adjusted OR 1.56, short overall duration of physical activity per week (OR 1.55, difference -1.3 hours/week, and high daily computer use (OR 2.51. They had a lower odds of active and passive smoking (OR 0.31 and OR 0.29, and high daily television time (OR 0.68. The odds of an at least good and excellent self-rated health status was increased with intense physical activity, and decreased with active smoking and prolonged daily use of computer and television. Active smoking and prolonged daily use of computer were associated with higher HbA1c. CONCLUSIONS: Children and adolescents with type 1 diabetes showed a different profile of health behaviour. Their overall health may improve if their education stresses specifically frequent physical activity with longer overall duration and less frequent television or computer use.

  3. Defining And Characterizing Sample Representativeness For DWPF Melter Feed Samples

    Energy Technology Data Exchange (ETDEWEB)

    Shine, E. P.; Poirier, M. R.

    2013-10-29

    Representative sampling is important throughout the Defense Waste Processing Facility (DWPF) process, and the demonstrated success of the DWPF process to achieve glass product quality over the past two decades is a direct result of the quality of information obtained from the process. The objective of this report was to present sampling methods that the Savannah River Site (SRS) used to qualify waste being dispositioned at the DWPF. The goal was to emphasize the methodology, not a list of outcomes from those studies. This methodology includes proven methods for taking representative samples, the use of controlled analytical methods, and data interpretation and reporting that considers the uncertainty of all error sources. Numerous sampling studies were conducted during the development of the DWPF process and still continue to be performed in order to evaluate options for process improvement. Study designs were based on use of statistical tools applicable to the determination of uncertainties associated with the data needs. Successful designs are apt to be repeated, so this report chose only to include prototypic case studies that typify the characteristics of frequently used designs. Case studies have been presented for studying in-tank homogeneity, evaluating the suitability of sampler systems, determining factors that affect mixing and sampling, comparing the final waste glass product chemical composition and durability to that of the glass pour stream sample and other samples from process vessels, and assessing the uniformity of the chemical composition in the waste glass product. Many of these studies efficiently addressed more than one of these areas of concern associated with demonstrating sample representativeness and provide examples of statistical tools in use for DWPF. The time when many of these designs were implemented was in an age when the sampling ideas of Pierre Gy were not as widespread as they are today. Nonetheless, the engineers and

  4. Defining And Characterizing Sample Representativeness For DWPF Melter Feed Samples

    International Nuclear Information System (INIS)

    Representative sampling is important throughout the Defense Waste Processing Facility (DWPF) process, and the demonstrated success of the DWPF process to achieve glass product quality over the past two decades is a direct result of the quality of information obtained from the process. The objective of this report was to present sampling methods that the Savannah River Site (SRS) used to qualify waste being dispositioned at the DWPF. The goal was to emphasize the methodology, not a list of outcomes from those studies. This methodology includes proven methods for taking representative samples, the use of controlled analytical methods, and data interpretation and reporting that considers the uncertainty of all error sources. Numerous sampling studies were conducted during the development of the DWPF process and still continue to be performed in order to evaluate options for process improvement. Study designs were based on use of statistical tools applicable to the determination of uncertainties associated with the data needs. Successful designs are apt to be repeated, so this report chose only to include prototypic case studies that typify the characteristics of frequently used designs. Case studies have been presented for studying in-tank homogeneity, evaluating the suitability of sampler systems, determining factors that affect mixing and sampling, comparing the final waste glass product chemical composition and durability to that of the glass pour stream sample and other samples from process vessels, and assessing the uniformity of the chemical composition in the waste glass product. Many of these studies efficiently addressed more than one of these areas of concern associated with demonstrating sample representativeness and provide examples of statistical tools in use for DWPF. The time when many of these designs were implemented was in an age when the sampling ideas of Pierre Gy were not as widespread as they are today. Nonetheless, the engineers and

  5. Psychosocial workload and stress in the workers’ representative

    Directory of Open Access Journals (Sweden)

    Rabe Martin

    2012-10-01

    Full Text Available Abstract Background Using a data set of works councils of trade union IG Metal, this paper investigates psychosocial stress and strain on this specific group in comparison to employees working in administration in general (leadership and non-leadership-role and a national reference value. Methods For assessing psychosocial work factors on works councils within the sector represented by the trade union IG Metal in Germany, a research by using the German standard version of COPSOQ (Copenhagen Psychosocial Questionnaire was performed. The instrument includes 87 single items forming 25 aspects of strain and stress. Results from the study group of works councils were compared to those from employees working in administration and to the general population mean (COPSOQ database. Statistical analysis included t-tests, analysis of variance and multiple comparisons of means. To be significant in terms of statistics, p Results All in all, 309 works councils from a national survey of the German chemical and metalworking industries took part in the study. 113 were full-time works council members (exempted from the duty to perform their regular work, 196 were voluntary members (acting as employee representatives on an honorary basis alongside their normal duties. Comparison between works councils and employees working in administration (leadership roles (N=1810 and non-leadership roles (N=2970 and for employees in general (N=35.000 showed unfavourable values for works councils for most scales. Significantly higher values indicating higher strain and stress were found for the scales: emotional demands, work-privacy conflict, role conflicts, mobbing, cognitive stress symptoms and burnout. Unfavourable results were obtained for the aspects: quality of leadership, social support, sense of community and general health. Favourable findings were found on the scales: influence at work, quantity of social relations and the partly positive values for quantitative

  6. Hamiltonians representing equations of motion with damping due to friction

    Directory of Open Access Journals (Sweden)

    Stephen Montgomery-Smith

    2014-04-01

    Full Text Available Suppose that $H(q,p$ is a Hamiltonian on a manifold M, and $\\tilde L(q,\\dot q$, the Rayleigh dissipation function, satisfies the same hypotheses as a Lagrangian on the manifold M. We provide a Hamiltonian framework that gives the equation $$ \\dot q = \\frac{\\partial H}{\\partial p}(q,p , \\quad \\dot p = - \\frac{\\partial H}{\\partial q}(q,p - \\frac{\\partial \\tilde L}{\\partial \\dot q}(q,\\dot q $$ The method is to embed M into a larger framework where the motion drives a wave equation on the negative half line, where the energy in the wave represents heat being carried away from the motion. We obtain a version of Nother's Theorem that is valid for dissipative systems. We also show that this framework fits the widely held view of how Hamiltonian dynamics can lead to the ``arrow of time.''

  7. Hamiltonians representing equations of motion with damping due to friction

    CERN Document Server

    Montgomery-Smith, Stephen

    2013-01-01

    Suppose that $H(q,p)$ is a Hamiltonian on a manifold $M$, and $\\tilde L(q,\\dot q)$, the Rayleigh dissipation function, satisfies the same hypotheses as a Lagrangian on the manifold $M$. We provide a Hamiltonian framework that gives the equation $\\dot q = \\frac{\\partial H}{\\partial p}(q,p), \\quad \\dot p = - \\frac{\\partial H}{\\partial q}(q,p) - \\frac{\\partial \\tilde L}{\\partial \\dot q}(q,\\dot q)$. The method is to embed $M$ into a larger framework where the motion drives a wave equation on the negative half line, where the energy in the wave represents heat being carried away from the motion. We obtain a version of N\\"other's Theorem that is valid for dissipative systems. We also provide an explanation of the "arrow of time."

  8. Enterprise Systems Implementations: Organizational Influence Processes for Corporate User Representatives

    DEFF Research Database (Denmark)

    Nielsen, Peter Axel; Nordheim, Stig

    2008-01-01

    Enterprise system implementation is a complex and large undertaking. Business requirements does not necessarily fit the inherited as-is features of the software. To reach agreement on features to implement requires prudent management and astute exercise of power. In this paper we draw on an in-de...... rational persuasion and consultation. In addition, the corporate user representative benefits from a strong reference group to give input from the organization.......Enterprise system implementation is a complex and large undertaking. Business requirements does not necessarily fit the inherited as-is features of the software. To reach agreement on features to implement requires prudent management and astute exercise of power. In this paper we draw on an in...

  9. Use of S-α diagram for representing tokamak equilibrium

    International Nuclear Information System (INIS)

    A use of the S-α diagram is proposed as a tool for representing the plasma equilibrium with a qualitative characterization of its stability through pattern recognition. The diagram is an effective tool for visually presenting the relationship between the shear and dimensionless pressure gradient of an equilibrium. In the PBX-M tokamak, an H-mode operating regime with high poloidal β and L-mode regime with high toroidal β, obtained using different profile modification techniques, are found to have distinct S-α trajectory patterns. Pellet injection into a plasma in the H-mode regime with high toroidal β, obtained using different profile modification techniques, are found to have distinct S-α trajectory patterns. Pellet injection into a plasma in the H-mode regime results in favorable qualities of both regimes. The β collapse process and ELM event also manifest themselves as characteristic changes in the S-α pattern

  10. Frequency of lucid dreaming in a representative German sample.

    Science.gov (United States)

    Schredl, Michael; Erlacher, Daniel

    2011-02-01

    Lucid dreams occur when a person is aware that he is dreaming while he is dreaming. In a representative sample of German adults (N = 919), 51% of the participants reported that they had experienced a lucid dream at least once. Lucid dream recall was significantly higher in women and negatively correlated with age. However, these effects might be explained by the frequency of dream recall, as there was a correlation of .57 between frequency of dream recall and frequency of lucid dreams. Other sociodemographic variables like education, marital status, or monthly income were not related to lucid dream frequency. Given the relatively high prevalence of lucid dreaming reported in the present study, research on lucid dreams might be pursued in the sleep laboratory to expand the knowledge about sleep, dreaming, and consciousness processes in general.

  11. Representing ICD-11 JLMMS Using IHTSDO Representation Formalisms.

    Science.gov (United States)

    Mamou, Marzouk; Rector, Alan; Schulz, Stefan; Campbell, James; Solbrig, Harold; Rodrigues, Jean-Marie

    2016-01-01

    It is investigated whether the content of the Joint Linearization for Mortality and Morbidity Statistics of the 11th ICD revision can be semantically represented by formalisms acting on the clinical terminology SNOMED CT, viz. the IHTSDO Compositional Grammar (CG) and the Expression Constraint Language (ECL). Whereas CG provides a composition syntax for building coordinated SNOMED CT expressions, ECL provides a powerful query mechanism. Both formalisms can be leveraged to guarantee inter-operation between an ontology-based terminology like SNOMED CT and a statistical classification like ICD, characterized by single hierarchies and exhaustive, mutually exclusive classes. We test the feasibility of the method on the circulatory chapter of ICD-11 JLMMS. PMID:27577419

  12. COMAS: representative spreading experiments with view to core melt mitigation

    International Nuclear Information System (INIS)

    Within the COMAS (corium on material surfaces) project representative experimental and analytical investigations on the ex-vessel spreading behaviour of prototypic corium were performed to provide a realistic technical basis for the development of core catchers for future nuclear reactor generations. In various large-scale experiments melts in the Mg-range with real corium compositions and temperatures around 2000 C were tested using different substratum materials (concrete, ceramics, cast iron). The COMAS results indicate that for a sufficiently high melt release rate a quick and homogeneous coverage of an ex-vessel spreading compartment as realized in the Franco-German EPR project can be expected. Regarding the analytical assessment it can be concluded that some spreading codes have reached a sufficient level to provide guidelines for the evaluation of spreading concepts. Open questions are mainly related to segregation and immobilization of the melt. (orig.)

  13. Invariant Representative Cocycles of Cohomology Generators using Irregular Graph Pyramids

    CERN Document Server

    Gonzalez-Diaz, Rocio; Iglesias-Ham, Mabel; Kropatsch, Walter G; 10.1016/j.cviu.2010.12.009

    2011-01-01

    Structural pattern recognition describes and classifies data based on the relationships of features and parts. Topological invariants, like the Euler number, characterize the structure of objects of any dimension. Cohomology can provide more refined algebraic invariants to a topological space than does homology. It assigns `quantities' to the chains used in homology to characterize holes of any dimension. Graph pyramids can be used to describe subdivisions of the same object at multiple levels of detail. This paper presents cohomology in the context of structural pattern recognition and introduces an algorithm to efficiently compute representative cocycles (the basic elements of cohomology) in 2D using a graph pyramid. An extension to obtain scanning and rotation invariant cocycles is given.

  14. Reliability of structure tensors in representing soft tissues structure.

    Science.gov (United States)

    Lanir, Yoram; Namani, Ravi

    2015-06-01

    Structure tensors have been applied as descriptors of tissue morphology for constitutive modeling. Here the reliability of these tensors in representing tissues structure is investigated by model simulations of a few examples of generated and measured planar fiber orientation distributions. Reliability was evaluated by comparing the data with the orientation density distribution recovered from the structure tensor representation, and with a orientation density recovered from an alternative representation by Fourier series of spherical harmonics. The results show that except for the case of uniform or close to uniform orientation distributions, the distributions recovered from the structure tensor fit the data poorly. On the other hand, orientation distributions recovered from Fourier series of spherical harmonics converge to the data distributions provided sufficient terms are included in the truncated series. These results suggest that the structure tensor is a reliable descriptor of tissue structure only under very limited cases. PMID:25828155

  15. Representative Pathways of Excitation Migration in Photosystem I

    CERN Document Server

    Park, S; Lu, D; Schulten, K; Park, Sanghyun; Sener, Melih K.; Lu, Deyu; Schulten, Klaus

    2002-01-01

    Photosystem I is a protein-pigment complex that performs photosynthesis in plants, green algae, and cyanobacteria. It contains an aggregate of chlorophylls that absorbs light and delivers the resulting electronic excitation to the special pair of chlorophylls where the excitation energy is used for producing charge separation across the cell membrane. The seemingly random arrangement of chlorophylls in photosystem I poses the question which pathways excitation migration follows towards the special pair after absorption of light at any of its chlorophylls. We employ a master equation to describe the process of excitation migration in photosystem I, and find representative paths of excitation migration based on the mean first-passage time from each chlorophyll to the special pair. The resulting paths, beginning at each of the chlorophylls and ending at the special pair, provide a complete yet distilled picture of the excitation migration towards the special pair.

  16. Wave propagation in equivalent continuums representing truss lattice materials

    Energy Technology Data Exchange (ETDEWEB)

    Messner, Mark C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Barham, Matthew I. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Kumar, Mukul [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Barton, Nathan R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-07-29

    Stiffness scales linearly with density in stretch-dominated lattice meta-materials offering the possibility of very light yet very stiff structures. Current additive manufacturing techniques can assemble structures consisting of these lattice materials, but the design of such structures will require accurate, efficient simulation techniques. Equivalent continuum models have several advantages over discrete truss models of stretch dominated lattices, including computational efficiency and ease of model construction. However, the development an equivalent model suitable for representing the dynamic response of a periodic truss is complicated by microinertial effects. This paper derives a dynamic equivalent continuum model for periodic truss structures and verifies it against detailed finite element simulations. The model must incorporate microinertial effects to accurately reproduce long-wavelength characteristics of the response such as anisotropic elastic soundspeeds. The formulation presented here also improves upon previous work by preserving equilibrium at truss joints for affine lattice deformation and by improving numerical stability by eliminating vertices in the effective yield surface.

  17. Emergency preparedness training of tribal community health representatives.

    Science.gov (United States)

    Hites, Lisle S; Granillo, Brenda S; Garrison, Edward R; Cimetta, Adriana D; Serafin, Verena J; Renger, Ralph F; Wakelee, Jessica F; Burgess, Jefferey L

    2012-04-01

    This study describes the development and evaluation of online Public Health Emergency Preparedness (PHEP) training adapted to the learning styles and needs of tribal Community Health Representatives (CHRs). Working through a university-tribal community college partnership, the Arizona Center for Public Health Preparedness at the University of Arizona and Diné College of the Navajo Nation delivered a blended online and face-to-face public health preparedness certificate program based on core public health emergency preparedness competencies. This program was carefully adapted to meet the environmental and learning needs of the tribal CHRs. The certificate program was subsequently evaluated via a scenario-based decision-making methodology. Significant improvements in five of six competency areas were documented by comparison of pre- and post-certificate training testing. Based on statistical support for this pedagogical approach the cultural adaptations utilized in delivery of the certificate program appear to be effective for PHEP American Indian education.

  18. A representative density profile of the North Greenland snowpack

    Science.gov (United States)

    Florian Schaller, Christoph; Freitag, Johannes; Kipfstuhl, Sepp; Laepple, Thomas; Steen-Larsen, Hans Christian; Eisen, Olaf

    2016-09-01

    Along a traverse through North Greenland in May 2015 we collected snow cores up to 2 m depth and analyzed their density and water isotopic composition. A new sampling technique and an adapted algorithm for comparing data sets from different sites and aligning stratigraphic features are presented. We find good agreement of the density layering in the snowpack over hundreds of kilometers, which allows the construction of a representative density profile. The results are supported by an empirical statistical density model, which is used to generate sets of random profiles and validate the applied methods. Furthermore we are able to calculate annual accumulation rates, align melt layers and observe isotopic temperatures in the area back to 2010. Distinct relations of δ18O with both accumulation rate and density are deduced. Inter alia the depths of the 2012 melt layers and high-resolution densities are provided for applications in remote sensing.

  19. Frequency of lucid dreaming in a representative German sample.

    Science.gov (United States)

    Schredl, Michael; Erlacher, Daniel

    2011-02-01

    Lucid dreams occur when a person is aware that he is dreaming while he is dreaming. In a representative sample of German adults (N = 919), 51% of the participants reported that they had experienced a lucid dream at least once. Lucid dream recall was significantly higher in women and negatively correlated with age. However, these effects might be explained by the frequency of dream recall, as there was a correlation of .57 between frequency of dream recall and frequency of lucid dreams. Other sociodemographic variables like education, marital status, or monthly income were not related to lucid dream frequency. Given the relatively high prevalence of lucid dreaming reported in the present study, research on lucid dreams might be pursued in the sleep laboratory to expand the knowledge about sleep, dreaming, and consciousness processes in general. PMID:21466083

  20. Representing vegetation processes in hydrometeorological simulations using the WRF model

    DEFF Research Database (Denmark)

    Nielsen, Joakim Refslund

    to the occurrence of heat wave and drought conditions. The results of the sim-ulations over these regions obtained using the WRF model, at relatively low spatial resolution and using MODIS vegetation data sets, showed improved temperature predictions when using the quadratic approach. The quadratic MODIS vegetation......For accurate predictions of weather and climate, it is important that the land surface and its processes are well represented. In a mesoscale model the land surface processes are calculated in a land surface model (LSM). These pro-cesses include exchanges of energy, water and momentum between......-ments are still needed in the representation of the land surface variability and of some key land surface processes. This thesis explores two possibilities for improving the near-surface model predictions using the mesoscale Weather Research and Forecasting (WRF) model. In the _rst approach, data from satellite...