WorldWideScience

Sample records for active demethylation represent

  1. Active DNA Demethylation Mediated by DNA Glycosylases

    Zhu, Jian-Kang

    2009-01-01

    Active DNA demethylation is involved in many vital developmental and physiological processes of plants and animals. Recent genetic and biochemical studies in Arabidopsis have demonstrated that a subfamily of DNA glycosylases function to promote DNA demethylation through a base excision-repair pathway. These specialized bifunctional DNA glycosylases remove the 5-methylcytosine base and then cleave the DNA backbone at the abasic site, resulting in a gap that is then filled with an unmethylated ...

  2. Active DNA demethylation by oxidation and repair

    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.

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

    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. The role of active DNA demethylation and Tet enzyme function in memory formation and cocaine action.

    Alaghband, Yasaman; Bredy, Timothy W; Wood, Marcelo A

    2016-06-20

    Active DNA modification is a major epigenetic mechanism that regulates gene expression in an experience-dependent manner, which is thought to establish stable changes in neuronal function and behavior. Recent discoveries regarding the Ten eleven translocation (Tet1-3) family of DNA hydroxylases have provided a new avenue for the study of active DNA demethylation, and may thus help to advance our understanding of how dynamic DNA modifications lead to long-lasting changes in brain regions underlying learning and memory, as well as drug-seeking and propensity for relapse following abstinence. Drug addiction is a complex, relapsing disorder in which compulsive drug-seeking behavior can persist despite aversive consequences. Therefore, understanding the molecular mechanisms that underlie the onset and persistence of drug addiction, as well as the pronounced propensity for relapse observed in addicts, is necessary for the development of selective treatments and therapies. In this mini-review, we provide an overview of the involvement of active DNA demethylation with an emphasis on the Tet family of enzymes and 5-hydroxymethylcytosine (5-hmC) in learning and memory, as well as in drug-seeking behavior. Memory and addiction share overlapping molecular, cellular, and circuit functions allowing research in one area to inform the other. Current discrepancies and directions for future studies focusing on the dynamic interplay between DNA methylation and demethylation, and how they orchestrate gene expression required for neuronal plasticity underlying memory formation, are discussed. PMID:26806038

  5. SUMO-modification and elimination of the active DNA demethylation enzyme TDG in cultured human cells.

    Moriyama, Taishi; Fujimitsu, Yuka; Yoshikai, Yushi; Sasano, Takashi; Yamada, Koji; Murakami, Masataka; Urano, Takeshi; Sugasawa, Kaoru; Saitoh, Hisato

    2014-05-01

    Thymine DNA glycosylase (TDG) is a base excision repair enzyme that interacts with the small ubiquitin-related modifier (SUMO)-targeted ubiquitin E3 ligase RNF4 and functions in the active DNA demethylation pathway. Here we showed that both SUMOylated and non-modified forms of endogenous TDG fluctuated during the cell cycle and in response to drugs that perturbed cell cycle progression, including hydroxyurea and nocodazole. Additionally, we detected a SUMOylation-independent association between TDG and RNF4 in vitro as well as in vivo, and observed that both forms of TDG were efficiently degraded in RNF4-depleted cells when arrested at S phase. Our findings provide insights into the in vivo dynamics of TDG SUMOylation and further clarify the TDG-RNF4 interaction. PMID:24727457

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

    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 of this...

  7. IL-2 and GM-CSF are regulated by DNA demethylation during activation of T cells, B cells and macrophages

    Highlights: ► DNA methylation is dynamic and flexible and changes rapidly upon cell activation. ► DNA methylation controls the inducible gene expression in a given cell type. ► Some enzymes are involved in maintaining the methylation profile of immune cells. -- Abstract: DNA demethylation has been found to occur at the promoters of a number of actively expressed cytokines and is believed to play a critical role in transcriptional regulation. While many DNA demethylation studies have focused on T cell activation, proliferation and differentiation, changes in DNA methylation in other types of immune cells are less well studied. We found that the expression of two cytokines (IL-2 and GM-CSF) responded differently to activation in three types of immune cells: EL4, A20 and RAW264.7 cells. Using the McrBC and MeDIP approaches, we observed decreases in DNA methylation at a genome-wide level and at the promoters of the genes of these cytokines. The expression of several potential enzymes/co-enzymes involved in the DNA demethylation pathways seemed to be associated with immune cell activation.

  8. Regulation of Active DNA Demethylation by a Methyl-CpG-Binding Domain Protein in Arabidopsis thaliana.

    Qi Li

    2015-05-01

    Full Text Available Active DNA demethylation plays crucial roles in the regulation of gene expression in both plants and animals. In Arabidopsis thaliana, active DNA demethylation is initiated by the ROS1 subfamily of 5-methylcytosine-specific DNA glycosylases via a base excision repair mechanism. Recently, IDM1 and IDM2 were shown to be required for the recruitment of ROS1 to some of its target loci. However, the mechanism(s by which IDM1 is targeted to specific genomic loci remains to be determined. Affinity purification of IDM1- and IDM2- associating proteins demonstrated that IDM1 and IDM2 copurify together with two novel components, methyl-CpG-binding domain protein 7 (MBD7 and IDM2-like protein 1 (IDL1. IDL1 encodes an α-crystallin domain protein that shows high sequence similarity with IDM2. MBD7 interacts with IDM2 and IDL1 in vitro and in vivo and they form a protein complex associating with IDM1 in vivo. MBD7 directly binds to the target loci and is required for the H3K18 and H3K23 acetylation in planta. MBD7 dysfunction causes DNA hypermethylation and silencing of reporter genes and a subset of endogenous genes. Our results suggest that a histone acetyltransferase complex functions in active DNA demethylation and in suppression of gene silencing at some loci in Arabidopsis.

  9. Biochemical reconstitution of TET1-TDG-BER-dependent active DNA demethylation reveals a highly coordinated mechanism.

    Weber, Alain R; Krawczyk, Claudia; Robertson, Adam B; Kuśnierczyk, Anna; Vågbø, Cathrine B; Schuermann, David; Klungland, Arne; Schär, Primo

    2016-01-01

    Cytosine methylation in CpG dinucleotides is an epigenetic DNA modification dynamically established and maintained by DNA methyltransferases and demethylases. Molecular mechanisms of active DNA demethylation began to surface only recently with the discovery of the 5-methylcytosine (5mC)-directed hydroxylase and base excision activities of ten-eleven translocation (TET) proteins and thymine DNA glycosylase (TDG). This implicated a pathway operating through oxidation of 5mC by TET proteins, which generates substrates for TDG-dependent base excision repair (BER) that then replaces 5mC with C. Yet, direct evidence for a productive coupling of TET with BER has never been presented. Here we show that TET1 and TDG physically interact to oxidize and excise 5mC, and proof by biochemical reconstitution that the TET-TDG-BER system is capable of productive DNA demethylation. We show that the mechanism assures a sequential demethylation of symmetrically methylated CpGs, thereby avoiding DNA double-strand break formation but contributing to the mutability of methylated CpGs. PMID:26932196

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

    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

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

    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.

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

    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.

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

    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

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

    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

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

    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

  17. 5-Methylcytosine-DNA glycosylase activity is present in a cloned G/T mismatch DNA glycosylase associated with the chicken embryo DNA demethylation complex

    Zhu, Bing; Zheng, Yong; Hess, Daniel; Angliker, Herbert; Schwarz, Steffen; Siegmann, Michel; Thiry, Stéphane; Jost, Jean-Pierre

    2000-01-01

    We previously have shown that DNA demethylation by chicken embryo 5-methylcytosine DNA glycosylase (5-MCDG) needs both RNA and proteins. One of these proteins is a RNA helicase. Further peptides were sequenced, and three of them are identical to the mammalian G/T mismatch DNA glycosylase. A 3,233-bp cDNA coding for the chicken homologue of human G/T mismatch DNA glycosylase was isolated and sequenced. The derived amino acid sequence (408 aa) shows 80% identity with the human G/T mismatch DNA ...

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

    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.

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

    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

  20. Spatial control of protein phosphatase 2A (de)methylation

    Reversible methylation of the protein phosphatase 2A catalytic subunit (PP2AC) is an important regulatory mechanism playing a crucial role in the selective recruitment of regulatory B subunits. Here, we investigated the subcellular localization of leucine carboxyl methyltransferase (LCMT1) and protein phosphatase methylesterase (PME-1), the two enzymes catalyzing this process. The results show that PME-1 is predominantly localized in the nucleus and harbors a functional nuclear localization signal, whereas LCMT1 is underrepresented in the nucleus and mainly localizes to the cytoplasm, Golgi region and late endosomes. Indirect immunofluorescence with methylation-sensitive anti-PP2AC antibodies revealed a good correlation with the methylation status of PP2AC, demethylated PP2AC being substantially nuclear. Throughout mitosis, demethylated PP2AC is associated with the mitotic spindle and during cytokinesis with the cleavage furrow. Overexpression of PME-1, but not of an inactive mutant, results in increased demethylation of PP2AC in the nucleus, whereas overexpression of a cytoplasmic PME-1 mutant lacking the NLS results in increased demethylation in the cytoplasm-in all cases, however, without any obvious functional consequences. PME-1 associates with an inactive PP2A population, regardless of its esterase activity or localization. We propose that stabilization of this inactive, nuclear PP2A pool is a major in vivo function of PME-1

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

    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...

  2. Representing cognitive activities and errors in HRA trees

    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

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

    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

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

    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.

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

    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

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

    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.

  7. Identification of RING finger protein 4 (RNF4) as a modulator of DNA demethylation through a functional genomics screen.

    Hu, Xiaoyi V; Rodrigues, Tânia M A; Tao, Haiyan; Baker, Robert K; Miraglia, Loren; Orth, Anthony P; Lyons, Gary E; Schultz, Peter G; Wu, Xu

    2010-08-24

    DNA methylation is an important epigenetic modification involved in transcriptional regulation, nuclear organization, development, aging, and disease. Although DNA methyltransferases have been characterized, the mechanisms for DNA demethylation remain poorly understood. Using a cell-based reporter assay, we performed a functional genomics screen to identify genes involved in DNA demethylation. Here we show that RNF4 (RING finger protein 4), a SUMO-dependent ubiquitin E3-ligase previously implicated in maintaining genome stability, plays a key role in active DNA demethylation. RNF4 reactivates methylation-silenced reporters and promotes global DNA demethylation. Rnf4 deficiency is embryonic lethal with higher levels of methylation in genomic DNA. Mechanistic studies show that RNF4 interacts with and requires the base excision repair enzymes TDG and APE1 for active demethylation. This activity appears to occur by enhancing the enzymatic activities that repair DNA G:T mismatches generated from methylcytosine deamination. Collectively, our study reveals a unique function for RNF4, which may serve as a direct link between epigenetic DNA demethylation and DNA repair in mammalian cells. PMID:20696907

  8. Mining and representing recommendations in actively evolving recommender systems

    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...

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

    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.

  10. [Antiviral activity of representatives of the family Crassulaceae].

    Shirobokov, V P; Evtushenko, A I; Lapchik, V F; Shirobokova, D N; Suptel', E A

    1981-12-01

    The antiviral properties of the juice of 11 species of the orpine family were studied. 8 of them belonged to the genera Kalanchoe, i. e. Kalanchoe diagremontiona R. Hamet, K. pinnata (Zam.) Persoon, K. Peteri Werd., K. prolifera (Bovie) R. Hamet, K. marnierriana (Mann. et Boit) Jacobs; K. blossfeldiana v. Poelln, K. beharensis Drake del Gastillo, K. waldheimii R. Hamet et Perr and 3 belonged to the Sedum genera, i. e. Sedum telephium L., S. spectabile Boreau, S. acre L. A high virus neutralizing activity of the juice from 4 species of Kalanchoe, i. e. K. blossfeldiana, K. waldheimii, K. pinnata and K. beharensis was shown. Inhibition of the virus infecting activity was observed at the juice dilutions from 1-2 to 1-8000 and higher. The viricidal factor of Kalanchoe is stable. It is not destroyed by ether, alcohol and potassium periodate. It is not absorbed by bentonite at the acid pH values. Addition of cattle serum or purified proteins to the juice resulted in their precipitation which suppressed the viricidal activity of the juice. PMID:7198890

  11. Representing cognitive activities and errors in HRA trees

    This paper discusses development of a means by which to present cognitive information in human reliability assessment (HRA) event trees. The descriptions found in probabilistic risk assessments (PRAs) regarding the demands on, and the resulting performance of, nuclear power plant (NPP) crews often make use of the technique for human error rate prediction (THERP), which provides a mechanism, the HRA event tree, for presenting the analyst's conceptualization of the activities underlying performance and the errors associated with that performance. When using THERP, analysts have often omitted the more complex elements of human cognition from these trees. There has yet to be a concerted effort to take theory, principles, and data from cognitive psychology and wed it to the logic structure of the HRA event tree. This paper attempts to do so. The COGENT modeling scheme (cognitively based HRA event trees) adds two taxonomies to the HRA event tree proposed by Swain and Guttman. The first taxonomy, the one proposed by Norman and Reason, describes the type of error committed and implies something about the underlying cognition as well. The second of these, the Rasmussen taxonomy, provides description regarding the skill-based, rule-based, or knowledge-based behavior underlying the execution of tasks. It is not apparent and must be deduced from the pattern of errors exhibited by personnel

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

    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

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

    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.

  14. Demethylation and cleavage of dimethylsulfoniopropionate in marine intertidal sediments

    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.

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

    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...

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

    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

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

    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.

  18. Regioselective demethylation of quinoline derivatives. A DFT rationalization

    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).

  19. DNA oxidation as triggered by H3K9me2 demethylation drives estrogen-induced gene expression.

    Perillo, Bruno; Ombra, Maria Neve; Bertoni, Alessandra; Cuozzo, Concetta; Sacchetti, Silvana; Sasso, Annarita; Chiariotti, Lorenzo; Malorni, Antonio; Abbondanza, Ciro; Avvedimento, Enrico V

    2008-01-11

    Modifications at the N-terminal tails of nucleosomal histones are required for efficient transcription in vivo. We analyzed how H3 histone methylation and demethylation control expression of estrogen-responsive genes and show that a DNA-bound estrogen receptor directs transcription by participating in bending chromatin to contact the RNA polymerase II recruited to the promoter. This process is driven by receptor-targeted demethylation of H3 lysine 9 at both enhancer and promoter sites and is achieved by activation of resident LSD1 demethylase. Localized demethylation produces hydrogen peroxide, which modifies the surrounding DNA and recruits 8-oxoguanine-DNA glycosylase 1 and topoisomeraseIIbeta, triggering chromatin and DNA conformational changes that are essential for estrogen-induced transcription. Our data show a strategy that uses controlled DNA damage and repair to guide productive transcription. PMID:18187655

  20. N-demethylation of ethylmorphine in pregnant and non-pregnant women and in men: an evaluation of the effects of sex steroids.

    Gerdin, E; Rane, A

    1992-01-01

    1. The effects of oestrogens, testosterone, progesterone and medroxyprogesterone acetate (MPA) on the rate of N-demethylation of ethylmorphine (EM) to norethylmorphine (NEM) were studied in human adult liver microsomes. 2. N-Demethylase activity was found to be inhibited by progesterone and MPA to a similar extent while oestrogens and testosterone had no or negligible effects. 3. These findings prompted us to measure the N-demethylation of EM in relation to serum progesterone concentration in...

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

    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.

  2. Demethylation of arsenic limits its volatilization in fungi

    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

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

    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

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

    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.

  5. MES16, a member of the methylesterase protein family, specifically demethylates fluorescent chlorophyll catabolites during chlorophyll breakdown in Arabidopsis.

    Christ, Bastien; Schelbert, Silvia; Aubry, Sylvain; Süssenbacher, Iris; Müller, Thomas; Kräutler, Bernhard; Hörtensteiner, Stefan

    2012-02-01

    During leaf senescence, chlorophyll (Chl) is broken down to nonfluorescent chlorophyll catabolites (NCCs). These arise from intermediary fluorescent chlorophyll catabolites (FCCs) by an acid-catalyzed isomerization inside the vacuole. The chemical structures of NCCs from Arabidopsis (Arabidopsis thaliana) indicate the presence of an enzyme activity that demethylates the C13(2)-carboxymethyl group present at the isocyclic ring of Chl. Here, we identified this activity as methylesterase family member 16 (MES16; At4g16690). During senescence, mes16 leaves exhibited a strong ultraviolet-excitable fluorescence, which resulted from large amounts of different FCCs accumulating in the mutants. As confirmed by mass spectrometry, these FCCs had an intact carboxymethyl group, which slowed down their isomerization to respective NCCs. Like a homologous protein cloned from radish (Raphanus sativus) and named pheophorbidase, MES16 catalyzed the demethylation of pheophorbide, an early intermediate of Chl breakdown, in vitro, but MES16 also demethylated an FCC. To determine the in vivo substrate of MES16, we analyzed pheophorbide a oxygenase1 (pao1), which is deficient in pheophorbide catabolism and accumulates pheophorbide in the chloroplast, and a mes16pao1 double mutant. In the pao1 background, we additionally mistargeted MES16 to the chloroplast. Normally, MES16 localizes to the cytosol, as shown by analysis of a MES16-green fluorescent protein fusion. Analysis of the accumulating pigments in these lines revealed that pheophorbide is only accessible for demethylation when MES16 is targeted to the chloroplast. Together, these data demonstrate that MES16 is an integral component of Chl breakdown in Arabidopsis and specifically demethylates Chl catabolites at the level of FCCs in the cytosol. PMID:22147518

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

    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.

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

    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

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

    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

  9. Germline DNA demethylation dynamics and imprint erasure through 5-hydroxymethylcytosine.

    Hackett, Jamie A; Sengupta, Roopsha; Zylicz, Jan J; Murakami, Kazuhiro; Lee, Caroline; Down, Thomas A; Surani, M Azim

    2013-01-25

    Mouse primordial germ cells (PGCs) undergo sequential epigenetic changes and genome-wide DNA demethylation to reset the epigenome for totipotency. Here, we demonstrate that erasure of CpG methylation (5mC) in PGCs occurs via conversion to 5-hydroxymethylcytosine (5hmC), driven by high levels of TET1 and TET2. Global conversion to 5hmC initiates asynchronously among PGCs at embryonic day (E) 9.5 to E10.5 and accounts for the unique process of imprint erasure. Mechanistically, 5hmC enrichment is followed by its protracted decline thereafter at a rate consistent with replication-coupled dilution. The conversion to 5hmC is an important component of parallel redundant systems that drive comprehensive reprogramming in PGCs. Nonetheless, we identify rare regulatory elements that escape systematic DNA demethylation in PGCs, providing a potential mechanistic basis for transgenerational epigenetic inheritance. PMID:23223451

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

    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

  11. Electrophilicities and Protein Covalent Binding of Demethylation Metabolites of Colchicine.

    Guo, Xiucai; Lin, Dongju; Li, Weiwei; Wang, Kai; Peng, Ying; Zheng, Jiang

    2016-03-21

    Colchicine, an alkaloid existing in plants of Liliaceous colchicum, has been widely used in the treatment of gout and familial Mediterranean fever. The administration of colchicine was found to cause liver injury in humans. The mechanisms of colchicine-induced liver toxicity remain unknown. The objectives of this study were to determine the electrophilicities of demethylation metabolites of colchicine and investigate the protein adductions derived from the reactive metabolites of colchicine. Four demethylated colchicine (1-, 2-, 3-, and 10-DMCs), namely, M1-M4, were detected in colchicine-fortified microsomal incubations. Four N-acetyl cysteine (NAC) conjugates (M5-M8) derived from colchicine were detected in the microsomes in the presence of NAC. M5 and M6 were derived from 10-DMC. M7 resulted from the reaction of 2-DMC or 3-DMC with NAC, and M8 originated from 10-DMC. Microsomal protein covalent binding was observed after exposure to colchicine. Two cysteine adducts (CA-1 and CA-2) derived from 10-DMC were found in proteolytically digested microsomal protein samples after incubation with colchicine. The findings allow us to define the chemical property of demethylation metabolites of colchicine and the interaction between protein and the reactive metabolites of colchicine generated in situ. PMID:26845511

  12. Determination of representative nitrogen contents for the activity calculation of core components with respect to the C-14 activity

    Kruse, Philipp [GNS Gesellschaft fuer Nuklear-Service mbH, Essen (Germany); Huettner, Frank [Vattenfall Europe Nuclear, Hamburg (Germany); Phlippen, Peter-Wilhelm [WTI GmbH, Juelich (Germany)

    2015-10-15

    For the final repository Konrad during operating and decommissioning phase, ten radionuclides and two radionuclide groups are restricted regarding their maximum storable activity quantities. One of the ten relevant radionuclides is C-14. The determination of the C-14 activities within activation calculations is currently performed with conservative assumptions. With the results of the presented analysis a method for a realistic determination of representative C-14 contents of irradiated steels is available now. The relevant N-14 contents as a source for the C-14 amount are lower than previously estimated.

  13. Eastern region represents a worrying cluster of active hepatitis C in Algeria in 2012.

    Bensalem, Aïcha; Selmani, Karima; Hihi, Narjes; Bencherifa, Nesrine; Mostefaoui, Fatma; Kerioui, Cherif; Pineau, Pascal; Debzi, Nabil; Berkane, Saadi

    2016-08-01

    Algeria is the largest country of Africa, peopled with populations living a range of traditional/rural and modern/urban lifestyles. The variations of prevalence of chronic active hepatitis care poorly known on the Algerian territory. We conducted a retrospective survey on all patients (n = 998) referred to our institution in 2012 and confirmed by us for an active hepatitis C. Half of the hepatitis C virus (HCV) isolates were genotyped. Forty Algerian regions out of the 48 were represented in our study. Three geographical clusters (Aïn-Temouchent/SidiBelAbbes, Algiers, and a large Eastern region) with an excess of active hepatitis C were observed. Patients coming from the Eastern cluster (Batna, Khenchela, Oum el Bouaghi, and Tebessa) were strongly over-represented (49% of cases, OR = 14.5, P hepatitis C epidemics are currently affecting Algerian population. The most worrying situation is observed in rural regions located east of Algeria. J. Med. Virol. 88:1394-1403, 2016. © 2016 Wiley Periodicals, Inc. PMID:26856380

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

    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

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

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

    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

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

    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

  18. Poly(ADP-ribosylation acts in the DNA demethylation of mouse primordial germ cells also with DNA damage-independent roles.

    Fabio Ciccarone

    Full Text Available Poly(ADP-ribosylation regulates chromatin structure and transcription driving epigenetic events. In particular, Parp1 is able to directly influence DNA methylation patterns controlling transcription and activity of Dnmt1. Here, we show that ADP-ribose polymer levels and Parp1 expression are noticeably high in mouse primordial germ cells (PGCs when the bulk of DNA demethylation occurs during germline epigenetic reprogramming in the embryo. Notably, Parp1 activity is stimulated in PGCs even before its participation in the DNA damage response associated with active DNA demethylation. We demonstrate that PARP inhibition impairs both genome-wide and locus-specific DNA methylation erasure in PGCs. Moreover, we evidence that impairment of PARP activity causes a significant reduction of expression of the gene coding for Tet1 hydroxylases involved in active DNA demethylation. Taken together these results demonstrate new and adjuvant roles of poly(ADP-ribosylation during germline DNA demethylation and suggest its possible more general involvement in genome reprogramming.

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

    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

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

    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.

  1. Effects of fish CYP inducers on difloxacin N-demethylation in kidney cell of Chinese idle (Ctenopharyngodon idellus).

    Yu, Ling Zhi; Yang, Xian Le; Wang, Xiang Ling; Yu, Wen Juan; Hu, Kun

    2010-09-01

    A drug-drug interaction occurs when the effect of one drug is altered by the presence of another drug which is generally associated with the induction of cytochrome P450s (CYPs) activity. Thus, unexpected treatment failures often happen resulting from inappropriate coadministration in fisheries. However, little information is available about CYP induction in fish. The reaction of difloxacin (DIF) biotransformation to sarafloxacin (SAR) belongs to N-demethylation catalyzed mainly by CYP(s). In order to supply useful information on CYP induction, the present study assessed the effects of fish-specific CYP inducers on DIF N-demethylation and enzyme kinetics in kidney cell of Chinese idle (CIK; grass carp (Ctenopharyngodon idellus)) by RP-HPLC. Results demonstrated that the amounts of SAR formation and enzymatic parameters Clint and Vmax were significantly increased due to beta-naphthoflavone (BNF) pretreatment. Therefore, we suggest that CYP1A may be involved in DIF N-demethylation in CIK. This study provides instructive information to ensure treatment success via avoiding CYP induction in fisheries. PMID:19685219

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

    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.

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

    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.

  4. Effects of fish cytochromes P450 inducers and inhibitors on difloxacin N-demethylation in kidney of Chinese idle (Ctenopharyngodon idellus).

    Yu, Ling Zhi; Yang, Xian Le

    2010-05-01

    Cytochromes P450 (CYPs) play key roles in drug metabolism which are widely distributed in kidney in aquatic organisms. CYP(s) mainly catalyzed the N-demethylation reaction of difloxacin (DIF) biotransformation to sarafloxacin (SAR). However, limited information is available about CYP investigation in fish. In order to supply useful information on CYP(s) characterization for DIF N-demethylation, the present study assessed the effects of fish potent CYP inducers and inhibitors on DIF N-demethylation and the inductive and inhibitive enzyme kinetics in kidney of Chinese idle (Ctenopharyngodon idellus) by reversed-phase high-performance liquid chromatography (RP-HPLC). Results demonstrated that the amounts of SAR formation pretreated by β-naphthoflavone (BNF) increased by 1.1-fold and α-naphthoflavone (ANF) inhibited SAR formation level by 0.6-fold at the third day. Enzymatic parameters V(max) and Cl(int) of DIF N-demethylase were increased by 0.56- and 0.38-fold due to β-naphthoflavone (BNF) pretreatment. DIF N-demethylation inhibition by varying ANF concentrations represented a mixed-type inhibition with the value of the inhibition constants (K(i)) 12.9mg/kg. BNF and ANF are the separate typical inducer and inhibitor for CYP1A in fish. Thus, we suggest that CYP1A may be responsible for DIF N-demethylation in kidney. This study provides instructive information to ensure treatment success in fisheries medication with two or more drugs. PMID:21787603

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

    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

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

    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.

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

    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…

  8. NF-kappaB mediates Gadd45beta expression and DNA demethylation in the hippocampus during fear memory formation.

    Lubin, Farah D.

    2015-01-01

    Gadd45-mediated DNA demethylation mechanisms have been implicated in the process of memory formation. However, the transcriptional mechanisms involved in the regulation of Gadd45 gene expression during memory formation remain unexplored. NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) controls transcription of genes in neurons and is a critical regulator of synaptic plasticity and memory formation. In silico analysis revealed several NF-kB (p65/RelA and cRel) consensus...

  9. NF-κB mediates Gadd45β expression and DNA demethylation in the hippocampus during fear memory formation

    Jarome, Timothy J.; Butler, Anderson A.; Nichols, Jessica N.; Pacheco, Natasha L.; Lubin, Farah D.

    2015-01-01

    Gadd45-mediated DNA demethylation mechanisms have been implicated in the process of memory formation. However, the transcriptional mechanisms involved in the regulation of Gadd45 gene expression during memory formation remain unexplored. NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) controls transcription of genes in neurons and is a critical regulator of synaptic plasticity and memory formation. In silico analysis revealed several NF-κB (p65/RelA and cRel) consensus ...

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

    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 ...

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

    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.

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

    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.

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

    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

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

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

    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...

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

    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…

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

    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. DNA demethylation in normal colon tissue predicts predisposition to multiple cancers.

    Kamiyama, H; Suzuki, K; Maeda, T; Koizumi, K; Miyaki, Y; Okada, S; Kawamura, Y J; Samuelsson, J K; Alonso, S; Konishi, F; Perucho, M

    2012-11-29

    Some colon cancer (CC) patients present synchronous cancers at diagnosis and others develop metachronous neoplasms, but the risk factors are unclear for non-hereditary CC. We showed previously that global DNA demethylation increased with aging and correlated with genomic damage in CC, and we show now that preferentially associates to CCs with wild-type p53. This study aimed to elucidate the extent of DNA hypomethylation in patients with single and multiple CC, its relationship with aging, and its potential as predictive tool. We compared by real-time methylation-specific PCR the relative demethylation level (RDL) of long interspersed nucleotide element-1 (LINE-1) sequences in matched cancer tissues and non-cancerous colonic mucosa (NCM) from patients with single and multiple right-sided CCs. Although no RDL difference was found in NCM from single CC patients and healthy volunteers (P=0.5), there was more demethylation (higher RDL) in NCM from synchronous cancer patients (P=1.1 × 10(-5)) multiple CCs also were more demethylated than single CCs (P=0.0014). High NCM demethylation was predictive for metachronous neoplasms (P=0.003). In multivariate logistic regression analyses RDL was the only independent predictor for metachronous (P=0.02) and multiple (P=4.9 × 10(-5)) tumors. The higher LINE-1 demethylation in NCM from patients with multiple (synchronous and metachronous) tumors (P=9.6 × 10(-7)) was also very significant in patients with tumors without (P=3.8 × 10(-6)), but not with (P=0.16) microsatellite instability. NCM demethylation increased with aging in patients with single tumors, but decreased in those with multiple tumors. Moreover, the demethylation difference between patients with single vs multiple tumors appeared higher in younger (P=3.6 × 10(-4)) than in older (P=0.0016) patients. These results predict that LINE-1 hypomethylation in NCM can be used as an epigenetic predictive biomarker for multiple CC risk. The stronger association of

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

    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-...

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

    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...

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

    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

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

    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.

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

    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.

  4. Demethylation of Wheat Straw Alkali Lignin for Application in Phenol Formaldehyde Adhesives

    Yan Song

    2016-05-01

    Full Text Available Lignin is a natural biopolymer with a complex three-dimensional network. It is the second most abundant natural polymer on earth. Commercially, lignin is largely obtained from the waste liquors of pulping and bioethanol productions. In this study, wheat straw alkali lignin (WSAL was demethylated by using an in-situ generated Lewis acid under an optimized demethylation process. The demethylation process was monitored by a semi-quantitative Fourier Transform Infrared Spectroscopy (FTIR method. The demethylated wheat straw alkali lignin (D-WSAL was further characterized by Proton Nuclear Magnetic Resonance (1H NMR, Gel Permeation Chromatography (GPC, and titration methods. After the demethylation process, it was found that the relative value of the methoxy group decreased significantly from 0.82 to 0.17 and the phenolic hydroxyl group increased from 5.2% to 16.0%. Meanwhile, the hydroxyl content increased from 6.6% to 10.3%. GPC results suggested that the weighted averaged molecular weight of D-WSAL was lower than that of WSAL with a smaller polydispersity index. The D-WSAL was then used to replace 60 wt % of phenol to prepare lignin-based phenol formaldehyde adhesives (D-LPF. It was found that both the free formaldehyde content and the free phenol content in D-LPF were less than those of the lignin-based phenol formaldehyde adhesives without lignin demethylation (LPF. Gel time of D-LPF was shortened. Furthermore, the wet and dry bonding strengths of lap shear wood samples bonded using D-LPF were higher than those of the samples bonded using LPF. Therefore, D-WSAL has shown good potential for application in phenol formaldehyde adhesives.

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

    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...

  6. Antroquinonol D, isolated from Antrodia camphorata, with DNA demethylation and anticancer potential.

    Wang, Sheng-Chao; Lee, Tzong-Huei; Hsu, Chun-Hua; Chang, Yu-Jia; Chang, Man-Shan; Wang, Yi-Ching; Ho, Yuan-Soon; Wen, Wu-Che; Lin, Ruo-Kai

    2014-06-18

    DNA methyltransferase 1 (DNMT1) catalyzes DNA methylation and is overexpressed in various human diseases, including cancer. A rational approach to preventing tumorigenesis involves the use of pharmacologic inhibitors of DNA methylation; these inhibitors should reactivate tumor suppressor genes (TSGs) in tumor cells and restore tumor suppressor pathways. Antroquinonol D (3-demethoxyl antroquinonol), a new DNMT1 inhibitor, was isolated from Antrodia camphorata and identified using nuclear magnetic resonance. Antroquinonol D inhibited the growth of MCF7, T47D, and MDA-MB-231 breast cancer cells without harming normal MCF10A and IMR-90 cells. The SRB assay showed that the 50% growth inhibition (GI50) in MCF7, T47D, and MDA-MB-231 breast cancer cells following treatment with antroquinonol D was 8.01, 3.57, and 25.08 μM, respectively. d-Antroquinonol also inhibited the migratory ability of MDA-MB-231 breast cancer cells in wound healing and Transwell assays. In addition, antroquinonol D inhibited DNMT1 activity, as assessed by the DNMT1 methyltransferase activity assay. As the cofactor SAM level increased, the inhibitory effects of d-antroquinonol on DNMT1 gradually decreased. An enzyme activity assay and molecular modeling revealed that antroquinonol D is bound to the catalytic domain of DNMT1 and competes for the same binding pocket in the DNMT1 enzyme as the cofactor SAM, but does not compete for the binding pocket in the DNMT3B enzyme. An Illumina Methylation 450 K array-based assay and real-time PCR assay revealed that antroquinonol D decreased the methylation status and reactivated the expression of multiple TSGs in MDA-MB-231 breast cancer cells. In conclusion, we showed that antroquinonol D induces DNA demethylation and the recovery of multiple tumor suppressor genes, while inhibiting breast cancer growth and migration potential. PMID:24784321

  7. Value of the 14C-aminophenazone respiratory test: Inhibition of the demethylation function of the liver by cimetidine

    In 15 patients with healthy liver and peptic ulcer the demethylation capacity of the liver was determined by the 14C-aminophenazone breathing test before and during treatment with the H2 antagonist cimetidine (daily dose 1.0 g) measuring the expired 14CO2 (DPM/mmol CO2/70 kg body weight) before and 1 hour after intake. Influenced by cimetidine the mean 14CO2 value of 724.7 DPM (S.D. 127.7) decreased to 404.1 DPM (S.D. 153.1). The enzyme activities (ALAT, ASAT, AP, AAP, GGT, CHE) and the concentrations of serum bilirubin and serum albumin remained unchanged and did not correlate mutually and with the 14CO2 data. The aminophenazone test proved to be suitable technique for the recognition of disturbances of the MFO system. (author)

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

    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.

  9. Demethylation of host-cell DNA at the site of avian retrovirus integration

    Hejnar, Jiří; Elleder, Daniel; Hájková, P.; Walter, J.; Blažková, Jana; Svoboda, Jan

    2003-01-01

    Roč. 2003, č. 311 (2003), s. 641-648. ISSN 0006-291X Institutional research plan: CEZ:AV0Z5052915 Keywords : DNA methylation and demethylation * integration of retroviruses * gene silencing Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.836, year: 2003

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

    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.

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

    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

  12. FORMATION AND ACTIVITY OF REPRESENTATIVE ORGANS OF LOCAL SELF GOVERNMENT IN THE SECOND HALF OF THE XIX CENTURY

    Savchenko M. S.

    2015-04-01

    Full Text Available The article is devoted to the creation and activity of principally new organs of local self-government for Russian state – province and uyezd Zemstvos, which were formed by means of elections. Peculiarities of political and legal mechanism of formation of overall class organs of local authorities having too many powers in decision of questions of local sense are disclosed. Attention is paid to incompleteness of legislative regulation of many electoral procedures that made the sphere of administrative discretion significant. There were enlightened principally important characteristics of elections in Zemstvo which are overall class and combination of a principle of property qualification with noble family class representation, on the basis of which the author makes the conclusion on necessity of extension of representations of modern legal science on present qualifications. The comparative analysis of public polemic on the questions of results of Zemstvo reforms is conducted. In general bulk of ideas on extension of Zemstvo representative law the author was singled out two main trends: extension of quantity of voters by means of decrease of qualification limitations and equalization of representation of different social and class groups of population. On the basis of analysis of legal bases of formation and development of electoral process in XIX century the assessment of adequacy of modern system of Russian representative legislation is implemented

  13. 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

    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.

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

    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

  15. Chemotherapeutic Drug-Induced ABCG2 Promoter Demethylation as a Novel Mechanism of Acquired Multidrug Resistance

    Eran E. Bram

    2009-12-01

    Full Text Available ABCG2 is an efflux transporter conferring multidrug resistance (MDR on cancer cells. However, the initial molecular events leading to its up-regulation in MDR tumor cells are poorly understood. Herein, we explored the impact of drug treatment on the methylation status of the ABCG2 promoter and consequent reactivation of ABCG2 gene expression in parental tumor cell lines and their MDR sublines. We demonstrate that ABCG2 promoter methylation is common in T-cell acute lymphoblastic leukemia (T-ALL lines, also present in primary T-ALL lymphoblast specimens. Furthermore, drug selection with sulfasalazine and topotecan induced a complete demethylation of the ABCG2 promoter in the T-ALL and ovarian carcinoma model cell lines CCRF-CEM and IGROV1, respectively. This resulted in a dramatic induction of ABCG2 messenger RNA levels (235- and 743-fold, respectively and consequent acquisition of an ABCG2-dependent MDR phenotype. Quantitative genomic polymerase chain reaction and ABCG2 promoter-luciferase reporter assay did not reveal ABCG2 gene amplification or differential transcriptional trans-activation, which could account for ABCG2 up-regulation in these MDR cells. Remarkably, mimicking cytotoxic bolus drug treatment through 12- to 24-hour pulse exposure of ABCG2-silenced leukemia cells, to clinically relevant concentrations of the chemotherapeutic agents daunorubicin and mitoxantrone, resulted in a marked transcriptional up-regulation of ABCG2. Our findings establish that antitumor drug-induced epigenetic reactivation of ABCG2 gene expression in cancer cells is an early molecular event leading to MDR. These findings have important implications for the emergence, clonal selection, and expansion of malignant cells with the MDR phenotype during chemotherapy.

  16. Methylation of tumour suppressor genes APAF-1 and DAPK-1 and in vitro effects of demethylating agents in bladder and kidney cancer

    Christoph, F.; Kempkensteffen, C.; Weikert, S; Köllermann, J.; Krause, H.; Miller, K; Schostak, M; Schrader, M

    2006-01-01

    To examine the significance of the methylation level of the p53 target and tumour suppressor genes apoptotic protease activating factor-1 (APAF-1) and death-associated protein kinase-1 (DAPK-1) in 80 microdissected tumour samples from transitional cell carcinoma (TCC) of the bladder and 80 tumour samples from clear-cell renal cell carcinoma (RCC) as well as from non-tumourous bladder and kidney tissue. Growth-inhibitory effects of the demethylating agents 5-Aza-2′-deoxycytidine (5-Aza-CdR) an...

  17. Representing dispositions

    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.

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

    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. Sensory rhodopsins I and II modulate a methylation/demethylation system in Halobacterium halobium phototaxis

    This work demonstrates that phototaxis stimuli in the archaebacterium Halobacterium halobium control a methylation/demethylation system in vivo through photoactivation of sensory rhodopsin I (SR-I) in either its attractant or repellent signaling form as well as through the repellent receptor sensory rhodopsin II (SR-II, also called phoborhodopsin). The effects of positive stimuli that suppress swimming reversals (i.e., an increase in attractant or decrease in repellent light) and negative stimuli that induce swimming reversals (i.e., a decrease in attractant or increase in repellent light) through each photoreceptor were monitored by assaying release of volatile [3H]methyl groups. This assay has been used to measure [3H]methanol produced during the process of adaptation to chemotactic stimuli in eubacteria. In H. halobium positive photostimuli produce a transient increase in the rate of demethylation followed by a decrease below the unstimulated value, whereas negative photostimuli cause an increase followed by a rate similar to that of the unstimulated value. Photoactivation of the SR-I attractant and simultaneous photoactivation of the SR-II repellent receptors cancel in their effects on demethylation, demonstrating the methylation system is regulated by an integrated signal. Analysis of mutants indicates that the source for the volatile methyl groups is intrinsic membrane proteins distinct from the chromoproteins that share the membrane. A methyl-accepting protein (94 kDa) previously correlated in amount with the SR-I chromoprotein (25 kDa) is shown here to be missing in a recently isolated SR-I-SR-II+ mutant (Flx3b), thus confirming the association of this protein with SR-I. Photoactivated SR-II in mutant Flx3b controls demethylation, predicting the existence of a photomodulated methyl-accepting component distinct from the 94-kDa protein of SR-I

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

    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...

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

    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...

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

    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

  3. Demethylation of methylmercury in growing rice plants: An evidence of self-detoxification.

    Xu, Xiaohan; Zhao, Jiating; Li, Yunyun; Fan, Yuqin; Zhu, Nali; Gao, Yuxi; Li, Bai; Liu, Hanyu; Li, Yu-Feng

    2016-03-01

    Mercury (Hg) is a global pollutant that poses a serious threat to human and the environment. Rice was found as an important source for human exposure to Hg in some areas. In this study, the transportation and transformation of IHg and MeHg in rice plants exposed to IHg or MeHg were investigated. The IHg and MeHg concentrations in rice roots and shoots collected every five days were analyzed by HPLC-ICP-MS and SR-XANES. When exposed to MeHg, the percent of IHg in rice roots and shoots increased while MeHg decreased significantly, suggesting prominent demethylation of MeHg occurred. However no notable MeHg was found in both roots and shoots of rice plant when exposed to IHg. SR-XANES analysis further confirmed the demethylation of MeHg with rice. This study provides a new finding that demethylation of MeHg could occur in growing rice, which may be a self-defense process of rice plant. PMID:26708765

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

    Highlights: ► Estrogen signaling and demethylation can both control gene expression in breast cancers. ► Cross-talk between these mechanisms is investigated in human MCF-7 breast cancer cells. ► 137 genes are influenced by both 17β-estradiol and demethylating agent 5-aza-2′-deoxycytidine. ► A set of genes is identified as targets of both estrogen signaling and demethylation. ► 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 17β-estradiol (E2) and a demethylating agent 5-aza-2′-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 these genes in MCF-7 cells. In a further analysis of the potential interplay between estrogen signaling and DNA methylation, E2 treatment

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

    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

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

    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

  7. Vimentin-Mediated Steroidogenesis Induced by Phthalate Esters: Involvement of DNA Demethylation and Nuclear Factor κB

    Li, Yuan; Hu, Yanhui; Dong, Congcong; Lu, Hongchao; Zhang, Chang; Hu, Qi; Li, Shifeng; Qin, Heng; Li, Zhong; Wang, Yubang

    2016-01-01

    Di-n-butyl phthalate (DBP) and its active metabolite, monobutyl phthalate (MBP) are the most common endocrine disrupting chemicals. Many studies indicate that high-doses of DBP and/or MBP exhibit toxicity on testicular function, however, little attention have been paid to the effects of low levels of DBP/MBP on steroidogenesis. As we all know, the steroidogenic acute regulatory protein (StAR) is a key regulator involved in the steroidogenesis. Here we found that, in addition to StAR, MBP/DBP increased the steroidogenesis by a cytoskeletal protein, vimentin. Briefly, in murine adrenocortical tumor (Y1) and the mouse Leydig tumor (MLTC-1) cells, vimentin regulated the secretion of progesterone. When these two cells were exposure to MBP, the DNA demethylation in the vimentin promoter was observed. In addition, MBP also induced the activation of nuclear factor kappa B (NF-κB, a transcriptional regulator of vimentin). These two processes improved the transcriptional elevation of vimentin. Knockdown of NF-κB/vimentin signaling blocked the DBP/MBP-induced steroidogenesis. These in vitro results were also confirmed via an in vivo model. By identifying a mechanism whereby DBP/MBP regulates vimentin, our results expand the understanding of the endocrine disrupting potential of phthalate esters. PMID:26745512

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

    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.

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

    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

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

    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

  11. The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3

    Cloos, Paul A C; Christensen, Jesper; Agger, Karl; Maiolica, Alessio; Rappsilber, Juri; Antal, Torben; Hansen, Klaus H; Helin, Kristian

    2006-01-01

    Methylation of lysine and arginine residues on histone tails affects chromatin structure and gene transcription. Tri- and dimethylation of lysine 9 on histone H3 (H3K9me3/me2) is required for the binding of the repressive protein HP1 and is associated with heterochromatin formation and...... 2) subfamily of the jumonji family, and is also known as JMJD2C. Here we show that three members of this subfamily of proteins demethylate H3K9me3/me2 in vitro through a hydroxylation reaction requiring iron and alpha-ketoglutarate as cofactors. Furthermore, we demonstrate that ectopic expression of...

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

    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.)

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

    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...

  14. Genome-wide CpG island methylation and intergenic demethylation propensities vary among different tumor sites.

    Lee, Seung-Tae; Wiemels, Joseph L

    2016-02-18

    The epigenetic landscape of cancer includes both focal hypermethylation and broader hypomethylation in a genome-wide manner. By means of a comprehensive genomic analysis on 6637 tissues of 21 tumor types, we here show that the degrees of overall methylation in CpG island (CGI) and demethylation in intergenic regions, defined as 'backbone', largely vary among different tumors. Depending on tumor type, both CGI methylation and backbone demethylation are often associated with clinical, epidemiological and biological features such as age, sex, smoking history, anatomic location, histological type and grade, stage, molecular subtype and biological pathways. We found connections between CGI methylation and hypermutability, microsatellite instability, IDH1 mutation, 19p gain and polycomb features, and backbone demethylation with chromosomal instability, NSD1 and TP53 mutations, 5q and 19p loss and long repressive domains. These broad epigenetic patterns add a new dimension to our understanding of tumor biology and its clinical implications. PMID:26464434

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

    Huimin Cao

    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.

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

    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.

  17. Physical activity, screen time and obesity status in a nationally representative sample of Maltese youth with international comparisons

    Decelis, Andrew; Jago, Russell; Fox, Kenneth R.

    2014-01-01

    Background There is some evidence that physical activity (PA), sedentary time and screen time (ST) are associated with childhood obesity, but research is inconclusive and studies are mainly based on self-reported data. The literature is dominated by data from North American countries and there is a shortage of objective data from Malta which has one of the highest prevalences of childhood obesity in the world. The aims of this study were to assess the PA levels and ST patterns of Maltese boys...

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

    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...

  19. In vitro antiviral activity of a series of wild berry fruit extracts against representatives of Picorna-, Orthomyxo- and Paramyxoviridae.

    Nikolaeva-Glomb, Lubomira; Mukova, Luchia; Nikolova, Nadya; Badjakov, Ilian; Dincheva, Ivayla; Kondakova, Violeta; Doumanova, Lyuba; Galabov, Angel S

    2014-01-01

    Wild berry species are known to exhibit a wide range of pharmacological activities. They have long been traditionally applied for their antiseptic, antimicrobial, cardioprotective and antioxidant properties. The aim of the present study is to reveal the potential for selective antiviral activity of total methanol extracts, as well as that of the anthocyanins and the non-anthocyanins from the following wild berries picked in Bulgaria: strawberry (Fragaria vesca L.) and raspberry (Rubus idaeus L.) of the Rosaceae plant family, and bilberry (Vaccinium myrtillis L.) and lingonberry (Vaccinium vitis-idaea L) of the Ericaceae. The antiviral effect has been tested against viruses that are important human pathogens and for which chemotherapy and/or chemoprophylaxis is indicated, namely poliovirus type 1 (PV-1) and coxsackievirus B1 (CV-B1) from the Picornaviridae virus family, human respiratory syncytial virus A2 (HRSV-A2) from the Paramyxoviridae and influenza virus A/H3N2 of Orthomyxoviridae. Wild berry fruits are freeze-dried and ground, then total methanol extracts are prepared. Further the extracts are fractioned by solid phase extraction and the non-anthocyanin and anthocyanin fractions are eluted. The in vitro antiviral effect is examined by the virus cytopathic effect (CPE) inhibition test. The results reveal that the total extracts of all tested berry fruits inhibit the replication of CV-B1 and influenza A virus. CV-B1 is inhibited to the highest degree by both bilberry and strawberry, as well as by lingonberry total extracts, and influenza A by bilberry and strawberry extracts. Anthocyanin fractions of all wild berries strongly inhibit the replication of influenza virus A/H3N2. Given the obtained results it is concluded that wild berry species are a valuable resource of antiviral substances and the present study should serve as a basis for further detailed research on the matter. PMID:24660461

  20. The mechanics of activated semitendinosus are not representative of the pathological knee joint condition of children with cerebral palsy.

    Ateş, Filiz; Temelli, Yener; Yucesoy, Can A

    2016-06-01

    Characteristic cerebral palsy effects in the knee include a restricted joint range of motion and forcefully kept joint in a flexed position. To show whether the mechanics of activated spastic semitendinosus muscle are contributing to these effects, we tested the hypothesis that the muscle's joint range of force exertion is narrow and force production capacity in flexed positions is high. The isometric semitendinosus forces of children with cerebral palsy (n=7, mean (SD)=7years (8months), GMFCS levels III-IV, 12 limbs tested) were measured intra-operatively as a function of knee angle, from flexion (120°) to full extension (0°). Peak force measured in the most flexed position was considered as the benchmark. However, peak force (mean (SD)=112.4N (54.3N)) was measured either at intermediate or even full knee extension (three limbs) indicating no narrow joint range of force exertion. Lack of high force production capacity in flexed knee positions (e.g., at 120° negligible or below 22% of the peak force) was shown except for one limb. Therefore, our hypothesis was rejected for a vast majority of the limbs. These findings and those reported for spastic gracilis agree, indicating that the patients' pathological joint condition must rely on a more complex mechanism than the mechanics of individual spastic muscles. PMID:27128957

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

    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...

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

    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

  3. 5-azacytidine improves the osteogenic differentiation potential of aged human adipose-derived mesenchymal stem cells by DNA demethylation.

    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.

  4. 5-Azacytidine Improves the Osteogenic Differentiation Potential of Aged Human Adipose-Derived Mesenchymal Stem Cells by DNA Demethylation

    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

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

    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

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

    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

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

    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). PMID:25842335

  8. Enhanced binding capability of nuclear factor-κB with demethylated P2X3 receptor gene contributes to cancer pain in rats.

    Zhou, You-Lang; Jiang, Guo-Qin; Wei, Jinrong; Zhang, Hong-Hong; Chen, Wei; Zhu, Hongyan; Hu, Shufen; Jiang, Xinghong; Xu, Guang-Yin

    2015-10-01

    Nuclear factor-kappa B (NF-κB) signaling is implicated in both cancer development and inflammation processes. However, the roles and mechanisms of NF-κB signaling in the development of cancer-induced pain (CIP) remain unknown. This study was designed to investigate the roles of the p65 subunit of NF-κB in regulation of the purinergic receptor (P2X3R) plasticity in dorsal root ganglion (DRG) of CIP rats. We showed here that tumor cell injection produced mechanical and thermal hyperalgesia, and an enhanced body weight-bearing difference, which was correlated with an upregulation of p65 and P2X3R expression in lumber DRGs and a potentiation of ATP-evoked responses of tibia-innervating DRG neurons. Inhibition of NF-κB signaling using p65 inhibitor pyrrolidine dithiocarbamate, BAY-11-7082, or lentiviral-p65 short-hairpin RNA significantly attenuated CIP and reversed the activities of P2X3R. Interestingly, tumor cell injection led to a significant demethylation of CpG island in p2x3r gene promoter and enhanced ability of p65 to bind the promoter of p2x3r gene. Our findings suggest that upregulation of P2X3R expression was mediated by the enhanced binding capability of p65 with demethylated promoter of p2x3r gene, thus contributing to CIP. NF-κBp65 might be a potential target for treating CIP, a neuropathic pain generated by tumor cell-induced injury to nerves that innervate the skin. PMID:26049406

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

    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

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

    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...

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

    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

  12. 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

    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

  13. 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

    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...

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

    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 ...

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

    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)

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

    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.

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

    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

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

    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 other...... key residues conserved. By contrast, LlTrxD is more distantly related and contains a WCGDC motif. Bioinformatics analysis suggests that LlTrxD represents a subgroup of thioredoxins from Gram-positive bacteria. LlNrdH is a glutaredoxin-like electron donor for ribonucleotide reductase class Ib. Based on...... capacity to reduce insulin disulfides and their exposed active site thiol is alkylated at a similar rate at pH 7.0. LlTrxD on the other hand, is alkylated by iodoacetamide at almost 100 fold higher rate and shows no activity towards insulin disulfides. LlTrxA, LlTrxD and L1NrdH are all efficiently reduced...

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

    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

  20. Cotreatment with Smac mimetics and demethylating agents induces both apoptotic and necroptotic cell death pathways in acute lymphoblastic leukemia cells.

    Gerges, Steve; Rohde, Katharina; Fulda, Simone

    2016-05-28

    Treatment resistance in acute lymphoblastic leukemia (ALL) is often caused by defects in programmed cell death, e.g. by overexpression of Inhibitor of Apoptosis (IAP) proteins. Here, we report that small-molecule Smac mimetics (i.e. BV6, LCL161, birinapant) that neutralize x-linked IAP (XIAP), cellular IAP (cIAP)1 and cIAP2 cooperate with demethylating agents (i.e. 5-azacytidine (5AC) or 5-aza-2'-deoxycytidine (DAC)) to induce cell death in ALL cells. Molecular studies reveal that induction of cell death is preceded by BV6-mediated depletion of cIAP1 protein and involves tumor necrosis factor (TNF)α autocrine/paracrine signaling, since the TNFα-blocking antibody Enbrel significantly reduces BV6/5AC-induced cell death. While BV6/5AC cotreatment induces caspase-3 activation, the broad-range caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk) only partly rescues ALL cells from BV6/5AC-induced cell death. This indicates that BV6/5AC cotreatment engages non-apoptotic cell death upon caspase inhibition. Indeed, genetic silencing of key components of necroptosis such as Receptor-Interacting Protein (RIP)3 or mixed lineage kinase domain-like (MLKL) in parallel with administration of zVAD.fmk provides a significantly better protection against BV6/5AC-induced cell death compared to the use of zVAD.fmk alone. Similarly, concomitant administration of pharmacological inhibitors of necroptosis (i.e. necrostatin-1s, GSK'872, dabrafenib, NSA) together with zVAD.fmk is superior in rescuing cells from BV6/5AC-induced cell death compared to the use of zVAD.fmk alone. These findings demonstrate that in ALL cells BV6/5AC-induced cell death is mediated via both apoptotic and necroptotic pathways. Importantly, BV6/5AC cotreatment triggers necroptosis in ALL cells that are resistant to apoptosis due to caspase inhibition. This opens new perspectives to overcome apoptosis resistance with important implications for the development of new treatment strategies

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

    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

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

    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.

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

    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

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

    Increased awareness about the toxicity of mercury (Hg) has during the latest decades resulted in reduced use of Hg 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. The contribution of global Hg sources and the importance of other parameters to increased Hg levels encountered in hydroelectric reservoirs and other areas after flooding is not well understood, especially not in the tropics. The aim of the present study is to increase the knowledge about Hg transformations in tropical areas. Total Hg content in water, biota, and sediment will be determined by atomic absorption and fluorescence spectrophotometry and methyl Hg content in biota by gaschromatography after extraction with acids, hydroxides, and organic solvents. Mercury methylation capacity in sediments, water, and selected biota will be determined with 203Hg and subsequent radiological measurements of insitu incubations. Factors affecting the methylation and demethylation rates will be identified with laboratory incubations with 203Hg at varying environmental conditions such as organic matter, pH, redox potential, conductivity, light, temperature, geochemical factors and populations of bacteria. The populations of bacteria will be determined to quantity by isotope techniques. The first experiments indicate markedly larger methylation capacity as well as bacterial production of incubated samples of Eichhornia crassipes, originating from Brazil, compared to Myriophyllum spicatum from Sweden. The results are the first step to better understand the importance of environmental parameters and bacterial production for methylation of Hg. (author)

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

    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.

  7. 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

    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.

  8. 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.

    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

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

    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

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

    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

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

    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)

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

    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.

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

    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...

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

    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

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

    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

  16. Representative of the municipality

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

    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

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

    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...

  19. 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

    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...

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

    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

  1. The representative animal

    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...

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

    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.

  3. Psychological theory in an interdisciplinary context: psychological, demographic, health-related, social, and environmental correlates of physical activity in a representative cohort of community-dwelling older adults

    Sniehotta, Falko F; Gellert, Paul; Witham, Miles D; Donnan, Peter T.; Crombie, Iain K; McMurdo, Marion ET

    2013-01-01

    Background Physical activity (PA) in older adults is influenced by a range of environmental, demographic, health-related, social, and psychological variables. Social cognitive psychological models assume that all influences on behaviour operate indirectly through the models constructs, i.e., via intention and self-efficacy. We evaluated direct, indirect, and moderating relationships of a broad range of external variables with physical activity levels alongside intention and self-efficacy. Met...

  4. The clinical burden of generalized osteoarthritis represented by self-reported health-related quality of life and activity limitations: a cross-sectional study.

    Cuperus, Nienke; Vliet Vlieland, Thea P M; Mahler, Elien A M; Kersten, Clarinda C; Hoogeboom, Thomas J; van den Ende, Cornelia H M

    2015-05-01

    The involvement of multiple joints is common in osteoarthritis (OA), often referred to as generalized osteoarthritis (GOA). However, since research and practice mainly focus on a specific OA localization, the health status of patients with GOA is largely unknown. Therefore, we aimed to describe the clinical burden of GOA in terms of self-reported health-related quality of life (HRQoL) and activity limitations. In this cross-sectional study, individuals clinically diagnosed with GOA and referred to multidisciplinary treatment, completed questionnaires on socio-demographics, joint involvement, HRQoL (SF-36) and activity limitations (HAQ-DI). SF-36 physical (PCS) and mental component summary scores (MCS) were calculated using norm-based data. The patient's specific most important activity limitations were linked to the International Classification of Functioning, Disability and Health. A total of 147 patients participated [85 % female; mean (SD) age 60 (8) years]. The majority (93 %) had symptomatic OA in both the upper and lower extremities. Predominant joints with symptomatic OA were the hands (85 %) and knees (82 %). Mean (SD) SF-36 PCS and MCS scores were 37 (7) and 48 (10), respectively, showing a broad impact of GOA on the physical component of health. The mean (SD) HAQ-DI score was 1.27 (0.50) indicating moderate to severe functional limitations. Activities concerning mobility and domestic life were considered most important activity limitations, especially walking. The results show a high clinical burden of GOA in terms of HRQoL and activity limitations. This study points to the need of developing non-pharmacological interventions for patients with GOA that should target on improving the physical component of health and mobility limitations. PMID:25300731

  5. The relationship between chemical concentration and odor activity value explains the inconsistency in making a comprehensive surrogate scent training tool representative of illicit drugs.

    Rice, Somchai; Koziel, Jacek A

    2015-12-01

    This report highlights the importance of an individual chemical's odor impact in the olfactory identification of marijuana, cocaine, and heroin. There are small amounts of highly odorous compounds present in headspace of these drugs, with very low odor detection thresholds, that are more likely responsible for contributing to the overall odor of these drugs. Previous reports of the most abundant compounds in headspace can mislead researchers when dealing with whole odor of these drugs. Surrogate scent formulations, therefore, must match the odor impact of key compounds and not just the chemical abundance of compounds. The objective of this study was to compare odorous volatile organic compounds (VOCs) emitted from illicit drug samples of marijuana, cocaine, and heroin to surrogate smell formulations using simultaneous sensory (via human olfaction) and chemical analyses. Use of solid phase microextraction (SPME) allowed VOCs in drug headspace to be extracted and pre-concentrated on site, and analyzed by multidimensional gas chromatography-mass spectrometry-olfactometry (MDGC-MS-O). Use of MDGC-MS-O allowed for further separation of odorous compounds and simultaneous detection by the human nose of the separate odor parts that make up the total aroma of these drugs. The compounds most abundant in headspace were not the most odor impactful when ranked by odor activity values (OAVs) (defined as ratio of concentration to odor detection threshold, ODT). There were no apparent correlations between concentrations and OAVs. A 1g marijuana surrogate lacked in odor active acids, aldehydes, ethers, hydrocarbons, N-containing, and S-containing VOCs and was overabundant in odor active alcohols and aromatics compared with real marijuana. A 1g cocaine surrogate was overabundant in odor active alcohols, aldehydes, aromatics, esters, ethers, halogenates, hydrocarbons, ketones and N-containing compounds compared with real. A 1g heroin surrogate should contain less odor active acids

  6. OSMOSE experiment representativity studies

    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

  7. OSMOSE experiment representativity studies.

    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

  8. 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.

    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

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

    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

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

    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.

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

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

    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...

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

    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

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

    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...

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

    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.

  16. JMJD1C demethylates MDC1 to regulate the RNF8 and BRCA1-mediated chromatin response to DNA breaks

    Watanabe, Sugiko; Watanabe, Kenji; Akimov, Vyacheslav;

    2013-01-01

    Chromatin ubiquitylation flanking DNA double-strand breaks (DSBs), mediated by RNF8 and RNF168 ubiquitin ligases, orchestrates a two-branch pathway, recruiting repair factors 53BP1 or the RAP80-BRCA1 complex. We report that human demethylase JMJD1C regulates the RAP80-BRCA1 branch of this DNA......-damage response (DDR) pathway. JMJD1C was stabilized by interaction with RNF8, was recruited to DSBs, and was required for local ubiquitylations and recruitment of RAP80-BRCA1 but not 53BP1. JMJD1C bound to RNF8 and MDC1, and demethylated MDC1 at Lys45, thereby promoting MDC1-RNF8 interaction, RNF8-dependent MDC1...... ubiquitylation and recruitment of RAP80-BRCA1 to polyubiquitylated MDC1. Furthermore, JMJD1C restricted formation of RAD51 repair foci, and JMJD1C depletion caused resistance to ionizing radiation and PARP inhibitors, phenotypes relevant to aberrant loss of JMJD1C in subsets of breast carcinomas. These findings...

  17. 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

    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

  18. Representative offices of foreign companies in Romania

    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.

  19. Representative of the Media

    Francesc Domenech recalled that the Vandellos-I accident created a very difficult situation for the nuclear industry. During the crisis the nuclear sector decided not to participate in any media activities. Finally, the industry realised that not being open only exacerbated the credibility crisis. The closure of the Vandellos -I power plant decreased the stress and offered an opportunity for the nuclear sector to change its attitude and public relations. In Mr. Domenech's view the Vandellos-I decommissioning project is a technical challenge undertaken by society. ENRESA made great efforts to rebuild mutual trust between the nuclear industry and the media. For the first time, journalists were provided with fluid data, some of them very complex, which the media had to render more understandable for the public. Finally, Mr. Domenech observed that nowadays it is the regulator which most needs to gain credibility. (author)

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

    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

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

    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

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

    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

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

    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 ...

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

    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.

  5. 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

    Vlková, Veronika; Štěpánek, Ivan; Hrušková, Veronika; Šenigl, Filip; Mayerová, Veronika; Šrámek, Martin; Šímová, Jana; Bieblová, Jana; Indrová, Marie; Hejhal, Tomáš; Dérian, N.; Klatzmann, D.; Six, A.; Reiniš, Milan

    2014-01-01

    Roč. 5, č. 16 (2014), s. 6923-35. ISSN 1949-2553 R&D Projects: GA ČR GAP301/10/2174; GA MZd NT14461 EU Projects: European Commission(XE) 18933 - CLINIGENE Grant ostatní: French state funds within the Investissements d’Avenir program(FR) ANR-11-IDEX-0004-02 Institutional support: RVO:68378050 Keywords : IFNγ signalling pathway * DNA demethylation * tumour Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.359, year: 2014

  6. Identification of methylated genes in salivary gland adenoid cystic carcinoma xenografts using global demethylation and methylation microarray screening

    LING, SHIZHANG; RETTIG, ELENI M.; TAN, MARIETTA; CHANG, XIAOFEI; WANG, ZHIMING; BRAIT, MARIANA; BISHOP, JUSTIN A.; FERTIG, ELANA J.; CONSIDINE, MICHAEL; WICK, MICHAEL J.; HA, PATRICK K.

    2016-01-01

    Salivary gland adenoid cystic carcinoma (ACC) is a rare head and neck malignancy without molecular biomarkers that can be used to predict the chemotherapeutic response or prognosis of ACC. The regulation of gene expression of oncogenes and tumor suppressor genes (TSGs) through DNA promoter methylation may play a role in the carcinogenesis of ACC. To identify differentially methylated genes in ACC, a global demethylating agent, 5-aza-2′-deoxycytidine (5-AZA) was utilized to unmask putative TSG silencing in ACC xenograft models in mice. Fresh xenografts were passaged, implanted in triplicate in mice that were treated with 5-AZA daily for 28 days. These xenografts were then evaluated for genome-wide DNA methylation patterns using the Illumina Infinium HumanMethylation27 BeadChip array. Validation of the 32 candidate genes was performed by bisulfite sequencing (BS-seq) in a separate cohort of 6 ACC primary tumors and 6 normal control salivary gland tissues. Hypermethylation was identified in the HCN2 gene promoter in all 6 control tissues, but hypomethylation was found in all 6 ACC tumor tissues. Quantitative validation of HCN2 promoter methylation level in the region detected by BS-seq was performed in a larger cohort of primary tumors (n=32) confirming significant HCN2 hypomethylation in ACCs compared with normal samples (n=10; P=0.04). HCN2 immunohistochemical staining was performed on an ACC tissue microarray. HCN2 staining intensity and H-score, but not percentage of the positively stained cells, were significantly stronger in normal tissues than those of ACC tissues. With our novel screening and sequencing methods, we identified several gene candidates that were methylated. The most significant of these genes, HCN2, was actually hypomethylated in tumors. However, promoter methylation status does not appear to be a major determinant of HCN2 expression in normal and ACC tissues. HCN2 hypomethylation is a biomarker of ACC and may play an important role in the

  7. 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

    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

  8. Representative Ensembles in Statistical Mechanics

    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.

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

    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

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

    Hamelin, Stéphanie; Planas, Dolors; Amyot, Marc

    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 (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 (199)HgO and Me(200)Hg 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. PMID:25644842

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

    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.

  12. Potential Metabolic Activation of a Representative C2-Alkylated Polycyclic Aromatic Hydrocarbon 6-Ethylchrysene Associated with the Deepwater Horizon Oil Spill in Human Hepatoma (HepG2) Cells

    2016-01-01

    Exposure to polycyclic aromatic hydrocarbons (PAHs) is the major human health hazard associated with the Deepwater Horizon oil spill. C2-Chrysenes are representative PAHs present in crude oil and could contaminate the food chain. We describe the metabolism of a C2-chrysene regioisomer, 6-ethylchrysene (6-EC), in human HepG2 cells. The structures of the metabolites were identified by HPLC-UV-fluorescence detection and LC-MS/MS. 6-EC-tetraol isomers were identified as signature metabolites of the diol-epoxide pathway. O-Monomethyl-O-monosulfonated-6-EC-catechol, its monohydroxy products, and N-acetyl-l-cysteine(NAC)-6-EC-ortho-quinone were discovered as signature metabolites of the ortho-quinone pathway. Potential dual metabolic activation of 6-EC involving the formation of bis-electrophiles, i.e., a mono-diol-epoxide and a mono-ortho-quinone within the same structure, bis-diol-epoxides, and bis-ortho-quinones was observed as well. The identification of 6-EC-tetraol, O-monomethyl-O-monosulfonated-6-EC-catechol, its monohydroxy products, and NAC-6-EC-ortho-quinone supports potential metabolic activation of 6-EC by P450 and AKR enzymes followed by metabolic detoxification of the ortho-quinone through interception of its redox cycling capability by catechol-O-methyltransferase and sulfotransferase enzymes. The tetraols and catechol conjugates could be used as biomarkers of human exposure to 6-EC resulting from oil spills. PMID:27054409

  13. Potential Metabolic Activation of a Representative C2-Alkylated Polycyclic Aromatic Hydrocarbon 6-Ethylchrysene Associated with the Deepwater Horizon Oil Spill in Human Hepatoma (HepG2) Cells.

    Huang, Meng; Mesaros, Clementina; Zhang, Suhong; Blair, Ian A; Penning, Trevor M

    2016-06-20

    Exposure to polycyclic aromatic hydrocarbons (PAHs) is the major human health hazard associated with the Deepwater Horizon oil spill. C2-Chrysenes are representative PAHs present in crude oil and could contaminate the food chain. We describe the metabolism of a C2-chrysene regioisomer, 6-ethylchrysene (6-EC), in human HepG2 cells. The structures of the metabolites were identified by HPLC-UV-fluorescence detection and LC-MS/MS. 6-EC-tetraol isomers were identified as signature metabolites of the diol-epoxide pathway. O-Monomethyl-O-monosulfonated-6-EC-catechol, its monohydroxy products, and N-acetyl-l-cysteine(NAC)-6-EC-ortho-quinone were discovered as signature metabolites of the ortho-quinone pathway. Potential dual metabolic activation of 6-EC involving the formation of bis-electrophiles, i.e., a mono-diol-epoxide and a mono-ortho-quinone within the same structure, bis-diol-epoxides, and bis-ortho-quinones was observed as well. The identification of 6-EC-tetraol, O-monomethyl-O-monosulfonated-6-EC-catechol, its monohydroxy products, and NAC-6-EC-ortho-quinone supports potential metabolic activation of 6-EC by P450 and AKR enzymes followed by metabolic detoxification of the ortho-quinone through interception of its redox cycling capability by catechol-O-methyltransferase and sulfotransferase enzymes. The tetraols and catechol conjugates could be used as biomarkers of human exposure to 6-EC resulting from oil spills. PMID:27054409

  14. Demethylation by 5-aza-2'-deoxycytidine in colorectal cancer cells targets genomic DNA whilst promoter CpG island methylation persists

    DNA methylation and histone acetylation are epigenetic modifications that act as regulators of gene expression. Aberrant epigenetic gene silencing in tumours is a frequent event, yet the factors which dictate which genes are targeted for inactivation are unknown. DNA methylation and histone acetylation can be modified with the chemical agents 5-aza-2'-deoxycytidine (5-aza-dC) and Trichostatin A (TSA) respectively. The aim of this study was to analyse de-methylation and re-methylation and its affect on gene expression in colorectal cancer cell lines treated with 5-aza-dC alone and in combination with TSA. We also sought to identify methylation patterns associated with long term reactivation of previously silenced genes. Colorectal cancer cell lines were treated with 5-aza-dC, with and without TSA, to analyse global methylation decreases by High Performance Liquid Chromatography (HPLC). Re-methylation was observed with removal of drug treatments. Expression arrays identified silenced genes with differing patterns of expression after treatment, such as short term reactivation or long term reactivation. Sodium bisulfite sequencing was performed on the CpG island associated with these genes and expression was verified with real time PCR. Treatment with 5-aza-dC was found to affect genomic methylation and to a lesser extent gene specific methylation. Reactivated genes which remained expressed 10 days post 5-aza-dC treatment featured hypomethylated CpG sites adjacent to the transcription start site (TSS). In contrast, genes with uniformly hypermethylated CpG islands were only temporarily reactivated. These results imply that 5-aza-dC induces strong de-methylation of the genome and initiates reactivation of transcriptionally inactive genes, but this does not require gene associated CpG island de-methylation to occur. In addition, for three of our selected genes, hypomethylation at the TSS of an epigenetically silenced gene is associated with the long term reversion of

  15. Extranucleosomal DNA enhances the activity of the LSD1/CoREST histone demethylase complex

    Kim, Sang-Ah; Chatterjee, Nilanjana; Jennings, Matthew J.; Bartholomew, Blaine; Tan, Song

    2015-01-01

    The promoter regions of active genes in the eukaryotic genome typically contain nucleosomes post-translationally modified with a trimethyl mark on histone H3 lysine 4 (H3K4), while transcriptional enhancers are marked with monomethylated H3K4. The flavin-dependent monoamine oxidase LSD1 (lysine-specific demethylase 1, also known as KDM1) demethylates mono- and dimethylated H3K4 in peptide substrates, but requires the corepressor protein, CoREST, to demethylate nucleosome substrates. The molec...

  16. Representing Learning With Graphical Models

    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.

  17. Burnout in Customer Service Representatives

    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.(...

  18. Demethylation regulation of BDNF gene expression in dorsal root ganglion neurons is implicated in opioid-induced pain hypersensitivity in rats.

    Chao, Yu-Chieh; Xie, Fang; Li, Xueyang; Guo, Ruijuan; Yang, Ning; Zhang, Chen; Shi, Rong; Guan, Yun; Yue, Yun; Wang, Yun

    2016-07-01

    Repeated administration of morphine may result in opioid-induced hypersensitivity (OIH), which involves altered expression of numerous genes, including brain-derived neurotrophic factor (BDNF) in dorsal root ganglion (DRG) neurons. Yet, it remains unclear how BDNF expression is increased in DRG neurons after repeated morphine treatment. DNA methylation is an important mechanism of epigenetic control of gene expression. In the current study, we hypothesized that the demethylation regulation of certain BDNF gene promoters in DRG neurons may contribute to the development of OIH. Real-time RT-PCR was used to assess changes in the mRNA transcription levels of major BDNF exons including exon I, II, IV, VI, as well as total BDNF mRNA in DRGs from rats after repeated morphine administration. The levels of exon IV and total BDNF mRNA were significantly upregulated by repeated morphine administration, as compared to that in saline control group. Further, ELISA array and immunocytochemistry study revealed a robust upregulation of BDNF protein expression in DRG neurons after repeated morphine exposure. Correspondingly, the methylation levels of BDNF exon IV promoter showed a significant downregulation by morphine treatment. Importantly, intrathecal administration of a BDNF antibody, but not control IgG, significantly inhibited mechanical hypersensitivity that developed in rats after repeated morphine treatment. Conversely, intrathecal administration of an inhibitor of DNA methylation, 5-aza-2'-deoxycytidine (5-aza-dC) markedly upregulated the BDNF protein expression in DRG neurons and enhanced the mechanical allodynia after repeated morphine exposure. Together, our findings suggest that demethylation regulation of BDNF gene promoter may be implicated in the development of OIH through epigenetic control of BDNF expression in DRG neurons. PMID:26970395

  19. Marc Treib: Representing Landscape Architecture

    Braae, Ellen Marie

    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....

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

    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

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

    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. Representative process sampling - in practice

    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....../or periodicity; different nugget effects and process variations ranging from less than one lag to full variogram lag). Variogram data analysis leads to a fundamental decomposition into 0-D sampling vs. 1-D process variances, based on the three principal variogram parameters: range, sill and nugget effect....... The influence on the variogram from significant trends and outliers in the original data series receive special attention, due to their critical adverse effects. We highlight problem-dependent interpretation of variographic analysis a.o. the problem-dependent background for periodicities and trends. All...

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

    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. Representing culture in interstellar messages

    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.

  5. Representing objects, relations, and sequences.

    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

  6. Demethylation of oligogalacturonides by FaPE1 in the fruits of the wild strawberry Fragaria vesca triggers metabolic and transcriptional changes associated with defence and development of the fruit

    Osorio, S.; Bombarely, A.; Giavalisco, P; Usadel, B.; Stephens, C.; Araguez, I.; Medina-Escobar, N.; Botella, M.; Fernie, A.; Valpuesta, V.

    2011-01-01

    Ectopic expression of the strawberry (Fragariaxananassa) gene FaPE1 encoding pectin methyl esterase produced in the wild species Fragaria vesca partially demethylated oligogalacturonides (OGAs), which conferred partial resistance of ripe fruits to the fungus Botrytis cinerea. Analyses of metabolic and transcriptional changes in the receptacle of the transgenic fruits revealed channelling of metabolites to aspartate and aromatic amino acids as well as phenolics, flavanones, and sesquiterpenoid...

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

    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.

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

    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.

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

    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

  10. 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

    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.

  11. Want change? Call your representative

    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.

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

    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

    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.

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

    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. DNA Demethylation Rescues the Impaired Osteogenic Differentiation Ability of Human Periodontal Ligament Stem Cells in High Glucose

    Liu, Zhi; Chen, Tian; Sun, Wenhua; Yuan, Zongyi; Yu, Mei; Chen, Guoqing; Guo, Weihua; Xiao, Jingang; Tian, Weidong

    2016-01-01

    Diabetes mellitus, characterized by abnormally high blood glucose levels, gives rise to impaired bone remodeling. In response to high glucose (HG), the attenuated osteogenic differentiation capacity of human periodontal ligament stem cells (hPDLSCs) is associated with the loss of alveolar bone. Recently, DNA methylation was reported to affect osteogenic differentiation of stem cells in pathological states. However, the intrinsic mechanism linking DNA methylation to osteogenic differentiation ability in the presence of HG is still unclear. In this study, we found that diabetic rats with increased DNA methylation levels in periodontal ligaments exhibited reduced bone mass and density. In vitro application of 5-aza-2′-deoxycytidine (5-aza-dC), a DNA methyltransferase inhibitor, to decrease DNA methylation levels in hPDLSCs, rescued the osteogenic differentiation capacity of hPDLSCs under HG conditions. Moreover, we demonstrated that the canonical Wnt signaling pathway was activated during this process and, under HG circumstances, the 5-aza-dC-rescued osteogenic differentiation capacity was blocked by Dickkopf-1, an effective antagonist of the canonical Wnt signaling pathway. Taken together, these results demonstrate for the first time that suppression of DNA methylation is able to facilitate the osteogenic differentiation capacity of hPDLSCs exposed to HG, through activation of the canonical Wnt signaling pathway. PMID:27273319

  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

    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. Do pharmaceutical representatives misuse their drug samples?

    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...

  18. 10 CFR 63.332 - Representative volume.

    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....

  19. NASA: Changes to the scope, schedule, and estimated cost of the Earth Observing System. Report to the Chair, Government Activities and Transportation Subcommittee, Committee on Government Operations, House of Representatives

    Congress funded the Earth Observing System (EOS) as a new NASA program beginning in fiscal year 1991. NASA proposed to launch about 30 types of earth observing instruments beginning in 1998. These instruments were intended to improve satellite data about the earth and to provide new data to support interdisciplinary studies of the earth. EOS is seen by NASA as the first step toward a future period of space-based scientific observation of the earth. The program is directly linked to the objectives of the U.S. Global Change Research Program and international efforts to observe and study the earth. The U.S. Global Change Research Program, which is funded by 11 agencies, is an attempt to achieve these objectives and to improve predictions of climate and other forms of global change. Within that program, EOS is intended to significantly improve scientists' abilities to model, and thereby predict, broad natural relationships among the sea, land, and atmosphere; to observe how water, carbon, and other substances move on the planet or are affected by variations in the sun's radiation; and to assess the impact of human activities on the earth's climate. Ultimately, EOS is to help determine the extent to which human activities are affecting the earth's environment and to provide policymakers with the information they will need to preserve the earth

  20. 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.

    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

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

    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.

  2. Representing Uncertainty by Probability and Possibility

    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...

  3. KNOWLEDGE REPRESENTING FEATURES IN ROUGH SETS THEORY

    Užga-Rebrovs, Oļegs

    2015-01-01

    Knowledge discovering and representing in information systems has evolved into an important area of research because of theoretical challenges and practical representing unknown knowledge in data. Rough set theory is a mathematical formalism for representing uncertainty that can be considered a special extension of the set theory. In this paper is analyzed knowledge representing problem and attribute signification’s problem, based on rough sets approach.

  4. 5 CFR 511.608 - Employee representatives.

    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...

  5. Mining Representative Subset Based on Fuzzy Clustering

    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. Epigenetic identification of ZNF545 as a functional tumor suppressor in multiple myeloma via activation of p53 signaling pathway.

    Fan, Yu; Zhan, Qian; Xu, Hongying; Li, Lili; Li, Chen; Xiao, Qian; Xiang, Shili; Hui, Tianli; Xiang, Tingxiu; Ren, Guosheng

    2016-06-10

    The KRAB-zinc-finger protein ZNF545 was recently identified as a potential suppressor gene in several tumors. However, the regulatory mechanisms of ZNF545 in tumorigenesis remain unclear. In this study, we investigated the expression and roles of ZNF545 in multiple myeloma (MM). ZNF545 was frequently downregulated in MM tissues compared with non-tumor bone marrow tissues. ZNF545 expression was silenced by promoter methylation in MM cell lines, and could be restored by demethylation treatment. ZNF545 methylation was detected in 28.3% of MM tissues, compared with 4.3% of normal bone marrow tissues. ZNF545 transcriptionally activated the p53 signaling pathway but had no effect on Akt in MM, whereas ectopic expression of ZNF545 in silenced cells suppressed their proliferation and induced apoptosis. We therefore identified ZNF545 as a novel tumor suppressor inhibiting tumor growth through activation of the p53 pathway in MM. Moreover, tumor-specific methylation of ZNF545 may represent an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy. PMID:27150632

  7. EEG microstates during resting represent personality differences.

    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

  8. Representing Others in a Public Good Game

    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.

  9. Representing a public that does not exist

    Korsgaard, Morten Timmermann

    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 the...

  10. Representative Sampling for reliable data analysis

    Petersen, Lars; Esbensen, Kim Harry

    2005-01-01

    regime in order to secure the necessary reliability of: samples (which must be representative, from the primary sampling onwards), analysis (which will not mean anything outside the miniscule analytical volume without representativity ruling all mass reductions involved, also in the laboratory) and data...

  11. Representing Animal-Others in Educational Research

    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…

  12. 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

    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)

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

    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…

  14. 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

    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...

  15. Request by the Resident Representative of Iraq

    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

  16. Services Subcontract Technical Representative (STR) handbook

    The purpose of this handbook is to provide guidance to Bechtel Hanford, Inc. Subcontract Representatives in their assignments. It is the intention of this handbook to ensure that subcontract work is performed in accordance with the subcontract documents

  17. TET1 Suppresses Cancer Invasion by Activating the Tissue Inhibitors of Metalloproteinases

    Chih-Hung Hsu

    2012-09-01

    Full Text Available Tumor suppressor gene silencing through cytosine methylation contributes to cancer formation. Whether DNA demethylation enzymes counteract this oncogenic effect is unknown. Here, we show that TET1, a dioxygenase involved in cytosine demethylation, is downregulated in prostate and breast cancer tissues. TET1 depletion facilitates cell invasion, tumor growth, and cancer metastasis in prostate xenograft models and correlates with poor survival rates in breast cancer patients. Consistently, enforced expression of TET1 reduces cell invasion and breast xenograft tumor formation. Mechanistically, TET1 suppresses cell invasion through its dioxygenase and DNA binding activities. Furthermore, TET1 maintains the expression of tissue inhibitors of metalloproteinase (TIMP family proteins 2 and 3 by inhibiting their DNA methylation. Concurrent low expression of TET1 and TIMP2 or TIMP3 correlates with advanced node status in clinical samples. Together, these results illustrate a mechanism by which TET1 suppresses tumor development and invasion partly through downregulation of critical gene methylation.

  18. Digital Humanities 2014: representing a controverted definition

    Rodighiero, Dario

    2014-01-01

    The network portrays all keywords used in the Digital Humanities 2014 conference, which will take place in Lausanne, Switzerland. The keywords‚ represented by nodes‚have been freely chosen by each author attending the conference, contributed via their papers and posters. Edges represent keywords appearing together in a contribution. The weight of the edges measures the occurrence of keywords pairs, multiplied by the number of authors creating them. The visualization is meant as a talking poin...

  19. Representing Uncertainty on Model Analysis Plots

    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 met...

  20. Representative Democracy in Australian Local Government

    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...

  1. The descriptive theory of represented spaces

    Pauly, Arno

    2014-01-01

    This is a survey on the ongoing development of a descriptive theory of represented spaces, which is intended as an extension of both classical and effective descriptive set theory to deal with both sets and functions between represented spaces. Most material is from work-in-progress, and thus there may be a stronger focus on projects involving the author than an objective survey would merit.

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

    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.

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

    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

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

    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

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

    Bicknell, Helen; Knudsen, Herman Lyhne

    2006-01-01

    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...... 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, their...

  6. Do regional climate models represent regional climate?

    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

  7. 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

    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

  8. Nonequilibrium representative ensembles for isolated quantum systems

    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.

  9. 40 CFR 60.4112 - Changing Hg designated representative and alternate Hg designated representative; changes in...

    2010-07-01

    ... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Changing Hg designated representative and alternate Hg designated representative; changes in owners and operators. 60.4112 Section 60.4112... Generating Units Hg Designated Representative for Hg Budget Sources § 60.4112 Changing Hg...

  10. Representativeness elements of an hybrid reactor demonstrator

    This document deals with the quantification of the minimum thermal power level for a demonstrator and the definition of the physical criteria which define the representative character of a demonstrator towards a power reactor. Solutions allowing to keep an acceptable flow in an industrial core, have also been studied. The document is divided in three parts: the representativeness elements, the considered solutions and the characterization of the neutrons flows at the interfaces and the dose rates at the outer surface of the vessel. (A.L.B.)

  11. Representing Uncertainty on Model Analysis Plots

    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.

  12. Representative Democracy in Australian Local Government

    Colin Hearfield

    2009-01-01

    Full Text Available 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 deep-seated divisions emerging from the legal relationship between local and state governments and the resultant problems inherent in local government autonomy versus state intervention.

  13. Representative parameter of immunostimulatory ginseng polysaccharide to predict radioprotection

    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

  14. 28 CFR 104.4 - Personal Representative.

    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...

  15. The Role of the Faculty Athletics Representative.

    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…

  16. Strong imploding shock, the representative curve

    The representative curve of the ideal gas behind the front of a spherically, or cylindrically, symmetric strong imploding shock is shown to pass through the point where the reduced pressure is maximum, P(xisub(m)) = Psub(m)sub(a)sub(x). (orig.)

  17. A Framework for Representing Moving Objects

    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...

  18. Using Resource Graphs to Represent Conceptual Change

    Wittmann, Michael 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 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…

  19. Representing Context in Hypermedia Data Models

    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....

  20. Strong imploding shock - The representative curve

    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

    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. Meeting staff representatives of the European Agencies

    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...

  3. Representing Boolean Functions by Decision Trees

    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. Climate Change and the Representative Agent

    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.

  5. G&C Commercial Representative Leaders

    2013-01-01

    Creación de la empresa G&C Commercial Representative Leaders, las cual realizará actividades de representación, negociación, asesoría comercial y de servicios logísticos para las pequeñas y medianas empresas colombianas en especial para el sector de la manufactura, la cual facilite la comercialización y la exportación de sus bienes y servicios hacia al exterior y viceversa.

  6. Representative explanations for over-constrained problems

    O'Sullivan, Barry; Papadopoulos, Alexandre; Faltings, Boi; Pu, Pearl

    2007-01-01

    In many interactive decision making scenarios there is often no solution that satisfies all of the user's preferences. The decision process can be helped by providing explanations. Relaxations show sets of consistent preferences and, thus, indicate which preferences can be enforced, while exclusion sets show which preferences can be relaxed to obtain a solution. We propose a new approach to explanation based on the notion of a representative set of explanations. The size of the set of explana...

  7. Latency represents sound frequency in mouse IC

    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.

  8. Latency represents sound frequency in mouse IC

    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.

  9. Diversity and representativeness: two key factors

    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 ...

  10. Activities.

    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)

  11. Endeavors to Represent the Non-Representational

    Nørgård, Rikke Toft

    corporeal-locomotive dimension of gameplay where hands and bodies where moving to the (kin)aesthetic rhythms of the game’s choreography. Consequently, I found myself barred from ‘meaningfully’ communicating the expressive, sensuous and (kin)aesthetic meaning and significance of corporeal-locomotive gameplay......, appreciative and appropriate way and, on the other hand, was capable of communicating and representing this emerging new research field of ‘gameplay corporeality’ in a meaningful, proper and scholarly sound way. In short, I found myself taking a leap of faith, as I witnessed my Ph.D. thesis turn into a vibrant...

  12. Evaluating host rock representativeness through geostatistics

    The Nuclear Waste Policy Act of 1982 (NWPA) assigns the U.S. Department of Energy (DOE) the responsibility of locating, constructing, operating, closing and decommissioning a nuclear waste repository. Prior to submittal of a licensee application to the U.S. Nuclear Regulatory Commission, the DOE is required by 10 CFR part 60 to conduct a program of site characterization for the site to be described in such application. Site characterization includes an exploration and research program in the field and laboratory to determine the geologic conditions and ranges of those parameters which are necessary for determining the suitability of the site as a geologic repository. The information thus collected should be able to establish with reasonable assurance that the public and environment will be adequately protected from the hazards associated with a repository at the site. This paper demonstrates by example a geostatistical approach which, on the basis of the existing limited data base, can be used to evaluate (1) whether existing information on a certain parameter is adequate to be considered representative, (2) if additional information is required, where should the additional sampling or testing be performed, and (3) whether the newly acquired data along with the existing information constitute representative data

  13. Picturing and modelling catchments by representative hillslopes

    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. Using resource graphs to represent conceptual change

    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.

  15. Towards a representative periphytic diatom sample

    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.

  16. REPRESENTING MARKOV CHAINS WITH TRANSITION DIAGRAMS

    Farida Kachapova

    2013-01-01

    Full Text Available Stochastic processes have many useful applications and are taught in several university programmes. Students often encounter difficulties in learning stochastic processes and Markov chains, in particular. In this article we describe a teaching strategy that uses transition diagrams to represent a Markov chain and to re-define properties of its states in simple terms of directed graphs. This strategy utilises the students’ intuition and makes the learning of complex concepts about Markov chains faster and easier. The method is illustrated by worked examples. The described strategy helps students to master properties of finite Markov chains, so they have a solid basis for the study of infinite Markov chains and other stochastic processes.

  17. The Spitzer Extragalactic Representative Volume Survey

    Lacy, Mark; SERVS Team

    2009-05-01

    The Spitzer Extragalactic Representative Volume Survey (SERVS) will image a total of 18 deg2 of sky to micro-Jansky depth in the [3.6] and [4.5] micron bands split amongst the SWIRE ELAIS-S1, ELAIS-N1, XMM-LSS, Lockman and CDFS fields. SERVS will have substantial overlap with the VISTA/VIDEO and UKIDSS DXS near-infrared surveys, and the Hermes far-infrared survey with Herschel. Key science goals include: understanding stellar mass assembly in massive galaxies from z 5 to the present across a wide range of environments, studying the effects of AGN feedback on the formation of massive galaxies, and finding quasars at z>6.5. In this talk I shall describe the science possible with SERVS, the data taking and analysis schedule, plans for bandmerging with other surveys, and eventual public release.

  18. Using resource graphs to represent conceptual change

    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.

  19. Radical abdominoplasty, including body shaping: representative cases.

    Mühlbauer, W

    1989-01-01

    Even in the age of liposuction there exist certain situations for which abdominoplasty in its radical form is indicated--for example, redundant skin after radical weight loss, the stigmata of postpregnancy syndrome, and localized accumulation of adipose tissue--the lipodystrophies and resistant generalized obesity. Redundant skin after radical weight loss is resected simultaneously around the abdomen, the lumbar regions, the perineum, and the thighs. The typical stigmata of postpregnancy syndrome may be excised through an extended abdominoplasty combined with simultaneous excision and pexy of the inner aspects of the thighs leaving a "bikini" scar behind. A mastopexy may be added. Genetically predisposed localized lipodystrophies in the abdominal lumbar, and upper thigh region may be resected through a circular abdominoplasty with or without simultaneous resection of the perineum and inner thighs. Abdominal aprons often contain umbilical or ventral hernias that may need to be repaired simultaneously. Representative cases are presented and dangers and complications are discussed. PMID:2741749

  20. Representing the vacuum polarization on de Sitter

    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.

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

    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.

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

    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.

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

    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...

  4. Probability & Perception: The Representativeness Heuristic in Action

    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®…

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

    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...

  6. The Two Sides of the Representative Coin

    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.

  7. Multicriteria analysis of ontologically represented information

    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.

  8. EEG microstates during resting represent personality differences

    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 ...

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

    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.

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

    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....

  11. Hydrological studies in experimental and representative basins in Pernambuco State, Brazil

    Montenegro, S.M.G.L.; da Silva, B. B.; A. C. D. Antonino; J. R. S. Lima; E.S. Souza; de Oliveira, L. M. M.; de Moura, A. E. S. S.; Souza, R. M. S.

    2014-01-01

    Hydrological studies in experimental and representative basins are of fundamental importance for water resources management. This paper presents some activities of hydrological research in experimental and representative basins of the State of Pernambuco, Brazil. The study areas are located at Tapacurá and Mundaú representative basins and at the Gameleira experimental basin, and in experimental plots in Pajeú basin. In the Tapacurá basin, three studies were performed: (1) different monthly co...

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

    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

  13. Design and evaluation of representative indoor radon surveys

    We have developed a procedure to design and evaluate representative indoor radon surveys. The procedure is based on random sampling of a population of houses and careful statistical analysis of measured indoor radon concentrations. The method is designed to estimate the fraction of houses in which annual average 222Rn activity concentration may exceed a certain reference level. Measurements of annual average indoor 222Rn activity concentration were done in sleeping rooms at pillow level using etched track type radon detectors. We applied the above procedure in an old fashioned village and in a fast developing small city in Transylvania, Romania. In the village almost all houses were single floor wooden made houses without cellar built with traditional technology on a geologically uniform area. The distribution of indoor 222Rn activity concentration in a sample of 115 houses can almost perfectly be fitted with log-normal probability density function. The correlation coefficient of linear fitting on linearized scales was k = -0.9980. The percentages of houses expected to have annual average 222Rn activity concentration higher than 400 Bq m-3 is less than 1 %, and of those higher than 600 Bq m-3 can be estimated to be around 0.1 %. The small city, on the other hand lies on a geologically inhomogeneous area, and house construction technology has also changed dramatically in past decades. The resulting distribution of measured indoor 222Rn activity concentration in a sample of 116 houses cannot be fitted with any simple probability density function. Therefore the prediction of the fraction of houses in which the annual average 222Rn activity concentration may exceed a certain reference level could not be done adequately. With certain assumptions we estimated that the percentages of houses expected to have annual average 222Rn activity concentration higher than 400 Bq m-3 is between 3 and 7 %, and of those higher than 600 Bq m-3 can be estimated to be between 1 and 3

  14. TECHNICAL BASIS DOCUMENT FOR THE ABOVE GROUND TANK FAILURE REPRESENTATIVE ACCIDENT and ASSOCIATED REPRESENTED HAZARDOUS CONDITIONS

    This document analyzes aboveground tank failure accident scenarios. The radiological and toxicological consequences are determined for a range of aboveground tank failure accident scenarios to determine the representative accident. Based on the consequence results and accident frequency evaluations, risk bins are determined and control decisions are made. This revision deals with aboveground tank failure accidents during CH-TRUM operations

  15. Representing Identity and Equivalence for Scientific Data

    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

  16. Oxidative spectroelectrochemistry of two representative coumarins

    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.

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

    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.

  18. SERVS: the Spitzer Extragalactic Representative Volume Survey

    Lacy, Mark; Afonso, Jose; Alexander, Dave; Best, Philip; Bonfield, David; Castro, Nieves; Cava, Antonio; Chapman, Scott; Dunlop, James; Dyke, Eleanor; Edge, Alastair; Farrah, Duncan; Ferguson, Harry; Foucaud, Sebastian; Franceschini, Alberto; Geach, Jim; Gonzales, Eduardo; Hatziminaoglou, Evanthia; Hickey, Samantha; Ivison, Rob; Jarvis, Matt; Le Fèvre, Olivier; Lonsdale, Carol; Maraston, Claudia; McLure, Ross; Mortier, Angela; Oliver, Seb; Ouchi, Masami; Parish, Glen; Perez-Fournon, Ismael; Petric, Andreea; Pierre, Mauguerite; Readhead, Tony; Ridgway, Susan; Romer, Katherine; Rottgering, Huub; Rowan-Robinson, Michael; Sajina, Anna; Seymour, Nick; Smail, Ian; Surace, Jason; Thomas, Peter; Trichas, Markos; Vaccari, Mattia; Verma, Aprajita; Xu, Kevin; van Kampen, Eelco

    2008-12-01

    We will use warm Spitzer to image 18deg^2 of sky to microJy depth. This is deep enough to undertake a complete census of massive galaxies from z~6 to ~1 in a volume ~0.8Gpc^3, large enough to overcome the effects of cosmic variance, which place severe limitations on the conclusions that can be drawn from smaller fields. We will greatly enhance the diagnostic power of the Spitzer data by performing most of this survey in the region covered by the near-IR VISTA-VIDEO survey, and in other areas covered by near-IR, Herschel and SCUBA2 surveys. We will build complete near-infrared spectral energy distributions using the superb datasets from VIDEO, in conjunction with our Spitzer data, to derive accurate photometric redshifts and the key properties of stellar mass and star formation rates for a large sample of high-z galaxies. Obscured star formation rates and dust-shrouded BH growth phases will be uncovered by combining the Spitzer data with the Herschel and SCUBA2 surveys. We will thus build a complete picture of the formation of massive galaxies from z~6, where only about 1% of the stars in massive galaxies have formed, to z~1 where ~50% of them haveE Our large volume will allow us to also find examples of rare objects such as high-z quasars (~10-100 at z>6.5), high-z galaxy clusters (~20 at z>1.5 with dark halo masses >10^14 solar masses), and evaluate how quasar activity and galaxy environment affect star formation. This survey makes nearly optimal use of warm Spitzer; (a) all of the complementary data is either taken or will be taken in the very near future, and will be immediately publicly accessible, (b) the slew overheads are relatively small, (c) the observations are deep enough to detect high redshift galaxies but not so deep that source confusion reduces the effective survey area.

  19. Demethylation of the miR-146a promoter by 5-Aza-2’-deoxycytidine correlates with delayed progression of castration-resistant prostate cancer

    Androgen deprivation therapy is the primary strategy for the treatment of advanced prostate cancer; however, after an initial regression, most patients will inevitably develop a fatal androgen-independent tumor. Therefore, understanding the mechanisms of the transition to androgen independence prostate cancer is critical to identify new ways to treat older patients who are ineligible for conventional chemotherapy. The effects of 5-Aza-2’-deoxycytidine (5-Aza-CdR) on the viability and the apoptosis of the androgen-dependent (LNCaP) and androgen-independent (PC3) cell lines were examined by MTS assay and western blot analysis for the activation of caspase-3. The subcutaneous LNCaP xenografts were established in a nude mice model. MiR-146a and DNMTs expressions were analyzed by qRT-PCR and DNA methylation rates of LINE-1 were measured by COBRA-IRS to determine the global DNA methylation levels. The methylation levels of miR-146a promoter region in the different groups were quantified by the bisulfite sequencing PCR (BSP) assay. We validated that 5-Aza-CdR induced cell death and increased miR-146a expression in both LNCaP and PC3 cells. Notably, the expression of miR-146a in LNCaP cells was much higher than in PC3 cells. MiR-146a inhibitor was shown to suppress apoptosis in 5-Aza-CdR-treated cells. In a castrate mouse LNCaP xenograft model, 5-Aza-CdR significantly suppressed the tumors growth and also inhibited prostate cancer progression. Meanwhile, miR-146a expression was significantly enhanced in the tumor xenografts of 5-Aza-CdR-treated mice and the androgen-dependent but not the androgen-independent stage of castrated mice. In particular, the expression of miR-146a was significantly augmented in both stages of the combined treatment (castration and 5-Aza-CdR). Additionally, the methylation percentage of the two CpG sites (−444 bp and −433 bp), which were around the NF-κB binding site at miR-146a promoter, showed the lowest methylation levels among all Cp

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

    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

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

    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

  2. 5-Azacytidine Promotes an Inhibitory T-Cell Phenotype and Impairs Immune Mediated Antileukemic Activity

    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...

  3. 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

    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

  4. Statistics On Title II Direct Payments To Claimant Representatives

    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...

  5. Regional Tribal Operations Committee RTOC Areas and Representative Contact Info

    U.S. Environmental Protection Agency — The Regional Tribal Operations Committee (RTOC) is a working committee of EPA and Tribal personnel co-chaired by an EPA representative and a Tribal representative....

  6. Marketing Norm Perception Among Medical Representatives in Indian Pharmaceutical Industry

    Nagashekhara, Molugulu; Agil, Syed Omar Syed; Ramasamy, Ravindran

    2012-01-01

    Study of marketing norm perception among medical representatives is an under-portrayed component that deserves further perusal in the pharmaceutical industry. The purpose of this study is to find out the perception of marketing norms among medical representatives. The research design is quantitative and cross sectional study with medical representatives as unit of analysis. Data is collected from medical representatives (n=300) using a simple random and cluster sampling using a structured que...

  7. 22 CFR 23.4 - Representative value in exchange.

    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...

  8. 19 CFR 146.2 - Port director as Board representative.

    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....

  9. 20 CFR 205.7 - Termination of employee representative status.

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Termination of employee representative status... RETIREMENT ACT EMPLOYEE REPRESENTATIVE § 205.7 Termination of employee representative status. The employee... she is employed loses any of the characteristics essential to the existence of employee...

  10. 22 CFR 41.52 - Information media representative.

    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 representative. (a) Representative of foreign...

  11. 40 CFR 60.4111 - Alternate Hg designated representative.

    2010-07-01

    ... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Alternate Hg designated representative... Times for Coal-Fired Electric Steam Generating Units Hg Designated Representative for Hg Budget Sources § 60.4111 Alternate Hg designated representative. (a) A certificate of representation under §...

  12. 40 CFR 197.31 - What is a representative volume?

    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...

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

    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.

  14. Multi-mode entangled states represented as Grassmannian polynomials

    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. Clozapine disposition covaries with CYP1A2 activity determined by a caffeine test.

    Bertilsson, L; Carrillo, J A; Dahl, M L; Llerena, A; Alm, C; Bondesson, U; Lindström, L; Rodriguez de la Rubia, I; Ramos, S; Benitez, J

    1994-01-01

    In a previous study we showed that the disposition of clozapine after a single oral dose is unrelated to either debrisoquine or S-mephenytoin hydroxylation polymorphism. The same 14 healthy subjects studied in that investigation were given 150 mg of caffeine. The reciprocal of plasma clozapine AUC (0,24), was correlated with an index of the N3-demethylation of caffeine (rs = 0.84; P = 0.0024), used as a measure of cytochrome P4501A2 (CYP1A2) activity. N1- and N7-demethylation indices of caffeine also reflect CYP1A2 activity and were also correlated with clozapine clearance (rs = 0.89 and 0.85; P = 0.0013 and 0.0023; respectively). No significant relationships with xanthine oxidase and N-acetyl transferase activity, also assessed by a caffeine test, were found. This study suggests that clozapine is metabolised by CYP1A2 to a major extent. PMID:7893591

  16. Arctic indigenous peoples as representations and representatives of climate change.

    Martello, Marybeth Long

    2008-06-01

    Recent scientific findings, as presented in the Arctic Climate Impact Assessment (ACIA), indicate that climate change in the Arctic is happening now, at a faster rate than elsewhere in the world, and with major implications for peoples of the Arctic (especially indigenous peoples) and the rest of the planet. This paper examines scientific and political representations of Arctic indigenous peoples that have been central to the production and articulation of these claims. ACIA employs novel forms and strategies of representation that reflect changing conceptual models and practices of global change science and depict indigenous peoples as expert, exotic, and at-risk. These portrayals emerge alongside the growing political activism of Arctic indigenous peoples who present themselves as representatives or embodiments of climate change itself as they advocate for climate change mitigation policies. These mutually constitutive forms of representation suggest that scientific ways of seeing the global environment shape and are shaped by the public image and voice of global citizens. Likewise, the authority, credibility, and visibility of Arctic indigenous activists derive, in part, from their status as at-risk experts, a status buttressed by new scientific frameworks and methods that recognize and rely on the local experiences and knowledges of indigenous peoples. Analyses of these relationships linking scientific and political representations of Arctic climate change build upon science and technology studies (STS) scholarship on visualization, challenge conventional notions of globalization, and raise questions about power and accountability in global climate change research. PMID:19069077

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

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

    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...

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

    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...

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

    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

  1. Jmjd2C increases MyoD transcriptional activity through inhibiting G9a-dependent MyoD degradation.

    Jung, Eun-Shil; Sim, Ye-Ji; Jeong, Hoe-Su; Kim, Su-Jin; Yun, Ye-Jin; Song, Joo-Hoon; Jeon, Su-Hee; Choe, Chungyoul; Park, Kyung-Tae; Kim, Chang-Hoon; Kim, Kye-Seong

    2015-08-01

    Skeletal muscle cell differentiation requires a family of proteins called myogenic regulatory factors (MRFs) to which MyoD belongs. The activity of MyoD is under epigenetic regulation, however, the molecular mechanism by which histone KMTs and KDMs regulate MyoD transcriptional activity through methylation remains to be determined. Here we provide evidence for a unique regulatory mechanism of MyoD transcriptional activity through demethylation by Jmjd2C demethylase whose level increases during muscle differentiation. G9a decreases MyoD stability via methylation-dependent MyoD ubiquitination. Jmjd2C directly associates with MyoD in vitro and in vivo to demethylate and stabilize MyoD. The hypo-methylated MyoD due to Jmjd2C is significantly more stable than hyper-methylated MyoD by G9a. Cul4/Ddb1/Dcaf1 pathway is essential for the G9a-mediated MyoD degradation in myoblasts. By the stabilization of MyoD, Jmjd2C increases myogenic conversion of mouse embryonic fibroblasts and MyoD transcriptional activity with erasing repressive H3K9me3 level at the promoter of MyoD target genes. Collectively, Jmjd2C increases MyoD transcriptional activity to facilitate skeletal muscle differentiation by increasing MyoD stability through inhibiting G9a-dependent MyoD degradation. PMID:26149774

  2. Attitudes of general practitioners in New Zealand to pharmaceutical representatives.

    Thomson, A N; Craig, B J; Barham, P. M.

    1994-01-01

    BACKGROUND. Pharmaceutical representatives are a vital component of the marketing of pharmaceutical products and an important source of prescribing information for general practitioners. AIM. A study was undertaken to explore the attitudes of New Zealand general practitioners to pharmaceutical representatives. METHOD. A questionnaire survey of 100 general practitioners was undertaken to which 67 general practitioners responded. RESULTS. The provision of practical prescribing advice by represe...

  3. Fiscal year 1986, Department of Energy authorization (magnetic fusion energy and departmental administration and supporting services activities). Volume V. Hearings before the Subcommittee on Energy Research and Production of the Committee on Science and Technology, House of Representatives, Ninety-Ninth Congress, First Session, March 8, 18, 1985

    Volume V of the hearing record covers testimony given over two days on budgets for research on magnetic fusion energy and on the administration and support services of the DOE. The principal witness on the first day was Dr. Alvin Trivelpiece of DOE, who described adjustments in fusion funding that resulted from federal budget cuts. These led to delay and deferments in the program, and raised the issue of how to maintain balance in the program and still meet program goals. Trivelpiece emphasized that cuts for fusion research were consistent with other DOE reductions. Testimony on the second day came from representatives of fusion laboratories and the nuclear industry. Two appendices with additional questions and answers submitted for the record follow the testimony of the 16 witnesses

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

    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....... 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...

  5. Marketing norm perception among medical representatives in Indian pharmaceutical industry.

    Nagashekhara, Molugulu; Agil, Syed Omar Syed; Ramasamy, Ravindran

    2012-03-01

    Study of marketing norm perception among medical representatives is an under-portrayed component that deserves further perusal in the pharmaceutical industry. The purpose of this study is to find out the perception of marketing norms among medical representatives. The research design is quantitative and cross sectional study with medical representatives as unit of analysis. Data is collected from medical representatives (n=300) using a simple random and cluster sampling using a structured questionnaire. Results indicate that there is no difference in the perception of marketing norms among male and female medical representatives. But there is a difference in opinion among domestic and multinational company's medical representatives. Educational back ground of medical representatives also shows the difference in opinion among medical representatives. Degree holders and multinational company medical representatives have high perception of marketing norms compare to their counterparts. The researchers strongly believe that mandatory training on marketing norms is beneficial in decision making process during the dilemmas in the sales field. PMID:24826035

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

    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

  7. 42 CFR 441.480 - Use of a representative.

    2010-10-01

    ... may permit participants to appoint a representative to direct the provision of self-directed PAS on... PAS. (b) A person acting as a representative for a participant receiving self-directed PAS is prohibited from acting as a provider of self-directed PAS to the participant....

  8. 22 CFR 41.25 - NATO representatives, officials, and employees.

    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...

  9. 40 CFR 72.22 - Alternate designated representative.

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Alternate designated representative. 72.22 Section 72.22 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... company; and (ii) The designated representative for the units under paragraph (e)(1)(i) of this...

  10. 40 CFR 60.4114 - Objections concerning Hg designated representative.

    2010-07-01

    ... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Objections concerning Hg designated... Times for Coal-Fired Electric Steam Generating Units Hg Designated Representative for Hg Budget Sources § 60.4114 Objections concerning Hg designated representative. (a) Once a complete certificate...

  11. 40 CFR 96.82 - NOX authorized account representative.

    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...

  12. 40 CFR 97.82 - NOX authorized account representative.

    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...

  13. 40 CFR Appendix I to Part 261 - Representative Sampling Methods

    2010-07-01

    ... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Representative Sampling Methods I...—Representative Sampling Methods The methods and equipment used for sampling waste materials will vary with the form and consistency of the waste materials to be sampled. Samples collected using the...

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

    Geersbro, Jens; Ritter, Thomas

    2013-01-01

    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 dissemination of the definition of a "non-customer", higher prevalence of termination routines, and increasing degrees of termination incentives. Acceptance of relationship termination at the firm level does not appear to have a significant impact on sales representatives' relationship termination...

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

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

    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

  17. Representative recharge rates in a complex unsaturated hydrogeology

    This study summarizes analyses used for the determination of representative recharge rates in a semi-arid terrain of complex topography for the purpose of modeling the performance assessment of a mesa top disposal facility. Four recharge rates are identified based on different terrains. The terrain is first broadly grouped into canyon bottoms and mesa tops, with each covering about half the topography. The canyon bottoms are considered wet or dry depending on the local infiltration conditions and the influence of mans' activities. The mesa tops are separated into locations which are undisturbed and disturbed by laboratory operations. Disturbed locations at the disposal facility include the disposal pits utilized for shallow land burial of low-level radioactive waste, covering approximately half the mesa top area. Several sources of data and analyses have been synthesized to estimate the resulting recharge rates. Data and analyses include: (1) detailed surface water balance calculations with site-specific parameter values as input; (2) chloride ion profiles and analysis of implied flux at several borehole locations; (3) analyses of liquid and vapor phase vertical flux from moisture profiles with stratigraphic unit averaged unsaturated hydrologic properties; (4) comparison of moisture content field data with values implied from Darcy flux calculations for assumed unit gradient conditions and for stratigraphic unit averaged unsaturated hydrologic properties; (5) liquid flux calculated under self-consistent gradients from field observed moisture profiles and analytic determinations of in-situ moisture potential and conductivity at limited locations; (6) distributions in near surface soil moisture contents expressed as an equivalent vertical flux under unit gradient assumptions; and (7) limited comparisons to tracers available from past disposal operations

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

    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, ...

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

    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…

  20. 25 CFR 171.120 - What are the authorities and responsibilities of a representative organization?

    2010-04-01

    ... representing you may make rules, policies, and procedures it may find necessary to administer the activities it is authorized to perform. (b) An organization must not make rules, policies, or procedures that conflict with our regulations or any of our other written policies, procedures, directives, and manuals....

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

    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…

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

    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...

  3. The roles of co-chaperone CCRP/DNAJC7 in Cyp2b10 gene activation and steatosis development in mouse livers.

    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.

  4. 32 CFR 705.14 - Embarkation of media representatives.

    2010-07-01

    ... to avoid any interpretation of such review as “censorship” or interference with freedom of the press...) When more than one representative from the same medium is embarked, an attempt should be made to...

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

    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:...

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

    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....... 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......’s potential identity, others will do so only after prolonged contact, while others again will be able to influence the students potential identity and thus educational choices after just a brief meeting....

  7. Impact of pharmaceutical representative visits on GPs' drug preferences

    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......% CI, 1.19-1.93), while there was no significant change after the third visit (OR, 1.06; 95% CI, 0.94-1.20). Pharmaceutical sales representative visits did not influence the overall treatment pattern with inhaled steroids (OR, 1.01; 95% CI, 0.97-1.06). CONCLUSIONS: Pharmaceutical sales representative...

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

    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 ...

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

    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...

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

    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 ...

  11. Capturing and representing deliberation in participatory planning practices

    De Liddo, Anna; Buckingham Shum, Simon

    2010-01-01

    In this paper we argue for the importance of capturing and representing deliberation in participatory planning practices. We discuss the concept of deliberation in planning theory, and argue for a paradigm that puts deliberation at the centre of public participation to planning decision. We argue that in order to enable effective participation, the normally ephemeral delib- eration process needs to be captured and represented so that the information and knowledge gathered during deliberation ...

  12. The challenge of representative design in psychology and economics

    Hogarth, Robin

    2004-01-01

    The demands of representative design, as formulated by Egon Brunswik (1956), set a high methodological standard. Both experimental participants and the situations with which they are faced should be representative of the populations to which researchers claim to generalize results. Failure to observe the latter has led to notable experimental failures in psychology from which economics could learn. It also raises questions about the meaning of testing economic theories in ?abstract? environme...

  13. Disentangling the representativeness heuristic from the availability heuristic

    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...

  14. A Theory of Representative Behavior in the Dictator Game

    Giménez Gómez, José M. (José Manuel); Osório, António (António Miguel)

    2014-01-01

    In this paper we present a model of representative behavior in the dictator game. Individuals have simultaneous and non-contradictory preferences over monetary payoffs, altruistic actions and equity concerns. We require that these behaviors must be aggregated and founded in principles of representativeness and empathy. The model results match closely the observed mean split and replicate other empirical regularities (for instance, higher stakes reduce the willingness to give). In addition, we...

  15. An Approach to Representing the Process of Information Business Modeling

    Filipova, Nadezhda; Filipov, Filcho

    2008-01-01

    The compact and visualized documenting of information business modeling is a major prerequisite for comprehending its basic concepts, as well as for its effective application and improvement. The documenting of this process is related to its modeling. Thus, the process of information business modeling can be represented by its own tools. Being based on this thesis, the authors suggest an approach to representing the process of information business modeling. A profile for its d...

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

    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...

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

    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.

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

    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.

  19. Associated factors of obesity in Spanish representative samples.

    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

  20. Associated factors of obesity in Spanish representative samples

    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

  1. Selection of Representative Models for Decision Analysis Under Uncertainty

    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.

  2. Representing Topological Relationships Among Heterogeneous Geometry-Collection Features

    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.

  3. Representing Topological Relationships Among Heterogeneous Geometry-Collection Features

    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.

  4. A geometric language for representing structure in polyphonic music

    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...... is represented as a set of multidimensional points, generated by performing transformations on component patterns. The language introduces the concept of a periodic mask, a generalisation of Deutsch and Feroe’s notion of a pitch alphabet, that can be applied to any dimension of a geometric...

  5. Do trigeminal autonomic cephalalgias represent primary diagnoses or points on a continuum?

    Charleston, Larry

    2015-06-01

    The question of whether the trigeminal autonomic cephalalgias (TACs) represent primary diagnoses or points on a continuum has been debatable for a number of years. Patients with TACs may present with similar clinical characteristics, and occasionally, TACS respond to similar treatments. Prima facie, these disorders may seem to be intimately related. However, due to the current evidence, it would be challenging to accurately conclude whether they represent different primary headache diagnoses or the same primary headache disorder represented by different points on the same continuum. Ultimately, the TACs may utilize similar pathways and activate nociceptive responses that result in similar clinical phenotypes but "original and initiating" etiology may differ, and these disorders may not be points on the same continuum. This paper seeks to provide a brief comparison of TACs via diagnostic criteria, secondary causes, brief overview of pathophysiology, and the use of some key treatments and their mechanism of actions to illustrate the TAC similarities and differences. PMID:26021755

  6. Heterogeneous Antibody-Based Activity Assay for Lysine Specific Demethylase 1 (LSD1) on a Histone Peptide Substrate.

    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

  7. Enterprise Systems Implementations: Organizational Influence Processes for Corporate User Representatives

    Nielsen, Peter Axel; Nordheim, Stig

    2008-01-01

    -depth, interpretive study from the oil industry, where we analyze a case of innovative integration of an ECM system with collaboration technologies. The data collection has been longitudinal. The data analysis has been performed through the perspective of organizational influence processes. The main finding concerns...... an organizational role as corporate user representative to deal with the scale and complexities of implementation. A single person was particularly influential in the role. At the outset a user representative had to perform upward influence processes from a lower formal position. This is impeding the...

  8. Activated Carbon and Biochar Reduce Mercury Methylation Potentials in Aquatic Sediments.

    Bussan, Derek D; Sessums, Ryan F; Cizdziel, James V

    2016-04-01

    Much of the toxic methylmercury (MeHg) that biomagnifies in the aquatic food chain and accumulates in fish and seafood is believed to originate from microbial methylation of inorganic Hg(+2) in anoxic sediments. We examined the effect amending wetland sediments with activated carbon and biochar on Hg methylation potentials using microcosms and Hg stable isotope tracers. The inorganic (200)Hg(+2) spike was methylated at ~0.37 %/day in the untreated sediment, but that rate decreased to amended sediments, with 80 % and 88 % reductions in methylation rates for activated carbon and biochar amendments, respectively. Demethylation rates were relatively unchanged. Our key finding is that amending contaminated sediment with activated carbon and biochar decreases bioavailable Hg, and thus may also decrease Hg transfer into food webs. However, further research is needed to evaluate exactly how the sorbents impact Hg methylation rates and for related field studies. PMID:26779648

  9. Representativeness and seasonality of major ion records derived from NEEM firn cores

    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.

  10. Research Note: Representing Identity and Relationships in Information Systems

    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.

  11. Can Democracy Represent Children? Toward a Politics of Difference

    Wall, John

    2012-01-01

    Children and youth under 18 have made significant strides in recent years toward fuller inclusion in democratic processes. These strides, however, rarely rise to the level of direct political representation, whether in changing policies, making laws, or voting. This article argues that democracies will be able to represent children only by…

  12. Identifying and Representing Elements of Local Contexts in Namibia

    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 clea...

  13. Representing Mental Spaces and Dynamics of Natural Language Semantics

    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.

  14. Exhaustive search for conservation networks of populations representing genetic diversity.

    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. Party member recruitment and the representativeness of party membership

    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...

  16. Communication received from the Resident Representatives of Argentina and Brazil

    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

  17. 40 CFR 350.23 - Disclosure to authorized representatives.

    2010-07-01

    ... PLANNING AND COMMUNITY RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS... representatives. 350.23 Section 350.23 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... information to which this section applies, notwithstanding the fact that the information might otherwise...

  18. 26 CFR 31.3211-3 - Employee representative supplemental tax.

    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...

  19. 14 CFR 183.31 - Designated manufacturing inspection representatives.

    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... certificates for aircraft for which the manufacturer holds the type certificate and which have...

  20. Representing adaptive eLearning strategies in IMS Learning Design

    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

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

    Dellson, Pia; Nilbert, Mef; Carlsson, Christina

    2016-01-01

    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......, structured text and illustrations to improve the informed consent process and thereby patient enrolment into clinical trials....

  2. Professional Human Service Occupation Biases Represented in General Psychology Textbooks

    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,…

  3. Does density fractionation of SOC represent chemically different carbon pools?

    Mulvaney, Michael J.; Graham, M.; Xia, K.; Barrera, Victor H.; Botello, Rubén; Saavedra, Ana Karina; Mamani, P.

    2012-01-01

    Organic matter stabilization is thought to be a process of physical protection and chemical recalcitrance. The determination of recalcitrant soil organic carbon (SOC) often relies on operational definitions provided by various fractionation techniques, usually particle size or density fractionation. However, it is unknown if these operational definitions represent true chemical recalcitrance.

  4. Planning to Move: Effects on Representing the Currently Inhabited Environment.

    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…

  5. 20 CFR 410.583 - Responsibility of representative payee.

    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...

  6. 20 CFR 266.7 - Accountability of a representative payee.

    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...

  7. Teachers' Voices/Stories: Dilemmas in Representing the Research Data

    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…

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

    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...

  9. Representative sets and irrelevant vertices: New tools for kernelization

    Kratsch, Stefan

    2011-01-01

    Recent work of the present authors provided a polynomial kernel for Odd Cycle Transversal by introducing matroid-based tools into kernelization. In the current work we further establish the usefulness of matroid theory to kernelization by showing applications of a result on representative sets due to Lov\\'asz (Combinatorial Surveys 1977) and Marx (TCS 2009). We give two types of applications: 1. Direct applications of the representative objects idea. In this direction, we give a polynomial kernel for Almost 2-SAT by reducing the problem to a cut problem with pairs of vertices as sinks, and subsequently reducing the set of pairs to a representative subset of bounded size. This implies polynomial kernels for several other problems, including Vertex Cover parameterized by the size of the LP gap, and the RHorn-Backdoor Deletion Set problem from practical SAT solving. We also get a polynomial kernel for Multiway Cut with deletable terminals, by producing a representative set of vertices, of bounded size, which is ...

  10. 40 CFR 97.11 - Alternate NOX authorized account representative.

    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...

  11. 40 CFR 96.11 - Alternate NOX authorized account representative.

    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...

  12. Learning, Labour and Union Learning Representatives: Promoting Workplace Learning

    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…

  13. Twenty-sixth general conference meeting of representatives of RCA member states. Report

    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

  14. Patent Applications on Representative Sectors of Biotechnology in Brazil: an Analysis of the Last Decade

    Liliana Machado Mendes; Beatriz Amorim-Borher; Celso Lage

    2013-01-01

    The present article aims to assess the innovative activity in the Brazilian most representative sector in biotechnology field. The search was conducted through patent applications of residents at the National Institute of Industrial Property (INPI - Brazil), from 2000 to 2010. This article will also examine the patent applicants' profile and the partnerships among academic institutions and private firms in BrazilThe website of European Patent Office (EPO) patent database - Espacenet was used ...

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

    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...

  16. Representative Model Of The Learning Process 
In Virtual Spaces Supported By Ict

    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...

  17. Big Questions for Social Media Big Data: Representativeness, Validity and Other Methodological Pitfalls

    Tufekci, Zeynep

    2014-01-01

    Large-scale databases of human activity in social media have captured scientific and policy attention, producing a flood of research and discussion. This paper considers methodological and conceptual challenges for this emergent field, with special attention to the validity and representativeness of social media big data analyses. Persistent issues include the over-emphasis of a single platform, Twitter, sampling biases arising from selection by hashtags, and vague and unrepresentative sampli...

  18. Reactivation of a methylation-silenced gene in adenovirus-transformed cells by 5-azacytidine or by E1A trans activation.

    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

  19. A single spiking neuron that can represent interval timing: analysis, plasticity and multi-stability.

    Shouval, Harel Z; Gavornik, Jeffrey P

    2011-04-01

    The ability to represent interval timing is crucial for many common behaviors, such as knowing whether to stop when the light turns from green to yellow. Neural representations of interval timing have been reported in the rat primary visual cortex and we have previously presented a computational framework describing how they can be learned by a network of neurons. Recent experimental and theoretical results in entorhinal cortex have shown that single neurons can exhibit persistent activity, previously thought to be generated by a network of neurons. Motivated by these single neuron results, we propose a single spiking neuron model that can learn to compute and represent interval timing. We show that a simple model, reduced analytically to a single dynamical equation, captures the average behavior of the complete high dimensional spiking model very well. Variants of this model can be used to produce bi-stable or multi-stable persistent activity. We also propose a plasticity rule by which this model can learn to represent different intervals and different levels of persistent activity. PMID:20827572

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

    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

  1. Activation induced deaminase: how much and where?

    Orthwein, Alexandre; Di Noia, Javier M

    2012-08-01

    Activation induced deaminase (AID) plays a central role in adaptive immunity by initiating the processes of somatic hypermutation (SHM) and class switch recombination (CSR). On the other hand, AID also predisposes to lymphoma and plays a role in some autoimmune diseases, for which reasons AID expression and activity are regulated at various levels. Post-translational mechanisms regulating the amount and subcellular localization of AID are prominent in balancing AID physiological and pathological functions in B cells. Mechanisms regulating AID protein levels include stabilizing chaperones in the cytoplasm and proteins efficiently targeting AID to the proteasome within the nucleus. Nuclear export and cytoplasmic retention contribute to limit the amount of AID accessing the genome. Additionally, a number of factors have been implicated in AID active nuclear import. We review these intertwined mechanisms proposing two scenarios in which they could interact as a network or as a cycle for defining the optimal amount of AID protein. We also comparatively review the expression levels of AID necessary for its function during the immune response, present in different cancers as well as in those tissues in which AID has been implicated in epigenetic remodeling of the genome by demethylating DNA. PMID:22687198

  2. An affordable proxy of representative national survey on radon concentration in dwellings: Design, organisation and preliminary evaluation of representativeness

    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

  3. Processes, data structures, and apparatuses for representing knowledge

    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.

  4. Chaos control applied to cardiac rhythms represented by ECG signals

    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. (paper)

  5. Representing Scientific Communities by Data Visualization (1/2)

    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...

  6. Chaos control applied to cardiac rhythms represented by ECG signals

    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.

  7. Sexual desire in a nationally representative Danish population

    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...... the adult Danish population and to analyze the relationships between a number of relevant variables and sexual desire. METHODS: The study population (N = 10,458, response rate 84.8%) answered a questionnaire with questions on sexual matters. The representativity of the population was examined. The...... frequency of self-reported sexual desire and decrease in sexual desire over a 5-year period was calculated for the two genders across age cohorts. Multiple logistic regression analysis was used to analyze the relationship between potential determinants and sexual desire. MAIN OUTCOME MEASURES: The frequency...

  8. Representative longitudinal optical phonon modes in polar semiconductor quantum dots

    Highlights: ► We model the exciton-longitudinal optical phonon coupling for cylinder quantum dot. ► We predict a representative optical phonon mode for GaAs/AlAs quantum dot. ► Huang–Rhys factors increases with radius decreasing of GaAs/AlAs quantum dot. - Abstract: Existence of representative longitudinal optical (LO) phonon modes is theoretically discussed for the case of polar semiconductor cylindrical quantum dots embedded in a semiconductor matrix. The approach is developed within the dielectric continuum model considering the Fröhlich interaction between electrons and the confined LO phonons. The theory is applied to cylindrical GaAs/AlAs quantum dots within an adiabatic treatment.

  9. Qualitative interviewing of respondents in large representative surveys

    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...

  10. Forms representing forms and linear spaces on hypersurfaces

    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.

  11. Representing value judgements in the evaluation options for nuclear waste

    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)

  12. Representing and Reasoning over Topological Relations in OWL

    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...

  13. Learning and Representing Temporal Knowledge in Recurrent Networks

    Borges, Rafael; Garcez, A. d'Avila; Lamb, L C

    2011-01-01

    The effective integration of knowledge representation, reasoning, and learning in a robust computational model is one of the key challenges of computer science and artificial intelligence. In particular, temporal knowledge and models have been fundamental in describing the behavior of computational systems. However, knowledge acquisition of correct descriptions of a system's desired behavior is a complex task. In this paper, we present a novel neural-computation model capable of representing ...

  14. Peculiarities of accentuation of hightened speech responsibility profession representatives

    Корнєлаєва, Є. В.

    2015-01-01

    The article deals with the peculiarities of accentuation in the speech of politicians, actors, lecturers. Profession is one of the main components of the speaker's social status. Accentuation helps to reveal components of text which can be the communicative centre of the utterance. In this study an attempt is undertaken to describe the prosodic features of speech of the representatives of the professions with high voice responsibility in an extralinguistic situation without involving the dire...

  15. Representing electrons a biographical approach to theoretical entities

    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

  16. Representing young people's sexuality in the 'youth' media

    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...

  17. BRAIN MECHANISMS FOR REPRESENTING WHAT ANOTHER PERSON SEES

    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 ...

  18. The English Revolution and a Representative and Constitutional Government

    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.

  19. Representative landscapes in the forested area of Canada.

    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

  20. Representativeness of the European social partner organisations: Footwear industry - Netherlands

    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.

  1. BagPack: A general framework to represent semantic relations

    Herdağdelen, Amaç

    2009-01-01

    We introduce a way to represent word pairs instantiating arbitrary semantic relations that keeps track of the contexts in which the words in the pair occur both together and independently. The resulting features are of sufficient generality to allow us, with the help of a standard supervised machine learning algorithm, to tackle a variety of unrelated semantic tasks with good results and almost no task-specific tailoring.

  2. Representative Bodies: Greater publicity for unchanged rules of the game

    Dzmitry Kukhlei

    2014-01-01

    Priorities and trends of work of the representative bodies of the Parliament and local councils continue to be determined by the President, the government and executive authorities. The National Assembly demonstrates coordinated work and cooperation with the government, especially in matters of defending national interests vis-à-vis foreign partners. In the growing crisis of the Belarusian socio-economic model the Parliament begins to play a greater role in the adjustment processes of socio-e...

  3. Our (represented) World: A Quantum-Like Object

    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...

  4. Hydraulic behaviour of a representative structural volume for containment buildings

    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)

  5. Reference materials and representative test materials: the nanotechnology case

    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).

  6. Representing plants as rigid cylinders in experiments and models

    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.

  7. Selection of representative emerging micropollutants for drinking water treatment studies: a systematic approach.

    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

  8. 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

    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

  9. Synthesis, Characterization, and Agricultural Biological Activities of 5-Fluoro-2-hydroxy Butyrophenone

    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.

  10. Do capture data from mosquito traps represent reality?

    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...

  11. Hydrological studies in experimental and representative basins in Pernambuco State, Brazil

    Montenegro, S. M. G. L.; da Silva, B. B.; Antonino, A. C. D.; Lima, J. R. S.; de Souza, E. S.; de Oliveira, L. M. M.; de Moura, A. E. S. S.; Souza, R. M. S.

    2014-09-01

    Hydrological studies in experimental and representative basins are of fundamental importance for water resources management. This paper presents some activities of hydrological research in experimental and representative basins of the State of Pernambuco, Brazil. The study areas are located at Tapacurá and Mundaú representative basins and at the Gameleira experimental basin, and in experimental plots in Pajeú basin. In the Tapacurá basin, three studies were performed: (1) different monthly coefficients "k" of the Thornthwaite method were tested to calculate the effective temperature and, consequently, the reference evapotranspiration, giving rise to the method identified as Modified Thornthwaite; (2) the spatial variability of the retention curve and hydraulic conductivity parameters were analysed using the Beerkan method; (3) changes in vegetation cover were evaluated through the NDVI and NDWI indexes using TM-Landsat 5 images. In the Mundaú representative basin, the performance of different evapotranspiration methods was evaluated and compared to the FAO standard method, Penman-Monteith. In the Pajeú basin, the experimental plot is covered by pasture and sensors were installed to monitor the following variables: rainfall, air temperature, the energy balance components (net radiation, latent and sensible heat, and soil heat flux), wind velocity and CO2 flux into atmosphere, soil moisture and runoff.

  12. Doctors’ opinions of information provided by Libyan pharmaceutical company representatives

    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.

  13. 2009 North Dakota Agricultural Outlook: Representative Farms, 2009-2018

    Taylor, Richard D.; Koo, Won W.; Swenson, Andrew L.

    2009-01-01

    Net farm income for all representative farms in 2018 is projected to be lower than in 2008. Low-profit farms, which comprise 20% of the farms in the study, may not have financial resiliency to survive without off-farm income. Commodity prices are expected to fall from current levels however the final level is unknown. Commodity yields are projected to increase at historical trend-line rates and production expenses are expected to return to normal growth rates after 2009. Debt-to-asset ratios ...

  14. 2008 North Dakota Agricultural Outlook: Representative Farms, 2008-2017

    Taylor, Richard D.; Koo, Won W.; Swenson, Andrew L.

    2008-01-01

    Net farm income for nearly all representative farms in 2017 is projected to be lower than in 2007. Low profit farms, which comprise 20% of the farms in the study, may not have financial resiliency to survive without off-farm income. Commodity prices are expected to fall from current levels, however, the final level is unknown. Two price level scenarios were analyzed. Commodity yields are projected to increase at historical trend-line rates and production expenses are expected to return to nor...

  15. 2012 North Dakota Agricultural Outlook: Representative Farms, 2012-2021

    Taylor, Richard D.; Koo, Won W.; Swenson, Andrew L.

    2012-01-01

    Net farm income in North Dakota was at near record levels for most representative farms in 2011. However income in 2021 is projected to be lower than in 2011. Commodity prices are expected to decrease slowly from current levels. Commodity yields are projected to increase at historical trend-line rates and production expenses are expected to return to normal growth rates. Debt-to-asset ratios for all farms except for the low profit farm will decrease slightly throughout the forecast period. De...

  16. 2015 North Dakota Agricultural Outlook: Representative Farms, 2015-2024

    Taylor, Richard D.; Koo, Won W.

    2015-01-01

    Net farm income in North Dakota was at record levels for most representative farms in 2012. However, net farm income fell for both 2013 and 2014 and is expected to continue to fall through 2024. Commodity prices are expected to decrease slowly from current levels. Commodity yields are projected to increase at historical trend-line rates and production expenses are expected to return to normal growth rates. Debt-to-asset ratios for all farms except for the high profit farm will increase slight...

  17. 2010 North Dakota Agricultural Outlook: Representative Farms, 2010-2019

    Taylor, Richard D.; Koo, Won W.; Swenson, Andrew L.

    2010-01-01

    Net farm income for most representative farms in 2019 is projected to be lower than in 2009. Low-profit farms, which comprise 20% of the farms in the study, may not have financial resiliency to survive without off-farm income. Commodity prices are expected to increase slowly from current levels. Commodity yields are projected to increase at historical trend-line rates and production expenses are expected to return to normal growth rates. Debt-to-asset ratios for all farms except for the low p...

  18. 2014 North Dakota Agricultural Outlook: Representative Farms, 2014-2023

    Taylor, Richard D.; Koo, Won W.

    2014-01-01

    Net farm income in North Dakota was at record levels for most representative farms in 2012. However net farm income fell for 2013 and is expected to continue to fall through 2023. Commodity prices are expected to decrease slowly from current levels. Commodity yields are projected to increase at historical trend-line rates and production expenses are expected to return to normal growth rates. Debt-to-asset ratios for all farms except for the low profit farm will increase slightly throughout th...

  19. 2013 North Dakota Agricultural Outlook: Representative Farms, 2013-2022

    Taylor, Richard D.; Koo, Won W.; Swenson, Andrew L.

    2013-01-01

    Net farm income in North Dakota was at record levels for most representative farms in 2012. However income in 2022 is projected to be lower than in 2012. Commodity prices are expected to decrease slowly from current levels. Commodity yields are projected to increase at historical trend-line rates and production expenses are expected to return to normal growth rates. Debt-to-asset ratios for all farms except for the low profit farm are projected to decrease slightly throughout the forecast per...

  20. FEAT-REP : representing features in CAD/CAM

    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...

  1. Writing Irataba: On Representing Native Americans on Wikipedia

    Pharao Hansen, Magnus

    2016-01-01

    Wikipedia, the online encyclopedia that anyone can edit, is simultaneously an experiment in anarchic knowledge production and a realization of the long dream of modernity: storing all human knowledge. It is also a battleground for the politics of representation and for creating and circulating...... anthropological knowledge and Wikipedia's policies establishing how to authorize and re-represent narratives. These dilemmas point out to us, as 21st-century anthropologists, that we have a responsibility for being the stewards of the knowledge created by anthropologists past as well as for correcting their...

  2. Greening the U.S. House of Representatives

    Diamond

    2008-01-01

    The Greening the Capitol initiative was launched in March, 2007 with the threefold goals of making the U.S. House of Representatives: 1) carbon neutral within 18 months, 2) reducing energy use by 50percent in ten years, and 3) becoming a model of sustainable operations. We report on the recommendations to meet these goals, looking at the targets of opportunity at the Capitol Power Plant, the existing buildings, and the overall operations of the complex. Our findings have shown that these goal...

  3. Structural knowledge techniques for representing, conveying, and acquiring structural knowledge

    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

  4. The live album or many ways of representing performance

    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”.

  5. The Representatives of Amelanchier Medik. Genus in Ukraine

    Opalko Anatoliy Ivanovich

    2015-04-01

    Full Text Available The information on fruit and decorative value, honey and medicinal properties of the genus Amelanchier Medik. is generalized. Their biological characteristics, chemical composition and palatability traits of the fruit, the ways of consumption and processing, including drying, preparing juices, syrups, jams, candied fruit jellies, confiture, and fruit wine are specified. The environmental adaptability and effectiveness of using juneberry for phytomelioration are mentioned. Several versions of the origin of the genus Amelanchier name and interpretation of its specific epithets are described. The controversial issues of the genus Amelanchier system were discussed from the classical and molecular genetic approaches. The attention is focused on two main aspects of views on the place of the genus Amelanchier representatives of the family Rosaceae Juss. within the particular subfamily, namely the subfamily Pyroideae Burnett (Maloideae S. Weber or the subfamily Amygdaloideae Arn., which indicates the necessity for further comparative morphological and molecular genetic studies of the family Rosaceae. The directions of evolution, habitat and invasive ability of some species of the genus Amelanchier are characterised. The list of the genus Amelanchier representatives cultivated in Ukraine is given.

  6. Using Logic Programming to Represent Information Content Inclusion Relations

    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.

  7. Psychosocial workload and stress in the workers’ representative

    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

  8. Reduced-Reference Video Quality Estimation Using Representative Luminance

    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.

  9. Soil monitoring in Germany. Spatial representativity and methodical comparability

    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.)

  10. Human cytochrome P-450PA (P-450IA2), the phenacetin O-deethylase, is primarily responsible for the hepatic 3-demethylation of caffeine and N-oxidation of carcinogenic arylamines.

    Butler, M.A. (Mary A.); Iwasaki, M; Guengerich, F P; Kadlubar, F F

    1989-01-01

    Aromatic amines are well known as occupational carcinogens and are found in cooked foods, tobacco smoke, synthetic fuels, and agricultural chemicals. For the primary arylamines, metabolic N-oxidation by hepatic cytochromes P-450 is generally regarded as an initial activation step leading to carcinogenesis. The metabolic activation of 4-aminobiphenyl, 2-naphthylamine, and several heterocyclic amines has been shown recently to be catalyzed by rat cytochrome P-450ISF-G and by its human ortholog,...

  11. Health behaviour in children and adolescents with type 1 diabetes compared to a representative reference population.

    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.

  12. Challenges to Issues of Balance and Representativeness in African Lexicography

    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

  13. New Mechanism of Bone Cancer Pain: Tumor Tissue-Derived Endogenous Formaldehyde Induced Bone Cancer Pain via TRPV1 Activation.

    Wan, You

    2016-01-01

    In recent years, our serial investigations focused on the role of cancer cells-derived endogenous formaldehyde in bone cancer pain. We found that cancer cells produced formaldehyde through demethylation process by serine hydroxymethyltransferase (SHMT1 and SHMT2) and lysine-specific histone demethylase 1 (LSD1). When the cancer cells metastasized into bone marrow, the elevated endogenous formaldehyde induced bone cancer pain through activation on the transient receptor potential vanilloid subfamily member 1 (TRPV1) in the peripheral nerve fibers. More interestingly, TRPV1 expressions in the peripheral fibers were upregulated by the local insulin-like growth factor I (IGF-I) produced by the activated osteoblasts. In conclusion, tumor tissue-derived endogenous formaldehyde induced bone cancer pain via TRPV1 activation. PMID:26900062

  14. Selection of representative instruments for a global change technology architecture trade study

    Hypes, Warren D.; Keafer, Lloyd; Ross, Rogard T.; Knight, Heather R.; Jalink, Anthony; Allen, Cheryl L.

    1991-01-01

    The objectives of Task 2 of the Global Change Technology Initiative (GCTI) Architectural Trade Study were to select representative sets of instruments for making the science measurements specified in Task 1 and to identify instruments that, when flown together, form special complementary packages for measurement purposes. The list of representative instruments and their complementary relationships provide a payload manifest defined in terms of mass, power, size, viewing angles, data rates, etc. which can be used to focus spacecraft trade studies and the definition of a candidate GCTI fleet. Science requirements from Task 1 are given in tabular form. Numerous instruments are described, including visible-infrared radiometers, visible-infrared spectrometers, gas correction radiometers, active systems for Earth observation, Limb viewing instruments, visible-infrared and grating spectrometers, and microwave radiometers.

  15. Selecting representative climate stations for use in a building energy model

    Hadley, D.L.

    1993-11-01

    An energy impacts model is being refined to support ongoing development of major energy conservation standards for US commercial buildings. When completed, the model will be used to evaluate potential impacts (energy savings and associated costs) of implementing the proposed standards. To work as intended, the model must contain a set of climate stations to represent the wide range of climatic conditions that occur across the United States. Researchers developed a procedure that employs a user-selectable climate database (1) to objectively identify, using a clustering technique, a unique set of climate zones for a specified geographical area, and (2) to specify the single most representative station for each climate zone. The process provides a more objective, technically sound basis for selecting climate zones and stations, thereby minimizing researcher bias. The procedure and its application to US energy conservation standards development activities are described in this paper.

  16. Defining And Characterizing Sample Representativeness For DWPF Melter Feed Samples

    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

  17. Defining And Characterizing Sample Representativeness For DWPF Melter Feed Samples

    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

  18. Psychosocial workload and stress in the workers’ representative

    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

  19. Representative Pathways of Excitation Migration in Photosystem I

    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.

  20. [The concept of love in a Spanish representative sample].

    Ferrer Pérez, Victoria A; Bosch Fiol, Esperanza; Navarro Guzmán, Capilla; Ramis Palmer, M Carmen; García Buades, Esther

    2008-11-01

    The model of romantic love and the acceptance of related myths have been granted wide relevance in our context. It has also been suggested that the concept of love can play a role in the origin and maintenance of gender violence. As an initial step towards researching this relationship, the objective of this article is to study the prevailing concept of love in the Spanish population, as well as to analyze any differences that gender and age may introduce in this conception. A reduced version of the Love Attitudes Scale was administered to a representative sample of 1,351 people. Results show that both men and women widely accept the love styles Eros, Agape, Storge and Pragma, reject the Ludus style, and are indifferent to the Mania style. However, the order of preference for love styles is different for men and women and for different age groups. These results are analyzed and discussed. PMID:18940055

  1. Frequency of lucid dreaming in a representative German sample.

    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

  2. Use of S-α diagram for representing tokamak equilibrium

    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

  3. Epidermal characteristics in some representatives of Cactoideae (Cactaceae

    Galina V. Kalashnyk

    2015-05-01

    Full Text Available In this paper we analyzed the epidermis of 6-month old representatives of 11 species of the subfamily Cactoideae. The epidermal cells of examined species have sprawled and elongated projections with a sinuous outlines. Most of plants have large epidermal cells, whose number per unit area considerably varies. Stomatal index of the studied species is small and very small. Size of stomata is variation of 32,5±0,5×24,9±0,7 in Astrophytum myriostigma to 43,2±0,6×36,1±0,5 in Rebutia flavistyla. Large stomata are typical for three species of cacti. All examined species have paracytic stomata. The small prismatic crystals are in epidermal cells of three species. Astrophytum myriostigma and Mammillaria prolifera have papillaes and trichomes on the surface.

  4. [Involvement of medical representatives in team medical care].

    Hirotsu, Misaki; Sohma, Michiro; Takagi, Hidehiko

    2009-04-01

    In recent years, chemotherapies have been further advanced because of successive launch of new drugs, introduction of molecular targeting, etc., and the concept of so-called Team Medical Care ,the idea of sharing interdisciplinary expertise for collaborative treatment, has steadily penetrated in the Japanese medical society. Dr. Naoto Ueno is a medical oncologist at US MD Anderson Cancer Center, the birthplace of the Team Medical Care. He has advocated the concept of ABC of Team Oncology by positioning pharmaceutical companies as Team C. Under such team practice, we believe that medical representatives of a pharmaceutical company should also play a role as a member of the Team Medical Care by providing appropriate drug use information to healthcare professionals, supporting post-marketing surveillance of treated patients, facilitating drug information sharing among healthcare professionals at medical institutions, etc. PMID:19381051

  5. Representing ICD-11 JLMMS Using IHTSDO Representation Formalisms.

    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

  6. COMAS: representative spreading experiments with view to core melt mitigation

    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.)

  7. Seeking professional help for nightmares: a representative study

    Michael Schredl

    2013-12-01

    Full Text Available Background and Objectives: Nightmares are defined as disturbing mental experiences that generally occur during REM sleep and often result in awakening. Even though about 5% of the general population suffers from nightmares, little is known about seeking professional help in this patient group. Methods: A quota sample of 2019 participants representative for the German population was studied. Results: The findings indicate that every eighth person with frequent nightmares (cutoff: every other week or more often sought at one time of his/her life for professional help for coping with nightmares. Socio-demographic variables did not correlate with help-seeking behavior. Conclusions: Nightmares are an undertreated condition and future studies should aim at a more throughout understanding why nightmare sufferers rarely seek help for their condition.

  8. Representing vegetation processes in hydrometeorological simulations using the WRF model

    Nielsen, Joakim Refslund

    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...... the land surface components, such as vegetation and soil, and their interactions with the atmosphere. The land surface processes are complex and vary in time and space. Signi_cant e_ort by the land surface community has therefore been invested in improving the LSMs over the recent decades. However, improve......-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...

  9. Reliability of structure tensors in representing soft tissues structure.

    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

  10. Acute transient deafness representing a negative epileptic phenomenon.

    Shahar, Eli; Ravid, Sarit; Genizi, Jacob; Schif, Aharon

    2010-07-01

    We report herein 2 children who presented with acute deafness heralding an epileptic event manifesting thereafter by loss of consciousness and tonic generalized posturing, possibly reflecting a negative epileptic phenomenon. The first previously healthy male had 2 paroxysmal episodes 7 months apart, starting with acute deafness lasting for a few minutes followed by loss of consciousness and generalized tonic posturing for 10 minutes. Electroencephalography (EEG) during the second episodes demonstrated generalized epileptiform discharges. The second with previously controlled partial complex seizures presented with episodes of complete deafness lasting for a few minutes followed by loss of consciousness and focal tonic posturing lasting 10 minutes. Such acute deafness represented an aura of a focal seizure substantiated by right focal temporal epileptic discharges within the region of the primary auditory cortex. Therefore, EEG should be performed in any case of acute transient deafness, even in the absence of accompanying overt clinical seizures. PMID:20042694

  11. Representative Bureaucracy and the Role of Expertise in Politics

    Jarle Trondal

    2015-03-01

    Full Text Available The vast majority of existing studies on bureaucratic representation focus on bureaucracies’ permanent and internal staff. Yet, the rising sophistication of modern democracies and the technocratization of political life are gradually inducing an increased reliance on external experts to assist in the development and implementation of policy decisions. This trend, we argue, raises the need to extend studies of bureaucratic representation to such external and non-permanent experts in governmental affairs. In this article, we take a first step in this direction using seconded national experts (SNEs in the European Commission as our empirical laboratory. Our results highlight that Commission SNEs do not appear representative of their constituent population (i.e., the EU-27 population along a number of socio-demographic dimensions. Moreover, we find that the role perception of “experts” is primarily explained by organizational affiliation, and only secondarily by demographic characteristics (except, of course, education.

  12. Representing lexical components of medical terminologies in OWL.

    Supekar, Kaustubh; Chute, Christopher G; Solbrig, Harold

    2005-01-01

    Medical Terminologies play a vital role in clinical data capture, reporting, information integration, indexing and retrieval. The Web Ontology language (OWL) provides an opportunity for the medical community to leverage the capabilities of OWL semantics and tools to build formal, sound and consistent medical terminologies, and to provide a standard web accessible medium for inter-operability,access and reuse. One of the tasks facing the medical community today is to represent the extensive terminology content that already exists into this new medium. This paper addresses one aspect of this challenge - how to incorporate multilingual, structured lexical information such as definitions, synonyms, usage notes, etc. into the OWL ontology model in a standardized, consistent and useful fashion. PMID:16779134

  13. A representative study of hearing ability in North West Germany

    I. Holube

    2011-03-01

    Full Text Available The estimated hearing ability of German citizens is based on a comprehensive study published by von Stackelberg in 1986. At that time, 26.8% of West-Germany citizens were rated as hearing impaired. Because of the analyzing procedure used, these data cannot be used for comparison purposes with more recent international studies carried out e.g. by Uimonen et al. (1999, Wilson et al. (1999, Quaranta et al. (1996, and Johansson and Arlinger (2003. Other German data are based on non-representative evaluations or on subjective assessments. Therefore, the Institute of Hearing Technology and Audiology started HÖRSTAT, a two-year research project designed to fill this gap.

  14. Representative survey on the reprocessing of endodontic instruments in Germany.

    Sonntag, D; Martin, E; Raab, W H M

    2016-05-13

    Aim The aim of the study was to review the implementation of hygiene guidelines for the reprocessing of endodontic files in a representative survey and to determine the time needed for the procedure.Methods A questionnaire with nine items was sent to 4,000 German dentists. In addition to obtaining personal information, it asked for the total time required for the reprocessing of instruments and contained specific questions about the cleaning procedure in order to assess whether the requirements of the German Federal Ministry of Health, as defined by the Robert Koch Institute, were complied with. Approval by the Ethics Committee was obtained. The data were analysed statistically using the Chi-square test and Cramer's V as a measurement of effect size.Results The response rate was 29.4% (n = 1,177/4,000). On 59 questionnaires, answers to several questions were missing; 1,118 questionnaires (28.0%) could be included in the evaluation. With effect sizes between 0.12 and 0.21, the survey could be classified as statistically representative of German dentists in terms of age and gender. The guidelines were adhered to by 31.7% (n = 354/1118) of respondents, while 68.3% (n = 764/1118) adhered to them either not fully, or not at all (P instrument set was more than nine minutes for 68.1% of respondents, not including the time needed for sterilisation; 5% of respondents treated files as single-use instruments.Conclusions The guidelines of the German Federal Ministry of Health for cleaning, disinfecting and sterilising endodontic files are widely disregarded in Germany. The designation and use of endodontic files as single-use instruments should be considered. PMID:27173705

  15. The Korarchaeota: Archaeal orphans representing an ancestral lineage of life

    Elkins, James G.; Kunin, Victor; Anderson, Iain; Barry, Kerrie; Goltsman, Eugene; Lapidus, Alla; Hedlund, Brian; Hugenholtz, Phil; Kyrpides, Nikos; Graham, David; Keller, Martin; Wanner, Gerhard; Richardson, Paul; Stetter, Karl O.

    2007-05-01

    Based on conserved cellular properties, all life on Earth can be grouped into different phyla which belong to the primary domains Bacteria, Archaea, and Eukarya. However, tracing back their evolutionary relationships has been impeded by horizontal gene transfer and gene loss. Within the Archaea, the kingdoms Crenarchaeota and Euryarchaeota exhibit a profound divergence. In order to elucidate the evolution of these two major kingdoms, representatives of more deeply diverged lineages would be required. Based on their environmental small subunit ribosomal (ss RNA) sequences, the Korarchaeota had been originally suggested to have an ancestral relationship to all known Archaea although this assessment has been refuted. Here we describe the cultivation and initial characterization of the first member of the Korarchaeota, highly unusual, ultrathin filamentous cells about 0.16 {micro}m in diameter. A complete genome sequence obtained from enrichment cultures revealed an unprecedented combination of signature genes which were thought to be characteristic of either the Crenarchaeota, Euryarchaeota, or Eukarya. Cell division appears to be mediated through a FtsZ-dependent mechanism which is highly conserved throughout the Bacteria and Euryarchaeota. An rpb8 subunit of the DNA-dependent RNA polymerase was identified which is absent from other Archaea and has been described as a eukaryotic signature gene. In addition, the representative organism possesses a ribosome structure typical for members of the Crenarchaeota. Based on its gene complement, this lineage likely diverged near the separation of the two major kingdoms of Archaea. Further investigations of these unique organisms may shed additional light onto the evolution of extant life.

  16. Hydralab+: Representing timescales of biological change in flume experiments

    Baynes, Edwin; McLelland, Stuart; Parsons, Daniel

    2016-04-01

    Fluvial environments are vulnerable to future climate change due to non-linear responses to shifts in boundary conditions such as a migration to a hydrological regime characterised by more frequent extreme events. The biological component of these systems is critical for understanding the morphodynamic responses since organisms are often at the interface between water and sediment transport systems. Under a changing climate, the growth or decline of a particular species may change the flow dynamics and/or sediment transport. Hence, flume experiments that seek to accurately model the impact of climate change on the morphodynamics of sedimentary systems should consider the interaction between organisms and climate-induced changes in hydrodynamic forcing. This requires the ability to control and/or mimic biological components within flume experiments on timescales that are compatible with climate change forcing. Here, we present a review of existing research covering morphodynamics-biological interactions in flume experiments. We consider the approaches implemented to scale organisms (e.g. small-scale or chemical surrogates) and how these can be used to represent variations in the biological component over different timescales. Disparities in the scaling of hydrodynamics, morphodynamics and biota using these existing approaches are identified. During Hydralab+, this review will form the basis to develop innovative experimental protocols to represent total system response to climate change within a laboratory setting (e.g. developing new surrogates that can capture biological responses to climate forcing and enable modelling of longer time periods and longer-term trends). This will allow an improved understanding of the impact of climate change to be developed and potentially guide future adaptation strategies.

  17. Eye muscle proprioception is represented bilaterally in the sensorimotor cortex

    Balslev, Daniela; Albert, Neil B; Miall, Chris

    2011-01-01

    the proprioceptive representation for the left and the right eye separately. Data were acquired while passive eye movement was used to stimulate EOM proprioceptors in the absence of a motor command. We also controlled for the tactile stimulation of the eyelid by removing from the analysis voxels activated by eyelid...... touch alone. For either eye, the brain area commonly activated by passive and active eye movement was located bilaterally in the somatosensory area extending into the motor and premotor cytoarchitectonic areas. We suggest this is where EOM proprioception is processed. The bilateral representation......The cortical representation of eye position is still uncertain. In the monkey a proprioceptive representation of the extraocular muscles (EOM) of an eye were recently found within the contralateral central sulcus. In humans, we have previously shown a change in the perceived position of the right...

  18. Recruitment of representative samples for low incidence cancer populations: Do registries deliver?

    Sanson-Fisher Rob

    2011-01-01

    Full Text Available Abstract Background Recruiting large and representative samples of adolescent and young adult (AYA cancer survivors is important for gaining accurate data regarding the prevalence of unmet needs in this population. This study aimed to describe recruitment rates for AYAs recruited through a cancer registry with particular focus on: active clinician consent protocols, reasons for clinicians not providing consent and the representativeness of the final sample. Methods Adolescents and young adults aged 14 to19 years inclusive and listed on the cancer registry from January 1 2002 to December 31 2007 were identified. An active clinician consent protocol was used whereby the registry sent a letter to AYAs primary treating clinicians requesting permission to contact the survivors. The registry then sent survivors who received their clinician's consent a letter seeking permission to forward their contact details to the research team. Consenting AYAs were sent a questionnaire which assessed their unmet needs. Results The overall consent rate for AYAs identified as eligible by the registry was 7.8%. Of the 411 potentially eligible survivors identified, just over half (n = 232, 56% received their clinician's consent to be contacted. Of those 232 AYAs, 65% were unable to be contacted. Only 18 AYAs (7.8% refused permission for their contact details to be passed on to the research team. Of the 64 young people who agreed to be contacted, 50% (n = 32 completed the questionnaire. Conclusions Cancer registries which employ active clinician consent protocols may not be appropriate for recruiting large, representative samples of AYAs diagnosed with cancer. Given that AYA cancer survivors are highly mobile, alternative methods such as treatment centre and clinic based recruitment may need to be considered.

  19. Representing the Economic Geographies of "Others": Reconsidering the Global South

    Murphy, James T.

    2006-01-01

    This essay examines how undergraduate economic geography courses in Anglo-American institutions traditionally frame economic activities in developing regions and asserts that mainstream approaches have devalued the complexity and diversity of economic geographies in the Global South. Focusing on developmentalism as a commonly used heuristic frame,…

  20. 28 CFR 79.74 - Representatives and attorney's fees.

    2010-07-01

    ..., as described in paragraph (c) of this section, may receive from a claimant or beneficiary any fee in... beneficiary, may not receive from a claimant or beneficiary any fee for services rendered, including costs... active membership in good standing of the bar of the highest court of a state; and (2) A...

  1. Manipulating Models and Grasping the Ideas They Represent

    Bryce, T. G.; Blown, E. J.

    2016-01-01

    This article notes the convergence of recent thinking in neuroscience and grounded cognition regarding the way we understand mental representation and recollection: ideas are dynamic and multi-modal, actively created at the point of recall. Also, neurophysiologically, re-entrant signalling among cortical circuits allows non-conscious processing to…

  2. Research Regarding The Evolution Of Agrotourism In Several European Representative Destinations

    Ramona Ciolac

    2015-05-01

    Full Text Available The popularity of rural areas, as a possibility to spend the vacation has increased in recent years, in most countries. Changes in attitudes were parallel with changes in European styles to taking the holidays, but also in preferences to return to nature, and various local products. At the European level there is a large interest for the development of agrotourism and its ability to contribute to the development of rural areas, therefore there are countries that have made from agrotourism a lifestyle and additional incomes with witch that pride. Based on this statement this paper follows agrotourism activity in several European countries, considered most representative: Austria, Germany, Switzerland, Italy.  

  3. Incidence of invasive macrophytes on methylmercury budget in temperate lakes: Central role of bacterial periphytic communities

    Several studies demonstrated high mercury (Hg) methylation and demethylation in the periphyton associated with floating roots in tropical ecosystems. The importance of aquatic plants on methylmercury production in three temperate ecosystems from south-western France was evaluated through Hg species concentrations, and Hg methylation/demethylation activities by using stable isotopic tracers (199Hg(II), Me201Hg). Hg accumulation and high methylation and demethylation yields were detected in plant roots and periphyton, whereas results for sediment and water were low to insignificant. The presence of sulfate reducing prokaryotes was detected in all compartments (T-RFLP based on dsrAB amplified through nested PCR) and their main role in Hg methylation could be demonstrated. In turn, sulfate reduction inhibition did not affect demethylation activities. The estimation of net MeHg budgets in these ecosystems suggested that aquatic rhizosphere is the principal location for methylmercury production and may represent an important source for the contamination of the aquatic food chain. - Highlights: ► Both Hg methylation and demethylation occur in the periphyton of temperate ecosystems. ► Aquatic rhizosphere is the main compartment for net methylmercury production. ► Sulfate reducers are detected in all ecosystem compartments (water, sediment, periphyton). ► Sulfate reducers are responsible for methylmercury production in aquatic roots. - The incidence of periphytic microbial communities on net methylmercury production is highlighted in temperate aquatic ecosystems.

  4. Cyclophilin represents a novel class of protein kinases

    Cyclophilin (CyP, Mr 17,737, pI 9.6), a highly specific cytosolic receptor for cyclosporin A (CsA) has ser/thr protein kinase activity. Incorporation of 32P into bovine histone H3 (BH3) was catalyzed by major and minor CyP isozymes at the same rate. Salt effects were biphasic with optimal kinase activity between 50-100 mM Na+ or K+. Kinase activity was maximal at 370C, stable for 5 min at 450, labile at 560, optimal between pH 6.8 and 8.0 and had an apparent Km of 20 uM ATP with both isozymes. The specific activity of CyP was 1.0 nmole P/mg protein/min with chicken histone H1 (CH1), 0.2 nmoles P/mg prot/min with BH3 and less than 0.01 nmoles P/mg prot/min with synapsin, casein, phosvitin, and ribosomal protein S6. Cofactors including Mn++, Zn++, Ca++, phosphatidyl serine, diolein and phorbol ester, cAMP, cGMP and Ca++ did not affect basal CyP kinase activity. CsA (3 by 50% but did not inhibit phosphorylation of other histones; 2ug CsA/ml was required to cause 50% inhibition of cAMP and Ca++/CaM dependent kinases. A non-immunosuppressive analog (Me-leu-11-CsA) that does not bind to CyP did not inhibit CH3 phosphorylation. Thus, CyP is a novel protein kinase that mediates immunosuppression by CsA

  5. Simulating a Nationally Representative Housing Sample Using EnergyPlus

    Hopkins, Asa S.; Lekov, Alex; Lutz, James; Rosenquist, Gregory; Gu, Lixing

    2011-03-04

    This report presents a new simulation tool under development at Lawrence Berkeley National Laboratory (LBNL). This tool uses EnergyPlus to simulate each single-family home in the Residential Energy Consumption Survey (RECS), and generates a calibrated, nationally representative set of simulated homes whose energy use is statistically indistinguishable from the energy use of the single-family homes in the RECS sample. This research builds upon earlier work by Ritchard et al. for the Gas Research Institute and Huang et al. for LBNL. A representative national sample allows us to evaluate the variance in energy use between individual homes, regions, or other subsamples; using this tool, we can also evaluate how that variance affects the impacts of potential policies. The RECS contains information regarding the construction and location of each sampled home, as well as its appliances and other energy-using equipment. We combined this data with the home simulation prototypes developed by Huang et al. to simulate homes that match the RECS sample wherever possible. Where data was not available, we used distributions, calibrated using the RECS energy use data. Each home was assigned a best-fit location for the purposes of weather and some construction characteristics. RECS provides some detail on the type and age of heating, ventilation, and air-conditioning (HVAC) equipment in each home; we developed EnergyPlus models capable of reproducing the variety of technologies and efficiencies represented in the national sample. This includes electric, gas, and oil furnaces, central and window air conditioners, central heat pumps, and baseboard heaters. We also developed a model of duct system performance, based on in-home measurements, and integrated this with fan performance to capture the energy use of single- and variable-speed furnace fans, as well as the interaction of duct and fan performance with the efficiency of heating and cooling equipment. Comparison with RECS revealed

  6. Synthesis and structure-activity relationship of vicenistatin, a cytotoxic 20-membered macrolactam glycoside.

    Fukuda, Hayato; Nishiyama, Yuko; Nakamura, Shiina; Ohno, Yutaro; Eguchi, Tadashi; Iwabuchi, Yoshiharu; Usui, Takeo; Kanoh, Naoki

    2012-12-01

    We have developed two syntheses of vicenistatin and its analogues. Our first-generation strategy included the rapid and sequential assembly of the macrocyclic lactam by using an intermolecular Horner-Wadsworth-Emmons reaction between the C3-C13 fragment and the C1-C2, C14-C19 fragment, followed by an intramolecular Stille coupling reaction. The second-generation strategy utilized a ring-closing metathesis of a hexaene intermediate to generate the desired 20-membered macrolactam. This second-generation strategy made it possible to prepare synthetic analogues of vicenistatin, including the C20- and/or C23-demethyl analogues. Evaluation of the cytotoxic effect of these analogues indicated the importance of the fixed conformation of aglycon for determining the biological activity of the vicenistatins. PMID:23015368

  7. Social tagging: a model for representing information in the blogosphere

    Elaine Pérez Sanchidrián

    2015-04-01

    Full Text Available Objective: The study addresses the theoretical and conceptual aspects related to social labeling. Has the advantages of labels on different platforms of Web 2.0. Exposes some of the major sites of social labeling system including Flickr, Delicious, Technorati is destcan, among others. Terminologically analyzed using the tags in the blogosphere as a model for representing information. Methods: The research took as methods of qualitative content analysis to identify the behavior of the international literature on this subject and the metric analysis to characterize the use of social labeling in the blogosphere. Results: The study led to qualitatively describe the use of labels on blogs and their terminological particularities associated with the following aspects: creating labels in these spaces is related to a number of social issues among which we can highlight: Politics, Culture, economy, Gender, History, Sexuality, Discrimination, Health, Environment, Technology. The labels on these platforms are defined from the general to the particular and there is no limit concurrency for its creation, usually the authors cite for each post 4-7 labels in order to spread their content as possible in the community. Conclusions: This study enables reflect the social impact of using labels on platforms like blogs.

  8. Plasmodium falciparum dolichol phosphate mannose synthase represents a novel clade

    Dolichol phosphate mannose synthase (DPM) catalyzes the reaction between dolichol phosphate (Dol-P) and guanosine diphosphate mannose (GDP-Man) to form dolichol-phosphate-mannose (Dol-P-Man). This molecule acts as mannose donor for N-glycosylation and glycosylphosphatidylinositol (GPI) biosynthesis. The Plasmodium falciparum DPM1 (Pfdpm1) possesses a single predicted transmembrane region near the N-, but not the C-terminus. Here we show that the cloned Pfdpm1 gene failed to complement a Saccharomyces cerevisiae mutant indicating that the parasite gene does not belong to the baker's yeast group, as was previously assumed. Furthermore, Pfdpm1 was unable to complement a mouse mutant deficient in DPM but efficiently complements the Schizosaccharomyces pombe fission yeast mutant, indicating a difference between fission yeast and mammalian DPM genes. Therefore, we reanalyzed the hydrophobicity scales of all known DPMs and consequently reclassify the DPM clade into six major novel subgroups. Furthermore, we show that Pfdpm1 represents a unique enzyme among these subgroups

  9. Greening the U.S. House of Representatives

    Diamond, Rick; Diamond, Rick; Payne, Christopher

    2008-03-01

    The Greening the Capitol initiative was launched in March, 2007 with the threefold goals of making the U.S. House of Representatives: 1) carbon neutral within 18 months, 2) reducing energy use by 50percent in ten years, and 3) becoming a model of sustainable operations. We report on the recommendations to meet these goals, looking at the targets of opportunity at the Capitol Power Plant, the existing buildings, and the overall operations of the complex. Our findings have shown that these goals are achievable, and that through an integrated approach the savings in carbon and energy can be met. Specific examples include the lighting retrofits in the House offices, parking areas, and the Capitol dome; the retrofits to the HVAC systems and controls, including duct sealing, improving the efficiency of the energy and water use in the food service areas; and improved operations of the steam and chilled water distribution system. A key aspect has been better tracking and feedback to the building operators of the actual energy consumption. We report on the technical opportunities presented by these historic and symbolic buildings in becoming models of sustainability.

  10. Interaction of turbulent deflagrations with representative flow obstacles

    Durst, B.; Ardey, N.; Mayinger, F. [Lehrstul a fuer Thermodynamik, Technische Universitat Munchen (Germany)

    1997-03-01

    In the case of a gradual release of hydrogen in the course of an assumed, severe accident in a light water reactor, the combustion will normally start out as a slow deflagration. Acceleration of an initially slow flame due to interactions of chemical kinetics and turbulent heat and mass transfer can result in very high flame speeds. Therefore, in order to assess hydrogen mitigation techniques, detailed knowledge about flame acceleration and interaction of flames with obstacles is required. The reported investigations are aimed at the investigation of the mechanisms responsible for turbulent flame acceleration and improving present correlations for estimates and models for numerical simulations of hydrogen combustion processes. A medium-scale square cross-section setup is employed, using flow obstacles with shapes representative for reactor containments. The global flame speed is deduced from measurements using thermocouples, pressure transducers and photodiodes. Measurements using a two-component LDA-system are being carried through in order to correlate global flame spread and local turbulence parameters. Results indicate that low blockage-ratio obstacles only marginally influence the flame, as disturbances which are induced remain local to the vicinity of the obstacle and die out very quickly downstream thereof. Flow visualizations by means of a Schlieren setup indicate very complex flow structures in the vicinity of obstacles. The results are being used to validate turbulent reaction models. A model based on probability density functions (pdf) of assumed shape has been developed and initial calculations are presented. (author)

  11. Targeting Nucleophosmin 1 Represents a Rational Strategy for Radiation Sensitization

    Purpose: To test the hypothesis that small molecule targeting of nucleophosmin 1 (NPM1) represents a rational approach for radiosensitization. Methods and Materials: Wilde-type and NPM1-deficient mouse embryo fibroblasts (MEFs) were used to determine whether radiosensitization produced by the small molecule YTR107 was NPM1 dependent. The stress response to ionizing radiation was assessed by quantifying pNPM1, γH2AX, and Rad51 foci, neutral comet tail moment, and colony formation. NPM1 levels in a human-derived non-small-cell lung cancer (NSCLC) tissue microarray (TMA) were determined by immunohistochemistry. YTR107-mediated radiosensitization was assessed in NSCLC cell lines and xenografts. Results: Use of NPM1-null MEFs demonstrated that NPM1 is critical for DNA double- strand break (DSB) repair, that loss of NPM1 increases radiation sensitivity, and that YTR107-mediated radiosensitization is NPM1 dependent. YTR107 was shown to inhibit NPM1 oligomerization and impair formation of pNPM1 irradiation-induced foci that colocalized with γH2AX foci. Analysis of the TMA demonstrated that NPM1 is overexpressed in subsets of NSCLC. YTR107 inhibited DNA DSB repair and radiosensitized NSCLC lines and xenografts. Conclusions: These data demonstrate that YTR107-mediated targeting of NPM1 impairs DNA DSB repair, an event that increases radiation sensitivity

  12. Representative experiments on nuclear meltdowns. COMAS, HCTM, CORESA

    Nuclear meltdown accidents and the possibility of specific countermeasures have formed the focal point of discussions on reactor safety for ten years now, particularly following the events in Tschernobyl. One of these countermeasures is - assuming failure of the reactor pressure vessel - wide-area ex-vessel spreading of the meltdown product in a catchment system with subsequent water flooding. This proposed method corresponds to the current planning basis for the Franco-German Joint Project EPR. Since 1993, a German working group has been carrying out research into the control of nuclear meltdowns: Experiments with nuclear meltdown products, it is hoped, will provide information for the control of nuclear meltdown accidents. An exceptional feature of these investigations is the realisability of largescale experiments with prototypal corium-combinations and representative test conditions. The present article describes the setting-up and the results of the COMAS (Corium on Metal Surfaces)-spreading experiment and of the CORESA (Corium on Refractory and Sacrificial Materials)-test program in the commercial-scale radioactive meltdown system CARLA. (orig.)

  13. Learning and representing temporal knowledge in recurrent networks.

    Borges, Rafael V; Garcez, Artur d'Avila; Lamb, Luis C

    2011-12-01

    The effective integration of knowledge representation, reasoning, and learning in a robust computational model is one of the key challenges of computer science and artificial intelligence. In particular, temporal knowledge and models have been fundamental in describing the behavior of computational systems. However, knowledge acquisition of correct descriptions of a system's desired behavior is a complex task. In this paper, we present a novel neural-computation model capable of representing and learning temporal knowledge in recurrent networks. The model works in an integrated fashion. It enables the effective representation of temporal knowledge, the adaptation of temporal models given a set of desirable system properties, and effective learning from examples, which in turn can lead to temporal knowledge extraction from the corresponding trained networks. The model is sound from a theoretical standpoint, but it has also been tested on a case study in the area of model verification and adaptation. The results contained in this paper indicate that model verification and learning can be integrated within the neural computation paradigm, contributing to the development of predictive temporal knowledge-based systems and offering interpretable results that allow system researchers and engineers to improve their models and specifications. The model has been implemented and is available as part of a neural-symbolic computational toolkit. PMID:22010150

  14. Representative volume element of asphalt pavement for electromagnetic measurements

    Terhi Pellinen

    2015-02-01

    Full Text Available The motivation for this study was to investigate the representative volume element (RVE needed to correlate the nondestructive electromagnetic (EM measurements with the conventional destructive asphalt pavement quality control measurements. A large pavement rehabilitation contract was used as the test site for the experiment. Pavement cores were drilled from the same locations where the stationary and continuous Ground Penetrating Radar (GPR measurements were obtained. Laboratory measurements included testing the bulk density of cores using two methods, the surface-saturated dry method and determining bulk density by dimensions. Also, Vector Network Analyzer (VNA and the through specimen transmission configuration were employed at microwave frequencies to measure the reference dielectric constant of cores using two different footprint areas and therefore volume elements. The RVE for EM measurements turns out to be frequency dependent; therefore in addition to being dependent on asphalt mixture type and method of obtaining bulk density, it is dependent on the resolution of the EM method used. Then, although the average bulk property results agreed with theoretical formulations of higher core air void content giving a lower dielectric constant, for the individual cores there was no correlation for the VNA measurements because the volume element seizes deviated. Similarly, GPR technique was unable to capture the spatial variation of pavement air voids measured from the 150-mm drill cores. More research is needed to determine the usable RVE for asphalt.

  15. Representative concentration pathways and mitigation scenarios for nitrous oxide

    The challenges of mitigating nitrous oxide (N2O) emissions are substantially different from those for carbon dioxide (CO2) and methane (CH4), because nitrogen (N) is essential for food production, and over 80% of anthropogenic N2O emissions are from the agricultural sector. Here I use a model of emission factors of N2O to demonstrate the magnitude of improvements in agriculture and industrial sectors and changes in dietary habits that would be necessary to match the four representative concentration pathways (RCPs) now being considered in the fifth assessment report (AR5) of the Intergovernmental Panel on Climate Change (IPCC). Stabilizing atmospheric N2O by 2050, consistent with the most aggressive of the RCP mitigation scenarios, would require about 50% reductions in emission factors in all sectors and about a 50% reduction in mean per capita meat consumption in the developed world. Technologies exist to achieve such improved efficiencies, but overcoming social, economic, and political impediments for their adoption and for changes in dietary habits will present large challenges. (letter)

  16. Targeting Nucleophosmin 1 Represents a Rational Strategy for Radiation Sensitization

    Sekhar, Konjeti R. [Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Benamar, Mouadh [Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Venkateswaran, Amudhan; Sasi, Soumya [Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Penthala, Narsimha R.; Crooks, Peter A. [Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Hann, Stephen R. [Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Geng, Ling [Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Balusu, Ramesh [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas (United States); Abbas, Tarek [Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Freeman, Michael L., E-mail: michael.freeman@vanderbilt.edu [Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States)

    2014-08-01

    Purpose: To test the hypothesis that small molecule targeting of nucleophosmin 1 (NPM1) represents a rational approach for radiosensitization. Methods and Materials: Wilde-type and NPM1-deficient mouse embryo fibroblasts (MEFs) were used to determine whether radiosensitization produced by the small molecule YTR107 was NPM1 dependent. The stress response to ionizing radiation was assessed by quantifying pNPM1, γH2AX, and Rad51 foci, neutral comet tail moment, and colony formation. NPM1 levels in a human-derived non-small-cell lung cancer (NSCLC) tissue microarray (TMA) were determined by immunohistochemistry. YTR107-mediated radiosensitization was assessed in NSCLC cell lines and xenografts. Results: Use of NPM1-null MEFs demonstrated that NPM1 is critical for DNA double- strand break (DSB) repair, that loss of NPM1 increases radiation sensitivity, and that YTR107-mediated radiosensitization is NPM1 dependent. YTR107 was shown to inhibit NPM1 oligomerization and impair formation of pNPM1 irradiation-induced foci that colocalized with γH2AX foci. Analysis of the TMA demonstrated that NPM1 is overexpressed in subsets of NSCLC. YTR107 inhibited DNA DSB repair and radiosensitized NSCLC lines and xenografts. Conclusions: These data demonstrate that YTR107-mediated targeting of NPM1 impairs DNA DSB repair, an event that increases radiation sensitivity.

  17. Thyroglobulin Represents a Novel Molecular Architecture of Vertebrates.

    Holzer, Guillaume; Morishita, Yoshiaki; Fini, Jean-Baptiste; Lorin, Thibault; Gillet, Benjamin; Hughes, Sandrine; Tohmé, Marie; Deléage, Gilbert; Demeneix, Barbara; Arvan, Peter; Laudet, Vincent

    2016-08-01

    Thyroid hormones modulate not only multiple functions in vertebrates (energy metabolism, central nervous system function, seasonal changes in physiology, and behavior) but also in some non-vertebrates where they control critical post-embryonic developmental transitions such as metamorphosis. Despite their obvious biological importance, the thyroid hormone precursor protein, thyroglobulin (Tg), has been experimentally investigated only in mammals. This may bias our view of how thyroid hormones are produced in other organisms. In this study we searched genomic databases and found Tg orthologs in all vertebrates including the sea lamprey (Petromyzon marinus). We cloned a full-size Tg coding sequence from western clawed frog (Xenopus tropicalis) and zebrafish (Danio rerio). Comparisons between the representative mammal, amphibian, teleost fish, and basal vertebrate indicate that all of the different domains of Tg, as well as Tg regional structure, are conserved throughout the vertebrates. Indeed, in Xenopus, zebrafish, and lamprey Tgs, key residues, including the hormonogenic tyrosines and the disulfide bond-forming cysteines critical for Tg function, are well conserved despite overall divergence of amino acid sequences. We uncovered upstream sequences that include start codons of zebrafish and Xenopus Tgs and experimentally proved that these are full-length secreted proteins, which are specifically recognized by antibodies against rat Tg. By contrast, we have not been able to find any orthologs of Tg among non-vertebrate species. Thus, Tg appears to be a novel protein elaborated as a single event at the base of vertebrates and virtually unchanged thereafter. PMID:27311711

  18. Representing the retinal line spread shape with mathematical functions

    Yi-rong YANG; Justin WANEK; Mahnaz SHAHIDI

    2008-01-01

    Objective: To report a mathematical function that characterizes the double-pass line spread function (LSF) of the human eye. Determining analytical functions that represent the double-pass LSF is important because it allows modeling the optical performance of the eye. Methods: Optical section retinal images, generated in normal human eyes using a modified slit-lamp biomicroscope, were analyzed to derive the double-pass LSF by plotting the intensity distribution of laser light reflected/ scattered from the vitreoretinal interface. Three mathematical functions (Lorentzian, Gaussian, exponential) were fitted to the double-pass LSF and the root mean square error (RMSE) was calculated to provide a measure of the goodness of fit. Results: The Lorentzian function provided the best representation of the double-pass LSF of normal human eyes. The full width at half maximum (FWHM) of the Lorentzian fitted curve was positively correlated with age, indicating that the double-pass LSF broadens with age. Furthermore, the goodness of fit of the Lorentzian function was significantly better in younger subjects as compared with older subjects, suggesting that the fitted function to the double-pass LSF may vary according to age. Conclusion: The results demonstrate an age-related change in the double-pass LSF width and the goodness of fit of the Lorentzian function.

  19. Herbarium Areqvipense (HUSA: computerization and representativeness of its collection

    Italo F. Treviño

    2012-11-01

    Full Text Available Scientific collections and herbaria are essential sources of information and education for researchers and practitioners in biological sciences. The Herbarium Areqvipense (HUSA, registered at Index Herbariorum since 2004, holds one of the most important collections in Peru. In this paper we provide information about the collection, and its representativeness for the Peruvian flora. HUSA has more than 11000 specimens recorded to date, with more than 2300 determined species, consisting mostly of Magnoliophyta and Pteridophyta (ca. 98%, and a smaller proportion of Basidiomycetes, Ascomycetes (fungi and lichens and Bryophyta (mosses. The collection includes specimens from 23 departments of Peru, where the samples belonging to Arequipa have the largest number of individuals collected (3375 accounting for 31% of the collection. Asteraceae and Solanaceae are the most collected with 1571 and 964 specimens, respectively. The majority of geo-referenced specimens came from the tropical wet forest with 15%, followed by the tropical pre-montane wet forest with 8%. We also provide a list of the nomenclatural types and a brief summary of the history and development of HUSA since its creation.

  20. Dorsal Raphe Dopamine Neurons Represent the Experience of Social Isolation.

    Matthews, Gillian A; Nieh, Edward H; Vander Weele, Caitlin M; Halbert, Sarah A; Pradhan, Roma V; Yosafat, Ariella S; Glober, Gordon F; Izadmehr, Ehsan M; Thomas, Rain E; Lacy, Gabrielle D; Wildes, Craig P; Ungless, Mark A; Tye, Kay M

    2016-02-11

    The motivation to seek social contact may arise from either positive or negative emotional states, as social interaction can be rewarding and social isolation can be aversive. While ventral tegmental area (VTA) dopamine (DA) neurons may mediate social reward, a cellular substrate for the negative affective state of loneliness has remained elusive. Here, we identify a functional role for DA neurons in the dorsal raphe nucleus (DRN), in which we observe synaptic changes following acute social isolation. DRN DA neurons show increased activity upon social contact following isolation, revealed by in vivo calcium imaging. Optogenetic activation of DRN DA neurons increases social preference but causes place avoidance. Furthermore, these neurons are necessary for promoting rebound sociability following an acute period of isolation. Finally, the degree to which these neurons modulate behavior is predicted by social rank, together supporting a role for DRN dopamine neurons in mediating a loneliness-like state. PAPERCLIP. PMID:26871628