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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/

    Abstract Glutathione S-transferase P1 (GSTP1) gene is commonly silenced by CpG island promoter hypermethylation in prostate, breast, and liver cancers. However, mechanisms leading to GSTP1 repression by promoter hypermethylation in leukemia and its relationship with pathological alterations of the chromatin structure remain poorly understood. A panel of leukemia cell lines was analyzed for their GSTP1 expression, revealing cell lines with high, moderate or no detectable GSTP1 expression. Bisulfite sequencing, methylation-specific PCR and combined bisulfite restriction analysis revealed that GSTP1 promoter was completely methylated in transcriptionally inactive RAJI and MEG-01 cell lines. In contrast, cell lines expressing GSTP1 exhibited an unmethylated and transcriptionally active promoter. Furthermore, histone marks and effector proteins associated with transcriptional activity were detected by chromatin immunoprecipitation in the GSTP1 expressing hypomethylated K-562 cell line. However, repressive chromatin marks and the recruitment of silencing protein complexes were found in the non-expressing hypermethylated RAJI and MEG-01 cell lines. Finally, we provide evidence that treatment of RAJI and MEG-01 cells with the DNA demethylating agent, 5-Aza-2?-deoxycytidine, resulted in GSTP1 promoter demethylation, drastic changes of histone modifications and promoter associated proteins and GSTP1 gene activation. In contrast, treatments with HDAC inhibitors failed to demethylate and reactivate the GSTP1 gene. Our study extends the knowledge on leukemia-specific epigenetic alterations of GSTP1 gene. Furthermore, we are showing the correlation of DNA methylation and histone modifications with the positive/negative GSTP1 transcriptional expression state. Finally, these data support the concept of the dominance of DNA methylation over HDAC inhibitor-sensitive histone deacetylation in gene silencing. correspondence: Corresponding author. Laboratoire de Biologie Moleculaire et Cellulaire de Cancer, Hopital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg, Tel.: +352 2468 4040; fax: +352 2468 4060 (Diederich, Marc) marc.diederich@lbmcc.lu (Diederich, Marc) Laboratoire de Biologie Moleculaire et Cellulaire de Cancer, Hopital Kirchberg - 9--> , rue Edward Steichen--> , L-2540 Luxembourg--> - LUXEMBOURG (Karius, Tommy) Laboratoire de Biologie Moleculaire et Cellulaire de Cancer, Hopital Kirchberg - 9--> , rue Edward Steichen--> , L-2540 Luxembourg--> - LUXEMBOURG (Schnekenburger, Michael) Laboratoire de Biologie Moleculaire et Cellulaire de Cancer, Hopital Kirchberg - 9--> , rue Edward Steichen--> , L-2540 Luxembourg--> - LUXEMBOURG (Gelfi, Jenny) Institut fur Genetik - FB Biowissenschaften--> , Universitat des Saarlandes--> , Saarbrucken--> - GERMANY (Walter, Jorn) Laboratoire de Biologie Moleculaire et Cellulaire de Cancer, Hopital Kirchberg - 9--> , rue Edward Steichen--> , L-2540 Luxembourg--> - LUXEMBOURG (Dicato, Mario) Laboratoire de Biologie Moleculaire et Cellulaire de Cancer, Hopital Kirchberg - 9--> , rue Edward Steichen--> , L-2540 Luxembourg--> - LUXEMBOURG (Diederich, Marc) LUXEMBOURG (Diederich, Marc) GERMANY LUXEMBOURG Received: 2010-11-16 Revised: 2011-03-17 Accepted: 2011-03-21

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Trinity's Access to ...arrow_drop_down
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Trinity's Access to ...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/

    Abstract Resins based on melamine-formaldehyde and related analogues such as methylolated melamine are used to cross-link coatings used inside food cans and on the metal closures of glass jars. Thirteen commercially coated cans and closures representing 80% of the European market, were tested using simulants under realistic industrial heat-processing conditions for canned and jarred foods. The food simulants and the retort conditions used were 3% acetic acid for 1 hr at 100?C and 10% ethanol for 1 hr at 130?C. The highest migration level seen for melamine into simulant was 332 ?g/kg. There was no detectable migration of the melamine analogues cyanuric acid ( - YO41 1LZ - York - UNITED KINGDOM (Bradley, Emma) FERA, Food Safety & Quality - Sand Hutton--> - YO41 1LZ - York - UNITED KINGDOM (Day, Joanna) FERA, Food Safety & Quality - Sand Hutton--> - YO41 1LZ - York - UNITED KINGDOM (leak, jennifer) UNITED KINGDOM

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Trinity's Access to ...arrow_drop_down
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Trinity's Access to ...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/

    Abstract This paper presents a comparative analysis of factors contributing to the innovation performance of manufacturing firms in Georgia (USA), Wales (UK), the West Midlands (UK), and Catalonia (Spain). Enabled by comparable survey data, multiple probit models are developed to estimate how various types of firms? innovative activities are influenced by links to external knowledge sources, internal resources, absorptive capacity and public innovation support. Our results suggest the potential for mutual learning. For the European study regions there are insights about how universities in Georgia support innovation. For Georgia and Catalonia there are lessons from UK firms about better capturing potential complementarities between innovation activities. Additional implications for innovation measurement and knowledge base development are discussed. s.roper@aston.ac.uk (Roper, Stephen) jan.youtie@innovate.gatech.edu (Youtie, Jan) pshapira@gatech.edu (Shapira, Philip) af128@mail.gateh.edu (Fernandez Ribas, Andrea) Aston Business School - Aston Triangle--> - B4 7ET - Birmingham - UNITED KINGDOM (Roper, Stephen) Georgia Tech - Atlanta - UNITED STATES (Youtie, Jan) Georgia Tech - Atlanta - UNITED STATES (Shapira, Philip) Georgia Tech - Atlanta - UNITED STATES (Fernandez Ribas, Andrea) UNITED KINGDOM UNITED STATES

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Trinity's Access to ...arrow_drop_down
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Trinity's Access to ...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/

    Abstract The transmembrane domains of the envelope glycoprotein E1 and E2 have crucial multifunctional roles in the biogenesis of hepatitis C virus. We have performed molecular dynamics simulations to investigate a structural model of the transmembrane segments of the E1?E2 heterodimer. The simulations support the key role of the Lys370?Asp728 ion pair for mediating the E1?E2 heterodimerization. In comparison to these two residues, the simulation results also reveal the differential effect of the conserved Arg730 residue that has been observed in experimental studies. Furthermore, we discovered the formation of inter-helical hydrogen bonds via Asn367 that stabilize dimer formation. Simulations of single and double mutants further demonstrate the importance of the ion-pair and polar interactions between the interacting helix monomers. The conformation of the E1 fragment in the simulation of the E1?E2 heterodimer is in close agreement with an NMR structure of the E1 transmembrane segment. The proposed model of the E1?E2 heterodimer supports the postulated cooperative insertion of both helices by the translocon complex into the bilayer. volkhard.helms@bioinformatik.uni-saarland.de (Helms, Volkhard) Center for Bioinformatics, Saarland University - 66041 - Saarbruecken - GERMANY (Jusoh, Siti Azma) Faculty of Pharmacy, Universiti Technologi MARA - 40450 - Shah Alam - MALAYSIA (Jusoh, Siti Azma) Department of Internal Medicine I, Johann Wolfgang Goethe-University Hospital - 60590 - Frankfurt am Main - GERMANY (Welsch, Christoph) Computational Biology, Universitat Erlangen-Nurnberg, BTE Gebaude - Erwin-Rommel-Str.3 - 91058 - Erlangen - GERMANY (Siu, Shirley W. I.) Computational Biology, Universitat Erlangen-Nurnberg, BTE Gebaude - Erwin-Rommel-Str.3 - 91058 - Erlangen - GERMANY (Bockmann, Rainer A.) Center for Bioinformatics, Saarland University - 66041 - Saarbruecken - GERMANY (Helms, Volkhard) GERMANY MALAYSIA Registration: 2010-02-01 Received: 2009-11-24 Accepted: 2010-01-25 ePublished: 2010-03-02

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Trinity's Access to ...arrow_drop_down
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Trinity's Access to ...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/

    Abstract The limit behaviour of scan statistics in a form of maxima of moving sum processes with changing window size for detecting a transient change is studied. Approximate critical values obtained from tail behaviour of the limit variables that are maxima of some locally homogeneous Gaussian fields are compared with critical values obtained by simulation. correspondence: Corresponding author. Tel.: +420 241401261. (Jaruskova, Daniela) jarus@mat.fsv.cvut.cz (Jaruskova, Daniela) piter@mech.math.msu.su (Piterbarg, Vladimir I.) CZECH REPUBLIC (Jaruskova, Daniela) CZECH REPUBLIC Received: 2009-10-05 Revised: 2011-01-11 Accepted: 2011-01-11

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Trinity's Access to ...arrow_drop_down
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Trinity's Access to ...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/

    Abstract Intracellular and secreted cAMP play crucial roles in controlling cell movement and gene regulation throughout development of the social amoeba Dictyostelium discoideum. cAMP is produced by three structurally distinct adenylyl cyclases, ACA, ACG and ACB which have distinctive but overlapping patterns of expression and, as concluded from gene disruption studies, seemingly overlapping functions. In addition to gene disruption, acute pharmacological abrogation of protein activity can be a powerful tool to identify its role in the biology of the organism. We analysed the effects of a range of compounds on the activity of ACA, ACB and ACG to identify enzyme-specific modulators. Caffeine, which was previously used to specifically block ACA function, also inhibited cAMP accumulation by ACB and ACG. 2`3`-O-methyl isopropylidene adenosine (IPA) specifically inhibits ACA when measured in intact cells, without affecting ACB or ACG. All three enzymes are inhibited by the P-site inhibitor 2`5`dideoxyadenosine (DDA) when assayed in cell lysates, but not in intact cells. Tyrphostin A25 and SQ22536 proved to be effective and specific inhibitors for ACG and ACA respectively. Both compounds acted directly on enzyme activity assayed in cell lysates, but only SQ22536 was also a specific inhibitor when added to intact cells. p.schaap@dundee.ac.uk (Schaap, Pauline) School of Life Sciences, University of Dundee - UNITED KINGDOM (Schaap, Pauline) UNITED KINGDOM

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Trinity's Access to ...arrow_drop_down
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    Authors: McGuinness, Regina;

    Research suggests that children as young as eight are viewing online pornography, earlier than they receive primary school sex education, with potential risks of trauma, sexist role modelling, negative sexual consent attitudes, compulsive use, and viewing hard/torture porn. This study hypothesized that early exposure to online pornography (≤18 years) predicts more problematic pornography use and maladaptive sexual consent attitudes in later adulthood than exposure at ≥19 years, or never; and that this impact is stronger in males. A cross-sectional quantitative online survey of 74 adults (31 males, 43 females, aged 18-54), included the self-report Problematic Pornography Use Scale, and Sexual Consent Scale–Revised. Early exposure predicted higher problematic pornography use, but not sexual consent attitudes. Early viewers were predominantly male, aged 18-24, viewed online porn most frequently; 43% felt it influenced their sexual consent attitudes and behaviour. The findings endorse including online porn literacy in primary school sex education.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ DBS Esourcearrow_drop_down
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    DBS Esource
    2019
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    Abstract In this paper an innovative framework to apply Value Stream Mapping to products with complex Bill of Materials is presented. Value Stream Mapping is one of the best tools to map a process and to identify its main criticalities. Unfortunately it can be effectively applied only to linear systems. When the manufacturing process is complex with flows merging together, Value Stream Mapping cannot be straightly used. Thus, the main objective of this work consists in the solution of this limitation so that lean production can be enhanced in complex systems too. The proposed approach is based on seven iterative steps and integrates Value Stream Mapping with other tools typical of industrial engineering. The basic idea is to execute a preliminary analysis to identify the ?critical production path" using the Temporized Bill of Material. Then, improvements are made considering all possible sharing with others secondary paths, as possible constraints. Once the critical path has been optimized, a new one may become critical. Thus the analysis proceeds iteratively until the optimum is reached and the Work In Process level has decreased under a desired value. A case study taken from a real setting environment is finally presented to asses the validity of the methodology here proposed. : Max 1 paper per annum. Non Subscriber (Braglia, Marcello) m.braglia@ing.unipi.it (Braglia, Marcello) g.carmignani@ing.unipi.it (Carmignani, Gionata) francesco.zammori@ing.unipi.it (Zammori, Francesco Aldo) Universita di Pisa, Mechanical Nuclear and Production Engineering - Pisa - ITALY (Braglia, Marcello) Universita di Pisa, Mechanical Nuclear and Production Engineering - Pisa - ITALY (Carmignani, Gionata) Universita di Pisa, Mechanical Nuclear and Production Engineering - Pisa - ITALY (Zammori, Francesco Aldo) ITALY

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    Authors: O'Kelly, Erin;

    Leigheasanna Traidisiúnta. Interview with Kathleen O' Kelly on the topic of traditional medicines (Béaloidis Collection) No

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    Abstract The effect of mechanical deformation on the formation of quasicrystals in Zr57Ti8Nb2.5Cu13.9Ni11.1Al7.5 glassy ribbons has been investigated. The mechanical treatment drastically affects the crystallization behavior and, in particular, suppresses primary quasicrystal formation. However, quasicrystals can be formed by the addition of the appropriate amount of zirconium. This indicates that if a particular short-range (e.g., icosahedral) is required for quasicrystal formation and if this short-range order is altered during milling, it can be restored by appropriately adjusting the chemical composition. : Eckert, Jurgen, j.eckert@phm.tu-darmstadt.de merged with this user on 24-Jun-2008 by Office, Editorial; User ID: 448409 merged with this user on 05-Feb-2007 by Davis, E A (Eckert, J) s.scudino@ifw-dresden.de (Scudino, Sergio) j.eckert@ifw-dresden.de (Eckert, J) hergen.breitzke@physik.fu-berlin.de (Breitzke, Hergen) lueders@physik.fu-berlin.de (Luders, Klaus) l.schultz@ifw-dresden.de (Schultz, Ludwig) IFW Dresden, Institut fur Metallische Werkstoffe - Dresden - GERMANY (Scudino, Sergio) Technische Universitat Darmstadt, FB 11 Material- und Geowissenschaften - Darmstadt - GERMANY (Eckert, J) Freie Universitat Berlin, Fachbereich Physik - Berlin - GERMANY (Breitzke, Hergen) Freie Universitat Berlin, Fachbereich Physik - Berlin - GERMANY (Luders, Klaus) IFW Dresden, Institut fur Metallische Werkstoffe - Dresden - GERMANY (Schultz, Ludwig) GERMANY

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    Abstract Glutathione S-transferase P1 (GSTP1) gene is commonly silenced by CpG island promoter hypermethylation in prostate, breast, and liver cancers. However, mechanisms leading to GSTP1 repression by promoter hypermethylation in leukemia and its relationship with pathological alterations of the chromatin structure remain poorly understood. A panel of leukemia cell lines was analyzed for their GSTP1 expression, revealing cell lines with high, moderate or no detectable GSTP1 expression. Bisulfite sequencing, methylation-specific PCR and combined bisulfite restriction analysis revealed that GSTP1 promoter was completely methylated in transcriptionally inactive RAJI and MEG-01 cell lines. In contrast, cell lines expressing GSTP1 exhibited an unmethylated and transcriptionally active promoter. Furthermore, histone marks and effector proteins associated with transcriptional activity were detected by chromatin immunoprecipitation in the GSTP1 expressing hypomethylated K-562 cell line. However, repressive chromatin marks and the recruitment of silencing protein complexes were found in the non-expressing hypermethylated RAJI and MEG-01 cell lines. Finally, we provide evidence that treatment of RAJI and MEG-01 cells with the DNA demethylating agent, 5-Aza-2?-deoxycytidine, resulted in GSTP1 promoter demethylation, drastic changes of histone modifications and promoter associated proteins and GSTP1 gene activation. In contrast, treatments with HDAC inhibitors failed to demethylate and reactivate the GSTP1 gene. Our study extends the knowledge on leukemia-specific epigenetic alterations of GSTP1 gene. Furthermore, we are showing the correlation of DNA methylation and histone modifications with the positive/negative GSTP1 transcriptional expression state. Finally, these data support the concept of the dominance of DNA methylation over HDAC inhibitor-sensitive histone deacetylation in gene silencing. correspondence: Corresponding author. Laboratoire de Biologie Moleculaire et Cellulaire de Cancer, Hopital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg, Tel.: +352 2468 4040; fax: +352 2468 4060 (Diederich, Marc) marc.diederich@lbmcc.lu (Diederich, Marc) Laboratoire de Biologie Moleculaire et Cellulaire de Cancer, Hopital Kirchberg - 9--> , rue Edward Steichen--> , L-2540 Luxembourg--> - LUXEMBOURG (Karius, Tommy) Laboratoire de Biologie Moleculaire et Cellulaire de Cancer, Hopital Kirchberg - 9--> , rue Edward Steichen--> , L-2540 Luxembourg--> - LUXEMBOURG (Schnekenburger, Michael) Laboratoire de Biologie Moleculaire et Cellulaire de Cancer, Hopital Kirchberg - 9--> , rue Edward Steichen--> , L-2540 Luxembourg--> - LUXEMBOURG (Gelfi, Jenny) Institut fur Genetik - FB Biowissenschaften--> , Universitat des Saarlandes--> , Saarbrucken--> - GERMANY (Walter, Jorn) Laboratoire de Biologie Moleculaire et Cellulaire de Cancer, Hopital Kirchberg - 9--> , rue Edward Steichen--> , L-2540 Luxembourg--> - LUXEMBOURG (Dicato, Mario) Laboratoire de Biologie Moleculaire et Cellulaire de Cancer, Hopital Kirchberg - 9--> , rue Edward Steichen--> , L-2540 Luxembourg--> - LUXEMBOURG (Diederich, Marc) LUXEMBOURG (Diederich, Marc) GERMANY LUXEMBOURG Received: 2010-11-16 Revised: 2011-03-17 Accepted: 2011-03-21

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    Abstract Resins based on melamine-formaldehyde and related analogues such as methylolated melamine are used to cross-link coatings used inside food cans and on the metal closures of glass jars. Thirteen commercially coated cans and closures representing 80% of the European market, were tested using simulants under realistic industrial heat-processing conditions for canned and jarred foods. The food simulants and the retort conditions used were 3% acetic acid for 1 hr at 100?C and 10% ethanol for 1 hr at 130?C. The highest migration level seen for melamine into simulant was 332 ?g/kg. There was no detectable migration of the melamine analogues cyanuric acid ( - YO41 1LZ - York - UNITED KINGDOM (Bradley, Emma) FERA, Food Safety & Quality - Sand Hutton--> - YO41 1LZ - York - UNITED KINGDOM (Day, Joanna) FERA, Food Safety & Quality - Sand Hutton--> - YO41 1LZ - York - UNITED KINGDOM (leak, jennifer) UNITED KINGDOM

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    Abstract This paper presents a comparative analysis of factors contributing to the innovation performance of manufacturing firms in Georgia (USA), Wales (UK), the West Midlands (UK), and Catalonia (Spain). Enabled by comparable survey data, multiple probit models are developed to estimate how various types of firms? innovative activities are influenced by links to external knowledge sources, internal resources, absorptive capacity and public innovation support. Our results suggest the potential for mutual learning. For the European study regions there are insights about how universities in Georgia support innovation. For Georgia and Catalonia there are lessons from UK firms about better capturing potential complementarities between innovation activities. Additional implications for innovation measurement and knowledge base development are discussed. s.roper@aston.ac.uk (Roper, Stephen) jan.youtie@innovate.gatech.edu (Youtie, Jan) pshapira@gatech.edu (Shapira, Philip) af128@mail.gateh.edu (Fernandez Ribas, Andrea) Aston Business School - Aston Triangle--> - B4 7ET - Birmingham - UNITED KINGDOM (Roper, Stephen) Georgia Tech - Atlanta - UNITED STATES (Youtie, Jan) Georgia Tech - Atlanta - UNITED STATES (Shapira, Philip) Georgia Tech - Atlanta - UNITED STATES (Fernandez Ribas, Andrea) UNITED KINGDOM UNITED STATES

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    Abstract The transmembrane domains of the envelope glycoprotein E1 and E2 have crucial multifunctional roles in the biogenesis of hepatitis C virus. We have performed molecular dynamics simulations to investigate a structural model of the transmembrane segments of the E1?E2 heterodimer. The simulations support the key role of the Lys370?Asp728 ion pair for mediating the E1?E2 heterodimerization. In comparison to these two residues, the simulation results also reveal the differential effect of the conserved Arg730 residue that has been observed in experimental studies. Furthermore, we discovered the formation of inter-helical hydrogen bonds via Asn367 that stabilize dimer formation. Simulations of single and double mutants further demonstrate the importance of the ion-pair and polar interactions between the interacting helix monomers. The conformation of the E1 fragment in the simulation of the E1?E2 heterodimer is in close agreement with an NMR structure of the E1 transmembrane segment. The proposed model of the E1?E2 heterodimer supports the postulated cooperative insertion of both helices by the translocon complex into the bilayer. volkhard.helms@bioinformatik.uni-saarland.de (Helms, Volkhard) Center for Bioinformatics, Saarland University - 66041 - Saarbruecken - GERMANY (Jusoh, Siti Azma) Faculty of Pharmacy, Universiti Technologi MARA - 40450 - Shah Alam - MALAYSIA (Jusoh, Siti Azma) Department of Internal Medicine I, Johann Wolfgang Goethe-University Hospital - 60590 - Frankfurt am Main - GERMANY (Welsch, Christoph) Computational Biology, Universitat Erlangen-Nurnberg, BTE Gebaude - Erwin-Rommel-Str.3 - 91058 - Erlangen - GERMANY (Siu, Shirley W. I.) Computational Biology, Universitat Erlangen-Nurnberg, BTE Gebaude - Erwin-Rommel-Str.3 - 91058 - Erlangen - GERMANY (Bockmann, Rainer A.) Center for Bioinformatics, Saarland University - 66041 - Saarbruecken - GERMANY (Helms, Volkhard) GERMANY MALAYSIA Registration: 2010-02-01 Received: 2009-11-24 Accepted: 2010-01-25 ePublished: 2010-03-02

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    Abstract The limit behaviour of scan statistics in a form of maxima of moving sum processes with changing window size for detecting a transient change is studied. Approximate critical values obtained from tail behaviour of the limit variables that are maxima of some locally homogeneous Gaussian fields are compared with critical values obtained by simulation. correspondence: Corresponding author. Tel.: +420 241401261. (Jaruskova, Daniela) jarus@mat.fsv.cvut.cz (Jaruskova, Daniela) piter@mech.math.msu.su (Piterbarg, Vladimir I.) CZECH REPUBLIC (Jaruskova, Daniela) CZECH REPUBLIC Received: 2009-10-05 Revised: 2011-01-11 Accepted: 2011-01-11

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    Abstract Intracellular and secreted cAMP play crucial roles in controlling cell movement and gene regulation throughout development of the social amoeba Dictyostelium discoideum. cAMP is produced by three structurally distinct adenylyl cyclases, ACA, ACG and ACB which have distinctive but overlapping patterns of expression and, as concluded from gene disruption studies, seemingly overlapping functions. In addition to gene disruption, acute pharmacological abrogation of protein activity can be a powerful tool to identify its role in the biology of the organism. We analysed the effects of a range of compounds on the activity of ACA, ACB and ACG to identify enzyme-specific modulators. Caffeine, which was previously used to specifically block ACA function, also inhibited cAMP accumulation by ACB and ACG. 2`3`-O-methyl isopropylidene adenosine (IPA) specifically inhibits ACA when measured in intact cells, without affecting ACB or ACG. All three enzymes are inhibited by the P-site inhibitor 2`5`dideoxyadenosine (DDA) when assayed in cell lysates, but not in intact cells. Tyrphostin A25 and SQ22536 proved to be effective and specific inhibitors for ACG and ACA respectively. Both compounds acted directly on enzyme activity assayed in cell lysates, but only SQ22536 was also a specific inhibitor when added to intact cells. p.schaap@dundee.ac.uk (Schaap, Pauline) School of Life Sciences, University of Dundee - UNITED KINGDOM (Schaap, Pauline) UNITED KINGDOM

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    Authors: McGuinness, Regina;

    Research suggests that children as young as eight are viewing online pornography, earlier than they receive primary school sex education, with potential risks of trauma, sexist role modelling, negative sexual consent attitudes, compulsive use, and viewing hard/torture porn. This study hypothesized that early exposure to online pornography (≤18 years) predicts more problematic pornography use and maladaptive sexual consent attitudes in later adulthood than exposure at ≥19 years, or never; and that this impact is stronger in males. A cross-sectional quantitative online survey of 74 adults (31 males, 43 females, aged 18-54), included the self-report Problematic Pornography Use Scale, and Sexual Consent Scale–Revised. Early exposure predicted higher problematic pornography use, but not sexual consent attitudes. Early viewers were predominantly male, aged 18-24, viewed online porn most frequently; 43% felt it influenced their sexual consent attitudes and behaviour. The findings endorse including online porn literacy in primary school sex education.

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