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Sample records for dsb ic3 train

  1. Computing fundamentals IC3 edition

    CERN Document Server

    Wempen, Faithe

    2014-01-01

    Kick start your journey into computing and prepare for your IC3 certification With this essential course book you'll be sending e-mails, surfing the web and understanding the basics of computing in no time. Written by Faithe Wempen, a Microsoft Office Master Instructor and author of more than 120 books, this complete guide to the basics has been tailored to provide comprehensive instruction on the full range of entry-level computing skills. It is a must for students looking to move into almost any profession, as entry-level computing courses have become a compulsory requirement in the modern w

  2. Constructing Periodic Timetables using MIP - a case study from DSB S-train

    DEFF Research Database (Denmark)

    Nielsen, Morten N.; Hove, Bjørn; Clausen, Jens

    2006-01-01

    We describe a mathematical model to create operational timetable alternatives in DSB S-tog a/s. The model is a mixed integer program implemented in GAMS and solved by CPLEX. We investigate the impact of automatic merges of lines and perform scenario analysis for a subset of the parameters...

  3. Robustness and Recovery in Train Scheduling - a simulation study from DSB S-tog a/s

    DEFF Research Database (Denmark)

    Hofman, Mads A.; Madsen, Line; Groth, Julie Jespersen

    This paper presents a simulation model to study the robustness of timetables of DSB S-tog a/s, the city rail of Copenhagen. Dealing with rush hour scenarios only, the simulation model investigates the effects of disturbances on the S-tog network. Several timetables are analyzed with respect to ro...

  4. DSB Tilgængelighedsstandard

    DEFF Research Database (Denmark)

    Ginnerup, Søren

    2012-01-01

    I DSB's Tilgængelighedsstandard er der lagt vægt på at tilvejebringe et overskueligt og anvendeligt værktøj for tilgængelighed til dem der skal forestå fremtidens stationsindretning i forbindelse med nybyggeri, ombygning eller modernisering af stationerne for DSB Ejendomme......I DSB's Tilgængelighedsstandard er der lagt vægt på at tilvejebringe et overskueligt og anvendeligt værktøj for tilgængelighed til dem der skal forestå fremtidens stationsindretning i forbindelse med nybyggeri, ombygning eller modernisering af stationerne for DSB Ejendomme...

  5. The disulfide isomerase DsbC cooperates with the oxidase DsbA in a DsbD-independent manner

    OpenAIRE

    Vertommen, Didier; Depuydt, Matthieu; Pan, Jonathan; Leverrier, Pauline; Knoops, Laurent; Szikora, Jean-Pierre; Messens, Joris; Bardwell, James C. A.; Collet, Jean-Francois

    2007-01-01

    In Escherichia coli, DsbA introduces disulfide bonds into secreted proteins. DsbA is recycled by DsbB, which generates disulfides from quinone reduction. DsbA is not known to have any proofreading activity and can form incorrect disulfides in proteins with multiple cysteines. These incorrect disulfides are thought to be corrected by a protein disulfide isomerase, DsbC, which is kept in the reduced and active configuration by DsbD. The DsbC/DsbD isomerization pathway is considered to be isolat...

  6. Model Checking with Multi-Threaded IC3 Portfolios

    Science.gov (United States)

    2015-01-15

    Model Checking with Multi-Threaded IC3 Portfolios Sagar Chaki and Derrick Karimi Software Engineering Institute, Carnegie Mellon University {chaki...different runs varies randomly depending on the thread interleaving. The use of a portfolio of solvers to maximize the likelihood of a quick solution is...investigated. Using the Extreme Value theorem, the runtime of each variant, as well as their portfolios is analysed statistically. A formula for the

  7. Protein disulfide bond generation in Escherichia coli DsbB–DsbA

    OpenAIRE

    Inaba, Kenji

    2008-01-01

    Protein disulfide bond formation is catalyzed by a series of Dsb enzymes present in the periplasm of Escherichia coli. The crystal structure of the DsbB–DsbA–ubiquinone ternary complex provided important insights into mechanisms of the de novo disulfide bond generation cooperated by DsbB and ubiquinone and of the disulfide bond shuttle from DsbB to DsbA. The structural basis for prevention of the crosstalk between the DsbA–DsbB oxidative and the DsbC–DsbD reductive pathways has also been prop...

  8. Mutational Analysis of the Disulfide Catalysts DsbA and DsbB

    OpenAIRE

    Tan, Jacqueline; Lu, Ying; Bardwell, James C. A.

    2005-01-01

    In prokaryotes, disulfides are generated by the DsbA-DsbB system. DsbB functions to generate disulfides by quinone reduction. These disulfides are passed to the DsbA protein and then to folding proteins. To investigate the DsbA-DsbB catalytic system, we performed an in vivo selection for chromosomal dsbA and dsbB mutants. We rediscovered many residues previously shown to be important for the activity of these proteins. In addition, we obtained one novel DsbA mutant (M153R) and four novel DsbB...

  9. DsbC activation by the N-terminal domain of DsbD

    OpenAIRE

    Goldstone, David; Haebel, Peter W.; Katzen, Federico; Bader, Martin W.; Bardwell, James C. A.; Beckwith, Jon; Metcalf, Peter

    2001-01-01

    The correct formation of disulfide bonds in the periplasm of Escherichia coli involves Dsb proteins, including two related periplasmic disulfide-bond isomerases, DsbC and DsbG. DsbD is a membrane protein required to maintain the functional oxidation state of DsbC and DsbG. In this work, purified proteins were used to investigate the interaction between DsbD and DsbC. A 131-residue N-terminal fragment of DsbD (DsbDα) was expressed and purified and shown to form a fu...

  10. IC3 Internet and Computing Core Certification Global Standard 4 study guide

    CERN Document Server

    Rusen, Ciprian Adrian

    2015-01-01

    Hands-on IC3 prep, with expert instruction and loads of tools IC3: Internet and Computing Core Certification Global Standard 4 Study Guide is the ideal all-in-one resource for those preparing to take the exam for the internationally-recognized IT computing fundamentals credential. Designed to help candidates pinpoint weak areas while there's still time to brush up, this book provides one hundred percent coverage of the exam objectives for all three modules of the IC3-GS4 exam. Readers will find clear, concise information, hands-on examples, and self-paced exercises that demonstrate how to per

  11. DsbL and DsbI contribute to periplasmic disulfide bond formation in Salmonella enterica serovar Typhimurium

    OpenAIRE

    Lin, Dongxia; Kim, Byoungkwan; Slauch, James M.

    2009-01-01

    Disulfide bond formation in periplasmic proteins is catalysed by the DsbA/DsbB system in most Gram-negative bacteria. Salmonella enterica serovar Typhimurium also encodes a paralogous pair of proteins to DsbA and DsbB, DsbL and DsbI, respectively, downstream of a periplasmic arylsulfate sulfotransferase (ASST). We show that DsbL and DsbI function as a redox pair contributing to periplasmic disulfide bond formation and, as such, affect transcription of the Salmonella pathogenicity island 1 (SP...

  12. The impact of heterochromatin on DSB repair.

    Science.gov (United States)

    Goodarzi, Aaron A; Noon, Angela T; Jeggo, Penny A

    2009-06-01

    DNA NHEJ (non-homologous end-joining) is the major DNA DSB (double-strand break) repair pathway in mammalian cells. Although NHEJ-defective cell lines show marked DSB-repair defects, cells defective in ATM (ataxia telangiectasia mutated) repair most DSBs normally. Thus NHEJ functions independently of ATM signalling. However, approximately 15% of radiation-induced DSBs are repaired with slow kinetics and require ATM and the nuclease Artemis. DSBs persisting in the presence of an ATM inhibitor, ATMi, localize to heterochromatin, suggesting that ATM is required for repairing DSBs arising within or close to heterochromatin. Consistent with this, we show that siRNA (small interfering RNA) of key heterochromatic proteins, including KAP-1 [KRAB (Krüppel-associated box) domain-associated protein 1], HP1 (heterochromatin protein 1) and HDAC (histone deacetylase) 1/2, relieves the requirement for ATM for DSB repair. Furthermore, ATMi addition to cell lines with genetic alterations that have an impact on heterochromatin, including Suv39H1/2 (suppressor of variegation 3-9 homologue 1/2)-knockout, ICFa (immunodeficiency, centromeric region instability, facial anomalies syndrome type a) and Hutchinson-Guilford progeria cell lines, fails to have an impact on DSB repair. KAP-1 is a highly dose-dependent, transient and ATM-specific substrate, and mutation of the ATM phosphorylation site on KAP-1 influences DSB repair. Collectively, the findings show that ATM functions to overcome the barrier to DSB repair posed by heterochromatin. However, even in the presence of ATM, gamma-H2AX (phosphorylated histone H2AX) foci form on the periphery rather than within heterochromatic centres. Finally, we show that KAP-1's association with heterochromatin is diminished as cells progress through mitosis. We propose that KAP-1 is a critical heterochromatic factor that undergoes specific modifications to promote DSB repair and mitotic progression in a manner that allows localized and transient

  13. Expression on three dsb genes of Chlamydia trachomatis serovar F

    Institute of Scientific and Technical Information of China (English)

    XING DONG YE; LI SHEN; YOU XUN ZHANG

    2007-01-01

    To investigate the expression levels of three Dsb protein genes, dsbB, dsbD and dsbG, at different time points post C. trachomatis infection, mouse fibroblast L2 cells were chosen to be infected with C. trachomatis serovar F strain F/IC-Cal-13. C. trachomatis elementary body (EB)-infected L2cells were harvested immediately after EB attachment onto the cells and every 4 hours post infection (hpi)till 44 hpi for total RNA preparation. RT-PCR assays were then employed to amplify cDNA with primer pairs which are specific to C. trachomatis dsb genes dsbB, dsbD, dsbG and tufA respectively. The relative expression levels of Dsb protein genes were evaluated as cDNA ratios of gene dsb to gene tufA. Our results showed that the transcription of dsbG started from 12 hpi and gradually increased till 44 hpi. The transcription of dsbB and dsbD were detected at 16 hpi and reached their peaks at 28 hpi and 24-28 hpi,respectively. Moreover, there was obvious transcription of dsbB at the later stage (44 hpi), but none for dsbD at this time point. We came to the conclusion that the expression levels of the three Dsb protein genes are different during the developmental cycle of C. trachomatist. They may play a role in mid-to-late stage of the developmental cycle of C. trachomatis.

  14. The gene ICS3 from the yeast Saccharomyces cerevisiae is involved in copper homeostasis dependent on extracellular pH.

    Science.gov (United States)

    Alesso, C A; Discola, K F; Monteiro, G

    2015-09-01

    In the yeast Saccharomyces cerevisiae, many genes are involved in the uptake, transport, storage and detoxification of copper. Large scale studies have noted that deletion of the gene ICS3 increases sensitivity to copper, Sortin 2 and acid exposure. Here, we report a study on the Δics3 strain, in which ICS3 is related to copper homeostasis, affecting the intracellular accumulation of this metal. This strain is sensitive to hydrogen peroxide and copper exposure, but not to other tested transition metals. At pH 6.0, the Δics3 strain accumulates a larger amount of intracellular copper than the wild-type strain, explaining the sensitivity to oxidants in this condition. Unexpectedly, sensitivity to copper exposure only occurs in acidic conditions. This can be explained by the fact that the exposure of Δics3 cells to high copper concentrations at pH 4.0 results in over-accumulation of copper and iron. Moreover, the expression of ICS3 increases in acidic pH, and this is correlated with CCC2 gene expression, since both genes are regulated by Rim101 from the pH regulon. CCC2 is also upregulated in Δics3 in acidic pH. Together, these data indicate that ICS3 is involved in copper homeostasis and is dependent on extracellular pH. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Rolling Stock Planning at DSB S-tog - Processes, Cost Structures and Requirements

    DEFF Research Database (Denmark)

    Thorlacius, Per

    A central issue for operators of suburban passenger train transport systems is providing sufficient number of seats for the passengers while at the same time minimising operating costs. The process of providing this is called rolling stock planning. This technical report documents the terminology......, the processes, the cost structures and the requirements for rolling stock planning at DSB S-tog, the suburban passenger train operator of the City of Copenhagen. The focus of the technical report is directed at practical train operator oriented issues. The technical report is thought to serve as a basis...... for investigating better methods to perform the rolling stock planning (to be the topic of later papers). This technical report is produced as a part of the current industrial Ph. D. project to improve the rolling stock planning process of DSB S-tog....

  16. Comparative Sequence, Structure and Redox Analyses of Klebsiella pneumoniae DsbA Show That Anti-Virulence Target DsbA Enzymes Fall into Distinct Classes

    OpenAIRE

    Fabian Kurth; Kieran Rimmer; Lakshmanane Premkumar; Biswaranjan Mohanty; Wilko Duprez; Halili, Maria A; Shouldice, Stephen R.; Begoña Heras; Fairlie, David P.; Martin J. Scanlon; Jennifer L Martin

    2013-01-01

    Bacterial DsbA enzymes catalyze oxidative folding of virulence factors, and have been identified as targets for antivirulence drugs. However, DsbA enzymes characterized to date exhibit a wide spectrum of redox properties and divergent structural features compared to the prototypical DsbA enzyme of Escherichia coli DsbA (EcDsbA). Nonetheless, sequence analysis shows that DsbAs are more highly conserved than their known substrate virulence factors, highlighting the potential to inhibit virulenc...

  17. Defense Science Board (DSB) Summer Study Report on Strategic Surprise

    Science.gov (United States)

    2015-07-01

    DSB Summer Study Report on Strategic Surprise July 2015 Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden...SUBTITLE DSB Summer Study Report on Strategic Surprise 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Defense Science Board ( DSB ),The Pentagon ,OUSD(AT&L

  18. Becoming a crossover-competent DSB.

    Science.gov (United States)

    Lake, Cathleen M; Hawley, R Scott

    2016-06-01

    The proper execution of meiotic recombination (or crossing over) is essential for chromosome segregation during the first meiotic division, and thus this process is regulated by multiple, and often elaborate, mechanisms. Meiotic recombination begins with the programmed induction of DNA double-strand breaks (DSBs), of which only a subset are selected to be repaired into crossovers. This crossover selection process is carried out by a number of pro-crossover proteins that regulate the fashion in which DSBs are repaired. Here, we highlight recent studies regarding the process of DSB fate selection by a family of pro-crossover proteins known as the Zip-3 homologs.

  19. Distinct recognition of complement iC3b by integrins αXβ2 and αMβ2.

    Science.gov (United States)

    Xu, Shutong; Wang, Jianchuan; Wang, Jia-Huai; Springer, Timothy A

    2017-03-28

    Recognition by the leukocyte integrins αXβ2 and αMβ2 of complement iC3b-opsonized targets is essential for effector functions including phagocytosis. The integrin-binding sites on iC3b remain incompletely characterized. Here, we describe negative-stain electron microscopy and biochemical studies of αXβ2 and αMβ2 in complex with iC3b. Despite high homology, the two integrins bind iC3b at multiple distinct sites. αXβ2 uses the αX αI domain to bind iC3b on its C3c moiety at one of two sites: a major site at the interface between macroglobulin (MG) 3 and MG4 domains, and a less frequently used site near the C345C domain. In contrast, αMβ2 uses its αI domain to bind iC3b at the thioester domain and simultaneously interacts through a region near the αM β-propeller and β2 βI domain with a region of the C3c moiety near the C345C domain. Remarkably, there is no overlap between the primary binding site of αXβ2 and the binding site of αMβ2 on iC3b. Distinctive binding sites on iC3b by integrins αXβ2 and αMβ2 may be biologically beneficial for leukocytes to more efficiently capture opsonized pathogens and to avoid subversion by pathogen factors.

  20. Structure of a DsbF homologue from Corynebacterium diphtheriae.

    Science.gov (United States)

    Um, Si-Hyeon; Kim, Jin-Sik; Lee, Kangseok; Ha, Nam-Chul

    2014-09-01

    Disulfide-bond formation, mediated by the Dsb family of proteins, is important in the correct folding of secreted or extracellular proteins in bacteria. In Gram-negative bacteria, disulfide bonds are introduced into the folding proteins in the periplasm by DsbA. DsbE from Escherichia coli has been implicated in the reduction of disulfide bonds in the maturation of cytochrome c. The Gram-positive bacterium Mycobacterium tuberculosis encodes DsbE and its homologue DsbF, the structures of which have been determined. However, the two mycobacterial proteins are able to oxidatively fold a protein in vitro, unlike DsbE from E. coli. In this study, the crystal structure of a DsbE or DsbF homologue protein from Corynebacterium diphtheriae has been determined, which revealed a thioredoxin-like domain with a typical CXXC active site. Structural comparison with M. tuberculosis DsbF would help in understanding the function of the C. diphtheriae protein.

  1. Diversity of the Epsilonproteobacteria Dsb (disulfide bond) systems.

    Science.gov (United States)

    Bocian-Ostrzycka, Katarzyna M; Grzeszczuk, Magdalena J; Dziewit, Lukasz; Jagusztyn-Krynicka, Elżbieta K

    2015-01-01

    The bacterial proteins of the Dsb family-important components of the post-translational protein modification system-catalyze the formation of disulfide bridges, a process that is crucial for protein structure stabilization and activity. Dsb systems play an essential role in the assembly of many virulence factors. Recent rapid advances in global analysis of bacteria have thrown light on the enormous diversity among bacterial Dsb systems. While the Escherichia coli disulfide bond-forming system is quite well understood, the mechanisms of action of Dsb systems in other bacteria, including members of class Epsilonproteobacteria that contain pathogenic and non-pathogenic bacteria colonizing extremely diverse ecological niches, are poorly characterized. Here we present a review of current knowledge on Epsilonproteobacteria Dsb systems. We have focused on the Dsb systems of Campylobacter spp. and Helicobacter spp. because our knowledge about Dsb proteins of Wolinella and Arcobacter spp. is still scarce and comes mainly from bioinformatic studies. Helicobacter pylori is a common human pathogen that colonizes the gastric epithelium of humans with severe consequences. Campylobacter spp. is a leading cause of zoonotic enteric bacterial infections in most developed and developing nations. We focus on various aspects of the diversity of the Dsb systems and their influence on pathogenicity, particularly because Dsb proteins are considered as potential targets for a new class of anti-virulence drugs to treat human infections by Campylobacter or Helicobacter spp.

  2. Diversity of the Epsilonproteobacteria Dsb (disulfide bond systems

    Directory of Open Access Journals (Sweden)

    Katarzyna Marta Bocian-Ostrzycka

    2015-06-01

    Full Text Available The bacterial proteins of the Dsb family – important components of the posttranslational protein modification system – catalyze the formation of disulfide bridges, a process that is crucial for protein structure stabilization and activity. Dsb systems play an essential role in the assembly of many virulence factors. Recent rapid advances in global analysis of bacteria have thrown light on the enormous diversity among bacterial Dsb systems. While the Escherichia coli disulfide bond-forming system is quite well understood, the mechanisms of action of Dsb systems in other bacteria, including members of class Epsilonproteobacteria that contain pathogenic and non-pathogenic bacteria colonizing extremely diverse ecological niches, are poorly characterized. Here we present a review of current knowledge on Epsilonproteobacteria Dsb systems. We have focused on the Dsb systems of Campylobacter spp. and Helicobacter spp. because our knowledge about Dsb proteins of Wolinella and Arcobacter spp. is still scarce and comes mainly from bioinformatic studies. Helicobacter pylori is a common human pathogen that colonizes the gastric epithelium of humans with severe consequences. Campylobacter spp. is a leading cause of zoonotic enteric bacterial infections in most developed and developing nations. We focus on various aspects of the diversity of the Dsb systems and their influence on pathogenicity, particularly because Dsb proteins are considered as potential targets for a new class of anti-virulence drugs to treat human infections by Campylobacter or Helicobacter spp.

  3. Expression and crystallization of DsbA from Staphylococcus aureus

    Energy Technology Data Exchange (ETDEWEB)

    Heras, B., E-mail: b.heras@imb.uq.edu.au; Kurz, M.; Jarrott, R.; Byriel, K. A.; Jones, A. [Institute for Molecular Bioscience and ARC Special Research Centre for Functional and Applied Genomics, University of Queensland, Brisbane QLD 4072 (Australia); Thöny-Meyer, L. [EMPA, Abteilung Biokompatible Werkstoffe, Lerchenfeldstrasse 5, CH-9014 St Gallen (Switzerland); Martin, J. L., E-mail: b.heras@imb.uq.edu.au [Institute for Molecular Bioscience and ARC Special Research Centre for Functional and Applied Genomics, University of Queensland, Brisbane QLD 4072 (Australia)

    2007-11-01

    Free-interface diffusion crystallization chips were used to identify crystallization conditions for S. aureus DsbA, representing the first Gram-positive DsbA to be crystallized. Native and selenomethionine-derivative crystals diffracted to 2.1 and 2.4 Å resolution, respectively. Bacterial Dsb proteins catalyse the in vivo formation of disulfide bonds, a critical step in the stability and activity of many proteins. Most studies on Dsb proteins have focused on Gram-negative bacteria and thus the process of oxidative folding in Gram-positive bacteria is poorly understood. To help elucidate this process in Gram-positive bacteria, DsbA from Staphylococcus aureus (SaDsbA) has been focused on. Here, the expression, purification, crystallization and preliminary diffraction analysis of SaDsbA are reported. SaDsbA crystals diffract to a resolution limit of 2.1 Å and belong to the hexagonal space group P6{sub 5} or P6{sub 1}, with unit-cell parameters a = b = 72.1, c = 92.1 Å and one molecule in the asymmetric unit (64% solvent content)

  4. Evidence that the pathway of disulfide bond formation in Escherichia coli involves interactions between the cysteines of DsbB and DsbA.

    OpenAIRE

    Guilhot, C; Jander, G.; Martin, N L; Beckwith, J

    1995-01-01

    Disulfide bond formation is catalyzed in the periplasm of Escherichia coli. This process involves at least two proteins: DsbA and DsbB. Recent evidence suggests that DsbA, a soluble periplasmic protein directly catalyzes disulfide bond formation in proteins, whereas DsbB, an inner membrane protein, is involved in the reoxidation of DsbA. Here we present direct evidence of an interaction between DsbA and DsbB. (Kishigami et al. [Kishigami, S., Kanaya, E., Kikuchi, M. & Ito, K. (1995) J. Biol. ...

  5. Meiotic DSB patterning: A multifaceted process.

    Science.gov (United States)

    Cooper, Tim J; Garcia, Valerie; Neale, Matthew J

    2016-01-01

    Meiosis is a specialized two-step cell division responsible for genome haploidization and the generation of genetic diversity during gametogenesis. An integral and distinctive feature of the meiotic program is the evolutionarily conserved initiation of homologous recombination (HR) by the developmentally programmed induction of DNA double-strand breaks (DSBs). The inherently dangerous but essential act of DSB formation is subject to multiple forms of stringent and self-corrective regulation that collectively ensure fruitful and appropriate levels of genetic exchange without risk to cellular survival. Within this article we focus upon an emerging element of this control--spatial regulation--detailing recent advances made in understanding how DSBs are evenly distributed across the genome, and present a unified view of the underlying patterning mechanisms employed.

  6. DTU’s undersøgelser af lav adhæsion / glatte skinner for Transportministeriet og DSB

    DEFF Research Database (Denmark)

    Stockmarr, Anders; Ersbøll, Bjarne Kjær; Kotwa, Ewelina Katarzyna

    forhold. Delrapporter: 1) Analysis of the Probability for Blocking Flag Under Low Adhesion for IC3 and IC4 Trains, on the Route Copenhagen-Århus in the Leaf Fall Period. Anders Stockmarr, Bjarne Kjær Ersbøll, Ewelina Kotwa, Camilla Thyregod, DTU Compute 2) Management of low adhesion on railway tracks...

  7. The C. elegans DSB-2 protein reveals a regulatory network that controls competence for meiotic DSB formation and promotes crossover assurance.

    Science.gov (United States)

    Rosu, Simona; Zawadzki, Karl A; Stamper, Ericca L; Libuda, Diana E; Reese, Angela L; Dernburg, Abby F; Villeneuve, Anne M

    2013-01-01

    For most organisms, chromosome segregation during meiosis relies on deliberate induction of DNA double-strand breaks (DSBs) and repair of a subset of these DSBs as inter-homolog crossovers (COs). However, timing and levels of DSB formation must be tightly controlled to avoid jeopardizing genome integrity. Here we identify the DSB-2 protein, which is required for efficient DSB formation during C. elegans meiosis but is dispensable for later steps of meiotic recombination. DSB-2 localizes to chromatin during the time of DSB formation, and its disappearance coincides with a decline in RAD-51 foci marking early recombination intermediates and precedes appearance of COSA-1 foci marking CO-designated sites. These and other data suggest that DSB-2 and its paralog DSB-1 promote competence for DSB formation. Further, immunofluorescence analyses of wild-type gonads and various meiotic mutants reveal that association of DSB-2 with chromatin is coordinated with multiple distinct aspects of the meiotic program, including the phosphorylation state of nuclear envelope protein SUN-1 and dependence on RAD-50 to load the RAD-51 recombinase at DSB sites. Moreover, association of DSB-2 with chromatin is prolonged in mutants impaired for either DSB formation or formation of downstream CO intermediates. These and other data suggest that association of DSB-2 with chromatin is an indicator of competence for DSB formation, and that cells respond to a deficit of CO-competent recombination intermediates by prolonging the DSB-competent state. In the context of this model, we propose that formation of sufficient CO-competent intermediates engages a negative feedback response that leads to cessation of DSB formation as part of a major coordinated transition in meiotic prophase progression. The proposed negative feedback regulation of DSB formation simultaneously (1) ensures that sufficient DSBs are made to guarantee CO formation and (2) prevents excessive DSB levels that could have deleterious

  8. Double strand break (DSB) repair in heterochromatin and heterochromatin proteins in DSB repair.

    Science.gov (United States)

    Lemaître, Charlène; Soutoglou, Evi

    2014-07-01

    Chromosomal translocations are a hallmark of cancer cells and they represent a major cause of tumorigenesis. To avoid chromosomal translocations, faithful repair of DNA double strand breaks (DSBs) has to be ensured in the context of high ordered chromatin structure. However, chromatin compaction is proposed to represent a barrier for DSB repair. Here we review the different mechanisms cells use to alleviate the heterochromatic barrier for DNA repair. At the same time, we discuss the activating role of heterochromatin-associated proteins in this process, therefore proposing that chromatin structure, more than being a simple barrier, is a key modulator of DNA repair.

  9. Simulation of DSB yield for high LET radiation.

    Science.gov (United States)

    Friedrich, T; Durante, M; Scholz, M

    2015-09-01

    A simulation approach for the calculation of the LET-dependent yield of double-strand breaks (DSB) is presented. The model considers DSB formed as two close-lying single-strand breaks (SSB), whose formation is mediated by both intra-track processes (single electrons) or at local doses larger than about 1000 Gy in particle tracks also by electron inter-track processes (two independent electron tracks). A Monte Carlo algorithm and an analytical formula for the DSB yield are presented. The approach predicts that the DSB yield is enhanced after charged particle irradiation of high LET compared with X-ray or gamma radiation. It is used as an inherent part of the local effect model, which is applied to estimate the relative biological effectiveness of high LET radiation.

  10. Why is DsbA such an oxidizing disulfide catalyst?

    DEFF Research Database (Denmark)

    Grauschopf, U; Winther, Jakob R.; Korber, P;

    1995-01-01

    DsbA, a member of the thioredoxin family of disulfide oxidoreductases, acts in catalyzing disulfide bond formation by donating its disulfide to newly translocated proteins. We have found that the two central residues within the active site Cys-30-Pro-31-His-32-Cys-33 motif are critical in determi......DsbA, a member of the thioredoxin family of disulfide oxidoreductases, acts in catalyzing disulfide bond formation by donating its disulfide to newly translocated proteins. We have found that the two central residues within the active site Cys-30-Pro-31-His-32-Cys-33 motif are critical...... in determining the exceptional oxidizing power of DsbA. Mutations that change these two residues can alter the equilibrium oxidation potential of DsbA by more than 1000-fold. A quantitative explanation for the very high redox potential of DsbA was found by measuring the pKa of a single residue, Cys-30. The p......Ka of Cys-30 varied dramatically from mutant to mutant and could accurately predict the oxidizing power of each DsbA mutant protein....

  11. Mutants in DsbB that appear to Redirect Oxidation Through the Disulfide Isomerization Pathway

    OpenAIRE

    Pan, Jonathan L.; Sliskovic, Inga; Bardwell, James C. A.

    2008-01-01

    Disulfide bond formation occurs in secreted proteins in Escherichia coli when the disulfide oxidoreductase DsbA, a soluble periplasmic protein, nonspecifically transfers a disulfide to a substrate protein. The catalytic disulfide of DsbA is regenerated by the inner membrane protein DsbB. To help identify the specificity determinants in DsbB and to understand the nature of the kinetic barrier preventing direct oxidation of newly secreted proteins by DsbB, we imposed selective pressure to find ...

  12. Identification and Functional Analysis of an Immunoreactive DsbA-Like Thio-Disulfide Oxidoreductase of Ehrlichia spp.

    OpenAIRE

    McBride, Jere W.; Ndip, Lucy M.; Vsevolod L Popov; David H Walker

    2002-01-01

    Novel homologous DsbA-like disulfide bond formation (Dsb) proteins of Ehrlichia chaffeensis and Ehrlichia canis were identified which restored DsbA activity in complemented Escherichia coli dsbA mutants. Recombinant Ehrlichia Dsb (eDsb) proteins were recognized by sera from E. canis-infected dogs but not from E. chaffeensis-infected patients. The eDsb proteins were observed primarily in the periplasm of E. chaffeensis and E. canis.

  13. A simple two-step purification procedure for the iC3b binding collectin conglutinin

    DEFF Research Database (Denmark)

    Krogh-Meibom, Thomas; Ingvartsen, Klaus Lønne; Tornoe, Ida

    2010-01-01

    Bovine conglutinin is a serum protein involved in innate immunity. It binds calcium dependently to iC3b, a product of the complement component C3 deposited on cell surfaces, immune complexes or artificial surfaces after complement activation. We here present a simple and efficient two....... In the second step, conglutinin is separated from iC3b and IgM by ion-exchange chromatography. This purification procedure yielded 81 μg of conglutinin per ml of serum with a recovery of 61.2%. Surface plasmon resonance analysis showed that the purified conglutinin had a high affinity for mannan (K(d)=2.3-3.2 n...

  14. An approach to estimate radioadaptation from DSB repair efficiency.

    Science.gov (United States)

    Yatagai, Fumio; Sugasawa, Kaoru; Enomoto, Shuichi; Honma, Masamitsu

    2009-09-01

    In this review, we would like to introduce a unique approach for the estimation of radioadaptation. Recently, we proposed a new methodology for evaluating the repair efficiency of DNA double-strand breaks (DSB) using a model system. The model system can trace the fate of a single DSB, which is introduced within intron 4 of the TK gene on chromosome 17 in human lymphoblastoid TK6 cells by the expression of restriction enzyme I-SceI. This methodology was first applied to examine whether repair of the DSB (at the I-SceI site) can be influenced by low-dose, low-dose rate gamma-ray irradiation. We found that such low-dose IR exposure could enhance the activity of DSB repair through homologous recombination (HR). HR activity was also enhanced due to the pre-IR irradiation under the established conditions for radioadaptation (50 mGy X-ray-6 h-I-SceI treatment). Therefore, radioadaptation might account for the reduced frequency of homozygous loss of heterozygosity (LOH) events observed in our previous experiment (50 mGy X-ray-6 h-2 Gy X-ray). We suggest that the present evaluation of DSB repair using this I-SceI system, may contribute to our overall understanding of radioadaptation.

  15. Dehydrohalogenation and Dehydration Reactions of i-C3H7Br and i-C3H7OH by Sodium Ions Studied by Guided Ion Beam Techniques and Quantum Chemical Methods.

    Science.gov (United States)

    López, E; Lucas, J M; de Andrés, J; Albertí, M; Bofill, J M; Aguilar, A

    2016-07-14

    Dehydrohalogenation and dehydration reactions of gas-phase i-C3H7Br and i-C3H7OH molecules induced by collision with Na(+), all participants being in their electronic ground state, were studied experimentally in our laboratory using a radiofrequency-guided ion beam apparatus and covering the 0.10-10.00 eV center of mass (CM) energy range. In Na(+) + i-C3H7Br collisions the formation of [C3H6-Na](+) and [HBr-Na](+) by dehydrohalogenation was observed and quantified, as well as that of the ion-molecule adduct [Na-i-C3H7Br](+) together with its decomposition products C3H7(+) and NaBr. In Na(+) + i-C3H7OH collisions the dehydration product [H2O-Na](+) was also found, while [C3H6-Na](+) was hardly detected. Moreover, the [Na-i-C3H7OH](+) adduct formation as well as its decomposition into C3H7(+) and NaOH were also quantified. For all these processes, absolute reaction cross sections were measured as a function of the CM collision energy. From measured excitation functions, rate constants for the formation of [C3H6-Na](+), [HBr-Na](+), and [H2O-Na](+) at 303 K were obtained. Complementing the experiments, exhaustive ab initio structure calculations at the MP2 level of theory were performed, giving information on the most relevant features of the potential energy surfaces (PESs) where the dehydrohalogenation, dehydration, and decomposition reactions take place adiabatically for both collision systems. On these PESs different stationary points associated with potential energy minima and transition state barriers were characterized, and their connectivity was ensured using the intrinsic-reaction-coordinate method. The main topology features of the ab initio calculated PESs allowed a qualitative interpretation of the experimental data also exposing the role of the sodium ion as a catalyst in elimination reactions.

  16. Folding of DsbB in mixed micelles

    DEFF Research Database (Denmark)

    Otzen, Daniel

    2003-01-01

    is sensitive to changes in lipid and detergent composition. As an attempt to overcome this problem, I present a kinetic analysis of the folding of a membrane protein, disulfide bond reducing protein B (DsbB), in a mixed micelle system consisting of varying molar ratios of sodium dodecyl sulfate (SDS...... data are always open to alternative interpretations, time-resolved studies in mixed micelles provide a useful approach to measure membrane protein stability over a wide range of concentrations of SDS and DM, as well as a framework for the future characterization of the DsbB folding mechanism....

  17. Biomarkers for DNA DSB inhibitors and radiotherapy clinical trials.

    Science.gov (United States)

    Liu, Stanley K; Olive, Peggy L; Bristow, Robert G

    2008-09-01

    Major technical advances in radiotherapy, including IMRT and image-guided radiotherapy, have allowed for improved physical precision and increased dose delivery to the tumor, with better sparing of surrounding normal tissue. The development of inhibitors of the sensing and repair of DNA double-strand breaks (DSBs) is exciting and could be combined with precise radiotherapy targeting to improve local control following radiotherapy. However, caution must be exercised in order that DSB inhibitors are combined with radiotherapy in such a manner as to preserve the therapeutic ratio by exploiting repair deficiencies in malignant cells over that of normal cells. In this review, we discuss the rationale and current approaches to targeting DSB sensing and repair pathways in combined modality with radiotherapy. We also describe potential biomarkers that could be useful in detecting functional inhibition of DSB repair in a patient's tissues during clinical radiotherapy trials. Finally, we examine a number of issues relating to the use of DSB-inhibiting molecular agents and radiotherapy in the context of the tumor microenvironment, effects on normal tissues and the optimal timing and duration of the agent in relation to fractionated radiotherapy.

  18. A new light on the meiotic DSB catalytic complex.

    Science.gov (United States)

    Robert, Thomas; Vrielynck, Nathalie; Mézard, Christine; de Massy, Bernard; Grelon, Mathilde

    2016-06-01

    Meiotic recombination is initiated by the formation of programmed DNA double-strand breaks (DSBs). More than 15 years ago, Spo11 was identified as the protein responsible for meiotic DSB formation, notably because of its striking similarities with the A subunit of topoisomerase VI (TopoVI). TopoVI are enzymes that modify DNA topology by generating transient DSBs and are active as heterotetramers, composed of two A and two B subunits. A2 dimers catalyse the DNA cleavage reaction, whereas the B subunits regulate A2 conformation, DNA capture, cleavage and re-ligation. The recent identification in plants and mammals of a B-like TopoVI subunit that interacts with SPO11 and is required for meiotic DSB formation makes us to reconsider our understanding of the meiotic DSB catalytic complex. We provide here an overview of the knowledge on TopoVI structure and mode of action and we compare them with their meiotic counterparts. This allows us to discuss the nature, structure and functions of the meiotic TopoVI-like complex during meiotic DSB formation.

  19. Anterior segment optical coherence tomography for the diagnosis of corneal dystrophies according to the IC3D classification.

    Science.gov (United States)

    Siebelmann, Sebastian; Scholz, Paula; Sonnenschein, Simon; Bachmann, Björn; Matthaei, Mario; Cursiefen, Claus; Heindl, Ludwig M

    2017-08-09

    Corneal dystrophies are categorized according to the International Committee for Classification of Corneal Dystrophies (IC3D) classification, and their treatment depends on the affected structures and layer of the cornea. Therefore, estimating the depth and extent of the morphological changes due to the specific dystrophy is crucial when deciding between different treatment options. Besides superficial laser treatments and penetrating keratoplasty, minimal invasive lamellar keratoplasties such as Descemet membrane endothelial keratoplasty, deep anterior lamellar keratoplasty, or Descemet stripping automated keratoplasty have become increasingly popular to exchange the specific opaque layers in dystrophic eyes. To determine the morphological changes of the cornea in the different dystrophies, in addition to slit-lamp examination, anterior segment optical coherence tomography has become an important tool with nearly histological resolution. Nonetheless, only a few case series describe the characteristics of changes seen on anterior segment optical coherence tomography. Therefore, we summarize anterior segment optical coherence tomography signs and correlate with slit-lamp examination, as well as the histopathological findings, of corneal dystrophies according to the IC3D classification. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Budding yeast ATM/ATR control meiotic double-strand break (DSB) levels by down-regulating Rec114, an essential component of the DSB-machinery.

    Science.gov (United States)

    Carballo, Jesús A; Panizza, Silvia; Serrentino, Maria Elisabetta; Johnson, Anthony L; Geymonat, Marco; Borde, Valérie; Klein, Franz; Cha, Rita S

    2013-06-01

    An essential feature of meiosis is Spo11 catalysis of programmed DNA double strand breaks (DSBs). Evidence suggests that the number of DSBs generated per meiosis is genetically determined and that this ability to maintain a pre-determined DSB level, or "DSB homeostasis", might be a property of the meiotic program. Here, we present direct evidence that Rec114, an evolutionarily conserved essential component of the meiotic DSB-machinery, interacts with DSB hotspot DNA, and that Tel1 and Mec1, the budding yeast ATM and ATR, respectively, down-regulate Rec114 upon meiotic DSB formation through phosphorylation. Mimicking constitutive phosphorylation reduces the interaction between Rec114 and DSB hotspot DNA, resulting in a reduction and/or delay in DSB formation. Conversely, a non-phosphorylatable rec114 allele confers a genome-wide increase in both DSB levels and in the interaction between Rec114 and the DSB hotspot DNA. These observations strongly suggest that Tel1 and/or Mec1 phosphorylation of Rec114 following Spo11 catalysis down-regulates DSB formation by limiting the interaction between Rec114 and DSB hotspots. We also present evidence that Ndt80, a meiosis specific transcription factor, contributes to Rec114 degradation, consistent with its requirement for complete cessation of DSB formation. Loss of Rec114 foci from chromatin is associated with homolog synapsis but independent of Ndt80 or Tel1/Mec1 phosphorylation. Taken together, we present evidence for three independent ways of regulating Rec114 activity, which likely contribute to meiotic DSBs-homeostasis in maintaining genetically determined levels of breaks.

  1. Budding yeast ATM/ATR control meiotic double-strand break (DSB levels by down-regulating Rec114, an essential component of the DSB-machinery.

    Directory of Open Access Journals (Sweden)

    Jesús A Carballo

    2013-06-01

    Full Text Available An essential feature of meiosis is Spo11 catalysis of programmed DNA double strand breaks (DSBs. Evidence suggests that the number of DSBs generated per meiosis is genetically determined and that this ability to maintain a pre-determined DSB level, or "DSB homeostasis", might be a property of the meiotic program. Here, we present direct evidence that Rec114, an evolutionarily conserved essential component of the meiotic DSB-machinery, interacts with DSB hotspot DNA, and that Tel1 and Mec1, the budding yeast ATM and ATR, respectively, down-regulate Rec114 upon meiotic DSB formation through phosphorylation. Mimicking constitutive phosphorylation reduces the interaction between Rec114 and DSB hotspot DNA, resulting in a reduction and/or delay in DSB formation. Conversely, a non-phosphorylatable rec114 allele confers a genome-wide increase in both DSB levels and in the interaction between Rec114 and the DSB hotspot DNA. These observations strongly suggest that Tel1 and/or Mec1 phosphorylation of Rec114 following Spo11 catalysis down-regulates DSB formation by limiting the interaction between Rec114 and DSB hotspots. We also present evidence that Ndt80, a meiosis specific transcription factor, contributes to Rec114 degradation, consistent with its requirement for complete cessation of DSB formation. Loss of Rec114 foci from chromatin is associated with homolog synapsis but independent of Ndt80 or Tel1/Mec1 phosphorylation. Taken together, we present evidence for three independent ways of regulating Rec114 activity, which likely contribute to meiotic DSBs-homeostasis in maintaining genetically determined levels of breaks.

  2. Budding yeast ATM/ATR control meiotic double-strand break (DSB) levels by down-regulating Rec114, an essential component of the DSB-machinery.

    OpenAIRE

    Carballo, Jesús A.; Panizza, Silvia; Serrentino, Maria Elisabetta; Anthony L Johnson; Geymonat, Marco; Borde, Valérie; Klein, Franz; Cha, Rita S.

    2013-01-01

    An essential feature of meiosis is Spo11 catalysis of programmed DNA double strand breaks (DSBs). Evidence suggests that the number of DSBs generated per meiosis is genetically determined and that this ability to maintain a pre-determined DSB level, or "DSB homeostasis", might be a property of the meiotic program. Here, we present direct evidence that Rec114, an evolutionarily conserved essential component of the meiotic DSB-machinery, interacts with DSB hotspot DNA, and that Tel1 and Mec1, t...

  3. Unique structure of iC3b resolved at a resolution of 24 Å by 3D-electron microscopy.

    Science.gov (United States)

    Alcorlo, Martin; Martínez-Barricarte, Ruben; Fernández, Francisco J; Rodríguez-Gallego, César; Round, Adam; Vega, M Cristina; Harris, Claire L; de Cordoba, Santiago Rodríguez; Llorca, Oscar

    2011-08-01

    Activation of C3, deposition of C3b on the target surface, and subsequent amplification by formation of a C3-cleaving enzyme (C3-convertase; C3bBb) triggers the effector functions of complement that result in inflammation and cell lysis. Concurrently, surface-bound C3b is proteolyzed to iC3b by factor I and appropriate cofactors. iC3b then interacts with the complement receptors (CR) of the Ig superfamily, CR2 (CD21), CR3 (CD11b/CD18), and CR4 (CD11c/CD18) on leukocytes, down-modulating inflammation, enhancing B cell-mediated immunity, and targeting pathogens for clearance by phagocytosis. Using EM and small-angle X-ray scattering, we now present a medium-resolution structure of iC3b (24 Å). iC3b displays a unique conformation with structural features distinct from any other C3 fragment. The macroglobulin ring in iC3b is similar to that in C3b, whereas the TED (thioester-containing domain) domain and the remnants of the CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domain have moved to locations more similar to where they were in native C3. A consequence of this large conformational change is the disruption of the factor B binding site, which renders iC3b unable to assemble a C3-convertase. This structural model also justifies the decreased interaction between iC3b and complement regulators and the recognition of iC3b by the CR of the Ig superfamily, CR2, CR3, and CR4. These data further illustrate the extraordinary conformational versatility of C3 to accommodate a great diversity of functional activities.

  4. Unique structure of iC3b resolved at a resolution of 24 Å by 3D-electron microscopy

    Science.gov (United States)

    Alcorlo, Martin; Martínez-Barricarte, Ruben; Fernández, Francisco J.; Rodríguez-Gallego, César; Round, Adam; Vega, M. Cristina; Harris, Claire L.; de Cordoba, Santiago Rodríguez; Llorca, Oscar

    2011-01-01

    Activation of C3, deposition of C3b on the target surface, and subsequent amplification by formation of a C3-cleaving enzyme (C3-convertase; C3bBb) triggers the effector functions of complement that result in inflammation and cell lysis. Concurrently, surface-bound C3b is proteolyzed to iC3b by factor I and appropriate cofactors. iC3b then interacts with the complement receptors (CR) of the Ig superfamily, CR2 (CD21), CR3 (CD11b/CD18), and CR4 (CD11c/CD18) on leukocytes, down-modulating inflammation, enhancing B cell-mediated immunity, and targeting pathogens for clearance by phagocytosis. Using EM and small-angle X-ray scattering, we now present a medium-resolution structure of iC3b (24 Å). iC3b displays a unique conformation with structural features distinct from any other C3 fragment. The macroglobulin ring in iC3b is similar to that in C3b, whereas the TED (thioester-containing domain) domain and the remnants of the CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domain have moved to locations more similar to where they were in native C3. A consequence of this large conformational change is the disruption of the factor B binding site, which renders iC3b unable to assemble a C3-convertase. This structural model also justifies the decreased interaction between iC3b and complement regulators and the recognition of iC3b by the CR of the Ig superfamily, CR2, CR3, and CR4. These data further illustrate the extraordinary conformational versatility of C3 to accommodate a great diversity of functional activities. PMID:21788512

  5. Homeostatic regulation of meiotic DSB formation by ATM/ATR

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, Tim J.; Wardell, Kayleigh; Garcia, Valerie; Neale, Matthew J., E-mail: m.neale@sussex.ac.uk

    2014-11-15

    Ataxia–telangiectasia mutated (ATM) and RAD3-related (ATR) are widely known as being central players in the mitotic DNA damage response (DDR), mounting responses to DNA double-strand breaks (DSBs) and single-stranded DNA (ssDNA) respectively. The DDR signalling cascade couples cell cycle control to damage-sensing and repair processes in order to prevent untimely cell cycle progression while damage still persists [1]. Both ATM/ATR are, however, also emerging as essential factors in the process of meiosis; a specialised cell cycle programme responsible for the formation of haploid gametes via two sequential nuclear divisions. Central to achieving accurate meiotic chromosome segregation is the introduction of numerous DSBs spread across the genome by the evolutionarily conserved enzyme, Spo11. This review seeks to explore and address how cells utilise ATM/ATR pathways to regulate Spo11-DSB formation, establish DSB homeostasis and ensure meiosis is completed unperturbed.

  6. Homeostatic regulation of meiotic DSB formation by ATM/ATR.

    Science.gov (United States)

    Cooper, Tim J; Wardell, Kayleigh; Garcia, Valerie; Neale, Matthew J

    2014-11-15

    Ataxia-telangiectasia mutated (ATM) and RAD3-related (ATR) are widely known as being central players in the mitotic DNA damage response (DDR), mounting responses to DNA double-strand breaks (DSBs) and single-stranded DNA (ssDNA) respectively. The DDR signalling cascade couples cell cycle control to damage-sensing and repair processes in order to prevent untimely cell cycle progression while damage still persists [1]. Both ATM/ATR are, however, also emerging as essential factors in the process of meiosis; a specialised cell cycle programme responsible for the formation of haploid gametes via two sequential nuclear divisions. Central to achieving accurate meiotic chromosome segregation is the introduction of numerous DSBs spread across the genome by the evolutionarily conserved enzyme, Spo11. This review seeks to explore and address how cells utilise ATM/ATR pathways to regulate Spo11-DSB formation, establish DSB homeostasis and ensure meiosis is completed unperturbed.

  7. Spontaneous vesicle formation from DSB/AOT mixed system

    Institute of Scientific and Technical Information of China (English)

    CHEN Wenjun; ZHAI Limin; LI Ganzuo; MENG Xiangguang; ZENG Xiancheng

    2003-01-01

    Spontaneous vesicles from the aqueous mixtures of dodecyl sulfonate betaine (DSB) and sodium bis (2-ethylhexyl) sulfosuccinate (AOT) at certain mixingratios have been demonstrated by using calorimetry, freeze-frac- ture transmission electronic microscopy (TEM), negative- staining TEM and dynamic light scattering (DLS) methods. The addition of NaCl will promote vesicle formation and the heat effect of monodisperse vesicle system is greatest. Meanwhile the mechanism was analyzed from the viewpoint of packing parameter f, molecular geometry structure and interaction.

  8. Gene Targeting Without DSB Induction Is Inefficient in Barley.

    Science.gov (United States)

    Horvath, Mihaly; Steinbiss, Hans-Henning; Reiss, Bernd

    2016-01-01

    Double strand-break (DSB) induction allowed efficient gene targeting in barley (Hordeum vulgare), but little is known about efficiencies in its absence. To obtain such data, an assay system based on the acetolactate synthase (ALS) gene was established, a target gene which had been used previously in rice and Arabidopsis thaliana. Expression of recombinases RAD51 and RAD54 had been shown to improve gene targeting in A. thaliana and positive-negative (P-N) selection allows the routine production of targeted mutants without DSB induction in rice. We implemented these approaches in barley and analysed gene targeting with the ALS gene in wild type and RAD51 and RAD54 transgenic lines. In addition, P-N selection was tested. In contrast to the high gene targeting efficiencies obtained in the absence of DSB induction in A. thaliana or rice, not one single gene targeting event was obtained in barley. These data suggest that gene targeting efficiencies are very low in barley and can substantially differ between different plants, even at the same target locus. They also suggest that the amount of labour and time would become unreasonably high to use these methods as a tool in routine applications. This is particularly true since DSB induction offers efficient alternatives. Barley, unlike rice and A. thaliana has a large, complex genome, suggesting that genome size or complexity could be the reason for the low efficiencies. We discuss to what extent transformation methods, genome size or genome complexity could contribute to the striking differences in the gene targeting efficiencies between barley, rice and A. thaliana.

  9. PHF11 promotes DSB resection, ATR signaling, and HR

    Science.gov (United States)

    Gong, Yi; Handa, Naofumi; Kowalczykowski, Stephen C.; de Lange, Titia

    2017-01-01

    Resection of double-strand breaks (DSBs) plays a critical role in their detection and appropriate repair. The 3′ ssDNA protrusion formed through resection activates the ATR-dependent DNA damage response (DDR) and is required for DSB repair by homologous recombination (HR). Here we report that PHF11 (plant homeodomain finger 11) encodes a previously unknown DDR factor involved in 5′ end resection, ATR signaling, and HR. PHF11 was identified based on its association with deprotected telomeres and localized to sites of DNA damage in S phase. Depletion of PHF11 diminished the ATR signaling response to telomere dysfunction and genome-wide DNA damage, reduced end resection at sites of DNA damage, resulted in compromised HR and misrejoining of S-phase DSBs, and increased the sensitivity to DNA-damaging agents. PHF11 interacted with the ssDNA-binding protein RPA and was found in a complex with several nucleases, including the 5′ dsDNA exonuclease EXO1. Biochemical experiments demonstrated that PHF11 stimulates EXO1 by overcoming its inhibition by RPA, suggesting that PHF11 acts (in part) by promoting 5′ end resection at RPA-bound sites of DNA damage. These findings reveal a role for PHF11 in DSB resection, DNA damage signaling, and DSB repair. PMID:28115467

  10. PHF11 promotes DSB resection, ATR signaling, and HR.

    Science.gov (United States)

    Gong, Yi; Handa, Naofumi; Kowalczykowski, Stephen C; de Lange, Titia

    2017-01-01

    Resection of double-strand breaks (DSBs) plays a critical role in their detection and appropriate repair. The 3' ssDNA protrusion formed through resection activates the ATR-dependent DNA damage response (DDR) and is required for DSB repair by homologous recombination (HR). Here we report that PHF11 (plant homeodomain finger 11) encodes a previously unknown DDR factor involved in 5' end resection, ATR signaling, and HR. PHF11 was identified based on its association with deprotected telomeres and localized to sites of DNA damage in S phase. Depletion of PHF11 diminished the ATR signaling response to telomere dysfunction and genome-wide DNA damage, reduced end resection at sites of DNA damage, resulted in compromised HR and misrejoining of S-phase DSBs, and increased the sensitivity to DNA-damaging agents. PHF11 interacted with the ssDNA-binding protein RPA and was found in a complex with several nucleases, including the 5' dsDNA exonuclease EXO1. Biochemical experiments demonstrated that PHF11 stimulates EXO1 by overcoming its inhibition by RPA, suggesting that PHF11 acts (in part) by promoting 5' end resection at RPA-bound sites of DNA damage. These findings reveal a role for PHF11 in DSB resection, DNA damage signaling, and DSB repair.

  11. Cancer TARGETases: DSB repair as a pharmacological target.

    Science.gov (United States)

    Samadder, Pounami; Aithal, Rakesh; Belan, Ondrej; Krejci, Lumir

    2016-05-01

    Cancer is a disease attributed to the accumulation of DNA damages due to incapacitation of DNA repair pathways resulting in genomic instability and a mutator phenotype. Among the DNA lesions, double stranded breaks (DSBs) are the most toxic forms of DNA damage which may arise as a result of extrinsic DNA damaging agents or intrinsic replication stress in fast proliferating cancer cells. Accurate repair of DSBs is therefore paramount to the cell survival, and several classes of proteins such as kinases, nucleases, helicases or core recombinational proteins have pre-defined jobs in precise execution of DSB repair pathways. On one hand, the proper functioning of these proteins ensures maintenance of genomic stability in normal cells, and on the other hand results in resistance to various drugs employed in cancer therapy and therefore presents a suitable opportunity for therapeutic targeting. Higher relapse and resistance in cancer patients due to non-specific, cytotoxic therapies is an alarming situation and it is becoming more evident to employ personalized treatment based on the genetic landscape of the cancer cells. For the success of personalized treatment, it is of immense importance to identify more suitable targetable proteins in DSB repair pathways and also to explore new synthetic lethal interactions with these pathways. Here we review the various alternative approaches to target the various protein classes termed as cancer TARGETases in DSB repair pathway to obtain more beneficial and selective therapy.

  12. Engineered DsbC chimeras catalyze both protein oxidation and disulfide-bond isomerization in Escherichia coli: Reconciling two competing pathways

    OpenAIRE

    Segatori, Laura; Paukstelis, Paul J.; Gilbert, Hiram F.; Georgiou, George

    2004-01-01

    In the Escherichia coli periplasm, the formation of protein disulfide bonds is catalyzed by DsbA and DsbC. DsbA is a monomer that is maintained in a fully oxidized state by the membrane enzyme DsbB, whereas DsbC is a dimer that is kept reduced by a second membrane protein, DsbD. Although the catalytic regions of DsbA and DsbC are composed of structurally homologous thioredoxin motif domains, DsbA serves only as an oxidase in vivo, whereas DsbC catalyzes disulfide reduction and isomerization a...

  13. DNA DSB repair pathway choice: an orchestrated handover mechanism.

    Science.gov (United States)

    Kakarougkas, A; Jeggo, P A

    2014-03-01

    DNA double strand breaks (DSBs) are potential lethal lesions but can also lead to chromosome rearrangements, a step promoting carcinogenesis. DNA non-homologous end-joining (NHEJ) is the major DSB rejoining process and occurs in all cell cycle stages. Homologous recombination (HR) can additionally function to repair irradiation-induced two-ended DSBs in G2 phase. In mammalian cells, HR predominantly uses a sister chromatid as a template for DSB repair; thus HR functions only in late S/G2 phase. Here, we review current insight into the interplay between HR and NHEJ in G2 phase. We argue that NHEJ represents the first choice pathway, repairing approximately 80% of X-ray-induced DSBs with rapid kinetics. However, a subset of DSBs undergoes end resection and repair by HR. 53BP1 restricts resection, thereby promoting NHEJ. During the switch from NHEJ to HR, 53BP1 is repositioned to the periphery of enlarged irradiation-induced foci (IRIF) via a BRCA1-dependent process. K63-linked ubiquitin chains, which also form at IRIF, are also repositioned as well as receptor-associated protein 80 (RAP80), a ubiquitin binding protein. RAP80 repositioning requires POH1, a proteasome component. Thus, the interfacing barriers to HR, 53BP1 and RAP80 are relieved by POH1 and BRCA1, respectively. Removal of RAP80 from the IRIF core is required for loss of the ubiquitin chains and 53BP1, and for efficient replication protein A foci formation. We propose that NHEJ is used preferentially to HR because it is a compact process that does not necessitate extensive chromatin changes in the DSB vicinity.

  14. Negative Regulation of DsbA-L Gene Expression by the Transcription Factor Sp1

    OpenAIRE

    Fang, Qichen; Yang, Wenjing; Li, Huating; Hu, Wenxiu; Chen, Lihui; Jiang, Shan; Dong, Kun; Song, Qianqian; Wang, Chen; Chen, Shuo; LIU, FENG; Jia, Weiping

    2014-01-01

    Disulfide-bond A oxidoreductase-like protein (DsbA-L) possesses beneficial effects such as promoting adiponectin multimerization and stability, increasing insulin sensitivity, and enhancing energy metabolism. The expression level of DsbA-L is negatively correlated with obesity in mice and humans, but the underlying mechanisms remain unknown. To address this question, we generated reporter gene constructs containing the promoter sequence of the mouse DsbA-L gene. Deletion analysis showed that ...

  15. Characterization of new DsbB-like thiol-oxidoreductases of Campylobacter jejuni and Helicobacter pylori and classification of the DsbB family based on phylogenomic, structural and functional criteria.

    Science.gov (United States)

    Raczko, Anna M; Bujnicki, Janusz M; Pawlowski, Marcin; Godlewska, Renata; Lewandowska, Magdalena; Jagusztyn-Krynicka, Elzbieta K

    2005-01-01

    In Gram-negative bacterial cells, disulfide bond formation occurs in the oxidative environment of the periplasm and is catalysed by Dsb (disulfide bond) proteins found in the periplasm and in the inner membrane. In this report the identification of a new subfamily of disulfide oxidoreductases encoded by a gene denoted dsbI, and functional characterization of DsbI proteins from Campylobacter jejuni and Helicobacter pylori, as well as DsbB from C. jejuni, are described. The N-terminal domain of DsbI is related to DsbB proteins and comprises five predicted transmembrane segments, while the C-terminal domain is predicted to locate to the periplasm and to fold into a beta-propeller structure. The dsbI gene is co-transcribed with a small ORF designated dba (dsbI-accessory). Based on a series of deletion and complementation experiments it is proposed that DsbB can complement the lack of DsbI but not the converse. In the presence of DsbB, the activity of DsbI was undetectable, hence it probably acts only on a subset of possible substrates of DsbB. To reconstruct the principal events in the evolution of DsbB and DsbI proteins, sequences of all their homologues identifiable in databases were analysed. In the course of this study, previously undetected variations on the common thiol-oxidoreductase theme were identified, such as development of an additional transmembrane helix and loss or migration of the second pair of Cys residues between two distinct periplasmic loops. In conjunction with the experimental characterization of two members of the DsbI lineage, this analysis has resulted in the first comprehensive classification of the DsbB/DsbI family based on structural, functional and evolutionary criteria.

  16. Identification of DSB-1, a protein required for initiation of meiotic recombination in Caenorhabditis elegans, illuminates a crossover assurance checkpoint.

    Directory of Open Access Journals (Sweden)

    Ericca L Stamper

    Full Text Available Meiotic recombination, an essential aspect of sexual reproduction, is initiated by programmed DNA double-strand breaks (DSBs. DSBs are catalyzed by the widely-conserved Spo11 enzyme; however, the activity of Spo11 is regulated by additional factors that are poorly conserved through evolution. To expand our understanding of meiotic regulation, we have characterized a novel gene, dsb-1, that is specifically required for meiotic DSB formation in the nematode Caenorhabditis elegans. DSB-1 localizes to chromosomes during early meiotic prophase, coincident with the timing of DSB formation. DSB-1 also promotes normal protein levels and chromosome localization of DSB-2, a paralogous protein that plays a related role in initiating recombination. Mutations that disrupt crossover formation result in prolonged DSB-1 association with chromosomes, suggesting that nuclei may remain in a DSB-permissive state. Extended DSB-1 localization is seen even in mutants with defects in early recombination steps, including spo-11, suggesting that the absence of crossover precursors triggers the extension. Strikingly, failure to form a crossover precursor on a single chromosome pair is sufficient to extend the localization of DSB-1 on all chromosomes in the same nucleus. Based on these observations we propose a model for crossover assurance that acts through DSB-1 to maintain a DSB-permissive state until all chromosome pairs acquire crossover precursors. This work identifies a novel component of the DSB machinery in C. elegans, and sheds light on an important pathway that regulates DSB formation for crossover assurance.

  17. Identification of DSB-1, a protein required for initiation of meiotic recombination in Caenorhabditis elegans, illuminates a crossover assurance checkpoint.

    Science.gov (United States)

    Stamper, Ericca L; Rodenbusch, Stacia E; Rosu, Simona; Ahringer, Julie; Villeneuve, Anne M; Dernburg, Abby F

    2013-01-01

    Meiotic recombination, an essential aspect of sexual reproduction, is initiated by programmed DNA double-strand breaks (DSBs). DSBs are catalyzed by the widely-conserved Spo11 enzyme; however, the activity of Spo11 is regulated by additional factors that are poorly conserved through evolution. To expand our understanding of meiotic regulation, we have characterized a novel gene, dsb-1, that is specifically required for meiotic DSB formation in the nematode Caenorhabditis elegans. DSB-1 localizes to chromosomes during early meiotic prophase, coincident with the timing of DSB formation. DSB-1 also promotes normal protein levels and chromosome localization of DSB-2, a paralogous protein that plays a related role in initiating recombination. Mutations that disrupt crossover formation result in prolonged DSB-1 association with chromosomes, suggesting that nuclei may remain in a DSB-permissive state. Extended DSB-1 localization is seen even in mutants with defects in early recombination steps, including spo-11, suggesting that the absence of crossover precursors triggers the extension. Strikingly, failure to form a crossover precursor on a single chromosome pair is sufficient to extend the localization of DSB-1 on all chromosomes in the same nucleus. Based on these observations we propose a model for crossover assurance that acts through DSB-1 to maintain a DSB-permissive state until all chromosome pairs acquire crossover precursors. This work identifies a novel component of the DSB machinery in C. elegans, and sheds light on an important pathway that regulates DSB formation for crossover assurance.

  18. Staphylococcus aureus DsbA is a membrane-bound lipoprotein with thiol-disulfide oxidoreductase activity.

    Science.gov (United States)

    Dumoulin, Alexis; Grauschopf, Ulla; Bischoff, Markus; Thöny-Meyer, Linda; Berger-Bächi, Brigitte

    2005-11-01

    DsbA proteins, the primary catalysts of protein disulfide bond formation, are known to affect virulence and penicillin resistance in Gram-negative bacteria. We identified a putative DsbA homologue in the Gram-positive pathogen Staphylococcus aureus that was able to restore the motility phenotype of an Escherichia coli dsbA mutant and thus demonstrated a functional thiol oxidoreductase activity. The staphylococcal DsbA (SaDsbA) had a strong oxidative redox potential of -131 mV. The persistence of the protein throughout the growth cycle despite its predominant transcription during exponential growth phase suggested a rather long half-life for the SaDsbA. SaDsbA was found to be a membrane localised lipoprotein, supporting a role in disulfide bond formation. But so far, neither in vitro nor in vivo phenotype could be identified in a staphylococcal dsbA mutant, leaving its physiological role unknown. The inability of SaDsbA to interact with the E. coli DsbB and the lack of an apparent staphylococcal DsbB homologue suggest an alternative re-oxidation pathway for the SaDsbA.

  19. Functional and Bioinformatics Analysis of Two Campylobacter jejuni Homologs of the Thiol-Disulfide Oxidoreductase, DsbA

    Science.gov (United States)

    Grabowska, Anna D.; Wywiał, Ewa; Dunin-Horkawicz, Stanislaw; Łasica, Anna M.; Wösten, Marc M. S. M.; Nagy-Staroń, Anna; Godlewska, Renata; Bocian-Ostrzycka, Katarzyna; Pieńkowska, Katarzyna; Łaniewski, Paweł; Bujnicki, Janusz M.; van Putten, Jos P. M.; Jagusztyn-Krynicka, E. Katarzyna

    2014-01-01

    Background Bacterial Dsb enzymes are involved in the oxidative folding of many proteins, through the formation of disulfide bonds between their cysteine residues. The Dsb protein network has been well characterized in cells of the model microorganism Escherichia coli. To gain insight into the functioning of the Dsb system in epsilon-Proteobacteria, where it plays an important role in the colonization process, we studied two homologs of the main Escherichia coli Dsb oxidase (EcDsbA) that are present in the cells of the enteric pathogen Campylobacter jejuni, the most frequently reported bacterial cause of human enteritis in the world. Methods and Results Phylogenetic analysis suggests the horizontal transfer of the epsilon-Proteobacterial DsbAs from a common ancestor to gamma-Proteobacteria, which then gave rise to the DsbL lineage. Phenotype and enzymatic assays suggest that the two C. jejuni DsbAs play different roles in bacterial cells and have divergent substrate spectra. CjDsbA1 is essential for the motility and autoagglutination phenotypes, while CjDsbA2 has no impact on those processes. CjDsbA1 plays a critical role in the oxidative folding that ensures the activity of alkaline phosphatase CjPhoX, whereas CjDsbA2 is crucial for the activity of arylsulfotransferase CjAstA, encoded within the dsbA2-dsbB-astA operon. Conclusions Our results show that CjDsbA1 is the primary thiol-oxidoreductase affecting life processes associated with bacterial spread and host colonization, as well as ensuring the oxidative folding of particular protein substrates. In contrast, CjDsbA2 activity does not affect the same processes and so far its oxidative folding activity has been demonstrated for one substrate, arylsulfotransferase CjAstA. The results suggest the cooperation between CjDsbA2 and CjDsbB. In the case of the CjDsbA1, this cooperation is not exclusive and there is probably another protein to be identified in C. jejuni cells that acts to re-oxidize CjDsbA1. Altogether

  20. Functional and bioinformatics analysis of two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA.

    Directory of Open Access Journals (Sweden)

    Anna D Grabowska

    Full Text Available BACKGROUND: Bacterial Dsb enzymes are involved in the oxidative folding of many proteins, through the formation of disulfide bonds between their cysteine residues. The Dsb protein network has been well characterized in cells of the model microorganism Escherichia coli. To gain insight into the functioning of the Dsb system in epsilon-Proteobacteria, where it plays an important role in the colonization process, we studied two homologs of the main Escherichia coli Dsb oxidase (EcDsbA that are present in the cells of the enteric pathogen Campylobacter jejuni, the most frequently reported bacterial cause of human enteritis in the world. METHODS AND RESULTS: Phylogenetic analysis suggests the horizontal transfer of the epsilon-Proteobacterial DsbAs from a common ancestor to gamma-Proteobacteria, which then gave rise to the DsbL lineage. Phenotype and enzymatic assays suggest that the two C. jejuni DsbAs play different roles in bacterial cells and have divergent substrate spectra. CjDsbA1 is essential for the motility and autoagglutination phenotypes, while CjDsbA2 has no impact on those processes. CjDsbA1 plays a critical role in the oxidative folding that ensures the activity of alkaline phosphatase CjPhoX, whereas CjDsbA2 is crucial for the activity of arylsulfotransferase CjAstA, encoded within the dsbA2-dsbB-astA operon. CONCLUSIONS: Our results show that CjDsbA1 is the primary thiol-oxidoreductase affecting life processes associated with bacterial spread and host colonization, as well as ensuring the oxidative folding of particular protein substrates. In contrast, CjDsbA2 activity does not affect the same processes and so far its oxidative folding activity has been demonstrated for one substrate, arylsulfotransferase CjAstA. The results suggest the cooperation between CjDsbA2 and CjDsbB. In the case of the CjDsbA1, this cooperation is not exclusive and there is probably another protein to be identified in C. jejuni cells that acts to re

  1. Virtual Screening of Peptide and Peptidomimetic Fragments Targeted to Inhibit Bacterial Dithiol Oxidase DsbA.

    Directory of Open Access Journals (Sweden)

    Wilko Duprez

    Full Text Available Antibacterial drugs with novel scaffolds and new mechanisms of action are desperately needed to address the growing problem of antibiotic resistance. The periplasmic oxidative folding system in Gram-negative bacteria represents a possible target for anti-virulence antibacterials. By targeting virulence rather than viability, development of resistance and side effects (through killing host native microbiota might be minimized. Here, we undertook the design of peptidomimetic inhibitors targeting the interaction between the two key enzymes of oxidative folding, DsbA and DsbB, with the ultimate goal of preventing virulence factor assembly. Structures of DsbB--or peptides--complexed with DsbA revealed key interactions with the DsbA active site cysteine, and with a hydrophobic groove adjacent to the active site. The present work aimed to discover peptidomimetics that target the hydrophobic groove to generate non-covalent DsbA inhibitors. The previously reported structure of a Proteus mirabilis DsbA active site cysteine mutant, in a non-covalent complex with the heptapeptide PWATCDS, was used as an in silico template for virtual screening of a peptidomimetic fragment library. The highest scoring fragment compound and nine derivatives were synthesized and evaluated for DsbA binding and inhibition. These experiments discovered peptidomimetic fragments with inhibitory activity at millimolar concentrations. Although only weakly potent relative to larger covalent peptide inhibitors that interact through the active site cysteine, these fragments offer new opportunities as templates to build non-covalent inhibitors. The results suggest that non-covalent peptidomimetics may need to interact with sites beyond the hydrophobic groove in order to produce potent DsbA inhibitors.

  2. Kinetics of DSB rejoining and formation of simple chromosome exchange aberrations

    Science.gov (United States)

    Cucinotta, F. A.; Nikjoo, H.; O'Neill, P.; Goodhead, D. T.

    2000-01-01

    PURPOSE: To investigate the role of kinetics in the processing of DNA double strand breaks (DSB), and the formation of simple chromosome exchange aberrations following X-ray exposures to mammalian cells based on an enzymatic approach. METHODS: Using computer simulations based on a biochemical approach, rate-equations that describe the processing of DSB through the formation of a DNA-enzyme complex were formulated. A second model that allows for competition between two processing pathways was also formulated. The formation of simple exchange aberrations was modelled as misrepair during the recombination of single DSB with undamaged DNA. Non-linear coupled differential equations corresponding to biochemical pathways were solved numerically by fitting to experimental data. RESULTS: When mediated by a DSB repair enzyme complex, the processing of single DSB showed a complex behaviour that gives the appearance of fast and slow components of rejoining. This is due to the time-delay caused by the action time of enzymes in biomolecular reactions. It is shown that the kinetic- and dose-responses of simple chromosome exchange aberrations are well described by a recombination model of DSB interacting with undamaged DNA when aberration formation increases with linear dose-dependence. Competition between two or more recombination processes is shown to lead to the formation of simple exchange aberrations with a dose-dependence similar to that of a linear quadratic model. CONCLUSIONS: Using a minimal number of assumptions, the kinetics and dose response observed experimentally for DSB rejoining and the formation of simple chromosome exchange aberrations are shown to be consistent with kinetic models based on enzymatic reaction approaches. A non-linear dose response for simple exchange aberrations is possible in a model of recombination of DNA containing a DSB with undamaged DNA when two or more pathways compete for DSB repair.

  3. On the Jurisdiction of DSB in the Context of the Human Right Law%人权法视野下的 DSB 管辖权

    Institute of Scientific and Technical Information of China (English)

    曾炜; 谭和平

    2014-01-01

    管辖权的确定是任何争端解决的前提条件,对于WTO争端解决机构审理案件来说也概莫能外。通过分析启动WTO争端解决程序的条件和DSB管辖权的特点,指出DSB管辖权是有限的,进而强调DSB不能对人权事项行使管辖权,但这并不妨碍DSB以符合人权法的方式就争议问题作出裁决。%To confirm the jurisdiction is the precondition to resolve any dispute and the DSB of WTO is also not an exception before making a judgment .After analyzing the conditions of initiating the WTO dispute settlement mechanism and the charac-teristics of the jurisdiction of DSB ,the author points out that the jurisdiction of DSB is limited and DSB dose not have jurisdic-tion over the issues which relate to human rights .However ,this does not disturb DSB to make a judgment in conformity with human rights law .

  4. A receiver function study across the Dead Sea Basin (DSB)

    Science.gov (United States)

    Mohsen, A.; Asch, G.; Hofstetter, R.; Kind, R.; Weber, M.

    2008-12-01

    Beginning in September 2006, a temporary network of 30 broadband and 45 short-period seismic stations has been set up on both sides of the Dead Sea Basin (DSB). During one and a half year of successful operation, data were continuously recorded in the field at 100 Hz and 200 Hz sample frequency for the broadband and short-period seismic stations, respectively. The raw data were converted to miniseed format and archived as full seed volume in the GEOFON data center of the GFZ. In the present work, the Receiver Function Method has been applied to the three component passive source data to investigate seismic discontinuities from the crust down to the upper mantle. Unusual negative phases at about 1s delay time have been observed at several stations in the Dead Sea region on the top of the assumed salt diapir. First preliminary receiver function analysis reveals a crustal thickness of about 30 -35 km in the investigated area and possibly low-velocity layer beneath the Moho. It also shows a basin which is possibly filled with salt about 10 km thick beneath the Lisan peninsula (Dead Sea).

  5. Transcriptional regulation of the assT-dsbL-dsbI gene cluster in Salmonella enterica serovar Typhi IMSS-1 depends on LeuO, H-NS, and specific growth conditions.

    Science.gov (United States)

    Gallego-Hernández, A L; Hernández-Lucas, I; De la Cruz, M A; Olvera, L; Morett, E; Medina-Aparicio, L; Ramírez-Trujillo, J A; Vázquez, A; Fernández-Mora, M; Calva, E

    2012-05-01

    The assT gene encodes an arylsulfate sulfotransferase, an enzyme that catalyzes sulfuryl transfer from phenolic sulfate to a phenolic acceptor. In Salmonella enterica serovar Typhi IMSS-1, the assT gene is located upstream of the dsbL and dsbI genes, which are involved in a disulfide bond formation required for its activation. The assT-dsbL-dsbI gene cluster forms an operon transcribed by a LeuO-dependent promoter, in rich medium A (MA). Interestingly, in the absence of cloned leuO and in a ΔleuO background, two transcription start sites were detected for assT and two for dsbL-dsbI in minimal medium. The H-NS nucleoid protein repressed the expression of the assT-dsbL-dsbI LeuO-dependent operon, as well as of the assT transcriptional units. Thus, the expression of the assT-dsbL-dsbI gene cluster depends on the global regulatory proteins LeuO and H-NS, as well as on specific growth conditions.

  6. Radio-over-fiber DSB-to-SSB conversion using semiconductor lasers at stable locking dynamics.

    Science.gov (United States)

    Hsieh, Kun-Lin; Hung, Yu-Han; Hwang, Sheng-Kwang; Lin, Chien-Chung

    2016-05-01

    In radio-over-fiber systems, optical single-sideband (SSB) modulation signals are preferred to optical double-sideband (DSB) modulation signals for fiber distribution in order to mitigate the microwave power fading effect. However, typically adopted modulation schemes generate DSB signals, making DSB-to-SSB conversion necessary before or after fiber distribution. This study investigates a semiconductor laser at stable locking dynamics for such conversion. The conversion relies solely on the nonlinear dynamical interaction between an input DSB signal and the laser. Only a typical semiconductor laser is therefore required as the key conversion unit, and no pump or probe signal is necessary. The conversion can be achieved for a broad tunable range of microwave frequency up to at least 60 GHz. In addition, the conversion can be carried out even when the microwave frequency, the power of the input DSB signal, or the frequency of the input DSB signal fluctuates over a wide range, leading to high adaptability and stability of the conversion system. After conversion, while the microwave phase quality, such as linewidth and phase noise, is mainly preserved, a bit-error ratio down to 10-9 is achieved for a data rate up to at least 8 Gb/s with a detection sensitivity improvement of more than 1.5 dB.

  7. Gradual implementation of the meiotic recombination program via checkpoint pathways controlled by global DSB levels.

    Science.gov (United States)

    Joshi, Neeraj; Brown, M Scott; Bishop, Douglas K; Börner, G Valentin

    2015-03-05

    During meiosis, Spo11-induced double-strand breaks (DSBs) are processed into crossovers, ensuring segregation of homologous chromosomes (homologs). Meiotic DSB processing entails 5' end resection and preferred strand exchange with the homolog rather than the sister chromatid (homolog bias). In many organisms, DSBs appear gradually along the genome. Here we report unexpected effects of global DSB levels on local recombination events. Early-occurring, low-abundance "scout" DSBs lack homolog bias. Their resection and interhomolog processing are controlled by the conserved checkpoint proteins Tel1(ATM) kinase and Pch2(TRIP13) ATPase. Processing pathways controlled by Mec1(ATR) kinase take over these functions only above a distinct DSB threshold, resulting in progressive strengthening of the homolog bias. We conclude that Tel1(ATM)/Pch2 and Mec1(ATR) DNA damage response pathways are sequentially activated during wild-type meiosis because of their distinct sensitivities to global DSB levels. Moreover, relative DSB order controls the DSB repair pathway choice and, ultimately, recombination outcome.

  8. Crystallization and preliminary diffraction analysis of a DsbA homologue from Wolbachia pipientis

    Energy Technology Data Exchange (ETDEWEB)

    Kurz, M. [Institute for Molecular Bioscience and ARC Special Research Centre for Functional and Applied Genomics, University of Queensland, St Lucia, QLD 4072 (Australia); Iturbe-Ormaetxe, I. [School of Integrative Biology, The University of Queensland, St Lucia, QLD 4072 (Australia); Jarrott, R. [Institute for Molecular Bioscience and ARC Special Research Centre for Functional and Applied Genomics, University of Queensland, St Lucia, QLD 4072 (Australia); O’Neill, S. L. [School of Integrative Biology, The University of Queensland, St Lucia, QLD 4072 (Australia); Byriel, K. A.; Martin, J. L., E-mail: j.martin@imb.uq.edu.au; Heras, B., E-mail: j.martin@imb.uq.edu.au [Institute for Molecular Bioscience and ARC Special Research Centre for Functional and Applied Genomics, University of Queensland, St Lucia, QLD 4072 (Australia)

    2008-02-01

    The first crystallization of a W. pipientis protein, α-DsbA1, was achieved using hanging-drop and sitting-drop vapour diffusion. α-DsbA1 is one of two DsbA homologues encoded by the Gram-negative α-proteobacterium Wolbachia pipientis, an endosymbiont that can behave as a reproductive parasite in insects and as a mutualist in medically important filarial nematodes. The α-DsbA1 protein is thought to be important for the folding and secretion of Wolbachia proteins involved in the induction of reproductive distortions. Crystals of native and SeMet α-DsbA1 were grown by vapour diffusion and belong to the monoclinic space group C2, with unit-cell parameters a = 71.4, b = 49.5, c = 69.3 Å, β = 107.0° and one molecule in the asymmetric unit (44% solvent content). X-ray data were recorded from native crystals to a resolution of 2.01 Å using a copper anode and data from SeMet α-DsbA1 crystals were recorded to 2.45 Å resolution using a chromium anode.

  9. The effect of electroacupuncture at the MA-IC 3 endocrine ear acupoint on fasting blood glucose levels in type 2 diabetes mellitus patients

    Science.gov (United States)

    Simadibrata, C.; Budihardjo, F. A.; Srilestari, A.

    2017-08-01

    The management of diabetes mellitus (DM) involves education, nutritional intervention, and physical exercise, in addition to pharmacological interventions, with the long-term goal of preventing complications through the control of blood glucose levels. Several studies have shown that acupuncture, both conventional acupuncture and electroacupuncture, is useful for lowering blood glucose levels in patients with DM. This study aimed to determine the additional effect of electroacupuncture at the MA-IC 3 Endocrine ear acupoint on fasting blood glucose levels in patients with Type 2 DM who were receiving oral hypoglycemic agents at Banjar General Hospital. In this randomized controlled study, fifty-four study participants who were being treated with oral antidiabetics were allocated into two groups, receiving either electroacupuncture (EA) at the MA-IC 3 ear acupoint with dense disperse wave for 30 minutes or acupuncture at the same point and for the same duration but without EA (No EA). Fasting blood glucose levels were measured before and after the intervention. In Group A (EA), the mean fasting blood glucose (FBG) level decreased from 157.26±24.485 to 142.59±26.771 (p < 0.05), whereas in Group B (No EA), the mean FBG decreased from 149.67±21.485 to 148.74±21.326 (p < 0.05). The difference in the amount of FBG decrease between Group A (EA) and Group B (No EA) was statistically significant (p < 0.05). EA at the MA-IC 3 Endocrine lowers FBG levels to a greater degree than acupuncture with no EA in patients with type 2 DM.

  10. DSB:Ce3+ scintillation glass for future

    Science.gov (United States)

    Auffray, E.; Akchurin, N.; Benaglia, A.; Borisevich, A.; Cowden, C.; Damgov, J.; Dormenev, V.; Dragoiu, C.; Dudero, P.; Korjik, M.; Kozlov, D.; Kunori, S.; Lecoq, P.; Lee, S. W.; Lucchini, M.; Mechinsky, V.; Pauwels, K.

    2015-02-01

    One of the main challenges for detectors at future high-energy collider experiments is the high precision measurement of hadron and jet energy and momentum. One possibility to achieve this is the dual-readout technique, which allows recording simultaneously scintillation and Cherenkov light in an active medium in order to extract the electromagnetic fraction of the total shower energy on an event- by-event basis. Making use of this approach in the high luminosity LHC, however, puts stringent requirements on the active materials in terms of radiation hardness. Consequently, the R&D carried out on suitable scintillating materials focuses on the detector performance as well as on radiation tolerance. Among the different scintillating materials under study, scintillating glasses can be a suitable solution due to their relatively simple and cost effective production. Recently a new type of inorganic scintillating glass: Cerium doped DSB has been developed by Radiation Instruments and New Components LLC in Minsk for oil logging industry. This material can be produced either in form of bulk or fiber shape with diameter 0.3-2mm and length up to 2000 mm. It is obtained by standard glass production technology at temperature 1400°C with successive thermal annealing treatment at relatively low temperature. The production of large quantities is relatively easy and the production costs are significantly lower compared to crystal fibers. Therefore, this material is considered as an alternative and complementary solution to crystal fibers in view of a production at industrial scale, as required for a large dual readout calorimeter. In this paper, the first results on optical, scintillation properties as well as the radiation damage behaviour obtained on different samples made with different raw materials and various cerium concentrations will be presented.

  11. Legal Suggestions for Enforcement of DSB Reports in China%中国执行 DSB 裁决报告的法律对策和建议

    Institute of Scientific and Technical Information of China (English)

    李晓郛; 纪演娟

    2014-01-01

    When enforcing the DSB reports , there are two questions in front of China:one is that the DSB reports are related with many fields and the other is the difficulty of execution of DSB reports .As the most important member in WTO , US inclines to use pragmatism and considers the national interest as the start-ing point for execution of DSB reports .Harmonizing system which talkes USTR as the main point is con-sidered as a main characteristic .Union integration is the main reason if EU would like to carry out DSB reports .Based on Chinese conditions , combined with the practice of the most WTO members , there is no need to give DSB reports direct effect .The paper recommends China establish the general idea of the su-premacy of national interests and a coordination system with a committee of experts .Meanwhile , the do-mestic courts take judicial restraints when confronting DSB reports and related litigations .%执行所涉领域广、执行难度大是中国执行DSB裁决报告的两个主要难题。作为WTO最重要的成员方,美国以实用主义为先导、国家利益为出发点,执行DSB裁决报告,以USTR为主的协调机制亦是其一大特色;欧盟以有利于联盟一体化的态度执行DSB裁决报告。立足中国国情,结合WTO成员方的执行实践,建议今后在执行DSB裁决报告时,树立国家利益至上的总体思路,建立协调人制度,并设立专家委员会配合执行,国内法院以司法克制的态度处理DSB裁决报告及相关诉讼。

  12. Crustal structure of the Dead Sea Basin (DSB) from a receiver function analysis

    Science.gov (United States)

    Mohsen, A.; Asch, G.; Mechie, J.; Kind, R.; Hofstetter, R.; Weber, M.; Stiller, M.; Abu-Ayyash, K.

    2011-01-01

    The Dead Sea Transform (DST) is a major left-lateral strike-slip fault that accommodates the relative motion between the African and Arabian plates, connecting a region of extension in the Red Sea to the Taurus collision zone in Turkey over a length of about 1100 km. The Dead Sea Basin (DSB) is one of the largest basins along the DST. The DSB is a morphotectonic depression along the DST, divided into a northern and a southern sub-basin, separated by the Lisan salt diapir. We report on a receiver function study of the crust within the multidisciplinary geophysical project, DEad Sea Integrated REsearch (DESIRE), to study the crustal structure of the DSB. A temporary seismic network was operated on both sides of the DSB between 2006 October and 2008 April. The aperture of the network is approximately 60 km in the E-W direction crossing the DSB on the Lisan peninsula and about 100 km in the N-S direction. Analysis of receiver functions from the DESIRE temporary network indicates that Moho depths vary between 30 and 38 km beneath the area. These Moho depth estimates are consistent with results of near-vertical incidence and wide-angle controlled-source techniques. Receiver functions reveal an additional discontinuity in the lower crust, but only in the DSB and west of it. This leads to the conclusion that the internal crustal structure east and west of the DSB is different at the present-day. However, if the 107 km left-lateral movement along the DST is taken into account, then the region beneath the DESIRE array where no lower crustal discontinuity is observed would have lain about 18 Ma ago immediately adjacent to the region under the previous DESERT array west of the DST where no lower crustal discontinuity is recognized.

  13. DSB (Im)mobility and DNA repair compartmentalization in mammalian cells.

    Science.gov (United States)

    Lemaître, Charlène; Soutoglou, Evi

    2015-02-13

    Chromosomal translocations are considered as causal in approximately 20% of cancers. Therefore, understanding their mechanisms of formation is crucial in the prevention of carcinogenesis. The first step of translocation formation is the concomitant occurrence of double-strand DNA breaks (DSBs) in two different chromosomes. DSBs can be repaired by different repair mechanisms, including error-free homologous recombination (HR), potentially error-prone non-homologous end joining (NHEJ) and the highly mutagenic alternative end joining (alt-EJ) pathways. Regulation of DNA repair pathway choice is crucial to avoid genomic instability. In yeast, DSBs are mobile and can scan the entire nucleus to be repaired in specialized DNA repair centers or if they are persistent, in order to associate with the nuclear pores or the nuclear envelope where they can be repaired by specialized repair pathways. DSB mobility is limited in mammals; therefore, raising the question of whether the position at which a DSB occurs influences its repair. Here, we review the recent literature addressing this question. We first present the reports describing the extent of DSB mobility in mammalian cells. In a second part, we discuss the consequences of non-random gene positioning on chromosomal translocations formation. In the third part, we discuss the mobility of heterochromatic DSBs in light of our recent data on DSB repair at the nuclear lamina, and finally, we show that DSB repair compartmentalization at the nuclear periphery is conserved from yeast to mammals, further pointing to a role for gene positioning in the outcome of DSB repair. When regarded as a whole, the different studies reviewed here demonstrate the importance of nuclear architecture on DSB repair and reveal gene positioning as an important parameter in the study of tumorigenesis.

  14. Transcriptional Regulation of the assT-dsbL-dsbI Gene Cluster in Salmonella enterica Serovar Typhi IMSS-1 Depends on LeuO, H-NS, and Specific Growth Conditions

    OpenAIRE

    Gallego-Hernández, A. L.; Hernández-Lucas, I.; De la Cruz, M. A.; Olvera, L.; Morett, E; Medina-Aparicio, L.; Ramírez-Trujillo, J. A.; Vázquez, A.; Fernández-Mora, M.; Calva, E

    2012-01-01

    The assT gene encodes an arylsulfate sulfotransferase, an enzyme that catalyzes sulfuryl transfer from phenolic sulfate to a phenolic acceptor. In Salmonella enterica serovar Typhi IMSS-1, the assT gene is located upstream of the dsbL and dsbI genes, which are involved in a disulfide bond formation required for its activation. The assT-dsbL-dsbI gene cluster forms an operon transcribed by a LeuO-dependent promoter, in rich medium A (MA). Interestingly, in the absence of cloned leuO and in a Δ...

  15. Nonlinear Dynamics of Photonics for Optical Signal Processing - Optical Frequency Conversion and Optical DSB-to-SSB Conversion

    Science.gov (United States)

    2015-09-17

    processing - optical frequency conversion and optical DSB -to-SSB conversion 5a. CONTRACT NUMBER FA2386-14-1-0006 5b. GRANT NUMBER Grant 134113...nonlinear dynamics of semiconductor lasers for certain optical signal processing functionalities, including optical DSB -to-SSB conversion, photonic...conversion and optical DSB -to-SSB conversion Performance Period May 30, 2014 ~ May 29, 2015 Principal Investigator Name: Sheng-Kwang Hwang Position

  16. Biochemical DSB-repair model for mammalian cells in G1 and early S phases of the cell cycle.

    Science.gov (United States)

    Taleei, Reza; Nikjoo, Hooshang

    2013-08-30

    The paper presents a model of double strand breaks (DSB) repair in G1 and early S phases of the cell cycle. The model is based on a plethora of published information on biochemical modification of DSB induced by ionizing radiation. So far, three main DSB repair pathways have been identified, including nonhomologous end-joining (NHEJ), homologous recombination (HR), and microhomology-mediated end-joining (MMEJ). During G1 and early S phases of the cell cycle, NHEJ and MMEJ repair pathways are activated dependent on the type of double strand breaks. Simple DSB are a substrate for NHEJ, while complex DSB and DSB in heterochromatin require further end processing. Repair of all DSB start with NHEJ presynaptic processes, and depending on the type of DSB pursue simple ligation, further end processing prior to ligation, or resection. Using law of mass action the model is translated into a mathematical formalism. The solution of the formalism provides the step by step and overall repair kinetics. The overall repair kinetics are compared with the published experimental measurements. Our calculations are in agreement with the experimental results and show that the complex types of DSBs are repaired with slow repair kinetics. The G1 and early S phase model could be employed to predict the kinetics of DSB repair for damage induced by high LET radiation.

  17. Functional diversity of three different DsbA proteins from Neisseria meningitidis.

    Science.gov (United States)

    Sinha, Sunita; Langford, Paul R; Kroll, J Simon

    2004-09-01

    The genome of Neisseria meningitidis serogroup B strain MC58 contains three genes - nmb0278, nmb0294 and nmb0407 - encoding putative homologues of DsbA, a periplasmic thiol disulphide oxidoreductase protein-folding catalyst of the Dsb protein family. DsbA assists the folding of periplasmic and membrane proteins in diverse organisms. While all three cloned genes complemented the DTT sensitivity of dsbA-null Escherichia coli, they showed different activities in folding specific target proteins in this background. NMB0278 protein was the most active in complementing defects in motility and alkaline phosphatase activity, while NMB0294 was the most active in folding periplasmic MalF. NMB0407 showed the weakest activity in all assays. It is extremely unusual for organisms to contain more than one chromosomal dsbA. Among the members of the genus Neisseria, only the meningococcus carries all three of these genes. Strains of Neisseria gonorrhoeae, Neisseria lactamica, Neisseria cinerea and Neisseria polysaccharea contained only homologues of nmb0278 and nmb0407, while Neisseria flava, Neisseria subflava and Neisseria flavescens carried only nmb0294. It is speculated that the versatility of the meningococcus in surviving in different colonizing and invasive disease settings may be derived in part from an enhanced potential to deploy outer-membrane proteins, a consequence of carrying an extended repertoire of protein-folding catalysts.

  18. UbcH7 regulates 53BP1 stability and DSB repair.

    Science.gov (United States)

    Han, Xiangzi; Zhang, Lei; Chung, Jinsil; Mayca Pozo, Franklin; Tran, Amanda; Seachrist, Darcie D; Jacobberger, James W; Keri, Ruth A; Gilmore, Hannah; Zhang, Youwei

    2014-12-09

    DNA double-strand break (DSB) repair is not only key to genome stability but is also an important anticancer target. Through an shRNA library-based screening, we identified ubiquitin-conjugating enzyme H7 (UbcH7, also known as Ube2L3), a ubiquitin E2 enzyme, as a critical player in DSB repair. UbcH7 regulates both the steady-state and replicative stress-induced ubiquitination and proteasome-dependent degradation of the tumor suppressor p53-binding protein 1 (53BP1). Phosphorylation of 53BP1 at the N terminus is involved in the replicative stress-induced 53BP1 degradation. Depletion of UbcH7 stabilizes 53BP1, leading to inhibition of DSB end resection. Therefore, UbcH7-depleted cells display increased nonhomologous end-joining and reduced homologous recombination for DSB repair. Accordingly, UbcH7-depleted cells are sensitive to DNA damage likely because they mainly used the error-prone nonhomologous end-joining pathway to repair DSBs. Our studies reveal a novel layer of regulation of the DSB repair choice and propose an innovative approach to enhance the effect of radiotherapy or chemotherapy through stabilizing 53BP1.

  19. The power of DNA double-strand break (DSB) repair testing to predict breast cancer susceptibility.

    Science.gov (United States)

    Keimling, Marlen; Deniz, Miriam; Varga, Dominic; Stahl, Andreea; Schrezenmeier, Hubert; Kreienberg, Rolf; Hoffmann, Isabell; König, Jochem; Wiesmüller, Lisa

    2012-05-01

    Most presently known breast cancer susceptibility genes have been linked to DSB repair. To identify novel markers that may serve as indicators for breast cancer risk, we performed DSB repair analyses using a case-control design. Thus, we examined 35 women with defined familial history of breast and/or ovarian cancer (first case group), 175 patients with breast cancer (second case group), and 245 healthy women without previous cancer or family history of breast cancer (control group). We analyzed DSB repair in peripheral blood lymphocytes (PBLs) by a GFP-based test system using 3 pathway-specific substrates. We found increases of microhomology-mediated nonhomologous end joining (mmNHEJ) and nonconservative single-strand annealing (SSA) in women with familial risk vs. controls (P=0.0001-0.0022) and patients with breast cancer vs. controls (P=0.0004-0.0042). Young age (DSB repair activities in PBLs as method to estimate breast cancer susceptibility beyond limitations of genotyping and to predict responsiveness to therapeutics targeting DSB repair-dysfunctional tumors.

  20. In vivo generation of C4d, Bb, iC3b, and SC5b-9 after OKT3 administration in kidney and lung transplant recipients.

    Science.gov (United States)

    Vallhonrat, H; Williams, W W; Cosimi, A B; Tolkoff-Rubin, N; Ginns, L C; Wain, J C; Preffer, F; Olszak, I; Wee, S; Delmonico, F L; Pascual, M

    1999-01-27

    OKT3 monoclonal antibody therapy results in an acute clinical syndrome (ACS) associated with the release of tumor necrosis factor and sequestration of neutrophils in the lungs. We have previously shown that inhibition of tumor necrosis factor does not completely eliminate OKT3-ACS, suggesting that other factors also contribute to the ACS. The current studies analyzed complement activation in vivo during the first hour after OKT3 administration. Renal (n=4) and lung (n=4) transplant recipients received OKT3 as treatment for rejection and induction therapy, respectively. Complement activation products C4d, Bb, iC3b, and SC5b-9 were measured by ELISA. Hemodynamic parameters were also monitored in the lung transplant recipients. Neutrophil expression of CD11a, CD11b, and CD18 was monitored by flow cytometry. Controls included patients receiving methylprednisolone for rejection (n=4), two adults with adult respiratory distress syndrome who received extracorporeal membrane oxygenation, and normal volunteers (n=5). P values less than 0.05 (*) were considered significant. Increases in the plasma levels of C4d, Bb, iC3b, and SC5b-9 were observed in seven of eight patients after OKT3 administration. Mean values (n=8) at 0, 15, and 60 min (in microg/ml) were as follows-C4d: 1.865, 2.644*, and 2.607*; Bb: 0.245, 0.411, and 0.385; iC3b: 10.881, 17.242*, and 15.145*; and SC5b-9: 0.232, 0.269, and 0.302*. An increase in CD11b and CD18 and a decrease of CD11a on neutrophils in parallel with complement activation was observed. In lung transplant recipients, C3 activation correlated with increases in mean pulmonary and central venous pressures (P<0.05). As compared with extracorporeal membrane oxygenation, which activated classical and alternative pathways, OKT3 predominantly activated complement by the classical pathway. Methylprednisolone pulses did not activate complement. Complement activation is an early event after OKT3 administration and is associated with the increased expression of adhesion molecules on neutrophils and with pulmonary hemodynamic changes. Effective therapeutic approaches to the control of early monoclonal antibody side effects may require measures that limit complement activation in addition to reducing cytokine activity.

  1. Human transcriptional coactivator PC4 stimulates DNA end joining and activates DSB repair activity.

    Science.gov (United States)

    Batta, Kiran; Yokokawa, Masatoshi; Takeyasu, Kunio; Kundu, Tapas K

    2009-01-23

    Human transcriptional coactivator PC4 is a highly abundant nuclear protein that is involved in diverse cellular processes ranging from transcription to chromatin organization. Earlier, we have shown that PC4, a positive activator of p53, overexpresses upon genotoxic insult in a p53-dependent manner. In the present study, we show that PC4 stimulates ligase-mediated DNA end joining irrespective of the source of DNA ligase. Pull-down assays reveal that PC4 helps in the association of DNA ends through its C-terminal domain. In vitro nonhomologous end-joining assays with cell-free extracts show that PC4 enhances the joining of noncomplementary DNA ends. Interestingly, we found that PC4 activates double-strand break (DSB) repair activity through stimulation of DSB rejoining in vivo. Together, these findings demonstrate PC4 as an activator of nonhomologous end joining and DSB repair activity.

  2. OsSDS is essential for DSB formation in rice meiosis

    Directory of Open Access Journals (Sweden)

    Zhigang eWu

    2015-02-01

    Full Text Available SDS is a meiosis specific cyclin-like protein and required for DMC1 mediated double-strand break (DSB repairing in Arabidopsis. Here, we found its rice homolog, OsSDS, is essential for meiotic DSB formation. The Ossds mutant is normal in vegetative growth but both male and female gametes are inviable. The Ossds meiocytes exhibit severe defects in homologous pairing and synapsis. No γH2AX immunosignals in Ossds meiocytes together with the suppression of chromosome fragmentation in Ossds-1 Osrad51c, both provide strong evidences that OsSDS is essential for meiotic DSB formation. Immunostaining investigations revealed that meiotic chromosome axes are normally formed but both SC installation and localization of recombination elements are failed in Ossds. We suspected that this cyclin protein has been differentiated pretty much between monocots and dicots on its function in meiosis.

  3. Have a break: determinants of meiotic DNA double strand break (DSB) formation and processing in plants.

    Science.gov (United States)

    Edlinger, Bernd; Schlögelhofer, Peter

    2011-03-01

    Meiosis is an essential process for sexually reproducing organisms, leading to the formation of specialized generative cells. This review intends to highlight current knowledge of early events during meiosis derived from various model organisms, including plants. It will particularly focus on cis- and trans-requirements of meiotic DNA double strand break (DSB) formation, a hallmark event during meiosis and a prerequisite for recombination of genetic traits. Proteins involved in DSB formation in different organisms, emphasizing the known factors from plants, will be introduced and their functions outlined. Recent technical advances in DSB detection and meiotic recombination analysis will be reviewed, as these new tools now allow analysis of early meiotic recombination in plants with incredible accuracy. To anticipate future directions in plant meiosis research, unpublished results will be included wherever possible.

  4. OsSDS is essential for DSB formation in rice meiosis.

    Science.gov (United States)

    Wu, Zhigang; Ji, Jianhui; Tang, Ding; Wang, Hongjun; Shen, Yi; Shi, Wenqing; Li, Yafei; Tan, Xuelin; Cheng, Zhukuan; Luo, Qiong

    2015-01-01

    SDS is a meiosis specific cyclin-like protein and required for DMC1 mediated double-strand break (DSB) repairing in Arabidopsis. Here, we found its rice homolog, OsSDS, is essential for meiotic DSB formation. The Ossds mutant is normal in vegetative growth but both male and female gametes are inviable. The Ossds meiocytes exhibit severe defects in homologous pairing and synapsis. No γH2AX immunosignals in Ossds meiocytes together with the suppression of chromosome fragmentation in Ossds-1 Osrad51c, both provide strong evidences that OsSDS is essential for meiotic DSB formation. Immunostaining investigations revealed that meiotic chromosome axes are normally formed but both SC installation and localization of recombination elements are failed in Ossds. We suspected that this cyclin protein has been differentiated pretty much between monocots and dicots on its function in meiosis.

  5. 53BP1 regulates DSB repair using Rif1 to control 5' end resection.

    Science.gov (United States)

    Zimmermann, Michal; Lottersberger, Francisca; Buonomo, Sara B; Sfeir, Agnel; de Lange, Titia

    2013-02-08

    The choice between double-strand break (DSB) repair by either homology-directed repair (HDR) or nonhomologous end joining (NHEJ) is tightly regulated. Defects in this regulation can induce genome instability and cancer. 53BP1 is critical for the control of DSB repair, promoting NHEJ, and inhibiting the 5' end resection needed for HDR. Using dysfunctional telomeres and genome-wide DSBs, we identify Rif1 as the main factor used by 53BP1 to impair 5' end resection. Rif1 inhibits resection involving CtIP, BLM, and Exo1; limits accumulation of BRCA1/BARD1 complexes at sites of DNA damage; and defines one of the mechanisms by which 53BP1 causes chromosomal abnormalities in Brca1-deficient cells. These data establish Rif1 as an important contributor to the control of DSB repair by 53BP1.

  6. Heavy ion induced DNA-DSB in yeast and mammalian cells

    Science.gov (United States)

    Loebrich, M.; Ikpeme, S.; Kiefer, J.

    1994-01-01

    Molecular changes at the DNA are assumed to be the main cause for radiation effects in a number of organisms. During the course of the last decades techniques have been developed for measuring DNA double-strand breaks (dsb), generally assumed to be the most critical DNA lesions. The outcome of all those different approaches portrays a collection of data useful for a theoretical description of radiation action mechanisms. However, in the case of heavy ion induced DNA dsb the picture is not quite clear yet and further projects and strategies have to be developed. The biological systems studied in our group are yeast and mammalian cells. While in the case of yeast cells technical and methodical reasons highlight these organisms mammalian cells reach greater importance when dsb repair studies are performed. In both types of organisms the technique of pulsed-field gel electrophoresis (PFGE) is applied, although with different modifications and evaluation procedures mainly due to the different genome sizes.

  7. Higher-order chromatin structure in DSB induction, repair and misrepair.

    Science.gov (United States)

    Falk, Martin; Lukasova, Emilie; Kozubek, Stanislav

    2010-01-01

    Double-strand breaks (DSBs), continuously introduced into DNA by cell metabolism, ionizing radiation and some chemicals, are the biologically most deleterious type of genome damage, and must be accurately repaired to protect genomic integrity, ensure cell survival, and prevent carcinogenesis. Although a huge amount of information has been published on the molecular basis and biological significance of DSB repair, our understanding of DSB repair and its spatiotemporal arrangement is still incomplete. In particular, the role of higher-order chromatin structure in DSB induction and repair, movement of DSBs and the mechanism giving rise to chromatin exchanges, and many other currently disputed questions are discussed in this review. Finally, a model explaining the formation of chromosome translocations is proposed.

  8. Suppression of DNA-dependent protein kinase sensitize cells to radiation without affecting DSB repair.

    Science.gov (United States)

    Gustafsson, Ann-Sofie; Abramenkovs, Andris; Stenerlöw, Bo

    2014-11-01

    Efficient and correct repair of DNA double-strand break (DSB) is critical for cell survival. Defects in the DNA repair may lead to cell death, genomic instability and development of cancer. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is an essential component of the non-homologous end joining (NHEJ) which is the major DSB repair pathway in mammalian cells. In the present study, by using siRNA against DNA-PKcs in four human cell lines, we examined how low levels of DNA-PKcs affected cellular response to ionizing radiation. Decrease of DNA-PKcs levels by 80-95%, induced by siRNA treatment, lead to extreme radiosensitivity, similar to that seen in cells completely lacking DNA-PKcs and low levels of DNA-PKcs promoted cell accumulation in G2/M phase after irradiation and blocked progression of mitosis. Surprisingly, low levels of DNA-PKcs did not affect the repair capacity and the removal of 53BP1 or γ-H2AX foci and rejoining of DSB appeared normal. This was in strong contrast to cells completely lacking DNA-PKcs and cells treated with the DNA-PKcs inhibitor NU7441, in which DSB repair were severely compromised. This suggests that there are different mechanisms by which loss of DNA-PKcs functions can sensitize cells to ionizing radiation. Further, foci of phosphorylated DNA-PKcs (T2609 and S2056) co-localized with DSB and this was independent of the amount of DNA-PKcs but foci of DNA-PKcs was only seen in siRNA-treated cells. Our study emphasizes on the critical role of DNA-PKcs for maintaining survival after radiation exposure which is uncoupled from its essential function in DSB repair. This could have implications for the development of therapeutic strategies aiming to radiosensitize tumors by affecting the DNA-PKcs function.

  9. Suppression of DNA-dependent protein kinase sensitize cells to radiation without affecting DSB repair

    Energy Technology Data Exchange (ETDEWEB)

    Gustafsson, Ann-Sofie, E-mail: ann-sofie.gustafsson@bms.uu.se; Abramenkovs, Andris; Stenerlöw, Bo

    2014-11-15

    Highlights: • We reduced the level of DNA-PKcs with siRNA and examined cells after γ-irradiation. • Low DNA-PKcs levels lead to radiosensitivity but did not affect repair of DSB. • Low DNA-PKcs levels may block progression of mitosis. • DNA-PKcs role in mitotic progression is independent of its role in DSB repair. • We suggest different mechanisms by which loss of DNA-PKcs function sensitize cells. - Abstract: Efficient and correct repair of DNA double-strand break (DSB) is critical for cell survival. Defects in the DNA repair may lead to cell death, genomic instability and development of cancer. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is an essential component of the non-homologous end joining (NHEJ) which is the major DSB repair pathway in mammalian cells. In the present study, by using siRNA against DNA-PKcs in four human cell lines, we examined how low levels of DNA-PKcs affected cellular response to ionizing radiation. Decrease of DNA-PKcs levels by 80–95%, induced by siRNA treatment, lead to extreme radiosensitivity, similar to that seen in cells completely lacking DNA-PKcs and low levels of DNA-PKcs promoted cell accumulation in G2/M phase after irradiation and blocked progression of mitosis. Surprisingly, low levels of DNA-PKcs did not affect the repair capacity and the removal of 53BP1 or γ-H2AX foci and rejoining of DSB appeared normal. This was in strong contrast to cells completely lacking DNA-PKcs and cells treated with the DNA-PKcs inhibitor NU7441, in which DSB repair were severely compromised. This suggests that there are different mechanisms by which loss of DNA-PKcs functions can sensitize cells to ionizing radiation. Further, foci of phosphorylated DNA-PKcs (T2609 and S2056) co-localized with DSB and this was independent of the amount of DNA-PKcs but foci of DNA-PKcs was only seen in siRNA-treated cells. Our study emphasizes on the critical role of DNA-PKcs for maintaining survival after radiation exposure

  10. Rv2969c, essential for optimal growth in Mycobacterium tuberculosis, is a DsbA-like enzyme that interacts with VKOR-derived peptides and has atypical features of DsbA-like disulfide oxidases

    Energy Technology Data Exchange (ETDEWEB)

    Premkumar, Lakshmanane, E-mail: p.lakshmanane@imb.uq.edu.au; Heras, Begoña; Duprez, Wilko; Walden, Patricia; Halili, Maria; Kurth, Fabian; Fairlie, David P.; Martin, Jennifer L., E-mail: p.lakshmanane@imb.uq.edu.au [University of Queensland, St Lucia, QLD 4067 (Australia)

    2013-10-01

    The gene product of M. tuberculosis Rv2969c is shown to be a disulfide oxidase enzyme that has a canonical DsbA-like fold with novel structural and functional characteristics. The bacterial disulfide machinery is an attractive molecular target for developing new antibacterials because it is required for the production of multiple virulence factors. The archetypal disulfide oxidase proteins in Escherichia coli (Ec) are DsbA and DsbB, which together form a functional unit: DsbA introduces disulfides into folding proteins and DsbB reoxidizes DsbA to maintain it in the active form. In Mycobacterium tuberculosis (Mtb), no DsbB homologue is encoded but a functionally similar but structurally divergent protein, MtbVKOR, has been identified. Here, the Mtb protein Rv2969c is investigated and it is shown that it is the DsbA-like partner protein of MtbVKOR. It is found that it has the characteristic redox features of a DsbA-like protein: a highly acidic catalytic cysteine, a highly oxidizing potential and a destabilizing active-site disulfide bond. Rv2969c also has peptide-oxidizing activity and recognizes peptide segments derived from the periplasmic loops of MtbVKOR. Unlike the archetypal EcDsbA enzyme, Rv2969c has little or no activity in disulfide-reducing and disulfide-isomerase assays. The crystal structure of Rv2969c reveals a canonical DsbA fold comprising a thioredoxin domain with an embedded helical domain. However, Rv2969c diverges considerably from other DsbAs, including having an additional C-terminal helix (H8) that may restrain the mobility of the catalytic helix H1. The enzyme is also characterized by a very shallow hydrophobic binding surface and a negative electrostatic surface potential surrounding the catalytic cysteine. The structure of Rv2969c was also used to model the structure of a paralogous DsbA-like domain of the Ser/Thr protein kinase PknE. Together, these results show that Rv2969c is a DsbA-like protein with unique properties and a limited

  11. Peroxisome proliferator-activated receptor γ enhances adiponectin secretion via up-regulating DsbA-L expression.

    Science.gov (United States)

    Jin, Dan; Sun, Jun; Huang, Jing; Yu, Xiaoling; Yu, An; He, Yiduo; Li, Qiang; Yang, Zaiqing

    2015-08-15

    Disulfide-bond A oxidoreductase like-protein (DsbA-L) was identified as a molecular chaperone facilitating the assembly and secretion of adiponectin, an adipokine with multiple beneficial effects. In obesity the level of DsbA-L is reduced with a concomitant decrease of the circulating adiponectin level, especially of the high molecular weight form (HMW). Both rodent and human studies have shown that the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-γ agonists increase adiponectin levels in serum by activating PPARγ, which up-regulates critical endoplasmic reticulum (ER) chaperones thus facilitating protein folding. As shown in the present study, overexpression of PPARγ in human embryonic kidney (HEK) 293 cells elicited the cellular release of HMW adiponectin. PPARγ enhanced expression of DsbA-L by binding directly to peroxisome proliferator response element (PPRE) site within the DsbA-L promoter. Conversely, in differentiated 3T3-L1 cells, PPARγ knockdown resulted in decreased expression of Adiponectin, DsbA-L and ERp44. DsbA-L expression increased after PPARγ agonist treatment and decreased upon treatment with PPARγ antagonist in 3T3-L1 adipocytes. DsbA-L deficiency in differentiated 3T3-L1 cells impaired the secretion of adiponectin. We therefore propose that DsbA-L plays an important role in facilitating HMW adiponectin formation and release from cells under the regulation of PPARγ. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Functional and bioinformatics analysis of two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA

    NARCIS (Netherlands)

    Grabowska, Anna D; Wywiał, Ewa; Dunin-Horkawicz, Stanislaw; Łasica, Anna M; Wosten, M.M.S.M; Nagy-Staroń, Anna; Godlewska, Renata; Bocian-Ostrzycka, Katarzyna; Pieńkowska, Katarzyna; Łaniewski, Paweł; Bujnicki, Janusz M; van Putten, Jos P M; Jagusztyn-Krynicka, E Katarzyna

    2014-01-01

    BACKGROUND: Bacterial Dsb enzymes are involved in the oxidative folding of many proteins, through the formation of disulfide bonds between their cysteine residues. The Dsb protein network has been well characterized in cells of the model microorganism Escherichia coli. To gain insight into the funct

  13. HTP-3 links DSB formation with homolog pairing and crossing over during C. elegans meiosis.

    Science.gov (United States)

    Goodyer, William; Kaitna, Susanne; Couteau, Florence; Ward, Jordan D; Boulton, Simon J; Zetka, Monique

    2008-02-01

    Repair of the programmed meiotic double-strand breaks (DSBs) that initiate recombination must be coordinated with homolog pairing to generate crossovers capable of directing chromosome segregation. Chromosome pairing and synapsis proceed independently of recombination in worms and flies, suggesting a paradoxical lack of coregulation. Here, we find that the meiotic axis component HTP-3 links DSB formation with homolog pairing and synapsis. HTP-3 forms complexes with the DSB repair components MRE-11/RAD-50 and the meiosis-specific axis component HIM-3. Loss of htp-3 or mre-11 recapitulates meiotic phenotypes consistent with a failure to generate DSBs, suggesting that HTP-3 associates with MRE-11/RAD-50 in a complex required for meiotic DSB formation. Loss of HTP-3 eliminates HIM-3 localization to axes and HIM-3-dependent homolog alignment, synapsis, and crossing over. Our study reveals a mechanism for coupling meiotic DSB formation with homolog pairing through the essential participation of an axis component with complexes mediating both processes.

  14. Single molecule PCR reveals similar patterns of non-homologous DSB repair in tobacco and Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Andrew H Lloyd

    Full Text Available DNA double strand breaks (DSBs occur constantly in eukaryotes. These potentially lethal DNA lesions are repaired efficiently by two major DSB repair pathways: homologous recombination and non-homologous end joining (NHEJ. We investigated NHEJ in Arabidopsis thaliana and tobacco (Nicotiana tabacum by introducing DNA double-strand breaks through inducible expression of I-SceI, followed by amplification of individual repair junction sequences by single-molecule PCR. Using this process over 300 NHEJ repair junctions were analysed in each species. In contrast to previously published variation in DSB repair between Arabidopsis and tobacco, the two species displayed similar DSB repair profiles in our experiments. The majority of repair events resulted in no loss of sequence and small (1-20 bp deletions occurred at a minority (25-45% of repair junctions. Approximately ~1.5% of the observed repair events contained larger deletions (>20 bp and a similar percentage contained insertions. Strikingly, insertion events in tobacco were associated with large genomic deletions at the site of the DSB that resulted in increased micro-homology at the sequence junctions suggesting the involvement of a non-classical NHEJ repair pathway. The generation of DSBs through inducible expression of I-SceI, in combination with single molecule PCR, provides an effective and efficient method for analysis of individual repair junctions and will prove a useful tool in the analysis of NHEJ.

  15. Targeting Bacterial Dsb Proteins for the Development of Anti-Virulence Agents.

    Science.gov (United States)

    Smith, Roxanne P; Paxman, Jason J; Scanlon, Martin J; Heras, Begoña

    2016-07-16

    Recent years have witnessed a dramatic increase in bacterial antimicrobial resistance and a decline in the development of novel antibiotics. New therapeutic strategies are urgently needed to combat the growing threat posed by multidrug resistant bacterial infections. The Dsb disulfide bond forming pathways are potential targets for the development of antimicrobial agents because they play a central role in bacterial pathogenesis. In particular, the DsbA/DsbB system catalyses disulfide bond formation in a wide array of virulence factors, which are essential for many pathogens to establish infections and cause disease. These redox enzymes are well placed as antimicrobial targets because they are taxonomically widespread, share low sequence identity with human proteins, and many years of basic research have provided a deep molecular understanding of these systems in bacteria. In this review, we discuss disulfide bond catalytic pathways in bacteria and their significance in pathogenesis. We also review the use of different approaches to develop inhibitors against Dsb proteins as potential anti-virulence agents, including fragment-based drug discovery, high-throughput screening and other structure-based drug discovery methods.

  16. The Concerted Run on the DSB Bank: An Exploratory System Dynamics Approach

    NARCIS (Netherlands)

    Pruyt, E.; Hamarat, C.

    2010-01-01

    In this paper, an Exploratory System Dynamics model of a concerted run is first of all presented. The immediate cause for modelling a concerted bank run was the mediatised call for a run on the DSB bank. This Exploratory System Dynamics model was developed the morning of the call for the bank run, b

  17. Single molecule PCR reveals similar patterns of non-homologous DSB repair in tobacco and Arabidopsis.

    Science.gov (United States)

    Lloyd, Andrew H; Wang, Dong; Timmis, Jeremy N

    2012-01-01

    DNA double strand breaks (DSBs) occur constantly in eukaryotes. These potentially lethal DNA lesions are repaired efficiently by two major DSB repair pathways: homologous recombination and non-homologous end joining (NHEJ). We investigated NHEJ in Arabidopsis thaliana and tobacco (Nicotiana tabacum) by introducing DNA double-strand breaks through inducible expression of I-SceI, followed by amplification of individual repair junction sequences by single-molecule PCR. Using this process over 300 NHEJ repair junctions were analysed in each species. In contrast to previously published variation in DSB repair between Arabidopsis and tobacco, the two species displayed similar DSB repair profiles in our experiments. The majority of repair events resulted in no loss of sequence and small (1-20 bp) deletions occurred at a minority (25-45%) of repair junctions. Approximately ~1.5% of the observed repair events contained larger deletions (>20 bp) and a similar percentage contained insertions. Strikingly, insertion events in tobacco were associated with large genomic deletions at the site of the DSB that resulted in increased micro-homology at the sequence junctions suggesting the involvement of a non-classical NHEJ repair pathway. The generation of DSBs through inducible expression of I-SceI, in combination with single molecule PCR, provides an effective and efficient method for analysis of individual repair junctions and will prove a useful tool in the analysis of NHEJ.

  18. Quantitative analysis reveals asynchronous and more than DSB-associated histone H2AX phosphorylation after exposure to ionizing radiation.

    Science.gov (United States)

    Han, Jianxun; Hendzel, Michael J; Allalunis-Turner, Joan

    2006-03-01

    Rapid phosphorylation of histone H2AX after exposure of cells to ionizing radiation occurs at DSB sites and extends to a region including as much as 30 Mbp of chromatin to form visible microscopic structures called gamma-H2AX foci. Although the kinetics of total cellular histone H2AX phosphorylation after irradiation has been characterized, we still know little about the phosphorylation kinetics of individual gamma-H2AX foci. In addition, there are hundreds of smaller gamma-H2AX foci that are not associated with DNA double-strand breaks. We refer to these sites as DSB-unrelated gamma-H2AX foci. By using indirect immunofluorescence microscopy, deconvolution and three-dimensional image analysis, we established an objective method to quantitatively analyze each gamma-H2AX focus as well as to discriminate DSB-related gamma-H2AX foci from DSB-unrelated gamma-H2AX foci. Using this method, we found that histone H2AX phosphorylation at different DSB sites was asynchronous after exposure to ionizing radiation. This may reflect the heterogeneous characteristic of free DNA ends that are generated under these conditions. In addition, we found that increased histone H2AX phosphorylation also occurred outside of DSB sites after exposure to ionizing radiation. The function of this DSB-unassociated phosphorylation is not known.

  19. MutS homologue hMSH5: recombinational DSB repair and non-synonymous polymorphic variants.

    Science.gov (United States)

    Wu, Xiling; Xu, Yang; Feng, Katey; Tompkins, Joshua D; Her, Chengtao

    2013-01-01

    Double-strand breaks (DSBs) constitute the most deleterious form of DNA lesions that can lead to genome alterations and cell death, and the vast majority of DSBs arise pathologically in response to DNA damaging agents such as ionizing radiation (IR) and chemotherapeutic agents. Recent studies have implicated a role for the human MutS homologue hMSH5 in homologous recombination (HR)-mediated DSB repair and the DNA damage response. In the present study, we show that hMSH5 promotes HR-based DSB repair, and this property resides in the carboxyl-terminal portion of the protein. Our results demonstrate that DSB-triggered hMSH5 chromatin association peaks at the proximal regions of the DSB and decreases gradually with increased distance from the break. Furthermore, the DSB-triggered hMSH5 chromatin association is preceded by and relies on the assembly of hMRE11 and hRad51 at the proximal regions of the DSB. Lastly, the potential effects of hMSH5 non-synonymous variants (L85F, Y202C, V206F, R351G, L377F, and P786S) on HR and cell survival in response to DSB-inducing anticancer agents have been analyzed. These experiments show that the expression of hMSH5 variants elicits different survival responses to anticancer drugs cisplatin, bleomycin, doxorubicin and camptothecin. However, the effects of hMSH5 variants on survival responses to DSB-inducing agents are not directly correlated to their effects exerted on HR-mediated DSB repair, suggesting that the roles of hMSH5 variants in the processes of DNA damage response and repair are multifaceted.

  20. An RNA Polymerase II-coupled function for histone H3K36 methylation in checkpoint activation and DSB repair

    OpenAIRE

    Jha, Deepak Kumar; Brian D Strahl

    2014-01-01

    Histone modifications are major determinants of DNA double-strand break (DSB) response and repair. Here we elucidate a DSB repair function for transcription-coupled Set2 methylation at H3 lysine 36 (H3K36me). Cells devoid of Set2/H3K36me are hypersensitive to DNA-damaging agents and site-specific DSBs, fail to properly activate the DNA-damage checkpoint, and show genetic interactions with DSB-sensing and repair machinery. Set2/H3K36me3 is enriched at DSBs, and loss of Set2 results in altered ...

  1. Crystal Structure of DsbA from Corynebacterium diphtheriae and Its Functional Implications for CueP in Gram-Positive Bacteria.

    Science.gov (United States)

    Um, Si-Hyeon; Kim, Jin-Sik; Song, Saemee; Kim, Nam Ah; Jeong, Seong Hoon; Ha, Nam-Chul

    2015-08-01

    In Gram-negative bacteria in the periplasmic space, the dimeric thioredoxin-fold protein DsbC isomerizes and reduces incorrect disulfide bonds of unfolded proteins, while the monomeric thioredoxin-fold protein DsbA introduces disulfide bonds in folding proteins. In the Gram-negative bacteria Salmonella enterica serovar Typhimurium, the reduced form of CueP scavenges the production of hydroxyl radicals in the copper-mediated Fenton reaction, and DsbC is responsible for keeping CueP in the reduced, active form. Some DsbA proteins fulfill the functions of DsbCs, which are not present in Gram-positive bacteria. In this study, we identified a DsbA homologous protein (CdDsbA) in the Corynebacterium diphtheriae genome and determined its crystal structure in the reduced condition at 1.5 Å resolution. CdDsbA consists of a monomeric thioredoxin-like fold with an inserted helical domain and unique N-terminal extended region. We confirmed that CdDsbA has disulfide bond isomerase/reductase activity, and we present evidence that the N-terminal extended region is not required for this activity and folding of the core DsbA-like domain. Furthermore, we found that CdDsbA could reduce CueP from C. diphtheriae.

  2. DSB repair model for mammalian cells in early S and G1 phases of the cell cycle: application to damage induced by ionizing radiation of different quality.

    Science.gov (United States)

    Taleei, Reza; Girard, Peter M; Nikjoo, Hooshang

    2015-02-01

    The purpose of this work is to test the hypothesis that kinetics of double strand breaks (DSB) repair is governed by complexity of DSB. To test the hypothesis we used our recent published mechanistic mathematical model of DSB repair for DSB induced by selected protons, deuterons, and helium ions of different energies representing radiations of different qualities. In light of recent advances in experimental and computational techniques, the most appropriate method to study cellular responses in radiation therapy, and exposures to low doses of ionizing radiations is using mechanistic approaches. To this end, we proposed a 'bottom-up' approach to study cellular response that starts with the DNA damage. Monte Carlo track structure method was employed to simulate initial damage induced in the genomic DNA by direct and indirect effects. Among the different types of DNA damage, DSB are known to be induced in simple and complex forms. The DSB repair model in G1 and early S phases of the cell cycle was employed to calculate the repair kinetics. The model considers the repair of simple and complex DSB, and the DSB produced in the heterochromatin. The inverse sampling method was used to calculate the repair kinetics for each individual DSB. The overall repair kinetics for 500 DSB induced by single tracks of the radiation under test were compared with experimental results. The results show that the model is capable of predicting the repair kinetics for the DSB induced by radiations of different qualities within an accepted range of uncertainty.

  3. The spatial regulation of meiotic recombination hotspots: are all DSB hotspots crossover hotspots?

    Science.gov (United States)

    Serrentino, Maria-Elisabetta; Borde, Valérie

    2012-07-15

    A key step for the success of meiosis is programmed homologous recombination, during which crossovers, or exchange of chromosome arms, take place. Crossovers increase genetic diversity but their main function is to ensure accurate chromosome segregation. Defects in crossover number and position produce aneuploidies that represent the main cause of miscarriages and chromosomal abnormalities such as Down's syndrome. Recombination is initiated by the formation of programmed double strand breaks (DSBs), which occur preferentially at places called DSB hotspots. Among all DSBs generated, only a small fraction is repaired by crossover, the other being repaired by other homologous recombination pathways. Crossover maps have been generated in a number of organisms, defining crossover hotspots. With the availability of genome-wide maps of DSBs as well as the ability to measure genetically the repair outcome at several hotspots, it is becoming more and more clear that not all DSB hotspots behave the same for crossover formation, suggesting that chromosomal features distinguish different types of hotspots.

  4. 基于SystemView的DSB-SC通信系统的仿真与分析

    Institute of Scientific and Technical Information of China (English)

    谢莉

    2015-01-01

    SystemView是一种适于通信系统设计与仿真分析的软件工具.可以对通信系统的工作过程进行实时仿真分析,文章以DSB-SC通信系统为例,利用SystemView仿真软件对DSB-SC的调制解调过程进行了仿真.仿真结果表明,利用SystemView仿真软件可以很方便地得到通信系统的输出结果,从而说明电路各参数对系统性能的影响.

  5. MOF phosphorylation by ATM regulates 53BP1-mediated DSB repair pathway choice

    Science.gov (United States)

    Gupta, Arun; Hunt, Clayton R.; Hegdec, Muralidhar L.; Chakraborty, Sharmistha; Udayakumar, Durga; Horikoshi, Nobuo; Singh1, Mayank; Ramnarain, Deepti B.; Hittelman, Walter N.; Namjoshi, Sarita; Asaithamby, Aroumougame; Hazra, Tapas K.; Ludwig, Thomas; Pandita, Raj K.; Tyler, Jessica K.; Pandita, Tej K.

    2014-01-01

    Cell cycle phase is a critical determinant of the choice between DNA damage repair by non-homologous end joining (NHEJ) or homologous recombination (HR). Here we report that DSBs induce ATM-dependent MOF (a histone H4 acetyl-transferase) phosphorylation (p-T392-MOF) and that phosphorylated MOF co-localizes with γ-H2AX, ATM, and 53BP1 foci. Mutation of the phosphorylation site (MOF-T392A) impedes DNA repair in S- and G2-phase but not G1-phase cells. Expression of MOF-T392A also reverses the reduction in DSB associated 53BP1 seen in wild type S/G2-phase cells, resulting in enhanced 53BP1 and reduced BRCA1 association. Decreased BRCA1 levels at DSB sites correlates with defective repairosome formation, reduced HR repair and decreased cell survival following irradiation. These data support a model whereby ATM mediated MOF-T392 phosphorylation modulates 53BP1 function to facilitate the subsequent recruitment of HR repair proteins, uncovering a regulatory role for MOF in DSB repair pathway choice during S/G2-phase. PMID:24953651

  6. MRE11 is required for homologous synapsis and DSB processing in rice meiosis.

    Science.gov (United States)

    Ji, Jianhui; Tang, Ding; Wang, Mo; Li, Yafei; Zhang, Lei; Wang, Kejian; Li, Ming; Cheng, Zhukuan

    2013-10-01

    Mre11, a conserved protein found in organisms ranging from yeast to multicellular organisms, is required for normal meiotic recombination. Mre11 interacts with Rad50 and Nbs1/Xrs2 to form a complex (MRN/X) that participates in double-strand break (DSB) ends processing. In this study, we silenced the MRE11 gene in rice and detailed its function using molecular and cytological methods. The OsMRE11-deficient plants exhibited normal vegetative growth but could not set seed. Cytological analysis indicated that in the OsMRE11-deficient plants, homologous pairing was totally inhibited, and the chromosomes were completely entangled as a formation of multivalents at metaphase I, leading to the consequence of serious chromosome fragmentation during anaphase I. Immunofluorescence studies further demonstrated that OsMRE11 is required for homologous synapsis and DSB processing but is dispensable for meiotic DSB formation. We found that OsMRE11 protein was located on meiotic chromosomes from interphase to late pachytene. This protein showed normal localization in zep1, Oscom1 and Osmer3, as well as in OsSPO11-1(RNAi) plants, but not in pair2 and pair3 mutants. Taken together, our results provide evidence that OsMRE11 performs a function essential for maintaining the normal HR process and inhibiting non-homologous recombination during meiosis.

  7. Phosphorylation of Ku dictates DNA double-strand break (DSB) repair pathway choice in S phase.

    Science.gov (United States)

    Lee, Kyung-Jong; Saha, Janapriya; Sun, Jingxin; Fattah, Kazi R; Wang, Shu-Chi; Jakob, Burkhard; Chi, Linfeng; Wang, Shih-Ya; Taucher-Scholz, Gisela; Davis, Anthony J; Chen, David J

    2016-02-29

    Multiple DNA double-strand break (DSB) repair pathways are active in S phase of the cell cycle; however, DSBs are primarily repaired by homologous recombination (HR) in this cell cycle phase. As the non-homologous end-joining (NHEJ) factor, Ku70/80 (Ku), is quickly recruited to DSBs in S phase, we hypothesized that an orchestrated mechanism modulates pathway choice between HR and NHEJ via displacement of the Ku heterodimer from DSBs to allow HR. Here, we provide evidence that phosphorylation at a cluster of sites in the junction of the pillar and bridge regions of Ku70 mediates the dissociation of Ku from DSBs. Mimicking phosphorylation at these sites reduces Ku's affinity for DSB ends, suggesting that phosphorylation of Ku70 induces a conformational change responsible for the dissociation of the Ku heterodimer from DNA ends. Ablating phosphorylation of Ku70 leads to the sustained retention of Ku at DSBs, resulting in a significant decrease in DNA end resection and HR, specifically in S phase. This decrease in HR is specific as these phosphorylation sites are not required for NHEJ. Our results demonstrate that the phosphorylation-mediated dissociation of Ku70/80 from DSBs frees DNA ends, allowing the initiation of HR in S phase and providing a mechanism of DSB repair pathway choice in mammalian cells.

  8. 53BP1 and the LINC Complex Promote Microtubule-Dependent DSB Mobility and DNA Repair.

    Science.gov (United States)

    Lottersberger, Francisca; Karssemeijer, Roos Anna; Dimitrova, Nadya; de Lange, Titia

    2015-11-05

    Increased mobility of chromatin surrounding double-strand breaks (DSBs) has been noted in yeast and mammalian cells but the underlying mechanism and its contribution to DSB repair remain unclear. Here, we use a telomere-based system to track DNA damage foci with high resolution in living cells. We find that the greater mobility of damaged chromatin requires 53BP1, SUN1/2 in the linker of the nucleoskeleton, and cytoskeleton (LINC) complex and dynamic microtubules. The data further demonstrate that the excursions promote non-homologous end joining of dysfunctional telomeres and implicated Nesprin-4 and kinesins in telomere fusion. 53BP1/LINC/microtubule-dependent mobility is also evident at irradiation-induced DSBs and contributes to the mis-rejoining of drug-induced DSBs in BRCA1-deficient cells showing that DSB mobility can be detrimental in cells with numerous DSBs. In contrast, under physiological conditions where cells have only one or a few lesions, DSB mobility is proposed to prevent errors in DNA repair.

  9. An RNA polymerase II-coupled function for histone H3K36 methylation in checkpoint activation and DSB repair.

    Science.gov (United States)

    Jha, Deepak Kumar; Strahl, Brian D

    2014-06-09

    Histone modifications are major determinants of DNA double-strand break (DSB) response and repair. Here we elucidate a DSB repair function for transcription-coupled Set2 methylation at H3 lysine 36 (H3K36me). Cells devoid of Set2/H3K36me are hypersensitive to DNA-damaging agents and site-specific DSBs, fail to properly activate the DNA-damage checkpoint, and show genetic interactions with DSB-sensing and repair machinery. Set2/H3K36me3 is enriched at DSBs, and loss of Set2 results in altered chromatin architecture and inappropriate resection during G1 near break sites. Surprisingly, Set2 and RNA polymerase II are programmed for destruction after DSBs in a temporal manner--resulting in H3K36me3 to H3K36me2 transition that may be linked to DSB repair. Finally, we show a requirement of Set2 in DSB repair in transcription units--thus underscoring the importance of transcription-dependent H3K36me in DSB repair.

  10. Optimization of DsbA Purification from Recombinant Escherichia coil Broth Using Box-Behnken Design Methodology

    Institute of Scientific and Technical Information of China (English)

    LUO Man; GUAN Yixin; YAO Shanjing

    2013-01-01

    Disulfide bond formation protein A(DsbA)is one of the important helper proteins for folding in protein synthesis in vivo.In this study,purification of recombinant DsbA was investigated by examining four important factors with Box-Behnken design method,a statistic-based design of experiments.The optimal operation conditions were obtained by adopting the effectiveness coefficient method on the multi-objective problem,which takes the protein recovery,purification efficiency and throughput of ion-exchange chromatography into account.After the optimization,protein recovery of 96.8% and purity higher than 95% DsbA was achieved,and the productivity was (377.9±1.7)mg soluble DsbA per liter broth.The purified protein was identified by peptide mass fingerprinting matching the record of gil2624856,a mutant of DsbA.The DsbA was preliminarily applied to the refolding of denatured lysozyme m vitro.

  11. DNA double strand break (DSB) induction and cell survival in iodine-enhanced computed tomography (CT)

    Science.gov (United States)

    Streitmatter, Seth W.; Stewart, Robert D.; Jenkins, Peter A.; Jevremovic, Tatjana

    2017-08-01

    A multi-scale Monte Carlo model is proposed to assess the dosimetric and biological impact of iodine-based contrast agents commonly used in computed tomography. As presented, the model integrates the general purpose MCNP6 code system for larger-scale radiation transport and dose assessment with the Monte Carlo damage simulation to determine the sub-cellular characteristics and spatial distribution of initial DNA damage. The repair-misrepair-fixation model is then used to relate DNA double strand break (DSB) induction to reproductive cell death. Comparisons of measured and modeled changes in reproductive cell survival for ultrasoft characteristic k-shell x-rays (0.25-4.55 keV) up to orthovoltage (200-500 kVp) x-rays indicate that the relative biological effectiveness (RBE) for DSB induction is within a few percent of the RBE for cell survival. Because of the very short range of secondary electrons produced by low energy x-ray interactions with contrast agents, the concentration and subcellular distribution of iodine within and near cellular targets have a significant impact on the estimated absorbed dose and number of DSB produced in the cell nucleus. For some plausible models of the cell-level distribution of contrast agent, the model predicts an increase in RBE-weighted dose (RWD) for the endpoint of DSB induction of 1.22-1.40 for a 5-10 mg ml-1 iodine concentration in blood compared to an RWD increase of 1.07  ±  0.19 from a recent clinical trial. The modeled RWD of 2.58  ±  0.03 is also in good agreement with the measured RWD of 2.3  ±  0.5 for an iodine concentration of 50 mg ml-1 relative to no iodine. The good agreement between modeled and measured DSB and cell survival estimates provides some confidence that the presented model can be used to accurately assess biological dose for other concentrations of the same or different contrast agents.

  12. Campylobacter jejuni dsb gene expression is regulated by iron in a Fur-dependent manner and by a translational coupling mechanism

    Directory of Open Access Journals (Sweden)

    Grabowska Anna D

    2011-07-01

    Full Text Available Abstract Background Many bacterial extracytoplasmic proteins are stabilized by intramolecular disulfide bridges that are formed post-translationally between their cysteine residues. This protein modification plays an important role in bacterial pathogenesis, and is facilitated by the Dsb (disulfide bond family of the redox proteins. These proteins function in two parallel pathways in the periplasmic space: an oxidation pathway and an isomerization pathway. The Dsb oxidative pathway in Campylobacter jejuni is more complex than the one in the laboratory E. coli K-12 strain. Results In the C. jejuni 81-176 genome, the dsb genes of the oxidative pathway are arranged in three transcriptional units: dsbA2-dsbB-astA, dsbA1 and dba-dsbI. Their transcription responds to an environmental stimulus - iron availability - and is regulated in a Fur-dependent manner. Fur involvement in dsb gene regulation was proven by a reporter gene study in a C. jejuni wild type strain and its isogenic fur mutant. An electrophoretic mobility shift assay (EMSA confirmed that analyzed genes are members of the Fur regulon but each of them is regulated by a disparate mechanism, and both the iron-free and the iron-complexed Fur are able to bind in vitro to the C. jejuni promoter regions. This study led to identification of a new iron- and Fur-regulated promoter that drives dsbA1 gene expression in an indirect way. Moreover, the present work documents that synthesis of DsbI oxidoreductase is controlled by the mechanism of translational coupling. The importance of a secondary dba-dsbI mRNA structure for dsbI mRNA translation was verified by estimating individual dsbI gene expression from its own promoter. Conclusions The present work shows that iron concentration is a significant factor in dsb gene transcription. These results support the concept that iron concentration - also through its influence on dsb gene expression - might control the abundance of extracytoplasmic proteins

  13. Modulation of biofilm-formation in Salmonella enterica serovar Typhimurium by the periplasmic DsbA/DsbB oxidoreductase system requires the GGDEF-EAL domain protein STM3615.

    Directory of Open Access Journals (Sweden)

    Naeem Anwar

    Full Text Available In Salmonella enterica serovar Typhimurium (S. Typhimurium, biofilm-formation is controlled by the cytoplasmic intracellular small-molecular second messenger cyclic 3', 5'-di- guanosine monophosphate (c-di-GMP through the activities of GGDEF and EAL domain proteins. Here we describe that deleting either dsbA or dsbB, respectively encoding a periplasmic protein disulfide oxidase and a cytoplasmic membrane disulfide oxidoreductase, resulted in increased biofilm-formation on solid medium. This increased biofilm-formation, defined as a red, dry and rough (rdar colony morphotype, paralleled with enhanced expression of the biofilm master regulator CsgD and the biofilm-associated fimbrial subunit CsgA. Deleting csgD in either dsb mutant abrogated the enhanced biofilm-formation. Likewise, overexpression of the c-di-GMP phosphodiesterase YhjH, or mutationally inactivating the CsgD activator EAL-domain protein YdiV, reduced biofilm-formation in either of the dsb mutants. Intriguingly, deleting the GGDEF-EAL domain protein gene STM3615 (yhjK, previously not connected to rdar morphotype development, also abrogated the escalated rdar morphotype formation in dsb mutant backgrounds. Enhanced biofilm-formation in dsb mutants was furthermore annulled by exposure to the protein disulfide catalyst copper chloride. When analyzed for the effect of exogenous reducing stress on biofilm-formation, both dsb mutants initially showed an escalated rdar morphotype development that later dissolved to reveal a smooth mucoid colony morphotype. From these results we conclude that biofilm-development in S. Typhimurium is affected by periplasmic protein disulphide bond status through CsgD, and discuss the involvement of selected GGDEF/EAL domain protein(s as signaling mediators.

  14. Exo1 and Mre11 execute meiotic DSB end resection in the protist Tetrahymena.

    Science.gov (United States)

    Lukaszewicz, Agnieszka; Shodhan, Anura; Loidl, Josef

    2015-11-01

    The resection of 5'-DNA ends at a double-strand break (DSB) is an essential step in recombinational repair, as it exposes 3' single-stranded DNA (ssDNA) tails for interaction with a repair template. In mitosis, Exo1 and Sgs1 have a conserved function in the formation of long ssDNA tails, whereas this step in the processing of programmed meiotic DSBs is less well-characterized across model organisms. In budding yeast, which has been most intensely studied in this respect, Exo1 is a major meiotic nuclease. In addition, it exerts a nuclease-independent function later in meiosis in the conversion of DNA joint molecules into ZMM-dependent crossovers. In order to gain insight into the diverse meiotic roles of Exo1, we investigated the effect of Exo1 deletion in the ciliated protist Tetrahymena. We found that Exo1 together with Mre11, but without the help of Sgs1, promotes meiotic DSB end resection. Resection is completely eliminated only if both Mre11 and Exo1 are missing. This is consistent with the yeast model where Mre11 promotes resection in the 3'-5' direction and Exo1 in the opposite 5'-3' direction. However, while the endonuclease activity of Mre11 is essential to create an entry site for exonucleases and hence to start resection in budding yeast, Tetrahymena Exo1 is able to create single-stranded DNA in the absence of Mre11. Excluding a possible contribution of the Mre11 cofactor Sae2 (Com1) as an autonomous endonuclease, we conclude that there exists another unknown nuclease that initiates DSB processing in Tetrahymena. Consistent with the absence of the ZMM crossover pathway in Tetrahymena, crossover formation is independent of Exo1.

  15. Non-DSB clustered DNA lesions induced by ionizing radiation are largely responsible for the loss of plasmid DNA functionality in the presence of cisplatin.

    Science.gov (United States)

    Kouass Sahbani, S; Rezaee, M; Cloutier, P; Sanche, L; Hunting, D J

    2014-06-25

    The combination of cisplatin and ionizing radiation (IR) increases cell toxicity by both enhancing DNA damage and inhibiting repair mechanisms. Although the formation of cluster DNA lesions, particularly double-strand breaks (DSB) at the site of cisplatin-DNA-adducts has been reported to induce cell death, the contribution of DSB and non-DSB cluster lesions to the cellular toxicity is still unknown. Although both lesions are toxic, it is not always possible to measure their frequency and cell survival in the same model system. To overcome this problem, here, we investigate the effect of cisplatin-adducts on the induction of DSB and non-DSB cluster DNA lesions by IR and determine the impact of such lesions on plasmid functionality. Cluster lesions are two or more lesions on opposite DNA strands with a short distance such that error free repair is difficult or impossible. At a ratio of two cisplatin per plasmid, irradiation of platinated DNA in solution with (137)Cs γ-rays shows enhancements in the formation of DNA DSB and non-DSB cluster lesions by factors of 2.6 and 2.1, respectively, compared to unmodified DNA. However, in absolute terms, the yield for non-DSB cluster lesions is far larger than that for DSB, by a factor of 26. Unmodified and cisplatin-modified DNA were irradiated and subsequently transformed into Escherichia coli to give survival curves representing the functionality of the plasmid DNA as a function of radiation dose. Our results demonstrate that non-DSB cluster lesions are the only toxic lesions present at a sufficient frequency to account for the loss of DNA functionality. Our data also show that Frank-DSB lesions are simply too infrequent to account for the loss of DNA functionality. In conclusion, non-DSB cluster DNA damage is known to be difficult to repair and is probably the lesion responsible for the loss of functionality of DNA modified by cisplatin.

  16. Applied Railway Optimization in Production Planning at DSB-S-tog - Tasks, Tools and Challenges

    DEFF Research Database (Denmark)

    Clausen, Jens

    2007-01-01

    Efficient public transportation is becoming increasingly vital for modern capitals. DSB S-tog a/s is the major supplier of rail traffic on the infrastructure of the city-rail network in Copenhagen. S-tog has experienced a demand for increasing volume and quality of the transportation offered....... In addition we describe on-going efforts in using mathematical models in activities such as timetable design and work-force planning. We also identify some organizatorial key factors, which have paved the way for extended use of optimization methods in railway production planning....

  17. Análisis funcional de DsbA una tiol oxidorreductasa de Rhizobium leguminosarum

    OpenAIRE

    Vega de los Reyes, Rosa Mª

    2009-01-01

    Las proteínas que se exportan fuera del citoplasma bacteriano constituyen hasta un 20% del total de proteínas sintetizadas. Algunas de estas proteínas necesitan adquirir su conformación tridimensional particular en el citoplasma, incorporando frecuentemente cofactores metálicos antes de su transporte. Dicho transporte está mediado por el sistema Tat que es capaz de transportar proteínas que presentan un péptido señal característico en conformación plegada. Se ha postulado DsbA como proteína d...

  18. Suppressed expression of non-DSB repair genes inhibits gamma-radiation-induced cytogenetic repair and cell cycle arrest.

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H; Emami, Kamal; Hammond, Dianne; Casey, Rachael; Mehta, Satish K; Jeevarajan, Antony S; Pierson, Duane L; Wu, Honglu

    2008-11-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in double-strand break (DSB) repair, and its impact on cytogenetic responses has not been well studied. The purpose of this study is to identify new roles of IR inducible genes in regulating DSB repair and cell cycle progression. In this study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by small interfering RNA in human fibroblast cells. Frequency of micronuclei (MN) formation and chromosome aberrations were measured to determine efficiency of cytogenetic repair, especially DSB repair. In response to IR, the formation of MN was significantly increased by suppressed expression of five genes: Ku70 (DSB repair pathway), XPA (nucleotide excision repair pathway), RPA1 (mismatch repair pathway), RAD17 and RBBP8 (cell cycle control). Knocked-down expression of four genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Moreover, decreased XPA, p21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Nine of these eleven genes, whose knock-down expression affected cytogenetic repair, were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate IR-induced biological consequences. Furthermore, eight non-DBS repair genes showed involvement in regulating DSB repair, indicating that

  19. Characterization of Helicobacter pylori HP0231 (DsbK): role in disulfide bond formation, redox homeostasis and production of Helicobacter cystein-rich protein HcpE.

    Science.gov (United States)

    Lester, Jeffrey; Kichler, Sari; Oickle, Brandon; Fairweather, Spencer; Oberc, Alexander; Chahal, Jaspreet; Ratnayake, Dinath; Creuzenet, Carole

    2015-04-01

    Helicobacter pylori is a human gastric pathogen that colonizes ∼ 50% of the world's population. It can cause gastritis, gastric or duodenal ulcers and also gastric cancer. The numerous side effects of available treatments and the emergence of antibiotic resistant strains are severe concerns that justify further research into H. pylori's pathogenic mechanisms. H. pylori produces secreted proteins that may play a role in virulence, including the Helicobacter cysteine-rich protein HcpE (aka HP0235). We demonstrate herein that HcpE is secreted in the culture supernatant both as a soluble protein and in association with outer membrane vesicles. We show that the structure of HcpE comprises an organized array of disulfide bonds. We identify DsbK (aka HP0231) as a folding factor necessary for HcpE production and secretion in H. pylori and show that recombinant DsbK can interact with and refold unprocessed, reduced HcpE in vitro. These experiments highlight the first biologically relevant substrate for DsbK. Furthermore, we show that DsbK has disulfide bond (Dsb) forming activity on reduced lysozyme and demonstrate a DsbA-type of activity for DsbK upon expression in E. coli, despite its similarity with DsbG. Finally, we show a role of DsbK in maintaining redox homeostasis in H. pylori.

  20. Functional and evolutionary analyses of Helicobacter pylori HP0231 (DsbK protein with strong oxidative and chaperone activity characterized by a highly diverged dimerization domain

    Directory of Open Access Journals (Sweden)

    Katarzyna Marta Bocian-Ostrzycka

    2015-10-01

    Full Text Available Helicobacter pylori does not encode the classical DsbA/DsbB oxidoreductases that are crucial for oxidative folding of extracytoplasmic proteins. Instead, this microorganism encodes an untypical two proteins playing a role in disulfide bond formation – periplasmic HP0231, which structure resembles that of EcDsbC/DsbG, and its redox partner, a membrane protein HpDsbI (HP0595 with a -propeller structure. The aim of presented work was to assess relations between HP0231 structure and function.We showed that HP0231 is most closely related evolutionarily to the catalytic domain of DsbG, even though it possesses a catalytic motif typical for canonical DsbA proteins. Similarly, the highly diverged N-terminal dimerization domain is homologous to the dimerization domain of DsbG. To better understand the functioning of this atypical oxidoreductase, we examined its activity using in vivo and in vitro experiments. We found that HP0231 exhibits oxidizing and chaperone activities but no isomerizing activity, even though H. pylori does not contain a classical DsbC. We also show that HP0231 is not involved in the introduction of disulfide bonds into HcpC (Helicobacter cysteine-rich protein C, a protein involved in the modulation of the H. pylori interaction with its host. Additionally, we also constructed a truncated version of HP0231 lacking the dimerization domain, denoted HP0231m, and showed that it acts in E. coli cells in a DsbB-dependent manner. In contrast, HP0231m and classical monomeric EcDsbA (Escherichia coli DsbA protein were both unable to complement the lack of HP0231 in H. pylori cells, though they exist in oxidized forms. HP0231m is inactive in the insulin reduction assay and possesses high chaperone activity, in contrast to EcDsbA. In conclusion, HP0231 combines oxidative functions characteristic of DsbA proteins and chaperone activity characteristic of DsbC/DsbG, and it lacks isomerization activity.

  1. Effects of indirect actions and oxygen on relative biological effectiveness: estimate of DSB induction and conversion induced by gamma rays and helium ions.

    Science.gov (United States)

    Tsai, Ju-Ying; Chen, Fang-Hsin; Hsieh, Tsung-Yu; Hsiao, Ya-Yun

    2015-07-01

    Clustered DNA damage other than double-strand breaks (DSBs) can be detrimental to cells and can lead to mutagenesis or cell death. In addition to DSBs induced by ionizing radiation, misrepair of non-DSB clustered damage contributes extra DSBs converted from DNA misrepair via pathways for base excision repair and nucleotide excision repair. This study aimed to quantify the relative biological effectiveness (RBE) when DSB induction and conversion from non-DSB clustered damage misrepair were used as biological endpoints. The results showed that both linear energy transfer (LET) and indirect action had a strong impact on the yields for DSB induction and conversion. RBE values for DSB induction and maximum DSB conversion of helium ions (LET = 120 keV/μm) to (60)Co gamma rays were 3.0 and 3.2, respectively. These RBE values increased to 5.8 and 5.6 in the absence of interference of indirect action initiated by addition of 2-M dimethylsulfoxide. DSB conversion was ∼1-4% of the total non-DSB damage due to gamma rays, which was lower than the 10% estimate by experimental measurement. Five to twenty percent of total non-DSB damage due to helium ions was converted into DSBs. Hence, it may be possible to increase the yields of DSBs in cancerous cells through DNA repair pathways, ultimately enhancing cell killing.

  2. Functional and evolutionary analyses of Helicobacter pylori HP0231 (DsbK) protein with strong oxidative and chaperone activity characterized by a highly diverged dimerization domain.

    Science.gov (United States)

    Bocian-Ostrzycka, Katarzyna M; Łasica, Anna M; Dunin-Horkawicz, Stanisław; Grzeszczuk, Magdalena J; Drabik, Karolina; Dobosz, Aneta M; Godlewska, Renata; Nowak, Elżbieta; Collet, Jean-Francois; Jagusztyn-Krynicka, Elżbieta K

    2015-01-01

    Helicobacter pylori does not encode the classical DsbA/DsbB oxidoreductases that are crucial for oxidative folding of extracytoplasmic proteins. Instead, this microorganism encodes an untypical two proteins playing a role in disulfide bond formation - periplasmic HP0231, which structure resembles that of EcDsbC/DsbG, and its redox partner, a membrane protein HpDsbI (HP0595) with a β-propeller structure. The aim of presented work was to assess relations between HP0231 structure and function. We showed that HP0231 is most closely related evolutionarily to the catalytic domain of DsbG, even though it possesses a catalytic motif typical for canonical DsbA proteins. Similarly, the highly diverged N-terminal dimerization domain is homologous to the dimerization domain of DsbG. To better understand the functioning of this atypical oxidoreductase, we examined its activity using in vivo and in vitro experiments. We found that HP0231 exhibits oxidizing and chaperone activities but no isomerizing activity, even though H. pylori does not contain a classical DsbC. We also show that HP0231 is not involved in the introduction of disulfide bonds into HcpC (Helicobacter cysteine-rich protein C), a protein involved in the modulation of the H. pylori interaction with its host. Additionally, we also constructed a truncated version of HP0231 lacking the dimerization domain, denoted HP0231m, and showed that it acts in Escherichia coli cells in a DsbB-dependent manner. In contrast, HP0231m and classical monomeric EcDsbA (E. coli DsbA protein) were both unable to complement the lack of HP0231 in H. pylori cells, though they exist in oxidized forms. HP0231m is inactive in the insulin reduction assay and possesses high chaperone activity, in contrast to EcDsbA. In conclusion, HP0231 combines oxidative functions characteristic of DsbA proteins and chaperone activity characteristic of DsbC/DsbG, and it lacks isomerization activity.

  3. In vivo control of redox potential during protein folding catalyzed by bacterial protein disulfide-isomerase (DsbA).

    Science.gov (United States)

    Wunderlich, M; Glockshuber, R

    1993-11-25

    The formation of disulfide bonds in Escherichia coli is catalyzed by periplasmic protein disulfide-isomerase (DsbA). When the alpha-amylase/trypsin inhibitor from Ragi, a protein containing five intramolecular disulfide bridges, is secreted into the periplasm of E. coli, large amounts of misfolded inhibitor with incomplete or incorrect disulfides are accumulated. Folding of the inhibitor in the periplasm is not improved when DsbA is coexpressed and cosecreted. However, an up to 14-fold increase in correctly folded inhibitor is observed by co-expression of DsbA in conjugation with the addition of reduced glutathione to the growth medium. This peptide acts as a disulfide-shuffling reagent and can pass the outer membrane of E. coli. Since the influence of DsbA on the folding yield of the inhibitor is reduced in the presence of oxidized glutathione, the in vivo function of DsbA appears to be dependent on the ratio between oxidizing and reducing thiol equivalents in the periplasm. The high stability of thiol reagents against air oxidation during growth of E. coli allows the investigation of oxidative protein folding in vivo under controlled, thiol-dependent redox conditions.

  4. Biochemical Kinetics Model of DSB Repair and GammaH2AX FOCI by Non-homologous End Joining

    Science.gov (United States)

    Cucinotta, Francis, A.; Pluth, Janice M.; Anderson, Jennifer A.; Harper, Jane V.; O'Neill, Peter

    2007-01-01

    We developed a biochemical kinetics approach to describe the repair of double strand breaks (DSB) produced by low LET radiation by modeling molecular events associated with the mechanisms of non-homologous end-joining (NHEJ). A system of coupled non-linear ordinary differential equations describes the induction of DSB and activation pathways for major NHEJ components including Ku(sub 70/80), DNA-PK(sub cs), and the Ligase IV-XRCC4 hetero-dimer. The autophosphorylation of DNA-PK(sub cs and subsequent induction of gamma-H2AX foci observed after ionizing radiation exposure were modeled. A two-step model of DNA-PK(sub cs) regulation of repair was developed with the initial step allowing access of other NHEJ components to breaks, and a second step limiting access to Ligase IV-XRCC4. Our model assumes that the transition from the first to second-step depends on DSB complexity, with a much slower-rate for complex DSB. The model faithfully reproduced several experimental data sets, including DSB rejoining as measured by pulsed-field electrophoresis (PFGE), quantification of the induction of gamma-H2AX foci, and live cell imaging of the induction of Ku(sub 70/80). Predictions are made for the behaviors of NHEJ components at low doses and dose-rates, where a steady-state is found at dose-rates of 0.1 Gy/hr or lower.

  5. A sensitive test for the detection of specific DSB repair defects in primary cells from breast cancer specimens.

    Science.gov (United States)

    Keimling, Marlen; Kaur, Jatinder; Bagadi, Sarangadhara Appala Raju; Kreienberg, Rolf; Wiesmüller, Lisa; Ralhan, Ranju

    2008-08-01

    Increasing evidence indicates that breast cancer pathogenesis is linked with DNA double-strand break (DSB) repair dysfunction. This conclusion is based on advances in the study of functions of breast cancer susceptibility genes such as BRCA1 and BRCA2, on the identification of breast cancer-associated changes regarding the genetics, expression, and localization of multiple DSB repair factors, and on observations indicating enhanced radiation-induced chromosomal damage in cells from predisposed individuals and sporadic breast cancer patients. In this pilot study, we describe a sensitive method for the analysis of DSB repair functions in mammary carcinomas. Using this method we firstly document alterations in pathway-specific DSB repair activities in primary cells originating from familial as well as sporadic breast cancer. In particular, we identified increases in the mutagenic nonhomologous end joining and single-strand annealing mechanisms in sporadic breast cancers with wild-type BRCA1 and BRCA2, and, thus, similar phenotypes to tumors with mutant alleles of BRCA1 and BRCA2. This suggests that detection of error-prone DSB repair activities may be useful to extend the limits of genotypic characterization of high-risk susceptibility genes. This method may, therefore, serve as a marker for breast cancer risk assessment and, even more importantly, for the prediction of responsiveness to targeted therapies such as to inhibitors of poly(ADP-ribose)polymerase (PARP1).

  6. The Arabidopsis thaliana DSB formation (AtDFO) gene is required for meiotic double-strand break formation.

    Science.gov (United States)

    Zhang, Cheng; Song, Yao; Cheng, Zhi-hao; Wang, Ying-xiang; Zhu, Jun; Ma, Hong; Xu, Ling; Yang, Zhong-Nan

    2012-10-01

    DNA double-strand break (DSB) formation is the initial event for meiotic recombination catalyzed by the conserved Spo11 protein. In Arabidopsis, several proteins have been reported to be involved in DSB formation. Here, we report an Arabidopsis DSB forming (DFO) gene in Arabidopsis that is involved in DSB formation. The dfo mutant exhibits reduced fertility, producing polyads with an abnormal number of microspores, unlike the tetrads in the wild type. The dfo meiocytes were defective in homologous chromosome synapsis and segregation. Genetic analysis revealed that the homologous recombination of Atdfo-1 is severely affected in meiotic prophase I. DFO encodes a protein without any known conserved domain. There was no homologue identified outside the plant kingdom, indicating that AtDFO is a plant-specific protein. AtMRE11 has been reported to be responsible for processing SPO11-generated DSBs. The Atmre11 mutant displays chromosome fragmentation during meiosis. However, the Atdfo Atmre11 double mutant had no such chromosome fragmentation, indicating that AtDFO is required for DSB formation.

  7. ATM prevents DSB formation by coordinating SSB repair and cell cycle progression.

    Science.gov (United States)

    Khoronenkova, Svetlana V; Dianov, Grigory L

    2015-03-31

    DNA single-strand breaks (SSBs) arise as a consequence of spontaneous DNA instability and are also formed as DNA repair intermediates. Their repair is critical because they otherwise terminate gene transcription and generate toxic DNA double-strand breaks (DSBs) on replication. To prevent the formation of DSBs, SSB repair must be completed before DNA replication. To accomplish this, cells should be able to detect unrepaired SSBs, and then delay cell cycle progression to allow more time for repair; however, to date there is no evidence supporting the coordination of SSB repair and replication in human cells. Here we report that ataxia-telangiectasia mutated kinase (ATM) plays a major role in restricting the replication of SSB-containing DNA and thus prevents DSB formation. We show that ATM is activated by SSBs and coordinates their repair with DNA replication. SSB-mediated ATM activation is followed by a G1 cell cycle delay that allows more time for repair and thus prevents the replication of damaged DNA and DSB accrual. These findings establish an unanticipated role for ATM in the signaling of DNA SSBs and provide important insight into the molecular defects leading to genetic instability in patients with ataxia-telangiectasia.

  8. P31comet, a member of the synaptonemal complex, participates in meiotic DSB formation in rice.

    Science.gov (United States)

    Ji, Jianhui; Tang, Ding; Shen, Yi; Xue, Zhihui; Wang, Hongjun; Shi, Wenqing; Zhang, Chao; Du, Guijie; Li, Yafei; Cheng, Zhukuan

    2016-09-20

    The human mitotic arrest-deficient 2 (Mad2) binding protein p31(comet) participates in the spindle checkpoint and coordinates cell cycle events in mitosis although its function in meiosis remains unknown in all organisms. Here, we reveal P31(comet) as a synaptonemal complex (SC) protein in rice (Oryza sativa L.). In p31(comet), homologous pairing and synapsis are eliminated, leading to the homologous nondisjunction and complete sterility. The failure in loading of histone H2AX phosphorylation (γH2AX) in p31(comet), together with the suppressed chromosome fragmentation in rice completion of meiotic recombination 1 (com1) p31(comet) and radiation sensitive 51c (rad51c) p31(comet) double mutants, indicates that P31(comet) plays an essential role in double-strand break (DSB) formation. Interestingly, the dynamic colocalization pattern between P31(comet) and ZEP1 (a transverse filament protein of SC) by immunostaining, as well as the interaction between P31(comet) and CENTRAL REGION COMPONENT 1 (CRC1) in yeast two-hybrid assays, suggests possible involvement of P31(comet) in SC installation. Together, these data indicate that P31(comet) plays a key role in DSB formation and SC installation, mainly through its cooperation with CRC1.

  9. Analytical model of chemical phase and formation of DSB in chromosomes by ionizing radiation.

    Science.gov (United States)

    Barilla, Jiří; Lokajíček, Miloš; Pisaková, Hana; Simr, Pavel

    2013-03-01

    Mathematical analytical model of the processes running in individual radical clusters during the chemical phase (under the presence of radiomodifiers) proposed by us earlier has been further developed and improved. It has been applied to the data presented by Blok and Loman characterizing the oxygen effect in SSB and DSB formation (in water solution and at low-LET radiation) also in the region of very small oxygen concentrations, which cannot be studied with the help of experiments done with living cells. In this new analysis the values of all reaction rates and diffusion parameters known from literature have been made use of. The great increase of SSB and DSB at zero oxygen concentration may follow from the fact that at small oxygen concentrations the oxygen absorbs other radicals while at higher concentrations the formation of oxygen radicals prevails. It explains the double oxygen effect found already earlier by Ewing. The model may be easily extended to include also the effects of other radiomodifiers present in medium during irradiation.

  10. Non-DSB clustered DNA lesions. Does theory colocalize with the experiment?

    Science.gov (United States)

    Nikitaki, Zacharenia; Nikolov, Vladimir; Mavragani, Ifigeneia V.; Plante, Ianik; Emfietzoglou, Dimitris; Iliakis, George; Georgakilas, Alexandros G.

    2016-11-01

    Ionizing radiation results in various kinds of DNA lesions such as double strand breaks (DSBs) and other non-DSB base lesions. These lesions may be formed in close proximity (i.e., within a few nanometers) resulting in clustered types of DNA lesions. These damage clusters are considered the fingerprint of ionizing radiation, notably charged particles of high linear energy transfer (LET). Accumulating theoretical and experimental evidence suggests that the induction of these clustered lesions appears under various irradiation conditions but also as a result of high levels of oxidative stress. The biological significance of these clustered DNA lesions pertains to the inability of cells to process them efficiently compared to isolated DNA lesions. The results in the case of unsuccessful or erroneous repair can vary from mutations up to chromosomal instability. In this mini review, we discuss of several Monte Carlo simulations codes and experimental evidence regarding the induction and repair of radiation-induced non-DSB complex DNA lesions. We also critically present the most widely used methodologies (i.e., gel electrophoresis and fluorescence microscopy [in situ colocalization assays]). Based on the comparison of different approaches, we provide examples and suggestions for the improved detection of these lesions in situ. Based on the current status of knowledge, we conclude that there is a great need for improvement of the detection techniques at the cellular or tissue level, which will provide valuable information for understanding the mechanisms used by the cell to process clustered DNA lesions.

  11. Involvement of DNA-PK(sub cs) in DSB Repair Following Fe-56 Ion Irradiation

    Science.gov (United States)

    O'Neill, Peter; Harper, Jane; Anderson, Jennifer a.; Cucinnota, Francis A.

    2007-01-01

    When cells are exposed to radiation, cellular lesions are induced in the DNA including double strand breaks (DSBs), single strand breaks and clustered DNA damage, which if not repaired with high fidelity may lead to detrimental biological consequences. Complex DSBs are induced by ionizing radiation and characterized by the presence of base lesions close to the break termini. They are believed to be one of the major causes of the biological effects of IR. The complexity of DSBs increases with the ionization density of the radiation and these complex DSBs are distinct from the damage induced by sparsely ionizing gamma-radiation. It has been hypothesized that complex DSBs produced by heavy ions in space pose problems to the DNA repair machinery. We have used imm uno-cyto-chemical staining of phosphorylated histone H2AX (gamma-H2AX) foci, as a marker of DSBs. We have investigated the formation and loss of gamma-H2AX foci and RAD51 foci (a protein involved in the homologous recombination pathway) in mammalian cells induced by low fluences of low-LET gamma-radiation and high-LET Fe-56 ions (1GeV/n, 151 keV/micron LET). M059J and M059K cells, which are deficient and proficient in DNA-PK(sub cs) activity respectively, were used to examine the role of DNA-PK(sub cs), a key protein in the non-homologous end joining (NHEJ) pathway of DSB repair, along with HF19 human fibroblasts. Followi ng irradiation with Fe-56 ions the rate of repair was slower in M059J cells compared with that in M059K, indicating a role for DNA-PK(sub cs) in the repair of DSB induced by Fe-56 ions. However a small percentage of DSBs induced are rejoined within 5 h although many DSBs still persist up to 24 h. When RAD51 was examined in M059J/K cells, RAD51 foci are visible 24 hours after irradiation in approximately 40% of M059J cells compared with DSB induced by 56Fe ions. Vanillin, an inhibitor of DNA-PK(sub cs), reduces significantly the rate of DSB repair in HF19 cells following 1 Gy gamma

  12. The role of Li+ ions in the gas phase dehydrohalogenation and dehydration reactions of i-C3H7Br and i-C3H7OH molecules studied by radiofrequency-guided ion beam techniques and ab initio methods

    Science.gov (United States)

    López, E.; Lucas, J. M.; de Andrés, J.; Albertí, M.; Bofill, J. M.; Aguilar, A.

    2017-04-01

    Gas phase reactive collisions between lithium ions and i-C3H7X (X = Br, OH) molecules have been studied under single collision conditions in the center of mass (CM) 0.01-10.00 eV energy range using a radiofrequency-guided ion beam apparatus. Mass spectrometry analysis of the products did show the presence of [C3H6—Li]+, [HX—Li]+, C3H7+, and C2H3+ as well as of the [Li—i-C3H7Br]+ adduct while [Li—i-C3H7OH]+ was hardly detected. For all these reactive processes, the corresponding cross sections have been measured in absolute units as a function of the CM collision energy. Quantum chemistry ab initio calculations done at the second order Möller Plesset level have provided relevant information on the topology of the potential energy surfaces (PESs) where a reaction takes place allowing the characterization of the stationary points on the respective PESs along their reaction pathways. The connectivity of the different stationary points localized on the PESs was ensured by using the intrinsic reaction coordinate (IRC) method, confirming the adiabatic character of the reactions. The main topology features of the reactive PESs, in the absence of dynamical calculations, were used to interpret at the qualitative level the behavior of the experimental excitations functions, evidencing the role played by the potential energy barriers on the experimental dynamics of the reactions. Reaction rate constants at 303.2 K for different reactions have been calculated from measured excitation functions.

  13. Spp1, a member of the Set1 Complex, promotes meiotic DSB formation in promoters by tethering histone H3K4 methylation sites to chromosome axes.

    Science.gov (United States)

    Sommermeyer, Vérane; Béneut, Claire; Chaplais, Emmanuel; Serrentino, Maria Elisabetta; Borde, Valérie

    2013-01-10

    Meiotic chromosomes are organized into arrays of loops that are anchored to the chromosome axis structure. Programmed DNA double-strand breaks (DSBs) that initiate meiotic recombination, catalyzed by Spo11 and accessory DSB proteins, form in loop sequences in promoters, whereas the DSB proteins are located on chromosome axes. Mechanisms bridging these two chromosomal regions for DSB formation have remained elusive. Here we show that Spp1, a conserved member of the histone H3K4 methyltransferase Set1 complex, is required for normal levels of DSB formation and is associated with chromosome axes during meiosis, where it physically interacts with the Mer2 DSB protein. The PHD finger module of Spp1, which reads H3K4 methylation close to promoters, promotes DSB formation by tethering these regions to chromosome axes and activating cleavage by the DSB proteins. This paper provides the molecular mechanism linking DSB sequences to chromosome axes and explains why H3K4 methylation is important for meiotic recombination.

  14. Involvement of DNA-PK(sub cs) in DSB Repair Following Fe-56 Ion Irradiation

    Science.gov (United States)

    O'Neill, Peter; Harper, Jane; Anderson, Jennifer a.; Cucinnota, Francis A.

    2007-01-01

    When cells are exposed to radiation, cellular lesions are induced in the DNA including double strand breaks (DSBs), single strand breaks and clustered DNA damage, which if not repaired with high fidelity may lead to detrimental biological consequences. Complex DSBs are induced by ionizing radiation and characterized by the presence of base lesions close to the break termini. They are believed to be one of the major causes of the biological effects of IR. The complexity of DSBs increases with the ionization density of the radiation and these complex DSBs are distinct from the damage induced by sparsely ionizing gamma-radiation. It has been hypothesized that complex DSBs produced by heavy ions in space pose problems to the DNA repair machinery. We have used imm uno-cyto-chemical staining of phosphorylated histone H2AX (gamma-H2AX) foci, as a marker of DSBs. We have investigated the formation and loss of gamma-H2AX foci and RAD51 foci (a protein involved in the homologous recombination pathway) in mammalian cells induced by low fluences of low-LET gamma-radiation and high-LET Fe-56 ions (1GeV/n, 151 keV/micron LET). M059J and M059K cells, which are deficient and proficient in DNA-PK(sub cs) activity respectively, were used to examine the role of DNA-PK(sub cs), a key protein in the non-homologous end joining (NHEJ) pathway of DSB repair, along with HF19 human fibroblasts. Followi ng irradiation with Fe-56 ions the rate of repair was slower in M059J cells compared with that in M059K, indicating a role for DNA-PK(sub cs) in the repair of DSB induced by Fe-56 ions. However a small percentage of DSBs induced are rejoined within 5 h although many DSBs still persist up to 24 h. When RAD51 was examined in M059J/K cells, RAD51 foci are visible 24 hours after irradiation in approximately 40% of M059J cells compared with Vanillin, an inhibitor of DNA-PK(sub cs), reduces significantly the rate of DSB repair in HF19 cells following 1 Gy gamma-radiation but at 0.25 Gy gamma

  15. Transcriptional elongation factor ENL phosphorylated by ATM recruits polycomb and switches off transcription for DSB repair.

    Science.gov (United States)

    Ui, Ayako; Nagaura, Yuko; Yasui, Akira

    2015-05-07

    Transcription is repressed if a DNA double-strand break (DSB) is introduced in close proximity to a transcriptional activation site at least in part by H2A-ubiquitination. While ATM signaling is involved, how it controls H2A-ubiquitination remains unclear. Here, we identify that, in response to DSBs, a transcriptional elongation factor, ENL (MLLT1), is phosphorylated by ATM at conserved SQ sites. This phosphorylation increases the interaction between ENL and the E3-ubiquitin-ligase complex of Polycomb Repressive Complex 1 (PRC1) via BMI1. This interaction promotes enrichment of PRC1 at transcription elongation sites near DSBs to ubiquitinate H2A leading to transcriptional repression. ENL SQ sites and BMI1 are necessary for KU70 accumulation at DSBs near active transcription sites and cellular resistance to DSBs. Our data suggest that ATM-dependent phosphorylation of ENL functions as switch from elongation to Polycomb-mediated repression to preserve genome integrity.

  16. Erwinia carotovora DsbA mutants: evidence for a periplasmic-stress signal transduction system affecting transcription of genes encoding secreted proteins.

    Science.gov (United States)

    Vincent-Sealy, L V; Thomas, J D; Commander, P; Salmond, G P

    1999-08-01

    The dsbA genes, which encode major periplasmic disulfide-bond-forming proteins, were isolated from Erwinia carotovora subsp. carotovora (Ecc) and Erwinia carotovora subsp. atroseptica (Eca), and the dsbC gene, encoding another periplasmic disulfide oxidoreductase was isolated from Ecc. All three genes were sequenced and mutants deficient in these genes were created by marker exchange mutagenesis. The Ecc mutants were severely affected in activity and secretion of pectate lyase, probably due to the absence of functional PelC, which is predicted to require disulfide bond formation to achieve its correct conformation prior to secretion across the outer membrane. Similarly, endopolygalacturonase, also predicted to possess disulfide bonds, displayed reduced activity. The major Ecc cellulase (CelV) does not contain cysteine residues and was still secreted in dsbA-deficient strains. This observation demonstrated unequivocally that the localization and activity of the individual components of the Out apparatus are independent of disulfide bond formation. Surprisingly, cellulase activity was shown to be increased approximately two- to threefold in the DsbA mutant. This phenomenon resulted from transcriptional up-regulation of celV gene expression. In contrast, transcription of both pelC and peh were down-regulated in dsbA-deficient strains when compared to the wild-type. Protease (Prt) activity and secretion were unaffected in the Ecc dsbA mutant. Prt activity was considerably reduced in the double dsbA dsbC mutant. However Prt was secreted normally in this strain. The Eca dsbA mutant was found to be non-motile, suggesting that disulfide bond formation is essential for motility in this strain. All of the dsb mutants showed reduced tissue maceration in planta. These results suggest that a feedback regulation system operates in Ecc. In this system, defects in periplasmic disulfide bond formation act as a signal which is relayed to the transcription machinery regulating gene

  17. Optical transmission radiation damage and recovery stimulation of DSB: Ce3+ inorganic scintillation material

    Science.gov (United States)

    Borisevich, A.; Dormenev, V.; Korjik, M.; Kozlov, D.; Mechinsky, V.; Novotny, R. W.

    2015-02-01

    Recently, a new scintillation material DSB: Ce3+ was announced. It can be produced in a form of glass or nano-structured glass ceramics with application of standard glass production technology with successive thermal annealing. When doped with Ce3+, material can be applied as scintillator. Light yield of scintillation is near 100 phe/MeV. Un-doped material has a wide optical window from 4.5eV and can be applied to detect Cherenkov light. Temperature dependence of the light yield LY(T) is 0.05% which is 40 times less than in case of PWO. It can be used for detectors tolerant to a temperature variation between -20° to +20°C. Several samples with dimensions of 15x15x7 mm3 have been tested for damage effects on the optical transmission under irradiation with γ-quanta. It was found that the induced absorption in the scintillation range depends on the doping concentration and varies in range of 0.5-7 m-1. Spontaneous recovery of induced absorption has fast initial component. Up to 25% of the damaged transmission is recuperated in 6 hours. Afterwards it remains practically constant if the samples are kept in the dark. However, induced absorption is reduced by a factor of 2 by annealing at 50°C and completely removed in a short time when annealing at 100°C. A significant acceleration of the induced absorption recovery is observed by illumination with visible and IR light. This effect is observed for the first time in a Ce-doped scintillation material. It indicates, that radiation induced absorption in DSB: Ce scintillation material can be retained at the acceptable level by stimulation with light in a strong irradiation environment of collider experiments.

  18. Ndrg3 gene regulates DSB repair during meiosis through modulation the ERK signal pathway in the male germ cells

    Science.gov (United States)

    Pan, Hongjie; Zhang, Xuan; Jiang, Hanwei; Jiang, Xiaohua; Wang, Liu; Qi, Qi; Bi, Yuan; Wang, Jian; Shi, Qinghua; Li, Runsheng

    2017-01-01

    The N-myc downstream regulated gene (NDRG) family consists of 4 members, NDRG-1, -2, -3, -4. Physiologically, we found Ndrg3, a critical gene which led to homologous lethality in the early embryo development, regulated the male meiosis in mouse. The expression of Ndrg3 was enhanced specifically in germ cells, and reached its peak level in the pachytene stage spermatocyte. Haplo-insufficiency of Ndrg3 gene led to sub-infertility during the male early maturation. In the Ndrg3+/− germ cells, some meiosis events such as DSB repair and synaptonemal complex formation were impaired. Disturbances on meiotic prophase progression and spermatogenesis were observed. In mechanism, the attenuation of pERK1/2 signaling was detected in the heterozygous testis. With our primary spermatocyte culture system, we found that lactate promoted DSB repair via ERK1/2 signaling in the male mouse germ cells in vitro. Deficiency of Ndrg3 gene attenuated the activation of ERK which further led to the aberrancy of DSB repair in the male germ cells in mouse. Taken together, we reported that Ndrg3 gene modulated the lactate induced ERK pathway to facilitate DSB repair in male germ cells, which further regulated meiosis and subsequently fertility in male mouse. PMID:28290521

  19. Ndrg3 gene regulates DSB repair during meiosis through modulation the ERK signal pathway in the male germ cells.

    Science.gov (United States)

    Pan, Hongjie; Zhang, Xuan; Jiang, Hanwei; Jiang, Xiaohua; Wang, Liu; Qi, Qi; Bi, Yuan; Wang, Jian; Shi, Qinghua; Li, Runsheng

    2017-03-14

    The N-myc downstream regulated gene (NDRG) family consists of 4 members, NDRG-1, -2, -3, -4. Physiologically, we found Ndrg3, a critical gene which led to homologous lethality in the early embryo development, regulated the male meiosis in mouse. The expression of Ndrg3 was enhanced specifically in germ cells, and reached its peak level in the pachytene stage spermatocyte. Haplo-insufficiency of Ndrg3 gene led to sub-infertility during the male early maturation. In the Ndrg3(+/-) germ cells, some meiosis events such as DSB repair and synaptonemal complex formation were impaired. Disturbances on meiotic prophase progression and spermatogenesis were observed. In mechanism, the attenuation of pERK1/2 signaling was detected in the heterozygous testis. With our primary spermatocyte culture system, we found that lactate promoted DSB repair via ERK1/2 signaling in the male mouse germ cells in vitro. Deficiency of Ndrg3 gene attenuated the activation of ERK which further led to the aberrancy of DSB repair in the male germ cells in mouse. Taken together, we reported that Ndrg3 gene modulated the lactate induced ERK pathway to facilitate DSB repair in male germ cells, which further regulated meiosis and subsequently fertility in male mouse.

  20. Application of an InGaAsP diode laser to probe photodissociation dynamics - I(asterisk) quantum yields from n- and i-C3F7I and CH3I by laser gain vs absorption spectroscopy

    Science.gov (United States)

    Hess, W. P.; Kohler, S. J.; Haugen, H. K.; Leone, S. R.

    1986-01-01

    Initial measurements on I-asterisk yields of alkyl iodides at 266 nm are reported using gain vs. absorption spectroscopy with an InGaAsP diode probe laser. The results are 102 percent + or - 4 percent, 102 percent + or - 7 percent, and 73 percent + or - 4 percent for n-C3F7I, i-C3F7I, and CH3I respectively. Future prospects for the development of diode laser systems and for their use in dynamical studies are discussed.

  1. Cytogenetic Response to Ionizing Radiation Exposure in Human Fibroblasts with Suppressed Expression of Non-DSB Repair Genes

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Hammond, Dianne; Mehta, Satish K.; Jeevarajan, Antony S.; Pierson, Duane L.; Wu, Honglu

    2009-01-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in double-strand break (DSB) repair, and its impact on cytogenetic responses has not been well studied. The purpose of this study is to identify new roles of IR inducible genes in radiation-induced chromosome aberrations and micronuclei formation. In the study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by small interfering RNA in human fibroblast cells. Frequencies of micronuclei (MN) formation and chromosome aberrations were measured to determine the efficiency of cytogenetic repair, and the fraction of bi-nucleated cells in the MN analysis was used as a marker for cell cycle progression. In response to gamma radiation, the formation of MN was significantly increased by suppressed expression of five genes: Ku70 (DSB repair pathway), XPA (nucleotide excision repair pathway), RPA1 (mismatch repair pathway), RAD17 and RBBP8 (cell cycle control). Knocked-down expression of four genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Moreover, decreased XPA, p21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Nine of these eleven genes, whose knock-down expression affected cytogenetic repair, were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate IR

  2. Cytogenetic Response to Ionizing Radiation Exposure in Human Fibroblasts with Suppressed Expression of Non-DSB Repair Genes

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Hammond, Dianne; Mehta, Satish K.; Jeevarajan, Antony S.; Pierson, Duane L.; Wu, Honglu

    2009-01-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in double-strand break (DSB) repair, and its impact on cytogenetic responses has not been well studied. The purpose of this study is to identify new roles of IR inducible genes in radiation-induced chromosome aberrations and micronuclei formation. In the study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by small interfering RNA in human fibroblast cells. Frequencies of micronuclei (MN) formation and chromosome aberrations were measured to determine the efficiency of cytogenetic repair, and the fraction of bi-nucleated cells in the MN analysis was used as a marker for cell cycle progression. In response to gamma radiation, the formation of MN was significantly increased by suppressed expression of five genes: Ku70 (DSB repair pathway), XPA (nucleotide excision repair pathway), RPA1 (mismatch repair pathway), RAD17 and RBBP8 (cell cycle control). Knocked-down expression of four genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Moreover, decreased XPA, p21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Nine of these eleven genes, whose knock-down expression affected cytogenetic repair, were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate IR

  3. Integrated Rolling Stock Planning for Suburban Passenger Trains

    DEFF Research Database (Denmark)

    Thorlacius, Per

    used, the result being the loss of optimality. The talk will present a new, integrated rolling stock planning model in which the many requirements are handled all at the same time. Preliminary results from DSB S-tog, the suburban train operator of the City of Copenhagen will also be presented....

  4. DNA-DSB in CHO-K1 cells induced by heavy-ions: Break rejoining and residual damage (GSI)

    Science.gov (United States)

    Taucher-Scholz, G.; Heilmann, J.; Becher, G.; Kraft, G.

    1994-01-01

    DNA double strand breaks (DSB's) are the critical lesions involved in cellular effects of ionizing radiation. Therefore, the evaluation of DSB induction in mammalian cells after heavy ion irradiation is an essential task for the assessment of high-LET radiation risk in space. Of particular interest has been the question of how the biological efficiency for the cellular inactivation endpoint relates to the initial lesions (DSBs) at varying LETs. For cell killing, an increased Relative Biological Efficiency (RBE) has been determined for highLET radiation around 100-200 keV/mu m. At higher LET, the RBE's decrease again to values below one for the very heavy particles. At GSI, DSB-induction was measured in CHO-K1 cells following irradiation with accelerated particles covering a wide LET range. The electrophoretic elution of fragmented DNA out of agarose plugs in a constant electrical field was applied for the detection of DSB's. The fraction of DNA retained was determined considering the relative intensities of ethidium bromide fluorescence in the well and in the gel lane. Dose-effect curves were established, from which the RBE for DSB induction was calculated at a fraction of 0.7 of DNA retained In summary, these rejoining studies are in line with an enhanced severity of the DNA DSB's at higher LET's, resulting in a decreased repairability of the induced lesions. However, no information concerning the fidelity of strand breaks rejoining is provided in these studies. To assess correct rejoining of DNA fragments an experimental system involving individual DNA hybridization bands has been set up. In preliminary experiments Sal I generated DNA fragments of 0.9 Mbp were irradiated with xrays and incubated for repair However, restitution of the original signals was not observed, probably due to the high radiation dose necessary for breakage of a fragment of this size. A banding pattern with NotI hybridization signals in a higher MW range (3Mbp) has been obtained by varying

  5. Comparing Benign and Malignant Neoplasia and DSB Induction for Low-and High-LET Radiation

    Science.gov (United States)

    Burns, Fredric; (Eric) Tang, Moon-Shong; Wu, Feng

    One-and 2-stage models based on DNA double strand breaks (DSBs) have been developed to describe the dose and LET dependence of cancer induction in rat skin exposed to the Bragg plateau of several ion beams or electron radiation. Data are presented showing that carcinomas (malignant) and fibromas (benign) are induced differently by low and high LET radiation. DSBs are subject to complex repair processes, including homologous and non-homologous end joining, that slowly eliminate broken chromosome ends but at the expense of elevating genomic instability that increases the risk of neoplasia. In this formulation the initial molecular lesion in radiation carcinogenesis is assumed to be a DNA double strand break (DSB). The 2-event model assumes that pairs of DSBs join to create cellular genomic instability that eventually progresses to malignancy. The 1-event model assumes that joining is insignificant but that unrepaired DSBs remain and are sufficiently destabilizing to produce low-grade neoplasias. The respective expected relationships between neoplasia yield (Y), radiation dose (D) and LET (L) are: Y(D) = CLD + BD2 (A) for 2-events and Y(D) = CLD (B) for 1-event. Respective B and C values have been evaluated empirically for carcinomas, fibromas and DSBs, the latter via the -H2Ax technique in surrogate keratinocytes, for several types of radiations, including, 40Ar ions, 56Fe ions, 20Ne ions, protons, electrons and x-rays. Fibromas outnumber carcinomas by about 6:1 but are more sensitive than carcinomas to the cytolethal effect of the radiations. The 2-event model agrees well with carcinoma yields in rat skin but fails to model fibromas correctly. Instead the fibroma yields best fitted with the 1-event model for the high LET ion radiations, but at very low LET (electron radiation), an empirical D3 component becomes apparent which is not currently incorporated into the theoretical model. At higher LET values, the D3 component was not detected. The overall results are

  6. Analysis of DNA Double-strand Break (DSB) Repair in Mammalian Cells

    Science.gov (United States)

    Seluanov, Andrei; Mao, Zhiyong; Gorbunova, Vera

    2010-01-01

    DNA double-strand breaks are the most dangerous DNA lesions that may lead to massive loss of genetic information and cell death. Cells repair DSBs using two major pathways: nonhomologous end joining (NHEJ) and homologous recombination (HR). Perturbations of NHEJ and HR are often associated with premature aging and tumorigenesis, hence it is important to have a quantitative way of measuring each DSB repair pathway. Our laboratory has developed fluorescent reporter constructs that allow sensitive and quantitative measurement of NHEJ and HR. The constructs are based on an engineered GFP gene containing recognition sites for a rare-cutting I-SceI endonuclease for induction of DSBs. The starting constructs are GFP negative as the GFP gene is inactivated by an additional exon, or by mutations. Successful repair of the I-SceI-induced breaks by NHEJ or HR restores the functional GFP gene. The number of GFP positive cells counted by flow cytometry provides quantitative measure of NHEJ or HR efficiency. PMID:20864925

  7. Analysis of DNA double-strand break (DSB) repair in mammalian cells.

    Science.gov (United States)

    Seluanov, Andrei; Mao, Zhiyong; Gorbunova, Vera

    2010-09-08

    DNA double-strand breaks are the most dangerous DNA lesions that may lead to massive loss of genetic information and cell death. Cells repair DSBs using two major pathways: nonhomologous end joining (NHEJ) and homologous recombination (HR). Perturbations of NHEJ and HR are often associated with premature aging and tumorigenesis, hence it is important to have a quantitative way of measuring each DSB repair pathway. Our laboratory has developed fluorescent reporter constructs that allow sensitive and quantitative measurement of NHEJ and HR. The constructs are based on an engineered GFP gene containing recognition sites for a rare-cutting I-SceI endonuclease for induction of DSBs. The starting constructs are GFP negative as the GFP gene is inactivated by an additional exon, or by mutations. Successful repair of the I-SceI-induced breaks by NHEJ or HR restores the functional GFP gene. The number of GFP positive cells counted by flow cytometry provides quantitative measure of NHEJ or HR efficiency.

  8. Structural basis for a novel mechanism of DNA bridging and alignment in eukaryotic DSB DNA repair.

    Science.gov (United States)

    Gouge, Jérôme; Rosario, Sandrine; Romain, Félix; Poitevin, Frédéric; Béguin, Pierre; Delarue, Marc

    2015-04-15

    Eukaryotic DNA polymerase mu of the PolX family can promote the association of the two 3'-protruding ends of a DNA double-strand break (DSB) being repaired (DNA synapsis) even in the absence of the core non-homologous end-joining (NHEJ) machinery. Here, we show that terminal deoxynucleotidyltransferase (TdT), a closely related PolX involved in V(D)J recombination, has the same property. We solved its crystal structure with an annealed DNA synapsis containing one micro-homology (MH) base pair and one nascent base pair. This structure reveals how the N-terminal domain and Loop 1 of Tdt cooperate for bridging the two DNA ends, providing a templating base in trans and limiting the MH search region to only two base pairs. A network of ordered water molecules is proposed to assist the incorporation of any nucleotide independently of the in trans templating base. These data are consistent with a recent model that explains the statistics of sequences synthesized in vivo by Tdt based solely on this dinucleotide step. Site-directed mutagenesis and functional tests suggest that this structural model is also valid for Pol mu during NHEJ.

  9. Evaluation of local versus remote areas of CH4 sources at IC3 stations using a combined analysis of 222Rn tracer and Atmospheric Particles Transport Model (APTM) results. Application at the Gredos and Iruelas station (GIC3), Spain.

    Science.gov (United States)

    Grossi, Claudia; Morguí, Josep Anton; Curcoll, Roger; Àgueda, Alba; Arnold, Delia; Batet, Oscar; Cañas, Lidia; Nofuentes, Manel; Occhipinti, Paola; Vogel, Felix; Vargas, Arturo; Rodó, Xavier

    2014-05-01

    The Gredos and Iruelas station (GIC3) is part of the IC3 (Institut Català de Ciències del Clima) atmospheric monitoring network. This station is located in the Gredos Natural Park (40.22º N; -5.14º E) in the Spanish central plateau. The IC3 network consists of 8 stations distributed across Spain. It has been developed with the aim of studying climatic processes and the responses of impacted systems at different temporal and spatial scales. Since 2012, CO2, CH4, 222Rn (a natural radioactive gas) and meteorological variables are continuously measured at GIC3 at 20 m a.g.l. (1100 m a.s.l.). Furthermore, 4-days backward simulations are run daily for each IC3 station using the FLEXPART model. Simulations use ECMWF meteorological data as input and a horizontal spatial resolution of 0.2 degrees. The Laboratory of the Atmosphere and the Oceans (LAO) of the IC3 has elaborated a new approach to evaluate the local or remote greenhouse gases emissions using the radon gas as tracer and the atmospheric particles transport model FLEXPART under nocturnal and winter conditions. The ratios between the normalized and rescaled measured concentrations of CH4 and 222Rn during nocturnal hours (21h, 00h, 03h and 06h) and in the winter season, in order to reduce local radon flux and methane source due to seasonal livestock migration and to get stable atmospheric conditions, have been analyzed in relation to the influence of the local area (set to an initial dimension of 20x20 km2). The influence area (IA) has been defined as the percentage of the ratio between the residence time of the fictitious particles released in FLEXPART simulations over the area of interest (TLocal Area) and the residence time of these fictitious particles over the total area included in the simulation (TTotal Area ), i.e. IA = (TLocal Area/TTotal Area * 100). First results considering an area of interest of 20x20 km2 show a linear increase of the radon concentration with IA until reaching a maximum when IA is

  10. Identification of novel radiosensitizers in a high-throughput, cell-based screen for DSB repair inhibitors.

    Science.gov (United States)

    Goglia, Alexander G; Delsite, Robert; Luz, Antonio N; Shahbazian, David; Salem, Ahmed F; Sundaram, Ranjini K; Chiaravalli, Jeanne; Hendrikx, Petrus J; Wilshire, Jennifer A; Jasin, Maria; Kluger, Harriet M; Glickman, J Fraser; Powell, Simon N; Bindra, Ranjit S

    2015-02-01

    Most cancer therapies involve a component of treatment that inflicts DNA damage in tumor cells, such as double-strand breaks (DSBs), which are considered the most serious threat to genomic integrity. Complex systems have evolved to repair these lesions, and successful DSB repair is essential for tumor cell survival after exposure to ionizing radiation (IR) and other DNA-damaging agents. As such, inhibition of DNA repair is a potentially efficacious strategy for chemo- and radiosensitization. Homologous recombination (HR) and nonhomologous end-joining (NHEJ) represent the two major pathways by which DSBs are repaired in mammalian cells. Here, we report the design and execution of a high-throughput, cell-based small molecule screen for novel DSB repair inhibitors. We miniaturized our recently developed dual NHEJ and HR reporter system into a 384-well plate-based format and interrogated a diverse library of 20,000 compounds for molecules that selectively modulate NHEJ and HR repair in tumor cells. We identified a collection of novel hits that potently inhibit DSB repair, and we have validated their functional activity in a comprehensive panel of orthogonal secondary assays. A selection of these inhibitors was found to radiosensitize cancer cell lines in vitro, which suggests that they may be useful as novel chemo- and radio sensitizers. Surprisingly, we identified several FDA-approved drugs, including the calcium channel blocker mibefradil dihydrochloride, that demonstrated activity as DSB repair inhibitors and radiosensitizers. These findings suggest the possibility for repurposing them as tumor cell radiosensitizers in the future. Accordingly, we recently initiated a phase I clinical trial testing mibefradil as a glioma radiosensitizer.

  11. Participation of DNA-PKcs in DSB repair after exposure to high- and low-LET radiation.

    Science.gov (United States)

    Anderson, Jennifer A; Harper, Jane V; Cucinotta, Francis A; O'Neill, Peter

    2010-08-01

    Cellular lesions (e.g. DSBs) are induced into DNA upon exposure to radiation, with DSB complexity increasing with radiation ionization density. Using M059K and M059J human glioblastoma cells (proficient and deficient in DNA-PKcs activity, respectively), we investigated the repair of DNA damage, including DSBs, induced by high- and low-LET radiation [gamma rays, alpha particles and high-charge and energy (HZE) ions]. In the absence of DNA-PKcs activity, less DSB repair and increased recruitment of RAD51 was seen at 24 h. After exposure to (56)Fe heavy ions, the number of cells with RAD51 tracks was less than the number of cells with gamma-H2AX at 24 h with both cell lines. Using alpha particles, comparable numbers of cells with visible gamma-H2AX and RAD51 were seen at 24 h in both cell lines. M059J cells irradiated with alpha particles accumulated in S phase, with a greater number of cyclin A and RAD51 co-stained cells seen at 24 h compared with M059K cells, where an S-phase block is absent. It is proposed that DNA-PKcs plays a role in the repair of some frank DSBs, which are longer-lived in NHEJ-deficient cells, and some non-DSB clustered damage sites that are converted into DSBs at replication as the cell cycles through to S phase.

  12. Campylobacter jejuni dsb gene expression is regulated by iron in a Fur-dependent manner and by a translational coupling mechanism

    OpenAIRE

    Grabowska, AD; Wandel, MP; Łasica, AM; Nesteruk, M; Roszczenko, P; Wyszyńska, A; Godlewska, R; Jagusztyn-Krynicka, EK

    2011-01-01

    Abstract Background Many bacterial extracytoplasmic proteins are stabilized by intramolecular disulfide bridges that are formed post-translationally between their cysteine residues. This protein modification plays an important role in bacterial pathogenesis, and is facilitated by the Dsb (disulfide bond) family of the redox proteins. These proteins function in two parallel pathways in the periplasmic space: an oxidation pathway and an isomerization pathway. The Dsb oxidative pathway in Campyl...

  13. Rapid MCNP simulation of DNA double strand break (DSB) relative biological effectiveness (RBE) for photons, neutrons, and light ions.

    Science.gov (United States)

    Stewart, Robert D; Streitmatter, Seth W; Argento, David C; Kirkby, Charles; Goorley, John T; Moffitt, Greg; Jevremovic, Tatjana; Sandison, George A

    2015-11-07

    To account for particle interactions in the extracellular (physical) environment, information from the cell-level Monte Carlo damage simulation (MCDS) for DNA double strand break (DSB) induction has been integrated into the general purpose Monte Carlo N-particle (MCNP) radiation transport code system. The effort to integrate these models is motivated by the need for a computationally efficient model to accurately predict particle relative biological effectiveness (RBE) in cell cultures and in vivo. To illustrate the approach and highlight the impact of the larger scale physical environment (e.g. establishing charged particle equilibrium), we examined the RBE for DSB induction (RBEDSB) of x-rays, (137)Cs γ-rays, neutrons and light ions relative to γ-rays from (60)Co in monolayer cell cultures at various depths in water. Under normoxic conditions, we found that (137)Cs γ-rays are about 1.7% more effective at creating DSB than γ-rays from (60)Co (RBEDSB  =  1.017) whereas 60-250 kV x-rays are 1.1 to 1.25 times more efficient at creating DSB than (60)Co. Under anoxic conditions, kV x-rays may have an RBEDSB up to 1.51 times as large as (60)Co γ-rays. Fission neutrons passing through monolayer cell cultures have an RBEDSB that ranges from 2.6 to 3.0 in normoxic cells, but may be as large as 9.93 for anoxic cells. For proton pencil beams, Monte Carlo simulations suggest an RBEDSB of about 1.2 at the tip of the Bragg peak and up to 1.6 a few mm beyond the Bragg peak. Bragg peak RBEDSB increases with decreasing oxygen concentration, which may create opportunities to apply proton dose painting to help address tumor hypoxia. Modeling of the particle RBE for DSB induction across multiple physical and biological scales has the potential to aid in the interpretation of laboratory experiments and provide useful information to advance the safety and effectiveness of hadron therapy in the treatment of cancer.

  14. Spectrum of Radiation-Induced Clustered Non-DSB Damage - A Monte Carlo Track Structure Modeling and Calculations.

    Science.gov (United States)

    Watanabe, Ritsuko; Rahmanian, Shirin; Nikjoo, Hooshang

    2015-05-01

    The aim of this report is to present the spectrum of initial radiation-induced cellular DNA damage [with particular focus on non-double-strand break (DSB) damage] generated by computer simulations. The radiation types modeled in this study were monoenergetic electrons (100 eV-1.5 keV), ultrasoft X-ray photons Ck, AlK and TiK, as well as some selected ions including 3.2 MeV/u proton; 0.74 and 2.4 MeV/u helium ions; 29 MeV/u nitrogen ions and 950 MeV/u iron ions. Monte Carlo track structure methods were used to simulate damage induction by these radiation types in a cell-mimetic condition from a single-track action. The simulations took into account the action of direct energy deposition events and the reaction of hydroxyl radicals on atomistic linear B-DNA segments of a few helical turns including the water of hydration. Our results permitted the following conclusions: a. The absolute levels of different types of damage [base damage, simple and complex single-strand breaks (SSBs) and DSBs] vary depending on the radiation type; b. Within each damage class, the relative proportions of simple and complex damage vary with radiation type, the latter being higher with high-LET radiations; c. Overall, for both low- and high-LET radiations, the ratios of the yields of base damage to SSBs are similar, being about 3.0 ± 0.2; d. Base damage contributes more to the complexity of both SSBs and DSBs, than additional SSB damage and this is true for both low- and high-LET radiations; and e. The average SSB/DSB ratio for low-LET radiations is about 18, which is about 5 times higher than that for high-LET radiations. The hypothesis that clustered DNA damage is more difficult for cells to repair has gained currency among radiobiologists. However, as yet, there is no direct in vivo experimental method to validate the dependence of kinetics of DNA repair on DNA damage complexity (both DSB and non-DSB types). The data on the detailed spectrum of DNA damage presented here, in particular

  15. Rapid MCNP simulation of DNA double strand break (DSB) relative biological effectiveness (RBE) for photons, neutrons, and light ions

    Science.gov (United States)

    Stewart, Robert D.; Streitmatter, Seth W.; Argento, David C.; Kirkby, Charles; Goorley, John T.; Moffitt, Greg; Jevremovic, Tatjana; Sandison, George A.

    2015-11-01

    To account for particle interactions in the extracellular (physical) environment, information from the cell-level Monte Carlo damage simulation (MCDS) for DNA double strand break (DSB) induction has been integrated into the general purpose Monte Carlo N-particle (MCNP) radiation transport code system. The effort to integrate these models is motivated by the need for a computationally efficient model to accurately predict particle relative biological effectiveness (RBE) in cell cultures and in vivo. To illustrate the approach and highlight the impact of the larger scale physical environment (e.g. establishing charged particle equilibrium), we examined the RBE for DSB induction (RBEDSB) of x-rays, 137Cs γ-rays, neutrons and light ions relative to γ-rays from 60Co in monolayer cell cultures at various depths in water. Under normoxic conditions, we found that 137Cs γ-rays are about 1.7% more effective at creating DSB than γ-rays from 60Co (RBEDSB  =  1.017) whereas 60-250 kV x-rays are 1.1 to 1.25 times more efficient at creating DSB than 60Co. Under anoxic conditions, kV x-rays may have an RBEDSB up to 1.51 times as large as 60Co γ-rays. Fission neutrons passing through monolayer cell cultures have an RBEDSB that ranges from 2.6 to 3.0 in normoxic cells, but may be as large as 9.93 for anoxic cells. For proton pencil beams, Monte Carlo simulations suggest an RBEDSB of about 1.2 at the tip of the Bragg peak and up to 1.6 a few mm beyond the Bragg peak. Bragg peak RBEDSB increases with decreasing oxygen concentration, which may create opportunities to apply proton dose painting to help address tumor hypoxia. Modeling of the particle RBE for DSB induction across multiple physical and biological scales has the potential to aid in the interpretation of laboratory experiments and provide useful information to advance the safety and effectiveness of hadron therapy in the treatment of cancer.

  16. High throughput measurement of γH2AX DSB repair kinetics in a healthy human population.

    Science.gov (United States)

    Sharma, Preety M; Ponnaiya, Brian; Taveras, Maria; Shuryak, Igor; Turner, Helen; Brenner, David J

    2015-01-01

    The Columbia University RABiT (Rapid Automated Biodosimetry Tool) quantifies DNA damage using fingerstick volumes of blood. One RABiT protocol quantifies the total γ-H2AX fluorescence per nucleus, a measure of DNA double strand breaks (DSB) by an immunofluorescent assay at a single time point. Using the recently extended RABiT system, that assays the γ-H2AX repair kinetics at multiple time points, the present small scale study followed its kinetics post irradiation at 0.5 h, 2 h, 4 h, 7 h and 24 h in lymphocytes from 94 healthy adults. The lymphocytes were irradiated ex vivo with 4 Gy γ rays using an external Cs-137 source. The effect of age, gender, race, ethnicity, alcohol use on the endogenous and post irradiation total γ-H2AX protein yields at various time points were statistically analyzed. The endogenous γ-H2AX levels were influenced by age, race and alcohol use within Hispanics. In response to radiation, induction of γ-H2AX yields at 0.5 h and peak formation at 2 h were independent of age, gender, ethnicity except for race and alcohol use that delayed the peak to 4 h time point. Despite the shift in the peak observed, the γ-H2AX yields reached close to baseline at 24 h for all groups. Age and race affected the rate of progression of the DSB repair soon after the yields reached maximum. Finally we show a positive correlation between endogenous γ-H2AX levels with radiation induced γ-H2AX yields (RIY) (r=0.257, P=0.02) and a negative correlation with residuals (r=-0.521, P=DSB γ-H2AX repair kinetics as measured by RABiT immunofluorescent assay.

  17. 298 K rate coefficients for the reaction of OH with i-C3H7I, n-C3H7I and C3H8

    Directory of Open Access Journals (Sweden)

    J. N. Crowley

    2001-09-01

    Full Text Available The kinetics of the title reactions were investigated using the laser photolysis - resonance fluorescence method, employing the sequential two-photon dissociation of NO2 in the presence of H2 as the OH source. The 298 K rate constant for OH + C3H8 was found to be (1.15±0.1 × 10-12 cm3 s-1, in excellent agreement with the literature recommendation, and with a separate determination using HNO3 photolysis at 248 nm as the OH source. The 298 K rate constants for OH + n-C3H7I and i-C3H7I were measured for the first time and found to be (1.47±0.08 and (1.22±0.06 × 10-12 cm3 s-1, respectively. The errors include an assessment of systematic error due to concentration measurement, which, for the propyl-iodides was minimised by on-line UV-absorption spectroscopy. The implications of these results for the reactive iodine budget of the marine boundary layer are discussed.

  18. Relative quantum yield of I-asterisk(2P1/2) in the tunable laser UV photodissociation of i-C3F7I and n-C3F7I - Effect of temperature and exciplex emission

    Science.gov (United States)

    Smedley, J. E.; Leone, S. R.

    1983-01-01

    Wavelength-specific relative quantum yields of metastable I from pulsed laser photodissociation of i-C3F7I and n-C3F7I in the range 265-336 nm are determined by measuring the time-resolved infrared emission from the atomic I(P-2(1/2) P-2(3/2) transition. It is shown that although this yield appears to be unity from 265 to 298 nm, it decreases dramatically at longer wavelengths. Values are also reported for the enhancement of emission from metastable I due to exciplex formation at several temperatures. The exciplex formation emission increases linearly with parent gas pressure, but decreases with increasing temperature. Absorption spectra of i- and n-C3F7I between 303 and 497 K are presented, and the effect of temperature on the quantum yields at selected wavelengths greater than 300 nm, where increasing the temperature enhances the absorption considerably, are given. The results are discussed in regard to the development of solar-pumped iodine lasers.

  19. DSB-600A卫星电视接收机电路分析与故障检修

    Institute of Scientific and Technical Information of China (English)

    李育林; 雷新盛; 陈吉利

    2003-01-01

    @@ 1 DSB-600A卫星电视接收机电路分析 空中的卫星电视信号通过卫星接收天线接收和高频头下变频,变换为950~1 450 MHz的第一中频信号,由同轴电缆输送到卫星电视接收机的第二变频器,变频为510 MHz第二中频信号.

  20. Sent packing: protein engineering generates a new crystal form of Pseudomonas aeruginosa DsbA1 with increased catalytic surface accessibility

    Energy Technology Data Exchange (ETDEWEB)

    McMahon, Roisin M., E-mail: r.mcmahon1@uq.edu.au; Coinçon, Mathieu; Tay, Stephanie; Heras, Begoña [University of Queensland, 306 Carmody Road, Brisbane, Queensland 4072 (Australia); Morton, Craig J. [Biota Holdings Limited, Unit 10, 585 Blackburn Road, Notting Hill, Victoria 3168 (Australia); Scanlon, Martin J. [Monash University, 381 Royal Parade, Parkville, Victoria 3052 (Australia); Martin, Jennifer L. [University of Queensland, 306 Carmody Road, Brisbane, Queensland 4072 (Australia)

    2015-11-26

    The crystal structure of a P. aeruginosa DsbA1 variant is more suitable for fragment-based lead discovery efforts to identify inhibitors of this antimicrobial drug target. In the reported structures the active site of the protein can simultaneously bind multiple ligands introduced in the crystallization solution or via soaking. Pseudomonas aeruginosa is an opportunistic human pathogen for which new antimicrobial drug options are urgently sought. P. aeruginosa disulfide-bond protein A1 (PaDsbA1) plays a pivotal role in catalyzing the oxidative folding of multiple virulence proteins and as such holds great promise as a drug target. As part of a fragment-based lead discovery approach to PaDsbA1 inhibitor development, the identification of a crystal form of PaDsbA1 that was more suitable for fragment-soaking experiments was sought. A previously identified crystallization condition for this protein was unsuitable, as in this crystal form of PaDsbA1 the active-site surface loops are engaged in the crystal packing, occluding access to the target site. A single residue involved in crystal-packing interactions was substituted with an amino acid commonly found at this position in closely related enzymes, and this variant was successfully used to generate a new crystal form of PaDsbA1 in which the active-site surface is more accessible for soaking experiments. The PaDsbA1 variant displays identical redox character and in vitro activity to wild-type PaDsbA1 and is structurally highly similar. Two crystal structures of the PaDsbA1 variant were determined in complex with small molecules bound to the protein active site. These small molecules (MES, glycerol and ethylene glycol) were derived from the crystallization or cryoprotectant solutions and provide a proof of principle that the reported crystal form will be amenable to co-crystallization and soaking with small molecules designed to target the protein active-site surface.

  1. Induction of DNA DSB and its rejoining in clamped and non-clamped tumours after exposure to carbon ion beams in comparison to X rays.

    Science.gov (United States)

    Hirayama, R; Uzawa, A; Matsumoto, Y; Noguchi, M; Kase, Y; Takase, N; Ito, A; Koike, S; Ando, K; Okayasu, R; Furusawa, Y

    2011-02-01

    We studied double-strand breaks (DSB) induction and rejoining in clamped and non-clamped transplanted tumours in mice leg after exposure to 80 keV µm(-1) carbon ions and X rays. The yields of DSB in the tumours were analysed by a static-field gel electrophoresis. The OER of DSB after X rays was 1.68±0.31, and this value was not changed after 1 h rejoining time (1.40±0.26). These damages in oxygenated conditions were rejoined 60-70% within 1 h in situ. No difference was found between the exposure to X rays and carbon ions for the induction and rejoining of DSB. Thus, the values of OER and rejoined fraction after exposure to carbon ions were similar to those after X rays, and the calculated relative biological effectivenesses of carbon ion were around 1 under both oxygen conditions. The yields of DSB in vivo depend on exposure doses, oxygen conditions and rejoining time, but not on the types of radiation quality.

  2. A Nuclei Isolation-Filter Elution Assay for the Simultaneous Detection of DNA SSB and DSB of Compact Plant Donor%核分离-滤膜洗脱技术同时检测植物DNA SSB与DSB

    Institute of Scientific and Technical Information of China (English)

    刘晓; 赵玉芳; 凌备备

    2000-01-01

    采用核分离-滤膜洗脱技术,将分离的细胞核在微孔滤膜上裂解后相继用中性溶液和碱性溶液洗脱,研究了60Co-γ辐射引发的大麦种胚细胞DNA断裂.结果显示,50Gy的60Co-γ辐射主要引发DNA单链断裂(DNA SSB);50~100 Gy的辐射引发的DNA断裂包括单链断裂(SSB)与双链断裂(DSB);当辐射剂量大于100 Gy时,DNA断裂的增加部分则以DSB为主.所用的实验方法适用于质地致密的植物材料并可在一次实验中同时检测DNA的SSB与DSB,为植物细胞的DNA链断裂作为生物标志物应用于环境诱变因子监测提供了基础.

  3. miR-3940-5p enhances homologous recombination after DSB in Cr(VI) exposed 16HBE cell.

    Science.gov (United States)

    Li, Yang; Hu, Guiping; Li, Ping; Tang, Shichuan; Zhang, Ji; Jia, Guang

    2016-02-17

    Hexavalent chromium (Cr(VI)) is a well-recognized human carcinogen, yet the molecular mechanisms by which cause human cancer are still not well understood. MicroRNAs (miRNAs), which are small non-coding RNAs, are involved in carcinogenesis and DNA damage repair. Previous occupational population study showed that hexavalent chromium (Cr(VI)) downregulated plasma miR-3940-5p level, and a low miR-3940-5p level was associated with high XRCC2 expression in lymphocytes, indicating that miR-3940-5p maybe play a protective effect in Cr(VI) induced DNA damage. Here we investigated miR-3940-5p expression and its roles in DNA repair in Cr(VI)-treated 16HBE cells. miR-3940-5p change was detected by qRT-PCR. Rad51 foci formation and double strand break (DSB) were investigated to assess homologous recombination repair (HR) capacity by Immunofluorescent assay and Neutral Comet assay. XRCC2 expression was also evaluated after miRNA oligonucleotides transfection using Western blot. Cr(VI) treatment suppressed miR-3940-5p level in 16HBE cells. miR-3904-5p mimic downregulated XRCC2 expression. As a result, the formation of Rad51-foci was inhibited and DSB repair was prolonged. The results indicate that miR-3940-5p plays a protective effect in Cr(VI) induced DNA damage.

  4. Topoisomerase degradation, DSB repair, p53 and IAPs in cancer cell resistance to camptothecin-like topoisomerase I inhibitors.

    Science.gov (United States)

    Tomicic, Maja T; Kaina, Bernd

    2013-01-01

    Topoisomerase I (TOP1) inhibitors applied in cancer therapy such as topotecan and irinotecan are derivatives of the natural alkaloid camptothecin (CPT). The mechanism of CPT poisoning of TOP1 rests on inhibition of the re-ligation function of the enzyme resulting in the stabilization of the TOP1-cleavable complex. In the presence of CPTs this enzyme-DNA complex impairs transcription and DNA replication, resulting in fork stalling and the formation of DNA double-strand breaks (DSB) in proliferating cells. As with most chemotherapeutics, intrinsic and acquired drug resistance represents a hurdle that limits the success of CPT therapy. Preclinical data indicate that resistance to CPT-based drugs might be caused by factors such as (a) poor drug accumulation in the tumor, (b) high rate of drug efflux, (c) mutations in TOP1 leading to failure in CPT docking, or (d) altered signaling triggered by the drug-TOP1-DNA complex, (e) expression of DNA repair proteins, and (f) failure to activate cell death pathways. This review will focus on the issues (d-f). We discuss degradation of TOP1 as part of the repair pathway in the processing of TOP1 associated DNA damage, give a summary of proteins involved in repair of CPT-induced replication mediated DSB, and highlight the role of p53 and inhibitors of apoptosis proteins (IAPs), particularly XIAP and survivin, in cancer cell resistance to CPT-like chemotherapeutics.

  5. Increased sensitivity of BRCA defective triple negative breast tumors to plumbagin through induction of DNA Double Strand Breaks (DSB).

    Science.gov (United States)

    Nair, Rakesh Sathish; Kumar, Jerald Mahesh; Jose, Jedy; Somasundaram, Veena; Hemalatha, Sreelatha K; Sengodan, Satheesh Kumar; Nadhan, Revathy; Anilkumar, Thapasimuthu V; Srinivas, Priya

    2016-05-25

    We have earlier shown that Plumbagin (PB) can induce selective cytotoxicity to BRCA1 defective ovarian cancer cells; however, the effect of this molecule in BRCA1 mutated breast cancers has not been analyzed yet. Here, we report that reactive oxygen species (ROS) induced by PB resulted in DNA DSB and activates downstream signaling by ATR/ATM kinases and subsequent apoptosis. PB reduces DNA- dependent protein kinase (DNA-PK) expression and inhibits NHEJ (Non Homologous End Joining) activity in BRCA1 defective breast cancer cells. Also, PB induces apoptosis in two different BRCA1 conditional knock out murine models: MMTV-Cre; BRCA1(Co/Co) and WAP-Cre; BRCA1(Co/Co), at 2 mg/kg body weight, but 32 mg/kg of carboplatin (CN) was needed to induce apoptosis in them. This is the first study where two different tissue specific promoter driven transgenic mice models with BRCA1 exon 11 deletions are used for preclinical drug testing. The apoptosis induced by PB in HR (Homologous Recombination) defective triple negative BRCA1 mutant cell lines and in mouse models occur by inducing ROS mediated DNA DSB. The toxicity profile as compared with CN in transgenic mice provides evidence for PB's safer disposition as a therapeutic lead in breast cancer drug development.

  6. Co-expression of Dsb proteins enables soluble expression of a single-chain variable fragment (scFv) against human type 1 insulin-like growth factor receptor (IGF-1R) in E. coli.

    Science.gov (United States)

    Sun, Xue-Wen; Wang, Xiao-Hua; Yao, Yan-Bing

    2014-12-01

    Type 1 insulin-like growth factor receptor (IGF-1R) is a promising therapeutic target for cancer treatment. A single-chain variable fragment (scFv) against human IGF-1R forms inclusion body when expressed in periplasmic space of E. coli routinely. Here, we described that co-expression of appropriate disulfide bonds (Dsb) proteins known to catalyze the formation and isomerization of Dsb can markedly recover the soluble expression of target scFv in E. coli. A 50 % recovery in solubility of the scFv was observed upon co-expression of DsbC alone, and a maximum solubility (80 %) was obtained when DsbA and DsbC were co-expressed in combination. Furthermore, the soluble scFv present full antigen-binding activity with IGF-1R, suggesting its correct folding. This study also suggested that the selection of Dsb proteins should be tested case-by-case if the approach of co-expression of Dsb system is adopted to address the problem of insoluble expression of proteins carrying Dsb.

  7. High throughput measurement of γH2AX DSB repair kinetics in a healthy human population.

    Directory of Open Access Journals (Sweden)

    Preety M Sharma

    Full Text Available The Columbia University RABiT (Rapid Automated Biodosimetry Tool quantifies DNA damage using fingerstick volumes of blood. One RABiT protocol quantifies the total γ-H2AX fluorescence per nucleus, a measure of DNA double strand breaks (DSB by an immunofluorescent assay at a single time point. Using the recently extended RABiT system, that assays the γ-H2AX repair kinetics at multiple time points, the present small scale study followed its kinetics post irradiation at 0.5 h, 2 h, 4 h, 7 h and 24 h in lymphocytes from 94 healthy adults. The lymphocytes were irradiated ex vivo with 4 Gy γ rays using an external Cs-137 source. The effect of age, gender, race, ethnicity, alcohol use on the endogenous and post irradiation total γ-H2AX protein yields at various time points were statistically analyzed. The endogenous γ-H2AX levels were influenced by age, race and alcohol use within Hispanics. In response to radiation, induction of γ-H2AX yields at 0.5 h and peak formation at 2 h were independent of age, gender, ethnicity except for race and alcohol use that delayed the peak to 4 h time point. Despite the shift in the peak observed, the γ-H2AX yields reached close to baseline at 24 h for all groups. Age and race affected the rate of progression of the DSB repair soon after the yields reached maximum. Finally we show a positive correlation between endogenous γ-H2AX levels with radiation induced γ-H2AX yields (RIY (r=0.257, P=0.02 and a negative correlation with residuals (r=-0.521, P=<0.0001. A positive correlation was also observed between RIY and DNA repair rate (r=0.634, P<0.0001. Our findings suggest age, race, ethnicity and alcohol use influence DSB γ-H2AX repair kinetics as measured by RABiT immunofluorescent assay.

  8. Influence of chromatin condensation on the number of direct DSB damages induced by ions studied using a Monte Carlo code.

    Science.gov (United States)

    Dos Santos, M; Clairand, I; Gruel, G; Barquinero, J F; Incerti, S; Villagrasa, C

    2014-10-01

    The purpose of this work is to evaluate the influence of the chromatin condensation on the number of direct double-strand break (DSB) damages induced by ions. Two geometries of chromosome territories containing either condensed or decondensed chromatin were implemented as biological targets in the Geant4 Monte Carlo simulation code and proton and alpha irradiation was simulated using the Geant4-DNA processes. A DBSCAN algorithm was used in order to detect energy deposition clusters that could give rise to single-strand breaks or DSBs on the DNA molecule. The results of this study show an increase in the number and complexity of DNA DSBs in condensed chromatin when compared with decondensed chromatin.

  9. PISM-DSB原理及其仿真应用%The PISM-DSB Principle and Its Simulation Application

    Institute of Scientific and Technical Information of China (English)

    赵贤凌; 萧宝瑾

    2006-01-01

    反相对称调制(PISM)与普通双边带(DSB)调制相结合可以在同一载频上同时传输两路不同的信号,而在接收端采用两种解调方法可以分别接收到这两路不同的信号.将这一方法用于实际通信系统中会使信道利用率提高一倍.另外,PISM-DSB对他台干扰也有一定的抑制作用.论述了这一方法的基本原理,并对它进行了计算机仿真,得到了满意的结果.

  10. Requirement of Signal Peptidase ComC and Thiol-Disulfide Oxidoreductase DsbA for Optimal Cell Surface Display of Pseudopilin ComGC in Staphylococcus aureus

    NARCIS (Netherlands)

    van der Kooi-Pol, Magdalena M.; Reilman, Ewoud; Sibbald, Mark J. J. B.; Veenstra-Kyuchukova, Yanka K.; Kouwen, Thijs R. H. M.; Buist, Girbe; van Dijl, Jan Maarten

    2012-01-01

    Staphylococcus aureus is an important Gram-positive bacterial pathogen producing many secreted and cell surface-localized virulence factors. Here we report that the staphylococcal thiol-disulfide oxidoreductase DsbA is essential for stable biogenesis of the ComGC pseudopilin. The signal peptidase

  11. Tid1/Rdh54 translocase is phosphorylated through a Mec1- and Rad53-dependent manner in the presence of DSB lesions in budding yeast.

    Science.gov (United States)

    Ferrari, Matteo; Nachimuthu, Benjamin Tamilselvan; Donnianni, Roberto Antonio; Klein, Hannah; Pellicioli, Achille

    2013-05-01

    Saccharomyces cerevisiae cells with a single double-strand break (DSB) activate the ATR/Mec1-dependent checkpoint response as a consequence of extensive ssDNA accumulation. The recombination factor Tid1/Rdh54, a member of the Swi2-like family proteins, has an ATPase activity and may contribute to the remodelling of nucleosomes on DNA. Tid1 dislocates Rad51 recombinase from dsDNA, can unwind and supercoil DNA filaments, and has been implicated in checkpoint adaptation from a G2/M arrest induced by an unrepaired DSB. Here we show that both ATR/Mec1 and Chk2/Rad53 kinases are implicated in the phosphorylation of Tid1 in the presence of DNA damage, indicating that the protein is regulated during the DNA damage response. We show that Tid1 ATPase activity is dispensable for its phosphorylation and for its recruitment near a DSB, but it is required to switch off Rad53 activation and for checkpoint adaptation. Mec1 and Rad53 kinases, together with Rad51 recombinase, are also implicated in the hyper-phosphorylation of the ATPase defective Tid1-K318R variant and in the efficient binding of the protein to the DSB site. In summary, Tid1 is a novel target of the DNA damage checkpoint pathway that is also involved in checkpoint adaptation.

  12. Complex cisplatin-double strand break (DSB) lesions directly impair cellular non-homologous end-joining (NHEJ) independent of downstream damage response (DDR) pathways.

    Science.gov (United States)

    Sears, Catherine R; Turchi, John J

    2012-07-13

    The treatment for advanced stage non-small cell lung cancer (NSCLC) often includes platinum-based chemotherapy and IR. Cisplatin and IR combination therapy display schedule and dose-dependent synergy, the mechanism of which is not completely understood. In a series of in vitro and cell culture assays in a NSCLC model, we investigated both the downstream and direct treatment and damage effects of cisplatin on NHEJ catalyzed repair of a DNA DSB. The results demonstrate that extracts prepared from cisplatin-treated cells are fully capable of NHEJ catalyzed repair of a DSB using a non-cisplatin-damaged DNA substrate in vitro. Similarly, using two different host cell reactivation assays, treatment of cells prior to transfection of a linear, undamaged reporter plasmid revealed no reduction in NHEJ compared with untreated cells. In contrast, transfection of a linear GFP-reporter plasmid containing site-specific, cisplatin lesions 6-bp from the termini revealed a significant impairment in DSB repair of the cisplatin-damaged DNA substrates in the absence of cellular treatment with cisplatin. Together, these data demonstrate that impaired NHEJ in combined cisplatin-IR treated cells is likely the result of a direct effect of cisplatin-DNA lesions near a DSB and that the indirect cellular effects of cisplatin treatment are not significant contributors to the synergistic cytotoxicity observed with combination cisplatin-IR treatment.

  13. Novel Biological Approaches for Testing the Contributions of Single DSBs and DSB Clusters to the Biological Effects of High LET Radiation.

    Science.gov (United States)

    Mladenova, Veronika; Mladenov, Emil; Iliakis, George

    2016-01-01

    The adverse biological effects of ionizing radiation (IR) are commonly attributed to the generation of DNA double-strand breaks (DSBs). IR-induced DSBs are generated by clusters of ionizations, bear damaged terminal nucleotides, and frequently comprise base damages and single-strand breaks in the vicinity generating a unique DNA damage-clustering effect that increases DSB "complexity." The number of ionizations in clusters of different radiation modalities increases with increasing linear energy transfer (LET), and is thought to determine the long-known LET-dependence of the relative biological effectiveness (RBE). Multiple ionizations may also lead to the formation of DSB clusters, comprising two or more DSBs that destabilize chromatin further and compromise overall processing. DSB complexity and DSB-cluster formation are increasingly considered in the development of mathematical models of radiation action, which are then "tested" by fitting available experimental data. Despite a plethora of such mathematical models the ultimate goal, i.e., the "a priori" prediction of the radiation effect, has not yet been achieved. The difficulty partly arises from unsurmountable difficulties in testing the fundamental assumptions of such mathematical models in defined biological model systems capable of providing conclusive answers. Recently, revolutionary advances in methods allowing the generation of enzymatic DSBs at random or in well-defined locations in the genome, generate unique testing opportunities for several key assumptions frequently fed into mathematical modeling - including the role of DSB clusters in the overall effect. Here, we review the problematic of DSB-cluster formation in radiation action and present novel biological technologies that promise to revolutionize the way we address the biological consequences of such lesions. We describe new ways of exploiting the I-SceI endonuclease to generate DSB-clusters at random locations in the genome and describe the

  14. Evidence that the Nijmegen breakage syndrome protein, an early sensor of double-strand DNA breaks (DSB), is involved in HIV-1 post-integration repair by recruiting the ataxia telangiectasia-mutated kinase in a process similar to, but distinct from, cellular DSB repair.

    Science.gov (United States)

    Smith, Johanna A; Wang, Feng-Xiang; Zhang, Hui; Wu, Kou-Juey; Williams, Kevin Jon; Daniel, René

    2008-01-22

    Retroviral transduction involves integrase-dependent linkage of viral and host DNA that leaves an intermediate that requires post-integration repair (PIR). We and others proposed that PIR hijacks the host cell double-strand DNA break (DSB) repair pathways. Nevertheless, the geometry of retroviral DNA integration differs considerably from that of DSB repair and so the precise role of host-cell mechanisms in PIR remains unclear. In the current study, we found that the Nijmegen breakage syndrome 1 protein (NBS1), an early sensor of DSBs, associates with HIV-1 DNA, recruits the ataxia telangiectasia-mutated (ATM) kinase, promotes stable retroviral transduction, mediates efficient integration of viral DNA and blocks integrase-dependent apoptosis that can arise from unrepaired viral-host DNA linkages. Moreover, we demonstrate that the ATM kinase, recruited by NBS1, is itself required for efficient retroviral transduction. Surprisingly, recruitment of the ATR kinase, which in the context of DSB requires both NBS1 and ATM, proceeds independently of these two proteins. A model is proposed emphasizing similarities and differences between PIR and DSB repair. Differences between the pathways may eventually allow strategies to block PIR while still allowing DSB repair.

  15. Artemis is required to improve the accuracy of repair of double-strand breaks with 5'-blocked termini generated from non-DSB-clustered lesions.

    Science.gov (United States)

    Malyarchuk, Svitlana; Castore, Reneau; Shi, Runhua; Harrison, Lynn

    2013-05-01

    Clustered DNA lesions are defined as ≥2 damage events within 20 bp. Oxidised bases, abasic (AP) sites, single-strand breaks and double-strand breaks (DSBs) exist in radiation-induced clusters, and these lesions are more difficult to repair and can be more mutagenic than single lesions. Understanding clustered lesion repair is therefore important for the design of complementary treatments to enhance radiotherapy. Non-DSB-clustered lesions consisting of opposing AP sites can be converted to DSBs by base excision repair, and non-homologous end-joining (NHEJ) plays a role in repairing these DSBs. Artemis is an endonuclease that removes blocking groups from DSB termini during NHEJ. Hence, we hypothesised that Artemis plays a role in the processing of DSBs or complex DSBs generated from non-DSB-clustered lesions. We examined the repair of clusters containing two or three lesions in wild-type (WT) or Artemis-deficient (ART(-/-)) mouse fibroblasts using a reporter plasmid. Each cluster contained two opposing tetrahydrofurans (an AP site analogue), which AP endonuclease can convert to a DSB with blocked 5' termini. Loss of Artemis did not decrease plasmid survival, but did result in more mutagenic repair with plasmids containing larger deletions. This increase in deletions did not occur with ClaI-linearised plasmid. Since Mre11 has been implicated in deletional NHEJ, we used small interfering RNA to reduce Mre11 in WT and ART(-/-) cells, but decreasing Mre11 did not change the size of deletions in the repair products. This work implicates Artemis in limiting the deletions introduced during repair of 5'-blocked termini DSBs generated from non-DSB-clustered lesions. Decreasing repair accuracy without decreasing repair capacity could result in mutated cells surviving irradiation. Inhibiting Artemis in normal cells could promote carcinogenesis, while in tumour cells enhanced mutagenic repair following irradiation could promote tumour recurrence.

  16. Repair of I-SceI induced DSB at a specific site of chromosome in human cells: influence of low-dose, low-dose-rate gamma-rays.

    Science.gov (United States)

    Yatagai, Fumio; Suzuki, Masao; Ishioka, Noriaki; Ohmori, Hitoshi; Honma, Masamitsu

    2008-11-01

    We investigated the influence of low-dose, low-dose-rate gamma-ray irradiation on DNA double strand break (DSB) repair in human lymphoblastoid TK6 cells. A single DSB was introduced at intron 4 of the TK+ allele (chromosome 17) by transfection with the I-SceI expression vector pCBASce. We assessed for DSB repair due to non-homologous end-joining (NHEJ) by determining the generation of TK-deficient mutants in the TK6 derivative TSCE5 (TK +/-) carrying an I-SceI recognition site. We similarly estimated DSB repair via homologous recombination (HR) at the same site in the derived compound heterozygote (TK-/-) cell line TSCER2 that carries an additional point mutation in exon 5. The NHEJ repair of DSB was barely influenced by pre-irradiation of the cells with 30 mGy gamma-rays at 1.2 mGy h(-1). DSB repair by HR, in contrast, was enhanced by approximately 50% after pre-irradiation of the cells under these conditions. Furthermore, when I-SceI digestion was followed by irradiation at a dose of 8.5 mGy, delivered at a dose rate of only 0.125 mGy h(-1), HR repair efficiency was enhanced by approximately 80%. This experimental approach can be applied to characterize DSB repair in the low-dose region of ionizing radiation.

  17. In normal human fibroblasts variation in DSB repair capacity cannot be ascribed to radiation-induced changes in the localisation, expression or activity of major NHEJ proteins

    DEFF Research Database (Denmark)

    Kasten-Pisula, Ulla; Vronskaja, Svetlana; Overgaard, Jens

    2008-01-01

    BACKGROUND AND PURPOSE: The aim of the present study was to test whether for normal human fibroblasts the variation in double-strand break (DSB) repair capacity results from radiation-induced differences in localisation, expression or activity of major non-homologous end-joining (NHEJ) proteins....... MATERIALS AND METHODS: Experiments were performed with 11 normal human fibroblast strains AF01-11. NHEJ proteins were determined by Western blot and DNA-PK activity by pulldown-assay. RESULTS: The four NHEJ proteins tested (Ku70, Ku80, XRCC4 and DNA-PKcs) were found to be localised almost exclusively...... in the activity of the DNA-PK complex induced upon irradiation. CONCLUSIONS: For normal human fibroblasts, the level or activity of NHEJ proteins measured prior to or after irradiation cannot be used to predict the DSB repair capacity or cellular radiosensitivity. Udgivelsesdato: 2008-Mar...

  18. Genistein sensitizes sarcoma cells in vitro and in vivo by enhancing apoptosis and by inhibiting DSB repair pathways.

    Science.gov (United States)

    Liu, X X; Sun, C; Jin, X D; Li, P; Zheng, X G; Zhao, T; Li, Q

    2016-06-01

    The aim of this work was to investigate the radiosensitization effects of genistein on mice sarcoma cells and the corresponding biological mechanisms in vitro and in vivo Using the non-toxic dosage of 10 μM genistein, the sensitizer enhancement ratios after exposure to X-rays at 50% cell survival (IC50) was 1.45 for S180 cells. For mice cotreated with genistein and X-rays, the excised tumor tissues had reduced blood vessels and decreased size and volume compared with the control and irradiation-only groups. Moreover, a significant increase in apoptosis was accompanied by upregulation of Bax and downregulation of Bcl-2 in the mitochondria, and lots of cytochrome c being transferred to the cytoplasm. Furthermore, X-rays combined with genistein inhibited the activity of DNA-PKcs, so DNA-injured sites were dominated by Ku70/80, leading to incompleteness of homologous recombination (HR) and non-homologous end-joining (NHEJ) repairs and the eventual occurrence of cell apoptosis. Our study, for the first time, demonstrated that genistein sensitized sarcoma cells to X-rays and that this radiosensitizing effect depended on induction of the mitochondrial apoptosis pathway and inhibition of the double-strand break (DSB) repair pathways.

  19. KARP-1 works as a heterodimer with Ku70, but the function of KARP-1 cannot perfectly replace that of Ku80 in DSB repair.

    Science.gov (United States)

    Koike, Manabu; Yutoku, Yasutomo; Koike, Aki

    2011-10-01

    Ku, the heterodimer of Ku70 and Ku80, plays an essential role in the DNA double-strand break (DSB) repair pathway, i.e., non-homologous end-joining (NHEJ). Two isoforms of Ku80 encoded by the same genes, namely, Ku80 and KARP-1 are expressed and function in primate cells, but not in rodent cells. Ku80 works as a heterodimer with Ku70. However, it is not yet clear whether KARP-1 forms a heterodimer with Ku70 and works as a heterodimer. Although KARP-1 appears to work in NHEJ, its physiological role remains unclear. In this study, we established and characterized EGFP-KARP-1-expressing xrs-6 cell lines, EGFP-KARP-1/xrs-6. We found that nuclear localization signal (NLS) of KARP-1 is localized in the C-terminal region. Our data showed that KARP-1 localizes within the nucleus in NLS-dependent and NLS-independent manner and forms a heterodimer with Ku70, and stabilizes Ku70. On the other hand, EGFP-KARP-1 could not perfectly complement the radiosensitivity and DSB repair activity of Ku80-deficient xrs-6 cells. Furthermore, KARP-1 could not accumulate at DSBs faster than Ku80, although EGFP-KARP-1 accumulates at DSBs. Our data demonstrate that the function of KARP-1 could not perfectly replace that of Ku80 in DSB repair, although KARP-1 has some biochemical properties, which resemble those of Ku80, and works as a heterodimer with Ku70. On the other hand, the number of EGFP-KARP-1-expressing xrs-6 cells showing pan-nuclear γ-H2AX staining significantly increases following X-irradiation, suggesting that KARP-1 may have a novel role in DSB response. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. TODRA, a lncRNA at the RAD51 Locus, Is Oppositely Regulated to RAD51, and Enhances RAD51-Dependent DSB (Double Strand Break) Repair.

    Science.gov (United States)

    Gazy, Inbal; Zeevi, David A; Renbaum, Paul; Zeligson, Sharon; Eini, Lital; Bashari, Dana; Smith, Yoav; Lahad, Amnon; Goldberg, Michal; Ginsberg, Doron; Levy-Lahad, Ephrat

    2015-01-01

    Expression of RAD51, a crucial player in homologous recombination (HR) and DNA double-strand break (DSB) repair, is dysregulated in human tumors, and can contribute to genomic instability and tumor progression. To further understand RAD51 regulation we functionally characterized a long non-coding (lnc) RNA, dubbed TODRA (Transcribed in the Opposite Direction of RAD51), transcribed 69bp upstream to RAD51, in the opposite direction. We demonstrate that TODRA is an expressed transcript and that the RAD51 promoter region is bidirectional, supporting TODRA expression (7-fold higher than RAD51 in this assay, p = 0.003). TODRA overexpression in HeLa cells induced expression of TPIP, a member of the TPTE family which includes PTEN. Similar to PTEN, we found that TPIP co-activates E2F1 induction of RAD51. Analysis of E2F1's effect on the bidirectional promoter showed that E2F1 binding to the same site that promotes RAD51 expression, results in downregulation of TODRA. Moreover, TODRA overexpression induces HR in a RAD51-dependent DSB repair assay, and increases formation of DNA damage-induced RAD51-positive foci. Importantly, gene expression in breast tumors supports our finding that E2F1 oppositely regulates RAD51 and TODRA: increased RAD51 expression, which is associated with an aggressive tumor phenotype (e.g. negative correlation with positive ER (r = -0.22, p = 0.02) and positive PR status (r = -0.27, pDSB repair in malignancy. Importantly, gene expression in breast tumors supports our finding that E2F1 oppositely regulates RAD51 and TODRA: increased RAD51 expression, which is associated with an aggressive tumor phenotype (e.g. negative correlation with positive ER (r = -0.22, p = 0.02) and positive PR status (r = -0.27, pDSB repair in malignancy.

  1. Defective DSB repair correlates with abnormal nuclear morphology and is improved with FTI treatment in Hutchinson-Gilford progeria syndrome fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Constantinescu, Dan [Department of Cell Biology-Physiology, University of Pittsburgh, Pittsburgh, PA 15260 (United States); Pittsburgh Development Center, Magee-Women' s Research Institute, University of Pittsburgh, Pittsburgh, PA 15260 (United States); Csoka, Antonei B. [Division of Geriatrics, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15260 (United States); Navara, Christopher S. [Division of Developmental and Regenerative Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15260 (United States); Pittsburgh Development Center, Magee-Women' s Research Institute, University of Pittsburgh, Pittsburgh, PA 15260 (United States); Schatten, Gerald P., E-mail: schattengp@upmc.edu [Division of Developmental and Regenerative Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15260 (United States); Department of Cell Biology-Physiology, University of Pittsburgh, Pittsburgh, PA 15260 (United States); Pittsburgh Development Center, Magee-Women' s Research Institute, University of Pittsburgh, Pittsburgh, PA 15260 (United States)

    2010-10-15

    Impaired DSB repair has been implicated as a molecular mechanism contributing to the accelerating aging phenotype in Hutchinson-Gilford progeria syndrome (HGPS), but neither the extent nor the cause of the repair deficiency has been fully elucidated. Here we perform a quantitative analysis of the steady-state number of DSBs and the repair kinetics of ionizing radiation (IR)-induced DSBs in HGPS cells. We report an elevated steady-state number of DSBs and impaired repair of IR-induced DSBs, both of which correlated strongly with abnormal nuclear morphology. We recreated the HGPS cellular phenotype in human coronary artery endothelial cells for the first time by lentiviral transduction of GFP-progerin, which also resulted in impaired repair of IR-induced DSBs, and which correlated with abnormal nuclear morphology. Farnesyl transferase inhibitor (FTI) treatment improved the repair of IR-induced DSBs, but only in HGPS cells whose nuclear morphology was also normalized. Interestingly, FTI treatment did not result in a statistically significant reduction in the higher steady-state number of DSBs. We also report a delay in localization of phospho-NBS1 and MRE11, MRN complex repair factors necessary for homologous recombination (HR) repair, to DSBs in HGPS cells. Our results demonstrate a correlation between nuclear structural abnormalities and the DSB repair defect, suggesting a mechanistic link that may involve delayed repair factor localization to DNA damage. Further, our results show that similar to other HGPS phenotypes, FTI treatment has a beneficial effect on DSB repair.

  2. Rad52 competes with Ku70/Ku86 for binding to S-region DSB ends to modulate antibody class-switch DNA recombination

    Science.gov (United States)

    Zan, Hong; Tat, Connie; Qiu, Zhifang; Taylor, Julia R.; Guerrero, Justin A.; Shen, Tian; Casali, Paolo

    2017-01-01

    Antibody class-switch DNA recombination (CSR) is initiated by AID-introduced DSBs in the switch (S) regions targeted for recombination, as effected by Ku70/Ku86-mediated NHEJ. Ku-deficient B cells, however, undergo (reduced) CSR through an alternative(A)-NHEJ pathway, which introduces microhomologies in S–S junctions. As microhomology-mediated end-joining requires annealing of single-strand DNA ends, we addressed the contribution of single-strand annealing factors HR Rad52 and translesion DNA polymerase θ to CSR. Compared with their Rad52+/+ counterparts, which display normal CSR, Rad52−/− B cells show increased CSR, fewer intra-Sμ region recombinations, no/minimal microhomologies in S–S junctions, decreased c-Myc/IgH translocations and increased Ku70/Ku86 recruitment to S-region DSB ends. Rad52 competes with Ku70/Ku86 for binding to S-region DSB ends. It also facilitates a Ku-independent DSB repair, which favours intra-S region recombination and mediates, particularly in Ku absence, inter-S–S recombination, as emphasized by the significantly greater CSR reduction in Rad52−/− versus Rad52+/+ B cells on Ku86 knockdown. PMID:28176781

  3. DNA双链断裂NHEJ修复及其与肿瘤的研究%Non-homologous end joining pathway of DSB repair and cancer

    Institute of Scientific and Technical Information of China (English)

    张耀伟

    2010-01-01

    非同源末端连接是哺乳动物最主要的DNA双链断裂(DSB)连接方式.肿瘤细胞非同源末端连接能力的提高与其放化疗抵抗有关,抑制肿瘤细胞非同源末端连接能力,可能增加其对放化疗的敏感性.因此,参与非同源末端连接的修复因子可能成为肿瘤分子靶向治疗及放化疗增敏的新治疗点.%Non-homologous end joining (NHEJ) is the major pathway for repairing DNA doublestrand break (DSB) in mammalian species. The capacity of NHEJ increases in tumor cell,which plays a role in radiation/chemotherapy-resistant agent Inhibiting DSB rejoining may play a crucial role in the enhancement of cellular radiation/chemotherapy-sensitizing. Thus, the protein molecule enrolled in NHEJ may be new potential targets for radiation/chemotherapy -sensitizing.

  4. Overexpression of OsRecQl4 and/or OsExo1 enhances DSB-induced homologous recombination in rice.

    Science.gov (United States)

    Kwon, Yong-Ik; Abe, Kiyomi; Osakabe, Keishi; Endo, Masaki; Nishizawa-Yokoi, Ayako; Saika, Hiroaki; Shimada, Hiroaki; Toki, Seiichi

    2012-12-01

    During homologous recombination (HR)-mediated DNA double-strand break (DSB) repair in eukaryotes, an initial step is the creation of a 3'-single-stranded DNA (ssDNA) overhang via resection of a 5' end. Rad51 polymerizes on this ssDNA to search for a homologous sequence, and the gapped sequence is then repaired using an undamaged homologous DNA strand as template. Recent studies in eukaryotes indicate that resection of the DSB site is promoted by the cooperative action of RecQ helicase family proteins: Bloom helicase (BLM) in mammals or Sgs1 in yeast, and exonuclease 1 (Exo1). However, the role of RecQ helicase and exonuclease during the 5'-resection process of HR in plant cells has not yet been defined. Here, we demonstrate that overexpression of rice proteins OsRecQl4 (BLM counterpart) and/or OsExo1 (Exo1 homolog) can enhance DSB processing, as evaluated by recombination substrate reporter lines in rice. These results could be applied to construct an efficient gene targeting system in rice.

  5. Plant γH2AX foci are required for proper DNA DSB repair responses and colocalize with E2F factors.

    Science.gov (United States)

    Lang, Julien; Smetana, Ondrej; Sanchez-Calderon, Lenin; Lincker, Frédéric; Genestier, Julie; Schmit, Anne-Catherine; Houlné, Guy; Chabouté, Marie-Edith

    2012-04-01

    Cellular responses to DNA double-strand breaks (DSBs) are linked in mammals and yeasts to the phosphorylated histones H2AX (γH2AX) repair foci which are multiproteic nuclear complexes responsible for DSB sensing and signalling. However, neither the components of these foci nor their role are yet known in plants. In this paper, we describe the effects of γH2AX deficiency in Arabidopsis thaliana plants challenged with DSBs in terms of genotoxic sensitivity and E2F-mediated transcriptional responses. We further establish the existence, restrictive to the G1/S transition, of specific DSB-induced foci containing tobacco E2F transcription factors, in both A. thaliana roots and BY-2 tobacco cells. These E2F foci partially colocalize with γH2AX foci while their formation is ataxia telangiectasia mutated (ATM)-dependent, requires the E2F transactivation domain with its retinoblastoma-binding site and is optimal in the presence of functional H2AXs. Overall, our results unveil a new interplay between plant H2AX and E2F transcriptional activators during the DSB response.

  6. Rad52 competes with Ku70/Ku86 for binding to S-region DSB ends to modulate antibody class-switch DNA recombination.

    Science.gov (United States)

    Zan, Hong; Tat, Connie; Qiu, Zhifang; Taylor, Julia R; Guerrero, Justin A; Shen, Tian; Casali, Paolo

    2017-02-08

    Antibody class-switch DNA recombination (CSR) is initiated by AID-introduced DSBs in the switch (S) regions targeted for recombination, as effected by Ku70/Ku86-mediated NHEJ. Ku-deficient B cells, however, undergo (reduced) CSR through an alternative(A)-NHEJ pathway, which introduces microhomologies in S-S junctions. As microhomology-mediated end-joining requires annealing of single-strand DNA ends, we addressed the contribution of single-strand annealing factors HR Rad52 and translesion DNA polymerase θ to CSR. Compared with their Rad52(+/+) counterparts, which display normal CSR, Rad52(-/-) B cells show increased CSR, fewer intra-Sμ region recombinations, no/minimal microhomologies in S-S junctions, decreased c-Myc/IgH translocations and increased Ku70/Ku86 recruitment to S-region DSB ends. Rad52 competes with Ku70/Ku86 for binding to S-region DSB ends. It also facilitates a Ku-independent DSB repair, which favours intra-S region recombination and mediates, particularly in Ku absence, inter-S-S recombination, as emphasized by the significantly greater CSR reduction in Rad52(-/-) versus Rad52(+/+) B cells on Ku86 knockdown.

  7. Defective DSB repair correlates with abnormal nuclear morphology and is improved with FTI treatment in Hutchinson-Gilford progeria syndrome fibroblasts.

    Science.gov (United States)

    Constantinescu, Dan; Csoka, Antonei B; Navara, Christopher S; Schatten, Gerald P

    2010-10-15

    Impaired DSB repair has been implicated as a molecular mechanism contributing to the accelerating aging phenotype in Hutchinson-Gilford progeria syndrome (HGPS), but neither the extent nor the cause of the repair deficiency has been fully elucidated. Here we perform a quantitative analysis of the steady-state number of DSBs and the repair kinetics of ionizing radiation (IR)-induced DSBs in HGPS cells. We report an elevated steady-state number of DSBs and impaired repair of IR-induced DSBs, both of which correlated strongly with abnormal nuclear morphology. We recreated the HGPS cellular phenotype in human coronary artery endothelial cells for the first time by lentiviral transduction of GFP-progerin, which also resulted in impaired repair of IR-induced DSBs, and which correlated with abnormal nuclear morphology. Farnesyl transferase inhibitor (FTI) treatment improved the repair of IR-induced DSBs, but only in HGPS cells whose nuclear morphology was also normalized. Interestingly, FTI treatment did not result in a statistically significant reduction in the higher steady-state number of DSBs. We also report a delay in localization of phospho-NBS1 and MRE11, MRN complex repair factors necessary for homologous recombination (HR) repair, to DSBs in HGPS cells. Our results demonstrate a correlation between nuclear structural abnormalities and the DSB repair defect, suggesting a mechanistic link that may involve delayed repair factor localization to DNA damage. Further, our results show that similar to other HGPS phenotypes, FTI treatment has a beneficial effect on DSB repair.

  8. Identification and Analysis of MS5(d): A Gene That Affects Double-Strand Break (DSB) Repair during Meiosis I in Brassica napus Microsporocytes.

    Science.gov (United States)

    Zeng, Xinhua; Yan, Xiaohong; Yuan, Rong; Li, Keqi; Wu, Yuhua; Liu, Fang; Luo, Junling; Li, Jun; Wu, Gang

    2016-01-01

    Here, we report the identification of the Brassica-specific gene MS5(d), which is responsible for male sterility in Brassica napus. The MS5(d) gene is highly expressed in the microsporocyte and encodes a protein that localizes to the nucleus. Light microscopy analyses have demonstrated that the MS5(d) gene affects microsporocyte meiosis in the thermosensitive genic male sterility line TE5A. Sequence comparisons and genetic complementation revealed a C-to-T transition in MS5(d), encoding a Leu-to-Phe (L281F) substitution and causing abnormal male meiosis in TE5A. These findings suggest arrested meiotic chromosome dynamics at pachytene. Furthermore, immunofluorescence analyses showed that double-strand break (DSB) formation and axial elements were normal but that DSB repair and spindle behavior were aberrant in TE5A meiocytes. Collectively, our results indicate that MS5(d) likely encodes a protein required for chromosomal DSB repair at early stages of meiosis in B. napus.

  9. The UBC Domain Is Required for BRUCE to Promote BRIT1/MCPH1 Function in DSB Signaling and Repair Post Formation of BRUCE-USP8-BRIT1 Complex.

    Science.gov (United States)

    Ge, Chunmin; Che, Lixiao; Du, Chunying

    2015-01-01

    BRUCE is implicated in the regulation of DNA double-strand break response to preserve genome stability. It acts as a scaffold to tether USP8 and BRIT1, together they form a nuclear BRUCE-USP8-BRIT1 complex, where BRUCE holds K63-ubiquitinated BRIT1 from access to DSB in unstressed cells. Following DSB induction, BRUCE promotes USP8 mediated deubiquitination of BRIT1, a prerequisite for BRIT1 to be released from the complex and recruited to DSB by binding to γ-H2AX. BRUCE contains UBC and BIR domains, but neither is required for the scaffolding function of BRUCE mentioned above. Therefore, it remains to be determined whether they are required for BRUCE in DSB response. Here we show that the UBC domain, not the BIR domain, is required for BRUCE to promote DNA repair at a step post the formation of BRUCE-USP8-BRIT1 complex. Mutation or deletion of the BRUCE UBC domain did not disrupt the BRUCE-USP8-BRIT1 complex, but impaired deubiquitination and consequent recruitment of BRIT1 to DSB. This leads to impaired chromatin relaxation, decreased accumulation of MDC1, NBS1, pATM and RAD51 at DSB, and compromised homologous recombination repair of DNA DSB. These results demonstrate that in addition to the scaffolding function in complex formation, BRUCE has an E3 ligase function to promote BRIT1 deubiquitination by USP8 leading to accumulation of BRIT1 at DNA double-strand break. These data support a crucial role for BRUCE UBC activity in the early stage of DSB response.

  10. Integrated Rolling Stock Planning for Suburban Passenger Trains

    DEFF Research Database (Denmark)

    Thorlacius, Per

    A central issue for operators of passenger trains is providing sufficient number of seats while minimising operating costs. This process must be conducted taking a large number of practical, railway oriented requirements into account. Because of this complexity, a stepwise solution was previously...... used, the result being the loss of optimality. The talk will present a new, integrated rolling stock planning model in which the many requirements are handled all at the same time. Preliminary results from DSB S-tog, the suburban train operator of the City of Copenhagen will also be presented....

  11. Role of Artemis in DSB repair and guarding chromosomal stability following exposure to ionizing radiation at different stages of cell cycle

    Energy Technology Data Exchange (ETDEWEB)

    Darroudi, Firouz [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands)]. E-mail: F.Darroudi@LUMC.NL; Wiegant, Wouter [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands); Meijers, Matty [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands); Friedl, Anna A. [Radiobiological Institute, University of Munich, Munich (Germany); Institute of Radiobiology, GSF National Research Center for Environment and Health, Neuherberg (Germany); Burg, Mirjam van der [Department of Immunology, Erasmus Medical Centre, Rotterdam (Netherlands); Fomina, Janna [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands); Dongen, Jacques J.M. van [Department of Immunology, Erasmus Medical Centre, Rotterdam (Netherlands); Gent, Dik C. van [Department of Cell Biology and Genetics, Erasmus Medical Centre, Rotterdam (Netherlands); Zdzienicka, Malgorzata Z. [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands); Department of Molecular Cell Genetics, Collegium Medicum, N. Corpernicus University, Bydgoszcz (Poland)

    2007-02-03

    We analyzed the phenotype of cells derived from SCID patients with different mutations in the Artemis gene. Using clonogenic survival assay an increased sensitivity was found to X-rays (2-3-fold) and bleomycin (2-fold), as well as to etoposide, camptothecin and methylmethane sulphonate (up to 1.5-fold). In contrast, we did not find increased sensitivity to cross-linking agents mitomycin C and cis-platinum. The kinetics of DSB repair assessed by pulsed-field gel electrophoresis and {gamma}H2AX foci formation after ionizing irradiation, indicate that 15-20% of DSB are not repaired in Artemis-deficient cells. In order to get a better understanding of the repair defect in Artemis-deficient cells, we studied chromosomal damage at different stages of the cell cycle. In contrast to AT cells, Artemis-deficient cells appear to have a normal G{sub 1}/S-block that resulted in a similar frequency of dicentrics and translocations, however, frequency of acentrics fragments was found to be 2-4-fold higher compared to normal fibroblasts. Irradiation in G{sub 2} resulted in a higher frequency of chromatid-type aberrations (1.5-3-fold) than in normal cells, indicating that a fraction of DSB requires Artemis for proper repair. Our data are consistent with a function of Artemis protein in processing of a subset of complex DSB, without G{sub 1} cell cycle checkpoint defects. This type of DSB can be induced in high proportion and persist through S-phase and in part might be responsible for the formation of chromatid-type exchanges in G{sub 1}-irradiated Artemis-deficient cells. Among different human radiosensitive fibroblasts studied for endogenous (in untreated samples) as well as X-ray-induced DNA damage, the ranking order on the basis of higher incidence of spontaneously occurring chromosomal alterations and induced ones was: ligase 4 {>=} AT > Artemis. This observation implicates that in human fibroblasts following exposure to ionizing radiation a lower risk might be created when

  12. Role of Artemis in DSB repair and guarding chromosomal stability following exposure to ionizing radiation at different stages of cell cycle.

    Science.gov (United States)

    Darroudi, Firouz; Wiegant, Wouter; Meijers, Matty; Friedl, Anna A; van der Burg, Mirjam; Fomina, Janna; van Dongen, Jacques J M; van Gent, Dik C; Zdzienicka, Małgorzata Z

    2007-02-03

    We analyzed the phenotype of cells derived from SCID patients with different mutations in the Artemis gene. Using clonogenic survival assay an increased sensitivity was found to X-rays (2-3-fold) and bleomycin (2-fold), as well as to etoposide, camptothecin and methylmethane sulphonate (up to 1.5-fold). In contrast, we did not find increased sensitivity to cross-linking agents mitomycin C and cis-platinum. The kinetics of DSB repair assessed by pulsed-field gel electrophoresis and gammaH2AX foci formation after ionizing irradiation, indicate that 15-20% of DSB are not repaired in Artemis-deficient cells. In order to get a better understanding of the repair defect in Artemis-deficient cells, we studied chromosomal damage at different stages of the cell cycle. In contrast to AT cells, Artemis-deficient cells appear to have a normal G(1)/S-block that resulted in a similar frequency of dicentrics and translocations, however, frequency of acentrics fragments was found to be 2-4-fold higher compared to normal fibroblasts. Irradiation in G(2) resulted in a higher frequency of chromatid-type aberrations (1.5-3-fold) than in normal cells, indicating that a fraction of DSB requires Artemis for proper repair. Our data are consistent with a function of Artemis protein in processing of a subset of complex DSB, without G(1) cell cycle checkpoint defects. This type of DSB can be induced in high proportion and persist through S-phase and in part might be responsible for the formation of chromatid-type exchanges in G(1)-irradiated Artemis-deficient cells. Among different human radiosensitive fibroblasts studied for endogenous (in untreated samples) as well as X-ray-induced DNA damage, the ranking order on the basis of higher incidence of spontaneously occurring chromosomal alterations and induced ones was: ligase 4> or =AT>Artemis. This observation implicates that in human fibroblasts following exposure to ionizing radiation a lower risk might be created when cells are devoid of

  13. Novel Image Processing Interface to Relate DSB Spatial Distribution from Immunofluorescence Foci Experiments to the State-of-the-Art Models of DNA Breakage

    Science.gov (United States)

    Ponomarev, A. L.; Cucinotta, F. A.

    2004-01-01

    A recently developed software (NASARadiationTrackImage) allows a quick and automatic segmentation of foci that indicate spatial localization of specific proteins that are visualized by immunofluorescence. Of interest are the spatial and temporal distribution of foci such as gammaH2AX, a signal of the phosphorylation of a variant of the histone H2A that has been shown to correspond to DSBs, or proteins involved in DSB processing, such as ATM, Rad51, and p53, following exposures of human cells to high charge and energy (HZE) ion irradiation. Experimental data are recorded as sets of two-dimensional images in color with cells and foci of gammaH2AX, ATM, Rad51 or others shown. Different cells, levels of radiation and timing after radiation were recorded. The software allows us to calculate the number of foci per cell, overall intensity of light in foci and their spatial organization. A simple statistical model allows for testing of foci overlap (eclipse). A more complex statistical model previously known as DNAbreak simulates track structure and random chromosome geometry. It has one adjustable parameter corresponding to an average intensity of DSB creation in cubic micrometers of DNA volume per particle track or unit dose. Its limitation is the low-resolution limit both in physical space and DSB's along DNA. It works adequately on the scale of a cell and provides further insights on how the geometry of tracks and DNA affects genomic damage of the cell and subsequent repair. Future developments of the model for the description of the time evolution of DNA damage response proteins, and more robust track structure models will be discussed.

  14. The Train Driver Recovery Problem - a Set Partitioning Based Model and Solution Method

    DEFF Research Database (Denmark)

    Rezanova, Natalia Jurjevna; Ryan, David

    The need to recover a train driver schedule occurs during major disruptions in the daily railway operations. Using data from the train driver schedule of the Danish passenger railway operator DSB S-tog A/S, a solution method to the Train Driver Recovery Problem (TDRP) is developed. The TDRP is fo...... the depth-first search of the Branch & Bound tree. Preliminarily results are encouraging, showing that nearly all tested real-life instances produce integer solutions to the LP relaxation and solutions are found within a few seconds....

  15. DSB型低氮旋流燃烧器冷态试验研究%COLD-STATE TEST STUDY ON DSB TYPE LOW NOx CYCLONE BURNER

    Institute of Scientific and Technical Information of China (English)

    梁法光; 周虹光; 张开飞

    2010-01-01

    通过测量不同工况下的出口风量和火花示踪试验,对双分级旋流燃烧器(DSB)进行了冷态试验研究.试验结果表明,DSB燃烧器一次风速调节范围宽,可将空气分级和燃料分级相结合,因此具有很好的多煤种适应性和NOx控制性能.

  16. Asymmetrical TWDM-PON with 4 × 25-Gb/s downstream DSB OFDM and 4 × 10-Gb/s upstream OOK modulations

    Science.gov (United States)

    Lin, Bangjiang; Li, Yiwei; Zhang, Shihao; Tang, Xuan

    2015-12-01

    We propose and experimentally demonstrate an asymmetrical time wavelength division multiplexing passive optical network (TWDM-PON) scheme with 100-Gb/s downstream and 40-Gb/s upstream capacity using four pairs of wavelengths. Double sideband (DSB) orthogonal frequency division multiplexing (OFDM) with 16-QAM mapping is used for downstream transmission, while on-off keying (OOK) modulation is used for upstream transmission. The experimental results show that the power budget for bidirectional transmission is more than 35.5-dB. This scheme can be a promising solution for 100-Gb/s TWDM-PON with high power budget.

  17. The inhibition of assembly of HIV-1 virus-like particles by 3-O-(3',3'-dimethylsuccinyl betulinic acid (DSB is counteracted by Vif and requires its Zinc-binding domain

    Directory of Open Access Journals (Sweden)

    Bouaziz Serge

    2008-12-01

    Full Text Available Abstract Background DSB, the 3-O-(3',3'dimethylsuccinyl derivative of betulinic acid, blocks the last step of protease-mediated processing of HIV-1 Gag precursor (Pr55Gag, which leads to immature, noninfectious virions. When administered to Pr55Gag-expressing insect cells (Sf9, DSB inhibits the assembly and budding of membrane-enveloped virus-like particles (VLP. In order to explore the possibility that viral factors could modulate the susceptibility to DSB of the VLP assembly process, several viral proteins were coexpressed individually with Pr55Gag in DSB-treated cells, and VLP yields assayed in the extracellular medium. Results Wild-type Vif (Vifwt restored the VLP production in DSB-treated cells to levels observed in control, untreated cells. DSB-counteracting effect was also observed with Vif mutants defective in encapsidation into VLP, suggesting that packaging and anti-DSB effect were separate functions in Vif. The anti-DSB effect was abolished for VifC133S and VifS116V, two mutants which lacked the zinc binding domain (ZBD formed by the four H108C114C133H139 coordinates with a Zn atom. Electron microscopic analysis of cells coexpressing Pr55Gag and Vifwt showed that a large proportion of VLP budded into cytoplasmic vesicles and were released from Sf9 cells by exocytosis. However, in the presence of mutant VifC133S or VifS116V, most of the VLP assembled and budded at the plasma membrane, as in control cells expressing Pr55Gag alone. Conclusion The function of HIV-1 Vif protein which negated the DSB inhibition of VLP assembly was independent of its packaging capability, but depended on the integrity of ZBD. In the presence of Vifwt, but not with ZBD mutants VifC133S and VifS116V, VLP were redirected to a vesicular compartment and egressed via the exocytic pathway.

  18. Importance of the cell cycle phase for the choice of the appropriate DSB repair pathway, for genome stability maintenance: the trans-S double-strand break repair model.

    Science.gov (United States)

    Delacôte, Fabien; Lopez, Bernard S

    2008-01-01

    A DNA double-strand break (DSB) is a highly harmful lesion that can lead to genome rearrangements. Two main pathways compete for DSB repair: homologous recombination (HR) and nonhomologous end-joining (NHEJ). Depending on the cell cycle phase, the choice of one DSB repair pathway over the other will secure genome stability maintenance or in contrast will increase the risk of genetic instability. HR with the sister chromatid is an efficient way to maintain genome stability, for damage occurring at a post-replication stage. However, in G(1) checkpoint-defective cells, DSBs produced in the G(1) phase and not repaired by NHEJ, can progress through S phase and be processed by HR in late S/G(2) phase. We propose the "trans-S DSB repair" model to account for these data. In this situation HR cannot use the sister chromatid (which is also broken at the same locus) and is thus forced to use ectopic homologous sequences dispersed through the genome, increasing the risk of genetic instability. This shows that the two DSB repair pathways can compete through the cell cycle and underlines the importance of the association between the cell cycle checkpoint and the appropriate DNA repair pathway for genome stability maintenance.

  19. Blockage of Autophagy in C6 Glioma Cells Enhanced Radiosensitivity Possibly by Attenuating DNA-PK-Dependent DSB Due to Limited Ku Nuclear Translocation and DNA Binding.

    Science.gov (United States)

    Liu, C; He, W; Jin, M; Li, H; Xu, H; Liu, H; Yang, K; Zhang, T; Wu, G; Ren, J

    2015-01-01

    Glioblastoma multiforme (GBM) is the most lethal brain tumor and notorious for its resistance to ionizing radiation (IR). Recent evidence suggests that one possible mechanism that enables resistance to IR and protects cells against therapeutic stress is cellular autophagy. The molecular basis for this pro-survival function, however, remains elusive. Herein, we report a molecular mechanism by which IR-induced autophagy accelerates the repair of DNA double-strand breaks (DSB). We demonstrate that IR induces the accumulation of autophagosomes, which is accompanied by elevated expression of autophagyrelated genes beclin-1, atg5, atg7, and atg12. Beclin-1 knockdown impaired the induction of IR-mediated autophagy and significantly sensitized glioma cells to radiation therapy in vitro and in vivo. Furthermore, our data is the first to demonstrate that the radiosensitizing effect of beclin-1 knockdown may result from the disruption of nuclear translocation and DNA binding activity of Ku proteins and consequent attenuation of DSB repair. Our findings help advance our understanding of the molecular mechanisms underlying IR-induced autophagy and provide a promising adjunctive therapeutic strategy for the radiosensitization of malignant glioma.

  20. Induction and Processing of the Radiation-Induced Gamma-H2AX Signal and Its Link to the Underlying Pattern of DSB: A Combined Experimental and Modelling Study.

    Science.gov (United States)

    Tommasino, Francesco; Friedrich, Thomas; Jakob, Burkhard; Meyer, Barbara; Durante, Marco; Scholz, Michael

    2015-01-01

    We present here an analysis of DSB induction and processing after irradiation with X-rays in an extended dose range based on the use of the γH2AX assay. The study was performed by quantitative flow cytometry measurements, since the use of foci counting would result in reasonable accuracy only in a limited dose range of a few Gy. The experimental data are complemented by a theoretical analysis based on the GLOBLE model. In fact, original aim of the study was to test GLOBLE predictions against new experimental data, in order to contribute to the validation of the model. Specifically, the γH2AX signal kinetics has been investigated up to 24 h after exposure to increasing photon doses between 2 and 500 Gy. The prolonged persistence of the signal at high doses strongly suggests dose dependence in DSB processing after low LET irradiation. Importantly, in the framework of our modelling analysis, this is related to a gradually increased fraction of DSB clustering at the micrometre scale. The parallel study of γH2AX dose response curves shows the onset of a pronounced saturation in two cell lines at a dose of about 20 Gy. This dose is much lower than expected according to model predictions based on the values usually adopted for the DSB induction yield (≈ 30 DSB/Gy) and for the γH2AX foci extension of approximately 2 Mbp around the DSB. We show and discuss how theoretical predictions and experimental findings can be in principle reconciled by combining an increased DSB induction yield with the assumption of a larger genomic extension for the single phosphorylated regions. As an alternative approach, we also considered in our model the possibility of a 3D spreading-mechanism of the H2AX phosphorylation around the induced DSB, and applied it to the analysis of both the aspects considered. Our results are found to be supportive for the basic assumptions on which GLOBLE is built. Apart from giving new insights into the H2AX phosphorylation process, experiments performed

  1. TODRA, a lncRNA at the RAD51 Locus, Is Oppositely Regulated to RAD51, and Enhances RAD51-Dependent DSB (Double Strand Break) Repair

    Science.gov (United States)

    Renbaum, Paul; Zeligson, Sharon; Eini, Lital; Bashari, Dana; Smith, Yoav; Lahad, Amnon; Goldberg, Michal; Ginsberg, Doron; Levy-Lahad, Ephrat

    2015-01-01

    Expression of RAD51, a crucial player in homologous recombination (HR) and DNA double-strand break (DSB) repair, is dysregulated in human tumors, and can contribute to genomic instability and tumor progression. To further understand RAD51 regulation we functionally characterized a long non-coding (lnc) RNA, dubbed TODRA (Transcribed in the Opposite Direction of RAD51), transcribed 69bp upstream to RAD51, in the opposite direction. We demonstrate that TODRA is an expressed transcript and that the RAD51 promoter region is bidirectional, supporting TODRA expression (7-fold higher than RAD51 in this assay, p = 0.003). TODRA overexpression in HeLa cells induced expression of TPIP, a member of the TPTE family which includes PTEN. Similar to PTEN, we found that TPIP co-activates E2F1 induction of RAD51. Analysis of E2F1's effect on the bidirectional promoter showed that E2F1 binding to the same site that promotes RAD51 expression, results in downregulation of TODRA. Moreover, TODRA overexpression induces HR in a RAD51-dependent DSB repair assay, and increases formation of DNA damage-induced RAD51-positive foci. Importantly, gene expression in breast tumors supports our finding that E2F1 oppositely regulates RAD51 and TODRA: increased RAD51 expression, which is associated with an aggressive tumor phenotype (e.g. negative correlation with positive ER (r = -0.22, p = 0.02) and positive PR status (r = -0.27, p<0.001); positive correlation with ki67 status (r = 0.36, p = 0.005) and HER2 amplification (r = 0.41, p = 0.001)), correlates as expected with lower TODRA and higher E2F1 expression. However, although E2F1 induction resulted in TPIP downregulation in cell lines, we find that TPIP expression in tumors is not reduced despite higher E2F1 expression, perhaps contributing to increased RAD51 expression. Our results identify TPIP as a novel E2F1 co-activator, suggest a similar role for other TPTEs, and indicate that the TODRA lncRNA affects RAD51 dysregulation and RAD51

  2. Legal Interpretation and Institutionalization of WTO/DSB's Power%WTO争端解决机构的法律解释权及其制度化

    Institute of Scientific and Technical Information of China (English)

    李路根

    2012-01-01

    WTO争端解决机构(DSB)法律解释权的制度化旨在建立起DSB法律解释权的完整制度,同时也是对于DSB“司法造法”为标志的WTO司法能动主义倾向的一种制度回应.DSB法律解释权的制度化应立足现实需要,确定制度理念及原则.明确制度要素与模式,界定DSB法律解释权的内涵.在未来谈判中,应将DSB法律解释权制度纳入DSU体系.

  3. 论我国如何运用DSB解决贸易争端%Application of DSB to settling the Trade Dispute

    Institute of Scientific and Technical Information of China (English)

    黄元超; 蒋海勇; 周涛

    2005-01-01

    近年来我国取代日本成为世界经济贸易中反倾销的最大对象,但由于对WTO下的争端解决机制缺乏深刻的了解,未能有效运用其争端解决机构(DSB)来处理争端,使得我国在国际贸易中处于十分被动的地位.有鉴于此,笔者拟在本文中通过对DSB相关程序的介绍,进而分析我国运用其解决争端的可行性,并提出若干对策.

  4. PISM-DSB原理及其应用%The Theory of Phase-Inversion Symmetric Modulation-DSB and the Application

    Institute of Scientific and Technical Information of China (English)

    赵贤凌; 萧宝瑾

    2006-01-01

    反相对称调制(PISM)与普通双边带(DSB)调制相结合可在同一载频上同时传输2路不同的信号,而在接收端采用2种解调方法可以分别接收到这2路不同的信号.将这一方法用于实际通信系统中会使信道利用率提高1倍.另外PISM-DSB对它台干扰也有一定的抑制作用.本文论述了这一方法的基本原理,并对它进行了计算机仿真,得到了满意的结果.

  5. High atomic weight, high-energy radiation (HZE induces transcriptional responses shared with conventional stresses in addition to a core DSB response specific to clastogenic treatments.

    Directory of Open Access Journals (Sweden)

    Victor eMissirian

    2014-08-01

    Full Text Available Plants exhibit a robust transcriptional response to gamma radiation which includes the induction of transcripts required for homologous recombination and the suppression of transcripts that promote cell cycle progression. Various DNA damaging agents induce different spectra of DNA damage as well as collateral damage to other cellular components and therefore are not expected to provoke identical responses by the cell. Here we study the effects of two different types of ionizing radiation (IR treatment, HZE (1 GeV Fe26+ high mass, high charge, and high energy relativistic particles and gamma photons, on the transcriptome of Arabidopsis thaliana seedlings. Both types of IR induce small clusters of radicals that can result in the formation of double strand breaks (DSBs, but HZE also produces linear arrays of extremely clustered damage. We performed these experiments across a range of time points (1.5 to 24 hours after irradiation in both wild-type plants and in mutants defective in the DSB-sensing protein kinase ATM. The two types of IR exhibit a shared double strand break-repair-related damage response, although they differ slightly in the timing, degree, and ATM-dependence of the response. The ATM-dependent, DNA metabolism-related transcripts of the DSB response were also induced by other DNA damaging agents, but were not induced by conventional stresses. Both Gamma and HZE irradiation induced, at 24 hours post-irradiation, ATM-dependent transcripts associated with a variety of conventional stresses; these were overrepresented for pathogen response, rather than DNA metabolism. In contrast, only HZE-irradiated plants, at 1.5 hr after irradiation, exhibited an additional and very extensive transcriptional response, shared with plants experiencing extended night. This response was not apparent in gamma-irradiated plants.

  6. High atomic weight, high-energy radiation (HZE) induces transcriptional responses shared with conventional stresses in addition to a core "DSB" response specific to clastogenic treatments.

    Science.gov (United States)

    Missirian, Victor; Conklin, Phillip A; Culligan, Kevin M; Huefner, Neil D; Britt, Anne B

    2014-01-01

    Plants exhibit a robust transcriptional response to gamma radiation which includes the induction of transcripts required for homologous recombination and the suppression of transcripts that promote cell cycle progression. Various DNA damaging agents induce different spectra of DNA damage as well as "collateral" damage to other cellular components and therefore are not expected to provoke identical responses by the cell. Here we study the effects of two different types of ionizing radiation (IR) treatment, HZE (1 GeV Fe(26+) high mass, high charge, and high energy relativistic particles) and gamma photons, on the transcriptome of Arabidopsis thaliana seedlings. Both types of IR induce small clusters of radicals that can result in the formation of double strand breaks (DSBs), but HZE also produces linear arrays of extremely clustered damage. We performed these experiments across a range of time points (1.5-24 h after irradiation) in both wild-type plants and in mutants defective in the DSB-sensing protein kinase ATM. The two types of IR exhibit a shared double strand break-repair-related damage response, although they differ slightly in the timing, degree, and ATM-dependence of the response. The ATM-dependent, DNA metabolism-related transcripts of the "DSB response" were also induced by other DNA damaging agents, but were not induced by conventional stresses. Both Gamma and HZE irradiation induced, at 24 h post-irradiation, ATM-dependent transcripts associated with a variety of conventional stresses; these were overrepresented for pathogen response, rather than DNA metabolism. In contrast, only HZE-irradiated plants, at 1.5 h after irradiation, exhibited an additional and very extensive transcriptional response, shared with plants experiencing "extended night." This response was not apparent in gamma-irradiated plants.

  7. Integrating rolling stock scheduling with train unit shunting

    DEFF Research Database (Denmark)

    Haahr, Jørgen Thorlund; Lusby, Richard Martin

    2017-01-01

    In this paper, we consider integrating two important railway optimization problems, in particular the Rolling Stock Scheduling Problem and the Train Unit Shunting Problem. We present two similar branch-and-cut based approaches to solve this integrated problem and, in addition, provide a comparison...... of different approaches to solve the so-called Track Assignment Problem, a subcomponent of the Train Unit Shunting problem. In this analysis we demonstrate, by way of a counter example, the heuristic nature of a previously argued optimal approach. For the integrated problem we analyze the performance...... of the proposed approaches on several real-life case studies provided by DSB S-tog, a suburban train operator in the greater Copenhagen area. Computational results confirm the necessity of the integrated approach; high quality solutions to the integrated problem are obtained on instances where a conventional...

  8. Manganese supplementation increases adiponectin and lowers ICAM-1 and creatinine blood levels in Zucker type 2 diabetic rats, and downregulates ICAM-1 by upregulating adiponectin multimerization protein (DsbA-L) in endothelial cells.

    Science.gov (United States)

    Burlet, Elodie; Jain, Sushil K

    2017-05-01

    Blood and tissue levels of manganese (Mn) are lower in type 2 diabetic and atherosclerosis patients compared with healthy subjects. Adiponectin has anti-diabetic and anti-atherogenic properties. Impairment in Disulfide bond A-like protein (DsbA-L) is associated with low adiponectin levels and diabetes. This study investigates the hypothesis that the beneficial effects of Mn supplementation are mediated by adiponectin and DsbA-L. At 6 weeks of age, Male Zucker diabetic fatty rats (ZDF) were randomly divided into two groups: diabetic controls and Mn-supplemented diabetic rats. Each rat was supplemented with Mn (D+Mn, 16 mg/kg BW) or water (placebo, D+P) daily for 7 weeks by oral gavage. For cell culture studies, Human Umbilical Vein Endothelial Cells (HUVEC) or 3T3L1 adipocytes were pretreated with Mn (0-10 µM MnCl2) for 24 h, followed by high glucose (HG, 25 mM) or normal glucose (5 mM) exposure for another 24 h. Mn supplementation resulted in higher adiponectin (p = 0.01), and lower ICAM-1 (p = 0.04) and lower creatinine (p = 0.04) blood levels compared to those in control ZDF rats. Mn-supplemented rats also caused reduced oxidative stress (ROS) and NADPH oxidase, and higher DsbA-L expression in the liver (p = 0.03) of ZDF rats compared to those in livers of control rats; however, Fe levels in liver were lower but not significant (p = 0.08). Similarly, treatment with high glucose (25 mM) caused a decrease in DsbA-L, which was prevented by Mn supplementation in HUVEC and adipocytes. Mechanistic studies with DsbA-L siRNA showed that the beneficial effects of Mn supplementation on ROS, NOX4, and ICAM-1 expression were abolished in DsbA-L knock-down HUVEC. These studies demonstrate that DsbA-L-linked adiponectin mediates the beneficial effects observed with Mn supplementation and provides evidence for a novel mechanism by which Mn supplementation can increase adiponectin and reduce the biomarkers of endothelial dysfunction in diabetes.

  9. TU-EF-304-10: Efficient Multiscale Simulation of the Proton Relative Biological Effectiveness (RBE) for DNA Double Strand Break (DSB) Induction and Bio-Effective Dose in the FLUKA Monte Carlo Radiation Transport Code

    Energy Technology Data Exchange (ETDEWEB)

    Moskvin, V; Tsiamas, P; Axente, M; Farr, J [St. Jude Children’s Research Hospital, Memphis, TN (United States); Stewart, R [University of Washington, Seattle, WA. (United States)

    2015-06-15

    Purpose: One of the more critical initiating events for reproductive cell death is the creation of a DNA double strand break (DSB). In this study, we present a computationally efficient way to determine spatial variations in the relative biological effectiveness (RBE) of proton therapy beams within the FLUKA Monte Carlo (MC) code. Methods: We used the independently tested Monte Carlo Damage Simulation (MCDS) developed by Stewart and colleagues (Radiat. Res. 176, 587–602 2011) to estimate the RBE for DSB induction of monoenergetic protons, tritium, deuterium, hellium-3, hellium-4 ions and delta-electrons. The dose-weighted (RBE) coefficients were incorporated into FLUKA to determine the equivalent {sup 6}°60Co γ-ray dose for representative proton beams incident on cells in an aerobic and anoxic environment. Results: We found that the proton beam RBE for DSB induction at the tip of the Bragg peak, including primary and secondary particles, is close to 1.2. Furthermore, the RBE increases laterally to the beam axis at the area of Bragg peak. At the distal edge, the RBE is in the range from 1.3–1.4 for cells irradiated under aerobic conditions and may be as large as 1.5–1.8 for cells irradiated under anoxic conditions. Across the plateau region, the recorded RBE for DSB induction is 1.02 for aerobic cells and 1.05 for cells irradiated under anoxic conditions. The contribution to total effective dose from secondary heavy ions decreases with depth and is higher at shallow depths (e.g., at the surface of the skin). Conclusion: Multiscale simulation of the RBE for DSB induction provides useful insights into spatial variations in proton RBE within pristine Bragg peaks. This methodology is potentially useful for the biological optimization of proton therapy for the treatment of cancer. The study highlights the need to incorporate spatial variations in proton RBE into proton therapy treatment plans.

  10. Impaired 53BP1/RIF1 DSB mediated end-protection stimulates CtIP-dependent end resection and switches the repair to PARP1-dependent end joining in G1.

    Science.gov (United States)

    Bakr, Ali; Köcher, Sabrina; Volquardsen, Jennifer; Petersen, Cordula; Borgmann, Kerstin; Dikomey, Ekkehard; Rothkamm, Kai; Mansour, Wael Y

    2016-09-06

    End processing at DNA double strand breaks (DSB) is a decisive step in repair pathway selection. Here, we investigated the role of 53BP1/RIF1 in limiting BRCA1/CtIP-mediated end resection to control DSB repair pathway choice. ATM orchestrates this process through 53BP1 phosphorylation to promote RIF1 recruitment. As cells enter S/G2-phase, end resection is activated, which displaces pATM from DSB sites and diminishes 53BP1 phosphorylation and RIF1 recruitment. Consistently, the kinetics of ATM and 53BP1 phosphorylation in S/G2-phase concur. We show that defective 53BP1/RIF1-mediated DSB end-protection in G1-phase stimulates CtIP/MRE11-dependent end-resection, which requires Polo-like kinase 3. This end resection activity in G1 was shown to produce only short tracks of ssDNA overhangs, as evidenced by the findings that in 53BP1 depleted cells, (i) RPA focus intensity was significantly lower in G1 compared to that in S/G2 phase, and (ii) EXO1 knockdown did not alter either number or intensity of RPA foci in G1 but significantly decreased the RPA focus intensity in S/G2 phase. Importantly, we report that the observed DSB end resection in G1 phase inhibits DNA-PK-dependent nonhomologous end joining but is not sufficient to stimulate HR. Instead, it switches the repair to the alternative PARP1-dependent end joining pathway.

  11. Language Training: English Training

    CERN Multimedia

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. Language Training Françoise Benz tel. 73127 language.training@cern.ch General and Professional English Courses The next session will take place: from 1st March to 25 June 2004 (2 weeks break at Easter). These courses are open to all persons working on the Cern site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mr. Liptow: tel. 72957.

  12. Language Training: English Training

    CERN Multimedia

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. LANGUAGE TRAINING Françoise Benz tel. 73127 language.training@cern.ch General and Professional English Courses The next session will take place: from 1st March to 25 June 2004 (2 weeks break at Easter). These courses are open to all persons working on the Cern site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mr. Liptow: tel. 72957.

  13. Development and evaluation of a loop-mediated isothermal amplification (LAMP assay for rapid detection of Actinobacillus pleuropneumoniae based the dsbE-like gene

    Directory of Open Access Journals (Sweden)

    Hongwei Ji

    2012-08-01

    Full Text Available This paper reports on the development and validation of a loop-mediated isothermal amplification assay (LAMP for the rapid and specific detection of Actinobacillus pleuropneumoniae (A. pleuropneumoniae. A set of six primers were designed derived from the dsbE-like gene of A.pleuropneumoniae and validate the assay using 9 A. pleuropneumoniae reference/field strains, 132 clinical isolates and 9 other pathogens. The results indicated that positive reactions were confirmed for all A. pleuropneumoniae strains and specimens by LAMP at 63ºC for 60 min and no cross-reactivity were observed from other non-A.pleuropneumoniae including Haemophilus parasuis, Escherichia coli, Pasteurella multocida, Bordetella bronchiseptica, Streptococcus suis, Salmonella enterica, Staphylococcus, porcine reproductive and respiratory syndrome virus (PRRSV, and Pseudorabies virus. The detection limit of the conventional PCR was 10² CFU per PCR test tube, while that of the LAMP was 5 copies per tube. Therefore, the sensitivity of LAMP was higher than that of PCR. Moreover, the LAMP assay provided a rapid yet simple test of A. pleuropneumoniae suitable for laboratory diagnosis and pen-side detection due to ease of operation and the requirement of only a regular water bath or heat block for the reaction.

  14. Phylogeny of the Vitamin K 2,3-Epoxide Reductase (VKOR Family and Evolutionary Relationship to the Disulfide Bond Formation Protein B (DsbB Family

    Directory of Open Access Journals (Sweden)

    Carville G. Bevans

    2015-07-01

    Full Text Available In humans and other vertebrate animals, vitamin K 2,3-epoxide reductase (VKOR family enzymes are the gatekeepers between nutritionally acquired K vitamins and the vitamin K cycle responsible for posttranslational modifications that confer biological activity upon vitamin K-dependent proteins with crucial roles in hemostasis, bone development and homeostasis, hormonal carbohydrate regulation and fertility. We report a phylogenetic analysis of the VKOR family that identifies five major clades. Combined phylogenetic and site-specific conservation analyses point to clade-specific similarities and differences in structure and function. We discovered a single-site determinant uniquely identifying VKOR homologs belonging to human pathogenic, obligate intracellular prokaryotes and protists. Building on previous work by Sevier et al. (Protein Science 14:1630, we analyzed structural data from both VKOR and prokaryotic disulfide bond formation protein B (DsbB families and hypothesize an ancient evolutionary relationship between the two families where one family arose from the other through a gene duplication/deletion event. This has resulted in circular permutation of primary sequence threading through the four-helical bundle protein folds of both families. This is the first report of circular permutation relating distant a-helical membrane protein sequences and folds. In conclusion, we suggest a chronology for the evolution of the five extant VKOR clades.

  15. Phylogeny of the Vitamin K 2,3-Epoxide Reductase (VKOR) Family and Evolutionary Relationship to the Disulfide Bond Formation Protein B (DsbB) Family.

    Science.gov (United States)

    Bevans, Carville G; Krettler, Christoph; Reinhart, Christoph; Watzka, Matthias; Oldenburg, Johannes

    2015-07-29

    In humans and other vertebrate animals, vitamin K 2,3-epoxide reductase (VKOR) family enzymes are the gatekeepers between nutritionally acquired K vitamins and the vitamin K cycle responsible for posttranslational modifications that confer biological activity upon vitamin K-dependent proteins with crucial roles in hemostasis, bone development and homeostasis, hormonal carbohydrate regulation and fertility. We report a phylogenetic analysis of the VKOR family that identifies five major clades. Combined phylogenetic and site-specific conservation analyses point to clade-specific similarities and differences in structure and function. We discovered a single-site determinant uniquely identifying VKOR homologs belonging to human pathogenic, obligate intracellular prokaryotes and protists. Building on previous work by Sevier et al. (Protein Science 14:1630), we analyzed structural data from both VKOR and prokaryotic disulfide bond formation protein B (DsbB) families and hypothesize an ancient evolutionary relationship between the two families where one family arose from the other through a gene duplication/deletion event. This has resulted in circular permutation of primary sequence threading through the four-helical bundle protein folds of both families. This is the first report of circular permutation relating distant a-helical membrane protein sequences and folds. In conclusion, we suggest a chronology for the evolution of the five extant VKOR clades.

  16. On the New Developments of Trade and Environmental Disputes under the WTO/DSB%论WTO/DSB贸易与环境争端的新发展

    Institute of Scientific and Technical Information of China (English)

    李威

    2012-01-01

    随着国际环境法发展完善的外部推动,WTO/DSB (WTO争端解决机构)通过司法造法逐步确立了贸易与环境争端“环境优先”的裁决思路,促进了贸易与环境的平衡发展.然而,气候国际法进程的停滞和各国低碳转型的经济发展需求,造成以单边可再生能源产业措施为核心的气候与贸易争端频繁发生,DSB面临气候国际法与WTO法规则冲突的解决和协调,并将通过司法造法淡化“环境优先”的裁决思路,这一转型将对气候与环境争端确立可予遵循的新判例.

  17. 论DSB报告对我国立法和司法的影响%The Effect of DSB Report on China's Legislation and Judicature

    Institute of Scientific and Technical Information of China (English)

    程宗璋

    2003-01-01

    争端解决机制作为世界贸易组织(简称WTO)的基石,是乌拉圭回合谈判的重大成果.它的核心是争端解决机构(简称DSB)以采纳专家组或上诉机构报告的方式来解决成员方之间的相关争议.通过对(简称DSU)的条文分析以及对关贸总协定(简称GATT)和世界贸易组织争端解决实践的研究,文章探讨了以下几个问题:第一,DSB所采纳的报告是否具有国际法上的效力;第二,各成员方执行报告的情况如何;第三,DSB报告对中国的立法和司法实践会产生怎样的影响.

  18. AM信号到DSB信号的连续过渡与同步检波%Continuous Transition and Synchronous Detection from AM Signal to DSB Signal

    Institute of Scientific and Technical Information of China (English)

    博战捷; 董辉

    2005-01-01

    现今模拟调制AM(Amplitude Modulation)信号到DSB(Double sideband)信号不能连续过渡的限制,是出于长期以来在许多文献中一直沿用的调幅信号调幅系数ma不能大于1的结论.采用四象限模拟乘法器和同步检波相结合的方法,从原理与技术上跨越了模拟调制AM调幅信号的调幅系数ma不能大于l的片面结论,给出了AM信号到DSB信号连续过渡进行调制和解调的原理电路.论证结果表明,调幅系数ma大于1的已调信号在调制端是可实现的,在接收端也是可以解调的.从而实现了AM信号到DSB信号的连续过渡与解调,因此也否定了一些对AM信号所作分析的历史结论.

  19. Sound distortion Of DSB method for parametric loudspeaker%参量扬声器DSB法的互调失真研究

    Institute of Scientific and Technical Information of China (English)

    张德银

    2009-01-01

    参量扬声器是近年来出现的一种新的声源.根据宽带参量阵理论的"Berktay远场解",对参量扬声器的一种信号处理方法--DSB(Double Side Band)法的互调失真问题进行了理论与实验研究.研究发现,DSB法除了存在幅值失真、谐波失真外,还存在互调失真,且实测互调失真较理论预测的复杂.在此基础上指出,"Berktay远场解"只能在一定程度上作为参量扬声器信号处理的理论依据,寻找更为精确的自解调理论模型是解决参量扬声器信号处理问题的根本途径.

  20. A human iPSC model of Ligase IV deficiency reveals an important role for NHEJ-mediated-DSB repair in the survival and genomic stability of induced pluripotent stem cells and emerging haematopoietic progenitors.

    Science.gov (United States)

    Tilgner, K; Neganova, I; Moreno-Gimeno, I; Al-Aama, J Y; Burks, D; Yung, S; Singhapol, C; Saretzki, G; Evans, J; Gorbunova, V; Gennery, A; Przyborski, S; Stojkovic, M; Armstrong, L; Jeggo, P; Lako, M

    2013-08-01

    DNA double strand breaks (DSBs) are the most common form of DNA damage and are repaired by non-homologous-end-joining (NHEJ) or homologous recombination (HR). Several protein components function in NHEJ, and of these, DNA Ligase IV is essential for performing the final 'end-joining' step. Mutations in DNA Ligase IV result in LIG4 syndrome, which is characterised by growth defects, microcephaly, reduced number of blood cells, increased predisposition to leukaemia and variable degrees of immunodeficiency. In this manuscript, we report the creation of a human induced pluripotent stem cell (iPSC) model of LIG4 deficiency, which accurately replicates the DSB repair phenotype of LIG4 patients. Our findings demonstrate that impairment of NHEJ-mediated-DSB repair in human iPSC results in accumulation of DSBs and enhanced apoptosis, thus providing new insights into likely mechanisms used by pluripotent stem cells to maintain their genomic integrity. Defects in NHEJ-mediated-DSB repair also led to a significant decrease in reprogramming efficiency of human cells and accumulation of chromosomal abnormalities, suggesting a key role for NHEJ in somatic cell reprogramming and providing insights for future cell based therapies for applications of LIG4-iPSCs. Although haematopoietic specification of LIG4-iPSC is not affected per se, the emerging haematopoietic progenitors show a high accumulation of DSBs and enhanced apoptosis, resulting in reduced numbers of mature haematopoietic cells. Together our findings provide new insights into the role of NHEJ-mediated-DSB repair in the survival and differentiation of progenitor cells, which likely underlies the developmental abnormalities observed in many DNA damage disorders. In addition, our findings are important for understanding how genomic instability arises in pluripotent stem cells and for defining appropriate culture conditions that restrict DNA damage and result in ex vivo expansion of stem cells with intact genomes.

  1. Language Training: French Training

    CERN Multimedia

    Françoise Benz

    2004-01-01

    General and Professional French Courses The next session will take place from 11 October to 17 December 2004. These courses are open to all persons working on the CERN site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mrs. Fontbonne: Tel. 72844. Writing Professional Documents in French This course is designed for people with a good level of spoken French. Duration: 30 hours Price: 660 CHF (for 8 students) For further information and registration, please consult our Web pages: http://cern.ch/Training or contact Mrs. Fontbonne: tel. 72844. FORMATION EN LANGUES LANGUAGE TRAINING Françoise Benz 73127 language.training@cern.ch

  2. Language Training: French Training

    CERN Document Server

    Françoise Benz

    2005-01-01

    General and Professional French Courses The next session will take place from 18 April to 30 June 2005. These courses are open to all persons working on the CERN site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mrs. Benz : Tel. 73127. Writing Professional Documents in French The next session will take place from 18 April to 30 June 2005. This course is designed for people with a good level of spoken French. Duration: 30 hours Price: 660 CHF (for 8 students) For further information and registration, please consult our Web pages: http://cern.ch/Training or contact Mrs. Benz : Tel. 73127. FORMATION EN LANGUES LANGUAGE TRAINING Françoise Benz 73127 language.training@cern.ch

  3. Language Training: French Training

    CERN Multimedia

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. LANGUAGE TRAINING Françoise Benz tel. 73127 language.training@cern.ch General and Professional French Courses The next session will take place from 26 April to 02 July 2004. These courses are open to all persons working on the Cern site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mrs. Benz: Tel. 73127. Writing Professional Documents in French The next session will take place from 26 April to 02 July 2004. This course is designed for people with a good level...

  4. Language Training: French Training

    CERN Document Server

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. LANGUAGE TRAINING Françoise Benz tel. 73127 language.training@cern.ch General and Professional French Courses The next session will take place from 26 April to 02 July 2004. These courses are open to all persons working on the Cern site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mrs. Benz: Tel. 73127. Writing Professional Documents in French The next session will take place from 26 April to 02 July 2004. This course is designed for people with a good level of s...

  5. The Time & Frequency Domain Model and Simulation Analysis on Simulink of DSB Communication System%DSB通信系统的Simulink时域频域模型与仿真分析

    Institute of Scientific and Technical Information of China (English)

    刘婷婷; 杨云

    2013-01-01

    基于Matlab的Simulink仿真平台,研究了单频信号下DSB通信系统的传输原理,提出了一种新的DSB通信系统时域频域模型并进行仿真。仿真结果表明,通过该模型的信号特性能够与理论分析保持一致,符合DSB通信系统的要求,并且能够同时观察信号的信号波形与频谱结构,为更深一步的理论研究和分析提供了更加便利的环境。%Simulink simulation platform based on the Matla, the DSB communication system under the single-frequency signal transmission principle is researched, this paper proposes a new DSB communication system time domain and fre-quency domain model and carries on the simulation. Simulation results show that get through the signal characteristics of the model can be consistent with the theoretical analysis, accord with the requirement of DSB communication system, and can be observed signal of the signal waveform and spectrum structure at the same time, for a further theoretical research and analysis provided a more convenient environment.

  6. Training safely, Training safety

    Directory of Open Access Journals (Sweden)

    Jianjun Wu

    2014-09-01

    Full Text Available It is the basic requirement of maritime safety education to guarantee the safety of teaching operation while training the crew's occupation safety capability. Marine Training Center of Shanghai Maritime University has undertaken the practical teaching of "marine survival" for many years and come up with the whole safety procedures of training. Based on the requirements of SOLAS convention and regulations of STCW over crew training, this paper introduces the safety allocation, utilization and maintenance of teaching equipments. Through the investigation of the safety situation of students' practical operation, the safety teaching method named "four in one" has been put forward, which includes the pre-teaching safety precaution, the whole monitor during the teaching process, the post-teaching summary evaluation, and the reset and standby of teaching facilities. Finally, during the learning and training of "marine survival", crews and students are called on to place priority on personal safety rather than acquisition of knowledge and skills. Only in this way can they be capable of self-protection and protection of others in the career of seafaring.

  7. Evaluating Training

    Institute of Scientific and Technical Information of China (English)

    Zhang Huanhai; Zhang Lei's

    2008-01-01

    @@ Clause 6.2.2: Competence, Awareness and Training in ISO9001:2000 standard sets the training requirements for organizations. Problems with evaluating the outcomes of training arise during examination and verification.

  8. The type and yield of ionising radiation induced chromosomal aberrations depend on the efficiency of different DSB repair pathways in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Natarajan, Adayapalam T.; Berni, Andrea; Marimuthu, Kodumudi M. [Department of Agrobiology and Agrochemistry, University of Tuscia, Via San Camillo de Lellis, 01100 Viterbo (Italy); Palitti, Fabrizio [Department of Agrobiology and Agrochemistry, University of Tuscia, Via San Camillo de Lellis, 01100 Viterbo (Italy)], E-mail: palitti@unitus.it

    2008-07-03

    In order to evaluate the relative role of two major DNA double strand break repair pathways, i.e., non-homologous end joining (NHEJ) and homologous recombination repair (HRR), CHO mutants deficient in these two pathways and the parental cells (AA8) were X-irradiated with various doses. The cells were harvested at different times after irradiation, representing G{sub 2}, S and G{sub 1} phase at the time of irradiation, The mutant cell lines used were V33 (NHEJ deficient), Irs1SF, 51-D1 (HRR deficient). In addition to parental cell line (AA8), a revertant of V33, namely V33-155 was employed. Both types of mutant cells responded with increased frequencies of chromosomal aberrations at all recovery times in comparison to the parental and revertant cells. Mutant cells deficient in NHEJ were more sensitive in all cell stages in comparison to HRR deficient mutant cells, indicating NHEJ is the major repair pathway for DSB repair through out the cell cycle. Both chromosome and chromatid types of exchange aberrations were observed following G{sub 1} irradiation (16 and 24 h recovery). Interestingly, configurations involving both chromosome (dicentrics) and chromatid exchanges were encountered in G{sub 1} irradiated V33 cells. This may indicate that unrepaired DSBs accumulate in G{sub 1} in these mutant cells and carried over to S phase, where they are repaired by HRR or other pathways such as B-NHEJ (back up NHEJ), which appear to be highly error prone. Both NHEJ and HRR, which share some of the same proteins in their pathways, are involved in the repair of DSBs leading to chromosomal aberrations, but with a major role of NHEJ in all stages of cell cycle.

  9. Language Training: English Training

    CERN Multimedia

    Françoise Benz

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an 'application for training' form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. General and Professional English Courses The next session will take place from 04 October 2004 to 11 February 2005 (3 weeks break at Christmas). These courses are open to all persons working on the CERN site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mr. Liptow, tel. 72957. Oral Expression This course is intended for people with a good knowledge of English who want to practise and maintain their speaking skills while extending their vocabulary. There will be approximately 8 participants in...

  10. SHP-1 overexpression increases the radioresistance of NPC cells by enhancing DSB repair, increasing S phase arrest and decreasing cell apoptosis.

    Science.gov (United States)

    Pan, Xiaofen; Mou, Jingjing; Liu, Sha; Sun, Ziyi; Meng, Rui; Zhou, Zhenwei; Wu, Gang; Peng, Gang

    2015-06-01

    The present study aimed to investigate the influence of SHP-1 on the radioresistance of the nasopharyngeal carcinoma (NPC) cell line CNE-2 and the relevant underlying mechanisms. The human NPC cell line CNE-2 was transfected with a lentivirus that contained the SHP-1 gene or a nonsense sequence (referred to as LP-H1802Lv201 and LP-NegLv201 cells, respectively). Cells were irradiated with different ionizing radiation (IR) doses. Cell survival, DNA double-strand breaks (DSBs), apoptosis, cell cycle distribution, and the expression of related proteins were assessed using colony formation assay, immunofluorescent assays (IFAs), flow cytometry (FCM) and western blot analyses, respectively. Compared with the control (CNE-2 cells) and LP-NegLv201 cells, LP-H1802Lv201 cells were more resistant to IR. IFAs showed that IR caused less histone H2AX phosphorylation (γH2AX) and RAD51 foci in the LP-H1802Lv201 cells. Compared with the control and LP-NegLv201 cells, LP-H1802Lv201 cells showed increased S phase arrest. After IR, the apoptotic rate of the LP-H1802Lv201 cells was lower in contrast to the control and LP-NegLv201 cells. Western blot analyses showed that IR increased the phosphorylation of ataxia telangiectasia mutated (ATM) kinase, checkpoint kinase 2 (CHK2), ataxia telangiectasia and Rad3-related (ATR) protein, checkpoint kinase 1 (CHK1) and p53. In LP-H1802Lv201 cells, the phosphorylation levels of ATM and CHK2 were significantly increased while the p53 phosphorylation level was decreased compared to these levels in the control and LP-NegLv201 cells. Phosphorylation of ATR and CHK1 did not show significant differences in the three cell groups. Overexpression of SHP-1 in the CNE-2 cells led to radioresistance and the radioresistance was related to enhanced DNA DSB repair, increased S phase arrest and decreased cell apoptosis.

  11. Development of a radiation track structure clustering algorithm for the prediction of DNA DSB yields and radiation induced cell death in Eukaryotic cells

    Science.gov (United States)

    Douglass, Michael; Bezak, Eva; Penfold, Scott

    2015-04-01

    The preliminary framework of a combined radiobiological model is developed and calibrated in the current work. The model simulates the production of individual cells forming a tumour, the spatial distribution of individual ionization events (using Geant4-DNA) and the stochastic biochemical repair of DNA double strand breaks (DSBs) leading to the prediction of survival or death of individual cells. In the current work, we expand upon a previously developed tumour generation and irradiation model to include a stochastic ionization damage clustering and DNA lesion repair model. The Geant4 code enabled the positions of each ionization event in the cells to be simulated and recorded for analysis. An algorithm was developed to cluster the ionization events in each cell into simple and complex double strand breaks. The two lesion kinetic (TLK) model was then adapted to predict DSB repair kinetics and the resultant cell survival curve. The parameters in the cell survival model were then calibrated using experimental cell survival data of V79 cells after low energy proton irradiation. A monolayer of V79 cells was simulated using the tumour generation code developed previously. The cells were then irradiated by protons with mean energies of 0.76 MeV and 1.9 MeV using a customized version of Geant4. By replicating the experimental parameters of a low energy proton irradiation experiment and calibrating the model with two sets of data, the model is now capable of predicting V79 cell survival after low energy (<2 MeV) proton irradiation for a custom set of input parameters. The novelty of this model is the realistic cellular geometry which can be irradiated using Geant4-DNA and the method in which the double strand breaks are predicted from clustering the spatial distribution of ionisation events. Unlike the original TLK model which calculates a tumour average cell survival probability, the cell survival probability is calculated for each cell in the geometric tumour model

  12. 将中美纺织品贸易争端提交DSB解决的理论研究%Studies of Bringing Sino-U.S. Disputes on Textile Trade to the DSB for Settlement

    Institute of Scientific and Technical Information of China (English)

    刘阳

    2006-01-01

    "特保"和"特限"是中美纺织品争端的焦点.澄清有关"特保"和"特限"规则中的模糊之处是解决中美纺织品争端的关键.文章将中美纺织品贸易争端提交DSB,争取以判例的形式明确启动"特保"和"特限"应具备的法律要件,为我国纺织品出口创造较好的国际法律环境.

  13. Language Training - French Training

    CERN Multimedia

    2007-01-01

    General and Professional French Courses The next session will take place from 29 January to 30 March 2007. These courses are open to all persons working on the CERN site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mrs. Benz : Tel. 73127. Writing Professional Documents in French The next session will take place from 29 January to 30 March 2007. This course is designed for people with a good level of spoken French. Duration: 30 hours Price: 660 CHF (for 8 students) For further information and registration, please consult our Web pages:   http://cern.ch/Training or contact Mrs. Benz : Tel. 73127. Writing Professional Documents in English The next session will take place from January to June 2007 (break at Easter). This course is designed for people with a good level of spoken English. Duration: 30 hours Price: 660 CHF (for 8 students) Timetable will be fixed after discussion with the students. For registratio...

  14. Language Training: English Training

    CERN Multimedia

    Françoise Benz

    2004-01-01

    La prochaine session se déroulera du 04 octobre 2004 au 11 février 2005 (interruption de 3 semaines à Noël). Ces cours s'adressent à toute personne travaillant au CERN ainsi qu'à leur conjoint. Pour vous inscrire et voir tout le détail des cours proposés, consultez nos pages Web : http://cern.ch/Training Vous pouvez aussi contacter M. Liptow, tél. 72957. General and Professional English Courses The next session will take place from 04 October 2004 to 11 February 2005 (3 weeks break at Christmas). These courses are open to all persons working on the CERN site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mr. Liptow, tel. 72957. Oral Expression This course is intended for people with a good knowledge of English who want to practise and maintain their speaking skills while extending their vocabulary. There will be approximately 8 participants ...

  15. Language Training: English Training

    CERN Multimedia

    Françoise Benz

    2004-01-01

    General and Professional English Courses The next session will take place from 04 October 2004 to 11 February 2005 (3 weeks break at Christmas). These courses are open to all persons working on the CERN site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mr. Liptow, tel. 72957. Oral Expression This course is intended for people with a good knowledge of English who want to practise and maintain their speaking skills while extending their vocabulary. There will be approximately 8 participants in a class. Speaking activities will include discussions, meeting simulations, role-plays etc. depending on the needs of the students. Duration: 20 hours (2 hours a week) Price: 440 CHF (for 8 students) For further information, please contact Mr. Liptow, tel. 72957. Date and timetable will be fixed when there are sufficient participants enrolled. FORMATION EN LANGUES LANGUAGE TRAINING Françoise Benz 73127 langua...

  16. Language Training: English Training

    CERN Multimedia

    Françoise Benz

    2004-01-01

    General and Professional English Courses The next session will take place from 04 October 2004 to 11 February 2005 (3 weeks break at Christmas). These courses are open to all persons working on the CERN site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mr. Liptow, tel. 72957. Oral Expression This course is intended for people with a good knowledge of English who want to practise and maintain their speaking skills while extending their vocabulary. There will be approximately 8 participants in a class. Speaking activities will include discussions, meeting simulations, role-plays etc. depending on the needs of the students. Duration: 20 hours (2 hours a week) Price: 440 CHF (for 8 students) For further information, please contact Mr. Liptow, tel. 72957. Date and timetable will be fixed when there are sufficient participants enrolled. FORMATION EN LANGUES LANGUAGE TRAINING Françoise Benz 73127 languag...

  17. Language Training: English Training

    CERN Multimedia

    Françoise Benz

    2004-01-01

    General and Professional English Courses The next session will take place from 04 October 2004 to 11 February 2005 (3 weeks break at Christmas). These courses are open to all persons working on the CERN site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mr. Liptow, tel. 72957. Oral Expression This course is intended for people with a good knowledge of English who want to practise and maintain their speaking skills while extending their vocabulary. There will be approximately 8 participants in a class. Speaking activities will include discussions, meeting simulations, role-plays etc. depending on the needs of the students. Duration: 20 hours (2 hours a week) Price: 440 CHF (for 8 students) For further information, please contact Mr. Liptow, tel. 72957. Date and timetable will be fixed when there are sufficient participants enrolled. FORMATION EN LANGUES LANGUAGE TRAINING Françoise Benz 73127 langua...

  18. Strength Training

    Science.gov (United States)

    ... strengthens your heart and lungs. When you strength train with weights, you're using your muscles to ... see there are lots of different ways to train with weights. Try a few good basic routines ...

  19. 十字花科黑腐病菌dsbA基因控制的亚细胞蛋白质组分析%Identification of Subcellular Proteomes Controlled by ds bA in Xanthomonas campestris pv.campestris

    Institute of Scientific and Technical Information of China (English)

    岑卫健; 刘龙宇; 于凯; 甘永亮; 付强; 姜伯乐

    2016-01-01

    本研究以十字花科黑腐病菌(Xanthomonas campestris pv.campestris,Xcc)8004菌株为研究对象,采用双向电泳—质谱技术分析比较了dsbA1A2突变体和野生型菌株的分泌蛋白、周质蛋白表达谱.与野生型菌株相比,选取的31个差异蛋白中,14个蛋白点显著上调,17个蛋白点显著下调.对这些蛋白质点进行质谱鉴定和分析,结果显示,dsbA1A2基因的缺失导致了周质蛋白中与β桶结构膜蛋白形成有关的伴侣蛋白SurA的含量降低,几种未知功能的分泌蛋白的分泌量减少以及外膜蛋白OmpW、OmpW1在周质空间的积累.推测这些蛋白质对Xcc8004的致病性至关重要,为进一步研究Xcc8004中DSB系统的作用机理提供了依据.

  20. Language Training - English Training

    CERN Multimedia

    HR Department

    2009-01-01

    General and Professional English Courses The next session will take place: from 2nd March to end of June 2009 (1/2 weeks break at Easter). These courses are open to all persons working on the CERN site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Nathalie Dumeaux, tel. 78144. Oral Expression The next session will take place from 2nd March to end of June 2009 (1/2 weeks break at Easter). This course is intended for people with a good knowledge of English who want to enhance their speaking skills. There will be on average of 8 participants in a class. Speaking activities will include discussions, meeting simulations, role-plays etc. depending on the needs of the students. Duration: 30 hours Price: 660 CHF (for a minimum of 8 students) Writing Professional Documents in English The next session will take place from 2nd March to end of June 2009 (1/2 weeks break at Easter). This course is designed for people w...

  1. Language Training - English Training

    CERN Multimedia

    HR Department

    2009-01-01

    General and Professional English Courses The next session will take place: from 2nd March to end of June 2009 (1/2 weeks break at Easter). These courses are open to all persons working on the CERN site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Nathalie Dumeaux, tel. 78144. Oral Expression The next session will take place from 2nd March to end of June 2009 (1/2 weeks break at Easter). This course is intended for people with a good knowledge of English who want to enhance their speaking skills. There will be an average of 8 participants per class. Speaking activities will include discussions, meeting simulations, role-plays, etc., depending on the needs of the students. Duration: 30 hours Price: 660 CHF (for a minimum of 8 students) Writing Professional Documents in English The next session will take place from 2nd March to end of June 2009 (1/2 weeks break at Easter). This course is designed for people ...

  2. Comparison of DSB effects of the beta particles of iodine-131 and 6 MV X-ray at a dose of 2 Gy in the presence of 2-Methoxyestradiol, IUdR, and TPT in glioblastoma spheroids

    Science.gov (United States)

    Neshasteh-Riz, Ali; Eyvazzadeh, Nazila; Koosha, Fereshteh; Cheraghi, Susan

    2017-02-01

    Glioblastoma is one of the lethal brain tumors and one of the resistant tumors against radiotherapy. Multiple treatment methods and different types of radiation and Radiosensitizers drugs have been combined to optimize the efficacy of radiotherapy. Radiosensitizers are employed to reinforce tumor cell killing and have much fewer effects on the normal tissue. Inducing DNA double strand break in tumoral cells is a major goal of radiation sensitivity. In this study, the level of DNA double strand break in glioblastoma spheroids irradiated by 2 Gy beta particles of iodine-131 and 6 MV X-rays in the presence of 2-Methoxyestradiol (2ME2), iodo-deoxy-uridine (IUdR) and Topotecan (TPT) was measured using the PicoGreen method. Spheroids of the U87MG cell line were cultured to reach a 300 μm diameter. In the phase one of the study, the spheroids were treated in four groups individually, including 2 Gy of iodine-131, TPT+iodine-131, IUdR+iodine-131, IUdR+2ME2+iodine-131. In the next phase, the cells were treated with 2 Gy of 6 MV X-ray, TPT+6 MV X-ray, IUdR+6 MV X-ray, TPT+IUdR+6 MV X-ray. DSB lesions were measured by the Pico Green assay. The amount of DSB lesions in groups irradiated with iodine-131 individually was greater than the group irradiated with 6 MV X-ray (pindependent groups of TPT+IUdR+2ME2+iodine-131 and TPT+IUdR+2ME2+6 MV X-ray was approximately in the same range (P>0.05). The level of DNA double strand breaks in cells irradiated with Iodine-131 was higher than cells irradiated with 6 MV X-ray at the same dose and Topotecan had a positive effect on inducing the damage. The role of 2ME2+IUdR in increasing the damage caused by beta particles of iodine-131 was not significant. Iodine-131 could lead to major DSB damage than 6 MV X-ray at the same dose due to its cross fire effect and spatial distribution of energy in different angels. This study showed that a combination of chemotherapy and iodine-131 had better efficacy than radiotherapy with 6 MV X-ray in the

  3. ENGLISH TRAINING

    CERN Multimedia

    2003-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. LANGUAGE TRAINING Françoise Benz tel. 73127 language.training@cern.ch PLACES AVAILABLE Writing Professional Documents in English This course is designed for people with a good level of spoken English who need to improve their professional writing (administrative, scientific, technical). Duration: 20 hours (2 hours a week) Price: 440 CHF (for 8 students) Date and timetable will be fixed when there are sufficient participants enrolled. Oral Expression This course is intended for people with a good knowledge of English who want to practise and maintain their sp...

  4. LANGUAGE TRAINING

    CERN Multimedia

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. LANGUAGE TRAINING Françoise Benz tel. 73127 language.training@cern.ch FRENCH TRAINING General and Professional French Courses The next session will take place from 26 January to 02 April 2004. These courses are open to all persons working on the Cern site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mrs. Benz: Tel. 73127. Writing Professional Documents in French The next session will take place from 26 January to 02 April 2004. This course is designed for people wi...

  5. LANGUAGE TRAINING

    CERN Multimedia

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. LANGUAGE TRAINING Françoise Benz tel. 73127 language.training@cern.ch FRENCH TRAINING General and Professional French Courses The next session will take place from 26 January to 02 April 2004. These courses are open to all persons working on the Cern site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mrs. Benz : Tel. 73127. Writing Professional Documents in French The next session will take place from 26 January to 02 April 2004. This course is designed for peop...

  6. Training Attestations

    CERN Multimedia

    HR Department

    2004-01-01

    In the past, paper Training Attestations were printed during the first quarter of a New Year for Staff Members having followed courses and seminars the previous year in the context of CERN's official Training Programmes.  The attestations were sent to Divisional Training Officers (DTO's) for distribution to all Staff Members concerned within their Division. In practise many Staff Members did not find this paper useful, however some expressed a wish to be able to have access to a self-service facility in case of need. This change was discussed by the Joint Training Board (JTB) and with the DTO's during 2003 and was supported. As a consequence, following a collaboration between HR-PMD and IT-AIS, from 2004 onwards paper Training Attestations will no longer be printed and distributed as before. Those requiring a list of training followed in the past can now obtain their attestation directly from the Human Resources Toolkit (HRT) application for all training followed since 1997. https://hrt.cern...

  7. Supervisor training

    DEFF Research Database (Denmark)

    Pedersen, Inge Nygaard

    2015-01-01

    This article fills a gap in knowledge about supervisor training programmes in the field of music therapy in Europe. Sparse research exists which demonstrates evidence of effective professional supervision upon the outcome of music therapy clinical practice. The article has its focus on the experi......This article fills a gap in knowledge about supervisor training programmes in the field of music therapy in Europe. Sparse research exists which demonstrates evidence of effective professional supervision upon the outcome of music therapy clinical practice. The article has its focus...... on the experience of an integrated supervisor training programme offered in Aalborg, Denmark in 2009/2010. In this programme general issues of professional supervision and the application of artistic media as a core element in the supervisory process were Integrated. It is the hope of the author that this article...... will inspire other music therapists to develop supervisor training programmes for professional music therapists and also to undertake further research into professional supervision....

  8. Officer Training

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — This dataset shows the time spent by currently active Pittsburgh Police Officers in professional development training. Officers who are no longer employed in the...

  9. Strength Training

    Science.gov (United States)

    ... en español Entrenamiento de la fuerza muscular Strength training is a vital part of a balanced exercise routine that includes aerobic activity and flexibility exercises. Regular aerobic exercise, such as running or ...

  10. French Training

    CERN Multimedia

    Françoise Benz

    2003-01-01

    General and Professional French Courses The next session will take place: from 13 October to 19 December 2003. These courses are open to all persons working on the CERN site, and to their spouses. For registration and further information on the courses, please consult our Web pages or contact Mrs. Fontbonne: Tel. 72844. Writing Professional Documents in French This course is designed for people with a good level of spoken French. Duration: 30 hours Price: 660 CHF (for 8 students) For further information and registration, please consult our Web pages or contact Mrs. Fontbonne: Tel. 72844. Language Training Françoise Benz Tel.73127 language.training@cern.ch

  11. Athletic training. Personal performance development and training.

    OpenAIRE

    Broda, Michal

    2011-01-01

    Athletic training. Personal performance development and training. Objectives: The aim of this study was to analyze performance development and training of Michal Broda during his existing athletic career with focus on training after year 2004. We investigated the use of heart rate monitoring for training optimization. We also discussed training adequacy in terms of annual training cycle. Methods: In our work we used empirical methods of pedagogical research. We obtained different qualitative ...

  12. 组蛋白去乙酰化酶抑制剂对DNA双链断裂修复路径的作用%Effect of Histone Deacetylase Inhibitors on DNA DSB Repair

    Institute of Scientific and Technical Information of China (English)

    孙有湘; 周克元; 李莉萍

    2013-01-01

    DNA双链断裂(double strand breaks,DSBs)对细胞生存是致命的.细胞内非同源末端连接(NHEJ)、重组修复(HDR)、单链退火修复(SSA)和微同源序列末端连接(MMEJ)等通路可竞争性修复DNA双链断裂损伤.在肿瘤细胞DNA中制造难以修复的基因损伤,诱导肿瘤细胞周期中止、坏死和凋亡是临床放、化疗的主要策略.组蛋白去乙酰化酶(histone deacetylase)作为抗肿瘤治疗的新靶标,其抑制剂(histone deacetylase inhibitors,HDACi)可显著降低肿瘤细胞DSBs修复能力,增强肿瘤细胞的放、化疗敏感性.研究显示,HDACi抑制了肿瘤细胞中具有正确修复倾向的HDR和经典NHEJ通路,具有错误修复倾向的SSA和MMEJ路径也可能牵涉其中.目前,HDACi作用于DSBs修复通路的分子机制已取得较大进展,但仍有许多问题有待阐明.%DNA double strand break (DSB) can be fatal to cells.The non-homologous end joining (NHEJ),homologous direct recombination (HDR),single strand annealing (SSA) and micro-homology mediated end joining (MMEJ) pathways are able to repair DSBs in vivo.A main strategy of clinical radiotherapy and chemotherapy is to induce chromosomal DNA damage that are difficult to repair,thus to cause cell cycle arrest,apoptosis or necrosis in tumor cells.As a new target of anti-tumor medicine,histonc deacetylase inhibitor (HDACi) effectively suppresses DSBs repair capacity and sensitize tumor cells to radiotherapy or chemotherapy.Recent research suggested that the error-free DSBs repair pathways HDR and classical-NHEJ were suppressed by HDACi in tumor cells,and the error-prone SSA and MMEJ pathways might also involved in.Although much progress have acquired on the mechanism of how HDACi affecting DSB repair pathways,there are still many questions need to be elucidated.

  13. ACADEMIC TRAINING

    CERN Multimedia

    Françoise Benz

    2002-01-01

    12, 13, 14, March LECTURE SERIES from 11.00 to 12.00 hrs - Auditorium, bldg. 500 POSTPONED! - Modern Project Management Methods - POSTPONED! By G. Vallet / Ed. Highware, Paris, F. Academic Training Françoise Benz Secretariat Tel. 73127 francoise.benz@cern.ch

  14. Language training

    CERN Multimedia

    2006-01-01

    If you wish to participate in one of the following courses, please tell to your supervisor and apply electronically from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an 'application for training' form available from your Departmental Secretariat or from your DTO (Departmental Training Officer). Applications will be accepted in the order in which they are received. General and Professional English Courses The next session will take place from beginning of October 2006 to beginning of February 2007 (3 weeks break at Christmas).These courses are open to all persons working on the CERN site and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Tessa Osborne, tel.16 23 40. Oral Expression The next session will take place from beginning of October 2006 to beginning of February 2007 (3 weeks break at Christmas).This course is intended for people with a good knowl...

  15. Language Training

    CERN Multimedia

    Françoise Benz

    2005-01-01

    If you wish to participate in one of the following courses, please tell to your supervisor and apply electronically from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an 'application for training' form available from your Departmental Secretariat or from your DTO (Departmental Training Officer). Applications will be accepted in the order in which they are received. General and Professional English Courses The next session will take place: from end of September 2005 to middle of February 2006 (2/ 3 weeks break at Christmas). These courses are open to all persons working on the CERN site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mr. Liptow: tel. 72957. Oral Expression The next session will take place from end of September to December 2005. This course is intended for people with a good knowledge of English who want to practise and maintain the...

  16. Language training

    CERN Multimedia

    Françoise Benz

    2006-01-01

    If you wish to participate in one of the following courses, please tell to your supervisor and apply electronically from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an 'application for training'form available from your Departmental Secretariat or from your DTO (Departmental Training Officer). Applications will be accepted in the order in which they are received. General and Professional English Courses The next session will take place from beginning of October 2006 to beginning of February 2007 (3 weeks break at Christmas).These courses are open to all persons working on the CERN site and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Tessa Osborne, tel.16 23 40. Oral Expression The next session will take place from beginning of October 2006 to beginning of February 2007 (3 weeks break at Christmas).This course is intended for people with a goo...

  17. Technical Training: Technical Training Seminar

    CERN Multimedia

    2004-01-01

    TECHNICAL TRAINING Monique Duval tel. 74924 technical.training@cern.ch Monday 9 February 2004 From 10:00 to 12:00 - IT Auditorium - bldg. 31, 3rd floor ANSOFT High-Frequency Seminar David Prestaux, Application Engineer, ANSOFT F-78535 BUC, France This Technical Training seminar will present two Ansoft application products: Ansoft HFSS and Ansoft Designer. Ansoft HFSS makes use of the Finite Element Method (FEM) to calculate field solutions from first principles. It can accurately predict all high-frequency behaviours such as dispersion, mode conversion, and losses due to materials and radiation. Ansoft Designer is a suite of design tools to fully integrate high-frequency, physics-based electromagnetic simulations into a seamless system-level simulation environment. Ansoft Designer uses a simple interface to give complete control over every design task, by a method allowing multiple solvers, Solver on Demand. • Introduction • Overview of the Ansoft Total solution • Ansoft HFSS 9...

  18. 从条约适用角度研究WTO争端裁决报告的执行%Research on Executing the Award of DSB from the Perspective of Treaty Application

    Institute of Scientific and Technical Information of China (English)

    李晓郛; 都陪丽

    2013-01-01

    作为WTO争端解决实体的DSB (Dispute Settlement Body),其裁决报告对WTO争端解决有重要意义.美国以实用主义为先导、国家利益为出发点执行DSB裁决报告,以USTR为主的协调机制亦是其一大特色;欧盟以有利于联盟一体化的态度执行DSB裁决报告.立足中国国情,结合大多数WTO成员方未给予DSB裁决报告直接效力的执行实践,建议今后执行DSB裁决报告时,树立国家利益至上的总体思路,建立协调人制度,并设立专家委员会配合执行,国内法院以司法克制的态度处理DSB裁决报告及相关诉讼.

  19. Sports Training

    Science.gov (United States)

    1988-01-01

    Practitioners of martial arts have long seen a need for a precise method of measuring the power of a karate kick or a boxer's punch in training and competition. Impax sensor is a piezoelectric film less than one thousandth of an inch thick, yet extremely durable. They give out a voltage impulse when struck, the greater the force of impact, the higher the voltage. The impulse is transmitted to a compact electronics package where voltage is translated into a force-pounds reading shown on a digital display. Impax, manufactured by Impulse Technology, Inc. is used by martial arts instructors, practitioners, U.S. Olympic Committee Training Center, football blocking sleds, and boxers as well as police defensive tactics, providing a means of evaluating the performance of recruits.

  20. Language Training

    CERN Multimedia

    HR Department

    Permanence A "permanence" for language Training has been set up. If anyone has a question or requires information on any aspect of English or French training please come to our office 5 4-016 at the following times. Lucette Fournier - French courses Monday 13.30 - 15.30 Tuesday\t10.30 - 12.30 Tessa Osborne - English courses Wednesday\t12.00 - 14.00 Thursday\t11.00 - 13.00   New courses Specific English and French courses - Exam preparation/ We are now offering specific courses in English and French leading to a recognised external examination (e.g. Cambridge, DELF, DALF). If you are interested in following one of these courses and have at least an upper intermediate level of English or French, please enrol through the following link:  English courses French courses Or contact: Tessa Osborne 72957 (English courses) Lucette Fournier 73483 (French courses) Language Training Nathalie Dumeaux Tel. 78144 nathalie.dumeaux@cern.ch

  1. Language Training

    CERN Multimedia

    HR Department

    2009-01-01

    PermanenceA "permanence" for language Training has been set up. If anyone has a question or requires information on any aspect of English or French training please come to our office 5 4-016 at the following times. Lucette Fournier French courses Monday 13.30 - 15.30 Tuesday\t10.30 - 12.30 Tessa Osborne English courses Wednesday\t12.00 - 14.00 Thursday\t11.00 - 13.00 New courses Specific English and French courses - Exam preparation/ We are now offering specific courses in English and French leading to a recognised external examination (e.g. Cambridge, DELF and BULATS). If you are interested in following one of these courses and have at least an upper intermediate level of English or French, please enrol through the following link: http://English courses http://French courses Or contact: Tessa Osborne 72957 (English courses) Lucette Fournier 73483 (French courses) Language Training Nathalie Dumeaux Tel. 78144 mailto:nathalie.dumeaux@cern.ch

  2. Technical Training: Technical Training Seminar

    CERN Multimedia

    2004-01-01

    TECHNICAL TRAINING Monique Duval tel. 74924 technical.training@cern.ch Tuesday 3 February 2004 From 09:00 to 13:30 - Training Centre Auditorium - bldg. 593, room 11 USB (Universal Serial Bus) CYPRESS Seminar Claudia Colombini, Field Application Engineer CYPRESS ActiveComp Electronic GmbH D-85077 MANCHING, Germany As a pioneer in USB, CYPRESS sets the standard for cost-effective solutions without sacrificing functionality, performance or reliability. Having shipped over 200 million USB devices, Cypress is the undisputed market leader and demonstrates unmatched USB expertise. With the industry's broadest selection of USB solutions, Cypress has the right silicon, software and support for every USB application, from Low-speed to High-Speed and USB On-The-Go (OTG). 9:00 - 10:30 Overview of USB systems. USB CYPRESS product overview. Peripherals: Low Speed, Full Speed, High Speed (1.1 and 2.0). Hub Solutions, Embedded Host Solutions, On-The-Go (OTG) and wireless USB. USB Development Tools (first part) 10:30 -...

  3. ACADEMIC TRAINING

    CERN Multimedia

    Françoise Benz

    2002-01-01

    6, 7 May LECTURE SERIES from 11.00 to 12.00 hrs - Auditorium, bldg. 500 Decoding the Human Genome, Scientific basis and ethic and social aspects by S.E. Antonarakis and A. Mauron / Univ. of Geneva Decoding the Human genome is a very up-to-date topic, raising several questions besides purely scientific, in view of the two competing teams (public and private), the ethics of using the results, and the fact that the project went apparently faster and easier than expected. The lecture series will address the following chapters: Scientific basis and challenges, Ethical and social aspects of genomics. Academic Training Françoise Benz Tel. 73127

  4. Media Training

    CERN Document Server

    CERN. Geneva

    2009-01-01

    With the LHC starting up soon, the world's media are again turning their attention to CERN. We're all likely to be called upon to explain what is happening at CERN to media, friends and neighbours. The seminar will be given by BBC television news journalists Liz Pike and Nadia Marchant, and will deal with the kind of questions we're likely to be confronted with through the restart period. The training is open for everybody. Make sure you arrive early enough to get a seat - there are only 200 seats in the Globe. The session will also be webcast: http://webcast.cern.ch/

  5. Strength Training. A Key to Athletic Training.

    Science.gov (United States)

    Whiteside, Patricia W.

    Characteristics of an effective strength training program are analyzed and descriptions are offered of different kinds of weight training activities. Comparisons are made between concentric, isometric, eccentric, and isokinetic training methods. The fundamentals and techniques of an exemplary training program are outlined and the organization and…

  6. SELECTING AND TRAINING THE TRAINING OFFICER.

    Science.gov (United States)

    TAYLOR, NANCY

    TO ACHIEVE THE OBJECTIVES OF TRAINING IN INDUSTRY--TECHNICAL AND LIBERAL EDUCATION, SPECIFIC JOB SKILLS, AND THE DEVELOPMENT OF ATTITUDES--THE TRAINING OFFICER MUST KNOW THE COMPANY WITHIN WHICH HE IS WORKING, AS WELL AS MANAGEMENT THEORY AND TRAINING METHODS. THE SELECTION OF TRAINING OFFICERS IS BASED ON A JOB SPECIFICATION, AN OUTGROWTH OF A…

  7. French training

    CERN Multimedia

    2007-01-01

    The next session will take place from 29 January to 30 March 2007. These courses are open to all persons working on the CERN site, and their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mrs. Benz: tel. 73127. Writing Professional Documents in French The next session will take place from 29 January to 30 March 2007. This course is designed for people with a good level of spoken French. Duration: 30 hours Price: 660 CHF (for 8 students) For further information and registration, please consult our Web pages: http://cern.ch/Training or contact Mrs. Benz: tel. 73127. Writing Professional Documents in English The next session will take place from January to June 2007 (break at Easter). This course is designed for people with a good level of spoken English. Duration: 30 hours Price: 660 CHF (for 8 students) Timetable will be fixed after discussion with the students. For further information and registration, please consu...

  8. Language Training

    CERN Multimedia

    2003-01-01

    Formation en anglais Cours d'anglais général et professionnel La prochaine session se déroulera: du 06 octobre 2003 au 13 février 2004 (interruption de 3/4 semaines à Noël). Ces cours s'adressent à toute personne travaillant au CERN ainsi qu'à leur conjoint. Pour vous inscrire et voir tout le détail des cours proposés, consultez nos pages Web: http://cern.ch/Training Vous pouvez aussi contacter Mme Benz, tél. 73127 ou Mr Liptow, tél. 72957. General and Professional English Courses The next session will take place: from 06 October 2003 to 13 February 2004 (3/4 weeks break at Christmas). These courses are open to all persons working on the Cern site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mrs. Benz: tel. 73127 or Mr. Liptow: tel. 72957. Writing Professional Documents in English This course is designed for people with a good level of spoken English. Duration: 20 hours (2 hours a week) Price: ...

  9. Language Training

    CERN Multimedia

    2003-01-01

    Formation en anglais Cours d'anglais général et professionnel La prochaine session se déroulera: du 06 octobre 2003 au 13 février 2004 (interruption de 3/4 semaines à Noël). Ces cours s'adressent à toute personne travaillant au CERN ainsi qu'à leur conjoint. Pour vous inscrire et voir tout le détail des cours proposés, consultez nos pages Web: http://cern.ch/Training Vous pouvez aussi contacter M. Liptow, tél. 72957. General and Professional English Courses The next session will take place: from 06 October 2003 to 13 February 2004 (3/4 weeks break at Christmas). These courses are open to all persons working on the Cern site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mr. Liptow: tel. 72957. Writing Professional Documents in English This course is designed for people with a good level of...

  10. Language Training

    CERN Multimedia

    2003-01-01

    Formation en anglais Cours d'anglais général et professionnel La prochaine session se déroulera: du 06 octobre 2003 au 13 février 2004 (interruption de 3/4 semaines à Noël). Ces cours s'adressent à toute personne travaillant au CERN ainsi qu'à leur conjoint. Pour vous inscrire et voir tout le détail des cours proposés, consultez nos pages Web: http://cern.ch/Training Vous pouvez aussi contacter Mme Benz, tél. 73127 ou Mr Liptow, tél. 72957. General and Professional English Courses The next session will take place: from 06 October 2003 to 13 February 2004 (3/4 weeks break at Christmas). These courses are open to all persons working on the Cern site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mrs. Benz: tel. 73127 or Mr. Liptow: tel. 72957. Writing Professional Documents in Engl...

  11. English Training

    CERN Multimedia

    2003-01-01

    General and Professional English Courses The next session will take place: from 03 March to 28 June 2003 (2 weeks break at Easter). These courses are open to all persons working on the Cern site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mrs. Benz: tel.73127 or Mr. Liptow: tel.72957. Writing Professional Documents in English This course is designed for people with a good level of spoken English. Duration: 20 hours (2 hours a week) Price: 440 CHF (for 8 students) For registration and further information, please consult our Web pages: http://cern.ch/Training or contact Mrs. Tessa Osborne: Tessa.Osborne@cern. Oral Expression This course is intended for people with a good knowledge of English who want to practise and maintain their speaking skills while extending their vocabulary. There will be approximately 8 participants in a class. Speaking activities will include discussions, meeting simulations, role-p...

  12. English Training

    CERN Multimedia

    2003-01-01

    General and Professional English Courses The next session will take place: from 03 March to 28 June 2003 (2 weeks break at Easter). These courses are open to all persons working on the Cern site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mrs. Benz: tel.73127 or Mr. Liptow: tel.72957. Writing Professional Documents in English This course is designed for people with a good level of spoken English. Duration: 20 hours (2 hours a week) Price: 440 CHF (for 8 students) For registration and further information, please consult our Web pages: http://cern.ch/Training or contact Mrs. Tessa Osborne: Tessa.Osborne@cern. Oral Expression This course is intended for people with a good knowledge of English who want to practise and maintain their speaking skills while extending their vocabulary. There will be approximately 8 participants in a class. Speaking activities will include discussions, meeting simulations, rol...

  13. ACADEMIC TRAINING

    CERN Multimedia

    Françoise Benz

    2002-01-01

    25, 26, 27, 28 February and 1st March from 11.00 to 12.00 hrs - Auditorium, bldg. 500 LECTURE SERIES Neutrino masses and oscillations by A. de Rujula / CERN-TH This course will not cover its subject in the customary way. The emphasis will be on the simple theoretical concepts (helicity, handedness, chirality, Majorana masses) which are obscure in most of the literature, and on the quantum mechanics of oscillations, that ALL books get wrong. Which, hopefully, will not deter me from discussing some of the most interesting results from the labs and from the cosmos. Academic Training Françoise Benz Secretariat Tel. 73127 francoise.benz@cern.ch

  14. English training

    CERN Multimedia

    2003-01-01

    You have a good level of English BUT... You still need to improve your speaking or You have problems writing professional documents Would you like to work in a small group on either of these areas? Then, the following courses are for you! Writing Professional Documents in English The aim of the course is for students to improve their professional writing. Participants will work on technical, scientific or administrative documents depending on the needs of the group. Duration: 20 hours (2 hours a week) Price: 440 CHF (for 8 students) Oral Expression The emphasis will be on oral expression with necessary feed-back. Speaking activities will include discussions, meeting simulations, role-plays etc. Duration: 20 hours (2 hours a week) Price: 440 CHF (for 8 students) For registration and further information, please consult our Web pages: http://cern.ch/Training or contact Mr. Liptow: tel. 72957 / Mrs. Tessa Osborne: Tessa.Osborne@cern.ch.

  15. English Training

    CERN Multimedia

    2003-01-01

    You have a good level of English BUT... You still need to improve your speaking or You have problems writing professional documents Would you like to work in a small group on either of these areas? Then, the following courses are for you! Writing Professional Documents in English The aim of the course is for students to improve their professional writing. Participants will work on technical, scientific or administrative documents depending on the needs of the group. Duration: 20 hours (2 hours a week) Price: 440 CHF (for 8 students) Oral Expression The emphasis will be on oral expression with necessary feed-back. Speaking activities will include discussions, meeting simulations, role-plays etc. Duration: 20 hours (2 hours a week) Price: 440 CHF (for 8 students) For registration and further information, please consult our Web pages: http://cern.ch/Training or contact Mr. Liptow: tel. 72957 / Mrs. Tessa Osborne: Tessa.Osborne@cern.ch.

  16. "Training Floors" and "Training Ceilings": Metonyms for Understanding Training Trends

    Science.gov (United States)

    Felstead, Alan; Jewson, Nick

    2014-01-01

    This article outlines a conceptual framework for mapping and understanding training trends. It uses the metonyms of floors and ceilings to distinguish between different types of training configurations. The argument is made that the ups and downs of employer reports of training activity are a crude basis on which to make judgements about the…

  17. Nuclear manpower training

    Energy Technology Data Exchange (ETDEWEB)

    Suh, In Suk; Lee, H. Y.; Joe, B. J.; Lee, S. H.; Lee, E. J.; Yoo, B. H.; Seo, K. W.; Lee, W. K.; Jun, H. I.; Yang, K. N.; Kim, Y. J.; Kim, I. H.; Kim, M. Y.; Ju, Y. C.; Hyun, H. Y.; Choi, I. G.; Hong, C. S.; Won, J. Y.; Nam, J. Y.; Lee, H. J.

    1997-01-01

    This report describes the annual results of training courses. the scope and contents are as follows: 1. Regional and interregional training courses 2. Training courses assisted by foreign experts 3. Training courses for nuclear industry personnel 4. Training courses for internal staff-members 5. Training courses under the law. This Nuclear Training Center executed the open-door training courses for 2,400 engineers/scientists from the regulatory body, nuclear industries, research institutes and other related organizations by means of offering 51 training courses during the fiscal year 1996. (author). 23 refs.

  18. F-35 Embedded Training

    Science.gov (United States)

    2009-10-01

    from the pilot vehicle interface ( PVI ), which enables weapon and expendable countermeasures employment simulations. From TRAIN mode the pilot can...Scenario Debrief Data Aircraft Data Transfer Device ET Scenarios controlled via TRAIN Mode PVI TRAIN Mode Infrastructure JSF OMS VT Scenario...TRAIN mode from the pilot vehicle interface ( PVI ), which enables weapon and expendable countermeasures employment simulations. From TRAIN mode the

  19. Spaced cognitive training promotes training transfer

    Directory of Open Access Journals (Sweden)

    Zuowei eWang

    2014-04-01

    Full Text Available Cognitive training studies yield wildly inconsistent results. One dimension on which studies vary is the scheduling of training sessions (Morrison & Chein, 2011. In this study, we systematically address whether or not spacing of practice influences training and transfer. We randomly assigned 115 fifth grade children to an active control group or one of four training groups who received working memory training based on a running span task (Zhao et al., 2011. All groups received the same total amount of training: 20 sessions of training with 60 trials for an average of 20 minutes per session. The training was spread across 2 days, 5 days, 10 days, or 20 days. The active control group received 20-minute sessions of math instruction for 20 sessions. Before and after training participants in all five groups performed a single transfer test that assessed fluid intelligence, the Raven's Progressive Matrices Test. Overall, participants in all four training groups improved significantly on the training task (at least partially, as reflected by increased speed. More importantly, the only training group to show significant improvement on the Raven's was the group who had the greatest amount of spacing (20 days group during training and improvement in this group was significantly higher than that of the control group.

  20. Spaced cognitive training promotes training transfer.

    Science.gov (United States)

    Wang, Zuowei; Zhou, Renlai; Shah, Priti

    2014-01-01

    Cognitive training studies yield wildly inconsistent results. One dimension on which studies vary is the scheduling of training sessions (Morrison and Chein, 2011). In this study, we systematically address whether or not spacing of practice influences training and transfer. We randomly assigned 115 fifth grade children to an active control group or one of four training groups who received working memory training based on a "running span" task (Zhao et al., 2011). All groups received the same total amount of training: 20 sessions of training with 60 trials for an average of 20 min per session. The training was spread across 2, 5, 10, or 20 days. The active control group received 20-min sessions of math instruction for 20 sessions. Before and after training participants in all five groups performed a single transfer test that assessed fluid intelligence, the Raven's Progressive Matrices Test. Overall, participants in all four training groups improved significantly on the training task (at least partially), as reflected by increased speed. More importantly, the only training group to show significant improvement on the Raven's was the group who had the greatest amount of spacing (20 days group) during training and improvement in this group was significantly higher than that of the control group.

  1. Training the Sales Neophyte

    Science.gov (United States)

    Harris, Clyde E., Jr.

    1975-01-01

    The article reappraises initial sales training and presents a program emphasizing objectives, responsibility for training, program content, and teaching techniques. Formal Initial Responsive Sales Training System (FIRSTS) is the name of the program explored and evaluated. (Author/MW)

  2. Toilet training tips

    Science.gov (United States)

    Potty training ... show signs that they are ready for toilet training between ages 18 and 30 months. Before 18 ... way that she is ready to start toilet training. Children are ready when they: Show interest in ...

  3. Language training

    CERN Multimedia

    Françoise Benz

    2005-01-01

    General and Professional English Courses The next session will take place: from end of September 2005 to middle of February 2006 (2/ 3 weeks break at Christmas). These courses are open to all persons working on the CERN site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mr. Liptow: tel. 72957. Oral Expression in English The next session will take place from end of September to December 2005. This course is intended for people with a good knowledge of English who want to practise and maintain their speaking skills while extending their vocabulary. There will be a maximum of 10 participants in a class. Speaking activities will include discussions, meeting simulations, role-plays etc. depending on the needs of the students. Duration: 20 hours Price: 440 CHF (for a minimum of 8 students) Writing Professional Documents in English The next session will take place from end of September 2005 to middle of Feb...

  4. Language training

    CERN Multimedia

    2007-01-01

    General and Professional English Courses The next session will take place from 26 February or 5 March to end of June 2007 (1/2 weeks break at Easter). These courses are open to all persons working on the CERN site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Françoise Benz, tel. 73127. Oral Expression The next session will take place from 26 February or 5 March to end of June 2007 (1/2 weeks break at Easter). This course is intended for people with a good knowledge of English who want to practise and maintain their speaking skills while extending their vocabulary. There will be a maximum of 10 participants in a class. Speaking activities will include discussions, meeting simulations, role-plays etc. depending on the needs of the students. Duration: 30 hours Price: 660 CHF (for a minimum of 8 students). Writing Professional Documents in English The next session will take place from 26 February or...

  5. Language training

    CERN Multimedia

    Françoise Benz

    2005-01-01

    General and Professional English Courses The next session will take place: from end of September 2005 to middle of February 2006 (2/ 3 weeks break at Christmas). These courses are open to all persons working on the CERN site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mr. Liptow: tel. 72957. Oral Expression in English The next session will take place from end of September to December 2005. This course is intended for people with a good knowledge of English who want to practise and maintain their speaking skills while extending their vocabulary. There will be a maximum of 10 participants in a class. Speaking activities will include discussions, meeting simulations, role-plays etc. depending on the needs of the students. Duration: 20 hours Price: 440 CHF (for a minimum of 8 students) Writing Professional Documents in English The next session will take place from end of September 2005 to middle of Feb...

  6. Language training

    CERN Multimedia

    2007-01-01

    General and Professional English Courses The next session will take place: from 26 February or 5 March to end of June 2007 (1/2 weeks break at Easter). These courses are open to all persons working on the CERN site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Françoise Benz, tel. 73127. Oral Expression The next session will take place from 26 February or 5 March to end of June 2007 (1/2 weeks break at Easter). This course is intended for people with a good knowledge of English who want to practise and maintain their speaking skills while extending their vocabulary. There will be a maximum of 10 participants in a class. Speaking activities will include discussions, meeting simulations, role-plays etc. depending on the needs of the students. Duration: 30 hours Price: 660 CHF (for a minimum of 8 students). Writing Professional Documents in English The next session will take place from 26 February or 5 M...

  7. Language Training

    CERN Multimedia

    Françoise Benz

    2005-01-01

    General and Professional English Courses The next session will take place: from end of September 2005 to middle of February 2006 (2/ 3 weeks break at Christmas). These courses are open to all persons working on the CERN site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mr. Liptow: tel. 72957. Oral Expression in English The next session will take place from end of September to December 2005. This course is intended for people with a good knowledge of English who want to practise and maintain their speaking skills while extending their vocabulary. There will be a maximum of 10 participants in a class. Speaking activities will include discussions, meeting simulations, role-plays etc. depending on the needs of the students. Duration: 20 hours Price: 440 CHF (for a minimum of 8 students) Writing Professional Documents in English The next session will take place from end of September 2005 to middle of Febr...

  8. Language training

    CERN Multimedia

    2006-01-01

    General and Professional English Courses The next session will take place from beginning of October 2006 to beginning of February 2007 (3 weeks break at Christmas).These courses are open to all persons working on the CERN site and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Tessa Osborne, tel.16 23 40. Oral Expression The next session will take place from beginning of October 2006 to beginning of February 2007 (3 weeks break at Christmas).This course is intended for people with a good knowledge of English who want to practise and maintain their speaking skills while extending their vocabulary. There will be a maximum of 10 participants in a class. Speaking activities will include discussions, meeting simulations, role-plays etc., depending on the needs of the students. Duration: 30 hours (2 hours a week) Price: 660 CHF (for a minimum of 8 students). Writing Professional Documents in English The next ses...

  9. Dynamic training devices in CRM training

    Science.gov (United States)

    Lawver, J.

    1984-01-01

    Pilot training effectiveness and flying safety of a seasonal tour flight company are described. The change from single pilot to two pilot operated twin otters is examined. The use of the ATC 810 training device, its possibilities and training capacity is outlined. Problem areas which may arise, emergency system and pilot/passenger interaction are analyzed.

  10. Privacy Training Program

    Science.gov (United States)

    Recognizing that training and awareness are critical to protecting agency Personally Identifiable Information (PII), the EPA is developing online training for privacy contacts in its programs and regions.

  11. DSB Task Force on Cyber Supply Chain

    Science.gov (United States)

    2017-04-01

    The task force assessed the organization, missions, and authorities that encompass the use of microelectronics and components in Department of... assess potential vulnerabilities in hardware and software; • the extent to which commercial off the shelf vulnerabilities have been reported and...Exploitation of Latent Vulnerabilities ........................................................ 2 Overview of the Cyber Supply Chain Landscape

  12. DSB Task Force on Cyber Supply Chain

    Science.gov (United States)

    2017-02-06

    activation, and effect.8 Complex microelectronics will inevitably contain latent vulnerabilities. Diligent test protocols, while an essential best ...supply agencies and maintenance depots. Buyer- seller relationships in this environment are fluid. Visibility to the lowest level of supply is obscured by... best . Sharing threat, vulnerability, and mitigation information across program PPPs is not well supported in current practice. While the PPP fits

  13. Technical Training: Technical Training Seminar

    CERN Multimedia

    2004-01-01

    Tuesday 30 March TECHNICAL TRAINING SEMINAR From 9:00 to 12:00 and from 13:00 to 16:00 hrs - Council Chamber, Salle B, Salle des Pas Perdus National Instruments (NI) on Tour 2004 Claudia Jüngel, Evrem Yarkin, Joel Clerc, Hervé Baour / NATIONAL INSTRUMENTS The special event NI on Tour 2004, run in Germany, Austria and Switzerland, will be at CERN on March 30. Technical seminars and free introductory courses will be offered all day long in the Council Chamber, Salle B, and Salle des Pas Perdus (buildings 61 and 503). Technical conferences: 09:00 - 12:00 Data acquisition systems on PCs. Industrial measurement and control techniques. 13:00 - 16:00 Advanced LabVIEW software and PXI instrumentation. Measuring instruments and system components for teststand automation. Introductory courses: 09:00 - 12:00 DIAdem: Data analysis and presentation 13:00 - 16:00 Data acquisition with LabVIEW Language: English and French Free special seminar. Registration is recommended with National Instruments Swi...

  14. Technical Training: Technical Training Seminar

    CERN Multimedia

    2004-01-01

    Tuesday 30 March TECHNICAL TRAINING SEMINAR From 9:00 to 12:00 and from 13:00 to 16:00 hrs - Council Chamber, Salle B, Salle des Pas Perdus National Instruments (NI) on Tour 2004 Claudia Jüngel, Evrem Yarkin, Joel Clerc, Hervé Baour / NATIONAL INSTRUMENTS The special event NI on Tour 2004, run in Germany, Austria and Switzerland, will be at CERN on March 30. Technical seminars and free introductory courses will be offered all day long in the Council Chamber, Salle B, and Salle des Pas Perdus (buildings 61 and 503). Technical conferences: 09:00 - 12:00 Data acquisition systems on PCs. Industrial measurement and control techniques. 13:00 - 16:00 Advanced LabVIEW software and PXI instrumentation. Measuring instruments and system components for teststand automation. Introductory courses: 09:00 - 12:00 DIAdem: Data analysis and presentation 13:00 - 16:00 Data acquisition with LabVIEW Language: English and French Free special seminar. Registration is recommended with National Instruments Switzerland (please sp...

  15. Generic Training Materials.

    Science.gov (United States)

    National Paralegal Inst., Washington, DC.

    Part of the National Paralegal Institute's curriculum for short-term intensive training sessions for paralegals, or legal assistants, the document outlines the format for training sessions concerning: (1) initial training to examine the functions of the paralegal and stimulate commitment to the entire training program, (2) legal research, (3)…

  16. Training in Inductive Reasoning.

    Science.gov (United States)

    Tomic, Welko

    This study investigated the effects of K. J. Klauer's (1989) inductive reasoning training program of teaching children. Effects of training and the range of transfer of the training were assessed. The subjects were 34 third-grade Dutch children of average ability, matched on age, sex, and IQ. Children from the training condition (N=17) received…

  17. Mental Health Training

    Science.gov (United States)

    2016-01-01

    most militaries have a robust physical fitness training program, mental health training programs are less common, if present at all. Yet, military...STO-TR-HFM-203 2.2.4 Trainers/Instructors The training is delivered by either trained soldiers/peers (4), military or sports instructors (2...Drill Instructor yelling at me – Being away from home – Not enough sleep – Lack of privacy – Learning new things/being tested – Physical training

  18. Training In Diversity Management

    Directory of Open Access Journals (Sweden)

    Sonja Treven

    2011-07-01

    Full Text Available The labor force all around the world is becoming increasingly diverse. Thus, organizations that can manage employee diversity effectively gain a competitive advantage. In such organizations diversity training is a necessity. Diversity training helps managers understand and value individual differences and develop strong diagnostic skills. The paper explores various approaches to training, like awareness-based and skill-based diversity training. A special attention to potential problems that may occur in the process of diversity training is given.

  19. Technical training - places available

    CERN Multimedia

    2013-01-01

    If you would like more information on a course, or have any other inquiry/suggestions, please contact Technical.Training@cern.ch. Eva Stern and Elise Romero, Technical Training Administration (Tel: 74924)

  20. Technical training: places available

    CERN Multimedia

    2014-01-01

    If you would like more information on a course, or have any other inquiry/suggestions, please contact Technical.Training@cern.ch. Eva Stern and Marie Lahchimi, Technical Training Administration (Tel: 74924)

  1. Technical training: places available

    CERN Multimedia

    2013-01-01

    If you would like more information on a course, or for any other inquiry/suggestions, please contact Technical.Training@cern.ch. Eva Stern and Elise Romero, Technical Training Administration (Tel: 74924)

  2. Technical training: places available

    CERN Multimedia

    2013-01-01

    If you would like more information on a course, or for any other inquiry/suggestions, please contact Technical.Training@cern.ch. Eva Stern and Elise Romero, Technical Training Administration (Tél : 74924)  

  3. Technical training: places available

    CERN Multimedia

    2014-01-01

    If you would like more information on a course, or have any other inquiry/suggestions, please contact Technical.Training@cern.ch. Eva Stern and Elise Romero, Technical Training Administration (Tel: 74924)

  4. Orthopaedic training in Kenya

    African Journals Online (AJOL)

    medical training takes five academic years. In the 3rd year ... Some have been trained in the college system, through the College of ... CT scans, MRI, Isotopic scans, laboratory, radiotherapy ... who to register as an orthopaedic surgeon.

  5. Importance of Gait Training

    Science.gov (United States)

    ... amputation exercises done under the supervision of a physical therapist, the initial training is provided by the prosthetist ... this stage, it is best to involve a physical therapist for regular gait training sessions. Once it is ...

  6. Moldova - Value Chain Training

    Data.gov (United States)

    Millennium Challenge Corporation — The evaluation of the GHS value chain training subactivity wwas designed to measure the extent, if any, to which the training activities improved the productivity...

  7. Criticality safety training

    Energy Technology Data Exchange (ETDEWEB)

    Woodruff, S.K. [Los Alamos National Lab., NM (United States)

    1997-06-01

    Criticality safety training is an important element of the Plutonium Facility safety program at Los Alamos National Laboratory. Training consists of student self-study handbooks and hands-on performance-based training in a mock-up laboratory containing gloveboxes, trolley conveyor system, and self-monitoring instruments. A 10-minute video tape and lecture was presented to describe how training in this area is conducted.

  8. Strength Training for Girls.

    Science.gov (United States)

    Connaughton, Daniel; Connaughton, Angela; Poor, Linda

    2001-01-01

    Strength training can be fun, safe, and appropriate for young girls and women and is an important component of any fitness program when combined with appropriate cardiovascular and flexibility activities. Concerns and misconceptions regarding girls' strength training are discussed, presenting general principles of strength training for children…

  9. Hard-Nosed Training

    Science.gov (United States)

    Willard, Norman, Jr.

    1973-01-01

    Training supervisor at Citibank accepts role as manager and considers aim to increase corporate earnings through cost-effective training. Based on an address delivered at the First Annual Training in Business and Industry Conference in New York, New York. (DS)

  10. Strength Training for Girls.

    Science.gov (United States)

    Connaughton, Daniel; Connaughton, Angela; Poor, Linda

    2001-01-01

    Strength training can be fun, safe, and appropriate for young girls and women and is an important component of any fitness program when combined with appropriate cardiovascular and flexibility activities. Concerns and misconceptions regarding girls' strength training are discussed, presenting general principles of strength training for children…

  11. Training and Learning

    Science.gov (United States)

    Luntley, Michael

    2008-01-01

    Some philosophers of education think that there is a pedagogically informative concept of training that can be gleaned from Wittgenstein's later writings: training as initiation into a form of life. Stickney, in "Training and Mastery of Techniques in Wittgenstein's Later Philosophy: A response to Michael Luntley" takes me to task for ignoring this…

  12. Human Factors in Training

    Science.gov (United States)

    Barshi, Immanuel; Byrne, Vicky; Arsintescu, Lucia; Connell, Erin

    2010-01-01

    Future space missions will be significantly longer than current shuttle missions and new systems will be more complex than current systems. Increasing communication delays between crews and Earth-based support means that astronauts need to be prepared to handle the unexpected on their own. As crews become more autonomous, their potential span of control and required expertise must grow to match their autonomy. It is not possible to train for every eventuality ahead of time on the ground, or to maintain trained skills across long intervals of disuse. To adequately prepare NASA personnel for these challenges, new training approaches, methodologies, and tools are required. This research project aims at developing these training capabilities. By researching established training principles, examining future needs, and by using current practices in space flight training as test beds, both in Flight Controller and Crew Medical domains, this research project is mitigating program risks and generating templates and requirements to meet future training needs. Training efforts in Fiscal Year 09 (FY09) strongly focused on crew medical training, but also began exploring how Space Flight Resource Management training for Mission Operations Directorate (MOD) Flight Controllers could be integrated with systems training for optimal Mission Control Center (MCC) operations. The Training Task addresses Program risks that lie at the intersection of the following three risks identified by the Project: 1) Risk associated with poor task design; 2) Risk of error due to inadequate information; and 3) Risk associated with reduced safety and efficiency due to poor human factors design.

  13. District nurse training

    OpenAIRE

    Elliott, Arnold; Freeling, Paul; Owen, John

    1980-01-01

    Training for district nursing is being reviewed. By 1981 district nurses will have a new administrative structure, a new curriculum, and a new examination. Training for nursing, like that for general practice, is to become mandatory. The history of the development of district nurse training is briefly described.

  14. Training and Learning

    Science.gov (United States)

    Luntley, Michael

    2008-01-01

    Some philosophers of education think that there is a pedagogically informative concept of training that can be gleaned from Wittgenstein's later writings: training as initiation into a form of life. Stickney, in "Training and Mastery of Techniques in Wittgenstein's Later Philosophy: A response to Michael Luntley" takes me to task for ignoring this…

  15. Employment and Training Programs.

    Science.gov (United States)

    Minnesota State Office of the Legislative Auditor, St. Paul. Program Evaluation Div.

    This report examines the effectiveness of employment and training programs in Minnesota and discusses the impact of the 1985 Jobs Bill state legislation. Chapter 1 provides an introduction to Minnesota's programs and to studies of employment and training programs conducted nationwide. Chapter 2 studies the use of Job Training Partnership Act funds…

  16. Computer Based Training Authors' and Designers' training

    Directory of Open Access Journals (Sweden)

    Frédéric GODET

    2016-03-01

    Full Text Available This communication, through couple of studies driven since 10 years, tries to show how important is the training of authors in Computer Based Training (CBT. We submit here an approach to prepare designers mastering Interactive Multimedia modules in this domain. Which institutions are really dedicating their efforts in training authors and designers in this area of CBTs? Television devices and broadcast organisations offered since year 60s' a first support for Distance Learning. New media, New Information and Communication Technologies (NICT allowed several public and private organisations to start Distance Learning projects. As usual some of them met their training objectives, other of them failed. Did their really failed? Currently, nobody has the right answer. Today, we do not have enough efficient tools allowing us to evaluate trainees' acquisition in a short term view. Training evaluation needs more than 10 to 20 years of elapsed time to bring reliable measures. Nevertheless, given the high investments already done in this area, we cannot wait until the final results of the pedagogical evaluation. A lot of analyses showed relevant issues which can be used as directions for CBTs authors and designers training. Warning - Our studies and the derived conclusions are mainly based on projects driven in the field. We additionally bring our several years experience in the training of movie film authors in the design of interactive multimedia products. Some of our examples are extracting from vocational training projects where we were involved in all development phases from the analysis of needs to the evaluation of the acquisition within the trainee's / employee job's. Obviously, we cannot bring and exhaustive approach in this domain where a lot of parameters are involved as frame for the CBT interactive multimedia modules authors' and designers' training.

  17. Radiological worker training

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-10-01

    This Handbook describes an implementation process for core training as recommended in Implementation Guide G441.12, Radiation Safety Training, and as outlined in the DOE Radiological Control Standard (RCS). The Handbook is meant to assist those individuals within the Department of Energy, Managing and Operating contractors, and Managing and Integrating contractors identified as having responsibility for implementing core training recommended by the RCS. This training is intended for radiological workers to assist in meeting their job-specific training requirements of 10 CFR 835. While this Handbook addresses many requirements of 10 CFR 835 Subpart J, it must be supplemented with facility-specific information to achieve full compliance.

  18. Workmanship Training Industry

    Science.gov (United States)

    Patterson, Ashley; Sikes, Larry; Corbin, Cheryl; Rucka, Rebecca

    2015-01-01

    Special processes require special skills, knowledge and experienced application. For over 15 years, the NASA Johnson Space Center's Receiving, Inspection and Test Facility (RITF) has provided Workmanship Standards compliance training, issuing more than 500 to 800 training completion certificates annually. It is critical that technicians and inspectors are trained and that they maintain their proficiency to implement the applicable standards and specifications. Training services include 'hands-on' training to engineers, technicians, and inspectors in the areas of electrostatic discharge (ESD), soldering, fiber optics, lithium battery handling, torque and wire safety, and wire wrapping.

  19. Strength Training and Your Child

    Science.gov (United States)

    ... Feeding Your 1- to 2-Year-Old Strength Training and Your Child KidsHealth > For Parents > Strength Training ... prevent injuries and speed up recovery. About Strength Training Strength training is the practice of using free ...

  20. [The robotic surgeon training].

    Science.gov (United States)

    Crestani, Alessandro; Rossanese, Marta; Abbinante, Maria; Calandriello, Mattia; Kungulli, Afrovita; Giannarini, Gianluca; Ficarra, Vincenzo

    2015-10-01

    The widespread robotic surgery in the world highlighted the relevance of the training programs for young urologists and residents. In the last years, urologic societies and some independent robotic surgeons strongly worked to standardize some general and specific training modules. Theoretical and practical sections of robotic training programs have been recently specified. The role of simulators, dry and wet laboratories, bedside assistance, and modular (step-by-step) training at console represent the most relevant elements of robotic surgeon training. Ideally, these didactic tools should be available in modern training centers. The development of structured robotic training programs should be considered as one of the priorities that the urologic community must take into account in the near future.

  1. Academic Training: Academic Training Lectures-Questionnaire

    CERN Multimedia

    2004-01-01

    ACADEMIC TRAINING Françoise Benz tel. 73127 academic.training@cern.ch SUGGEST AND WIN! Its time to plan the 2004-2005 lecture series. From today until March 19 you have the chance to give your contribution to planning for next year's Academic Training Lecture Series. At the web site: http://cern.ch/Academic.Training/questionnaire you will find questionnaires proposing topics in high energy physics, applied physics and science and society. Answering the questionnaire will help ensure that the selected topics are as close as possible to your interests. In particular requests and comments from students will be much appreciated. To encourage your contribution, the AT Committee will reward one lucky winner with a small prize, a 50 CHF coupon for a book purchase at the CERN bookshop.

  2. Portable Virtual Training Units

    Science.gov (United States)

    Malone, Reagan; Johnston, Alan

    2015-01-01

    The Mission Operations Lab initiated a project to design, develop, deliver, test, and validate a unique training system for astronaut and ground support personnel. In an effort to keep training costs low, virtual training units (VTUs) have been designed based on images of actual hardware and manipulated by a touch screen style interface for ground support personnel training. This project helped modernized the training system and materials by integrating them with mobile devices for training when operators or crew are unavailable to physically train in the facility. This project also tested the concept of a handheld remote device to control integrated trainers using International Space Station (ISS) training simulators as a platform. The portable VTU can interface with the full-sized VTU, allowing a trainer co-located with a trainee to remotely manipulate a VTU and evaluate a trainee's response. This project helped determine if it is useful, cost effective, and beneficial for the instructor to have a portable handheld device to control the behavior of the models during training. This project has advanced NASA Marshall Space Flight Center's (MSFC's) VTU capabilities with modern and relevant technology to support space flight training needs of today and tomorrow.

  3. Safety training news

    CERN Multimedia

    Safety Training, HSE Unit

    2014-01-01

      SELF-RESCUE MASK The "Self-Rescue Mask" face-to-face training course has been replaced by a revised version. This measure concerns both the initial and the refresher course. For personnel who have successfully attended the initial or refresher Self-Rescue Mask training within the last three years, their Self-Rescue Mask training will still be valid.  The course description and registration form can be found in the training catalogue on the Safety Training Service’s website or catalogue. The Self-Rescue Mask training course is a mandatory prerequisite for following the new "Portable ODH Detector" e-learning course.   PORTABLE ODH DETECTOR A new e-learning awareness course, "Portable ODH Detector", is available via the SIR application on CERN’s intranet. Personnel requiring a portable ODH detector of the DRÄGER x-am 5000 type to allowed access th...

  4. Academic Training: String Theory

    CERN Multimedia

    Françoise Benz

    2005-01-01

    2004-2005 ACADEMIC TRAINING PROGRAMME LECTURE SERIES 6, 7, 8, 9 and 10 June from 11.00 to 12.00 hrs - Auditorium, bldg. 500 on 6, 7, 8 & 10 June, TH Auditorium, bldg. 4, 3rd floor on 9 June String Theory by C. Johnson / Univ. of Southern California, USA ENSEIGNEMENT ACADEMIQUE ACADEMIC TRAINING Françoise Benz 73127 academic.training@cern.ch If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an 'application for training' form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt.

  5. Training Recurrent Networks

    DEFF Research Database (Denmark)

    Pedersen, Morten With

    1997-01-01

    Training recurrent networks is generally believed to be a difficult task. Excessive training times and lack of convergence to an acceptable solution are frequently reported. In this paper we seek to explain the reason for this from a numerical point of view and show how to avoid problems when tra...... training. In particular we investigate ill-conditioning, the need for and effect of regularization and illustrate the superiority of second-order methods for training......Training recurrent networks is generally believed to be a difficult task. Excessive training times and lack of convergence to an acceptable solution are frequently reported. In this paper we seek to explain the reason for this from a numerical point of view and show how to avoid problems when...

  6. Cross cultural training

    Institute of Scientific and Technical Information of China (English)

    王容

    2014-01-01

    Under the background of economic globalization, the globalization of human resources management determines the success of enterprise success or failure, in a sense, human resource is the first resource of the enterprise. Cross-cultural training is the core problems in global human resource management, it can let employees quickly familiar with the company's business and job content, understand the enterprise culture and core idea, to play a huge role in promoting enterprise development. Therefore, strengthen enterprise staff training, improve the comprehensive quality of enterprise personnel has become the urgent problems now in the process of enterprise development. Articles in samsung electronics of South Korea, for example, introduces the samsung especial y cross-cultural training content, training method and training effect. And analysis of cross-cultural training impact in the global business team and establish business relationship.

  7. Language Training: Anglais

    CERN Document Server

    Françoise Benz

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an 'application for training' form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. Writing Professional Documents in English This course is designed for people with a good level of spoken English. Duration: 2 hours a week between 26 April and 1 July 2004. Timetable: Thursdays 12.00 to 14.00 Price: 440 CHF (for 8 students and 20 hours) For registration and further information, please consult our Web pages: http://cern.ch/Training or contact Mr. Liptow: tel. 72957 FORMATION EN LANGUES LANGUAGE TRAINING Françoise Benz 73127 language.training@cern.ch

  8. Universal Drive Train Facility

    Data.gov (United States)

    Federal Laboratory Consortium — This vehicle drive train research facility is capable of evaluating helicopter and ground vehicle power transmission technologies in a system level environment. The...

  9. Virtual Training Devices Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Virtual Training Devices (VTD) Laboratory at the Life Cycle Software Engineering Center, Picatinny Arsenal, provides a software testing and support environment...

  10. Criterion-based laparoscopic training reduces total training time

    NARCIS (Netherlands)

    Brinkman, W.M.; Buzink, S.N.; Alevizos, L.; De Hingh, I.H.J.T.; Jakimowicz, J.J.

    2011-01-01

    The benefits of criterion-based laparoscopic training over time-oriented training are unclear. The purpose of this study is to compare these types of training based on training outcome and time efficiency. Methods During four training sessions within 1 week (one session per day) 34 medical interns (

  11. Criterion-based laparoscopic training reduces total training time

    NARCIS (Netherlands)

    Brinkman, W.M.; Buzink, S.N.; Alevizos, L.; De Hingh, I.H.J.T.; Jakimowicz, J.J.

    2012-01-01

    The benefits of criterion-based laparoscopic training over time-oriented training are unclear. The purpose of this study is to compare these types of training based on training outcome and time efficiency. Methods During four training sessions within 1 week (one session per day) 34 medical interns (

  12. Correctional Training. Institution Familiarization. Part II: The Training Program.

    Science.gov (United States)

    Bureau of Prisons (Dept. of Justice), Washington, DC.

    Designed to assist training coordinators in the initial institution familiarization training for new employees in correctional institutions, this manual consists of two documents: a training coordinator's guide (Part I - CE 017 285) and this document, the training program (Part II). Four training areas are treated: (1) an introduction consisting…

  13. Criterion-based laparoscopic training reduces total training time

    NARCIS (Netherlands)

    Brinkman, W.M.; Buzink, S.N.; Alevizos, L.; De Hingh, I.H.J.T.; Jakimowicz, J.J.

    2012-01-01

    The benefits of criterion-based laparoscopic training over time-oriented training are unclear. The purpose of this study is to compare these types of training based on training outcome and time efficiency. Methods During four training sessions within 1 week (one session per day) 34 medical interns

  14. Criterion-based laparoscopic training reduces total training time

    NARCIS (Netherlands)

    Brinkman, W.M.; Buzink, S.N.; Alevizos, L.; De Hingh, I.H.J.T.; Jakimowicz, J.J.

    2011-01-01

    The benefits of criterion-based laparoscopic training over time-oriented training are unclear. The purpose of this study is to compare these types of training based on training outcome and time efficiency. Methods During four training sessions within 1 week (one session per day) 34 medical interns

  15. Positive reinforcement training in rhesus macaques-training progress as a result of training frequency.

    Science.gov (United States)

    Fernström, A-L; Fredlund, H; Spångberg, M; Westlund, K

    2009-05-01

    Positive reinforcement training (PRT) efficiency was examined as a function of training frequency in 33 pair- or triple-housed female rhesus macaques. The animals were trained three times a week, once a day or twice a day, using PRT and a clicker as a secondary reinforcer. All animals were trained on 30 sessions, with an average of 5 min per training session per animal. The behaviors, trained in succession, were Targeting (reliably touching and following a Target); Collaborating (dominant animals allowing subordinates to train while stationing); Box-training (accepting being enclosed in a small compartment while responding to Target training) and initial Injection training.Fulfilled criteria for Targeting were obtained in 32/33 animals in a median of nine training sessions. Collaboration was obtained in 27/33 animals in a median of 15 training sessions. However, only four animals completed Box-training during the 30 training sessions and started Injection training. When comparing training success in terms of number of training sessions, training twice a day was less efficient than the other two treatments. In terms of daily progress, our results suggest that from a management perspective, daily training is more conducive to quick training success than thrice weekly training. In addition, in this study no further advantages could be gained from training twice a day.

  16. Outsourcing of Training

    Energy Technology Data Exchange (ETDEWEB)

    GAMIN, J.E.

    1999-06-17

    Several lessons are covered that has been learned at Fluor Daniel Hanford during their outsourcing effort. We have overcome problems because of our joint commitment to success. We continue to work our way through issues as they arise. On the positive side, several good things have happened as a result of outsourcing. Our training provider (EXITECH) has proven to be very responsive to our many different customers. We have been able to establish and support a 6-month training schedule for the first time. This has allowed the different facilities who send workers to training with more flexibility in planning their workers' time away from their jobs. In addition to the master training schedule, each facility on the Hanford Site has its own special or emergent training needs, and EXITECH has been very responsive in meeting these individual facilities' needs. Student and supervisor feedback on the quality and effectiveness of environmental, safety and health training provided by EXITECH has been very positive. Worker and supervisor feedback indicates the ''hands-on'' training serves their needs, and focuses on what they need to know to be able to perform work safely and efficiently. EXITECH strives very hard at presenting training so students can become successful in their training efforts. The workforce has noticed EXITECH's training philosophy is based on shared success with the trainee, not failure. Along the way, FDH has saved money as a result of this outsourcing. During our first year of the contract, we estimated a $400,000 savings. The decision as to outsource training is likely the most important you will make for your organization. In our situation, it fit the business goals we had established in our bid for the Hanford contract. However, if we were to begin again, we would factor some of the valuable lessons learned experienced during the first 16 months of our current outsourcing.

  17. Proactive driver training program

    Energy Technology Data Exchange (ETDEWEB)

    Vossler, W. [Kinetic Safety Consulting Inc., Grande Prairie, AB (Canada)

    2005-07-01

    Skid avoidance training is a recent approach to driver training and has been employed in various countries with a high degree of success. Among top ranked countries, motor vehicle incidents trends indicate higher incident rates among drivers are often due to lack of knowledge, experience and risk awareness. If lowered age limit experience is attained under direct supervision and in safe training conditions, it was suggested, incident frequency is reduced. A Norway study confirmed an increase in vehicle incident rates after drivers had received skid control training. The drivers were unable to maintain skill levels needed to react to critical driving tasks and had unrealistic expectations of skill after training. However, a skid avoidance training program launched in Sweden in 1999 has resulted in a 50 per cent reduction of vehicle incidents in the last 2 years. Details of the Skidcar System were presented, including details of the driving simulator, where simulation of actual driving situations is achieved by simply adjusting the amount of grip the vehicle has with the driving surface. Instructors modify driving behaviors based upon the driver's ability to maintain grip. There are over 200 units in North America. In addition, a Proactive Light Vehicle Driver Training/ Heavy Vehicle Assessment Program was initiated in 2003, with a motor vehicle incident rate reduction of 50 per cent at the end of 2004. Various examples of situations in which drivers have used their skid avoidance skills to avoid incidents were included. It was noted that the trend among driver training professionals has been towards decision-based rather than skills-based training, as skills-based training will diminish over time, and requires frequent re-training periods. Cognitive and perceptual skills were examined, as well as cognitive, associative and autonomous learning phases. It was concluded that skid avoidance is largely a decision-based skill. tabs, figs.

  18. Management of nuclear training center

    Energy Technology Data Exchange (ETDEWEB)

    Seo, In Suk; Lee, Han Young; Cho, Boung Jae; Lee, Seung Hee; Lee, Eoi Jin; You, Byung Hoon; Lee, Won Ku; Jeon, Hyung Ryeon; Seo, Kyung Won; Kim, Young Joong; Kim, Ik Hyun; Hyun, Ha Il; Choi, Il Ki; Hong, Choon Sun; Won, Jong Yeul; Joo, Yong Chang; Nam, Jae Yeul; Sin, Eun Jeong [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1996-02-01

    This report describes the annual results of training courses. The scope and contents are as follows : 1. Regional and interregional training courses, 2. Training courses assisted by foreign experts, 3. Training courses for nuclear industry personnel, 4. Training courses for internal staff-members, 5. Training courses under the law. The nuclear training center executed the open-door training courses for 2,699 engineers/scientists from the regulatory body, nuclear industries, research institutes and other related organizations by means of offering 69 training courses during the fiscal year 1995. (Author) .new.

  19. Trains across the USA

    Science.gov (United States)

    McIntosh, Phyllis

    2013-01-01

    This feature article explores the topic of trains from their early history to recent trends in railroading. A glossary provides related vocabulary, a sidebar called "Romance of the Rails" adds colorful detail about train songs and railroad lore. An additional section, "Classroom Activities," by John Silver, presents three…

  20. Training Restricted Boltzmann Machines

    DEFF Research Database (Denmark)

    Fischer, Asja

    Restricted Boltzmann machines (RBMs) are probabilistic graphical models that can also be interpreted as stochastic neural networks. Training RBMs is known to be challenging. Computing the likelihood of the model parameters or its gradient is in general computationally intensive. Thus, training...

  1. Simulators in driver training.

    NARCIS (Netherlands)

    2009-01-01

    In 2010, about 150 driving simulators were being used for the basic driver training in the Netherlands. According to theories about how people learn, simulator training has both advantages and disadvantages. In order to be able to learn something from a simulator, its technical quality must be

  2. Simulators in driver training.

    NARCIS (Netherlands)

    2009-01-01

    In 2010, about 150 driving simulators were being used for the basic driver training in the Netherlands. According to theories about how people learn, simulator training has both advantages and disadvantages. In order to be able to learn something from a simulator, its technical quality must be adequ

  3. Visual Impairment Training Reviewed.

    Science.gov (United States)

    Maychell, Karen; Smart, David

    1989-01-01

    A British study of training provided for social services workers with the visually impaired found that emphasis was on workers' learning the skills their clients would need, rather than on how to teach those skills; most training is geared toward the totally blind, a small proportion of the population; and workers felt the need to acquire…

  4. Can Trains Really Float?

    Science.gov (United States)

    McCartney, Robin Ward; Deroche, Sarah; Pontiff, Danielle

    2008-01-01

    Have you ever heard of a Maglev train? Who would be crazy enough to think that exploring how a high-tech train little known in the United States works with a group of fourth-grade students would yield understandings about the properties of magnetism, force and motion, and inquiry science? Fortunately, the authors--a college methods professor and…

  5. Training the Trainer.

    Science.gov (United States)

    Veri, Clive C.; Vonder Haar, T. A.

    Guidelines are furnished for application of psychological theory (including principles of learning, motivation, and reinforcement) in the training room, job or task analysis, formation of learning objectives, and selection of appropriate training techniques and audiovisual aids. The importance of clear communication and a supportive learning…

  6. Constructing Training Demonstrations

    Science.gov (United States)

    2009-01-16

    training (BMT) is one of the most extensively used training methods available to modern organizations [25]. BMT is based on Bandura’s social learning theory [13...Utilizing the model provided by social learning theory , BMT includes processes such as modeling, a retention process, behavioral rehearsal

  7. Training Needs Analysis. A Resource for Identifying Training Needs, Selecting Training Strategies, and Developing Training Plans.

    Science.gov (United States)

    Bartram, Sharon; Gibson, Brenda

    Designed as a practical tool for trainers, this manual contains 22 instruments and documents for gathering and processing information about training and development issues within an organization. Part one of the two-part manual examines the process of identifying and analyzing training needs. It reviews the different types of information the…

  8. Job Instruction Training.

    Science.gov (United States)

    Pfau, Richard H.

    Job Instruction Training (JIT) is a step-by-step, relatively simple technique used to train employees on the job. It is especially suitable for teaching manual skills or procedures; the trainer is usually an employee's supervisor but can be a co-worker. The JIT technique consists of a series of steps that a supervisor or other instructor follows…

  9. Training a cataract surgeon

    Directory of Open Access Journals (Sweden)

    M Babar Qureshi

    2014-07-01

    Full Text Available Training in cataract surgery is one of the key factors needed to ensure high quality cataract surgery with good visual outcomes and patient satisfaction. The training has to impart the right skills to the right person by the right trainer and in the right environment.

  10. Low-cost training technology

    Science.gov (United States)

    Lee, A. T.

    1984-01-01

    The differences between flight training technology and flight simulation technology are highlighted. Examples of training technologies are provided, including the Navy's training system and the interactive cockpit training device. Training problems that might arise in the near future are discussed. These challenges follow from the increased amount and variety of information that a pilot must have access to in the cockpit.

  11. All aboard the Safety Train(ing)!

    CERN Multimedia

    Rosaria Marraffino

    2015-01-01

    Would you like to influence CERN’s safety courses? Do you want to help build better training courses? If your answer is yes to one or both of these questions: now is the time! The Safety Training section is looking for volunteers from the whole CERN community to test new courses before they go online for all members of the personnel.    The Safety Training section is redesigning the CERN e-learning package in order to adopt a more educational approach and to make the courses a more enjoyable experience. The section is now calling for volunteers. “We know we can do much more with testers’ help and feedback,” explains Christoph Balle, Safety Training section leader. “By having the end users actively involved in the process, we’ll achieve our goal of communicating safety in the best possible way. As the volunteers will play an active role in the development of the courses, they will be providing a service to the whole community.&am...

  12. Academic Training: 2004 - 2005 ACADEMIC TRAINING PROGRAMME

    CERN Multimedia

    Françoise Benz

    2004-01-01

    1st Term - 01 October to 17 December 2004 REGULAR LECTURE PROGRAMME New Trends in Fusion Research by A. Fasoli, EPFL, Lausanne, CH 11, 12, 13 October Physics at e+e- linear collider by K. Desch, DESY, Hamburg, D 15, 16, 17, 18, 19 November LECTURE SERIES FOR POSTGRADUATE STUDENTS Standard Model by R. Barbieri, CERN-PH-TH 6, 7, 8, 9 10 December The lectures are open to all those interested, without application. The abstract of the lectures, as well as any change to the above information (title, dates, time, place etc) will be published in the CERN Bulletin, the WWW, and by notices before each term and for each series of lectures. ENSEIGNEMENT ACADEMIQUE ACADEMIC TRAINING Françoise Benz 73127 academic.training@cern.ch If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an 'application for training' form a...

  13. Do Sectoral Training Funds Stimulate Training?

    Science.gov (United States)

    Kamphuis, Pascal; Glebbeek, Arie C.; Van Lieshout, Harm

    2010-01-01

    Sectoral levelling funds are an arrangement aimed at alleviating a well-known theoretical problem of underinvestment in worker training because of free-rider behaviour of firms. In the Netherlands, collective agreements require firms to participate in such funds in a number of sectors. Using a comprehensive dataset of Dutch firms, we attempt to…

  14. Intercultural Training: Six Measures Assessing Training Needs

    Science.gov (United States)

    Graf, Andrea; Mertesacker, Marion

    2009-01-01

    Purpose: The purpose of this paper is to develop recommendations for measures assessing intercultural training needs for international human resource management. Based on scientific as well as application-oriented criteria the aim is to select six measures assessing general intercultural competencies and with the help of behaviour ratings in…

  15. Time Use on Trains

    DEFF Research Database (Denmark)

    Bjørner, Thomas

    2016-01-01

    This study explores how travel time is used and how passengers conceptualise travel time in Danish intercity trains and intercity fast trains. The new contribution to the literature this study can offer is in the inclusion of all kinds of passengers in the different compartments to understand train...... travel as a dynamic act of moving with shifts in activities. A mixed-method approach is used with self-completed questionnaires, frequency observations, shadowing observations and interviews. The findings reveal that the train passengers’ acts on the move are framed by both macro- and microstructures....... The passengers create a travel space in which they make dynamic shifts in different kinds of activities: media use, media non-use, social interactions and non-social interactions. Passengers expect the train operator to provide the travel space for different activities (including the possibility of mobile...

  16. Training Public Health Advisors.

    Science.gov (United States)

    Meyer, Pamela A; Brusuelas, Kristin M; Baden, Daniel J; Duncan, Heather L

    2015-01-01

    Federal public health advisors provide guidance and assistance to health departments to improve public health program work. The Centers for Disease Control and Prevention (CDC) prepares them with specialized training in administering public health programs. This article describes the evolving training and is based on internal CDC documents and interviews. The first federal public health advisors worked in health departments to assist with controlling syphilis after World War II. Over time, more CDC prevention programs hired them. To meet emerging needs, 3 major changes occurred: the Public Health Prevention Service, a fellowship program, in 1999; the Public Health Associate Program in 2007; and integration of those programs. Key components of the updated training are competency-based training, field experience, supervision, recruitment and retention, and stakeholder support. The enduring strength of the training has been the experience in a public health agency developing practical skills for program implementation and management.

  17. Technical Training: Places available

    CERN Multimedia

    Monique Duval

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an 'application for training' form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. The number of places available may vary. Please check our Web site to find out the current availability. Places are available in the following courses: The Joint PVSS JCOP Framework: 14 - 18.6.2004 (5 days) EXCEL 2003 - niveau 2 : 17 & 18.6.2004 (2 jours) MAGNE-04 : Magnétisme pour l'électrotechnique : 6 au 8.7.2004 (3 jours) Technical Training Monique Duval - Tel.74924 technical.training@cern.ch

  18. LEAH interdisciplinary training program.

    Science.gov (United States)

    Robbins, Cynthia L; Rickert, Vaughn D

    2016-08-01

    This article describes the Leadership Education in Adolescent Health (LEAH) interdisciplinary training program in the United States. The Maternal and Child Health Bureau authorized by legislation provides monies to train leaders in adolescent health through a competitive grant process. Currently, seven academic medical centers have funding to provide leadership in adolescent health (LEAH) training in five core disciplines: medicine, nursing, psychology, social work and nutrition. LEAH training programs both ensure high clinical competence in core disciplines serving adolescents and prepare trainees for leadership positions in adolescent health and public health care realms. Together, these programs trained almost 1000 long-term trainees across these five disciplines, and graduates from these programs are working in 45 of the 50 states within the United States. About 90% of these graduates are working with maternal and child/adolescent health populations, and almost all have held leadership positions in the areas of public health, advocacy, public policy, academic medical centers and/or clinical care settings.

  19. Monitoring spike train synchrony

    CERN Document Server

    Kreuz, Thomas; Houghton, Conor; Andrzejak, Ralph G; Mormann, Florian

    2012-01-01

    Recently, the SPIKE-distance has been proposed as a parameter-free and time-scale independent measure of spike train synchrony. This measure is time-resolved since it relies on instantaneous estimates of spike train dissimilarity. However, its original definition led to spuriously high instantaneous values for event-like firing patterns. Here we present a substantial improvement of this measure which eliminates this shortcoming. The reliability gained allows us to track changes in instantaneous clustering, i.e., time-localized patterns of (dis)similarity among multiple spike trains. Additional new features include selective and triggered temporal averaging as well as the instantaneous comparison of spike train groups. In a second step, a causal SPIKE-distance is defined such that the instantaneous values of dissimilarity rely on past information only so that time-resolved spike train synchrony can be estimated in real-time. We demonstrate that these methods are capable of extracting valuable information from ...

  20. Developing a training package.

    Science.gov (United States)

    Minogue, Virginia; Donskoy, Anne-Laure

    2017-06-12

    Purpose The purpose of this paper is to outline the development of a training package for service users and carers with an interest in NHS health and social care research. It demonstrates how the developers used their unique experience and expertise as service users and carers to inform their work. Design/methodology/approach Service users and carers, NHS Research and Development Forum working group members, supported by health professionals, identified a need for research training that was tailored to other service user and carer needs. After reviewing existing provision and drawing on their training and support experience, they developed a training package. Sessions from the training package were piloted, which evaluated positively. In trying to achieve programme accreditation and training roll-out beyond the pilots, the group encountered several challenges. Findings The training package development group formed good working relationships and a co-production model that proved sustainable. However, challenges were difficult to overcome owing to external factors and financial constraints. Practical implications Lessons learnt by the team are useful for other service users and carer groups working with health service professionals. Training for service users and carers should be designed to meet their needs; quality and consistency are also important. The relationships between service user and carer groups, and professionals are important to understanding joint working. Recognising and addressing challenges at the outset can help develop strategies to overcome challenges and ensure project success. Originality/value The training package was developed by service users and carers for other service users and carers. Their unique health research experience underpinned the group's values and training development.

  1. Cognitive training for dementia

    Directory of Open Access Journals (Sweden)

    Konta, Brigitte

    2005-12-01

    Full Text Available The aim of the HTA report is to evaluate the effectiveness of cognitive training methods to treat cognitive disorders of dementia and other diseases with cognitive deficits. For this purpose, a systematic literature search was carried out first based on the DIMDI superbase retrieval. The identified publications were judged and selected by two independent, methodically competent experts. 33 publications were included in the report. Based on the studies for a normal cognitive development in old age a theory that healthy older people have a considerable capacity reserve for an improved performance in abstract abilities of thinking can be assumed. The first symptoms for older people at risk for dementia are a reduced cognitive capacity reserve. Cognitive training methods therefore focus abilities of abstract memory. Apart from types of dementia another two groups of diseases with cognitive deficits were included in the HTA report: cerebral lesions and schizophrenic psychoses. Studies with mild as well as forms of dementia heavy forms including the Alzheimer disease were included. The described training methods were very heterogeneous with regard to their contents, the temporal sequence and the outcome parameter. The studies were methodically partly contestable. Approximately a third of the studies of all publications could show improvements in the cognitive achievements by the training. Three studies concerning cognitive training methods in case of cerebral lesions were included. All three studies demonstrated a significant improvement in the training group in some outcome parameters. Special cognitive training methods were used for the treatment of cognitive deficits at schizophrenic psychoses. The neurocognitive training (NET, the "Cognitive Remediation Therapy" as well as the strategic training with coaching proved to be effective. The studies, however, were hardly comparable and very heterogeneous in detail. Summarising the cognitive training

  2. 24 CFR 964.140 - Resident training.

    Science.gov (United States)

    2010-04-01

    ..., rights and responsibilities training; and (4) Business entrepreneurial training, planning and job skills...: (1) Community organization and leadership training; (2) Organizational development training for...

  3. Small Business's Big Training Needs.

    Science.gov (United States)

    Kelly, Leslie

    1984-01-01

    Discusses the training needs of small businesses in light of their high failure rate (50 percent). Includes characteristics of successful small businesses, potential training needs, training methods, and topics for seminars. (JOW)

  4. Nuclear Manpower Training

    Energy Technology Data Exchange (ETDEWEB)

    Min, B. J.; Han, K. W.; Lee, H. Y. and others

    2006-01-15

    Through the project on nuclear human resources development in 2005, the Nuclear Training Center of KAERI has provided 67 nuclear education and training courses for 3,658 persons from the domestic nuclear related organizations such as Government Agencies, nuclear industries, R and D institutes, universities, and public as well as from IAEA Member States. In addition, 6 students (MS and Ph D.) have taken nuclear technology related courses offered by UST-KAERI. The project has developed 8 programs and 12 courses. They includes programs for IAEA training, bilateral education and training, and in-house training as well as courses dealing with maintenance of nuclear power plants and management of electricity generation, thermal-hydraulics nuclear hydrogen, nuclear safeguards, radiation emergency preparedness and etc. National and international cooperation has been promoted. For ANENT, test operation, data loading and revision of the web-portal have been undertaken. Also the web-portal operation system has been established. For FNCA, NTC has cooperated for the establishment of a model of human resource development and the exchange of information/materials. With WNU, the NTC has made an effort for hosting 2007 WNU Summer Institute. The infrastructure for nuclear education and training has been strengthened. Basic directions for providing the customers with better service, This includes showing kindness to the customer, renovation of the interior of training facilities, and upgrading of web-based management system for learning and using facilities of NTC. Other efforts have resulted in the publication of 25 course materials (10 for international courses and 15 for national courses), and the improvement of education and training equipment. The International Nuclear Training and Education Center (INTEC), which was opened in 2002, has hosted 296 international and domestic events in 2005.

  5. Employee Training: An International Perspective

    OpenAIRE

    Kapsalis, Constantine

    1997-01-01

    Canada’s training effort relative to the rest of the IALS countries, measured in terms of hours of training per employee, was found to be average. The average employee in Canada received 44 hours of training in 1994, similar to the hours of training per employee in Switzerland, the United States and Germany. However, Canada’s training effort was considerably less than the Netherlands (74 hours per employee). One finding of particular interest to Canada is the virtual equality of training ...

  6. Corporate Training in Virtual Worlds

    Directory of Open Access Journals (Sweden)

    Charles Nebolsky

    2004-12-01

    Full Text Available This paper presents virtual training worlds that are relatively low-cost distributed collaborative learning environments suitable for corporate training. A virtual training world allows a facilitator, experts and trainees communicating and acting in the virtual environment for practicing skills during collaborative problem solving. Using these environments is beneficial to both trainees and corporations. Two system prototypes – the sales training and the leadership training virtual worlds – are described. The leadership training course design is discussed in details.

  7. MODALITIES OF TRAINING PARAMETER ALTERNATION IN NOWADAYS STRENGTH TRAINING PRACTICE

    Directory of Open Access Journals (Sweden)

    RANISAVLJEV IGOR

    2010-12-01

    Full Text Available Large number of variables could be alternated during the process of planning and programming in sports training. Superior training results in majority of sports are achieved by optimally manipulating training parameters in appropriate sequences and combinations. Additionally, in some sports they might be the result of appropriate periodization pattern. Today's tendency in strength training practice is training movements instead of training muscles. Exercise classification according to the dominant movement types, allows creating new modalities in training alternation. Additional variations in volume, intensity, rest brakes, repetition velocity andinter-repetition rest can be the important part of functional strength training program. Alternation and combination of different training parameters makes appropriate training stimulus for strength increase in the most of nowadays sports. Optimal alternation of basic training parameters should be the first part in the processof planning and programming. As a result, majority of athletes might not need advanced periodization patterns for optimal improvement in muscle strength and power

  8. Team training/simulation.

    Science.gov (United States)

    Clark, Erin A S; Fisher, Janet; Arafeh, Julia; Druzin, Maurice

    2010-03-01

    Obstetrical emergencies require the rapid formation of a team with clear communication, strong leadership, and appropriate decision-making to ensure a positive patient outcome. Obstetric teams can improve their emergency response capability and efficiency through team and simulation training. Postpartum hemorrhage is an ideal model for team and simulation training, as postpartum hemorrhage requires a multidisciplinary team with the capability to produce a protocol-driven, rapid response. This article provides an overview of team and simulation training and focuses on applications within obstetrics, particularly preparation for postpartum hemorrhage.

  9. Physical Training and Cardioprotection

    Institute of Scientific and Technical Information of China (English)

    Ping Zhang; Keith L. March; Dongming Hou

    2003-01-01

    Experimental, clinical and epidemiologic studies have provided strong evidence that physical training has beneficial effects on cardiovascular health. Numerous investigations have demonstrated that exercise increases coronary blood flow and myocardial perfusion. Importantly, training also can stimulate angiogenesis and accelerate collateral vessel growth in animal models with coronary artery occlusion. Cardiac adaptation such as increased vascularity or capillary density has been evidenced after regular endurance exercises. More recently, several studies indicate that physical training induces high levels of myocardial heat shock protein and antioxidant protein expression, which may play an important role in myocardial protection against ischemia-reperfusion injury.

  10. CERN Technical Training : Vista !

    CERN Multimedia

    HR Department

    2008-01-01

    You are running Vista on your new PC – or are planning to install it? The Technical Training service is organizing a half-day training course on the new features of the VISTA operating system. This course introduces the new interfaces and presents the new functionalities for people who are experienced in the use of Windows XP. The next bilingual sessions of this course will take place on 12 December 2008 and 30 January 2009. Register using our catalogue: http://cta.cern.ch/cta2/f?p=110:9 or contact us with your questions/comments at mailto:Technical.Training@cern.ch

  11. CERN Technical Training : Vista !

    CERN Multimedia

    HR Department

    2008-01-01

    Are you running Vista on your new PC – or are you planning to install it? The Technical Training service is organizing a half-day training course on the new features of the VISTA operating system. This course introduces the new interfaces and presents the new functionalities for people who are experienced in the use of Windows XP. The next bilingual sessions of this course will take place on 12 December 2008 and 30 January 2009. Register using our catalogue: http://cta.cern.ch/cta2/f?p=110:9 or contact us with your questions/comments at mailto:Technical.Training@cern.ch

  12. CERN Technical Training : Vista !

    CERN Multimedia

    HR Department

    2008-01-01

    Are you running Vista on your new PC – or are planning to install it? The Technical Training service is organizing a half-day training course on the new features of the VISTA operating system. This course introduces the new interfaces and presents the new functionalities for people who are experienced in the use of Windows XP. The next bilingual sessions of this course will take place on 12 December 2008 and 30 January 2009. Register using our catalogue: http://cta.cern.ch/cta2/f?p=110:9 or contact us with your questions/comments at Technical.Training@cern.ch

  13. CERN Technical Training : Vista !

    CERN Multimedia

    HR Department

    2009-01-01

    Are you running Vista on your new PC – or are you planning to install it? The Technical Training service is organizing a half-day training course on the new features of the VISTA operating system. This course introduces the new interfaces and presents the new functionalities for people who are experienced in the use of Windows XP. The next bilingual session of this course will take place on 30 January 2009. Register using our catalogue: http://cta.cern.ch/cta2/f?p=110:9 or contact us with your questions/comments at mailto:Technical.Training@cern.ch

  14. CERN Technical Training : Vista !

    CERN Multimedia

    HR Department

    2008-01-01

    You are running Vista on your new PC – or are planning to install it? The Technical Training service is organizing a half-day training on the new features of the VISTA operating system. This course introduces the new interfaces and presents the new functionalities for people who are experienced using Windows XP. The next bilingual sessions of this course will take place on December 12, 2008 and January 30, 2009. Register using our catalogue : http://cta.cern.ch/cta2/f?p=110:9 or contact us with your questions/comments at Technical.Training@cern.ch

  15. Space Age Training

    Science.gov (United States)

    1996-01-01

    Teledyne Brown developed a computer-based interactive multimedia training system for use with the Crystal Growth Furnace in the U.S. Microgravity Laboratory-2 mission on the Space Shuttle. Teledyne Brown commercialized the system and customized it for PPG Industries Aircraft Products. The system challenges learners with role-playing scenarios and software-driven simulations engaging all the senses using text, video, animation, voice, sounds and music. The transfer of this technology to commercial industrial process training has resulted in significant improvements in effectiveness, standardization, and quality control, as well as cost reductions over the usual classroom and on-the- job training approaches.

  16. Auditory Integration Training

    Directory of Open Access Journals (Sweden)

    Zahra Jafari

    2002-07-01

    Full Text Available Auditory integration training (AIT is a hearing enhancement training process for sensory input anomalies found in individuals with autism, attention deficit hyperactive disorder, dyslexia, hyperactivity, learning disability, language impairments, pervasive developmental disorder, central auditory processing disorder, attention deficit disorder, depressin, and hyperacute hearing. AIT, recently introduced in the United States, and has received much notice of late following the release of The Sound of a Moracle, by Annabel Stehli. In her book, Mrs. Stehli describes before and after auditory integration training experiences with her daughter, who was diagnosed at age four as having autism.

  17. TAP 1: Training Program Manual

    Energy Technology Data Exchange (ETDEWEB)

    1993-08-01

    The Training Accreditation Program (TAP) was established by the Department of Energy (DOE) to assist in achieving excellence in the development and implementation of performance-based nuclear facility training programs. The TAP establishes the objectives and criteria against which DOE nuclear facility training is evaluated for accreditation. The TAP Staff provides assistance to contractors, develops training guidelines, and evaluates the quality and effectiveness of facility training. This manual describes the accreditation process, provides functional descriptions for positions which require accredited training programs, provides a brief discussion of performance-based training, contains the objectives and criteria that must be addressed in training programs subject to accreditation, and includes a glossary.

  18. Academic Training: 2004 - 2005 ACADEMIC TRAINING PROGRAMME

    CERN Multimedia

    Françoise Benz

    2004-01-01

    1st Term - 01 October to 17 December 2004 REGULAR LECTURE PROGRAMME New Trends in Fusion Research by A. Fasoli, EPFL, Lausanne, CH 11, 12, 13 October Physics at e+e- linear collider by K. Desch, DESY, Hamburg, D 15, 16, 17, 18, 19 November LECTURE SERIES FOR POSTGRADUATE STUDENTS Standard Model by R. Barbieri, CERN-PH-TH 6, 7, 8, 9 10 December The lectures are open to all those interested, without application. The abstract of the lectures, as well as any change to the above information (title, dates, time, place etc) will be published in the CERN Bulletin, the WWW, and by notices before each term and for each series of lectures. ENSEIGNEMENT ACADEMIQUE ACADEMIC TRAINING Françoise Benz 73127 academic.training@cern.ch

  19. Interactive Karyotyping Training

    Directory of Open Access Journals (Sweden)

    Ashwin Kotwaliwale

    2013-01-01

    Full Text Available Despite the wide use of newer techniques in genetic diagnostics, there remains a need for technologists to learn human chromosome morphology, identify abnormal metaphases and report clinical abnormalities. Global short age of cytogenetic trainers and a time consuming training process makes Karyotyping training difficult. We have developed a web based interactive Karyotyping training tool, KaryoTutor©, that allows technologists to learn karyotyping in an interactive environment and aids the trainer in the training process. KaryoTutor©provides visual clues for identifying abnormal chromosomes, provides instant test scores and includes a reference library of ideograms,sample chromosome images and reference materials. Trainees are able to recursively work on a case till a satisfactory result is achieved,with KaryoTutor providing interactive inputs.Additionally, trainers can assign cases and monitor trainee progress using audit trail management and other administrative features.

  20. Boiler Operator Training.

    Science.gov (United States)

    Miller, Stanton S.

    1978-01-01

    This program, developed by the Nalco Chemical Company, helps with energy conservation in industrial plants. The program takes four to six weeks to complete. The training sessions last for about two hours. (BB)

  1. The Last Horse Trains

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    Horse trains used to be the chief means of transport in southwest China's mountainous areas, areas that were almost inaccessible because of the difficult terrain. They have largely disappeared as most such areas are already serviced by modern road systems. At binzhonluo, however, the last horse trains can still be found, their drivers being Nus, Lisus and Tibetans. As I discovered at country fairs, goods shipped in by horse trains from Tibetan are mostly butter tea, edible fungus and wild orchid plants, and goods shipped to Tibet include drinks, batteries, salt and instant noodles. For centuries,horse trains have traversed the Nujiang Canyon or the Tibetan-Yi Corridor which, to be accurate, should be called an economic and cultural corridor linking Tibet and the rest of China.

  2. Plutonium Training Opportunities

    Energy Technology Data Exchange (ETDEWEB)

    Balatsky, Galya Ivanovna [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Wolkov, Benjamin [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-03-26

    This report was created to examine the current state of plutonium training in the United States and to discover ways in which to ensure that the next generation of plutonium workers are fully qualified.

  3. The Future Training Room.

    Science.gov (United States)

    Barbian, Jeff

    2001-01-01

    Looks at some of the electronic learning technology that has already been developed and will become common for training, including robots, lucid dreaming, tele-immersion, human interface technology, among others. (JOW)

  4. Memory training in depression

    NARCIS (Netherlands)

    Becker, E.S.; Vanderhasselt, M.A.; Vrijsen, J.N.

    2015-01-01

    Memory biases, that is, general memory impairments as well as specific mood-congruent memory biases, are important vulnerability factors in depression. Recently, computerized memory trainings have been developed to target these biases, reducing rumination and lightening depressive symptoms. This

  5. Apprentices for training

    CERN Multimedia

    1992-01-01

    Every year CERN recruits and trains six technical and two administrative apprentices to the level of the Federal Certificate of Competence. This is performed in accordance with the laws and practice applicable in the Canton of Geneva.

  6. Climate Change Adaptation Training

    Science.gov (United States)

    A list of on-line training modules to help local government officials and those interested in water management issues better understand how the changing climate affects the services and resources they care about

  7. Language Training: French

    CERN Multimedia

    Françoise Benz

    2005-01-01

    General and Professional French Courses The next session will take place from 24 January to 18 March 2005. These courses are open to all persons working on the CERN site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://www.cern.ch/Training/ or contact Mrs. Benz : Tel. 73127. Writing Professional Documents in French The next session will take place from 24 January to 18 March 2005. This course is designed for people with a good level of spoken French. Duration: 24 hours Price: 528 CHF (for 8 students) For further information and registration, please consult our Web pages: http://www.cern.ch/Training/ or contact Mrs. Benz : Tel. 73127. FORMATION EN LANGUES LANGUAGE TRAINING Françoise Benz 73127 language.training@cern.ch

  8. Language Training: French

    CERN Document Server

    Françoise Benz

    2005-01-01

    General and Professional French Courses The next session will take place from 18 April to 30 June 2005. These courses are open to all persons working on the CERN site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mrs. Benz : Tel. 73127. Writing Professional Documents in French The next session will take place from 18 April to 30 June 2005. This course is designed for people with a good level of spoken French. Duration: 30 hours Price: 660 CHF (for 8 students) For further information and registration, please consult our Web pages: http://cern.ch/Training or contact Mrs. Benz : Tel. 73127. FORMATION EN LANGUES LANGUAGE TRAINING Françoise Benz 73127 language.training@cern.ch

  9. Language Training: French

    CERN Multimedia

    Françoise Benz

    2005-01-01

    General and Professional French Courses The next session will take place from 24 January to 18 March 2005. These courses are open to all persons working on the CERN site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mrs. Benz : Tel. 73127. Writing Professional Documents in French The next session will take place from 24 January to 18 March 2005. This course is designed for people with a good level of spoken French. Duration: 24 hours Price: 528 CHF (for 8 students) For further information and registration, please consult our Web pages: http://cern.ch/Training or contact Mrs. Benz : Tel. 73127. FORMATION EN LANGUES LANGUAGE TRAINING Françoise Benz 73127 language.training@cern.ch

  10. Does CRM training work?

    Science.gov (United States)

    Helmreich, R. L.

    1991-01-01

    Formal cockpit resource management training in crew coordination concepts increases the percentage of crews rated as above average in performance and decreases the percentage of crews rated as below average.

  11. Osaka Train System

    OpenAIRE

    Novak,

    2017-01-01

    Supplementary soundscape recording for “A Beautiful Noise Emerging from the Apparatus of an Obstacle: Trains and the Sound of the Japanese City.” In The Acoustic City, Matthew Gandy and Benny Nilsen, eds. Berlin: Jovis.

  12. Training brain networks and states.

    Science.gov (United States)

    Tang, Yi-Yuan; Posner, Michael I

    2014-07-01

    Brain training refers to practices that alter the brain in a way that improves cognition, and performance in domains beyond those involved in the training. We argue that brain training includes network training through repetitive practice that exercises specific brain networks and state training, which changes the brain state in a way that influences many networks. This opinion article considers two widely used methods - working memory training (WMT) and meditation training (MT) - to demonstrate the similarities and differences between network and state training. These two forms of training involve different areas of the brain and different forms of generalization. We propose a distinction between network and state training methods to improve understanding of the most effective brain training.

  13. Training cleanroom personnel.

    Science.gov (United States)

    Dixon, A M

    1991-01-01

    PEOPLE: the one resource that all companies have in common. Companies in general, and especially those involved in the clean or aseptic manufacturing environments cannot rely solely on technological innovation to increase quality and productivity. They must optimize their human assets to raise performance levels. Training is a critical factor. The training process is not simply to impart knowledge; but through education and involvement on a personal level, to alter behavior: CULTURE.

  14. Effects of teacher training

    DEFF Research Database (Denmark)

    Wahlgren, Bjarne; Larsen, Lea Lund

    2010-01-01

    The article gives a short overview over existing knowledge concerning the effect of teacher training in relation to adult learning. It presents a research design for measuring the effect of teacher traning.......The article gives a short overview over existing knowledge concerning the effect of teacher training in relation to adult learning. It presents a research design for measuring the effect of teacher traning....

  15. Future Naval Training Environments

    Science.gov (United States)

    2002-11-01

    Marine Corps for the future. By considering these future concepts relative to today’s training requirements, we were able to articulate the trends for...objective 24 research articulating what skills and behaviors simulators can, and cannot, train. We also see that the requirements for emotional...Operations, March 1995 74 [28] Coast Guard Response to Camp LeJeune request for Firing over intercostal waterway [29] Senior Study Group (co-chaired by

  16. Altitude and endurance training.

    Science.gov (United States)

    Rusko, Heikki K; Tikkanen, Heikki O; Peltonen, Juha E

    2004-10-01

    The benefits of living and training at altitude (HiHi) for an improved altitude performance of athletes are clear, but controlled studies for an improved sea-level performance are controversial. The reasons for not having a positive effect of HiHi include: (1) the acclimatization effect may have been insufficient for elite athletes to stimulate an increase in red cell mass/haemoglobin mass because of too low an altitude (stress with possible overtraining symptoms and an increased frequency of infections. Moreover, the effects of hypoxia in the brain may influence both training intensity and physiological responses during training at altitude. Thus, interrupting hypoxic exposure by training in normoxia may be a key factor in avoiding or minimizing the noxious effects that are known to occur in chronic hypoxia. When comparing HiHi and HiLo (living high and training low), it is obvious that both can induce a positive acclimatization effect and increase the oxygen transport capacity of blood, at least in 'responders', if certain prerequisites are met. The minimum dose to attain a haematological acclimatization effect is > 12 h a day for at least 3 weeks at an altitude or simulated altitude of 2100-2500 m. Exposure to hypoxia appears to have some positive transfer effects on subsequent training in normoxia during and after HiLo. The increased oxygen transport capacity of blood allows training at higher intensity during and after HiLo in subsequent normoxia, thereby increasing the potential to improve some neuromuscular and cardiovascular determinants of endurance performance. The effects of hypoxic training and intermittent short-term severe hypoxia at rest are not yet clear and they require further study.

  17. National Biocontainment Training Center

    Science.gov (United States)

    2013-07-01

    Gina Papadakis ’ training included a review of the Galveston National Laboratory’s biosafety requirements for BSL2, 3 and 4 as well as BSL4 facility...training and BSL4 emergency procedures and incident response. Working with the NBTC’s expert staff, Drs. Druce and Papadakis spent time engaged in...Gina Papadakis , BSL4 Trainer Jet Newton, Dr. Julian Druce and GNL Director Dr. James LeDuc. Previous page right: The group is pictured with

  18. Vocational Training Today: The Changing Relationship between Training and Employment.

    Science.gov (United States)

    Ducray, Gabriel

    1979-01-01

    Focusing on the changing relationship between training and employment, this article discusses (1) limitations of traditional vocational training policies, (2) the relationship between training and employment today, (3) changes in skills and the effects of structural factors on the employment situation, and (4) a modern vocational training policy.…

  19. Effects of Correspondence Training in an Abduction Prevention Training Program.

    Science.gov (United States)

    Olsen-Woods, Laurie A.; Miltenberger, Raymond G.; Foreman, Greg

    1998-01-01

    Examines the effects of adding correspondence training to a behavioral skills training package that taught abduction prevention skills to 31 children, ages 4-5 years. Results indicate that correspondence training did not improve correspondence between saying and doing target behaviors. However, both training approaches were equally effective in…

  20. Evolution of gastroenterology training.

    Science.gov (United States)

    Telleman, Hanna; Burger, Trevlyn Felicity; Mulder, Chris Jacob Johan

    2009-04-21

    There have been rapid developments in gastroenterology (GE) over the last decade. Up until the late 1980s, GE-training was incorporated in Internal Medicine training. The introduction of endoscopy has necessitated the need for additional training. Around the world different national boards have developed their own curricula which will be discussed in this paper. Emphasis will be placed on the curriculum recently introduced in The Netherlands. The internal medicine component has become a two-year requirement (Common Trunk) and the duration of training in GE has been extended to four years. Because of the growing complexity of GE, there are now four subspecialties: Interventional Endoscopy, Neuromotility, Oncology and Hepatology that trainees can choose from. These subspecialties each have predefined specific requirements. The World Gastroenterology Organization has drawn up a standard curriculum which can be of help to the boards in different countries. The curriculum emphasizes the knowledge and skill components. The curriculum also defines the training recommendations, the requirements of training facilities and competence evaluation of fellows and facilities, while less is said about research, finance and the number of gastroenterologists required. In the coming decades the curriculum will need to be revised continuously. Personalization of the curriculum will be the next challenge for the years to come.

  1. Learning without training.

    Science.gov (United States)

    Beste, Christian; Dinse, Hubert R

    2013-06-03

    Achieving high-level skills is generally considered to require intense training, which is thought to optimally engage neuronal plasticity mechanisms. Recent work, however, suggests that intensive training may not be necessary for skill learning. Skills can be effectively acquired by a complementary approach in which the learning occurs in response to mere exposure to repetitive sensory stimulation. Such training-independent sensory learning induces lasting changes in perception and goal-directed behaviour in humans, without any explicit task training. We suggest that the effectiveness of this form of learning in different sensory domains stems from the fact that the stimulation protocols used are optimized to alter synaptic transmission and efficacy. While this approach directly links behavioural research in humans with studies on cellular plasticity, other approaches show that learning can occur even in the absence of an actual stimulus. These include learning through imagery or feedback-induced cortical activation, resulting in learning without task training. All these approaches challenge our understanding of the mechanisms that mediate learning. Apparently, humans can learn under conditions thought to be impossible a few years ago. Although the underlying mechanisms are far from being understood, training-independent sensory learning opens novel possibilities for applications aimed at augmenting human cognition.

  2. Evolution of gastroenterology training

    Institute of Scientific and Technical Information of China (English)

    Hanna Telleman; Trevlyn Felicity Burger; Chris Jacob Johan Mulder

    2009-01-01

    There have been rapid developments in gastroenterology (GE) over the last decade. Up until the late 1980s, GE-training was incorporated in Internal Medicine training. The introduction of endoscopy has necessitated the need for additional training. Around the world different national boards have developed their own curricula which will be discussed in this paper. Emphasis will be placed on the curriculum recently introduced in The Netherlands. The internal medicine component has become a two-year requirement (Common Trunk) and the duration of training in GE has been extended to four years. Because of the growing complexity of GE, there are now four subspecialties: Interventional Endoscopy, Neuromotility, Oncology and Hepatology that trainees can choose from. These subspecialties each have predefined specific requirements. The World Gastroenterology Organization has drawn up a standard curriculum which can be of help to the boards in different countries. The curriculum emphasizes the knowledge and skill components. The curriculum also defines the training recommendations, the requirements of training facilities and competence evaluation of fellows and facilities, while less is said about research, finance and the number of gastroenterologists required. In the coming decades the curriculum will need to be revised continuously. Personalization of the curriculum will be the next challenge for the years to come.

  3. Monitoring spike train synchrony.

    Science.gov (United States)

    Kreuz, Thomas; Chicharro, Daniel; Houghton, Conor; Andrzejak, Ralph G; Mormann, Florian

    2013-03-01

    Recently, the SPIKE-distance has been proposed as a parameter-free and timescale-independent measure of spike train synchrony. This measure is time resolved since it relies on instantaneous estimates of spike train dissimilarity. However, its original definition led to spuriously high instantaneous values for eventlike firing patterns. Here we present a substantial improvement of this measure that eliminates this shortcoming. The reliability gained allows us to track changes in instantaneous clustering, i.e., time-localized patterns of (dis)similarity among multiple spike trains. Additional new features include selective and triggered temporal averaging as well as the instantaneous comparison of spike train groups. In a second step, a causal SPIKE-distance is defined such that the instantaneous values of dissimilarity rely on past information only so that time-resolved spike train synchrony can be estimated in real time. We demonstrate that these methods are capable of extracting valuable information from field data by monitoring the synchrony between neuronal spike trains during an epileptic seizure. Finally, the applicability of both the regular and the real-time SPIKE-distance to continuous data is illustrated on model electroencephalographic (EEG) recordings.

  4. Annual training manual for security training: Protective force

    Energy Technology Data Exchange (ETDEWEB)

    1990-10-01

    Westinghouse is committed to high quality training relevant to the need of the Protective Forces at the Waste Isolation Pilot Plant (WIPP). The training programs at WIPP are designed to qualify Security personnel to perform WIPP security missions in a professional and responsible manner. The program consists of basic as well as sustainment training, as further described in this plan. This plan documents the WIPP Security training program for security personnel for calendar year 1990. The programs detailed in this plan are designed to adequately train persons to ensure the uninterrupted continuity of Department of Energy (DOE)/Westinghouse operations. The Security Training Program consists of four basic elements. These elements are (1) basic level training; (2) on-the-job training; (3) refresher training; and (4) in-service training.

  5. Training induced cortical plasticity compared between three tongue training paradigms

    DEFF Research Database (Denmark)

    Kothari, Mohit; Svensson, Peter; Jensen, Jim

    2013-01-01

    The primary aim of this study was to investigate the effect of different training types and secondary to test gender differences on the training-related cortical plasticity induced by three different tongue training paradigms: 1. Therapeutic tongue exercises (TTE), 2. Playing computer games......) (control) were established using transcranial magnetic stimulation (TMS) at three time-points: (1) before tongue training, (2) immediately after training, (3) 1 h after training. Subject-based reports of motivation, fun, pain and fatigue were evaluated on 0-10 numerical rating scales (NRS) after training......-points. No significant effect of tongue training on FDI MEPs was observed (P>0.335). The tongue cortical motor map areas were not significantly increased by training (P>0.142). Training with TDS was most motivating and fun (Plevel was not different between groups...

  6. Aircraft Simulators and Pilot Training.

    Science.gov (United States)

    Caro, Paul W.

    Flight simulators are built as realistically as possible, presumably to enhance their training value. Yet, their training value is determined by the way they are used. Traditionally, simulators have been less important for training than have aircraft, but they are currently emerging as primary pilot training vehicles. This new emphasis is an…

  7. Customer Satisfaction with Training Programs.

    Science.gov (United States)

    Mulder, Martin

    2001-01-01

    A model for evaluating customer satisfaction with training programs was tested with training purchasers. The model confirmed two types of projects: training aimed at achieving learning results and at changing job performance. The model did not fit for training intended to support organizational change. (Contains 31 references.) (SK)

  8. Customer Satisfaction with Training Programs.

    Science.gov (United States)

    Mulder, Martin

    2001-01-01

    A model for evaluating customer satisfaction with training programs was tested with training purchasers. The model confirmed two types of projects: training aimed at achieving learning results and at changing job performance. The model did not fit for training intended to support organizational change. (Contains 31 references.) (SK)

  9. Male urination in the train

    NARCIS (Netherlands)

    Loth, M.; Molenbroek, J.F.M.

    2011-01-01

    This paper presents the results of a study about hygiene in train toilets. The central problem is that with the existing train toilet design and the different groups of users it is impossible to keep the train toilet clean. In a conventional train, it is especially difficult for men to urinate

  10. Sustainable Library Development Training Package

    Science.gov (United States)

    Peace Corps, 2012

    2012-01-01

    This Sustainable Library Development Training Package supports Peace Corps' Focus In/Train Up strategy, which was implemented following the 2010 Comprehensive Agency Assessment. Sustainable Library Development is a technical training package in Peace Corps programming within the Education sector. The training package addresses the Volunteer…

  11. Employer Training Needs in Hawaii

    OpenAIRE

    Woodbury, Stephen A.

    1992-01-01

    The Survey of Employer Training Needs in Hawaii was undertaken to gather information and data on the needs and preferences of employers in Hawaii regarding government assistance with training. The need for such information was created by passage of Act 68, Session Laws of Hawaii 1991, which created the Hawaii Employment and Training Fund "to assist employers and workers through innovative programs to include, but not be limited to, business-specific training, upgrade training, new occupationa...

  12. Identifying discharge practice training needs.

    Science.gov (United States)

    Lees, L; Emmerson, K

    A training needs analysis tool was developed to identify nurses' discharge training needs and to improve discharge practice. The tool includes 49 elements of discharge practice subdivided into four areas: corporate, operational, clinical and nurse-led discharge. The tool was disseminated to 15 wards on two hospital sites with assistance from the practice development team. Analysis of discharge training is important to assess discharge training needs and to identify staff who may assist with training.

  13. Trainee Readiness For Diversity Training

    Directory of Open Access Journals (Sweden)

    Yunhyung Chung

    2013-11-01

    Full Text Available Although trainee readiness is critical for diversity training effectiveness, extant research has not paid attention to the relationship between trainee readiness for diversity training and diversity training outcomes. This study identifies motivational, behavioral, and cognitive trainee readiness for diversity training and proposes a theoretical framework of how individual characteristics (perceived discrimination, demographic attributes, and previous diversity-related experience and organizational characteristics (diversity climate and demographic dissimilarity influence motivational, behavioral, and cognitive trainee readiness for diversity training.

  14. Ethics Training in Psychiatry

    Directory of Open Access Journals (Sweden)

    Sinan Guloksuz

    2009-09-01

    Full Text Available Although ethics training is one of the core components of psychiatric education, it is not sufficiently addressed in the curricula of many educational institutions. It is shown that many of the psychiatry residents received no ethics training in both residency and medical school. Predictably, over half of the psychiatry residents had faced an ethical dilemma that they felt unprepared to meet, and nearly all of them indicated ethics education would have helped them to solve this dilemma. In addition to learning about the fundamental topics of ethics like confidentiality, boundary violations, justice, benefience and nonmaleficence, psychiatrists must also learn to deal with other hidden ethical dilemmas which are mostly due to the changing world order. It is obvious that residency training should include a well developed ethics curriculum. However, some still believe that ethical principles cannot be taught and are formed in one’s early moral development. Accepting the fact that teaching ethics is difficult, we believe that it is getting easier with the new methods for teaching in medicine. These methods are clinical supervisions, rol-models, case studies, role playing, small group discussions, team based learning and “let’s talking medicine” groups which is a useful methods for discussing ethics dilemmas on daily practice and C.A.R.E (Core Beliefs, Actions, Reasons, Experience which is a special training method for teaching ethics. In this review, the need of ethics training in residency curriculum will be discussed and new methods for teaching ethics will be proposed.

  15. Technical Training: Places available**

    CERN Multimedia

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. TECHNICAL TRAINING Monique Duval tel. 74924 technical.training@cern.ch ** The number of places available may vary. Please check our Web site to find out the current availability. Places are available in the following courses: The JAVA Programming Language Level 1 : 9 & 10.1.2004 (2 days) LabVIEW TestStand I (E) : 23 & 24.2.2004 (2 days) LabVIEW base 1 : 25 - 27.2.2004 (3 jours) CLEAN-2002 : Working in a Cleanroom : 10.3.2004 (afternoon - free of charge) C++ for Particle Physicists : 8 - 12.3.2004 ( 6 X 4-hour sessions) LabVIEW hands-on (E) 16.3...

  16. Technical Training: Places available

    CERN Multimedia

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. TECHNICAL TRAINING Monique Duval tel. 74924 technical.training@cern.ch The number of places available may vary. Please check our Web site to find out the current availability. Places are available in the following courses: LabVIEW base 1 : 25 - 27.2.2004(3 jours) Instructor-led WBTechT study or follow-up for Microsoft applications : 26.2.2004 (morning) CLEAN-2002 : Working in a Cleanroom : 10.3.2004 (afternoon - free of charge) C++ for Particle Physicists : 8 - 12.3.2004 (6 X 4-hour sessions) LabVIEW hands-on (E) : 16.3.2004 (afternoon) LabVIEW Basics 1 : 22 - 24.3.2004 ...

  17. Technical Training: Places available

    CERN Multimedia

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. TECHNICAL TRAINING Monique Duval tel. 74924 technical.training@cern.ch The number of places available may vary. Please check our Web site to find out the current availability. Places are available in the following courses: Instructor-led WBTechT study or follow-up for Microsoft applications : 19.2.2004 (morning) LabVIEW TestStand I (E) : 23 & 24.2.2004 (2 days) LabVIEW base 1 : 25 - 27.2.2004 (3 jours) Instructor-led WBTechT study or follow-up for Microsoft applications : 26.2.2004 (morning) CLEAN-2002 : Working in a Cleanroom : 10.3.2004 (afternoon - free of charge) C++ for Pa...

  18. TECHNICAL TRAINING: Places available**

    CERN Multimedia

    2003-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. TECHNICAL TRAINING Monique Duval tel. 74924 technical.training@cern.ch ** The number of places available may vary. Please check our Web site to find out the current availability. Places are available in the following courses: Hands-on Introduction to Python Programming : 12 - 14.11.03(3 days) ACCESS 2000 - niveau 1 : 13 & 14.11.03 (2 jours) C++ for Particle Physicists : 17 - 21.11.03 (6 X 3-hour lectures) Programmation automate Schneider TSX Premium - niveau 2 : 18 - 21.11.03 (4 jours) Project Planning with MS-Project  (free of charg...

  19. Technical Training: Places available

    CERN Multimedia

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. TECHNICAL TRAINING Monique Duval tel. 74924 technical.training@cern.ch The number of places available may vary. Please check our Web site to find out the current availability. Places are available in the following courses: Instructor-led WBTechT study or follow-up for Microsoft applications : 1.4.2004 (morning) FrontPage XP - niveau 1 : 5 & 6.4.2004 (2 jours) AutoCAD 2002 - niveau 1 : 19, 20.4 et 3, 4.5.2004 (4 jours) Oracle 8i/9i - Develop Web-based Applications with PL/SQL : 19 & 20.4.2004 (2 days) Introduction to ANSYS : 20 - 23.4.2004 (4 day...

  20. Technical Training: Places available

    CERN Multimedia

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. TECHNICAL TRAINING Monique Duval tel. 74924 technical.training@cern.ch The number of places available may vary. Please check our Web site to find out the current availability. Places are available in the following courses: FrontPage XP - niveau 2 : 26 & 27.4.2004 (2 jours) The Joint PVSS JCOP Framework : 26 - 30.4.2004 (5 days) Computational Electromagnetics with the ELEKTRA Module of OPERA-3D : 27 & 28.4.2004 (2 days) Hands-on Introduction to Python Programming : 3 - 5.5.2004 (3 days) LabVIEW Base 2 : 6 & 7.5.2004 (2 jours) Project Pla...

  1. TECHNICAL TRAINING: Places available**

    CERN Multimedia

    2003-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. TECHNICAL TRAINING Monique Duval Tel. 74924 technical.training@cern.ch ** The number of places available may vary. Please check our Web site to find out the current availability. Places are available in the following courses: The EDMS-MTF in practice (free of charge) : 28 -  30.10.03 (6 half-day sessions) AutoCAD 2002 – Level 1 : 3, 4, 12, 13.11.03 (4 days) LabVIEW TestStand ver. 3 : 4 & 5.11.03 (2 days) Introduction to PSpice : 4.11.03 p.m. (half-day) Hands-on Introduction to Python Programming : 12 – 14.11.03 (3 days) ACCESS ...

  2. Technical Training: Places available

    CERN Multimedia

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. TECHNICAL TRAINING Monique Duval tel. 74924 technical.training@cern.ch The number of places available may vary. Please check our Web site to find out the current availability. Places are available in the following courses: Instructor-led WBTechT study for Microsoft applications :12.2.2004 (morning) Instructor-led WBTechT study or follow-up for Microsoft applications : 19.2.2004 (morning) LabVIEW TestStand I (E) : 23 & 24.2.2004 (2 days) LabVIEW base 1 : 25 - 27.2.2004 (3 jours) Instructor-led WBTechT study or follow-up for Microsoft applications : 19.2.2004 (morning) CLEAN-2002 ...

  3. Technical Training: Places Available

    CERN Multimedia

    Monique Duval

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an 'application for training' form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. Technical Training Monique Duval - Tel.74924 technical.training@cern.ch The number of places available may vary. Please check our Web site to find out the current availability. Places are available in the following courses: Oracle 9i: SQL: 17 - 19.5.2004 (3 days) Word 2003 - niveau 2 : 24 & 25.5.2004 (2 jours) EXCEL 2003 - niveau 1 : 27 & 28.5.2004 (2 jours) STEP7 Programming Level 1: 1 - 4.6.2004 (4 days) Oracle 9i : Programming with PL/SQL: 2 - 4.6.2004 (3 days) CST Microwave Studio: 3 & 4.6.2004 (2 days) Oracle 9i : New f...

  4. Technical Training: Places available

    CERN Multimedia

    Monique Duval

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. TECHNICAL TRAINING Monique Duval tel. 74924 technical.training@cern.ch The number of places available may vary. Please check our Web site to find out the current availability. Places are available in the following courses: C++ for Particle Physicists : 8 - 12.3.2004 (6 X 4-hour sessions) Introduction to the CERN EDMS : 9.3.2004 (1 day, free of charge) The EDMS MTF in Practice : 10.3.2004 (morning, free of charge) CLEAN-2002: Working in a Cleanroom : 10.3.2004 (afternoon, free of charge) The CERN EDMS for Engineers : 11.3.2004 (1 day, free of charge) LabVIEW hands-on (E):...

  5. Technical Training: Places available

    CERN Multimedia

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. TECHNICAL TRAINING Monique Duval tel. 74924 technical.training@cern.ch The number of places available may vary. Please check our Web site to find out the current availability. Places are available in the following courses: Project Planning with MS-Project :6 & 13.5.2004 (2 days) Word 2003 - niveau 1 : 10 & 11.5.2004 (2 jours) Oracle 9i : SQL : 17 - 19.5.2004 (3 days) Word 2003 - niveau 2 : 24 & 25.5.2004 (2 jours) EXCEL 2003 - niveau 1: 27 & 28.5.2004 (2 jours) STEP7 Programming Level 1 : 1 - 4.6.2004 (4 days) Oracle 9i : Programming with PL/SQL : 2 - 4.6.2...

  6. Technical Training: Places available

    CERN Multimedia

    Monique Duval

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an 'application for training' form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. Technical Training Monique Duval - Tel.74924 technical.training@cern.ch The number of places available may vary. Please check our Web site to find out the current availability. Places are available in the following courses: Word 2003 - niveau 2 : 24 & 25.5.2004 (2 jours) VisualEliteHDL : 25 & 26.5.2004 (2 days) EXCEL 2003 - niveau 1 : 27 & 28.5.2004 (2 jours) STEP7 Programming Level 1: 1 - 4.6.2004 (4 days) Oracle 9i : Programming with PL/SQL: 2 - 4.6.2004 (3 days) CST Microwave Studio: 3 & 4.6.2004 (2 days) Oracle 9...

  7. Technical Training: Places available

    CERN Multimedia

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. TECHNICAL TRAINING Monique Duval tel. 74924 technical.training@cern.ch The number of places available may vary. Please check our Web site to find out the current availability. Places are available in the following courses: Computational Electromagnetics with the ELEKTRA Module of OPERA-3D : 27 & 28.4.2004 (2 days) Hands-on Introduction to Python Programming : 3 - 5.5.2004 (3 days) LabVIEW Base 2 : 6 & 7.5.2004 (2 jours) Project Planning with MS-Project : 6 & 13.5.2004 (2 days) Word 2003 - niveau 1 : 10 & 11.5.2004 (2 jours) Oracle 9i : SQL : 10 - 12.5.2004 (3...

  8. Technical Training: Places available

    CERN Multimedia

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. TECHNICAL TRAINING Monique Duval tel. 74924 technical.training@cern.ch The number of places available may vary. Please check our Web site to find out the current availability. Places are available in the following courses: AutoCAD 2002 - niveau 1 : 19, 20.4 et 3, 4.5.2004 (4 jours) Oracle 8i/9i - Develop Web-based Applications with PL/SQL : 19 & 20.4.2004 (2 days) Introduction to ANSYS : 20 - 23.4.2004 (4 days) LabVIEW Hands-on : 20.4.2004 (half-day, p.m.) FrontPage XP - niveau 2 : 26 & 27.4.2004 (2 jours) The Joint PVSS JCOP Framework : 26 -...

  9. Technical Training: Places available

    CERN Multimedia

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. TECHNICAL TRAINING Monique Duval tel. 74924 technical.training@cern.ch The number of places available may vary. Please check our Web site to find out the current availability. Places are available in the following courses: C++ for Particle Physicists : 8 - 12.3.2004 (6 X 4-hour sessions) Introduction to the CERN EDMS : 9.3.2004 (1 day, free of charge) The EDMS MTF in Practice : 10.3.2004 (morning, free of charge) CLEAN-2002 : Working in a Cleanroom : 10.3.2004 (afternoon, free of charge) The CERN EDMS for Engineers : 11.3.2004 (1 day, free of charge) LabVIEW...

  10. Nuclear Manpower Training

    Energy Technology Data Exchange (ETDEWEB)

    Min, B. J.; Yoo, B. H.; Lee, E. J. (and others)

    2007-01-15

    Nuclear Training Center (NTC) has concentrated its efforts on the systemisation and specialization of education and training and has actively carried out diverse activities to create new education courses based on the experience accumulated so far. The systematic and comprehensive education systems have been set up by streamlining the education systems for internal employees conducted sporadically over the past years and expansion and diversification of education and training has been built through a study on Systematic Approach to Training (SAT) methodology for the development of efficient education courses and a survey of manpower development in on-site industry. The 6 education programs have been developed and 15 courses were newly developed and improved. Especially to be noted in relation to education program development is that NTC has compiled and published a book titled 'current status of research ethics of science and technology and cases' and has also conducted a survey targeted at the 30 electric power/electricity industries related to nuclear power. The total number of people who receive education for the year of 2006 was 4,186 and a total of 130 training courses were established and 125 times operated. Among them, the number of collective education was 64 courses, 104 times operated and 3,190 persons participated while as for cyber education(on-line language education), 39 courses in 3 foreign language areas established, 21 times operated and 996 persons participated.

  11. Language Training : English Training

    CERN Multimedia

    Françoise Benz

    2004-01-01

    General and Professional English Courses The next session will take place from 04 October 2004 to 11 February 2005 (3 weeks break at Christmas). These courses are open to all persons working on the CERN site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mr. Liptow, tel. 72957. Oral Expression This course is intended for people with a good knowledge of English who want to practise and maintain their speaking skills while extending their vocabulary. There will be approximately 8 participants in a class. Speaking activities will include discussions, meeting simulations, role-plays etc. depending on the needs of the students. Duration: 20 hours (2 hours a week) Price: 440 CHF (for 8 students) For further information, please contact Mr. Liptow, tel. 72957. Date and timetable will be fixed when there are sufficient participants enrolled. FORMATION EN LANGUES LANGUAGE TRAINING Françoise Benz 73127 languag...

  12. Academic Training: 2003 - 2004 Academic Training Programme

    CERN Multimedia

    2004-01-01

    ACADEMIC TRAINING Françoise Benz tel. 73127 academic.training@cern.ch 3rd Term - 5 April to 2nd July 2004 REGULAR LECTURE PROGRAMME 19, 20, 21, 22, 23 April Complex Systems, Chaos and Measurements by P. Collet / Ecole Polytechnique, Palaiseau, France 26, 27, 28, 29 April The Theory of Heavy Ion Collisions by U. Wiedemann / CERN-PH/TH 10, 11, 12, 13, 14 May Particle Identification at the LHC by D. Fournier / LAL, Orsay, France 1, 2, 3, 4 June Neural Systems, Genetic Algorithms by V. Robles Forcada and M. Perez Hernandez / Univ. Politecnica de Madrid E. 7, 8, 9, June Real Time Process Control by T. Riesco / CERN-TS 14, 15, 16, 17, 18 June The Cosmic Microwave Background by M. Zaldarriaga / Harvard University, USA 21, 22, 23, June Fixed Target Physics at CERN : Results and Prospects by J. Engelen / CERN-DG 28, 29, 30 June, 1, 2, July Search for Dark Matter by B. Sadoulet / Univ. of California, Berkeley, USA The lectures are open to all those interested, without application. The abstrac...

  13. Academic Training: 2003 - 2004 Academic Training Programme

    CERN Multimedia

    2004-01-01

    ACADEMIC TRAINING Françoise Benz tel. 73127 academic.training@cern.ch 3rd Term - 5 April to 2nd July 2004 REGULAR LECTURE PROGRAMME 19, 20, 21, 22, 23 April Complex Systems, Chaos and Measurements by P. Collet / Ecole Polytechnique, Palaiseau, France 26, 27, 28, 29 April The Theory of Heavy Ion Collisions by U. Wiedemann / CERN-PH/TH 10, 11, 12, 13, 14 May Particle Identification at the LHC by D. Fournier / LAL, Orsay, France 1, 2, 3, 4 June Neural Systems, Genetic Algorithms by V. Robles Forcada and M. Perez Hernandez / Univ. Politecnica de Madrid E. 7, 8, 9, June Real Time Process Control by T. Riesco / CERN-TS 14, 15, 16, 17, 18 June The Cosmic Microwave Background by M. Zaldarriaga / Harvard University, USA 21, 22, 23, June Fixed Target Physics at CERN : Results and Prospects by J. Engelen / CERN-DG 28, 29, 30 June, 1, 2, July Search for Dark Matter by B. Sadoulet / Univ. of California, Berkeley, USA The lectures are open to all those interested, without application. The abstrac...

  14. 论DSB对《反倾销协定》解释的边界--《反倾销协定》第17.6(ii)条评析%The Limit of DSB's Construction of the Anti-dumping Agreement: Evaluation and Analysis of Articles 17.6(ii)of Anti-dumping Agreement

    Institute of Scientific and Technical Information of China (English)

    贺小勇

    2005-01-01

    WTO一方面对各成员方实施的反倾销措施从程序和实体上均设置了限制条件;另一方面又以第17.6(ii)条限制了争端解决机构(DSB)审查反倾销贸易争端时法律解释的权限,即DSB应尊重反倾销当局对协定进行的"可允许性"解释,这表明该协定对反倾销措施的矛盾态度.然而,在争端解决实践中,DSB屡屡突破这一限制.这种突破一方面有利于贸易自由化法律精神的弘扬;另一方面又与国家经济主权相冲突.从中国国家利益立场出发,似应支持DSB的现有立场.

  15. New method for researching the distribution of residual oil in buried hill fracturd reservoirs——taken DSB reservoir as a%潜山裂缝油藏剩余油分布研究新方法——以DSB油田为例

    Institute of Scientific and Technical Information of China (English)

    赵靖康; 王姝; 李娟; 黄小荣

    2011-01-01

    DSB变质岩潜山油藏1983年投入开采以来,经历27年的开发,目前进入高含水开发后期。如何准确认识潜山裂缝内部油藏剩余油分布,改善油田开发效果,是目前油田开发中的主要问题。在裂缝建模技术的基础上,利用油藏水锥研究与双孔双渗油藏数值模拟相结合且互为验证,对DSB变质岩潜山油藏进行了研究,清晰展现油田剩余油空间分布,为油田调整挖潜提供依据。%DSB metamorphic hill reservoir was put into development in 1983.After 27 years development,later stage of high water-cut development has come,and the problem in this stage is how to make clear the distribution of residual oil in buried hill reservoir to i

  16. 38 CFR 21.4265 - Practical training approved as institutional training or on-job training.

    Science.gov (United States)

    2010-07-01

    ...) The clinical training is; (a) An integral part of the course; (b) A prerequisite to the successful... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Practical training approved as institutional training or on-job training. 21.4265 Section 21.4265 Pensions, Bonuses,...

  17. Perceptual training for visual search.

    Science.gov (United States)

    Schuster, David; Rivera, Javier; Sellers, Brittany C; Fiore, Stephen M; Jentsch, Florian

    2013-01-01

    People are better at visual search than the best fully automated methods. Despite this, visual search remains a difficult perceptual task. The goal of this investigation was to experimentally test the ways in which visual search performance could be improved through two categories of training interventions: perceptual training and conceptual training. To determine the effects of each training on a later performance task, the two types of trainings were manipulated using a between-subjects design (conceptual vs. perceptual × training present vs. training absent). Perceptual training led to speed and accuracy improvements in visual search. Issues with the design and administration of the conceptual training limited conclusions on its effectiveness but provided useful lessons for conceptual training design. The results suggest that when the visual search task involves detecting heterogeneous or otherwise unpredictable stimuli, perceptual training can improve visual search performance. Similarly, careful consideration of the performance task and training design is required to evaluate the effectiveness of conceptual training. Visual search is a difficult, yet critical, task in industries such as baggage screening and radiology. This study investigated the effectiveness of perceptual training for visual search. The results suggest that when visual search involves detecting heterogeneous or otherwise unpredictable stimuli, perceptual training may improve the speed and accuracy of visual search.

  18. Training SVMs without offset

    Energy Technology Data Exchange (ETDEWEB)

    Steinwart, Ingo [Los Alamos National Laboratory; Hush, Don [Los Alamos National Laboratory; Scovel, Clint [Los Alamos National Laboratory

    2009-01-01

    We develop, analyze, and test a training algorithm for support vector machine cla.'>sifiers without offset. Key features of this algorithm are a new stopping criterion and a set of working set selection strategies that, although inexpensive, do not lead to substantially more iterations than the optimal working set selection strategy. For these working set strategies, we establish convergence rates that coincide with the best known rates for SYMs with offset. We further conduct various experiments that investigate both the run time behavior and the performed iterations of the new training algorithm. It turns out, that the new algorithm needs less iterations and run-time than standard training algorithms for SYMs with offset.

  19. Training and natural immunity

    DEFF Research Database (Denmark)

    Pedersen, Bente Klarlund; Helge, Jørn Wulff; Richter, Erik

    2000-01-01

    The purpose of the study was to investigate whether a carbohydrate-rich versus fat-rich diet influenced the effect of training on the immune system. Ten untrained young men ingested a carbohydrate-rich diet [65 energy percent (E%) carbohydrate] and ten subjects a fat-rich diet (62E% fat) while...... endurance training was performed 3-4 times a week for 7 weeks. Maximal oxygen uptake increased by 11% in both groups. Blood samples for immune monitoring were collected before and at the end of the study. Blood samples were also collected, in parallel, from 20 age-matched subjects, and data from...... these subjects were used to eliminate day-to-day variation in the immunological tests. Independently of diet, training increased the percentage of CD3-CD16+ CD56+ natural killer (NK) cells from [mean (SEM)] 14 (1) % to 20 (3) % (P = 0.05), whereas the NK-cell activity, either unstimulated or stimulated...

  20. Alliance-focused training.

    Science.gov (United States)

    Eubanks-Carter, Catherine; Muran, J Christopher; Safran, Jeremy D

    2015-06-01

    Alliance-focused training (AFT) aims to increase therapists' ability to recognize, tolerate, and negotiate alliance ruptures by increasing the therapeutic skills of self-awareness, affect regulation, and interpersonal sensitivity. In AFT, therapists are encouraged to draw on these skills when metacommunicating about ruptures with patients. In this article, we present the 3 main supervisory tasks of AFT: videotape analysis of rupture moments, awareness-oriented role-plays, and mindfulness training. We describe the theoretical and empirical support for each supervisory task, provide examples based on actual supervision sessions, and present feedback about the usefulness of the techniques from trainees in our program. We also note some of the challenges involved in conducting AFT and the importance of maintaining a strong supervisory alliance when using this training approach.

  1. Train operation in emergencies

    CERN Document Server

    Jia, Limin; Qin, Yong

    2017-01-01

    This book presents the latest findings on train operation theories and methods in the context of emergencies. It examines and assesses a range of aspects—including the definition of a railway emergency, transport organization modes in emergencies, calculating railway transport capacity in emergencies, line planning in emergencies, train re-pathing in emergencies and train re-scheduling in emergencies—that are urgently needed in the railway transportation field, which faces the serious challenge of dealing with emergencies worldwide. The book highlights the latest research results in an integrated and systematic way, and the methodology presented is oriented on real-world problems, allowing it to be used not only directly in railway operational management, but also as the point of departure for further applications or theoretical research. As such, the book will be of considerable interest to graduate students and researchers in the field of traffic and transportation engineering.>.

  2. E-groups training

    CERN Multimedia

    HR Department

    2012-01-01

    There will be an e-groups training course on 16 March 2012 which will cover the main e-groups functionalities i.e.: creating and managing e-groups, difference between static and dynamic e-groups, configuring posting restrictions and archives, examples of where e-groups can be used in daily work. Even if you have already worked with e-groups, this may be a good opportunity to learn about the best practices and security related recommendations when using e-groups. You can find more details as well as enrolment form for the training (it’s free) here. The number of places is limited, so enrolling early is recommended.   Technical Training Tel. 72844

  3. Simulators and endourological training.

    Science.gov (United States)

    Laguna, M Pilar; Hatzinger, Martin; Rassweiler, Jens

    2002-05-01

    Acquisition of skills laboratory training seems to be of importance in the training of surgeons, and is intended to cover the gap between theoretical learning and real practice. Economic and ethical reasons limit the use of animals during the learning process, while trends in medical change have severely restricted the available time to teach and to learn. With the incorporation of laparoscopy and the blossoming of minimally invasive techniques, mainly endoscopy, simulators have gained wide acceptance as an important tool in the surgeon's learning process. Two types of simulators are currently available: inanimates or mannequins and virtual reality simulators. A review of the recent literature shows that there is generally a significant improvement in dexterity after using simulators, whichever type is used. It is still unknown whether training simulation influences the patient's outcome positively.

  4. Simulation in resuscitation training.

    Science.gov (United States)

    Perkins, Gavin D

    2007-05-01

    The quality of education, CPR guidelines and the chain of survival all contribute to patient outcome following cardiac arrest. Increasing concerns about patient safety have focused attention on the methods used to train and prepare doctors for clinical practice. Reductions in clinical exposure at both undergraduate and postgraduate level have been implicated in junior doctors inability to recognise and manage critically ill patients. Simulation is used as a central training tool in contemporary advanced life support teaching. Simulation provides a learning opportunity for controlled clinical practice without putting patients or others at risk. This review examines the history and rationale for simulation training in resuscitation and provides some background to the learning theories that underpin it. The role of task trainers, high and low fidelity patient simulators and computer assisted simulation as teaching tools are discussed.

  5. INITIAL TRAINING OF RESEARCHERS

    Directory of Open Access Journals (Sweden)

    Karina Alejandra Cruz-Pallares

    2015-07-01

    Full Text Available The document presents results of a research that used as strategy a complementary training project with thirty-three students of a Bachelors Degree in Primary School 1997(DPS,1997 of an Education Faculty for the initial training of investigators, applied by four teachers members of the academic research group in Mexico; that develops through process of action research methodology. Highlighted in results is the strengthening of the competition of reading, understanding and writing scientific texts, which is analogous to the first feature of the graduate profile called intellectual skills. Among the conclusions it is emphasized that the initial training of teachers in a task that is quite interesting, challenging and complex, as is the educational complex phenomenon.

  6. Transportation safety training

    Energy Technology Data Exchange (ETDEWEB)

    Jones, E.

    1990-01-01

    Over the past 25 years extensive federal legislation involving the handling and transport of hazardous materials/waste has been passed that has resulted in numerous overlapping regulations administered and enforced by different federal agencies. The handling and transport of hazardous materials/waste involves a significant number of workers who are subject to a varying degree of risk should an accident occur during handling or transport. Effective transportation training can help workers address these risks and mitigate them, and at the same time enable ORNL to comply with the federal regulations concerning the transport of hazardous materials/waste. This presentation will outline how the Environmental and Health Protection Division's Technical Resources and Training Section at the Oak Ridge National Laboratory, working with transportation and waste disposal personnel, have developed and implemented a comprehensive transportation safety training program to meet the needs of our workers while satisfying appropriate federal regulations. 8 refs., 3 tabs.

  7. Radioprotection and training

    Energy Technology Data Exchange (ETDEWEB)

    Nolibe, D. [Institut National des Sciences et Techniques Nucleaires (INSTN), Centre d`Etudes de Saclay, 91 - Gif-sur-Yvette (France); Zackova, H.

    1994-12-31

    In a country where 75% of its electric power production is nuclear-based and where the health industry is making more and more use of ionizing radiation, Radioprotection education in France is necessarily characterized by a wide diversity in the trainings delivered and a significant increase in the number of actors providing these training programs. From the isolated worker using an industrial gammagraphy device to the thousands of persons working in major nuclear installations, it is estimated that more than 100,000 workers are exposed to ionizing radiation. Due to the seriousness of the pathological consequences resulting from overexposure to ionizing radiation, the volume of population concerned ant the media impact generated by the problem, one of the basic requirements formulated at the very early stages of the legislation is the obligation of informing workers of the hazards of exposure and the preventive measures to be taken. Employers are legally required to inform their personnel of the risks taken when handling equipment generating ionizing radiation of when using radio-nuclides. This obligation translates concretely by the need for the employer to name a qualified Radioprotection Department. The Qualified Officer or the Radioprotection Department are responsible for, among other tasks, ensuring training of workers. Two training orientations can be distinguished, each having different goals: - the first consists in training a body of highly-skilled Radioprotection professionals or managers (Qualified Officers), - the second consists in training all workers having any contact with ionizing radiation; each person should be capable of ensuring his own Radioprotection regardless of the presence of Qualified Officers. (authors).

  8. Technical Training: WBTechT offers online training

    CERN Multimedia

    Monique Duval

    2005-01-01

    CERN Technical Training 2005 The 2005 CERN Web-Based Technical Training (WBTechT) portal is a computer-skills site offering multimedia learning. Visit http://www.course-source.net/sites/cern/ to self-register, consult the available programmes or request a course via EDH. A self-directed online course costs 50.- CHF for desktop applications and 90.- CHF for technical applications for three months' unlimited access. Visit the WBTechT portal or http://www.cern.ch/TechnicalTraining, and contact Technical.Training@cern.ch or your DTO to find out more information. ENSEIGNEMENT TECHNIQUE TECHNICAL TRAINING Monique Duval 74924 technical.training@cern.ch

  9. Technical Training: WBTechT offers online training

    CERN Document Server

    Monique Duval

    2005-01-01

    CERN Technical Training 2005 The 2005 CERN Web-Based Technical Training portal is a computer-skills site offering multimedia learning. Visit http://www.course-source.net/sites/cern/ to self-register, consult the available programmes or request a course via EDH. A self-directed online course costs 50.- CHF for desktop applications and 90.- CHF for technical applications for three months' unlimited access. Visit the WBTechT portal or http://www.cern.ch/TechnicalTraining, and contact Technical.Training@cern.ch or your DTOs to find out more information. ENSEIGNEMENT TECHNIQUE TECHNICAL TRAINING Monique Duval 74924 technical.training@cern.ch

  10. [Hand surgery training].

    Science.gov (United States)

    Moutet, F; Haloua, J P

    2003-10-01

    Training of the hand surgeon HAND SURGEON A CONCEPT: The hand surgeon is supposed to be in charge of all the hand lesions regarding, skeleton, muscles, tendons, nerves and vessels. He has to be able to insure reparation and coverage of all of them. So he is involved in all the structures, which insure integrity and function of the hand. PURPOSE AND WAYS OF TRAINING: To obtain the asked ability, the hand surgeon training has to be global and sustained by two underlying surgical specialities: orthopedic surgery and plastic and reconstructive surgery. From 2000 after many years of dealings, a Right to the Title in Hand Surgery was born. This Right to the Title wants to be the formal recognition of the specific training of the hand surgeon. For the well-recognized ancient hand surgeons they need to be confirmed by one's peers. Now a day the hand surgeon has to satisfy to this specific training: Passed the complete training and exam of the Orthopedic or Plastic surgery board. Spent at least 6 months as resident in the other underlying specialty. Passed a microsurgery examination. Passed one of the four national Hand Surgery diplomas (DIU/Inter-Universitary Diploma). The examinations have been harmonized. A common formation is delivered regarding hand surgery, the way of examination is the same and the formation is 2 years long. The final exam is presented in front of board of examiners where a teacher of one of the other three national diplomas is present. Spent at least 2 years in a formative hand surgery unit, listed by the French College of Hand Surgeons, as senior surgeon. Those requirements are heavy to assume and need a heavy personal involvement. That seems to be necessary to have an ability level as high as possible. Emergency surgery practice is absolutely necessary in this training. All the 17 university formative hand surgery units listed by the French College of Hand Surgeons are members of the FESUM (European Federation of the Emergency Hand Units

  11. National Biocontainment Training Center

    Science.gov (United States)

    2010-06-01

    experimentally infected animals, including non- human primates, under containment conditions. As our animal handling in containment training module...Theoretical non 16 0 0 0 16 human primate BSL3 mentorship 26 10 0 17 53 Specialized 0 18 0 17 35 training (Assay Development division) BSL3...39% 4% 11% Su ent:fk f acdity Jnd M<.)nlen<.tn ct~ ··· Onwr> (IT, i\\RC, Non ;ocntdK) tr High >chool Underr . rdd Stude nt Graduate St u(~cnt s

  12. Nuclear education and training

    CERN Document Server

    2012-01-01

    The OECD Nuclear Energy Agency (NEA) first published in 2000 Nuclear Education and Training: Cause for Concern? , which highlighted significant issues in the availability of human resources for the nuclear industry. Ten years on, Nuclear Education and Training: From Concern to Capability considers what has changed in that time and finds that, while some countries have taken positive actions, in a number of others human resources could soon be facing serious challenges in coping with existing and potential new nuclear facilities. This is exacerbated by the increasing rate of retirement as the w

  13. Turning training into play

    DEFF Research Database (Denmark)

    Aarhus, Rikke; Grönvall, Erik; Larsen, Simon Bo;

    2011-01-01

    Embodied gaming has been adopted and gained credibility in the field of physical rehabilitation. In this paper, we report on findings from a six-month-long study of three groups of senior citizens, and their use of Nintendo Wii Fit in a supervised physical training context. We argue that the study...... participants generally found physical training both fun and socially engaging, and experienced improved fitness. We also argue that embodied gaming motivates seniors to do more than they think themselves capable of, and allows seniors with different mental and physical capabilities to play together. However...

  14. Adding flexibility to physician training.

    Science.gov (United States)

    Mahady, Suzanne E

    2011-05-02

    Demographic changes among junior doctors are driving demand for increased flexibility in advanced physician training, but flexible training posts are lacking. Suitable flexible training models include flexible full-time, job-share and part-time positions. Major barriers to establishing flexible training positions include difficulty in finding job-share partners, lack of funding for creating supernumerary positions, and concern over equivalence of educational quality compared with full-time training. Pilot flexible training positions should be introduced across the medical specialties and educational outcomes examined prospectively.

  15. Hard Training Bears Fruit

    Institute of Scientific and Technical Information of China (English)

    1996-01-01

    Perfect skills take time to acquire. An outstanding performance, while it may be short, is the harvest of many years’ training. Hearty rounds of applause Reward the artists’ diligence. The flowers of the arts are fertilized with sweat; Consummate skills bridge all ages, And new always springs from old

  16. Dental Training Films.

    Science.gov (United States)

    Veterans Administration Medical Center, Washington, DC.

    This dental training films catalog is organized into two sections. Section I is a category listing of the films by number and title, indexed according to generalized headings; categories are as follow: anatomy, articulator systems, complete dentures, dental assisting, dental laboratory technology, dental materials, dental office emergencies,…

  17. Technician Training Experience

    CERN Multimedia

    2015-01-01

    There is a real shortage of skilled engineers & technicians in Europe and yet at the same time high unemployment levels. For years CERN has offered a great training ground for engineers & physicists and we are now aiming to do the same for technicians. Th

  18. Slow Train Coming

    Science.gov (United States)

    McNair, Stephen

    2011-01-01

    The battle for an adequate careers guidance service for adults has been a long one. A succession of governments have been formally committed to lifelong learning, to broadening choice and diversity in education and training, and to asking individuals to take more control of (and pay more for) their education, but only in the last few years have…

  19. Bicycle Purchaser Training Workshop.

    Science.gov (United States)

    Schwarz, William

    A course was developed to provide data to buyers of new bicycles so they could make an informed decision about their purchases. The instructional systems design process (analysis, design, development, implementation, and evaluation) was used to analyze the need for a training course on buying and fitting a bicycle. Information was collected…

  20. Motivation for media training

    Directory of Open Access Journals (Sweden)

    Anita Mikulič

    2008-12-01

    Full Text Available Readers have been reading more than only texts in books, magazines, newspapers, but also texts in films and TV screens, mobile phones and similar. Moreover, at present we’ve been surrounded by images, which we have yet to learn to read, judge critically and use as a form of articulation. This article, thus, presents useful suggestions for media training.

  1. Gamification for astronaut training

    NARCIS (Netherlands)

    Cornelissen, F.; Neerincx, M.A.; Smets, N.J.J.M.; Breebaart, L.; Dujardin, P.; Wolff, M.

    2012-01-01

    This paper reports on the use and the evaluation of applying gaming aspects as a means to promote self-study and increase motivation to train for executing operations on human space flight missions that have a duration that exceeds the typical duration of low earth orbit missions. The gaming aspects

  2. Training for Leadership.

    Science.gov (United States)

    Adair, John

    An indepth study of how to select and train for effective leadership is based on the belief that though innate character traits play a role of leadership, leadership potential can be developed. The author's theory known as "functional leadership," stresses that leadership is an interaction among leader, group members, and situation. The good…

  3. Training for Hospitality.

    Science.gov (United States)

    Herman, Francine A.; Eller, Martha E.

    1991-01-01

    The labor problems of hotels and restaurants are being addressed with partnership training initiatives. Examples are the Stratford Chef's School in Ontario, the University of Hawaii's Tourism Industry Management Program, and an English-as-a-Second-Language program sponsored by labor and management in New York City hotels. (SK)

  4. Technical Training: Places available

    CERN Multimedia

    Monique Duval

    2005-01-01

    The number of places available may vary. Please check our Web site to find out the current availability. Places are available on the following courses: LabVIEW Migration 6 to 7: 14.6.2005 (1 day) IT3T/1 - Read your mail and more with Outlook 2003 : 14.6.2005 (IT Technical Training Tutorial, free of charge) IT3T/2 - Creating, managing and using distribution lists with Simba2 : 16.6.2005 (IT Technical Training Tutorial, free of charge) FrontPage 2003 - niveau 2 : 16 & 17.6.2005 (2 jours) size="2">(1journée) Hands-on Introduction to Python Programming: 28 - 30.6.2005 (3 days) Introduction to ANSYS: 21 - 24.6.2005 (4 days) IT3T/3 - Working remotely with Windows XP: 28.6.2005 (IT Technical Training Tutorial, free of charge) IT3T/4 - Editing Websites with Frontpage 2003: 30.6.2005 (IT Technical Training Tutorial, free of charge) LabVIEW base 1 : 4 - 6.7.2005 (3 jours) LabVIEW Basics 2: AutoCorrect, Find/Replace) : 4.7.2005 (afternoon) WORD 2003 (Shor...

  5. Technical Training: Places available

    CERN Multimedia

    Monique Duval

    2005-01-01

    The number of places available may vary. Please check our Web site to find out the current availability. Places are available on the following courses: LabVIEW Real-Time (F) : 7 - 9.6.2005 (3 jours) LabVIEW Migration 6 to 7: 14.6.2005 (1 day) IT3T/1 - Read your mail and more with Outlook 2003 : 14.6.2005 (IT Technical Training Tutorial, free of charge) IT3T/2 - Creating, managing and using distribution lists with Simba2 : 16.6.2005 (IT Technical Training Tutorial, free of charge) FrontPage 2003 - niveau 2 : 16 & 17.6.2005 (2 jours) Utilisation de fichiers PDF avec ACROBAT 6.0 : 20.6.2005 (1journée) Introduction to ANSYS: 21 - 24.6.2005 (4 days) IT3T/3 - Working remotely with Windows XP : 28.6.2005 (IT Technical Training Tutorial, free of charge) IT3T/4 - Editing Websites with Frontpage 2003 : 30.6.2005 (IT Technical Training Tutorial, free of charge) WORD 2003 (Short Course I) - HowTo... Work with repetitive tasks /AutoText, AutoFormat, AutoC...

  6. Technical Training: Places available

    CERN Multimedia

    Monique Duval

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an 'application for training' form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. The number of places available may vary. Please check our Web site to find out the current availability. Places are available in the following courses: AutoCAD 2002 - niveau 1 : 13, 14, 23, 24.09.2004 (4 jours) Introduction to the CERN EDMS : 22.6.2004 (1 day) The CERN EDMS for local administrators : 23 & 24.6.2004 (2 days) MAGNE-04 : Magnétisme pour l'électrotechnique : 6 - 8.7.2004 (3 jours) Introduction au VHDL et utilisation du simulateur NCVHDL de CADENCE : 7 & 8.9.2004 (2 jours) ENSEIGNEMENT TECHNIQUE TECHNICAL TRAINING...

  7. Constructing Virtual Training Demonstrations

    Science.gov (United States)

    2008-12-01

    Taylor, Russ-Eft, & Chan, 2005). BMT is based on Bandura’s social learning theory (Hogan, Hakel, & Decker, 1986). Utilizing the model provided by... social learning theory , BMT includes processes such as modeling, a retention process, behavioral rehearsal, feedback, and methods of training transfer

  8. Vocational Training in Ireland.

    Science.gov (United States)

    Dooney, Roy; Dunne, Paul

    This monograph, one of a series of studies of vocational education in the countries of the European Communities, describes the vocational training system in Ireland. The study was compiled from existing statistics and descriptions, and most figures cited refer to 1984. The report is organized in eight chapters. Chapter 1 covers population,…

  9. Teacher-Training Projects

    Science.gov (United States)

    Greer, Leslie

    1977-01-01

    The Sociedade Brasileira de Cultura Inglesa of Sao Paolo, Brazil, is an English teaching center which also runs an introductory course to train teachers of English. This article describes some of the projects completed by prospective teachers; they include language games, pictures, cartoons, role-playing and writing creative dialogue. (CHK)

  10. Drive-Through Training

    Science.gov (United States)

    Carter, Margie

    2010-01-01

    In this article, the author discusses how the early childhood field's approach to staff training reflects the drive-through, fast-food culture. Year after year directors send their teachers to workshops to get some quick refresher techniques. The author suggests that rather than focusing professional development on topics, focus on observing…

  11. Training International Journalists.

    Science.gov (United States)

    Bartram, John

    2000-01-01

    Examines eight key issues in training journalists. Argues: journalism educators should still be teaching the basic journalism skills that are of practical use in the marketplace; they should not show an exaggerated interest in the Ph.D. research that attracts so much coveted university funding; and they must try to put the interests and needs of…

  12. Vocational Education and Training.

    Science.gov (United States)

    van Leeuwen, Fred, Ed.

    2000-01-01

    This issue of the quarterly Education International focuses on vocational education and training (VET). The editorial, "Education and the Wealth of Nations" (Fred van Leeuwen), focuses on provision of quality education for all. "Education International's (EI's) First Joint Worldwide Action on Education Issues" (Elie Jouen) describes the Global…

  13. Language Training: French

    CERN Multimedia

    Françoise Benz

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an 'application for training' form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt.General and Professional French Courses The next session will take place from 26 April to 02 July 2004. These courses are open to all persons working on the Cern site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mrs. Benz: Tel. 73127. Writing Professional Documents in French The next session will take place from 26 April to 02 July 2004. This course is designed for people with a good level of spoken French. Duration: 30 hours Price: 660 CHF (for 8 students) For further information and registra...

  14. Otologic Skills Training

    DEFF Research Database (Denmark)

    Wiet, Gregory J; Sørensen, Mads Sølvsten; Andersen, Steven Arild Wuyts

    2017-01-01

    This article presents a summary of the current simulation training for otologic skills. There is a wide variety of educational approaches, assessment tools, and simulators in use, including simple low-cost task trainers to complex computer-based virtual reality systems. A systematic approach...

  15. Training International Journalists.

    Science.gov (United States)

    Bartram, John

    2000-01-01

    Examines eight key issues in training journalists. Argues: journalism educators should still be teaching the basic journalism skills that are of practical use in the marketplace; they should not show an exaggerated interest in the Ph.D. research that attracts so much coveted university funding; and they must try to put the interests and needs of…

  16. Strength training and aerobic exercise training for muscle disease (Review)

    NARCIS (Netherlands)

    Voet, N.B.M.; Kooi, E.L. van der; Riphagen, I.I.; Lindeman, E.; Engelen, B.G.M. van; Geurts, A.C.H.

    2010-01-01

    BACKGROUND: Strength training or aerobic exercise programmes might optimise muscle and cardiorespiratory function and prevent additional disuse atrophy and deconditioning in people with a muscle disease. OBJECTIVES: To examine the safety and efficacy of strength training and aerobic exercise trainin

  17. Strength training and aerobic exercise training for muscle disease (Review)

    NARCIS (Netherlands)

    Voet, N.B.M.; Kooi, E.L. van der; Riphagen, I.I.; Lindeman, E.; Engelen, B.G.M. van; Geurts, A.C.H.

    2010-01-01

    BACKGROUND: Strength training or aerobic exercise programmes might optimise muscle and cardiorespiratory function and prevent additional disuse atrophy and deconditioning in people with a muscle disease. OBJECTIVES: To examine the safety and efficacy of strength training and aerobic exercise trainin

  18. 30 CFR 75.834 - Training.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Training. 75.834 Section 75.834 Mineral....834 Training. In addition to existing part 48 task training, hazard training, training for qualified persons under existing § 75.153, and annual refresher training, the following specialized training...

  19. Training Directors' Perceptions about the Successful Implementation of Supervisory Training.

    Science.gov (United States)

    Taylor, Paul

    1992-01-01

    In a sample of 285 (of 1,363) corporations, reports of supervisor reaction to supervisory training were assessed to measure program success. Results highlight the importance of training administrators' role in convincing supervisors and their superiors of the value of training before implementation. (SK)

  20. The Efficacy of Stuttering Measurement Training: Evaluating Two Training Programs

    Science.gov (United States)

    Bainbridge, Lauren A.; Stavros, Candace; Ebrahimian, Mineh; Wang, Yuedong; Ingham, Roger J.

    2015-01-01

    Purpose: Two stuttering measurement training programs currently used for training clinicians were evaluated for their efficacy in improving the accuracy of total stuttering event counting. Method: Four groups, each with 12 randomly allocated participants, completed a pretest-posttest design training study. They were evaluated by their counts of…

  1. Peace Corps Aquaculture Training Manual. Training Manual T0057.

    Science.gov (United States)

    Peace Corps, Washington, DC. Information Collection and Exchange Div.

    This Peace Corps training manual was developed from two existing manuals to provide a comprehensive training program in fish production for Peace Corps volunteers. The manual encompasses the essential elements of the University of Oklahoma program that has been training volunteers in aquaculture for 25 years. The 22 chapters of the manual are…

  2. Making Training Core Business: Enterprise Registered Training Organisations in Australia

    Science.gov (United States)

    Smith, Erica; Smith, Andy

    2009-01-01

    This paper examines the Australian phenomenon of Enterprise Registered Training Organizations (RTOs). These are organizations that do not have training as their main business but that are accredited to deliver training and award qualifications, primarily to their own workers. Although Enterprise RTOs have been in existence in one form or another…

  3. Making Training Core Business: Enterprise Registered Training Organisations in Australia

    Science.gov (United States)

    Smith, Erica; Smith, Andy

    2009-01-01

    This paper examines the Australian phenomenon of Enterprise Registered Training Organizations (RTOs). These are organizations that do not have training as their main business but that are accredited to deliver training and award qualifications, primarily to their own workers. Although Enterprise RTOs have been in existence in one form or another…

  4. Training report of the FBR cycle training facility in 2001

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Toshio; Sasaki, Kazuichi; Sawada, Makoto [Japan Nuclear Cycle Development Inst., Tsuruga, Fukui (Japan); Ozawa, Kazumasa [Hitachi Ltd., Tokyo (Japan); Nagai, Humio [Fast Technology Engineering Co. (Japan)

    2002-08-01

    The FBR Cycle Training Facility has been operating since Sep. 2000 for staff of FBR 'Monju' and ATR 'Fugen' and fireman of the local community, etc. In 2000, 6 courses of the sodium handling training were held 22 times and also eight courses of the maintenance training were 11 times and total participants were 305. In order to grade up the trainigs for providing restarting of 'Monju', the corresponding training course on sodium piping leakage accident was added as newly sodium handling training course and partial contents of some courses were devised based on some comments by the training discussing committee organized in our center. In 2001, seven sodium handling training courses were carried out 25 times and eight maintenance courses were conducted 11 times and total participated number was 220, i.e. 157 trainees for sodium training courses and 63 trainees for maintenance training courses. Additionally, since a new licensed sodium training course for sodium handling workers included head of worker will be introduced from next year owing to the fire accident of maintenance building in the experimental fast reactor 'JOYO' occurred Oct in 2001, which was coursed by sodium spontaneous combustion due to inefficient handling on tidy up of the sodium handling working, training curriculum, training text and questions for examination are provided as for preparing its course cooperated with Oarai Engineering Center. (author)

  5. The Efficacy of Stuttering Measurement Training: Evaluating Two Training Programs

    Science.gov (United States)

    Bainbridge, Lauren A.; Stavros, Candace; Ebrahimian, Mineh; Wang, Yuedong; Ingham, Roger J.

    2015-01-01

    Purpose: Two stuttering measurement training programs currently used for training clinicians were evaluated for their efficacy in improving the accuracy of total stuttering event counting. Method: Four groups, each with 12 randomly allocated participants, completed a pretest-posttest design training study. They were evaluated by their counts of…

  6. Training Guide for Identifying, Meeting, and Evaluating Training Needs.

    Science.gov (United States)

    Federal Highway Administration (DOT), Washington, DC. National Highway Inst.

    This manual is a guide for the training supervisor, specialist, or other official who has to plan, develop, and carry through a training program for improving the effectiveness of the employee development program, particularly in a governmental department of highways. The content is in three chapters: (1) Identifying Training Needs briefly…

  7. Financing Training: Issues and Options.

    Science.gov (United States)

    Dougherty, Christopher; Tan, Jee-Peng

    1999-01-01

    Economic changes and retrenchment have led to reconsideration of the role of government and the private sector in financing training. When private sector-sponsored training displays inadequacies, government intervention may be necessary. (SK)

  8. Heavy resistance training and lymphedema

    DEFF Research Database (Denmark)

    Bloomquist, Kira; Karlsmark, Tonny; Christensen, Karl Bang

    2014-01-01

    BACKGROUND: There is limited knowledge regarding progressive resistance training during adjuvant chemotherapy and the risk of developing breast cancer-related lymphedema (BCRL). Furthermore, no studies have investigated the safety of resistance training with heavy loads (> 80% 1 repetition maximum...

  9. Pelvic floor muscle training exercises

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003975.htm Pelvic floor muscle training exercises To use the sharing features on this page, please enable JavaScript. Pelvic floor muscle training exercises are a series of exercises ...

  10. Transportation Conformity Training and Presentations

    Science.gov (United States)

    EPA's OTAQ has provided multiple conformity training sessions in the past to assist state and local governments in implementing conformity requirements. As training information is prepared for other venues, it will be posted on this page.

  11. Creating a Toilet Training Plan

    Science.gov (United States)

    ... Size Email Print Share Creating a Toilet Training Plan Page Content Article Body These are the tools ... will need to create your own toilet-training plan and implement it at the best time for ...

  12. Theories Supporting Transfer of Training.

    Science.gov (United States)

    Yamnill, Siriporn; McLean, Gary N.

    2001-01-01

    Reviews theories about factors affecting the transfer of training, including theories on motivation (expectancy, equity, goal setting), training transfer design (identical elements, principle, near and far), and transfer climate (organizational). (Contains 36 references.) (SK)

  13. Quality Assurance Training Tracking (QATTS)

    Data.gov (United States)

    U.S. Environmental Protection Agency — This is metadata documentation for the Quality Assurance Training Tracking System (QATTS) which tracks Quality Assurace training given by R7 QA staff to in-house...

  14. Payload IVA training and simulation

    Science.gov (United States)

    Monsees, J. H.

    1982-01-01

    The development of a training program for the intravehicular operation of space shuttle payloads is discussed. The priorities for the program are compliance with established training standards, and accommodating changes. Simulation devices are also reviewed.

  15. Train suicides in The Netherlands

    NARCIS (Netherlands)

    van Houwelingen, Cornelis A. J.; Kerkhof, Ad J. F. M.; Beersma, Domien G. M.

    2010-01-01

    Background: Little is known about train suicide and factors influencing its prevalence. This study tests the hypotheses that railway density, railway transportation volume, familiarity with railway transportation and population density contribute to train suicide. It also tests the relationship

  16. Training Results and Information Network

    Data.gov (United States)

    US Agency for International Development — TraiNet is USAID's official training data management system that is accessed from a web browser and the entry point for data about training programs and participants...

  17. Training Materials for Release 3

    DEFF Research Database (Denmark)

    Wake, Jo Dugstad; Hansen, Cecilie; Debus, Kolja;

    This document, D7.4 – training materials for release 3, provides an overview of the training material for version 3 of the NEXT-TELL tools and methods. Previous documents submitted as part of work package 7, which is about teacher training, are D7.1 – Training Concept, D7.2 – Training Materials...... for Release 1 and D7.3 – Training Materials for Release 2. D7.4 builds on D7.1 and D7.2 and D7.3. D7.4 contains further development of previous work within WP7, essentially a revised theoretical approach to the teacher training, and expansion of the notion of tool training. The media in use have been expanded...

  18. Radiological training for tritium facilities

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-01

    This program management guide describes a recommended implementation standard for core training as outlined in the DOE Radiological Control Manual (RCM). The standard is to assist those individuals, both within DOE and Managing and Operating contractors, identified as having responsibility for implementing the core training recommended by the RCM. This training may also be given to radiological workers using tritium to assist in meeting their job specific training requirements of 10 CFR 835.

  19. Residency Training: Work engagement during neurology training.

    Science.gov (United States)

    Zis, Panagiotis; Anagnostopoulos, Fotios; Artemiadis, Artemios K

    2016-08-02

    Work engagement, defined as a positive, fulfilling, work-related state of mind that is characterized by vigor, dedication, and absorption, can ameliorate patient care and reduce medical errors. The purpose of this cross-sectional study was to investigate work engagement among neurology residents in the region of Attica, Greece. In total, 113 residents participated in this study. Demographic and work-related characteristics, as well as emotional exhaustion and personality traits (neuroticism), were examined via an anonymous questionnaire. Work engagement was measured by the Utrecht Work Engagement Scale. The study sample had a mean age of 34.6 ± 3.6 years, ranging from 26 to 45 years. Sixty-two (54.9%) participants were women and 45 (39.8%) were married. After adjusting for sex, emotional exhaustion, and neuroticism, the main factors associated with work engagement were autonomy and chances for professional development. Providing more chances for trainees' professional development as well as allowing for and supporting greater job autonomy may improve work engagement during neurology training. © 2016 American Academy of Neurology.

  20. Guidance for training program evaluation

    Energy Technology Data Exchange (ETDEWEB)

    1984-01-01

    An increased concern about the training of nuclear reactor operators resulted from the incident at TMI-2 in 1979. Purpose of this guide is to provide a general framework for the systematic evaluation of training programs for DOE Category-A reactors. The primary goal of such evaluations is to promote continuing quality improvements in the selection, training and qualification programs.