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Sample records for glycosylases excising analogous

  1. Inhibition of DNA glycosylases via small molecule purine analogs.

    Directory of Open Access Journals (Sweden)

    Aaron C Jacobs

    Full Text Available Following the formation of oxidatively-induced DNA damage, several DNA glycosylases are required to initiate repair of the base lesions that are formed. Recently, NEIL1 and other DNA glycosylases, including OGG1 and NTH1 were identified as potential targets in combination chemotherapeutic strategies. The potential therapeutic benefit for the inhibition of DNA glycosylases was validated by demonstrating synthetic lethality with drugs that are commonly used to limit DNA replication through dNTP pool depletion via inhibition of thymidylate synthetase and dihydrofolate reductase. Additionally, NEIL1-associated synthetic lethality has been achieved in combination with Fanconi anemia, group G. As a prelude to the development of strategies to exploit the potential benefits of DNA glycosylase inhibition, it was necessary to develop a reliable high-throughput screening protocol for this class of enzymes. Using NEIL1 as the proof-of-principle glycosylase, a fluorescence-based assay was developed that utilizes incision of site-specifically modified oligodeoxynucleotides to detect enzymatic activity. This assay was miniaturized to a 1536-well format and used to screen small molecule libraries for inhibitors of the combined glycosylase/AP lyase activities. Among the top hits of these screens were several purine analogs, whose postulated presence in the active site of NEIL1 was consistent with the paradigm of NEIL1 recognition and excision of damaged purines. Although a subset of these small molecules could inhibit other DNA glycosylases that excise oxidatively-induced DNA adducts, they could not inhibit a pyrimidine dimer-specific glycosylase.

  2. Base excision repair deficient mice lacking the Aag alkyladenine DNA glycosylase.

    NARCIS (Netherlands)

    B.P. Engelward (Bevin); G. Weeda (Geert); M.D. Wyatt; J.L.M. Broekhof (Jose'); J. de Wit (Jan); I. Donker (Ingrid); J.M. Allan (James); B. Gold (Bert); J.H.J. Hoeijmakers (Jan); L.D. Samson (Leona)

    1997-01-01

    textabstract3-methyladenine (3MeA) DNA glycosylases remove 3MeAs from alkylated DNA to initiate the base excision repair pathway. Here we report the generation of mice deficient in the 3MeA DNA glycosylase encoded by the Aag (Mpg) gene. Alkyladenine DNA glycosylase turns out to be the major DNA

  3. Selective base excision repair of DNA damage by the non-base-flipping DNA glycosylase AlkC

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Rongxin; Mullins, Elwood A.; Shen, Xing; #8208; Xing; Lay, Kori T.; Yuen, Philip K.; David, Sheila S.; Rokas, Antonis; Eichman, Brandt F. (UCD); (Vanderbilt)

    2017-10-20

    DNA glycosylases preserve genome integrity and define the specificity of the base excision repair pathway for discreet, detrimental modifications, and thus, the mechanisms by which glycosylases locate DNA damage are of particular interest. Bacterial AlkC and AlkD are specific for cationic alkylated nucleobases and have a distinctive HEAT-like repeat (HLR) fold. AlkD uses a unique non-base-flipping mechanism that enables excision of bulky lesions more commonly associated with nucleotide excision repair. In contrast, AlkC has a much narrower specificity for small lesions, principally N3-methyladenine (3mA). Here, we describe how AlkC selects for and excises 3mA using a non-base-flipping strategy distinct from that of AlkD. A crystal structure resembling a catalytic intermediate complex shows how AlkC uses unique HLR and immunoglobulin-like domains to induce a sharp kink in the DNA, exposing the damaged nucleobase to active site residues that project into the DNA. This active site can accommodate and excise N3-methylcytosine (3mC) and N1-methyladenine (1mA), which are also repaired by AlkB-catalyzed oxidative demethylation, providing a potential alternative mechanism for repair of these lesions in bacteria.

  4. In vivo excision of pyrimidine dimers is mediated by a DNA N-glycosylase in Micrococcus luteus but not in human fibroblasts

    International Nuclear Information System (INIS)

    La Belle, M.; Linn, S.

    1982-01-01

    It has been previously shown that Micrococcus luteus possesses a pyrimidine dimer-specific endonuclease which in vitro, functions as both an endonuclease and DNA-glycosylase. To determine if these combined activities function in vivo, the excision products of UV-irradiated M. luteus were isolated and examined. In addition, a procedure was devised to isolate and examine the excision products from UV-irradiated human fibroblasts to determine if an endonuclease/glycosylase activity functions in the excision of UV-induced pyrimidine dimers in human fibroblasts. It was shown that, in vivo, an endonuclease/glycosylase mechanism is utilized extensively in the repair of pyrimidine dimers by M. luteus, but that human fibroblasts do not appear to use this mechanism. (author)

  5. In vivo excision of pyrimidine dimers is mediated by a DNA N-glycosylase in Micrococcus luteus but not in human fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    La Belle, M; Linn, S [California Univ., Berkeley (USA). Dept. of Biochemistry

    1982-09-01

    It has been previously shown that Micrococcus luteus possesses a pyrimidine dimer-specific endonuclease which in vitro, functions as both an endonuclease and DNA-glycosylase. To determine if these combined activities function in vivo, the excision products of UV-irradiated M. luteus were isolated and examined. In addition, a procedure was devised to isolate and examine the excision products from UV-irradiated human fibroblasts to determine if an endonuclease/glycosylase activity functions in the excision of UV-induced pyrimidine dimers in human fibroblasts. It was shown that, in vivo, an endonuclease/glycosylase mechanism is utilized extensively in the repair of pyrimidine dimers by M. luteus, but that human fibroblasts do not appear to use this mechanism.

  6. Metal inhibition of human alkylpurine-DNA-N-glycosylase activityin base excision repair

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ping; Guliaev, Anton B.; Hang, Bo

    2006-02-28

    Cadmium (Cd{sup 2+}), nickel (Ni{sup 2+}) and cobalt (Co{sup 2+}) are human and/or animal carcinogens. Zinc (Zn{sup 2+}) is not categorized as a carcinogen, and rather an essential element to humans. Metals were recently shown to inhibit DNA repair proteins that use metals for their function and/or structure. Here we report that the divalent ions Cd{sup 2+}, Ni{sup 2+}, and Zn{sup 2+} can inhibit the activity of a recombinant human N-methylpurine-DNA glycosylase (MPG) toward a deoxyoligonucleotide with ethenoadenine (var epsilonA). MPG removes a variety of toxic/mutagenic alkylated bases and does not require metal for its catalytic activity or structural integrity. At concentrations starting from 50 to 1000 {micro}M, both Cd{sup 2+} and Zn{sup 2+} showed metal-dependent inhibition of the MPG catalytic activity. Ni{sup 2+} also inhibited MPG, but to a lesser extent. Such an effect can be reversed with EDTA addition. In contrast, Co{sup 2+} and Mg{sup 2+} did not inhibit the MPG activity in the same dose range. Experiments using HeLa cell-free extracts demonstrated similar patterns of inactivation of the var epsilonA excision activity by the same metals. Binding of MPG to the substrate was not significantly affected by Cd{sup 2+}, Zn{sup 2+}, and Ni{sup 2+} at concentrations that show strong inhibition of the catalytic function, suggesting that the reduced catalytic activity is not due to altered MPG binding affinity to the substrate. Molecular dynamics (MD) simulations with Zn{sup 2+} showed that the MPG active site has a potential binding site for Zn{sup 2+}, formed by several catalytically important and conserved residues. Metal binding to such a site is expected to interfere with the catalytic mechanism of this protein. These data suggest that inhibition of MPG activity may contribute to metal genotoxicity and depressed repair of alkylation damage by metals in vivo.

  7. DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers.

    Directory of Open Access Journals (Sweden)

    Ana Osorio

    2014-04-01

    Full Text Available Single Nucleotide Polymorphisms (SNPs in genes involved in the DNA Base Excision Repair (BER pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase, and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2. Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2 gene (HR: 1.09, 95% CI (1.03-1.16, p = 2.7 × 10(-3 for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3. DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.

  8. Excision of deaminated cytosine from the vertebrate genome: role of the SMUG1 uracil–DNA glycosylase

    Science.gov (United States)

    Nilsen, Hilde; Haushalter, Karl A.; Robins, Peter; Barnes, Deborah E.; Verdine, Gregory L.; Lindahl, Tomas

    2001-01-01

    Gene-targeted mice deficient in the evolutionarily conserved uracil–DNA glycosylase encoded by the UNG gene surprisingly lack the mutator phenotype characteristic of bacterial and yeast ung– mutants. A complementary uracil–DNA glycosylase activity detected in ung–/– murine cells and tissues may be responsible for the repair of deaminated cytosine residues in vivo. Here, specific neutralizing antibodies were used to identify the SMUG1 enzyme as the major uracil–DNA glycosylase in UNG-deficient mice. SMUG1 is present at similar levels in cell nuclei of non-proliferating and proliferating tissues, indicating a replication- independent role in DNA repair. The SMUG1 enzyme is found in vertebrates and insects, whereas it is absent in nematodes, plants and fungi. We propose a model in which SMUG1 has evolved in higher eukaryotes as an anti-mutator distinct from the UNG enzyme, the latter being largely localized to replication foci in mammalian cells to counteract de novo dUMP incorporation into DNA. PMID:11483530

  9. A TetR family transcriptional factor directly regulates the expression of a 3-methyladenine DNA glycosylase and physically interacts with the enzyme to stimulate its base excision activity in Mycobacterium bovis BCG.

    Science.gov (United States)

    Liu, Lei; Huang, Cheng; He, Zheng-Guo

    2014-03-28

    3-Methyladenine DNA glycosylase recognizes and excises a wide range of damaged bases and thus plays a critical role in base excision repair. However, knowledge on the regulation of DNA glycosylase in prokaryotes and eukaryotes is limited. In this study, we successfully characterized a TetR family transcriptional factor from Mycobacterium bovis bacillus Calmette-Guerin (BCG), namely BCG0878c, which directly regulates the expression of 3-methyladenine DNA glycosylase (designated as MbAAG) and influences the base excision activity of this glycosylase at the post-translational level. Using electrophoretic mobility shift assay and DNase I footprinting experiments, we identified two conserved motifs within the upstream region of mbaag specifically recognized by BCG0878c. Significant down-regulation of mbaag was observed in BCG0878c-overexpressed M. bovis BCG strains. By contrast, about 12-fold up-regulation of mbaag expression was found in bcg0878c-deleted mutant M. bovis BCG strains. β-Galactosidase activity assays also confirmed these results. Thus, BCG0878c can function as a negative regulator of mbaag expression. In addition, the regulator was shown to physically interact with MbAAG to enhance the ability of the glycosylase to bind damaged DNA. Interaction between the two proteins was further found to facilitate AAG-catalyzed removal of hypoxanthine from DNA. These results indicate that a TetR family protein can dually regulate the function of 3-methyladenine DNA glycosylase in M. bovis BCG both at the transcriptional and post-translational levels. These findings enhance our understanding of the expression and regulation of AAG in mycobacteria.

  10. RPA physically interacts with the human DNA glycosylase NEIL1 to regulate excision of oxidative DNA base damage in primer-template structures.

    Science.gov (United States)

    Theriot, Corey A; Hegde, Muralidhar L; Hazra, Tapas K; Mitra, Sankar

    2010-06-04

    The human DNA glycosylase NEIL1, activated during the S-phase, has been shown to excise oxidized base lesions in single-strand DNA substrates. Furthermore, our previous work demonstrating functional interaction of NEIL1 with PCNA and flap endonuclease 1 (FEN1) suggested its involvement in replication-associated repair. Here we show interaction of NEIL1 with replication protein A (RPA), the heterotrimeric single-strand DNA binding protein that is essential for replication and other DNA transactions. The NEIL1 immunocomplex isolated from human cells contains RPA, and its abundance in the complex increases after exposure to oxidative stress. NEIL1 directly interacts with the large subunit of RPA (K(d) approximately 20 nM) via the common interacting interface (residues 312-349) in NEIL1's disordered C-terminal region. RPA inhibits the base excision activity of both wild-type NEIL1 (389 residues) and its C-terminal deletion CDelta78 mutant (lacking the interaction domain) for repairing 5-hydroxyuracil (5-OHU) in a primer-template structure mimicking the DNA replication fork. This inhibition is reduced when the damage is located near the primer-template junction. Contrarily, RPA moderately stimulates wild-type NEIL1 but not the CDelta78 mutant when 5-OHU is located within the duplex region. While NEIL1 is inhibited by both RPA and Escherichia coli single-strand DNA binding protein, only inhibition by RPA is relieved by PCNA. These results showing modulation of NEIL1's activity on single-stranded DNA substrate by RPA and PCNA support NEIL1's involvement in repairing the replicating genome. Copyright 2010 Elsevier B.V. All rights reserved.

  11. Uracil DNA glycosylase counteracts APOBEC3G-induced hypermutation of hepatitis B viral genomes: excision repair of covalently closed circular DNA.

    Directory of Open Access Journals (Sweden)

    Kouichi Kitamura

    Full Text Available The covalently closed circular DNA (cccDNA of the hepatitis B virus (HBV plays an essential role in chronic hepatitis. The cellular repair system is proposed to convert cytoplasmic nucleocapsid (NC DNA (partially double-stranded DNA into cccDNA in the nucleus. Recently, antiviral cytidine deaminases, AID/APOBEC proteins, were shown to generate uracil residues in the NC-DNA through deamination, resulting in cytidine-to-uracil (C-to-U hypermutation of the viral genome. We investigated whether uracil residues in hepadnavirus DNA were excised by uracil-DNA glycosylase (UNG, a host factor for base excision repair (BER. When UNG activity was inhibited by the expression of the UNG inhibitory protein (UGI, hypermutation of NC-DNA induced by either APOBEC3G or interferon treatment was enhanced in a human hepatocyte cell line. To assess the effect of UNG on the cccDNA viral intermediate, we used the duck HBV (DHBV replication model. Sequence analyses of DHBV DNAs showed that cccDNA accumulated G-to-A or C-to-T mutations in APOBEC3G-expressing cells, and this was extensively enhanced by UNG inhibition. The cccDNA hypermutation generated many premature stop codons in the P gene. UNG inhibition also enhanced the APOBEC3G-mediated suppression of viral replication, including reduction of NC-DNA, pre-C mRNA, and secreted viral particle-associated DNA in prolonged culture. Enhancement of APOBEC3G-mediated suppression by UNG inhibition was not observed when the catalytic site of APOBEC3G was mutated. Transfection experiments of recloned cccDNAs revealed that the combination of UNG inhibition and APOBEC3G expression reduced the replication ability of cccDNA. Taken together, these data indicate that UNG excises uracil residues from the viral genome during or after cccDNA formation in the nucleus and imply that BER pathway activities decrease the antiviral effect of APOBEC3-mediated hypermutation.

  12. DNA Base Excision Repair (BER) and Cancer Gene Therapy: Use of the Human N-mythlpurien DNA Glycosylase (MPG) to Sensitize Breast Cancer Cells to Low Dose Chemotherapy

    National Research Council Canada - National Science Library

    Harvey, Tia

    2003-01-01

    The DNA Base Excision Repair (PER) pathway is responsible for the repair of alkylation and oxidative DNA damage resulting in protection against the deleterious effects of endogenous and exogenous agents encountered on a daily basis...

  13. DNA N-glycosylases and uv repair

    Energy Technology Data Exchange (ETDEWEB)

    Demple, B; Linn, S

    1980-09-18

    Repair of some DNA photoproducts can be mediated by glycosylic bond hydrolysis. Thus, Escherichia coli endonuclease III releases 5,6-hydrated thymines as free bases, while T4 uv endonuclease releases one of two glycosylic bonds holding pyrimidine dimers in DNA. In contrast, uninfected E. coli apparently does not excise pyrimidine dimers via a DNA glycosylase.

  14. DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

    DEFF Research Database (Denmark)

    Osorio, Ana; Milne, Roger L; Kuchenbaecker, Karoline

    2014-01-01

    Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of th...

  15. DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

    NARCIS (Netherlands)

    A. Osorio (Ana); R.L. Milne (Roger); K.B. Kuchenbaecker (Karoline); T. Vaclová (Tereza); G. Pita (Guillermo); R. Alonso (Rosario); P. Peterlongo (Paolo); I. Blanco (Ignacio); M. de La Hoya (Miguel); M. Durán (Mercedes); O. Díez (Orland); T. Ramon Y Cajal; I. Konstantopoulou (I.); C. Martínez-Bouzas (Cristina); R. Andrés Conejero (Raquel); P. Soucy (Penny); L. McGuffog (Lesley); D. Barrowdale (Daniel); A. Lee (Andrew); B. Arver (Brita Wasteson); J. Rantala (Johanna); N. Loman (Niklas); H. Ehrencrona (Hans); O.I. Olopade (Olofunmilayo); M.S. Beattie (Mary); S.M. Domchek (Susan); K.L. Nathanson (Katherine); R. Rebbeck (Timothy); B.K. Arun (Banu); B.Y. Karlan (Beth); C.S. Walsh (Christine); K.J. Lester (Kathryn); E.M. John (Esther); A.S. Whittemore (Alice); M.B. Daly (Mary); M.C. Southey (Melissa); J.L. Hopper (John); M.-B. Terry (Mary-Beth); S.S. Buys (Saundra); R. Janavicius (Ramunas); C.M. Dorfling (Cecilia); E.J. van Rensburg (Elizabeth); L. Steele (Linda); S.L. Neuhausen (Susan); Y.C. Ding (Yuan); T.V.O. Hansen (Thomas); L. Jønson (Lars); B. Ejlertsen (Bent); A-M. Gerdes (Anne-Marie); J. Infante (Jon); B. Herráez (Belén); L.T. Moreno (Leticia Thais); J.N. Weitzel (Jeffrey); J. Herzog (Josef); K. Weeman (Kisa); S. Manoukian (Siranoush); B. Peissel (Bernard); D. Zaffaroni (D.); G. Scuvera (Giulietta); B. Bonnani (Bernardo); F. Mariette (F.); S. Volorio (Sara); A. Viel (Alessandra); L. Varesco (Liliana); L. Papi (Laura); L. Ottini (Laura); M.G. Tibiletti (Maria Grazia); P. Radice (Paolo); D. Yannoukakos (Drakoulis); J. Garber; S.D. Ellis (Steve); D. Frost (Debra); R. Platte (Radka); E. Fineberg (Elena); D.G. Evans (Gareth); F. Lalloo (Fiona); L. Izatt (Louise); R. Eeles (Rosalind); J.W. Adlard (Julian); R. Davidson (Rosemarie); T.J. Cole (Trevor); D. Eccles (Diana); J. Cook (Jackie); S.V. Hodgson (Shirley); C. Brewer (Carole); M. Tischkowitz (Marc); F. Douglas (Fiona); M.E. Porteous (Mary); L. Side (Lucy); L.J. Walker (Lisa); P.J. Morrison (Patrick); A. Donaldson (Alan); J. Kennedy (John); C. Foo (Claire); A.K. Godwin (Andrew); R.K. Schmutzler (Rita); B. Wapenschmidt (Barbara); K. Rhiem (Kerstin); C.W. Engel (Christoph); A. Meindl (Alfons); N. Ditsch (Nina); N. Arnold (Norbert); H. Plendl (Hansjoerg); D. Niederacher (Dieter); C. Sutter (Christian); S. Wang-Gohrke (Shan); D. Steinemann (Doris); S. Preisler-Adams (Sabine); K. Kast (Karin); R. Varon-Mateeva (Raymonda); P.A. Gehrig (Paola A.); D. Stoppa-Lyonnet (Dominique); O. Sinilnikova (Olga); S. Mazoyer (Sylvie); F. Damiola (Francesca); B. Poppe (Bruce); K. Claes (Kathleen); M. Piedmonte (Marion); K. Tucker (Kathryn); F.J. Backes (Floor); P.M. Rodríguez; W. Brewster (Wendy); K. Wakeley (Katie); T. Rutherford (Thomas); T. Caldes (Trinidad); H. Nevanlinna (Heli); K. Aittomäki (Kristiina); M.A. Rookus (Matti); T.A.M. van Os (Theo); L. van der Kolk (Lizet); J.L. de Lange (J.); E.J. Meijers-Heijboer (Hanne); A.H. van der Hout (Annemarie); C.J. van Asperen (Christi); E.B. Gómez García (Encarna); N. Hoogerbrugge (Nicoline); J.M. Collée (Margriet); C.H.M. van Deurzen (Carolien); R.B. van der Luijt (Rob); P. Devilee (Peter); E. Olah (Edith); C. Lazaro (Conxi); A. Teulé (A.); M. Menéndez (Mireia); A. Jakubowska (Anna); C. Cybulski (Cezary); J. Gronwald (Jacek); J. Lubinski (Jan); K. Durda (Katarzyna); K. Jaworska-Bieniek (Katarzyna); O.T. Johannson (Oskar); C. Maugard; M. Montagna (Marco); S. Tognazzo (Silvia); P.J. Teixeira; S. Healey (Sue); C. Olswold (Curtis); L. Guidugli (Lucia); N.M. Lindor (Noralane); S. Slager (Susan); C. Szabo (Csilla); J. Vijai (Joseph); M. Robson (Mark); N. Kauff (Noah); L. Zhang (Lingling); R. Rau-Murthy (Rohini); A. Fink-Retter (Anneliese); C.F. Singer (Christian); C. Rappaport (Christine); D. Geschwantler Kaulich (Daphne); G. Pfeiler (Georg); M.-K. Tea; A. Berger (Annemarie); C. Phelan (Catherine); M.H. Greene (Mark); P.L. Mai (Phuong); F. Lejbkowicz (Flavio); I.L. Andrulis (Irene); A.M. Mulligan (Anna Marie); G. Glendon (Gord); A.E. Toland (Amanda); S.E. Bojesen (Stig); I.S. Pedersen (Inge Sokilde); L. Sunde (Lone); M. Thomassen (Mads); T.A. Kruse (Torben); U.B. Jensen; E. Friedman (Eitan); Y. Laitman (Yael); S.P. Shimon (Shani Paluch); J. Simard (Jacques); D.F. Easton (Douglas); K. Offit (Kenneth); F.J. Couch (Fergus); G. Chenevix-Trench (Georgia); A.C. Antoniou (Antonis); J. Benítez (Javier)

    2014-01-01

    textabstractSingle Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between

  16. DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers

    NARCIS (Netherlands)

    Osorio, A.; Milne, R.L.; Kuchenbaecker, K.; Vaclova, T.; Pita, G.; Alonso, R.; Peterlongo, P.; Blanco, I.; Hoya, M. de la; Duran, M.; Diez, O.; Ramon, Y.C.T.; Konstantopoulou, I.; Martinez-Bouzas, C.; Conejero, R. Andres; Soucy, P.; McGuffog, L.; Barrowdale, D.; Lee, A.; Swe, B.; Arver, B.; Rantala, J.; Loman, N.; Ehrencrona, H.; Olopade, O.I.; Beattie, M.S.; Domchek, S.M.; Nathanson, K.; Rebbeck, T.R.; Arun, B.K.; Karlan, B.Y.; Walsh, C.; Lester, J.; John, E.M.; Whittemore, A.S.; Daly, M.B.; Southey, M.; Hopper, J.; Terry, M.B.; Buys, S.S.; Janavicius, R.; Dorfling, C.M.; Rensburg, E.J. van; Steele, L.; Neuhausen, S.L.; Ding, Y.C.; Hansen, T.V.; Jonson, L.; Ejlertsen, B.; Gerdes, A.M.; Infante, M.; Herraez, B.; Moreno, L.T.; Weitzel, J.N.; Herzog, J.; Weeman, K.; Manoukian, S.; Peissel, B.; Zaffaroni, D.; Scuvera, G.; Bonanni, B.; Mariette, F.; Volorio, S.; Viel, A.; Varesco, L.; Papi, L.; Ottini, L.; Tibiletti, M.G.; Radice, P.; Yannoukakos, D.; Garber, J.; Ellis, S.; Frost, D.; Platte, R.; Fineberg, E.; Evans, G.; Lalloo, F.; Izatt, L.; Eeles, R.; Adlard, J.; Davidson, R.; Cole, T.; Eccles, D.; Cook, J; Hodgson, S.; Brewer, C.; Tischkowitz, M.; Douglas, F.; Porteous, M.; Side, L.; Walker, L.; Morrison, P.; Donaldson, A.; Kennedy, J.; Foo, C.; Godwin, A.K.; Schmutzler, R.K.; Wappenschmidt, B.; Rhiem, K.; Engel, C.; Hoogerbrugge-van der Linden, N.; et al.,

    2014-01-01

    Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the

  17. The mechanism of the glycosylase reaction with hOGG1 base-excision repair enzyme: concerted effect of Lys249 and Asp268 during excision of 8-oxoguanine

    Czech Academy of Sciences Publication Activity Database

    Šebera, Jakub; Hattori, Y.; Sato, D.; Řeha, David; Nencka, Radim; Kohno, T.; Kojima, C.; Tanaka, Y.; Sychrovský, Vladimír

    2017-01-01

    Roč. 45, č. 9 (2017), s. 5231-5242 ISSN 0305-1048 R&D Projects: GA ČR GA13-27676S Institutional support: RVO:61388963 ; RVO:61388971 Keywords : 8-oxoguanine * hOGG1 * QM/MM * NMR * base-excision repair Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry Impact factor: 10.162, year: 2016 https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkx157

  18. In vivo repair of methylation damage in Aag 3-methyladenine DNA glycosylase null mouse cells

    OpenAIRE

    Smith, Stephen A.; Engelward, Bevin P.

    2000-01-01

    3-Methyladenine (3MeA) DNA glycosylases initiate base excision repair by removing 3MeA. These glycosylases also remove a broad spectrum of spontaneous and environmentally induced base lesions in vitro. Mouse cells lacking the Aag 3MeA DNA glycosylase (also known as the Mpg, APNG or ANPG DNA glycosylase) are susceptible to 3MeA-induced S phase arrest, chromosome aberrations and apoptosis, but it is not known if Aag is solely responsible for repair of 3MeA in vivo. Here we show that in Aag–/– c...

  19. Poxvirus uracil-DNA glycosylase-An unusual member of the family I uracil-DNA glycosylases: Poxvirus Uracil-DNA Glycosylase

    Energy Technology Data Exchange (ETDEWEB)

    Schormann, Norbert [Department of Medicine, University of Alabama at Birmingham, Birmingham Alabama 35294; Zhukovskaya, Natalia [Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia Pennsylvania 19104; Bedwell, Gregory [Department of Microbiology, University of Alabama at Birmingham, Birmingham Alabama 35294; Nuth, Manunya [Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia Pennsylvania 19104; Gillilan, Richard [MacCHESS (Macromolecular Diffraction Facility at CHESS) Cornell University, Ithaca New York 14853; Prevelige, Peter E. [Department of Microbiology, University of Alabama at Birmingham, Birmingham Alabama 35294; Ricciardi, Robert P. [Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia Pennsylvania 19104; Abramson Cancer Center, School of Medicine, University of Pennsylvania, Philadelphia Pennsylvania 19104; Banerjee, Surajit [Department of Chemistry and Chemical Biology, Cornell University, and NE-CAT Argonne Illinois 60439; Chattopadhyay, Debasish [Department of Medicine, University of Alabama at Birmingham, Birmingham Alabama 35294

    2016-11-02

    We report that uracil-DNA glycosylases are ubiquitous enzymes, which play a key role repairing damages in DNA and in maintaining genomic integrity by catalyzing the first step in the base excision repair pathway. Within the superfamily of uracil-DNA glycosylases family I enzymes or UNGs are specific for recognizing and removing uracil from DNA. These enzymes feature conserved structural folds, active site residues and use common motifs for DNA binding, uracil recognition and catalysis. Within this family the enzymes of poxviruses are unique and most remarkable in terms of amino acid sequences, characteristic motifs and more importantly for their novel non-enzymatic function in DNA replication. UNG of vaccinia virus, also known as D4, is the most extensively characterized UNG of the poxvirus family. D4 forms an unusual heterodimeric processivity factor by attaching to a poxvirus-specific protein A20, which also binds to the DNA polymerase E9 and recruits other proteins necessary for replication. D4 is thus integrated in the DNA polymerase complex, and its DNA-binding and DNA scanning abilities couple DNA processivity and DNA base excision repair at the replication fork. In conclusion, the adaptations necessary for taking on the new function are reflected in the amino acid sequence and the three-dimensional structure of D4. We provide an overview of the current state of the knowledge on the structure-function relationship of D4.

  20. Structure of a DNA glycosylase that unhooks interstrand cross-links

    Energy Technology Data Exchange (ETDEWEB)

    Mullins, Elwood A.; Warren, Garrett M.; Bradley, Noah P.; Eichman, Brandt F. (Vanderbilt)

    2017-04-10

    DNA glycosylases are important editing enzymes that protect genomic stability by excising chemically modified nucleobases that alter normal DNA metabolism. These enzymes have been known only to initiate base excision repair of small adducts by extrusion from the DNA helix. However, recent reports have described both vertebrate and microbial DNA glycosylases capable of unhooking highly toxic interstrand cross-links (ICLs) and bulky minor groove adducts normally recognized by Fanconi anemia and nucleotide excision repair machinery, although the mechanisms of these activities are unknown. Here we report the crystal structure of Streptomyces sahachiroi AlkZ (previously Orf1), a bacterial DNA glycosylase that protects its host by excising ICLs derived from azinomycin B (AZB), a potent antimicrobial and antitumor genotoxin. AlkZ adopts a unique fold in which three tandem winged helix-turn-helix motifs scaffold a positively charged concave surface perfectly shaped for duplex DNA. Through mutational analysis, we identified two glutamine residues and a β-hairpin within this putative DNA-binding cleft that are essential for catalytic activity. Additionally, we present a molecular docking model for how this active site can unhook either or both sides of an AZB ICL, providing a basis for understanding the mechanisms of base excision repair of ICLs. Given the prevalence of this protein fold in pathogenic bacteria, this work also lays the foundation for an emerging role of DNA repair in bacteria-host pathogenesis.

  1. Hide and seek: How do DNA glycosylases locate oxidatively damaged DNA bases amidst a sea of undamaged bases?

    Science.gov (United States)

    Lee, Andrea J; Wallace, Susan S

    2017-06-01

    The first step of the base excision repair (BER) pathway responsible for removing oxidative DNA damage utilizes DNA glycosylases to find and remove the damaged DNA base. How glycosylases find the damaged base amidst a sea of undamaged bases has long been a question in the BER field. Single molecule total internal reflection fluorescence microscopy (SM TIRFM) experiments have allowed for an exciting look into this search mechanism and have found that DNA glycosylases scan along the DNA backbone in a bidirectional and random fashion. By comparing the search behavior of bacterial glycosylases from different structural families and with varying substrate specificities, it was found that glycosylases search for damage by periodically inserting a wedge residue into the DNA stack as they redundantly search tracks of DNA that are 450-600bp in length. These studies open up a wealth of possibilities for further study in real time of the interactions of DNA glycosylases and other BER enzymes with various DNA substrates. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Pre-steady-state fluorescence analysis of damaged DNA transfer from human DNA glycosylases to AP endonuclease APE1.

    Science.gov (United States)

    Kuznetsova, Alexandra A; Kuznetsov, Nikita A; Ishchenko, Alexander A; Saparbaev, Murat K; Fedorova, Olga S

    2014-10-01

    DNA glycosylases remove the modified, damaged or mismatched bases from the DNA by hydrolyzing the N-glycosidic bonds. Some enzymes can further catalyze the incision of a resulting abasic (apurinic/apyrimidinic, AP) site through β- or β,δ-elimination mechanisms. In most cases, the incision reaction of the AP-site is catalyzed by special enzymes called AP-endonucleases. Here, we report the kinetic analysis of the mechanisms of modified DNA transfer from some DNA glycosylases to the AP endonuclease, APE1. The modified DNA contained the tetrahydrofurane residue (F), the analogue of the AP-site. DNA glycosylases AAG, OGG1, NEIL1, MBD4(cat) and UNG from different structural superfamilies were used. We found that all DNA glycosylases may utilise direct protein-protein interactions in the transient ternary complex for the transfer of the AP-containing DNA strand to APE1. We hypothesize a fast "flip-flop" exchange mechanism of damaged and undamaged DNA strands within this complex for monofunctional DNA glycosylases like MBD4(cat), AAG and UNG. Bifunctional DNA glycosylase NEIL1 creates tightly specific complex with DNA containing F-site thereby efficiently competing with APE1. Whereas APE1 fast displaces other bifunctional DNA glycosylase OGG1 on F-site thereby induces its shifts to undamaged DNA regions. Kinetic analysis of the transfer of DNA between human DNA glycosylases and APE1 allows us to elucidate the critical step in the base excision repair pathway. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. A novel monofunctional DNA glycosylase activity against thymine glycol in mouse cell nuclei

    International Nuclear Information System (INIS)

    Yamamoto, Ryohei; Akiyama, Miyuki; Matsuyama, Satoshi; Kubo, Kihei; Ide, Hiroshi; Yamamoto, Kazuo

    2008-01-01

    Reactive oxygen species continuously oxidize DNA bases and threaten the genetic integrity. Thymine glycol (TG), one of the representative oxidized products, is repaired mainly by base excision repair (BER). In Escherichia coli, endonuclease III (Nth) and endonuclease VIII (Nei) are known to actively remove TG from DNA, and the homologs are well conserved in various organisms. These are bifunctional glycosylases, also associated with apurinic/apyrimidinic (AP) lyase activity. In the present study, a monofunctional TG-DNA glycosylase activity is shown to be one of the predominant nuclear activities present in some mouse tissues. By combining hypertonic extraction and column chromatography, we successfully separated the novel activity from majority of the bifunctional activities. Since it has been reported that mNTH1 may not be a dominant nuclear activity, the monofunctional glycosylase activity, together with mNEIL1, may be the major TG-DNA glycosylases in the mouse nucleus. The optimal reaction conditions for the monofunctional activity were found to be pH 7-8 and 100-150 mM KC1, and the activity was resistant to 20 mM EDTA. High monofunctional activity was detected in the spleen and stomach, while the level was significantly lower in the liver, suggesting that the contribution of the monofunctional activity is variable among organs. (author)

  4. Modeling base excision repair in Escherichia coli bacterial cells

    International Nuclear Information System (INIS)

    Belov, O.V.

    2011-01-01

    A model describing the key processes in Escherichia coli bacterial cells during base excision repair is developed. The mechanism is modeled of damaged base elimination involving formamidopyrimidine DNA glycosylase (the Fpg protein), which possesses several types of activities. The modeling of the transitions between DNA states is based on a stochastic approach to the chemical reaction description

  5. Functional characterization of 8-oxoguanine DNA glycosylase of Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Carolina Furtado

    Full Text Available The oxidative lesion 8-oxoguanine (8-oxoG is removed during base excision repair by the 8-oxoguanine DNA glycosylase 1 (Ogg1. This lesion can erroneously pair with adenine, and the excision of this damaged base by Ogg1 enables the insertion of a guanine and prevents DNA mutation. In this report, we identified and characterized Ogg1 from the protozoan parasite Trypanosoma cruzi (TcOgg1, the causative agent of Chagas disease. Like most living organisms, T. cruzi is susceptible to oxidative stress, hence DNA repair is essential for its survival and improvement of infection. We verified that the TcOGG1 gene encodes an 8-oxoG DNA glycosylase by complementing an Ogg1-defective Saccharomyces cerevisiae strain. Heterologous expression of TcOGG1 reestablished the mutation frequency of the yeast mutant ogg1(-/- (CD138 to wild type levels. We also demonstrate that the overexpression of TcOGG1 increases T. cruzi sensitivity to hydrogen peroxide (H(2O(2. Analysis of DNA lesions using quantitative PCR suggests that the increased susceptibility to H(2O(2 of TcOGG1-overexpressor could be a consequence of uncoupled BER in abasic sites and/or strand breaks generated after TcOgg1 removes 8-oxoG, which are not rapidly repaired by the subsequent BER enzymes. This hypothesis is supported by the observation that TcOGG1-overexpressors have reduced levels of 8-oxoG both in the nucleus and in the parasite mitochondrion. The localization of TcOgg1 was examined in parasite transfected with a TcOgg1-GFP fusion, which confirmed that this enzyme is in both organelles. Taken together, our data indicate that T. cruzi has a functional Ogg1 ortholog that participates in nuclear and mitochondrial BER.

  6. Excision without excision

    International Nuclear Information System (INIS)

    Brown, David; Sarbach, Olivier; Schnetter, Erik; Diener, Peter; Tiglio, Manuel; Hawke, Ian; Pollney, Denis

    2007-01-01

    to turducken (turduckens, turduckening, turduckened, turduckened) [math.]: To stuff a black hole. We analyze and apply an alternative to black hole excision based on smoothing the interior of black holes with arbitrary initial data, and solving the vacuum Einstein evolution equations everywhere. By deriving the constraint propagation system for our hyperbolic formulation of the BSSN evolution system we rigorously prove that the constraints propagate causally and so any constraint violations introduced inside the black holes cannot affect the exterior spacetime. We present evolutions of Cook-Pfeiffer binary black hole initial configurations showing that these techniques appear to work robustly for generic data. We also present evidence from spherically symmetric evolutions that for the gauge conditions used the same stationary end-state is approached irrespective of the choice of initial data and smoothing procedure

  7. Structure of uracil-DNA glycosylase from Mycobacterium tuberculosis: insights into interactions with ligands

    International Nuclear Information System (INIS)

    Kaushal, Prem Singh; Talawar, Ramappa K.; Varshney, Umesh; Vijayan, M.

    2010-01-01

    The molecule of uracil-DNA glycosylase from M. tuberculosis exhibits domain motion on binding to DNA or a proteinaceous inhibitor. The highly conserved DNA-binding region interacts with a citrate ion in the structure. Uracil N-glycosylase (Ung) is the most thoroughly studied of the group of uracil DNA-glycosylase (UDG) enzymes that catalyse the first step in the uracil excision-repair pathway. The overall structure of the enzyme from Mycobacterium tuberculosis is essentially the same as that of the enzyme from other sources. However, differences exist in the N- and C-terminal stretches and some catalytic loops. Comparison with appropriate structures indicate that the two-domain enzyme closes slightly when binding to DNA, while it opens slightly when binding to the proteinaceous inhibitor Ugi. The structural changes in the catalytic loops on complexation reflect the special features of their structure in the mycobacterial protein. A comparative analysis of available sequences of the enzyme from different sources indicates high conservation of amino-acid residues in the catalytic loops. The uracil-binding pocket in the structure is occupied by a citrate ion. The interactions of the citrate ion with the protein mimic those of uracil, in addition to providing insights into other possible interactions that inhibitors could be involved in

  8. Overexpression, purification, crystallization and preliminary X-ray analysis of uracil N-glycosylase from Mycobacterium tuberculosis in complex with a proteinaceous inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Prem [Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012 (India); Talawar, Ramappa K.; Krishna, P. D. V.; Varshney, Umesh [Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012 (India); Vijayan, M., E-mail: mv@mbu.iisc.ernet.in [Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012 (India)

    2006-12-01

    Uracil N-glycosylase from M. tuberculosis has been crystallized in complex with a proteinaceous inhibitor (Ugi) and X-ray diffraction data have been collected. Uracil N-glycosylase is an enzyme which initiates the pathway of uracil-excision repair of DNA. The enzyme from Mycobacterium tuberculosis was co-expressed with a proteinaceous inhibitor from Bacillus subtilis phage and was crystallized in monoclinic space group C2, with unit-cell parameters a = 201.14, b = 64.27, c = 203.68 Å, β = 109.7°. X-ray data from the crystal have been collected for structure analysis.

  9. Overexpression, purification, crystallization and preliminary X-ray analysis of uracil N-glycosylase from Mycobacterium tuberculosis in complex with a proteinaceous inhibitor

    International Nuclear Information System (INIS)

    Singh, Prem; Talawar, Ramappa K.; Krishna, P. D. V.; Varshney, Umesh; Vijayan, M.

    2006-01-01

    Uracil N-glycosylase from M. tuberculosis has been crystallized in complex with a proteinaceous inhibitor (Ugi) and X-ray diffraction data have been collected. Uracil N-glycosylase is an enzyme which initiates the pathway of uracil-excision repair of DNA. The enzyme from Mycobacterium tuberculosis was co-expressed with a proteinaceous inhibitor from Bacillus subtilis phage and was crystallized in monoclinic space group C2, with unit-cell parameters a = 201.14, b = 64.27, c = 203.68 Å, β = 109.7°. X-ray data from the crystal have been collected for structure analysis

  10. Recognition and processing of a new repertoire of DNA substrates by human 3-methyladenine DNA glycosylase (AAG).

    Science.gov (United States)

    Lee, Chun-Yue I; Delaney, James C; Kartalou, Maria; Lingaraju, Gondichatnahalli M; Maor-Shoshani, Ayelet; Essigmann, John M; Samson, Leona D

    2009-03-10

    The human 3-methyladenine DNA glycosylase (AAG) recognizes and excises a broad range of purines damaged by alkylation and oxidative damage, including 3-methyladenine, 7-methylguanine, hypoxanthine (Hx), and 1,N(6)-ethenoadenine (epsilonA). The crystal structures of AAG bound to epsilonA have provided insights into the structural basis for substrate recognition, base excision, and exclusion of normal purines and pyrimidines from its substrate recognition pocket. In this study, we explore the substrate specificity of full-length and truncated Delta80AAG on a library of oligonucleotides containing structurally diverse base modifications. Substrate binding and base excision kinetics of AAG with 13 damaged oligonucleotides were examined. We found that AAG bound to a wide variety of purine and pyrimidine lesions but excised only a few of them. Single-turnover excision kinetics showed that in addition to the well-known epsilonA and Hx substrates, 1-methylguanine (m1G) was also excised efficiently by AAG. Thus, along with epsilonA and ethanoadenine (EA), m1G is another substrate that is shared between AAG and the direct repair protein AlkB. In addition, we found that both the full-length and truncated AAG excised 1,N(2)-ethenoguanine (1,N(2)-epsilonG), albeit weakly, from duplex DNA. Uracil was excised from both single- and double-stranded DNA, but only by full-length AAG, indicating that the N-terminus of AAG may influence glycosylase activity for some substrates. Although AAG has been primarily shown to act on double-stranded DNA, AAG excised both epsilonA and Hx from single-stranded DNA, suggesting the possible significance of repair of these frequent lesions in single-stranded DNA transiently generated during replication and transcription.

  11. Mitochondrial base excision repair assays

    DEFF Research Database (Denmark)

    Maynard, Scott; de Souza-Pinto, Nadja C; Scheibye-Knudsen, Morten

    2010-01-01

    The main source of mitochondrial DNA (mtDNA) damage is reactive oxygen species (ROS) generated during normal cellular metabolism. The main mtDNA lesions generated by ROS are base modifications, such as the ubiquitous 8-oxoguanine (8-oxoG) lesion; however, base loss and strand breaks may also occur....... Many human diseases are associated with mtDNA mutations and thus maintaining mtDNA integrity is critical. All of these lesions are repaired primarily by the base excision repair (BER) pathway. It is now known that mammalian mitochondria have BER, which, similarly to nuclear BER, is catalyzed by DNA...... glycosylases, AP endonuclease, DNA polymerase (POLgamma in mitochondria) and DNA ligase. This article outlines procedures for measuring oxidative damage formation and BER in mitochondria, including isolation of mitochondria from tissues and cells, protocols for measuring BER enzyme activities, gene...

  12. The Role of 8-Oxoguanine DNA Glycosylase-1 in Inflammation

    Directory of Open Access Journals (Sweden)

    Xueqing Ba

    2014-09-01

    Full Text Available Many, if not all, environmental pollutants/chemicals and infectious agents increase intracellular levels of reactive oxygen species (ROS at the site of exposure. ROS not only function as intracellular signaling entities, but also induce damage to cellular molecules including DNA. Among the several dozen ROS-induced DNA base lesions generated in the genome, 8-oxo-7,8-dihydroguanine (8-oxoG is one of the most abundant because of guanine’s lowest redox potential among DNA bases. In mammalian cells, 8-oxoG is repaired by the 8-oxoguanine DNA glycosylase-1 (OGG1-initiated DNA base excision repair pathway (OGG1–BER. Accumulation of 8-oxoG in DNA has traditionally been associated with mutagenesis, as well as various human diseases and aging processes, while the free 8-oxoG base in body fluids is one of the best biomarkers of ongoing pathophysiological processes. In this review, we discuss the biological significance of the 8-oxoG base and particularly the role of OGG1–BER in the activation of small GTPases and changes in gene expression, including those that regulate pro-inflammatory chemokines/cytokines and cause inflammation.

  13. The DNA glycosylases OGG1 and NEIL3 influence differentiation potential, proliferation, and senescence-associated signs in neural stem cells

    International Nuclear Information System (INIS)

    Reis, Amilcar; Hermanson, Ola

    2012-01-01

    Highlights: ► DNA glycosylases OGG1 and NEIL3 are required for neural stem cell state. ► No effect on cell viability by OGG1 or NEIL3 knockdown in neural stem cells. ► OGG1 or NEIL3 RNA knockdown result in decreased proliferation and differentiation. ► Increased HP1γ immunoreactivity after NEIL3 knockdown suggests premature senescence. -- Abstract: Embryonic neural stem cells (NSCs) exhibit self-renewal and multipotency as intrinsic characteristics that are key parameters for proper brain development. When cells are challenged by oxidative stress agents the resulting DNA lesions are repaired by DNA glycosylases through the base excision repair (BER) pathway as a means to maintain the fidelity of the genome, and thus, proper cellular characteristics. The functional roles for DNA glycosylases in NSCs have however remained largely unexplored. Here we demonstrate that RNA knockdown of the DNA glycosylases OGG1 and NEIL3 decreased NSC differentiation ability and resulted in decreased expression of both neuronal and astrocytic genes after mitogen withdrawal, as well as the stem cell marker Musashi-1. Furthermore, while cell survival remained unaffected, NEIL3 deficient cells displayed decreased cell proliferation rates along with an increase in HP1γ immunoreactivity, a sign of premature senescence. Our results suggest that DNA glycosylases play multiple roles in governing essential neural stem cell characteristics.

  14. The DNA glycosylases OGG1 and NEIL3 influence differentiation potential, proliferation, and senescence-associated signs in neural stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Reis, Amilcar [Linnaeus Center in Developmental Biology for Regenerative Medicine (DBRM), Department of Neuroscience, Karolinska Institutet, SE 17177 Stockholm (Sweden); Hermanson, Ola, E-mail: ola.hermanson@ki.se [Linnaeus Center in Developmental Biology for Regenerative Medicine (DBRM), Department of Neuroscience, Karolinska Institutet, SE 17177 Stockholm (Sweden)

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer DNA glycosylases OGG1 and NEIL3 are required for neural stem cell state. Black-Right-Pointing-Pointer No effect on cell viability by OGG1 or NEIL3 knockdown in neural stem cells. Black-Right-Pointing-Pointer OGG1 or NEIL3 RNA knockdown result in decreased proliferation and differentiation. Black-Right-Pointing-Pointer Increased HP1{gamma} immunoreactivity after NEIL3 knockdown suggests premature senescence. -- Abstract: Embryonic neural stem cells (NSCs) exhibit self-renewal and multipotency as intrinsic characteristics that are key parameters for proper brain development. When cells are challenged by oxidative stress agents the resulting DNA lesions are repaired by DNA glycosylases through the base excision repair (BER) pathway as a means to maintain the fidelity of the genome, and thus, proper cellular characteristics. The functional roles for DNA glycosylases in NSCs have however remained largely unexplored. Here we demonstrate that RNA knockdown of the DNA glycosylases OGG1 and NEIL3 decreased NSC differentiation ability and resulted in decreased expression of both neuronal and astrocytic genes after mitogen withdrawal, as well as the stem cell marker Musashi-1. Furthermore, while cell survival remained unaffected, NEIL3 deficient cells displayed decreased cell proliferation rates along with an increase in HP1{gamma} immunoreactivity, a sign of premature senescence. Our results suggest that DNA glycosylases play multiple roles in governing essential neural stem cell characteristics.

  15. Glycosylase-mediated repair of radiation-induced DNA bases: substrate specificities and mechanisms

    International Nuclear Information System (INIS)

    D'ham, Cedric

    1998-01-01

    Cellular DNA is subject to permanent damage and repair processes. One way to restore the integrity of DNA involves the base excision repair pathway. Glycosylases are the key-enzymes of this process. The present work deals with the determination of the substrate specificity and the mechanism of action of three glycosylases: endonuclease III and Fpg of Escherichia coli and Ogg1 of Saccharomyces cerevisiae. The present manuscript is divided into four parts: Endonuclease III-mediated excision of 5,6-dihydro-thymine and 5-hydroxy-5,6-dihydro-thymine from γ-irradiated DNA was analyzed by a gas chromatography-mass spectrometry assay, including a liquid chromatography pre-purification step. This was found to be necessary in order to separate the cis and trans isomers of 6-hydroxy-5,6-dihydro-thymine from the 5-hydroxy-5,6-dihydro-thymine. Modified oligonucleotides that contained a unique lesion, including thymine glycol, 5,6-dihydro-thymine and 5-hydroxy-cytosine were synthesized to assess the substrate specificity of endonuclease III and Fpg. The order of preference of the enzymes for the substrates was determined by the measurement of the Michaelis constants of the kinetics. Furthermore, the mechanism of action of endonuclease III has been reconsidered, after analysis using the MALDI mass spectrometry technique. These studies reveal that hydrolysis is the main pathway by which endonuclease III cleaves the DNA backbone. Using a modified oligonucleotide, 8-oxo-7,8-dihydro-adenine was shown to be a product of excision of the Ogg1 enzyme. The role of the complementary base towards the lesion was found to be preponderant in the damage excision. A last chapter concerns the synthesis and the characterization of the four isomers of 5(6)-hydroxy-6(5)-hydroperoxides of thymine. These products may be substrates for endonuclease III or Fpg. (author) [fr

  16. Evidence that OGG1 glycosylase protects neurons against oxidative DNA damage and cell death under ischemic conditions

    DEFF Research Database (Denmark)

    Liu, Dong; Croteau, Deborah L; Souza-Pinto, Nadja

    2011-01-01

    to ischemic and oxidative stress. After exposure of cultured neurons to oxidative and metabolic stress levels of OGG1 in the nucleus were elevated and mitochondria exhibited fragmentation and increased levels of the mitochondrial fission protein dynamin-related protein 1 (Drp1) and reduced membrane potential......7,8-Dihydro-8-oxoguanine DNA glycosylase (OGG1) is a major DNA glycosylase involved in base-excision repair (BER) of oxidative DNA damage to nuclear and mitochondrial DNA (mtDNA). We used OGG1-deficient (OGG1(-/-)) mice to examine the possible roles of OGG1 in the vulnerability of neurons....... Cortical neurons isolated from OGG1(-/-) mice were more vulnerable to oxidative insults than were OGG1(+/+) neurons, and OGG1(-/-) mice developed larger cortical infarcts and behavioral deficits after permanent middle cerebral artery occlusion compared with OGG1(+/+) mice. Accumulations of oxidative DNA...

  17. On-bead fluorescent DNA nanoprobes to analyze base excision repair activities

    Energy Technology Data Exchange (ETDEWEB)

    Gines, Guillaume; Saint-Pierre, Christine; Gasparutto, Didier, E-mail: didier.gasparutto@cea.fr

    2014-02-17

    Graphical abstract: -- Highlights: •On magnetic beads fluorescent enzymatic assays. •Simple, easy, non-radioactive and electrophoresis-free functional assay. •Lesion-containing hairpin DNA probes are selective for repair enzymes. •The biosensing platform allows the measurement of DNA repair activities from purified enzymes or within cell free extracts. -- Abstract: DNA integrity is constantly threatened by endogenous and exogenous agents that can modify its physical and chemical structure. Changes in DNA sequence can cause mutations sparked by some genetic diseases or cancers. Organisms have developed efficient defense mechanisms able to specifically repair each kind of lesion (alkylation, oxidation, single or double strand break, mismatch, etc). Here we report the adjustment of an original assay to detect enzymes’ activity of base excision repair (BER), that supports a set of lesions including abasic sites, alkylation, oxidation or deamination products of bases. The biosensor is characterized by a set of fluorescent hairpin-shaped nucleic acid probes supported on magnetic beads, each containing a selective lesion targeting a specific BER enzyme. We have studied the DNA glycosylase alkyl-adenine glycosylase (AAG) and the human AP-endonuclease (APE1) by incorporating within the DNA probe a hypoxanthine lesion or an abasic site analog (tetrahydrofuran), respectively. Enzymatic repair activity induces the formation of a nick in the damaged strand, leading to probe's break, that is detected in the supernatant by fluorescence. The functional assay allows the measurement of DNA repair activities from purified enzymes or in cell-free extracts in a fast, specific, quantitative and sensitive way, using only 1 pmol of probe for a test. We recorded a detection limit of 1 μg mL{sup −1} and 50 μg mL{sup −1} of HeLa nuclear extracts for APE1 and AAG enzymes, respectively. Finally, the on-bead assay should be useful to screen inhibitors of DNA repair

  18. On-bead fluorescent DNA nanoprobes to analyze base excision repair activities

    International Nuclear Information System (INIS)

    Gines, Guillaume; Saint-Pierre, Christine; Gasparutto, Didier

    2014-01-01

    Graphical abstract: -- Highlights: •On magnetic beads fluorescent enzymatic assays. •Simple, easy, non-radioactive and electrophoresis-free functional assay. •Lesion-containing hairpin DNA probes are selective for repair enzymes. •The biosensing platform allows the measurement of DNA repair activities from purified enzymes or within cell free extracts. -- Abstract: DNA integrity is constantly threatened by endogenous and exogenous agents that can modify its physical and chemical structure. Changes in DNA sequence can cause mutations sparked by some genetic diseases or cancers. Organisms have developed efficient defense mechanisms able to specifically repair each kind of lesion (alkylation, oxidation, single or double strand break, mismatch, etc). Here we report the adjustment of an original assay to detect enzymes’ activity of base excision repair (BER), that supports a set of lesions including abasic sites, alkylation, oxidation or deamination products of bases. The biosensor is characterized by a set of fluorescent hairpin-shaped nucleic acid probes supported on magnetic beads, each containing a selective lesion targeting a specific BER enzyme. We have studied the DNA glycosylase alkyl-adenine glycosylase (AAG) and the human AP-endonuclease (APE1) by incorporating within the DNA probe a hypoxanthine lesion or an abasic site analog (tetrahydrofuran), respectively. Enzymatic repair activity induces the formation of a nick in the damaged strand, leading to probe's break, that is detected in the supernatant by fluorescence. The functional assay allows the measurement of DNA repair activities from purified enzymes or in cell-free extracts in a fast, specific, quantitative and sensitive way, using only 1 pmol of probe for a test. We recorded a detection limit of 1 μg mL −1 and 50 μg mL −1 of HeLa nuclear extracts for APE1 and AAG enzymes, respectively. Finally, the on-bead assay should be useful to screen inhibitors of DNA repair activities

  19. Expression of human oxoguanine glycosylase 1 or formamidopyrimidine glycosylase in human embryonic kidney 293 cells exacerbates methylmercury toxicity in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ondovcik, Stephanie L.; Preston, Thomas J.; McCallum, Gordon P. [Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario M5S 3M2 (Canada); Wells, Peter G., E-mail: pg.wells@utoronto.ca [Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario M5S 3M2 (Canada); Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario M5S 1A8 (Canada)

    2013-08-15

    Exposure to methylmercury (MeHg) acutely at high levels, or via chronic low-level dietary exposure from daily fish consumption, can lead to adverse neurological effects in both the adult and developing conceptus. To determine the impact of variable DNA repair capacity, and the role of reactive oxygen species (ROS) and oxidatively damaged DNA in the mechanism of toxicity, transgenic human embryonic kidney (HEK) 293 cells that stably express either human oxoguanine glycosylase 1 (hOgg1) or its bacterial homolog, formamidopyrimidine glycosylase (Fpg), which primarily repair the oxidative lesion 8-oxo-2′-deoxyguanosine (8-oxodG), were used to assess the in vitro effects of MeHg. Western blotting confirmed the expression of hOgg1 or Fpg in both the nuclear and mitochondrial compartments of their respective cell lines. Following acute (1–2 h) incubations with 0–10 μM MeHg, concentration-dependent decreases in clonogenic survival and cell growth accompanied concentration-dependent increases in lactate dehydrogenase (LDH) release, ROS formation, 8-oxodG levels and apurinic/apyrimidinic (AP) sites, consistent with the onset of cytotoxicity. Paradoxically, hOgg1- and Fpg-expressing HEK 293 cells were more sensitive than wild-type cells stably transfected with the empty vector control to MeHg across all cellular and biochemical parameters, exhibiting reduced clonogenic survival and cell growth, and increased LDH release and DNA damage. Accordingly, upregulation of specific components of the base excision repair (BER) pathway may prove deleterious potentially due to the absence of compensatory enhancement of downstream processes to repair toxic intermediary abasic sites. Thus, interindividual variability in DNA repair activity may constitute an important risk factor for environmentally-initiated, oxidatively damaged DNA and its pathological consequences. - Highlights: • hOgg1 and Fpg repair oxidatively damaged DNA. • hOgg1- and Fpg-expressing cells are more

  20. A unique dual recognition hairpin probe mediated fluorescence amplification method for sensitive detection of uracil-DNA glycosylase and endonuclease IV activities.

    Science.gov (United States)

    Wu, Yushu; Yan, Ping; Xu, Xiaowen; Jiang, Wei

    2016-03-07

    Uracil-DNA glycosylase (UDG) and endonuclease IV (Endo IV) play cooperative roles in uracil base-excision repair (UBER) and inactivity of either will interrupt the UBER to cause disease. Detection of UDG and Endo IV activities is crucial to evaluate the UBER process in fundamental research and diagnostic application. Here, a unique dual recognition hairpin probe mediated fluorescence amplification method was developed for sensitively and selectively detecting UDG and Endo IV activities. For detecting UDG activity, the uracil base in the probe was excised by the target enzyme to generate an apurinic/apyrimidinic (AP) site, achieving the UDG recognition. Then, the AP site was cleaved by a tool enzyme Endo IV, releasing a primer to trigger rolling circle amplification (RCA) reaction. Finally, the RCA reaction produced numerous repeated G-quadruplex sequences, which interacted with N-methyl-mesoporphyrin IX to generate an enhanced fluorescence signal. Alternatively, for detecting Endo IV activity, the uracil base in the probe was first converted into an AP site by a tool enzyme UDG. Next, the AP site was cleaved by the target enzyme, achieving the Endo IV recognition. The signal was then generated and amplified in the same way as those in the UDG activity assay. The detection limits were as low as 0.00017 U mL(-1) for UDG and 0.11 U mL(-1) for Endo IV, respectively. Moreover, UDG and Endo IV can be well distinguished from their analogs. This method is beneficial for properly evaluating the UBER process in function studies and disease prognoses.

  1. A unique uracil-DNA binding protein of the uracil DNA glycosylase superfamily.

    Science.gov (United States)

    Sang, Pau Biak; Srinath, Thiruneelakantan; Patil, Aravind Goud; Woo, Eui-Jeon; Varshney, Umesh

    2015-09-30

    Uracil DNA glycosylases (UDGs) are an important group of DNA repair enzymes, which pioneer the base excision repair pathway by recognizing and excising uracil from DNA. Based on two short conserved sequences (motifs A and B), UDGs have been classified into six families. Here we report a novel UDG, UdgX, from Mycobacterium smegmatis and other organisms. UdgX specifically recognizes uracil in DNA, forms a tight complex stable to sodium dodecyl sulphate, 2-mercaptoethanol, urea and heat treatment, and shows no detectable uracil excision. UdgX shares highest homology to family 4 UDGs possessing Fe-S cluster. UdgX possesses a conserved sequence, KRRIH, which forms a flexible loop playing an important role in its activity. Mutations of H in the KRRIH sequence to S, G, A or Q lead to gain of uracil excision activity in MsmUdgX, establishing it as a novel member of the UDG superfamily. Our observations suggest that UdgX marks the uracil-DNA for its repair by a RecA dependent process. Finally, we observed that the tight binding activity of UdgX is useful in detecting uracils in the genomes. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  2. TET-mediated oxidation of methylcytosine causes TDG or NEIL glycosylase dependent gene reactivation.

    Science.gov (United States)

    Müller, Udo; Bauer, Christina; Siegl, Michael; Rottach, Andrea; Leonhardt, Heinrich

    2014-07-01

    The discovery of hydroxymethyl-, formyl- and carboxylcytosine, generated through oxidation of methylcytosine by TET dioxygenases, raised the question how these modifications contribute to epigenetic regulation. As they are subjected to complex regulation in vivo, we dissected links to gene expression with in vitro modified reporter constructs. We used an Oct4 promoter-driven reporter gene and demonstrated that in vitro methylation causes gene silencing while subsequent oxidation with purified catalytic domain of TET1 leads to gene reactivation. To identify proteins involved in this pathway we screened for TET interacting factors and identified TDG, PARP1, XRCC1 and LIG3 that are involved in base-excision repair. Knockout and rescue experiments demonstrated that gene reactivation depended on the glycosylase TDG, but not MBD4, while NEIL1, 2 and 3 could partially rescue the loss of TDG. These results clearly show that oxidation of methylcytosine by TET dioxygenases and subsequent removal by TDG or NEIL glycosylases and the BER pathway results in reactivation of epigenetically silenced genes. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. A combinatorial role for MutY and Fpg DNA glycosylases in mutation avoidance in Mycobacterium smegmatis

    International Nuclear Information System (INIS)

    Hassim, Farzanah; Papadopoulos, Andrea O.; Kana, Bavesh D.; Gordhan, Bhavna G.

    2015-01-01

    Highlights: • We studied the combined role of MutY and Fpg DNA glycosylases in M. smegmatis. • Loss of MutY showed increased sensitivity to oxidative damage. • Loss of MutY together with the Fpg glycosylases showed increased mutation rates. • Our data indicate interplay between these enzymes to control mutagenesis. - Abstract: Hydroxyl radical (·OH) among reactive oxygen species cause damage to nucleobases with thymine being the most susceptible, whilst in contrast, the singlet oxygen ( 1 0 2 ) targets only guanine bases. The high GC content of mycobacterial genomes predisposes these organisms to oxidative damage of guanine. The exposure of cellular DNA to ·OH and one-electron oxidants results in the formation of two main degradation products, the pro-mutagenic 8-oxo-7,8-dihydroguanine (8-oxoGua) and the cytotoxic 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua). These lesions are repaired through the base excision repair (BER) pathway and we previously, demonstrated a combinatorial role for the mycobacterial Endonuclease III (Nth) and the Nei family of DNA glycosylases in mutagenesis. In addition, the formamidopyrimidine (Fpg/MutM) and MutY DNA glycosylases have also been implicated in mutation avoidance and BER in mycobacteria. In this study, we further investigate the combined role of MutY and the Fpg/Nei DNA glycosylases in Mycobacterium smegmatis and demonstrate that deletion of mutY resulted in enhanced sensitivity to oxidative stress, an effect which was not exacerbated in Δfpg1 Δfpg2 or Δnei1 Δnei2 double mutant backgrounds. However, combinatorial loss of the mutY, fpg1 and fpg2 genes resulted in a significant increase in mutation rates suggesting interplay between these enzymes. Consistent with this, there was a significant increase in C → A mutations with a corresponding change in cell morphology of rifampicin resistant mutants in the Δfpg1 Δfpg2 ΔmutY deletion mutant. In contrast, deletion of mutY together with the nei homologues

  4. A combinatorial role for MutY and Fpg DNA glycosylases in mutation avoidance in Mycobacterium smegmatis

    Energy Technology Data Exchange (ETDEWEB)

    Hassim, Farzanah; Papadopoulos, Andrea O.; Kana, Bavesh D.; Gordhan, Bhavna G., E-mail: bhavna.gordhan@nhls.ac.za

    2015-09-15

    Highlights: • We studied the combined role of MutY and Fpg DNA glycosylases in M. smegmatis. • Loss of MutY showed increased sensitivity to oxidative damage. • Loss of MutY together with the Fpg glycosylases showed increased mutation rates. • Our data indicate interplay between these enzymes to control mutagenesis. - Abstract: Hydroxyl radical (·OH) among reactive oxygen species cause damage to nucleobases with thymine being the most susceptible, whilst in contrast, the singlet oxygen ({sup 1}0{sub 2}) targets only guanine bases. The high GC content of mycobacterial genomes predisposes these organisms to oxidative damage of guanine. The exposure of cellular DNA to ·OH and one-electron oxidants results in the formation of two main degradation products, the pro-mutagenic 8-oxo-7,8-dihydroguanine (8-oxoGua) and the cytotoxic 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua). These lesions are repaired through the base excision repair (BER) pathway and we previously, demonstrated a combinatorial role for the mycobacterial Endonuclease III (Nth) and the Nei family of DNA glycosylases in mutagenesis. In addition, the formamidopyrimidine (Fpg/MutM) and MutY DNA glycosylases have also been implicated in mutation avoidance and BER in mycobacteria. In this study, we further investigate the combined role of MutY and the Fpg/Nei DNA glycosylases in Mycobacterium smegmatis and demonstrate that deletion of mutY resulted in enhanced sensitivity to oxidative stress, an effect which was not exacerbated in Δfpg1 Δfpg2 or Δnei1 Δnei2 double mutant backgrounds. However, combinatorial loss of the mutY, fpg1 and fpg2 genes resulted in a significant increase in mutation rates suggesting interplay between these enzymes. Consistent with this, there was a significant increase in C → A mutations with a corresponding change in cell morphology of rifampicin resistant mutants in the Δfpg1 Δfpg2 ΔmutY deletion mutant. In contrast, deletion of mutY together with the nei

  5. Pms2 and uracil-DNA glycosylases act jointly in the mismatch repair pathway to generate Ig gene mutations at A-T base pairs.

    Science.gov (United States)

    Girelli Zubani, Giulia; Zivojnovic, Marija; De Smet, Annie; Albagli-Curiel, Olivier; Huetz, François; Weill, Jean-Claude; Reynaud, Claude-Agnès; Storck, Sébastien

    2017-04-03

    During somatic hypermutation (SHM) of immunoglobulin genes, uracils introduced by activation-induced cytidine deaminase are processed by uracil-DNA glycosylase (UNG) and mismatch repair (MMR) pathways to generate mutations at G-C and A-T base pairs, respectively. Paradoxically, the MMR-nicking complex Pms2/Mlh1 is apparently dispensable for A-T mutagenesis. Thus, how detection of U:G mismatches is translated into the single-strand nick required for error-prone synthesis is an open question. One model proposed that UNG could cooperate with MMR by excising a second uracil in the vicinity of the U:G mismatch, but it failed to explain the low impact of UNG inactivation on A-T mutagenesis. In this study, we show that uracils generated in the G1 phase in B cells can generate equal proportions of A-T and G-C mutations, which suggests that UNG and MMR can operate within the same time frame during SHM. Furthermore, we show that Ung -/- Pms2 -/- mice display a 50% reduction in mutations at A-T base pairs and that most remaining mutations at A-T bases depend on two additional uracil glycosylases, thymine-DNA glycosylase and SMUG1. These results demonstrate that Pms2/Mlh1 and multiple uracil glycosylases act jointly, each one with a distinct strand bias, to enlarge the immunoglobulin gene mutation spectrum from G-C to A-T bases. © 2017 Girelli Zubani et al.

  6. Mechanism of the Glycosidic Bond Cleavage of Mismatched Thymine in Human Thymine DNA Glycosylase Revealed by Classical Molecular Dynamics and Quantum Mechanical/Molecular Mechanical Calculations.

    Science.gov (United States)

    Kanaan, Natalia; Crehuet, Ramon; Imhof, Petra

    2015-09-24

    Base excision of mismatched or damaged nucleotides catalyzed by glycosylase enzymes is the first step of the base excision repair system, a machinery preserving the integrity of DNA. Thymine DNA glycosylase recognizes and removes mismatched thymine by cleaving the C1'-N1 bond between the base and the sugar ring. Our quantum mechanical/molecular mechanical calculations of this reaction in human thymine DNA glycosylase reveal a requirement for a positive charge in the active site to facilitate C1'-N1 bond scission: protonation of His151 significantly lowers the free energy barrier for C1'-N1 bond dissociation compared to the situation with neutral His151. Shuttling a proton from His151 to the thymine base further reduces the activation free energy for glycosidic bond cleavage. Classical molecular dynamics simulations of the H151A mutant suggest that the mutation to the smaller, neutral, residue increases the water accessibility of the thymine base, rendering direct proton transfer from the bulk feasible. Quantum mechanical/molecular mechanical calculations of the glycosidic bond cleavage reaction in the H151A mutant show that the activation free energy is slightly lower than in the wild-type enzyme, explaining the experimentally observed higher reaction rates in this mutant.

  7. Isolation and characterization of the human uracil DNA glycosylase gene

    International Nuclear Information System (INIS)

    Vollberg, T.M.; Siegler, K.M.; Cool, B.L.; Sirover, M.A.

    1989-01-01

    A series of anti-human placental uracil DNA glycosylase monoclonal antibodies was used to screen a human placental cDNA library in phage λgt11. Twenty-seven immunopositive plaques were detected and purified. One clone containing a 1.2-kilobase (kb) human cDNA insert was chosen for further study by insertion into pUC8. The resultant recombinant plasmid selected by hybridization a human placental mRNA that encoded a 37-kDa polypeptide. This protein was immunoprecipitated specifically by an anti-human placenta uracil DNA glycosylase monoclonal antibody. RNA blot-hybridization (Northern) analysis using placental poly(A) + RNA or total RNA from four different human fibroblast cell strains revealed a single 1.6-kb transcript. Genomic blots using DNA from each cell strain digested with either EcoRI or PstI revealed a complex pattern of cDNA-hydridizing restriction fragments. The genomic analysis for each enzyme was highly similar in all four human cell strains. In contrast, a single band was observed when genomic analysis was performed with the identical DNA digests with an actin gene probe. During cell proliferation there was an increase in the level of glycosylase mRNA that paralleled the increase in uracil DNA glycosylase enzyme activity. The isolation of the human uracil DNA glycosylase gene permits an examination of the structure, organization, and expression of a human DNA repair gene

  8. Repair of Alkylation Damage in Eukaryotic Chromatin Depends on Searching Ability of Alkyladenine DNA Glycosylase.

    Science.gov (United States)

    Zhang, Yaru; O'Brien, Patrick J

    2015-11-20

    Human alkyladenine DNA glycosylase (AAG) initiates the base excision repair pathway by excising alkylated and deaminated purine lesions. In vitro biochemical experiments demonstrate that AAG uses facilitated diffusion to efficiently search DNA to find rare sites of damage and suggest that electrostatic interactions are critical to the searching process. However, it remains an open question whether DNA searching limits the rate of DNA repair in vivo. We constructed AAG mutants with altered searching ability and measured their ability to protect yeast from alkylation damage in order to address this question. Each of the conserved arginine and lysine residues that are near the DNA binding interface were mutated, and the functional impacts were evaluated using kinetic and thermodynamic analysis. These mutations do not perturb catalysis of N-glycosidic bond cleavage, but they decrease the ability to capture rare lesion sites. Nonspecific and specific DNA binding properties are closely correlated, suggesting that the electrostatic interactions observed in the specific recognition complex are similarly important for DNA searching complexes. The ability of the mutant proteins to complement repair-deficient yeast cells is positively correlated with the ability of the proteins to search DNA in vitro, suggesting that cellular resistance to DNA alkylation is governed by the ability to find and efficiently capture cytotoxic lesions. It appears that chromosomal access is not restricted and toxic sites of alkylation damage are readily accessible to a searching protein.

  9. Destabilization of the PCNA trimer mediated by its interaction with the NEIL1 DNA glycosylase

    Energy Technology Data Exchange (ETDEWEB)

    Prakash, Aishwarya; Moharana, Kedar; Wallace, Susan S.; Doublié, Sylvie

    2016-12-19

    The base excision repair (BER) pathway repairs oxidized lesions in the DNA that result from reactive oxygen species generated in cells. If left unrepaired, these damaged DNA bases can disrupt cellular processes such as replication. NEIL1 is one of the 11 human DNA glycosylases that catalyze the first step of the BER pathway, i.e. recognition and excision of DNA lesions. NEIL1 interacts with essential replication proteins such as the ring-shaped homotrimeric proliferating cellular nuclear antigen (PCNA). We isolated a complex formed between NEIL1 and PCNA (±DNA) using size exclusion chromatography (SEC). This interaction was confirmed using native gel electrophoresis and mass spectrometry. Stokes radii measured by SEC hinted that PCNA in complex with NEIL1 (±DNA) was no longer a trimer. Height measurements and images obtained by atomic force microscopy also demonstrated the dissociation of the PCNA homotrimer in the presence of NEIL1 and DNA, while small-angle X-ray scattering analysis confirmed the NEIL1 mediated PCNA trimer dissociation and formation of a 1:1:1 NEIL1-DNA-PCNA(monomer) complex. Furthermore, ab initio shape reconstruction provides insights into the solution structure of this previously unreported complex. Together, these data point to a potential mechanistic switch between replication and BER.

  10. The oxidative DNA glycosylases of Mycobacterium tuberculosis exhibit different substrate preferences from their Escherichia coli counterparts.

    Science.gov (United States)

    Guo, Yin; Bandaru, Viswanath; Jaruga, Pawel; Zhao, Xiaobei; Burrows, Cynthia J; Iwai, Shigenori; Dizdaroglu, Miral; Bond, Jeffrey P; Wallace, Susan S

    2010-02-04

    The DNA glycosylases that remove oxidized DNA bases fall into two general families: the Fpg/Nei family and the Nth superfamily. Based on protein sequence alignments, we identified four putative Fpg/Nei family members, as well as a putative Nth protein in Mycobacterium tuberculosis H37Rv. All four Fpg/Nei proteins were successfully overexpressed using a bicistronic vector created in our laboratory. The MtuNth protein was also overexpressed in soluble form. The substrate specificities of the purified enzymes were characterized in vitro with oligodeoxynucleotide substrates containing single lesions. Some were further characterized by gas chromatography/mass spectrometry (GC/MS) analysis of products released from gamma-irradiated DNA. MtuFpg1 has substrate specificity similar to that of EcoFpg. Both EcoFpg and MtuFpg1 are more efficient at removing spiroiminodihydantoin (Sp) than 7,8-dihydro-8-oxoguanine (8-oxoG). However, MtuFpg1 shows a substantially increased opposite base discrimination compared to EcoFpg. MtuFpg2 contains only the C-terminal domain of an Fpg protein and has no detectable DNA binding activity or DNA glycosylase/lyase activity and thus appears to be a pseudogene. MtuNei1 recognizes oxidized pyrimidines on both double-stranded and single-stranded DNA and exhibits uracil DNA glycosylase activity. MtuNth recognizes a variety of oxidized bases, including urea, 5,6-dihydrouracil (DHU), 5-hydroxyuracil (5-OHU), 5-hydroxycytosine (5-OHC) and methylhydantoin (MeHyd). Both MtuNei1 and MtuNth excise thymine glycol (Tg); however, MtuNei1 strongly prefers the (5R) isomers, whereas MtuNth recognizes only the (5S) isomers. MtuNei2 did not demonstrate activity in vitro as a recombinant protein, but like MtuNei1 when expressed in Escherichia coli, it decreased the spontaneous mutation frequency of both the fpg mutY nei triple and nei nth double mutants, suggesting that MtuNei2 is functionally active in vivo recognizing both guanine and cytosine oxidation products

  11. Alkyladenine DNA glycosylase (Aag) in somatic hypermutation and class switch recombination.

    Science.gov (United States)

    Longerich, Simonne; Meira, Lisiane; Shah, Dharini; Samson, Leona D; Storb, Ursula

    2007-12-01

    Somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin (Ig) genes require the cytosine deaminase AID, which deaminates cytosine to uracil in Ig gene DNA. Paradoxically, proteins involved normally in error-free base excision repair and mismatch repair, seem to be co-opted to facilitate SHM and CSR, by recruiting error-prone translesion polymerases to DNA sequences containing deoxy-uracils created by AID. Major evidence supports at least one mechanism whereby the uracil glycosylase Ung removes AID-generated uracils creating abasic sites which may be used either as uninformative templates for DNA synthesis, or processed to nicks and gaps that prime error-prone DNA synthesis. We investigated the possibility that deamination at adenines also initiates SHM. Adenosine deamination would generate hypoxanthine (Hx), a substrate for the alkyladenine DNA glycosylase (Aag). Aag would generate abasic sites which then are subject to error-prone repair as above for AID-deaminated cytosine processed by Ung. If the action of an adenosine deaminase followed by Aag were responsible for significant numbers of mutations at A, we would find a preponderance of A:T>G:C transition mutations during SHM in an Aag deleted background. However, this was not observed and we found that the frequencies of SHM and CSR were not significantly altered in Aag-/- mice. Paradoxically, we found that Aag is expressed in B lymphocytes undergoing SHM and CSR and that its activity is upregulated in activated B cells. Moreover, we did find a statistically significant, albeit low increase of T:A>C:G transition mutations in Aag-/- animals, suggesting that Aag may be involved in creating the SHM A>T bias seen in wild type mice.

  12. Thymine DNA Glycosylase (TDG) is involved in the pathogenesis of intestinal tumors with reduced APC expression.

    Science.gov (United States)

    Xu, Jinfei; Cortellino, Salvatore; Tricarico, Rossella; Chang, Wen-Chi; Scher, Gabrielle; Devarajan, Karthik; Slifker, Michael; Moore, Robert; Bassi, Maria Rosaria; Caretti, Elena; Clapper, Margie; Cooper, Harry; Bellacosa, Alfonso

    2017-10-27

    Thymine DNA Glycosylase (TDG) is a base excision repair enzyme that acts as a thymine and uracil DNA N-glycosylase on G:T and G:U mismatches, thus protecting CpG sites in the genome from mutagenesis by deamination. In addition, TDG has an epigenomic function by removing the novel cytosine derivatives 5-formylcytosine and 5-carboxylcytosine (5caC) generated by Ten-Eleven Translocation (TET) enzymes during active DNA demethylation. We and others previously reported that TDG is essential for mammalian development. However, its involvement in tumor formation is unknown. To study the role of TDG in tumorigenesis, we analyzed the effects of its inactivation in a well-characterized model of tumor predisposition, the Apc Min mouse strain. Mice bearing a conditional Tdg flox allele were crossed with Fabpl ::Cre transgenic mice, in the context of the Apc Min mutation, in order to inactivate Tdg in the small intestinal and colonic epithelium. We observed an approximately 2-fold increase in the number of small intestinal adenomas in the test Tdg -mutant Apc Min mice in comparison to control genotypes (p=0.0001). This increase occurred in female mice, and is similar to the known increase in intestinal adenoma formation due to oophorectomy. In the human colorectal cancer (CRC) TCGA database, the subset of patients with TDG and APC expression in the lowest quartile exhibits an excess of female cases. We conclude that TDG inactivation plays a role in intestinal tumorigenesis initiated by mutation/underexpression of APC . Our results also indicate that TDG may be involved in sex-specific protection from CRC.

  13. Base excision DNA repair in the embryonic development of the sea urchin, Strongylocentrotus intermedius.

    Science.gov (United States)

    Torgasheva, Natalya A; Menzorova, Natalya I; Sibirtsev, Yurii T; Rasskazov, Valery A; Zharkov, Dmitry O; Nevinsky, Georgy A

    2016-06-21

    In actively proliferating cells, such as the cells of the developing embryo, DNA repair is crucial for preventing the accumulation of mutations and synchronizing cell division. Sea urchin embryo growth was analyzed and extracts were prepared. The relative activity of DNA polymerase, apurinic/apyrimidinic (AP) endonuclease, uracil-DNA glycosylase, 8-oxoguanine-DNA glycosylase, and other glycosylases was analyzed using specific oligonucleotide substrates of these enzymes; the reaction products were resolved by denaturing 20% polyacrylamide gel electrophoresis. We have characterized the profile of several key base excision repair activities in the developing embryos (2 blastomers to mid-pluteus) of the grey sea urchin, Strongylocentrotus intermedius. The uracil-DNA glycosylase specific activity sharply increased after blastula hatching, whereas the specific activity of 8-oxoguanine-DNA glycosylase steadily decreased over the course of the development. The AP-endonuclease activity gradually increased but dropped at the last sampled stage (mid-pluteus 2). The DNA polymerase activity was high at the first cleavage division and then quickly decreased, showing a transient peak at blastula hatching. It seems that the developing sea urchin embryo encounters different DNA-damaging factors early in development within the protective envelope and later as a free-floating larva, with hatching necessitating adaptation to the shift in genotoxic stress conditions. No correlation was observed between the dynamics of the enzyme activities and published gene expression data from developing congeneric species, S. purpuratus. The results suggest that base excision repair enzymes may be regulated in the sea urchin embryos at the level of covalent modification or protein stability.

  14. The contribution of Nth and Nei DNA glycosylases to mutagenesis in Mycobacterium smegmatis.

    Science.gov (United States)

    Moolla, Nabiela; Goosens, Vivianne J; Kana, Bavesh D; Gordhan, Bhavna G

    2014-01-01

    The increased prevalence of drug resistant strains of Mycobacterium tuberculosis (Mtb) indicates that significant mutagenesis occurs during tuberculosis disease in humans. DNA damage by host-derived reactive oxygen/nitrogen species is hypothesized to be critical for the mutagenic process in Mtb thus, highlighting an important role for DNA repair enzymes in maintenance of genome fidelity. Formamidopyrimidine (Fpg/MutM/Fapy) and EndonucleaseVIII (Nei) constitute the Fpg/Nei family of DNA glycosylases and together with EndonucleaseIII (Nth) are central to the base excision repair pathway in bacteria. In this study we assess the contribution of Nei and Nth DNA repair enzymes in Mycobacterium smegmatis (Msm), which retains a single nth homologue and duplications of the Fpg (fpg1 and fpg2) and Nei (nei1 and nei2) homologues. Using an Escherichia coli nth deletion mutant, we confirm the functionality of the mycobacterial nth gene in the base excision repair pathway. Msm mutants lacking nei1, nei2 and nth individually or in combination did not display aberrant growth in broth culture. Deletion of nth individually results in increased UV-induced mutagenesis and combinatorial deletion with the nei homologues results in reduced survival under oxidative stress conditions and an increase in spontaneous mutagenesis to rifampicin. Deletion of nth together with the fpg homolgues did not result in any growth/survival defects or changes in mutation rate. Furthermore, no differential emergence of the common rifampicin resistance conferring genotypes were noted. Collectively, these data confirm a role for Nth in base excision repair in mycobacteria and further highlight a novel interplay between the Nth and Nei homologues in spontaneous mutagenesis. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Uracil excision repair in Mycobacterium tuberculosis cell-free extracts.

    Science.gov (United States)

    Kumar, Pradeep; Bharti, Sanjay Kumar; Varshney, Umesh

    2011-05-01

    Uracil excision repair is ubiquitous in all domains of life and initiated by uracil DNA glycosylases (UDGs) which excise the promutagenic base, uracil, from DNA to leave behind an abasic site (AP-site). Repair of the resulting AP-sites requires an AP-endonuclease, a DNA polymerase, and a DNA ligase whose combined activities result in either short-patch or long-patch repair. Mycobacterium tuberculosis, the causative agent of tuberculosis, has an increased risk of accumulating uracils because of its G + C-rich genome, and its niche inside host macrophages where it is exposed to reactive nitrogen and oxygen species, two major causes of cytosine deamination (to uracil) in DNA. In vitro assays to study DNA repair in this important human pathogen are limited. To study uracil excision repair in mycobacteria, we have established assay conditions using cell-free extracts of M. tuberculosis and M. smegmatis (a fast-growing mycobacterium) and oligomer or plasmid DNA substrates. We show that in mycobacteria, uracil excision repair is completed primarily via long-patch repair. In addition, we show that M. tuberculosis UdgB, a newly characterized family 5 UDG, substitutes for the highly conserved family 1 UDG, Ung, thereby suggesting that UdgB might function as backup enzyme for uracil excision repair in mycobacteria. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. 8-oxoguanine DNA glycosylase (OGG1 deficiency elicits coordinated changes in lipid and mitochondrial metabolism in muscle.

    Directory of Open Access Journals (Sweden)

    Vladimir Vartanian

    Full Text Available Oxidative stress resulting from endogenous and exogenous sources causes damage to cellular components, including genomic and mitochondrial DNA. Oxidative DNA damage is primarily repaired via the base excision repair pathway that is initiated by DNA glycosylases. 8-oxoguanine DNA glycosylase (OGG1 recognizes and cleaves oxidized and ring-fragmented purines, including 8-oxoguanine, the most commonly formed oxidative DNA lesion. Mice lacking the OGG1 gene product are prone to multiple features of the metabolic syndrome, including high-fat diet-induced obesity, hepatic steatosis, and insulin resistance. Here, we report that OGG1-deficient mice also display skeletal muscle pathologies, including increased muscle lipid deposition and alterations in genes regulating lipid uptake and mitochondrial fission in skeletal muscle. In addition, expression of genes of the TCA cycle and of carbohydrate and lipid metabolism are also significantly altered in muscle of OGG1-deficient mice. These tissue changes are accompanied by marked reductions in markers of muscle function in OGG1-deficient animals, including decreased grip strength and treadmill endurance. Collectively, these data indicate a role for skeletal muscle OGG1 in the maintenance of optimal tissue function.

  17. A combinatorial role for MutY and Fpg DNA glycosylases in mutation avoidance in Mycobacterium smegmatis.

    Science.gov (United States)

    Hassim, Farzanah; Papadopoulos, Andrea O; Kana, Bavesh D; Gordhan, Bhavna G

    2015-09-01

    Hydroxyl radical (OH) among reactive oxygen species cause damage to nucleobases with thymine being the most susceptible, whilst in contrast, the singlet oxygen ((1)02) targets only guanine bases. The high GC content of mycobacterial genomes predisposes these organisms to oxidative damage of guanine. The exposure of cellular DNA to OH and one-electron oxidants results in the formation of two main degradation products, the pro-mutagenic 8-oxo-7,8-dihydroguanine (8-oxoGua) and the cytotoxic 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua). These lesions are repaired through the base excision repair (BER) pathway and we previously, demonstrated a combinatorial role for the mycobacterial Endonuclease III (Nth) and the Nei family of DNA glycosylases in mutagenesis. In addition, the formamidopyrimidine (Fpg/MutM) and MutY DNA glycosylases have also been implicated in mutation avoidance and BER in mycobacteria. In this study, we further investigate the combined role of MutY and the Fpg/Nei DNA glycosylases in Mycobacterium smegmatis and demonstrate that deletion of mutY resulted in enhanced sensitivity to oxidative stress, an effect which was not exacerbated in Δfpg1 Δfpg2 or Δnei1 Δnei2 double mutant backgrounds. However, combinatorial loss of the mutY, fpg1 and fpg2 genes resulted in a significant increase in mutation rates suggesting interplay between these enzymes. Consistent with this, there was a significant increase in C → A mutations with a corresponding change in cell morphology of rifampicin resistant mutants in the Δfpg1 Δfpg2 ΔmutY deletion mutant. In contrast, deletion of mutY together with the nei homologues did not result in any growth/survival defects or changes in mutation rates. Taken together these data indicate that the mycobacterial mutY, in combination with the Fpg DNA N-glycosylases, plays an important role in controlling mutagenesis under oxidative stress. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Synthetic Routes to N-9 Alkylated 8-Oxoguanines; Weak Inhibitors of the Human DNA Glycosylase OGG1

    Directory of Open Access Journals (Sweden)

    Tushar R. Mahajan

    2015-09-01

    Full Text Available The human 8-oxoguanine DNA glycosylase OGG1 is involved in base excision repair (BER, one of several DNA repair mechanisms that may counteract the effects of chemo- and radiation therapy for the treatment of cancer. We envisage that potent inhibitors of OGG1 may be found among the 9-alkyl-8-oxoguanines. Thus we explored synthetic routes to 8-oxoguanines and examined these as OGG1 inhibitors. The best reaction sequence started from 6-chloroguanine and involved N-9 alkylation, C-8 bromination, and finally simultaneous hydrolysis of both halides. Bromination before N-alkylation should only be considered when the N-substituent is not compatible with bromination conditions. The 8-oxoguanines were found to be weak inhibitors of OGG1. 6-Chloro-8-oxopurines, byproducts in the hydrolysis of 2,6-halopurines, turned out to be slightly better inhibitors than the corresponding 8-oxoguanines.

  19. Definitive characterization of human thymine glycol N-glycosylase activity

    International Nuclear Information System (INIS)

    Higgins, S.A.; Frenkel, K.; Cummings, A.; Teebor, G.W.

    1987-01-01

    An N-glycosylase activity that released cis-[ 3 H]-5,6-dihydroxy-5,6-dihydrothymine (thymine glycol, TG) from chemically oxidized poly(dA-[ 3 H]dT) was unambiguously characterized both in extracts of HeLa cells and in purified Escherichia coli endonuclease III. This was accomplished by use of a microderivatization procedure that quantitatively converted cis-TG to 5-hydroxy-5-methylhydantoin (HMH). The reaction products were analyzed by high-pressure liquid chromatography before and after derivation by using cis-[ 14 C]TG and [ 14 C]HMH, which had been independently synthesized, as reference compounds. This technique facilitated construction of a v/[E]/sub t/ plot for the enzyme activity in HeLa cells, permitting estimation of its specific activity. The results obtained prove the existence of both human and bacterial N-glycosylase activities that effect removal of TG from DNA

  20. Detrimental effects of hypoxia-specific expression of uracil DNA glycosylase (Ung) in Mycobacterium smegmatis.

    Science.gov (United States)

    Kurthkoti, Krishna; Varshney, Umesh

    2010-12-01

    Mycobacterium tuberculosis is known to reside latently in a significant fraction of the human population. Although the bacterium possesses an aerobic mode of metabolism, it adapts to persistence under hypoxic conditions such as those encountered in granulomas. While in mammalian systems hypoxia is a recognized DNA-damaging stress, aspects of DNA repair in mycobacteria under such conditions have not been studied. We subjected Mycobacterium smegmatis, a model organism, to the Wayne's protocol of hypoxia. Analysis of the mRNA of a key DNA repair enzyme, uracil DNA glycosylase (Ung), by real-time reverse transcriptase PCR (RT-PCR) revealed its downregulation during hypoxia. However, within an hour of recovery of the culture under normal oxygen levels, the Ung mRNA was restored. Analysis of Ung by immunoblotting and enzyme assays supported the RNA analysis results. To understand its physiological significance, we misexpressed Ung in M. smegmatis by using a hypoxia-responsive promoter of narK2 from M. tuberculosis. Although the misexpression of Ung during hypoxia decreased C-to-T mutations, it compromised bacterial survival upon recovery at normal oxygen levels. RT-PCR analysis of other base excision repair gene transcripts (UdgB and Fpg) suggested that these DNA repair functions also share with Ung the phenomenon of downregulation during hypoxia and recovery with return to normal oxygen conditions. We discuss the potential utility of this phenomenon in developing attenuated strains of mycobacteria.

  1. ATM regulates 3-methylpurine-DNA glycosylase and promotes therapeutic resistance to alkylating agents.

    Science.gov (United States)

    Agnihotri, Sameer; Burrell, Kelly; Buczkowicz, Pawel; Remke, Marc; Golbourn, Brian; Chornenkyy, Yevgen; Gajadhar, Aaron; Fernandez, Nestor A; Clarke, Ian D; Barszczyk, Mark S; Pajovic, Sanja; Ternamian, Christian; Head, Renee; Sabha, Nesrin; Sobol, Robert W; Taylor, Michael D; Rutka, James T; Jones, Chris; Dirks, Peter B; Zadeh, Gelareh; Hawkins, Cynthia

    2014-10-01

    Alkylating agents are a first-line therapy for the treatment of several aggressive cancers, including pediatric glioblastoma, a lethal tumor in children. Unfortunately, many tumors are resistant to this therapy. We sought to identify ways of sensitizing tumor cells to alkylating agents while leaving normal cells unharmed, increasing therapeutic response while minimizing toxicity. Using an siRNA screen targeting over 240 DNA damage response genes, we identified novel sensitizers to alkylating agents. In particular, the base excision repair (BER) pathway, including 3-methylpurine-DNA glycosylase (MPG), as well as ataxia telangiectasia mutated (ATM), were identified in our screen. Interestingly, we identified MPG as a direct novel substrate of ATM. ATM-mediated phosphorylation of MPG was required for enhanced MPG function. Importantly, combined inhibition or loss of MPG and ATM resulted in increased alkylating agent-induced cytotoxicity in vitro and prolonged survival in vivo. The discovery of the ATM-MPG axis will lead to improved treatment of alkylating agent-resistant tumors. Inhibition of ATM and MPG-mediated BER cooperate to sensitize tumor cells to alkylating agents, impairing tumor growth in vitro and in vivo with no toxicity to normal cells, providing an ideal therapeutic window. ©2014 American Association for Cancer Research.

  2. Aag DNA glycosylase promotes alkylation-induced tissue damage mediated by Parp1.

    Science.gov (United States)

    Calvo, Jennifer A; Moroski-Erkul, Catherine A; Lake, Annabelle; Eichinger, Lindsey W; Shah, Dharini; Jhun, Iny; Limsirichai, Prajit; Bronson, Roderick T; Christiani, David C; Meira, Lisiane B; Samson, Leona D

    2013-04-01

    Alkylating agents comprise a major class of front-line cancer chemotherapeutic compounds, and while these agents effectively kill tumor cells, they also damage healthy tissues. Although base excision repair (BER) is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental. Here we illustrate that the alkyladenine DNA glycosylase (AAG) mediates alkylation-induced tissue damage and whole-animal lethality following exposure to alkylating agents. Aag-dependent tissue damage, as observed in cerebellar granule cells, splenocytes, thymocytes, bone marrow cells, pancreatic β-cells, and retinal photoreceptor cells, was detected in wild-type mice, exacerbated in Aag transgenic mice, and completely suppressed in Aag⁻/⁻ mice. Additional genetic experiments dissected the effects of modulating both BER and Parp1 on alkylation sensitivity in mice and determined that Aag acts upstream of Parp1 in alkylation-induced tissue damage; in fact, cytotoxicity in WT and Aag transgenic mice was abrogated in the absence of Parp1. These results provide in vivo evidence that Aag-initiated BER may play a critical role in determining the side-effects of alkylating agent chemotherapies and that Parp1 plays a crucial role in Aag-mediated tissue damage.

  3. Aag DNA glycosylase promotes alkylation-induced tissue damage mediated by Parp1.

    Directory of Open Access Journals (Sweden)

    Jennifer A Calvo

    2013-04-01

    Full Text Available Alkylating agents comprise a major class of front-line cancer chemotherapeutic compounds, and while these agents effectively kill tumor cells, they also damage healthy tissues. Although base excision repair (BER is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental. Here we illustrate that the alkyladenine DNA glycosylase (AAG mediates alkylation-induced tissue damage and whole-animal lethality following exposure to alkylating agents. Aag-dependent tissue damage, as observed in cerebellar granule cells, splenocytes, thymocytes, bone marrow cells, pancreatic β-cells, and retinal photoreceptor cells, was detected in wild-type mice, exacerbated in Aag transgenic mice, and completely suppressed in Aag⁻/⁻ mice. Additional genetic experiments dissected the effects of modulating both BER and Parp1 on alkylation sensitivity in mice and determined that Aag acts upstream of Parp1 in alkylation-induced tissue damage; in fact, cytotoxicity in WT and Aag transgenic mice was abrogated in the absence of Parp1. These results provide in vivo evidence that Aag-initiated BER may play a critical role in determining the side-effects of alkylating agent chemotherapies and that Parp1 plays a crucial role in Aag-mediated tissue damage.

  4. Structure determination of uracil-DNA N-glycosylase from Deinococcus radiodurans in complex with DNA.

    Science.gov (United States)

    Pedersen, Hege Lynum; Johnson, Kenneth A; McVey, Colin E; Leiros, Ingar; Moe, Elin

    2015-10-01

    Uracil-DNA N-glycosylase (UNG) is a DNA-repair enzyme in the base-excision repair (BER) pathway which removes uracil from DNA. Here, the crystal structure of UNG from the extremophilic bacterium Deinococcus radiodurans (DrUNG) in complex with DNA is reported at a resolution of 1.35 Å. Prior to the crystallization experiments, the affinity between DrUNG and different DNA oligonucleotides was tested by electrophoretic mobility shift assays (EMSAs). As a result of this analysis, two 16 nt double-stranded DNAs were chosen for the co-crystallization experiments, one of which (16 nt AU) resulted in well diffracting crystals. The DNA in the co-crystal structure contained an abasic site (substrate product) flipped into the active site of the enzyme, with no uracil in the active-site pocket. Despite the high resolution, it was not possible to fit all of the terminal nucleotides of the DNA complex into electron density owing to disorder caused by a lack of stabilizing interactions. However, the DNA which was in contact with the enzyme, close to the active site, was well ordered and allowed detailed analysis of the enzyme-DNA interaction. The complex revealed that the interaction between DrUNG and DNA is similar to that in the previously determined crystal structure of human UNG (hUNG) in complex with DNA [Slupphaug et al. (1996). Nature (London), 384, 87-92]. Substitutions in a (here defined) variable part of the leucine loop result in a shorter loop (eight residues instead of nine) in DrUNG compared with hUNG; regardless of this, it seems to fulfil its role and generate a stabilizing force with the minor groove upon flipping out of the damaged base into the active site. The structure also provides a rationale for the previously observed high catalytic efficiency of DrUNG caused by high substrate affinity by demonstrating an increased number of long-range electrostatic interactions between the enzyme and the DNA. Interestingly, specific interactions between residues

  5. The disordered C-terminal domain of human DNA glycosylase NEIL1 contributes to its stability via intramolecular interactions.

    Science.gov (United States)

    Hegde, Muralidhar L; Tsutakawa, Susan E; Hegde, Pavana M; Holthauzen, Luis Marcelo F; Li, Jing; Oezguen, Numan; Hilser, Vincent J; Tainer, John A; Mitra, Sankar

    2013-07-10

    NEIL1 [Nei (endonuclease VIII)-like protein 1], one of the five mammalian DNA glycosylases that excise oxidized DNA base lesions in the human genome to initiate base excision repair, contains an intrinsically disordered C-terminal domain (CTD; ~100 residues), not conserved in its Escherichia coli prototype Nei. Although dispensable for NEIL1's lesion excision and AP lyase activities, this segment is required for efficient in vivo enzymatic activity and may provide an interaction interface for many of NEIL1's interactions with other base excision repair proteins. Here, we show that the CTD interacts with the folded domain in native NEIL1 containing 389 residues. The CTD is poised for local folding in an ordered structure that is induced in the purified fragment by osmolytes. Furthermore, deletion of the disordered tail lacking both Tyr and Trp residues causes a red shift in NEIL1's intrinsic Trp-specific fluorescence, indicating a more solvent-exposed environment for the Trp residues in the truncated protein, which also exhibits reduced stability compared to the native enzyme. These observations are consistent with stabilization of the native NEIL1 structure via intramolecular, mostly electrostatic, interactions that were disrupted by mutating a positively charged (Lys-rich) cluster of residues (amino acids 355-360) near the C-terminus. Small-angle X-ray scattering (SAXS) analysis confirms the flexibility and dynamic nature of NEIL1's CTD, a feature that may be critical to providing specificity for NEIL1's multiple, functional interactions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Molecular cloning and functional expression of a human cDNA encoding the antimutator enzyme 8-hydroxyguanine-DNA glycosylase

    Science.gov (United States)

    Roldán-Arjona, Teresa; Wei, Ying-Fei; Carter, Kenneth C.; Klungland, Arne; Anselmino, Catherine; Wang, Rui-Ping; Augustus, Meena; Lindahl, Tomas

    1997-01-01

    The major mutagenic base lesion in DNA caused by exposure to reactive oxygen species is 8-hydroxyguanine (8-oxo-7,8-dihydroguanine). In bacteria and Saccharomyces cerevisiae, this damaged base is excised by a DNA glycosylase with an associated lyase activity for chain cleavage. We have cloned, sequenced, and expressed a human cDNA with partial sequence homology to the relevant yeast gene. The encoded 47-kDa human enzyme releases free 8-hydroxyguanine from oxidized DNA and introduces a chain break in a double-stranded oligonucleotide specifically at an 8-hydroxyguanine residue base paired with cytosine. Expression of the human protein in a DNA repair-deficient E. coli mutM mutY strain partly suppresses its spontaneous mutator phenotype. The gene encoding the human enzyme maps to chromosome 3p25. These results show that human cells have an enzyme that can initiate base excision repair at mutagenic DNA lesions caused by active oxygen. PMID:9223306

  7. Initial steps of the base excision repair pathway within the nuclear architecture

    International Nuclear Information System (INIS)

    Amouroux, R.

    2009-09-01

    Oxidative stress induced lesions threaten aerobic organisms by representing a major cause of genomic instability. A common product of guanine oxidation, 8-oxo-guanine (8- oxoG) is particularly mutagenic by provoking G to T transversions. Removal of oxidised bases from DNA is initiated by the recognition and excision of the damaged base by a DNA glycosylase, initiating the base excision repair (BER) pathway. In mammals, 8-oxoG is processed by the 8-oxoG-DNA-glycosylase I (OGG1), which biochemical mechanisms has been well characterised in vitro. However how and where this enzyme finds the modified base within the complex chromatin architecture is not yet understood. We show that upon induction of 8-oxoG, OGG1, together with at least two other proteins involved in BER, is recruited from a soluble fraction to chromatin. Formation kinetics of this patches correlates with 8-oxoG excision, suggesting a direct link between presence of this chromatin-associated complexes and 8-oxoG repair. More precisely, these repair patches are specifically directed to euchromatin regions, and completely excluded from heterochromatin regions. Inducing of artificial chromatin compaction results in a complete inhibition of the in vivo repair of 8-oxoG, probably by impeding the access of OGG1 to the lesion. Using OGG1 mutants, we show that OGG1 direct recognition of 8-oxoG did not trigger its re-localisation to the chromatin. We conclude that in response to the induction of oxidative DNA damage, the DNA glycosylase is actively recruited to regions of open chromatin allowing the access of the BER machinery to the lesions. (author)

  8. Structural basis for the inhibition of human alkyladenine DNA glycosylase (AAG) by 3,N4-ethenocytosine-containing DNA.

    Science.gov (United States)

    Lingaraju, Gondichatnahalli M; Davis, C Ainsley; Setser, Jeremy W; Samson, Leona D; Drennan, Catherine L

    2011-04-15

    Reactive oxygen and nitrogen species, generated by neutrophils and macrophages in chronically inflamed tissues, readily damage DNA, producing a variety of potentially genotoxic etheno base lesions; such inflammation-related DNA damage is now known to contribute to carcinogenesis. Although the human alkyladenine DNA glycosylase (AAG) can specifically bind DNA containing either 1,N(6)-ethenoadenine (εA) lesions or 3,N(4)-ethenocytosine (εC) lesions, it can only excise εA lesions. AAG binds very tightly to DNA containing εC lesions, forming an abortive protein-DNA complex; such binding not only shields εC from repair by other enzymes but also inhibits AAG from acting on other DNA lesions. To understand the structural basis for inhibition, we have characterized the binding of AAG to DNA containing εC lesions and have solved a crystal structure of AAG bound to a DNA duplex containing the εC lesion. This study provides the first structure of a DNA glycosylase in complex with an inhibitory base lesion that is induced endogenously and that is also induced upon exposure to environmental agents such as vinyl chloride. We identify the primary cause of inhibition as a failure to activate the nucleotide base as an efficient leaving group and demonstrate that the higher binding affinity of AAG for εC versus εA is achieved through formation of an additional hydrogen bond between Asn-169 in the active site pocket and the O(2) of εC. This structure provides the basis for the design of AAG inhibitors currently being sought as an adjuvant for cancer chemotherapy.

  9. Important role of the nucleotide excision repair pathway in Mycobacterium smegmatis in conferring protection against commonly encountered DNA-damaging agents.

    Science.gov (United States)

    Kurthkoti, Krishna; Kumar, Pradeep; Jain, Ruchi; Varshney, Umesh

    2008-09-01

    Mycobacteria are an important group of human pathogens. Although the DNA repair mechanisms in mycobacteria are not well understood, these are vital for the pathogen's persistence in the host macrophages. In this study, we generated a null mutation in the uvrB gene of Mycobacterium smegmatis to allow us to compare the significance of the nucleotide excision repair (NER) pathway with two important base excision repair pathways, initiated by uracil DNA glycosylase (Ung) and formamidopyrimidine DNA glycosylase (Fpg or MutM), in an isogenic strain background. The strain deficient in NER was the most sensitive to commonly encountered DNA-damaging agents such as UV, low pH, reactive oxygen species, hypoxia, and was also sensitive to acidified nitrite. Taken together with previous observations on NER-deficient M. tuberculosis, these results suggest that NER is an important DNA repair pathway in mycobacteria.

  10. MutY DNA Glycosylase Protects Cells From Tumor Necrosis Factor Alpha-Induced Necroptosis.

    Science.gov (United States)

    Tran, An Hue Vy; Han, Se Hee; Kim, Joon; Grasso, Francesca; Kim, In San; Han, Ye Sun

    2017-07-01

    Numerous studies have implied that mutY DNA glycosylase (MYH) is involved in the repair of post-replicative mispairs and plays a critical role in the base excision repair pathway. Recent in vitro studies have shown that MYH interacts with tumor necrosis factor receptor type 1-associated death domain (TRADD), a key effector protein of tumor necrosis factor receptor-1 (TNFR1) signaling. The association between MYH and TRADD is reversed during tumor necrosis factor alpha (TNF-α)- and camptothecin (CPT)-induced apoptosis, and enhanced during TNF-α-induced survival. After investigating the role of MYH interacts with various proteins following TNF-α stimulation, here, we focus on MYH and TRADD interaction functions in necroptosis and its effects to related proteins. We report that the level of the MYH and TRADD complex was also reduced during necroptosis induced by TNF-α and zVAD-fmk. In particular, we also found that MYH is a biologically important necrosis suppressor. Under combined TNF-α and zVAD-fmk treatment, MYH-deficient cells were induced to enter the necroptosis pathway but primary mouse embryonic fibroblasts (MEFs) were not. Necroptosis in the absence of MYH proceeds via the inactivation of caspase-8, followed by an increase in the formation of the kinase receptor- interacting protein 1 (RIP1)-RIP3 complex. Our results suggested that MYH, which interacts with TRADD, inhibits TNF-α necroptotic signaling. Therefore, MYH inactivation is essential for necroptosis via the downregulation of caspase-8. J. Cell. Biochem. 118: 1827-1838, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. Two DNA glycosylases in Esherichia coli which release primarily 3-methyladenine

    International Nuclear Information System (INIS)

    Thomas, L.; Yang, C.; Goldthwait, D.A.

    1982-01-01

    Two enzymes have been partially purified from Escherichia coli and designated 3-methyladenine DNA glycosylases I and II. The apparent molecular weight of glycosylase I is 20,000, and that of II is 27,000. Glycosylase I releases 3-methyladenine (3-MeA) while II releases 3-MeA, 3-methylguanine (3-MeG), 7-methylguanine (7-MeG), and 7-methyladenine (7-MeA). The rate of release of 3-MeA by glycosylase II is 30 times that of 7-MeG. Glycosylase I is missing in mutants tag 1 and tag 2. In crude extracts, the 3-MeA activity of II is approximately 10% of the total 3-MeA activity. A 50% inactivation at 48 0 C required 5 min for I and 65 min for II. The 3-MeA and 7-MeG activities of the glycosylase II preparation could not be separated by isoelectric focusing, by chromatography of DEAE, Sephadex G-100, phosphocellulose, DNA-cellulose, or carboxymethylcellulose, or by heating at 50 0 C

  12. Differential role of base excision repair proteins in mediating cisplatin cytotoxicity.

    Science.gov (United States)

    Sawant, Akshada; Floyd, Ashley M; Dangeti, Mohan; Lei, Wen; Sobol, Robert W; Patrick, Steve M

    2017-03-01

    Interstrand crosslinks (ICLs) are covalent lesions formed by cisplatin. The mechanism for the processing and removal of ICLs by DNA repair proteins involves nucleotide excision repair (NER), homologous recombination (HR) and fanconi anemia (FA) pathways. In this report, we monitored the processing of a flanking uracil adjacent to a cisplatin ICL by the proteins involved in the base excision repair (BER) pathway. Using a combination of extracts, purified proteins, inhibitors, functional assays and cell culture studies, we determined the specific BER proteins required for processing a DNA substrate with a uracil adjacent to a cisplatin ICL. Uracil DNA glycosylase (UNG) is the primary glycosylase responsible for the removal of uracils adjacent to cisplatin ICLs, whereas other uracil glycosylases can process uracils in the context of undamaged DNA. Repair of the uracil adjacent to cisplatin ICLs proceeds through the classical BER pathway, highlighting the importance of specific proteins in this redundant pathway. Removal of uracil is followed by the generation of an abasic site and subsequent cleavage by AP endonuclease 1 (APE1). Inhibition of either the repair or redox domain of APE1 gives rise to cisplatin resistance. Inhibition of the lyase domain of Polymerase β (Polβ) does not influence cisplatin cytotoxicity. In addition, lack of XRCC1 leads to increased DNA damage and results in increased cisplatin cytotoxicity. Our results indicate that BER activation at cisplatin ICLs influences crosslink repair and modulates cisplatin cytotoxicity via specific UNG, APE1 and Polβ polymerase functions. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Characterization of the major formamidopyrimidine-DNA glycosylase homolog in Mycobacterium tuberculosis and its linkage to variable tandem repeats.

    Science.gov (United States)

    Olsen, Ingrid; Balasingham, Seetha V; Davidsen, Tonje; Debebe, Ephrem; Rødland, Einar A; van Soolingen, Dick; Kremer, Kristin; Alseth, Ingrun; Tønjum, Tone

    2009-07-01

    The ability to repair DNA damage is likely to play an important role in the survival of facultative intracellular parasites because they are exposed to high levels of reactive oxygen species and nitrogen intermediates inside phagocytes. Correcting oxidative damage in purines and pyrimidines is the primary function of the enzymes formamidopyrimidine (faPy)-DNA glycosylase (Fpg) and endonuclease VIII (Nei) of the base excision repair pathway, respectively. Four gene homologs, belonging to the fpg/nei family, have been identified in Mycobacterium tuberculosis H37Rv. The recombinant protein encoded by M. tuberculosis Rv2924c, termed Mtb-Fpg1, was overexpressed, purified and biochemically characterized. The enzyme removed faPy and 5-hydroxycytosine lesions, as well as 8-oxo-7,8-dihydroguanine (8oxoG) opposite to C, T and G. Mtb-Fpg1 thus exhibited substrate specificities typical for Fpg enzymes. Although Mtb-fpg1 showed nearly complete nucleotide sequence conservation in 32 M. tuberculosis isolates, the region upstream of Mtb-fpg1 in these strains contained tandem repeat motifs of variable length. A relationship between repeat length and Mtb-fpg1 expression level was demonstrated in M. tuberculosis strains, indicating that an increased length of the tandem repeats positively influenced the expression levels of Mtb-fpg1. This is the first example of such a tandem repeat region of variable length being linked to the expression level of a bacterial gene.

  14. Sensitization of human carcinoma cells to alkylating agents by small interfering RNA suppression of 3-alkyladenine-DNA glycosylase.

    Science.gov (United States)

    Paik, Johanna; Duncan, Tod; Lindahl, Tomas; Sedgwick, Barbara

    2005-11-15

    One of the major cytotoxic lesions generated by alkylating agents is DNA 3-alkyladenine, which can be excised by 3-alkyladenine DNA glycosylase (AAG). Inhibition of AAG may therefore result in increased cellular sensitivity to chemotherapeutic alkylating agents. To investigate this possibility, we have examined the role of AAG in protecting human tumor cells against such agents. Plasmids that express small interfering RNAs targeted to two different regions of AAG mRNA were transfected into HeLa cervical carcinoma cells and A2780-SCA ovarian carcinoma cells. Stable derivatives of both cell types with low AAG protein levels were sensitized to alkylating agents. Two HeLa cell lines with AAG protein levels reduced by at least 80% to 90% displayed a 5- to 10-fold increase in sensitivity to methyl methanesulfonate, N-methyl-N-nitrosourea, and the chemotherapeutic drugs temozolomide and 1,3-bis(2-chloroethyl)-1-nitrosourea. These cells showed no increase in sensitivity to UV light or ionizing radiation. After treatment with methyl methanesulfonate, AAG knockdown HeLa cells were delayed in S phase but accumulated in G2-M. Our data support the hypothesis that ablation of AAG activity in human tumor cells may provide a useful strategy to enhance the efficacy of current chemotherapeutic regimens that include alkylating agents.

  15. Arthroscopic excision of ganglion cysts.

    Science.gov (United States)

    Bontempo, Nicholas A; Weiss, Arnold-Peter C

    2014-02-01

    Arthroscopy is an advancing field in orthopedics, the applications of which have been expanding over time. Traditionally, excision of ganglion cysts has been done in an open fashion. However, more recently, studies show outcomes following arthroscopic excision to be as good as open excision. Cosmetically, the incisions are smaller and heal faster following arthroscopy. In addition, there is the suggested benefit that patients will regain function and return to work faster following arthroscopic excision. More prospective studies comparing open and arthroscopic excision of ganglion cysts need to be done in order to delineate if there is a true functional benefit. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Aag-initiated base excision repair promotes ischemia reperfusion injury in liver, brain, and kidney.

    Science.gov (United States)

    Ebrahimkhani, Mohammad R; Daneshmand, Ali; Mazumder, Aprotim; Allocca, Mariacarmela; Calvo, Jennifer A; Abolhassani, Nona; Jhun, Iny; Muthupalani, Sureshkumar; Ayata, Cenk; Samson, Leona D

    2014-11-11

    Inflammation is accompanied by the release of highly reactive oxygen and nitrogen species (RONS) that damage DNA, among other cellular molecules. Base excision repair (BER) is initiated by DNA glycosylases and is crucial in repairing RONS-induced DNA damage; the alkyladenine DNA glycosylase (Aag/Mpg) excises several DNA base lesions induced by the inflammation-associated RONS release that accompanies ischemia reperfusion (I/R). Using mouse I/R models we demonstrate that Aag(-/-) mice are significantly protected against, rather than sensitized to, I/R injury, and that such protection is observed across three different organs. Following I/R in liver, kidney, and brain, Aag(-/-) mice display decreased hepatocyte death, cerebral infarction, and renal injury relative to wild-type. We infer that in wild-type mice, Aag excises damaged DNA bases to generate potentially toxic abasic sites that in turn generate highly toxic DNA strand breaks that trigger poly(ADP-ribose) polymerase (Parp) hyperactivation, cellular bioenergetics failure, and necrosis; indeed, steady-state levels of abasic sites and nuclear PAR polymers were significantly more elevated in wild-type vs. Aag(-/-) liver after I/R. This increase in PAR polymers was accompanied by depletion of intracellular NAD and ATP levels plus the translocation and extracellular release of the high-mobility group box 1 (Hmgb1) nuclear protein, activating the sterile inflammatory response. We thus demonstrate the detrimental effects of Aag-initiated BER during I/R and sterile inflammation, and present a novel target for controlling I/R-induced injury.

  17. Analog computing

    CERN Document Server

    Ulmann, Bernd

    2013-01-01

    This book is a comprehensive introduction to analog computing. As most textbooks about this powerful computing paradigm date back to the 1960s and 1970s, it fills a void and forges a bridge from the early days of analog computing to future applications. The idea of analog computing is not new. In fact, this computing paradigm is nearly forgotten, although it offers a path to both high-speed and low-power computing, which are in even more demand now than they were back in the heyday of electronic analog computers.

  18. Base excision repair in Archaea: back to the future in DNA repair.

    Science.gov (United States)

    Grasso, Stefano; Tell, Gianluca

    2014-09-01

    Together with Bacteria and Eukarya, Archaea represents one of the three domain of life. In contrast with the morphological difference existing between Archaea and Eukarya, these two domains are closely related. Phylogenetic analyses confirm this evolutionary relationship showing that most of the proteins involved in DNA transcription and replication are highly conserved. On the contrary, information is scanty about DNA repair pathways and their mechanisms. In the present review the most important proteins involved in base excision repair, namely glycosylases, AP lyases, AP endonucleases, polymerases, sliding clamps, flap endonucleases, and ligases, will be discussed and compared with bacterial and eukaryotic ones. Finally, possible applications and future perspectives derived from studies on Archaea and their repair pathways, will be taken into account. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. New insights in the removal of the hydantoins, oxidation product of pyrimidines, via the base excision and nucleotide incision repair pathways.

    Directory of Open Access Journals (Sweden)

    Modesto Redrejo-Rodríguez

    Full Text Available BACKGROUND: Oxidative damage to DNA, if not repaired, can be both miscoding and blocking. These genetic alterations can lead to mutations and/or cell death, which in turn cause cancer and aging. Oxidized DNA bases are substrates for two overlapping repair pathways: base excision (BER and nucleotide incision repair (NIR. Hydantoin derivatives such as 5-hydroxyhydantoin (5OH-Hyd and 5-methyl-5-hydroxyhydantoin (5OH-5Me-Hyd, major products of cytosine and thymine oxidative degradation pathways, respectively, have been detected in cancer cells and ancient DNA. Hydantoins are blocking lesions for DNA polymerases and excised by bacterial and yeast DNA glycosylases in the BER pathway. However little is known about repair of pyrimidine-derived hydantoins in human cells. METHODOLOGY/PRINCIPAL FINDINGS: Here, using both denaturing PAGE and MALDI-TOF MS analyses we report that the bacterial, yeast and human AP endonucleases can incise duplex DNA 5' next to 5OH-Hyd and 5OH-5Me-Hyd thus initiating the NIR pathway. We have fully reconstituted the NIR pathway for these lesions in vitro using purified human proteins. Depletion of Nfo in E. coli and APE1 in HeLa cells abolishes the NIR activity in cell-free extracts. Importantly, a number of redundant DNA glycosylase activities can excise hydantoin residues, including human NTH1, NEIL1 and NEIL2 and the former protein being a major DNA glycosylase activity in HeLa cells extracts. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that both BER and NIR pathways can compete and/or back-up each other to remove hydantoin DNA lesions in vivo.

  20. Analog earthquakes

    International Nuclear Information System (INIS)

    Hofmann, R.B.

    1995-01-01

    Analogs are used to understand complex or poorly understood phenomena for which little data may be available at the actual repository site. Earthquakes are complex phenomena, and they can have a large number of effects on the natural system, as well as on engineered structures. Instrumental data close to the source of large earthquakes are rarely obtained. The rare events for which measurements are available may be used, with modfications, as analogs for potential large earthquakes at sites where no earthquake data are available. In the following, several examples of nuclear reactor and liquified natural gas facility siting are discussed. A potential use of analog earthquakes is proposed for a high-level nuclear waste (HLW) repository

  1. An unconventional family 1 uracil DNA glycosylase in Nitratifractor salsuginis.

    Science.gov (United States)

    Li, Jing; Chen, Ran; Yang, Ye; Zhang, Zhemin; Fang, Guang-Chen; Xie, Wei; Cao, Weiguo

    2017-12-01

    The uracil DNA glycosylase superfamily consists of at least six families with a diverse specificity toward DNA base damage. Family 1 uracil N-glycosylase (UNG) exhibits exclusive specificity on uracil-containing DNA. Here, we report a family 1 UNG homolog from Nitratifractor salsuginis with distinct biochemical features that differentiate it from conventional family 1 UNGs. Globally, the crystal structure of N. salsuginisUNG shows a few additional secondary structural elements. Biochemical and enzyme kinetic analysis, coupled with structural determination, molecular modeling, and molecular dynamics simulations, shows that N. salsuginisUNG contains a salt bridge network that plays an important role in DNA backbone interactions. Disruption of the amino acid residues involved in the salt bridges greatly impedes the enzymatic activity. A tyrosine residue in motif 1 (GQDPY) is one of the distinct sequence features setting family 1 UNG apart from other families. The crystal structure of Y81G mutant indicates that several subtle changes may account for its inactivity. Unlike the conventional family 1 UNG enzymes, N. salsuginisUNG is not inhibited by Ugi, a potent inhibitor specific for family 1 UNG. This study underscores the diversity of paths that a uracil DNA glycosylase may take to acquire its unique structural and biochemical properties during evolution. Structure data are available in the PDB under accession numbers 5X3G and 5X3H. © 2017 Federation of European Biochemical Societies.

  2. Impact of psychostimulants and atomoxetine on the expression of 8-hydroxyguanine glycosylase 1 in human cells.

    Science.gov (United States)

    Schmidt, Andreas Johannes; Clement, Hans-Willi; Gebhardt, Stefan; Hemmeter, Ulrich Michael; Schulz, Eberhard; Krieg, Jürgen-Christian; Kircher, Tilo; Heiser, Philip

    2010-06-01

    Oxidative DNA damage as one sign of reactive oxygen species induced oxidative stress is an important factor in the pathogenesis of various psychiatric disorders. Altered levels of DNA base damage products as well as the expression of the main repair enzyme 8-hydroxyguanine glycosylase 1 have been described. The aim of the present study was to examine the effects of drugs (amphetamine, methylphenidate and atomoxetine) used in the treatment of attention deficit-hyperactivity disorder on the expression of this enzyme via reverse transcriptase-polymerase chain reaction in human neuroblastoma SH-SY5Y and human monocytic U-937 cells at concentrations of 50, 500 and 5,000 ng/ml. We observed decreased expression of this enzyme for all applied substances. In U-937 cells, the significance level was reached after treatment with 5,000 ng/ml amphetamine as well as after treatment with 50, 500 and 5,000 ng/ml atomoxetine. Incubation of SH-SY5Y cells with 50 and 5,000 ng/ml amphetamine and 5,000 ng/ml methylphenidate led to significant decreases of 8-hydroxyguanine glycosylase 1. As a positive correlation between the expression of 8-hydroxyguanine glycosylase 1 and the level of oxidative DNA damage products has been described, we accordingly consider these substances (amphetamine, methylphenidate and atomoxetine) to possibly play a protective role in this process.

  3. Systematic analysis of DEMETER-like DNA glycosylase genes shows lineage-specific Smi-miR7972 involved in SmDML1 regulation in Salvia miltiorrhiza.

    Science.gov (United States)

    Li, Jiang; Li, Caili; Lu, Shanfa

    2018-05-08

    DEMETER-like DNA glycosylases (DMLs) initiate the base excision repair-dependent DNA demethylation to regulate a wide range of biological processes in plants. Six putative SmDML genes, termed SmDML1-SmDML6, were identified from the genome of S. miltiorrhiza, an emerging model plant for Traditional Chinese Medicine (TCM) studies. Integrated analysis of gene structures, sequence features, conserved domains and motifs, phylogenetic analysis and differential expression showed the conservation and divergence of SmDMLs. SmDML1, SmDML2 and SmDML4 were significantly down-regulated by the treatment of 5Aza-dC, a general DNA methylation inhibitor, suggesting involvement of SmDMLs in genome DNA methylation change. SmDML1 was predicted and experimentally validated to be target of Smi-miR7972. Computational analysis of forty whole genome sequences and almost all of RNA-seq data from Lamiids revealed that MIR7972s were only distributed in some plants of the three orders, including Lamiales, Solanales and Boraginales, and the number of MIR7972 genes varied among species. It suggests that MIR7972 genes underwent expansion and loss during the evolution of some Lamiids species. Phylogenetic analysis of MIR7972s showed closer evolutionary relationships between MIR7972s in Boraginales and Solanales in comparison with Lamiales. These results provide a valuable resource for elucidating DNA demethylation mechanism in S. miltiorrhiza.

  4. Nucleotide excision repair in yeast

    NARCIS (Netherlands)

    Eijk, Patrick van

    2012-01-01

    Nucleotide Excision Repair (NER) is a conserved DNA repair pathway capable of removing a broad spectrum of DNA damage. In human cells a defect in NER leads to the disorder Xeroderma pigmentosum (XP). The yeast Saccharomyces cerevisiae is an excellent model organism to study the mechanism of NER. The

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

    KAUST Repository

    La, Honggui; Ding, Bo; Mishra, Gyan Prakash; Zhou, Bo; Yang, Hongmei; Bellizzi, Maria Del Rosario; Chen, Songbiao; Meyers, Blake C.; Peng, Zhaohua; Zhu, Jian-Kang; Wang, Guoliang

    2011-01-01

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

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

    KAUST Repository

    La, Honggui

    2011-09-06

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

  7. Lumbar disc excision through fenestration

    Directory of Open Access Journals (Sweden)

    Sangwan S

    2006-01-01

    Full Text Available Background : Lumbar disc herniation often causes sciatica. Many different techniques have been advocated with the aim of least possible damage to other structures while dealing with prolapsed disc surgically in the properly selected and indicated cases. Methods : Twenty six patients with clinical symptoms and signs of prolapsed lumbar intervertebral disc having radiological correlation by MRI study were subjected to disc excision by interlaminar fenestration method. Results : The assessment at follow-up showed excellent results in 17 patients, good in 6 patients, fair in 2 patients and poor in 1 patient. The mean preoperative and postoperative Visual Analogue Scores were 9.34 ±0.84 and 2.19 ±0.84 on scale of 0-10 respectively. These were statistically significant (p value< 0.001, paired t test. No significant complications were recorded. Conclusion : Procedures of interlaminar fenestration and open disc excision under direct vision offers sufficient adequate exposure for lumbar disc excision with a smaller incision, lesser morbidity, shorter convalescence, early return to work and comparable overall results in the centers where recent laser and endoscopy facilities are not available.

  8. DENV gene of bacteriophage T4 codes for both pyrimidine dimer-DNA glycosylase and apyrimidinic endonuclease activities

    International Nuclear Information System (INIS)

    McMillan, S.; Edenberg, H.J.; Radany, E.H.; Friedberg, R.C.; Friedberg, E.C.

    1981-01-01

    Recent studies have shown that purified preparations of phage T4 UV DNA-incising activity (T4 UV endonuclease or endonuclease V of phase T4) contain a pyrimidine dimer-DNA glycosylase activity that catalyzes hydrolysis of the 5' glycosyl bond of dimerized pyrimidines in UV-irradiated DNA. Such enzyme preparations have also been shown to catalyze the hydrolysis of phosphodiester bonds in UV-irradiated DNA at a neutral pH, presumably reflecting the action of an apurinic/apyrimidinic endonuclease at the apyrimidinic sites created by the pyrimidine dimer-DNA glycosylase. In this study we found that preparations of T4 UV DNA-incising activity contained apurinic/apyrimidinic endonuclease activity that nicked depurinated form I simian virus 40 DNA. Apurinic/apyrimidinic endonuclease activity was also found in extracts of Escherichia coli infected with T4 denV + phage. Extracts of cells infected with T4 denV mutants contained significantly lower levels of apurinic/apyrimidinic endonuclease activity; these levels were no greater than the levels present in extracts of uninfected cells. Furthermore, the addition of DNA containing UV-irradiated DNA and T4 enzyme resulted in competition for pyrimidine dimer-DNA glycosylase activity against the UV-irradiated DNA. On the basis of these results, we concluded that apurinic/apyrimidinic endonuclease activity is encoded by the denV gene of phage T4, the same gene that codes for pyrimidine dimer-DNA glycosylase activity

  9. Tungsten disulfide nanosheet and exonuclease III co-assisted amplification strategy for highly sensitive fluorescence polarization detection of DNA glycosylase activity

    International Nuclear Information System (INIS)

    Zhao, Jingjin; Ma, Yefei; Kong, Rongmei; Zhang, Liangliang; Yang, Wen; Zhao, Shulin

    2015-01-01

    Herein, we introduced a tungsten disulfide (WS 2 ) nanosheet and exonuclease III (Exo III) co-assisted signal amplification strategy for highly sensitive fluorescent polarization (FP) assay of DNA glycosylase activity. Two DNA glycosylases, uracil-DNA glycosylase (UDG) and human 8-oxoG DNA glycosylase 1 (hOGG1), were tested. A hairpin-structured probe (HP) which contained damaged bases in the stem was used as the substrate. The removal of damaged bases from substrate by DNA glycosylase would lower the melting temperature of HP. The HP was then opened and hybridized with a FAM dye-labeled single strand DNA (DP), generating a duplex with a recessed 3′-terminal of DP. This design facilitated the Exo III-assisted amplification by repeating the hybridization and digestion of DP, liberating numerous FAM fluorophores which could not be adsorbed on WS 2 nanosheet. Thus, the final system exhibited a small FP signal. However, in the absence of DNA glycosylases, no hybridization between DP and HP was occurred, hampering the hydrolysis of DP by Exo III. The intact DP was then adsorbed on the surface of WS 2 nanosheet that greatly amplified the mass of the labeled-FAM fluorophore, resulting in a large FP value. With the co-assisted amplification strategy, the sensitivity was substantially improved. In addition, this method was applied to detect UDG activity in cell extracts. The study of the inhibition of UDG was also performed. Furthermore, this method is simple in design, easy in implementation, and selective, which holds potential applications in the DNA glycosylase related mechanism research and molecular diagnostics. - Highlights: • A fluorescence polarization strategy for DNA glycosylase activity detection was developed. • The present method was based on WS 2 nanosheet and exonuclease III co-assisted signal amplification. • A high sensitivity and desirable selectivity were achieved. • This method provides a promising universal platform for DNA glycosylase

  10. Transmission of the PabI family of restriction DNA glycosylase genes: mobility and long-term inheritance.

    Science.gov (United States)

    Kojima, Kenji K; Kobayashi, Ichizo

    2015-10-19

    R.PabI is an exceptional restriction enzyme that functions as a DNA glycosylase. The enzyme excises an unmethylated base from its recognition sequence to generate apurinic/apyrimidinic (AP) sites, and also displays AP lyase activity, cleaving the DNA backbone at the AP site to generate the 3'-phospho alpha, beta-unsaturated aldehyde end in addition to the 5'-phosphate end. The resulting ends are difficult to religate with DNA ligase. The enzyme was originally isolated in Pyrococcus, a hyperthermophilic archaeon, and additional homologs subsequently identified in the epsilon class of the Gram-negative bacterial phylum Proteobacteria, such as Helicobacter pylori. Systematic analysis of R.PabI homologs and their neighboring genes in sequenced genomes revealed co-occurrence of R.PabI with M.PabI homolog methyltransferase genes. R.PabI and M.PabI homolog genes are occasionally found at corresponding (orthologous) loci in different species, such as Helicobacter pylori, Helicobacter acinonychis and Helicobacter cetorum, indicating long-term maintenance of the gene pair. One R.PabI and M.PabI homolog gene pair is observed immediately after the GMP synthase gene in both Campylobacter and Helicobacter, representing orthologs beyond genera. The mobility of the PabI family of restriction-modification (RM) system between genomes is evident upon comparison of genomes of sibling strains/species. Analysis of R.PabI and M.PabI homologs in H. pylori revealed an insertion of integrative and conjugative elements (ICE), and replacement with a gene of unknown function that may specify a membrane-associated toxin (hrgC). In view of the similarity of HrgC with toxins in type I toxin-antitoxin systems, we addressed the biological significance of this substitution. Our data indicate that replacement with hrgC occurred in the common ancestor of hspAmerind and hspEAsia. Subsequently, H. pylori with and without hrgC were intermixed at this locus, leading to complex distribution of hrgC in East

  11. Feasibility study of transanal total mesorectal excision

    NARCIS (Netherlands)

    Velthuis, S.; Boezem, P.B. van den; Peet, D.L. van der; Cuesta, M.A.; Sietses, C.

    2013-01-01

    BACKGROUND: Laparoscopic resection of colorectal cancers is a safe alternative to open surgery. The conversion rate to open surgery remains fairly constant but is associated with increased morbidity. A new approach to the surgical excision of rectal cancer is transanal total mesorectal excision

  12. Different organization of base excision repair of uracil in DNA in nuclei and mitochondria and selective upregulation of mitochondrial uracil-DNA glycosylase after oxidative stress

    DEFF Research Database (Denmark)

    Akbari, M; Otterlei, M; Pena Diaz, Javier

    2007-01-01

    , indicating regulatory effects of oxidative stress on mitochondrial BER. To examine the overall organization of uracil-BER in nuclei and mitochondria, we constructed cell lines expressing EYFP (enhanced yellow fluorescent protein) fused to UNG1 or UNG2. These were used to investigate the possible presence...... BER processes are differently organized. Furthermore, the upregulation of mRNA for mitochondrial UNG1 after oxidative stress indicates that it may have an important role in repair of oxidized pyrimidines....

  13. The base excision repair pathway is required for efficient lentivirus integration.

    Directory of Open Access Journals (Sweden)

    Kristine E Yoder

    Full Text Available An siRNA screen has identified several proteins throughout the base excision repair (BER pathway of oxidative DNA damage as important for efficient HIV infection. The proteins identified included early repair factors such as the base damage recognition glycosylases OGG1 and MYH and the late repair factor POLß, implicating the entire BER pathway. Murine cells with deletions of the genes Ogg1, Myh, Neil1 and Polß recapitulate the defect of HIV infection in the absence of BER. Defective infection in the absence of BER proteins was also seen with the lentivirus FIV, but not the gammaretrovirus MMLV. BER proteins do not affect HIV infection through its accessory genes nor the central polypurine tract. HIV reverse transcription and nuclear entry appear unaffected by the absence of BER proteins. However, HIV integration to the host chromosome is reduced in the absence of BER proteins. Pre-integration complexes from BER deficient cell lines show reduced integration activity in vitro. Integration activity is restored by addition of recombinant BER protein POLß. Lentiviral infection and integration efficiency appears to depend on the presence of BER proteins.

  14. The Influence of Hepatitis C Virus Therapy on the DNA Base Excision Repair System of Peripheral Blood Mononuclear Cells.

    Science.gov (United States)

    Czarny, Piotr; Merecz-Sadowska, Anna; Majchrzak, Kinga; Jabłkowski, Maciej; Szemraj, Janusz; Śliwiński, Tomasz; Karwowski, Bolesław

    2017-07-01

    Hepatitis C virus (HCV) can infect extrahepatic tissues, including lymphocytes, creating reservoir of the virus. Moreover, HCV proteins can interact with DNA damage response proteins of infected cells. In this article we investigated the influence of the virus infection and a new ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) anti-HCV therapy on the PBMCs (peripheral blood mononuclear cells, mainly lymphocytes) DNA base excision repair (BER) system. BER protein activity was analyzed in the nuclear and mitochondrial extracts (NE and ME) of PBMC isolated from patients before and after therapy, and from subjects without HCV, using modeled double-strand DNA, with 2'-deoxyuridine substitution as the DNA damage. The NE and ME obtained from patients before therapy demonstrated lower efficacy of 2'-deoxyuridine removal and DNA repair polymerization than those of the control group or patients after therapy. Moreover, the extracts from the patients after therapy had similar activity to those from the control group. However, the efficacy of apurinic/apyrimidinic site excision in NE did not differ between the studied groups. We postulate that infection of lymphocytes by the HCV can lead to a decrease in the activity of BER enzymes. However, the use of novel therapy results in the improvement of glycosylase activity as well as the regeneration of endonuclease and other crucial repair enzymes.

  15. Oxidatively-induced DNA damage and base excision repair in euthymic patients with bipolar disorder.

    Science.gov (United States)

    Ceylan, Deniz; Tuna, Gamze; Kirkali, Güldal; Tunca, Zeliha; Can, Güneş; Arat, Hidayet Ece; Kant, Melis; Dizdaroglu, Miral; Özerdem, Ayşegül

    2018-05-01

    Oxidatively-induced DNA damage has previously been associated with bipolar disorder. More recently, impairments in DNA repair mechanisms have also been reported. We aimed to investigate oxidatively-induced DNA lesions and expression of DNA glycosylases involved in base excision repair in euthymic patients with bipolar disorder compared to healthy individuals. DNA base lesions including both base and nucleoside modifications were measured using gas chromatography-tandem mass spectrometry and liquid chromatography-tandem mass spectrometry with isotope-dilution in DNA samples isolated from leukocytes of euthymic patients with bipolar disorder (n = 32) and healthy individuals (n = 51). The expression of DNA repair enzymes OGG1 and NEIL1 were measured using quantitative real-time polymerase chain reaction. The levels of malondialdehyde were measured using high performance liquid chromatography. Seven DNA base lesions in DNA of leukocytes of patients and healthy individuals were identified and quantified. Three of them had significantly elevated levels in bipolar patients when compared to healthy individuals. No elevation of lipid peroxidation marker malondialdehyde was observed. The level of OGG1 expression was significantly reduced in bipolar patients compared to healthy individuals, whereas the two groups exhibited similar levels of NEIL1 expression. Our results suggest that oxidatively-induced DNA damage occurs and base excision repair capacity may be decreased in bipolar patients when compared to healthy individuals. Measurement of oxidatively-induced DNA base lesions and the expression of DNA repair enzymes may be of great importance for large scale basic research and clinical studies of bipolar disorder. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Repair of 3-methyladenine and abasic sites by base excision repair mediates glioblastoma resistance to temozolomide

    Energy Technology Data Exchange (ETDEWEB)

    Bobola, Michael S.; Kolstoe, Douglas D.; Blank, A. [Department of Neurological Surgery, University of Washington Medical Center, Seattle, WA (United States); Chamberlain, Marc C. [Department of Neurological Surgery, University of Washington Medical Center, Seattle, WA (United States); Department of Neurology, University of Washington Medical Center, Seattle, WA (United States); Silber, John R., E-mail: jrsilber@u.washington.edu [Department of Neurological Surgery, University of Washington Medical Center, Seattle, WA (United States)

    2012-11-30

    Alkylating agents have long played a central role in the adjuvant therapy of glioblastoma (GBM). More recently, inclusion of temozolomide (TMZ), an orally administered methylating agent with low systemic toxicity, during and after radiotherapy has markedly improved survival. Extensive in vitro and in vivo evidence has shown that TMZ-induced O{sup 6}-methylguanine (O{sup 6}-meG) mediates GBM cell killing. Moreover, low or absent expression of O{sup 6}-methylguanine-DNA methyltransferase (MGMT), the sole human repair protein that removes O{sup 6}-meG from DNA, is frequently associated with longer survival in GBMs treated with TMZ, promoting interest in developing inhibitors of MGMT to counter resistance. However, the clinical efficacy of TMZ is unlikely to be due solely to O{sup 6}-meG, as the agent produces approximately a dozen additional DNA adducts, including cytotoxic N3-methyladenine (3-meA) and abasic sites. Repair of 3-meA and abasic sites, both of which are produced in greater abundance than O{sup 6}-meG, is mediated by the base excision repair (BER) pathway, and occurs independently of removal of O{sup 6}-meG. These observations indicate that BER activities are also potential targets for strategies to potentiate TMZ cytotoxicity. Here we review the evidence that 3-meA and abasic sites mediate killing of GBM cells. We also present in vitro and in vivo evidence that alkyladenine-DNA glycosylase, the sole repair activity that excises 3-meA from DNA, and Ape1, the major human abasic site endonuclease, mediate TMZ resistance in GBMs and represent potential anti-resistance targets.

  17. Science Teachers' Analogical Reasoning

    Science.gov (United States)

    Mozzer, Nilmara Braga; Justi, Rosária

    2013-08-01

    Analogies can play a relevant role in students' learning. However, for the effective use of analogies, teachers should not only have a well-prepared repertoire of validated analogies, which could serve as bridges between the students' prior knowledge and the scientific knowledge they desire them to understand, but also know how to introduce analogies in their lessons. Both aspects have been discussed in the literature in the last few decades. However, almost nothing is known about how teachers draw their own analogies for instructional purposes or, in other words, about how they reason analogically when planning and conducting teaching. This is the focus of this paper. Six secondary teachers were individually interviewed; the aim was to characterize how they perform each of the analogical reasoning subprocesses, as well as to identify their views on analogies and their use in science teaching. The results were analyzed by considering elements of both theories about analogical reasoning: the structural mapping proposed by Gentner and the analogical mechanism described by Vosniadou. A comprehensive discussion of our results makes it evident that teachers' content knowledge on scientific topics and on analogies as well as their pedagogical content knowledge on the use of analogies influence all their analogical reasoning subprocesses. Our results also point to the need for improving teachers' knowledge about analogies and their ability to perform analogical reasoning.

  18. Alkyladenine DNA glycosylase (AAG) localizes to mitochondria and interacts with mitochondrial single-stranded binding protein (mtSSB)

    OpenAIRE

    van Loon, Barbara; Samson, Leona D.

    2013-01-01

    Due to a harsh environment mitochondrial genomes accumulate high levels of DNA damage, in particular oxidation, hydrolytic deamination, and alkylation adducts. While repair of alkylated bases in nuclear DNA has been explored in detail, much less is known about the repair of DNA alkylation damage in mitochondria. Alkyladenine DNA glycosylase (AAG) recognizes and removes numerous alkylated bases, but to date AAG has only been detected in the nucleus, even though mammalian mitochondria are known...

  19. Identification of a residue critical for the excision of 3′-blocking ends in apurinic/apyrimidinic endonucleases of the Xth family

    Science.gov (United States)

    Castillo-Acosta, Víctor M.; Ruiz-Pérez, Luis M.; Yang, Wei; González-Pacanowska, Dolores; Vidal, Antonio E.

    2009-01-01

    DNA single-strand breaks containing 3′-blocking groups are generated from attack of the sugar backbone by reactive oxygen species or after base excision by DNA glycosylase/apurinic/apyrimidinic (AP) lyases. In human cells, APE1 excises sugar fragments that block the 3′-ends thus facilitating DNA repair synthesis. In Leishmania major, the causal agent of leishmaniasis, the APE1 homolog is the class II AP endonuclease LMAP. Expression of LMAP but not of APE1 reverts the hypersensitivity of a xth nfo repair-deficient Escherichia coli strain to the oxidative compound hydrogen peroxide (H2O2). To identify the residues specifically involved in the repair of oxidative DNA damage, we generated random mutations in the ape1 gene and selected those variants that conferred protection against H2O2. Among the resistant clones, we isolated a mutant in the nuclease domain of APE1 (D70A) with an increased capacity to remove 3′-blocking ends in vitro. D70 of APE1 aligns with A138 of LMAP and mutation of the latter to aspartate significantly reduces its 3′-phosphodiesterase activity. Kinetic analysis shows a novel role of residue D70 in the excision rate of 3′-blocking ends. The functional and structural differences between the parasite and human enzymes probably reflect a divergent molecular evolution of their DNA repair responses to oxidative damage. PMID:19181704

  20. Intuitive analog circuit design

    CERN Document Server

    Thompson, Marc

    2013-01-01

    Intuitive Analog Circuit Design outlines ways of thinking about analog circuits and systems that let you develop a feel for what a good, working analog circuit design should be. This book reflects author Marc Thompson's 30 years of experience designing analog and power electronics circuits and teaching graduate-level analog circuit design, and is the ideal reference for anyone who needs a straightforward introduction to the subject. In this book, Dr. Thompson describes intuitive and ""back-of-the-envelope"" techniques for designing and analyzing analog circuits, including transistor amplifi

  1. Nucleotide excision repair in the test tube.

    NARCIS (Netherlands)

    N.G.J. Jaspers (Nicolaas); J.H.J. Hoeijmakers (Jan)

    1995-01-01

    textabstractThe eukaryotic nucleotide excision-repair pathway has been reconstituted in vitro, an achievement that should hasten the full enzymological characterization of this highly complex DNA-repair pathway.

  2. Structural plasticity in Mycobacterium tuberculosis uracil-DNA glycosylase (MtUng) and its functional implications.

    Science.gov (United States)

    Arif, S M; Geethanandan, K; Mishra, P; Surolia, A; Varshney, U; Vijayan, M

    2015-07-01

    17 independent crystal structures of family I uracil-DNA glycosylase from Mycobacterium tuberculosis (MtUng) and its complexes with uracil and its derivatives, distributed among five distinct crystal forms, have been determined. Thermodynamic parameters of binding in the complexes have been measured using isothermal titration calorimetry. The two-domain protein exhibits open and closed conformations, suggesting that the closure of the domain on DNA binding involves conformational selection. Segmental mobility in the enzyme molecule is confined to a 32-residue stretch which plays a major role in DNA binding. Uracil and its derivatives can bind to the protein in two possible orientations. Only one of them is possible when there is a bulky substituent at the 5' position. The crystal structures of the complexes provide a reasonable rationale for the observed thermodynamic parameters. In addition to providing fresh insights into the structure, plasticity and interactions of the protein molecule, the results of the present investigation provide a platform for structure-based inhibitor design.

  3. Analysis of substrate specificity of Schizosaccharomyces pombe Mag1 alkylpurine DNA glycosylase

    Energy Technology Data Exchange (ETDEWEB)

    Adhikary, Suraj; Eichman, Brandt F. (Vanderbilt)

    2014-10-02

    DNA glycosylases specialized for the repair of alkylation damage must identify, with fine specificity, a diverse array of subtle modifications within DNA. The current mechanism involves damage sensing through interrogation of the DNA duplex, followed by more specific recognition of the target base inside the active site pocket. To better understand the physical basis for alkylpurine detection, we determined the crystal structure of Schizosaccharomyces pombe Mag1 (spMag1) in complex with DNA and performed a mutational analysis of spMag1 and the close homologue from Saccharomyces cerevisiae (scMag). Despite strong homology, spMag1 and scMag differ in substrate specificity and cellular alkylation sensitivity, although the enzymological basis for their functional differences is unknown. We show that Mag preference for 1,N{sup 6}-ethenoadenine ({var_epsilon}A) is influenced by a minor groove-interrogating residue more than the composition of the nucleobase-binding pocket. Exchanging this residue between Mag proteins swapped their {var_epsilon}A activities, providing evidence that residues outside the extrahelical base-binding pocket have a role in identification of a particular modification in addition to sensing damage.

  4. Is Human Oxoguanine Glycosylase 1 Genetic Variant Successful Even on Oral Squamous Cell Carcinoma?

    Science.gov (United States)

    Aydemir, Levent; Bireller, Elif Sinem; Avci, Hakan; Boy Metin, Zeynep; Deger, Kemal; Unur, Meral; Cakmakoglu, Bedia

    2017-01-01

    Oral squamous cell carcinoma (OSCC) is one of the most widespread cancer types that arise from different sites of oral cavity and has a 5-year survival rate. This study is aimed at investigating the human oxoguanine glycosylase 1 (hOGG1)-Ser326Cys and APE-Asp148Glu polymorphisms of DNA repair genes in OSCC. We investigated the hOGG1-Ser326Cys and APE-Asp148Glu polymorphisms of DNA repair genes in the oral cavity. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymorphism analysis based on 132 patients who were diagnosed as having OSCC and 160 healthy subjects. Individuals with the genotype hOGG1-Ser326Cys, Cys allele carriers, were found significantly more frequently in the patient group compared to the control group as increase in risk (p oral squamous cancer. In view of our results, further studies including expression levels are required in which hOGG1-Ser326Cys should be investigated as molecular biomarkers for the early prediction of squamous cell carcinoma. © 2017 S. Karger AG, Basel.

  5. Direct detection of chicken genomic DNA for gender determination by thymine-DNA glycosylase.

    Science.gov (United States)

    Porat, N; Bogdanov, K; Danielli, A; Arie, A; Samina, I; Hadani, A

    2011-02-01

    1. Birds, especially nestlings, are generally difficult to sex by morphology and early detection of chick gender in ovo in the hatchery would facilitate removal of unwanted chicks and diminish welfare objections regarding culling after hatch. 2. We describe a method to determine chicken gender without the need for PCR via use of Thymine-DNA Glycosylase (TDG). TDG restores thymine (T)/guanine (G) mismatches to cytosine (C)/G. We show here, that like DNA Polymerase, TDG can recognise, bind and function on a primer hybridised to chicken genomic DNA. 3. The primer contained a T to mismatch a G in a chicken genomic template and the T/G was cleaved with high fidelity by TDG. Thus, the chicken genomic DNA can be identified without PCR amplification via direct and linear detection. Sensitivity was increased using gender specific sequences from the chicken genome. 4. Currently, these are laboratory results, but we anticipate that further development will allow this method to be used in non-laboratory settings, where PCR cannot be employed.

  6. Rhetoric and analogies

    OpenAIRE

    Aragonès, Enriqueta; Gilboa, Itzhak; Postlewaite, Andrew; Schmeidler, David; Universitat Autònoma de Barcelona. Unitat de Fonaments de l'Anàlisi Econòmica; Universitat Autònoma de Barcelona. Institut d'Anàlisi Econòmica

    2013-01-01

    The art of rhetoric may be defined as changing other people's minds (opinions, beliefs) without providing them new information. One tech- nique heavily used by rhetoric employs analogies. Using analogies, one may draw the listener's attention to similarities between cases and to re-organize existing information in a way that highlights certain reg- ularities. In this paper we offer two models of analogies, discuss their theoretical equivalence, and show that finding good analogies is a com- p...

  7. Kinetics and Thermodynamics of DNA Processing by Wild Type DNA-Glycosylase Endo III and Its Catalytically Inactive Mutant Forms

    Directory of Open Access Journals (Sweden)

    Olga A. Kladova

    2018-03-01

    Full Text Available Endonuclease III (Endo III or Nth is one of the key enzymes responsible for initiating the base excision repair of oxidized or reduced pyrimidine bases in DNA. In this study, a thermodynamic analysis of structural rearrangements of the specific and nonspecific DNA-duplexes during their interaction with Endo III is performed based on stopped-flow kinetic data. 1,3-diaza-2-oxophenoxazine (tCO, a fluorescent analog of the natural nucleobase cytosine, is used to record multistep DNA binding and lesion recognition within a temperature range (5–37 °C. Standard Gibbs energy, enthalpy, and entropy of the specific steps are derived from kinetic data using Van’t Hoff plots. The data suggest that enthalpy-driven exothermic 5,6-dihydrouracil (DHU recognition and desolvation-accompanied entropy-driven adjustment of the enzyme–substrate complex into a catalytically active state play equally important parts in the overall process. The roles of catalytically significant amino acids Lys120 and Asp138 in the DNA lesion recognition and catalysis are identified. Lys120 participates not only in the catalytic steps but also in the processes of local duplex distortion, whereas substitution Asp138Ala leads to a complete loss of the ability of Endo III to distort a DNA double chain during enzyme–DNA complex formation.

  8. Tungsten disulfide nanosheet and exonuclease III co-assisted amplification strategy for highly sensitive fluorescence polarization detection of DNA glycosylase activity

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Jingjin; Ma, Yefei [Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources of Education Ministry, Guangxi Normal University, Guilin, 541004 (China); Kong, Rongmei [The Key Laboratory of Life-Organic Analysis, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, Shandong 273165 (China); Zhang, Liangliang, E-mail: liangzhang319@163.com [Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources of Education Ministry, Guangxi Normal University, Guilin, 541004 (China); Yang, Wen; Zhao, Shulin [Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources of Education Ministry, Guangxi Normal University, Guilin, 541004 (China)

    2015-08-05

    Herein, we introduced a tungsten disulfide (WS{sub 2}) nanosheet and exonuclease III (Exo III) co-assisted signal amplification strategy for highly sensitive fluorescent polarization (FP) assay of DNA glycosylase activity. Two DNA glycosylases, uracil-DNA glycosylase (UDG) and human 8-oxoG DNA glycosylase 1 (hOGG1), were tested. A hairpin-structured probe (HP) which contained damaged bases in the stem was used as the substrate. The removal of damaged bases from substrate by DNA glycosylase would lower the melting temperature of HP. The HP was then opened and hybridized with a FAM dye-labeled single strand DNA (DP), generating a duplex with a recessed 3′-terminal of DP. This design facilitated the Exo III-assisted amplification by repeating the hybridization and digestion of DP, liberating numerous FAM fluorophores which could not be adsorbed on WS{sub 2} nanosheet. Thus, the final system exhibited a small FP signal. However, in the absence of DNA glycosylases, no hybridization between DP and HP was occurred, hampering the hydrolysis of DP by Exo III. The intact DP was then adsorbed on the surface of WS{sub 2} nanosheet that greatly amplified the mass of the labeled-FAM fluorophore, resulting in a large FP value. With the co-assisted amplification strategy, the sensitivity was substantially improved. In addition, this method was applied to detect UDG activity in cell extracts. The study of the inhibition of UDG was also performed. Furthermore, this method is simple in design, easy in implementation, and selective, which holds potential applications in the DNA glycosylase related mechanism research and molecular diagnostics. - Highlights: • A fluorescence polarization strategy for DNA glycosylase activity detection was developed. • The present method was based on WS{sub 2} nanosheet and exonuclease III co-assisted signal amplification. • A high sensitivity and desirable selectivity were achieved. • This method provides a promising universal platform for DNA

  9. Altered DNA Methylation and Expression Profiles of 8-Oxoguanine DNA Glycosylase 1 in Lens Tissue from Age-related Cataract Patients.

    Science.gov (United States)

    Wang, Yong; Li, Fei; Zhang, Guowei; Kang, Lihua; Qin, Bai; Guan, Huaijin

    2015-01-01

    Oxidative stress and DNA damage contribute to the pathogenesis of age-related cataract (ARC). Most oxidative DNA lesions are repaired via the base excision repair (BER) proteins including 8-oxoguanine DNA glycosylase 1 (OGG1). This study examined DNA methylation of CpG islands upstream of OGG1 and their relation to the gene expression in lens cortex from ARC patients. The clinical case-control study consisted of 15 cortical type of ARC patients and 15 age-matched non-ARC controls who received transparent lens extraction due to vitreoretinal diseases. OGG1 expression in lens cortex was analyzed by qRT-PCR and Western blot. The localization and the proportion of cells positive for OGG1 were determined by immunofluorescence. Bisulfite-sequencing PCR (BSP) was performed to evaluate the methylation status of CpG islands near OGG1 in DNA extracted from lens cortex. To test relationship between the methylation and the expression of the gene of interest, 5-Aza-2'-deoxycytidine (5-Aza-dC) was used to induce demethylation of cultured human lens epithelium B-3 (HLE B-3). To test the role of OGG1 in the repair of cellular damage, HLE B-3 was transfected with OGG1 vector, followed by ultraviolet radiation b (UVB) exposure to induce apoptosis. The mRNA and protein levels of OGG1 were significantly reduced in the lens cortex of ARC. Immunofluorescence showed that the proportion of OGG1-positive cells decreased significantly in ARC cortex in comparison with the control. The CpG island in first exon of OGG1 displayed hypermethylation in the DNA extracted from the lens cortex of ARC. Treatment of HLEB-3 cells with 5-Aza-dC upregulated OGG1 expression. UVB-induced apoptosis was attenuated after transfection with OGG1. A reduced OGG1 expression was correlated with hypermethylation of a CpG island of OGG1 in lens cortex of ARC. The role of epigenetic change in OGG1 gene in the susceptibility to oxidative stress induced cortical ARC is warranted to further study.

  10. Analog and hybrid computing

    CERN Document Server

    Hyndman, D E

    2013-01-01

    Analog and Hybrid Computing focuses on the operations of analog and hybrid computers. The book first outlines the history of computing devices that influenced the creation of analog and digital computers. The types of problems to be solved on computers, computing systems, and digital computers are discussed. The text looks at the theory and operation of electronic analog computers, including linear and non-linear computing units and use of analog computers as operational amplifiers. The monograph examines the preparation of problems to be deciphered on computers. Flow diagrams, methods of ampl

  11. Structured Analog CMOS Design

    CERN Document Server

    Stefanovic, Danica

    2008-01-01

    Structured Analog CMOS Design describes a structured analog design approach that makes it possible to simplify complex analog design problems and develop a design strategy that can be used for the design of large number of analog cells. It intentionally avoids treating the analog design as a mathematical problem, developing a design procedure based on the understanding of device physics and approximations that give insight into parameter interdependences. The proposed transistor-level design procedure is based on the EKV modeling approach and relies on the device inversion level as a fundament

  12. Detecting analogies unconsciously

    Directory of Open Access Journals (Sweden)

    Thomas Peter Reber

    2014-01-01

    Full Text Available Analogies may arise from the conscious detection of similarities between a present and a past situation. In this functional magnetic resonance imaging study, we tested whether young volunteers would detect analogies unconsciously between a current supraliminal (visible and a past subliminal (invisible situation. The subliminal encoding of the past situation precludes awareness of analogy detection in the current situation. First, participants encoded subliminal pairs of unrelated words in either one or nine encoding trials. Later, they judged the semantic fit of supraliminally presented new words that either retained a previously encoded semantic relation (‘analog’ or not (‘broken analog’. Words in analogs versus broken analogs were judged closer semantically, which reflects unconscious analogy detection. Hippocampal activity associated with subliminal encoding correlated with the behavioral measure of unconscious analogy detection. Analogs versus broken analogs were processed with reduced prefrontal but enhanced medial temporal activity. We conclude that analogous episodes can be detected even unconsciously drawing on the episodic memory network.

  13. Ulnar nerve entrapment complicating radial head excision

    Directory of Open Access Journals (Sweden)

    Kevin Parfait Bienvenu Bouhelo-Pam

    Full Text Available Introduction: Several mechanisms are involved in ischemia or mechanical compression of ulnar nerve at the elbow. Presentation of case: We hereby present the case of a road accident victim, who received a radial head excision for an isolated fracture of the radial head and complicated by onset of cubital tunnel syndrome. This outcome could be the consequence of an iatrogenic valgus of the elbow due to excision of the radial head. Hitherto the surgical treatment of choice it is gradually been abandoned due to development of radial head implant arthroplasty. However, this management option is still being performed in some rural centers with low resources. Discussion: The radial head plays an important role in the stability of the elbow and his iatrogenic deformity can be complicated by cubital tunnel syndrome. Conclusion: An ulnar nerve release was performed with favorable outcome. Keywords: Cubital tunnel syndrome, Peripheral nerve palsy, Radial head excision, Elbow valgus

  14. Elliptical excisions: variations and the eccentric parallelogram.

    Science.gov (United States)

    Goldberg, Leonard H; Alam, Murad

    2004-02-01

    The elliptical (fusiform) excision is a basic tool of cutaneous surgery. To assess the design, functionality, ease of construction, and aesthetic outcomes of the ellipse. A systematic review of elliptical designs and their site-specific benefits and limitations. In particular, we consider the (1). context of prevailing relaxed skin tension lines and tissue laxity; and (2). removal of the smallest possible amount of tissue around the lesion and in the "dog-ears." Attention is focused on intuitive methods that can be reproducibly planned and executed. Elliptical variations are easily designed and can be adapted to many situations. The eccentric parallelogram excision is offered as a new technique that minimizes notching and focal tension in the center of an elliptical closure. Conclusion The elliptical (fusiform) excision is an efficient, elegant, and versatile technique that will remain a mainstay of the cutaneous surgical armamentarium.

  15. Release of 3-methyladenine from linker and core DNA of chromatin by a purified DNA glycosylase

    International Nuclear Information System (INIS)

    Heller, E.P.; Goldthwait, D.A.

    1983-01-01

    Oligonucleosomes were isolated from [ 14 C]thymidine-labeled HeLa cells by digestion of the nuclei with micrococcal nuclease and were then alkylated with [ 3 H]methylnitrosourea. Nucleosome core particles were also prepared by further digestion of the oligonucleosomes. The distribution of 3 H-labeled methyl groups in the linker versus the core DNA was established by a determination of 3 H: 14 C ratios in oligonucleosome and core DNA. The ratios in the core DNA of 145 and 165 base pair DNA fragments were 5.2 and 5.4, respectively, while the ratio in the oligonucleosomal DNA was 8.2. Assuming an equal mixture (as determined) of 145 and 165 base pair fragments of DNA in the 185 base pair repeat, the relative concentration of 3 H methyl groups in the linker versus the core DNA was 4.2. Thus, 45% of the 3 H methyl groups were in the linker DNA, and 55% were in the core DNA. Some shielding of the DNA was evident during alkylation. The concentrations of alkyl groups on the linker and core DNA were 67 and 12% of that found on free DNA alkylated under comparable conditions. No evidence for preferential shielding of the major or minor groove was observed. The purified 3-methyladenine DNA glycosylase I of Escherichia coli released approximately 37% of the 3-methyladenine from the linker DNA and 13% from the core DNA. The limited enzymatic removal of 3-methyladenine in vitro compared to the efficient removal in vivo suggests that conformational changes of the oligonucleosome and core structure must occur for total repair

  16. Analog circuit design

    CERN Document Server

    Dobkin, Bob

    2012-01-01

    Analog circuit and system design today is more essential than ever before. With the growth of digital systems, wireless communications, complex industrial and automotive systems, designers are being challenged to develop sophisticated analog solutions. This comprehensive source book of circuit design solutions aids engineers with elegant and practical design techniques that focus on common analog challenges. The book's in-depth application examples provide insight into circuit design and application solutions that you can apply in today's demanding designs. <

  17. Analog synthetic biology.

    Science.gov (United States)

    Sarpeshkar, R

    2014-03-28

    We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog-digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA-protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations.

  18. Robotic Extramucosal Excision of Bladder Wall Leiomyoma

    Directory of Open Access Journals (Sweden)

    Khalid E. Al-Othman

    2014-01-01

    Full Text Available Introduction: Multiple case reports and reviews have been described in the literature for bladder wall leiomyoma resection via different approaches. The minimally invasive partial cystectomy remains the most widely accepted technique; however, case reports for enucleation of bladder wall leiomyoma have also been described. The purpose of this video is to demonstrate the robotic extramucosal excision of a bladder wall leiomyoma, without cystotomy, but with complete removal of the muscular layer. Materials and Methods: A 35-year old male present with lower urinary tract symptoms and imaging showed bladder wall mass with histopathology showed leiomyoma. The patient consented for mass excision with the possibility of a partial cystectomy. The patient was placed in the supine, 30-degree Trendelenburg position during the procedure. A total of 4 ports were inserted. A 3-arm da Vinci robotic surgical system was docked, and the arms were connected. Extramucosal excision was accomplished without cystotomy and muscle approximation was achieved by 2 0 Vicryle. Result: The operative time was 90 minutes, blood loss of approximately 50mL and the patient was discharged after 72 hours with no immediate complications and a 6 months follow-up showed no recurrence. Conclusion: Such a technique results in complete excision of the tumor, without cystotomy, and also maintains an intact mucosa. These steps, in addition to decreasing the risk of local recurrence, also shorten the period of postoperative catheterization and hospitalization.

  19. Base excision repair, aging and health span

    Czech Academy of Sciences Publication Activity Database

    Xu, G.; Herzig, M.; Rotrekl, Vladimír; Walter, Ch. A.

    2008-01-01

    Roč. 129, 7-8 (2008), s. 366-382 ISSN 0047-6374 Institutional research plan: CEZ:AV0Z50390512 Keywords : base excision repair * aging * DNA damage Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.915, year: 2008

  20. Uracil Excision for Assembly of Complex Pathways

    DEFF Research Database (Denmark)

    Cavaleiro, Mafalda; Nielsen, Morten Thrane; Kim, Se Hyeuk

    2015-01-01

    Despite decreasing prices on synthetic DNA constructs, higher-order assembly of PCR-generated DNA continues to be an important exercise in molecular and synthetic biology. Simplicity and robustness are attractive features met by the uracil excision DNA assembly method, which is one of the most in...

  1. Challenges in Using Analogies

    Science.gov (United States)

    Lin, Shih-Yin; Singh, Chandralekha

    2011-01-01

    Learning physics requires understanding the applicability of fundamental principles in a variety of contexts that share deep features. One way to help students learn physics is via analogical reasoning. Students can be taught to make an analogy between situations that are more familiar or easier to understand and another situation where the same…

  2. Hydraulic Capacitor Analogy

    Science.gov (United States)

    Baser, Mustafa

    2007-01-01

    Students have difficulties in physics because of the abstract nature of concepts and principles. One of the effective methods for overcoming students' difficulties is the use of analogies to visualize abstract concepts to promote conceptual understanding. According to Iding, analogies are consistent with the tenets of constructivist learning…

  3. Optical analogy. Synthesis report

    International Nuclear Information System (INIS)

    1965-01-01

    The authors report the study of conditions under which light attenuation (reflection, diffusion, absorption) and the attenuation of some radiations (notably thermal neutrons) can be described with analogical calculations. The analogy between light physical properties and neutron properties is not searched for, but the analogy between their attenuation characteristics. After having discussed this possible analogy, they propose a mathematical formulation of neutron and optical phenomena which could theoretically justify the optical analogy. The second part reports a more practical study of optics problems such as the study of simple optics materials and illumination measurements, or more precisely the study of angular distributions of optical reflections, a determination of such angular distributions, and an experimental determination of the albedo

  4. DNA polymerases beta and lambda mediate overlapping and independent roles in base excision repair in mouse embryonic fibroblasts.

    Directory of Open Access Journals (Sweden)

    Elena K Braithwaite

    2010-08-01

    Full Text Available Base excision repair (BER is a DNA repair pathway designed to correct small base lesions in genomic DNA. While DNA polymerase beta (pol beta is known to be the main polymerase in the BER pathway, various studies have implicated other DNA polymerases in back-up roles. One such polymerase, DNA polymerase lambda (pol lambda, was shown to be important in BER of oxidative DNA damage. To further explore roles of the X-family DNA polymerases lambda and beta in BER, we prepared a mouse embryonic fibroblast cell line with deletions in the genes for both pol beta and pol lambda. Neutral red viability assays demonstrated that pol lambda and pol beta double null cells were hypersensitive to alkylating and oxidizing DNA damaging agents. In vitro BER assays revealed a modest contribution of pol lambda to single-nucleotide BER of base lesions. Additionally, using co-immunoprecipitation experiments with purified enzymes and whole cell extracts, we found that both pol lambda and pol beta interact with the upstream DNA glycosylases for repair of alkylated and oxidized DNA bases. Such interactions could be important in coordinating roles of these polymerases during BER.

  5. Circumareolar Incision‑subdermal Tunneling Dissection for Excision ...

    African Journals Online (AJOL)

    2017 Nigerian Journal of Surgery | Published by Wolters Kluwer - Medknow. Excision of ... This is a report of excision of MF in multiple quadrants of the breast using a ... Agodirin, et al. .... the breast: The Ribeiro technique modified by Rezai.

  6. Meat analog: a review.

    Science.gov (United States)

    Malav, O P; Talukder, S; Gokulakrishnan, P; Chand, S

    2015-01-01

    The health-conscious consumers are in search of nutritious and convenient food item which can be best suited in their busy life. The vegetarianism is the key for the search of such food which resembles the meat in respect of nutrition and sensory characters, but not of animal origin and contains vegetable or its modified form, this is the point when meat analog evolved out and gets shape. The consumers gets full satisfaction by consumption of meat analog due to its typical meaty texture, appearance and the flavor which are being imparted during the skilled production of meat analog. The supplement of protein in vegetarian diet through meat alike food can be fulfilled by incorporating protein-rich vegetative food grade materials in meat analog and by adopting proper technological process which can promote the proper fabrication of meat analog with acceptable meat like texture, appearance, flavor, etc. The easily available vegetables, cereals, and pulses in India have great advantages and prospects to be used in food products and it can improve the nutritional and functional characters of the food items. The various form and functional characters of food items are available world over and attracts the meat technologists and the food processors to bring some innovativeness in meat analog and its presentation and marketability so that the acceptability of meat analog can be overgrown by the consumers.

  7. Troubleshooting analog circuits

    CERN Document Server

    Pease, Robert A

    1991-01-01

    Troubleshooting Analog Circuits is a guidebook for solving product or process related problems in analog circuits. The book also provides advice in selecting equipment, preventing problems, and general tips. The coverage of the book includes the philosophy of troubleshooting; the modes of failure of various components; and preventive measures. The text also deals with the active components of analog circuits, including diodes and rectifiers, optically coupled devices, solar cells, and batteries. The book will be of great use to both students and practitioners of electronics engineering. Other

  8. Unique features of the structure and interactions of mycobacterial uracil-DNA glycosylase: structure of a complex of the Mycobacterium tuberculosis enzyme in comparison with those from other sources.

    Science.gov (United States)

    Kaushal, Prem Singh; Talawar, Ramappa K; Krishna, P D V; Varshney, Umesh; Vijayan, M

    2008-05-01

    Uracil-DNA glycosylase (UNG), a repair enzyme involved in the excision of uracil from DNA, from mycobacteria differs from UNGs from other sources, particularly in the sequence in the catalytically important loops. The structure of the enzyme from Mycobacterium tuberculosis (MtUng) in complex with a proteinaceous inhibitor (Ugi) has been determined by X-ray analysis of a crystal containing seven crystallographically independent copies of the complex. This structure provides the first geometric characterization of a mycobacterial UNG. A comparison of the structure with those of other UNG proteins of known structure shows that a central core region of the molecule is relatively invariant in structure and sequence, while the N- and C-terminal tails exhibit high variability. The tails are probably important in folding and stability. The mycobacterial enzyme exhibits differences in UNG-Ugi interactions compared with those involving UNG from other sources. The MtUng-DNA complex modelled on the basis of the known structure of the complex involving the human enzyme indicates a domain closure in the enzyme when binding to DNA. The binding involves a larger burial of surface area than is observed in binding by human UNG. The DNA-binding site of MtUng is characterized by the presence of a higher proportion of arginyl residues than is found in the binding site of any other UNG of known structure. In addition to the electrostatic effects produced by the arginyl residues, the hydrogen bonds in which they are involved compensate for the loss of some interactions arising from changes in amino-acid residues, particularly in the catalytic loops. The results arising from the present investigation represent unique features of the structure and interaction of mycobacterial Ungs.

  9. 29 CFR 779.264 - Excise taxes separately stated.

    Science.gov (United States)

    2010-07-01

    ... AS APPLIED TO RETAILERS OF GOODS OR SERVICES Employment to Which the Act May Apply; Enterprise Coverage Excise Taxes § 779.264 Excise taxes separately stated. A tax is separately stated where it clearly... 29 Labor 3 2010-07-01 2010-07-01 false Excise taxes separately stated. 779.264 Section 779.264...

  10. 75 FR 9359 - Drawback of Internal Revenue Excise Tax

    Science.gov (United States)

    2010-03-02

    ... Drawback of Internal Revenue Excise Tax AGENCY: Customs and Border Protection, Department of Homeland... substitution drawback claim for internal revenue excise tax paid on imported merchandise in situations where no excise tax was paid upon the substituted merchandise or where the substituted merchandise is the subject...

  11. Histone displacement during nucleotide excision repair

    DEFF Research Database (Denmark)

    Dinant, C.; Bartek, J.; Bekker-Jensen, S.

    2012-01-01

    Nucleotide excision repair (NER) is an important DNA repair mechanism required for cellular resistance against UV light and toxic chemicals such as those found in tobacco smoke. In living cells, NER efficiently detects and removes DNA lesions within the large nuclear macromolecular complex called...... of histone variants and histone displacement (including nucleosome sliding). Here we review current knowledge, and speculate about current unknowns, regarding those chromatin remodeling activities that physically displace histones before, during and after NER....

  12. Symptomatic pancreatic heterotopia treated by local excision.

    Science.gov (United States)

    De Friend, D J; Saa-Gandi, F W; Humphrey, C S; Foster, D N

    1991-01-01

    Non-ulcer dyspepsia is a continuing problem and in many cases a precise cause is never identified. We present five patients with an allegedly uncommon condition--pancreatic heterotopia. They were managed by local excision of the tumour and after a mean (range) follow up of 42 (9-80) months all remain free of the original symptoms. Images Figure 1 Figure 2 PMID:2013433

  13. Relativistic hydrodynamic evolutions with black hole excision

    International Nuclear Information System (INIS)

    Duez, Matthew D.; Shapiro, Stuart L.; Yo, H.-J.

    2004-01-01

    We present a numerical code designed to study astrophysical phenomena involving dynamical spacetimes containing black holes in the presence of relativistic hydrodynamic matter. We present evolutions of the collapse of a fluid star from the onset of collapse to the settling of the resulting black hole to a final stationary state. In order to evolve stably after the black hole forms, we excise a region inside the hole before a singularity is encountered. This excision region is introduced after the appearance of an apparent horizon, but while a significant amount of matter remains outside the hole. We test our code by evolving accurately a vacuum Schwarzschild black hole, a relativistic Bondi accretion flow onto a black hole, Oppenheimer-Snyder dust collapse, and the collapse of nonrotating and rotating stars. These systems are tracked reliably for hundreds of M following excision, where M is the mass of the black hole. We perform these tests both in axisymmetry and in full 3+1 dimensions. We then apply our code to study the effect of the stellar spin parameter J/M 2 on the final outcome of gravitational collapse of rapidly rotating n=1 polytropes. We find that a black hole forms only if J/M 2 2 >1, the collapsing star forms a torus which fragments into nonaxisymmetric clumps, capable of generating appreciable 'splash' gravitational radiation

  14. Pisiform excision for pisotriquetral instability and arthritis.

    Science.gov (United States)

    Campion, Heather; Goad, Andrea; Rayan, Ghazi; Porembski, Margaret

    2014-07-01

    To evaluate wrist strength and kinematics after pisiform excision and preservation of its soft tissue confluence for pisotriquetral instability and arthritis. We evaluated 12 patients, (14 wrists) subjectively and objectively an average of 7.5 years after pisiform excision. Three additional patients were interviewed by phone. Subjective evaluation included inquiry about pain and satisfaction with the treatment. Objective testing included measuring wrist flexion and extension range of motion, grip strength, and static and dynamic flexion and ulnar deviation strengths of the operative hand compared with the nonsurgical normal hand. Four patients had concomitant ulnar nerve decompression at the wrist. All patients were satisfied with the outcome. Wrist flexion averaged 99% and wrist extension averaged 95% of the nonsurgical hand. Mean grip strength of the operative hand was 90% of the nonsurgical hand. Mean static flexion strength of the operative hand was 94% of the nonsurgical hand, whereas mean dynamic flexion strength was 113%. Mean static ulnar deviation strength of the operative hand was 87% of the nonsurgical hand. The mean dynamic ulnar deviation strength of the operative hand was 103% of the nonsurgical hand. Soft tissue confluence-preserving pisiform excision relieved pain and retained wrist motion and static and dynamic strength. Associated ulnar nerve compression was a confounding factor that may have affected outcomes. Therapeutic IV. Copyright © 2014 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  15. Transvaginal sling excision: tips and tricks.

    Science.gov (United States)

    Clifton, Marisa M; Goldman, Howard B

    2017-01-01

    Complications of synthetic midurethral sling surgery include bladder outlet obstruction, mesh extrusion, and vaginal pain. A treatment of these complications is transvaginal mesh removal. The objectives of this video are to present cases of complications after sling placement and describe techniques to help with successful sling removal. Three patients are presented in this video. One experienced urinary hesitancy and was found to have bladder outlet obstruction on urodynamic study. The second patient presented to the clinic with diminished force of stream and significant dyspareunia. The last patient presented with mesh extrusion. After discussion of management options, all three patients wished to pursue transvaginal sling excision. All patients had successful removal of a portion of their synthetic midurethral sling. This video presents techniques to aide with dissection, mesh excision and prevention of further mesh complications. These include using an individualized surgical technique based on patient presentation and surgeon expertise, planning surgical incisions based on where mesh can be identified or palpated, using a cystoscope sheath or urethral dilator to identify any bladder outlet obstruction, and using a knife blade to identify mesh from surrounding tissue. Sling excision can be successfully performed with careful surgical technique and dissection.

  16. Analog circuits cookbook

    CERN Document Server

    Hickman, Ian

    2013-01-01

    Analog Circuits Cookbook presents articles about advanced circuit techniques, components and concepts, useful IC for analog signal processing in the audio range, direct digital synthesis, and ingenious video op-amp. The book also includes articles about amplitude measurements on RF signals, linear optical imager, power supplies and devices, and RF circuits and techniques. Professionals and students of electrical engineering will find the book informative and useful.

  17. FGF growth factor analogs

    Science.gov (United States)

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

    2012-07-24

    The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

  18. Multidirectional Vector Excision Leads to Better Outcomes than Traditional Elliptical Excision of Facial Congenital Melanocytic Nevus

    Directory of Open Access Journals (Sweden)

    Seung Il Oh

    2013-09-01

    Full Text Available Background The elliptical excision is the standard method of removing benign skin lesions,such as congenital melanocytic nevi. This technique allows for primary closure, with little to nodog-ear deformity, but may sacrifice normal tissue adjacent to the lesion, resulting in scarswhich are unnecessarily long. This study was designed to compare the predicted results ofelliptical excision with those resulting from our excision technique.Methods Eighty-two patients with congenital melanocytic nevus on the face were prospectivelystudied. Each lesion was examined and an optimal ellipse was designed and marked onthe skin. After an incision on one side of the nevus margin, subcutaneous undermining wasperformed in the appropriate direction. The skin flap was pulled up and approximated alongseveral vectors to minimize the occurrence of dog-ear deformity.Results Overall, the final wound length was 21.1% shorter than that achieved by ellipticalexcision. Only 8.5% of the patients required dog-ear repair. There was no significant distortionof critical facial structures. All of the scars were deemed aesthetically acceptable based ontheir Patient and Observer Scar Assessment Scale scores.Conclusions When compared to elliptical excision, our technique appears to minimize dogeardeformity and decrease the final wound length. This technique should be considered analternative method for excision of facial nevi.

  19. Electrical Circuits and Water Analogies

    Science.gov (United States)

    Smith, Frederick A.; Wilson, Jerry D.

    1974-01-01

    Briefly describes water analogies for electrical circuits and presents plans for the construction of apparatus to demonstrate these analogies. Demonstrations include series circuits, parallel circuits, and capacitors. (GS)

  20. Alkyladenine DNA glycosylase (AAG) localizes to mitochondria and interacts with mitochondrial single-stranded binding protein (mtSSB).

    Science.gov (United States)

    van Loon, Barbara; Samson, Leona D

    2013-03-01

    Due to a harsh environment mitochondrial genomes accumulate high levels of DNA damage, in particular oxidation, hydrolytic deamination, and alkylation adducts. While repair of alkylated bases in nuclear DNA has been explored in detail, much less is known about the repair of DNA alkylation damage in mitochondria. Alkyladenine DNA glycosylase (AAG) recognizes and removes numerous alkylated bases, but to date AAG has only been detected in the nucleus, even though mammalian mitochondria are known to repair DNA lesions that are specific substrates of AAG. Here we use immunofluorescence to show that AAG localizes to mitochondria, and we find that native AAG is present in purified human mitochondrial extracts, as well as that exposure to alkylating agent promotes AAG accumulation in the mitochondria. We identify mitochondrial single-stranded binding protein (mtSSB) as a novel interacting partner of AAG; interaction between mtSSB and AAG is direct and increases upon methyl methanesulfonate (MMS) treatment. The consequence of this interaction is specific inhibition of AAG glycosylase activity in the context of a single-stranded DNA (ssDNA), but not a double-stranded DNA (dsDNA) substrate. By inhibiting AAG-initiated processing of damaged bases, mtSSB potentially prevents formation of DNA breaks in ssDNA, ensuring that base removal primarily occurs in dsDNA. In summary, our findings suggest the existence of AAG-initiated BER in mitochondria and further support a role for mtSSB in DNA repair. Copyright © 2012. Published by Elsevier B.V.

  1. CMOS analog circuit design

    CERN Document Server

    Allen, Phillip E

    1987-01-01

    This text presents the principles and techniques for designing analog circuits to be implemented in a CMOS technology. The level is appropriate for seniors and graduate students familiar with basic electronics, including biasing, modeling, circuit analysis, and some familiarity with frequency response. Students learn the methodology of analog integrated circuit design through a hierarchically-oriented approach to the subject that provides thorough background and practical guidance for designing CMOS analog circuits, including modeling, simulation, and testing. The authors' vast industrial experience and knowledge is reflected in the circuits, techniques, and principles presented. They even identify the many common pitfalls that lie in the path of the beginning designer--expert advice from veteran designers. The text mixes the academic and practical viewpoints in a treatment that is neither superficial nor overly detailed, providing the perfect balance.

  2. Analogical Reasoning in Geometry Education

    Science.gov (United States)

    Magdas, Ioana

    2015-01-01

    The analogical reasoning isn't used only in mathematics but also in everyday life. In this article we approach the analogical reasoning in Geometry Education. The novelty of this article is a classification of geometrical analogies by reasoning type and their exemplification. Our classification includes: analogies for understanding and setting a…

  3. Digital and analog communication systems

    Science.gov (United States)

    Shanmugam, K. S.

    1979-01-01

    The book presents an introductory treatment of digital and analog communication systems with emphasis on digital systems. Attention is given to the following topics: systems and signal analysis, random signal theory, information and channel capacity, baseband data transmission, analog signal transmission, noise in analog communication systems, digital carrier modulation schemes, error control coding, and the digital transmission of analog signals.

  4. Analogs for transuranic elements

    International Nuclear Information System (INIS)

    Weimer, W.C.; Laul, J.C.; Kutt, J.C.

    1981-01-01

    A combined theoretical and experimental approach is being used to estimate the long-term environmental and biogeochemical behaviors of selected transuranic elements. The objective of this research is to estimate the effect that long-term (hundreds of years) environmental weathering has on the behavior of the transuranic elements americium and curium. This is achieved by investigating the actual behavior of naturally occurring rare earth elements, especially neodymium, that serve as transuranic analogs. Determination of the analog element behavior provides data that can be used to estimate the ultimate availability to man of transuranic materials released into the environment

  5. Value of histopathologic analysis of subcutis excisions by general practitioners

    Directory of Open Access Journals (Sweden)

    Verweij Wim

    2007-01-01

    Full Text Available Abstract Background Only around 60% of skin lesions excised by GPs are referred to a pathologist. Clinical diagnoses of skin excisions by GPs may not be very accurate. Subcutis excisions are rarely done by GPs, and there is hence little information in the literature on the histopathological yield of subcutis excisions by GPs with regard to malignancies. The aim of this study was to evaluate the yield of histopathological investigation of a relatively large group of subcutis excisions by GPs, with special emphasis on discrepancies between clinical and histopathological diagnoses of malignancy. Methods We investigated a series of 90 subcutis excisions, which was derived from a database of consecutive GP submissions from the years 1999–2000 where in the same time period 4595 skin excisions were performed by the same group of GPs. This underlines the apparent reluctance of GPs to perform subcutis excisions. Results The final diagnosis was benign in 88 cases (97.8% and malignant in 2 cases (2.2%. Seven cases had no clinical diagnosis, all of which were benign. Of the 83 clinically benign cases, 81 (97.6% were indeed benign and 2 (2.4% were malignant: one Merkel cell carcinoma and one dermatofibrosarcoma protuberans. The former was clinically thought to be a lipoma, and the latter a trichilemmal cyst. The dermatofibrosarcoma protuberans presented at the age of 27, and the Merkel cell carcinoma at the age of 60. Both were incompletely removed and required re-excision by a surgical oncologist. Conclusion Histopathological investigation of subcutis excisions by GPs yields unexpected and rare malignancies in about 2% of cases that may initially be excised inadequately. Based on these data, and because of the relatively rareness of these type of excisions, it could be argued that it may be worthwhile to have all subcutis excisions by GPs routinely investigated by histopathology.

  6. Terrestrial Analogs to Mars

    Science.gov (United States)

    Farr, T. G.; Arcone, S.; Arvidson, R. W.; Baker, V.; Barlow, N. G.; Beaty, D.; Bell, M. S.; Blankenship, D. D.; Bridges, N.; Briggs, G.; Bulmer, M.; Carsey, F.; Clifford, S. M.; Craddock, R. A.; Dickerson, P. W.; Duxbury, N.; Galford, G. L.; Garvin, J.; Grant, J.; Green, J. R.; Gregg, T. K. P.; Guinness, E.; Hansen, V. L.; Hecht, M. H.; Holt, J.; Howard, A.; Keszthelyi, L. P.; Lee, P.; Lanagan, P. D.; Lentz, R. C. F.; Leverington, D. W.; Marinangeli, L.; Moersch, J. E.; Morris-Smith, P. A.; Mouginis-Mark, P.; Olhoeft, G. R.; Ori, G. G.; Paillou, P.; Reilly, J. F., II; Rice, J. W., Jr.; Robinson, C. A.; Sheridan, M.; Snook, K.; Thomson, B. J.; Watson, K.; Williams, K.; Yoshikawa, K.

    2002-08-01

    It is well recognized that interpretations of Mars must begin with the Earth as a reference. The most successful comparisons have focused on understanding geologic processes on the Earth well enough to extrapolate to Mars' environment. Several facets of terrestrial analog studies have been pursued and are continuing. These studies include field workshops, characterization of terrestrial analog sites, instrument tests, laboratory measurements (including analysis of Martian meteorites), and computer and laboratory modeling. The combination of all these activities allows scientists to constrain the processes operating in specific terrestrial environments and extrapolate how similar processes could affect Mars. The Terrestrial Analogs for Mars Community Panel has considered the following two key questions: (1) How do terrestrial analog studies tie in to the Mars Exploration Payload Assessment Group science questions about life, past climate, and geologic evolution of Mars, and (2) How can future instrumentation be used to address these questions. The panel has considered the issues of data collection, value of field workshops, data archiving, laboratory measurements and modeling, human exploration issues, association with other areas of solar system exploration, and education and public outreach activities.

  7. Reasoning through Instructional Analogies

    Science.gov (United States)

    Kapon, Shulamit; diSessa, Andrea A.

    2012-01-01

    This article aims to account for students' assessments of the plausibility and applicability of analogical explanations, and individual differences in these assessments, by analyzing properties of students' underlying knowledge systems. We developed a model of explanation and change in explanation focusing on knowledge elements that provide a…

  8. The Paradox of Analogy

    Directory of Open Access Journals (Sweden)

    David Botting

    2012-03-01

    Full Text Available I will show that there is a type of analogical reasoning that instantiates a pattern of reasoning in confirmation theory that is considered at best paradoxical and at worst fatal to the entire syntactical approach to confirmation and explanation. However, I hope to elaborate conditions under which this is a sound (although not necessarily strong method of reasoning.

  9. Analogy, explanation, and proof

    Science.gov (United States)

    Hummel, John E.; Licato, John; Bringsjord, Selmer

    2014-01-01

    People are habitual explanation generators. At its most mundane, our propensity to explain allows us to infer that we should not drink milk that smells sour; at the other extreme, it allows us to establish facts (e.g., theorems in mathematical logic) whose truth was not even known prior to the existence of the explanation (proof). What do the cognitive operations underlying the inference that the milk is sour have in common with the proof that, say, the square root of two is irrational? Our ability to generate explanations bears striking similarities to our ability to make analogies. Both reflect a capacity to generate inferences and generalizations that go beyond the featural similarities between a novel problem and familiar problems in terms of which the novel problem may be understood. However, a notable difference between analogy-making and explanation-generation is that the former is a process in which a single source situation is used to reason about a single target, whereas the latter often requires the reasoner to integrate multiple sources of knowledge. This seemingly small difference poses a challenge to the task of marshaling our understanding of analogical reasoning to understanding explanation. We describe a model of explanation, derived from a model of analogy, adapted to permit systematic violations of this one-to-one mapping constraint. Simulation results demonstrate that the resulting model can generate explanations for novel explananda and that, like the explanations generated by human reasoners, these explanations vary in their coherence. PMID:25414655

  10. How Analogy Drives Physics

    International Nuclear Information System (INIS)

    Hofstadter, Doug

    2004-01-01

    Many new ideas in theoretical physics come from analogies to older ideas in physics. For instance, the abstract notion of 'isospin' (or isotopic spin) originated in the prior concept of 'spin' (quantized angular momentum); likewise, the concept of 'phonon' (quantum of sound, or quantized collective excitation of a crystal) was based on the prior concept of 'photon' (quantum of light, or quantized element of the electromagnetic field). But these two examples, far from being exceptions, in fact represent the bread and butter of inventive thinking in physics. In a nutshell, intraphysics analogy-making -- borrowing by analogy with something already known in another area of physics -- is central to the progress of physics. The aim of this talk is to reveal the pervasiveness -- indeed, the indispensability -- of this kind of semi-irrational, wholly intuitive type of thinking (as opposed to more deductive mathematical inference) in the mental activity known as 'doing physics'. Speculations as to why wild analogical leaps are so crucial to the act of discovery in physics (as opposed to other disciplines) will be offered.

  11. Quantum Analog Computing

    Science.gov (United States)

    Zak, M.

    1998-01-01

    Quantum analog computing is based upon similarity between mathematical formalism of quantum mechanics and phenomena to be computed. It exploits a dynamical convergence of several competing phenomena to an attractor which can represent an externum of a function, an image, a solution to a system of ODE, or a stochastic process.

  12. Alar base reduction: the boomerang-shaped excision.

    Science.gov (United States)

    Foda, Hossam M T

    2011-04-01

    A boomerang-shaped alar base excision is described to narrow the nasal base and correct the excessive alar flare. The boomerang excision combined the external alar wedge resection with an internal vestibular floor excision. The internal excision was inclined 30 to 45 degrees laterally to form the inner limb of the boomerang. The study included 46 patients presenting with wide nasal base and excessive alar flaring. All cases were followed for a mean period of 18 months (range, 8 to 36 months). The laterally oriented vestibular floor excision allowed for maximum preservation of the natural curvature of the alar rim where it meets the nostril floor and upon its closure resulted in a considerable medialization of alar lobule, which significantly reduced the amount of alar flare and the amount of external alar excision needed. This external alar excision measured, on average, 3.8 mm (range, 2 to 8 mm), which is significantly less than that needed when a standard vertical internal excision was used ( P boomerang alar base excision proved to be a safe and effective technique for narrowing the nasal base and elimination of the excessive flaring and resulted in a natural, well-proportioned nasal base with no obvious scarring. © Thieme Medical Publishers.

  13. Surgical excision of eroded mesh after prior abdominal sacrocolpopexy.

    Science.gov (United States)

    South, Mary M T; Foster, Raymond T; Webster, George D; Weidner, Alison C; Amundsen, Cindy L

    2007-12-01

    We previously described an endoscopic-assisted transvaginal mesh excision technique. This study compares surgical outcomes after transvaginal mesh excision vs endoscopic-assisted transvaginal mesh excision. In addition, we reviewed our postoperative outcomes with excision via laparotomy. This was an inclusive retrospective analysis of patients presenting to our institution from 1997 to 2006 for surgical management of vaginal erosion of permanent mesh after sacrocolpopexy. Three techniques were utilized: transvaginal, endoscopic-assisted transvaginal, and laparotomy. For the patients undergoing transvaginal excision, data recorded included number and type of excisions performed, number of prior excisions performed at outside facilities, intraoperative and postoperative complications (including blood transfusions, pelvic abscess, or bowel complications), use of postoperative antibiotics, persistent symptoms of vaginal bleeding and discharge at follow-up, and demographic characteristics. The intraoperative and postoperative complications and the postoperative symptoms were recorded for the laparotomy cases. Thirty-one patients underwent transvaginal mesh excision during this time period: 17 endoscopic-assisted transvaginal and 14 transvaginal without endoscope assistance. In addition, a total of 7 patients underwent abdominal excision via laparotomy. Comparison of the 2 vaginal methods revealed no difference in the demographics or success rate, with success defined as no symptoms at follow-up. Endoscopic-assisted transvaginal excision was successful in 7 of 17 patients and transvaginal without endoscopic assistance in 9 of 13 patients (1 patient excluded for lack of follow-up data) for a total vaginal success rate of 53.3%. No intraoperative and only minor postoperative complications occurred with either vaginal method. Three patients underwent 3 vaginal attempts to achieve complete symptom resolution. The average follow-up time for the entire vaginal group was 14

  14. Trans-sphenoidal excision of craniopharyngiomas.

    Directory of Open Access Journals (Sweden)

    Nagpal R

    1991-04-01

    Full Text Available Craniopharyngiomas have been by and large excised by the transcranial route. Since 1982, 11 patients have been operated by the traus-sphensidal route in the department. The clinical features with which they were presented, diagnostic investigations, details of surgical procedures and follow-up analysis is being presented here. A retrospective study of radiological investigation was done to determine the features that help decide the choice of surgical approach to these lesions. Only lesions that were primarily intrasellar, cystic and those that expanded the sella could be treated by the trans-sphenoidal route. Associated suprasellar extensions could also be removed. Predominantly calcified or firm, fleshy tumours lent themselves poorly to removal by the trans-sphenoidal route.

  15. Regulation of nucleotide excision repair through ubiquitination

    Institute of Scientific and Technical Information of China (English)

    Jia Li; Audesh Bhat; Wei Xiao

    2011-01-01

    Nucleotide excision repair (NER) is the most versatile DNA-repair pathway in all organisms.While bacteria require only three proteins to complete the incision step of NER,eukaryotes employ about 30 proteins to complete the same step.Here we summarize recent studies demonstrating that ubiquitination,a post-translational modification,plays critical roles in regulating the NER activity either dependent on or independent of ubiquitin-proteolysis.Several NER components have been shown as targets of ubiquitination while others are actively involved in the ubiquitination process.We argue through this analysis that ubiquitination serves to coordinate various steps of NER and meanwhile connect NER with other related pathways to achieve the efficient global DNA-damage response.

  16. Piezosurgery for Excision of Large Osteoid Osteoma.

    Science.gov (United States)

    Gadre, Pushkar; Singh, Divya; Gadre, Kiran; Khan, Imran

    2016-10-01

    Osteoid osteoma, a rare benign osteoblastic tumor first described by Jaffe in 1935, is characterized as a small but painful lesion that mostly affects younger people. Usually benign and harmless, osteomas are removed for pain or esthetic reasons.Piezoelectric surgery is also increasingly being used effectively in major and minor osseous oral and maxillofacial surgeries, in delicate areas. It is used regularly for various procedures, including sinus lift procedures, bone graft harvesting, osteogenic distraction, ridge expansion, inferior alveolar nerve decompression and lateralization, cyst removal, dental extraction, and impacted tooth removal.The following report presents a patient of intraoral excision of a large osteoid osteoma from lingual aspect of mandibular lower border in the body region using piezoelectric surgery.

  17. Effect of cordycepin(3'-deoxyadenosine) on excision repair of 5,6-dihydroxy-dihydrothymine-type products from the DNA of Micrococcus radiodurans

    International Nuclear Information System (INIS)

    Patil, M.S.; Tundo, V.J.; Locher, S.E.; Hariharan, P.V.

    1983-01-01

    Cordycepin(3'-deoxyadenosine), a nucleoside analog, has been shown to enhance radiation-induced cell killing. In an effort to elucidate the possible mechanism for enhancement of cell killing, the effect of cordycepin on the excision repair of radiation-induced 5,6-dihydroxy-dihydrothymine-type (t') products from the DNA of wild type Micrococcus radiodurans was investigated. The capacity of M. radiodurans to excise nondimeric (t') products from its DNA was significantly impaired after cordycepin treatment. The results suggest that the increased radiation sensitivity of cordycepin-treated cells could be due to alterations in cellular processes that repair DNA damage

  18. Terrestrial Spaceflight Analogs: Antarctica

    Science.gov (United States)

    Crucian, Brian

    2013-01-01

    Alterations in immune cell distribution and function, circadian misalignment, stress and latent viral reactivation appear to persist during Antarctic winterover at Concordia Station. Some of these changes are similar to those observed in Astronauts, either during or immediately following spaceflight. Others are unique to the Concordia analog. Based on some initial immune data and environmental conditions, Concordia winterover may be an appropriate analog for some flight-associated immune system changes and mission stress effects. An ongoing smaller control study at Neumayer III will address the influence of the hypoxic variable. Changes were observed in the peripheral blood leukocyte distribution consistent with immune mobilization, and similar to those observed during spaceflight. Alterations in cytokine production profiles were observed during winterover that are distinct from those observed during spaceflight, but potentially consistent with those observed during persistent hypobaric hypoxia. The reactivation of latent herpesviruses was observed during overwinter/isolation, that is consistently associated with dysregulation in immune function.

  19. Analog storage integrated circuit

    Science.gov (United States)

    Walker, J.T.; Larsen, R.S.; Shapiro, S.L.

    1989-03-07

    A high speed data storage array is defined utilizing a unique cell design for high speed sampling of a rapidly changing signal. Each cell of the array includes two input gates between the signal input and a storage capacitor. The gates are controlled by a high speed row clock and low speed column clock so that the instantaneous analog value of the signal is only sampled and stored by each cell on coincidence of the two clocks. 6 figs.

  20. Analogy, Explanation, and Proof

    Directory of Open Access Journals (Sweden)

    John eHummel

    2014-11-01

    Full Text Available People are habitual explanation generators. At its most mundane, our propensity to explain allows us to infer that we should not drink milk that smells sour; at the other extreme, it allows us to establish facts (e.g., theorems in mathematical logic whose truth was not even known prior to the existence of the explanation (proof. What do the cognitive operations underlying the (inductive inference that the milk is sour have in common with the (deductive proof that, say, the square root of two is irrational? Our ability to generate explanations bears striking similarities to our ability to make analogies. Both reflect a capacity to generate inferences and generalizations that go beyond the featural similarities between a novel problem and familiar problems in terms of which the novel problem may be understood. However, a notable difference between analogy-making and explanation-generation is that the former is a process in which a single source situation is used to reason about a single target, whereas the latter often requires the reasoner to integrate multiple sources of knowledge. This small-seeming difference poses a challenge to the task of marshaling our understanding of analogical reasoning in the service of understanding explanation. We describe a model of explanation, derived from a model of analogy, adapted to permit systematic violations of this one-to-one mapping constraint. Simulation results demonstrate that the resulting model can generate explanations for novel explananda and that, like the explanations generated by human reasoners, these explanations vary in their coherence.

  1. Component Processes in Analogical Reasoning

    Science.gov (United States)

    Sternberg, Robert J.

    1977-01-01

    Describes alternative theoretical positions regarding (a) the component information processes used in analogical reasoning and (b) strategies for combining these processes. Also presents results from three experiments on analogical reasoning. (Author/RK)

  2. Inductive, Analogical, and Communicative Generalization

    Directory of Open Access Journals (Sweden)

    Adri Smaling

    2003-03-01

    Full Text Available Three forms of inductive generalization - statistical generalization, variation-based generalization and theory-carried generalization - are insufficient concerning case-to-case generalization, which is a form of analogical generalization. The quality of case-to-case generalization needs to be reinforced by setting up explicit analogical argumentation. To evaluate analogical argumentation six criteria are discussed. Good analogical reasoning is an indispensable support to forms of communicative generalization - receptive and responsive (participative generalization — as well as exemplary generalization.

  3. Excision technique in constrained formulations of Einstein equations: collapse scenario

    International Nuclear Information System (INIS)

    Cordero-Carrión, I; Vasset, N; Novak, J; Jaramillo, J L

    2015-01-01

    We present a new excision technique used in constrained formulations of Einstein equations to deal with black hole in numerical simulations. We show the applicability of this scheme in several scenarios. In particular, we present the dynamical evolution of the collapse of a neutron star to a black hole, using the CoCoNuT code and this excision technique. (paper)

  4. Revenue and Health Impacts of Restructuring Tobacco Excise Tax ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Revenue and Health Impacts of Restructuring Tobacco Excise Tax in the Philippines. A proposed law in the Philippines to increase the excise tax on tobacco by 215% will likely have implications for tobacco control and consumption, and public health, not just for that country but for the region. Although half of deaths due to ...

  5. Circumareolar Incision‑subdermal Tunneling Dissection for Excision ...

    African Journals Online (AJOL)

    Excision of multiple fibroadenomas (MF) in separate breast quadrants presents difficulties of number and location of incision(s) and extent of tissue dissection and may be associated with more complications and poorer cosmetic outcome. This is a report of excision of MF in multiple quadrants of the breast using a ...

  6. Effects of burn wound excision on bacterial colonization and invasion

    NARCIS (Netherlands)

    Barret, JP; Herndon, DN

    Rates of survival after thermal injury have improved in the past two decades, and rates of wound infections and sepsis have decreased during the same period. Early excision has been advocated as one of the major factors, but its safety and efficacy and the exact timing of burn excision are still

  7. P element excision in drosophila melanogaster and related drosophilids

    Science.gov (United States)

    The frequency of P element excision and the structure of the resulting excision products were determined in three drosophilid species, Drosophila melanogaster, D. virilis, and Chymomyza procnemis. A transient P element mobility assay was conducted in the cells of developing insect embryos, but unlik...

  8. Analogical Reasoning and Computer Programming.

    Science.gov (United States)

    Clement, Catherine A.; And Others

    1986-01-01

    A study of correlations between analogical reasoning and Logo programming mastery among female high school students related the results of pretests of analogical reasoning to posttests of programming mastery. A significant correlation was found between analogical reasoning and the ability to write subprocedures for use in several different…

  9. DNA methylation patterns of candidate genes regulated by thymine DNA glycosylase in patients with TP53 germline mutations

    Energy Technology Data Exchange (ETDEWEB)

    Fortes, F.P. [CIPE, Laboratrio de Oncogentica Molecular, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Kuasne, H. [CIPE, Laboratrio NeoGene, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Departamento de Urologia, Faculdade de Medicina, Universidade Estadual Paulista, Botucatu, SP (Brazil); Marchi, F.A. [CIPE, Laboratrio NeoGene, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Programa Inter-Institucional em Bioinformtica, Instituto de Matemtica e Estatstica, Universidade So Paulo, So Paulo, SP (Brazil); Miranda, P.M. [CIPE, Laboratrio NeoGene, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Rogatto, S.R. [CIPE, Laboratrio NeoGene, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Departamento de Urologia, Faculdade de Medicina, Universidade Estadual Paulista, Botucatu, SP (Brazil); Achatz, M.I. [CIPE, Laboratrio de Oncogentica Molecular, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Departamento de Oncogentica, A.C. Camargo Cancer Center, So Paulo, SP (Brazil)

    2015-04-28

    Li-Fraumeni syndrome (LFS) is a rare, autosomal dominant, hereditary cancer predisposition disorder. In Brazil, the p.R337H TP53 founder mutation causes the variant form of LFS, Li-Fraumeni-like syndrome. The occurrence of cancer and age of disease onset are known to vary, even in patients carrying the same mutation, and several mechanisms such as genetic and epigenetic alterations may be involved in this variability. However, the extent of involvement of such events has not been clarified. It is well established that p53 regulates several pathways, including the thymine DNA glycosylase (TDG) pathway, which regulates the DNA methylation of several genes. This study aimed to identify the DNA methylation pattern of genes potentially related to the TDG pathway (CDKN2A, FOXA1, HOXD8, OCT4, SOX2, and SOX17) in 30 patients with germline TP53mutations, 10 patients with wild-type TP53, and 10 healthy individuals. We also evaluated TDG expression in patients with adrenocortical tumors (ADR) with and without the p.R337H TP53 mutation. Gene methylation patterns of peripheral blood DNA samples assessed by pyrosequencing revealed no significant differences between the three groups. However, increased TDG expression was observed by quantitative reverse transcription PCR in p.R337H carriers with ADR. Considering the rarity of this phenotype and the relevance of these findings, further studies using a larger sample set are necessary to confirm our results.

  10. Analogical scaffolding: Making meaning in physics through representation and analogy

    Science.gov (United States)

    Podolefsky, Noah Solomon

    This work reviews the literature on analogy, introduces a new model of analogy, and presents a series of experiments that test and confirm the utility of this model to describe and predict student learning in physics with analogy. Pilot studies demonstrate that representations (e.g., diagrams) can play a key role in students' use of analogy. A new model of analogy, Analogical Scaffolding, is developed to explain these initial empirical results. This model will be described in detail, and then applied to describe and predict the outcomes of further experiments. Two large-scale (N>100) studies will demonstrate that: (1) students taught with analogies, according to the Analogical Scaffolding model, outperform students taught without analogies on pre-post assessments focused on electromagnetic waves; (2) the representational forms used to teach with analogy can play a significant role in student learning, with students in one treatment group outperforming students in other treatment groups by factors of two or three. It will be demonstrated that Analogical Scaffolding can be used to predict these results, as well as finer-grained results such as the types of distracters students choose in different treatment groups, and to describe and analyze student reasoning in interviews. Abstraction in physics is reconsidered using Analogical Scaffolding. An operational definition of abstraction is developed within the Analogical Scaffolding framework and employed to explain (a) why physicists consider some ideas more abstract than others in physics, and (b) how students conceptions of these ideas can be modeled. This new approach to abstraction suggests novel approaches to curriculum design in physics using Analogical Scaffolding.

  11. 76 FR 52862 - Time for Payment of Certain Excise Taxes, and Quarterly Excise Tax Payments for Small Alcohol...

    Science.gov (United States)

    2011-08-24

    ... 40 Cigars and cigarettes, Claims, Electronic fund transfers, Excise taxes, Labeling, Packaging and... that are not required to pay taxes through electronic funds transfer (EFT), this first payment period..., Electronic funds transfers, Excise taxes, Exports, Food additives, Fruit juices, Labeling, Liquors, Packaging...

  12. Discrete Calculus by Analogy

    CERN Document Server

    Izadi, F A; Bagirov, G

    2009-01-01

    With its origins stretching back several centuries, discrete calculus is now an increasingly central methodology for many problems related to discrete systems and algorithms. The topics covered here usually arise in many branches of science and technology, especially in discrete mathematics, numerical analysis, statistics and probability theory as well as in electrical engineering, but our viewpoint here is that these topics belong to a much more general realm of mathematics; namely calculus and differential equations because of the remarkable analogy of the subject to this branch of mathemati

  13. ESD analog circuits and design

    CERN Document Server

    Voldman, Steven H

    2014-01-01

    A comprehensive and in-depth review of analog circuit layout, schematic architecture, device, power network and ESD design This book will provide a balanced overview of analog circuit design layout, analog circuit schematic development, architecture of chips, and ESD design.  It will start at an introductory level and will bring the reader right up to the state-of-the-art. Two critical design aspects for analog and power integrated circuits are combined. The first design aspect covers analog circuit design techniques to achieve the desired circuit performance. The second and main aspect pres

  14. Metabolic modulation of mammalian DNA excision repair

    Energy Technology Data Exchange (ETDEWEB)

    Schrader, T.J.

    1988-01-01

    First, ultraviolet light (UVL)- and dimethylsulfate (DMS)-induced excision repair was examined in quiescent and lectin-stimulated bovine lymphocytes. Upon mitogenic stimulation, UVL-induced repair increased by a factor of 2 to 3, and reached this maximum 2 days before the onset of DNA replication. However, DMS-induced repair increased sevenfold in parallel with DNA replication. Repair patch sizes were smaller for DMS-induced damage reflecting patches of 7 nucleotides in quiescent lymphocytes compared to 20 nucleotides induced by UVL. The patch size increased during lymphocyte stimulation until one day prior to the peak of DNA replication when patch sizes of 45 and 35 nucleotides were produced in response to UVL- and DMS-induced damage, respectively. At the peak of DNA replication, the patch sizes were equal for both damaging agents at 34 nucleotides. In the second study, a small amount of repair replication was observed in undamaged quiescent and concanavalin A-stimulated bovine lymphocytes as well as in human T98G glioblastoma cells. Repair incorporation doubled in the presence of hydroxyurea. Thirdly, the enhanced repair replication induced by the poly (ADP-ribose) polymerase inhibitor, 3-aminobenzamide, (3-AB), could not be correlated either with an increased rate of repair in the presence of 3-AB or with the use of hydroxyurea in the repair protocol. Finally, treatment of unstimulated lymphocytes with hyperthermia was accompanied by decreased repair replication while the repair patches remained constant at 20 nucleotides.

  15. Diode Laser Excision of Oral Benign Lesions.

    Science.gov (United States)

    Mathur, Ena; Sareen, Mohit; Dhaka, Payal; Baghla, Pallavi

    2015-01-01

    Lasers have made tremendous progress in the field of dentistry and have turned out to be crucial in oral surgery as collateral approach for soft tissue surgery. This rapid progress can be attributed to the fact that lasers allow efficient execution of soft tissue procedures with excellent hemostasis and field visibility. When matched to scalpel, electrocautery or high frequency devices, lasers offer maximum postoperative patient comfort. Four patients agreed to undergo surgical removal of benign lesions of the oral cavity. 810 nm diode lasers were used in continuous wave mode for excisional biopsy. The specimens were sent for histopathological examination and patients were assessed on intraoperative and postoperative complications. Diode laser surgery was rapid, bloodless and well accepted by patients and led to complete resolution of the lesions. The excised specimen proved adequate for histopathological examination. Hemostasis was achieved immediately after the procedure with minimal postoperative problems, discomfort and scarring. We conclude that diode lasers are rapidly becoming the standard of care in contemporary dental practice and can be employed in procedures requiring excisional biopsy of oral soft tissue lesions with minimal problems in histopathological diagnosis.

  16. Lingual Thyroid Excision with Transoral Robotic Surgery

    Directory of Open Access Journals (Sweden)

    Elif Ersoy Callıoglu

    2015-01-01

    Full Text Available Ectopic thyroid gland may be detected at any place between foramen caecaum and normal thyroid localization due to inadequacy of the embryological migration of the thyroid gland. It has a prevalence varying between 1/10.000 and 1/100000 in the community. Usually follow-up without treatment is preferred except for obstructive symptoms, bleeding, and suspicion of malignity. Main symptoms are dysphagia, dysphonia, bleeding, dyspnea, and obstructive sleep apnea. In symptomatic cases, the first described method in surgical treatment is open approach since it is a region difficult to have access to. However, this approach has an increased risk of morbidity and postoperative complications. Transoral robotic surgery, which is a minimally invasive surgical procedure, has advantages such as larger three-dimensional point of view and ease of manipulation due to robotic instruments. In this report, a case at the age of 49 who presented to our clinic with obstructive symptoms increasing within the last year and was found to have lingual thyroid and underwent excision of ectopic thyroid tissue by da Vinci surgical system is presented.

  17. Nasal encephalocele: endoscopic excision with anesthetic consideration.

    Science.gov (United States)

    Abdel-Aziz, Mosaad; El-Bosraty, Hussam; Qotb, Mohamed; El-Hamamsy, Mostafa; El-Sonbaty, Mohamed; Abdel-Badie, Hazem; Zynabdeen, Mustapha

    2010-08-01

    Nasal encephalocele may presents as a nasal mass, its treatment is surgical and it should be done early in life. When removal is indicated, there are multiple surgical approaches; including lateral rhinotomy, a transnasal approach and a coronal flap approach. However, the treatment of a basal intranasal encephalocele using transnasal endoscopic approach could obviates the possible morbidity associated with other approaches. The aim of this study was to evaluate the efficacy of endoscopic removal of intranasal encephalocele, also to document the role of anesthetist in the operative and postoperative periods. Nine cases with nasal encephalocele were included in this study; CT and/or MRI were used in their examination. The lesions were removed via transnasal endoscopic approach. Preoperative evaluation, intervention and postoperative follow-up were presented with discussion of anesthesia used for those children. The lesions of all patients were removed successfully with no recurrence through the follow-up period of at least 21 months. No cases showed morbidity or mortality intra- or post-operatively. Endoscopic excision of intranasal encephalocele is an effective method with high success rate. Anesthetist plays an important role in the operative and postoperative period, even during the endoscopic follow up; sedation of the children is usually needed. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  18. Uptake of benzyladenine by excised watermelon cotyledons.

    Science.gov (United States)

    Lampugnani, M G; Fantelli, R; Longo, G P; Longo, C P; Rossi, G

    1981-07-01

    The uptake of 8-[(14)C]N(6)-benzyladenine (BA) was studied in excised watermelon (Citrullus vulgaris Schrad.) cotyledons 24 hours after the start of imbibition. The passive nature of this uptake is suggested by the following evidence: (a) no sign of saturation on increasing external concentration of BA; (b) no decrease in uptake under conditions that inhibit ATP synthesis; (c) no change in amount of radioactivity absorbed when cotyledons are frozen and thawed before the uptake test. About two-thirds of the radioactivity taken up is released after 12 hours of washing. If the washing is performed at 2 C very little radioactivity is released.There seems to be a correlation between the level of radioactivity (i.e. of BA + derivatives) present in the cotyledons and the magnitude of hormonal responses that are observed four days after uptake. This relationship holds regardless of whether a given level of radioactivity has been reached after a short period of uptake or after a long period of uptake followed by washing.

  19. Albert Einstein, Analogizer Extraordinaire

    CERN Multimedia

    CERN. Geneva

    2007-01-01

    Where does deep insight in physics come from? It is tempting to think that it comes from the purest and most precise of reasoning, following ironclad laws of thought that compel the clear mind completely rigidly. And yet the truth is quite otherwise. One finds, when one looks closely at any major discovery, that the greatest of physicists are, in some sense, the most crazily daring and irrational of all physicists. Albert Einstein exemplifies this thesis in spades. In this talk I will describe the key role, throughout Albert Einstein's fabulously creative life, played by wild guesses made by analogy lacking any basis whatsoever in pure reasoning. In particular, in this year of 2007, the centenary of 1907, I will describe how over the course of two years (1905 through 1907) of pondering, Einstein slowly came, via analogy, to understand the full, radical consequences of the equation that he had first discovered and published in 1905, arguably the most famous equation of all time: E = mc2.

  20. Repair of DNA-polypeptide crosslinks by human excision nuclease

    Science.gov (United States)

    Reardon, Joyce T.; Sancar, Aziz

    2006-03-01

    DNA-protein crosslinks are relatively common DNA lesions that form during the physiological processing of DNA by replication and recombination proteins, by side reactions of base excision repair enzymes, and by cellular exposure to bifunctional DNA-damaging agents such as platinum compounds. The mechanism by which pathological DNA-protein crosslinks are repaired in humans is not known. In this study, we investigated the mechanism of recognition and repair of protein-DNA and oligopeptide-DNA crosslinks by the human excision nuclease. Under our assay conditions, the human nucleotide excision repair system did not remove a 16-kDa protein crosslinked to DNA at a detectable level. However, 4- and 12-aa-long oligopeptides crosslinked to the DNA backbone were recognized by some of the damage recognition factors of the human excision nuclease with moderate selectivity and were excised from DNA at relatively efficient rates. Our data suggest that, if coupled with proteolytic degradation of the crosslinked protein, the human excision nuclease may be the major enzyme system for eliminating protein-DNA crosslinks from the genome. damage recognition | nucleotide excision repair

  1. The Strategy of Excise Taxation of Tobacco Products in Ukraine

    Directory of Open Access Journals (Sweden)

    Pasichnyi Mykola D.

    2017-06-01

    Full Text Available The article is aimed at disclosing and improving approaches to the development of a strategy of excise tax policy in Ukraine, taking into account the foreign experience of harmonizing tax legislation in this sphere. An analysis of the implementation of the EU directives on the regulation of the minimum excise tax liability for the payment of excise taxes on tobacco products in the countries with transformational economies has been carried out. It has been found that, in cases of excessive tax pressure, the equilibrium of the market is disrupted, its shadow component is growing, and the overall economic efficiency level decreases. It has been determined that for the period of 2007-2016 the availability index for cigarettes in Ukraine decreased 2,3 times, which in some way demotivated their consumption. However, the change in the approach of calculation of ad valorem rate for the excise tax and introduction of the excise tax on the sub-excise goods sold by the retailers led to manipulative actions by the major actors in the market concerning the price of cigarettes, which impacted both the increase in the availability of cigarettes in 2016 and the decline in budget revenues. Regulation of the minimum excise duty is the most effective instrument of fiscal policy to achieve goals in the area of limitation of smoking.

  2. Nasal base narrowing: the combined alar base excision technique.

    Science.gov (United States)

    Foda, Hossam M T

    2007-01-01

    To evaluate the role of the combined alar base excision technique in narrowing the nasal base and correcting excessive alar flare. The study included 60 cases presenting with a wide nasal base and excessive alar flaring. The surgical procedure combined an external alar wedge resection with an internal vestibular floor excision. All cases were followed up for a mean of 32 (range, 12-144) months. Nasal tip modification and correction of any preexisting caudal septal deformities were always completed before the nasal base narrowing. The mean width of the external alar wedge excised was 7.2 (range, 4-11) mm, whereas the mean width of the sill excision was 3.1 (range, 2-7) mm. Completing the internal excision first resulted in a more conservative external resection, thus avoiding any blunting of the alar-facial crease. No cases of postoperative bleeding, infection, or keloid formation were encountered, and the external alar wedge excision healed with an inconspicuous scar that was well hidden in the depth of the alar-facial crease. Finally, the risk of notching of the alar rim, which can occur at the junction of the external and internal excisions, was significantly reduced by adopting a 2-layered closure of the vestibular floor (P = .01). The combined alar base excision resulted in effective narrowing of the nasal base with elimination of excessive alar flare. Commonly feared complications, such as blunting of the alar-facial crease or notching of the alar rim, were avoided by using simple modifications in the technique of excision and closure.

  3. Laparoscopic excision of a newborn rectal duplication cyst.

    Science.gov (United States)

    Hartin, Charles W; Lau, Stanley T; Escobar, Mauricio A; Glick, Philip L

    2008-08-01

    Congenital rectal duplication cyst is a rare entity treated with surgical excision. Without treatment, a rectal duplication cyst may cause a variety of complications, most notably, transforming into a malignancy. We report on a 7-week-old girl who was found to have a rectal duplication cyst. The rectal duplication cyst was successfully excised laparoscopically. Rectal duplication cysts are rare alimentary tract anomalies generally discovered during childhood. Complications include symptoms arising from the cyst and the possibility of malignant degeneration. They are typically managed by surgical excision.

  4. Detecting analogical resemblance without retrieving the source analogy.

    Science.gov (United States)

    Kostic, Bogdan; Cleary, Anne M; Severin, Kaye; Miller, Samuel W

    2010-06-01

    We examined whether people can detect analogical resemblance to an earlier experimental episode without being able to recall the experimental source of the analogical resemblance. We used four-word analogies (e.g., robin-nest/beaver-dam), in a variation of the recognition-without-cued-recall method (Cleary, 2004). Participants studied word pairs (e.g., robin-nest) and were shown new word pairs at test, half of which analogically related to studied word pairs (e.g., beaver-dam) and half of which did not. For each test pair, participants first attempted to recall an analogically similar pair from the study list. Then, regardless of whether successful recall occurred, participants were prompted to rate the familiarity of the test pair, which was said to indicate the likelihood that a pair that was analogically similar to the test pair had been studied. Across three experiments, participants demonstrated an ability to detect analogical resemblance without recalling the source analogy. Findings are discussed in terms of their potential relevance to the study of analogical reasoning and insight, as well as to the study of familiarity and recognition memory.

  5. Nucleotide excision repair in differentiated cells

    Energy Technology Data Exchange (ETDEWEB)

    Wees, Caroline van der [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Department of Cardiology, Leiden University Medical Center, Leiden (Netherlands); Jansen, Jacob [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Vrieling, Harry [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Laarse, Arnoud van der [Department of Cardiology, Leiden University Medical Center, Leiden (Netherlands); Zeeland, Albert van [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Mullenders, Leon [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands)]. E-mail: l.mullenders@lumc.nl

    2007-01-03

    Nucleotide excision repair (NER) is the principal pathway for the removal of a wide range of DNA helix-distorting lesions and operates via two NER subpathways, i.e. global genome repair (GGR) and transcription-coupled repair (TCR). Although detailed information is available on expression and efficiency of NER in established mammalian cell lines, little is known about the expression of NER pathways in (terminally) differentiated cells. The majority of studies in differentiated cells have focused on repair of UV-induced cyclobutane pyrimidine dimers (CPD) and 6-4-photoproducts (6-4PP) because of the high frequency of photolesions at low level of toxicity and availability of sensitive technologies to determine photolesions in defined regions of the genome. The picture that emerges from these studies is blurred and rather complex. Fibroblasts and terminally differentiated myocytes of the rat heart display equally efficient GGR of 6-4PP but poor repair of CPD due to the absence of p48 expression. This repair phenotype is clearly different from human terminal differentiated neurons. Furthermore, both cell types were found to carry out TCR of CPD, thus mimicking the repair phenotype of established rodent cell lines. In contrast, in intact rat spermatogenic cells repair was very inefficient at the genome overall level and in transcriptionally active genes indicating that GGR and TCR are non-functional. Also, non-differentiated mouse embryonic stem (ES) cells exhibit low levels of NER after UV irradiation. However, the mechanisms that lead to low NER activity are clearly different: in differentiated spermatogenic cells differences in chromatin compaction and sequestering of NER proteins may underlie the lack of NER activity in pre-meiotic cells, whereas in non-differentiated ES cells NER is impaired by a strong apoptotic response.

  6. DNA excision repair in permeable human fibroblasts

    International Nuclear Information System (INIS)

    Kaufmann, W.K.; Bodell, W.J.; Cleaver, J.E.

    1983-01-01

    U.v. irradiation of confluent human fibroblasts activated DNA repair, aspects of which were characterized in the cells after they were permeabilized. Incubation of intact cells for 20 min between irradiation and harvesting was necessary to obtain a maximum rate of reparative DNA synthesis. Cells harvested immediately after irradiation before repair was initiated displayed only a small stimulation of DNA synthesis, indicating that permeable cells have a reduced capacity to recognize pyrimidine dimers and activate repair. The distribution of sizes of DNA strands labeled during 10 min of reparative DNA synthesis resembled that of parental DNA. However, during a 60-min incubation of permeable cells at 37 degrees C, parental DNA and DNA labeled by reparative DNA synthesis were both cleaved to smaller sizes. Cleavage also occurred in unirradiated cells, indicating that endogenous nuclease was active during incubation. Repair patches synthesized in permeable cells displayed increased sensitivity to digestion by micrococcal nuclease. However, the change in sensitivity during a chase with unlabeled DNA precursors was small, suggesting that reassembly of nucleosome structure at sites of repair was impaired. To examine whether this deficiency was due to a preponderance of incomplete or unligated repair patches, 3H-labeled (repaired) DNA was purified, then digested with exonuclease III and nuclease S1 to probe for free 3' ends and single-stranded regions. About 85% of the [3H]DNA synthesized during a 10-min pulse resisted digestion, suggesting that a major fraction of the repair patches that were filled were also ligated. U.v. light-activated DNA synthesis in permeable cells, therefore, appears to represent the continuation of reparative gap-filling at sites of excision repair activated within intact cells. Gap-filling and ligation were comparatively efficient processes in permeable cells

  7. Feedback in analog circuits

    CERN Document Server

    Ochoa, Agustin

    2016-01-01

    This book describes a consistent and direct methodology to the analysis and design of analog circuits with particular application to circuits containing feedback. The analysis and design of circuits containing feedback is generally presented by either following a series of examples where each circuit is simplified through the use of insight or experience (someone else’s), or a complete nodal-matrix analysis generating lots of algebra. Neither of these approaches leads to gaining insight into the design process easily. The author develops a systematic approach to circuit analysis, the Driving Point Impedance and Signal Flow Graphs (DPI/SFG) method that does not require a-priori insight to the circuit being considered and results in factored analysis supporting the design function. This approach enables designers to account fully for loading and the bi-directional nature of elements both in the feedback path and in the amplifier itself, properties many times assumed negligible and ignored. Feedback circuits a...

  8. DNA translocation by human uracil DNA glycosylase: the case of single-stranded DNA and clustered uracils.

    Science.gov (United States)

    Schonhoft, Joseph D; Stivers, James T

    2013-04-16

    Human uracil DNA glycosylase (hUNG) plays a central role in DNA repair and programmed mutagenesis of Ig genes, requiring it to act on sparsely or densely spaced uracil bases located in a variety of contexts, including U/A and U/G base pairs, and potentially uracils within single-stranded DNA (ssDNA). An interesting question is whether the facilitated search mode of hUNG, which includes both DNA sliding and hopping, changes in these different contexts. Here we find that hUNG uses an enhanced local search mode when it acts on uracils in ssDNA, and also, in a context where uracils are densely clustered in duplex DNA. In the context of ssDNA, hUNG performs an enhanced local search by sliding with a mean sliding length larger than that of double-stranded DNA (dsDNA). In the context of duplex DNA, insertion of high-affinity abasic product sites between two uracil lesions serves to significantly extend the apparent sliding length on dsDNA from 4 to 20 bp and, in some cases, leads to directionally biased 3' → 5' sliding. The presence of intervening abasic product sites mimics the situation where hUNG acts iteratively on densely spaced uracils. The findings suggest that intervening product sites serve to increase the amount of time the enzyme remains associated with DNA as compared to nonspecific DNA, which in turn increases the likelihood of sliding as opposed to falling off the DNA. These findings illustrate how the search mechanism of hUNG is not predetermined but, instead, depends on the context in which the uracils are located.

  9. Toehold-mediated strand displacement reaction-dependent fluorescent strategy for sensitive detection of uracil-DNA glycosylase activity.

    Science.gov (United States)

    Wu, Yushu; Wang, Lei; Jiang, Wei

    2017-03-15

    Sensitive detection of uracil-DNA glycosylase (UDG) activity is beneficial for evaluating the repairing process of DNA lesions. Here, toehold-mediated strand displacement reaction (TSDR)-dependent fluorescent strategy was constructed for sensitive detection of UDG activity. A single-stranded DNA (ssDNA) probe with two uracil bases and a trigger sequence were designed. A hairpin probe with toehold domain was designed, and a reporter probe was also designed. Under the action of UDG, two uracil bases were removed from ssDNA probe, generating apurinic/apyrimidinic (AP) sites. Then, the AP sites could inhibit the TSDR between ssDNA probe and hairpin probe, leaving the trigger sequence in ssDNA probe still free. Subsequently, the trigger sequence was annealed with the reporter probe, initiating the polymerization and nicking amplification reaction. As a result, numerous G-quadruplex (G4) structures were formed, which could bind with N-methyl-mesoporphyrin IX (NMM) to generate enhanced fluorescent signal. In the absence of UDG, the ssDNA probe could hybridize with the toehold domain of the hairpin probe to initiate TSDR, blocking the trigger sequence, and then the subsequent amplification reaction would not occur. The proposed strategy was successfully implemented for detecting UDG activity with a detection limit of 2.7×10 -5 U/mL. Moreover, the strategy could distinguish UDG well from other interference enzymes. Furthermore, the strategy was also applied for detecting UDG activity in HeLa cells lysate with low effect of cellular components. These results indicated that the proposed strategy offered a promising tool for sensitive quantification of UDG activity in UDG-related function study and disease prognosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Human cytomegalovirus uracil DNA glycosylase associates with ppUL44 and accelerates the accumulation of viral DNA

    Directory of Open Access Journals (Sweden)

    Dixon Melissa

    2005-07-01

    Full Text Available Abstract Background Human cytomegalovirus UL114 encodes a uracil-DNA glycosylase homolog that is highly conserved in all characterized herpesviruses that infect mammals. Previous studies demonstrated that the deletion of this nonessential gene delays significantly the onset of viral DNA synthesis and results in a prolonged replication cycle. The gene product, pUL114, also appears to be important in late phase DNA synthesis presumably by introducing single stranded breaks. Results A series of experiments was performed to formally assign the observed phenotype to pUL114 and to characterize the function of the protein in viral replication. A cell line expressing pUL114 complemented the observed phenotype of a UL114 deletion virus in trans, confirming that the observed defects were the result of a deficiency in this gene product. Stocks of recombinant viruses without elevated levels of uracil were produced in the complementing cells; however they retained the phenotype of poor growth in normal fibroblasts suggesting that poor replication was unrelated to uracil content of input genomes. Recombinant viruses expressing epitope tagged versions of this gene demonstrated that pUL114 was expressed at early times and that it localized to viral replication compartments. This protein also coprecipitated with the DNA polymerase processivity factor, ppUL44 suggesting that these proteins associate in infected cells. This apparent interaction did not appear to require other viral proteins since ppUL44 could recruit pUL114 to the nucleus in uninfected cells. An analysis of DNA replication kinetics revealed that the initial rate of DNA synthesis and the accumulation of progeny viral genomes were significantly reduced compared to the parent virus. Conclusion These data suggest that pUL114 associates with ppUL44 and that it functions as part of the viral DNA replication complex to increase the efficiency of both early and late phase viral DNA synthesis.

  11. Triphlorethol-A from Ecklonia cava Up-Regulates the Oxidant Sensitive 8-Oxoguanine DNA Glycosylase 1

    Directory of Open Access Journals (Sweden)

    Ki Cheon Kim

    2014-10-01

    Full Text Available This study investigated the protective mechanisms of triphlorethol-A, isolated from Ecklonia cava, against oxidative stress-induced DNA base damage, especially 8-oxoguanine (8-oxoG, in Chinese hamster lung fibroblast V79-4 cells. 8-Oxoguanine DNA glycosylase-1 (OGG1 plays an important role in the removal of 8-oxoG during the cellular response to DNA base damage. Triphlorethol-A significantly decreased the levels of 8-oxoG induced by H2O2, and this correlated with increases in OGG1 mRNA and OGG1 protein levels. Furthermore, siOGG1-transfected cell attenuated the protective effect of triphlorethol-A against H2O2 treatment. Nuclear factor erythroid 2–related factor 2 (Nrf2 is a transcription factor for OGG1, and Nrf2 combines with small Maf proteins in the nucleus to bind to antioxidant response elements (ARE in the upstream promoter region of the OGG1 gene. Triphlorethol-A restored the expression of nuclear Nrf2, small Maf protein, and the Nrf2-Maf complex, all of which were reduced by oxidative stress. Furthermore, triphlorethol-A increased Nrf2 binding to ARE sequences and the resulting OGG1 promoter activity, both of which were also reduced by oxidative stress. The levels of the phosphorylated forms of Akt kinase, downstream of phosphatidylinositol 3-kinase (PI3K, and Erk, which are regulators of OGG1, were sharply decreased by oxidative stress, but these decreases were prevented by triphlorethol-A. Specific PI3K, Akt, and Erk inhibitors abolished the cytoprotective effects of triphlorethol-A, suggesting that OGG1 induction by triphlorethol-A involves the PI3K/Akt and Erk pathways. Taken together, these data indicate that by activating the DNA repair system, triphlorethol-A exerts protective effects against DNA base damage induced by oxidative stress.

  12. Both base excision repair and nucleotide excision repair in humans are influenced by nutritional factors.

    Science.gov (United States)

    Brevik, Asgeir; Karlsen, Anette; Azqueta, Amaya; Tirado, Anna Estaban; Blomhoff, Rune; Collins, Andrew

    2011-01-01

    Lack of reliable assays for DNA repair has largely prevented measurements of DNA repair from being included in human biomonitoring studies. Using newly developed modifications of the comet assay we tested whether a fruit- and antioxidant-rich plant-based intervention could affect base excision repair (BER) and nucleotide excision repair (NER) in a group of 102 male volunteers. BER and NER repair capacities were measured in lymphocytes before and after a dietary intervention lasting 8 weeks. The study had one control group, one group consuming three kiwifruits per day and one group consuming a variety of antioxidant-rich fruits and plant products in addition to their normal diet. DNA strand breaks were reduced following consumption of both kiwifruits (13%, p = 0.05) and antioxidant-rich plant products (20%, p = 0.02). Increased BER (55%, p = 0.01) and reduced NER (-39%, p plant products. Reduced NER was also observed in the kiwifruit group (-38%, p = 0.05), but BER was not affected in this group. Here we have demonstrated that DNA repair is affected by diet and that modified versions of the comet assay can be used to assess activity of different DNA repair pathways in human biomonitoring studies. Copyright © 2010 John Wiley & Sons, Ltd.

  13. Beginning analog electronics through projects

    CERN Document Server

    Singmin, Andrew

    2001-01-01

    Analog electronics is the simplest way to start a fun, informative, learning program. Beginning Analog Electronics Through Projects, Second Edition was written with the needs of beginning hobbyists and students in mind. This revision of Andrew Singmin's popular Beginning Electronics Through Projects provides practical exercises, building techniques, and ideas for useful electronics projects. Additionally, it features new material on analog and digital electronics, and new projects for troubleshooting test equipment.Published in the tradition of Beginning Electronics Through Projects an

  14. Technique for laparoscopic autonomic nerve preserving total mesorectal excision.

    Science.gov (United States)

    Breukink, S O; Pierie, J P E N; Hoff, C; Wiggers, T; Meijerink, W J H J

    2006-05-01

    With the introduction of total mesorectal excision (TME) for treatment of rectal cancer, the prognosis of patients with rectal cancer is improved. With this better prognosis, there is a growing awareness about the quality of life of patients after rectal carcinoma. Laparoscopic total mesorectal excision (LTME) for rectal cancer offers several advantages in comparison with open total mesorectal excision (OTME), including greater patient comfort and an earlier return to daily activities while preserving the oncologic radicality of the procedure. Moreover, laparoscopy allows good exposure of the pelvic cavity because of magnification and good illumination. The laparoscope seems to facilitate pelvic dissection including identification and preservation of critical structures such as the autonomic nervous system. The technique for laparoscopic autonomic nerve preserving total mesorectal excision is reported. A three- or four-port technique is used. Vascular ligation, sharp mesorectal dissection and identification and preservation of the autonomic pelvic nerves are described.

  15. Nuclear translocation contributes to regulation of DNA excision repair activities

    DEFF Research Database (Denmark)

    Knudsen, Nina Østergaard; Andersen, Sofie Dabros; Lützen, Anne

    2009-01-01

    for regulation of nuclear import that is necessary for proper localization of the repair proteins. This review summarizes the current knowledge on nuclear import mechanisms of DNA excision repair proteins and provides a model that categorizes the import by different mechanisms, including classical nuclear import......DNA mutations are circumvented by dedicated specialized excision repair systems, such as the base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR) pathways. Although the individual repair pathways have distinct roles in suppressing changes in the nuclear DNA......, it is evident that proteins from the different DNA repair pathways interact [Y. Wang, D. Cortez, P. Yazdi, N. Neff, S.J. Elledge, J. Qin, BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures, Genes Dev. 14 (2000) 927-939; M. Christmann, M...

  16. Development of excise on automotive fuels in the neighbouring countries

    International Nuclear Information System (INIS)

    Bleijenberg, A.N.; Janse, P.

    1994-04-01

    The political options for the Netherlands to implement the pricing policy for road traffic by means of an increase of excise, as formulated in the Second Transport Structure Plan (SVV-2), are limited by the excise level in neighbouring countries. Therefore, a study on the title subject has been carried out. First, an overview is given of the historical development of sales prices since 1980 for Belgium, Germany, Luxembourg and France with special attention for the large price differences. Next, insight into the effects of a price difference at the borders is given. Subsequently the development in the policy of the European Union with regard to harmonization of excise tariffs is discussed. Environmental organizations in Belgium and Luxembourg were contacted to learn about the expected development of excises in those countries. 5 figs., 6 tabs., 4 appendices, 10 refs

  17. Impacts of restructuring tabacco excise tax in the Philippines

    International Development Research Centre (IDRC) Digital Library (Canada)

    A recently approved law restructuring tobacco taxes in the. Philippines includes a steep increase in the excise tax (the tax paid by producers which ... part of Canada's International Development Research Centre. (IDRC), a Canadian Crown ...

  18. Comparison between preoperative biopsy and post-excision ...

    African Journals Online (AJOL)

    Comparison between preoperative biopsy and post-excision histology results in sarcoma: Experience at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa. KG Panda, MJ Hale, D Kruger, TE Luvhengo ...

  19. Excision of Mucocele Using Diode Laser in Lower Lip

    Directory of Open Access Journals (Sweden)

    Subramaniam Ramkumar

    2016-01-01

    Full Text Available Mucoceles are nonneoplastic cystic lesions of major and minor salivary glands which result from the accumulation of mucus. These lesions are most commonly seen in children. Though usually these lesions can be treated by local surgical excision, in our case, to avoid intraoperative surgical complications like bleeding and edema and to enable better healing, excision was done using a diode laser in the wavelength of 940 nm.

  20. Determining Factors for Fast Corneal Sensitivity Recovery After Pterygium Excision

    OpenAIRE

    Julio Morán, Gemma; Campos, Pamela; Pujol Vives, Pere; Munguia, Aitana; Mas Aixalà, Enric

    2016-01-01

    Purpose: To establish determining factors for fast corneal sensitivity (CS) recovery after pterygium excision. Methods: Thirty-two eyes of 14 males and 18 females with primary nasal pterygium were recruited. Differences in CS (in the 4 quadrants and the center using a Cochet–Bonnet esthesiometer), pterygium corneal area (PCA), tear osmolarity, tear break-up time, Schirmer test, and ocular symptoms were analyzed before and 1 month after lesion excision. The relationship between CS recovery...

  1. Children's Development of Analogical Reasoning: Insights from Scene Analogy Problems

    Science.gov (United States)

    Richland, Lindsey E.; Morrison, Robert G.; Holyoak, Keith J.

    2006-01-01

    We explored how relational complexity and featural distraction, as varied in scene analogy problems, affect children's analogical reasoning performance. Results with 3- and 4-year-olds, 6- and 7-year-olds, 9- to 11-year-olds, and 13- and 14-year-olds indicate that when children can identify the critical structural relations in a scene analogy…

  2. Genomic island excisions in Bordetella petrii

    Directory of Open Access Journals (Sweden)

    Levillain Erwan

    2009-07-01

    Full Text Available Abstract Background Among the members of the genus Bordetella B. petrii is unique, since it is the only species isolated from the environment, while the pathogenic Bordetellae are obligately associated with host organisms. Another feature distinguishing B. petrii from the other sequenced Bordetellae is the presence of a large number of mobile genetic elements including several large genomic regions with typical characteristics of genomic islands collectively known as integrative and conjugative elements (ICEs. These elements mainly encode accessory metabolic factors enabling this bacterium to grow on a large repertoire of aromatic compounds. Results During in vitro culture of Bordetella petrii colony variants appear frequently. We show that this variability can be attributed to the presence of a large number of metastable mobile genetic elements on its chromosome. In fact, the genome sequence of B. petrii revealed the presence of at least seven large genomic islands mostly encoding accessory metabolic functions involved in the degradation of aromatic compounds and detoxification of heavy metals. Four of these islands (termed GI1 to GI3 and GI6 are highly related to ICEclc of Pseudomonas knackmussii sp. strain B13. Here we present first data about the molecular characterization of these islands. We defined the exact borders of each island and we show that during standard culture of the bacteria these islands get excised from the chromosome. For all but one of these islands (GI5 we could detect circular intermediates. For the clc-like elements GI1 to GI3 of B. petrii we provide evidence that tandem insertion of these islands which all encode highly related integrases and attachment sites may also lead to incorporation of genomic DNA which originally was not part of the island and to the formation of huge composite islands. By integration of a tetracycline resistance cassette into GI3 we found this island to be rather unstable and to be lost from

  3. Optical analog transmission device

    International Nuclear Information System (INIS)

    Ikawa, Shinji.

    1994-01-01

    The present invention concerns a device such as electro-optical conversion elements, optoelectric-electric elements and optical transmission channel, not undergoing deleterious effects on the efficiency of conversion and transmission due to temperature, and aging change. That is, a sine wave superposing means superposes, on a detector signal to be transmitted, a sine-wave signal having a predetermined amplitude and at a frequency lower than that of the detector signal. An optoelectric conversion means converts the electric signal as the signal of the sine-wave signal superposing means into an optical signal and outputs the same to an optical transmitting channel. The optoelectric conversion means converts the transmitted signal to an electric signal. A discriminating means discriminates the electric signal into a detector signal and a sine-wave signal. A calculating means calculates an optical transmitting efficiency of the transmitting channel based on the amplitude of the discriminated sine-wave signal. A processing means compensates an amplitude value of the detector signals discriminated by the discriminating means based on the optical transmission efficiency. As a result, an optical analog transmission device can be attained, which conducts optical transmission at a high accuracy without undergoing the defective effects of the optical transmission efficiency. (I.S.)

  4. Conjecturing via Reconceived Classical Analogy

    Science.gov (United States)

    Lee, Kyeong-Hwa; Sriraman, Bharath

    2011-01-01

    Analogical reasoning is believed to be an efficient means of problem solving and construction of knowledge during the search for and the analysis of new mathematical objects. However, there is growing concern that despite everyday usage, learners are unable to transfer analogical reasoning to learning situations. This study aims at facilitating…

  5. Musik som analogi og metafor

    DEFF Research Database (Denmark)

    Bonde, Lars Ole

    2014-01-01

    Indeholder underkapitlerne: 2.5.1 Musik som analogi 2.5.2 Musik som metafor 2.5.3 Musikkens psykologiske funktioner - en taxonomi og metaforisk lytning til fire baroksatser......Indeholder underkapitlerne: 2.5.1 Musik som analogi 2.5.2 Musik som metafor 2.5.3 Musikkens psykologiske funktioner - en taxonomi og metaforisk lytning til fire baroksatser...

  6. Drawing Analogies in Environmental Education

    Science.gov (United States)

    Affifi, Ramsey

    2014-01-01

    Reconsidering the origin, process, and outcomes of analogy-making suggests practices for environmental educators who strive to disengage humans from the isolating illusions of dichotomizing frameworks. We can view analogies as outcomes of developmental processes within which human subjectivity is but an element, threading our sense of self back…

  7. Physical association of pyrimidine dimer DNA glycosylase and apurinic/apyrimidinic DNA endonuclease essential for repair of ultraviolet-damaged DNA

    International Nuclear Information System (INIS)

    Nakabeppu, Y.; Sekiguchi, M.

    1981-01-01

    T4 endonuclease, which is involved in repair of uv-damaged DNA, has been purified to apparent physical homogeneity. Incubation of uv-irradiated poly(dA).poly(dT) with the purified enzyme preparations resulted in production of alkali-labile apyrimidinic sites, followed by formation of nicks in the polymer. By performing a limited reaction with T4 endonuclease V at pH 8.5, irradiated polymer was converted to an intermediate form that carried a large number of alkali-labile sites but only a few nicks. The intermediate was used as substrate for the assay of apurinic/apyrimidinic DNA endonuclease activity. The two activities, a pyrimidine dimer DNA glycosylase and an apurinic/apyrimidinic DNA endonuclease, were copurified and found in enzyme preparations that contained only a 16,000-dalton polypeptide. These results strongly suggested that a DNA glycosylase specific for pyrimidine dimers and an apurinic/apyrimidinic DNA endonuclease reside in a single polypeptide chain coded by the denV gene of bacteriophage T4

  8. 29 CFR 779.262 - Excise taxes at the retail level.

    Science.gov (United States)

    2010-07-01

    ... AS APPLIED TO RETAILERS OF GOODS OR SERVICES Employment to Which the Act May Apply; Enterprise Coverage Excise Taxes § 779.262 Excise taxes at the retail level. (a) Federal excise taxes are imposed at... 29 Labor 3 2010-07-01 2010-07-01 false Excise taxes at the retail level. 779.262 Section 779.262...

  9. Analog-to-digital conversion

    CERN Document Server

    Pelgrom, Marcel J M

    2010-01-01

    The design of an analog-to-digital converter or digital-to-analog converter is one of the most fascinating tasks in micro-electronics. In a converter the analog world with all its intricacies meets the realm of the formal digital abstraction. Both disciplines must be understood for an optimum conversion solution. In a converter also system challenges meet technology opportunities. Modern systems rely on analog-to-digital converters as an essential part of the complex chain to access the physical world. And processors need the ultimate performance of digital-to-analog converters to present the results of their complex algorithms. The same progress in CMOS technology that enables these VLSI digital systems creates new challenges for analog-to-digital converters: lower signal swings, less power and variability issues. Last but not least, the analog-to-digital converter must follow the cost reduction trend. These changing boundary conditions require micro-electronics engineers to consider their design choices for...

  10. Analog fourier transform channelizer and OFDM receiver

    OpenAIRE

    2007-01-01

    An OFDM receiver having an analog multiplier based I-Q channelizing filter, samples and holds consecutive analog I-Q samples of an I-Q baseband, the I-Q basebands having OFDM sub-channels. A lattice of analog I-Q multipliers and analog I-Q summers concurrently receives the held analog I-Q samples, performs analog I-Q multiplications and analog I-Q additions to concurrently generate a plurality of analog I-Q output signals, representing an N-point discrete Fourier transform of the held analog ...

  11. Molecular modeling of fentanyl analogs

    Directory of Open Access Journals (Sweden)

    LJILJANA DOSEN-MICOVIC

    2004-11-01

    Full Text Available Fentanyl is a highly potent and clinically widely used narcotic analgesic. A large number of its analogs have been synthesized, some of which (sufentanil and alfentanyl are also in clinical use. Theoretical studies, in recent years, afforded a better understanding of the structure-activity relationships of this class of opiates and allowed insight into the molecular mechanism of the interactions of fentanyl analogs with their receptors. An overview of the current computational techniques for modeling fentanyl analogs, their receptors and ligand-receptor interactions is presented in this paper.

  12. Gemini analogs of vitamin D.

    Science.gov (United States)

    Pazos, Gonzalo; Rivadulla, Marcos L; Pérez-García, Xenxo; Gandara, Zoila; Pérez, Manuel

    2014-01-01

    The Gemini analogs are the last significant contribution to the family of vitamin D derivatives in medicine, for the treatment of cancer. The first Gemini analog was characterized by two symmetric side chains at C-20. Following numerous modifications, the most active analog bears a C-23-triple bond, C-26, 27- hexafluoro substituents on one side chain and a terminal trideuteromethylhydroxy group on the other side chain. This progression was possible due to improvements in the synthetic methods for the preparation of these derivatives, which allowed for increasing molecular complexity and complete diastereoselective control at C-20 and the substituted sidechains.

  13. Total excision of intramedullary epidermoid cyst in one case

    Directory of Open Access Journals (Sweden)

    PU Ke

    2013-12-01

    Full Text Available Clinical experience of total excision in a 14-year-old female with intramedullary epidermoid cyst was reported. The patient with L3-4 intramedullary epidermoid cyst underwent total excision through posterior median approach under microscopy. The patient was admitted for progressive strephexopodia and urinary and fecal incontinence. Preoperative imaging examination showed scoliosis, incontionous L4-S1 and abnormal signal of L3-4. Total excision and spinal remodeling were performed under intraoperative neurophysiological monitoning. Epidermoid cyst and its membrane were totally removed without aseptic meningitis after surgery, and the neurologic symptoms of the patient were gradually improved. Completely removing the membrane of epidermoid cyst is the key point to prevent recurrence and aseptic meningitis postoperatively. Dissection should be strictly in accordance with the boundaries of the membrane and the spinal cord, in order to avoid spinal cord injury.

  14. Excision of oral mucocele by different wavelength lasers

    Directory of Open Access Journals (Sweden)

    Umberto Romeo

    2013-01-01

    Full Text Available Background: Mucocele is a common benign neoplasm of oral soft tissues and the most common after fibroma. It generally occurs in the lower lip and its treatment includes excision of cyst and the responsible salivary gland, in order to prevent recurrences. Aims: To evaluate the capability of three different lasers in performing the excision of labial mucocele with two different techniques. Materials and Methods: In the presented cases, excision was performed using two different techniques (circumferential incision technique and mucosal preservation technique and three different laser wavelengths (Er,Cr:YSGG 2780 nm, diode 808 nm, and KTP 532 nm. Results: All the tested lasers, regardless of wavelength, showed many advantages (bloodless surgical field, no postoperative pain, relative speed, and easy execution. The most useful surgical technique depends on clinical features of the lesion. Conclusion: Tested lasers, with both techniques, are helpful in the management of labial mucocele.

  15. CELL POPULATION KINETICS OF EXCISED ROOTS OF PISUM SATIVUM

    Science.gov (United States)

    Van't Hof, Jack

    1965-01-01

    The cell population kinetics of excised, cultured pea roots was studied with the use of tritiated thymidine and colchicine to determine (1) the influence of excision, (2) the influence of sucrose concentration, (3) the average mitotic cycle duration, and (4) the duration of mitosis and the G 1, S, and G 2 periods of interphase.1 The results indicate that the process of excision causes a drop in the frequency of mitotic figures when performed either at the beginning of the culture period or after 100 hours in culture. This initial decrease in frequency of cell division is independent of sucrose concentration, but the subsequent rise in frequency of division, after 12 hours in culture, is dependent upon sucrose concentration. Two per cent sucrose maintains the shortest mitotic cycle duration. The use of colchicine indicated an average cycle duration of 20 hours, whereas the use of tritiated thymidine produced an average cycle duration of 17 hours. PMID:5857253

  16. Analog filters in nanometer CMOS

    CERN Document Server

    Uhrmann, Heimo; Zimmermann, Horst

    2014-01-01

    Starting from the basics of analog filters and the poor transistor characteristics in nanometer CMOS 10 high-performance analog filters developed by the authors in 120 nm and 65 nm CMOS are described extensively. Among them are gm-C filters, current-mode filters, and active filters for system-on-chip realization for Bluetooth, WCDMA, UWB, DVB-H, and LTE applications. For the active filters several operational amplifier designs are described. The book, furthermore, contains a review of the newest state of research on low-voltage low-power analog filters. To cover the topic of the book comprehensively, linearization issues and measurement methods for the characterization of advanced analog filters are introduced in addition. Numerous elaborate illustrations promote an easy comprehension. This book will be of value to engineers and researchers in industry as well as scientists and Ph.D students at universities. The book is also recommendable to graduate students specializing on nanoelectronics, microelectronics ...

  17. Union Women, the Tobacco Industry, and Excise Taxes

    Science.gov (United States)

    Balbach, Edith D.; Campbell, Richard B.

    2009-01-01

    Between 1987 and 1997, the tobacco industry used the issue of cigarette excise tax increases to create a political partnership with the Coalition of Labor Union Women (CLUW), a group representing female trade unionists in the U.S. This paper documents how the industry created this relationship and the lessons tobacco-control advocates can learn from the industry’s example, in order to mitigate possible unintended consequences of advocating excise tax increases In 1998, under the terms of the Master Settlement Agreement, the tobacco industry began making documents produced in litigation available publicly. Currently, approximately 50 million pages are available online, including substantial documentation of the industry–CLUW relationship. For this study, a comprehensive search of these documents was conducted. The tobacco industry encouraged CLUW’s opposition to excise tax increases by emphasizing the economic regressivity of these taxes, discussing excise taxes generically to deflect attention from cigarettes, and encouraging opposition to earmarking cigarette taxes to pay for specific programs. In addition, CLUW received at least $221,500 in financial support between 1987 and 1997 and in-kind support for its conferences, membership materials, and other services. Excise tax increases, if pursued without considering the impacts they may have on low-SES populations, may have unintended consequences. In this case, such proposals may have helped to create a relationship between CLUW and the tobacco industry. Because excise taxes are endorsed in the Framework Convention on Tobacco Control, tobacco-control advocates must understand how to build relationships with low-SES populations and mitigate potential alliances with the tobacco industry. PMID:19591750

  18. Black-hole excision with multiple grid patches

    International Nuclear Information System (INIS)

    Thornburg, Jonathan

    2004-01-01

    When using black-hole excision to numerically evolve a black-hole spacetime with no continuous symmetries, most 3 + 1 finite differencing codes use a Cartesian grid. It is difficult to do excision on such a grid because the natural r = constant excision surface must be approximated either by a very different shape such as a contained cube, or by an irregular and non-smooth 'LEGO 1 sphere' which may introduce numerical instabilities into the evolution. In this paper I describe an alternate scheme which uses multiple {r x (angular coordinates)} grid patches, each patch using a different (nonsingular) choice of angular coordinates. This allows excision on a smooth r = constant 2-sphere. I discuss the key design choices in such a multiple-patch scheme, including the choice of ghost-zone versus internal-boundary treatment of the interpatch boundaries (I use a ghost-zone scheme), the number and shape of the patches (I use a 6-patch 'inflated-cube' scheme), the details of how the ghost zones are 'synchronized' by interpolation from neighbouring patches, the tensor basis for the Einstein equations in each patch, and the handling of non-tensor field variables such as the BSSN Γ-tilde i (I use a scheme which requires ghost zones which are twice as wide for the BSSN conformal factor φ as for Γ-tilde i and the other BSSN field variables). I present sample numerical results from a prototype implementation of this scheme. This code simulates the time evolution of the (asymptotically flat) spacetime around a single (excised) black hole, using fourth-order finite differencing in space and time. Using Kerr initial data with J/m 2 = 0.6, I present evolutions to t ∼> 1500m. The lifetime of these evolutions appears to be limited only by outer boundary instabilities, not by any excision instabilities or by any problems inherent to the multiple-patch scheme

  19. Analog elements for transuranic chemistries

    International Nuclear Information System (INIS)

    Weimer, W.C.

    1982-01-01

    The analytical technique for measuring trace concentrations of the analog rare earth elements has been refined for optimal detection. The technique has been used to determine the rare earth concentrations in a series of geological and biological materials, including samples harvested from controlled lysimeter investigations. These studies have demonstrated that any of the trivalent rare earth elements may be used as analog elements for the trivalent transuranics, americium and curium

  20. CMOS Analog IC Design: Fundamentals

    OpenAIRE

    Bruun, Erik

    2018-01-01

    This book is intended for use as the main textbook for an introductory course in CMOS analog integrated circuit design. It is aimed at electronics engineering students who have followed basic courses in mathematics, physics, circuit theory, electronics and signal processing. It takes the students directly from a basic level to a level where they can start working on simple analog IC design projects or continue their studies using more advanced textbooks in the field. A distinct feature of thi...

  1. Recurred Myofibroblastoma of Breast After Excision: A Case Report

    International Nuclear Information System (INIS)

    Cha, Yoon Ki; Kim, Ji Young; Jeong, Myeong Ja; Kim, Jae Hyung; Kim, Soung Hee; Kim, Soo Hyun; Jun, Woo Sun; Park, Kyeong Mee; Yang, Keun Ho

    2010-01-01

    Myofibroblastoma of the breast is a rare benign mesenchymal tumor that is known to occur in middle-aged and elderly men, yet there are some recent reports showing no certain difference for the gender distribution of this malady. Localized mass excision can usually provide a complete cure. To the best of our knowledge, there have been no reports of metastasis or recurrence of this tumor. Here we describe the sonographic findings of a case of recurrent myofibroblastoma after surgical excision for suspected fibroadenomas in both breasts of a 25-year-old woman

  2. A seventh complementation group in excision-deficient xeroderma pigmentosum

    International Nuclear Information System (INIS)

    Keijzer, W.; Jaspers, N.G.J.; Bootsma, D.; Abrahams, P.J.; Taylor, A.M.R.; Arlett, C.F.; Zelle, B.; Kinmont, P.D.S.

    1979-01-01

    Cells from a xeroderma pigmentosum patient XP2B1 who has reached 17 years of age with no keratoses or skin tumours constitute a new, 7th complementation group G. These cells exhibit a low residual level of excision repair, 2% of normal after a UV dose of 5 J/m 2 and an impairment of post-replication repair characteristic of excision-defective XPs. They are also sensitive to the lethal effects of UV and defective in host-cell reactivation of UV-irradiated SV40 DNA. (Auth.)

  3. Analogical proportions: another logical view

    Science.gov (United States)

    Prade, Henri; Richard, Gilles

    This paper investigates the logical formalization of a restricted form of analogical reasoning based on analogical proportions, i.e. statements of the form a is to b as c is to d. Starting from a naive set theoretic interpretation, we highlight the existence of two noticeable companion proportions: one states that a is to b the converse of what c is to d (reverse analogy), while the other called paralogical proportion expresses that what a and b have in common, c and d have it also. We identify the characteristic postulates of the three types of proportions and examine their consequences from an abstract viewpoint. We further study the properties of the set theoretic interpretation and of the Boolean logic interpretation, and we provide another light on the understanding of the role of permutations in the modeling of the three types of proportions. Finally, we address the use of these proportions as a basis for inference in a propositional setting, and relate it to more general schemes of analogical reasoning. The differences between analogy, reverse-analogy, and paralogy is still emphasized in a three-valued setting, which is also briefly presented.

  4. An inverse switch in DNA base excision and strand break repair contributes to melphalan resistance in multiple myeloma cells.

    Directory of Open Access Journals (Sweden)

    Mirta M L Sousa

    Full Text Available Alterations in checkpoint and DNA repair pathways may provide adaptive mechanisms contributing to acquired drug resistance. Here, we investigated the levels of proteins mediating DNA damage signaling and -repair in RPMI8226 multiple myeloma cells and its Melphalan-resistant derivative 8226-LR5. We observed markedly reduced steady-state levels of DNA glycosylases UNG2, NEIL1 and MPG in the resistant cells and cross-resistance to agents inducing their respective DNA base lesions. Conversely, repair of alkali-labile sites was apparently enhanced in the resistant cells, as substantiated by alkaline comet assay, autoribosylation of PARP-1, and increased sensitivity to PARP-1 inhibition by 4-AN or KU58684. Reduced base-excision and enhanced single-strand break repair would both contribute to the observed reduction in genomic alkali-labile sites, which could jeopardize productive processing of the more cytotoxic Melphalan-induced interstrand DNA crosslinks (ICLs. Furthermore, we found a marked upregulation of proteins in the non-homologous end-joining (NHEJ pathway of double-strand break (DSB repair, likely contributing to the observed increase in DSB repair kinetics in the resistant cells. Finally, we observed apparent upregulation of ATR-signaling and downregulation of ATM-signaling in the resistant cells. This was accompanied by markedly increased sensitivity towards Melphalan in the presence of ATR-, DNA-PK, or CHK1/2 inhibitors whereas no sensitizing effect was observed subsequent to ATM inhibition, suggesting that replication blocking lesions are primary triggers of the DNA damage response in the Melphalan resistant cells. In conclusion, Melphalan resistance is apparently contributed by modulation of the DNA damage response at multiple levels, including downregulation of specific repair pathways to avoid repair intermediates that could impair efficient processing of cytotoxic ICLs and ICL-induced DSBs. This study has revealed several novel

  5. Producing and Recognizing Analogical Relations

    Science.gov (United States)

    Lipkens, Regina; Hayes, Steven C

    2009-01-01

    Analogical reasoning is an important component of intelligent behavior, and a key test of any approach to human language and cognition. Only a limited amount of empirical work has been conducted from a behavior analytic point of view, most of that within Relational Frame Theory (RFT), which views analogy as a matter of deriving relations among relations. The present series of four studies expands previous work by exploring the applicability of this model of analogy to topography-based rather than merely selection-based responses and by extending the work into additional relations, including nonsymmetrical ones. In each of the four studies participants pretrained in contextual control over nonarbitrary stimulus relations of sameness and opposition, or of sameness, smaller than, and larger than, learned arbitrary stimulus relations in the presence of these relational cues and derived analogies involving directly trained relations and derived relations of mutual and combinatorial entailment, measured using a variety of productive and selection-based measures. In Experiment 1 participants successfully recognized analogies among stimulus networks containing same and opposite relations; in Experiment 2 analogy was successfully used to extend derived relations to pairs of novel stimuli; in Experiment 3 the procedure used in Experiment 1 was extended to nonsymmetrical comparative relations; in Experiment 4 the procedure used in Experiment 2 was extended to nonsymmetrical comparative relations. Although not every participant showed the effects predicted, overall the procedures occasioned relational responses consistent with an RFT account that have not yet been demonstrated in a behavior-analytic laboratory setting, including productive responding on the basis of analogies. PMID:19230515

  6. Overexpression of transcription factor AP-2 stimulates the PA promoter of the human uracil-DNA glycosylase (UNG) gene through a mechanism involving derepression

    DEFF Research Database (Denmark)

    Aas, Per Arne; Pena Diaz, Javier; Liabakk, Nina Beate

    2009-01-01

    within the region of DNA marked by PA. Footprinting analysis and electrophoretic mobility shift assays of PA and putative AP-2 binding regions with HeLa cell nuclear extract and recombinant AP-2alpha protein indicate that AP-2 transcription factors are central in the regulated expression of UNG2 m......The PA promoter in the human uracil-DNA glycosylase gene (UNG) directs expression of the nuclear form (UNG2) of UNG proteins. Using a combination of promoter deletion and mutation analyses, and transient transfection of HeLa cells, we show that repressor and derepressor activities are contained......alpha, lacking the activation domain but retaining the DNA binding and dimerization domains, stimulated PA to a level approaching that of full-length AP-2, suggesting that AP-2 overexpression stimulates PA activity by a mechanism involving derepression rather than activation, possibly by neutralizing...

  7. Results of surgical excision of urethral prolapse in symptomatic patients.

    Science.gov (United States)

    Hall, Mary E; Oyesanya, Tola; Cameron, Anne P

    2017-11-01

    Here, we present the clinical presentation and surgical outcomes of women with symptomatic urethral prolapse presenting to our institution over 20 years, and seek to provide treatment recommendations for management of symptomatic urethral prolapse and caruncle. A retrospective review of medical records from female patients who underwent surgery for symptomatic urethral prolapse from June 1995 to August 2015 was performed. Surgical technique consisted of a four-quadrant excisional approach for repair of urethral prolapse. A total of 26 patients were identified with a mean age of 38.8 years (range 3-81). The most common presentations were vaginal bleeding, hematuria, pain, and dysuria. All patients underwent surgical excision of urethral prolapse via a standard approach. Follow-up data was available in 24 patients. Six patients experienced temporary postoperative bleeding, and one patient required placement of a Foley catheter for tamponade. One patient experienced temporary postoperative urinary retention requiring Foley catheter placement. Three patients had visible recurrence of urethral prolapse, for which one later underwent re-excision. Surgical excision of urethral prolapse is a reasonable treatment option in patients who have tried conservative management without relief, as well as in those who present with severe symptoms. Possible complications following excision include postoperative bleeding and recurrence, and patients must be counseled accordingly. In this work, we propose a treatment algorithm for symptomatic urethral prolapse. © 2017 Wiley Periodicals, Inc.

  8. Revenue and Health Impacts of Restructuring Tobacco Excise Tax ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    A proposed law in the Philippines to increase the excise tax on tobacco by ... developing countries to reduce demand for tobacco through price and tax measures. Southeast Asian countries are struggling with how to implement the main provisions of the Convention. ... Far East Asia, Philippines, Central Asia, South Asia ...

  9. Positive malignant margins in clinically diagnosed and excised be ...

    African Journals Online (AJOL)

    This study was aimed at utilizing retrospective descriptive data to evaluate the percentage of clini-cally benign breast lumps that turned out to be histologically malignant and the prevalence of posi-tive tumour margins among the malignant cases. A total of 2,917 registered cases of excised breast lump at the Department of ...

  10. Comparison between preoperative biopsy and post-excision ...

    African Journals Online (AJOL)

    peripheral nerve sheath tumour (6%).[6] Soft-tissue sarcomas most frequently affect the extremities and include MFH (40%), lipo- sarcoma (25%), synovial sarcoma and fibrosarcoma.[7]. Appropriate management is reliant on an accurate preoperative histology result. Excision biopsy is recommended for tumours. <3 cm in ...

  11. The safety of complete mesocolic excision once again confirmed

    DEFF Research Database (Denmark)

    Bertelsen, C A; Neuenschwander, A U

    2018-01-01

    We would like to commend Bernhoff and colleagues (1) for publishing further evidence supporting complete mesocolic excision (CME) as a safe approach in colon cancer surgery. They report no increased risk of 30-day mortality or reoperation after right-sided CME in a nested case-control study...

  12. 26 CFR 25.2512-7 - Effect of excise tax.

    Science.gov (United States)

    2010-04-01

    ... by a taxpayer and made the subject of gifts within a reasonable time after purchase, the purchase...-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) ESTATE AND GIFT TAXES GIFT TAX; GIFTS MADE AFTER DECEMBER 31, 1954 Transfers § 25.2512-7 Effect of excise tax. If...

  13. Nucleotide excision repair II: From yeast to mammals

    NARCIS (Netherlands)

    J.H.J. Hoeijmakers (Jan)

    1993-01-01

    textabstractAn intricate network of repair systems safeguards the integrity of genetic material, by eliminating DNA lesions induced by numerous environmental and endogenous genotoxic agents. Nucleotide excision repair (NER) is one of the most versatile DNA repair systems. Deficiencies in this

  14. Peri-operative management for excision of plexiform ...

    African Journals Online (AJOL)

    Case report: A 28-year-old female weighing 78 kilograms presented at the University of Port Harcourt Teaching Hospital (UPTH) with a huge left thigh mass, nodules and brownish skin patches (café-au-lait spots) all over her body. Plexiform neurofibromatosis was diagnosed. The mass was subsequently excised under ...

  15. Excise Taxes and the Price Elasticity of Demand.

    Science.gov (United States)

    Gamble, Ralph C., Jr.

    1989-01-01

    Points out that, although the analysis of the imposition of an excise tax is widely used in economics courses, the consequences of a change in the tax rate are different and ignored. This article presents an effective way to teach about such a change. (GG)

  16. A Method To Determine Adhesion Of Suppository Mass On Excised ...

    African Journals Online (AJOL)

    A method to determine adhesion of suppository mass to intestinal tissue was developed using excised pig intestine. The method which employs the principe of drainage unto and subsequent detachment from the mucosa, of an adherent suppository mass is simple, inexpensive and accurate. Fully optimised, it can be used ...

  17. A Rat Excised Larynx Model of Vocal Fold Scar

    Science.gov (United States)

    Welham, Nathan V.; Montequin, Douglas W.; Tateya, Ichiro; Tateya, Tomoko; Choi, Seong Hee; Bless, Diane M.

    2009-01-01

    Purpose: To develop and evaluate a rat excised larynx model for the measurement of acoustic, aerodynamic, and vocal fold vibratory changes resulting from vocal fold scar. Method: Twenty-four 4-month-old male Sprague-Dawley rats were assigned to 1 of 4 experimental groups: chronic vocal fold scar, chronic vocal fold scar treated with 100-ng basic…

  18. Papillary lesions of the breast: To excise or observe?

    Science.gov (United States)

    Khan, Sidrah; Diaz, Adrian; Archer, Kellie J; Lehman, Rebecca R; Mullins, Tiffany; Cardenosa, Gilda; Bear, Harry D

    2018-05-01

    Papillary lesions of the breast range from benign to atypical to malignant. Although papillomas without frank cancer are benign, their management remains controversial. When a core needle biopsy of a lesion yields a diagnosis of intraductal papilloma with atypia, excision is generally recommended to rule out a concurrent malignant neoplasm. For intraductal papillomas without atypia, however, recommendations for excision versus observation are variable. The aims of this study are to evaluate the rate of concurrent malignancies for intraductal papilloma diagnosed on core needle biopsy and to assess the long-term risk of developing cancer after the diagnosis of a papillary lesion. This single institution retrospective study analyzed 259 patients that were diagnosed with intraductal papilloma (IDP) by core needle biopsy from 1995 to 2010. Patients were grouped by initial diagnosis into three groups (papilloma without atypia, papilloma with atypia, and papilloma with atypical duct hyperplasia or atypical lobular hyperplasia (ADH/ALH) and followed up for long-term outcomes. After a core needle biopsy showing IDP with atypia or IDP + ADH/ALH, surgical excision yielded a diagnosis of concomitant invasive or ductal in situ cancer in greater that 30% of cases. For intraductal papilloma without atypia, the likelihood of cancer was much lower. Moreover, even with excision, the finding of intraductal papilloma with atypia carries a significant risk of developing cancer long-term, and such patients should be followed carefully and perhaps should be considered for chemoprevention. © 2017 Wiley Periodicals, Inc.

  19. 76 FR 46677 - Indoor Tanning Services; Cosmetic Services Excise Taxes

    Science.gov (United States)

    2011-08-03

    ... DEPARTMENT OF THE TREASURY Internal Revenue Service 26 CFR Parts 40 and 49 [REG-112841-10] RIN 1545-BJ40 Indoor Tanning Services; Cosmetic Services Excise Taxes AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of public hearing on proposed rulemaking. SUMMARY: This document provides notice...

  20. 75 FR 33740 - Indoor Tanning Services; Cosmetic Services; Excise Taxes

    Science.gov (United States)

    2010-06-15

    ... 1545-BJ40 Indoor Tanning Services; Cosmetic Services; Excise Taxes AGENCY: Internal Revenue Service.... 7805. * * * Par. 5. Section 49.0-3 is added to read as follows: Sec. 49.0-3 Introduction; cosmetic...--Cosmetic Services Sec. 49.5000B-1 Indoor tanning services. [The text of this proposed Sec. 49.5000B-1 is...

  1. of lung metastases carcinoma of the cervix Surgical excision from ...

    African Journals Online (AJOL)

    of lung metastases carcinoma of the cervix. Surgical excision from squamous. A report of 2 cases. N. G. DE MOOR, A. V. BERRY, M. M. NISSENBAUM. These2casereportsservetoemphasizetwoimpor- tant points concerning carcinoma of the cervix: (i) blood-borne metastases are now frequently encountered in this disease; ...

  2. Clinical trial comparing excision and primary closure with modified ...

    African Journals Online (AJOL)

    The aim of this study was to compare modified Limberg flap procedure with excision and primary closure in the treatment of uncomplicated pilonidal disease. Methods: This study was conducted on 120 patients with uncomplicated sacrococcygeal pilonidal disease that were randomly allocated into two groups: group I ...

  3. Microendoscopic excision of C2 osteoid osteoma: a technical report.

    Science.gov (United States)

    Kulkarni, Arvind G; Dhruv, Abhilash N; Bassi, Anupreet J

    2013-09-01

    Case report and description of technique. To describe a microendoscopic posterior approach for excision of an osteoid osteoma of C2. Microendoscopic techniques are widely used in the management of degenerative disorders of the spine. This is the first report of their use in the management of an osteoid osteoma via the posterior approach. A 12-year-old-boy presented with left-sided neck pain of 3-month duration. Investigations revealed an osteoid osteoma of C2 lamina-lateral mass complex. The patient underwent a posterior microendoscopic excision using 18-mm diameter METRx system (Medtronic Sofamor Danek, Memphis, TN) of tubular retractors. A postoperative computed tomographic scan was done and preoperative and postoperative visual analogue scale and Neck Disability Index were evaluated. The patient was periodically followed up for 1 year. The postoperative computed tomographic scan revealed complete excision of the tumor. The visual analogue scale score for neck pain improved from 3/5 (preoperative) to 0/5 (postoperative) and Neck Disability Index from 33.33 (preoperative) to 0 (postoperative) at 1-year follow-up. Microendoscopic techniques can be extended to excise lesions of the spine. It is a safe procedure in experienced hands. The advantages are minimal morbidity, minimal postoperative pain and discomfort, less analgesic dependence, and better cosmesis. The authors recommend this technique for accessible lesions involving the spine.

  4. Modulation of DNA base excision repair during neuronal differentiation

    DEFF Research Database (Denmark)

    Sykora, Peter; Yang, Jenq-Lin; Ferrarelli, Leslie K

    2013-01-01

    DNA damage susceptibility and base excision DNA repair (BER) capacity in undifferentiated and differentiated human neural cells. The results show that undifferentiated human SH-SY5Y neuroblastoma cells are less sensitive to oxidative damage than their differentiated counterparts, in part because...

  5. Principles of Periocular Reconstruction following Excision of Cutaneous Malignancy

    International Nuclear Information System (INIS)

    Hayano, S. M.; Whipple, K. M.; Korn, B. S.; Kikkawa, D. O.

    2012-01-01

    Reconstruction of periocular defects following excision of cutaneous malignancy can present difficulties for oculofacial and reconstructive surgeons. The intricate anatomy of the eyelids and face requires precise restoration in order to avoid postoperative functional anesthetic concerns. Various reconstructive procedures based on common principles, location and size of the defect, can be applied to achieve restoration with the best possible functional and aesthetic outcomes.

  6. Surgical excision of lung metastases from squamous carcinoma of ...

    African Journals Online (AJOL)

    These 2 case reports serveto emphasizetwo important points concerning carcinoma of the cervix: (i) blood-borne metastases are now frequently encountered in this disease; and (ii). in selected cases surgical excision of a secondary deposit in the lung is the treatment of choice and may even result -in cure.

  7. Deficiency of UV-induced excision repair in human thymocytes

    International Nuclear Information System (INIS)

    Gensler, H.L.; Lindberg, R.E.; Pinnas, J.L.; Jones, J.F.

    1985-01-01

    The capacity of human thymocytes and of differentiated lymphocytes circulating in peripheral blood to perform unscheduled DNA synthesis (a measure of nucleotide excision repair) after UV irradiation was measured by radioautographic analysis. Only 4% of immature T lymphocytes, but 68% of circulating lymphocytes exhibited unscheduled DNA synthesis. When UV sensitivity of peripheral blood lymphocytes and thymocytes from the same donor were compared, the thymocytes, in each case, were significantly more UV sensitive than were the circulating lymphocytes. Peripheral blood lymphocytes from subjects undergoing halothane and morphine anesthesia during surgery showed 56% less excision repair capacity than those from unanesthetized donors. The difference occurred in the number of cells capable of repair rather than in the extent of repair synthesis per cell. Ultraviolet-induced unscheduled DNA synthesis occurred in only 3% of the thymocytes removed from rats killed by cervical dislocation. Therefore, the deficiency of excision repair was observed in rat thymocytes which had not been affected by anesthesia or surgical trauma. The results indicate that immature T-cells are deficient in nucleotide excision repair whereas the majority of mature peripheral blood lymphocytes exhibit such repair. (author)

  8. Excision Les jeunes changent l'Afrique par les TIC

    International Development Research Centre (IDRC) Digital Library (Canada)

    Comité Inter-Africain sur les Pratiques Traditionnelles ayant effet sur la santé des ... Planche 7 - Perception genrée de la citoyenneté : les dire des femmes. 90 ...... dans le monde avec les migrations internationales, l'excision ne semble pas être ...... En utilisant les TIC pour exprimer leurs attentes et leurs besoins, les jeunes, ...

  9. Selective inhibition by methoxyamine of the apurinic/apyrimidinic endonuclease activity associated with pyrimidine dimer-DNA glycosylases from Micrococcus luteus and bacteriophage T4

    International Nuclear Information System (INIS)

    Liuzzi, M.; Weinfeld, M.; Paterson, M.C.

    1987-01-01

    The UV endonucleases from Micrococcus luteus and bacteriophage T4 possess two catalytic activities specific for the site of cyclobutane pyrimidine dimers in UV-irradiated DNA: a DNA glycosylase that cleaves the 5'-glycosyl bond of the dimerized pyrimidines and an apurinic/apyrimidinic (AP) endonuclease that thereupon incises the phosphodiester bond 3' to the resulting apyrimidinic site. The authors have explored the potential use of methoxyamine, a chemical that reacts at neutral pH with AP sites in DNA, as a selective inhibitor of the AP endonuclease activities residing in the M. luteus and T4 enzymes. The presence of 50 mM methoxyamine during incubation of UV-treated, [ 3 H]thymine-labeled poly(dA) x poly(dT) with either enzyme preparation was found to protect completely the irradiated copolymer from endonucleolytic attack at dimer sites, as assayed by yield of acid-soluble radioactivity. In contrast, the dimer-DNA glycosylase activity of each enzyme remained fully functional, as monitored retrospectively by release of free thymine after either photochemical-(5 kJ/m 2 , 254 nm) or photoenzymic- (Escherichia coli photolyase plus visible light) induced reversal of pyrimidine dimers in the UV-damaged substrate. The data demonstrate that the inhibition of the strand-incision reaction arises because of chemical modification of the AP sites and is not due to inactivation of the enzyme by methoxyamine. The results, combined with earlier findings for 5'-acting AP endonucleases, strongly suggest that methoxyamine is a highly specific inhibitor of virtually all AP endonucleases, irrespective of their modes of action, and may therefore prove useful in a wide variety of DNA repair studies

  10. Structural and biophysical analysis of interactions between cod and human uracil-DNA N-glycosylase (UNG) and UNG inhibitor (Ugi)

    Energy Technology Data Exchange (ETDEWEB)

    Assefa, Netsanet Gizaw [UiT The Arctic University of Norway, 9037 Tromsø (Norway); Niiranen, Laila [UiT The Arctic University of Norway, 9037 Tromsø (Norway); University of Turku, FIN-20014 Turku (Finland); Johnson, Kenneth A.; Leiros, Hanna-Kirsti Schrøder; Smalås, Arne Oskar; Willassen, Nils Peder [UiT The Arctic University of Norway, 9037 Tromsø (Norway); Moe, Elin, E-mail: elin.moe@uit.no [UiT The Arctic University of Norway, 9037 Tromsø (Norway); Universidade Nova de Lisboa, Avenida da Republica (EAN), 2780-157 Oeiras (Portugal)

    2014-08-01

    A structural and biophysical study of the interactions between cod and human uracil-DNA N-glycosylase (UNG) and their inhibitor Ugi is presented. The stronger interaction between cod UNG and Ugi can be explained by a greater positive electrostatic surface potential. Uracil-DNA N-glycosylase from Atlantic cod (cUNG) shows cold-adapted features such as high catalytic efficiency, a low temperature optimum for activity and reduced thermal stability compared with its mesophilic homologue human UNG (hUNG). In order to understand the role of the enzyme–substrate interaction related to the cold-adapted properties, the structure of cUNG in complex with a bacteriophage encoded natural UNG inhibitor (Ugi) has been determined. The interaction has also been analyzed by isothermal titration calorimetry (ITC). The crystal structure of cUNG–Ugi was determined to a resolution of 1.9 Å with eight complexes in the asymmetric unit related through noncrystallographic symmetry. A comparison of the cUNG–Ugi complex with previously determined structures of UNG–Ugi shows that they are very similar, and confirmed the nucleotide-mimicking properties of Ugi. Biophysically, the interaction between cUNG and Ugi is very strong and shows a binding constant (K{sub b}) which is one order of magnitude larger than that for hUNG–Ugi. The binding of both cUNG and hUNG to Ugi was shown to be favoured by both enthalpic and entropic forces; however, the binding of cUNG to Ugi is mainly dominated by enthalpy, while the entropic term is dominant for hUNG. The observed differences in the binding properties may be explained by an overall greater positive electrostatic surface potential in the protein–Ugi interface of cUNG and the slightly more hydrophobic surface of hUNG.

  11. DNA alkylation lesions and their repair in human cells: modification of the comet assay with 3-methyladenine DNA glycosylase (AlkD).

    Science.gov (United States)

    Hašplová, Katarína; Hudecová, Alexandra; Magdolénová, Zuzana; Bjøras, Magnar; Gálová, Eliška; Miadoková, Eva; Dušinská, Mária

    2012-01-05

    3-methyladenine DNA glycosylase (AlkD) belongs to a new family of DNA glycosylases; it initiates repair of cytotoxic and promutagenic alkylated bases (its main substrates being 3-methyladenine and 7-methylguanine). The modification of the comet assay (single cell gel electrophoresis) using AlkD enzyme thus allows assessment of specific DNA alkylation lesions. The resulting baseless sugars are alkali-labile, and under the conditions of the alkaline comet assay they appear as DNA strand breaks. The alkylating agent methyl methanesulfonate (MMS) was used to induce alkylation lesions and to optimize conditions for the modified comet assay method with AlkD on human lymphoblastoid (TK6) cells. We also studied cellular and in vitro DNA repair of alkylated bases in DNA in TK6 cells after treatment with MMS. Results from cellular repair indicate that 50% of DNA alkylation is repaired in the first 60 min. The in vitro repair assay shows that while AlkD recognises most alkylation lesions after 60 min, a cell extract from TK6 cells recognises most of the MMS-induced DNA adducts already in the first 15 min of incubation, with maximum detection of lesions after 60 min' incubation. Additionally, we tested the in vitro repair capacity of human lymphocyte extracts from 5 individuals and found them to be able to incise DNA alkylations in the same range as AlkD. The modification of the comet assay with AlkD can be useful for in vitro and in vivo genotoxicity studies to detect alkylation damage and repair and also for human biomonitoring and molecular epidemiology studies. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. Fast multichannel analog storage system

    International Nuclear Information System (INIS)

    Freytag, D.R.

    1982-11-01

    A Multichannel Analog Storage System based on a commercial 32-channel parallel in/serial out (PISO) analog shift register is described. The basic unit is a single width CAMAC module containing 512 analog cells and the associated logic for data storage and subsequent readout. At sampling rates of up to 30 MHz the signals are strobed directly into the PISO. At higher rates signals are strobed into a fast presampling stage and subsequently transferred in block form into an array of PISO's. Sampling rates of 300 MHz have been achieved with the present device and 1000 MHz are possible with improved signal drivers. The system is well suited for simultaneous handling of many signal channels with moderate numbers of samples in each channel. RMS noise over full scale signal has been measured as 1:3000 (approx. = 11 bit). However, nonlinearities in the response and differences in sensitivity of the analog cells require an elaborate calibration system in order to realize 11 bit accuracy for the analog information

  13. Obturator foramen dissection for excision of symptomatic transobturator mesh.

    Science.gov (United States)

    Reynolds, W Stuart; Kit, Laura Chang; Kaufman, Melissa R; Karram, Mickey; Bales, Gregory T; Dmochowski, Roger R

    2012-05-01

    Groin pain after transobturator synthetic mesh placement can be recalcitrant to conservative therapy and ultimately requires surgical excision. We describe our experiences with and technique of obturator foramen dissection for mesh excision. The records of 8 patients treated from 2005 to 2010, were reviewed. Obturator dissection was performed via a lateral groin incision over the inferior pubic ramus at the level of the obturator foramen, typically in conjunction with orthopedic surgery. Five patients had transobturator mid urethral sling surgery for stress urinary incontinence, 2 had mid urethral sling and trocar based anterior vaginal wall mesh kits with transobturator passage of mesh arms for stress urinary incontinence and pelvic organ prolapse, and 1 had an anterior vaginal wall mesh kit for pelvic organ prolapse. Patients had 0 to 2 prior transvaginal mesh excisions before obturator surgery. All patients presented with intractable pain in the area of the obturator foramen and/or medial groin for which conservative treatment measures had failed. Six patients underwent concurrent vaginal and obturator dissection and 2 underwent obturator dissection alone. In all cases residual mesh (3 to 11 cm) was identified and excised from the obturator foramen. Mesh was closely associated to or traversing the adductor longus muscle and tendon with significant fibrous reaction in all cases. Postoperatively 5 patients were cured of pain and/or infection, and 3 reported no or some improvement at a mean followup of 6 months (range 1 to 12). Our experience suggests that surgical excision of residual mesh can alleviate many of the symptoms in many patients. In all cases mesh remnants were identified and removed, and typically involved neuromuscular structures adjacent to the obturator foramen. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  14. Outcome of excision of megarectum in children with anorectal malformation.

    Science.gov (United States)

    Keshtgar, Alireza S; Ward, Harry C; Richards, Catherine; Clayden, Graham S

    2007-01-01

    Megarectum in association with anorectal malformation contributes to chronic constipation and fecal incontinence. Resection of megarectum in anorectal malformation improves bowel function, but neuropathy and poor sphincter quality may affect the outcome of fecal continence adversely. The aim of this study was to evaluate the benefits of resection of megarectum in anorectal malformation and to ascertain the impact of anal sphincter quality and neuropathy on the outcome. We studied 62 children with intractable fecal incontinence after repair of anorectal malformation between January 1991 and January 2005. All patients were investigated with anorectal manometry and anal endosonography under ketamine anesthesia. On endosonography, an intact or scarred internal anal sphincter (IAS) was classified as good and a fragmented or absent IAS as poor. On manometry, a resting anal sphincter pressure equal to or more than 30 mm Hg was classified as good and a lower pressure as poor. Functional assessment of fecal continence was done before and after excision of megarectum using a modified Wingfield scores. Sixteen children had excision of megarectum with median age of 9 years (range, 2-15 years) and postoperative follow-up of 5 years (range, 1-10 years). Seven had formation of antegrade continent enema stoma before excision of megarectum. Children were classified into three groups of anomalies: low (n = 6), intermediate (n = 4), and high (n = 6). All children were incontinent of feces. After excision of megarectum, of the 9 children with good IAS and no neuropathy, 7 became continent of feces. Of the remaining 7 children, 4 had poor IAS and 3 had neuropathy, 5 of whom required an antegrade continent enema stoma to be clean. Excision of megarectum in children who had previous repair of anorectal malformation results in fecal continence in the presence of a good IAS and absence of neuropathy. Patients with a poor IAS or neuropathy will often require artificial means of fecal

  15. Biochemical properties and base excision repair complex formation of apurinic/apyrimidinic endonuclease from Pyrococcus furiosus

    OpenAIRE

    Kiyonari, Shinichi; Tahara, Saki; Shirai, Tsuyoshi; Iwai, Shigenori; Ishino, Sonoko; Ishino, Yoshizumi

    2009-01-01

    Apurinic/apyrimidinic (AP) sites are the most frequently found mutagenic lesions in DNA, and they arise mainly from spontaneous base loss or modified base removal by damage-specific DNA glycosylases. AP sites are cleaved by AP endonucleases, and the resultant gaps in the DNA are repaired by DNA polymerase/DNA ligase reactions. We identified the gene product that is responsible for the AP endonuclease activity in the hyperthermophilic euryarchaeon, Pyrococcus furiosus. Furthermore, we detected...

  16. Analog electronics for radiation detection

    CERN Document Server

    2016-01-01

    Analog Electronics for Radiation Detection showcases the latest advances in readout electronics for particle, or radiation, detectors. Featuring chapters written by international experts in their respective fields, this authoritative text: Defines the main design parameters of front-end circuitry developed in microelectronics technologies Explains the basis for the use of complementary metal oxide semiconductor (CMOS) image sensors for the detection of charged particles and other non-consumer applications Delivers an in-depth review of analog-to-digital converters (ADCs), evaluating the pros and cons of ADCs integrated at the pixel, column, and per-chip levels Describes incremental sigma delta ADCs, time-to-digital converter (TDC) architectures, and digital pulse-processing techniques complementary to analog processing Examines the fundamental parameters and front-end types associated with silicon photomultipliers used for single visible-light photon detection Discusses pixel sensors ...

  17. Natural analogs for Yucca Mountain

    International Nuclear Information System (INIS)

    Murphy, W.M.

    1995-01-01

    High-level radioactive waste in the US, spent fuels from commercial reactors and nuclear materials generated by defense activities, will remain potentially hazardous for thousands of years. Demonstrable long-term stability of certain geologic and geochemical systems motivates and sustains the concept that high-level waste can be safely isolated in geologic repositories for requisite periods of time. Each geologic repository is unique in its properties and performance with reguard to isolation of nuclear wastes. Studies of processes analogous to waste-form alteration and radioelement transport in environments analogous to Yucca Mountain are being conducted at two sites, described in this article to illustrate uses of natural analog data: the Nopal I uranium deposit in the Sierra Pena Blanca, Mexico, and the Akrotiri archaeological site on the island of Santorini, Greece

  18. 76 FR 3502 - Time for Payment of Certain Excise Taxes, and Quarterly Excise Tax Payments for Small Alcohol...

    Science.gov (United States)

    2011-01-20

    ..., Surety bonds, Virgin Islands, Warehouses. 27 CFR Part 40 Cigars and cigarettes, Claims, Electronic fund... required to pay taxes through electronic funds transfer (EFT), this first payment period ends on September... Part 19 Caribbean Basin Initiative, Claims, Electronic funds transfers, Excise taxes, Exports, Gasohol...

  19. 76 FR 3584 - Time for Payment of Certain Excise Taxes, and Quarterly Excise Tax Payments for Small Alcohol...

    Science.gov (United States)

    2011-01-20

    ... 40 Cigars and cigarettes, Claims, Electronic fund transfers, Excise taxes, Labeling, Packaging and..., Regulations.gov , we will post, and you may view, copies of this notice, any electronic or mailed comments we... material that we consider unsuitable for posting. You also may view copies of this notice, any electronic...

  20. Synthetic Analogs of Phospholipid Metabolites as Antimalarials.

    Science.gov (United States)

    1979-07-01

    phosphatidic acid analogs containing ether and phosphonate groups; completely non- hydrolyzable lecithin analogs containing phosphinate and ether groups...substance is a completely non- hydrolyzable analog of lecithin containing ether and phosphonate moieties instead of the normally labile carboxylic and...and also ant-i-phospholipase C (clostridial enzyme) activity. This substance Is a completely non- hydrolyzable analog of lecithin containing ether

  1. Base excision repair efficiency and mechanism in nuclear extracts are influenced by the ratio between volume of nuclear extraction buffer and nuclei—Implications for comparative studies

    International Nuclear Information System (INIS)

    Akbari, Mansour; Krokan, Hans E.

    2012-01-01

    Highlights: • We examine effect of volume of extraction buffer relative to volume of isolated nuclei on repair activity of nuclear extract. • Base excision repair activity of nuclear extracts prepared from the same batch and number of nuclei varies inversely with the volume of nuclear extraction buffer. • Effect of the volume of extraction buffer on BER activity of nuclear extracts can only be partially reversed after concentration of the more diluted extract by ultrafiltration. - Abstract: The base excision repair (BER) pathway corrects many different DNA base lesions and is important for genomic stability. The mechanism of BER cannot easily be investigated in intact cells and therefore in vitro methods that reflect the in vivo processes are in high demand. Reconstitution of BER using purified proteins essentially mirror properties of the proteins used, and does not necessarily reflect the mechanism as it occurs in the cell. Nuclear extracts from cultured cells have the capacity to carry out complete BER and can give important information on the mechanism. Furthermore, candidate proteins in extracts can be inhibited or depleted in a controlled way, making defined extracts an important source for mechanistic studies. The major drawback is that there is no standardized method of preparing nuclear extract for BER studies, and it does not appear to be a topic given much attention. Here we have examined BER activity of nuclear cell extracts from HeLa cells, using as substrate a circular DNA molecule with either uracil or an AP-site in a defined position. We show that BER activity of nuclear extracts from the same batch of cells varies inversely with the volume of nuclear extraction buffer relative to nuclei volume, in spite of identical protein concentrations in the BER assay mixture. Surprisingly, the uracil–DNA glycosylase activity (mainly UNG2), but not amount of UNG2, also correlated negatively with the volume of extraction buffer. These studies demonstrate

  2. Robotic transanal total mesorectal excision for rectal cancer: experience with a first case

    NARCIS (Netherlands)

    Verheijen, P.M.; Consten, E.C.J.; Broeders, Ivo Adriaan Maria Johannes

    2014-01-01

    Background: A transanal approach for total mesorectal excision (TME) using a single incision port is feasible. The disadvantages are technical difficulties associated with limited manoeuvrability. Methods: We present our first experience with robotic-assisted transanal total mesorectal excision. A

  3. Black-hole excision with multiple grid patches

    Energy Technology Data Exchange (ETDEWEB)

    Thornburg, Jonathan [Max-Planck-Institut fuer Gravitationsphysik, Albert-Einstein-Institut, Am Muehlenberg 1, D-14476 Golm (Germany)

    2004-08-07

    When using black-hole excision to numerically evolve a black-hole spacetime with no continuous symmetries, most 3 + 1 finite differencing codes use a Cartesian grid. It is difficult to do excision on such a grid because the natural r = constant excision surface must be approximated either by a very different shape such as a contained cube, or by an irregular and non-smooth 'LEGO{sup 1} sphere' which may introduce numerical instabilities into the evolution. In this paper I describe an alternate scheme which uses multiple {l_brace}r x (angular coordinates){r_brace} grid patches, each patch using a different (nonsingular) choice of angular coordinates. This allows excision on a smooth r = constant 2-sphere. I discuss the key design choices in such a multiple-patch scheme, including the choice of ghost-zone versus internal-boundary treatment of the interpatch boundaries (I use a ghost-zone scheme), the number and shape of the patches (I use a 6-patch 'inflated-cube' scheme), the details of how the ghost zones are 'synchronized' by interpolation from neighbouring patches, the tensor basis for the Einstein equations in each patch, and the handling of non-tensor field variables such as the BSSN {gamma}-tilde{sup i} (I use a scheme which requires ghost zones which are twice as wide for the BSSN conformal factor {phi} as for {gamma}-tilde{sup i} and the other BSSN field variables). I present sample numerical results from a prototype implementation of this scheme. This code simulates the time evolution of the (asymptotically flat) spacetime around a single (excised) black hole, using fourth-order finite differencing in space and time. Using Kerr initial data with J/m{sup 2} = 0.6, I present evolutions to t {approx}> 1500m. The lifetime of these evolutions appears to be limited only by outer boundary instabilities, not by any excision instabilities or by any problems inherent to the multiple-patch scheme.

  4. Resolution of vitiligo following excision of halo congenital melanocytic nevus: a rare case report.

    Science.gov (United States)

    Wang, Kai; Wang, Zhi; Huang, Weiqing

    2016-05-01

    Halo congenital melanocytic nevus (CMN) associated with vitiligo is rare, especially with regard to CMN excision. Only two reports of excision of halo CMN following repigmentation of vitiligo are found in the literature. We present a case of a girl with halo CMN and periorbital vitiligo. The halo CMN was excised and followed by spontaneous improvement of vitiligo. The result suggests excision of the inciting lesion may be a promising way to control vitiligo. © 2015 Wiley Periodicals, Inc.

  5. Multichannel analog temperature sensing system

    International Nuclear Information System (INIS)

    Gribble, R.

    1985-08-01

    A multichannel system that protects the numerous and costly water-cooled magnet coils on the translation section of the FRX-C/T magnetic fusion experiment is described. The system comprises a thermistor for each coil, a constant current circuit for each thermistor, and a multichannel analog-to-digital converter interfaced to the computer

  6. 49205 ANALOGE OG DIGITALE FILTRE

    DEFF Research Database (Denmark)

    Gaunholt, Hans

    1997-01-01

    Theese lecture notes treats the fundamental theory and the most commonly used design methods for passive- active and digital filters with special emphasis on microelectronic realizations. The lecture notes covers 75% of the material taught in the course 49205 Analog and Digital Filters...

  7. Drawing Analogies to Deepen Learning

    Science.gov (United States)

    Fava, Michelle

    2017-01-01

    This article offers examples of how drawing can facilitate thinking skills that promote analogical reasoning to enable deeper learning. The instructional design applies cognitive principles, briefly described here. The workshops were developed iteratively, through feedback from student and teacher participants. Elements of the UK National…

  8. 29 CFR 779.263 - Excise taxes not at the retail level.

    Science.gov (United States)

    2010-07-01

    ... ACT AS APPLIED TO RETAILERS OF GOODS OR SERVICES Employment to Which the Act May Apply; Enterprise Coverage Excise Taxes § 779.263 Excise taxes not at the retail level. There are also a wide variety of... 29 Labor 3 2010-07-01 2010-07-01 false Excise taxes not at the retail level. 779.263 Section 779...

  9. First observation of excision and integration in Class 1 integron in ...

    African Journals Online (AJOL)

    So in this study, we tested in S. aureus, the class 1 integron mediated excision and integration. We first asked 8 plasmids from previous studies, then established some transformants and perform the excision and integration reaction. As the results revealed, we observed positive excision assay, which had been confirmed by ...

  10. Bayesian analogy with relational transformations.

    Science.gov (United States)

    Lu, Hongjing; Chen, Dawn; Holyoak, Keith J

    2012-07-01

    How can humans acquire relational representations that enable analogical inference and other forms of high-level reasoning? Using comparative relations as a model domain, we explore the possibility that bottom-up learning mechanisms applied to objects coded as feature vectors can yield representations of relations sufficient to solve analogy problems. We introduce Bayesian analogy with relational transformations (BART) and apply the model to the task of learning first-order comparative relations (e.g., larger, smaller, fiercer, meeker) from a set of animal pairs. Inputs are coded by vectors of continuous-valued features, based either on human magnitude ratings, normed feature ratings (De Deyne et al., 2008), or outputs of the topics model (Griffiths, Steyvers, & Tenenbaum, 2007). Bootstrapping from empirical priors, the model is able to induce first-order relations represented as probabilistic weight distributions, even when given positive examples only. These learned representations allow classification of novel instantiations of the relations and yield a symbolic distance effect of the sort obtained with both humans and other primates. BART then transforms its learned weight distributions by importance-guided mapping, thereby placing distinct dimensions into correspondence. These transformed representations allow BART to reliably solve 4-term analogies (e.g., larger:smaller::fiercer:meeker), a type of reasoning that is arguably specific to humans. Our results provide a proof-of-concept that structured analogies can be solved with representations induced from unstructured feature vectors by mechanisms that operate in a largely bottom-up fashion. We discuss potential implications for algorithmic and neural models of relational thinking, as well as for the evolution of abstract thought. Copyright 2012 APA, all rights reserved.

  11. Crows spontaneously exhibit analogical reasoning.

    Science.gov (United States)

    Smirnova, Anna; Zorina, Zoya; Obozova, Tanya; Wasserman, Edward

    2015-01-19

    Analogical reasoning is vital to advanced cognition and behavioral adaptation. Many theorists deem analogical thinking to be uniquely human and to be foundational to categorization, creative problem solving, and scientific discovery. Comparative psychologists have long been interested in the species generality of analogical reasoning, but they initially found it difficult to obtain empirical support for such thinking in nonhuman animals (for pioneering efforts, see [2, 3]). Researchers have since mustered considerable evidence and argument that relational matching-to-sample (RMTS) effectively captures the essence of analogy, in which the relevant logical arguments are presented visually. In RMTS, choice of test pair BB would be correct if the sample pair were AA, whereas choice of test pair EF would be correct if the sample pair were CD. Critically, no items in the correct test pair physically match items in the sample pair, thus demanding that only relational sameness or differentness is available to support accurate choice responding. Initial evidence suggested that only humans and apes can successfully learn RMTS with pairs of sample and test items; however, monkeys have subsequently done so. Here, we report that crows too exhibit relational matching behavior. Even more importantly, crows spontaneously display relational responding without ever having been trained on RMTS; they had only been trained on identity matching-to-sample (IMTS). Such robust and uninstructed relational matching behavior represents the most convincing evidence yet of analogical reasoning in a nonprimate species, as apes alone have spontaneously exhibited RMTS behavior after only IMTS training. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Excise Tax Avoidance: The Case of State Cigarette Taxes

    Science.gov (United States)

    DeCicca, Philip; Kenkel, Donald; Liu, Feng

    2013-01-01

    We conduct an applied welfare economics analysis of cigarette tax avoidance. We develop an extension of the standard formula for the optimal Pigouvian corrective tax to incorporate the possibility that consumers avoid the tax by making purchases in nearby lower-tax jurisdictions. To provide a key parameter for our formula, we estimate a structural endogenous switching regression model of border-crossing and cigarette prices. In illustrative calculations, we find that for many states, after taking into account tax avoidance the optimal tax is at least 20 percent smaller than the standard Pigouvian tax that simply internalizes external costs. Our empirical estimate that tax avoidance strongly responds to the price differential is the main reason for this result. We also use our results to examine the benefits of replacing avoidable state excise taxes with a harder-to-avoid federal excise tax on cigarettes. PMID:24140760

  13. Transanal vs laparoscopic total mesorectal excision for rectal cancer

    DEFF Research Database (Denmark)

    Perdawood, Sharaf; Al Khefagie, Ghalib Ali Abod

    2016-01-01

    BACKGROUND: Laparoscopic total mesorectal excision (LaTME) has improved short-term outcomes of rectal cancer surgery with comparable oncological results to open approach. LaTME can be difficult in the lower most part of the rectum, leading potentially to higher rates of complications, conversion...... to open surgery and probably suboptimal oncological quality. Transanal TME (TaTME) can potentially solve these problems. The aim of this study was to compare the short-term results after TaTME with those after LaTME. METHODS: A prospectively collected database of consecutive patients who underwent Ta......TME was maintained. Results were compared with those underwent LaTME in the preceding period. Patients who underwent low anterior resection or intersphincteric abdominoperineal excision (APE) were included. Primary end-points were radical resection and specimen quality. Secondary end-points were complications, rates...

  14. Excise tax avoidance: the case of state cigarette taxes.

    Science.gov (United States)

    DeCicca, Philip; Kenkel, Donald; Liu, Feng

    2013-12-01

    We conduct an applied welfare economics analysis of cigarette tax avoidance. We develop an extension of the standard formula for the optimal Pigouvian corrective tax to incorporate the possibility that consumers avoid the tax by making purchases in nearby lower tax jurisdictions. To provide a key parameter for our formula, we estimate a structural endogenous switching regression model of border-crossing and cigarette prices. In illustrative calculations, we find that for many states, after taking into account tax avoidance the optimal tax is at least 20% smaller than the standard Pigouvian tax that simply internalizes external costs. Our empirical estimate that tax avoidance strongly responds to the price differential is the main reason for this result. We also use our results to examine the benefits of replacing avoidable state excise taxes with a harder-to-avoid federal excise tax on cigarettes. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Isolated myocardial hydatid cyst: Managed with total curative excision

    Directory of Open Access Journals (Sweden)

    Santosh Kumar Sinha

    2016-01-01

    Full Text Available Hydatid disease is still prevalent in developing countries, and isolated cardiac hydatid cysts are the rarest presentation. We report a 40-year-old nondiabetic, nonhypertensive female who presented with low-grade fever for 2 months shortness of breath and orthopnea for 2 weeks. Transthoracic echocardiography revealed a large, round cystic lesion with multiple daughter cysts without any obvious intraluminal detached membranes with mass effect on the left ventricular outflow tract. After total excision, residual tissue was closed with Teflon patch. Germinative membrane and hundreds of daughter cysts were seen. Following total excision of the cyst from myocardium, myocardial cavity was washed thoroughly with 10% Betadine solution. Pathological examination confirmed the diagnosis of hydatid cyst. Preoperatively started albendazole was continued for 4 weeks even after the operation. On follow-up after 4 weeks, the patient is doing well and cardiac imaging showed normal contours of the heart.

  16. Principles of Periocular Reconstruction following Excision of Cutaneous Malignancy

    Directory of Open Access Journals (Sweden)

    Scott M. Hayano

    2012-01-01

    Full Text Available Reconstruction of periocular defects following excision of cutaneous malignancy can present difficulties for oculofacial and reconstructive surgeons. The intricate anatomy of the eyelids and face requires precise restoration in order to avoid postoperative functional anesthetic concerns. Various reconstructive procedures based on common principles, location and size of the defect, can be applied to achieve restoration with the best possible functional and aesthetic outcomes.

  17. Increased Ac excision (iae): Arabidopsis thaliana mutations affecting Ac transposition

    International Nuclear Information System (INIS)

    Jarvis, P.; Belzile, F.; Page, T.; Dean, C.

    1997-01-01

    The maize transposable element Ac is highly active in the heterologous hosts tobacco and tomato, but shows very much reduced levels of activity in Arabidopsis. A mutagenesis experiment was undertaken with the aim of identifying Arabidopsis host factors responsible for the observed low levels of Ac activity. Seed from a line carrying a single copy of the Ac element inserted into the streptomycin phosphotransferase (SPT) reporter fusion, and which displayed typically low levels of Ac activity, were mutagenized using gamma rays. Nineteen mutants displaying high levels of somatic Ac activity, as judged by their highly variegated phenotypes, were isolated after screening the M2 generation on streptomycin-containing medium. The mutations fall into two complementation groups, iae1 and iae2, are unlinked to the SPT::Ac locus and segregate in a Mendelian fashion. The iae1 mutation is recessive and the iae2 mutation is semi-dominant. The iae1 and iae2 mutants show 550- and 70-fold increases, respectively, in the average number of Ac excision sectors per cotyledon. The IAE1 locus maps to chromosome 2, whereas the SPT::Ac reporter maps to chromosome 3. A molecular study of Ac activity in the iae1 mutant confirmed the very high levels of Ac excision predicted using the phenotypic assay, but revealed only low levels of Ac re-insertion. Analyses of germinal transposition in the iae1 mutant demonstrated an average germinal excision frequency of 3% and a frequency of independent Ac re-insertions following germinal excision of 22%. The iae mutants represents a possible means of improving the efficiency of Ac/Ds transposon tagging systems in Arabidopsis, and will enable the dissection of host involvement in Ac transposition and the mechanisms employed for controlling transposable element activity

  18. Norwegian NOx emissions excise duty hits shipping and offshore industry

    International Nuclear Information System (INIS)

    Gulseth, Oeystein Arff; Fjeld-Nielsen, Siri

    2007-01-01

    The regulatory framework concerning the new excise duty appears as complex and unfinished, raising more questions than providing answers. The duty will entail a significant expense item for the businesses liable to register and it is therefore important to have an overview of how the regulatory framework should be understood. Errors made since 1 January 2007 may lead to future reassessments of duties, with interest (author) (ml)

  19. European Union Harmonized Excise Taxation : Occasional Importation Process

    OpenAIRE

    Tanhua, Taina

    2013-01-01

    This thesis was written with the intent to compile the information related to occasional importation process and European Union harmonized taxation into a single package. The process is based on European Union legislation and the aim of it is to unify the taxation within the internal market area. The national excise duties are not part of the occasional importation process but are partly linked to it. The first part of the thesis discusses the occasional importation of goods subject to ha...

  20. Temporal flap approach for preauricular epidermal cyst excision

    OpenAIRE

    Harshavardhan N Reddy; D R Srinivas; Konappa E Reddy; C Chandrakiran

    2011-01-01

    A 40-year-old male presented with a fluctuant swelling in front of the right ear. His past history is significant for having undergone surgery for the swelling four times in the past 6 years with recurrence each time. We excised the swelling by using a preauricular incision with reverse question mark type extension into the temporal area. The advantages are complete unhindered exposure, excellent cosmesis, and prevention of damage to the temporal branch of facial nerve.

  1. Endoscope-assisted approach to excision of branchial cleft cysts.

    Science.gov (United States)

    Teng, Stephanie E; Paul, Benjamin C; Brumm, John D; Fritz, Mark; Fang, Yixin; Myssiorek, David

    2016-06-01

    The purpose of this study is to describe an endoscope-assisted surgical technique for the excision of branchial cleft cysts and compare it to the standard approach. Retrospective case series review. Twenty-seven cases described as branchial cleft excisions performed by a single surgeon at one academic medical center were identified between 2007 and 2014. Twenty-five cases (8 endoscopic, 17 standard approach) were included in the study. Cases were excluded if final pathology was malignant. Patient charts were reviewed, and two techniques were compared through analysis of incision size, operative time, and surgical outcomes. This study showed that the length of incision required for the endoscopic approach (mean = 2.13 ± 0.23) was significantly less than that of the standard approach (mean = 4.10 ± 1.46, P = 0.008) despite the fact that there was no significant difference in cyst size between the two groups (P = 0.09). The other variables examined, including operative time and surgical outcomes, were not significantly different between the two groups. This transcervical endoscope-assisted approach to branchial cleft cyst excision is a viable option for uncomplicated cases. It provides better cosmetic results than the standard approach and does not negatively affect outcomes, increase operative time, or result in recurrence. 4. Laryngoscope, 126:1339-1342, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  2. Do alcohol excise taxes affect traffic accidents? Evidence from Estonia.

    Science.gov (United States)

    Saar, Indrek

    2015-01-01

    This article examines the association between alcohol excise tax rates and alcohol-related traffic accidents in Estonia. Monthly time series of traffic accidents involving drunken motor vehicle drivers from 1998 through 2013 were regressed on real average alcohol excise tax rates while controlling for changes in economic conditions and the traffic environment. Specifically, regression models with autoregressive integrated moving average (ARIMA) errors were estimated in order to deal with serial correlation in residuals. Counterfactual models were also estimated in order to check the robustness of the results, using the level of non-alcohol-related traffic accidents as a dependent variable. A statistically significant (P traffic accidents was disclosed under alternative model specifications. For instance, the regression model with ARIMA (0, 1, 1)(0, 1, 1) errors revealed that a 1-unit increase in the tax rate is associated with a 1.6% decrease in the level of accidents per 100,000 population involving drunk motor vehicle drivers. No similar association was found in the cases of counterfactual models for non-alcohol-related traffic accidents. This article indicates that the level of alcohol-related traffic accidents in Estonia has been affected by changes in real average alcohol excise taxes during the period 1998-2013. Therefore, in addition to other measures, the use of alcohol taxation is warranted as a policy instrument in tackling alcohol-related traffic accidents.

  3. The Impact of Pterygium Excision on Corneal Astigmatism

    International Nuclear Information System (INIS)

    Khan, F. A.; Niazi, S. P. K.; Khan, D. A.

    2014-01-01

    Objective: To compare the corneal astigmatism before and after the excision of pterygium and also to determine the correlation of pterygium size with the postoperative corneal astigmatism. Study Design: Cross-sectional interventional study. Place and Duration of Study: Eye Department, Combined Military Hospital, Abbottabad, from May 2011 to March 2012. Methodology: Thirty patients underwent pterygium excision. Pre-operatively Snellen visual acuity, manifest refraction and slit lamp examination was done. The size of the pterygium was recorded in mm by projecting a horizontal slit lamp beam from the limbus to the apex. All the pterygium were equal to or greater than 2.5 mm. Keratometry was performed with an automated keratometer. Keratometric data was recorded pre-operatively and at 28 days postoperatively. Wilcoxon signed rank test was used for comparing the pre-operative and the postoperative corneal astigmatism. Spearman's rank order was calculated to observe correlation of pterygium size with the postoperative astigmatism. Results: The median (mean rank) pre-operative astigmatism of 2.25 (15.50) reduced to a median (mean rank) postoperative astigmatism of 1.30 (14.96). This decrease in the postoperative astigmatism was statistically significant (p < 0.001). There was a statistically non-significant correlation between the postoperative astigmatism and the pterygium size (rs = -0.29, p = 0.12). Conclusion: Pterygium excision caused significant reduction in corneal astigmatism. (author)

  4. Recombinant methods for screening human DNA excision repair proficiency

    International Nuclear Information System (INIS)

    Athas, W.F.

    1988-01-01

    A method for measuring DNA excision repair in response to ultraviolet radiation (UV)-induced DNA damage has been developed, validated, and field-tested in cultured human lymphocytes. The methodology is amenable to population-based screening and should facilitate future epidemiologic studies seeking to investigate associations between excision repair proficiency and cancer susceptibility. The impetus for such endeavors derives from the belief that the high incidence of skin cancer in the genetic disorder xeroderma pigmentosum (XP) primarily is a result of the reduced capacity of patients cells to repair UV-induced DNA damage. For assay, UV-irradiated non-replicating recombinant plasmid DNA harboring a chloramphenicol acetyltransferase (CAT) indicator gene is introduced into lymphocytes using DEAE-dextran short-term transfection conditions. Exposure to UV induces transcriptionally-inactivating DNA photoproducts in the plasmid DNA which inactivate CAT gene expression. Excision repair of the damaged CAT gene is monitored indirectly as a function of reactivated CAT enzyme activity following a 40 hour repair/expression incubation period

  5. C → T mutagenesis and γ-radiation sensitivity due to deficiency in the Smug1 and Ung DNA glycosylases

    Science.gov (United States)

    An, Qian; Robins, Peter; Lindahl, Tomas; Barnes, Deborah E

    2005-01-01

    The most common genetic change in aerobic organisms is a C:G to T:A mutation. C → T transitions can arise through spontaneous hydrolytic deamination of cytosine to give a miscoding uracil residue. This is also a frequent DNA lesion induced by oxidative damage, through exposure to agents such as ionizing radiation, or from endogenous sources that are implicated in the aetiology of degenerative diseases, ageing and cancer. The Ung and Smug1 enzymes excise uracil from DNA to effect repair in mammalian cells, and gene-targeted Ung−/− mice exhibit a moderate increase in genome-wide spontaneous mutagenesis. Here, we report that stable siRNA-mediated silencing of Smug1 in mouse embryo fibroblasts also generates a mutator phenotype. However, an additive 10-fold increase in spontaneous C:G to T:A transitions in cells deficient in both Smug1 and Ung demonstrates that these enzymes have distinct and nonredundant roles in suppressing C → T mutability at non-CpG sites. Such cells are also hypersensitive to ionizing radiation, and reveal a role of Smug1 in the repair of lesions generated by oxidation of cytosine. PMID:15902269

  6. Analog circuit design art, science and personalities

    CERN Document Server

    Williams, Jim

    1991-01-01

    This book is far more than just another tutorial or reference guide - it's a tour through the world of analog design, combining theory and applications with the philosophies behind the design process. Readers will learn how leading analog circuit designers approach problems and how they think about solutions to those problems. They'll also learn about the `analog way' - a broad, flexible method of thinking about analog design tasks.A comprehensive and useful guide to analog theory and applications. Covers visualizing the operation of analog circuits. Looks at how to rap

  7. Excision of x-ray-induced thymine damage in chromatin from heated cells

    International Nuclear Information System (INIS)

    Warters, R.L.; Roti Roti, J.L.

    1979-01-01

    Experiments were performed to distinguish between two possible modes of hyperthermia-induced inhibition of thymine base damage excision from the DNA of CHO cells: (1) heat denaturation of excision enzyme(s) or (2) heat-induced alteration of the substrate for damage excision (chromatin). While hyperthermia (45 0 C, 15 min) had no apparent effect on the capacity of the excision enzymes to excise damage from DNA it had a dramatic effect (ca. 80% inhibition) on the ability of chromatin to serve as a substrate for unheated enzymes. These results suggest that hyperthermia-induced radiosensitization of CHO cells may be due primarily to lesions in the cellular chromatin

  8. Conserved XPB Core Structure and Motifs for DNA Unwinding:Implications for Pathway Selection of Transcription or ExcisionRepair

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Li; Arval, Andrew S.; Cooper, Priscilla K.; Iwai, Shigenori; Hanaoka, Fumio; Tainer, John A.

    2005-04-01

    The human xeroderma pigmentosum group B (XPB) helicase is essential for transcription, nucleotide excision repair, and TFIIH functional assembly. Here, we determined crystal structures of an Archaeoglobus fulgidus XPB homolog (AfXPB) that characterize two RecA-like XPB helicase domains and discover a DNA damage recognition domain (DRD), a unique RED motif, a flexible thumb motif (ThM), and implied conformational changes within a conserved functional core. RED motif mutations dramatically reduce helicase activity, and the DRD and ThM, which flank the RED motif, appear structurally as well as functionally analogous to the MutS mismatch recognition and DNA polymerase thumb domains. Substrate specificity is altered by DNA damage, such that AfXPB unwinds dsDNA with 3' extensions, but not blunt-ended dsDNA, unless it contains a lesion, as shown for CPD or (6-4) photoproducts. Together, these results provide an unexpected mechanism of DNA unwinding with Implications for XPB damage verification in nucleotide excision repair.

  9. Analog-to-digital conversion

    CERN Document Server

    Pelgrom, Marcel

    2017-01-01

    This textbook is appropriate for use in graduate-level curricula in analog-to-digital conversion, as well as for practicing engineers in need of a state-of-the-art reference on data converters. It discusses various analog-to-digital conversion principles, including sampling, quantization, reference generation, nyquist architectures and sigma-delta modulation. This book presents an overview of the state of the art in this field and focuses on issues of optimizing accuracy and speed, while reducing the power level. This new, third edition emphasizes novel calibration concepts, the specific requirements of new systems, the consequences of 22-nm technology and the need for a more statistical approach to accuracy. Pedagogical enhancements to this edition include additional, new exercises, solved examples to introduce all key, new concepts and warnings, remarks and hints, from a practitioner’s perspective, wherever appropriate. Considerable background information and practical tips, from designing a PCB, to lay-o...

  10. Analogies between antiferromagnets and antiferroelectrics

    International Nuclear Information System (INIS)

    Enz, C.P.; Matthias, B.T.

    1980-01-01

    Ferro- and antiferromagnetism in the Laves phase TiBesub(2-x) Cusub(x) occurs for 0.1 4 H 2 PO 4 and its solid solutions with TlH 2 PO 4 and with the ferroelectric KH 2 PO 4 are discussed as function of deuteration and of pressure. Another analogy as function of pressure is established with the antiferroelectric perovskite PbZrO 3 . (author)

  11. Novel phosphanucleoside analogs of dideoxynucleosides

    Czech Academy of Sciences Publication Activity Database

    Páv, Ondřej; Buděšínský, Miloš; Rosenberg, Ivan

    2017-01-01

    Roč. 73, č. 34 (2017), s. 5220-5228 ISSN 0040-4020 R&D Projects: GA ČR(CZ) GA17-12703S; GA ČR GA13-26526S; GA MZd NV15-31604A Institutional support: RVO:61388963 Keywords : phosphanucleoside * nucleoside analog * ring-closing metathesis * stereoselective hydroboration * chiral resolution Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 2.651, year: 2016

  12. Higher Volume at Time of Breast Conserving Surgery Reduces Re-Excision in DCIS

    Directory of Open Access Journals (Sweden)

    J. H. Wolf

    2011-01-01

    Full Text Available Purpose. The purpose of this study was to compare the surgical and pathological variables which impact rate of re-excision following breast conserving therapy (BCS with or without concurrent additional margin excision (AM. Methods. The pathology database was queried for all patients with DCIS from January 2004 to September 2008. Pathologic assessment included volume of excision, subtype, size, distance from margin, grade, necrosis, multifocality, calcifications, and ER/PR status. Results. 405 cases were identified and 201 underwent BCS, 151-BCS-AM, and 53-mastectomy. Among the 201 BCS patients, 190 underwent re-excision for close or involved margins. 129 of these were treated with BCS and 61 with BCS-AM (P<.0001. The incidence of residual DCIS in the re-excision specimens was 32% (n=65 for BCS and 22% (n=33 for BCS-AM (P<.05. For both the BCS and the BCS-AM cohorts, volume of tissue excised is inversely correlated to the rate of re-excision (P=.0284. Multifocality (P=.0002 and ER status (P=.0382 were also significant predictors for rate of re-excision and variation in surgical technique was insignificant. Conclusions. The rate of positive margins, re-excision, and residual disease was significantly higher in patients with lower volume of excision. The performance of concurrent additional margin excision increases the efficacy of BCS for DCIS.

  13. Electrostatic analogy for symmetron gravity

    Science.gov (United States)

    Ogden, Lillie; Brown, Katherine; Mathur, Harsh; Rovelli, Kevin

    2017-12-01

    The symmetron model is a scalar-tensor theory of gravity with a screening mechanism that suppresses the effect of the symmetron field at high densities characteristic of the Solar System and laboratory scales but allows it to act with gravitational strength at low density on the cosmological scale. We elucidate the screening mechanism by showing that in the quasistatic Newtonian limit there are precise analogies between symmetron gravity and electrostatics for both strong and weak screening. For strong screening we find that large dense bodies behave in a manner analogous to perfect conductors in electrostatics. Based on this analogy we find that the symmetron field exhibits a lightning rod effect wherein the field gradients are enhanced near the ends of pointed or elongated objects. An ellipsoid placed in a uniform symmetron gradient is shown to experience a torque. By symmetry there is no gravitational torque in this case. Hence this effect unmasks the symmetron and might serve as the basis for future laboratory experiments. The symmetron force between a point mass and a large dense body includes a component corresponding to the interaction of the point mass with its image in the larger body. None of these effects have counterparts in the Newtonian limit of Einstein gravity. We discuss the similarities between symmetron gravity and the chameleon model as well as the differences between the two.

  14. 8-Oxoguanine DNA glycosylase 1 (ogg1) maintains the function of cardiac progenitor cells during heart formation in zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Lifeng [State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029 (China); Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029 (China); Zhou, Yong [Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Yu, Shanhe [Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025 (China); Ji, Guixiang [Nanjing Institute of Environmental Sciences/Key Laboratory of Pesticide Environmental Assessment and Pollution Control, Ministry of Environmental Protection, Nanjing 210042 (China); Wang, Lei [Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Liu, Wei [State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029 (China); Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029 (China); Gu, Aihua, E-mail: aihuagu@njmu.edu.cn [State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029 (China); Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029 (China)

    2013-11-15

    Genomic damage may devastate the potential of progenitor cells and consequently impair early organogenesis. We found that ogg1, a key enzyme initiating the base-excision repair, was enriched in the embryonic heart in zebrafish. So far, little is known about DNA repair in cardiogenesis. Here, we addressed the critical role of ogg1 in cardiogenesis for the first time. ogg1 mainly expressed in the anterior lateral plate mesoderm (ALPM), the primary heart tube, and subsequently the embryonic myocardium by in situ hybridisation. Loss of ogg1 resulted in severe cardiac morphogenesis and functional abnormalities, including the short heart length, arrhythmia, decreased cardiomyocytes and nkx2.5{sup +} cardiac progenitor cells. Moreover, the increased apoptosis and repressed proliferation of progenitor cells caused by ogg1 deficiency might contribute to the heart phenotype. The microarray analysis showed that the expression of genes involved in embryonic heart tube morphogenesis and heart structure were significantly changed due to the lack of ogg1. Among those, foxh1 is an important partner of ogg1 in the cardiac development in response to DNA damage. Our work demonstrates the requirement of ogg1 in cardiac progenitors and heart development in zebrafish. These findings may be helpful for understanding the aetiology of congenital cardiac deficits. - Highlights: • A key DNA repair enzyme ogg1 is expressed in the embryonic heart in zebrafish. • We found that ogg1 is essential for normal cardiac morphogenesis in zebrafish. • The production of embryonic cardiomyocytes requires appropriate ogg1 expression. • Ogg1 critically regulated proliferation of cardiac progenitor cells in zebrafish. • foxh1 is a partner of ogg1 in the cardiac development in response to DNA damage.

  15. The Development of Analogical Reasoning Processes.

    Science.gov (United States)

    Sternberg, Robert J.; Rifkin, Bathsheva

    1979-01-01

    Two experiments were conducted to test the generalizability to children of a theory of analogical reasoning processes, originally proposed for adults, and to examine the development of analogical reasoning processes in terms of five proposed sources of cognitive development. (MP)

  16. 16-channel analog store and multiplexer unit

    Energy Technology Data Exchange (ETDEWEB)

    Brossard, M; Kulka, Z [Clermont-Ferrand-2 Univ., 63 - Aubiere (France). Lab. de Physique Corpusculaire

    1979-03-15

    A 16-channel analog store and multiplexer unit is described. The unit enables storing and selection of analog information which is then digitally encoded by single ADC. This solution becomes economically attractive particularly in multidetector pulse height analysis systems.

  17. Atheism and Analogy: Aquinas Against the Atheists

    OpenAIRE

    Linford, Daniel J.

    2014-01-01

    In the 13th century, Thomas Aquinas developed two models for how humans may speak of God - either by the analogy of proportion or by the analogy of proportionality. Aquinas's doctrines initiated a theological debate concerning analogy that spanned several centuries. In the 18th century, there appeared two closely related arguments for atheism which both utilized analogy for their own purposes. In this thesis, I show that one argument, articulated by the French materialist Paul-Henri Thiry Bar...

  18. Enhancing programming logic thinking using analogy mapping

    Science.gov (United States)

    Sukamto, R. A.; Megasari, R.

    2018-05-01

    Programming logic thinking is the most important competence for computer science students. However, programming is one of the difficult subject in computer science program. This paper reports our work about enhancing students' programming logic thinking using Analogy Mapping for basic programming subject. Analogy Mapping is a computer application which converts source code into analogies images. This research used time series evaluation and the result showed that Analogy Mapping can enhance students' programming logic thinking.

  19. Analogies and the 5E Model

    Science.gov (United States)

    Orgill, Mary Kay; Thomas, Megan

    2007-01-01

    Science classes are full of abstract or challenging concepts that are easier to understand if an analogy is used to illustrate the points. Effective analogies motivate students, clarify students' thinking, help students overcome misconceptions, and give students ways to visualize abstract concepts. When they are used appropriately, analogies can…

  20. Science Teachers' Analogical Reasoning

    Science.gov (United States)

    Mozzer, Nilmara Braga; Justi, Rosária

    2013-01-01

    Analogies can play a relevant role in students' learning. However, for the effective use of analogies, teachers should not only have a well-prepared repertoire of validated analogies, which could serve as bridges between the students' prior knowledge and the scientific knowledge they desire them to understand, but also know how to…

  1. The Micro-Category Account of Analogy

    Science.gov (United States)

    Green, Adam E.; Fugelsang, Jonathan A.; Kraemer, David J. M.; Dunbar, Kevin N.

    2008-01-01

    Here, we investigate how activation of mental representations of categories during analogical reasoning influences subsequent cognitive processing. Specifically, we present and test the central predictions of the "Micro-Category" account of analogy. This account emphasizes the role of categories in aligning terms for analogical mapping. In a…

  2. Descriptive Study of Patients Receiving Excision and Radiotherapy for Keloids

    International Nuclear Information System (INIS)

    Speranza, Giovanna; Sultanem, Khalil M.D.; Muanza, Thierry

    2008-01-01

    Purpose: To review and describe our institution's outcomes in patients treated with external beam radiotherapy after keloid excision. Methods and Materials: This was a retrospective study. Patients who received radiotherapy between July 1994 and January 2004 after keloid excision were identified. A questionnaire was mailed regarding sociodemographic factors, early and late radiation toxicities, the need for additional therapy, and satisfaction level. All patients had received a total of 15 Gy in three daily 5-Gy fractions. Treatment started within 24 h after surgery and was delivered on a Siemens orthovoltage machine. The data were analyzed using the STATA statistical package. Results: A total of 234 patients were approached. The response rate was 41%, and 75% were female. The mean age was 36.5 years (range, 16-69 years). The patients were mainly of European (53.1%) or African (19.8%) descent. For early toxicity outcomes, 54.2% reported skin redness and 24% reported skin peeling. For late toxicity outcomes, 27% reported telangiectasia and 62% reported permanent skin color changes. No association was found with gender, skin color, or age for the late toxicity outcomes. Of the patients responding, 14.6% required adjuvant treatment. On a visual scale of 1-10 for the satisfaction level, 60% reported a satisfaction level of ≥8. Telangiectasia was the most significant predictor of a low satisfaction level (≤3, p < 0.005). Conclusion: The results of our study have shown that orthovoltage-based radiotherapy after surgical excision for keloids is a good method for the prevention of relapse. It is well tolerated, causes little toxicity, and leads to a high patient satisfaction level

  3. Inverted 'V' osteotomy excision arthroplasty for bony ankylosed elbows

    Directory of Open Access Journals (Sweden)

    Rex Chadrabose

    2011-12-01

    Full Text Available Abstract Background Bony ankylosis of elbow is challenging and difficult problem to treat. The options are excision arthroplasty and total elbow replacement. We report our midterm results on nine patients, who underwent inverted 'V' osteotomy excision arthroplasty in our hospital with good functional results. Materials Our case series includes 9 patients (seven males and two females with the mean age of 34 years (13-56 years. Five patients had trauma, two had pyogenic arthritis, one had tuberculous arthritis, and one had pyogenic arthritis following surgical fixation. Results The average duration of follow up is 65 months (45 months-80 months. The mean Mayo's elbow performance score (MEPS preoperatively was 48 (35-70. The MEPS at final follow up was 80 (60-95. With no movement at elbow and fixed in various degrees of either flexion or extension preoperatively, the mean preoperative position of elbow was 64°(30°to 100°. The mean post operative range of motion at final follow up was 27°of extension (20-500, 116°of flexion (1100-1300, and the arc of motion was 88°(800-1000. One patient had ulnar nerve neuropraxia and another patient developed median nerve neuropraxia, and both recovered completely in six weeks. No patient had symptomatic instability of the elbow. All patients were asymptomatic except one patient, who had pain mainly on heavy activities. Conclusion We conclude that inverted 'V' osteotomy excision arthroplasty is a viable option in the treatment of bony ankylosis of the elbow in young patients.

  4. Female urogenital dysfunction following total mesorectal excision for rectal cancer

    Directory of Open Access Journals (Sweden)

    Raja Ashraf

    2006-01-01

    Full Text Available Abstract Background The effect of Total Mesorectal Excision (TME on sexual function in the male is well documented. However, there is little literature in female patients. The aim of this study was to review the pelvic autonomic nervous anatomy in the female and to perform a retrospective audit of urinary and sexual function in women following surgery for rectal cancer where TME had been performed. Urogenital dysfunction was assessed through interview and questionnaire. Method Twenty-three questionnaires, eighteen returned, were sent to women with a mean age 65.5 yrs (range 34–86. All had undergone total mesorectal excision for rectal cancer between 1998–2001. Mean follow-up was 18.8 months (range 3–35. Results Preoperatively 5/18 (28% were sexually active, 3/18 (17% of patients described urinary frequency and nocturia and 7/18 (39% described symptoms of stress incontinence prior to surgery. Postoperatively all sexually active patients remained active although all described some discomfort with penetration. Two of the patients sexually active described reduced libido secondary to the stoma. Postoperative urinary symptoms developed with 59% reporting the development of nocturia, 18% developed stress incontinence and one patient required a permanent catheter. Of those with symptoms, 80% persisted longer than three months from surgery. Symptoms were predominant in those patients with low rectal cancers, particularly those undergoing abdomino-perineal excision and in those who had previously undergone abdominal hysterectomy. Conclusion The treatment of rectal cancer involves surgery to the pelvic floor. Despite nerve preservation this is associated with the development of worsening nocturia and stress incontinence. This is most marked in those patients who had previously undergone a hysterectomy. Further studies are warranted to assess the interaction with previous gynaecological surgery.

  5. Abscisic Acid Stimulates Elongation of Excised Pea Root Tips

    Science.gov (United States)

    Gaither, Douglas H.; Lutz, Donald H.; Forrence, Leonard E.

    1975-01-01

    Excised Pisum sativum L. root tips were incubated in a pH 5.2 sucrose medium containing abscisic acid. Elongation growth was inhibited by 100 μm abscisic acid. However, decreasing the abscisic acid concentration caused stimulation of elongation, the maximum response (25% to 30%) occurring at 1 μm abscisic acid. Prior to two hours, stimulation of elongation by 1 μm abscisic acid was not detectable. Increased elongation did not occur in abscisic acid-treated root tips of Lens culinaris L., Phaseolus vulgaris L., or Zea mays L. PMID:16659198

  6. Pyrimidine dimer excision in human cells and skin cancer

    International Nuclear Information System (INIS)

    Regan, J.D.; Carrier, W.L.; Smith, D.P.; Waters, R.

    1977-01-01

    We have compared three different methods for estimating the induction and removal of uv induced pyrimidine dimers from the DNA of human fibroblasts. Results indicate that after uv doses of 5-20 J/m 2 50% of the dimers are removed by 24 hours after irradiation. Almost complete excision can be observed if the cells are incubated for periods not less than 72 hours after 5 J/m 2 . After higher doses it probably takes even longer fr such complete removal to be seen

  7. Excised Abdominoplasty Material as a Systematic Plastic Surgical Training Model

    Directory of Open Access Journals (Sweden)

    M. Erol Demirseren

    2012-01-01

    Full Text Available Achieving a level of technical skill and confidence in surgical operations is the main goal of plastic surgical training. Operating rooms were accepted as the practical teaching venues of the traditional apprenticeship model. However, increased patient population, time, and ethical and legal considerations made preoperation room practical work a must for plastic surgical training. There are several plastic surgical teaching models and simulators which are very useful in preoperation room practical training and the evaluation of plastic surgery residents. The full thickness skin with its vascular network excised in abdominoplasty procedures is an easily obtainable real human tissue which could be used as a training model in plastic surgery.

  8. Use of Preputial Skin as Cutaneous Graft after Nevus Excision

    Directory of Open Access Journals (Sweden)

    A. D'Alessio

    2010-01-01

    Full Text Available We report a four-year-old boy with a nevus covering all the plantar side of his second finger on the left foot. He was also affected by congenital phimosis. Surgical excision of the nevus was indicated, but the skin defect would have been too large to be directly closed. The foreskin was taken as a full-thickness skin graft to cover the cutaneous defect of the finger. The graft intake was favourable and provided a functional repair with good aesthetic characteristic.

  9. Base excision repair mechanisms and relevance to cancer susceptibility

    International Nuclear Information System (INIS)

    Dogliotti, E.; Wilson, S.H.

    2009-01-01

    The base excision repair (BER) pathway is considered the predominant DNA repair system in mammalian cells for eliminating small DNA lesions generated at DNA bases either exogenously by environmental agents or endogenously by normal cellular metabolic processes (e.g. production of oxyradical species, alkylating agents, etc). The main goal of this project is the understanding of the involvement of BER in genome stability and in particular in sporadic cancer development associated with inflammation such as gastric cancer (GC). A major risk factor of GC is the infection by Helicobacter pylori, which causes oxidative stress. Oxidative DNA damage is mainly repaired by BER

  10. Pure transvaginal excision of mesh erosion involving the bladder.

    Science.gov (United States)

    Firoozi, Farzeen; Goldman, Howard B

    2013-06-01

    We present a pure transvaginal approach to the removal of eroded mesh involving the bladder secondary to placement of transvaginal mesh for management of pelvic organ prolapse (POP) using a mesh kit. Although technically challenging, we demonstrate the feasibility of a purely transvaginal approach, avoiding a potentially more morbid transabdominal approach. The video presents the surgical technique of pure transvaginal excision of mesh erosion involving the bladder after mesh placement using a prolapse kit was performed. This video shows that purely transvaginal removal of mesh erosion involving the bladder can be done safely and is feasible.

  11. Exercise-Induced Neuroprotection of Hippocampus in APP/PS1 Transgenic Mice via Upregulation of Mitochondrial 8-Oxoguanine DNA Glycosylase

    Directory of Open Access Journals (Sweden)

    Hai Bo

    2014-01-01

    Full Text Available Improving mitochondrial function has been proposed as a reasonable therapeutic strategy to reduce amyloid-β (Aβ load and to modify the progression of Alzheimer’s disease (AD. However, the relationship between mitochondrial adaptation and brain neuroprotection caused by physical exercise in AD is poorly understood. This study was undertaken to investigate the effects of long-term treadmill exercise on mitochondrial 8-oxoguanine DNA glycosylase-1 (OGG1 level, mtDNA oxidative damage, and mitochondrial function in the hippocampus of APP/PS1 transgenic mouse model of AD. In the present study, twenty weeks of treadmill training significantly improved the cognitive function and reduced the expression of Aβ-42 in APP/PS1 transgenic (Tg mice. Training also ameliorated mitochondrial respiratory function by increasing the complexes I, and IV and ATP synthase activities, whereas it attenuated ROS generation and mtDNA oxidative damage in Tg mice. Furthermore, the impaired mitochondrial antioxidant enzymes and mitochondrial OGG1 activities seen in Tg mice were restored with training. Acetylation level of mitochondrial OGG1 and MnSOD was markedly suppressed in Tg mice after exercise training, in parallel with increased level of SIRT3. These findings suggest that exercise training could increase mtDNA repair capacity in the mouse hippocampus, which in turn would result in protection against AD-related mitochondrial dysfunction and phenotypic deterioration.

  12. Accelerated repair and reduced mutagenicity of DNA damage induced by cigarette smoke in human bronchial cells transfected with E.coli formamidopyrimidine DNA glycosylase.

    Directory of Open Access Journals (Sweden)

    Mara Foresta

    Full Text Available Cigarette smoke (CS is associated to a number of pathologies including lung cancer. Its mutagenic and carcinogenic effects are partially linked to the presence of reactive oxygen species and polycyclic aromatic hydrocarbons (PAH inducing DNA damage. The bacterial DNA repair enzyme formamidopyrimidine DNA glycosylase (FPG repairs both oxidized bases and different types of bulky DNA adducts. We investigated in vitro whether FPG expression may enhance DNA repair of CS-damaged DNA and counteract the mutagenic effects of CS in human lung cells. NCI-H727 non small cell lung carcinoma cells were transfected with a plasmid vector expressing FPG fused to the Enhanced Green Fluorescent Protein (EGFP. Cells expressing the fusion protein EGFP-FPG displayed accelerated repair of adducts and DNA breaks induced by CS condensate. The mutant frequencies induced by low concentrations of CS condensate to the Na(+K(+-ATPase locus (oua(r were significantly reduced in cells expressing EGFP-FPG. Hence, expression of the bacterial DNA repair protein FPG stably protects human lung cells from the mutagenic effects of CS by improving cells' capacity to repair damaged DNA.

  13. Are all analogies created equal? Prefrontal cortical functioning may predict types of analogical reasoning.

    Science.gov (United States)

    Chrysikou, Evangelia G; Thompson-Schill, Sharon L

    2010-06-01

    Abstract The proposed theory can account for analogies based on learned relationships between elements in the source and target domains. However, its explanatory power regarding the discovery of new relationships during analogical reasoning is limited. We offer an alternative perspective for the role of PFC in analogical thought that may better address different types of analogical mappings.

  14. 26 CFR 55.4981-2 - Imposition of excise tax with respect to certain undistributed income of real estate investment...

    Science.gov (United States)

    2010-04-01

    ... certain undistributed income of real estate investment trusts; calendar years beginning after December 31... (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) EXCISE TAX ON REAL ESTATE INVESTMENT TRUSTS AND REGULATED INVESTMENT COMPANIES Excise Tax on Real Estate Investment Trusts § 55.4981-2 Imposition of excise tax with...

  15. Practical analog electronics for technicians

    CERN Document Server

    Kimber, W A

    2013-01-01

    'Practical Analog Electronics for Technicians' not only provides an accessible introduction to electronics, but also supplies all the problems and practical activities needed to gain hands-on knowledge and experience. This emphasis on practice is surprisingly unusual in electronics texts, and has already gained Will Kimber popularity through the companion volume, 'Practical Digital Electronics for Technicians'. Written to cover the Advanced GNVQ optional unit in electronics, this book is also ideal for BTEC National, A-level electronics and City & Guilds courses. Together with 'Practical Digit

  16. Resistive RAMs as analog trimming elements

    Science.gov (United States)

    Aziza, H.; Perez, A.; Portal, J. M.

    2018-04-01

    This work investigates the use of Resistive Random Access Memory (RRAM) as an analog trimming device. The analog storage feature of the RRAM cell is evaluated and the ability of the RRAM to hold several resistance states is exploited to propose analog trim elements. To modulate the memory cell resistance, a series of short programming pulses are applied across the RRAM cell allowing a fine calibration of the RRAM resistance. The RRAM non volatility feature makes the analog device powers up already calibrated for the system in which the analog trimmed structure is embedded. To validate the concept, a test structure consisting of a voltage reference is evaluated.

  17. Analog and mixed-signal electronics

    CERN Document Server

    Stephan, Karl

    2015-01-01

    A practical guide to analog and mixed-signal electronics, with an emphasis on design problems and applications This book provides an in-depth coverage of essential analog and mixed-signal topics such as power amplifiers, active filters, noise and dynamic range, analog-to-digital and digital-to-analog conversion techniques, phase-locked loops, and switching power supplies. Readers will learn the basics of linear systems, types of nonlinearities and their effects, op-amp circuits, the high-gain analog filter-amplifier, and signal generation. The author uses system design examples to motivate

  18. Analog circuit design art, science, and personalities

    CERN Document Server

    Williams, Jim

    1991-01-01

    Analog Circuit Design: Art, Science, and Personalities discusses the many approaches and styles in the practice of analog circuit design. The book is written in an informal yet informative manner, making it easily understandable to those new in the field. The selection covers the definition, history, current practice, and future direction of analog design; the practice proper; and the styles in analog circuit design. The book also includes the problems usually encountered in analog circuit design; approach to feedback loop design; and other different techniques and applications. The text is

  19. Aag-initiated base excision repair drives alkylation-induced retinal degeneration in mice.

    Science.gov (United States)

    Meira, Lisiane B; Moroski-Erkul, Catherine A; Green, Stephanie L; Calvo, Jennifer A; Bronson, Roderick T; Shah, Dharini; Samson, Leona D

    2009-01-20

    Vision loss affects >3 million Americans and many more people worldwide. Although predisposing genes have been identified their link to known environmental factors is unclear. In wild-type animals DNA alkylating agents induce photoreceptor apoptosis and severe retinal degeneration. Alkylation-induced retinal degeneration is totally suppressed in the absence of the DNA repair protein alkyladenine DNA glycosylase (Aag) in both differentiating and postmitotic retinas. Moreover, transgenic expression of Aag activity restores the alkylation sensitivity of photoreceptors in Aag null animals. Aag heterozygotes display an intermediate level of retinal degeneration, demonstrating haploinsufficiency and underscoring that Aag expression confers a dominant retinal degeneration phenotype.

  20. Framing the policy debate over spirits excise tax in Poland.

    Science.gov (United States)

    Zatonski, Mateusz; Hawkins, Benjamin; McKee, Martin

    2018-06-01

    Industry lobbying remains an obstacle to effective health-oriented alcohol policy. In 2013, an increase in excise tax on spirits was announced by the Polish government. This article presents a qualitative analysis of the public debate that ensued on the potential economic, health and social effects of the policy. It focuses on how competing groups, including industry actors, framed their position and sought to dominate the debate. Online archives of five Polish national newspapers, two spirits trade associations, and parliamentary and ministerial archives were searched. A thematic content analysis of the identified sources was conducted. The overall findings were compared with existing research on the framing of the Minimum Unit Pricing (MUP) debate in the UK. A total of 155 sources were analysed. Two main frames were identified: health, and economic. The spirits industry successfully promoted the economic frame in their own publications and in the media. The debate was dominated by arguments about potential growth of the grey market and losses in tax revenue that might result from the excise tax increase. The framing of the debate in Poland differed from the framing of the MUP debate in the United Kingdom. The Polish public health community was unsuccessful in making health considerations a significant element of the alcohol policy debate. The strategies pursued by UK health advocates offer lessons for how to make a more substantial impact on media coverage and promote health-oriented legislation.

  1. Validating excised rodent lungs for functional hyperpolarized xenon-129 MRI.

    Directory of Open Access Journals (Sweden)

    David M L Lilburn

    Full Text Available Ex vivo rodent lung models are explored for physiological measurements of respiratory function with hyperpolarized (hp (129Xe MRI. It is shown that excised lung models allow for simplification of the technical challenges involved and provide valuable physiological insights that are not feasible using in vivo MRI protocols. A custom designed breathing apparatus enables MR images of gas distribution on increasing ventilation volumes of actively inhaled hp (129Xe. Straightforward hp (129Xe MRI protocols provide residual lung volume (RV data and permit for spatially resolved tracking of small hp (129Xe probe volumes during the inhalation cycle. Hp (129Xe MRI of lung function in the excised organ demonstrates the persistence of post mortem airway responsiveness to intravenous methacholine challenges. The presented methodology enables physiology of lung function in health and disease without additional regulatory approval requirements and reduces the technical and logistical challenges with hp gas MRI experiments. The post mortem lung functional data can augment histological measurements and should be of interest for drug development studies.

  2. Analogical reasoning in schizophrenic delusions.

    Science.gov (United States)

    Simpson, Jane; Done, D John

    2004-09-01

    Reasoning ability has often been argued to be impaired in people with schizophrenic delusions, although evidence for this is far from convincing. This experiment examined the analogical reasoning abilities of several groups of patients, including non-deluded and deluded schizophrenics, to test the hypothesis that performance by the deluded schizophrenic group would be impaired. Eleven deluded schizophrenics, 10 depressed subjects, seven non-deluded schizophrenics and 16 matched non-psychiatric controls, who were matched on a number of key variables, were asked to solve an analogical reasoning task. Performance by the deluded schizophrenic group was certainly impaired when compared with the depressed and non-psychiatric control groups though less convincingly so when compared with the non-deluded schizophrenic group. The impairment shown by the deluded schizophrenic group seemed to occur at the initial stage of the reasoning task. The particular type of impairment shown by the deluded subjects was assessed in relation to other cognitive problems already researched and the implications of these problems on reasoning tasks and theories of delusions was discussed.

  3. Reliability of analog quantum simulation

    Energy Technology Data Exchange (ETDEWEB)

    Sarovar, Mohan [Sandia National Laboratories, Digital and Quantum Information Systems, Livermore, CA (United States); Zhang, Jun; Zeng, Lishan [Shanghai Jiao Tong University, Joint Institute of UMich-SJTU, Key Laboratory of System Control and Information Processing (MOE), Shanghai (China)

    2017-12-15

    Analog quantum simulators (AQS) will likely be the first nontrivial application of quantum technology for predictive simulation. However, there remain questions regarding the degree of confidence that can be placed in the results of AQS since they do not naturally incorporate error correction. Specifically, how do we know whether an analog simulation of a quantum model will produce predictions that agree with the ideal model in the presence of inevitable imperfections? At the same time there is a widely held expectation that certain quantum simulation questions will be robust to errors and perturbations in the underlying hardware. Resolving these two points of view is a critical step in making the most of this promising technology. In this work we formalize the notion of AQS reliability by determining sensitivity of AQS outputs to underlying parameters, and formulate conditions for robust simulation. Our approach naturally reveals the importance of model symmetries in dictating the robust properties. To demonstrate the approach, we characterize the robust features of a variety of quantum many-body models. (orig.)

  4. Analog-to-digital conversion

    CERN Document Server

    Pelgrom, Marcel J. M

    2013-01-01

    This textbook is appropriate for use in graduate-level curricula in analog to digital conversion, as well as for practicing engineers in need of a state-of-the-art reference on data converters.  It discusses various analog-to-digital conversion principles, including sampling, quantization, reference generation, nyquist architectures and sigma-delta modulation.  This book presents an overview of the state-of-the-art in this field and focuses on issues of optimizing accuracy and speed, while reducing the power level. This new, second edition emphasizes novel calibration concepts, the specific requirements of new systems, the consequences of 45-nm technology and the need for a more statistical approach to accuracy.  Pedagogical enhancements to this edition include more than twice the exercises available in the first edition, solved examples to introduce all key, new concepts and warnings, remarks and hints, from a practitioner’s perspective, wherever appropriate.  Considerable background information and pr...

  5. Economic Impact of Imposing Excise Tax on Plastic Bottles of Drinks

    Directory of Open Access Journals (Sweden)

    Eugenia Mardanugraha

    2018-03-01

    Full Text Available This research simulates the effect of imposing excise tax on plastic container of drinks towards economic performance of beverage industry in Indonesia and governmentâ˘A ´Zs tax revenue. The results showed that by imposing excise tax on plastic cups and plastic bottles the government would lose tax revenue from value added tax (PPN and corporate income tax (PPh badan more than they gain additional revenue from excise tax. Hence, imposing excise tax on drink containers should serve a clear purpose and an undeniable reason. This paper recommends the government to develop proper excise infrastructure to extend the goods or services to be taxed. This paper also recommends the required stages for extending the excise tax.

  6. Excision repair in MUT-mutants of Proteus mirabilis after UV-irradiation

    International Nuclear Information System (INIS)

    Stoerl, K.; Mund, C.

    1977-01-01

    The behaviour of MUT-mutants of P.mirabilis to perform certain steps of excision repair after U.V.-irradiation is described. MUT-mutants introduce single-strand breaks in the DNA immediately after U.V.-irradiation, but their ability to excise pyrimidine dimers from the DNA is very diminished. Moreover, they are not able to accomplish the excision repair by rejoining of the single-strand breaks. The connection between the incomplete excision repair and the mutator phenotype of these mutants is discussed. (author)

  7. Automatic activation of categorical and abstract analogical relations in analogical reasoning.

    Science.gov (United States)

    Green, Adam E; Fugelsang, Jonathan A; Dunbar, Kevin N

    2006-10-01

    We examined activation of concepts during analogical reasoning. Subjects made either analogical judgments or categorical judgments about four-word sets. After each four-word set, they named the ink color of a single word in a modified Stroop task. Words that referred to category relations were primed (as indicated by longer response times on Stroop color naming) subsequent to analogical judgments and categorical judgments. This finding suggests that activation of category concepts plays a fundamental role in analogical thinking. When colored words referred to analogical relations, priming occurred subsequent to analogical judgments, but not to categorical judgments, even though identical four-word stimuli were used for both types of judgments. This finding lends empirical support to the hypothesis that, when people comprehend the analogy between two items, they activate an abstract analogical relation that is distinct from the specific content items that compose the analogy.

  8. Total mesorectal excision for the treatment of rectal cancer.

    Science.gov (United States)

    Zedan, Ali; Salah, Tareq

    2015-12-01

    In the surgical treatment of rectal cancer, a clear circumferential resection margin and distal resection margin should be obtained. The aim of this study was to determine the morbidity, mortality, survival outcome, and local failure after total mesorectal excision (TME) in the surgical treatment of rectal cancer. This retrospective study was conducted on 101 patients treated for rectal cancer using low anterior resection (LAR), abdominoperinial resection (APR), or Hartmaan's technique. In all operative procedures, total mesorectal excisions (TMEs) were done. The patients were treated from November 2000 to April 2011 in the South Egypt Cancer Institute (SECI) of Assuit University (Egypt). Neo-adjuvant therapy was given to those patients with serosalin filtration, lymph node involvement, and sexual and urinary function impairment. Data were analyzed using IBM-SPSS version 21, and survival rates were estimated using the Kaplan-Meier method. One hundred one patients were evaluable (61 males, 40 females). Regarding the operative procedure used, it was: (APR), LAR, Hartmaan's technique in 15.8%, 71.3%, and 12.9% of patients, respectively. Operation-related mortality during the 30 days after surgery was 3%. The operations resulted in morbidity in 25% of the patients, anastomotic site leak in 5.9% of the patients, urinary dysfynction in 9.9% of the patients, and erectile dysfunction in 15.8% of the male patients. Regarding safety margin, the median distances were distal/radial margin, 23/12 mm, distal limit 7 cm. Median lymph nodes harvest 19 nodes. Primary tumor locations were anteriorly 23.8%, laterally 13.9%, posteriorly 38.6%, and circumferential 23.8%. Protective stoma 16.8%. Primary Tumor TNM classification (T1, T2, T3, and T4; 3, 28.7, 55.4, and 12.9%, respectively). Nodes Metastases (N0, N1, and N2; 57.4, 31.7, and 10.9%, respectively). TNM staging (I, II, III, and IV; 15.8, 29.7, 46.5, and 7.9%, respectively). Chemotherapy was administered to 67.3% of the

  9. The Young Solar Analogs Project

    Science.gov (United States)

    Gray, Richard O.; Saken, J. M.; Corbally, C. J.; Fuller, V.; Kahvaz, Y.; Lambert, R.; Newsome, I.; Seeds, M.

    2013-01-01

    We are carrying out a long-term project of measuring chromospheric activity and brightness variations in 31 young solar analogs (YSAs) using facilities at the Dark Sky Observatory (DSO - Appalachian State University) and the Vatican Advanced Technology Telescope (VATT). These YSAs are solar-type (spectral types F8 - K2) stars with ages ranging from 0.3 - 1.5 Gyr. The goal of this project is to gain better understanding of the magnetic activity of the early Sun, and especially how that activity may have impacted the development of life on the Earth. This project will also yield insights into the space environments experienced by young Earth analogs. We are currently in the 6th year of spectroscopic measurements of these stars: these data include Ca II H & K chromospheric flux measurements, and narrow-band measurements in the photospheric G-band, both obtained with the G/M spectrograph on the DSO 32-inch telescope. We will present evidence of activity cycles in a number of our stars, as well as periods determined from rotational modulation of the spectroscopic indices. The relationship between the Ca II activity index and the G-band index will be explored. NSF support for our project has provided funds for the construction of a robotic photometric telescope to monitor the program stars in a 5-passband system (Strömgren-v, Johnson-Cousins B, V, and R, and a 3-nm wide Hα filter). The robotic telescope has been functional since April 2012 and observes the program stars on every clear night; combined with the Piggy-back telescope attached to the DSO 32-inch, we now have photometric observations on over 130 nights stretching over nearly 2 years. We will examine the relationships between variations in the Ca II H & K index, the G-band index and the photometric bands. This project is supported by the National Science Foundation, grant AST-1109158.

  10. The Young Solar Analogs Project

    Science.gov (United States)

    Gray, Richard O.; Saken, J. M.; Corbally, C. J.; Seeds, M. F.; Morrison, S. S.

    2012-01-01

    We are carrying out a long-term project of measuring chromospheric activity and brightness variations in 31 young solar analogs (YSAs) using the Dark Sky Observatory (DSO -- Appalachian State University) 32-inch telescope and the G/M spectrograph. These YSAs are solar-type (spectral types F8 - K2) stars with ages ranging from 0.3 - 1.5 Gyr. The goal of this project is to gain better understanding of the magnetic activity of the early Sun, and especially how that activity may have impacted the development of life on the Earth. This project will also yield insights into the space environments experienced by young Earth analogs. We are currently in our 5th year of obtaining Ca II K & H chromospheric flux measurements, and are beginning to see signs of long-term activity cycles in a number of our stars. In addition, rotational modulation of the chromospheric fluxes is detectable in our data, and we have determined rotational periods for many of our stars. Short timescale increases in the K & H fluxes have been observed in a number of our stars; these events may be related to stellar flares. VATTSpec, a new moderate-resolution spectrograph on the 1.8-m Vatican Telescope in Arizona, has recently become involved with the project. This spectrograph will increase our ability to detect short-term changes in stellar activity on timescales of hours to minutes. We have been monitoring the program stars for one year in a multi-band photometric system consisting of Stromgren-v, and Johnson B, V, and R filters. We will soon add a narrow-band H-alpha filter to the system. Photometry is being carried out with a small piggy-back telescope on the 32-inch, but a robotic photometric telescope is currently being installed at DSO for this purpose. This project is supported by the National Science Foundation.

  11. Priming analogical reasoning with false memories.

    Science.gov (United States)

    Howe, Mark L; Garner, Sarah R; Threadgold, Emma; Ball, Linden J

    2015-08-01

    Like true memories, false memories are capable of priming answers to insight-based problems. Recent research has attempted to extend this paradigm to more advanced problem-solving tasks, including those involving verbal analogical reasoning. However, these experiments are constrained inasmuch as problem solutions could be generated via spreading activation mechanisms (much like false memories themselves) rather than using complex reasoning processes. In three experiments we examined false memory priming of complex analogical reasoning tasks in the absence of simple semantic associations. In Experiment 1, we demonstrated the robustness of false memory priming in analogical reasoning when backward associative strength among the problem terms was eliminated. In Experiments 2a and 2b, we extended these findings by demonstrating priming on newly created homonym analogies that can only be solved by inhibiting semantic associations within the analogy. Overall, the findings of the present experiments provide evidence that the efficacy of false memory priming extends to complex analogical reasoning problems.

  12. Neural correlates of creativity in analogical reasoning.

    Science.gov (United States)

    Green, Adam E; Kraemer, David J M; Fugelsang, Jonathan A; Gray, Jeremy R; Dunbar, Kevin N

    2012-03-01

    Brain-based evidence has implicated the frontal pole of the brain as important for analogical mapping. Separately, cognitive research has identified semantic distance as a key determinant of the creativity of analogical mapping (i.e., more distant analogies are generally more creative). Here, we used functional magnetic resonance imaging to assess brain activity during an analogy generation task in which we varied the semantic distance of analogical mapping (as derived quantitatively from a latent semantic analysis). Data indicated that activity within an a priori region of interest in left frontopolar cortex covaried parametrically with increasing semantic distance, even after removing effects of task difficulty. Results implicate increased recruitment of frontopolar cortex as a mechanism for integrating semantically distant information to generate solutions in creative analogical reasoning. 2012 APA, all rights reserved

  13. An emergent approach to analogical inference

    Science.gov (United States)

    Thibodeau, Paul H.; Flusberg, Stephen J.; Glick, Jeremy J.; Sternberg, Daniel A.

    2013-03-01

    In recent years, a growing number of researchers have proposed that analogy is a core component of human cognition. According to the dominant theoretical viewpoint, analogical reasoning requires a specific suite of cognitive machinery, including explicitly coded symbolic representations and a mapping or binding mechanism that operates over these representations. Here we offer an alternative approach: we find that analogical inference can emerge naturally and spontaneously from a relatively simple, error-driven learning mechanism without the need to posit any additional analogy-specific machinery. The results also parallel findings from the developmental literature on analogy, demonstrating a shift from an initial reliance on surface feature similarity to the use of relational similarity later in training. Variants of the model allow us to consider and rule out alternative accounts of its performance. We conclude by discussing how these findings can potentially refine our understanding of the processes that are required to perform analogical inference.

  14. Laser excision of a mucocele: A case report

    Directory of Open Access Journals (Sweden)

    Rajashree Ganguly

    2015-01-01

    Full Text Available A mucous cyst (mucocele, mucous retention cyst, ranula, and epulis is usually a painless, thin sac on the inner surface of the lips. It contains clear fluid. It is painless but can be bothersome. The cyst is thought to be caused due to sucking of the lip membranes between the teeth. A mucous cyst is common and harmless. However, if left untreated, it can organize and form a permanent bump on the inner surface of the lip. A mucous cyst is called ranula when it occurs on the floor of the mouth and epulis when it occurs on the gums. The sac may also be formed around the jewellery (piercings that has been inserted into the lips or the tongue. This article highlights the use of lasers in the treatment of the excision of mucocele.

  15. [A modified technique of liposuction with excision for gynecomastia].

    Science.gov (United States)

    Yang, Hong-Yan; Xu, Jun; Yan, Xiao-Qing; You, Lei

    2007-11-20

    To introduce a modified technique of liposuction with excision for gynecomastia. From 2003 to 2007, 32 cases of gynecomastia were treated with the modified technique: the operative region was divided into central and periphery parts, liposuction was performed only in the periphery part and the deep layer of the central part, while the breast gland in the superficial layer of the central part underwent sharp dissection, the subcutaneous tissue of the central part was conserved, and blood supply was reserved and saucer deformity was avoided. Follow-up was conducted for 3.0 - 18.5 months. Normal men breast appearance was achieved. No complication happened such as hematoma, seroma, saucer deformity, and necrosis in nipple and areola. This modified operative technique for gynecomastia proves to be an excellent and effective technique.

  16. Terahertz pulsed imaging of freshly excised human colonic tissues

    Energy Technology Data Exchange (ETDEWEB)

    Reid, Caroline B; Gibson, Adam P [Department of Medical Physics and Bioengineering, University College London, London, WC1E 6BT (United Kingdom); Fitzgerald, Anthony; Wallace, Vincent P [School of Physics, University of Western Australia, Crawley 6009 (Australia); Reese, George; Tekkis, Paris [Division of Surgery, Chelsea and Westminster Campus, Imperial College London, London (United Kingdom); Goldin, Robert [Centre for Pathology, Imperial College London, St Mary' s Campus, London (United Kingdom); O' Kelly, P S [TeraView Ltd, Platinum Building, St John' s Innovation Park, Cowley Road, Cambridge, CB4 0WS (United Kingdom); Pickwell-MacPherson, Emma, E-mail: c.reid@medphys.ucl.ac.uk [Department of Electronic Engineering, Chinese University of Hong Kong, Shatin, NT (Hong Kong)

    2011-07-21

    We present the results from a feasibility study which measures properties in the terahertz frequency range of excised cancerous, dysplastic and healthy colonic tissues from 30 patients. We compare their absorption and refractive index spectra to identify trends which may enable different tissue types to be distinguished. In addition, we present statistical models based on variations between up to 17 parameters calculated from the reflected time and frequency domain signals of all the measured tissues. These models produce a sensitivity of 82% and a specificity of 77% in distinguishing between healthy and all diseased tissues and a sensitivity of 89% and a specificity of 71% in distinguishing between dysplastic and healthy tissues. The contrast between the tissue types was supported by histological staining studies which showed an increased vascularity in regions of increased terahertz absorption.

  17. Harmonization of chosen excise duty in the EU

    Directory of Open Access Journals (Sweden)

    Petr David

    2008-01-01

    Full Text Available The level and structure of cigarettes taxation are very much in the news these days. In the field of tax on cigarettes in the European Union there is the question of whether specific rate or ad valorem rate should be used. The choice between these two rates depends on primary aim of tax policy in each European Union member state. The founding is that differential excises could be used as pro­tec­tio­nist trade barriers. Decision about tax rate on cigarettes can bring some other related effects. That is the reason why European Union established some restrictions in the field of level and structure of cigarettes taxation.

  18. Terahertz pulsed imaging of freshly excised human colonic tissues

    International Nuclear Information System (INIS)

    Reid, Caroline B; Gibson, Adam P; Fitzgerald, Anthony; Wallace, Vincent P; Reese, George; Tekkis, Paris; Goldin, Robert; O'Kelly, P S; Pickwell-MacPherson, Emma

    2011-01-01

    We present the results from a feasibility study which measures properties in the terahertz frequency range of excised cancerous, dysplastic and healthy colonic tissues from 30 patients. We compare their absorption and refractive index spectra to identify trends which may enable different tissue types to be distinguished. In addition, we present statistical models based on variations between up to 17 parameters calculated from the reflected time and frequency domain signals of all the measured tissues. These models produce a sensitivity of 82% and a specificity of 77% in distinguishing between healthy and all diseased tissues and a sensitivity of 89% and a specificity of 71% in distinguishing between dysplastic and healthy tissues. The contrast between the tissue types was supported by histological staining studies which showed an increased vascularity in regions of increased terahertz absorption.

  19. Analog techniques in CEBAF's RF control system

    International Nuclear Information System (INIS)

    Hovater, C.; Fugitt, J.

    1989-01-01

    Recent developments in high-speed analog technology have progressed into the areas of traditional RF technology. Diode related devices are being replaced by analog IC's in the CEBAF RF control system. Complex phase modulators and attenuators have been successfully tested at 70 MHz. They have three advantages over existing technology: lower cost, less temperature sensitivity, and more linearity. RF signal conditioning components and how to implement the new analog IC's will be covered in this paper. 4 refs., 5 figs

  20. Analog techniques in CEBAF'S RF control system

    International Nuclear Information System (INIS)

    Hovater, C.; Fugitt, J.

    1989-01-01

    Recent developments in high-speed analog technology have progressed into the areas of traditional rf technology. Diode-related devices are being replaced by analog IC's in the CEBAF rf control system. Complex phase modulators and attenuators have been successfully tested at 70 MHz. They have three advantages over existing technology: lower cost, less temperature sensitivity, and more linearity. Rf signal conditioning components and how to implement the new analog IC's will be covered in this paper. 4 refs., 5 figs

  1. Design and Analysis of Reconfigurable Analog System

    Science.gov (United States)

    2011-02-01

    34010010" �" �" �" �" �" �" �±" N3 N2 N± P1 P2 P3 * Current sources $RR = 1; *Ramp Rate (slope of the...2008/12/12/31e83bac-500f-4182- acca -4d360295fd9c.pdf, Analog Devices, Analog Dialogue 39-06, June 2005. [15] D. A. Johns, K. Martin "Analog Integrated

  2. Reverse-hybrid robotic mesorectal excision for rectal cancer.

    Science.gov (United States)

    Park, In Ja; You, Y Nancy; Schlette, Erika; Nguyen, Sa; Skibber, John M; Rodriguez-Bigas, Miguel A; Chang, George J

    2012-02-01

    The robotic system offers potential technical advantages over laparoscopy for total mesorectal excision with radical lymphadenectomy for rectal cancer. However, the requirement for fixed docking limits its utility when the working volume is large or patient repositioning is required. The purpose of this study was to evaluate short-term outcomes associated with a novel setup to perform total mesorectal excision and radical lymphadenectomy for rectal cancer by the use of a "reverse" hybrid robotic-laparoscopic approach. This is a prospective consecutive cohort observational study of patients who underwent robotic rectal cancer resection from January 2009 to March 2011. During the study period, a technique of reverse-hybrid robotic-laparoscopic rectal resection with radical lymphadenectomy was developed. This technique involves reversal of the operative sequence with lymphovascular and rectal dissection to precede proximal colonic mobilization. This technique evolved from a conventional-hybrid resection with laparoscopic vascular control, colonic mobilization, and robotic pelvic dissection. Perioperative and short-term oncologic outcomes were analyzed. Thirty patients underwent reverse-hybrid resection. Median tumor location was 5 cm (interquartile range 3-9) from the anal verge. Median BMI was 27.6 (interquartile range 25.0-32.1 kg/m). Twenty (66.7%) received neoadjuvant chemoradiation. There were no conversions. Median blood loss was 100 mL (interquartile range 75-200). Total operation time was a median 369 (interquartile range 306-410) minutes. Median docking time was 6 (interquartile range 5-8) minutes, and console time was 98 (interquartile range 88-140) minutes. Resection was R0 in all patients; no patients had an incomplete mesorectal resection. Six patients (20%) underwent extended lymph node dissection or en bloc resection. Reverse-hybrid robotic surgery for rectal cancer maximizes the therapeutic applicability of the robotic and conventional laparoscopic

  3. N-methylpurine DNA glycosylase inhibits p53-mediated cell cycle arrest and coordinates with p53 to determine sensitivity to alkylating agents.

    Science.gov (United States)

    Song, Shanshan; Xing, Guichun; Yuan, Lin; Wang, Jian; Wang, Shan; Yin, Yuxin; Tian, Chunyan; He, Fuchu; Zhang, Lingqiang

    2012-08-01

    Alkylating agents induce genome-wide base damage, which is repaired mainly by N-methylpurine DNA glycosylase (MPG). An elevated expression of MPG in certain types of tumor cells confers higher sensitivity to alkylation agents because MPG-induced apurinic/apyrimidic (AP) sites trigger more strand breaks. However, the determinant of drug sensitivity or insensitivity still remains unclear. Here, we report that the p53 status coordinates with MPG to play a pivotal role in such process. MPG expression is positive in breast, lung and colon cancers (38.7%, 43.4% and 25.3%, respectively) but negative in all adjacent normal tissues. MPG directly binds to the tumor suppressor p53 and represses p53 activity in unstressed cells. The overexpression of MPG reduced, whereas depletion of MPG increased, the expression levels of pro-arrest gene downstream of p53 including p21, 14-3-3σ and Gadd45 but not proapoptotic ones. The N-terminal region of MPG was specifically required for the interaction with the DNA binding domain of p53. Upon DNA alkylation stress, in p53 wild-type tumor cells, p53 dissociated from MPG and induced cell growth arrest. Then, AP sites were repaired efficiently, which led to insensitivity to alkylating agents. By contrast, in p53-mutated cells, the AP sites were repaired with low efficacy. To our knowledge, this is the first direct evidence to show that a DNA repair enzyme functions as a selective regulator of p53, and these findings provide new insights into the functional linkage between MPG and p53 in cancer therapy.

  4. Detection of endonuclease III- and 8-oxoguanine glycosylase-sensitive base modifications in γ-irradiated DNA and cells by the aldehyde reactive probe (ARP) assay

    International Nuclear Information System (INIS)

    Mohsin Ali, M.; Kurisu, Satofumi; Yoshioka, Yoshihiro; Terato, Hiroaki; Ohyama, Yoshihiko; Ide Hiroshi; Kubo, Kihei

    2004-01-01

    Ionizing radiation generates diverse DNA lesions that differentially induce cell death and mutations. In the present study, calf thymus DNA (400 μg/ml) and HeLa cells were irradiated by 60 Co γ-rays, and abasic (AP) sites and endonuclease (Endo) III- and 8-oxoguanine glycosylase (hOGG1)-sensitive base modifications in DNA were quantitated by the aldehyde reactive probe (ARP) assay. The irradiation of calf thymus DNA in phosphate buffer generated 91 Endo III- and 100 hOGG1-sensitive base modifications and 110 AP sites per 10 6 base pairs (bp) per Gy. The yield of the lesions in Tris buffer was 41- to 91-fold lower than that in phosphate, demonstrating a radioprotective effect of Tris. The HeLa cell chromosomal DNA contained 12 Endo III- and 3.8 hOGG1-sensitive base modifications and less than 1 AP sites per 10 6 bp as endogenous damage, and their level was increased by irradiation. The yields of the damage at 1 Gy (roughly equivalent to the lethal dose of HeLa cells [1.6-1.8 Gy]) were 0.13 Endo III, 0.091 hOGG1, and 0.065 AP sites per 10 6 bp, showing that irradiation with a lethal dose brought about only a marginal increase in base damage relative to an endogenous one. A comparison of the present data with those reported for DNA strand breaks supports the primary importance of double-strand breaks and clustered lesions as lethal damages formed by ionizing radiation. (author)

  5. Fermilab accelerator control system: Analog monitoring facilities

    International Nuclear Information System (INIS)

    Seino, K.; Anderson, L.; Smedinghoff, J.

    1987-10-01

    Thousands of analog signals are monitored in different areas of the Fermilab accelerator complex. For general purposes, analog signals are sent over coaxial or twinaxial cables with varying lengths, collected at fan-in boxes and digitized with 12 bit multiplexed ADCs. For higher resolution requirements, analog signals are digitized at sources and are serially sent to the control system. This paper surveys ADC subsystems that are used with the accelerator control systems and discusses practical problems and solutions, and it describes how analog data are presented on the console system

  6. Relations as transformations: implications for analogical reasoning.

    Science.gov (United States)

    Leech, Robert; Mareschal, Denis; Cooper, Richard P

    2007-07-01

    We present two experiments assessing whether the size of a transformation instantiating a relation between two states of the world (e.g., shrinks) is a performance factor affecting analogical reasoning. The first experiment finds evidence of transformation size as a significant factor in adolescent analogical problem solving while the second experiment finds a similar effect on adult analogical reasoning using a markedly different analogical completion paradigm. The results are interpreted as providing evidence for the more general framework that cognitive representations of relations are best understood as mental transformations.

  7. Epistemology of analogy: Knowledge, society and expression

    Directory of Open Access Journals (Sweden)

    Mauricio Beuchot

    2017-06-01

    Full Text Available In this article we expose the bases of analog epistemology. This theory of knowledge is between an extreme subjectivism and an extreme objectivism. Analog hermeneutics is a realistic hermeneutics. She seeks the truth, but incorporates the meaning and emotion. We have separated the reason from the experience, the praxis theory, the mind or the soul of the body. We have to get them back together, if we do not get lost in the rational (which says little of the human being, or we lose ourselves in the emotional (without logical consistency. The analogical hermeneutic realism is able, thanks to the analogy itself, to mediate in this way of union.

  8. Impact of cigarette taxation policy on excise revenues and cigarette consumption in Uzbekistan

    Directory of Open Access Journals (Sweden)

    Konstantin S. Krasovsky

    2013-05-01

    Full Text Available BACKGROUND: In 2012, Uzbekistan ratified the Framework Convention on Tobacco Control, which states that price and tax measures are an effective means of reducing tobacco consumption. We aimed to explore the effect of taxation policies on revenues and cigarette consumption. METHODS: Data on tax rates, revenues, cigarette sales were taken from national reports. To forecast potential revenues, a scenario analysis was performed. RESULTS: In 1991-2004, ad valorem excise system was in place in Uzbekistan, which was later replaced by the specific excise system. In 1997-2011, the nominal average excise has increased by a factor of twenty, but in real terms, after a sharp increase in 1999, average excise declined annually and increased only in 2010-2011. Annual cigarette sales per capita of adult population in 1999-2007 constituted 17-25 cigarette packs, while in 2008-2011 it increased to 30-37 packs. Four scenarios of excise tax increases in 2012 were developed: one actual scenario based on the rates effective in Uzbekistan in 2012, and three hypothetical ones anticipating excise rates increase by 1.5, 2 and 3-fold. With actual excise increase in 2012, the inflation-adjusted budget revenues would grow by 5%, and with three hypothetical - by 17%, 35% and 66% respectively, despite the decline of tax-paid cigarette sales. CONCLUSION: Stabilization or reduction in cigarette excises in Uzbekistan in 2002-2008 led to a decline in real excise revenues and the growth of cigarette sales. In 1999 and 2010-2011, excises were significantly increased and the real revenues have risen, despite the decline in cigarette sales. As cigarette prices are low, the illegal outflow of cigarettes from Uzbekistan apparently exceeds the illegal inflow. A significant increase in cigarette excise (1.5-3 fold can both increase budget revenues and reduce cigarette consumption, with greater increase yielding more benefits.

  9. Expert analogy use in a naturalistic setting

    Science.gov (United States)

    Kretz, Donald R.; Krawczyk, Daniel C.

    2014-01-01

    The use of analogy is an important component of human cognition. The type of analogy we produce and communicate depends heavily on a number of factors, such as the setting, the level of domain expertise present, and the speaker's goal or intent. In this observational study, we recorded economics experts during scientific discussion and examined the categorical distance and structural depth of the analogies they produced. We also sought to characterize the purpose of the analogies that were generated. Our results supported previous conclusions about the infrequency of superficial similarity in subject-generated analogs, but also showed that distance and depth characteristics were more evenly balanced than in previous observational studies. This finding was likely due to the nature of the goals of the participants, as well as the broader nature of their expertise. An analysis of analogical purpose indicated that the generation of concrete source examples of more general target concepts was most prevalent. We also noted frequent instances of analogies intended to form visual images of source concepts. Other common purposes for analogies were the addition of colorful speech, inclusion (i.e., subsumption) of a target into a source concept, or differentiation between source and target concepts. We found no association between depth and either of the other two characteristics, but our findings suggest a relationship between purpose and distance; i.e., that visual imagery typically entailed an outside-domain source whereas exemplification was most frequently accomplished using within-domain analogies. Overall, we observed a rich and diverse set of spontaneously produced analogical comparisons. The high degree of expertise within the observed group along with the richly comparative nature of the economics discipline likely contributed to this analogical abundance. PMID:25505437

  10. Expert Analogy Use in a Naturalistic Setting

    Directory of Open Access Journals (Sweden)

    Donald R Kretz

    2014-11-01

    Full Text Available The use of analogy is an important component of human cognition. The type of analogy we produce and communicate depends heavily on a number of factors, such as the setting, the level of domain expertise present, and the speaker’s goal or intent. In this observational study, we recorded economics experts during scientific discussion and examined the categorical distance and structural depth of the analogies they produced. We also sought to characterize the purpose of the analogies that were generated. Our results supported previous conclusions about the infrequency of superficial similarity in subject-generated analogs, but also showed that distance and depth characteristics were more evenly balanced than in previous observational studies. This finding was likely due to the nature of the goals of the participants, as well as the broader nature of their expertise. An analysis of analogical purpose indicated that the generation of concrete source examples of more general target concepts was most prevalent. We also noted frequent instances of analogies intended to form visual images of source concepts. Other common purposes for analogies were the addition of colorful speech, inclusion (i.e., subsumption of a target into a source concept, or differentiation between source and target concepts. We found no association between depth and either of the other two characteristics, but our findings suggest a relationship between purpose and distance; i.e., that visual imagery typically entailed an outside-domain source whereas exemplification was most frequently accomplished using within-domain analogies. Overall, we observed a rich and diverse set of spontaneously produced analogical comparisons. The high degree of expertise within the observed group along with the richly comparative nature of the economics discipline likely contributed to this analogical abundance.

  11. Oesophageal pseudodiverticulum after foregut duplication cyst excision: Case report and literature review

    Directory of Open Access Journals (Sweden)

    Iuliana D Bobanga

    2016-01-01

    Full Text Available Oesophageal pseudodiverticula rarely occur after excision of benign oesophageal neoplasms. While management and outcomes have been reported in the adult leiomyoma literature, sparse data exist on the occurrence and management of pseudodiverticula after foregut duplication cyst excision. We discuss our experience with a paediatric patient and review relevant literature regarding operative techniques and surgical outcomes.

  12. Aerodynamic and Nonlinear Dynamic Acoustic Analysis of Tension Asymmetry in Excised Canine Larynges

    Science.gov (United States)

    Devine, Erin E.; Bulleit, Erin E.; Hoffman, Matthew R.; McCulloch, Timothy M.; Jiang, Jack J.

    2012-01-01

    Purpose: To model tension asymmetry caused by superior laryngeal nerve paralysis (SLNP) in excised larynges and apply perturbation, nonlinear dynamic, and aerodynamic analyses. Method: SLNP was modeled in 8 excised larynges using sutures and weights to mimic cricothyroid (CT) muscle function. Weights were removed from one side to create tension…

  13. 77 FR 43157 - Disregarded Entities and the Indoor Tanning Services Excise Tax; Correction

    Science.gov (United States)

    2012-07-24

    ... Disregarded Entities and the Indoor Tanning Services Excise Tax; Correction AGENCY: Internal Revenue Service... tax. DATES: This correction is effective on July 24, 2012, and applies on and after June 25, 2012. FOR... Subjects in 26 CFR Part 301 Employment taxes, Estate taxes, Excise taxes, Gift taxes, Income taxes...

  14. Excision repair of bulky lesions in the DNA of mammalian cells

    International Nuclear Information System (INIS)

    Setlow, R.B.; Grist, E.

    1980-01-01

    The report examines the process of excision repair of pyrimidine dimers from uv-irradiated and chemically challenged human cells. It is shown by means of a sensitive endonuclease assay that the amount of excision observed depends upon the isotope used to label cells, and that XP heterozygotes are between normals and XPs

  15. Connective tissue: cancer patients’ attitudes towards medical research using excised (tumour) tissue

    NARCIS (Netherlands)

    Vermeulen, E.; Schmidt, M.K.; Cornel, M.C.; Knoppers, B.M.; van Leeuwen, F.E.; Aaronson, N.K.

    2011-01-01

    The objective of this article is to explore the views of Dutch cancer patients on the use of excised and stored (tumor) tissues in medical research. Excised tissues are routinely stored in hospitals for future diagnostic use. They are also important for scientific research. This article discusses

  16. Posterior Endoscopic Excision of Os Trigonum in Professional National Ballet Dancers.

    Science.gov (United States)

    Ballal, Moez S; Roche, Andy; Brodrick, Anna; Williams, R Lloyd; Calder, James D F

    2016-01-01

    Previous studies have compared the outcomes after open and endoscopic excision of an os trigonum in patients of mixed professions. No studies have compared the differences in outcomes between the 2 procedures in elite ballet dancers. From October 2005 to February 2010, 35 professional ballet dancers underwent excision of a symptomatic os trigonum of the ankle after a failed period of nonoperative treatment. Of the 35 patients, 13 (37.1%) underwent endoscopic excision and 22 (62.9%) open excision. We compared the outcomes, complications, and time to return to dancing. The open excision group experienced a significantly greater incidence of flexor hallucis longus tendon decompression compared with the endoscopic group. The endoscopic release group returned to full dance earlier at a mean of 9.8 (range 6.5 to 16.1) weeks and those undergoing open excision returned to full dance at a mean of 14.9 (range 9 to 20) weeks (p = .001). No major complications developed in either group, such as deep infection or nerve or vessel injury. We have concluded that both techniques are safe and effective in the treatment of symptomatic os trigonum in professional ballet dancers. Endoscopic excision of the os trigonum offers a more rapid return to full dance compared with open excision. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  17. Re-excision of margins before breast radiation-diagnostic or therapeutic?

    International Nuclear Information System (INIS)

    Chism, Derek B.; Freedman, Gary M.; Li, Tianyu; Anderson, Penny R.

    2006-01-01

    Purpose: To identify factors in breast cancer patients that predict the pathologic results of re-excision for close or positive margins and to determine the effect on local control. Methods and Materials: We divided 1,044 patients with Stage I-II breast cancer with a close (≤2 mm) or positive margin after initial excision into three groups. Group 1 included 199 patients without additional excision, Group 2 included 546 patients with re-excision found to be free of cancer, and Group 3 included 299 patients with re-excision and residual cancer. All patients were treated with radiotherapy with a median follow-up of 6.7 years. Results: The 10-year local control rate was 95% for Group 1 and 94% for Groups 2 and 3 (p = 0.788). Of the 846 patients, 65% had no residual disease on re-excision and 35% did have residual tumor. The factors significantly associated with positive re-excision findings were initial positive margins, positive nodes, Stage T2 tumor, and an extensive intraductal component. The 10-year local control rate was 95% for Group 2 vs. 91% for Group 3 (p = 0.038). Conclusion: The low recurrence rates seen in this study suggest that selected patients with non-negative margins, particularly those with a low risk of having residual disease at re-excision, may be treated with radiotherapy

  18. Young Children's Analogical Reasoning in Science Domains

    Science.gov (United States)

    Haglund, Jesper; Jeppsson, Fredrik; Andersson, Johanna

    2012-01-01

    This exploratory study in a classroom setting investigates first graders' (age 7-8 years, N = 25) ability to perform analogical reasoning and create their own analogies for two irreversible natural phenomena: mixing and heat transfer. We found that the children who contributed actively to a full-class discussion were consistently successful at…

  19. Children's Use of Analogy during Collaborative Reasoning

    Science.gov (United States)

    Lin, Tzu-Jung; Anderson, Richard C.; Hummel, John E.; Jadallah, May; Miller, Brian W.; Nguyen-Jahiel, Kim; Morris, Joshua A.; Kuo, Li-Jen; Kim, Il-Hee; Wu, Xiaoying; Dong, Ting

    2012-01-01

    This microgenetic study examined social influences on children's development of analogical reasoning during peer-led small-group discussions of stories about controversial issues. A total of 277 analogies were identified among 7,215 child turns for speaking during 54 discussions from 18 discussion groups in 6 fourth-grade classrooms (N = 120; age…

  20. Patterns of Analogical Reasoning among Beginning Readers

    Science.gov (United States)

    Farrington-Flint, Lee; Wood, Clare; Canobi, Katherine H.; Faulkner, Dorothy

    2004-01-01

    Despite compelling evidence that analogy skills are available to beginning readers, few studies have actually explored the possibility of identifying individual differences in young children's analogy skills in early reading. The present study examined individual differences in children's use of orthographic and phonological relations between…

  1. ANALOGICAL REASONING USING TRANSFORMATIONS OF RULES

    OpenAIRE

    Haraguchi, Makoto; 原口, 誠

    1986-01-01

    A formalism of analogical reasoning is presented. The analogical reasoning can be considered as a deduction with a function of transforming logical rules. From this viewpoint, the reasoning is defined in terms of deduction, and is therefore realized in a logic programming system. The reasoning system is described as an extension of Prolog interpreter.

  2. Analogies in high school Brazilian chemistry textbooks

    Directory of Open Access Journals (Sweden)

    Rosária Justi

    2000-05-01

    Full Text Available This paper presents and discusses an analysis of the analogies presented by Brazilian chemistry textbooks for the medium level. The main aim of the analysis is to discuss whether such analogies can be said good teaching models. From the results, some aspects concerning with teachers' role are discussed. Finally, some new research questions are emphasised.

  3. Spectrometric analog-to-digital converter

    International Nuclear Information System (INIS)

    Ormandzhiev, S.I.; Jordanov, V.T.

    1988-01-01

    Converter of digit-by-digit counterbalancing with slipping dial with number of channels equal to total number of states of the main digital-to-analog converter of digit-by-digit counterbalancing systems is presented. Algorithm for selection of digital-to-analog converters, which must be used by means of computer is suggested

  4. An Analog Computer for Electronic Engineering Education

    Science.gov (United States)

    Fitch, A. L.; Iu, H. H. C.; Lu, D. D. C.

    2011-01-01

    This paper describes a compact analog computer and proposes its use in electronic engineering teaching laboratories to develop student understanding of applications in analog electronics, electronic components, engineering mathematics, control engineering, safe laboratory and workshop practices, circuit construction, testing, and maintenance. The…

  5. PEMETAAN ANALOGI PADA KONSEP ABSTRAK FISIKA

    Directory of Open Access Journals (Sweden)

    Nyoto Suseno

    2014-11-01

    Full Text Available The research of any where founded majority students have common difficulties in abstract physics concept. The result of observation, lecturers have problem  in teaching implementation of abstract concepts on physics learning. The objective of this research is to find out the ways how to overcome this problem. The research place of  physics education programs and senior high school. The data are colected by quetionere, observation and interview. The lecturer behavior to making out this case is use of analogy to make concrete a abstract concept. This action is true, because the analogies are dynamic tools that facilitate understanding, rather than representations of the correct and static explanations. Using analogies not only promoted profound understanding of abstract concept, but also helped students overcome their misconceptions. However used analogy in teaching not yet planed with seriousness, analogy used spontanously with the result that less optimal. By planing and selecting right analogy, the role of analogy can be achieved the optimal result. Therefore, it is important to maping analogies of abstract consepts on physics learning.

  6. Computational approaches to analogical reasoning current trends

    CERN Document Server

    Richard, Gilles

    2014-01-01

    Analogical reasoning is known as a powerful mode for drawing plausible conclusions and solving problems. It has been the topic of a huge number of works by philosophers, anthropologists, linguists, psychologists, and computer scientists. As such, it has been early studied in artificial intelligence, with a particular renewal of interest in the last decade. The present volume provides a structured view of current research trends on computational approaches to analogical reasoning. It starts with an overview of the field, with an extensive bibliography. The 14 collected contributions cover a large scope of issues. First, the use of analogical proportions and analogies is explained and discussed in various natural language processing problems, as well as in automated deduction. Then, different formal frameworks for handling analogies are presented, dealing with case-based reasoning, heuristic-driven theory projection, commonsense reasoning about incomplete rule bases, logical proportions induced by similarity an...

  7. Structure problems in the analog computation

    International Nuclear Information System (INIS)

    Braffort, P.L.

    1957-01-01

    The recent mathematical development showed the importance of elementary structures (algebraic, topological, etc.) in abeyance under the great domains of classical analysis. Such structures in analog computation are put in evidence and possible development of applied mathematics are discussed. It also studied the topological structures of the standard representation of analog schemes such as additional triangles, integrators, phase inverters and functions generators. The analog method gives only the function of the variable: time, as results of its computations. But the course of computation, for systems including reactive circuits, introduces order structures which are called 'chronological'. Finally, it showed that the approximation methods of ordinary numerical and digital computation present the same structure as these analog computation. The structure analysis permits fruitful comparisons between the several domains of applied mathematics and suggests new important domains of application for analog method. (M.P.)

  8. Lower Lip Reconstruction after Wide Excision of a Malignancy with Barrel-Shaped Excision or the Webster Modification of the Bernard Operation

    Directory of Open Access Journals (Sweden)

    Hyung Joon Seo

    2013-01-01

    Full Text Available BackgroundBecause there are numerous methods for reconstruction of the lower lip, it is not easy to choose the optimal method. In choosing the surgical method for lower lip reconstruction, we obtained acceptable outcomes based on our treatment strategy, which included either a barrel-shaped excision or the Webster modification of the Bernard operation. We report on the surgical outcomes based on our treatment strategy.MethodsThis study included 26 patients who underwent lower lip reconstructive surgery from September 1996 to September 2010. The operation was done using either a barrel-shaped excision or the Webster modification, considering the location of the defect, the size of the defect, and the amount of residual tissue on the lateral side of the vermilion after excision.ResultsIn our series, 3 patients underwent a single barrel-shaped excision, and nine patients underwent a double barrel-shaped excision. In addition, the unilateral Webster modification was performed on in 6 patients, and there were eight cases of bilateral Webster modification. All of the patients except one were satisfied with the postoperative shape of the lip. In one case both recurrence and dehiscence occurred. One patient had a good postoperative lip shape, but had difficulty wearing a denture, and also underwent commissuroplasty. Furthermore, there were two patients who complained of drooling, and 4 with paresthesia.ConclusionsA soft tissue defect resulting from wide excision of a lower lip malignancy can be successfully reconstructed using only one of two surgical methods: the barrel-shaped excision or the Webster modification of the Bernard operation.

  9. Generating explanations via analogical comparison.

    Science.gov (United States)

    Hoyos, Christian; Gentner, Dedre

    2017-10-01

    Generating explanations can be highly effective in promoting learning in both adults and children. Our interest is in the mechanisms that underlie this effect and in whether and how they operate in early learning. In adult reasoning, explanation may call on many subprocesses-including comparison, counterfactual reasoning, and reasoning by exclusion; but it is unlikely that all these processes are available to young children. We propose that one process that may serve both children and adults is comparison. In this study, we asked whether children would use the results of a comparison experience when asked to explain why a model skyscraper was stable. We focused on a challenging principle-that diagonal cross-bracing lends stability to physical structures (Gentner et al., Cognitive Science, 40, 224-240, 2016). Six-year-olds either received no training or interacted with model skyscrapers in one of three different conditions, designed to vary in their potential to invite and support comparison. In the Single Model condition, children interacted with a single braced model. In the comparison conditions (Low Alignability and High Alignability), children compared braced and unbraced models. Following experience with the models, children were asked to explain why the braced model was stable. They then received two transfer tasks. We found that children who received highly alignable pairs were most likely to (a) produce brace-based explanations and (b) transfer the brace principle to a dissimilar context. This provides evidence that children can benefit from analogical comparison in generating explanations and also suggests limitations on this ability.

  10. Post-operative outcomes following the excision of dorsal wrist ganglions with/without the use of Methylene Blue

    Directory of Open Access Journals (Sweden)

    Suleyman Tas

    2016-04-01

    Conclusions: The recurrence of cysts is rare after complete excision, particularly when rupture is prevented. Methylene blue injection is useful for ensuring complete excision and, therefore, to prevent recurrence. [Hand Microsurg 2016; 5(1.000: 1-6

  11. Retropharyngeal Schwannoma Excised Through a Transoral Approach: A Case Report

    Directory of Open Access Journals (Sweden)

    Chia-Ying Hsieh

    2006-09-01

    Full Text Available The contents of the retropharyngeal space are limited to fat and retropharyngeal nodes. Primary tumors originating from the retropharyngeal space are rare. More than 25% of schwannomas are found in the head and neck region, and they are rarely found in the retropharyngeal space. Here, we report the case of a 44-year-old woman with a schwannoma confined to the left retropharyngeal space, who presented with snoring and a mild lump in the throat sensation. Physical examination revealed anterior bulging of the left oropharyngeal wall, with intact mucosa. Magnetic resonance imaging showed a well-defined, encapsulated tumor in the left retropharyngeal space with bright signal intensity on T2-weighted images and low signal intensity on T1-weighted images, which was strongly enhanced after gadolinium administration. The tumor was removed through a transoral approach, resulting in a short postoperative recovery time without complications. The pathologic diagnosis was schwannoma. The patient has been well and free of tumor recurrence for 2 years. From anatomic and physiologic viewpoints, excision through a transoral approach is a good choice for a confined retropharyngeal schwannoma.

  12. Implication of SUMO E3 ligases in nucleotide excision repair.

    Science.gov (United States)

    Tsuge, Maasa; Kaneoka, Hidenori; Masuda, Yusuke; Ito, Hiroki; Miyake, Katsuhide; Iijima, Shinji

    2015-08-01

    Post-translational modifications alter protein function to mediate complex hierarchical regulatory processes that are crucial to eukaryotic cellular function. The small ubiquitin-like modifier (SUMO) is an important post-translational modification that affects transcriptional regulation, nuclear localization, and the maintenance of genome stability. Nucleotide excision repair (NER) is a very versatile DNA repair system that is essential for protection against ultraviolet (UV) irradiation. The deficiencies in NER function remarkably increase the risk of skin cancer. Recent studies have shown that several NER factors are SUMOylated, which influences repair efficiency. However, how SUMOylation modulates NER has not yet been elucidated. In the present study, we performed RNAi knockdown of SUMO E3 ligases and found that, in addition to PIASy, the polycomb protein Pc2 affected the repair of cyclobutane pyrimidine dimers. PIAS1 affected both the removal of 6-4 pyrimidine pyrimidone photoproducts and cyclobutane pyrimidine dimers, whereas other SUMO E3 ligases did not affect the removal of either UV lesion.

  13. Base Sequence Context Effects on Nucleotide Excision Repair

    Directory of Open Access Journals (Sweden)

    Yuqin Cai

    2010-01-01

    Full Text Available Nucleotide excision repair (NER plays a critical role in maintaining the integrity of the genome when damaged by bulky DNA lesions, since inefficient repair can cause mutations and human diseases notably cancer. The structural properties of DNA lesions that determine their relative susceptibilities to NER are therefore of great interest. As a model system, we have investigated the major mutagenic lesion derived from the environmental carcinogen benzo[a]pyrene (B[a]P, 10S (+-trans-anti-B[a]P-2-dG in six different sequence contexts that differ in how the lesion is positioned in relation to nearby guanine amino groups. We have obtained molecular structural data by NMR and MD simulations, bending properties from gel electrophoresis studies, and NER data obtained from human HeLa cell extracts for our six investigated sequence contexts. This model system suggests that disturbed Watson-Crick base pairing is a better recognition signal than a flexible bend, and that these can act in concert to provide an enhanced signal. Steric hinderance between the minor groove-aligned lesion and nearby guanine amino groups determines the exact nature of the disturbances. Both nearest neighbor and more distant neighbor sequence contexts have an impact. Regardless of the exact distortions, we hypothesize that they provide a local thermodynamic destabilization signal for repair.

  14. Germline excision of transgenes in Aedes aegypti by homing endonucleases.

    Science.gov (United States)

    Aryan, Azadeh; Anderson, Michelle A E; Myles, Kevin M; Adelman, Zach N

    2013-01-01

    Aedes (Ae.) aegypti is the primary vector for dengue viruses (serotypes1-4) and chikungunya virus. Homing endonucleases (HEs) are ancient selfish elements that catalyze double-stranded DNA breaks (DSB) in a highly specific manner. In this report, we show that the HEs Y2-I-AniI, I-CreI and I-SceI are all capable of catalyzing the excision of genomic segments from the Ae. aegypti genome in a heritable manner. Y2-I-AniI demonstrated the highest efficiency at two independent genomic targets, with 20-40% of Y2-I-AniI-treated individuals producing offspring that had lost the target transgene. HE-induced DSBs were found to be repaired via the single-strand annealing (SSA) and non-homologous end-joining (NHEJ) pathways in a manner dependent on the availability of direct repeat sequences in the transgene. These results support the development of HE-based gene editing and gene drive strategies in Ae. aegypti, and confirm the utility of HEs in the manipulation and modification of transgenes in this important vector.

  15. Quantitative imaging of excised osteoarthritic cartilage using spectral CT

    Energy Technology Data Exchange (ETDEWEB)

    Rajendran, Kishore; Bateman, Christopher J.; Younis, Raja Aamir; De Ruiter, Niels J.A.; Ramyar, Mohsen; Anderson, Nigel G. [University of Otago - Christchurch, Department of Radiology, Christchurch (New Zealand); Loebker, Caroline [University of Otago, Christchurch Regenerative Medicine and Tissue Engineering Group, Department of Orthopaedic Surgery and Musculoskeletal Medicine, Christchurch (New Zealand); University of Twente, Department of Developmental BioEngineering, Enschede (Netherlands); Schon, Benjamin S.; Hooper, Gary J.; Woodfield, Tim B.F. [University of Otago, Christchurch Regenerative Medicine and Tissue Engineering Group, Department of Orthopaedic Surgery and Musculoskeletal Medicine, Christchurch (New Zealand); Chernoglazov, Alex I. [University of Canterbury, Human Interface Technology Laboratory New Zealand, Christchurch (New Zealand); Butler, Anthony P.H. [University of Otago - Christchurch, Department of Radiology, Christchurch (New Zealand); European Organisation for Nuclear Research (CERN), Geneva (Switzerland); MARS Bioimaging, Christchurch (New Zealand)

    2017-01-15

    To quantify iodine uptake in articular cartilage as a marker of glycosaminoglycan (GAG) content using multi-energy spectral CT. We incubated a 25-mm strip of excised osteoarthritic human tibial plateau in 50 % ionic iodine contrast and imaged it using a small-animal spectral scanner with a cadmium telluride photon-processing detector to quantify the iodine through the thickness of the articular cartilage. We imaged both spectroscopic phantoms and osteoarthritic tibial plateau samples. The iodine distribution as an inverse marker of GAG content was presented in the form of 2D and 3D images after applying a basis material decomposition technique to separate iodine in cartilage from bone. We compared this result with a histological section stained for GAG. The iodine in cartilage could be distinguished from subchondral bone and quantified using multi-energy CT. The articular cartilage showed variation in iodine concentration throughout its thickness which appeared to be inversely related to GAG distribution observed in histological sections. Multi-energy CT can quantify ionic iodine contrast (as a marker of GAG content) within articular cartilage and distinguish it from bone by exploiting the energy-specific attenuation profiles of the associated materials. (orig.)

  16. Implications of raising cigarette excise taxes in Peru

    Directory of Open Access Journals (Sweden)

    Martin Gonzalez-Rozada

    Full Text Available ABSTRACT Objective To assess how raising cigarette excise taxes in Peru might impact cigarette consumption, and to determine if higher taxes would be regressive. Methods Total demand price elasticity was estimated by income groups using two datasets: quarterly time-series data from 1993 – 2012 and data from a cross-sectional survey of income and expenses conducted in 2008 – 2009 . A functional form of the cigarette demand in Peru was specified using the quarterly data set, and the demand price elasticity was estimated for the short and long run. Using the second data set and Deaton methodology, the implementation of elasticity estimation and by groups’ elasticity was done in a two-step procedure. Results Demand price elasticity was −0.7, implying that a 10% price increase via a new tax would reduce consumption by 7%. Demand price elasticity estimations by income group suggested that poorer families are not more price sensitive than richer ones, which implies that increasing cigarette taxes could be regressive. Conclusions Increasing cigarette taxes is the most efficient policy for inducing a reduction in smoking. However, in the case of Peru, an increase in cigarette taxes could be regressive.

  17. A retrospective study of surgically excised phaeochromocytomas in Newfoundland, Canada

    Directory of Open Access Journals (Sweden)

    Joanna Holland

    2014-01-01

    Full Text Available Objective: A retrospective study detailing the circumstances surrounding diagnosis and treatment of pheochromocytomas with the associated genetic disorders. Materials and Methods: All patients with surgically excised pheochromocytomas in the Health Sciences Center, St. John′s, Newfoundland, Canada between January 2001 and December 2010 were retrospectively analyzed to determine associated familial syndromes, age, tumor size, symptomatology, and percentage of paragangliomas and bilateral pheochromocytomas. Pathology specimen reports, adrenalectomy lists and Meditech (electronic medical record diagnostic codes provided a comprehensive database for this study. Results: Twenty-four patients were studied; familial disorder patients comprised 42% (10/24. Average age at diagnosis was 57 among the sporadic and 34 in familial disorder groups (P = 0.006. Average tumor size was 4.5 cm in the sporadic group and 3 cm in the familial disorder group (P = 0.19. All atypical cases including bilateral or extra-adrenal tumors and malignancy occurred in familial disorder patients. Conclusions: The proportion of familial disorder patients (42% was higher in this study than would be expected, likely a result of the relatively high incidence of hereditary autosomal dominant disorders within Newfoundland. Among familial disorder patients, the average younger age at diagnosis and the smaller tumor size suggest syndromic pheochromocytomas may develop earlier, however they are more likely to be diagnosed sooner due to biochemical surveillance testing in known genetic disorder patients. We also demonstrate a relatively high incidence of surgically resected pheochromocytomas of 4.679/million/year in Newfoundland.

  18. Implication of Posttranslational Histone Modifications in Nucleotide Excision Repair

    Directory of Open Access Journals (Sweden)

    Shisheng Li

    2012-09-01

    Full Text Available Histones are highly alkaline proteins that package and order the DNA into chromatin in eukaryotic cells. Nucleotide excision repair (NER is a conserved multistep reaction that removes a wide range of generally bulky and/or helix-distorting DNA lesions. Although the core biochemical mechanism of NER is relatively well known, how cells detect and repair lesions in diverse chromatin environments is still under intensive research. As with all DNA-related processes, the NER machinery must deal with the presence of organized chromatin and the physical obstacles it presents. A huge catalogue of posttranslational histone modifications has been documented. Although a comprehensive understanding of most of these modifications is still lacking, they are believed to be important regulatory elements for many biological processes, including DNA replication and repair, transcription and cell cycle control. Some of these modifications, including acetylation, methylation, phosphorylation and ubiquitination on the four core histones (H2A, H2B, H3 and H4 or the histone H2A variant H2AX, have been found to be implicated in different stages of the NER process. This review will summarize our recent understanding in this area.

  19. Total Humeral Endoprosthetic Replacement following Excision of Malignant Bone Tumors

    Directory of Open Access Journals (Sweden)

    Suhel Kotwal

    2016-01-01

    Full Text Available Humerus is a common site for malignant tumors. Advances in adjuvant therapies and reconstructive methods provide salvage of the upper limb with improved outcomes. Reports of limb salvage with total humeral replacement in extensive humeral tumors are sparse. We undertook a retrospective study of 20 patients who underwent total humeral endoprosthetic replacement as limb salvage following excision of extensile malignant tumor from 1990 to 2011. With an average followup of 42.9, functional and oncological outcomes were analyzed. Ten patients were still alive at the time of review. Mean estimated blood loss was 1131 mL and duration of surgery was 314 minutes. Deep infection was encountered in one patient requiring debridement while mechanical loosening of ulnar component was identified in one patient. Subluxation of prosthetic humeral head was noted in 3 patients. Mean active shoulder abduction was 12.5° and active flexion was 15°. Incompetence of abduction mechanism was the major determinant of poor active functional outcome. Mean elbow flexion was 103.5° with 30.5° flexion contracture in 10 patients with good and useful hand function. Average MSTS score was 71.5%. Total humeral replacement is a reliable treatment option in restoring mechanical stability and reasonable functional results without compromising patient survival, with low complication rate.

  20. Frontopolar cortex mediates abstract integration in analogy.

    Science.gov (United States)

    Green, Adam E; Fugelsang, Jonathan A; Kraemer, David J M; Shamosh, Noah A; Dunbar, Kevin N

    2006-06-22

    Integration of abstractly similar relations during analogical reasoning was investigated using functional magnetic resonance imaging. Activation elicited by an analogical reasoning task that required both complex working memory and integration of abstractly similar relations was compared to activation elicited by a non-analogical task that required complex working memory in the absence of abstract relational integration. A left-sided region of the frontal pole of the brain (BA 9/10) was selectively active for the abstract relational integration component of analogical reasoning. Analogical reasoning also engaged a left-sided network of parieto-frontal regions. Activity in this network during analogical reasoning is hypothesized to reflect categorical alignment of individual component terms that make up analogies. This parieto-frontal network was also engaged by the complex control task, which involved explicit categorization, but not by a simpler control task, which did not involve categorization. We hypothesize that frontopolar cortex mediates abstract relational integration in complex reasoning while parieto-frontal regions mediate working memory processes, including manipulation of terms for the purpose of categorical alignment, that facilitate this integration.

  1. Advances in Analog Circuit Design 2015

    CERN Document Server

    Baschirotto, Andrea; Harpe, Pieter

    2016-01-01

    This book is based on the 18 tutorials presented during the 24th workshop on Advances in Analog Circuit Design. Expert designers present readers with information about a variety of topics at the frontier of analog circuit design, including low-power and energy-efficient analog electronics, with specific contributions focusing on the design of efficient sensor interfaces and low-power RF systems. This book serves as a valuable reference to the state-of-the-art, for anyone involved in analog circuit research and development. ·         Provides a state-of-the-art reference in analog circuit design, written by experts from industry and academia; ·         Presents material in a tutorial-based format; ·         Includes coverage of high-performance analog-to-digital and digital to analog converters, integrated circuit design in scaled technologies, and time-domain signal processing.

  2. The force of dissimilar analogies in bioethics.

    Science.gov (United States)

    Mertes, Heidi; Pennings, Guido

    2011-04-01

    Although analogical reasoning has long been a popular method of reasoning in bioethics, current literature does not sufficiently grasp its variety. We assert that the main shortcoming is the fact that an analogy's value is often judged on the extent of similarity between the source situation and the target situation, while in (bio)ethics, analogies are often used because of certain dissimilarities rather than in spite of them. We make a clear distinction between dissimilarities that aim to reinforce a similar approach in the source situation and the target situation and dissimilarities that aim to undermine or denounce a similar approach. The former kind of dissimilarity offers the analogy more normative force than if there were no dissimilarities present; this is often overlooked by authors who regard all relevant dissimilarities as detrimental to the analogy's strength. Another observation is that an evaluation of the normative force of an analogy cannot be made independently of moral principles or theories. Without these, one cannot select which elements in an analogy are morally relevant nor determine how they should be interpreted.

  3. Extralevator Abdominal Perineal Excision Versus Standard Abdominal Perineal Excision: Impact on Quality of the Resected Specimen and Postoperative Morbidity.

    Science.gov (United States)

    Habr-Gama, Angelita; São Julião, Guilherme P; Mattacheo, Adrian; de Campos-Lobato, Luiz Felipe; Aleman, Edgar; Vailati, Bruna B; Gama-Rodrigues, Joaquim; Perez, Rodrigo Oliva

    2017-08-01

    Abdominal perineal excision (APE) has been associated with a high risk of positive circumferential resection margin (CRM+) and local recurrence rates in the treatment of rectal cancer. An alternative extralevator approach (ELAPE) has been suggested to improve the quality of resection by avoiding coning of the specimen decreasing the risk of tumor perforation and CRM+. The aim of this study is to compare the quality of the resected specimen and postoperative complication rates between ELAPE and "standard" APE. All patients between 1998 and 2014 undergoing abdominal perineal excision for primary or recurrent rectal cancer at a single Institution were reviewed. Between 1998 and 2008, all patients underwent standard APE. In 2009 ELAPE was introduced at our Institution and all patients requiring APE underwent this alternative procedure (ELAPE). The groups were compared according to pathological characteristics, specimen quality (CRM status, perforation and failure to provide the rectum and anus in a single specimen-fragmentation) and postoperative morbidity. Fifty patients underwent standard APEs, while 22 underwent ELAPE. There were no differences in CRM+ (10.6 vs. 13.6%; p = 0.70) or tumor perforation rates (8 vs. 0%; p = 0.30) between APE and ELAPE. However, ELAPE were less likely to result in a fragmented specimen (42 vs. 4%; p = 0.002). Advanced pT-stage was also a risk factor for specimen fragmentation (p = 0.03). There were no differences in severe (Grade 3/4) postoperative morbidity (13 vs. 10%; p = 0.5). Perineal wound dehiscences were less frequent among ELAPE (52 vs 13%; p < 0.01). Despite short follow-up (median 21 mo.), 2-year local recurrence-free survival was better for patients undergoing ELAPE when compared to APE (87 vs. 49%; p = 0.04). ELAPE may be safely implemented into routine clinical practice with no increase in postoperative morbidity and considerable improvements in the quality of the resected specimen of patients with low rectal

  4. THE IMPACT OF VISIONARY LEADERSHIP, LEARNING ORGANIZATION AND INNOVATIVE BEHAVIOR TO PERFORMANCE OF CUSTOMS AND EXCISE FUNCTIONAL

    OpenAIRE

    Anshar, Muhammad

    2017-01-01

    This research aims to determine the impact of visionary leadership, learning organization, and innovative behavior on the performance of Functional Officers of Customs and Excise Inspectors at Tanjung Priok Customs and Excise Main Service Office. The research was conducted at Tanjung Priok Customs and Excise Service Office using the number of samples of 78 Functional Officers of Customs and Excise Inspectors. The sample was selected using simple random sampling technique. Data collection was ...

  5. Cigarette price minimization strategies in the United States: price reductions and responsiveness to excise taxes.

    Science.gov (United States)

    Pesko, Michael F; Licht, Andrea S; Kruger, Judy M

    2013-11-01

    Because cigarette price minimization strategies can provide substantial price reductions for individuals continuing their usual smoking behaviors following federal and state cigarette excise tax increases, we examined independent price reductions compensating for overlapping strategies. The possible availability of larger independent price reduction opportunities in states with higher cigarette excise taxes is explored. Regression analysis used the 2006-2007 Tobacco Use Supplement of the Current Population Survey (N = 26,826) to explore national and state-level independent price reductions that smokers obtained from purchasing cigarettes (a) by the carton, (b) in a state with a lower average after-tax cigarette price than in the state of residence, and (c) in "some other way," including online or in another country. Price reductions from these strategies are estimated jointly to compensate for known overlapping strategies. Each strategy reduced the price of cigarettes by 64-94 cents per pack. These price reductions are 9%-22% lower than conventionally estimated results not compensating for overlapping strategies. Price reductions vary substantially by state. Following cigarette excise tax increases, the price reduction available from purchasing cigarettes by cartons increased. Additionally, the price reduction from purchasing cigarettes in a state with a lower average after-tax cigarette price is positively associated with state cigarette excise tax rates and border state cigarette excise tax rate differentials. Findings from this large, nationally representative study of cigarette smokers suggest that price reductions are larger in states with higher cigarette excise taxes, and increase as cigarette excise taxes rise.

  6. The influence of pH on the excision of UV-photoproducts from HeLa cells

    International Nuclear Information System (INIS)

    Masek, F.; Hochmann, J.; Duraj, J.

    1977-01-01

    Excision of pyrimidine dimers with pH decreasing in UV irradiated HeLa cells can be depressed. This depression is independent of the UV dose within the investigated range. The excision capacity of the HeLa repair system from absolute amount of excised dimers is shown. (author)

  7. Substrate overlap and functional competition between human nucleotide excision repair and Escherichia coli photolyase and (A)BC excision nuclease

    International Nuclear Information System (INIS)

    Sibghat-Ullah; Sancar, Z.

    1990-01-01

    Human cell free extract prepared by the method of Manley et al. carries out repair synthesis on UV-irradiated DNA. Removal of pyrimidine dimers by photoreactivation with DNA photolyase reduces repair synthesis by about 50%. With excess enzyme in the reaction mixture photolyase reduced the repair signal by the same amount even in the absence of photoreactivating light, presumably by binding to pyrimidine dimers and interfering with the binding of human damage recognition protein. Similarly, the UvrB subunit of Escherichia coli (A)BC excinuclease when loaded onto UV-irradiated or psoralen-adducted DNA inhibited repair synthesis by cell-free extract by 75-80%. The opposite was true also as HeLa cell free extract specifically inhibited the photorepair of a thymine dimer by DNA photolyase and its removal by (A)BC excinuclease. Cell-free extracts from xeroderma pigmentosum (XP) complementation groups A and C were equally effective in blocking the E. coli repair proteins, while extracts from complementation groups D and E were ineffective in blocking the E. coli enzyme. These results suggest that XP-D and XP-E cells are defective in the damage recognition subunits(s) of human excision nuclease

  8. Frequency and outcomes of biopsy-proven fibroadenomas recommended for surgical excision.

    Science.gov (United States)

    Lee, Shimwoo; Mercado, Cecilia L; Cangiarella, Joan F; Chhor, Chloe M

    2017-12-16

    Our aim was to investigate the outcomes of fibroadenomas recommended for surgical excision due to large size (>2cm) or interval growth. A retrospective review of our institutional radiology database from 2007 to 2015 was performed. We identified 167 biopsy-proven fibroadenomas recommended for surgical consultation. Of these, 75 (45%) cases actually underwent excision, 7 (9%, 95% CI: 4-18%) of which were upgraded to phyllodes tumors upon histopathological examination. Our results support the current recommendation to surgically excise breast lesions diagnosed as fibroadenomas with size >2cm or with interval growth due to the considerable risk of finding phyllodes tumors. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Involvement of UV-inducible repair in pyrimidine dimer excision in Escherichia coli

    International Nuclear Information System (INIS)

    Masek, F.; Sedliakova, M.

    1978-01-01

    The influence of UV radiation on pyrimidine dimer excision in the cells of three excision-proficient E.coli strains was studied. For this purpose cells were irradiated with a first fluence of 300 ergs/mm 2 and at different time intervals with a second fluence of 500 ergs/mm 2 . After the second fluence dimer excision was found to be partly inhibited in E.coli B/r Hcr + and E.coli 15 555-7, but not in E.coli K12 SR20. (author)

  10. Induction of the Tn10 Precise Excision in E. coli Cells after Accelerated Heavy Ions Irradiation

    CERN Document Server

    Zhuravel, D V

    2003-01-01

    The influence of the irradiation of different kinds on the indication of the structural mutations in the bacteria Escherichia coli is considered. The regularities of the Tn10 precise excision after accelerated ^{4}He and ^{12}C ions irradiations with different linear energy transfer (LET) were investigated. Dose dependences of the survival and relative frequency of the Tn10 precise excision were obtained. It was shown, that the relative frequency of the Tn10 precise excision is the exponential function from the irradiation dose. Relative biological efficiency (RBE), and relative genetic efficiency (RGE) were calculated, and were treated as the function of the LET.

  11. Periprosthetic soft tissue recurrence of chondroblastoma after attempted en bloc excision from the proximal humerus

    Energy Technology Data Exchange (ETDEWEB)

    Hammond, G.W.; Tehranzadeh, J.; Hoang, B.H. [University of California, Irvine, Department of Orthopaedic Surgery, Orange (United States); Gu, M. [University of California, Irvine, Department of Pathology, Orange (United States)

    2006-01-01

    A case of soft tissue recurrence of chondroblastoma after attempted en bloc excision and endoprosthetic replacement is described. This tumor in the proximal humerus recurred after initial curettage and was subsequently treated by attempted en bloc excision with positive microscopic margins. The patient then presented with a large soft tissue recurrence surrounding the endoprosthesis. This periprosthetic recurrence necessitated re-excision and revision of the endoprosthesis. Recurrence is not uncommon following curettage of chondroblastoma. However, less is known about soft tissue recurrence after en bloc resection of this tumor with positive margins. A subset of chondroblastoma may exist with more locally aggressive behavior. (orig.)

  12. DNA excision repair as a component of adaptation to low doses of ionizing radiation Escherichia coli

    International Nuclear Information System (INIS)

    Huang, H.; Claycamp, H.G.

    1993-01-01

    In this study the authors examined whether or not DNA excision repair is a component of adaptation induced by very low-dose ionizing radiation in Escherichia coli, a well-characterized prokaryote, and investigated the relationship between enhanced excision repair and the SOS response. Their data suggest that there seems to be narrow 'windows' of dose-effect for the induction of SOS-independent DNA excision repair. Being similar to mammalian cell studies, the dose range for this effect was about 200-fold less than D 37 for radiation survival. (author)

  13. Involvement of UV-inducible repair in pyrimidine dimer excision in Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Masek, F; Sedliakova, M [Slovenska Akademia Vied, Bratislava (Czechoslovakia)

    1978-11-15

    The influence of UV radiation on pyrimidine dimer excision in the cells of three excision-proficient E.coli strains was studied. For this purpose cells were irradiated with a first fluence of 300 ergs/mm/sup 2/ and at different time intervals with a second fluence of 500 ergs/mm/sup 2/. After the second fluence dimer excision was found to be partly inhibited in E.coli B/r Hcr/sup +/ and E.coli 15 555-7, but not in E.coli K12 SR20.

  14. Selective termination, fetal reduction and analogical reasoning.

    Science.gov (United States)

    Pennings, G

    2013-06-01

    Analogical reasoning is a basic method in bioethics. Its main purpose is to transfer the rule from an existing or known situation to a new and problematic situation. This commentary applies the lifeboat analogy to the context of selective termination and fetal reduction. It turns out that the analogy is only partially helpful as the main principle in the case of selective termination is the procreative beneficence principle. However, the wide person-affecting form of this principle doubly justifies selective termination: i.e. one prevents the harm caused by the birth of an affected child and one increases the life chances of the remaining fetuses. I conclude, however, that all analogies are basically flawed since they assume that fetuses as such have interests. I argue that fetuses only have interests to the extent that they are potential future persons. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  15. An Electrical Analog Computer for Poets

    Science.gov (United States)

    Bruels, Mark C.

    1972-01-01

    Nonphysics majors are presented with a direct current experiment beyond Ohms law and series and parallel laws. This involves construction of an analog computer from common rheostats and student-assembled voltmeters. (Author/TS)

  16. Pentagastrin analogs containing α-aminooxy acids

    International Nuclear Information System (INIS)

    Balaspiri, L.; Kovacs, L.; Kovacs, K.; Varga, L.; Varro, V.; Schoen, I.; Kisfaludy, L.

    1982-01-01

    Two 14 C-labelled pentagastrin analogs of different specific radioactivities, containing α-aminooxy acids, have been synthesised to study their biological effects in the gastro-intestinal tract. (U.K.)

  17. Quantum States Transfer by Analogous Bell States

    International Nuclear Information System (INIS)

    Mei Di; Li Chong; Yang Guohui; Song Heshan

    2008-01-01

    Transmitting quantum states by channels of analogous Bell states is studied in this paper. We analyze the transmitting process, constructed the probabilitic unitary operator, and gain the largest successful transfer quantum state probability.

  18. Ku80-deleted cells are defective at base excision repair

    International Nuclear Information System (INIS)

    Li, Han; Marple, Teresa; Hasty, Paul

    2013-01-01

    Graphical abstract: - Highlights: • Ku80-deleted cells are hypersensitive to ROS and alkylating agents. • Cells deleted for Ku80, but not Ku70 or Lig4, have reduced BER capacity. • OGG1 rescues hypersensitivity to H 2 O 2 and paraquat in Ku80-mutant cells. • Cells deleted for Ku80, but not Lig4, are defective at repairing AP sites. • Cells deleted for Ku80, but not Lig4 or Brca2 exon 27, exhibit increased PAR. - Abstract: Ku80 forms a heterodimer with Ku70, called Ku, that repairs DNA double-strand breaks (DSBs) via the nonhomologous end joining (NHEJ) pathway. As a consequence of deleting NHEJ, Ku80-mutant cells are hypersensitive to agents that cause DNA DSBs like ionizing radiation. Here we show that Ku80 deletion also decreased resistance to ROS and alkylating agents that typically cause base lesions and single-strand breaks (SSBs). This is unusual since base excision repair (BER), not NHEJ, typically repairs these types of lesions. However, we show that deletion of another NHEJ protein, DNA ligase IV (Lig4), did not cause hypersensitivity to these agents. In addition, the ROS and alkylating agents did not induce γ-H2AX foci that are diagnostic of DSBs. Furthermore, deletion of Ku80, but not Lig4 or Ku70, reduced BER capacity. Ku80 deletion also impaired BER at the initial lesion recognition/strand scission step; thus, involvement of a DSB is unlikely. Therefore, our data suggests that Ku80 deletion impairs BER via a mechanism that does not repair DSBs

  19. Ku80-deleted cells are defective at base excision repair

    Energy Technology Data Exchange (ETDEWEB)

    Li, Han [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029 (Spain); Marple, Teresa [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Hasty, Paul, E-mail: hastye@uthscsa.edu [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029 (Spain)

    2013-05-15

    Graphical abstract: - Highlights: • Ku80-deleted cells are hypersensitive to ROS and alkylating agents. • Cells deleted for Ku80, but not Ku70 or Lig4, have reduced BER capacity. • OGG1 rescues hypersensitivity to H{sub 2}O{sub 2} and paraquat in Ku80-mutant cells. • Cells deleted for Ku80, but not Lig4, are defective at repairing AP sites. • Cells deleted for Ku80, but not Lig4 or Brca2 exon 27, exhibit increased PAR. - Abstract: Ku80 forms a heterodimer with Ku70, called Ku, that repairs DNA double-strand breaks (DSBs) via the nonhomologous end joining (NHEJ) pathway. As a consequence of deleting NHEJ, Ku80-mutant cells are hypersensitive to agents that cause DNA DSBs like ionizing radiation. Here we show that Ku80 deletion also decreased resistance to ROS and alkylating agents that typically cause base lesions and single-strand breaks (SSBs). This is unusual since base excision repair (BER), not NHEJ, typically repairs these types of lesions. However, we show that deletion of another NHEJ protein, DNA ligase IV (Lig4), did not cause hypersensitivity to these agents. In addition, the ROS and alkylating agents did not induce γ-H2AX foci that are diagnostic of DSBs. Furthermore, deletion of Ku80, but not Lig4 or Ku70, reduced BER capacity. Ku80 deletion also impaired BER at the initial lesion recognition/strand scission step; thus, involvement of a DSB is unlikely. Therefore, our data suggests that Ku80 deletion impairs BER via a mechanism that does not repair DSBs.

  20. Oncological outcome after laparoscopic abdominoperineal excision of the rectum.

    Science.gov (United States)

    Jefferies, M T; Evans, M D; Hilton, J; Chandrasekaran, T V; Beynon, J; Khot, U

    2012-08-01

    Abdominoperineal excision of the rectum (APER) for cancer has been associated with higher circumferential resection margin (CRM) involvement and failure of local disease control. The aim of this study was to investigate whether the introduction of laparoscopic APER altered the incidence of CRM involvement. Consecutive patients undergoing open or laparoscopic APER for adenocarcinomas of the rectum were studied. Patient demographics, preoperative staging, neoadjuvant treatment, operative findings, length of stay and pathological details were collected from operative and radiology databases and compared. There were 16 laparoscopic and 25 open APER performed over a 3-year period. Neoadjuvant therapy was given to 43.8% (7/16) of the laparoscopic group and 56.0% (14/25) of the open group. Complete laparoscopic resection was possible in 14 (87.5%) of 16 patients. The median harvested number of nodes was 14 (4-33) in both groups. The median length of stay was 7 (3-13) and 15 (9-40) days in the laparoscopic and open groups (P CRM was clear in all cases. There was no local recurrence in either group at a median follow-up of 23 months. There were no in-hospital deaths and no significant differences in overall survival. There were no significant differences in preoperative or postoperative histopathological T stage between the two groups (P = 0.057 and P = 0.121). Laparoscopic APER for selected rectal cancers can achieve comparable oncological outcome to open surgery but is associated with a much shorter length of stay. Patient and tumour characteristics must be taken into consideration when deciding on a laparoscopic approach for low rectal cancer. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.

  1. Base excision repair deficiency in acute myeloid leukemia

    International Nuclear Information System (INIS)

    Scheer, N.M.

    2009-01-01

    Acute myeloid leukemia (AML) is an aggressive malignancy of the hematopoietic system arising from a transformed myeloid progenitor cell. Genomic instability is the hallmark of AML and characterized by a variety of cytogenetic and molecular abnormalities. Whereas 10% to 20% of AML cases reflect long-term sequelae of cytotoxic therapies for a primary disorder, the etiology for the majority of AMLs remains unknown. The integrity of DNA is under continuous attack from a variety of exogenous and endogenous DNA damaging agents. The majority of DNA damage is caused by constantly generated reactive oxygen species (ROS) resulting from metabolic by-products. Base excision repair (BER) is the major DNA repair mechanism dealing with DNA base lesions that are induced by oxidative stress or alkylation. In this study we investigated the BER in AML. Primary AML patients samples as well as AML cell lines were treated with hydrogen peroxide (H 2 O 2 ). DNA damage induction and repair was monitored by the alkaline comet assay. In 15/30 leukemic samples from patients with therapy-related AML, in 13/35 with de novo AML and 14/26 with AML following a myelodysplastic syndrome, significantly reduced single strand breaks (SSBs) representing BER intermediates were found. In contrast, normal SSB formation was seen in mononuclear cells of 30 healthy individuals and 30/31 purified hematopoietic stem- and progenitor cell preparations obtained from umbilical cord blood. Additionally, in 5/10 analyzed AML cell lines, no SSBs were formed upon H 2 O 2 treatment, either. Differences in intracellular ROS concentrations or apoptosis could be excluded as reason for this phenomenon. A significantly diminished cleavage capacity for 7,8-dihydro-8-oxoguanine as well as for Furan was observed in cell lines that exhibited no SSB formation. These data demonstrate for the first time that initial steps of BER are impaired in a proportion of AML cell lines and leukemic cells from patients with different forms of

  2. Laparoscopic versus open total mesorectal excision for rectal cancer.

    Science.gov (United States)

    Vennix, Sandra; Pelzers, Loeki; Bouvy, Nicole; Beets, Geerard L; Pierie, Jean-Pierre; Wiggers, Theo; Breukink, Stephanie

    2014-04-15

    Colorectal cancer including rectal cancer is the third most common cause of cancer deaths in the western world. For colon carcinoma, laparoscopic surgery is proven to result in faster postoperative recovery, fewer complications and better cosmetic results with equal oncologic results. These short-term benefits are expected to be similar for laparoscopic rectal cancer surgery. However, the oncological safety of laparoscopic surgery for rectal cancer remained controversial due to the lack of definitive long-term results. Thus, the expected short-term benefits can only be of interest when oncological results are at least equal. To evaluate the differences in short- and long-term results after elective laparoscopic total mesorectal excision (LTME) for the resection of rectal cancer compared with open total mesorectal excision (OTME). We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2013, Issue 2), MEDLINE (January 1990 to February 2013), EMBASE (January 1990 to February 2013), ClinicalTrials.gov (February 2013) and Current Controlled Trials (February 2013). We handsearched the reference lists of the included articles for missed studies. Only randomised controlled trials (RCTs) comparing LTME and OTME, reporting at least one of our outcome measures, was considered for inclusion. Two authors independently assessed study quality according to the CONSORT statement, and resolved disagreements by discussion. We rated the quality of the evidence using GRADE methods. We identified 45 references out of 953 search results, of which 14 studies met the inclusion criteria involving 3528 rectal cancer patients. We did not consider the risk of bias of the included studies to have impacted on the quality of the evidence. Data were analysed according to an intention-to-treat principle with a mean conversion rate of 14.5% (range 0% to 35%) in the laparoscopic group.There was moderate quality evidence that laparoscopic and open TME had similar

  3. High-frequency analog integrated circuit design

    CERN Document Server

    1995-01-01

    To learn more about designing analog integrated circuits (ICs) at microwave frequencies using GaAs materials, turn to this text and reference. It addresses GaAs MESFET-based IC processing. Describes the newfound ability to apply silicon analog design techniques to reliable GaAs materials and devices which, until now, was only available through technical papers scattered throughout hundred of articles in dozens of professional journals.

  4. Emergent Explorations: Analog and Digital Scripting

    OpenAIRE

    Worden, Alexander

    2011-01-01

    This book documents an exploration of emergent and linear modes of defining space, form, and structure. The thesis highlights a dialog between analog and digital modeling techniques, in concept and project development. It identifies that analog modeling techniques, coupled with judgment, can be used to develop complex forms. The thesis project employs critical judgment and the textile techniques of crochet as a vehicle generate form. Crochet lends itself to this investigation because it ...

  5. An analog integrated circuit design laboratory

    OpenAIRE

    Mondragon-Torres, A.F.; Mayhugh, Jr.; Pineda de Gyvez, J.; Silva-Martinez, J.; Sanchez-Sinencio, E.

    2003-01-01

    We present the structure of an analog integrated circuit design laboratory to instruct at both, senior undergraduate and entry graduate levels. The teaching material includes: a laboratory manual with analog circuit design theory, pre-laboratory exercises and circuit design specifications; a reference web page with step by step instructions and examples; the use of mathematical tools for automation and analysis; and state of the art CAD design tools in use by industry. Upon completion of the ...

  6. HAPS, a Handy Analog Programming System

    DEFF Research Database (Denmark)

    Højberg, Kristian Søe

    1975-01-01

    HAPS (Hybrid Analog Programming System) is an analog compiler that can be run on a minicomputer in an interactive mode. Essentially HAPS is written in FORTRAN. The equations to be programmed for an ana log computer are read in by using a FORTRAN-like notation. The input must contain maximum...... and emphasizes the limitations HAPS puts on equation structure, types of computing circuit, scaling, and static testing....

  7. Children's analogical reasoning about natural phenomena.

    Science.gov (United States)

    Pauen, S; Wilkening, F

    1997-10-01

    This report investigates children's analogical reasoning in a physics task, using an analogy generated by the children rather than by the experimenter. A total of 127 elementary school children took part in three related studies. Children learned to predict the behavior of a balance scale. Later, they were asked to solve a force interaction problem. Two versions of the balance scale training were devised: version A suggested an incorrect solution to the target problem (negative analogy), and version B suggested a correct solution to the target problem (positive analogy). In Study 1, 9- to 10-year-olds showed spontaneous transfer in both training conditions. In Study 2, 7-year-olds did not show any transfer in the positive analogy condition. Study 3 revealed that the lack of transfer in younger children was not due to a failure either to notice the analogy or to perform the mapping. Instead, 7-year-olds transferred only selected aspects of the correct solution. Copyright 1997 Academic Press.

  8. Working memory predicts children's analogical reasoning.

    Science.gov (United States)

    Simms, Nina K; Frausel, Rebecca R; Richland, Lindsey E

    2018-02-01

    Analogical reasoning is the cognitive skill of drawing relationships between representations, often between prior knowledge and new representations, that allows for bootstrapping cognitive and language development. Analogical reasoning proficiency develops substantially during childhood, although the mechanisms underlying this development have been debated, with developing cognitive resources as one proposed mechanism. We explored the role of executive function (EF) in supporting children's analogical reasoning development, with the goal of determining whether predicted aspects of EF were related to analogical development at the level of individual differences. We assessed 5- to 11-year-old children's working memory, inhibitory control, and cognitive flexibility using measures from the National Institutes of Health Toolbox Cognition battery. Individual differences in children's working memory best predicted performance on an analogical mapping task, even when controlling for age, suggesting a fundamental interrelationship between analogical reasoning and working memory development. These findings underscore the need to consider cognitive capacities in comprehensive theories of children's reasoning development. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Quantitative characterization of pyrimidine dimer excision from UV-irradiated DNA (excision capacity) by cell-free extracts of the yeast Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Bekker, M.L.; Kaboev, O.K.; Akhmedov, A.T.; Luchkina, L.A.

    1984-01-01

    Cell-free extracts from wild-type yeast (RAD + ) and from rad mutants belonging to the RAD3 epistatic group (rad1-1, rad2-1, rad3-1, rad4-1) contain activities catalyzing the excision of pyrimidine dimers (PD) from purified ultraviolet-irradiated DNA which was not pre-treated with exogenous UV-endonuclease. The level of these activities in cell-free extracts from rad mutants did not differ from that in wild-type extract and was close to the in vivo excision capacity of the latter calculated from the LD 37 (about 10 4 PD per haploid genome). (Auth.)

  10. Flurbiprofen Axetil Enhances Analgesic Effects of Sufentanil and Attenuates Postoperative Emergence Agitation and Systemic Proinflammation in Patients Undergoing Tangential Excision Surgery

    Directory of Open Access Journals (Sweden)

    Wujun Geng

    2015-01-01

    Full Text Available Objective. Our present study tested whether flurbiprofen axetil could reduce perioperative sufentanil consumption and provide postoperative analgesia with decrease in emergency agitation and systemic proinflammatory cytokines release. Methods. Ninety patients undergoing tangential excision surgery were randomly assigned to three groups: (1 preoperative dose of 100 mg flurbiprofen axetil and a postoperative dose of 2 μg/kg sufentanil and 10 mL placebo by patient-controlled analgesia (PCA pump, (2 preoperative dose of 100 mg flurbiprofen axetil and a postoperative dose of 2 μg/kg sufentanil and 100 mg flurbiprofen axetil by PCA pump, and (3 10 mL placebo and a postoperative dose of 2 μg/kg sufentanil and 10 mL placebo by PCA pump. Results. Preoperative administration of flurbiprofen axetil decreased postoperative tramadol consumption and the visual analog scale at 4, 6, 12, and 24 h after surgery, which were further decreased by postoperative administration of flurbiprofen axetil. Furthermore, flurbiprofen axetil attenuated emergency agitation score and Ramsay score at 0, 5, and 10 min after extubation and reduced the TNF-α and interleukin- (IL- 6 levels at 24 and 48 h after the operation. Conclusion. Flurbiprofen axetil enhances analgesic effects of sufentanil and attenuates emergence agitation and systemic proinflammation in patients undergoing tangential excision surgery.

  11. Flurbiprofen Axetil Enhances Analgesic Effects of Sufentanil and Attenuates Postoperative Emergence Agitation and Systemic Proinflammation in Patients Undergoing Tangential Excision Surgery.

    Science.gov (United States)

    Geng, Wujun; Hong, Wandong; Wang, Junlu; Dai, Qinxue; Mo, Yunchang; Shi, Kejian; Sun, Jiehao; Qin, Jinling; Li, Mei; Tang, Hongli

    2015-01-01

    Our present study tested whether flurbiprofen axetil could reduce perioperative sufentanil consumption and provide postoperative analgesia with decrease in emergency agitation and systemic proinflammatory cytokines release. Ninety patients undergoing tangential excision surgery were randomly assigned to three groups: (1) preoperative dose of 100 mg flurbiprofen axetil and a postoperative dose of 2 μg/kg sufentanil and 10 mL placebo by patient-controlled analgesia (PCA) pump, (2) preoperative dose of 100 mg flurbiprofen axetil and a postoperative dose of 2 μg/kg sufentanil and 100 mg flurbiprofen axetil by PCA pump, and (3) 10 mL placebo and a postoperative dose of 2 μg/kg sufentanil and 10 mL placebo by PCA pump. Preoperative administration of flurbiprofen axetil decreased postoperative tramadol consumption and the visual analog scale at 4, 6, 12, and 24 h after surgery, which were further decreased by postoperative administration of flurbiprofen axetil. Furthermore, flurbiprofen axetil attenuated emergency agitation score and Ramsay score at 0, 5, and 10 min after extubation and reduced the TNF-α and interleukin- (IL-) 6 levels at 24 and 48 h after the operation. Flurbiprofen axetil enhances analgesic effects of sufentanil and attenuates emergence agitation and systemic proinflammation in patients undergoing tangential excision surgery.

  12. ESTHETIC OUTCOME OF SURGICAL EXCISION VERSUS ANTIBIOTIC THERAPY FOR NONTUBERCULOUS MYCOBACTERIAL CERVICOFACIAL LYMPHADENITIS IN CHILDREN

    NARCIS (Netherlands)

    Lindeboom, Jerome A.; Lindeboom, Robert; Bruijnesteijn van Coppenraet, Elisabeth S.; Kuijper, Ed J.; Tuk, Jacco; Prins, Jan M.

    2009-01-01

    One hundred children with microbiologically proven nontuberculous mycobacterial cervicofacial lymphadenitis were randomly assigned to excision of the involved lymph nodes, or antibiotic therapy consisting of clarithromycin and rifabutin. The esthetic outcome was rated using a revised and weighted

  13. Esthetic outcome of surgical excision versus antibiotic therapy for nontuberculous mycobacterial cervicofacial lymphadenitis in children

    NARCIS (Netherlands)

    Lindeboom, J.A.; Lindeboom, R.; Bruijnesteijn van Coppenraet, E.S.; Kuijper, E.J.; Tuk, J.; Prins, J.M.

    2009-01-01

    One hundred children with microbiologically proven nontuberculous mycobacterial cervicofacial lymphadenitis were randomly assigned to excision of the involved lymph nodes, or antibiotic therapy consisting of clarithromycin and rifabutin. The esthetic outcome was rated using a revised and weighted

  14. A Novel Technique of Branchial Fistula Tract Delineation and Excision In Children Allergic To Dyes

    Directory of Open Access Journals (Sweden)

    Swagatam Banerjee

    2015-08-01

    Surgical excision of branchial fistulas in children with allergy to dyes can be challenging. Insertion of a polypropylene thread into the fistula tract makes its subsequent dissection easy with minimal disruption of adjacent structures.

  15. The financial burden of reexcising incompletely excised soft tissue sarcomas: a cost analysis.

    Science.gov (United States)

    Alamanda, Vignesh K; Delisca, Gadini O; Mathis, Shannon L; Archer, Kristin R; Ehrenfeld, Jesse M; Miller, Mark W; Homlar, Kelly C; Halpern, Jennifer L; Schwartz, Herbert S; Holt, Ginger E

    2013-09-01

    Although survival outcomes have been evaluated between those undergoing a planned primary excision and those undergoing a reexcision following an unplanned resection, the financial implications associated with a reexcision have yet to be elucidated. A query for financial data (professional, technical, indirect charges) for soft tissue sarcoma excisions from 2005 to 2008 was performed. A total of 304 patients (200 primary excisions and 104 reexcisions) were identified. Wilcoxon rank sum tests and χ2 or Fisher's exact tests were used to compare differences in demographics and tumor characteristics. Multivariable linear regression analyses were performed with bootstrapping techniques. The average professional charge for a primary excision was $9,694 and $12,896 for a reexcision (pfinancial burden nearly doubles.

  16. Accurate DNA assembly and genome engineering with optimized uracil excision cloning

    DEFF Research Database (Denmark)

    Cavaleiro, Mafalda; Kim, Se Hyeuk; Seppala, Susanna

    2015-01-01

    Simple and reliable DNA editing by uracil excision (a.k.a. USER cloning) has been described by several research groups, but the optimal design of cohesive DNA ends for multigene assembly remains elusive. Here, we use two model constructs based on expression of gfp and a four-gene pathway that pro......Simple and reliable DNA editing by uracil excision (a.k.a. USER cloning) has been described by several research groups, but the optimal design of cohesive DNA ends for multigene assembly remains elusive. Here, we use two model constructs based on expression of gfp and a four-gene pathway...... that produces β-carotene to optimize assembly junctions and the uracil excision protocol. By combining uracil excision cloning with a genomic integration technology, we demonstrate that up to six DNA fragments can be assembled in a one-tube reaction for direct genome integration with high accuracy, greatly...... facilitating the advanced engineering of robust cell factories....

  17. Surgical Excision of Non–Melanoma Skin Cancer in an Elderly Veteran’s Affairs Population

    Directory of Open Access Journals (Sweden)

    C. Malcolm M. Stewart, BS

    2014-12-01

    Conclusions: Although reduction of residual tumor at reexcision is noted with both BCC and even more so with SCC, the rate at which this occurs is not sufficient that a general recommendation to forgo surgical excision can be made.

  18. Orange Peel Excision of Gland: A Novel Surgical Technique for Treatment of Gynecomastia.

    Science.gov (United States)

    S S, Shirol

    2016-12-01

    Gynecomastia is a common aesthetic problem faced by men with reported incidence as high as 65% with serious psychosocial impact. Although various techniques of liposculpture combined with glandular excision is the standard of treatment, many of the glandular excision techniques have inherent limitations and complications such as leaving a long scar, long operative time, contour abnormalities, and increased risk of hematoma. Here, we describe an innovative "the orange peel excision of gland (OPEG) technique" which overcomes these limitations with excellent cosmetic results. A total of 38 breasts were operated in 20 patients (18 bilateral and 2 unilateral). All the patients underwent suction-assisted liposuction and glandular excision under general anesthesia by our OPEG technique. The average operative time per breast was 60 minutes. One patient had a small hematoma which did not require evacuation. The patient satisfaction rate was 95%. The technique has reduced operative time and avoids residual gland and hematoma with excellent aesthetic outcome.

  19. Surgical Excision of Benign Papillomas Diagnosed with Core Biopsy: A Community Hospital Approach

    International Nuclear Information System (INIS)

    Rozentsvayg, Eka; Carver, Kristen; Borkar, Sunita; Mathew, Melvy; Enis, Sean; Friedman, Paul

    2011-01-01

    Our goal was to assess the value of surgical excision of benign papillomas of the breast diagnosed on percutaneous core biopsy by determining the frequency of upgrade to malignancies and high risk lesions on a final surgical pathology. We reviewed 67 patients who had biopsies yielding benign papilloma and underwent subsequent surgical excision. Surgical pathology of the excised lesions was compared with initial core biopsy pathology results. 54 patients had concordant benign core and excisional pathology. Cancer (ductal carcinoma in situ and invasive ductal carcinoma) was diagnosed in five (7%) patients. Surgery revealed high-risk lesions in 8 (12%) patients, including atypical ductal hyperplasia, atypical lobular hyperplasia, and lobular carcinoma in situ. Cancer and high risk lesions accounted for 13 (19%) upstaging events from benign papilloma diagnosis. Our data suggests that surgical excision is warranted with core pathology of benign papilloma

  20. Evaluation of endoscopic laser excision of polypropylene mesh/sutures following anti-incontinence procedures.

    LENUS (Irish Health Repository)

    Davis, N F

    2012-11-01

    We reviewed our experience with and outcome of the largest series to our knowledge of patients who underwent endoscopic laser excision of eroded polypropylene mesh or sutures as a complication of previous anti-incontinence procedures.

  1. Incomplete excision repair process after UV-irradiation in MUT-mutants of Proteus mirabillis

    International Nuclear Information System (INIS)

    Stoerl, K.

    1977-01-01

    MUT-mutants of P. mirabilis seem to be able to perform the incision step in the course of excision repair. In contrast to the corresponding wildtype strains with MUT-mutants the number of single-strand breaks formed after UV-irradiation is independent of the UV-dose up to about 720 erg/mm 2 . Incubation in minimal medium over a longer time does not result in completion of excision repair; about 3-6 single-strand breaks in the DNA of these mutants remain open. Likewise, the low molecular weight of the newly synthesized daughter DNA confirms an incompletely proceeding or delayed repair process. As a possible reason for the mutator phenotype an alteration of the DNA-polymerase playing a role in excision and resynthesis steps of excision repair is discussed. (author)

  2. Endoscopic excision of a lateral ventricular epidermoid—A case report of a novel technique

    Directory of Open Access Journals (Sweden)

    Arjun Shetty

    2014-01-01

    CONCLUSION: A multi portal endoscope that allows use of routine pituitary instruments would enable the surgeon to achieve haemostasis effectively and, in our opinion, should be a viable alternative to microscope for excision of intra ventricular tumours.

  3. Harmonisation of Excise Duties on Energy Products and Electricity in Central and Eastern European Countries

    OpenAIRE

    Ma?cu Simona; Burlacu Valentin; Cojocaru Diana

    2013-01-01

    The field of excise duty taxes focuses on the use of these economic instruments designed by the European law in the context of protecting the environment and public health and to establish a prudent and rational utilisation of natural resources. Focusing mainly on deriving and explaining economic impacts of the minimum energy taxes rates corresponding to the EU Directive (2003/96/EC) in CEE countries, this article outlines the degree of harmonisation of excise duty on energy products among th...

  4. Deficiency of gamma-ray excision repair in skin fibroblasts from patients with Fanconi's anemia

    International Nuclear Information System (INIS)

    Remsen, J.F.; Cerutti, P.A.

    1976-01-01

    The capacity of preparations of skin fibroblasts from normal individuals and patients with Fanconi's anemia to excise gamma-ray products of the 5,6-dihydroxydihydrothymine type from exogenous DNA was investigated. The excision capacity of whole-cell homogenates of fibroblasts from two of four patients with Fanconi's anemia was substantially below normal. This repair deficiency was further pronounced in nuclear preparations from cells of the same two patients

  5. A history of the DNA repair and mutagenesis field: The discovery of base excision repair.

    Science.gov (United States)

    Friedberg, Errol C

    2016-01-01

    This article reviews the early history of the discovery of an DNA repair pathway designated as base excision repair (BER), since in contrast to the enzyme-catalyzed removal of damaged bases from DNA as nucleotides [called nucleotide excision repair (NER)], BER involves the removal of damaged or inappropriate bases, such as the presence of uracil instead of thymine, from DNA as free bases. Copyright © 2015. Published by Elsevier B.V.

  6. Management of post-traumatic elbow instability after failed radial head excision: A case report

    OpenAIRE

    Touloupakis, Georgios; Theodorakis, Emmanouil; Favetti, Fabio; Nannerini, Massimiliano

    2017-01-01

    Radial head excision has always been a safe commonly used surgical procedure with a satisfactory clinical outcome for isolated comminuted radial head fractures. However, diagnosis of elbow instability is still very challenging and often underestimated in routine orthopaedic evaluation. We present the case of a 21-years old female treated with excision after radial head fracture, resulting in elbow instability. The patient underwent revision surgery after four weeks. We believe that ligament r...

  7. Is surgical excision necessary for the treatment of Granulomatous lobular mastitis?

    Science.gov (United States)

    Shin, Young Duck; Park, Sung Su; Song, Young Jin; Son, Seung-Myoung; Choi, Young Jin

    2017-07-24

    We aimed to investigate the role of surgical excision in treating granulomatous lobular mastitis. We performed a retrospective chart review of patients with granulomatous lobular mastitis treated from March 2008 to March 2014. We analyzed clinical features and therapeutic modalities and compared the patient outcomes based on treatment. During the study period, a total of 34 patients were diagnosed with granulomatous lobular mastitis and treated. Initial treatments included wide excision (18), oral steroids after incision and drainage (14), and antibiotic therapy (2). The patients receiving only antibiotic therapy showed no improvement after 1 month and wide excision was then performed. Wide excision resulted in nine case of delayed wound healing with fistula. These patients were treated with oral steroids for 1.5-5 months, with subsequent improvement. Overall, 11 out of 20 patients who had underwent wide excision showed improvement without additional treatment. Fourteen patients who had initially received oral steroids for 1 to 6 months (average, 2.8 months) after incision and drainage showed complete remission. During the median follow-up period with 45.5 months (range, 22-98 months), six patients (17.6%) experienced recurrence. Wide excision group experienced recurrence in five (25%) and steroid and drainage group experienced recurrence in one (7.1%). All six recurrences responded to additional steroid therapy for average 3.5 months. Most wide excision group left extensive breast scarring with deformation that was not in steroid and drainage group. Wide excision resulted high recurrence than steroid and drainage group and left extensive scarring. Steroid therapy with or without abscess drainage may be the first choice of treatment for majority cases with granulomatous lobular mastitis.

  8. Re-excision rates after breast conserving surgery following the 2014 SSO-ASTRO guidelines.

    Science.gov (United States)

    Heelan Gladden, Alicia A; Sams, Sharon; Gleisner, Ana; Finlayson, Christina; Kounalakis, Nicole; Hosokawa, Patrick; Brown, Regina; Chong, Tae; Mathes, David; Murphy, Colleen

    2017-12-01

    In 2014, SSO-ASTRO published guidelines which recommended "no ink on tumor" as adequate margins for patients undergoing breast conservation for invasive breast cancer. In 2016, new SSO-ASTRO-ASCO guidelines recommended 2 mm margins for DCIS. We evaluated whether these guidelines affected re-excision rates at our institution. Patients treated with breast conservation surgery from January 1, 2010-March 1, 2016 were identified. Re-excision rates, tumor characteristics, and presence of residual disease were recorded. The 2016 guidelines were retrospectively applied to the same cohort and expected re-excision rates calculated. Re-excision rates did not significantly decline before and after 2014 guideline adoption (11.9% before, 10.9% after; p = 0.65) or when the 2016 guidelines were retrospectively applied (8.4%; p = 0.10). The 2014 and 2016 guidelines had minimal impact on our re-excision rates, as most re-excisions were done for DCIS and 2016 guidelines supported our prior institutional practices of 2 mm margins for these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Three surgical planes identified in laparoscopic complete mesocolic excision for right-sided colon cancer.

    Science.gov (United States)

    Zhu, Da-Jian; Chen, Xiao-Wu; OuYang, Man-Zhao; Lu, Yan

    2016-01-12

    Complete mesocolic excision provides a correct anatomical plane for colon cancer surgery. However, manifestation of the surgical plane during laparoscopic complete mesocolic excision versus in computed tomography images remains to be examined. Patients who underwent laparoscopic complete mesocolic excision for right-sided colon cancer underwent an abdominal computed tomography scan. The spatial relationship of the intraoperative surgical planes were examined, and then computed tomography reconstruction methods were applied. The resulting images were analyzed. In 44 right-sided colon cancer patients, the surgical plane for laparoscopic complete mesocolic excision was found to be composed of three surgical planes that were identified by computed tomography imaging with cross-sectional multiplanar reconstruction, maximum intensity projection, and volume reconstruction. For the operations performed, the mean bleeding volume was 73±32.3 ml and the mean number of harvested lymph nodes was 22±9.7. The follow-up period ranged from 6-40 months (mean 21.2), and only two patients had distant metastases. The laparoscopic complete mesocolic excision surgical plane for right-sided colon cancer is composed of three surgical planes. When these surgical planes were identified, laparoscopic complete mesocolic excision was a safe and effective procedure for the resection of colon cancer.

  10. Anti-Plasmodium activity of ceramide analogs

    Directory of Open Access Journals (Sweden)

    Gatt Shimon

    2004-12-01

    Full Text Available Abstract Background Sphingolipids are key molecules regulating many essential functions in eukaryotic cells and ceramide plays a central role in sphingolipid metabolism. A sphingolipid metabolism occurs in the intraerythrocytic stages of Plasmodium falciparum and is associated with essential biological processes. It constitutes an attractive and potential target for the development of new antimalarial drugs. Methods The anti-Plasmodium activity of a series of ceramide analogs containing different linkages (amide, methylene or thiourea linkages between the fatty acid part of ceramide and the sphingoid core was investigated in culture and compared to the sphingolipid analog PPMP (d,1-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol. This analog is known to inhibit the parasite sphingomyelin synthase activity and block parasite development by preventing the formation of the tubovesicular network that extends from the parasitophorous vacuole to the red cell membrane and delivers essential extracellular nutrients to the parasite. Results Analogs containing methylene linkage showed a considerably higher anti-Plasmodium activity (IC50 in the low nanomolar range than PPMP and their counterparts with a natural amide linkage (IC50 in the micromolar range. The methylene analogs blocked irreversibly P. falciparum development leading to parasite eradication in contrast to PPMP whose effect is cytostatic. A high sensitivity of action towards the parasite was observed when compared to their effect on the human MRC-5 cell growth. The toxicity towards parasites did not correlate with the inhibition by methylene analogs of the parasite sphingomyelin synthase activity and the tubovesicular network formation, indicating that this enzyme is not their primary target. Conclusions It has been shown that ceramide analogs were potent inhibitors of P. falciparum growth in culture. Interestingly, the nature of the linkage between the fatty acid part and the

  11. The future of vitamin D analogs

    Directory of Open Access Journals (Sweden)

    Carlien eLeyssens

    2014-04-01

    Full Text Available The active form of vitamin D3, 1,25-dihydroxyvitamin D3, is a major regulator of bone and calcium homeostasis. In addition, this hormone also inhibits the proliferation and stimulates the differentiation of normal as well as malignant cells. Supraphysiological doses of 1,25-dihydroxyvitamin D3 are required to reduce cancer cell proliferation. However, these doses will lead in vivo to calcemic side effects such as hypercalcemia and hypercalciuria. During the last 25 years, many structural analogs of 1,25-dihydroxyvitamin D3 have been synthesized by the introduction of chemical modifications in the A-ring, central CD-ring region or side chain of 1,25-dihydroxyvitamin D3 in the hope to find molecules with a clear dissociation between the beneficial antiproliferative effects and adverse calcemic side effects. One example of such an analog with a good dissociation ratio is calcipotriol (DaivonexR, which is clinically used to treat the hyperproliferative skin disease psoriasis. Other vitamin D analogs were clinically approved for the treatment of osteoporosis or secondary hyperparathyroidism. No vitamin D analog is currently used in the clinic for the treatment of cancer although several analogs have been shown to be potent drugs in animal models of cancer. Omics studies as well as in vitro cell biological experiments unraveled basic mechanisms involved in the antineoplastic effects of vitamin D and its analogs. 1,25-dihydroxyvitamin D3 and analogs act in a cell type- and tissue-specific manner. Moreover, a blockade in the transition of the G0/1 towards S phase of the cell cycle, induction of apoptosis, inhibition of migration and invasion of tumor cells together with effects on angiogenesis and inflammation have been implicated in the pleiotropic effects of 1,25-dihydroxyvitamin D3 and its analogs. In this review we will give an overview of the action of vitamin D analogs in tumor cells and look forward how these compounds could be introduced in the

  12. NaturAnalogs for the Unsaturated Zone

    Energy Technology Data Exchange (ETDEWEB)

    A. Simmons; A. Unger; M. Murrell

    2000-03-08

    The purpose of this Analysis/Model Report (AMR) is to document natural and anthropogenic (human-induced) analog sites and processes that are applicable to flow and transport processes expected to occur at the potential Yucca Mountain repository in order to build increased confidence in modeling processes of Unsaturated Zone (UZ) flow and transport. This AMR was prepared in accordance with ''AMR Development Plan for U0135, Natural Analogs for the UZ'' (CRWMS 1999a). Knowledge from analog sites and processes is used as corroborating information to test and build confidence in flow and transport models of Yucca Mountain, Nevada. This AMR supports the Unsaturated Zone (UZ) Flow and Transport Process Model Report (PMR) and the Yucca Mountain Site Description. The objectives of this AMR are to test and build confidence in the representation of UZ processes in numerical models utilized in the UZ Flow and Transport Model. This is accomplished by: (1) applying data from Boxy Canyon, Idaho in simulations of UZ flow using the same methodologies incorporated in the Yucca Mountain UZ Flow and Transport Model to assess the fracture-matrix interaction conceptual model; (2) Providing a preliminary basis for analysis of radionuclide transport at Pena Blanca, Mexico as an analog of radionuclide transport at Yucca Mountain; and (3) Synthesizing existing information from natural analog studies to provide corroborating evidence for representation of ambient and thermally coupled UZ flow and transport processes in the UZ Model.

  13. Analog forecasting with dynamics-adapted kernels

    Science.gov (United States)

    Zhao, Zhizhen; Giannakis, Dimitrios

    2016-09-01

    Analog forecasting is a nonparametric technique introduced by Lorenz in 1969 which predicts the evolution of states of a dynamical system (or observables defined on the states) by following the evolution of the sample in a historical record of observations which most closely resembles the current initial data. Here, we introduce a suite of forecasting methods which improve traditional analog forecasting by combining ideas from kernel methods developed in harmonic analysis and machine learning and state-space reconstruction for dynamical systems. A key ingredient of our approach is to replace single-analog forecasting with weighted ensembles of analogs constructed using local similarity kernels. The kernels used here employ a number of dynamics-dependent features designed to improve forecast skill, including Takens’ delay-coordinate maps (to recover information in the initial data lost through partial observations) and a directional dependence on the dynamical vector field generating the data. Mathematically, our approach is closely related to kernel methods for out-of-sample extension of functions, and we discuss alternative strategies based on the Nyström method and the multiscale Laplacian pyramids technique. We illustrate these techniques in applications to forecasting in a low-order deterministic model for atmospheric dynamics with chaotic metastability, and interannual-scale forecasting in the North Pacific sector of a comprehensive climate model. We find that forecasts based on kernel-weighted ensembles have significantly higher skill than the conventional approach following a single analog.

  14. Analogy, higher order thinking, and education.

    Science.gov (United States)

    Richland, Lindsey Engle; Simms, Nina

    2015-01-01

    Analogical reasoning, the ability to understand phenomena as systems of structured relationships that can be aligned, compared, and mapped together, plays a fundamental role in the technology rich, increasingly globalized educational climate of the 21st century. Flexible, conceptual thinking is prioritized in this view of education, and schools are emphasizing 'higher order thinking', rather than memorization of a cannon of key topics. The lack of a cognitively grounded definition for higher order thinking, however, has led to a field of research and practice with little coherence across domains or connection to the large body of cognitive science research on thinking. We review literature on analogy and disciplinary higher order thinking to propose that relational reasoning can be productively considered the cognitive underpinning of higher order thinking. We highlight the utility of this framework for developing insights into practice through a review of mathematics, science, and history educational contexts. In these disciplines, analogy is essential to developing expert-like disciplinary knowledge in which concepts are understood to be systems of relationships that can be connected and flexibly manipulated. At the same time, analogies in education require explicit support to ensure that learners notice the relevance of relational thinking, have adequate processing resources available to mentally hold and manipulate relations, and are able to recognize both the similarities and differences when drawing analogies between systems of relationships. © 2015 John Wiley & Sons, Ltd.

  15. An analog silicon retina with multichip configuration.

    Science.gov (United States)

    Kameda, Seiji; Yagi, Tetsuya

    2006-01-01

    The neuromorphic silicon retina is a novel analog very large scale integrated circuit that emulates the structure and the function of the retinal neuronal circuit. We fabricated a neuromorphic silicon retina, in which sample/hold circuits were embedded to generate fluctuation-suppressed outputs in the previous study [1]. The applications of this silicon retina, however, are limited because of a low spatial resolution and computational variability. In this paper, we have fabricated a multichip silicon retina in which the functional network circuits are divided into two chips: the photoreceptor network chip (P chip) and the horizontal cell network chip (H chip). The output images of the P chip are transferred to the H chip with analog voltages through the line-parallel transfer bus. The sample/hold circuits embedded in the P and H chips compensate for the pattern noise generated on the circuits, including the analog communication pathway. Using the multichip silicon retina together with an off-chip differential amplifier, spatial filtering of the image with an odd- and an even-symmetric orientation selective receptive fields was carried out in real time. The analog data transfer method in the present multichip silicon retina is useful to design analog neuromorphic multichip systems that mimic the hierarchical structure of neuronal networks in the visual system.

  16. A fast multichannel analog storage system

    International Nuclear Information System (INIS)

    Freytag, D.R.

    1983-01-01

    A Multichannel Analog Storage System based on a commercial 32-channel parallel in/serial out (PISO) analog shift register is described. The basic unit is a single width CAMAC module containing 512 analog cells and the associated logic for data storage and subsequent readout. At sampling rates of up to 30 MHz the signals are strobed directly into the PISO. At higher rates signals are strobed into a fast presampling stage and subsequently transferred in block form into an array of PISO's. Sampling rates of 300 MHz have been achieved with the present device and 1000 MHz are possible with improved signal drivers. The system is well suited for simultaneous handling of many signal channels with moderate numbers of samples in each channel. RMS noise over full scale signal has been measured as 1:3000 (approx. =11 bit). However, nonlinearities in the response and differences in sensitivity of the analog cells require an elaborate calibration system in order to realize 11 bit accuracy for the analog information

  17. Neurotoxic Alkaloids: Saxitoxin and Its Analogs

    Directory of Open Access Journals (Sweden)

    Troco K. Mihali

    2010-07-01

    Full Text Available Saxitoxin (STX and its 57 analogs are a broad group of natural neurotoxic alkaloids, commonly known as the paralytic shellfish toxins (PSTs. PSTs are the causative agents of paralytic shellfish poisoning (PSP and are mostly associated with marine dinoflagellates (eukaryotes and freshwater cyanobacteria (prokaryotes, which form extensive blooms around the world. PST producing dinoflagellates belong to the genera Alexandrium, Gymnodinium and Pyrodinium whilst production has been identified in several cyanobacterial genera including Anabaena, Cylindrospermopsis, Aphanizomenon Planktothrix and Lyngbya. STX and its analogs can be structurally classified into several classes such as non-sulfated, mono-sulfated, di-sulfated, decarbamoylated and the recently discovered hydrophobic analogs—each with varying levels of toxicity. Biotransformation of the PSTs into other PST analogs has been identified within marine invertebrates, humans and bacteria. An improved understanding of PST transformation into less toxic analogs and degradation, both chemically or enzymatically, will be important for the development of methods for the detoxification of contaminated water supplies and of shellfish destined for consumption. Some PSTs also have demonstrated pharmaceutical potential as a long-term anesthetic in the treatment of anal fissures and for chronic tension-type headache. The recent elucidation of the saxitoxin biosynthetic gene cluster in cyanobacteria and the identification of new PST analogs will present opportunities to further explore the pharmaceutical potential of these intriguing alkaloids.

  18. Natural Analogs for the Unsaturated Zone

    International Nuclear Information System (INIS)

    Simmons, A.; Unger, A.; Murrell, M.

    2000-01-01

    The purpose of this Analysis/Model Report (AMR) is to document natural and anthropogenic (human-induced) analog sites and processes that are applicable to flow and transport processes expected to occur at the potential Yucca Mountain repository in order to build increased confidence in modeling processes of Unsaturated Zone (UZ) flow and transport. This AMR was prepared in accordance with ''AMR Development Plan for U0135, Natural Analogs for the UZ'' (CRWMS 1999a). Knowledge from analog sites and processes is used as corroborating information to test and build confidence in flow and transport models of Yucca Mountain, Nevada. This AMR supports the Unsaturated Zone (UZ) Flow and Transport Process Model Report (PMR) and the Yucca Mountain Site Description. The objectives of this AMR are to test and build confidence in the representation of UZ processes in numerical models utilized in the UZ Flow and Transport Model. This is accomplished by: (1) applying data from Boxy Canyon, Idaho in simulations of UZ flow using the same methodologies incorporated in the Yucca Mountain UZ Flow and Transport Model to assess the fracture-matrix interaction conceptual model; (2) Providing a preliminary basis for analysis of radionuclide transport at Pena Blanca, Mexico as an analog of radionuclide transport at Yucca Mountain; and (3) Synthesizing existing information from natural analog studies to provide corroborating evidence for representation of ambient and thermally coupled UZ flow and transport processes in the UZ Model

  19. Incidental intraductal papillomas (breast diagnosed on needle core biopsy do not need to be excised.

    Science.gov (United States)

    Jaffer, Shabnam; Bleiweiss, Ira J; Nagi, Chandandeep

    2013-01-01

    Most authors recommend excision of intraductal papillomas diagnosed on core needle biopsy. This leads to the question of whether or not excision is necessary for incidental intraductal papillomas on core needle biopsy as opposed to those corresponding to imaging findings. Using the pathology computerized data base we retrospectively identified 46 incidental intraductal papillomas diagnosed on core needle biopsy from 1/2000 to 12/2008. Clinical, radiologic, and pathologic information was gathered and correlated. All core needle biopsies were reviewed to confirm the diagnosis of incidental intraductal papillomas, and excision specimens reviewed when available. Of the 46 patients, follow-up information was available in only 38. The age of the patients ranged from 39 to 82 years (mean = 48 years). Most incidental intraductal papillomas were diagnosed by mammotome core needle biopsy (36 cases). A total of 33 cases were performed for calcifications with the following indications: clustered = 21, new = 4, pleomorphic = 3, increasing = 3, indeterminant = 2. The correlating diagnoses included the following: fibrocystic changes with calcium phosphate = 18 or calcium oxalate = 10, fibroadenoma with calcifications = 5. The three masses were: two cases of cystic papillary apocrine metaplasia (I Ultrasound and 1 MRI) and 1 fibroadenoma (Ultrasound). In all cases, the intraductal papillomas were ≤0.2 cm, were not associated with calcifications, and were incidental to them or the underlying mass. A total of 14 patients underwent excision, whereas the remaining 24 have remained radiologically stable for over 12 months. The excision specimen findings were: fibrocystic changes = 8 and intraductal papilloma = 6. With the exception of one case, all the intraductal papilloma remained incidental to imaging findings. In this solitary case, the calcifications were described as pleomorphic and corresponded to fibrocystic changes calcifications on core needle

  20. Students' Pre- and Post-Teaching Analogical Reasoning when They Draw Their Analogies

    Science.gov (United States)

    Mozzer, Nilmara Braga; Justi, Rosaria

    2012-01-01

    Analogies are parts of human thought. From them, we can acquire new knowledge or change that which already exists in our cognitive structure. In this sense, understanding the analogical reasoning process becomes an essential condition to understand how we learn. Despite the importance of such an understanding, there is no general agreement in…

  1. Changes in analogical reasoning in adulthood.

    Science.gov (United States)

    Clark, E; Gardner, M K; Brown, G; Howell, R J

    1990-01-01

    This study sought to investigate adult intellectual development through an analysis of a particular type of cognitive ability, verbal analogical reasoning. The performance of 60 individuals between the ages of 20 and 79 was compared on 100 verbal analogies. The subjects consisted of six groups of ten individuals each (five males and five females), matched as a group for education and gender. Solution times and error rates served as the dependent measures. Results showed that there was a significant trend for the older subjects (60- and 70-year-olds) to be slower than the young subjects (20-, 30-, 40-, and 50-year-olds), but not necessarily more error prone. These data suggest that verbal analogical reasoning changes with age. Supplemental data demonstrated a change in other abilities as well (i.e., decline in perceptual-motor speed and spatial skill).

  2. Electronic devices for analog signal processing

    CERN Document Server

    Rybin, Yu K

    2012-01-01

    Electronic Devices for Analog Signal Processing is intended for engineers and post graduates and considers electronic devices applied to process analog signals in instrument making, automation, measurements, and other branches of technology. They perform various transformations of electrical signals: scaling, integration, logarithming, etc. The need in their deeper study is caused, on the one hand, by the extension of the forms of the input signal and increasing accuracy and performance of such devices, and on the other hand, new devices constantly emerge and are already widely used in practice, but no information about them are written in books on electronics. The basic approach of presenting the material in Electronic Devices for Analog Signal Processing can be formulated as follows: the study with help from self-education. While divided into seven chapters, each chapter contains theoretical material, examples of practical problems, questions and tests. The most difficult questions are marked by a diamon...

  3. Electrical analog of a Josephson junction

    International Nuclear Information System (INIS)

    Goldman, A.M.

    1979-01-01

    It is noted that a mathematical description of the phase-coupling of two oscillators synchronized by a phase-lock-loop under the influence of thermal white noise is analogous to that of the phase coupling of two superconductors in a Josephson junction also under the influence of noise. This analogy may be useful in studying threshold instabilities of the Josephson junction in regimes not restricted to the case of large damping. This is of interest because the behavior of the mean voltage near the threshold current can be characterized by critical exponents which resemble those exhibited by an order parameter of a continuous phase transition. As it is possible to couple a collection of oscillators together in a chain, the oscillator analogy may also be useful in exploring the dynamics and statistical mechanics of coupled junctions

  4. On Lovelock analogs of the Riemann tensor

    Science.gov (United States)

    Camanho, Xián O.; Dadhich, Naresh

    2016-03-01

    It is possible to define an analog of the Riemann tensor for Nth order Lovelock gravity, its characterizing property being that the trace of its Bianchi derivative yields the corresponding analog of the Einstein tensor. Interestingly there exist two parallel but distinct such analogs and the main purpose of this note is to reconcile both formulations. In addition we will introduce a simple tensor identity and use it to show that any pure Lovelock vacuum in odd d=2N+1 dimensions is Lovelock flat, i.e. any vacuum solution of the theory has vanishing Lovelock-Riemann tensor. Further, in the presence of cosmological constant it is the Lovelock-Weyl tensor that vanishes.

  5. Analogical reasoning for reliability analysis based on generic data

    Energy Technology Data Exchange (ETDEWEB)

    Kozin, Igor O

    1996-10-01

    The paper suggests using the systemic concept 'analogy' for the foundation of an approach to analyze system reliability on the basis of generic data, describing the method of structuring the set that defines analogical models, an approach of transition from the analogical model to a reliability model and a way of obtaining reliability intervals of analogous objects.

  6. Analogical reasoning for reliability analysis based on generic data

    International Nuclear Information System (INIS)

    Kozin, Igor O.

    1996-01-01

    The paper suggests using the systemic concept 'analogy' for the foundation of an approach to analyze system reliability on the basis of generic data, describing the method of structuring the set that defines analogical models, an approach of transition from the analogical model to a reliability model and a way of obtaining reliability intervals of analogous objects

  7. Analogy-Enhanced Instruction: Effects on Reasoning Skills in Science

    Science.gov (United States)

    Remigio, Krisette B.; Yangco, Rosanelia T.; Espinosa, Allen A.

    2014-01-01

    The study examined the reasoning skills of first year high school students after learning general science concepts through analogies. Two intact heterogeneous sections were randomly assigned to Analogy-Enhanced Instruction (AEI) group and Non Analogy-Enhanced (NAEI) group. Various analogies were incorporated in the lessons of the AEI group for…

  8. Perceptions of Rebuttal Analogy: Politeness and Implications for Persuasion.

    Science.gov (United States)

    Whaley, Bryan B.

    1997-01-01

    States that recent theorizing about the role of analogy in persuasion suggests that "rebuttal" analogy addresses two communicative functions by serving as argument and a method of social attack. Examines message receivers' perceptions of rebuttal analogy and rebuttal analogy users. Finds that participants perceived the communicator using…

  9. The spectrum of skin biopsies and excisions in a pediatric skin center.

    Science.gov (United States)

    Theiler, Martin; Neuhaus, Kathrin; Kerl, Katrin; Weibel, Lisa

    2017-12-01

    Little is known about the spectrum of pediatric skin disorders requiring biopsy/excision, their indication, impact on further management, and the accuracy of clinical diagnosis. We aimed to address these questions in the patient population seen at our Swiss University referral center for Pediatric Dermatology and Plastic Surgery. All skin biopsies/excisions performed in patients aged ≤ 16 years over a period of 2 years were retrospectively analyzed. A total of 506 samples were included. The majority of biopsies/excisions (n = 413, 82%) was performed for tumors, cysts, and hamartomas and 18% for other skin conditions. Malignant tumors were found in 12 samples (2%) from four patients. In 121 (24%) patients, the histopathology had an important impact on patient management. In 80 (16%) cases, the pathology did not match with the clinical diagnosis. In 382 (75%) cases, excision was the treatment of choice. Of these, the indication for surgery was based on patient's request in 181 (47%) cases. Surgical interventions for pediatric skin disorders are performed for diagnostic and therapeutic reasons. In this cohort, histopathology was essential for treatment in one quarter of cases. Skin tumors, cysts, and hamartomas often require excision during childhood, with families' request and esthetic considerations playing an important role. What is Known: • The spectrum of pediatric skin conditions has been studied in outpatient, inpatient, and emergency settings. • In contrast, no data exist on the spectrum of pediatric skin disorders undergoing biopsy/excision specifically. What is New: • We analyze biopsies/excisions in children, focusing on diagnosis, indication, and impact on patient management. • Surgical interventions for skin disorders in children are often performed for tumors and hamartomas with esthetic considerations playing a relevant role. If used for diagnostic purposes, they are often performed to confirm or rule out severe skin disease.

  10. The effect of excise tax increases on cigarette prices in South Africa.

    Science.gov (United States)

    Linegar, Daniel J; van Walbeek, Corne

    2018-01-01

    The effectiveness of excise tax increases as a tool for reducing tobacco consumption depends largely on how the tax increases impact the retail price. We estimate this relationship in South Africa for 2001-2015. Statistics South Africa provided disaggregated cigarette price data, used in the calculation of the Consumers' Price Index. Data on the excise tax per cigarette were obtained from Budget Reviews prepared by the National Treasury of South Africa. Regression equations were estimated for each month. The month-on-month change in cigarette prices in February through April was regressed against March's excise tax change to estimate the pass-through coefficient. For the other 9 months, the month-on-month change in cigarette price was regressed against monthly dummy variables to determine the size of the non-tax-related price increase in each of these months. The analysis was performed in both nominal and real (inflation-adjusted) terms. Expressed in real terms, the excise tax was undershifted. A R1.00 (one rand) increase in the excise tax is associated with an increase in the retail price of cigarettes of R0.90 in the pre-2010 period, and R0.49 in the post-2010 period. In the pre-2010 period, the tobacco industry increased the retail price of cigarettes in July/August, independent of the excise tax increase. The discretionary July/August price increases largely disappeared after 2010, primarily because the market became more competitive. The degree of excise tax pass-through, and the magnitude of discretionary increases in cigarette prices, is significantly determined by the competitive environment in the cigarette market. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. The effect of excise tax increases on cigarette prices in South Africa

    Science.gov (United States)

    Linegar, Daniel J; van Walbeek, Corne

    2018-01-01

    Introduction The effectiveness of excise tax increases as a tool for reducing tobacco consumption depends largely on how the tax increases impact the retail price. We estimate this relationship in South Africa for 2001–2015. Data Statistics South Africa provided disaggregated cigarette price data, used in the calculation of the Consumers’ Price Index. Data on the excise tax per cigarette were obtained from Budget Reviews prepared by the National Treasury of South Africa. Methods Regression equations were estimated for each month. The month-on-month change in cigarette prices in February through April was regressed against March’s excise tax change to estimate the pass-through coefficient. For the other 9 months, the month-on-month change in cigarette price was regressed against monthly dummy variables to determine the size of the non-tax-related price increase in each of these months. The analysis was performed in both nominal and real (inflation-adjusted) terms. Findings Expressed in real terms, the excise tax was undershifted. A R1.00 (one rand) increase in the excise tax is associated with an increase in the retail price of cigarettes of R0.90 in the pre-2010 period, and R0.49 in the post-2010 period. In the pre-2010 period, the tobacco industry increased the retail price of cigarettes in July/August, independent of the excise tax increase. The discretionary July/August price increases largely disappeared after 2010, primarily because the market became more competitive. Conclusion The degree of excise tax pass-through, and the magnitude of discretionary increases in cigarette prices, is significantly determined by the competitive environment in the cigarette market. PMID:28341767

  12. Words, Concepts, and the Geometry of Analogy

    Directory of Open Access Journals (Sweden)

    Stephen McGregor

    2016-08-01

    Full Text Available This paper presents a geometric approach to the problem of modelling the relationship between words and concepts, focusing in particular on analogical phenomena in language and cognition. Grounded in recent theories regarding geometric conceptual spaces, we begin with an analysis of existing static distributional semantic models and move on to an exploration of a dynamic approach to using high dimensional spaces of word meaning to project subspaces where analogies can potentially be solved in an online, contextualised way. The crucial element of this analysis is the positioning of statistics in a geometric environment replete with opportunities for interpretation.

  13. Analogical reasoning abilities of recovering alcoholics.

    Science.gov (United States)

    Gardner, M K; Clark, E; Bowman, M A; Miller, P J

    1989-08-01

    This study investigated analogical reasoning abilities of alcoholics who had been abstinent from alcohol for at least 1 year. Their performance was compared to that of nonalcoholic controls matched as a group for education, age, and gender. Solution times and error rates were modeled using a regression model. Results showed a nonsignificant trend for alcoholics to be faster, but more error prone, than controls. The same componential model applied to both groups, and fit them equally well. Although differences have been found in analogical reasoning ability between controls and alcoholics immediately following detoxification, we find no evidence of differences after extended periods of sobriety.

  14. Analogy in systems management: a theoretical inquiry

    Energy Technology Data Exchange (ETDEWEB)

    Silverman, B.G.

    1983-11-01

    This theoretical analysis of the intuitive and diffuse characteristics of analogical reasoning processes is the first step in a research effort intended to lead to: understanding of common (and possibly costly) errors, pitfalls, travails, and problem-solving impediments; possible recommendations for improvements to organizational structures, control and coordination processes, and management information flows, and guidelines for a generalized analogical reasoning support framework (e.g., a handbook, a knowledge bank design, and/or even a software package/artificial intelligence program). 233 references.

  15. Analysis of Recurrent Analog Neural Networks

    Directory of Open Access Journals (Sweden)

    Z. Raida

    1998-06-01

    Full Text Available In this paper, an original rigorous analysis of recurrent analog neural networks, which are built from opamp neurons, is presented. The analysis, which comes from the approximate model of the operational amplifier, reveals causes of possible non-stable states and enables to determine convergence properties of the network. Results of the analysis are discussed in order to enable development of original robust and fast analog networks. In the analysis, the special attention is turned to the examination of the influence of real circuit elements and of the statistical parameters of processed signals to the parameters of the network.

  16. Analogy Mapping Development for Learning Programming

    Science.gov (United States)

    Sukamto, R. A.; Prabawa, H. W.; Kurniawati, S.

    2017-02-01

    Programming skill is an important skill for computer science students, whereas nowadays, there many computer science students are lack of skills and information technology knowledges in Indonesia. This is contrary with the implementation of the ASEAN Economic Community (AEC) since the end of 2015 which is the qualified worker needed. This study provided an effort for nailing programming skills by mapping program code to visual analogies as learning media. The developed media was based on state machine and compiler principle and was implemented in C programming language. The state of every basic condition in programming were successful determined as analogy visualization.

  17. Design of analog integrated circuits and systems

    CERN Document Server

    Laker, Kenneth R

    1994-01-01

    This text is designed for senior or graduate level courses in analog integrated circuits or design of analog integrated circuits. This book combines consideration of CMOS and bipolar circuits into a unified treatment. Also included are CMOS-bipolar circuits made possible by BiCMOS technology. The text progresses from MOS and bipolar device modelling to simple one and two transistor building block circuits. The final two chapters present a unified coverage of sample-data and continuous-time signal processing systems.

  18. High-speed and high-resolution analog-to-digital and digital-to-analog converters

    NARCIS (Netherlands)

    van de Plassche, R.J.

    1989-01-01

    Analog-to-digital and digital-to-analog converters are important building blocks connecting the analog world of transducers with the digital world of computing, signal processing and data acquisition systems. In chapter two the converter as part of a system is described. Requirements of analog

  19. Process and circuiting arrangement for the conversion of analog signals to digital signals and digital signals to analog signals

    International Nuclear Information System (INIS)

    Wintzer, K.

    1977-01-01

    Process for analog-to-digital and digital-to-analog conversion in telecommunication systems whose outstations each have an analog transmitter and an analog receiver. The invention illustrates a method of reducing the power demand of the converters at times when no conversion processes take place. (RW) [de

  20. Pathogenicity Island Cross Talk Mediated by Recombination Directionality Factors Facilitates Excision from the Chromosome.

    Science.gov (United States)

    Carpenter, Megan R; Rozovsky, Sharon; Boyd, E Fidelma

    2015-12-14

    Pathogenicity islands (PAIs) are mobile integrated genetic elements (MIGEs) that contain a diverse range of virulence factors and are essential in the evolution of pathogenic bacteria. PAIs are widespread among bacteria and integrate into the host genome, commonly at a tRNA locus, via integrase-mediated site-specific recombination. The excision of PAIs is the first step in the horizontal transfer of these elements and is not well understood. In this study, we examined the role of recombination directionality factors (RDFs) and their relationship with integrases in the excision of two PAIs essential for Vibrio cholerae host colonization: Vibrio pathogenicity island 1 (VPI-1) and VPI-2. VPI-1 does not contain an RDF, which allowed us to answer the question of whether RDFs are an absolute requirement for excision. We found that an RDF was required for efficient excision of VPI-2 but not VPI-1 and that RDFs can induce excision of both islands. Expression data revealed that the RDFs act as transcriptional repressors to both VPI-1- and VPI-2-encoded integrases. We demonstrated that the RDFs Vibrio excision factor A (VefA) and VefB bind at the attachment sites (overlapping the int promoter region) of VPI-1 and VPI-2, thus supporting this mode of integrase repression. In addition, V. cholerae RDFs are promiscuous due to their dual functions of promoting excision of both VPI-1 and VPI-2 and acting as negative transcriptional regulators of the integrases. This is the first demonstration of cross talk between PAIs mediated via RDFs which reveals the complex interactions that occur between separately acquired MIGEs. Deciphering the mechanisms of pathogenicity island excision is necessary for understanding the evolution and spread of these elements to their nonpathogenic counterparts. Such mechanistic insight would assist in predicting the mobility of uncharacterized genetic elements. This study identified extensive RDF-mediated cross talk between two nonhomologous VPIs and

  1. Inhibition of excision repair of DNA in u.v.-irradiated Escherichia coli by phenethyl alcohol

    International Nuclear Information System (INIS)

    Tachibana, A.; Yonei, S.

    1985-01-01

    Membrane-specific drugs such as procaine and chlorpromazine have been shown to inhibit excision repair of DNA in u.v.-irradiated E. coli. One possible mechanism is that, if association of DNA with the cell membrane is essential for excision repair, this process may be susceptible to drugs affecting the structure of cell membranes. We examined the effect of phenethyl alcohol, which is a membrane-specific drug and known to dissociate the DNA-membrane complex, on excision repair of DNA in u.v.-irradiated E. coli cells. The cells were irradiated with u.v. light and then held at 30 0 C in buffer (liquid-holding) in the presence or absence of phenethyl alcohol. It was found that phenethyl alcohol inhibits the liquid-holding recovery in both wild-type and recA strains, corresponding to its dissociating action on the DNA-membrane complex. Thus, the association of DNA with cell membrane is an important factor for excision repair in E. coli. Procaine did not show the dissociating effect, suggesting that at least two different mechanisms are responsible for the involvement of cell membrane in excision repair of DNA in E. coli. (author)

  2. Laparoscopic complete mesocolic excision via combined medial and cranial approaches for transverse colon cancer.

    Science.gov (United States)

    Mori, Shinichiro; Kita, Yoshiaki; Baba, Kenji; Yanagi, Masayuki; Tanabe, Kan; Uchikado, Yasuto; Kurahara, Hiroshi; Arigami, Takaaki; Uenosono, Yoshikazu; Mataki, Yuko; Okumura, Hiroshi; Nakajo, Akihiro; Maemura, Kosei; Natsugoe, Shoji

    2017-05-01

    To evaluate the safety and feasibility of laparoscopic complete mesocolic excision via combined medial and cranial approaches with three-dimensional visualization around the gastrocolic trunk and middle colic vessels for transverse colon cancer. We evaluated prospectively collected data of 30 consecutive patients who underwent laparoscopic complete mesocolic excision between January 2010 and December 2015, 6 of whom we excluded, leaving 24 for the analysis. We assessed the completeness of excision, operative data, pathological findings, length of large bowel resected, complications, length of hospital stay, and oncological outcomes. Complete mesocolic excision completeness was graded as the mesocolic and intramesocolic planes in 21 and 3 patients, respectively. Eleven, two, eight, and three patients had T1, T2, T3, and T4a tumors, respectively; none had lymph node metastases. A mean of 18.3 lymph nodes was retrieved, and a mean of 5.4 lymph nodes was retrieved around the origin of the MCV. The mean large bowel length was 21.9 cm, operative time 274 min, intraoperative blood loss 41 mL, and length of hospital stay 15 days. There were no intraoperative and two postoperative complications. Our procedure for laparoscopic complete mesocolic excision via combined medial and cranial approaches is safe and feasible for transverse colon cancer.

  3. Circumareolar incision-subdermal tunneling dissection for excision of multiple breast fibroadenomata

    Directory of Open Access Journals (Sweden)

    S O Agodirin

    2017-01-01

    Full Text Available Excision of multiple fibroadenomas (MF in separate breast quadrants presents difficulties of number and location of incision(s and extent of tissue dissection and may be associated with more complications and poorer cosmetic outcome. This is a report of excision of MF in multiple quadrants of the breast using a modification of subcutaneous dissection technique dubbed the circumareolar incision and subdermal tunneling (CAST dissection. After exposure of the superficial fascia with circumareolar incision, subdermal cone-wise dissection was made to allow mobilization of the segment bearing the lump(s. The lump(s were enucleated and removed. MF were removed from four breasts in three young unmarried females. The first patient had multiple adenomas removed from three quadrants of both breasts: 14 on the right and six on the left. The second patient had excision of three lumps in three separate quadrants, and the third patient had excision of two lumps in two separate quadrants. All patients had edema and bruising. One breast had wound infection and dehiscence. There were no skin necrosis, no nipple loss, and no breast distortion. All ensuing scars were camouflaged. CAST dissection was used for excision of MF in multiple quadrants of the breast with preservation of excellent cosmetic outcome of a single circumareolar incision.

  4. Transaxillary Subcutaneouscopic Excision of Fibroadenoma of the Breast in Children: The Covert Scar Approach.

    Science.gov (United States)

    Gonzalez, Mirtha; Pimpalwar, Ashwin

    2016-02-01

    Fibroadenoma is a common condition in adolescent girls. Most tumors are excised either through a periareolar approach or the inframammary approach. Both approaches produce visible scars in adolescent girls. We propose a new cosmetic approach to this lesion and report our experience with the transaxillary subcutaneouscopic approach for excision of the fibroadenoma of the breast. The purpose of this case report is to delineate an innovative surgical approach to resection of a breast fibroadenoma that yields an adequate resection without possible damage to the ductal system while optimizing cosmetic results by avoiding scars. We retrospectively reviewed the medical records of four adolescent girls who underwent the above approach for excision of fibroadenoma of the breast. The age range was 14-16 years. There were no complications in all 4 patients. The final result at the 3-month follow-up revealed an esthetically pleasing skin incision that healed well and was hidden by the natural skin fold of the axilla. Transaxillary subcutaneouscopic excision of fibroadenoma of the breast in children is a safe and effective technique and should be considered for excision of benign breast lesions in children.

  5. The Relationship between Tax Rate, Penalty Rate, Tax Fairness and Excise Duty Non-compliance.

    Directory of Open Access Journals (Sweden)

    Sinnasamy Perabavathi

    2017-01-01

    Full Text Available The rise of indirect tax non-compliance by taxpayers became the main concern of most of the tax authorities around the globe. In Malaysia, non complaince such as smuggling and illegal trade activities by importers involving cigarettes, liquor and imported vehicles bound under Excise Act 1976 have caused revenue losses in monetary and non-monetary aspects. Therefore, the objective of this study is to examine the relationship of tax rate, penalty rate and tax fairness of excise duty non-compliance. This study uses the Deterrence Theory as a basis theory to investigate the phenomenon of excise duty non complaince. A total of 500 excise duty offenders throughout Malaysia responded to the survey. The model was empirically tested by using Partial Least Squares (PLS with disproportionate stratified random sampling technique. The results indicated that the perception of tax rate and penalty rate are positively related while tax fairness is negatively related to excise duty non-compliance among importers.

  6. Autobiographical memory of the recent past following frontal cortex or temporal lobe excisions.

    Science.gov (United States)

    Thaiss, Laila; Petrides, Michael

    2008-08-01

    Previous research has raised questions regarding the necessity of the frontal cortex in autobiographical memory and the role that it plays in actively retrieving contextual information associated with personally relevant events. Autobiographical memory was studied in patients with unilateral excisions restricted to the frontal cortex or temporal lobe involving the amygdalo-hippocampal region and in normal controls using an event-sampling method. We examined accuracy of free recall, use of strategies during retrieval and memory for specific aspects of the autobiographical events, including temporal order. Patients with temporal lobe excisions were impaired in autobiographical recall. By contrast, patients with frontal cortical excisions exhibited normal autobiographical recall but were less likely to use temporal order spontaneously to organize event retrieval. Instruction to organize retrieval by temporal order failed to improve recall in temporal lobe patients and increased the incidence of plausible intrusion errors in left temporal patients. In contrast, patients with frontal cortical excisions now surpassed control subjects in recall of autobiographical events. Furthermore, the retrieval accuracy for the temporal order of diary events was not impaired in these patients. In a subsequent cued recall test, temporal lobe patients were impaired in their memory for the details of the diary events and their context. In conclusion, a basic impairment in autobiographical memory (including memory for temporal context) results from damage to the temporal lobe and not the frontal cortex. Patients with frontal excisions fail to use organizational strategies spontaneously to aid retrieval but can use these effectively if instructed to do so.

  7. Methane. [biosynthesis from manure or analogous substance

    Energy Technology Data Exchange (ETDEWEB)

    Ducellier, G L.R.; Isman, M A

    1949-04-19

    CH/sub 4/ is produced by the fermentation of manure or analogous substances in a vat having a dome covering the vat, the lower edge of the dome being immersed in a liquid seal, and the dome being arranged to rise vertically in order to hold the CH/sub 4/ produced.

  8. Analog voicing detector responds to pitch

    Science.gov (United States)

    Abel, R. S.; Watkins, H. E.

    1967-01-01

    Modified electronic voice encoder /Vocoder/ includes an independent analog mode of operation in addition to the conventional digital mode. The Vocoder is a bandwidth compression equipment that permits voice transmission over channels, having only a fraction of the bandwidth required for conventional telephone-quality speech transmission.

  9. Invention through Form and Function Analogy

    Science.gov (United States)

    Rule, Audrey C.

    2015-01-01

    "Invention through Form and Function Analogy" is an invention book for teachers and other leaders working with youth who are involving students in the invention process. The book consists of an introduction and set of nine learning cycle formatted lessons for teaching the principles of invention through the science and engineering design…

  10. Formal analogies in physics teacher education

    DEFF Research Database (Denmark)

    Avelar Sotomaior Karam, Ricardo; Ricardo, Elio

    2012-01-01

    the exact same appearance. Coulomb’s law’s similarity with Newton’s, Maxwell’s application of fluid theory to electromagnetism and Hamilton’s optical mechanical analogy are some among many other examples. These cases illustrate the power of mathematics in providing unifying structures for physics. Despite...

  11. An iconic, analogical approach to grammaticalization

    NARCIS (Netherlands)

    Fischer, O.; Conradie, C.J.; Johl, R.; Beukes, M.; Fischer, O.; Ljungberg, C.

    2010-01-01

    This paper addresses a number of problems connected with the ‘apparatus’ used in grammaticalization theory. It will be argued that we get a better grip on what happens in processes of grammaticalization (and its ‘opposite’, lexicalization) if the process is viewed in terms of analogical processes,

  12. Analog and digital dividers for mass spectrometers

    International Nuclear Information System (INIS)

    Osipov, A.K.

    1980-01-01

    Errors of four different types of stress dividers used in statical mass-spectrometers for determination of mass number by accelerating stress are analyzed. The simplest flowsheet of the analog divider comprises operation amplifier, in the chain of the negative feedback of which a multiplication device on differential cascade is switched- in. This analog divider has high sensitivity to temperature and high error approximately 5%. Application of the multiplier on differential cascade with normalization permits to increase temperature stability and decrease the error up to 1%. Another type of the analog divider is a logarithmic divider the error of which is constant within the whole operation range and it constitutes 1-5%. The digital divider with a digital-analog transformer (DAT) has the error of +-0.015% which is determined by the error of detectors and resistance of keys in the locked state. Considered is the design of a divider based on transformation of the inlet stress into the time period. The error of the divider is determined in this case mainly by stress of the zero shift of the operation amplifier (it should be compensated) and relative threshold stability of the comparator triggering which equals (2-3)x10 -4 . It is noted that the divider with DAT application and the divider with the use of stress transformation within the time period are most perspective ones for statical mass-spectrometers [ru

  13. Analog Experiment for rootless cone eruption

    Science.gov (United States)

    Noguchi, R.; Hamada, A.; Suzuki, A.; Kurita, K.

    2017-09-01

    Rootless cone is a unique geomorphological landmark to specify igneous origin of investigated terrane, which is formed by magma-water interaction. To understand its formation mechanism we conducted analog experiment for heat-induced vesiculation by using hot syrup and sodium bicarbonate solution.

  14. SSERVI Analog Regolith Simulant Testbed Facility

    Science.gov (United States)

    Minafra, J.; Schmidt, G. K.

    2016-12-01

    SSERVI's goals include supporting planetary researchers within NASA, other government agencies; private sector and hardware developers; competitors in focused prize design competitions; and academic sector researchers. The SSERVI Analog Regolith Simulant Testbed provides opportunities for research scientists and engineers to study the effects of regolith analog testbed research in the planetary exploration field. This capability is essential to help to understand the basic effects of continued long-term exposure to a simulated analog test environment. The current facility houses approximately eight tons of JSC-1A lunar regolith simulant in a test bin consisting of a 4 meter by 4 meter area. SSERVI provides a bridge between several groups, joining together researchers from: 1) scientific and exploration communities, 2) multiple disciplines across a wide range of planetary sciences, and 3) domestic and international communities and partnerships. This testbed provides a means of consolidating the tasks of acquisition, storage and safety mitigation in handling large quantities of regolith simulant Facility hardware and environment testing scenarios include, but are not limited to the following; Lunar surface mobility, Dust exposure and mitigation, Regolith handling and excavation, Solar-like illumination, Lunar surface compaction profile, Lofted dust, Mechanical properties of lunar regolith, and Surface features (i.e. grades and rocks) Numerous benefits vary from easy access to a controlled analog regolith simulant testbed, and planetary exploration activities at NASA Research Park, to academia and expanded commercial opportunities in California's Silicon Valley, as well as public outreach and education opportunities.

  15. A physical analogy to fuzzy clustering

    DEFF Research Database (Denmark)

    Jantzen, Jan

    2004-01-01

    This tutorial paper provides an interpretation of the membership assignment in the fuzzy clustering algorithm fuzzy c-means. The membership of a data point to several clusters is shown to be analogous to the gravitational forces between bodies of mass. This provides an alternative way to explain...

  16. A high-speed analog neural processor

    NARCIS (Netherlands)

    Masa, P.; Masa, Peter; Hoen, Klaas; Hoen, Klaas; Wallinga, Hans

    1994-01-01

    Targeted at high-energy physics research applications, our special-purpose analog neural processor can classify up to 70 dimensional vectors within 50 nanoseconds. The decision-making process of the implemented feedforward neural network enables this type of computation to tolerate weight

  17. C4913 ANALOGE OG DIGITALE FILTRE

    DEFF Research Database (Denmark)

    Gaunholt, Hans

    1996-01-01

    Theese lecture notes treats the fundamental theory and the most commonly used design methods for passive- active and digital filters with special emphasis on microelectronic realizations. The lecture notes covers 75% of the material taught in the course C4913 Analog and Digital Filters...

  18. Analog circuit design automation for performance

    NARCIS (Netherlands)

    Ning, Zhen-Qiu; Ning, Zhen-Qiu; Kole, Marq; Kole, M.E.; Mouthaan, A.J.; Wallinga, Hans

    1992-01-01

    This paper describes an improved version of the program SEAS (a Simulated Evolution approach for Analog circuit Synthesis), in which an approach for selection of alternatives based on the evaluation of mutation values is developed, and design automafion for high performance comparators is covered.

  19. Hands Together! An Analog Clock Problem

    Science.gov (United States)

    Earnest, Darrell; Radtke, Susan; Scott, Siri

    2017-01-01

    In this article, the authors first present the Hands Together! task. The mathematics in this problem concerns the relationship of hour and minute durations as reflected in the oft-overlooked proportional movements of the two hands of an analog clock. The authors go on to discuss the importance of problem solving in general. They then consider…

  20. Analog subsystem for the plutonium protection system

    International Nuclear Information System (INIS)

    Arlowe, H.D.

    1978-12-01

    An analog subsystem is described which monitors certain functions in the Plutonium Protection System. Rotary and linear potentiometer output signals are digitized, as are the outputs from thermistors and container ''bulge'' sensors. This work was sponsored by the Department of Energy/Office of Safeguards and Security (DOE/OSS) as part of the overall Sandia Fixed Facility Physical Protection Program

  1. The GMO-Nanotech (Dis)Analogy?

    Science.gov (United States)

    Sandler, Ronald; Kay, W. D.

    2006-01-01

    The genetically-modified-organism (GMO) experience has been prominent in motivating science, industry, and regulatory communities to address the social and ethical dimensions of nanotechnology. However, there are some significant problems with the GMO-nanotech analogy. First, it overstates the likelihood of a GMO-like backlash against…

  2. A Mechanical Analogy for Ohm's Law.

    Science.gov (United States)

    do Couto Tavares, Milton; And Others

    1991-01-01

    A mechanical analogy between the microscopic motion of a charged carrier in an ordinary resistor and the macroscopic motion of a ball falling along a slanted board covered with a lattice of nails is introduced. The Drude model is also introduced to include the case of inelastic collisions. Computer simulation of the motion is described. (KR)

  3. Plasma analog of particle-pair production

    International Nuclear Information System (INIS)

    Tsidulko, Yu.A.; Berk, H.L.

    1996-09-01

    It is shown that the plasma axial shear flow instability satisfies the Klein-Gordon equation. The plasma instability is then shown to be analogous to spontaneous particle-pair production when a potential energy is present that is greater than twice the particle rest mass energy. Stability criteria can be inferred based on field theoretical conservation laws

  4. Performance of the Analog Moving Window Detector

    DEFF Research Database (Denmark)

    Hansen, V. Gregers

    1970-01-01

    A type of analog integrating moving window detector for use with a scanning pulse radar is examined. A performance analysis is carried out, which takes into account both the radiation pattern of the antenna and the dynamic character of the detection process due to the angular scanning...

  5. Insulin analogs with improved pharmacokinetic profiles.

    Science.gov (United States)

    Brange; Vølund

    1999-02-01

    The aim of insulin replacement therapy is to normalize blood glucose in order to reduce the complications of diabetes. The pharmacokinetics of the traditional insulin preparations, however, do not match the profiles of physiological insulin secretion. The introduction of the rDNA technology 20 years ago opened new ways to create insulin analogs with altered properties. Fast-acting analogs are based on the idea that an insulin with less tendency to self-association than human insulin would be more readily absorbed into the systemic circulation. Protracted-acting analogs have been created to mimic the slow, steady rate of insulin secretion in the fasting state. The present paper provides a historical review of the efforts to change the physicochemical and pharmacological properties of insulin in order to improve insulin therapy. The available clinical studies of the new insulins are surveyed and show, together with modeling results, that new strategies for optimal basal-bolus treatment are required for utilization of the new fast-acting analogs.

  6. Bootstrapped Low-Voltage Analog Switches

    DEFF Research Database (Denmark)

    Steensgaard-Madsen, Jesper

    1999-01-01

    Novel low-voltage constant-impedance analog switch circuits are proposed. The switch element is a single MOSFET, and constant-impedance operation is obtained using simple circuits to adjust the gate and bulk voltages relative to the switched signal. Low-voltage (1-volt) operation is made feasible...

  7. Effects of hyperthermia on radiation-induced chromosome breakage and loss in excision repair deficient Drosophila melanogaster

    International Nuclear Information System (INIS)

    Mittler, S.

    1986-01-01

    Hyperthermia increased radiosensitivity with respect to γ-ray induced chromosome loss and breakage in all stages of spermatogenesis in the wild type Oregon R strain of Drosophila melanogaster, whereas hyperthermia increased radiosensitivity to a lesser extent in cn mus(2) 201sup(D1), an excision repair mutant with 0 per cent excision capacity and in mus(3) 308sup(D1), a strain with 24 per cent excision capacity. The differences in hyperthermia-induced radiation sensitivity between the excision repair mutants and the wild strain may be due to the hyperthermia affecting the excision repair mechanism, suggesting that one of the possible mechanisms involved in hyperthermia-increased radiosensitivity is an effect on excision repair. (author)

  8. Analog-to-digital conversion using custom CMOS analog memory for the EOS time projection chamber

    International Nuclear Information System (INIS)

    Lee, K.L.; Arthur, A.A.; Jones, R.W.; Matis, H.S.; Nakamura, M.; Kleinfelder, S.A.; Ritter, H.G.; Wienman, H.H.

    1990-01-01

    This paper describes the multiplexing scheme of custom CMOS analog memory integrated circuits, 16 channels x 256 cells, into analog to digital converters (ADC's) to handle 15,360 signal channels of a time projection, chamber detector system. Primary requirements of this system are high density, low power and large dynamic range. The analog memory device multiplexing scheme was designed to digitize the information stored in the memory cells. The digitization time of the ADC's and the settling times for the memory unit were carefully interleaved to optimize the performance and timing during the multiplexing operation. This kept the total number of ADC's, a costly and power dissipative component, to an acceptable minimum

  9. A mutant Pfu DNA polymerase designed for advanced uracil-excision DNA engineering.

    Science.gov (United States)

    Nørholm, Morten H H

    2010-03-16

    The combined use of restriction enzymes with PCR has revolutionized molecular cloning, but is inherently restricted by the content of the manipulated DNA sequences. Uracil-excision based cloning is ligase and sequence independent and allows seamless fusion of multiple DNA sequences in simple one-tube reactions, with higher accuracy than overlapping PCR. Here, the addition of a highly efficient DNA polymerase and a low-background-, large-insertion- compatible site-directed mutagenesis protocol is described, largely expanding the versatility of uracil-excision DNA engineering. The different uracil-excision based molecular tools that have been developed in an open-source fashion, constitute a comprehensive, yet simple and inexpensive toolkit for any need in molecular cloning.

  10. Excision repair of 5,6-dihydroxydihydrothymine from the DNA of Micrococcus radiodurans

    International Nuclear Information System (INIS)

    Targovnik, H.S.; Hariharan, P.V.

    1980-01-01

    One of the major ionizing radiation products, 5,6-dihydroxydihydrothymine (thymine glycol), was measured in the DNA of Micrococcus radiodurans following exposure of cells to 6.8-MeV electrons or 254-nm ultraviolet light. Removal of 5,6-dihydroxydihydrothymine was measured in both an ionizing radiation-sensitive strain (262) and a highly radioresistant strain (the wild type W + ) of Micrococcus radiodurans. Within 30 min of incubation (33 0 C) following exposure to ultraviolet light (2400 J/m 2 ) approximately 60% of the thymine glycols were excised, whereas in the case of ionizing radiation (250 krad) only 35% were removed from the cellular DNA of the wild-type strain. In contrast less than 50% of the thymine glycols were excised from the sensitive strain. The amount of DNA degradation induced by radiation was less than 10% in both strains. The results suggest a possible correlation between reduced excision repair of base damage and increased radiation sensitivity

  11. Comparison of the effect of nalidixic acid and thymine deprivation on excision repair in Escherichia coli

    International Nuclear Information System (INIS)

    Masek, F.; Slezarikova, V.; Sedliakova, M.

    1975-01-01

    A difference was found in the extent of inhibition of thymine dimers (TT) excision in ultraviolet (UV) irradiated cells of E. coli after preirradiation depression of protein and DNA syntheses induced by a simultaneous removal of essential amino acids (AA - ) and thymine (T - ) or by the removal of essential amino acids and the addition of nalidixic acid (NAL + ). The difference was observed in both E. coli B/r Hcr + and E. coli K12 SR20 uvr + cells. The depression of DNA synthesis by nalidixic acid as an exogenous agent inhibited TT excision to a lower degree than the depression of DNA synthesis by thymine starvation. The extent of TT excision had no appreciable effect on the restoration of the sedimentation profile of a newly synthesized DNA nor on UV resistance of cells during dark repair. A DNA molecule having the size of a molecule of nonirradiated cells became synthesized while TT were still present in the DNA. (author)

  12. 'Batman excision' of ventral skin in hypospadias repair, clue to aesthetic repair (point of technique).

    Science.gov (United States)

    Hoebeke, P B; De Kuyper, P; Van Laecke, E

    2002-11-01

    In the hypospadiac penis the ventral skin is poorly developed, while dorsal skin is redundant. The classical Byars' flaps are a way to use the excess dorsal skin to cover the penile shaft. The appearance after Byars' flaps however is not natural. We use a more natural looking skin allocation with superior aesthetic results. The clue in this reconstruction is an inverted triangle shaped excision of ventral skin expanding over the edges of the hooded prepuce (which makes it look like Batman). After excision of the ventral skin it is possible to close the penile skin in the midline, thus mimicking the natural raphe. In case of preputial reconstruction the excised ventral skin makes the prepuce look more natural. The trend of further refining aesthetic appearance of the hypospadiac penis often neglects the penile skin reconstruction. A technique is presented by which the total penile appearances after surgery ameliorates due to better skin reconstruction.

  13. The Fanconi anaemia components UBE2T and FANCM are functionally linked to nucleotide excision repair.

    Directory of Open Access Journals (Sweden)

    Ian R Kelsall

    Full Text Available The many proteins that function in the Fanconi anaemia (FA monoubiquitylation pathway initiate replicative DNA crosslink repair. However, it is not clear whether individual FA genes participate in DNA repair pathways other than homologous recombination and translesion bypass. Here we show that avian DT40 cell knockouts of two integral FA genes--UBE2T and FANCM are unexpectedly sensitive to UV-induced DNA damage. Comprehensive genetic dissection experiments indicate that both of these FA genes collaborate to promote nucleotide excision repair rather than translesion bypass to protect cells form UV genotoxicity. Furthermore, UBE2T deficiency impacts on the efficient removal of the UV-induced photolesion cyclobutane pyrimidine dimer. Therefore, this work reveals that the FA pathway shares two components with nucleotide excision repair, intimating not only crosstalk between the two major repair pathways, but also potentially identifying a UBE2T-mediated ubiquitin-signalling response pathway that contributes to nucleotide excision repair.

  14. Conservative treatment of rectal cancer with local excision and postoperative radiation therapy

    International Nuclear Information System (INIS)

    Minsky, B.D.

    1995-01-01

    The conventional surgical treatment for patients with potentially curable transmural and/or node positive rectal cancer is a low anterior resection or abdominoperineal resection. Recently, there has been increasing interest in the use of local excision and postoperative radiation therapy as primary therapy for selected rectal cancers. The limited data suggest that the approach of local excision and postoperative radiation therapy should be limited to patients with either T 1 tumours with adverse pathological factors or T 2 tumours. Transmural tumours, which have a 24% local failure rate, are treated more effectively with standard surgery and pre- or postoperative therapy. The results of local excision and postoperative radiation therapy are encouraging, but more experience is needed to determine if this approach ultimately has similar local control and survival rates as standard surgery. (author)

  15. The influence of altered gravity on carbohydrate metabolism in excised wheat leaves

    Science.gov (United States)

    Obenland, D. M.; Brown, C. S.

    1994-01-01

    We developed a system to study the influence of altered gravity on carbohydrate metabolism in excised wheat leaves by means of clinorotation. The use of excised leaves in our clinostat studies offered a number of advantages over the use of whole plants, most important of which were minimization of exogenous mechanical stress and a greater amount of carbohydrate accumulation during the time of treatment. We found that horizontal clinorotation of excised wheat leaves resulted in significant reductions in the accumulation of fructose, sucrose, starch and fructan relative to control, vertically clinorotated leaves. Photosynthesis, dark respiration and the extractable activities of ADP glucose pyrophosphorylase (EC 2.7.7.27), sucrose phosphate synthase (EC 2.4.4.14), sucrose sucrose fructosyltransferase (EC 2.4.1.99), and fructan hydrolase (EC 3.2.1.80) were unchanged due to altered gravity treatment.

  16. Surgical pathology of excised heart valves in a referral hospital in iran

    International Nuclear Information System (INIS)

    Yaghoubi, A.R.; Raeesi, K.

    2007-01-01

    Assessment of surgical pathology of excised heart valves in a referral hospital in Iran in a five years period. This retrospective descriptive study was done from 2002 to 2005 in Rajaie heart center in Tehran, Iran. Surgery and pathology records of patients who underwent valve replacement or repair surgery were reviewed. Of 1563 patients 738 (47.2%) underwent mitral, 565 (36.1%) aortic, and 215 (14%) multivalve operation. Most common pathology of mitral valve was rheumatic (68%), while degenerative calcific pathology was dominant in aortic valve (52%). Rheumatic involvement was 46%, and degenerative pathology was common in tricuspid and pulmonary valves (50% and 67%, respectively). Time trend analysis shows no significant variation in excised valves pathology or pattern from 2002 to 2005 (p=0.112). Rheumatic pathology in excised heart valves is still common in this referral heart center in Iran, and no obvious change in this pattern was found during a 5 years period. (author)

  17. Adjuvant irradiation improves the outcome of patients with rectal cancer following local excision

    International Nuclear Information System (INIS)

    Chakravarti, Arnab; Willett, Christopher G.; Shellito, Paul; Kaufman, Donald; Daley, William J.

    1997-01-01

    PURPOSE: the long-term outcomes of patients undergoing local excision with or without pelvic irradiation were examined to define the role of adjuvant irradiation following local excision of T1 and T2 rectal cancers. METHODS: From January 1966 to January 1997, 114 patients underwent local excision for rectal cancer. Fifty-nine patients underwent local excision alone, and 55 patients received adjuvant pelvic irradiation (45 Gy to 65.8 Gy)+/-concurrent 5-fluorouracil chemotherapy. Outcome was assessed by treatment, stage, and pathologic features of tumor grade and lymphatic/venous vessel involvement. RESULTS: Of the 114 patients treated by local excision, 90 had T1/T2 tumors. The 5-year actuarial local control (LC) and recurrence-free survival (RFS) of these 90 patients are shown (with numbers of patients at risk at 5 years) in the table below. The 5-year actuarial local control and recurrence-free survival (RFS) for T1/T2 patients treated by local excision alone was 85% and 77%, respectively. The corresponding values for patients undergoing local excision and adjuvant irradiation alone were 88% and 78%, respectively. All 20 patients treated by adjuvant chemoradiation achieved 5-year actuarial local control and had a recurrence-free survival of 88%. The improved outcomes in the adjuvant radiation group become more impressive when the higher T stage distribution of this group is considered. Fifty-five percent of the group receiving adjuvant radiation were stage T2 compared to only 14% of patients treated by local excision alone. Subgroup analysis was performed on those features recognized as poor prognostic factors including poorly differentiated histology and lymphatic vascular invasion. Patients in the local excision alone group with one or more adverse pathologic features had reduced rates of local control compared to those with the absence of such features (38% vs. 91%, respectively, p=0.02). In comparison, the 5 patients with poor prognostic features treated by

  18. Frontal recurrence of medulloblastoma five years after excision and craniospinal irradiation

    Directory of Open Access Journals (Sweden)

    Roka Y

    2009-07-01

    Full Text Available Medulloblastomas were originally classified under gliomas of the cerebellum until Bailey and Cushing in 1925 named these tumors as medulloblastoma. At present these tumors are classified under primitive neuroectodermal tumor. Surgical excision followed by craniospinal irradiation is the treatment of choice. A 13-year-old-girl operated for posterior fossa medulloblastoma 5 years ago presented with history of headache and vomiting on and off for 4 days in late August 2008. The MRI showed left frontal tumor which on excision was reported as medulloblastoma. Even after optimal treatment reports of recurrence abound in literature. The most common location is in the posterior fossa, followed by spinal, supratentorial, and uncommonly, systemic metastases. We conclude that medulloblastomas are highly aggressive tumor with high local recurrences if the initial excision is incomplete and that recurrence in the supratentorial area although uncommon is still a possibility. This mandates regular follow up of these children till adulthood to catch early recurrences and metastatic disease.

  19. 2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: a randomised, multicentre trial

    DEFF Research Database (Denmark)

    Gillgren, Peter; Drzewiecki, Krzysztof T; Niin, Marianne

    2011-01-01

    Optimum surgical resection margins for patients with clinical stage IIA-C cutaneous melanoma thicker than 2 mm are controversial. The aim of the study was to test whether survival was different for a wide local excision margin of 2 cm compared with a 4-cm excision margin.......Optimum surgical resection margins for patients with clinical stage IIA-C cutaneous melanoma thicker than 2 mm are controversial. The aim of the study was to test whether survival was different for a wide local excision margin of 2 cm compared with a 4-cm excision margin....

  20. Abscisic Acid Accumulates at Positive Turgor Potential in Excised Soybean Seedling Growing Zones 1

    Science.gov (United States)

    Creelman, Robert A.; Mullet, John E.

    1991-01-01

    Abscisic acid (ABA) accumulated in soybean (Glycine max [L.] Merr. cv Williams) hypocotyl elongating regions when seedlings were transferred to low water potential vermiculite (Ψ = −0.3 megapascals) even though positive turgor is retained in this tissue. Accumulation of ABA in growing zones could occur from de novo biosynthesis within this tissue or transport from adjacent nongrowing zones. Both growing and nongrowing hypocotyl and root tissues accumulated significant levels of ABA when excised and dehydrated to reduce turgor. Surprisingly, excised growing zones (which experienced no water loss) also accumulated ABA when incubated in darkness for 4 hours at 100% relative humidity and 29°C. Induction of ABA accumulation in the excised elongating region of the hypocotyl was not caused by disruption of root pressure or wounding. While excision of hypocotyl elongating regions induced ABA accumulation, no change in either extensin or p33 mRNA levels was observed. Accumulation of extensin or p33 mRNA required more severe wounding. This suggests that ABA is not involved in the response of these genes in wounded tissue and that wound signals are not causing ABA accumulation in excised tissue. Accumulation of ABA in excised elongating regions was correlated with growth inhibition and a decline in turgor to the yield threshold (Ψ;p = 0.37 megapascals; R Matyssek, S Maruyama, JS Boyer [1988] Plant Physiol 86: 1163-1167). Inhibiting hypocotyl growth by transferring seedlings to lower temperatures or light did not cause ABA accumulation. We conclude that induction of ABA accumulation in growing zones is more sensitive to changes in turgor than the induction which occurs in mature tissues. Images Figure 2 PMID:16668113