WorldWideScience

Sample records for coding variant met72thr

  1. Turbo Codes Based on Time-Variant Memory-1 Convolutional Codes over Fq

    CERN Document Server

    Liva, Gianluigi; Scalise, Sandro; Chiani, Marco

    2011-01-01

    Two classes of turbo codes over high-order finite fields are introduced. The codes are derived from a particular protograph sub-ensemble of the (dv=2,dc=3) low-density parity-check code ensemble. A first construction is derived as a parallel concatenation of two non-binary, time-variant accumulators. The second construction is based on the serial concatenation of a non-binary, time-variant differentiator and of a non-binary, time-variant accumulator, and provides a highly-structured flexible encoding scheme for (dv=2,dc=4) ensemble codes. A cycle graph representation is provided. The proposed codes can be decoded efficiently either as low-density parity-check codes (via belief propagation decoding over the codes bipartite graph) or as turbo codes (via the forward-backward algorithm applied to the component codes trellis). The forward-backward algorithm for symbol maximum a posteriori decoding of the component codes is illustrated and simplified by means of the fast Fourier transform. The proposed codes provid...

  2. De Novo Coding Variants Are Strongly Associated with Tourette Disorder

    DEFF Research Database (Denmark)

    Willsey, A Jeremy; Fernandez, Thomas V; Yu, Dongmei

    2017-01-01

    Whole-exome sequencing (WES) and de novo variant detection have proven a powerful approach to gene discovery in complex neurodevelopmental disorders. We have completed WES of 325 Tourette disorder trios from the Tourette International Collaborative Genetics cohort and a replication sample of 186...... trios from the Tourette Syndrome Association International Consortium on Genetics (511 total). We observe strong and consistent evidence for the contribution of de novo likely gene-disrupting (LGD) variants (rate ratio [RR] 2.32, p = 0.002). Additionally, de novo damaging variants (LGD and probably...

  3. A variant of list plus CRC concatenated polar code

    OpenAIRE

    Bonik, Gregory; Goreinov, Sergei; Zamarashkin, Nickolai

    2012-01-01

    A new family of codes based on polar codes, soft concatenation and list+CRC decoding is proposed. Numerical experiments show the performance competitive with industry standards and Tal, Vardy approach.

  4. A systematic survey of loss-of-function variants in human protein-coding genes

    NARCIS (Netherlands)

    MacArthur, D.G.; Balasubramanian, S.; Frankish, A.; Huang, N.; Morris, J.; Walter, K.; Jostins, L.; Habegger, L.; Pickrell, J.K.; Montgomery, S.B.; Albers, C.A.; Zhang, Z.D.; Conrad, D.F.; Lunter, G.; Zheng, H.; Ayub, Q.; DePristo, M.A.; Banks, E.; Hu, M.; Handsaker, R.E.; Rosenfeld, J.A.; Fromer, M.; Jin, M.; Mu, X.J.; Khurana, E.; Ye, K.; Kay, M.; Saunders, G.I.; Suner, M.M.; Hunt, T.; Barnes, I.H.; Amid, C.; Carvalho-Silva, D.R.; Bignell, A.H.; Snow, C.; Yngvadottir, B.; Bumpstead, S.; Cooper, D.N.; Xue, Y.; Romero, I.G.; Genomes Project, C.; Wang, J.; Li, Y.; Gibbs, R.A.; McCarroll, S.A.; Dermitzakis, E.T.; Pritchard, J.K.; Barrett, J.C.; Harrow, J.; Hurles, M.E.; Gerstein, M.B.; Tyler-Smith, C.

    2012-01-01

    Genome-sequencing studies indicate that all humans carry many genetic variants predicted to cause loss of function (LoF) of protein-coding genes, suggesting unexpected redundancy in the human genome. Here we apply stringent filters to 2951 putative LoF variants obtained from 185 human genomes to det

  5. Rare and low-frequency coding variants alter human adult height

    NARCIS (Netherlands)

    Marouli, Eirini; Graff, Mariaelisa; Medina-Gomez, Carolina; Lo, Ken Sin; Wood, Andrew R; Kjaer, Troels R; Fine, Rebecca S; Lu, Yingchang; Schurmann, Claudia; Highland, Heather M; Rüeger, Sina; Thorleifsson, Gudmar; Justice, Anne E; Lamparter, David; Stirrups, Kathleen E; Turcot, Valérie; Young, Kristin L; Winkler, Thomas W; Esko, Tõnu; Karaderi, Tugce; Locke, Adam E; Masca, Nicholas G D; Ng, Maggie C Y; Mudgal, Poorva; Rivas, Manuel A; Vedantam, Sailaja; Mahajan, Anubha; Guo, Xiuqing; Abecasis, Goncalo; Aben, Katja K; Adair, Linda S; Alam, Dewan S; Albrecht, Eva; Allin, Kristine H; Allison, Matthew; Amouyel, Philippe; Appel, Emil V; Arveiler, Dominique; Asselbergs, Folkert W; Auer, Paul L; Balkau, Beverley; Banas, Bernhard; Bang, Lia E; Benn, Marianne; Bergmann, Sven; Bielak, Lawrence F; Blüher, Matthias; Boeing, Heiner; Boerwinkle, Eric; Böger, Carsten A; Bonnycastle, Lori L; Bork-Jensen, Jette; Bots, Michiel L; Bottinger, Erwin P; Bowden, Donald W; Brandslund, Ivan; Breen, Gerome; Brilliant, Murray H; Broer, Linda; Burt, Amber A; Butterworth, Adam S; Carey, David J; Caulfield, Mark J; Chambers, John C; Chasman, Daniel I; Chen, Yii-Der Ida; Chowdhury, Rajiv; Christensen, Cramer; Chu, Audrey Y; Cocca, Massimiliano; Collins, Francis S; Cook, James P; Corley, Janie; Galbany, Jordi Corominas; Cox, Amanda J; Cuellar-Partida, Gabriel; Danesh, John; Davies, Gail; de Bakker, Paul I W; de Borst, Gert J; de Denus, Simon; de Groot, Mark C H; de Mutsert, Renée; Deary, Ian J; Dedoussis, George; Demerath, Ellen W; den Hollander, Anneke I; Dennis, Joe G; Di Angelantonio, Emanuele; Drenos, Fotios; Du, Mengmeng; Dunning, Alison M; Easton, Douglas F; Ebeling, Tapani; Edwards, Todd L; Ellinor, Patrick T; Elliott, Paul; Evangelou, Evangelos; Farmaki, Aliki-Eleni; Faul, Jessica D; Feitosa, Mary F; Feng, Shuang; Ferrannini, Ele; Ferrario, Marco M; Ferrieres, Jean; Florez, Jose C; Ford, Ian; Fornage, Myriam; Franks, Paul W; Frikke-Schmidt, Ruth; Galesloot, Tessel E; Gan, Wei; Gandin, Ilaria; Gasparini, Paolo; Giedraitis, Vilmantas; Giri, Ayush; Girotto, Giorgia; Gordon, Scott D; Gordon-Larsen, Penny; Gorski, Mathias; Grarup, Niels; Grove, Megan L; Gudnason, Vilmundur; Gustafsson, Stefan; Hansen, Torben; Harris, Kathleen Mullan; Harris, Tamara B; Hattersley, Andrew T; Hayward, Caroline; He, Liang; Heid, Iris M; Heikkilä, Kauko; Helgeland, Øyvind; Hernesniemi, Jussi; Hewitt, Alex W; Hocking, Lynne J; Hollensted, Mette; Holmen, Oddgeir L; Hovingh, G Kees; Howson, Joanna M M; Hoyng, Carel B; Huang, Paul L; Hveem, Kristian; Ikram, M Arfan; Ingelsson, Erik; Jackson, Anne U; Jansson, Jan-Håkan; Jarvik, Gail P; Jensen, Gorm B; Jhun, Min A; Jia, Yucheng; Jiang, Xuejuan; Johansson, Stefan; Jørgensen, Marit E; Jørgensen, Torben; Jousilahti, Pekka; Jukema, J Wouter; Kahali, Bratati; Kahn, René S; Kähönen, Mika; Kamstrup, Pia R; Kanoni, Stavroula; Kaprio, Jaakko; Karaleftheri, Maria; Kardia, Sharon L R; Karpe, Fredrik; Kee, Frank; Keeman, Renske; Kiemeney, Lambertus A; Kitajima, Hidetoshi; Kluivers, Kirsten B; Kocher, Thomas; Komulainen, Pirjo; Kontto, Jukka; Kooner, Jaspal S; Kooperberg, Charles; Kovacs, Peter; Kriebel, Jennifer; Kuivaniemi, Helena; Küry, Sébastien; Kuusisto, Johanna; La Bianca, Martina; Laakso, Markku; Lakka, Timo A; Lange, Ethan M; Lange, Leslie A; Langefeld, Carl D; Langenberg, Claudia; Larson, Eric B; Lee, I-Te; Lehtimäki, Terho; Lewis, Cora E; Li, Huaixing; Li, Jin; Li-Gao, Ruifang; Lin, Honghuang; Lin, Li-An; Lin, Xu; Lind, Lars; Lindström, Jaana; Linneberg, Allan; Liu, Yeheng; Liu, Yongmei; Lophatananon, Artitaya; Luan, Jian'an; Lubitz, Steven A; Lyytikäinen, Leo-Pekka; Mackey, David A; Madden, Pamela A F; Manning, Alisa K; Männistö, Satu; Marenne, Gaëlle; Marten, Jonathan; Martin, Nicholas G; Mazul, Angela L; Meidtner, Karina; Metspalu, Andres; Mitchell, Paul; Mohlke, Karen L; Mook-Kanamori, Dennis O; Morgan, Anna; Morris, Andrew D; Morris, Andrew P; Müller-Nurasyid, Martina; Munroe, Patricia B; Nalls, Mike A; Nauck, Matthias; Nelson, Christopher P; Neville, Matt; Nielsen, Sune F; Nikus, Kjell; Njølstad, Pål R; Nordestgaard, Børge G; Ntalla, Ioanna; O'Connel, Jeffrey R; Oksa, Heikki; Loohuis, Loes M Olde; Ophoff, RA; Owen, Katharine R; Packard, Chris J; Padmanabhan, Sandosh; Palmer, Colin N A; Pasterkamp, Gerard; Patel, Aniruddh P; Pattie, Alison; Pedersen, Oluf; Peissig, Peggy L; Peloso, Gina M; Pennell, Craig E; Perola, Markus; Perry, James A; Perry, John R B; Person, Thomas N; Pirie, Ailith; Polasek, Ozren; Posthuma, Danielle; Raitakari, Olli T; Rasheed, Asif; Rauramaa, Rainer; Reilly, Dermot F; Reiner, Alex P; Renström, Frida; Ridker, Paul M; Rioux, John D; Robertson, Neil; Robino, Antonietta; Rolandsson, Olov; Rudan, Igor; Ruth, Katherine S; Saleheen, Danish; Salomaa, Veikko; Samani, Nilesh J; Sandow, Kevin; Sapkota, Yadav; Sattar, Naveed; Schmidt, Marjanka K; Schreiner, Pamela J; Schulze, Matthias B; Scott, Robert A; Segura-Lepe, Marcelo P; Shah, Svati; Sim, Xueling; Sivapalaratnam, Suthesh; Small, Kerrin S; Smith, Albert Vernon; Smith, Jennifer A; Southam, Lorraine; Spector, Timothy D; Speliotes, Elizabeth K; Starr, John M; Steinthorsdottir, Valgerdur; Stringham, Heather M; Stumvoll, Michael; Surendran, Praveen; 't Hart, Leen M; Tansey, Katherine E; Tardif, Jean-Claude; Taylor, Kent D; Teumer, Alexander; Thompson, Deborah J; Thorsteinsdottir, Unnur; Thuesen, Betina H; Tönjes, Anke; Tromp, Gerard; Trompet, Stella; Tsafantakis, Emmanouil; Tuomilehto, Jaakko; Tybjaerg-Hansen, Anne; Tyrer, Jonathan P; Uher, Rudolf; Uitterlinden, André G; Ulivi, Sheila; van der Laan, Sander W; Van Der Leij, Andries R; van Duijn, Cornelia M; van Schoor, Natasja M; van Setten, Jessica; Varbo, Anette; Varga, Tibor V; Varma, Rohit; Edwards, Digna R Velez; Vermeulen, Sita H; Vestergaard, Henrik; Vitart, Veronique; Vogt, Thomas F; Vozzi, Diego; Walker, Mark; Wang, Feijie; Wang, Carol A; Wang, Shuai; Wang, Yiqin; Wareham, Nicholas J; Warren, Helen R; Wessel, Jennifer; Willems, Sara M; Wilson, James G; Witte, Daniel R; Woods, Michael O; Wu, Ying; Yaghootkar, Hanieh; Yao, Jie; Yao, Pang; Yerges-Armstrong, Laura M; Young, Robin; Zeggini, Eleftheria; Zhan, Xiaowei; Zhang, Weihua; Zhao, Jing Hua; Zhao, Wei; Zhao, Wei; Zheng, He; Zhou, Wei; Rotter, Jerome I; Boehnke, Michael; Kathiresan, Sekar; McCarthy, Mark I; Willer, Cristen J; Stefansson, Kari; Borecki, Ingrid B; Liu, Dajiang J; North, Kari E; Heard-Costa, Nancy L; Pers, Tune H; Lindgren, Cecilia M; Oxvig, Claus; Kutalik, Zoltán; Rivadeneira, Fernando; Loos, Ruth J F; Frayling, Timothy M; Hirschhorn, Joel N; Deloukas, Panos; Lettre, Guillaume

    2017-01-01

    Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to

  6. Rare and low-frequency coding variants alter human adult height

    DEFF Research Database (Denmark)

    Marouli, Eirini; Graff, Mariaelisa; Medina-Gómez, Carolina

    2017-01-01

    Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up ...

  7. De Novo Coding Variants Are Strongly Associated with Tourette Disorder.

    Science.gov (United States)

    Willsey, A Jeremy; Fernandez, Thomas V; Yu, Dongmei; King, Robert A; Dietrich, Andrea; Xing, Jinchuan; Sanders, Stephan J; Mandell, Jeffrey D; Huang, Alden Y; Richer, Petra; Smith, Louw; Dong, Shan; Samocha, Kaitlin E; Neale, Benjamin M; Coppola, Giovanni; Mathews, Carol A; Tischfield, Jay A; Scharf, Jeremiah M; State, Matthew W; Heiman, Gary A

    2017-05-03

    Whole-exome sequencing (WES) and de novo variant detection have proven a powerful approach to gene discovery in complex neurodevelopmental disorders. We have completed WES of 325 Tourette disorder trios from the Tourette International Collaborative Genetics cohort and a replication sample of 186 trios from the Tourette Syndrome Association International Consortium on Genetics (511 total). We observe strong and consistent evidence for the contribution of de novo likely gene-disrupting (LGD) variants (rate ratio [RR] 2.32, p = 0.002). Additionally, de novo damaging variants (LGD and probably damaging missense) are overrepresented in probands (RR 1.37, p = 0.003). We identify four likely risk genes with multiple de novo damaging variants in unrelated probands: WWC1 (WW and C2 domain containing 1), CELSR3 (Cadherin EGF LAG seven-pass G-type receptor 3), NIPBL (Nipped-B-like), and FN1 (fibronectin 1). Overall, we estimate that de novo damaging variants in approximately 400 genes contribute risk in 12% of clinical cases. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. De Novo Coding Variants Are Strongly Associated with Tourette Disorder

    NARCIS (Netherlands)

    Willsey, A. Jeremy; Fernandez, Thomas V.; Yu, Dongmei; King, Robert A.; Dietrich, Andrea; Xing, Jinchuan; Sanders, Stephan J.; Mandell, Jeffrey D.; Huang, Alden Y.; Richer, Petra; Smith, Louw; Dong, Shan; Samocha, Kaitlin E.; Neale, Benjamin M.; Coppola, Giovanni; Mathews, Carol A.; Tischfield, Jay A.; Scharf, Jeremiah M.; State, Matthew W.; Heiman, Gary A.

    2017-01-01

    Whole-exome sequencing (WES) and de novo variant detection have proven a powerful approach to gene discovery in complex neurodevelopmental disorders. We have completed WES of 325 Tourette disorder trios from the Tourette International Collaborative Genetics cohort and a replication sample of 186

  9. De Novo Coding Variants Are Strongly Associated with Tourette Disorder

    NARCIS (Netherlands)

    Willsey, A. Jeremy; Fernandez, Thomas V.; Yu, Dongmei; King, Robert A.; Dietrich, Andrea; Xing, Jinchuan; Sanders, Stephan J.; Mandell, Jeffrey D.; Huang, Alden Y.; Richer, Petra; Smith, Louw; Dong, Shan; Samocha, Kaitlin E.; Neale, Benjamin M.; Coppola, Giovanni; Mathews, Carol A.; Tischfield, Jay A.; Scharf, Jeremiah M.; State, Matthew W.; Heiman, Gary A.

    2017-01-01

    Whole-exome sequencing (WES) and de novo variant detection have proven a powerful approach to gene discovery in complex neurodevelopmental disorders. We have completed WES of 325 Tourette disorder trios from the Tourette International Collaborative Genetics cohort and a replication sample of 186 tri

  10. Interpreting functional effects of coding variants: challenges in proteome-scale prediction, annotation and assessment.

    Science.gov (United States)

    Shameer, Khader; Tripathi, Lokesh P; Kalari, Krishna R; Dudley, Joel T; Sowdhamini, Ramanathan

    2016-09-01

    Accurate assessment of genetic variation in human DNA sequencing studies remains a nontrivial challenge in clinical genomics and genome informatics. Ascribing functional roles and/or clinical significances to single nucleotide variants identified from a next-generation sequencing study is an important step in genome interpretation. Experimental characterization of all the observed functional variants is yet impractical; thus, the prediction of functional and/or regulatory impacts of the various mutations using in silico approaches is an important step toward the identification of functionally significant or clinically actionable variants. The relationships between genotypes and the expressed phenotypes are multilayered and biologically complex; such relationships present numerous challenges and at the same time offer various opportunities for the design of in silico variant assessment strategies. Over the past decade, many bioinformatics algorithms have been developed to predict functional consequences of single nucleotide variants in the protein coding regions. In this review, we provide an overview of the bioinformatics resources for the prediction, annotation and visualization of coding single nucleotide variants. We discuss the currently available approaches and major challenges from the perspective of protein sequence, structure, function and interactions that require consideration when interpreting the impact of putatively functional variants. We also discuss the relevance of incorporating integrated workflows for predicting the biomedical impact of the functionally important variations encoded in a genome, exome or transcriptome. Finally, we propose a framework to classify variant assessment approaches and strategies for incorporation of variant assessment within electronic health records.

  11. Rare coding variants and X-linked loci associated with age at menarche

    NARCIS (Netherlands)

    K.L. Lunetta (Kathryn); F.R. Day (Felix); P. Sulem (Patrick); K.S. Ruth (Katherine S.); J.Y. Tung (Joyce Y.); D.A. Hinds (David A.); T. Esko (Tõnu); C.E. Elks (Cathy); E.L. Altmaier (Elizabeth); C. He (Chunyan); J.E. Huffman (Jennifer); E. Mihailov (Evelin); E. Porcu (Eleonora); A. Robino (Antonietta); L.M. Rose (Lynda); U.M. Schick (Ursula); L. Stolk (Lisette); A. Teumer (Alexander); D. Thompson (Deborah); M. Traglia (Michela); C.A. Wang (Carol A.); L.M. Yerges-Armstrong (Laura); A.C. Antoniou (Antonis C.); C. Barbieri (Caterina); A.D. Coviello (Andrea); F. Cucca (Francesco); E.W. Demerath (Ellen); A.M. Dunning (Alison); I. Gandin (Ilaria); M.L. Grove (Megan L.); D.F. Gudbjartsson (Daniel); L.J. Hocking (Lynne); A. Hofman (Albert); J. Huang (Jian); R.D. Jackson (Rebecca); D. Karasik (David); J. Kriebel (Jennifer); E.M. Lange (Ethan); L.A. Lange (Leslie); C. Langenberg (Claudia); X. Li (Xin); J. Luan; R. Mägi (Reedik); A.C. Morrison (Alanna); S. Padmanabhan (Sandosh); A. Pirie (Ailith); O. Polasek (Ozren); D.J. Porteous (David J.); A. Reiner (Alexander); F. Rivadeneira Ramirez (Fernando); I. Rudan (Igor); C. Sala (Cinzia); D. Schlessinger (David); R.A. Scott (Robert); D. Stöckl (Doris); J.A. Visser (Jenny); U. Völker (Uwe); D. Vozzi (Diego); J.G. Wilson (James); M. Zygmunt (Marek); E.A. Boerwinkle (Eric); J.E. Buring (Julie); L. Crisponi (Laura); D.F. Easton (Douglas); C. Hayward (Caroline); F.B. Hu (Frank); S. Liu (Simin); A. Metspalu (Andres); C.E. Pennell (Craig); P.M. Ridker (Paul); K. Strauch (Konstantin); E.A. Streeten (Elizabeth); D. Toniolo (Daniela); A.G. Uitterlinden (André); S. Ulivi (Shelia); H. Völzke (Henry); N.J. Wareham (Nick); M. Wellons (Melissa); N. Franceschini (Nora); D.I. Chasman (Daniel); U. Thorsteinsdottir (Unnur); A. Murray (Anna); J-A. Zwart (John-Anker); J. Murabito (Joanne); K.K. Ong (Ken); J.R.B. Perry (John); N.G. Forouhi (Nita G.); N.D. Kerrison (Nicola D.); S.J. Sharp (Stephen J.); M.A. Sims (Matthew); I. Barroso (Inês); P. Deloukas (Panagiotis); M.I. McCarthy (Mark); L. Arriola (Larraitz); B. Balkau (Beverley); A. Barricarte (Aurelio); H. Boeing (Heiner); P.W. Franks; C. Gonzalez (Carlos); S. Grioni (Sara); R. Kaaks (Rudolf); T.J. Key (Timothy J.); C. Navarro (Carmen); P.M. Nilsson (Peter M.); K. Overvad (Kim); D. Palli (Domenico); S. Panico (Salvatore); J.R. Quirós; O. Rolandsson (Olov); C. Sacerdote (Carlotta); M.-J. Sánchez (María-José); N. Slimani (Nadia); A. Tjonneland (Anne); R. Tumino (Rosario); D.L. Van Der A (Daphne L.); Y.T. van der Schouw (Yvonne); E. Riboli (Elio); B.H. Smith (Blair); A. Campbell (Archie); I.J. Deary (Ian J.); A.M. McIntosh (Andrew)

    2015-01-01

    textabstractMore than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only ∼ 3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency protein-coding variants

  12. A nondegenerate code of deleterious variants in Mendelian loci contributes to complex disease risk.

    Science.gov (United States)

    Blair, David R; Lyttle, Christopher S; Mortensen, Jonathan M; Bearden, Charles F; Jensen, Anders Boeck; Khiabanian, Hossein; Melamed, Rachel; Rabadan, Raul; Bernstam, Elmer V; Brunak, Søren; Jensen, Lars Juhl; Nicolae, Dan; Shah, Nigam H; Grossman, Robert L; Cox, Nancy J; White, Kevin P; Rzhetsky, Andrey

    2013-09-26

    Although countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. By mining the medical records of over 110 million patients, we examine the extent to which Mendelian variation contributes to complex disease risk. We detect thousands of associations between Mendelian and complex diseases, revealing a nondegenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated with complex diseases are enriched in the genes indicated by this "Mendelian code." Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute nonadditively to the risk for a subset of complex diseases. Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. A Non-Degenerate Code of Deleterious Variants in Mendelian Loci Contributes to Complex Disease Risk

    Science.gov (United States)

    Blair, David R.; Lyttle, Christopher S.; Mortensen, Jonathan M.; Bearden, Charles F.; Jensen, Anders Boeck; Khiabanian, Hossein; Melamed, Rachel; Rabadan, Raul; Bernstam, Elmer V.; Brunak, Søren; Jensen, Lars Juhl; Nicolae, Dan; Shah, Nigam H.; Grossman, Robert L.; Cox, Nancy J.; White, Kevin P.; Rzhetsky, Andrey

    2013-01-01

    Summary Whereas countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. Here, we examine the extent to which Mendelian variation contributes to complex disease risk by mining the medical records of over 110 million patients. We detect thousands of associations between Mendelian and complex diseases, revealing a non-degenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated with complex diseases are enriched in the genes indicated by this “Mendelian code.” Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute non-additively to the risk for a subset of complex diseases. Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases. PMID:24074861

  14. A Nondegenerate Code of Deleterious Variants in Mendelian Loci Contributes to Complex Disease Risk

    DEFF Research Database (Denmark)

    Blair, David R.; Lyttle, Christopher S.; Mortensen, Jonathan M.

    2013-01-01

    with complex diseases are enriched in the genes indicated by this ‘‘Mendelian code.’’ Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute nonadditively to the risk for a subset......Although countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. By mining the medical records of over 110 million patients, we examine the extent to which Mendelian variation contributes...... to complex disease risk. We detect thousands of associations between Mendelian and complex diseases, revealing a nondegenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated...

  15. Non-coding keratin variants associate with liver fibrosis progression in patients with hemochromatosis.

    Directory of Open Access Journals (Sweden)

    Pavel Strnad

    Full Text Available BACKGROUND: Keratins 8 and 18 (K8/K18 are intermediate filament proteins that protect the liver from various forms of injury. Exonic K8/K18 variants associate with adverse outcome in acute liver failure and with liver fibrosis progression in patients with chronic hepatitis C infection or primary biliary cirrhosis. Given the association of K8/K18 variants with end-stage liver disease and progression in several chronic liver disorders, we studied the importance of keratin variants in patients with hemochromatosis. METHODS: The entire K8/K18 exonic regions were analyzed in 162 hemochromatosis patients carrying homozygous C282Y HFE (hemochromatosis gene mutations. 234 liver-healthy subjects were used as controls. Exonic regions were PCR-amplified and analyzed using denaturing high-performance liquid chromatography and DNA sequencing. Previously-generated transgenic mice overexpressing K8 G62C were studied for their susceptibility to iron overload. Susceptibility to iron toxicity of primary hepatocytes that express K8 wild-type and G62C was also assessed. RESULTS: We identified amino-acid-altering keratin heterozygous variants in 10 of 162 hemochromatosis patients (6.2% and non-coding heterozygous variants in 6 additional patients (3.7%. Two novel K8 variants (Q169E/R275W were found. K8 R341H was the most common amino-acid altering variant (4 patients, and exclusively associated with an intronic KRT8 IVS7+10delC deletion. Intronic, but not amino-acid-altering variants associated with the development of liver fibrosis. In mice, or ex vivo, the K8 G62C variant did not affect iron-accumulation in response to iron-rich diet or the extent of iron-induced hepatocellular injury. CONCLUSION: In patients with hemochromatosis, intronic but not exonic K8/K18 variants associate with liver fibrosis development.

  16. Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer's disease

    Science.gov (United States)

    2014-01-01

    Genome-wide association studies (GWAS) have identified several risk variants for late-onset Alzheimer's disease (LOAD). These common variants have replicable but small effects on LOAD risk and generally do not have obvious functional effects. Low-frequency coding variants, not detected by GWAS, are predicted to include functional variants with larger effects on risk. To identify low-frequency coding variants with large effects on LOAD risk, we carried out whole-exome sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large LOAD case-control data sets. A rare variant in PLD3 (phospholipase D3; Val232Met) segregated with disease status in two independent families and doubled risk for Alzheimer's disease in seven independent case-control series with a total of more than 11,000 cases and controls of European descent. Gene-based burden analyses in 4,387 cases and controls of European descent and 302 African American cases and controls, with complete sequence data for PLD3, reveal that several variants in this gene increase risk for Alzheimer's disease in both populations. PLD3 is highly expressed in brain regions that are vulnerable to Alzheimer's disease pathology, including hippocampus and cortex, and is expressed at significantly lower levels in neurons from Alzheimer's disease brains compared to control brains. Overexpression of PLD3 leads to a significant decrease in intracellular amyloid-β precursor protein (APP) and extracellular Aβ42 and Aβ40 (the 42- and 40-residue isoforms of the amyloid-β peptide), and knockdown of PLD3 leads to a significant increase in extracellular Aβ42 and Aβ40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a twofold increased risk for LOAD and that PLD3 influences APP processing. This study provides an example of how densely affected families may help to identify rare variants with large effects on risk for disease or other complex

  17. Whole-Exome Sequencing Identifies Rare and Low-Frequency Coding Variants Associated with LDL Cholesterol

    Science.gov (United States)

    Lange, Leslie A.; Hu, Youna; Zhang, He; Xue, Chenyi; Schmidt, Ellen M.; Tang, Zheng-Zheng; Bizon, Chris; Lange, Ethan M.; Smith, Joshua D.; Turner, Emily H.; Jun, Goo; Kang, Hyun Min; Peloso, Gina; Auer, Paul; Li, Kuo-ping; Flannick, Jason; Zhang, Ji; Fuchsberger, Christian; Gaulton, Kyle; Lindgren, Cecilia; Locke, Adam; Manning, Alisa; Sim, Xueling; Rivas, Manuel A.; Holmen, Oddgeir L.; Gottesman, Omri; Lu, Yingchang; Ruderfer, Douglas; Stahl, Eli A.; Duan, Qing; Li, Yun; Durda, Peter; Jiao, Shuo; Isaacs, Aaron; Hofman, Albert; Bis, Joshua C.; Correa, Adolfo; Griswold, Michael E.; Jakobsdottir, Johanna; Smith, Albert V.; Schreiner, Pamela J.; Feitosa, Mary F.; Zhang, Qunyuan; Huffman, Jennifer E.; Crosby, Jacy; Wassel, Christina L.; Do, Ron; Franceschini, Nora; Martin, Lisa W.; Robinson, Jennifer G.; Assimes, Themistocles L.; Crosslin, David R.; Rosenthal, Elisabeth A.; Tsai, Michael; Rieder, Mark J.; Farlow, Deborah N.; Folsom, Aaron R.; Lumley, Thomas; Fox, Ervin R.; Carlson, Christopher S.; Peters, Ulrike; Jackson, Rebecca D.; van Duijn, Cornelia M.; Uitterlinden, André G.; Levy, Daniel; Rotter, Jerome I.; Taylor, Herman A.; Gudnason, Vilmundur; Siscovick, David S.; Fornage, Myriam; Borecki, Ingrid B.; Hayward, Caroline; Rudan, Igor; Chen, Y. Eugene; Bottinger, Erwin P.; Loos, Ruth J.F.; Sætrom, Pål; Hveem, Kristian; Boehnke, Michael; Groop, Leif; McCarthy, Mark; Meitinger, Thomas; Ballantyne, Christie M.; Gabriel, Stacey B.; O’Donnell, Christopher J.; Post, Wendy S.; North, Kari E.; Reiner, Alexander P.; Boerwinkle, Eric; Psaty, Bruce M.; Altshuler, David; Kathiresan, Sekar; Lin, Dan-Yu; Jarvik, Gail P.; Cupples, L. Adrienne; Kooperberg, Charles; Wilson, James G.; Nickerson, Deborah A.; Abecasis, Goncalo R.; Rich, Stephen S.; Tracy, Russell P.; Willer, Cristen J.; Gabriel, Stacey B.; Altshuler, David M.; Abecasis, Gonçalo R.; Allayee, Hooman; Cresci, Sharon; Daly, Mark J.; de Bakker, Paul I.W.; DePristo, Mark A.; Do, Ron; Donnelly, Peter; Farlow, Deborah N.; Fennell, Tim; Garimella, Kiran; Hazen, Stanley L.; Hu, Youna; Jordan, Daniel M.; Jun, Goo; Kathiresan, Sekar; Kang, Hyun Min; Kiezun, Adam; Lettre, Guillaume; Li, Bingshan; Li, Mingyao; Newton-Cheh, Christopher H.; Padmanabhan, Sandosh; Peloso, Gina; Pulit, Sara; Rader, Daniel J.; Reich, David; Reilly, Muredach P.; Rivas, Manuel A.; Schwartz, Steve; Scott, Laura; Siscovick, David S.; Spertus, John A.; Stitziel, Nathaniel O.; Stoletzki, Nina; Sunyaev, Shamil R.; Voight, Benjamin F.; Willer, Cristen J.; Rich, Stephen S.; Akylbekova, Ermeg; Atwood, Larry D.; Ballantyne, Christie M.; Barbalic, Maja; Barr, R. Graham; Benjamin, Emelia J.; Bis, Joshua; Boerwinkle, Eric; Bowden, Donald W.; Brody, Jennifer; Budoff, Matthew; Burke, Greg; Buxbaum, Sarah; Carr, Jeff; Chen, Donna T.; Chen, Ida Y.; Chen, Wei-Min; Concannon, Pat; Crosby, Jacy; Cupples, L. Adrienne; D’Agostino, Ralph; DeStefano, Anita L.; Dreisbach, Albert; Dupuis, Josée; Durda, J. Peter; Ellis, Jaclyn; Folsom, Aaron R.; Fornage, Myriam; Fox, Caroline S.; Fox, Ervin; Funari, Vincent; Ganesh, Santhi K.; Gardin, Julius; Goff, David; Gordon, Ora; Grody, Wayne; Gross, Myron; Guo, Xiuqing; Hall, Ira M.; Heard-Costa, Nancy L.; Heckbert, Susan R.; Heintz, Nicholas; Herrington, David M.; Hickson, DeMarc; Huang, Jie; Hwang, Shih-Jen; Jacobs, David R.; Jenny, Nancy S.; Johnson, Andrew D.; Johnson, Craig W.; Kawut, Steven; Kronmal, Richard; Kurz, Raluca; Lange, Ethan M.; Lange, Leslie A.; Larson, Martin G.; Lawson, Mark; Lewis, Cora E.; Levy, Daniel; Li, Dalin; Lin, Honghuang; Liu, Chunyu; Liu, Jiankang; Liu, Kiang; Liu, Xiaoming; Liu, Yongmei; Longstreth, William T.; Loria, Cay; Lumley, Thomas; Lunetta, Kathryn; Mackey, Aaron J.; Mackey, Rachel; Manichaikul, Ani; Maxwell, Taylor; McKnight, Barbara; Meigs, James B.; Morrison, Alanna C.; Musani, Solomon K.; Mychaleckyj, Josyf C.; Nettleton, Jennifer A.; North, Kari; O’Donnell, Christopher J.; O’Leary, Daniel; Ong, Frank; Palmas, Walter; Pankow, James S.; Pankratz, Nathan D.; Paul, Shom; Perez, Marco; Person, Sharina D.; Polak, Joseph; Post, Wendy S.; Psaty, Bruce M.; Quinlan, Aaron R.; Raffel, Leslie J.; Ramachandran, Vasan S.; Reiner, Alexander P.; Rice, Kenneth; Rotter, Jerome I.; Sanders, Jill P.; Schreiner, Pamela; Seshadri, Sudha; Shea, Steve; Sidney, Stephen; Silverstein, Kevin; Smith, Nicholas L.; Sotoodehnia, Nona; Srinivasan, Asoke; Taylor, Herman A.; Taylor, Kent; Thomas, Fridtjof; Tracy, Russell P.; Tsai, Michael Y.; Volcik, Kelly A.; Wassel, Chrstina L.; Watson, Karol; Wei, Gina; White, Wendy; Wiggins, Kerri L.; Wilk, Jemma B.; Williams, O. Dale; Wilson, Gregory; Wilson, James G.; Wolf, Phillip; Zakai, Neil A.; Hardy, John; Meschia, James F.; Nalls, Michael; Singleton, Andrew; Worrall, Brad; Bamshad, Michael J.; Barnes, Kathleen C.; Abdulhamid, Ibrahim; Accurso, Frank; Anbar, Ran; Beaty, Terri; Bigham, Abigail; Black, Phillip; Bleecker, Eugene; Buckingham, Kati; Cairns, Anne Marie; Caplan, Daniel; Chatfield, Barbara; Chidekel, Aaron; Cho, Michael; Christiani, David C.; Crapo, James D.; Crouch, Julia; Daley, Denise; Dang, Anthony; Dang, Hong; De Paula, Alicia; DeCelie-Germana, Joan; Drumm, Allen DozorMitch; Dyson, Maynard; Emerson, Julia; Emond, Mary J.; Ferkol, Thomas; Fink, Robert; Foster, Cassandra; Froh, Deborah; Gao, Li; Gershan, William; Gibson, Ronald L.; Godwin, Elizabeth; Gondor, Magdalen; Gutierrez, Hector; Hansel, Nadia N.; Hassoun, Paul M.; Hiatt, Peter; Hokanson, John E.; Howenstine, Michelle; Hummer, Laura K.; Kanga, Jamshed; Kim, Yoonhee; Knowles, Michael R.; Konstan, Michael; Lahiri, Thomas; Laird, Nan; Lange, Christoph; Lin, Lin; Lin, Xihong; Louie, Tin L.; Lynch, David; Make, Barry; Martin, Thomas R.; Mathai, Steve C.; Mathias, Rasika A.; McNamara, John; McNamara, Sharon; Meyers, Deborah; Millard, Susan; Mogayzel, Peter; Moss, Richard; Murray, Tanda; Nielson, Dennis; Noyes, Blakeslee; O’Neal, Wanda; Orenstein, David; O’Sullivan, Brian; Pace, Rhonda; Pare, Peter; Parker, H. Worth; Passero, Mary Ann; Perkett, Elizabeth; Prestridge, Adrienne; Rafaels, Nicholas M.; Ramsey, Bonnie; Regan, Elizabeth; Ren, Clement; Retsch-Bogart, George; Rock, Michael; Rosen, Antony; Rosenfeld, Margaret; Ruczinski, Ingo; Sanford, Andrew; Schaeffer, David; Sell, Cindy; Sheehan, Daniel; Silverman, Edwin K.; Sin, Don; Spencer, Terry; Stonebraker, Jackie; Tabor, Holly K.; Varlotta, Laurie; Vergara, Candelaria I.; Weiss, Robert; Wigley, Fred; Wise, Robert A.; Wright, Fred A.; Wurfel, Mark M.; Zanni, Robert; Zou, Fei; Nickerson, Deborah A.; Rieder, Mark J.; Green, Phil; Shendure, Jay; Akey, Joshua M.; Bustamante, Carlos D.; Crosslin, David R.; Eichler, Evan E.; Fox, P. Keolu; Fu, Wenqing; Gordon, Adam; Gravel, Simon; Jarvik, Gail P.; Johnsen, Jill M.; Kan, Mengyuan; Kenny, Eimear E.; Kidd, Jeffrey M.; Lara-Garduno, Fremiet; Leal, Suzanne M.; Liu, Dajiang J.; McGee, Sean; O’Connor, Timothy D.; Paeper, Bryan; Robertson, Peggy D.; Smith, Joshua D.; Staples, Jeffrey C.; Tennessen, Jacob A.; Turner, Emily H.; Wang, Gao; Yi, Qian; Jackson, Rebecca; Peters, Ulrike; Carlson, Christopher S.; Anderson, Garnet; Anton-Culver, Hoda; Assimes, Themistocles L.; Auer, Paul L.; Beresford, Shirley; Bizon, Chris; Black, Henry; Brunner, Robert; Brzyski, Robert; Burwen, Dale; Caan, Bette; Carty, Cara L.; Chlebowski, Rowan; Cummings, Steven; Curb, J. David; Eaton, Charles B.; Ford, Leslie; Franceschini, Nora; Fullerton, Stephanie M.; Gass, Margery; Geller, Nancy; Heiss, Gerardo; Howard, Barbara V.; Hsu, Li; Hutter, Carolyn M.; Ioannidis, John; Jiao, Shuo; Johnson, Karen C.; Kooperberg, Charles; Kuller, Lewis; LaCroix, Andrea; Lakshminarayan, Kamakshi; Lane, Dorothy; Lasser, Norman; LeBlanc, Erin; Li, Kuo-Ping; Limacher, Marian; Lin, Dan-Yu; Logsdon, Benjamin A.; Ludlam, Shari; Manson, JoAnn E.; Margolis, Karen; Martin, Lisa; McGowan, Joan; Monda, Keri L.; Kotchen, Jane Morley; Nathan, Lauren; Ockene, Judith; O’Sullivan, Mary Jo; Phillips, Lawrence S.; Prentice, Ross L.; Robbins, John; Robinson, Jennifer G.; Rossouw, Jacques E.; Sangi-Haghpeykar, Haleh; Sarto, Gloria E.; Shumaker, Sally; Simon, Michael S.; Stefanick, Marcia L.; Stein, Evan; Tang, Hua; Taylor, Kira C.; Thomson, Cynthia A.; Thornton, Timothy A.; Van Horn, Linda; Vitolins, Mara; Wactawski-Wende, Jean; Wallace, Robert; Wassertheil-Smoller, Sylvia; Zeng, Donglin; Applebaum-Bowden, Deborah; Feolo, Michael; Gan, Weiniu; Paltoo, Dina N.; Sholinsky, Phyliss; Sturcke, Anne

    2014-01-01

    Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98th or <2nd percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments. PMID:24507775

  18. Clustered coding variants in the glutamate receptor complexes of individuals with schizophrenia and bipolar disorder.

    Science.gov (United States)

    Frank, René A W; McRae, Allan F; Pocklington, Andrew J; van de Lagemaat, Louie N; Navarro, Pau; Croning, Mike D R; Komiyama, Noboru H; Bradley, Sophie J; Challiss, R A John; Armstrong, J Douglas; Finn, Robert D; Malloy, Mary P; MacLean, Alan W; Harris, Sarah E; Starr, John M; Bhaskar, Sanjeev S; Howard, Eleanor K; Hunt, Sarah E; Coffey, Alison J; Ranganath, Venkatesh; Deloukas, Panos; Rogers, Jane; Muir, Walter J; Deary, Ian J; Blackwood, Douglas H; Visscher, Peter M; Grant, Seth G N

    2011-04-29

    Current models of schizophrenia and bipolar disorder implicate multiple genes, however their biological relationships remain elusive. To test the genetic role of glutamate receptors and their interacting scaffold proteins, the exons of ten glutamatergic 'hub' genes in 1304 individuals were re-sequenced in case and control samples. No significant difference in the overall number of non-synonymous single nucleotide polymorphisms (nsSNPs) was observed between cases and controls. However, cluster analysis of nsSNPs identified two exons encoding the cysteine-rich domain and first transmembrane helix of GRM1 as a risk locus with five mutations highly enriched within these domains. A new splice variant lacking the transmembrane GPCR domain of GRM1 was discovered in the human brain and the GRM1 mutation cluster could perturb the regulation of this variant. The predicted effect on individuals harbouring multiple mutations distributed in their ten hub genes was also examined. Diseased individuals possessed an increased load of deleteriousness from multiple concurrent rare and common coding variants. Together, these data suggest a disease model in which the interplay of compound genetic coding variants, distributed among glutamate receptors and their interacting proteins, contribute to the pathogenesis of schizophrenia and bipolar disorders.

  19. Clustered coding variants in the glutamate receptor complexes of individuals with schizophrenia and bipolar disorder.

    Directory of Open Access Journals (Sweden)

    René A W Frank

    Full Text Available Current models of schizophrenia and bipolar disorder implicate multiple genes, however their biological relationships remain elusive. To test the genetic role of glutamate receptors and their interacting scaffold proteins, the exons of ten glutamatergic 'hub' genes in 1304 individuals were re-sequenced in case and control samples. No significant difference in the overall number of non-synonymous single nucleotide polymorphisms (nsSNPs was observed between cases and controls. However, cluster analysis of nsSNPs identified two exons encoding the cysteine-rich domain and first transmembrane helix of GRM1 as a risk locus with five mutations highly enriched within these domains. A new splice variant lacking the transmembrane GPCR domain of GRM1 was discovered in the human brain and the GRM1 mutation cluster could perturb the regulation of this variant. The predicted effect on individuals harbouring multiple mutations distributed in their ten hub genes was also examined. Diseased individuals possessed an increased load of deleteriousness from multiple concurrent rare and common coding variants. Together, these data suggest a disease model in which the interplay of compound genetic coding variants, distributed among glutamate receptors and their interacting proteins, contribute to the pathogenesis of schizophrenia and bipolar disorders.

  20. Special issue on epigenetic inheritance by histone modifications, histone variants and non-coding RNAs

    Institute of Scientific and Technical Information of China (English)

    Xiaofeng CAO

    2011-01-01

    @@ Keeping in view the ever-growing importance of understanding the epigenetic phenomena shaping the behavior of life, our team decided to embark on the idea to organize this special issue of Frontiers in Biology on Epigenetics.Epigenetics refers to the study of heritable changes in gene expression without changes in DNA sequence, which is accomplished by DNA methylation, histone modifications, histone variants, chromatin remodeling, and non-coding RNAs.

  1. DeepSAGE reveals genetic variants associated with alternative polyadenylation and expression of coding and non-coding transcripts.

    Directory of Open Access Journals (Sweden)

    Daria V Zhernakova

    2013-06-01

    Full Text Available Many disease-associated variants affect gene expression levels (expression quantitative trait loci, eQTLs and expression profiling using next generation sequencing (NGS technology is a powerful way to detect these eQTLs. We analyzed 94 total blood samples from healthy volunteers with DeepSAGE to gain specific insight into how genetic variants affect the expression of genes and lengths of 3'-untranslated regions (3'-UTRs. We detected previously unknown cis-eQTL effects for GWAS hits in disease- and physiology-associated traits. Apart from cis-eQTLs that are typically easily identifiable using microarrays or RNA-sequencing, DeepSAGE also revealed many cis-eQTLs for antisense and other non-coding transcripts, often in genomic regions containing retrotransposon-derived elements. We also identified and confirmed SNPs that affect the usage of alternative polyadenylation sites, thereby potentially influencing the stability of messenger RNAs (mRNA. We then combined the power of RNA-sequencing with DeepSAGE by performing a meta-analysis of three datasets, leading to the identification of many more cis-eQTLs. Our results indicate that DeepSAGE data is useful for eQTL mapping of known and unknown transcripts, and for identifying SNPs that affect alternative polyadenylation. Because of the inherent differences between DeepSAGE and RNA-sequencing, our complementary, integrative approach leads to greater insight into the molecular consequences of many disease-associated variants.

  2. Association studies of low-frequency coding variants in nonsyndromic cleft lip with or without cleft palate

    DEFF Research Database (Denmark)

    Leslie, Elizabeth J; Carlson, Jenna C; Shaffer, John R

    2017-01-01

    Test (SKAT) and Combined Multivariate and Collapsing (CMC) method using two minor allele frequency cutoffs (1% and 5%). We found that a burden of low-frequency coding variants in N4BP2, CDSN, PRTG, and AHRR were associated with increased risk of NSCL/P. Low-frequency variants in other genes were...... associated with decreased risk of NSCL/P. These results demonstrate that low-frequency variants contribute to the genetic etiology of NSCL/P....

  3. Analysis of non-synonymous-coding variants of Parkinson's disease-related pathogenic and susceptibility genes in East Asian populations.

    Science.gov (United States)

    Foo, Jia Nee; Tan, Louis C; Liany, Herty; Koh, Tat Hung; Irwan, Ishak D; Ng, Yen Yek; Ahmad-Annuar, Azlina; Au, Wing-Lok; Aung, Tin; Chan, Anne Y Y; Chong, Siow-Ann; Chung, Sun Ju; Jung, Yusun; Khor, Chiea Chuen; Kim, Juyeon; Lee, Jimmy; Lim, Shen-Yang; Mok, Vincent; Prakash, Kumar-M; Song, Kyuyoung; Tai, E-Shyong; Vithana, Eranga N; Wong, Tien-Yin; Tan, Eng-King; Liu, Jianjun

    2014-07-15

    To evaluate the contribution of non-synonymous-coding variants of known familial and genome-wide association studies (GWAS)-linked genes for Parkinson's disease (PD) to PD risk in the East Asian population, we sequenced all the coding exons of 39 PD-related disease genes and evaluated the accumulation of rare non-synonymous-coding variants in 375 early-onset PD cases and 399 controls. We also genotyped 782 non-synonymous-coding variants of these genes in 710 late-onset PD cases and 9046 population controls. Significant enrichment of LRRK2 variants was observed in both early- and late-onset PD (odds ratio = 1.58; 95% confidence interval = 1.29-1.93; P = 8.05 × 10(-6)). Moderate enrichment was also observed in FGF20, MCCC1, GBA and ITGA8. Half of the rare variants anticipated to cause loss of function of these genes were present in healthy controls. Overall, non-synonymous-coding variants of known familial and GWAS-linked genes appear to make a limited contribution to PD risk, suggesting that clinical sequencing of these genes will provide limited information for risk prediction and molecular diagnosis.

  4. Functional testing strategy for coding genetic variants of unclear significance in MLH1 in Lynch syndrome diagnosis.

    Science.gov (United States)

    Hinrichsen, Inga; Schäfer, Dieter; Langer, Deborah; Köger, Nicole; Wittmann, Margarethe; Aretz, Stefan; Steinke, Verena; Holzapfel, Stefanie; Trojan, Jörg; König, Rainer; Zeuzem, Stefan; Brieger, Angela; Plotz, Guido

    2015-02-01

    Lynch syndrome is caused by inactivating mutations in the MLH1 gene, but genetic variants of unclear significance frequently preclude diagnosis. Functional testing can reveal variant-conferred defects in gene or protein function. Based on functional defect frequencies and clinical applicability of test systems, we developed a functional testing strategy aimed at efficiently detecting pathogenic defects in coding MLH1 variants. In this strategy, tests of repair activity and expression are prioritized over analyses of subcellular protein localization and messenger RNA (mRNA) formation. This strategy was used for four unclear coding MLH1 variants (p.Asp41His, p.Leu507Phe, p.Gln689Arg, p.Glu605del + p.Val716Met). Expression was analyzed using a transfection system, mismatch repair (MMR) activity by complementation in vitro, mRNA formation by reverse transcriptase-PCR in carrier lymphocyte mRNA, and subcellular localization with dye-labeled fusion constructs. All tests included clinically meaningful controls. The strategy enabled efficient identification of defects in two unclear variants: the p.Asp41His variant showed loss of MMR activity, whereas the compound variant p.Glu605del + p.Val716Met had a defect of expression. This expression defect was significantly stronger than the pathogenic expression reference variant analyzed in parallel, therefore the defect of the compound variant is also pathogenic. Interestingly, the expression defect was caused additively by both of the compound variants, at least one of which is non-pathogenic when occurring by itself. Tests were neutral for p.Leu507Phe and p.Gln689Arg, and the results were consistent with available clinical data. We finally discuss the improved sensitivity and efficiency of the applied strategy and its limitations in analyzing unclear coding MLH1 variants.

  5. Targeted deep resequencing identifies coding variants in the PEAR1 gene that play a role in platelet aggregation.

    Directory of Open Access Journals (Sweden)

    Yoonhee Kim

    Full Text Available Platelet aggregation is heritable, and genome-wide association studies have detected strong associations with a common intronic variant of the platelet endothelial aggregation receptor1 (PEAR1 gene both in African American and European American individuals. In this study, we used a sequencing approach to identify additional exonic variants in PEAR1 that may also determine variability in platelet aggregation in the GeneSTAR Study. A 0.3 Mb targeted region on chromosome 1q23.1 including the entire PEAR1 gene was Sanger sequenced in 104 subjects (45% male, 49% African American, age = 52±13 selected on the basis of hyper- and hypo- aggregation across three different agonists (collagen, epinephrine, and adenosine diphosphate. Single-variant and multi-variant burden tests for association were performed. Of the 235 variants identified through sequencing, 61 were novel, and three of these were missense variants. More rare variants (MAF<5% were noted in African Americans compared to European Americans (108 vs. 45. The common intronic GWAS-identified variant (rs12041331 demonstrated the most significant association signal in African Americans (p = 4.020×10(-4; no association was seen for additional exonic variants in this group. In contrast, multi-variant burden tests indicated that exonic variants play a more significant role in European Americans (p = 0.0099 for the collective coding variants compared to p = 0.0565 for intronic variant rs12041331. Imputation of the individual exonic variants in the rest of the GeneSTAR European American cohort (N = 1,965 supports the results noted in the sequenced discovery sample: p = 3.56×10(-4, 2.27×10(-7, 5.20×10(-5 for coding synonymous variant rs56260937 and collagen, epinephrine and adenosine diphosphate induced platelet aggregation, respectively. Sequencing approaches confirm that a common intronic variant has the strongest association with platelet aggregation in African Americans

  6. Inherited coding variants at the CDKN2A locus influence susceptibility to acute lymphoblastic leukaemia in children

    DEFF Research Database (Denmark)

    Xu, Heng; Zhang, Hui; Yang, Wenjian;

    2015-01-01

    There is increasing evidence from genome-wide association studies for a strong inherited genetic basis of susceptibility to acute lymphoblastic leukaemia (ALL) in children, yet the effects of protein-coding variants on ALL risk have not been systematically evaluated. Here we show a missense variant...... of haematopoietic progenitor cells, and is preferentially retained in ALL tumour cells. Resequencing the CDKN2A-CDKN2B locus in 2,407 childhood ALL cases reveals 19 additional putative functional germline variants. These results provide direct functional evidence for the influence of inherited genetic variation...

  7. Genome-Wide Functional Annotation of Human Protein-Coding Splice Variants Using Multiple Instance Learning.

    Science.gov (United States)

    Panwar, Bharat; Menon, Rajasree; Eksi, Ridvan; Li, Hong-Dong; Omenn, Gilbert S; Guan, Yuanfang

    2016-06-03

    The vast majority of human multiexon genes undergo alternative splicing and produce a variety of splice variant transcripts and proteins, which can perform different functions. These protein-coding splice variants (PCSVs) greatly increase the functional diversity of proteins. Most functional annotation algorithms have been developed at the gene level; the lack of isoform-level gold standards is an important intellectual limitation for currently available machine learning algorithms. The accumulation of a large amount of RNA-seq data in the public domain greatly increases our ability to examine the functional annotation of genes at isoform level. In the present study, we used a multiple instance learning (MIL)-based approach for predicting the function of PCSVs. We used transcript-level expression values and gene-level functional associations from the Gene Ontology database. A support vector machine (SVM)-based 5-fold cross-validation technique was applied. Comparatively, genes with multiple PCSVs performed better than single PCSV genes, and performance also improved when more examples were available to train the models. We demonstrated our predictions using literature evidence of ADAM15, LMNA/C, and DMXL2 genes. All predictions have been implemented in a web resource called "IsoFunc", which is freely available for the global scientific community through http://guanlab.ccmb.med.umich.edu/isofunc .

  8. Functional Studies and In Silico Analyses to Evaluate Non-Coding Variants in Inherited Cardiomyopathies

    Science.gov (United States)

    Frisso, Giulia; Detta, Nicola; Coppola, Pamela; Mazzaccara, Cristina; Pricolo, Maria Rosaria; D’Onofrio, Antonio; Limongelli, Giuseppe; Calabrò, Raffaele; Salvatore, Francesco

    2016-01-01

    Point mutations are the most common cause of inherited diseases. Bioinformatics tools can help to predict the pathogenicity of mutations found during genetic screening, but they may work less well in determining the effect of point mutations in non-coding regions. In silico analysis of intronic variants can reveal their impact on the splicing process, but the consequence of a given substitution is generally not predictable. The aim of this study was to functionally test five intronic variants (MYBPC3-c.506-2A>C, MYBPC3-c.906-7G>T, MYBPC3-c.2308+3G>C, SCN5A-c.393-5C>A, and ACTC1-c.617-7T>C) found in five patients affected by inherited cardiomyopathies in the attempt to verify their pathogenic role. Analysis of the MYBPC3-c.506-2A>C mutation in mRNA from the peripheral blood of one of the patients affected by hypertrophic cardiac myopathy revealed the loss of the canonical splice site and the use of an alternative splicing site, which caused the loss of the first seven nucleotides of exon 5 (MYBPC3-G169AfsX14). In the other four patients, we generated minigene constructs and transfected them in HEK-293 cells. This minigene approach showed that MYBPC3-c.2308+3G>C and SCN5A-c.393-5C>A altered pre-mRNA processing, thus resulting in the skipping of one exon. No alterations were found in either MYBPC3-c.906-7G>T or ACTC1-c.617-7T>C. In conclusion, functional in vitro analysis of the effects of potential splicing mutations can confirm or otherwise the putative pathogenicity of non-coding mutations, and thus help to guide the patient's clinical management and improve genetic counseling in affected families. PMID:27834932

  9. Exome-Wide Association Study Identifies New Low-Frequency and Rare UGT1A1 Coding Variants and UGT1A6 Coding Variants Influencing Serum Bilirubin in Elderly Subjects: A Strobe Compliant Article.

    Science.gov (United States)

    Oussalah, Abderrahim; Bosco, Paolo; Anello, Guido; Spada, Rosario; Guéant-Rodriguez, Rosa-Maria; Chery, Céline; Rouyer, Pierre; Josse, Thomas; Romano, Antonino; Elia, Maurizzio; Bronowicki, Jean-Pierre; Guéant, Jean-Louis

    2015-06-01

    Genome-wide association studies (GWASs) have identified loci contributing to total serum bilirubin level. However, no exome-wide approaches have been performed to address this question. Using exome-wide approach, we assessed the influence of protein-coding variants on unconjugated, conjugated, and total serum bilirubin levels in a well-characterized cohort of 773 ambulatory elderly subjects from Italy. Coding variants were replicated in 227 elderly subjects from the same area. We identified 4 missense rare (minor allele frequency, MAF bilirubin level (P = 2.34 × 10(-34), P = 7.02 × 10(-34), and P = 8.27 × 10(-34)), as well as unconjugated, and conjugated bilirubin levels. We also identified UGT1A6 variants in association with total (rs6759892, p.Ser7Ala, P = 1.98 × 10(-26); rs2070959, p.Thr181Ala, P = 2.87 × 10(-27); and rs1105879, p.Arg184Ser, P = 3.27 × 10(-29)), unconjugated, and conjugated bilirubin levels. All UGT1A1 intronic variants (rs887829, rs6742078, and rs4148325) and UGT1A6 coding variants (rs6759892, rs2070959, and rs1105879) were significantly associated with gallstone-related cholecystectomy risk. The UGT1A6 variant rs2070959 (p.Thr181Ala) was associated with the highest risk of gallstone-related cholecystectomy (OR, 4.58; 95% CI, 1.58-13.28; P = 3.21 × 10(-3)). Using an exome-wide approach we identified coding variants on UGT1A1 and UGT1A6 genes in association with serum bilirubin level and hyperbilirubinemia risk in elderly subjects. UGT1A1 intronic single-nucleotide polymorphisms (SNPs) (rs6742078, rs887829, rs4148324) serve as proxy markers for the low-frequency and rare UGT1A1 variants, thereby providing mechanistic explanation to the relationship between UGT1A1 intronic SNPs and the UGT1A1 enzyme activity. UGT1A1 and UGT1A6 variants might be potentially associated with gallstone-related cholecystectomy risk.

  10. Resequencing of 200 human exomes identifies an excess of low-frequency non-synonymous coding variants

    DEFF Research Database (Denmark)

    Li, Yingrui; Vinckenbosch, Nicolas; Tian, Geng

    2010-01-01

    Targeted capture combined with massively parallel exome sequencing is a promising approach to identify genetic variants implicated in human traits. We report exome sequencing of 200 individuals from Denmark with targeted capture of 18,654 coding genes and sequence coverage of each individual exome...

  11. Discovery of coding genetic variants influencing diabetes-related serum biomarkers and their impact on risk of type 2 diabetes

    DEFF Research Database (Denmark)

    Ahluwalia, Tarun Veer Singh; Allin, Kristine Højgaard; Sandholt, Camilla Helene;

    2015-01-01

    CONTEXT: Type 2 diabetes (T2D) prevalence is spiraling globally, and knowledge of its pathophysiological signatures is crucial for a better understanding and treatment of the disease. OBJECTIVE: We aimed to discover underlying coding genetic variants influencing fasting serum levels of nine...

  12. DeepSAGE Reveals Genetic Variants Associated with Alternative Polyadenylation and Expression of Coding and Non-coding Transcripts

    NARCIS (Netherlands)

    Zhernakova, Daria V.; de Klerk, Eleonora; Westra, Harm-Jan; Mastrokolias, Anastasios; Amini, Shoaib; Ariyurek, Yavuz; Jansen, Rick; Penninx, Brenda W.; Hottenga, Jouke J.; Willemsen, Gonneke; de Geus, Eco J.; Boomsma, Dorret I.; Veldink, Jan H.; van den Berg, Leonard H.; Wijmenga, Cisca; den Dunnen, Johan T.; van Ommen, Gert-Jan B.; 't Hoen, Peter A. C.; Franke, Lude

    2013-01-01

    Many disease-associated variants affect gene expression levels (expression quantitative trait loci, eQTLs) and expression profiling using next generation sequencing (NGS) technology is a powerful way to detect these eQTLs. We analyzed 94 total blood samples from healthy volunteers with DeepSAGE to g

  13. DeepSAGE Reveals Genetic Variants Associated with Alternative Polyadenylation and Expression of Coding and Non-coding Transcripts

    NARCIS (Netherlands)

    Zhernakova, Daria V.; de Klerk, Eleonora; Westra, Harm-Jan; Mastrokolias, Anastasios; Amini, Shoaib; Ariyurek, Yavuz; Jansen, Rick; Penninx, Brenda W.; Hottenga, Jouke J.; Willemsen, Gonneke; de Geus, Eco J.; Boomsma, Dorret I.; Veldink, Jan H.; van den Berg, Leonard H.; Wijmenga, Cisca; den Dunnen, Johan T.; van Ommen, Gert-Jan B.; 't Hoen, Peter A. C.; Franke, Lude

    2013-01-01

    Many disease-associated variants affect gene expression levels (expression quantitative trait loci, eQTLs) and expression profiling using next generation sequencing (NGS) technology is a powerful way to detect these eQTLs. We analyzed 94 total blood samples from healthy volunteers with DeepSAGE to g

  14. A cytogenetic abnormality and rare coding variants identify ABCA13 as a candidate gene in schizophrenia, bipolar disorder, and depression.

    Science.gov (United States)

    Knight, Helen M; Pickard, Benjamin S; Maclean, Alan; Malloy, Mary P; Soares, Dinesh C; McRae, Allan F; Condie, Alison; White, Angela; Hawkins, William; McGhee, Kevin; van Beck, Margaret; MacIntyre, Donald J; Starr, John M; Deary, Ian J; Visscher, Peter M; Porteous, David J; Cannon, Ronald E; St Clair, David; Muir, Walter J; Blackwood, Douglas H R

    2009-12-01

    Schizophrenia and bipolar disorder are leading causes of morbidity across all populations, with heritability estimates of approximately 80% indicating a substantial genetic component. Population genetics and genome-wide association studies suggest an overlap of genetic risk factors between these illnesses but it is unclear how this genetic component is divided between common gene polymorphisms, rare genomic copy number variants, and rare gene sequence mutations. We report evidence that the lipid transporter gene ABCA13 is a susceptibility factor for both schizophrenia and bipolar disorder. After the initial discovery of its disruption by a chromosome abnormality in a person with schizophrenia, we resequenced ABCA13 exons in 100 cases with schizophrenia and 100 controls. Multiple rare coding variants were identified including one nonsense and nine missense mutations and compound heterozygosity/homozygosity in six cases. Variants were genotyped in additional schizophrenia, bipolar, depression (n > 1600), and control (n > 950) cohorts and the frequency of all rare variants combined was greater than controls in schizophrenia (OR = 1.93, p = 0.0057) and bipolar disorder (OR = 2.71, p = 0.00007). The population attributable risk of these mutations was 2.2% for schizophrenia and 4.0% for bipolar disorder. In a study of 21 families of mutation carriers, we genotyped affected and unaffected relatives and found significant linkage (LOD = 4.3) of rare variants with a phenotype including schizophrenia, bipolar disorder, and major depression. These data identify a candidate gene, highlight the genetic overlap between schizophrenia, bipolar disorder, and depression, and suggest that rare coding variants may contribute significantly to risk of these disorders.

  15. Novel Ciliate Genetic Code Variants Including the Reassignment of All Three Stop Codons to Sense Codons in Condylostoma magnum.

    Science.gov (United States)

    Heaphy, Stephen M; Mariotti, Marco; Gladyshev, Vadim N; Atkins, John F; Baranov, Pavel V

    2016-11-01

    mRNA translation in many ciliates utilizes variant genetic codes where stop codons are reassigned to specify amino acids. To characterize the repertoire of ciliate genetic codes, we analyzed ciliate transcriptomes from marine environments. Using codon substitution frequencies in ciliate protein-coding genes and their orthologs, we inferred the genetic codes of 24 ciliate species. Nine did not match genetic code tables currently assigned by NCBI. Surprisingly, we identified a novel genetic code where all three standard stop codons (TAA, TAG, and TGA) specify amino acids in Condylostoma magnum We provide evidence suggesting that the functions of these codons in C. magnum depend on their location within mRNA. They are decoded as amino acids at internal positions, but specify translation termination when in close proximity to an mRNA 3' end. The frequency of stop codons in protein coding sequences of closely related Climacostomum virens suggests that it may represent a transitory state. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  16. A role for coding functional variants in HNF4A in type 2 diabetes susceptibility

    DEFF Research Database (Denmark)

    Jafar-Mohammadi, B; Groves, C J; Gjesing, A P;

    2011-01-01

    allele frequency [MAF] ~0.1%; T130I, MAF ~3.0%)-known to influence downstream HNF-4A target gene expression-are of interest, but previous type 2 diabetes association reports were inconclusive. We aimed to evaluate the contribution of these variants to type 2 diabetes susceptibility through large......Rare mutations in the gene HNF4A, encoding the transcription factor hepatocyte nuclear factor 4a (HNF-4A), account for ~5% of cases of MODY and more frequent variants in this gene may be involved in multifactorial forms of diabetes. Two low-frequency, non-synonymous variants in HNF4A (V255M, minor...

  17. Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus

    Science.gov (United States)

    Mahajan, Anubha; Sim, Xueling; Ng, Hui Jin; Manning, Alisa; Rivas, Manuel A.; Highland, Heather M.; Locke, Adam E.; Grarup, Niels; Im, Hae Kyung; Cingolani, Pablo; Flannick, Jason; Fontanillas, Pierre; Fuchsberger, Christian; Gaulton, Kyle J.; Teslovich, Tanya M.; Rayner, N. William; Robertson, Neil R.; Beer, Nicola L.; Rundle, Jana K.; Bork-Jensen, Jette; Ladenvall, Claes; Blancher, Christine; Buck, David; Buck, Gemma; Burtt, Noël P.; Gabriel, Stacey; Gjesing, Anette P.; Groves, Christopher J.; Hollensted, Mette; Huyghe, Jeroen R.; Jackson, Anne U.; Jun, Goo; Justesen, Johanne Marie; Mangino, Massimo; Murphy, Jacquelyn; Neville, Matt; Onofrio, Robert; Small, Kerrin S.; Stringham, Heather M.; Syvänen, Ann-Christine; Trakalo, Joseph; Abecasis, Goncalo; Bell, Graeme I.; Blangero, John; Cox, Nancy J.; Duggirala, Ravindranath; Hanis, Craig L.; Seielstad, Mark; Wilson, James G.; Christensen, Cramer; Brandslund, Ivan; Rauramaa, Rainer; Surdulescu, Gabriela L.; Doney, Alex S. F.; Lannfelt, Lars; Linneberg, Allan; Isomaa, Bo; Tuomi, Tiinamaija; Jørgensen, Marit E.; Jørgensen, Torben; Kuusisto, Johanna; Uusitupa, Matti; Salomaa, Veikko; Spector, Timothy D.; Morris, Andrew D.; Palmer, Colin N. A.; Collins, Francis S.; Mohlke, Karen L.; Bergman, Richard N.; Ingelsson, Erik; Lind, Lars; Tuomilehto, Jaakko; Hansen, Torben; Watanabe, Richard M.; Prokopenko, Inga; Dupuis, Josee; Karpe, Fredrik; Groop, Leif; Laakso, Markku; Pedersen, Oluf; Florez, Jose C.; Morris, Andrew P.; Altshuler, David; Meigs, James B.; Boehnke, Michael; McCarthy, Mark I.; Lindgren, Cecilia M.; Gloyn, Anna L.

    2015-01-01

    Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights. PMID:25625282

  18. Identification and functional characterization of G6PC2 coding variants influencing glycemic traits define an effector transcript at the G6PC2-ABCB11 locus.

    Directory of Open Access Journals (Sweden)

    Anubha Mahajan

    2015-01-01

    Full Text Available Genome wide association studies (GWAS for fasting glucose (FG and insulin (FI have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7 evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF=1.5% influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1% influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D, the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights.

  19. Rare coding variants and X-linked loci associated with age at menarche

    NARCIS (Netherlands)

    Lunetta, Kathryn L.; Day, Felix R.; Sulem, Patrick; Ruth, Katherine S.; Tung, Joyce Y.; Hinds, David A.; Esko, Tonu; Elks, Cathy E.; Altmaier, Elisabeth; He, Chunyan; Huffman, Jennifer E.; Mihailov, Evelin; Porcu, Eleonora; Robino, Antonietta; Rose, Lynda M.; Schick, Ursula M.; Stolk, Lisette; Teumer, Alexander; Thompson, Deborah J.; Traglia, Michela; Wang, Carol A.; Yerges-Armstrong, Laura M.; Antoniou, Antonis C.; Barbieri, Caterina; Coviello, Andrea D.; Cucca, Francesco; Demerath, Ellen W.; Dunning, Alison M.; Gandin, Ilaria; Grove, Megan L.; Gudbjartsson, Daniel F.; Hocking, Lynne J.; Hofman, Albert; Huang, Jinyan; Jackson, Rebecca D.; Karasik, David; Kriebel, Jennifer; Lange, Ethan M.; Lange, Leslie A.; Langenberg, Claudia; Li, Xin; Luan, Jian'an; Maegi, Reedik; Morrison, Alanna C.; Padmanabhan, Sandosh; Pirie, Ailith; Polasek, Ozren; Porteous, David; Reiner, Alex P.; Rivadeneira, Fernando; Rudan, Igor; Sala, Cinzia F.; Schlessinger, David; Scott, Robert A.; Stoeckl, Doris; Visser, Jenny A.; Voelker, Uwe; Vozzi, Diego; Wilson, James G.; Zygmunt, Marek; Boerwinkle, Eric; Buring, Julie E.; Crisponi, Laura; Easton, Douglas F.; Hayward, Caroline; Hu, Frank B.; Liu, Simin; Metspalu, Andres; Pennell, Craig E.; Ridker, Paul M.; Strauch, Konstantin; Streeten, Elizabeth A.; Toniolo, Daniela; Uitterlinden, Andre G.; Ulivi, Sheila; Voelzke, Henry; Wareham, Nicholas J.; Wellons, Melissa; Franceschini, Nora; Chasman, Daniel I.; Thorsteinsdottir, Unnur; Murray, Anna; Stefansson, Kari; Murabito, Joanne M.; Ong, Ken K.; Perry, John R. B.; Forouhi, Nita G.; Kerrison, Nicola D.; Sharp, Stephen J.; Sims, Matt; Barroso, Ines; Deloukas, Panos; McCarthy, Mark I.; Arriola, Larraitz; Balkau, Beverley; Barricarte, Aurelio; Boeing, Heiner; Franks, Paul W.; Gonzalez, Carlos; Grioni, Sara; Kaaks, Rudolf; Key, Timothy J.; Navarro, Carmen; Nilsson, Peter M.; Overvad, Kim; Palli, Domenico; Panico, Salvatore; Ramon Quiros, J.; Rolandsson, Olov; Sacerdote, Carlotta; Sanchez, Maria-Jose; Slimani, Nadia; Tjonneland, Anne; Tumino, Rosario; van der A, Daphne L.; van der Schouw, Yvonne T.; Riboli, Elio; Smith, Blair H.; Campbell, Archie; Deary, Ian J.; McIntosh, Andrew M.

    2015-01-01

    More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only similar to 3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency proteincoding variants and

  20. Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol

    NARCIS (Netherlands)

    L.A. Lange (Leslie); Y. Hu (Youna); H. Zhang (He); C. Xue (Chenyi); E.M. Schmidt (Ellen); Z.-Z. Tang (Zheng-Zheng); C. Bizon (Chris); E.M. Lange (Ethan); G.D. Smith; E.H. Turner (Emily); Y. Jun (Yang); H.M. Kang (Hyun Min); G.M. Peloso (Gina); P. Auer (Paul); K.-P. Li (Kuo-Ping); J. Flannick (Jason); J. Zhang (Ji); C. Fuchsberger (Christian); K. Gaulton (Kyle); C.M. Lindgren (Cecilia); A. Locke (Adam); A.K. Manning (Alisa); X. Sim (Xueling); M.A. Rivas (Manuel); O.L. Holmen (Oddgeir); R.F. Gottesman (Rebecca); Y. Lu (Yingchang); D. Ruderfer (Douglas); E.A. Stahl (Eli); Q. Duan (Qing); Y. Li (Yun); P. Durda (Peter); S. Jiao (Shuo); A.J. Isaacs (Aaron); A. Hofman (Albert); J.C. Bis (Joshua); D.D. Correa; M.D. Griswold (Michael); M. Jakobsdottir (Margret); G.D. Smith; P.J. Schreiner (Pamela); M.F. Feitosa (Mary Furlan); Q. Zhang (Qunyuan); J.E. Huffman (Jennifer); S. Crosby; C.L. Wassel (Christina); R. Do (Ron); N. Franceschini (Nora); L.W. Martin (Lisa); J.G. Robinson (Jennifer); T.L. Assimes (Themistocles); D.R. Crosslin (David); E.A. Rosenthal (Elisabeth); M.Y. Tsai (Michael); M. Rieder (Mark); D.N. Farlow (Deborah); A.R. Folsom (Aaron); T. Lumley (Thomas); E.R. Fox (Ervin); C.S. Carlson (Christopher); U. Peters (Ulrike); R.D. Jackson (Rebecca); C.M. van Duijn (Cock); A.G. Uitterlinden (André); D. Levy (Daniel); J.I. Rotter (Jerome); H.A. Taylor (Herman); V. Gudnason (Vilmundur); D.S. Siscovick (David); M. Fornage (Myriam); I.B. Borecki (Ingrid); C. Hayward (Caroline); I. Rudan (Igor); Y.E. Chen (Y. Eugene); E.P. Bottinger (Erwin); R.J.F. Loos (Ruth); P. Sætrom (Pål); K. Hveem (Kristian); M. Boehnke (Michael); L. Groop (Leif); M.I. McCarthy (Mark); T. Meitinger (Thomas); C. Ballantyne (Christie); S.B. Gabriel (Stacey); C.J. O'Donnell (Christopher); W.S. Post (Wendy S.); K.E. North (Kari); A. Reiner (Alexander); E.A. Boerwinkle (Eric); B.M. Psaty (Bruce); D. Altshuler (David); S. Kathiresan (Sekar); D.Y. Lin (Dan); G.P. Jarvik (Gail); L.A. Cupples (Adrienne); C. Kooperberg (Charles); J.G. Wilson (James); D.A. Nickerson (Deborah); G.R. Abecasis (Gonçalo); S.S. Rich (Stephen); R.P. Tracy (Russell); C.J. Willer (Cristen)

    2014-01-01

    textabstractElevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency

  1. Quantum-Mechanical Variant of the Thouless-Anderson-Palmer Equation for Error-Correcting Codes

    Science.gov (United States)

    Inoue, J.; Saika, Y.; Okada, M.

    Statistical mechanics of information has been applied to problems in various research topics of information science and technology [1],[2]. Among those research topics, error-correcting code is one of the most developed subjects. In the research field of error-correcting codes, Nicolas Sourlas showed that the so-called convolutional codes can be constructed by spin glass with infinite range p-body interactions and the decoded message should be corresponded to the ground state of the Hamiltonian [3]. Ruján pointed out that the bit error can be suppressed if one uses finite temperature equilibrium states as the decoding result, instead of the ground state [4], and the so-called Bayes-optimal decoding at some specific condition was proved by Nishimori [5] and Nishimori and Wong [6]. Kabashima and Saad succeeded in constructing more practical codes, namely low-density parity check (LDPC) codes by using the infinite range spin glass model with finite connectivities [7]. They used the so-called TAP (Thouless-Anderson-Palmer) equations to decode the original message for a given parity check.

  2. Rare, Low-Frequency, and Common Variants in the Protein-Coding Sequence of Biological Candidate Genes from GWASs Contribute to Risk of Rheumatoid Arthritis

    Science.gov (United States)

    Diogo, Dorothée; Kurreeman, Fina; Stahl, Eli A.; Liao, Katherine P.; Gupta, Namrata; Greenberg, Jeffrey D.; Rivas, Manuel A.; Hickey, Brendan; Flannick, Jason; Thomson, Brian; Guiducci, Candace; Ripke, Stephan; Adzhubey, Ivan; Barton, Anne; Kremer, Joel M.; Alfredsson, Lars; Sunyaev, Shamil; Martin, Javier; Zhernakova, Alexandra; Bowes, John; Eyre, Steve; Siminovitch, Katherine A.; Gregersen, Peter K.; Worthington, Jane; Klareskog, Lars; Padyukov, Leonid; Raychaudhuri, Soumya; Plenge, Robert M.

    2013-01-01

    The extent to which variants in the protein-coding sequence of genes contribute to risk of rheumatoid arthritis (RA) is unknown. In this study, we addressed this issue by deep exon sequencing and large-scale genotyping of 25 biological candidate genes located within RA risk loci discovered by genome-wide association studies (GWASs). First, we assessed the contribution of rare coding variants in the 25 genes to the risk of RA in a pooled sequencing study of 500 RA cases and 650 controls of European ancestry. We observed an accumulation of rare nonsynonymous variants exclusive to RA cases in IL2RA and IL2RB (burden test: p = 0.007 and p = 0.018, respectively). Next, we assessed the aggregate contribution of low-frequency and common coding variants to the risk of RA by dense genotyping of the 25 gene loci in 10,609 RA cases and 35,605 controls. We observed a strong enrichment of coding variants with a nominal signal of association with RA (p A [p.His266Gln]), and a noncoding variant, rs624988, reside on distinct haplotypes and independently contribute to the risk of RA (p = 4.6 × 10−6). Overall, our results indicate that variants (distributed across the allele-frequency spectrum) within the protein-coding portion of a subset of biological candidate genes identified by GWASs contribute to the risk of RA. Further, we have demonstrated that very large sample sizes will be required for comprehensively identifying the independent alleles contributing to the missing heritability of RA. PMID:23261300

  3. Genetic variants in long non-coding RNA MIAT contribute to risk of paranoid schizophrenia in a Chinese Han population.

    Science.gov (United States)

    Rao, Shu-Quan; Hu, Hui-Ling; Ye, Ning; Shen, Yan; Xu, Qi

    2015-08-01

    The heritability of schizophrenia has been reported to be as high as ~80%, but the contribution of genetic variants identified to this heritability remains to be estimated. Long non-coding RNAs (LncRNAs) are involved in multiple processes critical to normal cellular function and dysfunction of lncRNA MIAT may contribute to the pathophysiology of schizophrenia. However, the genetic evidence of lncRNAs involved in schizophrenia has not been documented. Here, we conducted a two-stage association analysis on 8 tag SNPs that cover the whole MIAT locus in two independent Han Chinese schizophrenia case-control cohorts (discovery sample from Shanxi Province: 1093 patients with paranoid schizophrenia and 1180 control subjects; replication cohort from Jilin Province: 1255 cases and 1209 healthy controls). In discovery stage, significant genetic association with paranoid schizophrenia was observed for rs1894720 (χ(2)=74.20, P=7.1E-18), of which minor allele (T) had an OR of 1.70 (95% CI=1.50-1.91). This association was confirmed in the replication cohort (χ(2)=22.66, P=1.9E-06, OR=1.32, 95%CI 1.18-1.49). Besides, a weak genotypic association was detected for rs4274 (χ(2)=4.96, df=2, P=0.03); the AA carriers showed increased disease risk (OR=1.30, 95%CI=1.03-1.64). No significant association was found between any haplotype and paranoid schizophrenia. The present studies showed that lncRNA MIAT was a novel susceptibility gene for paranoid schizophrenia in the Chinese Han population. Considering that most lncRNAs locate in non-coding regions, our result may explain why most susceptibility loci for schizophrenia identified by genome wide association studies were out of coding regions.

  4. Rare, Low-Frequency, and Common Variants in the Protein-Coding Sequence of Biological Candidate Genes from GWASs Contribute to Risk of Rheumatoid Arthritis

    NARCIS (Netherlands)

    Diogo, Dorothee; Kurreeman, Fina; Stahl, Eli A.; Liao, Katherine P.; Gupta, Namrata; Greenberg, Jeffrey D.; Rivas, Manuel A.; Hickey, Brendan; Flannick, Jason; Thomson, Brian; Guiducci, Candace; Ripke, Stephan; Adzhubey, Ivan; Barton, Anne; Kremer, Joel M.; Alfredsson, Lars; Sunyaev, Shamil; Martin, Javier; Zhernakova, Alexandra; Bowes, John; Eyre, Steve; Siminovitch, Katherine A.; Gregersen, Peter K.; Worthington, Jane; Klareskog, Lars; Padyukov, Leonid; Raychaudhuri, Soumya; Plenge, Robert M.

    2013-01-01

    The extent to which variants in the protein-coding sequence of genes contribute to risk of rheumatoid arthritis (RA) is unknown. In this study, we addressed this issue by deep exon sequencing and large-scale genotyping of 25 biological candidate genes located within RA risk loci discovered by genome

  5. Whole-Exome Sequencing of 2,000 Danish Individuals and the Role of Rare Coding Variants in Type 2 Diabetes

    DEFF Research Database (Denmark)

    Lohmueller, Kirk E.; Sparsø, Thomas; Li, Qibin;

    2013-01-01

    It has been hypothesized that, in aggregate, rare variants in coding regions of genes explain a substantial fraction of the heritability of common diseases. We sequenced the exomes of 1,000 Danish cases with common forms of type 2 diabetes (including body mass index > 27.5 kg/m2 and hypertension)...

  6. Association of low-frequency and rare coding-sequence variants with blood lipids and Coronary Heart Disease in 56,000 whites and blacks

    Science.gov (United States)

    Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncerta...

  7. Rare, low frequency and common coding variants in CHRNA5 and their contribution to nicotine dependence in European and African Americans

    NARCIS (Netherlands)

    E. Olfson (Emily); N.L. Saccone (Nancy); E.O. Johnson; L.-S. Chen; R. Culverhouse; K.F. Doheny (Kimberly); S.M. Foltz; L. Fox; S.M. Gogarten; S.M. Hartz (Sarah); K. Hetrick; C.C. Laurie (Cathy); B. Marosy; N. Amin; D. Arnett; R.G. Barr (R. Graham); T.M. Bartz (Traci M.); S. Bertelsen; I.B. Borecki (Ingrid); M.R. Brown; D.I. Chasman (Daniel); C.M. van Duijn (Cornelia M.); M.F. Feitosa; E.R. Fox; N. Franceschini; O.H. Franco; M.L. Grove; X. Guo; A. Hofman (Albert); S.L.R. Kardia (Sharon); A.C. Morrison (Alanna); S. Musani (Solomon); B.M. Psaty (Bruce); D.C. Rao; A. Reiner (Alexander); K.M. Rice (Kenneth); P.M. Ridker (Paul); L.M. Rose; U.M. Schick (Ursula); K. Schwander; A.G. Uitterlinden (André); D. Vojinovic; J.C. Wang (Jen ); E.B. Ware (Erin B.); G. Wilson; J. Yao; W. Zhao; N. Breslau (Naomi); T.S. Hatsukami (Thomas); J.A. Stitzel; J.P. Rice (John); A.M. Goate (Alison M.); L.J. Bierut

    2016-01-01

    textabstractThe common nonsynonymous variant rs16969968 in the α5 nicotinic receptor subunit gene (CHRNA5) is the strongest genetic risk factor for nicotine dependence in European Americans and contributes to risk in African Americans. To comprehensively examine whether other CHRNA5 coding variation

  8. Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks

    NARCIS (Netherlands)

    G.M. Peloso (Gina); P. Auer (Paul); J.C. Bis (Joshua); J.M. Voorman (Jeanine); A.C. Morrison (Alanna); N.O. Stitziel (Nathan); J. Brody (Jennifer); S.A. Khetarpal (Sumeet); S. Crosby; M. Fornage (Myriam); A.J. Isaacs (Aaron); M. Jakobsdottir (Margret); M.F. Feitosa (Mary Furlan); G. Davies (Gail); J.E. Huffman (Jennifer); A. Manichaikul (Ani); B. Davis (Brian); K. Lohman (Kurt); A.Y. Joon (Aron); G.D. Smith; M.L. Grove (Megan); P. Zanoni (Paolo); V. Redon (Valeska); S. Demissie (Serkalem); K. Lawson (Kim); U. Peters (Ulrike); C.S. Carlson (Christopher); R.D. Jackson (Rebecca); K.K. Ryckman (Kelli); R.H. MacKey (Rachel); J.G. Robinson (Jennifer); D.S. Siscovick (David); P.J. Schreiner (Pamela); J.C. Mychaleckyj (Josyf); J.S. Pankow (James); A. Hofman (Albert); A.G. Uitterlinden (André); T.B. Harris (Tamara); K.D. Taylor (Kent); M. Stafford; L.M. Reynolds (Lindsay); R.E. Marioni (Riccardo); A. Dehghan (Abbas); O.H. Franco (Oscar); A.P. Patel (Aniruddh); Y. Lu (Yingchang); G. Hindy (George); R.F. Gottesman (Rebecca); E.P. Bottinger (Erwin); O. Melander (Olle); M. Orho-Melander (Marju); R.J.F. Loos (Ruth); S. Duga (Stefano); P.A. Merlini (Piera); M. Farrall (Martin); A. Goel (Anuj); R. Asselta (Rosanna); D. Girelli (Domenico); N. Martinelli (Nicola); S.H. Shah (Svati); T. Kraus (Thomas); X. Li (Xiaohui); D.J. Rader (Daniel); M.P. Reilly (Muredach); R. McPherson (Ruth); H. Watkins (Hugh); D. Ardissino (Diego); Q. Zhang (Qunyuan); J. Wang (Judy); M.Y. Tsai (Michael); H.A. Taylor (Herman); D.D. Correa; M.D. Griswold (Michael); L.A. Lange (Leslie); J.M. Starr (John); I. Rudan (Igor); G. Eiriksdottir (Gudny); L.J. Launer (Lenore); J.M. Ordovas (Jose); D. Levy (Daniel); Y.-D.I. Chen (Y.-D. Ida); A. Reiner (Alexander); C. Hayward (Caroline); O. Polasek (Ozren); I.J. Deary (Ian); I.B. Borecki (Ingrid); Y. Liu (Yongmei); V. Gudnason (Vilmundur); J.G. Wilson (James); C.M. van Duijn (Cock); C. Kooperberg (Charles); S.S. Rich (Stephen); B.M. Psaty (Bruce); J.I. Rotter (Jerome); C.J. O'Donnell (Christopher); K.M. Rice (Kenneth); E.A. Boerwinkle (Eric); S. Kathiresan (Sekar); L.A. Cupples (Adrienne)

    2014-01-01

    textabstractLow-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. I

  9. Identification and characterisation of coding tandem repeat variants in incA gene of Chlamydophila pecorum.

    Science.gov (United States)

    Yousef Mohamad, Khalil; Rekiki, Abdessalem; Myers, Garry; Bavoil, Patrik M; Rodolakis, Annie

    2008-01-01

    Bacteria of the family Chlamydiaceae are obligate intracellular pathogens of human and animals. Chlamydophila pecorum is associated with different pathological conditions in ruminants, swine and koala. To characterize a coding tandem repeat (CTR) identified at the 3' end of incA gene of C. pecorum, 51 strains of different chlamydial species were examined. The CTR were observed in 18 of 18 tested C. pecorum isolates including symptomatic and asymptomatic animals from diverse geographical origins. The CTR were also found in two strains of C. abortus respectively isolated from faeces from a healthy ewe and from a goat belonging to asymptomatic herds, but were absent in C. abortus strains isolated from clinical disease specimens, and in tested strains of C. psittaci, C. caviae, C. felis and C. trachomatis. The number of CTR repeats is variable and encode several motifs that are rich in alanine and proline. The CTR-derived variable structure of incA, which encode the Chlamydiaceae-specific type III secreted inclusion membrane protein, IncA, may be involved in the adaptation of C. pecorum to its environment by allowing it to persist in the host cell.

  10. Genetic variants in promoters and coding regions of the muscle glycogen synthase and the insulin-responsive GLUT4 genes in NIDDM

    DEFF Research Database (Denmark)

    Bjørbaek, C; Echwald, Søren Morgenthaler; Hubricht, P

    1994-01-01

    regions and regions of importance for translation, as well as coding sequences of the two genes, were studied using single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. The genetic analyses were performed in subgroups of 52 Caucasian NIDDM patients and 25 age-matched healthy......To examine the hypothesis that variants in the regulatory or coding regions of the glycogen synthase (GS) and insulin-responsive glucose transporter (GLUT4) genes contribute to insulin-resistant glucose processing of muscle from non-insulin-dependent diabetes mellitus (NIDDM) patients, promoter......'-untranslated region, and the coding region of the GLUT4 gene showed four polymorphisms, all single nucleotide substitutions, positioned at -581, 1, 30, and 582. None of the three changes in the regulatory region of the gene had any major influence on expression of the GLUT4 gene in muscle. The variant at 582...

  11. Correlation of rare coding variants in the gene encoding human glucokinase regulatory protein with phenotypic, cellular, and kinetic outcomes.

    Science.gov (United States)

    Rees, Matthew G; Ng, David; Ruppert, Sarah; Turner, Clesson; Beer, Nicola L; Swift, Amy J; Morken, Mario A; Below, Jennifer E; Blech, Ilana; Mullikin, James C; McCarthy, Mark I; Biesecker, Leslie G; Gloyn, Anna L; Collins, Francis S

    2012-01-01

    Defining the genetic contribution of rare variants to common diseases is a major basic and clinical science challenge that could offer new insights into disease etiology and provide potential for directed gene- and pathway-based prevention and treatment. Common and rare nonsynonymous variants in the GCKR gene are associated with alterations in metabolic traits, most notably serum triglyceride levels. GCKR encodes glucokinase regulatory protein (GKRP), a predominantly nuclear protein that inhibits hepatic glucokinase (GCK) and plays a critical role in glucose homeostasis. The mode of action of rare GCKR variants remains unexplored. We identified 19 nonsynonymous GCKR variants among 800 individuals from the ClinSeq medical sequencing project. Excluding the previously described common missense variant p.Pro446Leu, all variants were rare in the cohort. Accordingly, we functionally characterized all variants to evaluate their potential phenotypic effects. Defects were observed for the majority of the rare variants after assessment of cellular localization, ability to interact with GCK, and kinetic activity of the encoded proteins. Comparing the individuals with functional rare variants to those without such variants showed associations with lipid phenotypes. Our findings suggest that, while nonsynonymous GCKR variants, excluding p.Pro446Leu, are rare in individuals of mixed European descent, the majority do affect protein function. In sum, this study utilizes computational, cell biological, and biochemical methods to present a model for interpreting the clinical significance of rare genetic variants in common disease.

  12. Sequencing the GRHL3 Coding Region Reveals Rare Truncating Mutations and a Common Susceptibility Variant for Nonsyndromic Cleft Palate

    Science.gov (United States)

    Mangold, Elisabeth; Böhmer, Anne C.; Ishorst, Nina; Hoebel, Ann-Kathrin; Gültepe, Pinar; Schuenke, Hannah; Klamt, Johanna; Hofmann, Andrea; Gölz, Lina; Raff, Ruth; Tessmann, Peter; Nowak, Stefanie; Reutter, Heiko; Hemprich, Alexander; Kreusch, Thomas; Kramer, Franz-Josef; Braumann, Bert; Reich, Rudolf; Schmidt, Gül; Jäger, Andreas; Reiter, Rudolf; Brosch, Sibylle; Stavusis, Janis; Ishida, Miho; Seselgyte, Rimante; Moore, Gudrun E.; Nöthen, Markus M.; Borck, Guntram; Aldhorae, Khalid A.; Lace, Baiba; Stanier, Philip; Knapp, Michael; Ludwig, Kerstin U.

    2016-01-01

    Nonsyndromic cleft lip with/without cleft palate (nsCL/P) and nonsyndromic cleft palate only (nsCPO) are the most frequent subphenotypes of orofacial clefts. A common syndromic form of orofacial clefting is Van der Woude syndrome (VWS) where individuals have CL/P or CPO, often but not always associated with lower lip pits. Recently, ∼5% of VWS-affected individuals were identified with mutations in the grainy head-like 3 gene (GRHL3). To investigate GRHL3 in nonsyndromic clefting, we sequenced its coding region in 576 Europeans with nsCL/P and 96 with nsCPO. Most strikingly, nsCPO-affected individuals had a higher minor allele frequency for rs41268753 (0.099) than control subjects (0.049; p = 1.24 × 10−2). This association was replicated in nsCPO/control cohorts from Latvia, Yemen, and the UK (pcombined = 2.63 × 10−5; ORallelic = 2.46 [95% CI 1.6–3.7]) and reached genome-wide significance in combination with imputed data from a GWAS in nsCPO triads (p = 2.73 × 10−9). Notably, rs41268753 is not associated with nsCL/P (p = 0.45). rs41268753 encodes the highly conserved p.Thr454Met (c.1361C>T) (GERP = 5.3), which prediction programs denote as deleterious, has a CADD score of 29.6, and increases protein binding capacity in silico. Sequencing also revealed four novel truncating GRHL3 mutations including two that were de novo in four families, where all nine individuals harboring mutations had nsCPO. This is important for genetic counseling: given that VWS is rare compared to nsCPO, our data suggest that dominant GRHL3 mutations are more likely to cause nonsyndromic than syndromic CPO. Thus, with rare dominant mutations and a common risk variant in the coding region, we have identified an important contribution for GRHL3 in nsCPO. PMID:27018475

  13. Deep resequencing of CFTR in 762 F508del homozygotes reveals clusters of non-coding variants associated with cystic fibrosis disease traits

    Science.gov (United States)

    Vecchio-Pagán, Briana; Blackman, Scott M; Lee, Melissa; Atalar, Melis; Pellicore, Matthew J; Pace, Rhonda G; Franca, Arianna L; Raraigh, Karen S; Sharma, Neeraj; Knowles, Michael R; Cutting, Garry R

    2016-01-01

    Extensive phenotypic variability is commonly observed in individuals with Mendelian disorders, even among those with identical genotypes in the disease-causing gene. To determine whether variants within and surrounding CFTR contribute to phenotypic variability in cystic fibrosis (CF), we performed deep sequencing of CFTR in 762 patients homozygous for the common CF-causing variant, F508del. In phase 1, ~200 kb encompassing CFTR and extending 10 kb 5′ and 5 kb 3′ of the gene was sequenced in 486 F508del homozygotes selected from the extremes of sweat chloride concentration. In phase 2, a 510 kb region, which included the entire topologically associated domain of CFTR, was sequenced in 276 F508del homozygotes drawn from extremes of lung function. An additional 163 individuals who carried F508del and a different CF-causing variant were sequenced to inform haplotype construction. Region-based burden testing of both common and rare variants revealed seven regions of significance (α=0.01), five of which overlapped known regulatory elements or chromatin interactions. Notably, the −80 kb locus known to interact with the CFTR promoter was associated with variation in both CF traits. Haplotype analysis revealed a single rare recombination event (1.9% frequency) in intron 15 of CFTR bearing the F508del variant. Otherwise, the majority of F508del chromosomes were markedly similar, consistent with a single origin of the F508del allele. Together, these high-resolution variant analyses of the CFTR locus suggest a role for non-coding regulatory motifs in trait variation among individuals carrying the common CF allele. PMID:27917292

  14. Characterization of coding synonymous and non-synonymous variants in ADAMTS13 using ex vivo and in silico approaches.

    Directory of Open Access Journals (Sweden)

    Nathan C Edwards

    Full Text Available Synonymous variations, which are defined as codon substitutions that do not change the encoded amino acid, were previously thought to have no effect on the properties of the synthesized protein(s. However, mounting evidence shows that these "silent" variations can have a significant impact on protein expression and function and should no longer be considered "silent". Here, the effects of six synonymous and six non-synonymous variations, previously found in the gene of ADAMTS13, the von Willebrand Factor (VWF cleaving hemostatic protease, have been investigated using a variety of approaches. The ADAMTS13 mRNA and protein expression levels, as well as the conformation and activity of the variants have been compared to that of wild-type ADAMTS13. Interestingly, not only the non-synonymous variants but also the synonymous variants have been found to change the protein expression levels, conformation and function. Bioinformatic analysis of ADAMTS13 mRNA structure, amino acid conservation and codon usage allowed us to establish correlations between mRNA stability, RSCU, and intracellular protein expression. This study demonstrates that variants and more specifically, synonymous variants can have a substantial and definite effect on ADAMTS13 function and that bioinformatic analysis may allow development of predictive tools to identify variants that will have significant effects on the encoded protein.

  15. Fine-mapping the HOXB region detects common variants tagging a rare coding allele: evidence for synthetic association in prostate cancer.

    Directory of Open Access Journals (Sweden)

    Edward J Saunders

    2014-02-01

    Full Text Available The HOXB13 gene has been implicated in prostate cancer (PrCa susceptibility. We performed a high resolution fine-mapping analysis to comprehensively evaluate the association between common genetic variation across the HOXB genetic locus at 17q21 and PrCa risk. This involved genotyping 700 SNPs using a custom Illumina iSelect array (iCOGS followed by imputation of 3195 SNPs in 20,440 PrCa cases and 21,469 controls in The PRACTICAL consortium. We identified a cluster of highly correlated common variants situated within or closely upstream of HOXB13 that were significantly associated with PrCa risk, described by rs117576373 (OR 1.30, P = 2.62×10(-14. Additional genotyping, conditional regression and haplotype analyses indicated that the newly identified common variants tag a rare, partially correlated coding variant in the HOXB13 gene (G84E, rs138213197, which has been identified recently as a moderate penetrance PrCa susceptibility allele. The potential for GWAS associations detected through common SNPs to be driven by rare causal variants with higher relative risks has long been proposed; however, to our knowledge this is the first experimental evidence for this phenomenon of synthetic association contributing to cancer susceptibility.

  16. Screening for coding variants in FTO and SH2B1 genes in Chinese patients with obesity.

    Directory of Open Access Journals (Sweden)

    Zhaojing Zheng

    Full Text Available OBJECTIVE: To investigate potential functional variants in FTO and SH2B1 genes among Chinese children with obesity. METHODS: Sanger sequencing of PCR products of all FTO and SH2B1 exons and their flanking regions were performed in 338 Chinese Han children with obesity and 221 age- and sex-matched lean controls. RESULTS: A total of seven and five rare non-synonymous variants were identified in FTO and SH2B1, respectively. The overall frequencies of FTO and SH2B1 rare non-synonymous variants were similar in obese and lean children (2.37% and 0.90% vs. 1.81% and 1.36%, P>0.05. However, four out of the seven variants in FTO were novel and all were unique to obese children (p>0.05. None of the novel variants was consistently being predicted to be deleterious. Four out of five variants in SH2B1 were novel and one was unique to obese children (p>0.05. One variant (L293R that was consistently being predicted as deleterious in SH2B1 gene was unique to lean control. While rare missense mutations were more frequently detected in girls from obesity as well as lean control than boys, the difference was not statistically significant. In addition, it's shown that the prevalence of rare missense mutations of FTO as well as SH2B1 was similar across different ethnic groups. CONCLUSION: The rare missense mutations of FTO and SH2B1 did not confer risks of obesity in Chinese Han children in our cohort.

  17. Screening for Coding Variants in FTO and SH2B1 Genes in Chinese Patients with Obesity

    Science.gov (United States)

    Huang, Xiaodong; Yang, Peirong; Li, Juan; Ding, Yu; Yao, Ru-en; Geng, Juan; Shen, Yongnian; Shen, Yiping; Fu, Qihua; Yu, Yongguo

    2013-01-01

    Objective To investigate potential functional variants in FTO and SH2B1 genes among Chinese children with obesity. Methods Sanger sequencing of PCR products of all FTO and SH2B1 exons and their flanking regions were performed in 338 Chinese Han children with obesity and 221 age- and sex-matched lean controls. Results A total of seven and five rare non-synonymous variants were identified in FTO and SH2B1, respectively. The overall frequencies of FTO and SH2B1 rare non-synonymous variants were similar in obese and lean children (2.37% and 0.90% vs. 1.81% and 1.36%, P>0.05). However, four out of the seven variants in FTO were novel and all were unique to obese children (p>0.05). None of the novel variants was consistently being predicted to be deleterious. Four out of five variants in SH2B1 were novel and one was unique to obese children (p>0.05). One variant (L293R) that was consistently being predicted as deleterious in SH2B1 gene was unique to lean control. While rare missense mutations were more frequently detected in girls from obesity as well as lean control than boys, the difference was not statistically significant. In addition, it's shown that the prevalence of rare missense mutations of FTO as well as SH2B1 was similar across different ethnic groups. Conclusion The rare missense mutations of FTO and SH2B1 did not confer risks of obesity in Chinese Han children in our cohort. PMID:23825611

  18. Construction of the coding sequence of the transcription variant 2 of the human Renalase gene and its expression in the prokaryotic system.

    Science.gov (United States)

    Fedchenko, Valerii I; Kaloshin, Alexei A; Mezhevikina, Lyudmila M; Buneeva, Olga A; Medvedev, Alexei E

    2013-06-19

    Renalase is a recently discovered protein, involved in regulation of blood pressure in humans and animals. Although several splice variants of human renalase mRNA transcripts have been recognized, only one protein product, hRenalase1, has been found so far. In this study, we have used polymerase chain reaction (PCR)-based amplification of individual exons of the renalase gene and their joining for construction of full-length hRenalase2 coding sequence followed by expression of hRenalase2 as a polyHis recombinant protein in Escherichia coli cells. To date this is the first report on synthesis and purification of hRenalase2. Applicability of this approach was verified by constructing hRenalase1 coding sequence, its sequencing and expression in E. coli cells. hRenalase1 was used for generation of polyclonal antiserum in sheep. Western blot analysis has shown that polyclonal anti-renalase1 antibodies effectively interact with the hRenalase2 protein. The latter suggests that some functions and expression patterns of hRenalase1 documented by antibody-based data may be attributed to the presence of hRenalase2. The realized approach may be also used for construction of coding sequences of various (especially weakly expressible) genes, their transcript variants, etc.

  19. Construction of the Coding Sequence of the Transcription Variant 2 of the Human Renalase Gene and Its Expression in the Prokaryotic System

    Directory of Open Access Journals (Sweden)

    Alexei E. Medvedev

    2013-06-01

    Full Text Available Renalase is a recently discovered protein, involved in regulation of blood pressure in humans and animals. Although several splice variants of human renalase mRNA transcripts have been recognized, only one protein product, hRenalase1, has been found so far. In this study, we have used polymerase chain reaction (PCR-based amplification of individual exons of the renalase gene and their joining for construction of full-length hRenalase2 coding sequence followed by expression of hRenalase2 as a polyHis recombinant protein in Escherichia coli cells. To date this is the first report on synthesis and purification of hRenalase2. Applicability of this approach was verified by constructing hRenalase1 coding sequence, its sequencing and expression in E. coli cells. hRenalase1 was used for generation of polyclonal antiserum in sheep. Western blot analysis has shown that polyclonal anti-renalase1 antibodies effectively interact with the hRenalase2 protein. The latter suggests that some functions and expression patterns of hRenalase1 documented by antibody-based data may be attributed to the presence of hRenalase2. The realized approach may be also used for construction of coding sequences of various (especially weakly expressible genes, their transcript variants, etc.

  20. TYK2 Protein-Coding Variants Protect against Rheumatoid Arthritis and Autoimmunity, with No Evidence of Major Pleiotropic Effects on Non-Autoimmune Complex Traits

    Science.gov (United States)

    Diogo, Dorothée; Bastarache, Lisa; Liao, Katherine P.; Graham, Robert R.; Fulton, Robert S.; Greenberg, Jeffrey D.; Eyre, Steve; Bowes, John; Cui, Jing; Lee, Annette; Pappas, Dimitrios A.; Kremer, Joel M.; Barton, Anne; Coenen, Marieke J. H.; Franke, Barbara; Kiemeney, Lambertus A.; Mariette, Xavier; Richard-Miceli, Corrine; Canhão, Helena; Fonseca, João E.; de Vries, Niek; Tak, Paul P.; Crusius, J. Bart A.; Nurmohamed, Michael T.; Kurreeman, Fina; Mikuls, Ted R.; Okada, Yukinori; Stahl, Eli A.; Larson, David E.; Deluca, Tracie L.; O'Laughlin, Michelle; Fronick, Catrina C.; Fulton, Lucinda L.; Kosoy, Roman; Ransom, Michael; Bhangale, Tushar R.; Ortmann, Ward; Cagan, Andrew; Gainer, Vivian; Karlson, Elizabeth W.; Kohane, Isaac; Murphy, Shawn N.; Martin, Javier; Zhernakova, Alexandra; Klareskog, Lars; Padyukov, Leonid; Worthington, Jane; Mardis, Elaine R.; Seldin, Michael F.; Gregersen, Peter K.; Behrens, Timothy; Raychaudhuri, Soumya; Denny, Joshua C.; Plenge, Robert M.

    2015-01-01

    Despite the success of genome-wide association studies (GWAS) in detecting a large number of loci for complex phenotypes such as rheumatoid arthritis (RA) susceptibility, the lack of information on the causal genes leaves important challenges to interpret GWAS results in the context of the disease biology. Here, we genetically fine-map the RA risk locus at 19p13 to define causal variants, and explore the pleiotropic effects of these same variants in other complex traits. First, we combined Immunochip dense genotyping (n = 23,092 case/control samples), Exomechip genotyping (n = 18,409 case/control samples) and targeted exon-sequencing (n = 2,236 case/controls samples) to demonstrate that three protein-coding variants in TYK2 (tyrosine kinase 2) independently protect against RA: P1104A (rs34536443, OR = 0.66, P = 2.3x10-21), A928V (rs35018800, OR = 0.53, P = 1.2x10-9), and I684S (rs12720356, OR = 0.86, P = 4.6x10-7). Second, we show that the same three TYK2 variants protect against systemic lupus erythematosus (SLE, Pomnibus = 6x10-18), and provide suggestive evidence that two of the TYK2 variants (P1104A and A928V) may also protect against inflammatory bowel disease (IBD; Pomnibus = 0.005). Finally, in a phenome-wide association study (PheWAS) assessing >500 phenotypes using electronic medical records (EMR) in >29,000 subjects, we found no convincing evidence for association of P1104A and A928V with complex phenotypes other than autoimmune diseases such as RA, SLE and IBD. Together, our results demonstrate the role of TYK2 in the pathogenesis of RA, SLE and IBD, and provide supporting evidence for TYK2 as a promising drug target for the treatment of autoimmune diseases. PMID:25849893

  1. TYK2 protein-coding variants protect against rheumatoid arthritis and autoimmunity, with no evidence of major pleiotropic effects on non-autoimmune complex traits.

    Directory of Open Access Journals (Sweden)

    Dorothée Diogo

    Full Text Available Despite the success of genome-wide association studies (GWAS in detecting a large number of loci for complex phenotypes such as rheumatoid arthritis (RA susceptibility, the lack of information on the causal genes leaves important challenges to interpret GWAS results in the context of the disease biology. Here, we genetically fine-map the RA risk locus at 19p13 to define causal variants, and explore the pleiotropic effects of these same variants in other complex traits. First, we combined Immunochip dense genotyping (n = 23,092 case/control samples, Exomechip genotyping (n = 18,409 case/control samples and targeted exon-sequencing (n = 2,236 case/controls samples to demonstrate that three protein-coding variants in TYK2 (tyrosine kinase 2 independently protect against RA: P1104A (rs34536443, OR = 0.66, P = 2.3 x 10(-21, A928V (rs35018800, OR = 0.53, P = 1.2 x 10(-9, and I684S (rs12720356, OR = 0.86, P = 4.6 x 10(-7. Second, we show that the same three TYK2 variants protect against systemic lupus erythematosus (SLE, Pomnibus = 6 x 10(-18, and provide suggestive evidence that two of the TYK2 variants (P1104A and A928V may also protect against inflammatory bowel disease (IBD; P(omnibus = 0.005. Finally, in a phenome-wide association study (PheWAS assessing >500 phenotypes using electronic medical records (EMR in >29,000 subjects, we found no convincing evidence for association of P1104A and A928V with complex phenotypes other than autoimmune diseases such as RA, SLE and IBD. Together, our results demonstrate the role of TYK2 in the pathogenesis of RA, SLE and IBD, and provide supporting evidence for TYK2 as a promising drug target for the treatment of autoimmune diseases.

  2. Genetic variants in promoters and coding regions of the muscle glycogen synthase and the insulin-responsive GLUT4 genes in NIDDM

    DEFF Research Database (Denmark)

    Bjørbaek, C; Echwald, Søren Morgenthaler; Hubricht, P

    1994-01-01

    regions and regions of importance for translation, as well as coding sequences of the two genes, were studied using single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. The genetic analyses were performed in subgroups of 52 Caucasian NIDDM patients and 25 age-matched healthy......'-untranslated region, and the coding region of the GLUT4 gene showed four polymorphisms, all single nucleotide substitutions, positioned at -581, 1, 30, and 582. None of the three changes in the regulatory region of the gene had any major influence on expression of the GLUT4 gene in muscle. The variant at 582...... volunteers. By applying inverse polymerase chain reaction and direct DNA sequencing, 532 base pairs (bp) of the GS promoter were identified and the transcriptional start site determined by primer extension. SSCP scanning of the promoter region detected five single nucleotide substitutions, positioned at 42...

  3. Pharmacological profile of brain-derived neurotrophic factor (BDNF) splice variant translation using a novel drug screening assay: a "quantitative code".

    Science.gov (United States)

    Vaghi, Valentina; Polacchini, Alessio; Baj, Gabriele; Pinheiro, Vera L M; Vicario, Annalisa; Tongiorgi, Enrico

    2014-10-03

    The neurotrophin brain-derived neurotrophic factor (BDNF) is a key regulator of neuronal development and plasticity. BDNF is a major pharmaceutical target in neurodevelopmental and psychiatric disorders. However, pharmacological modulation of this neurotrophin is challenging because BDNF is generated by multiple, alternatively spliced transcripts with different 5'- and 3'UTRs. Each BDNF mRNA variant is transcribed independently, but translation regulation is unknown. To evaluate the translatability of BDNF transcripts, we developed an in vitro luciferase assay in human neuroblastoma cells. In unstimulated cells, each BDNF 5'- and 3'UTR determined a different basal translation level of the luciferase reporter gene. However, constructs with either a 5'UTR or a 3'UTR alone showed poor translation modulation by BDNF, KCl, dihydroxyphenylglycine, AMPA, NMDA, dopamine, acetylcholine, norepinephrine, or serotonin. Constructs consisting of the luciferase reporter gene flanked by the 5'UTR of one of the most abundant BDNF transcripts in the brain (exons 1, 2c, 4, and 6) and the long 3'UTR responded selectively to stimulation with the different receptor agonists, and only transcripts 2c and 6 were increased by the antidepressants desipramine and mirtazapine. We propose that BDNF mRNA variants represent "a quantitative code" for regulated expression of the protein. Thus, to discriminate the efficacy of drugs in stimulating BDNF synthesis, it is appropriate to use variant-specific in vitro screening tests.

  4. Coding variants at hexa-allelic amino acid 13 of HLA-DRB1 explain independent SNP associations with follicular lymphoma risk.

    Science.gov (United States)

    Foo, Jia Nee; Smedby, Karin E; Akers, Nicholas K; Berglund, Mattias; Irwan, Ishak D; Jia, Xiaoming; Li, Yi; Conde, Lucia; Darabi, Hatef; Bracci, Paige M; Melbye, Mads; Adami, Hans-Olov; Glimelius, Bengt; Khor, Chiea Chuen; Hjalgrim, Henrik; Padyukov, Leonid; Humphreys, Keith; Enblad, Gunilla; Skibola, Christine F; de Bakker, Paul I W; Liu, Jianjun

    2013-07-11

    Non-Hodgkin lymphoma represents a diverse group of blood malignancies, of which follicular lymphoma (FL) is a common subtype. Previous genome-wide association studies (GWASs) have identified in the human leukocyte antigen (HLA) class II region multiple independent SNPs that are significantly associated with FL risk. To dissect these signals and determine whether coding variants in HLA genes are responsible for the associations, we conducted imputation, HLA typing, and sequencing in three independent populations for a total of 689 cases and 2,446 controls. We identified a hexa-allelic amino acid polymorphism at position 13 of the HLA-DR beta chain that showed the strongest association with FL within the major histocompatibility complex (MHC) region (multiallelic p = 2.3 × 10⁻¹⁵). Out of six possible amino acids that occurred at that position within the population, we classified two as high risk (Tyr and Phe), two as low risk (Ser and Arg), and two as moderate risk (His and Gly). There was a 4.2-fold difference in risk (95% confidence interval = 2.9-6.1) between subjects carrying two alleles encoding high-risk amino acids and those carrying two alleles encoding low-risk amino acids (p = 1.01 × 10⁻¹⁴). This coding variant might explain the complex SNP associations identified by GWASs and suggests a common HLA-DR antigen-driven mechanism for the pathogenesis of FL and rheumatoid arthritis.

  5. Two Human ACAT2 mRNA Variants Produced by Alternative Splicing and Coding for Novel Isoenzymes

    Institute of Scientific and Technical Information of China (English)

    Xiao-Min YAO; Bo-Liang LI; Can-Hua WANG; Bao-Liang SONG; Xin-Ying YANG; Zhen-Zhen WANG; Wei QI; Zhi-Xin LIN; Catherine C. Y. CHANG; Ta-Yuan CHANG

    2005-01-01

    Acyl coenzyme A:cholesterol acyltransferase 2 (ACAT2) plays an important role in cholesterol absorption. Human ACAT2 is highly expressed in small intestine and fetal liver, but its expression is greatly diminished in adult liver. The full-length human ACAT2 mRNA encodes a protein, designated ACAT2a, with 522 amino acids. We have previously reported the organization of the human ACAT2 gene and the differentiation-dependent promoter activity in intestinal Caco-2 cells. In the current work, two human ACAT2 mRNA variants produced by alternative splicing are cloned and predicted to encode two novel ACAT2 isoforms,named ACAT2b and ACAT2c, with 502 and 379 amino acids, respectively. These mRNA variants differ from ACAT2a mRNA by lack of the exon 4 (ACAT2b mRNA) and exons 4-5 plus 8-9-10 (ACAT2c mRNA).Significantly, comparable amounts of the alternatively spliced ACAT2 mRNA variants were detected by RTPCR, and Western blot analysis confirmed the presence of their corresponding proteins in human liver and intestine cells. Furthermore, phosphorylation and enzymatic activity analyses demonstrated that the novel isoenzymes ACAT2b and ACAT2c lacked the phosphorylatable site SLLD, and their enzymatic activities reduced to 25%-35% of that of ACAT2a. These evidences indicate that alternative splicing produces two human ACAT2 mRNA variants that encode the novel ACAT2 isoenzymes. Our findings might help to understand the regulation of the ACAT2 gene expression under certain physiological and pathological conditions.

  6. A non-synonymous coding variant (L616F in the TLR5 gene is potentially associated with Crohn's disease and influences responses to bacterial flagellin.

    Directory of Open Access Journals (Sweden)

    Jared Sheridan

    Full Text Available BACKGROUND AND OBJECTIVES: Although numerous studies have implicated TLR5, or its ligands, bacterial flagellins, in the pathogenesis of Crohn's disease (CD, genome-wide association studies (GWAS have not reported associations with the TLR5 gene. We aimed to examine potential CD-associated TLR5 variants and assess whether they modified inflammatory responses to bacterial flagellins. METHODS AND PRINCIPAL RESULTS: A two-stage study was carried out. In stage 1, we genotyped tagging single-nucleotide polymorphisms (tag-SNPs in the TLR5 gene in a sample of CD cases (<20 years of age, N = 566 and controls (N = 536. Single SNP and haplotype analysis was carried out. In Stage 2, we assessed the functional significance of potential CD-associated variant(s vis-à-vis effects on the inflammatory response to bacterial flagellin using HEK293T cells. We observed marginal association between a non-synonymous coding SNP rs5744174 (p = 0.05 and CD. Associations between SNP rs851139 that is in high linkage disequilibrium (LD with SNP rs5744174 were also suggested (p = 0.07. Haplotype analysis revealed that a 3 marker haplotype was significantly associated with CD (p = 0.01. Functional studies showed that the risk allele (616F (corresponding to the C allele of SNP rs5744174 conferred significantly greater production of CCL20 in response to a range of flagellin doses than the comparator allele (616L. CONCLUSIONS: Our findings suggest that a non-synonymous coding variation in the TLR5 gene may confer modest susceptibility for CD.

  7. SLC6A3 coding variant Ala559Val found in two autism probands alters dopamine transporter function and trafficking.

    Science.gov (United States)

    Bowton, E; Saunders, C; Reddy, I A; Campbell, N G; Hamilton, P J; Henry, L K; Coon, H; Sakrikar, D; Veenstra-VanderWeele, J M; Blakely, R D; Sutcliffe, J; Matthies, H J G; Erreger, K; Galli, A

    2014-10-14

    Emerging evidence associates dysfunction in the dopamine (DA) transporter (DAT) with the pathophysiology of autism spectrum disorder (ASD). The human DAT (hDAT; SLC6A3) rare variant with an Ala to Val substitution at amino acid 559 (hDAT A559V) was previously reported in individuals with bipolar disorder or attention-deficit hyperactivity disorder (ADHD). We have demonstrated that this variant is hyper-phosphorylated at the amino (N)-terminal serine (Ser) residues and promotes an anomalous DA efflux phenotype. Here, we report the novel identification of hDAT A559V in two unrelated ASD subjects and provide the first mechanistic description of its impaired trafficking phenotype. DAT surface expression is dynamically regulated by DAT substrates including the psychostimulant amphetamine (AMPH), which causes hDAT trafficking away from the plasma membrane. The integrity of DAT trafficking directly impacts DA transport capacity and therefore dopaminergic neurotransmission. Here, we show that hDAT A559V is resistant to AMPH-induced cell surface redistribution. This unique trafficking phenotype is conferred by altered protein kinase C β (PKCβ) activity. Cells expressing hDAT A559V exhibit constitutively elevated PKCβ activity, inhibition of which restores the AMPH-induced hDAT A559V membrane redistribution. Mechanistically, we link the inability of hDAT A559V to traffic in response to AMPH to the phosphorylation of the five most distal DAT N-terminal Ser. Mutation of these N-terminal Ser to Ala restores AMPH-induced trafficking. Furthermore, hDAT A559V has a diminished ability to transport AMPH, and therefore lacks AMPH-induced DA efflux. Pharmacological inhibition of PKCβ or Ser to Ala substitution in the hDAT A559V background restores AMPH-induced DA efflux while promoting intracellular AMPH accumulation. Although hDAT A559V is a rare variant, it has been found in multiple probands with neuropsychiatric disorders associated with imbalances in DA neurotransmission

  8. Physical exercise and antidepressants enhance BDNF targeting in hippocampal CA3 dendrites: further evidence of a spatial code for BDNF splice variants.

    Science.gov (United States)

    Baj, Gabriele; D'Alessandro, Valentina; Musazzi, Laura; Mallei, Alessandra; Sartori, Cesar R; Sciancalepore, Marina; Tardito, Daniela; Langone, Francesco; Popoli, Maurizio; Tongiorgi, Enrico

    2012-06-01

    Brain-derived neurotrophic factor (BDNF) is encoded by multiple BDNF transcripts, whose function is unclear. We recently showed that a subset of BDNF transcripts can traffic into distal dendrites in response to electrical activity, while others are segregated into the somatoproximal domains. Physical exercise and antidepressant treatments exert their beneficial effects through upregulation of BDNF, which is required to support survival and differentiation of newborn dentate gyrus (DG) neurons. While these DG processes are required for the antidepressant effect, a role for CA1 in antidepressant action has been excluded, and the effect on CA3 neurons remains unclear. Here, we show for the first time that physical exercise and antidepressants induce local increase of BDNF in CA3. Voluntary physical exercise for 28 consecutive days, or 2-week treatment with 10 mg/kg per day fluoxetine or reboxetine, produced a global increase of BDNF mRNA and protein in the neuronal somata of the whole hippocampus and a specific increase of BDNF in dendrites of CA3 neurons. This increase was accounted for by BDNF exon 6 variant. In cultured hippocampal neurons, application of serotonin or norepinephrine (10-50 μM) induced increase in synaptic transmission and targeting of BDNF mRNA in dendrites. The increased expression of BDNF in CA3 dendrites following antidepressants or exercise further supports the neurotrophin hypothesis of antidepressants action and confirms that the differential subcellular localization of BDNF mRNA splice variants provides a spatial code for a selective expression of BDNF in specific subcellular districts. This selective expression may be exploited to design more specific antidepressants.

  9. Characterization of an Equine α-S2-Casein Variant Due to a 1.3 kb Deletion Spanning Two Coding Exons.

    Directory of Open Access Journals (Sweden)

    Julia Brinkmann

    Full Text Available The production and consumption of mare's milk in Europe has gained importance, mainly based on positive health effects and a lower allergenic potential as compared to cows' milk. The allergenicity of milk is to a certain extent affected by different genetic variants. In classical dairy species, much research has been conducted into the genetic variability of milk proteins, but the knowledge in horses is scarce. Here, we characterize two major forms of equine αS2-casein arising from genomic 1.3 kb in-frame deletion involving two coding exons, one of which represents an equid specific duplication. Findings at the DNA-level have been verified by cDNA sequencing from horse milk of mares with different genotypes. At the protein-level, we were able to show by SDS-page and in-gel digestion with subsequent LC-MS analysis that both proteins are actually expressed. The comparison with published sequences of other equids revealed that the deletion has probably occurred before the ancestor of present-day asses and zebras diverged from the horse lineage.

  10. MBL2 gene variants coding for mannose-binding lectin deficiency are associated with increased risk of nephritis in Danish patients with systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Tanha, N; Troelsen, L; From Hermansen, M-L;

    2014-01-01

    OBJECTIVES: Autoimmunity may in part result from deficiencies in the processing of apoptotic debris. As mannose-binding lectin (MBL) is involved in such processes, we hypothesized that the variants in the MBL2 gene resulting in MBL deficiency confer an increased risk of nephritis in systemic lupus...... erythematosus (SLE). METHODS: A total of 171 SLE patients attending a Danish tertiary rheumatology referral center were included. Common variant alleles in exon 1 of the MBL2 gene (R52C, rs5030737; G54D, rs1800450; G57E, rs1800451) were genotyped. The normal allele and variant alleles are termed A and O...

  11. Functional Investigation of a Non-coding Variant Associated with Adolescent Idiopathic Scoliosis in Zebrafish: Elevated Expression of the Ladybird Homeobox Gene Causes Body Axis Deformation.

    Directory of Open Access Journals (Sweden)

    Long Guo

    2016-01-01

    Full Text Available Previously, we identified an adolescent idiopathic scoliosis susceptibility locus near human ladybird homeobox 1 (LBX1 and FLJ41350 by a genome-wide association study. Here, we characterized the associated non-coding variant and investigated the function of these genes. A chromosome conformation capture assay revealed that the genome region with the most significantly associated single nucleotide polymorphism (rs11190870 physically interacted with the promoter region of LBX1-FLJ41350. The promoter in the direction of LBX1, combined with a 590-bp region including rs11190870, had higher transcriptional activity with the risk allele than that with the non-risk allele in HEK 293T cells. The ubiquitous overexpression of human LBX1 or either of the zebrafish lbx genes (lbx1a, lbx1b, and lbx2, but not FLJ41350, in zebrafish embryos caused body curvature followed by death prior to vertebral column formation. Such body axis deformation was not observed in transcription activator-like effector nucleases mediated knockout zebrafish of lbx1b or lbx2. Mosaic expression of lbx1b driven by the GATA2 minimal promoter and the lbx1b enhancer in zebrafish significantly alleviated the embryonic lethal phenotype to allow observation of the later onset of the spinal curvature with or without vertebral malformation. Deformation of the embryonic body axis by lbx1b overexpression was associated with defects in convergent extension, which is a component of the main axis-elongation machinery in gastrulating embryos. In embryos overexpressing lbx1b, wnt5b, a ligand of the non-canonical Wnt/planar cell polarity (PCP pathway, was significantly downregulated. Injection of mRNA for wnt5b or RhoA, a key downstream effector of Wnt/PCP signaling, rescued the defective convergent extension phenotype and attenuated the lbx1b-induced curvature of the body axis. Thus, our study presents a novel pathological feature of LBX1 and its zebrafish homologs in body axis deformation at

  12. Joint source channel coding using arithmetic codes

    CERN Document Server

    Bi, Dongsheng

    2009-01-01

    Based on the encoding process, arithmetic codes can be viewed as tree codes and current proposals for decoding arithmetic codes with forbidden symbols belong to sequential decoding algorithms and their variants. In this monograph, we propose a new way of looking at arithmetic codes with forbidden symbols. If a limit is imposed on the maximum value of a key parameter in the encoder, this modified arithmetic encoder can also be modeled as a finite state machine and the code generated can be treated as a variable-length trellis code. The number of states used can be reduced and techniques used fo

  13. BAG3 (Bcl-2-Associated Athanogene-3) Coding Variant in Mice Determines Susceptibility to Ischemic Limb Muscle Myopathy by Directing Autophagy.

    Science.gov (United States)

    McClung, Joseph M; McCord, Timothy J; Ryan, Terence E; Schmidt, Cameron A; Green, Tom D; Southerland, Kevin W; Reinardy, Jessica L; Mueller, Sarah B; Venkatraman, Talaignair N; Lascola, Christopher D; Keum, Sehoon; Marchuk, Douglas A; Spangenburg, Espen E; Dokun, Ayotunde; Annex, Brian H; Kontos, Christopher D

    2017-07-18

    Critical limb ischemia is a manifestation of peripheral artery disease that carries significant mortality and morbidity risk in humans, although its genetic determinants remain largely unknown. We previously discovered 2 overlapping quantitative trait loci in mice, Lsq-1 and Civq-1, that affected limb muscle survival and stroke volume after femoral artery or middle cerebral artery ligation, respectively. Here, we report that a Bag3 variant (Ile81Met) segregates with tissue protection from hind-limb ischemia. We treated mice with either adeno-associated viruses encoding a control (green fluorescent protein) or 2 BAG3 (Bcl-2-associated athanogene-3) variants, namely Met81 or Ile81, and subjected the mice to hind-limb ischemia. We found that the BAG3 Ile81Met variant in the C57BL/6 (BL6) mouse background segregates with protection from tissue necrosis in a shorter congenic fragment of Lsq-1 (C.B6-Lsq1-3). BALB/c mice treated with adeno-associated virus encoding the BL6 BAG3 variant (Ile81; n=25) displayed reduced limb-tissue necrosis and increased limb tissue perfusion compared with Met81- (n=25) or green fluorescent protein- (n=29) expressing animals. BAG3(Ile81), but not BAG3(Met81), improved ischemic muscle myopathy and muscle precursor cell differentiation and improved muscle regeneration in a separate, toxin-induced model of injury. Systemic injection of adeno-associated virus-BAG3(Ile81) (n=9), but not BAG3(Met81) (n=10) or green fluorescent protein (n=5), improved ischemic limb blood flow and limb muscle histology and restored muscle function (force production). Compared with BAG3(Met81), BAG3(Ile81) displayed improved binding to the small heat shock protein (HspB8) in ischemic skeletal muscle cells and enhanced ischemic muscle autophagic flux. Taken together, our data demonstrate that genetic variation in BAG3 plays an important role in the prevention of ischemic tissue necrosis. These results highlight a pathway that preserves tissue survival and muscle

  14. Cellulase variants

    Energy Technology Data Exchange (ETDEWEB)

    Blazej, Robert; Toriello, Nicholas; Emrich, Charles; Cohen, Richard N.; Koppel, Nitzan

    2015-07-14

    This invention provides novel variant cellulolytic enzymes having improved activity and/or stability. In certain embodiments the variant cellulotyic enzymes comprise a glycoside hydrolase with or comprising a substitution at one or more positions corresponding to one or more of residues F64, A226, and/or E246 in Thermobifida fusca Cel9A enzyme. In certain embodiments the glycoside hydrolase is a variant of a family 9 glycoside hydrolase. In certain embodiments the glycoside hydrolase is a variant of a theme B family 9 glycoside hydrolase.

  15. A Novel Genetic Variant in Long Non-coding RNA Gene NEXN-AS1 is Associated with Risk of Lung Cancer

    Science.gov (United States)

    Yuan, Hua; Liu, Hongliang; Liu, Zhensheng; Owzar, Kouros; Han, Younghun; Su, Li; Wei, Yongyue; Hung, Rayjean J.; McLaughlin, John; Brhane, Yonathan; Brennan, Paul; Bickeboeller, Heike; Rosenberger, Albert; Houlston, Richard S.; Caporaso, Neil; Landi, Maria Teresa; Heinrich, Joachim; Risch, Angela; Christiani, David C.; Gümüş, Zeynep H.; Klein, Robert J.; Amos, Christopher I.; Wei, Qingyi

    2016-01-01

    Lung cancer etiology is multifactorial, and growing evidence has indicated that long non-coding RNAs (lncRNAs) are important players in lung carcinogenesis. We performed a large-scale meta-analysis of 690,564 SNPs in 15,531 autosomal lncRNAs by using datasets from six previously published genome-wide association studies (GWASs) from the Transdisciplinary Research in Cancer of the Lung (TRICL) consortium in populations of European ancestry. Previously unreported significant SNPs (P value < 1 × 10−7) were further validated in two additional independent lung cancer GWAS datasets from Harvard University and deCODE. In the final meta-analysis of all eight GWAS datasets with 17,153 cases and 239,337 controls, a novel risk SNP rs114020893 in the lncRNA NEXN-AS1 region at 1p31.1 remained statistically significant (odds ratio = 1.17; 95% confidence interval = 1.11–1.24; P = 8.31 × 10−9). In further in silico analysis, rs114020893 was predicted to change the secondary structure of the lncRNA. Our finding indicates that SNP rs114020893 of NEXN-AS1 at 1p31.1 may contribute to lung cancer susceptibility. PMID:27713484

  16. Molecular Characterization of the Tumor Suppressor Candidate 5 Gene: Regulation by PPARγ and Identification of TUSC5 Coding Variants in Lean and Obese Humans

    Directory of Open Access Journals (Sweden)

    Trina A. Knotts

    2009-01-01

    Full Text Available Tumor suppressor candidate 5 (TUSC5 is a gene expressed abundantly in white adipose tissue (WAT, brown adipose tissue (BAT, and peripheral afferent neurons. Strong adipocyte expression and increased expression following peroxisome proliferator activated receptor γ (PPARγ agonist treatment of 3T3-L1 adipocytes suggested a role for Tusc5 in fat cell proliferation and/or metabolism. However, the regulation of Tusc5 in WAT and its potential association with obesity phenotypes remain unclear. We tested the hypothesis that the TUSC5 gene is a bona fide PPARγ target and evaluated whether its WAT expression or single-nucleotide polymorphisms (SNPs in the TUSC5 coding region are associated with human obesity. Induction of Tusc5 mRNA levels in 3T3-L1 adipocytes by troglitazone and GW1929 followed a dose-response consistent with these agents' binding affinities for PPARγ. Chromatin immunoprecipitation (ChIP experiments confirmed that PPARγ protein binds a ∼−1.1 kb promotor sequence of murine TUSC5 transiently during 3T3-L1 adipogenesis, concurrent with histone H3 acetylation. No change in Tusc5 mRNA or protein levels was evident in type 2 diabetic patients treated with pioglitazone. Tusc5 expression was not induced appreciably in liver preparations overexpressing PPARs, suggesting that tissue-specific factors regulate PPARγ responsiveness of the TUSC5 gene. Finally, we observed no differences in Tusc5 WAT expression or prevalence of coding region SNPs in lean versus obese human subjects. These studies firmly establish the murine TUSC5 gene locus as a PPARγ target, but the significance of Tusc5 in obesity phenotypes or in the pharmacologic actions of PPARγ agonists in humans remains equivocal.

  17. The microRNAs in an ancient protist repress the variant-specific surface protein expression by targeting the entire coding sequence.

    Directory of Open Access Journals (Sweden)

    Ashesh A Saraiya

    2014-02-01

    Full Text Available microRNAs (miRNA have been detected in the deeply branched protist, Giardia lamblia, and shown to repress expression of the family of variant-specific surface proteins (VSPs, only one of which is expressed in Giardia trophozoite at a given time. Three next-generation sequencing libraries of Giardia Argonaute-associated small RNAs were constructed and analyzed. Analysis of the libraries identified a total of 99 new putative miRNAs with a size primarily in the 26 nt range similar to the size previously predicted by the Giardia Dicer crystal structure and identified by our own studies. Bioinformatic analysis identified multiple putative miRNA target sites in the mRNAs of all 73 VSPs. The effect of miRNA target sites within a defined 3'-region were tested on two vsp mRNAs. All the miRNAs showed partial repression of the corresponding vsp expression and were additive when the targeting sites were separately located. But the combined repression still falls short of 100%. Two other relatively short vsp mRNAs with 15 and 11 putative miRNA target sites identified throughout their ORFs were tested with their corresponding miRNAs. The results indicate that; (1 near 100% repression of vsp mRNA expression can be achieved through the combined action of multiple miRNAs on target sites located throughout the ORF; (2 the miRNA machinery could be instrumental in repressing the expression of vsp genes in Giardia; (3 this is the first time that all the miRNA target sites in the entire ORF of a mRNA have been tested and shown to be functional.

  18. Evolution of naturally occurring 5'non-coding region variants of Hepatitis C virus in human populations of the South American region

    Directory of Open Access Journals (Sweden)

    García-Aguirre Laura

    2007-08-01

    Full Text Available Abstract Background Hepatitis C virus (HCV has been the subject of intense research and clinical investigation as its major role in human disease has emerged. Previous and recent studies have suggested a diversification of type 1 HCV in the South American region. The degree of genetic variation among HCV strains circulating in Bolivia and Colombia is currently unknown. In order to get insight into these matters, we performed a phylogenetic analysis of HCV 5' non-coding region (5'NCR sequences from strains isolated in Bolivia, Colombia and Uruguay, as well as available comparable sequences of HCV strains isolated in South America. Methods Phylogenetic tree analysis was performed using the neighbor-joining method under a matrix of genetic distances established under the Kimura-two parameter model. Signature pattern analysis, which identifies particular sites in nucleic acid alignments of variable sequences that are distinctly representative relative to a background set, was performed using the method of Korber & Myers, as implemented in the VESPA program. Prediction of RNA secondary structures was done by the method of Zuker & Turner, as implemented in the mfold program. Results Phylogenetic tree analysis of HCV strains isolated in the South American region revealed the presence of a distinct genetic lineage inside genotype 1. Signature pattern analysis revealed that the presence of this lineage is consistent with the presence of a sequence signature in the 5'NCR of HCV strains isolated in South America. Comparisons of these results with the ones found for Europe or North America revealed that this sequence signature is characteristic of the South American region. Conclusion Phylogentic analysis revealed the presence of a sequence signature in the 5'NCR of type 1 HCV strains isolated in South America. This signature is frequent enough in type 1 HCV populations circulating South America to be detected in a phylogenetic tree analysis as a distinct

  19. Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus

    DEFF Research Database (Denmark)

    Mahajan, Anubha; Sim, Xueling; Ng, Hui Jin

    2015-01-01

    Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic varian...

  20. Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus

    DEFF Research Database (Denmark)

    Mahajan, Anubha; Sim, Xueling; Ng, Hui Jin

    2015-01-01

    Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic varian...

  1. Coded MapReduce

    OpenAIRE

    Li, Songze; Maddah-Ali, Mohammad Ali; Avestimehr, A. Salman

    2015-01-01

    MapReduce is a commonly used framework for executing data-intensive jobs on distributed server clusters. We introduce a variant implementation of MapReduce, namely "Coded MapReduce", to substantially reduce the inter-server communication load for the shuffling phase of MapReduce, and thus accelerating its execution. The proposed Coded MapReduce exploits the repetitive mapping of data blocks at different servers to create coding opportunities in the shuffling phase to exchange (key,value) pair...

  2. Duals of Affine Grassmann Codes and Their Relatives

    DEFF Research Database (Denmark)

    Beelen, P.; Ghorpade, S. R.; Hoholdt, T.

    2012-01-01

    Affine Grassmann codes are a variant of generalized Reed-Muller codes and are closely related to Grassmann codes. These codes were introduced in a recent work by Beelen Here, we consider, more generally, affine Grassmann codes of a given level. We explicitly determine the dual of an affine Grassm...

  3. Prefix Codes: Equiprobable Words, Unequal Letter Costs

    OpenAIRE

    Golin, Mordecai; Young, Neal E.

    2002-01-01

    Describes a near-linear-time algorithm for a variant of Huffman coding, in which the letters may have non-uniform lengths (as in Morse code), but with the restriction that each word to be encoded has equal probability. [See also ``Huffman Coding with Unequal Letter Costs'' (2002).

  4. Modifier effects between regulatory and protein-coding variation.

    Directory of Open Access Journals (Sweden)

    Antigone S Dimas

    2008-10-01

    Full Text Available Genome-wide associations have shown a lot of promise in dissecting the genetics of complex traits in humans with single variants, yet a large fraction of the genetic effects is still unaccounted for. Analyzing genetic interactions between variants (epistasis is one of the potential ways forward. We investigated the abundance and functional impact of a specific type of epistasis, namely the interaction between regulatory and protein-coding variants. Using genotype and gene expression data from the 210 unrelated individuals of the original four HapMap populations, we have explored the combined effects of regulatory and protein-coding single nucleotide polymorphisms (SNPs. We predict that about 18% (1,502 out of 8,233 nsSNPs of protein-coding variants are differentially expressed among individuals and demonstrate that regulatory variants can modify the functional effect of a coding variant in cis. Furthermore, we show that such interactions in cis can affect the expression of downstream targets of the gene containing the protein-coding SNP. In this way, a cis interaction between regulatory and protein-coding variants has a trans impact on gene expression. Given the abundance of both types of variants in human populations, we propose that joint consideration of regulatory and protein-coding variants may reveal additional genetic effects underlying complex traits and disease and may shed light on causes of differential penetrance of known disease variants.

  5. Modifier effects between regulatory and protein-coding variation.

    Science.gov (United States)

    Dimas, Antigone S; Stranger, Barbara E; Beazley, Claude; Finn, Robert D; Ingle, Catherine E; Forrest, Matthew S; Ritchie, Matthew E; Deloukas, Panos; Tavaré, Simon; Dermitzakis, Emmanouil T

    2008-10-01

    Genome-wide associations have shown a lot of promise in dissecting the genetics of complex traits in humans with single variants, yet a large fraction of the genetic effects is still unaccounted for. Analyzing genetic interactions between variants (epistasis) is one of the potential ways forward. We investigated the abundance and functional impact of a specific type of epistasis, namely the interaction between regulatory and protein-coding variants. Using genotype and gene expression data from the 210 unrelated individuals of the original four HapMap populations, we have explored the combined effects of regulatory and protein-coding single nucleotide polymorphisms (SNPs). We predict that about 18% (1,502 out of 8,233 nsSNPs) of protein-coding variants are differentially expressed among individuals and demonstrate that regulatory variants can modify the functional effect of a coding variant in cis. Furthermore, we show that such interactions in cis can affect the expression of downstream targets of the gene containing the protein-coding SNP. In this way, a cis interaction between regulatory and protein-coding variants has a trans impact on gene expression. Given the abundance of both types of variants in human populations, we propose that joint consideration of regulatory and protein-coding variants may reveal additional genetic effects underlying complex traits and disease and may shed light on causes of differential penetrance of known disease variants.

  6. Embedded foveation image coding.

    Science.gov (United States)

    Wang, Z; Bovik, A C

    2001-01-01

    The human visual system (HVS) is highly space-variant in sampling, coding, processing, and understanding. The spatial resolution of the HVS is highest around the point of fixation (foveation point) and decreases rapidly with increasing eccentricity. By taking advantage of this fact, it is possible to remove considerable high-frequency information redundancy from the peripheral regions and still reconstruct a perceptually good quality image. Great success has been obtained previously by a class of embedded wavelet image coding algorithms, such as the embedded zerotree wavelet (EZW) and the set partitioning in hierarchical trees (SPIHT) algorithms. Embedded wavelet coding not only provides very good compression performance, but also has the property that the bitstream can be truncated at any point and still be decoded to recreate a reasonably good quality image. In this paper, we propose an embedded foveation image coding (EFIC) algorithm, which orders the encoded bitstream to optimize foveated visual quality at arbitrary bit-rates. A foveation-based image quality metric, namely, foveated wavelet image quality index (FWQI), plays an important role in the EFIC system. We also developed a modified SPIHT algorithm to improve the coding efficiency. Experiments show that EFIC integrates foveation filtering with foveated image coding and demonstrates very good coding performance and scalability in terms of foveated image quality measurement.

  7. Rare variants in XRCC2 as breast cancer susceptibility alleles

    NARCIS (Netherlands)

    Hilbers, F.S.; Wijnen, J.T.; Hoogerbrugge-van der Linden, N.; Oosterwijk, J.C.; Collee, M.J.; Peterlongo, P.; Radice, P.; Manoukian, S.; Feroce, I.; Capra, F.; Couch, F.J.; Wang, X.; Guidugli, L.; Offit, K.; Shah, S.; Campbell, I.G.; Thompson, E.R.; James, P.A.; Trainer, A.H.; Gracia, J.; Benitez, J.; Asperen, C.J. van; Devilee, P.

    2012-01-01

    BACKGROUND: Recently, rare germline variants in XRCC2 were detected in non-BRCA1/2 familial breast cancer cases, and a significant association with breast cancer was reported. However, the breast cancer risk associated with these variants needs further evaluation. METHODS: The coding regions and exo

  8. Splicing variants of porcine synphilin-1

    DEFF Research Database (Denmark)

    Larsen, Knud Erik; Madsen, Lone Bruhn; Farajzadeh, Leila

    2015-01-01

    RNA was investigated by RNAseq. The presented work reports the molecular cloning and characterization of the porcine (Sus scrofa) synphilin-1 cDNA (SNCAIP) and three splice variants hereof. The porcine SNCAIP cDNA codes for a protein (synphilin-1) of 919 amino acids which shows a high similarity to human (90...

  9. Coding Partitions

    Directory of Open Access Journals (Sweden)

    Fabio Burderi

    2007-05-01

    Full Text Available Motivated by the study of decipherability conditions for codes weaker than Unique Decipherability (UD, we introduce the notion of coding partition. Such a notion generalizes that of UD code and, for codes that are not UD, allows to recover the ``unique decipherability" at the level of the classes of the partition. By tacking into account the natural order between the partitions, we define the characteristic partition of a code X as the finest coding partition of X. This leads to introduce the canonical decomposition of a code in at most one unambiguouscomponent and other (if any totally ambiguouscomponents. In the case the code is finite, we give an algorithm for computing its canonical partition. This, in particular, allows to decide whether a given partition of a finite code X is a coding partition. This last problem is then approached in the case the code is a rational set. We prove its decidability under the hypothesis that the partition contains a finite number of classes and each class is a rational set. Moreover we conjecture that the canonical partition satisfies such a hypothesis. Finally we consider also some relationships between coding partitions and varieties of codes.

  10. P-adic arithmetic coding

    CERN Document Server

    Rodionov, Anatoly

    2007-01-01

    A new incremental algorithm for data compression is presented. For a sequence of input symbols algorithm incrementally constructs a p-adic integer number as an output. Decoding process starts with less significant part of a p-adic integer and incrementally reconstructs a sequence of input symbols. Algorithm is based on certain features of p-adic numbers and p-adic norm. p-adic coding algorithm may be considered as of generalization a popular compression technique - arithmetic coding algorithms. It is shown that for p = 2 the algorithm works as integer variant of arithmetic coding; for a special class of models it gives exactly the same codes as Huffman's algorithm, for another special model and a specific alphabet it gives Golomb-Rice codes.

  11. Holographic codes

    CERN Document Server

    Latorre, Jose I

    2015-01-01

    There exists a remarkable four-qutrit state that carries absolute maximal entanglement in all its partitions. Employing this state, we construct a tensor network that delivers a holographic many body state, the H-code, where the physical properties of the boundary determine those of the bulk. This H-code is made of an even superposition of states whose relative Hamming distances are exponentially large with the size of the boundary. This property makes H-codes natural states for a quantum memory. H-codes exist on tori of definite sizes and get classified in three different sectors characterized by the sum of their qutrits on cycles wrapped through the boundaries of the system. We construct a parent Hamiltonian for the H-code which is highly non local and finally we compute the topological entanglement entropy of the H-code.

  12. Sharing code

    OpenAIRE

    Kubilius, Jonas

    2014-01-01

    Sharing code is becoming increasingly important in the wake of Open Science. In this review I describe and compare two popular code-sharing utilities, GitHub and Open Science Framework (OSF). GitHub is a mature, industry-standard tool but lacks focus towards researchers. In comparison, OSF offers a one-stop solution for researchers but a lot of functionality is still under development. I conclude by listing alternative lesser-known tools for code and materials sharing.

  13. Speaking Code

    DEFF Research Database (Denmark)

    Cox, Geoff

    Speaking Code begins by invoking the “Hello World” convention used by programmers when learning a new language, helping to establish the interplay of text and code that runs through the book. Interweaving the voice of critical writing from the humanities with the tradition of computing and software...

  14. Polar Codes

    Science.gov (United States)

    2014-12-01

    QPSK Gaussian channels . .......................................................................... 39 vi 1. INTRODUCTION Forward error correction (FEC...Capacity of BSC. 7 Figure 5. Capacity of AWGN channel . 8 4. INTRODUCTION TO POLAR CODES Polar codes were introduced by E. Arikan in [1]. This paper...Under authority of C. A. Wilgenbusch, Head ISR Division EXECUTIVE SUMMARY This report describes the results of the project “More reliable wireless

  15. Histone Variants and Epigenetics

    Science.gov (United States)

    Henikoff, Steven; Smith, M. Mitchell

    2015-01-01

    Histones package and compact DNA by assembling into nucleosome core particles. Most histones are synthesized at S phase for rapid deposition behind replication forks. In addition, the replacement of histones deposited during S phase by variants that can be deposited independently of replication provide the most fundamental level of chromatin differentiation. Alternative mechanisms for depositing different variants can potentially establish and maintain epigenetic states. Variants have also evolved crucial roles in chromosome segregation, transcriptional regulation, DNA repair, and other processes. Investigations into the evolution, structure, and metabolism of histone variants provide a foundation for understanding the participation of chromatin in important cellular processes and in epigenetic memory. PMID:25561719

  16. Variant profiling of evolving prokaryotic populations

    Science.gov (United States)

    Zojer, Markus; Schuster, Lisa N.; Schulz, Frederik; Pfundner, Alexander; Horn, Matthias

    2017-01-01

    Genomic heterogeneity of bacterial species is observed and studied in experimental evolution experiments and clinical diagnostics, and occurs as micro-diversity of natural habitats. The challenge for genome research is to accurately capture this heterogeneity with the currently used short sequencing reads. Recent advances in NGS technologies improved the speed and coverage and thus allowed for deep sequencing of bacterial populations. This facilitates the quantitative assessment of genomic heterogeneity, including low frequency alleles or haplotypes. However, false positive variant predictions due to sequencing errors and mapping artifacts of short reads need to be prevented. We therefore created VarCap, a workflow for the reliable prediction of different types of variants even at low frequencies. In order to predict SNPs, InDels and structural variations, we evaluated the sensitivity and accuracy of different software tools using synthetic read data. The results suggested that the best sensitivity could be reached by a union of different tools, however at the price of increased false positives. We identified possible reasons for false predictions and used this knowledge to improve the accuracy by post-filtering the predicted variants according to properties such as frequency, coverage, genomic environment/localization and co-localization with other variants. We observed that best precision was achieved by using an intersection of at least two tools per variant. This resulted in the reliable prediction of variants above a minimum relative abundance of 2%. VarCap is designed for being routinely used within experimental evolution experiments or for clinical diagnostics. The detected variants are reported as frequencies within a VCF file and as a graphical overview of the distribution of the different variant/allele/haplotype frequencies. The source code of VarCap is available at https://github.com/ma2o/VarCap. In order to provide this workflow to a broad community

  17. Mutation Update: The Spectra of Nebulin Variants and Associated Myopathies

    Science.gov (United States)

    Lehtokari, Vilma-Lotta; Kiiski, Kirsi; Sandaradura, Sarah A.; Laporte, Jocelyn; Repo, Pauliina; Frey, Jennifer A.; Donner, Kati; Marttila, Minttu; Saunders, Carol; Barth, Peter G.; den Dunnen, Johan T.; Beggs, Alan H.; Clarke, Nigel F.; North, Kathryn N.; Laing, Nigel G.; Romero, Norma B.; Winder, Thomas L.; Pelin, Katarina; Wallgren-Pettersson, Carina

    2015-01-01

    A mutation update on the nebulin gene (NEB) is necessary because of recent developments in analysis methodology, the identification of increasing numbers and novel types of variants, and a widening in the spectrum of clinical and histological phenotypes associated with this gigantic, 183 exons containing gene. Recessive pathogenic variants in NEB are the major cause of nemaline myopathy (NM), one of the most common congenital myopathies. Moreover, pathogenic NEB variants have been identified in core-rod myopathy and in distal myopathies. In this update, we present the disease-causing variants in NEB in 159 families, 143 families with NM, and 16 families with NM-related myopathies. Eighty-eight families are presented here for the first time. We summarize 86 previously published and 126 unpublished variants identified in NEB. Furthermore, we have analyzed the NEB variants deposited in the Exome Variant Server (http://evs.gs.washington.edu/EVS/), identifying that pathogenic variants are a minor fraction of all coding variants (~7%). This indicates that nebulin tolerates substantial changes in its amino acid sequence, providing an explanation as to why variants in such a large gene result in relatively rare disorders. Lastly, we discuss the difficulties of drawing reliable genotype–phenotype correlations in NEB-associated disease. PMID:25205138

  18. Speech coding

    Energy Technology Data Exchange (ETDEWEB)

    Ravishankar, C., Hughes Network Systems, Germantown, MD

    1998-05-08

    Speech is the predominant means of communication between human beings and since the invention of the telephone by Alexander Graham Bell in 1876, speech services have remained to be the core service in almost all telecommunication systems. Original analog methods of telephony had the disadvantage of speech signal getting corrupted by noise, cross-talk and distortion Long haul transmissions which use repeaters to compensate for the loss in signal strength on transmission links also increase the associated noise and distortion. On the other hand digital transmission is relatively immune to noise, cross-talk and distortion primarily because of the capability to faithfully regenerate digital signal at each repeater purely based on a binary decision. Hence end-to-end performance of the digital link essentially becomes independent of the length and operating frequency bands of the link Hence from a transmission point of view digital transmission has been the preferred approach due to its higher immunity to noise. The need to carry digital speech became extremely important from a service provision point of view as well. Modem requirements have introduced the need for robust, flexible and secure services that can carry a multitude of signal types (such as voice, data and video) without a fundamental change in infrastructure. Such a requirement could not have been easily met without the advent of digital transmission systems, thereby requiring speech to be coded digitally. The term Speech Coding is often referred to techniques that represent or code speech signals either directly as a waveform or as a set of parameters by analyzing the speech signal. In either case, the codes are transmitted to the distant end where speech is reconstructed or synthesized using the received set of codes. A more generic term that is applicable to these techniques that is often interchangeably used with speech coding is the term voice coding. This term is more generic in the sense that the

  19. Speaking Code

    DEFF Research Database (Denmark)

    Cox, Geoff

    ; alternatives to mainstream development, from performances of the live-coding scene to the organizational forms of commons-based peer production; the democratic promise of social media and their paradoxical role in suppressing political expression; and the market’s emptying out of possibilities for free...... development, Speaking Code unfolds an argument to undermine the distinctions between criticism and practice, and to emphasize the aesthetic and political aspects of software studies. Not reducible to its functional aspects, program code mirrors the instability inherent in the relationship of speech...... expression in the public realm. The book’s line of argument defends language against its invasion by economics, arguing that speech continues to underscore the human condition, however paradoxical this may seem in an era of pervasive computing....

  20. Desmoplastic variant of ameloblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Jeong Ick; Kim, Dong Youn; Choi, Karp Shik [Dept. of Dental Radiology, College of Dentistry, Kyungpook National University, Daegu (Korea, Republic of)

    1995-02-15

    Desmoplastic variant of ameloblastoma is new and unusual variant of ameloblastoma with extensive stromal desmoplastic proliferation. The authors experienced a case of desmoplastic variant of amleloblastoma with moderate-defined radiolucency on the right maxillary anterior area in 62-year-old female. As a result of careful analysis of clinical, radiological examinations, we diagnosed it as desmoplastic variant of ameloblastoma. The following results were obtained; 1. Main clinical symptoms were nontender bony swelling with normal intact overlying mucosa on the right maxillary anterior area. 2. Radiographically, moderate-defined, multilocular radioluceney on the right maxillary anterior area were shown, and severe cortical bony thinning and expansion to labial and palatal sides were also observed. And this lesion was shown to be extended to the right nasal cavity. 3. Histopathologically, follicle-like epithelial islands with densely abundant collagenous stroma were morphologically compressed.

  1. The Aster code; Code Aster

    Energy Technology Data Exchange (ETDEWEB)

    Delbecq, J.M

    1999-07-01

    The Aster code is a 2D or 3D finite-element calculation code for structures developed by the R and D direction of Electricite de France (EdF). This dossier presents a complete overview of the characteristics and uses of the Aster code: introduction of version 4; the context of Aster (organisation of the code development, versions, systems and interfaces, development tools, quality assurance, independent validation); static mechanics (linear thermo-elasticity, Euler buckling, cables, Zarka-Casier method); non-linear mechanics (materials behaviour, big deformations, specific loads, unloading and loss of load proportionality indicators, global algorithm, contact and friction); rupture mechanics (G energy restitution level, restitution level in thermo-elasto-plasticity, 3D local energy restitution level, KI and KII stress intensity factors, calculation of limit loads for structures), specific treatments (fatigue, rupture, wear, error estimation); meshes and models (mesh generation, modeling, loads and boundary conditions, links between different modeling processes, resolution of linear systems, display of results etc..); vibration mechanics (modal and harmonic analysis, dynamics with shocks, direct transient dynamics, seismic analysis and aleatory dynamics, non-linear dynamics, dynamical sub-structuring); fluid-structure interactions (internal acoustics, mass, rigidity and damping); linear and non-linear thermal analysis; steels and metal industry (structure transformations); coupled problems (internal chaining, internal thermo-hydro-mechanical coupling, chaining with other codes); products and services. (J.S.)

  2. Optimal codes as Tanner codes with cyclic component codes

    DEFF Research Database (Denmark)

    Høholdt, Tom; Pinero, Fernando; Zeng, Peng

    2014-01-01

    In this article we study a class of graph codes with cyclic code component codes as affine variety codes. Within this class of Tanner codes we find some optimal binary codes. We use a particular subgraph of the point-line incidence plane of A(2,q) as the Tanner graph, and we are able to describe...... the codes succinctly using Gröbner bases....

  3. CooVar: Co-occurring variant analyzer

    Directory of Open Access Journals (Sweden)

    Vergara Ismael A

    2012-11-01

    Full Text Available Abstract Background Evaluating the impact of genomic variations (GV on protein-coding transcripts is an important step in identifying variants of functional significance. Currently available programs for variant annotation depend on external databases or annotate multiple variants affecting the same transcript independently, which limits program use to organisms available in these databases or results in potentially incorrect or incomplete annotations. Findings We have developed CooVar (Co-occurring Variant Analyzer, a database-independent program for assessing the impact of GVs on protein-coding transcripts. CooVar takes GVs, reference genome sequence, and protein-coding exons as input and provides annotated GVs and transcripts as output. Other than similar programs, CooVar considers the combined impact of all GVs affecting the same transcript, generating biologically more accurate annotations. CooVar is operated from the command-line and supports standard file formats VCF, GFF/GTF, and GVF, which makes it easy to integrate into existing computational pipelines. We have extensively tested CooVar on worm and human data sets and demonstrate that it generates correct annotations in only a short amount of time. Conclusions CooVar is an easy-to-use and lightweight variant annotation tool that considers the combined impact of GVs on protein-coding transcripts. CooVar is freely available at http://genome.sfu.ca/projects/coovar/.

  4. Private mitochondrial DNA variants in danish patients with hypertrophic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Christian M Hagen

    Full Text Available Hypertrophic cardiomyopathy (HCM is a genetic cardiac disease primarily caused by mutations in genes coding for sarcomeric proteins. A molecular-genetic etiology can be established in ~60% of cases. Evolutionarily conserved mitochondrial DNA (mtDNA haplogroups are susceptibility factors for HCM. Several polymorphic mtDNA variants are associated with a variety of late-onset degenerative diseases and affect mitochondrial function. We examined the role of private, non-haplogroup associated, mitochondrial variants in the etiology of HCM. In 87 Danish HCM patients, full mtDNA sequencing revealed 446 variants. After elimination of 312 (69.9% non-coding and synonymous variants, a further 109 (24.4% with a global prevalence > 0.1%, three (0.7% haplogroup associated and 19 (2.0% variants with a low predicted in silico likelihood of pathogenicity, three variants: MT-TC: m.5772G>A, MT-TF: m.644A>G, and MT-CYB: m.15024G>A, p.C93Y remained. A detailed analysis of these variants indicated that none of them are likely to cause HCM. In conclusion, private mtDNA mutations are frequent, but they are rarely, if ever, associated with HCM.

  5. Modern Code Reviews in Open-Source Projects: Which Problems Do They Fix?

    NARCIS (Netherlands)

    Beller, M.; Bacchelli, A.; Zaidman, A.E.; Juergens, E.

    2014-01-01

    Code review is the manual assessment of source code by humans, mainly intended to identify defects and quality problems. Modern Code Review (MCR), a lightweight variant of the code inspections investigated since the 1970s, prevails today both in industry and open-source software (OSS) systems. The

  6. On Using Goldbach G0 Codes and Even-Rodeh Codes for Text Compression on Using Goldbach G0 Codes and Even-Rodeh Codes for Text Compression

    Science.gov (United States)

    Budiman, M. A.; Rachmawati, D.

    2017-03-01

    This research aims to study the efficiency of two variants of variable-length codes (i.e., Goldbach G0 codes and Even-Rodeh codes) in compressing texts. The parameters being examined are the ratio of compression, the space savings, and the bit rate. As a benchmark, all of the original (uncompressed) texts are assumed to be encoded in American Standard Codes for Information Interchange (ASCII). Several texts, including those derived from some corpora (the Artificial corpus, the Calgary corpus, the Canterbury corpus, the Large corpus, and the Miscellaneous corpus) are tested in the experiment. The overall result shows that the Even-Rodeh codes are consistently more efficient to compress texts than the unoptimzed Goldbach G0 codes.

  7. Hemoglobin Variants in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Popp, Raymond A.

    1965-04-22

    Variability among mammalian hemoglobins was observed many years ago (35). The chemical basis for differences among hemoglobins from different species of mammals has been studied by several investigators (5, 11, 18, 48). As well as interspecies differences, hemoglobin variants are frequently found within a species of mammals (2, 3, 7, 16) The inheritance of these intraspecies variants can be studied, and pedigrees indicate that the type of hemoglobin synthesized in an individual is genetically controlled (20). Several of the variant human hemoglobins are f'unctionally deficient (7, 16). Such hemoglobin anomalies are of basic interest to man because of the vital role of hemoglobin for transporting oxygen to all tissues of the body.

  8. Rare variants in PLXNA4 and Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Eva C Schulte

    Full Text Available Approximately 20% of individuals with Parkinson's disease (PD report a positive family history. Yet, a large portion of causal and disease-modifying variants is still unknown. We used exome sequencing in two affected individuals from a family with late-onset familial PD followed by frequency assessment in 975 PD cases and 1014 ethnically-matched controls and linkage analysis to identify potentially causal variants. Based on the predicted penetrance and the frequencies, a variant in PLXNA4 proved to be the best candidate and PLXNA4 was screened for additional variants in 862 PD cases and 940 controls, revealing an excess of rare non-synonymous coding variants in PLXNA4 in individuals with PD. Although we cannot conclude that the variant in PLXNA4 is indeed the causative variant, these findings are interesting in the light of a surfacing role of axonal guidance mechanisms in neurodegenerative disorders but, at the same time, highlight the difficulties encountered in the study of rare variants identified by next-generation sequencing in diseases with autosomal dominant or complex patterns of inheritance.

  9. Association analysis identifies ZNF750 regulatory variants in psoriasis

    Directory of Open Access Journals (Sweden)

    Birnbaum Ramon Y

    2011-12-01

    Full Text Available Abstract Background Mutations in the ZNF750 promoter and coding regions have been previously associated with Mendelian forms of psoriasis and psoriasiform dermatitis. ZNF750 encodes a putative zinc finger transcription factor that is highly expressed in keratinocytes and represents a candidate psoriasis gene. Methods We examined whether ZNF750 variants were associated with psoriasis in a large case-control population. We sequenced the promoter and exon regions of ZNF750 in 716 Caucasian psoriasis cases and 397 Caucasian controls. Results We identified a total of 47 variants, including 38 rare variants of which 35 were novel. Association testing identified two ZNF750 haplotypes associated with psoriasis (p ZNF750 promoter and 5' UTR variants displayed a 35-55% reduction of ZNF750 promoter activity, consistent with the promoter activity reduction seen in a Mendelian psoriasis family with a ZNF750 promoter variant. However, the rare promoter and 5' UTR variants identified in this study did not strictly segregate with the psoriasis phenotype within families. Conclusions Two haplotypes of ZNF750 and rare 5' regulatory variants of ZNF750 were found to be associated with psoriasis. These rare 5' regulatory variants, though not causal, might serve as a genetic modifier of psoriasis.

  10. Splicing variants of porcine synphilin-1

    Directory of Open Access Journals (Sweden)

    Knud Larsen

    2015-09-01

    Full Text Available Parkinson's disease (PD, idiopathic and familial, is characterized by degradation of dopaminergic neurons and the presence of Lewy bodies (LB in the substantia nigra. LBs contain aggregated proteins of which α-synuclein is the major component. The protein synphilin-1 interacts and colocalizes with α-synuclein in LBs. The aim of this study was to isolate and characterize porcine synphilin-1 and isoforms hereof with the future perspective to use the pig as a model for Parkinson's disease. The porcine SNCAIP cDNA was cloned by reverse transcriptase PCR. The spatial expression of SNCAIP mRNA was investigated by RNAseq. The presented work reports the molecular cloning and characterization of the porcine (Sus scrofa synphilin-1 cDNA (SNCAIP and three splice variants hereof. The porcine SNCAIP cDNA codes for a protein (synphilin-1 of 919 amino acids which shows a high similarity to human (90% and to mouse (84% synphilin-1. Three shorter transcript variants of the synphilin-1 gene were identified, all lacking one or more exons. SNCAIP transcripts were detected in most examined organs and tissues and the highest expression was found in brain tissues and lung. Conserved splicing variants and a novel splice form of synhilin-1 were found in this study. All synphilin-1 isoforms encoded by the identified transcript variants lack functional domains important for protein degradation.

  11. PIN1 gene variants in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Siedlecki Janusz

    2009-11-01

    Full Text Available Abstract Background Peptidyl-prolyl isomerase, NIMA-interacting 1 (PIN1 plays a significant role in the brain and is implicated in numerous cellular processes related to Alzheimer's disease (AD and other neurodegenerative conditions. There are confounding results concerning PIN1 activity in AD brains. Also PIN1 genetic variation was inconsistently associated with AD risk. Methods We performed analysis of coding and promoter regions of PIN1 in early- and late-onset AD and frontotemporal dementia (FTD patients in comparison with healthy controls. Results Analysis of eighteen PIN1 common polymorphisms and their haplotypes in EOAD, LOAD and FTD individuals in comparison with the control group did not reveal their contribution to disease risk. In six unrelated familial AD patients four novel PIN1 sequence variants were detected. c.58+64C>T substitution that was identified in three patients, was located in an alternative exon. In silico analysis suggested that this variant highly increases a potential affinity for a splicing factor and introduces two intronic splicing enhancers. In the peripheral leukocytes of one living patient carrying the variant, a 2.82 fold decrease in PIN1 expression was observed. Conclusion Our data does not support the role of PIN1 common polymorphisms as AD risk factor. However, we suggest that the identified rare sequence variants could be directly connected with AD pathology, influencing PIN1 splicing and/or expression.

  12. NOVEL BIPHASE CODE -INTEGRATED SIDELOBE SUPPRESSION CODE

    Institute of Scientific and Technical Information of China (English)

    Wang Feixue; Ou Gang; Zhuang Zhaowen

    2004-01-01

    A kind of novel binary phase code named sidelobe suppression code is proposed in this paper. It is defined to be the code whose corresponding optimal sidelobe suppression filter outputs the minimum sidelobes. It is shown that there do exist sidelobe suppression codes better than the conventional optimal codes-Barker codes. For example, the sidelobe suppression code of length 11 with filter of length 39 has better sidelobe level up to 17dB than that of Barker code with the same code length and filter length.

  13. Evaluation of non-coding variation in GLUT1 deficiency.

    Science.gov (United States)

    Liu, Yu-Chi; Lee, Jia Wei Audrey; Bellows, Susannah T; Damiano, John A; Mullen, Saul A; Berkovic, Samuel F; Bahlo, Melanie; Scheffer, Ingrid E; Hildebrand, Michael S

    2016-12-01

    Loss-of-function mutations in SLC2A1, encoding glucose transporter-1 (GLUT-1), lead to dysfunction of glucose transport across the blood-brain barrier. Ten percent of cases with hypoglycorrhachia (fasting cerebrospinal fluid [CSF] glucose <2.2mmol/L) do not have mutations. We hypothesized that GLUT1 deficiency could be due to non-coding SLC2A1 variants. We performed whole exome sequencing of one proband with a GLUT1 phenotype and hypoglycorrhachia negative for SLC2A1 sequencing and copy number variants. We studied a further 55 patients with different epilepsies and low CSF glucose who did not have exonic mutations or copy number variants. We sequenced non-coding promoter and intronic regions. We performed mRNA studies for the recurrent intronic variant. The proband had a de novo splice site mutation five base pairs from the intron-exon boundary. Three of 55 patients had deep intronic SLC2A1 variants, including a recurrent variant in two. The recurrent variant produced less SLC2A1 mRNA transcript. Fasting CSF glucose levels show an age-dependent correlation, which makes the definition of hypoglycorrhachia challenging. Low CSF glucose levels may be associated with pathogenic SLC2A1 mutations including deep intronic SLC2A1 variants. Extending genetic screening to non-coding regions will enable diagnosis of more patients with GLUT1 deficiency, allowing implementation of the ketogenic diet to improve outcomes. © 2016 Mac Keith Press.

  14. From concatenated codes to graph codes

    DEFF Research Database (Denmark)

    Justesen, Jørn; Høholdt, Tom

    2004-01-01

    We consider codes based on simple bipartite expander graphs. These codes may be seen as the first step leading from product type concatenated codes to more complex graph codes. We emphasize constructions of specific codes of realistic lengths, and study the details of decoding by message passing...

  15. Variant profiling of evolving prokaryotic populations

    Directory of Open Access Journals (Sweden)

    Markus Zojer

    2017-02-01

    Full Text Available Genomic heterogeneity of bacterial species is observed and studied in experimental evolution experiments and clinical diagnostics, and occurs as micro-diversity of natural habitats. The challenge for genome research is to accurately capture this heterogeneity with the currently used short sequencing reads. Recent advances in NGS technologies improved the speed and coverage and thus allowed for deep sequencing of bacterial populations. This facilitates the quantitative assessment of genomic heterogeneity, including low frequency alleles or haplotypes. However, false positive variant predictions due to sequencing errors and mapping artifacts of short reads need to be prevented. We therefore created VarCap, a workflow for the reliable prediction of different types of variants even at low frequencies. In order to predict SNPs, InDels and structural variations, we evaluated the sensitivity and accuracy of different software tools using synthetic read data. The results suggested that the best sensitivity could be reached by a union of different tools, however at the price of increased false positives. We identified possible reasons for false predictions and used this knowledge to improve the accuracy by post-filtering the predicted variants according to properties such as frequency, coverage, genomic environment/localization and co-localization with other variants. We observed that best precision was achieved by using an intersection of at least two tools per variant. This resulted in the reliable prediction of variants above a minimum relative abundance of 2%. VarCap is designed for being routinely used within experimental evolution experiments or for clinical diagnostics. The detected variants are reported as frequencies within a VCF file and as a graphical overview of the distribution of the different variant/allele/haplotype frequencies. The source code of VarCap is available at https://github.com/ma2o/VarCap. In order to provide this workflow to

  16. Towards a universal code formatter through machine learning

    NARCIS (Netherlands)

    Parr, T. (Terence); J.J. Vinju (Jurgen)

    2016-01-01

    textabstractThere are many declarative frameworks that allow us to implement code formatters relatively easily for any specific language, but constructing them is cumbersome. The first problem is that "everybody" wants to format their code differently, leading to either many formatter variants or a

  17. Good Codes From Generalised Algebraic Geometry Codes

    CERN Document Server

    Jibril, Mubarak; Ahmed, Mohammed Zaki; Tjhai, Cen

    2010-01-01

    Algebraic geometry codes or Goppa codes are defined with places of degree one. In constructing generalised algebraic geometry codes places of higher degree are used. In this paper we present 41 new codes over GF(16) which improve on the best known codes of the same length and rate. The construction method uses places of small degree with a technique originally published over 10 years ago for the construction of generalised algebraic geometry codes.

  18. List Decoding of Algebraic Codes

    DEFF Research Database (Denmark)

    Nielsen, Johan Sebastian Rosenkilde

    We investigate three paradigms for polynomial-time decoding of Reed–Solomon codes beyond half the minimum distance: the Guruswami–Sudan algorithm, Power decoding and the Wu algorithm. The main results concern shaping the computational core of all three methods to a problem solvable by module...... give: a fast maximum-likelihood list decoder based on the Guruswami–Sudan algorithm; a new variant of Power decoding, Power Gao, along with some new insights into Power decoding; and a new, module based method for performing rational interpolation for theWu algorithm. We also show how to decode...

  19. Histone variants and lipid metabolism

    NARCIS (Netherlands)

    Borghesan, Michela; Mazzoccoli, Gianluigi; Sheedfar, Fareeba; Oben, Jude; Pazienza, Valerio; Vinciguerra, Manlio

    2014-01-01

    Within nucleosomes, canonical histones package the genome, but they can be opportunely replaced with histone variants. The incorporation of histone variants into the nucleosome is a chief cellular strategy to regulate transcription and cellular metabolism. In pathological terms, cellular steatosis

  20. Migraine Variants And Beyond

    Directory of Open Access Journals (Sweden)

    Chakravarty A

    2002-01-01

    Full Text Available The Classic presenting features of both migraine with and without aura have been clearly defined. Occasionally however migrainous headaches are accompanied by abrupt appearance of focal and ominous neurological signs. Such attacks can be labelled as migraine variants and the diagnosis in reality is one made by exclusion of other CNS diseases. Some but not all such conditions are mentioned in the International Headache Society (IHS classification under the general heading of migraine with aura. Rarely, the focal neurological deficit may outlast the migraine attack by days and occasionally with appearance of structural brain lesions on neuroimaging. Such attacks have been labelled as complicated Migraine by the IHS. The present review deal with the clinical, radiologic and pathophysiologic aspects of both these conditions - migraine variants and complicated migraine.

  1. Variants of Uncertainty

    Science.gov (United States)

    1981-05-15

    Variants of Uncertainty Daniel Kahneman University of British Columbia Amos Tversky Stanford University DTI-C &%E-IECTE ~JUNO 1i 19 8 1j May 15, 1981... Dennett , 1979) in which different parts have ac- cess to different data, assign then different weights and hold different views of the situation...2robable and t..h1 provable. Oxford- Claredor Press, 1977. Dennett , D.C. Brainstorms. Hassocks: Harvester, 1979. Donchin, E., Ritter, W. & McCallum, W.C

  2. Variants of glycoside hydrolases

    Energy Technology Data Exchange (ETDEWEB)

    Teter, Sarah; Ward, Connie; Cherry, Joel; Jones, Aubrey; Harris, Paul; Yi, Jung

    2017-07-11

    The present invention relates to variants of a parent glycoside hydrolase, comprising a substitution at one or more positions corresponding to positions 21, 94, 157, 205, 206, 247, 337, 350, 373, 383, 438, 455, 467, and 486 of amino acids 1 to 513 of SEQ ID NO: 2, and optionally further comprising a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2 a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2, wherein the variants have glycoside hydrolase activity. The present invention also relates to nucleotide sequences encoding the variant glycoside hydrolases and to nucleic acid constructs, vectors, and host cells comprising the nucleotide sequences.

  3. Variants of glycoside hydrolases

    Energy Technology Data Exchange (ETDEWEB)

    Teter, Sarah (Davis, CA); Ward, Connie (Hamilton, MT); Cherry, Joel (Davis, CA); Jones, Aubrey (Davis, CA); Harris, Paul (Carnation, WA); Yi, Jung (Sacramento, CA)

    2011-04-26

    The present invention relates to variants of a parent glycoside hydrolase, comprising a substitution at one or more positions corresponding to positions 21, 94, 157, 205, 206, 247, 337, 350, 373, 383, 438, 455, 467, and 486 of amino acids 1 to 513 of SEQ ID NO: 2, and optionally further comprising a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2 a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2, wherein the variants have glycoside hydrolase activity. The present invention also relates to nucleotide sequences encoding the variant glycoside hydrolases and to nucleic acid constructs, vectors, and host cells comprising the nucleotide sequences.

  4. Space Time Codes from Permutation Codes

    CERN Document Server

    Henkel, Oliver

    2006-01-01

    A new class of space time codes with high performance is presented. The code design utilizes tailor-made permutation codes, which are known to have large minimal distances as spherical codes. A geometric connection between spherical and space time codes has been used to translate them into the final space time codes. Simulations demonstrate that the performance increases with the block lengths, a result that has been conjectured already in previous work. Further, the connection to permutation codes allows for moderate complex en-/decoding algorithms.

  5. Fundamentals of convolutional coding

    CERN Document Server

    Johannesson, Rolf

    2015-01-01

    Fundamentals of Convolutional Coding, Second Edition, regarded as a bible of convolutional coding brings you a clear and comprehensive discussion of the basic principles of this field * Two new chapters on low-density parity-check (LDPC) convolutional codes and iterative coding * Viterbi, BCJR, BEAST, list, and sequential decoding of convolutional codes * Distance properties of convolutional codes * Includes a downloadable solutions manual

  6. Discriminative sparse coding on multi-manifolds

    KAUST Repository

    Wang, J.J.-Y.

    2013-09-26

    Sparse coding has been popularly used as an effective data representation method in various applications, such as computer vision, medical imaging and bioinformatics. However, the conventional sparse coding algorithms and their manifold-regularized variants (graph sparse coding and Laplacian sparse coding), learn codebooks and codes in an unsupervised manner and neglect class information that is available in the training set. To address this problem, we propose a novel discriminative sparse coding method based on multi-manifolds, that learns discriminative class-conditioned codebooks and sparse codes from both data feature spaces and class labels. First, the entire training set is partitioned into multiple manifolds according to the class labels. Then, we formulate the sparse coding as a manifold-manifold matching problem and learn class-conditioned codebooks and codes to maximize the manifold margins of different classes. Lastly, we present a data sample-manifold matching-based strategy to classify the unlabeled data samples. Experimental results on somatic mutations identification and breast tumor classification based on ultrasonic images demonstrate the efficacy of the proposed data representation and classification approach. 2013 The Authors. All rights reserved.

  7. Strong Trinucleotide Circular Codes

    Directory of Open Access Journals (Sweden)

    Christian J. Michel

    2011-01-01

    Full Text Available Recently, we identified a hierarchy relation between trinucleotide comma-free codes and trinucleotide circular codes (see our previous works. Here, we extend our hierarchy with two new classes of codes, called DLD and LDL codes, which are stronger than the comma-free codes. We also prove that no circular code with 20 trinucleotides is a DLD code and that a circular code with 20 trinucleotides is comma-free if and only if it is a LDL code. Finally, we point out the possible role of the symmetric group ∑4 in the mathematical study of trinucleotide circular codes.

  8. Rare variants in ischemic stroke: an exome pilot study.

    Directory of Open Access Journals (Sweden)

    John W Cole

    Full Text Available The genetic architecture of ischemic stroke is complex and is likely to include rare or low frequency variants with high penetrance and large effect sizes. Such variants are likely to provide important insights into disease pathogenesis compared to common variants with small effect sizes. Because a significant portion of human functional variation may derive from the protein-coding portion of genes we undertook a pilot study to identify variation across the human exome (i.e., the coding exons across the entire human genome in 10 ischemic stroke cases. Our efforts focused on evaluating the feasibility and identifying the difficulties in this type of research as it applies to ischemic stroke. The cases included 8 African-Americans and 2 Caucasians selected on the basis of similar stroke subtypes and by implementing a case selection algorithm that emphasized the genetic contribution of stroke risk. Following construction of paired-end sequencing libraries, all predicted human exons in each sample were captured and sequenced. Sequencing generated an average of 25.5 million read pairs (75 bp×2 and 3.8 Gbp per sample. After passing quality filters, screening the exomes against dbSNP demonstrated an average of 2839 novel SNPs among African-Americans and 1105 among Caucasians. In an aggregate analysis, 48 genes were identified to have at least one rare variant across all stroke cases. One gene, CSN3, identified by screening our prior GWAS results in conjunction with our exome results, was found to contain an interesting coding polymorphism as well as containing excess rare variation as compared with the other genes evaluated. In conclusion, while rare coding variants may predispose to the risk of ischemic stroke, this fact has yet to be definitively proven. Our study demonstrates the complexities of such research and highlights that while exome data can be obtained, the optimal analytical methods have yet to be determined.

  9. Model Children's Code.

    Science.gov (United States)

    New Mexico Univ., Albuquerque. American Indian Law Center.

    The Model Children's Code was developed to provide a legally correct model code that American Indian tribes can use to enact children's codes that fulfill their legal, cultural and economic needs. Code sections cover the court system, jurisdiction, juvenile offender procedures, minor-in-need-of-care, and termination. Almost every Code section is…

  10. VH-1: Multidimensional ideal compressible hydrodynamics code

    Science.gov (United States)

    Hawley, John; Blondin, John; Lindahl, Greg; Lufkin, Eric

    2012-04-01

    VH-1 is a multidimensional ideal compressible hydrodynamics code written in FORTRAN for use on any computing platform, from desktop workstations to supercomputers. It uses a Lagrangian remap version of the Piecewise Parabolic Method developed by Paul Woodward and Phil Colella in their 1984 paper. VH-1 comes in a variety of versions, from a simple one-dimensional serial variant to a multi-dimensional version scalable to thousands of processors.

  11. Product Variant Master as a Means to Handle Variant Design

    DEFF Research Database (Denmark)

    Hildre, Hans Petter; Mortensen, Niels Henrik; Andreasen, Mogens Myrup

    1996-01-01

    The overall time requiered to design a new product variant relies on two factor: how good the methods to design the new variant are and how good these method are supported by computers.It has been estimated that 80% of all design tasks are variational in that the goal of the design is to adapt an...

  12. Variants of windmill nystagmus.

    Science.gov (United States)

    Choi, Kwang-Dong; Shin, Hae Kyung; Kim, Ji-Soo; Kim, Sung-Hee; Choi, Jae-Hwan; Kim, Hyo-Jung; Zee, David S

    2016-07-01

    Windmill nystagmus is characterized by a clock-like rotation of the beating direction of a jerk nystagmus suggesting separate horizontal and vertical oscillators, usually 90° out of phase. We report oculographic characteristics in three patients with variants of windmill nystagmus in whom the common denominator was profound visual loss due to retinal diseases. Two patients showed a clock-like pattern, while in the third, the nystagmus was largely diagonal (in phase or 180° out of phase) but also periodically changed direction by 180°. We hypothesize that windmill nystagmus is a unique manifestation of "eye movements of the blind." It emerges when the central structures, including the cerebellum, that normally keep eye movements calibrated and gaze steady can no longer perform their task, because they are deprived of the retinal image motion that signals a need for adaptive recalibration.

  13. Rateless feedback codes

    DEFF Research Database (Denmark)

    Sørensen, Jesper Hemming; Koike-Akino, Toshiaki; Orlik, Philip

    2012-01-01

    This paper proposes a concept called rateless feedback coding. We redesign the existing LT and Raptor codes, by introducing new degree distributions for the case when a few feedback opportunities are available. We show that incorporating feedback to LT codes can significantly decrease both...... the coding overhead and the encoding/decoding complexity. Moreover, we show that, at the price of a slight increase in the coding overhead, linear complexity is achieved with Raptor feedback coding....

  14. PRKG1基因非编码区多态与蒙古族原发性高血压的易感性研究%THE SUSCEPTIBILITY STUDIES OF NON-CODING REGION VARIANTS OF PRKG1 GENE AND ESSENTIAL HYPERTENSION IN MONGOLIAN POPULATION

    Institute of Scientific and Technical Information of China (English)

    常培叶; 赵平; 刘志跃; 秦莉

    2015-01-01

    Objective:Hypertension is a complex disease resulted from the interaction of genetic and environmental factors. We investigated the association between non-coding region variants of PRKG 1 gene and essential hypertension in Mongolian population in Xilin Gol League. Methods:Referring to the Chinese data in HapMap project, we conducted a case-control study, which collected 429 Mongolian specimens, including 212 cases of high blood pressure and 217 cases of normal blood pressure. The promoter and 3'untranslated region of PRKG 1 gene was sequenced. The genotyping was performed using the polymerase chain reaction ( PCR)/Ligase detection reaction assay. Results:Three mutations were found in PRKG 1 gene sequencing, there are PRKG 1-1, PRKG 1-2 and PRKG 1-3 respectively. In the Mongolian population, PRKG 1-2 and PRKG 1-3 loci detected only A allele and AA genotype, and the others were not detected. The distribution of genotype and allele frequencies of PRKG 1-1 were not significantly different between EH group and the control group. Conclusions:There was no significant correlation between promoter and 3 ’ untranslated region polymorphism of PRKG 1 gene and essential hypertension in Mongolian population.%目的::高血压是由遗传和环境因素共同作用而引起的复杂性疾病,本研究预探讨PRKG1基因非编码区多态在蒙古族原发性高血压中的作用。方法:采集内蒙古自治区锡林郭勒盟蒙古族标本429例,其中高血压212例,正常血压者217例。对 PRKG1基因的启动子和3’非翻译区进行测序后对突变位点进行基因分型。结果:PRKG1基因测序共发现3个突变位点,分别是 PRKG1-1,PRKG1-2和 PRKG1-3。在蒙古族人群中, PRKG1基因的PRKG1-2和PRKG1-3位点各检测到A等位基因和AA基因型,未检测到另一等位基因和和其对应的基因型,PRKG1-1位点的等位基因频率和基因型频率在高血压组和正常对照组间差异无统计学意义。结论:PRKG1

  15. Coding for dummies

    CERN Document Server

    Abraham, Nikhil

    2015-01-01

    Hands-on exercises help you learn to code like a pro No coding experience is required for Coding For Dummies,your one-stop guide to building a foundation of knowledge inwriting computer code for web, application, and softwaredevelopment. It doesn't matter if you've dabbled in coding or neverwritten a line of code, this book guides you through the basics.Using foundational web development languages like HTML, CSS, andJavaScript, it explains in plain English how coding works and whyit's needed. Online exercises developed by Codecademy, a leading online codetraining site, help hone coding skill

  16. Advanced video coding systems

    CERN Document Server

    Gao, Wen

    2015-01-01

    This comprehensive and accessible text/reference presents an overview of the state of the art in video coding technology. Specifically, the book introduces the tools of the AVS2 standard, describing how AVS2 can help to achieve a significant improvement in coding efficiency for future video networks and applications by incorporating smarter coding tools such as scene video coding. Topics and features: introduces the basic concepts in video coding, and presents a short history of video coding technology and standards; reviews the coding framework, main coding tools, and syntax structure of AV

  17. A rare myelin protein zero (MPZ variant alters enhancer activity in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Anthony Antonellis

    Full Text Available BACKGROUND: Myelin protein zero (MPZ is a critical structural component of myelin in the peripheral nervous system. The MPZ gene is regulated, in part, by the transcription factors SOX10 and EGR2. Mutations in MPZ, SOX10, and EGR2 have been implicated in demyelinating peripheral neuropathies, suggesting that components of this transcriptional network are candidates for harboring disease-causing mutations (or otherwise functional variants that affect MPZ expression. METHODOLOGY: We utilized a combination of multi-species sequence comparisons, transcription factor-binding site predictions, targeted human DNA re-sequencing, and in vitro and in vivo enhancer assays to study human non-coding MPZ variants. PRINCIPAL FINDINGS: Our efforts revealed a variant within the first intron of MPZ that resides within a previously described SOX10 binding site is associated with decreased enhancer activity, and alters binding of nuclear proteins. Additionally, the genomic segment harboring this variant directs tissue-relevant reporter gene expression in zebrafish. CONCLUSIONS: This is the first reported MPZ variant within a cis-acting transcriptional regulatory element. While we were unable to implicate this variant in disease onset, our data suggests that similar non-coding sequences should be screened for mutations in patients with neurological disease. Furthermore, our multi-faceted approach for examining the functional significance of non-coding variants can be readily generalized to study other loci important for myelin structure and function.

  18. Private mitochondrial DNA variants in danish patients with hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Hagen, Christian M; Aidt, Frederik H; Havndrup, Ole;

    2015-01-01

    Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease primarily caused by mutations in genes coding for sarcomeric proteins. A molecular-genetic etiology can be established in ~60% of cases. Evolutionarily conserved mitochondrial DNA (mtDNA) haplogroups are susceptibility factors for HCM....... Several polymorphic mtDNA variants are associated with a variety of late-onset degenerative diseases and affect mitochondrial function. We examined the role of private, non-haplogroup associated, mitochondrial variants in the etiology of HCM. In 87 Danish HCM patients, full mtDNA sequencing revealed 446......>G, and MT-CYB: m.15024G>A, p.C93Y remained. A detailed analysis of these variants indicated that none of them are likely to cause HCM. In conclusion, private mtDNA mutations are frequent, but they are rarely, if ever, associated with HCM....

  19. Histone variants and lipid metabolism

    NARCIS (Netherlands)

    Borghesan, Michela; Mazzoccoli, Gianluigi; Sheedfar, Fareeba; Oben, Jude; Pazienza, Valerio; Vinciguerra, Manlio

    2014-01-01

    Within nucleosomes, canonical histones package the genome, but they can be opportunely replaced with histone variants. The incorporation of histone variants into the nucleosome is a chief cellular strategy to regulate transcription and cellular metabolism. In pathological terms, cellular steatosis i

  20. CIViC is a community knowledgebase for expert crowdsourcing the clinical interpretation of variants in cancer

    Science.gov (United States)

    Griffith, Malachi; Spies, Nicholas C; Krysiak, Kilannin; McMichael, Joshua F; Coffman, Adam C; Danos, Arpad M; Ainscough, Benjamin J; Ramirez, Cody A; Rieke, Damian T; Kujan, Lynzey; Barnell, Erica K; Wagner, Alex H; Skidmore, Zachary L; Wollam, Amber; Liu, Connor J; Jones, Martin R; Bilski, Rachel L; Lesurf, Robert; Feng, Yan-Yang; Shah, Nakul M; Bonakdar, Melika; Trani, Lee; Matlock, Matthew; Ramu, Avinash; Campbell, Katie M; Spies, Gregory C; Graubert, Aaron P; Gangavarapu, Karthik; Eldred, James M; Larson, David E; Walker, Jason R; Good, Benjamin M; Wu, Chunlei; Su, Andrew I; Dienstmann, Rodrigo; Margolin, Adam A; Tamborero, David; Lopez-Bigas, Nuria; Jones, Steven J M; Bose, Ron; Spencer, David H; Wartman, Lukas D; Wilson, Richard K; Mardis, Elaine R; Griffith, Obi L

    2017-01-01

    CIViC is an expert-crowdsourced knowledgebase for Clinical Interpretation of Variants in Cancer describing the therapeutic, prognostic, diagnostic and predisposing relevance of inherited and somatic variants of all types. CIViC is committed to open-source code, open-access content, public application programming interfaces (APIs) and provenance of supporting evidence to allow for the transparent creation of current and accurate variant interpretations for use in cancer precision medicine. PMID:28138153

  1. Genetic variants of the human dipeptide transporter PEPT1

    DEFF Research Database (Denmark)

    Anderle, Pascale; Nielsen, Carsten Uhd; Pinsonneault, Julia

    2006-01-01

    We tested whether genetic polymorphisms affect activity of the dipeptide transporter PEPT1, which mediates bioavailability of peptidomimetic drugs. All 23 exons and adjoining intronic sections of PEPT1 (SLC15A1) were sequenced in 247 individuals of various ethnic origins (Coriell collection). Of 38...... single nucleotide polymorphisms (SNPs), 21 occurred in intronic and non-coding regions and 17 in exonic coding region, of which nine were nonsynonymous. Eight nonsynonymous variants were cloned into expression vectors and functionally characterized after transient transfection into Cos7 and Chinese...... formation of a splice variant (PEPT1-RF). PEPT1-RF mRNA levels ranged from 2 to 44% of total PEPT1-related mRNA, with potential consequences for drug absorption. Together with previous results, this study reveals a relatively low level of genetic variability in polymorphisms affecting both protein function...

  2. QC-LDPC code-based cryptography

    CERN Document Server

    Baldi, Marco

    2014-01-01

    This book describes the fundamentals of cryptographic primitives based on quasi-cyclic low-density parity-check (QC-LDPC) codes, with a special focus on the use of these codes in public-key cryptosystems derived from the McEliece and Niederreiter schemes. In the first part of the book, the main characteristics of QC-LDPC codes are reviewed, and several techniques for their design are presented, while tools for assessing the error correction performance of these codes are also described. Some families of QC-LDPC codes that are best suited for use in cryptography are also presented. The second part of the book focuses on the McEliece and Niederreiter cryptosystems, both in their original forms and in some subsequent variants. The applicability of QC-LDPC codes in these frameworks is investigated by means of theoretical analyses and numerical tools, in order to assess their benefits and drawbacks in terms of system efficiency and security. Several examples of QC-LDPC code-based public key cryptosystems are prese...

  3. Cellobiohydrolase variants and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Wogulis, Mark

    2017-04-04

    The present invention relates to variants of a parent cellobiohydrolase II. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants.

  4. Locally Orderless Registration Code

    DEFF Research Database (Denmark)

    2012-01-01

    This is code for the TPAMI paper "Locally Orderless Registration". The code requires intel threadding building blocks installed and is provided for 64 bit on mac, linux and windows.......This is code for the TPAMI paper "Locally Orderless Registration". The code requires intel threadding building blocks installed and is provided for 64 bit on mac, linux and windows....

  5. Locally orderless registration code

    DEFF Research Database (Denmark)

    2012-01-01

    This is code for the TPAMI paper "Locally Orderless Registration". The code requires intel threadding building blocks installed and is provided for 64 bit on mac, linux and windows.......This is code for the TPAMI paper "Locally Orderless Registration". The code requires intel threadding building blocks installed and is provided for 64 bit on mac, linux and windows....

  6. QR Codes 101

    Science.gov (United States)

    Crompton, Helen; LaFrance, Jason; van 't Hooft, Mark

    2012-01-01

    A QR (quick-response) code is a two-dimensional scannable code, similar in function to a traditional bar code that one might find on a product at the supermarket. The main difference between the two is that, while a traditional bar code can hold a maximum of only 20 digits, a QR code can hold up to 7,089 characters, so it can contain much more…

  7. Constructing quantum codes

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Quantum error correcting codes are indispensable for quantum information processing and quantum computation.In 1995 and 1996,Shor and Steane gave first several examples of quantum codes from classical error correcting codes.The construction of efficient quantum codes is now an active multi-discipline research field.In this paper we review the known several constructions of quantum codes and present some examples.

  8. Spatially-varying IIR filter banks for image coding

    Science.gov (United States)

    Chung, Wilson C.; Smith, Mark J. T.

    1992-01-01

    This paper reports on the application of spatially variant infinite impulse response (IIR) filter banks to subband image coding. The new filter bank is based on computationally efficient recursive polyphase decompositions that dynamically change in response to the input signal. In the absence of quantization, reconstruction can be made exact. However, by proper choice of an adaptation scheme, we show that subband image coding based on time varying filter banks can yield improvement over the use of conventional filter banks.

  9. Certain variants of multipermutohedron ideals

    Indian Academy of Sciences (India)

    AJAY KUMAR; CHANCHAL KUMAR

    2016-10-01

    Multipermutohedron ideals have rich combinatorial properties. An explicit combinatorial formula for the multigraded Betti numbers of a multipermutohedron ideal and their Alexander duals are known. Also, the dimension of the Artinian quotient of an Alexander dual of a multipermutohedron ideal is the number of generalized parking functions. In this paper, monomial ideals which are certain variants of multipermutohedron ideals are studied. Multigraded Betti numbers of these variant monomial ideals and their Alexander duals are obtained. Further, many interesting combinatorial properties of multipermutohedron ideals are extended to these variant monomial ideals.

  10. Functionally significant, rare transcription factor variants in tetralogy of Fallot.

    Directory of Open Access Journals (Sweden)

    Ana Töpf

    Full Text Available Rare variants in certain transcription factors involved in cardiac development cause Mendelian forms of congenital heart disease. The purpose of this study was to systematically assess the frequency of rare transcription factor variants in sporadic patients with the cardiac outflow tract malformation tetralogy of Fallot (TOF.We sequenced the coding, 5'UTR, and 3'UTR regions of twelve transcription factor genes implicated in cardiac outflow tract development (NKX2.5, GATA4, ISL1, TBX20, MEF2C, BOP/SMYD1, HAND2, FOXC1, FOXC2, FOXH, FOXA2 and TBX1 in 93 non-syndromic, non-Mendelian TOF cases. We also analysed Illumina Human 660W-Quad SNP Array data for copy number variants in these genes; none were detected. Four of the rare variants detected have previously been shown to affect transactivation in in vitro reporter assays: FOXC1 p.P297S, FOXC2 p.Q444R, FOXH1 p.S113T and TBX1 p.P43_G61del PPPPRYDPCAAAAPGAPGP. Two further rare variants, HAND2 p.A25_A26insAA and FOXC1 p.G378_G380delGGG, A488_491delAAAA, affected transactivation in in vitro reporter assays. Each of these six functionally significant variants was present in a single patient in the heterozygous state; each of the four for which parental samples were available were maternally inherited. Thus in the 93 TOF cases we identified six functionally significant mutations in the secondary heart field transcriptional network.This study indicates that rare genetic variants in the secondary heart field transcriptional network with functional effects on protein function occur in 3-13% of patients with TOF. This is the first report of a functionally significant HAND2 mutation in a patient with congenital heart disease.

  11. Functionally significant, rare transcription factor variants in tetralogy of Fallot.

    Science.gov (United States)

    Töpf, Ana; Griffin, Helen R; Glen, Elise; Soemedi, Rachel; Brown, Danielle L; Hall, Darroch; Rahman, Thahira J; Eloranta, Jyrki J; Jüngst, Christoph; Stuart, A Graham; O'Sullivan, John; Keavney, Bernard D; Goodship, Judith A

    2014-01-01

    Rare variants in certain transcription factors involved in cardiac development cause Mendelian forms of congenital heart disease. The purpose of this study was to systematically assess the frequency of rare transcription factor variants in sporadic patients with the cardiac outflow tract malformation tetralogy of Fallot (TOF). We sequenced the coding, 5'UTR, and 3'UTR regions of twelve transcription factor genes implicated in cardiac outflow tract development (NKX2.5, GATA4, ISL1, TBX20, MEF2C, BOP/SMYD1, HAND2, FOXC1, FOXC2, FOXH, FOXA2 and TBX1) in 93 non-syndromic, non-Mendelian TOF cases. We also analysed Illumina Human 660W-Quad SNP Array data for copy number variants in these genes; none were detected. Four of the rare variants detected have previously been shown to affect transactivation in in vitro reporter assays: FOXC1 p.P297S, FOXC2 p.Q444R, FOXH1 p.S113T and TBX1 p.P43_G61del PPPPRYDPCAAAAPGAPGP. Two further rare variants, HAND2 p.A25_A26insAA and FOXC1 p.G378_G380delGGG, A488_491delAAAA, affected transactivation in in vitro reporter assays. Each of these six functionally significant variants was present in a single patient in the heterozygous state; each of the four for which parental samples were available were maternally inherited. Thus in the 93 TOF cases we identified six functionally significant mutations in the secondary heart field transcriptional network. This study indicates that rare genetic variants in the secondary heart field transcriptional network with functional effects on protein function occur in 3-13% of patients with TOF. This is the first report of a functionally significant HAND2 mutation in a patient with congenital heart disease.

  12. Genetic variation in the non-coding genome : Involvement of micro-RNAs and long non-coding RNAs in disease

    NARCIS (Netherlands)

    Hrdlickova, Barbara; de Almeida, Rodrigo Coutinho; Borek, Zuzanna; Withoff, Sebo

    2014-01-01

    It has been found that the majority of disease-associated genetic variants identified by genome-wide association studies are located outside of protein-coding regions, where they seem to affect regions that control transcription (promoters, enhancers) and non-coding RNAs that also can influence gene

  13. Turbo Codes Extended with Outer BCH Code

    DEFF Research Database (Denmark)

    Andersen, Jakob Dahl

    1996-01-01

    The "error floor" observed in several simulations with the turbo codes is verified by calculation of an upper bound to the bit error rate for the ensemble of all interleavers. Also an easy way to calculate the weight enumerator used in this bound is presented. An extended coding scheme is proposed...

  14. Rare Coding Variation and Risk of Intracerebral Hemorrhage

    Science.gov (United States)

    Radmanesh, Farid; Falcone, Guido J.; Anderson, Christopher D.; McWilliams, David; Devan, William J.; Brown, W Mark; Battey, Thomas W. K.; Ayres, Alison M.; Raffeld, Miriam R.; Schwab, Kristin; Sun, Guangyun; Deka, Ranjan; Viswanathan, Anand; Goldstein, Joshua N.; Greenberg, Steven M.; Tirschwell, David L.; Silliman, Scott L.; Selim, Magdy; Meschia, James F.; Brown, Devin L.; Worrall, Bradford B.; Langefeld, Carl D.; Woo, Daniel; Rosand, Jonathan

    2015-01-01

    Background and Purpose Intracerebral hemorrhage (ICH) has a substantial genetic component. We performed a preliminary search for rare coding variants associated with ICH. Methods 757 cases and 795 controls were genotyped using the Illumina HumanExome Beadchip (Illumina, Inc. San Diego, CA, USA). Meta-analyses of single-variant and gene-based association were computed. Results No rare coding variants were associated with ICH. Three common variants on chromosome 19q13 at an established susceptibility locus, encompassing TOMM40, APOE, and APOC1 met genome-wide significance (p<5e-08). After adjusting for the APOE epsilon alleles, this locus was no longer convincingly associated with ICH. No gene reached genome-wide significance level in gene-based association testing. Conclusions While no coding variants of large effect were detected, this study further underscores a major challenge for the study of genetic susceptibility loci – large sample sizes are required for sufficient power except for loci with large effects. PMID:26111891

  15. Gene Variants Reduce Opioid Risks

    Science.gov (United States)

    ... Opioids Prescription Drugs & Cold Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/Nicotine ... variant of the gene for the μ-opioid receptor (OPRM1) with a decreased risk for addiction to ...

  16. Hybrid Noncoherent Network Coding

    CERN Document Server

    Skachek, Vitaly; Nedic, Angelia

    2011-01-01

    We describe a novel extension of subspace codes for noncoherent networks, suitable for use when the network is viewed as a communication system that introduces both dimension and symbol errors. We show that when symbol erasures occur in a significantly large number of different basis vectors transmitted through the network and when the min-cut of the networks is much smaller then the length of the transmitted codewords, the new family of codes outperforms their subspace code counterparts. For the proposed coding scheme, termed hybrid network coding, we derive two upper bounds on the size of the codes. These bounds represent a variation of the Singleton and of the sphere-packing bound. We show that a simple concatenated scheme that represents a combination of subspace codes and Reed-Solomon codes is asymptotically optimal with respect to the Singleton bound. Finally, we describe two efficient decoding algorithms for concatenated subspace codes that in certain cases have smaller complexity than subspace decoder...

  17. Mining the LIPG allelic spectrum reveals the contribution of rare and common regulatory variants to HDL cholesterol.

    Directory of Open Access Journals (Sweden)

    Sumeet A Khetarpal

    2011-12-01

    Full Text Available Genome-wide association studies (GWAS have successfully identified loci associated with quantitative traits, such as blood lipids. Deep resequencing studies are being utilized to catalogue the allelic spectrum at GWAS loci. The goal of these studies is to identify causative variants and missing heritability, including heritability due to low frequency and rare alleles with large phenotypic impact. Whereas rare variant efforts have primarily focused on nonsynonymous coding variants, we hypothesized that noncoding variants in these loci are also functionally important. Using the HDL-C gene LIPG as an example, we explored the effect of regulatory variants identified through resequencing of subjects at HDL-C extremes on gene expression, protein levels, and phenotype. Resequencing a portion of the LIPG promoter and 5' UTR in human subjects with extreme HDL-C, we identified several rare variants in individuals from both extremes. Luciferase reporter assays were used to measure the effect of these rare variants on LIPG expression. Variants conferring opposing effects on gene expression were enriched in opposite extremes of the phenotypic distribution. Minor alleles of a common regulatory haplotype and noncoding GWAS SNPs were associated with reduced plasma levels of the LIPG gene product endothelial lipase (EL, consistent with its role in HDL-C catabolism. Additionally, we found that a common nonfunctional coding variant associated with HDL-C (rs2000813 is in linkage disequilibrium with a 5' UTR variant (rs34474737 that decreases LIPG promoter activity. We attribute the gene regulatory role of rs34474737 to the observed association of the coding variant with plasma EL levels and HDL-C. Taken together, the findings show that both rare and common noncoding regulatory variants are important contributors to the allelic spectrum in complex trait loci.

  18. Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease

    DEFF Research Database (Denmark)

    Stitziel, Nathan O; Stirrups, Kathleen E; Masca, Nicholas G D

    2016-01-01

    BACKGROUND: The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets. METHODS: Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with ...

  19. Diversity and impact of rare variants in genes encoding the platelet G protein-coupled receptors

    OpenAIRE

    Jones, M.L.; Norman, J E; Morgan, N. V.; Mundell, S J; Lordkipanidze, M.; Lowe, G. C.; Daly, M E; Simpson, M.A.; Drake, S.; Watson, S P; Mumford, A D; UKGAPPS,

    2016-01-01

    Platelet responses to activating agonists are influenced by common\\ud population variants within or near G protein-coupled receptor (GPCR)\\ud genes that affect receptor activity. However, the impact of rare GPCR\\ud gene variants is unknown. We describe the rare single nucleotide variants\\ud (SNVs) in the coding and splice regions of 18 GPCR genes in\\ud 7,595 exomes from the 1,000-genomes and Exome Sequencing\\ud Project databases and in 31 cases with inherited platelet function disorders\\ud (I...

  20. Network coding for computing: Linear codes

    CERN Document Server

    Appuswamy, Rathinakumar; Karamchandani, Nikhil; Zeger, Kenneth

    2011-01-01

    In network coding it is known that linear codes are sufficient to achieve the coding capacity in multicast networks and that they are not sufficient in general to achieve the coding capacity in non-multicast networks. In network computing, Rai, Dey, and Shenvi have recently shown that linear codes are not sufficient in general for solvability of multi-receiver networks with scalar linear target functions. We study single receiver networks where the receiver node demands a target function of the source messages. We show that linear codes may provide a computing capacity advantage over routing only when the receiver demands a `linearly-reducible' target function. % Many known target functions including the arithmetic sum, minimum, and maximum are not linearly-reducible. Thus, the use of non-linear codes is essential in order to obtain a computing capacity advantage over routing if the receiver demands a target function that is not linearly-reducible. We also show that if a target function is linearly-reducible,...

  1. Rare and low-frequency variants in human common diseases and other complex traits.

    Science.gov (United States)

    Lettre, Guillaume

    2014-11-01

    In humans, most of the genetic variation is rare and often population-specific. Whereas the role of rare genetic variants in familial monogenic diseases is firmly established, we are only now starting to explore the contribution of this class of genetic variation to human common diseases and other complex traits. Such large-scale experiments are possible due to the development of next-generation DNA sequencing. Early findings suggested that rare and low-frequency coding variation might have a large effect on human phenotypes (eg, PCSK9 missense variants on low-density lipoprotein-cholesterol and coronary heart diseases). This observation sparked excitement in prognostic and diagnostic medicine, as well as in genetics-driven strategies to develop new drugs. In this review, I describe results and present initial conclusions regarding some of the recent rare and low-frequency variant discoveries. We can already assume that most phenotype-associated rare and low-frequency variants have modest-to-weak phenotypical effect. Thus, we will need large cohorts to identify them, as for common variants in genome-wide association studies. As we expand the list of associated rare and low-frequency variants, we can also better recognise the current limitations: we need to develop better statistical methods to optimally test association with rare variants, including non-coding variation, and to account for potential confounders such as population stratification.

  2. BARD1 variants are not associated with breast cancer risk in Australian familial breast cancer.

    Science.gov (United States)

    Gorringe, Kylie L; Choong, David Y H; Visvader, Jane E; Lindeman, Geoffrey J; Campbell, Ian G

    2008-10-01

    Several studies in various populations have suggested that non-synonymous BARD1 variants are associated with increased breast cancer risk. Using DHPLC analysis we screened the coding region of BARD1 for variants in 210 probands of breast cancer families including 129 families with no mutations in BRCA1 or BRCA2. These families were ascertained in Australia through the Kathleen Cunningham Foundation Consortium for Research into Familial Breast Cancer (kConFab). Nine coding variants were detected among the kConFab families, including two novel variants (Thr598Ile and Ile692Thr). The frequency of five of these variants were evaluated in 258 non-cancer controls and 401 women with sporadic breast cancer. Three variants (1139del21, G1756C and A2285G) were detected in all three groups at a similar frequency suggesting that these do not represent BRCAX candidates. Two variants (Thr598Ile and Ile692Thr) were not detected in any of the 659 sporadic breast cancer cases and controls and were assessed for segregation with breast cancer in the families of the probands. However, neither variant was identified in any other breast cancer case in either family suggesting that these variants are non-pathogenic polymorphisms. We have found no evidence to support involvement of BARD1 in familial breast cancer risk in the Australian population. In addition, three variants previously reported to be pathogenic in other populations are likely to represent benign polymorphisms and therefore we conclude that BARD1 is unlikely to represent a high-penetrance breast cancer susceptibility gene.

  3. Practices in Code Discoverability

    CERN Document Server

    Teuben, Peter; Nemiroff, Robert J; Shamir, Lior

    2012-01-01

    Much of scientific progress now hinges on the reliability, falsifiability and reproducibility of computer source codes. Astrophysics in particular is a discipline that today leads other sciences in making useful scientific components freely available online, including data, abstracts, preprints, and fully published papers, yet even today many astrophysics source codes remain hidden from public view. We review the importance and history of source codes in astrophysics and previous efforts to develop ways in which information about astrophysics codes can be shared. We also discuss why some scientist coders resist sharing or publishing their codes, the reasons for and importance of overcoming this resistance, and alert the community to a reworking of one of the first attempts for sharing codes, the Astrophysics Source Code Library (ASCL). We discuss the implementation of the ASCL in an accompanying poster paper. We suggest that code could be given a similar level of referencing as data gets in repositories such ...

  4. Coding for optical channels

    CERN Document Server

    Djordjevic, Ivan; Vasic, Bane

    2010-01-01

    This unique book provides a coherent and comprehensive introduction to the fundamentals of optical communications, signal processing and coding for optical channels. It is the first to integrate the fundamentals of coding theory and optical communication.

  5. Enhancing QR Code Security

    OpenAIRE

    Zhang, Linfan; Zheng, Shuang

    2015-01-01

    Quick Response code opens possibility to convey data in a unique way yet insufficient prevention and protection might lead into QR code being exploited on behalf of attackers. This thesis starts by presenting a general introduction of background and stating two problems regarding QR code security, which followed by a comprehensive research on both QR code itself and related issues. From the research a solution taking advantages of cloud and cryptography together with an implementation come af...

  6. Refactoring test code

    NARCIS (Netherlands)

    A. van Deursen (Arie); L.M.F. Moonen (Leon); A. van den Bergh; G. Kok

    2001-01-01

    textabstractTwo key aspects of extreme programming (XP) are unit testing and merciless refactoring. Given the fact that the ideal test code / production code ratio approaches 1:1, it is not surprising that unit tests are being refactored. We found that refactoring test code is different from

  7. Informal Control code logic

    CERN Document Server

    Bergstra, Jan A

    2010-01-01

    General definitions as well as rules of reasoning regarding control code production, distribution, deployment, and usage are described. The role of testing, trust, confidence and risk analysis is considered. A rationale for control code testing is sought and found for the case of safety critical embedded control code.

  8. Gauge color codes

    DEFF Research Database (Denmark)

    Bombin Palomo, Hector

    2015-01-01

    Color codes are topological stabilizer codes with unusual transversality properties. Here I show that their group of transversal gates is optimal and only depends on the spatial dimension, not the local geometry. I also introduce a generalized, subsystem version of color codes. In 3D they allow...

  9. Refactoring test code

    NARCIS (Netherlands)

    Deursen, A. van; Moonen, L.M.F.; Bergh, A. van den; Kok, G.

    2001-01-01

    Two key aspects of extreme programming (XP) are unit testing and merciless refactoring. Given the fact that the ideal test code / production code ratio approaches 1:1, it is not surprising that unit tests are being refactored. We found that refactoring test code is different from refactoring product

  10. ARC Code TI: CODE Software Framework

    Data.gov (United States)

    National Aeronautics and Space Administration — CODE is a software framework for control and observation in distributed environments. The basic functionality of the framework allows a user to observe a distributed...

  11. ARC Code TI: ROC Curve Code Augmentation

    Data.gov (United States)

    National Aeronautics and Space Administration — ROC (Receiver Operating Characteristic) curve Code Augmentation was written by Rodney Martin and John Stutz at NASA Ames Research Center and is a modification of ROC...

  12. Fountain Codes: LT And Raptor Codes Implementation

    Directory of Open Access Journals (Sweden)

    Ali Bazzi, Hiba Harb

    2017-01-01

    Full Text Available Digital fountain codes are a new class of random error correcting codes designed for efficient and reliable data delivery over erasure channels such as internet. These codes were developed to provide robustness against erasures in a way that resembles a fountain of water. A digital fountain is rateless in a way that sender can send limitless number of encoded packets. The receiver doesn’t care which packets are received or lost as long as the receiver gets enough packets to recover original data. In this paper, the design of the fountain codes is explored with its implementation of the encoding and decoding algorithm so that the performance in terms of encoding/decoding symbols, reception overhead, data length, and failure probability is studied.

  13. Variants associated with Gaucher disease in multiple system atrophy

    Science.gov (United States)

    Mitsui, Jun; Matsukawa, Takashi; Sasaki, Hidenao; Yabe, Ichiro; Matsushima, Masaaki; Dürr, Alexandra; Brice, Alexis; Takashima, Hiroshi; Kikuchi, Akio; Aoki, Masashi; Ishiura, Hiroyuki; Yasuda, Tsutomu; Date, Hidetoshi; Ahsan, Budrul; Iwata, Atsushi; Goto, Jun; Ichikawa, Yaeko; Nakahara, Yasuo; Momose, Yoshio; Takahashi, Yuji; Hara, Kenju; Kakita, Akiyoshi; Yamada, Mitsunori; Takahashi, Hitoshi; Onodera, Osamu; Nishizawa, Masatoyo; Watanabe, Hirohisa; Ito, Mizuki; Sobue, Gen; Ishikawa, Kinya; Mizusawa, Hidehiro; Kanai, Kazuaki; Hattori, Takamichi; Kuwabara, Satoshi; Arai, Kimihito; Koyano, Shigeru; Kuroiwa, Yoshiyuki; Hasegawa, Kazuko; Yuasa, Tatsuhiko; Yasui, Kenichi; Nakashima, Kenji; Ito, Hijiri; Izumi, Yuishin; Kaji, Ryuji; Kato, Takeo; Kusunoki, Susumu; Osaki, Yasushi; Horiuchi, Masahiro; Kondo, Tomoyoshi; Murayama, Shigeo; Hattori, Nobutaka; Yamamoto, Mitsutoshi; Murata, Miho; Satake, Wataru; Toda, Tatsushi; Filla, Alessandro; Klockgether, Thomas; Wüllner, Ullrich; Nicholson, Garth; Gilman, Sid; Tanner, Caroline M; Kukull, Walter A; Stern, Mathew B; Lee, Virginia M-Y; Trojanowski, John Q; Masliah, Eliezer; Low, Phillip A; Sandroni, Paola; Ozelius, Laurie J; Foroud, Tatiana; Tsuji, Shoji

    2015-01-01

    Objective Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). To investigate the role of GBA variants in multiple system atrophy (MSA), we analyzed GBA variants in a large case–control series. Methods We sequenced coding regions and flanking splice sites of GBA in 969 MSA patients (574 Japanese, 223 European, and 172 North American) and 1509 control subjects (900 Japanese, 315 European, and 294 North American). We focused solely on Gaucher-disease-causing GBA variants. Results In the Japanese series, we found nine carriers among the MSA patients (1.65%) and eight carriers among the control subjects (0.89%). In the European series, we found three carriers among the MSA patients (1.35%) and two carriers among the control subjects (0.63%). In the North American series, we found five carriers among the MSA patients (2.91%) and one carrier among the control subjects (0.34%). Subjecting each series to a Mantel–Haenszel analysis yielded a pooled odds ratio (OR) of 2.44 (95% confidence interval [CI], 1.14–5.21) and a P-value of 0.029 without evidence of significant heterogeneity. Logistic regression analysis yielded similar results, with an adjusted OR of 2.43 (95% CI 1.15–5.37) and a P-value of 0.022. Subtype analysis showed that Gaucher-disease-causing GBA variants are significantly associated with MSA cerebellar subtype (MSA-C) patients (P = 7.3 × 10−3). Interpretation The findings indicate that, as in PD and DLB, Gaucher-disease-causing GBA variants are associated with MSA. PMID:25909086

  14. Universal Rateless Codes From Coupled LT Codes

    CERN Document Server

    Aref, Vahid

    2011-01-01

    It was recently shown that spatial coupling of individual low-density parity-check codes improves the belief-propagation threshold of the coupled ensemble essentially to the maximum a posteriori threshold of the underlying ensemble. We study the performance of spatially coupled low-density generator-matrix ensembles when used for transmission over binary-input memoryless output-symmetric channels. We show by means of density evolution that the threshold saturation phenomenon also takes place in this setting. Our motivation for studying low-density generator-matrix codes is that they can easily be converted into rateless codes. Although there are already several classes of excellent rateless codes known to date, rateless codes constructed via spatial coupling might offer some additional advantages. In particular, by the very nature of the threshold phenomenon one expects that codes constructed on this principle can be made to be universal, i.e., a single construction can uniformly approach capacity over the cl...

  15. Software Certification - Coding, Code, and Coders

    Science.gov (United States)

    Havelund, Klaus; Holzmann, Gerard J.

    2011-01-01

    We describe a certification approach for software development that has been adopted at our organization. JPL develops robotic spacecraft for the exploration of the solar system. The flight software that controls these spacecraft is considered to be mission critical. We argue that the goal of a software certification process cannot be the development of "perfect" software, i.e., software that can be formally proven to be correct under all imaginable and unimaginable circumstances. More realistically, the goal is to guarantee a software development process that is conducted by knowledgeable engineers, who follow generally accepted procedures to control known risks, while meeting agreed upon standards of workmanship. We target three specific issues that must be addressed in such a certification procedure: the coding process, the code that is developed, and the skills of the coders. The coding process is driven by standards (e.g., a coding standard) and tools. The code is mechanically checked against the standard with the help of state-of-the-art static source code analyzers. The coders, finally, are certified in on-site training courses that include formal exams.

  16. Coding for Electronic Mail

    Science.gov (United States)

    Rice, R. F.; Lee, J. J.

    1986-01-01

    Scheme for coding facsimile messages promises to reduce data transmission requirements to one-tenth current level. Coding scheme paves way for true electronic mail in which handwritten, typed, or printed messages or diagrams sent virtually instantaneously - between buildings or between continents. Scheme, called Universal System for Efficient Electronic Mail (USEEM), uses unsupervised character recognition and adaptive noiseless coding of text. Image quality of resulting delivered messages improved over messages transmitted by conventional coding. Coding scheme compatible with direct-entry electronic mail as well as facsimile reproduction. Text transmitted in this scheme automatically translated to word-processor form.

  17. Variants in the ASB10 Gene Are Associated with Primary Open Angle Glaucoma.

    Directory of Open Access Journals (Sweden)

    Shazia Micheal

    Full Text Available Recently nonsynonymous coding variants in the ankyrin repeats and suppressor of cytokine signaling box-containing protein 10 (ASB10 gene were found to be associated with primary open angle glaucoma (POAG in cohorts from Oregon and Germany, but this finding was not confirmed in an independent cohort from Iowa. The aim of the current study was to assess the role of ASB10 gene variants in Pakistani glaucoma patients.Sanger sequencing of the coding exons and splice junctions of the ASB10 gene was performed in 30 probands of multiplex POAG families, 208 sporadic POAG patients and 151 healthy controls from Pakistan. Genotypic associations of individual variants with POAG were analyzed with the Fisher's exact or Chi-square test.In total 24 variants were identified in POAG probands and sporadic patients, including 11 novel variants and 13 known variants. 13 of the variants were nonsynonymous, 6 were synonymous, and 5 were intronic. Three nonsynonymous variants (p.Arg49Cys, p.Arg237Gly, p.Arg453Cys identified in the probands were not segregating in the respective families. This is not surprising since glaucoma is a multifactorial disease, and multiple factors are likely to be involved in the disease manifestation in these families. However a nonsynonymous variant, p.Arg453Cys (rs3800791, was found in 6 sporadic POAG patients but not in controls, suggesting that it infers increased risk for the disease. In addition, one synonymous variant was found to be associated with sporadic POAG: p.Ala290Ala and the association of the variant with POAG remained significant after correction for multiple testing (uncorrected p-value 0.002, corrected p-value 0.047. The cumulative burden of rare, nonsynonymous variants was significantly higher in sporadic POAG patients compared to control individuals (p-value 0.000006.Variants in ASB10 were found to be significantly associated with sporadic POAG in the Pakistani population. This supports previous findings that sequence

  18. Noisy Network Coding

    CERN Document Server

    Lim, Sung Hoon; Gamal, Abbas El; Chung, Sae-Young

    2010-01-01

    A noisy network coding scheme for sending multiple sources over a general noisy network is presented. For multi-source multicast networks, the scheme naturally extends both network coding over noiseless networks by Ahlswede, Cai, Li, and Yeung, and compress-forward coding for the relay channel by Cover and El Gamal to general discrete memoryless and Gaussian networks. The scheme also recovers as special cases the results on coding for wireless relay networks and deterministic networks by Avestimehr, Diggavi, and Tse, and coding for wireless erasure networks by Dana, Gowaikar, Palanki, Hassibi, and Effros. The scheme involves message repetition coding, relay signal compression, and simultaneous decoding. Unlike previous compress--forward schemes, where independent messages are sent over multiple blocks, the same message is sent multiple times using independent codebooks as in the network coding scheme for cyclic networks. Furthermore, the relays do not use Wyner--Ziv binning as in previous compress-forward sch...

  19. Testing algebraic geometric codes

    Institute of Scientific and Technical Information of China (English)

    CHEN Hao

    2009-01-01

    Property testing was initially studied from various motivations in 1990's.A code C (∩)GF(r)n is locally testable if there is a randomized algorithm which can distinguish with high possibility the codewords from a vector essentially far from the code by only accessing a very small (typically constant) number of the vector's coordinates.The problem of testing codes was firstly studied by Blum,Luby and Rubinfeld and closely related to probabilistically checkable proofs (PCPs).How to characterize locally testable codes is a complex and challenge problem.The local tests have been studied for Reed-Solomon (RS),Reed-Muller (RM),cyclic,dual of BCH and the trace subcode of algebraicgeometric codes.In this paper we give testers for algebraic geometric codes with linear parameters (as functions of dimensions).We also give a moderate condition under which the family of algebraic geometric codes cannot be locally testable.

  20. Chinese remainder codes

    Institute of Scientific and Technical Information of China (English)

    ZHANG Aili; LIU Xiufeng

    2006-01-01

    Chinese remainder codes are constructed by applying weak block designs and the Chinese remainder theorem of ring theory.The new type of linear codes take the congruence class in the congruence class ring R/I1 ∩ I2 ∩…∩ In for the information bit,embed R/Ji into R/I1 ∩ I2 ∩…∩ In,and assign the cosets of R/Ji as the subring of R/I1 ∩ I2 ∩…∩ In and the cosets of R/Ji in R/I1 ∩ I2 ∩…∩ In as check lines.Many code classes exist in the Chinese remainder codes that have high code rates.Chinese remainder codes are the essential generalization of Sun Zi codes.

  1. Chinese Remainder Codes

    Institute of Scientific and Technical Information of China (English)

    张爱丽; 刘秀峰; 靳蕃

    2004-01-01

    Chinese Remainder Codes are constructed by applying weak block designs and Chinese Remainder Theorem of ring theory. The new type of linear codes take the congruence class in the congruence class ring R/I1∩I2∩…∩In for the information bit, embed R/Ji into R/I1∩I2∩…∩In, and asssign the cosets of R/Ji as the subring of R/I1∩I2∩…∩In and the cosets of R/Ji in R/I1∩I2∩…∩In as check lines. There exist many code classes in Chinese Remainder Codes, which have high code rates. Chinese Remainder Codes are the essential generalization of Sun Zi Codes.

  2. Code of Ethics

    DEFF Research Database (Denmark)

    Adelstein, Jennifer; Clegg, Stewart

    2016-01-01

    Ethical codes have been hailed as an explicit vehicle for achieving more sustainable and defensible organizational practice. Nonetheless, when legal compliance and corporate governance codes are conflated, codes can be used to define organizational interests ostentatiously by stipulating norms...... for employee ethics. Such codes have a largely cosmetic and insurance function, acting subtly and strategically to control organizational risk management and protection. In this paper, we conduct a genealogical discourse analysis of a representative code of ethics from an international corporation...... to understand how management frames expectations of compliance. Our contribution is to articulate the problems inherent in codes of ethics, and we make some recommendations to address these to benefit both an organization and its employees. In this way, we show how a code of ethics can provide a foundation...

  3. Defeating the coding monsters.

    Science.gov (United States)

    Colt, Ross

    2007-02-01

    Accuracy in coding is rapidly becoming a required skill for military health care providers. Clinic staffing, equipment purchase decisions, and even reimbursement will soon be based on the coding data that we provide. Learning the complicated myriad of rules to code accurately can seem overwhelming. However, the majority of clinic visits in a typical outpatient clinic generally fall into two major evaluation and management codes, 99213 and 99214. If health care providers can learn the rules required to code a 99214 visit, then this will provide a 90% solution that can enable them to accurately code the majority of their clinic visits. This article demonstrates a step-by-step method to code a 99214 visit, by viewing each of the three requirements as a monster to be defeated.

  4. Testing algebraic geometric codes

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Property testing was initially studied from various motivations in 1990’s. A code C  GF (r)n is locally testable if there is a randomized algorithm which can distinguish with high possibility the codewords from a vector essentially far from the code by only accessing a very small (typically constant) number of the vector’s coordinates. The problem of testing codes was firstly studied by Blum, Luby and Rubinfeld and closely related to probabilistically checkable proofs (PCPs). How to characterize locally testable codes is a complex and challenge problem. The local tests have been studied for Reed-Solomon (RS), Reed-Muller (RM), cyclic, dual of BCH and the trace subcode of algebraicgeometric codes. In this paper we give testers for algebraic geometric codes with linear parameters (as functions of dimensions). We also give a moderate condition under which the family of algebraic geometric codes cannot be locally testable.

  5. Serially Concatenated IRA Codes

    CERN Document Server

    Cheng, Taikun; Belzer, Benjamin J

    2007-01-01

    We address the error floor problem of low-density parity check (LDPC) codes on the binary-input additive white Gaussian noise (AWGN) channel, by constructing a serially concatenated code consisting of two systematic irregular repeat accumulate (IRA) component codes connected by an interleaver. The interleaver is designed to prevent stopping-set error events in one of the IRA codes from propagating into stopping set events of the other code. Simulations with two 128-bit rate 0.707 IRA component codes show that the proposed architecture achieves a much lower error floor at higher SNRs, compared to a 16384-bit rate 1/2 IRA code, but incurs an SNR penalty of about 2 dB at low to medium SNRs. Experiments indicate that the SNR penalty can be reduced at larger blocklengths.

  6. Two new splice variants in porcine PPARGC1A

    Directory of Open Access Journals (Sweden)

    Peelman Luc J

    2008-12-01

    Full Text Available Abstract Background Peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A is a coactivator with a vital and central role in fat and energy metabolism. It is considered to be a candidate gene for meat quality in pigs and is involved in the development of obesity and diabetes in humans. How its many functions are regulated, is however still largely unclear. Therefore a transcription profile of PPARGC1A in 32 tissues and 4 embryonic developmental stages in the pig was constructed by screening its cDNA for possible splice variants with exon-spanning primers. Findings This led to the discovery of 2 new splice variants in the pig, which were subsequently also detected in human tissues. In these variants, exon 8 was either completely or partly (the last 66 bp were conserved spliced out, potentially coding for a much shorter protein of respectively 337 and 359 amino acids (aa, of which the first 291 aa would be the same compared to the complete protein (796 aa. Conclusion Considering the functional domains of the PPARGC1A protein, it is very likely these splice variants considerably affect the function of the protein and alternative splicing could be one of the mechanisms by which the diverse functions of PPARGC1A are regulated.

  7. A PYY Q62P variant linked to human obesity

    Energy Technology Data Exchange (ETDEWEB)

    Ahituv, Nadav; Kavaslar, Nihan; Schackwitz, Wendy; Ustaszewska,Anna; Collier, John Michael; Hebert, Sybil; Doelle, Heather; Dent,Robert; Pennacchio, Len A.; McPherson, Ruth

    2005-06-27

    Members of the pancreatic polypeptide family and the irreceptors have been implicated in the control of food intake in rodents and humans. To investigate whether nucleotide changes in these candidate genes result in abnormal weight in humans, we sequenced the coding exons and splice sites of seven family members (NPY, PYY, PPY, NPY1R, NPY2R, NPY4R, and NPY5R) in a large cohort of extremely obese (n=379) and lean (n=378) individuals. In total we found eleven rare non-synonymous variants, four of which exhibited familial segregation, NPY1R L53P and PPY P63L with leanness and NPY2R D42G and PYY Q62P with obesity. Functional analysis of the obese variants revealed NPY2R D42G to have reduced cell surface expression, while previous cell culture based studies indicated variant PYY Q62P to have altered receptor binding selectivity and we show that it fails to reduce food intake through mouse peptide injection experiments. These results support that rare non-synonymous variants within these genes can alter susceptibility to human body mass index extremes.

  8. Emotive codes in Dostoevsky's "The Gambler"

    Directory of Open Access Journals (Sweden)

    Iskhakova Z.Z.

    2016-10-01

    Full Text Available This article is devoted to encoding and decoding the emotional image of F.M Dostoyevsky through the variant emotive deictic field with its emotive codes in the sphere. The object is the emotional speech of the characters in the works of F.M. Dostoyevsky. The subject of the study are the emotive signs in the emotional speech of the characters of F.M. Dostoyevsky. The aim of the article is to identify the most frequent emotive signs in Dostoevsky's "The Gambler", reflecting the emotional state of the characters, through which Russian writer expresses himself.

  9. Data-variant kernel analysis

    CERN Document Server

    Motai, Yuichi

    2015-01-01

    Describes and discusses the variants of kernel analysis methods for data types that have been intensely studied in recent years This book covers kernel analysis topics ranging from the fundamental theory of kernel functions to its applications. The book surveys the current status, popular trends, and developments in kernel analysis studies. The author discusses multiple kernel learning algorithms and how to choose the appropriate kernels during the learning phase. Data-Variant Kernel Analysis is a new pattern analysis framework for different types of data configurations. The chapters include

  10. A new hypercube variant: Fractal Cubic Network Graph

    Directory of Open Access Journals (Sweden)

    Ali Karci

    2015-03-01

    Full Text Available Hypercube is a popular and more attractive interconnection networks. The attractive properties of hypercube caused the derivation of more variants of hypercube. In this paper, we have proposed two variants of hypercube which was called as “Fractal Cubic Network Graphs”, and we have investigated the Hamiltonian-like properties of Fractal Cubic Network Graphs FCNGr(n. Firstly, Fractal Cubic Network Graphs FCNGr(n are defined by a fractal structure. Further, we show the construction and characteristics analyses of FCNGr(n where r=1 or r=2. Therefore, FCNGr(n is a Hamiltonian graph which is obtained by using Gray Code for r=2 and FCNG1(n is not a Hamiltonian Graph. Furthermore, we have obtained a recursive algorithm which is used to label the nodes of FCNG2(n. Finally, we get routing algorithms on FCNG2(n by utilizing routing algorithms on the hypercubes.

  11. Mucolipidosis types II and III and non-syndromic stuttering are associated with different variants in the same genes.

    Science.gov (United States)

    Raza, M Hashim; Domingues, Carlos E F; Webster, Ronald; Sainz, Eduardo; Paris, Emily; Rahn, Rachel; Gutierrez, Joanne; Chow, Ho Ming; Mundorff, Jennifer; Kang, Chang-Soo; Riaz, Naveeda; Basra, Muhammad A R; Khan, Shaheen; Riazuddin, Sheikh; Moretti-Ferreira, Danilo; Braun, Allen; Drayna, Dennis

    2016-04-01

    Homozygous mutations in GNPTAB and GNPTG are classically associated with mucolipidosis II (ML II) alpha/beta and mucolipidosis III (ML III) alpha/beta/gamma, which are rare lysosomal storage disorders characterized by multiple pathologies. Recently, variants in GNPTAB, GNPTG, and the functionally related NAGPA gene have been associated with non-syndromic persistent stuttering. In a worldwide sample of 1013 unrelated individuals with non-syndromic persistent stuttering we found 164 individuals who carried a rare non-synonymous coding variant in one of these three genes. We compared the frequency of these variants with those in population-matched controls and genomic databases, and their location with those reported in mucolipidosis. Stuttering subjects displayed an excess of non-synonymous coding variants compared to controls and individuals in the 1000 Genomes and Exome Sequencing Project databases. We identified a total of 81 different variants in our stuttering cases. Virtually all of these were missense substitutions, only one of which has been previously reported in mucolipidosis, a disease frequently associated with complete loss-of-function mutations. We hypothesize that rare non-synonymous coding variants in GNPTAB, GNPTG, and NAGPA may account for as much as 16% of persistent stuttering cases, and that variants in GNPTAB and GNPTG are at different sites and may in general, cause less severe effects on protein function than those in ML II alpha/beta and ML III alpha/beta/gamma.

  12. Fast Density Codes for Image Data

    CERN Document Server

    Courrieu, Pierre

    2008-01-01

    Recently, a new method for encoding data sets in the form of "Density Codes" was proposed in the literature (Courrieu, 2006). This method allows to compare sets of points belonging to every multidimensional space, and to build shape spaces invariant to a wide variety of affine and non-affine transformations. However, this general method does not take advantage of the special properties of image data, resulting in a quite slow encoding process that makes this tool practically unusable for processing large image databases with conventional computers. This paper proposes a very simple variant of the density code method that directly works on the image function, which is thousands times faster than the original Parzen window based method, without loss of its useful properties.

  13. Variant Creutzfeldt-Jakob disease

    NARCIS (Netherlands)

    E.A. Croes (Esther); C.M. van Duijn (Cock)

    2003-01-01

    textabstractA variant form of Creutzfeldt-Jakob disease (vCJD) has had major impact in Europe during the last decade. In this article, we review the aetiology of vCJD and its relation with bovine spongiform encephalopathy. Further, treatment of the disease, the strategies focusing on prevention of t

  14. Rewriting the Genetic Code.

    Science.gov (United States)

    Mukai, Takahito; Lajoie, Marc J; Englert, Markus; Söll, Dieter

    2017-09-08

    The genetic code-the language used by cells to translate their genomes into proteins that perform many cellular functions-is highly conserved throughout natural life. Rewriting the genetic code could lead to new biological functions such as expanding protein chemistries with noncanonical amino acids (ncAAs) and genetically isolating synthetic organisms from natural organisms and viruses. It has long been possible to transiently produce proteins bearing ncAAs, but stabilizing an expanded genetic code for sustained function in vivo requires an integrated approach: creating recoded genomes and introducing new translation machinery that function together without compromising viability or clashing with endogenous pathways. In this review, we discuss design considerations and technologies for expanding the genetic code. The knowledge obtained by rewriting the genetic code will deepen our understanding of how genomes are designed and how the canonical genetic code evolved.

  15. On Polynomial Remainder Codes

    CERN Document Server

    Yu, Jiun-Hung

    2012-01-01

    Polynomial remainder codes are a large class of codes derived from the Chinese remainder theorem that includes Reed-Solomon codes as a special case. In this paper, we revisit these codes and study them more carefully than in previous work. We explicitly allow the code symbols to be polynomials of different degrees, which leads to two different notions of weight and distance. Algebraic decoding is studied in detail. If the moduli are not irreducible, the notion of an error locator polynomial is replaced by an error factor polynomial. We then obtain a collection of gcd-based decoding algorithms, some of which are not quite standard even when specialized to Reed-Solomon codes.

  16. Identification of organization name variants in large databases using rule-based scoring and clustering: With a case study on the web of science database

    OpenAIRE

    Caron, Emiel; Daniels, Hennie

    2016-01-01

    textabstractThis research describes a general method to automatically clean organizational and business names variants within large databases, such as: patent databases, bibliographic databases, databases in business information systems, or any other database containing organisational name variants. The method clusters name variants of organizations based on similarities of their associated meta-data, like, for example, postal code and email domain data. The method is divided into a rule-base...

  17. Generating code adapted for interlinking legacy scalar code and extended vector code

    Science.gov (United States)

    Gschwind, Michael K

    2013-06-04

    Mechanisms for intermixing code are provided. Source code is received for compilation using an extended Application Binary Interface (ABI) that extends a legacy ABI and uses a different register configuration than the legacy ABI. First compiled code is generated based on the source code, the first compiled code comprising code for accommodating the difference in register configurations used by the extended ABI and the legacy ABI. The first compiled code and second compiled code are intermixed to generate intermixed code, the second compiled code being compiled code that uses the legacy ABI. The intermixed code comprises at least one call instruction that is one of a call from the first compiled code to the second compiled code or a call from the second compiled code to the first compiled code. The code for accommodating the difference in register configurations is associated with the at least one call instruction.

  18. The aeroelastic code FLEXLAST

    Energy Technology Data Exchange (ETDEWEB)

    Visser, B. [Stork Product Eng., Amsterdam (Netherlands)

    1996-09-01

    To support the discussion on aeroelastic codes, a description of the code FLEXLAST was given and experiences within benchmarks and measurement programmes were summarized. The code FLEXLAST has been developed since 1982 at Stork Product Engineering (SPE). Since 1992 FLEXLAST has been used by Dutch industries for wind turbine and rotor design. Based on the comparison with measurements, it can be concluded that the main shortcomings of wind turbine modelling lie in the field of aerodynamics, wind field and wake modelling. (au)

  19. Opening up codings?

    DEFF Research Database (Denmark)

    Steensig, Jakob; Heinemann, Trine

    2015-01-01

    We welcome Tanya Stivers’s discussion (Stivers, 2015/this issue) of coding social interaction and find that her descriptions of the processes of coding open up important avenues for discussion, among other things of the precise ad hoc considerations that researchers need to bear in mind, both when....... Instead we propose that the promise of coding-based research lies in its ability to open up new qualitative questions....

  20. Industrial Computer Codes

    Science.gov (United States)

    Shapiro, Wilbur

    1996-01-01

    This is an overview of new and updated industrial codes for seal design and testing. GCYLT (gas cylindrical seals -- turbulent), SPIRALI (spiral-groove seals -- incompressible), KTK (knife to knife) Labyrinth Seal Code, and DYSEAL (dynamic seal analysis) are covered. CGYLT uses G-factors for Poiseuille and Couette turbulence coefficients. SPIRALI is updated to include turbulence and inertia, but maintains the narrow groove theory. KTK labyrinth seal code handles straight or stepped seals. And DYSEAL provides dynamics for the seal geometry.

  1. ARC Code TI: ACCEPT

    Data.gov (United States)

    National Aeronautics and Space Administration — ACCEPT consists of an overall software infrastructure framework and two main software components. The software infrastructure framework consists of code written to...

  2. QR codes for dummies

    CERN Document Server

    Waters, Joe

    2012-01-01

    Find out how to effectively create, use, and track QR codes QR (Quick Response) codes are popping up everywhere, and businesses are reaping the rewards. Get in on the action with the no-nonsense advice in this streamlined, portable guide. You'll find out how to get started, plan your strategy, and actually create the codes. Then you'll learn to link codes to mobile-friendly content, track your results, and develop ways to give your customers value that will keep them coming back. It's all presented in the straightforward style you've come to know and love, with a dash of humor thrown

  3. Tokamak Systems Code

    Energy Technology Data Exchange (ETDEWEB)

    Reid, R.L.; Barrett, R.J.; Brown, T.G.; Gorker, G.E.; Hooper, R.J.; Kalsi, S.S.; Metzler, D.H.; Peng, Y.K.M.; Roth, K.E.; Spampinato, P.T.

    1985-03-01

    The FEDC Tokamak Systems Code calculates tokamak performance, cost, and configuration as a function of plasma engineering parameters. This version of the code models experimental tokamaks. It does not currently consider tokamak configurations that generate electrical power or incorporate breeding blankets. The code has a modular (or subroutine) structure to allow independent modeling for each major tokamak component or system. A primary benefit of modularization is that a component module may be updated without disturbing the remainder of the systems code as long as the imput to or output from the module remains unchanged.

  4. MORSE Monte Carlo code

    Energy Technology Data Exchange (ETDEWEB)

    Cramer, S.N.

    1984-01-01

    The MORSE code is a large general-use multigroup Monte Carlo code system. Although no claims can be made regarding its superiority in either theoretical details or Monte Carlo techniques, MORSE has been, since its inception at ORNL in the late 1960s, the most widely used Monte Carlo radiation transport code. The principal reason for this popularity is that MORSE is relatively easy to use, independent of any installation or distribution center, and it can be easily customized to fit almost any specific need. Features of the MORSE code are described.

  5. Annotation of the protein coding regions of the equine genome

    DEFF Research Database (Denmark)

    Hestand, Matthew S.; Kalbfleisch, Theodore S.; Coleman, Stephen J.

    2015-01-01

    Current gene annotation of the horse genome is largely derived from in silico predictions and cross-species alignments. Only a small number of genes are annotated based on equine EST and mRNA sequences. To expand the number of equine genes annotated from equine experimental evidence, we sequenced m...... and appear to be small errors in the equine reference genome, since they are also identified as homozygous variants by genomic DNA resequencing of the reference horse. Taken together, we provide a resource of equine mRNA structures and protein coding variants that will enhance equine and cross...

  6. A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk

    DEFF Research Database (Denmark)

    Manning, Alisa K; Highland, Heather M.; Gasser, Jessica

    2017-01-01

    To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normog...

  7. Variants in the ASB10 Gene Are Associated with Primary Open Angle Glaucoma

    NARCIS (Netherlands)

    Micheal, S.; Ayub, H.; Islam, F.; Siddiqui, S.N.; Khan, W.A.; Akhtar, F.; Qamar, R.; Khan, M.I.; Hollander, A.I. den

    2015-01-01

    BACKGROUND: Recently nonsynonymous coding variants in the ankyrin repeats and suppressor of cytokine signaling box-containing protein 10 (ASB10) gene were found to be associated with primary open angle glaucoma (POAG) in cohorts from Oregon and Germany, but this finding was not confirmed in an indep

  8. Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits

    DEFF Research Database (Denmark)

    Chami, Nathalie; Chen, Ming-Huei; Slater, Andrew J

    2016-01-01

    Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome ar...

  9. Draft Genome Sequences of Five Yersinia pseudotuberculosis ST19 Isolates and One Isolate Variant.

    Science.gov (United States)

    Platonov, Mikhail E; Blouin, Yann; Evseeva, Vera V; Afanas'ev, Maxim V; Pourcel, Christine; Balakhonov, Sergey V; Vergnaud, Gilles; Anisimov, Andrey P

    2013-04-11

    We report the first draft genome sequences of five Yersinia pseudotuberculosis isolates of sequence type (ST) 19 and of a variant from one of the five isolates. The total length of assemblies ranged from 4,226,485 bp to 4,274,148 bp, including between 3,808 and 3,843 predicted coding sequences.

  10. Dietary factors impact on the association between CTSS variants and obesity related traits

    DEFF Research Database (Denmark)

    Hooton, Henri; Ängquist, Lars Henrik; Holst, Claus;

    2012-01-01

    Cathepsin S, a protein coded by the CTSS gene, is implicated in adipose tissue biology--this protein enhances adipose tissue development. Our hypothesis is that common variants in CTSS play a role in body weight regulation and in the development of obesity and that these effects are influenced...... by dietary factors--increased by high protein, glycemic index and energy diets....

  11. Investigation of Exomic Variants Associated with Overall Survival in Ovarian Cancer

    DEFF Research Database (Denmark)

    Winham, Stacey J; Pirie, Ailith; Chen, Yian Ann

    2016-01-01

    Background: While numerous susceptibility loci for epithelial ovarian cancer (EOC) have been identified, few associations have been reported with overall survival. In the absence of common prognostic genetic markers, we hypothesize that rare coding variants may be associated with overall EOC surv...

  12. Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits

    NARCIS (Netherlands)

    Chami, N. (Nathalie); M.-H. Chen (Ming-Huei); Slater, A.J. (Andrew J.); Eicher, J.D. (John D.); E. Evangelou (Evangelos); Tajuddin, S.M. (Salman M.); Love-Gregory, L. (Latisha); T. Kacprowski (Tim); U.M. Schick (Ursula); Nomura, A. (Akihiro); Giri, A. (Ayush); Lessard, S. (Samuel); J. Brody (Jennifer); C. Schurmann (Claudia); V.S. Pankratz (Shane); L.R. Yanek (Lisa); A. Manichaikul (Ani); R. Pazoki (Raha); E. Mihailov (Evelin); W.D. Hill (W. David); Raffield, L.M. (Laura M.); A.D. Burt (Alastair); T.M. Bartz (Traci M.); D.M. Becker (Diane); L.C. Becker (Lewis); E.A. Boerwinkle (Eric); J. Bork-Jensen (Jette); E.P. Bottinger (Erwin); M.L. O'Donoghue (Michelle L.); D.R. Crosslin (David); de Denus, S. (Simon); Dubé, M.-P. (Marie-Pierre); P. Elliott (Paul); G. Engström; M. Evans (Michele); J. Floyd (James); M. Fornage (Myriam); Gao, H. (He); A. Greinacher (Andreas); V. Gudnason (Vilmundur); T. Hansen (T.); T.B. Harris (Tamara); C. Hayward (Caroline); Hernesniemi, J. (Jussi); H. Highland (Heather); J.N. Hirschhorn (Joel); Hofman, A. (Albert); Irvin, M.R. (Marguerite R.); M. Kähönen (Mika); E.M. Lange (Ethan); Launer, L.J. (Lenore J.); T. Lehtimäki (Terho); Li, J. (Jin); D.C. Liewald (David C.); A. Linneberg (Allan); Y. Liu (Yongmei); Y. Lu (Yingchang); L.-P. Lyytikäinen (Leo-Pekka); R. Mägi (Reedik); J. Mathias (Jasmine); O. Melander (Olle); A. Metspalu (Andres); K. Mononen (Kari); M.A. Nalls (Michael); D.A. Nickerson (Deborah); K. Nikus (Kjell); C.J. O'Donnell (Christopher); M. Orho-Melander (Marju); O. Pedersen (Oluf); A. Petersmann (Astrid); Polfus, L. (Linda); B.M. Psaty (Bruce); O.T. Raitakari (Olli T.); Raitoharju, E. (Emma); Richard, M. (Melissa); K.M. Rice (Kenneth); F. Rivadeneira Ramirez (Fernando); Rotter, J.I. (Jerome I.); Schmidt, F. (Frank); A.V. Smith (Albert Vernon); J.M. Starr (John); K.D. Taylor (Kent); A. Teumer (Alexander); Thuesen, B.H. (Betina H.); Torstenson, E.S. (Eric S.); R.P. Tracy (Russell); I. Tzoulaki; N.A. Zakai (Neil); Vacchi-Suzzi, C. (Caterina); C.M. van Duijn (Cock); F.J.A. van Rooij (Frank); M. Cushman (Mary Ann); I.J. Deary (Ian J.); Velez Edwards, D.R. (Digna R.); Vergnaud, A.-C. (Anne-Claire); L.C. Wallentin (Lars); D. Waterworth (Dawn); White, H.D. (Harvey D.); J.F. Wilson (James); A.B. Zonderman; S. Kathiresan (Sekar); N. Grarup (Niels); T. Esko (Tõnu); R.J.F. Loos (Ruth); L.A. Lange (Leslie); Faraday, N. (Nauder); Abumrad, N.A. (Nada A.); T.L. Edwards (Todd L.); S.K. Ganesh (Santhi); P. Auer (Paul); A.D. Johnson (Andrew); A. Reiner (Alexander); G. Lettre (Guillaume)

    2016-01-01

    textabstractRed blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an

  13. STRONG GRAVITATIONAL LENS MODELING WITH SPATIALLY VARIANT POINT-SPREAD FUNCTIONS

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, Adam; Fiege, Jason D. [Department of Physics and Astronomy, University of Manitoba, Winnipeg, Manitoba, R3T-2N2 (Canada)

    2011-12-10

    Astronomical instruments generally possess spatially variant point-spread functions, which determine the amount by which an image pixel is blurred as a function of position. Several techniques have been devised to handle this variability in the context of the standard image deconvolution problem. We have developed an iterative gravitational lens modeling code called Mirage that determines the parameters of pixelated source intensity distributions for a given lens model. We are able to include the effects of spatially variant point-spread functions using the iterative procedures in this lensing code. In this paper, we discuss the methods to include spatially variant blurring effects and test the results of the algorithm in the context of gravitational lens modeling problems.

  14. Swine Influenza/Variant Influenza Viruses

    Science.gov (United States)

    ... Address What's this? Submit What's this? Submit Button Influenza Types Seasonal Avian Swine Variant Other Information on Swine Influenza/Variant Influenza Virus Language: English (US) Español ...

  15. A comparison of cosmological hydrodynamic codes

    Science.gov (United States)

    Kang, Hyesung; Ostriker, Jeremiah P.; Cen, Renyue; Ryu, Dongsu; Hernquist, Lars; Evrard, August E.; Bryan, Greg L.; Norman, Michael L.

    1994-01-01

    We present a detailed comparison of the simulation results of various hydrodynamic codes. Starting with identical initial conditions based on the cold dark matter scenario for the growth of structure, with parameters h = 0.5 Omega = Omega(sub b) = 1, and sigma(sub 8) = 1, we integrate from redshift z = 20 to z = O to determine the physical state within a representative volume of size L(exp 3) where L = 64 h(exp -1) Mpc. Five indenpendent codes are compared: three of them Eulerian mesh-based and two variants of the smooth particle hydrodynamics 'SPH' Lagrangian approach. The Eulerian codes were run at N(exp 3) = (32(exp 3), 64(exp 3), 128(exp 3), and 256(exp 3)) cells, the SPH codes at N(exp 3) = 32(exp 3) and 64(exp 3) particles. Results were then rebinned to a 16(exp 3) grid with the exception that the rebinned data should converge, by all techniques, to a common and correct result as N approaches infinity. We find that global averages of various physical quantities do, as expected, tend to converge in the rebinned model, but that uncertainites in even primitive quantities such as (T), (rho(exp 2))(exp 1/2) persists at the 3%-17% level achieve comparable and satisfactory accuracy for comparable computer time in their treatment of the high-density, high-temeprature regions as measured in the rebinned data; the variance among the five codes (at highest resolution) for the mean temperature (as weighted by rho(exp 2) is only 4.5%. Examined at high resolution we suspect that the density resolution is better in the SPH codes and the thermal accuracy in low-density regions better in the Eulerian codes. In the low-density, low-temperature regions the SPH codes have poor accuracy due to statiscal effects, and the Jameson code gives the temperatures which are too high, due to overuse of artificial viscosity in these high Mach number regions. Overall the comparison allows us to better estimate errors; it points to ways of improving this current generation ofhydrodynamic

  16. Research on universal combinatorial coding.

    Science.gov (United States)

    Lu, Jun; Zhang, Zhuo; Mo, Juan

    2014-01-01

    The conception of universal combinatorial coding is proposed. Relations exist more or less in many coding methods. It means that a kind of universal coding method is objectively existent. It can be a bridge connecting many coding methods. Universal combinatorial coding is lossless and it is based on the combinatorics theory. The combinational and exhaustive property make it closely related with the existing code methods. Universal combinatorial coding does not depend on the probability statistic characteristic of information source, and it has the characteristics across three coding branches. It has analyzed the relationship between the universal combinatorial coding and the variety of coding method and has researched many applications technologies of this coding method. In addition, the efficiency of universal combinatorial coding is analyzed theoretically. The multicharacteristic and multiapplication of universal combinatorial coding are unique in the existing coding methods. Universal combinatorial coding has theoretical research and practical application value.

  17. Diversity and Impact of Rare Variants in Genes Encoding the Platelet G Protein-Coupled Receptors

    Science.gov (United States)

    Jones, Matthew L.; Norman, Jane E.; Morgan, Neil V.; Mundell, Stuart J.; Lordkipanidzé, Marie; Lowe, Gillian C.; Daly, Martina E.; Simpson, Michael A.; Drake, Sian; Watson, Steve P.

    2015-01-01

    Summary Platelet responses to activating agonists are influenced by common population variants within or near G protein-coupled receptor (GPCR) genes that affect receptor activity. However, the impact of rare GPCR gene variants is unknown. We describe the rare single nucleotide variants (SNVs) in the coding and splice regions of 18 GPCR genes in 7,595 exomes from the 1,000-genomes and Exome Sequencing Project databases and in 31 cases with inherited platelet function disorders (IPFDs). In the population databases, the GPCR gene target regions contained 740 SNVs (318 synonymous, 410 missense, 7 stop gain and 6 splice region) of which 70% had global minor allele frequency (MAF) low individual frequencies, but are collectively abundant in the population. Potentially damaging variants are also present in pedigrees with IPFDs and may contribute to complex laboratory phenotypes. PMID:25567036

  18. Diversity and impact of rare variants in genes encoding the platelet G protein-coupled receptors.

    Science.gov (United States)

    Jones, Matthew L; Norman, Jane E; Morgan, Neil V; Mundell, Stuart J; Lordkipanidzé, Marie; Lowe, Gillian C; Daly, Martina E; Simpson, Michael A; Drake, Sian; Watson, Steve P; Mumford, Andrew D

    2015-04-01

    Platelet responses to activating agonists are influenced by common population variants within or near G protein-coupled receptor (GPCR) genes that affect receptor activity. However, the impact of rare GPCR gene variants is unknown. We describe the rare single nucleotide variants (SNVs) in the coding and splice regions of 18 GPCR genes in 7,595 exomes from the 1,000-genomes and Exome Sequencing Project databases and in 31 cases with inherited platelet function disorders (IPFDs). In the population databases, the GPCR gene target regions contained 740 SNVs (318 synonymous, 410 missense, 7 stop gain and 6 splice region) of which 70 % had global minor allele frequency (MAF) low individual frequencies, but are collectively abundant in the population. Potentially damaging variants are also present in pedigrees with IPFDs and may contribute to complex laboratory phenotypes.

  19. Resistance of Abaca Somaclonal Variant Against Fusarium

    OpenAIRE

    RULLY DYAH PURWATI; SUDARSONO

    2007-01-01

    The objectives of this study were (i) to evaluate responses against F. oxysporum f.sp. cubense (Foc) infection of abaca variants regenerated using four different methods, (ii) to determine initial root length and plant height effects on survival of inoculated abaca variants, and (iii) to identify Foc resistance abaca variants. In the previous experiment, four abaca variant lines were regenerated from (i) embryogenic calli (TC line), (ii) ethyl methyl sulphonate (EMS) treated embryogenic calli...

  20. Identification of novel splice variants of Adhesion G protein-coupled receptors.

    Science.gov (United States)

    Bjarnadóttir, Thóra K; Geirardsdóttir, Kristín; Ingemansson, Malena; Mirza, Majd A I; Fredriksson, Robert; Schiöth, Helgi B

    2007-01-31

    Alternative splicing is an important mechanism to generate proteome diversity in higher eukaryotic organisms. We searched for splice variants of the human Adhesion family of G protein-coupled receptors (GPCRs) using mRNA sequences and expressed sequence tags. The results presented here describe 53 human splice variants among the 33 Adhesion GPCRs. Many of these variants appear to be coding for "functional" proteins (29) while the others are seemingly "non-functional" (24). Novel functional splice variants were found for: CD97, CELR3, EMR2, EMR3, GPR56, GPR110, GPR112-GPR114, GPR116, GPR123-GPR126, GPR133, HE6, and LEC1-LEC3. Splice variants for GPR116, GPR125, GPR126, and HE6 were found conserved in other species. Several of the functional splice variants lack one or more of the functional domains that are found in the N-termini of these receptors. These functional domains are likely to affect ligand binding or interaction with other proteins and these novel splice variants may have important roles for the specificity of interactions between these receptors and extracellular molecules. Another type of splice variants found here lacks a GPCR proteolytic site (GPS). The GPS domain has been shown to be essential for the proteolytic cleavage of the receptors N-termini and for cellular surface expression. We suggest that these alternative splice variants may be crucial for the function of the receptors while the seemingly non-functional splice variants may be a part of a regulative mechanism.

  1. A Protein Domain and Family Based Approach to Rare Variant Association Analysis

    Science.gov (United States)

    Richardson, Tom G.; Shihab, Hashem A.; Rivas, Manuel A.; McCarthy, Mark I.; Campbell, Colin; Timpson, Nicholas J.; Gaunt, Tom R.

    2016-01-01

    Background It has become common practice to analyse large scale sequencing data with statistical approaches based around the aggregation of rare variants within the same gene. We applied a novel approach to rare variant analysis by collapsing variants together using protein domain and family coordinates, regarded to be a more discrete definition of a biologically functional unit. Methods Using Pfam definitions, we collapsed rare variants (Minor Allele Frequency ≤ 1%) together in three different ways 1) variants within single genomic regions which map to individual protein domains 2) variants within two individual protein domain regions which are predicted to be responsible for a protein-protein interaction 3) all variants within combined regions from multiple genes responsible for coding the same protein domain (i.e. protein families). A conventional collapsing analysis using gene coordinates was also undertaken for comparison. We used UK10K sequence data and investigated associations between regions of variants and lipid traits using the sequence kernel association test (SKAT). Results We observed no strong evidence of association between regions of variants based on Pfam domain definitions and lipid traits. Quantile-Quantile plots illustrated that the overall distributions of p-values from the protein domain analyses were comparable to that of a conventional gene-based approach. Deviations from this distribution suggested that collapsing by either protein domain or gene definitions may be favourable depending on the trait analysed. Conclusion We have collapsed rare variants together using protein domain and family coordinates to present an alternative approach over collapsing across conventionally used gene-based regions. Although no strong evidence of association was detected in these analyses, future studies may still find value in adopting these approaches to detect previously unidentified association signals. PMID:27128313

  2. A Protein Domain and Family Based Approach to Rare Variant Association Analysis.

    Directory of Open Access Journals (Sweden)

    Tom G Richardson

    Full Text Available It has become common practice to analyse large scale sequencing data with statistical approaches based around the aggregation of rare variants within the same gene. We applied a novel approach to rare variant analysis by collapsing variants together using protein domain and family coordinates, regarded to be a more discrete definition of a biologically functional unit.Using Pfam definitions, we collapsed rare variants (Minor Allele Frequency ≤ 1% together in three different ways 1 variants within single genomic regions which map to individual protein domains 2 variants within two individual protein domain regions which are predicted to be responsible for a protein-protein interaction 3 all variants within combined regions from multiple genes responsible for coding the same protein domain (i.e. protein families. A conventional collapsing analysis using gene coordinates was also undertaken for comparison. We used UK10K sequence data and investigated associations between regions of variants and lipid traits using the sequence kernel association test (SKAT.We observed no strong evidence of association between regions of variants based on Pfam domain definitions and lipid traits. Quantile-Quantile plots illustrated that the overall distributions of p-values from the protein domain analyses were comparable to that of a conventional gene-based approach. Deviations from this distribution suggested that collapsing by either protein domain or gene definitions may be favourable depending on the trait analysed.We have collapsed rare variants together using protein domain and family coordinates to present an alternative approach over collapsing across conventionally used gene-based regions. Although no strong evidence of association was detected in these analyses, future studies may still find value in adopting these approaches to detect previously unidentified association signals.

  3. Safety Code A12

    CERN Multimedia

    SC Secretariat

    2005-01-01

    Please note that the Safety Code A12 (Code A12) entitled "THE SAFETY COMMISSION (SC)" is available on the web at the following url: https://edms.cern.ch/document/479423/LAST_RELEASED Paper copies can also be obtained from the SC Unit Secretariat, e-mail: sc.secretariat@cern.ch SC Secretariat

  4. Dress Codes for Teachers?

    Science.gov (United States)

    Million, June

    2004-01-01

    In this article, the author discusses an e-mail survey of principals from across the country regarding whether or not their school had a formal staff dress code. The results indicate that most did not have a formal dress code, but agreed that professional dress for teachers was not only necessary, but showed respect for the school and had a…

  5. Nuremberg code turns 60

    OpenAIRE

    Thieren, Michel; Mauron, Alex

    2007-01-01

    This month marks sixty years since the Nuremberg code – the basic text of modern medical ethics – was issued. The principles in this code were articulated in the context of the Nuremberg trials in 1947. We would like to use this anniversary to examine its ability to address the ethical challenges of our time.

  6. Pseudonoise code tracking loop

    Science.gov (United States)

    Laflame, D. T. (Inventor)

    1980-01-01

    A delay-locked loop is presented for tracking a pseudonoise (PN) reference code in an incoming communication signal. The loop is less sensitive to gain imbalances, which can otherwise introduce timing errors in the PN reference code formed by the loop.

  7. Scrum Code Camps

    DEFF Research Database (Denmark)

    Pries-Heje, Jan; Pries-Heje, Lene; Dahlgaard, Bente

    2013-01-01

    is required. In this paper we present the design of such a new approach, the Scrum Code Camp, which can be used to assess agile team capability in a transparent and consistent way. A design science research approach is used to analyze properties of two instances of the Scrum Code Camp where seven agile teams...

  8. Scrum Code Camps

    DEFF Research Database (Denmark)

    Pries-Heje, Jan; Pries-Heje, Lene; Dahlgaard, Bente

    2013-01-01

    is required. In this paper we present the design of such a new approach, the Scrum Code Camp, which can be used to assess agile team capability in a transparent and consistent way. A design science research approach is used to analyze properties of two instances of the Scrum Code Camp where seven agile teams...

  9. READING A NEURAL CODE

    NARCIS (Netherlands)

    BIALEK, W; RIEKE, F; VANSTEVENINCK, RRD; WARLAND, D

    1991-01-01

    Traditional approaches to neural coding characterize the encoding of known stimuli in average neural responses. Organisms face nearly the opposite task - extracting information about an unknown time-dependent stimulus from short segments of a spike train. Here the neural code was characterized from

  10. The materiality of Code

    DEFF Research Database (Denmark)

    Soon, Winnie

    2014-01-01

    , Twitter and Facebook). The focus is not to investigate the functionalities and efficiencies of the code, but to study and interpret the program level of code in order to trace the use of various technological methods such as third-party libraries and platforms’ interfaces. These are important...

  11. Variant Humicola grisea CBH1.1

    Energy Technology Data Exchange (ETDEWEB)

    Goedegebuur, Frits; Gualfetti, Peter; Mitchinson, Colin; Larenas, Edmund

    2017-05-09

    Disclosed are variants of Humicola grisea CeI7A (CBH1.1), H. jecorina CBH1 variant or S. thermophilium CBH1, nucleic acids encoding the same and methods for producing the same. The variant cellulases have the amino acid sequence of a glycosyl hydrolase of family 7A wherein one or more amino acid residues are substituted.

  12. DHAD variants and methods of screening

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, Kristen J.; Ye, Rick W.

    2017-02-28

    Methods of screening for dihydroxy-acid dehydratase (DHAD) variants that display increased DHAD activity are disclosed, along with DHAD variants identified by these methods. Such enzymes can result in increased production of compounds from DHAD requiring biosynthetic pathways. Also disclosed are isolated nucleic acids encoding the DHAD variants, recombinant host cells comprising the isolated nucleic acid molecules, and methods of producing butanol.

  13. Transformation invariant sparse coding

    DEFF Research Database (Denmark)

    Mørup, Morten; Schmidt, Mikkel Nørgaard

    2011-01-01

    Sparse coding is a well established principle for unsupervised learning. Traditionally, features are extracted in sparse coding in specific locations, however, often we would prefer invariant representation. This paper introduces a general transformation invariant sparse coding (TISC) model....... The model decomposes images into features invariant to location and general transformation by a set of specified operators as well as a sparse coding matrix indicating where and to what degree in the original image these features are present. The TISC model is in general overcomplete and we therefore invoke...... sparse coding to estimate its parameters. We demonstrate how the model can correctly identify components of non-trivial artificial as well as real image data. Thus, the model is capable of reducing feature redundancies in terms of pre-specified transformations improving the component identification....

  14. The SIFT Code Specification

    Science.gov (United States)

    1983-01-01

    The specification of Software Implemented Fault Tolerance (SIFT) consists of two parts, the specifications of the SIFT models and the specifications of the SIFT PASCAL program which actually implements the SIFT system. The code specifications are the last of a hierarchy of models describing the operation of the SIFT system and are related to the SIFT models as well as the PASCAL program. These Specifications serve to link the SIFT models to the running program. The specifications are very large and detailed and closely follow the form and organization of the PASCAL code. In addition to describing each of the components of the SIFT code, the code specifications describe the assumptions of the upper SIFT models which are required to actually prove that the code will work as specified. These constraints are imposed primarily on the schedule tables.

  15. The Aesthetics of Coding

    DEFF Research Database (Denmark)

    Andersen, Christian Ulrik

    2007-01-01

    discusses code as the artist’s material and, further, formulates a critique of Cramer. The seductive magic in computer-generated art does not lie in the magical expression, but nor does it lie in the code/material/text itself. It lies in the nature of code to do something – as if it was magic......Computer art is often associated with computer-generated expressions (digitally manipulated audio/images in music, video, stage design, media facades, etc.). In recent computer art, however, the code-text itself – not the generated output – has become the artwork (Perl Poetry, ASCII Art, obfuscated...... avant-garde’. In line with Cramer, the artists Alex McLean and Adrian Ward (aka Slub) declare: “art-oriented programming needs to acknowledge the conditions of its own making – its poesis.” By analysing the Live Coding performances of Slub (where they program computer music live), the presentation...

  16. Combustion chamber analysis code

    Science.gov (United States)

    Przekwas, A. J.; Lai, Y. G.; Krishnan, A.; Avva, R. K.; Giridharan, M. G.

    1993-05-01

    A three-dimensional, time dependent, Favre averaged, finite volume Navier-Stokes code has been developed to model compressible and incompressible flows (with and without chemical reactions) in liquid rocket engines. The code has a non-staggered formulation with generalized body-fitted-coordinates (BFC) capability. Higher order differencing methodologies such as MUSCL and Osher-Chakravarthy schemes are available. Turbulent flows can be modeled using any of the five turbulent models present in the code. A two-phase, two-liquid, Lagrangian spray model has been incorporated into the code. Chemical equilibrium and finite rate reaction models are available to model chemically reacting flows. The discrete ordinate method is used to model effects of thermal radiation. The code has been validated extensively against benchmark experimental data and has been applied to model flows in several propulsion system components of the SSME and the STME.

  17. Astrophysics Source Code Library

    CERN Document Server

    Allen, Alice; Berriman, Bruce; Hanisch, Robert J; Mink, Jessica; Teuben, Peter J

    2012-01-01

    The Astrophysics Source Code Library (ASCL), founded in 1999, is a free on-line registry for source codes of interest to astronomers and astrophysicists. The library is housed on the discussion forum for Astronomy Picture of the Day (APOD) and can be accessed at http://ascl.net. The ASCL has a comprehensive listing that covers a significant number of the astrophysics source codes used to generate results published in or submitted to refereed journals and continues to grow. The ASCL currently has entries for over 500 codes; its records are citable and are indexed by ADS. The editors of the ASCL and members of its Advisory Committee were on hand at a demonstration table in the ADASS poster room to present the ASCL, accept code submissions, show how the ASCL is starting to be used by the astrophysics community, and take questions on and suggestions for improving the resource.

  18. Identification of Three Novel Splicing Variants and Expression Analysis of Chicken GPR1 Gene

    Directory of Open Access Journals (Sweden)

    Xueyou Zhang

    2017-01-01

    Full Text Available GPR1 is a G protein-coupled receptor that plays critical roles in eukaryotic cells: typically, response to glucose stimulation, lipid accumulation, and transmitting nutrition signals to cAMP pathway. However, the alternative splicing of the GPR1 gene and its expression pattern in chicken tissues and ovarian follicles were unknown. In our current study, we used RACE-PCR to identify three GPR1 variants, including the full-length variant (GPR1-va1 and two alternatively spliced variants (GPR1-va2, GPR1-vb. Quantitative real-time PCR examined the expression pattern of GPR1 mRNA in chicken tissues and ovarian follicles. The result reveals that the coding sequence of the three variants cDNA is 1053, 1053, and 627 bp in length, encoding 350, 350, and 208 amino acids, respectively. The three variants of GPR1 show similar tissue distributions; GPR1 expression was abundant in the abdominal fat, lung, and heart. With the follicular development, the expression of GPR1 gene gradually increased, and GPR1-va1 and GPR1-va2 spliced variants expression in F2 were significantly higher than in F5, F4, and prehierarchical follicles (P<0.05. Taken together, we found three novel variants of GPR1, and the results of GPR1 expression profiling in adipose tissues and ovarian follicles suggest that GPR1 may play a significant role in the lipid accumulation and progression of follicular development.

  19. Identification of Three Novel Splicing Variants and Expression Analysis of Chicken GPR1 Gene.

    Science.gov (United States)

    Zhang, Xueyou; Xiao, Qihai; Tian, Kai; Wang, Yan; Zhao, Xiaoling; Yin, Huadong; Li, Diyan; Zhu, Qing

    2017-01-01

    GPR1 is a G protein-coupled receptor that plays critical roles in eukaryotic cells: typically, response to glucose stimulation, lipid accumulation, and transmitting nutrition signals to cAMP pathway. However, the alternative splicing of the GPR1 gene and its expression pattern in chicken tissues and ovarian follicles were unknown. In our current study, we used RACE-PCR to identify three GPR1 variants, including the full-length variant (GPR1-va1) and two alternatively spliced variants (GPR1-va2, GPR1-vb). Quantitative real-time PCR examined the expression pattern of GPR1 mRNA in chicken tissues and ovarian follicles. The result reveals that the coding sequence of the three variants cDNA is 1053, 1053, and 627 bp in length, encoding 350, 350, and 208 amino acids, respectively. The three variants of GPR1 show similar tissue distributions; GPR1 expression was abundant in the abdominal fat, lung, and heart. With the follicular development, the expression of GPR1 gene gradually increased, and GPR1-va1 and GPR1-va2 spliced variants expression in F2 were significantly higher than in F5, F4, and prehierarchical follicles (P < 0.05). Taken together, we found three novel variants of GPR1, and the results of GPR1 expression profiling in adipose tissues and ovarian follicles suggest that GPR1 may play a significant role in the lipid accumulation and progression of follicular development.

  20. Identification of copy number variants in horses

    KAUST Repository

    Doan, R.

    2012-03-01

    Copy number variants (CNVs) represent a substantial source of genetic variation in mammals. However, the occurrence of CNVs in horses and their subsequent impact on phenotypic variation is unknown. We performed a study to identify CNVs in 16 horses representing 15 distinct breeds (Equus caballus) and an individual gray donkey (Equus asinus) using a whole-exome tiling array and the array comparative genomic hybridization methodology. We identified 2368 CNVs ranging in size from 197 bp to 3.5 Mb. Merging identical CNVs from each animal yielded 775 CNV regions (CNVRs), involving 1707 protein- and RNA-coding genes. The number of CNVs per animal ranged from 55 to 347, with median and mean sizes of CNVs of 5.3 kb and 99.4 kb, respectively. Approximately 6% of the genes investigated were affected by a CNV. Biological process enrichment analysis indicated CNVs primarily affected genes involved in sensory perception, signal transduction, and metabolism. CNVs also were identified in genes regulating blood group antigens, coat color, fecundity, lactation, keratin formation, neuronal homeostasis, and height in other species. Collectively, these data are the first report of copy number variation in horses and suggest that CNVs are common in the horse genome and may modulate biological processes underlying different traits observed among horses and horse breeds.

  1. Clinical variants of lichen planus.

    Science.gov (United States)

    Wagner, Gunnar; Rose, Christian; Sachse, Michael Max

    2013-04-01

    Lichen planus is characterized by lichenoid, polygonal papules with fine white lines, called Wickham striae. Lesions most commonly occur on the limbs and on the dorsal aspect of the trunk. At the same time often leukoplakia of mucous membranes as well as nail disorders are seen. There are numerous variants of lichen planus which can be distinguished from the classical form on the basis of morphology and distribution of the lesions. The typical primary lesion of lichen planus may be replaced by other forms, such as patches, hyperkeratoses, ulcerations, or bullous lesions. Moreover, distribution patterns of these lesions may vary and include erythrodermic, inverse or linear arrangements. In contrast to these numerous clinical features, histologic findings remain characteristic in the variants, so that the diagnosis can be made securely. Differential diagnoses of lichen planus include diverse dermatoses such as bullous pemphigoid or paronychia.

  2. Coronary artery anatomy and variants

    Energy Technology Data Exchange (ETDEWEB)

    Malago, Roberto; Pezzato, Andrea; Barbiani, Camilla; Alfonsi, Ugolino; Nicoli, Lisa; Caliari, Giuliana; Pozzi Mucelli, Roberto [Policlinico G.B. Rossi, University of Verona, Department of Radiology, Verona (Italy)

    2011-12-15

    Variants and congenital anomalies of the coronary arteries are usually asymptomatic, but may present with severe chest pain or cardiac arrest. The introduction of multidetector CT coronary angiography (MDCT-CA) allows the detection of significant coronary artery stenosis. Improved performance with isotropic spatial resolution and higher temporal resolution provides a valid alternative to conventional coronary angiography (CCA) in many patients. MDCT-CA is now considered the ideal tool for three-dimensional visualization of the complex and tortuous anatomy of the coronary arteries. With multiplanar and volume-rendered reconstructions, MDCT-CA may even outperform CCA in determining the relative position of vessels, thus providing a better view of the coronary vascular anatomy. The purpose of this review is to describe the normal anatomy of the coronary arteries and their main variants based on MDCT-CA with appropriate reconstructions. (orig.)

  3. [Mirizzi syndrome and its variants].

    Science.gov (United States)

    Meyer, G J; Runge, D; Gebhardt, J

    1990-04-01

    Between 1981 and 1987 5434 patients were studied by ERCP in Allgemeines Krankenhaus Hamburg-Barmbeck. 26 (i.e. 0.43%) suffered from Mirizze syndrome with the triad of cholelithiasis, cholecystitis and obstructive biliary disease. They were classified in four different types according to the variable localisation and origin of the biliary obstruction. 16 patients corresponded to the classical type (I and II) with compression, penetration, and obturation by the concrement, five patients matched borderline with infiltration (III) and five patients were classified as variants of this syndrome. A mild elevation of serum bilirubine and alkaline phosphatase indicated more likely the benign etiology of type I to III, however, a marked elevation of alkaline phosphatase in the variants suggested more likely a malignant underlying disease. The diagnosis was ascertained in all cases by ERC and sonography preoperatively and was verified by laparotomy (n = 18) and follow-up (n = 6).

  4. Variants of lumbosacral elastic band.

    Directory of Open Access Journals (Sweden)

    Carlos Cesar Santín Alfaro

    2011-06-01

    Full Text Available It is made an intervention research, qualitative and quantitative of two variants of lumbosacral elastic bands used in Provincial Laboratory of Technical Orthopedics in Sancti Spiritus Province, taking into account the high demand for this device and that the laboratory do not often count with the raw material needed for the original lumbosacral belt made by denim cloth which is the conventional belt. The main goal of this research is to explain the technological process and to compare the cost of production of both elastic variants with lumbosacral belt made by cloth which are offer to patients who look for this service , giving them a rapid solution so that they can feel comfortable.

  5. Unusual variant of Cantrell's pentalogy?

    OpenAIRE

    Kumar, Basant; Sharma, S.B.; Kandpal, Deepak K.; Agrawal, L. D.

    2008-01-01

    A 12-hour-old male infant presented with prolapsed abdominal content through a defect on left side of chest wall with respiratory distress. A thorough clinical examination suggested absence of ectopia cordis, abdominal wall defect, and any bony anomaly. The child expired after 6 hours of admission because of respiratory distress and electrolyte imbalance. Is congenital defect of chest wall associated with diaphragmatic hernia without ectopia cordis and omphalocele, an unusual variant of Cantr...

  6. Dorsal variant blister aneurysm repair.

    Science.gov (United States)

    Couldwell, William T; Chamoun, Roukoz

    2012-01-01

    Dorsal variant proximal carotid blister aneurysms are treacherous lesions to manage. It is important to recognize this variant on preoperative angiographic imaging, in anticipation of surgical strategies for their treatment. Strategies include trapping the involved segment and revascularization if necessary. Other options include repair of the aneurysm rupture site directly. Given that these are not true berry aneurysms, repair of the rupture site involves wrapping or clip-grafting techniques. The case presented here was a young woman with a subarachnoid hemorrhage from a ruptured dorsal variant blister aneurysm. The technique used is demonstrated in the video and is a modified clip-wrap technique using woven polyester graft material. The patient was given aspirin preoperatively as preparation for the clip-wrap technique. It is the authors' current protocol to attempt a direct repair with clip-wrapping and leaving artery sacrifice with or without bypass as a salvage therapy if direct repair is not possible. Assessment of vessel patency after repair is performed by intraoperative Doppler and indocyanine green angiography. Intraoperative somatosensory and motor evoked potential monitoring is performed in all cases. The video can be found here: http://youtu.be/crUreWGQdGo.

  7. Microcystic Variant of Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Anthony Kodzo-Grey Venyo

    2013-01-01

    Full Text Available Background. Microcystic variant of urothelial carcinoma is one of the new variants of urothelial carcinoma that was added to the WHO classification in 2004. Aims. To review the literature on microcystic variant of urothelial carcinoma. Methods. Various internet search engines were used to identify reported cases of the tumour. Results. Microscopic features of the tumour include: (i Conspicuous intracellular and intercellular lumina/microcysts encompassed by malignant urothelial or squamous cells. (ii The lumina are usually empty; may contain granular eosinophilic debris, mucin, or necrotic cells. (iii The cysts may be variable in size; round, or oval, up to 2 mm; lined by urothelium which are either flattened cells or low columnar cells however, they do not contain colonic epithelium or goblet cells; are infiltrative; invade the muscularis propria; mimic cystitis cystica and cystitis glandularis; occasionally exhibit neuroendocrine differentiation. (iv Elongated and irregular branching spaces are usually seen. About 17 cases of the tumour have been reported with only 2 patients who have survived. The tumour tends to be of high-grade and high-stage. There is no consensus opinion on the best option of treatment of the tumour. Conclusions. It would prove difficult at the moment to be dogmatic regarding its prognosis but it is a highly aggressive tumour. New cases of the tumour should be reported in order to document its biological behaviour.

  8. Fulcrum Network Codes

    DEFF Research Database (Denmark)

    2015-01-01

    Fulcrum network codes, which are a network coding framework, achieve three objectives: (i) to reduce the overhead per coded packet to almost 1 bit per source packet; (ii) to operate the network using only low field size operations at intermediate nodes, dramatically reducing complexity in the net...... the number of dimensions seen by the network using a linear mapping. Receivers can tradeoff computational effort with network delay, decoding in the high field size, the low field size, or a combination thereof.......Fulcrum network codes, which are a network coding framework, achieve three objectives: (i) to reduce the overhead per coded packet to almost 1 bit per source packet; (ii) to operate the network using only low field size operations at intermediate nodes, dramatically reducing complexity...... in the network; and (iii) to deliver an end-to-end performance that is close to that of a high field size network coding system for high-end receivers while simultaneously catering to low-end ones that can only decode in a lower field size. Sources may encode using a high field size expansion to increase...

  9. Report number codes

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, R.N. (ed.)

    1985-05-01

    This publication lists all report number codes processed by the Office of Scientific and Technical Information. The report codes are substantially based on the American National Standards Institute, Standard Technical Report Number (STRN)-Format and Creation Z39.23-1983. The Standard Technical Report Number (STRN) provides one of the primary methods of identifying a specific technical report. The STRN consists of two parts: The report code and the sequential number. The report code identifies the issuing organization, a specific program, or a type of document. The sequential number, which is assigned in sequence by each report issuing entity, is not included in this publication. Part I of this compilation is alphabetized by report codes followed by issuing installations. Part II lists the issuing organization followed by the assigned report code(s). In both Parts I and II, the names of issuing organizations appear for the most part in the form used at the time the reports were issued. However, for some of the more prolific installations which have had name changes, all entries have been merged under the current name.

  10. Application of RS Codes in Decoding QR Code

    Institute of Scientific and Technical Information of China (English)

    Zhu Suxia(朱素霞); Ji Zhenzhou; Cao Zhiyan

    2003-01-01

    The QR Code is a 2-dimensional matrix code with high error correction capability. It employs RS codes to generate error correction codewords in encoding and recover errors and damages in decoding. This paper presents several QR Code's virtues, analyzes RS decoding algorithm and gives a software flow chart of decoding the QR Code with RS decoding algorithm.

  11. Evaluation Codes from an Affine Veriety Code Perspective

    DEFF Research Database (Denmark)

    Geil, Hans Olav

    2008-01-01

    Evaluation codes (also called order domain codes) are traditionally introduced as generalized one-point geometric Goppa codes. In the present paper we will give a new point of view on evaluation codes by introducing them instead as particular nice examples of affine variety codes. Our study...

  12. Distributed multiple description coding

    CERN Document Server

    Bai, Huihui; Zhao, Yao

    2011-01-01

    This book examines distributed video coding (DVC) and multiple description coding (MDC), two novel techniques designed to address the problems of conventional image and video compression coding. Covering all fundamental concepts and core technologies, the chapters can also be read as independent and self-sufficient, describing each methodology in sufficient detail to enable readers to repeat the corresponding experiments easily. Topics and features: provides a broad overview of DVC and MDC, from the basic principles to the latest research; covers sub-sampling based MDC, quantization based MDC,

  13. Cryptography cracking codes

    CERN Document Server

    2014-01-01

    While cracking a code might seem like something few of us would encounter in our daily lives, it is actually far more prevalent than we may realize. Anyone who has had personal information taken because of a hacked email account can understand the need for cryptography and the importance of encryption-essentially the need to code information to keep it safe. This detailed volume examines the logic and science behind various ciphers, their real world uses, how codes can be broken, and the use of technology in this oft-overlooked field.

  14. Classical Holographic Codes

    CERN Document Server

    Brehm, Enrico M

    2016-01-01

    In this work, we introduce classical holographic codes. These can be understood as concatenated probabilistic codes and can be represented as networks uniformly covering hyperbolic space. In particular, classical holographic codes can be interpreted as maps from bulk degrees of freedom to boundary degrees of freedom. Interestingly, they are shown to exhibit features similar to those expected from the AdS/CFT correspondence. Among these are a version of the Ryu-Takayanagi formula and intriguing properties regarding bulk reconstruction and boundary representations of bulk operations. We discuss the relation of our findings with expectations from AdS/CFT and, in particular, with recent results from quantum error correction.

  15. Fitting of two and three variant polynomials from experimental data through the least squares method. (Using of the codes AJUS-2D, AJUS-3D and LEGENDRE-2D); Ajuste de polinomios en dos y tres variables independientes por el metodo de minimos cuadrados. (Desarrollo de los codigos AJUS-2D, AJUS-3D y LEGENDRE-2D)

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez Miro, J. J.; Sanz Martin, J. C.

    1994-07-01

    Obtaining polynomial fittings from observational data in two and three dimensions is an interesting and practical task. Such an arduous problem suggests the development of an automatic code. The main novelty we provide lies in the generalization of the classical least squares method in three FORTRAN 77 programs usable in any sampling problem. Furthermore, we introduce the orthogonal 2D-Legendre function in the fitting process. These FORTRAN 77 programs are equipped with the options to calculate the approximation quality standard indicators, obviously generalized to two and three dimensions (correlation nonlinear factor, confidence intervals, cuadratic mean error, and so on). The aim of this paper is to rectify the absence of fitting algorithms for more than one independent variable in mathematical libraries. (Author) 10 refs.

  16. Genetic variants in epigenetic genes and breast cancer risk.

    Science.gov (United States)

    Cebrian, Arancha; Pharoah, Paul D; Ahmed, Shahana; Ropero, Santiago; Fraga, Mario F; Smith, Paula L; Conroy, Don; Luben, Robert; Perkins, Barbara; Easton, Douglas F; Dunning, Alison M; Esteller, Manel; Ponder, Bruce A J

    2006-08-01

    Epigenetic events, resulting changes in gene expression capacity, are important in tumour progression, and variation in genes involved in epigenetic mechanisms might therefore be important in cancer susceptibility. To evaluate this hypothesis, we examined common variants in 12 genes coding for DNA methyltransferases (DNMT), histone acetyltransferases, histone deacetyltransferases, histone methyltrasferases and methyl-CpG binding domain proteins, for association with breast cancer in a large case-control study (N cases = 4474 and N controls = 4580). We identified 63 single nucleotide polymorphisms (SNPs) that efficiently tag all the known common variants in these genes, and are also expected to tag any unknown SNP in each gene. We found some evidence for association for six SNPs: DNMT3b-c31721t [P (2 df) = 0.007], PRDM2-c99243 t [P (2 df) = 0.03] and t105413c [P-recessive = 0.05], EHMT1-g-9441a [P (2df) = 0.05] and g41451t (P-trend = 0.04), and EHMT2-S237S [P (2df) = 0.04]. The most significant result was for DNMT3b-c31721t (P-trend = 0.124 after adjusting for multiple testing). However, there were three other results with P variants in histone methyltransferases, and warrant the design of larger epidemiological and biochemical studies to establish the true meaning of these findings.

  17. The algorithm of malicious code detection based on data mining

    Science.gov (United States)

    Yang, Yubo; Zhao, Yang; Liu, Xiabi

    2017-08-01

    Traditional technology of malicious code detection has low accuracy and it has insufficient detection capability for new variants. In terms of malicious code detection technology which is based on the data mining, its indicators are not accurate enough, and its classification detection efficiency is relatively low. This paper proposed the information gain ratio indicator based on the N-gram to choose signature, this indicator can accurately reflect the detection weight of the signature, and helped by C4.5 decision tree to elevate the algorithm of classification detection.

  18. The fast code

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, L.N.; Wilson, R.E. [Oregon State Univ., Dept. of Mechanical Engineering, Corvallis, OR (United States)

    1996-09-01

    The FAST Code which is capable of determining structural loads on a flexible, teetering, horizontal axis wind turbine is described and comparisons of calculated loads with test data are given at two wind speeds for the ESI-80. The FAST Code models a two-bladed HAWT with degrees of freedom for blade bending, teeter, drive train flexibility, yaw, and windwise and crosswind tower motion. The code allows blade dimensions, stiffnesses, and weights to differ and models tower shadow, wind shear, and turbulence. Additionally, dynamic stall is included as are delta-3 and an underslung rotor. Load comparisons are made with ESI-80 test data in the form of power spectral density, rainflow counting, occurrence histograms, and azimuth averaged bin plots. It is concluded that agreement between the FAST Code and test results is good. (au)

  19. VT ZIP Code Areas

    Data.gov (United States)

    Vermont Center for Geographic Information — (Link to Metadata) A ZIP Code Tabulation Area (ZCTA) is a statistical geographic entity that approximates the delivery area for a U.S. Postal Service five-digit...

  20. Fulcrum Network Codes

    DEFF Research Database (Denmark)

    2015-01-01

    Fulcrum network codes, which are a network coding framework, achieve three objectives: (i) to reduce the overhead per coded packet to almost 1 bit per source packet; (ii) to operate the network using only low field size operations at intermediate nodes, dramatically reducing complexity...... in the network; and (iii) to deliver an end-to-end performance that is close to that of a high field size network coding system for high-end receivers while simultaneously catering to low-end ones that can only decode in a lower field size. Sources may encode using a high field size expansion to increase...... the number of dimensions seen by the network using a linear mapping. Receivers can tradeoff computational effort with network delay, decoding in the high field size, the low field size, or a combination thereof....

  1. GOOGLE SUMMER OF CODE

    National Research Council Canada - National Science Library

    Leslie Hawthorn

    2008-01-01

      This article examines the Google Summer of Code (GSoC) program, the world's first global initiative to introduce College and University students to free/libre open source software (F/LOSS) development...

  2. Importance of Building Code

    Directory of Open Access Journals (Sweden)

    Reshmi Banerjee

    2015-06-01

    Full Text Available A building code, or building control, is a set of rules that specify the minimum standards for constructed objects such as buildings and non building structures. The main purpose of building codes are to protect public health, safety and general welfare as they relate to the construction and occupancy of buildings and structures. The building code becomes law of a particular jurisdiction when formally enacted by the appropriate governmental or private authority. Building codes are generally intended to be applied by architects, engineers, constructors and regulators but are also used for various purposes by safety inspectors, environmental scientists, real estate developers, subcontractors, manufacturers of building products and materials, insurance companies, facility managers, tenants and others.

  3. Bandwidth efficient coding

    CERN Document Server

    Anderson, John B

    2017-01-01

    Bandwidth Efficient Coding addresses the major challenge in communication engineering today: how to communicate more bits of information in the same radio spectrum. Energy and bandwidth are needed to transmit bits, and bandwidth affects capacity the most. Methods have been developed that are ten times as energy efficient at a given bandwidth consumption as simple methods. These employ signals with very complex patterns and are called "coding" solutions. The book begins with classical theory before introducing new techniques that combine older methods of error correction coding and radio transmission in order to create narrowband methods that are as efficient in both spectrum and energy as nature allows. Other topics covered include modulation techniques such as CPM, coded QAM and pulse design.

  4. Coded Random Access

    DEFF Research Database (Denmark)

    Paolini, Enrico; Stefanovic, Cedomir; Liva, Gianluigi

    2015-01-01

    , in which the structure of the access protocol can be mapped to a structure of an erasure-correcting code defined on graph. This opens the possibility to use coding theory and tools for designing efficient random access protocols, offering markedly better performance than ALOHA. Several instances of coded......The rise of machine-to-machine communications has rekindled the interest in random access protocols as a support for a massive number of uncoordinatedly transmitting devices. The legacy ALOHA approach is developed under a collision model, where slots containing collided packets are considered...... as waste. However, if the common receiver (e.g., base station) is capable to store the collision slots and use them in a transmission recovery process based on successive interference cancellation, the design space for access protocols is radically expanded. We present the paradigm of coded random access...

  5. Code Disentanglement: Initial Plan

    Energy Technology Data Exchange (ETDEWEB)

    Wohlbier, John Greaton [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Kelley, Timothy M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Rockefeller, Gabriel M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Calef, Matthew Thomas [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-01-27

    The first step to making more ambitious changes in the EAP code base is to disentangle the code into a set of independent, levelized packages. We define a package as a collection of code, most often across a set of files, that provides a defined set of functionality; a package a) can be built and tested as an entity and b) fits within an overall levelization design. Each package contributes one or more libraries, or an application that uses the other libraries. A package set is levelized if the relationships between packages form a directed, acyclic graph and each package uses only packages at lower levels of the diagram (in Fortran this relationship is often describable by the use relationship between modules). Independent packages permit independent- and therefore parallel|development. The packages form separable units for the purposes of development and testing. This is a proven path for enabling finer-grained changes to a complex code.

  6. Annotated Raptor Codes

    CERN Document Server

    Mahdaviani, Kaveh; Tellambura, Chintha

    2011-01-01

    In this paper, an extension of raptor codes is introduced which keeps all the desirable properties of raptor codes, including the linear complexity of encoding and decoding per information bit, unchanged. The new design, however, improves the performance in terms of the reception rate. Our simulations show a 10% reduction in the needed overhead at the benchmark block length of 64,520 bits and with the same complexity per information bit.

  7. Robust Nonlinear Neural Codes

    Science.gov (United States)

    Yang, Qianli; Pitkow, Xaq

    2015-03-01

    Most interesting natural sensory stimuli are encoded in the brain in a form that can only be decoded nonlinearly. But despite being a core function of the brain, nonlinear population codes are rarely studied and poorly understood. Interestingly, the few existing models of nonlinear codes are inconsistent with known architectural features of the brain. In particular, these codes have information content that scales with the size of the cortical population, even if that violates the data processing inequality by exceeding the amount of information entering the sensory system. Here we provide a valid theory of nonlinear population codes by generalizing recent work on information-limiting correlations in linear population codes. Although these generalized, nonlinear information-limiting correlations bound the performance of any decoder, they also make decoding more robust to suboptimal computation, allowing many suboptimal decoders to achieve nearly the same efficiency as an optimal decoder. Although these correlations are extremely difficult to measure directly, particularly for nonlinear codes, we provide a simple, practical test by which one can use choice-related activity in small populations of neurons to determine whether decoding is suboptimal or optimal and limited by correlated noise. We conclude by describing an example computation in the vestibular system where this theory applies. QY and XP was supported by a grant from the McNair foundation.

  8. Scalable motion vector coding

    Science.gov (United States)

    Barbarien, Joeri; Munteanu, Adrian; Verdicchio, Fabio; Andreopoulos, Yiannis; Cornelis, Jan P.; Schelkens, Peter

    2004-11-01

    Modern video coding applications require transmission of video data over variable-bandwidth channels to a variety of terminals with different screen resolutions and available computational power. Scalable video coding is needed to optimally support these applications. Recently proposed wavelet-based video codecs employing spatial domain motion compensated temporal filtering (SDMCTF) provide quality, resolution and frame-rate scalability while delivering compression performance comparable to that of the state-of-the-art non-scalable H.264-codec. These codecs require scalable coding of the motion vectors in order to support a large range of bit-rates with optimal compression efficiency. Scalable motion vector coding algorithms based on the integer wavelet transform followed by embedded coding of the wavelet coefficients were recently proposed. In this paper, a new and fundamentally different scalable motion vector codec (MVC) using median-based motion vector prediction is proposed. Extensive experimental results demonstrate that the proposed MVC systematically outperforms the wavelet-based state-of-the-art solutions. To be able to take advantage of the proposed scalable MVC, a rate allocation mechanism capable of optimally dividing the available rate among texture and motion information is required. Two rate allocation strategies are proposed and compared. The proposed MVC and rate allocation schemes are incorporated into an SDMCTF-based video codec and the benefits of scalable motion vector coding are experimentally demonstrated.

  9. On Expanded Cyclic Codes

    CERN Document Server

    Wu, Yingquan

    2008-01-01

    The paper has a threefold purpose. The first purpose is to present an explicit description of expanded cyclic codes defined in $\\GF(q^m)$. The proposed explicit construction of expanded generator matrix and expanded parity check matrix maintains the symbol-wise algebraic structure and thus keeps many important original characteristics. The second purpose of this paper is to identify a class of constant-weight cyclic codes. Specifically, we show that a well-known class of $q$-ary BCH codes excluding the all-zero codeword are constant-weight cyclic codes. Moreover, we show this class of codes achieve the Plotkin bound. The last purpose of the paper is to characterize expanded cyclic codes utilizing the proposed expanded generator matrix and parity check matrix. We analyze the properties of component codewords of a codeword and particularly establish the precise conditions under which a codeword can be represented by a subbasis. With the new insights, we present an improved lower bound on the minimum distance of...

  10. Genome-wide family-based linkage analysis of exome chip variants and cardiometabolic risk.

    Science.gov (United States)

    Hellwege, Jacklyn N; Palmer, Nicholette D; Raffield, Laura M; Ng, Maggie C Y; Hawkins, Gregory A; Long, Jirong; Lorenzo, Carlos; Norris, Jill M; Ida Chen, Y-D; Speliotes, Elizabeth K; Rotter, Jerome I; Langefeld, Carl D; Wagenknecht, Lynne E; Bowden, Donald W

    2014-05-01

    Linkage analysis of complex traits has had limited success in identifying trait-influencing loci. Recently, coding variants have been implicated as the basis for some biomedical associations. We tested whether coding variants are the basis for linkage peaks of complex traits in 42 African-American (n = 596) and 90 Hispanic (n = 1,414) families in the Insulin Resistance Atherosclerosis Family Study (IRASFS) using Illumina HumanExome Beadchips. A total of 92,157 variants in African Americans (34%) and 81,559 (31%) in Hispanics were polymorphic and tested using two-point linkage and association analyses with 37 cardiometabolic phenotypes. In African Americans 77 LOD scores greater than 3 were observed. The highest LOD score was 4.91 with the APOE SNP rs7412 (MAF = 0.13) with plasma apolipoprotein B (ApoB). This SNP was associated with ApoB (P-value = 4 × 10(-19)) and accounted for 16.2% of the variance in African Americans. In Hispanic families, 104 LOD scores were greater than 3. The strongest evidence of linkage (LOD = 4.29) was with rs5882 (MAF = 0.46) in CETP with HDL. CETP variants were strongly associated with HDL (0.00049 evidence of strong linkage in this genome wide survey of primarily coding variants was uncommon. Loci with strong evidence of linkage was characterized by large contributions to the variance, and, in these cases, are common variants. Less compelling evidence of linkage and association was observed with additional loci that may require larger family sets to confirm. © 2014 WILEY PERIODICALS, INC.

  11. Association of Germline CHEK2 Gene Variants with Risk and Prognosis of Non-Hodgkin Lymphoma.

    Directory of Open Access Journals (Sweden)

    Ondrej Havranek

    Full Text Available The checkpoint kinase 2 gene (CHEK2 codes for the CHK2 protein, an important mediator of the DNA damage response pathway. The CHEK2 gene has been recognized as a multi-cancer susceptibility gene; however, its role in non-Hodgkin lymphoma (NHL remains unclear. We performed mutation analysis of the entire CHEK2 coding sequence in 340 NHL patients using denaturing high-performance liquid chromatography (DHPLC and multiplex ligation-dependent probe amplification (MLPA. Identified hereditary variants were genotyped in 445 non-cancer controls. The influence of CHEK2 variants on disease risk was statistically evaluated. Identified CHEK2 germline variants included four truncating mutations (found in five patients and no control; P = 0.02 and nine missense variants (found in 21 patients and 12 controls; P = 0.02. Carriers of non-synonymous variants had an increased risk of NHL development [odds ratio (OR 2.86; 95% confidence interval (CI 1.42-5.79] and an unfavorable prognosis [hazard ratio (HR of progression-free survival (PFS 2.1; 95% CI 1.12-4.05]. In contrast, the most frequent intronic variant c.319+43dupA (identified in 22% of patients and 31% of controls was associated with a decreased NHL risk (OR = 0.62; 95% CI 0.45-0.86, but its positive prognostic effect was limited to NHL patients with diffuse large B-cell lymphoma (DLBCL treated by conventional chemotherapy without rituximab (HR-PFS 0.4; 94% CI 0.17-0.74. Our results show that germ-line CHEK2 mutations affecting protein coding sequence confer a moderately-increased risk of NHL, they are associated with an unfavorable NHL prognosis, and they may represent a valuable predictive biomarker for patients with DLBCL.

  12. Mitochondrial DNA polymerase gamma variants in idiopathic sporadic Parkinson disease.

    Science.gov (United States)

    Luoma, P T; Eerola, J; Ahola, S; Hakonen, A H; Hellström, O; Kivistö, K T; Tienari, P J; Suomalainen, A

    2007-09-11

    Dysfunction of mitochondrial DNA polymerase gamma (POLG) has been recently recognized as an important cause of inherited neurodegenerative diseases. We have reported dominant and recessive inheritance of parkinsonism, mitochondrial myopathy, and premature amenorrhea in five ethnically distinct families with POLG1 mutations. This prompted us to carry out a detailed analysis of the coding region and intron-exon boundaries of POLG1 in Finnish patients with idiopathic sporadic Parkinson disease (PD) and in nonparkinsonian controls. The coding region of POLG1 was analyzed in 140 Finnish patients with PD and their 127 spouses as age- and ethnically matched controls. Further, we analyzed the intragenic CAG-repeat region of POLG1 in 126 additional patients with nonparkinsonian neurologic disorders and in 516 Finnish population controls. We found clustering of rare variants of the POLG1 CAG-repeat, encoding a polyglutamine tract, in Finnish patients with idiopathic PD as compared to their spouses (p = 0.003; OR 3.01, 95% CI 1.35 to 6.71), population controls (p = 0.001; OR 2.45, 95% CI 1.45 to 4.14), and patients with nonparkinsonian neurologic disorders (p = 0.05, OR 1.98, 95% CI 0.97 to 4.05). We found several amino acid substitutions, none of them associating with PD. These included a previously parkinsonism-associated POLG variant Y831C, found in one patient with PD, but also in five controls, suggesting that it is a neutral amino acid polymorphism. Our results suggest that POLG polyglutamine tract variants should be considered as a predisposing genetic factor in idiopathic sporadic Parkinson disease.

  13. Non-Binary Polar Codes using Reed-Solomon Codes and Algebraic Geometry Codes

    CERN Document Server

    Mori, Ryuhei

    2010-01-01

    Polar codes, introduced by Arikan, achieve symmetric capacity of any discrete memoryless channels under low encoding and decoding complexity. Recently, non-binary polar codes have been investigated. In this paper, we calculate error probability of non-binary polar codes constructed on the basis of Reed-Solomon matrices by numerical simulations. It is confirmed that 4-ary polar codes have significantly better performance than binary polar codes on binary-input AWGN channel. We also discuss an interpretation of polar codes in terms of algebraic geometry codes, and further show that polar codes using Hermitian codes have asymptotically good performance.

  14. Distributed Video Coding: Iterative Improvements

    DEFF Research Database (Denmark)

    Luong, Huynh Van

    Nowadays, emerging applications such as wireless visual sensor networks and wireless video surveillance are requiring lightweight video encoding with high coding efficiency and error-resilience. Distributed Video Coding (DVC) is a new coding paradigm which exploits the source statistics...

  15. Polynomial weights and code constructions

    DEFF Research Database (Denmark)

    Massey, J; Costello, D; Justesen, Jørn

    1973-01-01

    polynomial included. This fundamental property is then used as the key to a variety of code constructions including 1) a simplified derivation of the binary Reed-Muller codes and, for any primepgreater than 2, a new extensive class ofp-ary "Reed-Muller codes," 2) a new class of "repeated-root" cyclic codes...... that are subcodes of the binary Reed-Muller codes and can be very simply instrumented, 3) a new class of constacyclic codes that are subcodes of thep-ary "Reed-Muller codes," 4) two new classes of binary convolutional codes with large "free distance" derived from known binary cyclic codes, 5) two new classes...... of long constraint length binary convolutional codes derived from2^r-ary Reed-Solomon codes, and 6) a new class ofq-ary "repeated-root" constacyclic codes with an algebraic decoding algorithm....

  16. In vivo exploration of the functional activity of the non-coding 8q24 prostate cancer risk locus

    Institute of Scientific and Technical Information of China (English)

    Dolores J. Lamb; Mounia Tannour-Louet

    2010-01-01

    @@ Genome-wide association studies (GWAS) have successfully identified a substantial number of risk variants for prostate cancer [1-10]. In total, more than 20 single nucleotide polymorphisms (SNPs) that predispose to prostate malignancy have been found scat-tered throughout the genome in coding and non-coding regions.

  17. Discovery and functional annotation of SIX6 variants in primary open-angle glaucoma.

    Directory of Open Access Journals (Sweden)

    Megan Ulmer Carnes

    Full Text Available Glaucoma is a leading cause of blindness worldwide. Primary open-angle glaucoma (POAG is the most common subtype and is a complex trait with multigenic inheritance. Genome-wide association studies have previously identified a significant association between POAG and the SIX6 locus (rs10483727, odds ratio (OR = 1.32, p = 3.87×10(-11. SIX6 plays a role in ocular development and has been associated with the morphology of the optic nerve. We sequenced the SIX6 coding and regulatory regions in 262 POAG cases and 256 controls and identified six nonsynonymous coding variants, including five rare and one common variant, Asn141His (rs33912345, which was associated significantly with POAG (OR = 1.27, p = 4.2×10(-10 in the NEIGHBOR/GLAUGEN datasets. These variants were tested in an in vivo Danio rerio (zebrafish complementation assay to evaluate ocular metrics such as eye size and optic nerve structure. Five variants, found primarily in POAG cases, were hypomorphic or null, while the sixth variant, found only in controls, was benign. One variant in the SIX6 enhancer increased expression of SIX6 and disrupted its regulation. Finally, to our knowledge for the first time, we have identified a clinical feature in POAG patients that appears to be dependent upon SIX6 genotype: patients who are homozygous for the SIX6 risk allele (His141 have a statistically thinner retinal nerve fiber layer than patients homozygous for the SIX6 non-risk allele (Asn141. Our results, in combination with previous SIX6 work, lead us to hypothesize that SIX6 risk variants disrupt the development of the neural retina, leading to a reduced number of retinal ganglion cells, thereby increasing the risk of glaucoma-associated vision loss.

  18. Product Codes for Optical Communication

    DEFF Research Database (Denmark)

    Andersen, Jakob Dahl

    2002-01-01

    Many optical communicaton systems might benefit from forward-error-correction. We present a hard-decision decoding algorithm for the "Block Turbo Codes", suitable for optical communication, which makes this coding-scheme an alternative to Reed-Solomon codes.......Many optical communicaton systems might benefit from forward-error-correction. We present a hard-decision decoding algorithm for the "Block Turbo Codes", suitable for optical communication, which makes this coding-scheme an alternative to Reed-Solomon codes....

  19. Some new ternary linear codes

    Directory of Open Access Journals (Sweden)

    Rumen Daskalov

    2017-07-01

    Full Text Available Let an $[n,k,d]_q$ code be a linear code of length $n$, dimension $k$ and minimum Hamming distance $d$ over $GF(q$. One of the most important problems in coding theory is to construct codes with optimal minimum distances. In this paper 22 new ternary linear codes are presented. Two of them are optimal. All new codes improve the respective lower bounds in [11].

  20. Algebraic geometric codes with applications

    Institute of Scientific and Technical Information of China (English)

    CHEN Hao

    2007-01-01

    The theory of linear error-correcting codes from algebraic geomet-ric curves (algebraic geometric (AG) codes or geometric Goppa codes) has been well-developed since the work of Goppa and Tsfasman, Vladut, and Zink in 1981-1982. In this paper we introduce to readers some recent progress in algebraic geometric codes and their applications in quantum error-correcting codes, secure multi-party computation and the construction of good binary codes.

  1. Coded-aperture imaging in nuclear medicine

    Science.gov (United States)

    Smith, Warren E.; Barrett, Harrison H.; Aarsvold, John N.

    1989-01-01

    Coded-aperture imaging is a technique for imaging sources that emit high-energy radiation. This type of imaging involves shadow casting and not reflection or refraction. High-energy sources exist in x ray and gamma-ray astronomy, nuclear reactor fuel-rod imaging, and nuclear medicine. Of these three areas nuclear medicine is perhaps the most challenging because of the limited amount of radiation available and because a three-dimensional source distribution is to be determined. In nuclear medicine a radioactive pharmaceutical is administered to a patient. The pharmaceutical is designed to be taken up by a particular organ of interest, and its distribution provides clinical information about the function of the organ, or the presence of lesions within the organ. This distribution is determined from spatial measurements of the radiation emitted by the radiopharmaceutical. The principles of imaging radiopharmaceutical distributions with coded apertures are reviewed. Included is a discussion of linear shift-variant projection operators and the associated inverse problem. A system developed at the University of Arizona in Tucson consisting of small modular gamma-ray cameras fitted with coded apertures is described.

  2. Optical coding theory with Prime

    CERN Document Server

    Kwong, Wing C

    2013-01-01

    Although several books cover the coding theory of wireless communications and the hardware technologies and coding techniques of optical CDMA, no book has been specifically dedicated to optical coding theory-until now. Written by renowned authorities in the field, Optical Coding Theory with Prime gathers together in one volume the fundamentals and developments of optical coding theory, with a focus on families of prime codes, supplemented with several families of non-prime codes. The book also explores potential applications to coding-based optical systems and networks. Learn How to Construct

  3. Algebraic and stochastic coding theory

    CERN Document Server

    Kythe, Dave K

    2012-01-01

    Using a simple yet rigorous approach, Algebraic and Stochastic Coding Theory makes the subject of coding theory easy to understand for readers with a thorough knowledge of digital arithmetic, Boolean and modern algebra, and probability theory. It explains the underlying principles of coding theory and offers a clear, detailed description of each code. More advanced readers will appreciate its coverage of recent developments in coding theory and stochastic processes. After a brief review of coding history and Boolean algebra, the book introduces linear codes, including Hamming and Golay codes.

  4. Golden Coded Multiple Beamforming

    CERN Document Server

    Li, Boyu

    2010-01-01

    The Golden Code is a full-rate full-diversity space-time code, which achieves maximum coding gain for Multiple-Input Multiple-Output (MIMO) systems with two transmit and two receive antennas. Since four information symbols taken from an M-QAM constellation are selected to construct one Golden Code codeword, a maximum likelihood decoder using sphere decoding has the worst-case complexity of O(M^4), when the Channel State Information (CSI) is available at the receiver. Previously, this worst-case complexity was reduced to O(M^(2.5)) without performance degradation. When the CSI is known by the transmitter as well as the receiver, beamforming techniques that employ singular value decomposition are commonly used in MIMO systems. In the absence of channel coding, when a single symbol is transmitted, these systems achieve the full diversity order provided by the channel. Whereas this property is lost when multiple symbols are simultaneously transmitted. However, uncoded multiple beamforming can achieve the full div...

  5. Coded source neutron imaging

    Energy Technology Data Exchange (ETDEWEB)

    Bingham, Philip R [ORNL; Santos-Villalobos, Hector J [ORNL

    2011-01-01

    Coded aperture techniques have been applied to neutron radiography to address limitations in neutron flux and resolution of neutron detectors in a system labeled coded source imaging (CSI). By coding the neutron source, a magnified imaging system is designed with small spot size aperture holes (10 and 100 m) for improved resolution beyond the detector limits and with many holes in the aperture (50% open) to account for flux losses due to the small pinhole size. An introduction to neutron radiography and coded aperture imaging is presented. A system design is developed for a CSI system with a development of equations for limitations on the system based on the coded image requirements and the neutron source characteristics of size and divergence. Simulation has been applied to the design using McStas to provide qualitative measures of performance with simulations of pinhole array objects followed by a quantitative measure through simulation of a tilted edge and calculation of the modulation transfer function (MTF) from the line spread function. MTF results for both 100um and 10um aperture hole diameters show resolutions matching the hole diameters.

  6. Coded source neutron imaging

    Science.gov (United States)

    Bingham, Philip; Santos-Villalobos, Hector; Tobin, Ken

    2011-03-01

    Coded aperture techniques have been applied to neutron radiography to address limitations in neutron flux and resolution of neutron detectors in a system labeled coded source imaging (CSI). By coding the neutron source, a magnified imaging system is designed with small spot size aperture holes (10 and 100μm) for improved resolution beyond the detector limits and with many holes in the aperture (50% open) to account for flux losses due to the small pinhole size. An introduction to neutron radiography and coded aperture imaging is presented. A system design is developed for a CSI system with a development of equations for limitations on the system based on the coded image requirements and the neutron source characteristics of size and divergence. Simulation has been applied to the design using McStas to provide qualitative measures of performance with simulations of pinhole array objects followed by a quantitative measure through simulation of a tilted edge and calculation of the modulation transfer function (MTF) from the line spread function. MTF results for both 100μm and 10μm aperture hole diameters show resolutions matching the hole diameters.

  7. Germline miRNA DNA variants and the risk of colorectal cancer by subtype

    Science.gov (United States)

    Larson, Melissa C.; DeRycke, Melissa S.; McDonnell, Shannon K.; Baheti, Saurabh; Fogarty, Zachary C.; Win, Aung Ko; Potter, John D.; Buchanan, Daniel D.; Clendenning, Mark; Newcomb, Polly A.; Casey, Graham; Gallinger, Steven; Le Marchand, Loïc; Hopper, John L.; Jenkins, Mark A.; Goode, Ellen L.; Thibodeau, Stephen N.

    2016-01-01

    MicroRNAs (miRNAs) regulate up to one‐third of all protein‐coding genes including genes relevant to cancer. Variants within miRNAs have been reported to be associated with prognosis, survival, response to chemotherapy across cancer types, in vitro parameters of cell growth, and altered risks for development of cancer. Five miRNA variants have been reported to be associated with risk for development of colorectal cancer (CRC). In this study, we evaluated germline genetic variation in 1,123 miRNAs in 899 individuals with CRCs categorized by clinical subtypes and in 204 controls. The role of common miRNA variation in CRC was investigated using single variant and miRNA‐level association tests. Twenty‐nine miRNAs and 30 variants exhibited some marginal association with CRC in at least one subtype of CRC. Previously reported associations were not confirmed (n = 4) or could not be evaluated (n = 1). The variants noted for the CRCs with deficient mismatch repair showed little overlap with the variants noted for CRCs with proficient mismatch repair, consistent with our evolving understanding of the distinct biology underlying these two groups. © 2016 The Authors Genes, Chromosomes & Cancer Published by Wiley Periodicals, Inc. PMID:27636879

  8. Germline miRNA DNA variants and the risk of colorectal cancer by subtype.

    Science.gov (United States)

    Lindor, Noralane M; Larson, Melissa C; DeRycke, Melissa S; McDonnell, Shannon K; Baheti, Saurabh; Fogarty, Zachary C; Win, Aung Ko; Potter, John D; Buchanan, Daniel D; Clendenning, Mark; Newcomb, Polly A; Casey, Graham; Gallinger, Steven; Le Marchand, Loïc; Hopper, John L; Jenkins, Mark A; Goode, Ellen L; Thibodeau, Stephen N

    2017-03-01

    MicroRNAs (miRNAs) regulate up to one-third of all protein-coding genes including genes relevant to cancer. Variants within miRNAs have been reported to be associated with prognosis, survival, response to chemotherapy across cancer types, in vitro parameters of cell growth, and altered risks for development of cancer. Five miRNA variants have been reported to be associated with risk for development of colorectal cancer (CRC). In this study, we evaluated germline genetic variation in 1,123 miRNAs in 899 individuals with CRCs categorized by clinical subtypes and in 204 controls. The role of common miRNA variation in CRC was investigated using single variant and miRNA-level association tests. Twenty-nine miRNAs and 30 variants exhibited some marginal association with CRC in at least one subtype of CRC. Previously reported associations were not confirmed (n = 4) or could not be evaluated (n = 1). The variants noted for the CRCs with deficient mismatch repair showed little overlap with the variants noted for CRCs with proficient mismatch repair, consistent with our evolving understanding of the distinct biology underlying these two groups. © 2016 The Authors Genes, Chromosomes & Cancer Published by Wiley Periodicals, Inc.

  9. Chronic Rhinosinusitis Patients Show Accumulation of Genetic Variants in PARS2.

    Directory of Open Access Journals (Sweden)

    Viktor Henmyr

    Full Text Available Genetic studies of chronic rhinosinusitis (CRS have identified a total of 53 CRS-associated SNPs that were subsequently evaluated for their reproducibility in a recent study. The rs2873551 SNP in linkage disequilibrium with PARS2 showed the strongest association signal. The present study aims to comprehensively screen for rare variants in PARS2 and evaluate for accumulation of such variants in CRS-patients. Sanger sequencing and long-range PCR were used to screen for rare variants in the putative promoter region and coding sequence of 310 CRS-patients and a total of 21 variants were detected. The mutation spectrum was then compared with data from European populations of the 1000Genomes project (EUR and the Exome Aggregation Consortium (ExAC. The CRS population showed a significant surplus of low-frequency variants compared with ExAC data. Haplotype analysis of the region showed a significant excess of rare haplotypes in the CRS population compared to the EUR population. Two missense mutations were also genotyped in the 310 CRS patients and 372 CRS-negative controls, but no associations with the disease were found. This is the first re-sequencing study in CRS research and also the first study to show an association of rare variants with the disease.

  10. Speech coding code- excited linear prediction

    CERN Document Server

    Bäckström, Tom

    2017-01-01

    This book provides scientific understanding of the most central techniques used in speech coding both for advanced students as well as professionals with a background in speech audio and or digital signal processing. It provides a clear connection between the whys hows and whats thus enabling a clear view of the necessity purpose and solutions provided by various tools as well as their strengths and weaknesses in each respect Equivalently this book sheds light on the following perspectives for each technology presented Objective What do we want to achieve and especially why is this goal important Resource Information What information is available and how can it be useful and Resource Platform What kind of platforms are we working with and what are their capabilities restrictions This includes computational memory and acoustic properties and the transmission capacity of devices used. The book goes on to address Solutions Which solutions have been proposed and how can they be used to reach the stated goals and ...

  11. Phase-coded pulse aperiodic transmitter coding

    Directory of Open Access Journals (Sweden)

    I. I. Virtanen

    2009-07-01

    Full Text Available Both ionospheric and weather radar communities have already adopted the method of transmitting radar pulses in an aperiodic manner when measuring moderately overspread targets. Among the users of the ionospheric radars, this method is called Aperiodic Transmitter Coding (ATC, whereas the weather radar users have adopted the term Simultaneous Multiple Pulse-Repetition Frequency (SMPRF. When probing the ionosphere at the carrier frequencies of the EISCAT Incoherent Scatter Radar facilities, the range extent of the detectable target is typically of the order of one thousand kilometers – about seven milliseconds – whereas the characteristic correlation time of the scattered signal varies from a few milliseconds in the D-region to only tens of microseconds in the F-region. If one is interested in estimating the scattering autocorrelation function (ACF at time lags shorter than the F-region correlation time, the D-region must be considered as a moderately overspread target, whereas the F-region is a severely overspread one. Given the technical restrictions of the radar hardware, a combination of ATC and phase-coded long pulses is advantageous for this kind of target. We evaluate such an experiment under infinitely low signal-to-noise ratio (SNR conditions using lag profile inversion. In addition, a qualitative evaluation under high-SNR conditions is performed by analysing simulated data. The results show that an acceptable estimation accuracy and a very good lag resolution in the D-region can be achieved with a pulse length long enough for simultaneous E- and F-region measurements with a reasonable lag extent. The new experiment design is tested with the EISCAT Tromsø VHF (224 MHz radar. An example of a full D/E/F-region ACF from the test run is shown at the end of the paper.

  12. Nested Quantum Error Correction Codes

    CERN Document Server

    Wang, Zhuo; Fan, Hen; Vedral, Vlatko

    2009-01-01

    The theory of quantum error correction was established more than a decade ago as the primary tool for fighting decoherence in quantum information processing. Although great progress has already been made in this field, limited methods are available in constructing new quantum error correction codes from old codes. Here we exhibit a simple and general method to construct new quantum error correction codes by nesting certain quantum codes together. The problem of finding long quantum error correction codes is reduced to that of searching several short length quantum codes with certain properties. Our method works for all length and all distance codes, and is quite efficient to construct optimal or near optimal codes. Two main known methods in constructing new codes from old codes in quantum error-correction theory, the concatenating and pasting, can be understood in the framework of nested quantum error correction codes.

  13. MHD Generation Code

    CERN Document Server

    Frutos-Alfaro, Francisco

    2015-01-01

    A program to generate codes in Fortran and C of the full Magnetohydrodynamic equations is shown. The program used the free computer algebra system software REDUCE. This software has a package called EXCALC, which is an exterior calculus program. The advantage of this program is that it can be modified to include another complex metric or spacetime. The output of this program is modified by means of a LINUX script which creates a new REDUCE program to manipulate the MHD equations to obtain a code that can be used as a seed for a MHD code for numerical applications. As an example, we present part of output of our programs for Cartesian coordinates and how to do the discretization.

  14. Autocatalysis, information and coding.

    Science.gov (United States)

    Wills, P R

    2001-01-01

    Autocatalytic self-construction in macromolecular systems requires the existence of a reflexive relationship between structural components and the functional operations they perform to synthesise themselves. The possibility of reflexivity depends on formal, semiotic features of the catalytic structure-function relationship, that is, the embedding of catalytic functions in the space of polymeric structures. Reflexivity is a semiotic property of some genetic sequences. Such sequences may serve as the basis for the evolution of coding as a result of autocatalytic self-organisation in a population of assignment catalysts. Autocatalytic selection is a mechanism whereby matter becomes differentiated in primitive biochemical systems. In the case of coding self-organisation, it corresponds to the creation of symbolic information. Prions are present-day entities whose replication through autocatalysis reflects aspects of biological semiotics less obvious than genetic coding.

  15. Coded Splitting Tree Protocols

    DEFF Research Database (Denmark)

    Sørensen, Jesper Hemming; Stefanovic, Cedomir; Popovski, Petar

    2013-01-01

    This paper presents a novel approach to multiple access control called coded splitting tree protocol. The approach builds on the known tree splitting protocols, code structure and successive interference cancellation (SIC). Several instances of the tree splitting protocol are initiated, each...... instance is terminated prematurely and subsequently iterated. The combined set of leaves from all the tree instances can then be viewed as a graph code, which is decodable using belief propagation. The main design problem is determining the order of splitting, which enables successful decoding as early...... as possible. Evaluations show that the proposed protocol provides considerable gains over the standard tree splitting protocol applying SIC. The improvement comes at the expense of an increased feedback and receiver complexity....

  16. Adjoint code generator

    Institute of Scientific and Technical Information of China (English)

    CHENG Qiang; CAO JianWen; WANG Bin; ZHANG HaiBin

    2009-01-01

    The adjoint code generator (ADG) is developed to produce the adjoint codes, which are used to analytically calculate gradients and the Hessian-vector products with the costs independent of the number of the independent variables. Different from other automatic differentiation tools, the implementation of ADG has advantages of using the least program behavior decomposition method and several static dependence analysis techniques. In this paper we first address the concerned concepts and fundamentals, and then introduce the functionality and the features of ADG. In particular, we also discuss the design architecture of ADG and implementation details including the recomputation and storing strategy and several techniques for code optimization. Some experimental results in several applications are presented at the end.

  17. Code query by example

    Science.gov (United States)

    Vaucouleur, Sebastien

    2011-02-01

    We introduce code query by example for customisation of evolvable software products in general and of enterprise resource planning systems (ERPs) in particular. The concept is based on an initial empirical study on practices around ERP systems. We motivate our design choices based on those empirical results, and we show how the proposed solution helps with respect to the infamous upgrade problem: the conflict between the need for customisation and the need for upgrade of ERP systems. We further show how code query by example can be used as a form of lightweight static analysis, to detect automatically potential defects in large software products. Code query by example as a form of lightweight static analysis is particularly interesting in the context of ERP systems: it is often the case that programmers working in this field are not computer science specialists but more of domain experts. Hence, they require a simple language to express custom rules.

  18. Spread codes and spread decoding in network coding

    OpenAIRE

    Manganiello, F; Gorla, E.; Rosenthal, J.

    2008-01-01

    In this paper we introduce the class of spread codes for the use in random network coding. Spread codes are based on the construction of spreads in finite projective geometry. The major contribution of the paper is an efficient decoding algorithm of spread codes up to half the minimum distance.

  19. Graph Codes with Reed-Solomon Component Codes

    DEFF Research Database (Denmark)

    Høholdt, Tom; Justesen, Jørn

    2006-01-01

    We treat a specific case of codes based on bipartite expander graphs coming from finite geometries. The code symbols are associated with the branches and the symbols connected to a given node are restricted to be codewords in a Reed-Solomon code. We give results on the parameters of the codes...

  20. Principles of speech coding

    CERN Document Server

    Ogunfunmi, Tokunbo

    2010-01-01

    It is becoming increasingly apparent that all forms of communication-including voice-will be transmitted through packet-switched networks based on the Internet Protocol (IP). Therefore, the design of modern devices that rely on speech interfaces, such as cell phones and PDAs, requires a complete and up-to-date understanding of the basics of speech coding. Outlines key signal processing algorithms used to mitigate impairments to speech quality in VoIP networksOffering a detailed yet easily accessible introduction to the field, Principles of Speech Coding provides an in-depth examination of the

  1. Securing mobile code.

    Energy Technology Data Exchange (ETDEWEB)

    Link, Hamilton E.; Schroeppel, Richard Crabtree; Neumann, William Douglas; Campbell, Philip LaRoche; Beaver, Cheryl Lynn; Pierson, Lyndon George; Anderson, William Erik

    2004-10-01

    If software is designed so that the software can issue functions that will move that software from one computing platform to another, then the software is said to be 'mobile'. There are two general areas of security problems associated with mobile code. The 'secure host' problem involves protecting the host from malicious mobile code. The 'secure mobile code' problem, on the other hand, involves protecting the code from malicious hosts. This report focuses on the latter problem. We have found three distinct camps of opinions regarding how to secure mobile code. There are those who believe special distributed hardware is necessary, those who believe special distributed software is necessary, and those who believe neither is necessary. We examine all three camps, with a focus on the third. In the distributed software camp we examine some commonly proposed techniques including Java, D'Agents and Flask. For the specialized hardware camp, we propose a cryptographic technique for 'tamper-proofing' code over a large portion of the software/hardware life cycle by careful modification of current architectures. This method culminates by decrypting/authenticating each instruction within a physically protected CPU, thereby protecting against subversion by malicious code. Our main focus is on the camp that believes that neither specialized software nor hardware is necessary. We concentrate on methods of code obfuscation to render an entire program or a data segment on which a program depends incomprehensible. The hope is to prevent or at least slow down reverse engineering efforts and to prevent goal-oriented attacks on the software and execution. The field of obfuscation is still in a state of development with the central problem being the lack of a basis for evaluating the protection schemes. We give a brief introduction to some of the main ideas in the field, followed by an in depth analysis of a technique called &apos

  2. Truncating variants in the majority of the cytoplasmic domain of PCDH15 are unlikely to cause Usher syndrome 1F.

    Science.gov (United States)

    Perreault-Micale, Cynthia; Frieden, Alexander; Kennedy, Caleb J; Neitzel, Dana; Sullivan, Jessica; Faulkner, Nicole; Hallam, Stephanie; Greger, Valerie

    2014-11-01

    Loss of function variants in the PCDH15 gene can cause Usher syndrome type 1F, an autosomal recessive disease associated with profound congenital hearing loss, vestibular dysfunction, and retinitis pigmentosa. The Ashkenazi Jewish population has an increased incidence of Usher syndrome type 1F (founder variant p.Arg245X accounts for 75% of alleles), yet the variant spectrum in a panethnic population remains undetermined. We sequenced the coding region and intron-exon borders of PCDH15 using next-generation DNA sequencing technology in approximately 14,000 patients from fertility clinics. More than 600 unique PCDH15 variants (single nucleotide changes and small indels) were identified, including previously described pathogenic variants p.Arg3X, p.Arg245X (five patients), p.Arg643X, p.Arg929X, and p.Arg1106X. Novel truncating variants were also found, including one in the N-terminal extracellular domain (p.Leu877X), but all other novel truncating variants clustered in the exon 33 encoded C-terminal cytoplasmic domain (52 patients, 14 variants). One variant was observed predominantly in African Americans (carrier frequency of 2.3%). The high incidence of truncating exon 33 variants indicates that they are unlikely to cause Usher syndrome type 1F even though many remove a large portion of the gene. They may be tolerated because PCDH15 has several alternate cytoplasmic domain exons and differentially spliced isoforms may function redundantly. Effects of some PCDH15 truncating variants were addressed by deep sequencing of a panethnic population.

  3. Analysis of rare variants in the C3 gene in patients with age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Maheswara R Duvvari

    Full Text Available Age-related macular degeneration (AMD is a progressive retinal disorder affecting over 33 million people worldwide. Genome-wide association studies (GWASs for AMD identified common variants at 19 loci accounting for 15-65% of the heritability and it has been hypothesized that the missing heritability may be attributed to rare variants with large effect sizes. Common variants in the complement component 3 (C3 gene have been associated with AMD and recently a rare C3 variant (Lys155Gln was identified which exerts a large effect on AMD susceptibility independent of the common variants. To explore whether additional rare variants in the C3 gene are associated with AMD, we sequenced all coding exons in 84 unrelated AMD cases. Subsequently, we genotyped all identified variants in 1474 AMD cases and 2258 controls. Additionally, because of the known genetic overlap between AMD and atypical hemolytic uremic syndrome (aHUS, we genotyped two recurrent aHUS-associated C3 mutations in the entire cohort. Overall, we identified three rare variants (Lys65Gln (P=0.04, Arg735Trp (OR=17.4, 95% CI=2.2-136; P=0.0003, and Ser1619Arg (OR=5.2, 95% CI=1.0-25; P=0.05 at the C3 locus that are associated with AMD in our EUGENDA cohort. However, the Arg735Trp and Ser1619Arg variants were not found to be associated with AMD in the Rotterdam Study. The Lys65Gln variant was only identified in patients from Nijmegen, the Netherlands, and thus may represent a region-specific AMD risk variant.

  4. Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits.

    Science.gov (United States)

    Chami, Nathalie; Chen, Ming-Huei; Slater, Andrew J; Eicher, John D; Evangelou, Evangelos; Tajuddin, Salman M; Love-Gregory, Latisha; Kacprowski, Tim; Schick, Ursula M; Nomura, Akihiro; Giri, Ayush; Lessard, Samuel; Brody, Jennifer A; Schurmann, Claudia; Pankratz, Nathan; Yanek, Lisa R; Manichaikul, Ani; Pazoki, Raha; Mihailov, Evelin; Hill, W David; Raffield, Laura M; Burt, Amber; Bartz, Traci M; Becker, Diane M; Becker, Lewis C; Boerwinkle, Eric; Bork-Jensen, Jette; Bottinger, Erwin P; O'Donoghue, Michelle L; Crosslin, David R; de Denus, Simon; Dubé, Marie-Pierre; Elliott, Paul; Engström, Gunnar; Evans, Michele K; Floyd, James S; Fornage, Myriam; Gao, He; Greinacher, Andreas; Gudnason, Vilmundur; Hansen, Torben; Harris, Tamara B; Hayward, Caroline; Hernesniemi, Jussi; Highland, Heather M; Hirschhorn, Joel N; Hofman, Albert; Irvin, Marguerite R; Kähönen, Mika; Lange, Ethan; Launer, Lenore J; Lehtimäki, Terho; Li, Jin; Liewald, David C M; Linneberg, Allan; Liu, Yongmei; Lu, Yingchang; Lyytikäinen, Leo-Pekka; Mägi, Reedik; Mathias, Rasika A; Melander, Olle; Metspalu, Andres; Mononen, Nina; Nalls, Mike A; Nickerson, Deborah A; Nikus, Kjell; O'Donnell, Chris J; Orho-Melander, Marju; Pedersen, Oluf; Petersmann, Astrid; Polfus, Linda; Psaty, Bruce M; Raitakari, Olli T; Raitoharju, Emma; Richard, Melissa; Rice, Kenneth M; Rivadeneira, Fernando; Rotter, Jerome I; Schmidt, Frank; Smith, Albert Vernon; Starr, John M; Taylor, Kent D; Teumer, Alexander; Thuesen, Betina H; Torstenson, Eric S; Tracy, Russell P; Tzoulaki, Ioanna; Zakai, Neil A; Vacchi-Suzzi, Caterina; van Duijn, Cornelia M; van Rooij, Frank J A; Cushman, Mary; Deary, Ian J; Velez Edwards, Digna R; Vergnaud, Anne-Claire; Wallentin, Lars; Waterworth, Dawn M; White, Harvey D; Wilson, James G; Zonderman, Alan B; Kathiresan, Sekar; Grarup, Niels; Esko, Tõnu; Loos, Ruth J F; Lange, Leslie A; Faraday, Nauder; Abumrad, Nada A; Edwards, Todd L; Ganesh, Santhi K; Auer, Paul L; Johnson, Andrew D; Reiner, Alexander P; Lettre, Guillaume

    2016-07-01

    Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 × 10(-10) for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p < 3 × 10(-8) for hematocrit [HCT] and HGB). In African Americans, we identified a nonsense variant in CD36 associated with higher RBC distribution width (rs3211938, MAF = 8.7%, p = 7 × 10(-11)) and showed that it is associated with lower CD36 expression and strong allelic imbalance in ex vivo differentiated human erythroblasts. We also identified a rare missense variant in ALAS2 (rs201062903, MAF = 0.2%) associated with lower mean corpuscular volume and mean corpuscular hemoglobin (p < 8 × 10(-9)). Mendelian mutations in ALAS2 are a cause of sideroblastic anemia and erythropoietic protoporphyria. Gene-based testing highlighted three rare missense variants in PKLR, a gene mutated in Mendelian non-spherocytic hemolytic anemia, associated with HGB and HCT (SKAT p < 8 × 10(-7)). These rare, low-frequency, and common RBC variants showed pleiotropy, being also associated with platelet, white blood cell, and lipid traits. Our association results and functional annotation suggest the involvement of new genes in human erythropoiesis. We also confirm that rare and low-frequency variants play a role in the architecture of complex human traits, although their phenotypic effect is generally smaller than originally anticipated.

  5. Hypomorphic variants of cationic amino acid transporter 3 in males with autism spectrum disorders.

    Science.gov (United States)

    Nava, Caroline; Rupp, Johanna; Boissel, Jean-Paul; Mignot, Cyril; Rastetter, Agnès; Amiet, Claire; Jacquette, Aurélia; Dupuits, Céline; Bouteiller, Delphine; Keren, Boris; Ruberg, Merle; Faudet, Anne; Doummar, Diane; Philippe, Anne; Périsse, Didier; Laurent, Claudine; Lebrun, Nicolas; Guillemot, Vincent; Chelly, Jamel; Cohen, David; Héron, Delphine; Brice, Alexis; Closs, Ellen I; Depienne, Christel

    2015-12-01

    Cationic amino acid transporters (CATs) mediate the entry of L-type cationic amino acids (arginine, ornithine and lysine) into the cells including neurons. CAT-3, encoded by the SLC7A3 gene on chromosome X, is one of the three CATs present in the human genome, with selective expression in brain. SLC7A3 is highly intolerant to variation in humans, as attested by the low frequency of deleterious variants in available databases, but the impact on variants in this gene in humans remains undefined. In this study, we identified a missense variant in SLC7A3, encoding the CAT-3 cationic amino acid transporter, on chromosome X by exome sequencing in two brothers with autism spectrum disorder (ASD). We then sequenced the SLC7A3 coding sequence in 148 male patients with ASD and identified three additional rare missense variants in unrelated patients. Functional analyses of the mutant transporters showed that two of the four identified variants cause severe or moderate loss of CAT-3 function due to altered protein stability or abnormal trafficking to the plasma membrane. The patient with the most deleterious SLC7A3 variant had high-functioning autism and epilepsy, and also carries a de novo 16p11.2 duplication possibly contributing to his phenotype. This study shows that rare hypomorphic variants of SLC7A3 exist in male individuals and suggest that SLC7A3 variants possibly contribute to the etiology of ASD in male subjects in association with other genetic factors.

  6. Discriminant Kernel Assignment for Image Coding.

    Science.gov (United States)

    Deng, Yue; Zhao, Yanyu; Ren, Zhiquan; Kong, Youyong; Bao, Feng; Dai, Qionghai

    2017-06-01

    This paper proposes discriminant kernel assignment (DKA) in the bag-of-features framework for image representation. DKA slightly modifies existing kernel assignment to learn width-variant Gaussian kernel functions to perform discriminant local feature assignment. When directly applying gradient-descent method to solve DKA, the optimization may contain multiple time-consuming reassignment implementations in iterations. Accordingly, we introduce a more practical way to locally linearize the DKA objective and the difficult task is cast as a sequence of easier ones. Since DKA only focuses on the feature assignment part, it seamlessly collaborates with other discriminative learning approaches, e.g., discriminant dictionary learning or multiple kernel learning, for even better performances. Experimental evaluations on multiple benchmark datasets verify that DKA outperforms other image assignment approaches and exhibits significant efficiency in feature coding.

  7. New code match strategy for wideband code division multiple access code tree management

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Orthogonal variable spreading factor channelization codes are widely used to provide variable data rates for supporting different bandwidth requirements in wideband code division multiple access (WCDMA) systems. A new code match scheme for WCDMA code tree management was proposed. The code match scheme is similar to the existing crowed-first scheme. When choosing a code for a user, the code match scheme only compares the one up layer of the allocated codes, unlike the crowed-first scheme which perhaps compares all up layers. So the operation of code match scheme is simple, and the average time delay is decreased by 5.1%. The simulation results also show that the code match strategy can decrease the average code blocking probability by 8.4%.

  8. Resistance of Abaca Somaclonal Variant Against Fusarium

    Directory of Open Access Journals (Sweden)

    RULLY DYAH PURWATI

    2007-12-01

    Full Text Available The objectives of this study were (i to evaluate responses against F. oxysporum f.sp. cubense (Foc infection of abaca variants regenerated using four different methods, (ii to determine initial root length and plant height effects on survival of inoculated abaca variants, and (iii to identify Foc resistance abaca variants. In the previous experiment, four abaca variant lines were regenerated from (i embryogenic calli (TC line, (ii ethyl methyl sulphonate (EMS treated embryogenic calli (EMS line, (iii EMS treated embryogenic calli, followed by in vitro selection on Foc culture filtrate (EMS+CF line, and (iv EMS treated embryogenic calli, followed by in vitro selection on fusaric acid (EMS+FA line. All abaca variants were grown in a glasshouse and inoculated with Banyuwangi isolate of Foc (Foc Bw. Initial root length (RL and plant height (PH of the abaca variants were recorded before inoculation, while scores of plant damage (SPD, and their survival were recorded at 60 days after inoculation (DAI. The results showed that the initial RL and PH did not affect survival of the tested abaca variants. Regardless of their initial RL and PH, susceptible abaca variants died before 60 DAI while resistance ones still survived. Abaca variants regenerated from single clump of embryogenic callus showed an array of responses against Foc Bw infection, indicating the existence of a mix cells population. The Foc Bw resistance abaca variants were successfully identified from four tested abaca variant lines, although with different frequencies. However, more Foc Bw resistance abaca plants were identified from EMS+CF line than the others. Using the developed procedures, 8 resistance abaca plants were identified from abaca cv. Tangongon and 12 from abaca cv. Sangihe-1.

  9. Reed-Solomon convolutional codes

    NARCIS (Netherlands)

    Gluesing-Luerssen, H; Schmale, W

    2005-01-01

    In this paper we will introduce a specific class of cyclic convolutional codes. The construction is based on Reed-Solomon block codes. The algebraic parameters as well as the distance of these codes are determined. This shows that some of these codes are optimal or near optimal.

  10. Expression profiles of long non-coding RNAs located in autoimmune disease-associated regions reveal immune cell-type specificity

    NARCIS (Netherlands)

    Hrdlickova, Barbara; Kumar, Vinod; Kanduri, Kartiek; Zhernakova, Daria V.; Tripathi, Subhash; Karjalainen, Juha; Lund, Riikka J.; Li, Yang; Ullah, Ubaid; Modderman, Rutger; Abdulahad, Wayel; Lahdesmaki, Harri; Franke, Lude; Lahesmaa, Riitta; Wijmenga, Cisca; Withoff, Sebo

    2014-01-01

    Background: Although genome-wide association studies (GWAS) have identified hundreds of variants associated with a risk for autoimmune and immune-related disorders (AID), our understanding of the disease mechanisms is still limited. In particular, more than 90% of the risk variants lie in non-coding

  11. New code of conduct

    CERN Multimedia

    Laëtitia Pedroso

    2010-01-01

    During his talk to the staff at the beginning of the year, the Director-General mentioned that a new code of conduct was being drawn up. What exactly is it and what is its purpose? Anne-Sylvie Catherin, Head of the Human Resources (HR) Department, talked to us about the whys and wherefores of the project.   Drawing by Georges Boixader from the cartoon strip “The World of Particles” by Brian Southworth. A code of conduct is a general framework laying down the behaviour expected of all members of an organisation's personnel. “CERN is one of the very few international organisations that don’t yet have one", explains Anne-Sylvie Catherin. “We have been thinking about introducing a code of conduct for a long time but lacked the necessary resources until now”. The call for a code of conduct has come from different sources within the Laboratory. “The Equal Opportunities Advisory Panel (read also the "Equal opportuni...

  12. Physical layer network coding

    DEFF Research Database (Denmark)

    Fukui, Hironori; Popovski, Petar; Yomo, Hiroyuki

    2014-01-01

    Physical layer network coding (PLNC) has been proposed to improve throughput of the two-way relay channel, where two nodes communicate with each other, being assisted by a relay node. Most of the works related to PLNC are focused on a simple three-node model and they do not take into account...

  13. Corporate governance through codes

    NARCIS (Netherlands)

    Haxhi, I.; Aguilera, R.V.; Vodosek, M.; den Hartog, D.; McNett, J.M.

    2014-01-01

    The UK's 1992 Cadbury Report defines corporate governance (CG) as the system by which businesses are directed and controlled. CG codes are a set of best practices designed to address deficiencies in the formal contracts and institutions by suggesting prescriptions on the preferred role and compositi

  14. Polar Code Validation

    Science.gov (United States)

    1989-09-30

    SUMMARY OF POLAR ACHIEVEMENTS ..... .......... 3 3. POLAR CODE PHYSICAL MODELS ..... ............. 5 3.1 PL- ASMA Su ^"ru5 I1LS SH A...of this problem. 1.1. The Charge-2 Rocket The Charge-2 payload was launched on a Black Brant VB from White Sands Mis- sile Range in New Mexico in

  15. Corporate governance through codes

    NARCIS (Netherlands)

    Haxhi, I.; Aguilera, R.V.; Vodosek, M.; den Hartog, D.; McNett, J.M.

    2014-01-01

    The UK's 1992 Cadbury Report defines corporate governance (CG) as the system by which businesses are directed and controlled. CG codes are a set of best practices designed to address deficiencies in the formal contracts and institutions by suggesting prescriptions on the preferred role and

  16. (Almost) practical tree codes

    KAUST Repository

    Khina, Anatoly

    2016-08-15

    We consider the problem of stabilizing an unstable plant driven by bounded noise over a digital noisy communication link, a scenario at the heart of networked control. To stabilize such a plant, one needs real-time encoding and decoding with an error probability profile that decays exponentially with the decoding delay. The works of Schulman and Sahai over the past two decades have developed the notions of tree codes and anytime capacity, and provided the theoretical framework for studying such problems. Nonetheless, there has been little practical progress in this area due to the absence of explicit constructions of tree codes with efficient encoding and decoding algorithms. Recently, linear time-invariant tree codes were proposed to achieve the desired result under maximum-likelihood decoding. In this work, we take one more step towards practicality, by showing that these codes can be efficiently decoded using sequential decoding algorithms, up to some loss in performance (and with some practical complexity caveats). We supplement our theoretical results with numerical simulations that demonstrate the effectiveness of the decoder in a control system setting.

  17. Corner neutronic code

    Directory of Open Access Journals (Sweden)

    V.P. Bereznev

    2015-10-01

    An iterative solution process is used, including external iterations for the fission source and internal iterations for the scattering source. The paper presents the results of a cross-verification against the Monte Carlo MMK code [3] and on a model of the BN-800 reactor core.

  18. Ready, steady… Code!

    CERN Multimedia

    Anaïs Schaeffer

    2013-01-01

    This summer, CERN took part in the Google Summer of Code programme for the third year in succession. Open to students from all over the world, this programme leads to very successful collaborations for open source software projects.   Image: GSoC 2013. Google Summer of Code (GSoC) is a global programme that offers student developers grants to write code for open-source software projects. Since its creation in 2005, the programme has brought together some 6,000 students from over 100 countries worldwide. The students selected by Google are paired with a mentor from one of the participating projects, which can be led by institutes, organisations, companies, etc. This year, CERN PH Department’s SFT (Software Development for Experiments) Group took part in the GSoC programme for the third time, submitting 15 open-source projects. “Once published on the Google Summer for Code website (in April), the projects are open to applications,” says Jakob Blomer, one of the o...

  19. Focusing Automatic Code Inspections

    NARCIS (Netherlands)

    Boogerd, C.J.

    2010-01-01

    Automatic Code Inspection tools help developers in early detection of defects in software. A well-known drawback of many automatic inspection approaches is that they yield too many warnings and require a clearer focus. In this thesis, we provide such focus by proposing two methods to prioritize

  20. From Single Variants to Protein Cascades: MULTISCALE MODELING OF SINGLE NUCLEOTIDE VARIANT SETS IN GENETIC DISORDERS.

    Science.gov (United States)

    Mueller, Sabine C; Sommer, Björn; Backes, Christina; Haas, Jan; Meder, Benjamin; Meese, Eckart; Keller, Andreas

    2016-01-22

    Understanding the role of genetics in disease has become a central part of medical research. Non-synonymous single nucleotide variants (nsSNVs) in coding regions of human genes frequently lead to pathological phenotypes. Beyond single variations, the individual combination of nsSNVs may add to pathogenic processes. We developed a multiscale pipeline to systematically analyze the existence of quantitative effects of multiple nsSNVs and gene combinations in single individuals on pathogenicity. Based on this pipeline, we detected in a data set of 842 nsSNVs discovered in 76 genes related to cardiomyopathies, associated nsSNV combinations in seven genes present in at least 70% of all 639 patient samples, but not in a control cohort of healthy humans. Structural analyses of these revealed primarily an influence on the protein stability. For amino acid substitutions located at the protein surface, we generally observed a proximity to putative binding pockets. To computationally analyze cumulative effects and their impact, pathogenicity methods are currently being developed. Our approach supports this process, as shown on the example of a cardiac phenotype but can be likewise applied to other diseases such as cancer.

  1. Exome Sequencing in an Admixed Isolated Population Indicates NFXL1 Variants Confer a Risk for Specific Language Impairment

    Science.gov (United States)

    Villanueva, Pía; Nudel, Ron; Hoischen, Alexander; Fernández, María Angélica; Simpson, Nuala H.; Gilissen, Christian; Reader, Rose H.; Jara, Lillian; Echeverry, Maria Magdalena; Francks, Clyde; Baird, Gillian; Conti-Ramsden, Gina; O’Hare, Anne; Bolton, Patrick F.; Hennessy, Elizabeth R.; Palomino, Hernán; Carvajal-Carmona, Luis; Veltman, Joris A.; Cazier, Jean-Baptiste; De Barbieri, Zulema

    2015-01-01

    Children affected by Specific Language Impairment (SLI) fail to acquire age appropriate language skills despite adequate intelligence and opportunity. SLI is highly heritable, but the understanding of underlying genetic mechanisms has proved challenging. In this study, we use molecular genetic techniques to investigate an admixed isolated founder population from the Robinson Crusoe Island (Chile), who are affected by a high incidence of SLI, increasing the power to discover contributory genetic factors. We utilize exome sequencing in selected individuals from this population to identify eight coding variants that are of putative significance. We then apply association analyses across the wider population to highlight a single rare coding variant (rs144169475, Minor Allele Frequency of 4.1% in admixed South American populations) in the NFXL1 gene that confers a nonsynonymous change (N150K) and is significantly associated with language impairment in the Robinson Crusoe population (p = 2.04 × 10–4, 8 variants tested). Subsequent sequencing of NFXL1 in 117 UK SLI cases identified four individuals with heterozygous variants predicted to be of functional consequence. We conclude that coding variants within NFXL1 confer an increased risk of SLI within a complex genetic model. PMID:25781923

  2. Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment.

    Directory of Open Access Journals (Sweden)

    Pía Villanueva

    2015-03-01

    Full Text Available Children affected by Specific Language Impairment (SLI fail to acquire age appropriate language skills despite adequate intelligence and opportunity. SLI is highly heritable, but the understanding of underlying genetic mechanisms has proved challenging. In this study, we use molecular genetic techniques to investigate an admixed isolated founder population from the Robinson Crusoe Island (Chile, who are affected by a high incidence of SLI, increasing the power to discover contributory genetic factors. We utilize exome sequencing in selected individuals from this population to identify eight coding variants that are of putative significance. We then apply association analyses across the wider population to highlight a single rare coding variant (rs144169475, Minor Allele Frequency of 4.1% in admixed South American populations in the NFXL1 gene that confers a nonsynonymous change (N150K and is significantly associated with language impairment in the Robinson Crusoe population (p = 2.04 × 10-4, 8 variants tested. Subsequent sequencing of NFXL1 in 117 UK SLI cases identified four individuals with heterozygous variants predicted to be of functional consequence. We conclude that coding variants within NFXL1 confer an increased risk of SLI within a complex genetic model.

  3. Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment.

    Science.gov (United States)

    Villanueva, Pía; Nudel, Ron; Hoischen, Alexander; Fernández, María Angélica; Simpson, Nuala H; Gilissen, Christian; Reader, Rose H; Jara, Lillian; Echeverry, María Magdalena; Echeverry, Maria Magdalena; Francks, Clyde; Baird, Gillian; Conti-Ramsden, Gina; O'Hare, Anne; Bolton, Patrick F; Hennessy, Elizabeth R; Palomino, Hernán; Carvajal-Carmona, Luis; Veltman, Joris A; Cazier, Jean-Baptiste; De Barbieri, Zulema; Fisher, Simon E; Newbury, Dianne F

    2015-03-01

    Children affected by Specific Language Impairment (SLI) fail to acquire age appropriate language skills despite adequate intelligence and opportunity. SLI is highly heritable, but the understanding of underlying genetic mechanisms has proved challenging. In this study, we use molecular genetic techniques to investigate an admixed isolated founder population from the Robinson Crusoe Island (Chile), who are affected by a high incidence of SLI, increasing the power to discover contributory genetic factors. We utilize exome sequencing in selected individuals from this population to identify eight coding variants that are of putative significance. We then apply association analyses across the wider population to highlight a single rare coding variant (rs144169475, Minor Allele Frequency of 4.1% in admixed South American populations) in the NFXL1 gene that confers a nonsynonymous change (N150K) and is significantly associated with language impairment in the Robinson Crusoe population (p = 2.04 × 10-4, 8 variants tested). Subsequent sequencing of NFXL1 in 117 UK SLI cases identified four individuals with heterozygous variants predicted to be of functional consequence. We conclude that coding variants within NFXL1 confer an increased risk of SLI within a complex genetic model.

  4. Fundamentals of coding and reimbursement.

    Science.gov (United States)

    Price, Paula

    2002-01-01

    After completing this introduction to radiology coding and reimbursement, readers will: Understand how health care reimbursement evolved over the past 50 years. Know the importance of documenting the patient's history. Have an overall picture of the standardized numerical coding system. Understand how accurate coding affects reimbursement. Understand coding functions as they pertain to regulatory compliance in the radiology department. Be familiar with the U.S. Justice Department's use of coding in tracking health care fraud.

  5. On Asymmetric Quantum MDS Codes

    CERN Document Server

    Ezerman, Martianus Frederic; Ling, San

    2010-01-01

    Assuming the validity of the MDS Conjecture, the weight distribution of all MDS codes is known. Using a recently-established characterization of asymmetric quantum error-correcting codes, linear MDS codes can be used to construct asymmetric quantum MDS codes with $d_{z} \\geq d_{x}\\geq 2$ for all possible values of length $n$ for which linear MDS codes over $\\F_{q}$ are known to exist.

  6. Identification of hemoglobin variants by top-down mass spectrometry using selected diagnostic product ions.

    Science.gov (United States)

    Coelho Graça, Didia; Hartmer, Ralf; Jabs, Wolfgang; Beris, Photis; Clerici, Lorella; Stoermer, Carsten; Samii, Kaveh; Hochstrasser, Denis; Tsybin, Yury O; Scherl, Alexander; Lescuyer, Pierre

    2015-04-01

    Hemoglobin disorder diagnosis is a complex procedure combining several analytical steps. Due to the lack of specificity of the currently used protein analysis methods, the identification of uncommon hemoglobin variants (proteoforms) can become a hard task to accomplish. The aim of this work was to develop a mass spectrometry-based approach to quickly identify mutated protein sequences within globin chain variants. To reach this goal, a top-down electron transfer dissociation mass spectrometry method was developed for hemoglobin β chain analysis. A diagnostic product ion list was established with a color code strategy allowing to quickly and specifically localize a mutation in the hemoglobin β chain sequence. The method was applied to the analysis of rare hemoglobin β chain variants and an (A)γ-β fusion protein. The results showed that the developed data analysis process allows fast and reliable interpretation of top-down electron transfer dissociation mass spectra by nonexpert users in the clinical area.

  7. Anjozorobe hantavirus, a new genetic variant of Thailand virus detected in rodents from Madagascar.

    Science.gov (United States)

    Reynes, Jean-Marc; Razafindralambo, Nadia Kaloina; Lacoste, Vincent; Olive, Marie-Marie; Barivelo, Tony Andrianaivo; Soarimalala, Voahangy; Heraud, Jean-Michel; Lavergne, Anne

    2014-03-01

    Until now, there was only serological evidence that hantaviruses were circulating in rodents and infecting humans from Madagascar. To assess the presence of a hantavirus on the island, between October, 2008, and March, 2010, we sampled 585 rodents belonging to seven species in the Anjozorobe-Angavo forest corridor, 70 km north from the capital city Antananarivo. A hantavirus was detected from organs of the ubiquist roof rat (Rattus rattus) and of the endemic Major's tufted-tailed rat (Eliurus majori). Amazingly, sequence analysis of the S (small), M (medium), and L (large) coding DNA sequence of this virus showed that the Anjozorobe strain (proposed name) was a new genetic variant of Thailand virus (THAIV) that comprises other variants found in Southeast Asia. Because THAIV is suspected of causing hemorrhagic fever with renal syndrome in humans, ongoing studies are addressing the risk of infection by this new variant in the Malagasy population.

  8. Semantic prioritization of novel causative genomic variants

    KAUST Repository

    Boudellioua, Imane

    2017-04-17

    Discriminating the causative disease variant(s) for individuals with inherited or de novo mutations presents one of the main challenges faced by the clinical genetics community today. Computational approaches for variant prioritization include machine learning methods utilizing a large number of features, including molecular information, interaction networks, or phenotypes. Here, we demonstrate the PhenomeNET Variant Predictor (PVP) system that exploits semantic technologies and automated reasoning over genotype-phenotype relations to filter and prioritize variants in whole exome and whole genome sequencing datasets. We demonstrate the performance of PVP in identifying causative variants on a large number of synthetic whole exome and whole genome sequences, covering a wide range of diseases and syndromes. In a retrospective study, we further illustrate the application of PVP for the interpretation of whole exome sequencing data in patients suffering from congenital hypothyroidism. We find that PVP accurately identifies causative variants in whole exome and whole genome sequencing datasets and provides a powerful resource for the discovery of causal variants.

  9. Fundamental Characteristics of Industrial Variant Specification Systems

    DEFF Research Database (Denmark)

    Hansen, Benjamin Loer; Hvam, Lars

    2004-01-01

    fundamental concepts related to this task, which are relevant to understand for academia and practitioners working with the subject. This is done through a description of variant specification tasks and typical aspects of system solutions. To support the description of variant specification tasks and systems...

  10. Beta-glucosidase I variants with improved properties

    Energy Technology Data Exchange (ETDEWEB)

    Bott, Richard R.; Kaper, Thijs; Kelemen, Bradley; Goedegebuur, Frits; Hommes, Ronaldus Wilhelmus; Kralj, Slavko; Kruithof, Paulien; Nikolaev, Igor; Van Der Kley, Wilhelmus Antonious Hendricus; Van Lieshout, Johannes Franciscus Thomas; Van Stigt Thans, Sander

    2016-09-20

    The present disclosure is generally directed to enzymes and in particular beta-glucosidase variants. Also described are nucleic acids encoding beta-glucosidase variants, compositions comprising beta-glucosidase variants, methods of using beta-glucosidase variants, and methods of identifying additional useful beta-glucosidase variants.

  11. Rate-adaptive BCH codes for distributed source coding

    DEFF Research Database (Denmark)

    Salmistraro, Matteo; Larsen, Knud J.; Forchhammer, Søren

    2013-01-01

    This paper considers Bose-Chaudhuri-Hocquenghem (BCH) codes for distributed source coding. A feedback channel is employed to adapt the rate of the code during the decoding process. The focus is on codes with short block lengths for independently coding a binary source X and decoding it given its...... strategies for improving the reliability of the decoded result are analyzed, and methods for estimating the performance are proposed. In the analysis, noiseless feedback and noiseless communication are assumed. Simulation results show that rate-adaptive BCH codes achieve better performance than low...... correlated side information Y. The proposed codes have been analyzed in a high-correlation scenario, where the marginal probability of each symbol, Xi in X, given Y is highly skewed (unbalanced). Rate-adaptive BCH codes are presented and applied to distributed source coding. Adaptive and fixed checking...

  12. Novel oxytocin receptor variants in laboring women requiring high doses of oxytocin.

    Science.gov (United States)

    Reinl, Erin L; Goodwin, Zane A; Raghuraman, Nandini; Lee, Grace Y; Jo, Erin Y; Gezahegn, Beakal M; Pillai, Meghan K; Cahill, Alison G; de Guzman Strong, Cristina; England, Sarah K

    2017-08-01

    Although oxytocin commonly is used to augment or induce labor, it is difficult to predict its effectiveness because oxytocin dose requirements vary significantly among women. One possibility is that women requiring high or low doses of oxytocin have variations in the oxytocin receptor gene. To identify oxytocin receptor gene variants in laboring women with low and high oxytocin dosage requirements. Term, nulliparous women requiring oxytocin doses of ≤4 mU/min (low-dose-requiring, n = 83) or ≥20 mU/min (high-dose-requiring, n = 104) for labor augmentation or induction provided consent to a postpartum blood draw as a source of genomic DNA. Targeted-amplicon sequencing (coverage >30×) with MiSeq (Illumina) was performed to discover variants in the coding exons of the oxytocin receptor gene. Baseline relevant clinical history, outcomes, demographics, and oxytocin receptor gene sequence variants and their allele frequencies were compared between low-dose-requiring and high-dose-requiring women. The Scale-Invariant Feature Transform algorithm was used to predict the effect of variants on oxytocin receptor function. The Fisher exact or χ(2) tests were used for categorical variables, and Student t tests or Wilcoxon rank sum tests were used for continuous variables. A P value labor induction and required prostaglandins. High-dose-requiring women were more likely to undergo cesarean delivery for first-stage arrest and less likely to undergo cesarean delivery for nonreassuring fetal status. Targeted sequencing of the oxytocin receptor gene in the total cohort (n = 187) revealed 30 distinct coding variants: 17 nonsynonymous, 11 synonymous, and 2 small structural variants. One novel variant (A243T) was found in both the low- and high-dose-requiring groups. Three novel variants (Y106H, A240_A249del, and P197delfs*206) resulting in an amino acid substitution, loss of 9 amino acids, and a frameshift stop mutation, respectively, were identified only in low

  13. Novel variants of the 5S rRNA genes in Eruca sativa.

    Science.gov (United States)

    Singh, K; Bhatia, S; Lakshmikumaran, M

    1994-02-01

    The 5S ribosomal RNA (rRNA) genes of Eruca sativa were cloned and characterized. They are organized into clusters of tandemly repeated units. Each repeat unit consists of a 119-bp coding region followed by a noncoding spacer region that separates it from the coding region of the next repeat unit. Our study reports novel gene variants of the 5S rRNA genes in plants. Two families of the 5S rDNA, the 0.5-kb size family and the 1-kb size family, coexist in the E. sativa genome. The 0.5-kb size family consists of the 5S rRNA genes (S4) that have coding regions similar to those of other reported plant 5S rDNA sequences, whereas the 1-kb size family consists of the 5S rRNA gene variants (S1) that exist as 1-kb BamHI tandem repeats. S1 is made up of two variant units (V1 and V2) of 5S rDNA where the BamHI site between the two units is mutated. Sequence heterogeneity among S4, V1, and V2 units exists throughout the sequence and is not limited to the noncoding spacer region only. The coding regions of V1 and V2 show approximately 20% dissimilarity to the coding regions of S4 and other reported plant 5S rDNA sequences. Such a large variation in the coding regions of the 5S rDNA units within the same plant species has been observed for the first time. Restriction site variation is observed between the two size classes of 5S rDNA in E. sativa.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Local binary patterns new variants and applications

    CERN Document Server

    Jain, Lakhmi; Nanni, Loris; Lumini, Alessandra

    2014-01-01

    This book introduces Local Binary Patterns (LBP), arguably one of the most powerful texture descriptors, and LBP variants. This volume provides the latest reviews of the literature and a presentation of some of the best LBP variants by researchers at the forefront of textual analysis research and research on LBP descriptors and variants. The value of LBP variants is illustrated with reported experiments using many databases representing a diversity of computer vision applications in medicine, biometrics, and other areas. There is also a chapter that provides an excellent theoretical foundation for texture analysis and LBP in particular. A special section focuses on LBP and LBP variants in the area of face recognition, including thermal face recognition. This book will be of value to anyone already in the field as well as to those interested in learning more about this powerful family of texture descriptors.

  15. Histones in functional diversification. Core histone variants.

    Science.gov (United States)

    Pusarla, Rama-Haritha; Bhargava, Purnima

    2005-10-01

    Recent research suggests that minor changes in the primary sequence of the conserved histones may become major determinants for the chromatin structure regulating gene expression and other DNA-related processes. An analysis of the involvement of different core histone variants in different nuclear processes and the structure of different variant nucleosome cores shows that this may indeed be so. Histone variants may also be involved in demarcating functional regions of the chromatin. We discuss in this review why two of the four core histones show higher variation. A comparison of the status of variants in yeast with those from higher eukaryotes suggests that histone variants have evolved in synchrony with functional requirement of the cell.

  16. Fundamental Characteristics of Industrial Variant Specification Systems

    DEFF Research Database (Denmark)

    Hansen, Benjamin Loer; Hvam, Lars

    2004-01-01

    This paper focuses on the operational task of creating customised variants of industrial specifications (e.g. drawings, routings and bill-of-materials). Rooted in a lack of existing literature on the subject the paper describes the nature of variant specification systems. It introduces some funda...... examples. In general the paper discusses an important focus area within mass customization and build-to-order production: the nature of industrial variant specification systems.......This paper focuses on the operational task of creating customised variants of industrial specifications (e.g. drawings, routings and bill-of-materials). Rooted in a lack of existing literature on the subject the paper describes the nature of variant specification systems. It introduces some...

  17. Fountain Codes with Multiplicatively Repeated Non-Binary LDPC Codes

    CERN Document Server

    Kasai, Kenta

    2010-01-01

    We study fountain codes transmitted over the binary-input symmetric-output channel. For channels with small capacity, receivers needs to collects many channel outputs to recover information bits. Since a collected channel output yields a check node in the decoding Tanner graph, the channel with small capacity leads to large decoding complexity. In this paper, we introduce a novel fountain coding scheme with non-binary LDPC codes. The decoding complexity of the proposed fountain code does not depend on the channel. Numerical experiments show that the proposed codes exhibit better performance than conventional fountain codes, especially for small number of information bits.

  18. Quantum codes from linear codes over finite chain rings

    Science.gov (United States)

    Liu, Xiusheng; Liu, Hualu

    2017-10-01

    In this paper, we provide two methods of constructing quantum codes from linear codes over finite chain rings. The first one is derived from the Calderbank-Shor-Steane (CSS) construction applied to self-dual codes over finite chain rings. The second construction is derived from the CSS construction applied to Gray images of the linear codes over finite chain ring {\\mathbb {F}}_{p^{2m}}+u{\\mathbb {F}}_{p^{2m}}. The good parameters of quantum codes from cyclic codes over finite chain rings are obtained.

  19. Mutation analysis of NR0B2 among 1545 Danish men identifies a novel c.278G>A (p.G93D) variant with reduced functional activity

    DEFF Research Database (Denmark)

    Echwald, Søren Morgenthaler; Andersen, Kirstine L; Sørensen, Thorkild I A

    2004-01-01

    .G171A] polymorphism was identified. The 171A allele was not associated with obesity (p = 0.07). The 34G, 93D, and 139H-alleles were rare variants, which were found only among obese subjects. Among the four coding region variants, the 93D-allele showed a reduced in vitro inhibition of the HNF-4alpha...

  20. PLS3 sequencing in childhood-onset primary osteoporosis identifies two novel disease-causing variants.

    Science.gov (United States)

    Kämpe, A J; Costantini, A; Mäkitie, R E; Jäntti, N; Valta, H; Mäyränpää, M; Kröger, H; Pekkinen, M; Taylan, F; Jiao, H; Mäkitie, O

    2017-07-26

    Altogether 95 children with primary bone fragility were screened for variants in PLS3, the gene underlying X-linked osteoporosis. Two children with multiple peripheral and spinal fractures and low BMD had novel disease-causing PLS3 variants. Children with milder phenotypes had no pathogenic variants. PLS3 screening is indicated in childhood-onset primary osteoporosis. The study aimed to determine the role of pathogenic PLS3 variants in children's bone fragility and to elucidate the associated phenotypic features. Two cohorts of children with bone fragility were screened for variants in PLS3, the gene underlying X-linked osteoporosis. Cohort I comprised 31 patients with childhood-onset primary osteoporosis of unknown etiology. Cohort II comprised 64 children who had sustained multiple fractures but were otherwise healthy. Clinical and radiological data were reviewed. Peripheral blood DNA was Sanger sequenced for coding exons and flanking intronic regions of PLS3. In two patients of cohort I, where other common genetic causes had been excluded, we identified two novel disease-causing PLS3 variants. Patient 1 was a male with bilateral femoral fractures at 10 years, low BMD (Z-score -4.1; 18 years), and multiple vertebral compression fractures. He had a novel nonsense variant in PLS3. Patient 2 was a girl with multiple long bone and vertebral fractures and low BMD (Z-score -6.6 at 6 years). She had a de novo missense variant in PLS3; whole exome sequencing and array-CGH identified no other genetic causes. Iliac crest bone biopsies confirmed low-turnover osteoporosis in both patients. In cohort II, no pathogenic PLS3 variants were identified in any of the subjects. Two novel disease-causing variants in PLS3 were identified in a boy and a girl with multiple peripheral and spinal fractures and very low BMD while no pathogenic variants were identified in children with less severe skeletal fragility. PLS3 screening is warranted in male and female patients with childhood

  1. Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility

    NARCIS (Netherlands)

    Wessel, Jennifer; Chu, Audrey Y.; Willems, Sara M.; Wang, Shuai; Yaghootkar, Hanieh; Brody, Jennifer A.; Dauriz, Marco; Hivert, Marie-France; Raghavan, Sridharan; Lipovich, Leonard; Hidalgo, Bertha; Fox, Keolu; Huffman, Jennifer E.; An, Ping; Lu, Yingchang; Rasmussen-Torvik, Laura J.; Grarup, Niels; Ehm, Margaret G.; Li, Li; Baldridge, Abigail S.; Stancakova, Alena; Abrol, Ravinder; Besse, Celine; Boland, Anne; Bork-Jensen, Jette; Fornage, Myriam; Freitag, Daniel F.; Garcia, Melissa E.; Guo, Xiuqing; Hara, Kazuo; Isaacs, Aaron; Jakobsdottir, Johanna; Lange, Leslie A.; Layton, Jill C.; Li, Man; Zhao, Jing Hua; Meidtner, Karina; Morrison, Alanna C.; Nalls, Mike A.; Peters, Marjolein J.; Sabater-Lleal, Maria; Schurmann, Claudia; Silveira, Angela; Smith, Albert V.; Southam, Lorraine; Stoiber, Marcus H.; Strawbridge, Rona J.; Taylor, Kent D.; Varga, Tibor V.; Allin, Kristine H.; Amin, Najaf; Aponte, Jennifer L.; Aung, Tin; Barbieri, Caterina; Bihlmeyer, Nathan A.; Boehnke, Michael; Bombieri, Cristina; Bowden, Donald W.; Burns, Sean M.; Chen, Yuning; Chen, Yii-Deri; Cheng, Ching-Yu; Correa, Adolfo; Czajkowski, Jacek; Dehghan, Abbas; Ehret, Georg B.; Eiriksdottir, Gudny; Escher, Stefan A.; Farmaki, Aliki-Eleni; Franberg, Mattias; Gambaro, Giovanni; Giulianini, Franco; Goddard, William A.; Goel, Anuj; Gottesman, Omri; Grove, Megan L.; Gustafsson, Stefan; Hai, Yang; Hallmans, Goeran; Heo, Jiyoung; Hoffmann, Per; Ikram, Mohammad K.; Jensen, Richard A.; Jorgensen, Marit E.; Jorgensen, Torben; Karaleftheri, Maria; Khor, Chiea C.; Kirkpatrick, Andrea; Kraja, Aldi T.; Kuusisto, Johanna; Lange, Ethan M.; Lee, I. T.; Lee, Wen-Jane; Leong, Aaron; Liao, Jiemin; Liu, Chunyu; Liu, Yongmei; Lindgren, Cecilia M.; Linneberg, Allan; Malerba, Giovanni; Mamakou, Vasiliki; Marouli, Eirini; Maruthur, Nisa M.; Matchan, Angela; McKean-Cowdin, Roberta; McLeod, Olga; Metcalf, Ginger A.; Mohlke, Karen L.; Muzny, Donna M.; Ntalla, Ioanna; Palmer, Nicholette D.; Pasko, Dorota; Peter, Andreas; Rayner, Nigel W.; Renstroem, Frida; Rice, Ken; Sala, Cinzia F.; Sennblad, Bengt; Serafetinidis, Ioannis; Smith, Jennifer A.; Soranzo, Nicole; Speliotes, Elizabeth K.; Stahl, Eli A.; Stirrups, Kathleen; Tentolouris, Nikos; Thanopoulou, Anastasia; Torres, Mina; Traglia, Michela; Tsafantakis, Emmanouil; Javad, Sundas; Yanek, Lisa R.; Zengini, Eleni; Becker, Diane M.; Bis, Joshua C.; Brown, James B.; Cupples, L. Adrienne; Hansen, Torben; Ingelsson, Erik; Karter, Andrew J.; Lorenzo, Carlos; Mathias, Rasika A.; Norris, Jill M.; Peloso, Gina M.; Sheu, Wayne H. -H.; Toniolo, Daniela; Vaidya, Dhananjay; Varma, Rohit; Wagenknecht, Lynne E.; Boeing, Heiner; Bottinger, Erwin P.; Dedoussis, George; Deloukas, Panos; Ferrannini, Ele; Franco, Oscar H.; Franks, Paul W.; Gibbs, Richard A.; Gudnason, Vilmundur; Hamsten, Anders; Harris, Tamara B.; Hattersley, Andrew T.; Hayward, Caroline; Hofman, Albert; Jansson, Jan-Hakan; Langenberg, Claudia; Launer, Lenore J.; Levy, Daniel; Oostra, Ben A.; O'Donnell, Christopher J.; O'Rahilly, Stephen; Padmanabhan, Sandosh; Pankow, James S.; Polasek, Ozren; Province, Michael A.; Rich, Stephen S.; Ridker, Paul M.; Rudan, Igor; Schulze, Matthias B.; Smith, Blair H.; Uitterlinden, Andre G.; Walker, Mark; Watkins, Hugh; Wong, Tien Y.; Zeggini, Eleftheria; Laakso, Markku; Borecki, Ingrid B.; Chasman, Daniel I.; Pedersen, Oluf; Psaty, Bruce M.; Tai, E. Shyong; van Duijn, Cornelia M.; Wareham, Nicholas J.; Waterworth, Dawn M.; Boerwinkle, Eric; Kao, W. H. Linda; Florez, Jose C.; Loos, Ruth J. F.; Wilson, James G.; Frayling, Timothy M.; Siscovick, David S.; Dupuis, Josee; Rotter, Jerome I.; Meigs, James B.; Scott, Robert A.; Goodarzi, Mark O.; Sharp, Stephen J.; Forouhi, Nita G.; Kerrison, Nicola D.; Lucarelli, Debora M. E.; Sims, Matt; Barroso, Ines; McCarthy, Mark I.; Arriola, Larraitz; Balkau, Beverley; Barricarte, Aurelio; Gonzalez, Carlos; Grioni, Sara; Kaaks, Rudolf; Key, Timothy J.; Navarro, Carmen; Nilsson, Peter M.; Overvad, Kim; Palli, Domenico; Panico, Salvatore; Quiros, J. Ramon; Rolandsson, Olov; Sacerdote, Carlotta; Sanchez, Maria-Jose; Slimani, Nadia; Tjonneland, Anne; Tumino, Rosario; van der A, Daphne L.; van der Schouw, Yvonne T.|info:eu-repo/dai/nl/073449253; Riboli, Elio

    2015-01-01

    Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of

  2. Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility

    NARCIS (Netherlands)

    Wessel, Jennifer; Chu, Audrey Y.; Willems, Sara M.; Wang, Shuai; Yaghootkar, Hanieh; Brody, Jennifer A.; Dauriz, Marco; Hivert, Marie-France; Raghavan, Sridharan; Lipovich, Leonard; Hidalgo, Bertha; Fox, Keolu; Huffman, Jennifer E.; An, Ping; Lu, Yingchang; Rasmussen-Torvik, Laura J.; Grarup, Niels; Ehm, Margaret G.; Li, Li; Baldridge, Abigail S.; Stancakova, Alena; Abrol, Ravinder; Besse, Celine; Boland, Anne; Bork-Jensen, Jette; Fornage, Myriam; Freitag, Daniel F.; Garcia, Melissa E.; Guo, Xiuqing; Hara, Kazuo; Isaacs, Aaron; Jakobsdottir, Johanna; Lange, Leslie A.; Layton, Jill C.; Li, Man; Zhao, Jing Hua; Meidtner, Karina; Morrison, Alanna C.; Nalls, Mike A.; Peters, Marjolein J.; Sabater-Lleal, Maria; Schurmann, Claudia; Silveira, Angela; Smith, Albert V.; Southam, Lorraine; Stoiber, Marcus H.; Strawbridge, Rona J.; Taylor, Kent D.; Varga, Tibor V.; Allin, Kristine H.; Amin, Najaf; Aponte, Jennifer L.; Aung, Tin; Barbieri, Caterina; Bihlmeyer, Nathan A.; Boehnke, Michael; Bombieri, Cristina; Bowden, Donald W.; Burns, Sean M.; Chen, Yuning; Chen, Yii-Deri; Cheng, Ching-Yu; Correa, Adolfo; Czajkowski, Jacek; Dehghan, Abbas; Ehret, Georg B.; Eiriksdottir, Gudny; Escher, Stefan A.; Farmaki, Aliki-Eleni; Franberg, Mattias; Gambaro, Giovanni; Giulianini, Franco; Goddard, William A.; Goel, Anuj; Gottesman, Omri; Grove, Megan L.; Gustafsson, Stefan; Hai, Yang; Hallmans, Goeran; Heo, Jiyoung; Hoffmann, Per; Ikram, Mohammad K.; Jensen, Richard A.; Jorgensen, Marit E.; Jorgensen, Torben; Karaleftheri, Maria; Khor, Chiea C.; Kirkpatrick, Andrea; Kraja, Aldi T.; Kuusisto, Johanna; Lange, Ethan M.; Lee, I. T.; Lee, Wen-Jane; Leong, Aaron; Liao, Jiemin; Liu, Chunyu; Liu, Yongmei; Lindgren, Cecilia M.; Linneberg, Allan; Malerba, Giovanni; Mamakou, Vasiliki; Marouli, Eirini; Maruthur, Nisa M.; Matchan, Angela; McKean-Cowdin, Roberta; McLeod, Olga; Metcalf, Ginger A.; Mohlke, Karen L.; Muzny, Donna M.; Ntalla, Ioanna; Palmer, Nicholette D.; Pasko, Dorota; Peter, Andreas; Rayner, Nigel W.; Renstroem, Frida; Rice, Ken; Sala, Cinzia F.; Sennblad, Bengt; Serafetinidis, Ioannis; Smith, Jennifer A.; Soranzo, Nicole; Speliotes, Elizabeth K.; Stahl, Eli A.; Stirrups, Kathleen; Tentolouris, Nikos; Thanopoulou, Anastasia; Torres, Mina; Traglia, Michela; Tsafantakis, Emmanouil; Javad, Sundas; Yanek, Lisa R.; Zengini, Eleni; Becker, Diane M.; Bis, Joshua C.; Brown, James B.; Cupples, L. Adrienne; Hansen, Torben; Ingelsson, Erik; Karter, Andrew J.; Lorenzo, Carlos; Mathias, Rasika A.; Norris, Jill M.; Peloso, Gina M.; Sheu, Wayne H. -H.; Toniolo, Daniela; Vaidya, Dhananjay; Varma, Rohit; Wagenknecht, Lynne E.; Boeing, Heiner; Bottinger, Erwin P.; Dedoussis, George; Deloukas, Panos; Ferrannini, Ele; Franco, Oscar H.; Franks, Paul W.; Gibbs, Richard A.; Gudnason, Vilmundur; Hamsten, Anders; Harris, Tamara B.; Hattersley, Andrew T.; Hayward, Caroline; Hofman, Albert; Jansson, Jan-Hakan; Langenberg, Claudia; Launer, Lenore J.; Levy, Daniel; Oostra, Ben A.; O'Donnell, Christopher J.; O'Rahilly, Stephen; Padmanabhan, Sandosh; Pankow, James S.; Polasek, Ozren; Province, Michael A.; Rich, Stephen S.; Ridker, Paul M.; Rudan, Igor; Schulze, Matthias B.; Smith, Blair H.; Uitterlinden, Andre G.; Walker, Mark; Watkins, Hugh; Wong, Tien Y.; Zeggini, Eleftheria; Laakso, Markku; Borecki, Ingrid B.; Chasman, Daniel I.; Pedersen, Oluf; Psaty, Bruce M.; Tai, E. Shyong; van Duijn, Cornelia M.; Wareham, Nicholas J.; Waterworth, Dawn M.; Boerwinkle, Eric; Kao, W. H. Linda; Florez, Jose C.; Loos, Ruth J. F.; Wilson, James G.; Frayling, Timothy M.; Siscovick, David S.; Dupuis, Josee; Rotter, Jerome I.; Meigs, James B.; Scott, Robert A.; Goodarzi, Mark O.; Sharp, Stephen J.; Forouhi, Nita G.; Kerrison, Nicola D.; Lucarelli, Debora M. E.; Sims, Matt; Barroso, Ines; McCarthy, Mark I.; Arriola, Larraitz; Balkau, Beverley; Barricarte, Aurelio; Gonzalez, Carlos; Grioni, Sara; Kaaks, Rudolf; Key, Timothy J.; Navarro, Carmen; Nilsson, Peter M.; Overvad, Kim; Palli, Domenico; Panico, Salvatore; Quiros, J. Ramon; Rolandsson, Olov; Sacerdote, Carlotta; Sanchez, Maria-Jose; Slimani, Nadia; Tjonneland, Anne; Tumino, Rosario; van der A, Daphne L.; van der Schouw, Yvonne T.; Riboli, Elio

    2015-01-01

    Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of

  3. Rare ATAD5 missense variants in breast and ovarian cancer patients.

    Science.gov (United States)

    Maleva Kostovska, Ivana; Wang, Jing; Bogdanova, Natalia; Schürmann, Peter; Bhuju, Sabin; Geffers, Robert; Dürst, Matthias; Liebrich, Clemens; Klapdor, Rüdiger; Christiansen, Hans; Park-Simon, Tjoung-Won; Hillemanns, Peter; Plaseska-Karanfilska, Dijana; Dörk, Thilo

    2016-06-28

    ATAD5/ELG1 is a protein crucially involved in replication and maintenance of genome stability. ATAD5 has recently been identified as a genomic risk locus for both breast and ovarian cancer through genome-wide association studies. We aimed to investigate the spectrum of coding ATAD5 germ-line mutations in hospital-based series of patients with triple-negative breast cancer or serous ovarian cancer compared with healthy controls. The ATAD5 coding and adjacent splice site regions were analyzed by targeted next-generation sequencing of DNA samples from 273 cancer patients, including 114 patients with triple-negative breast cancer and 159 patients with serous epithelial ovarian cancer, and from 276 healthy females. Among 42 different variants identified, twenty-two were rare missense substitutions, of which 14 were classified as pathogenic by at least one in silico prediction tool. Three of four novel missense substitutions (p.S354I, p.H974R and p.K1466N) were predicted to be pathogenic and were all identified in ovarian cancer patients. Overall, rare missense variants with predicted pathogenicity tended to be enriched in ovarian cancer patients (14/159) versus controls (11/276) (p = 0.05, 2df). While truncating germ-line variants in ATAD5 were not detected, it remains possible that several rare missense variants contribute to genetic susceptibility toward epithelial ovarian carcinomas.

  4. Reserved-Length Prefix Coding

    CERN Document Server

    Baer, Michael B

    2008-01-01

    Huffman coding finds an optimal prefix code for a given probability mass function. Consider situations in which one wishes to find an optimal code with the restriction that all codewords have lengths that lie in a user-specified set of lengths (or, equivalently, no codewords have lengths that lie in a complementary set). This paper introduces a polynomial-time dynamic programming algorithm that finds optimal codes for this reserved-length prefix coding problem. This has applications to quickly encoding and decoding lossless codes. In addition, one modification of the approach solves any quasiarithmetic prefix coding problem, while another finds optimal codes restricted to the set of codes with g codeword lengths for user-specified g (e.g., g=2).

  5. Decoding Generalized Concatenated Codes Using Interleaved Reed-Solomon Codes

    CERN Document Server

    Senger, Christian; Bossert, Martin; Zyablov, Victor

    2008-01-01

    Generalized Concatenated codes are a code construction consisting of a number of outer codes whose code symbols are protected by an inner code. As outer codes, we assume the most frequently used Reed-Solomon codes; as inner code, we assume some linear block code which can be decoded up to half its minimum distance. Decoding up to half the minimum distance of Generalized Concatenated codes is classically achieved by the Blokh-Zyablov-Dumer algorithm, which iteratively decodes by first using the inner decoder to get an estimate of the outer code words and then using an outer error/erasure decoder with a varying number of erasures determined by a set of pre-calculated thresholds. In this paper, a modified version of the Blokh-Zyablov-Dumer algorithm is proposed, which exploits the fact that a number of outer Reed-Solomon codes with average minimum distance d can be grouped into one single Interleaved Reed-Solomon code which can be decoded beyond d/2. This allows to skip a number of decoding iterations on the one...

  6. The NIMROD Code

    Science.gov (United States)

    Schnack, D. D.; Glasser, A. H.

    1996-11-01

    NIMROD is a new code system that is being developed for the analysis of modern fusion experiments. It is being designed from the beginning to make the maximum use of massively parallel computer architectures and computer graphics. The NIMROD physics kernel solves the three-dimensional, time-dependent two-fluid equations with neo-classical effects in toroidal geometry of arbitrary poloidal cross section. The NIMROD system also includes a pre-processor, a grid generator, and a post processor. User interaction with NIMROD is facilitated by a modern graphical user interface (GUI). The NIMROD project is using Quality Function Deployment (QFD) team management techniques to minimize re-engineering and reduce code development time. This paper gives an overview of the NIMROD project. Operation of the GUI is demonstrated, and the first results from the physics kernel are given.

  7. Epetra developers coding guidelines.

    Energy Technology Data Exchange (ETDEWEB)

    Heroux, Michael Allen; Sexton, Paul Michael

    2003-12-01

    Epetra is a package of classes for the construction and use of serial and distributed parallel linear algebra objects. It is one of the base packages in Trilinos. This document describes guidelines for Epetra coding style. The issues discussed here go beyond correct C++ syntax to address issues that make code more readable and self-consistent. The guidelines presented here are intended to aid current and future development of Epetra specifically. They reflect design decisions that were made in the early development stages of Epetra. Some of the guidelines are contrary to more commonly used conventions, but we choose to continue these practices for the purposes of self-consistency. These guidelines are intended to be complimentary to policies established in the Trilinos Developers Guide.

  8. Efficient convolutional sparse coding

    Energy Technology Data Exchange (ETDEWEB)

    Wohlberg, Brendt

    2017-06-20

    Computationally efficient algorithms may be applied for fast dictionary learning solving the convolutional sparse coding problem in the Fourier domain. More specifically, efficient convolutional sparse coding may be derived within an alternating direction method of multipliers (ADMM) framework that utilizes fast Fourier transforms (FFT) to solve the main linear system in the frequency domain. Such algorithms may enable a significant reduction in computational cost over conventional approaches by implementing a linear solver for the most critical and computationally expensive component of the conventional iterative algorithm. The theoretical computational cost of the algorithm may be reduced from O(M.sup.3N) to O(MN log N), where N is the dimensionality of the data and M is the number of elements in the dictionary. This significant improvement in efficiency may greatly increase the range of problems that can practically be addressed via convolutional sparse representations.

  9. Decoding the productivity code

    DEFF Research Database (Denmark)

    Hansen, David

    .e., to be prepared to initiate improvement. The study shows how the effectiveness of the improvement system depends on the congruent fit between the five elements as well as the bridging coherence between the improvement system and the work system. The bridging coherence depends on how improvements are activated...... approach often ends up with demanding intense employee focus to sustain improvement and engagement. Likewise, a single-minded employee development approach often ends up demanding rationalization to achieve the desired financial results. These ineffective approaches make organizations react like pendulums...... that swing between rationalization and employee development. The productivity code is the lack of alternatives to this ineffective approach. This thesis decodes the productivity code based on the results from a 3-year action research study at a medium-sized manufacturing facility. During the project period...

  10. Codes of Good Governance

    DEFF Research Database (Denmark)

    Beck Jørgensen, Torben; Sørensen, Ditte-Lene

    2013-01-01

    Good governance is a broad concept used by many international organizations to spell out how states or countries should be governed. Definitions vary, but there is a clear core of common public values, such as transparency, accountability, effectiveness, and the rule of law. It is quite likely......, however, that national views of good governance reflect different political cultures and institutional heritages. Fourteen national codes of conduct are analyzed. The findings suggest that public values converge and that they match model codes from the United Nations and the European Council as well...... as conceptions of good governance from other international organizations. While values converge, they are balanced and communicated differently, and seem to some extent to be translated into the national cultures. The set of global public values derived from this analysis include public interest, regime dignity...

  11. Confocal coded aperture imaging

    Energy Technology Data Exchange (ETDEWEB)

    Tobin, Jr., Kenneth William (Harriman, TN); Thomas, Jr., Clarence E. (Knoxville, TN)

    2001-01-01

    A method for imaging a target volume comprises the steps of: radiating a small bandwidth of energy toward the target volume; focusing the small bandwidth of energy into a beam; moving the target volume through a plurality of positions within the focused beam; collecting a beam of energy scattered from the target volume with a non-diffractive confocal coded aperture; generating a shadow image of said aperture from every point source of radiation in the target volume; and, reconstructing the shadow image into a 3-dimensional image of the every point source by mathematically correlating the shadow image with a digital or analog version of the coded aperture. The method can comprise the step of collecting the beam of energy scattered from the target volume with a Fresnel zone plate.

  12. MetaNetVar: Pipeline for applying network analysis tools for genomic variants analysis.

    Science.gov (United States)

    Moyer, Eric; Hagenauer, Megan; Lesko, Matthew; Francis, Felix; Rodriguez, Oscar; Nagarajan, Vijayaraj; Huser, Vojtech; Busby, Ben

    2016-01-01

    Network analysis can make variant analysis better. There are existing tools like HotNet2 and dmGWAS that can provide various analytical methods. We developed a prototype of a pipeline called MetaNetVar that allows execution of multiple tools. The code is published at https://github.com/NCBI-Hackathons/Network_SNPs. A working prototype is published as an Amazon Machine Image - ami-4510312f .

  13. The Phantom SPH code

    Science.gov (United States)

    Price, Daniel; Wurster, James; Nixon, Chris

    2016-05-01

    I will present the capabilities of the Phantom SPH code for global simulations of dust and gas in protoplanetary discs. I will present our new algorithms for simulating both small and large grains in discs, as well as our progress towards simulating evolving grain populations and coupling with radiation. Finally, I will discuss our recent applications to HL Tau and the physics of dust gap opening.

  14. The Liege Oscillation Code

    CERN Document Server

    Scuflaire, R; Théado, S; Bourge, P -O; Miglio, A; Godart, M; Thoul, A; Noels, A

    2007-01-01

    The Liege Oscillation code can be used as a stand-alone program or as a library of subroutines that the user calls from a Fortran main program of his own to compute radial and non-radial adiabatic oscillations of stellar models. We describe the variables and the equations used by the program and the methods used to solve them. A brief account is given of the use and the output of the program.

  15. Status of MARS Code

    Energy Technology Data Exchange (ETDEWEB)

    N.V. Mokhov

    2003-04-09

    Status and recent developments of the MARS 14 Monte Carlo code system for simulation of hadronic and electromagnetic cascades in shielding, accelerator and detector components in the energy range from a fraction of an electronvolt up to 100 TeV are described. these include physics models both in strong and electromagnetic interaction sectors, variance reduction techniques, residual dose, geometry, tracking, histograming. MAD-MARS Beam Line Build and Graphical-User Interface.

  16. ARQ for Network Coding

    CERN Document Server

    Sundararajan, Jay Kumar; Médard, Muriel

    2008-01-01

    A new coding and queue management algorithm is proposed for communication networks that employ linear network coding. The algorithm has the feature that the encoding process is truly online, as opposed to a block-by-block approach. The setup assumes a packet erasure broadcast channel with stochastic arrivals and full feedback, but the proposed scheme is potentially applicable to more general lossy networks with link-by-link feedback. The algorithm guarantees that the physical queue size at the sender tracks the backlog in degrees of freedom (also called the virtual queue size). The new notion of a node "seeing" a packet is introduced. In terms of this idea, our algorithm may be viewed as a natural extension of ARQ schemes to coded networks. Our approach, known as the drop-when-seen algorithm, is compared with a baseline queuing approach called drop-when-decoded. It is shown that the expected queue size for our approach is $O(\\frac1{1-\\rho})$ as opposed to $\\Omega(\\frac1{(1-\\rho)^2})$ for the baseline approach...

  17. MELCOR computer code manuals

    Energy Technology Data Exchange (ETDEWEB)

    Summers, R.M.; Cole, R.K. Jr.; Smith, R.C.; Stuart, D.S.; Thompson, S.L. [Sandia National Labs., Albuquerque, NM (United States); Hodge, S.A.; Hyman, C.R.; Sanders, R.L. [Oak Ridge National Lab., TN (United States)

    1995-03-01

    MELCOR is a fully integrated, engineering-level computer code that models the progression of severe accidents in light water reactor nuclear power plants. MELCOR is being developed at Sandia National Laboratories for the U.S. Nuclear Regulatory Commission as a second-generation plant risk assessment tool and the successor to the Source Term Code Package. A broad spectrum of severe accident phenomena in both boiling and pressurized water reactors is treated in MELCOR in a unified framework. These include: thermal-hydraulic response in the reactor coolant system, reactor cavity, containment, and confinement buildings; core heatup, degradation, and relocation; core-concrete attack; hydrogen production, transport, and combustion; fission product release and transport; and the impact of engineered safety features on thermal-hydraulic and radionuclide behavior. Current uses of MELCOR include estimation of severe accident source terms and their sensitivities and uncertainties in a variety of applications. This publication of the MELCOR computer code manuals corresponds to MELCOR 1.8.3, released to users in August, 1994. Volume 1 contains a primer that describes MELCOR`s phenomenological scope, organization (by package), and documentation. The remainder of Volume 1 contains the MELCOR Users Guides, which provide the input instructions and guidelines for each package. Volume 2 contains the MELCOR Reference Manuals, which describe the phenomenological models that have been implemented in each package.

  18. Coexistence in Field Samples of Two Variants of the Infectious Salmon Anemia Virus: A Putative Shift to Pathogenicity

    Science.gov (United States)

    Cárdenas, Constanza; Carmona, Marisela; Gallardo, Alicia; Labra, Alvaro; Marshall, Sergio H.

    2014-01-01

    Genetic reassortment plays an important role in the evolution of several segmented RNA viruses and in the epidemiology of their associated diseases. In particular, orthomyxoviruses show rapid fluctuation in the proportion of viral variants coexisting in an infected individual, especially under strong selective pressure. This is particularly relevant in salmon production carried out under confined and stressful conditions where one of the most feared pathogenic agents is the Infectious Salmon Anemia Virus, an orthomyxovirus family member whose biological behavior is only recently beginning to be understood. Pathogenicity of the virus has been mainly associated with deletions of the HPR region in coding segment 6 and the presence or absence of a specific insertion in a key region in coding segment 5. In this study we report, for the first time in Chile, the coexistence of two variants in fully asymptomatic fish. Of five samples analyzed, two were identified as the non-pathogenic variant, HPR0, and two as the highly pathogenic HPR7b variant, though with no clinical signs detectable in the fish. Interestingly, one of the samples unequivocally carried both variants, again without any clinical signs. Considering that in none of the samples the typical insertion in coding segment 5 was detected, it is our impression that this may represent a shift from the non-pathogenic HPR0 variant towards the highly infective HPR7b variant. If this were the case, the transition may be triggered first by deleting the corresponding sequence of the HPR region of segment 6, followed by the putative insertion in segment 5 to generate a virulent strain. PMID:24498206

  19. Predictive coding and the slowness principle: an information-theoretic approach.

    Science.gov (United States)

    Creutzig, Felix; Sprekeler, Henning

    2008-04-01

    Understanding the guiding principles of sensory coding strategies is a main goal in computational neuroscience. Among others, the principles of predictive coding and slowness appear to capture aspects of sensory processing. Predictive coding postulates that sensory systems are adapted to the structure of their input signals such that information about future inputs is encoded. Slow feature analysis (SFA) is a method for extracting slowly varying components from quickly varying input signals, thereby learning temporally invariant features. Here, we use the information bottleneck method to state an information-theoretic objective function for temporally local predictive coding. We then show that the linear case of SFA can be interpreted as a variant of predictive coding that maximizes the mutual information between the current output of the system and the input signal in the next time step. This demonstrates that the slowness principle and predictive coding are intimately related.

  20. Genome-Wide Study of Structural Variants in Bovine Holstein, Montbéliarde and Normande Dairy Breeds

    Science.gov (United States)

    Boussaha, Mekki; Esquerré, Diane; Barbieri, Johanna; Djari, Anis; Pinton, Alain; Letaief, Rabia; Salin, Gérald; Escudié, Frédéric; Roulet, Alain; Fritz, Sébastien; Samson, Franck; Grohs, Cécile; Bernard, Maria; Klopp, Christophe; Boichard, Didier; Rocha, Dominique

    2015-01-01

    High-throughput sequencing technologies have offered in recent years new opportunities to study genome variations. These studies have mostly focused on single nucleotide polymorphisms, small insertions or deletions and on copy number variants. Other structural variants, such as large insertions or deletions, tandem duplications, translocations, and inversions are less well-studied, despite that some have an important impact on phenotypes. In the present study, we performed a large-scale survey of structural variants in cattle. We report the identification of 6,426 putative structural variants in cattle extracted from whole-genome sequence data of 62 bulls representing the three major French dairy breeds. These genomic variants affect DNA segments greater than 50 base pairs and correspond to deletions, inversions and tandem duplications. Out of these, we identified a total of 547 deletions and 410 tandem duplications which could potentially code for CNVs. Experimental validation was carried out on 331 structural variants using a novel high-throughput genotyping method. Out of these, 255 structural variants (77%) generated good quality genotypes and 191 (75%) of them were validated. Gene content analyses in structural variant regions revealed 941 large deletions removing completely one or several genes, including 10 single-copy genes. In addition, some of the structural variants are located within quantitative trait loci for dairy traits. This study is a pan-genome assessment of genomic variations in cattle and may provide a new glimpse into the bovine genome architecture. Our results may also help to study the effects of structural variants on gene expression and consequently their effect on certain phenotypes of interest. PMID:26317361

  1. Identification of rare X-linked neuroligin variants by massively parallel sequencing in males with autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Steinberg Karyn

    2012-09-01

    Full Text Available Abstract Background Autism spectrum disorder (ASD is highly heritable, but the genetic risk factors for it remain largely unknown. Although structural variants with large effect sizes may explain up to 15% ASD, genome-wide association studies have failed to uncover common single nucleotide variants with large effects on phenotype. The focus within ASD genetics is now shifting to the examination of rare sequence variants of modest effect, which is most often achieved via exome selection and sequencing. This strategy has indeed identified some rare candidate variants; however, the approach does not capture the full spectrum of genetic variation that might contribute to the phenotype. Methods We surveyed two loci with known rare variants that contribute to ASD, the X-linked neuroligin genes by performing massively parallel Illumina sequencing of the coding and noncoding regions from these genes in males from families with multiplex autism. We annotated all variant sites and functionally tested a subset to identify other rare mutations contributing to ASD susceptibility. Results We found seven rare variants at evolutionary conserved sites in our study population. Functional analyses of the three 3’ UTR variants did not show statistically significant effects on the expression of NLGN3 and NLGN4X. In addition, we identified two NLGN3 intronic variants located within conserved transcription factor binding sites that could potentially affect gene regulation. Conclusions These data demonstrate the power of massively parallel, targeted sequencing studies of affected individuals for identifying rare, potentially disease-contributing variation. However, they also point out the challenges and limitations of current methods of direct functional testing of rare variants and the difficulties of identifying alleles with modest effects.

  2. low bit rate video coding low bit rate video coding

    African Journals Online (AJOL)

    eobe

    ariable length bit rate (VLBR) broadly encompasses video coding which broadly encompasses ... for motion estimation and compensation to reduce the prediction sation to reduce the ... a special interest among the video coding community ...

  3. Decoding of concatenated codes with interleaved outer codes

    DEFF Research Database (Denmark)

    Justesen, Jørn; Thommesen, Christian; Høholdt, Tom

    2004-01-01

    Recently Bleichenbacher et al. proposed a decoding algorithm for interleaved Reed/Solomon codes, which allows close to errors to be corrected in many cases. We discuss the application of this decoding algorithm to concatenated codes. (NK) N-K...

  4. Random linear codes in steganography

    Directory of Open Access Journals (Sweden)

    Kamil Kaczyński

    2016-12-01

    Full Text Available Syndrome coding using linear codes is a technique that allows improvement in the steganographic algorithms parameters. The use of random linear codes gives a great flexibility in choosing the parameters of the linear code. In parallel, it offers easy generation of parity check matrix. In this paper, the modification of LSB algorithm is presented. A random linear code [8, 2] was used as a base for algorithm modification. The implementation of the proposed algorithm, along with practical evaluation of algorithms’ parameters based on the test images was made.[b]Keywords:[/b] steganography, random linear codes, RLC, LSB

  5. Multi-Trial Guruswami–Sudan Decoding for Generalised Reed–Solomon Codes

    DEFF Research Database (Denmark)

    Nielsen, Johan Sebastian Rosenkilde; Zeh, Alexander

    2013-01-01

    An iterated refinement procedure for the Guruswami–Sudan list decoding algorithm for Generalised Reed–Solomon codes based on Alekhnovich’s module minimisation is proposed. The method is parametrisable and allows variants of the usual list decoding approach. In particular, finding the list...

  6. A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation.

    NARCIS (Netherlands)

    Tarpey, P.S.; Smith, R.; Pleasance, E.; Whibley, A.; Edkins, S.; Hardy, C.; O'Meara, S.; Latimer, C.; Dicks, E.; Menzies, A.; Stephens, P.; Blow, M.; Greenman, C.; Xue, Y.; Tyler-Smith, C.; Thompson, D.; Gray, K.; Andrews, J.; Barthorpe, S.; Buck, G.; Cole, J.; Dunmore, R.; Jones, D.; Maddison, M.; Mironenko, T.; Turner, R.; Turrell, K.; Varian, J.; West, S.; Widaa, S.; Wray, P.; Teague, J.; Butler, A.; Jenkinson, A.; Jia, M.; Richardson, D.; Shepherd, R.; Wooster, R.; Tejada, M.I.; Martinez, F.; Carvill, G.; Goliath, R.; Brouwer, A.P.M. de; Bokhoven, H. van; Esch, H. van; Chelly, J.; Raynaud, M.; Ropers, H.H.; Abidi, F.E.; Srivastava, A.K.; Cox, J.; Luo, Y.; Mallya, U.; Moon, J.; Parnau, J.; Mohammed, S.; Tolmie, J.L.; Shoubridge, C.; Corbett, M.; Gardner, A.; Haan, E.; Rujirabanjerd, S.; Shaw, M.A.; Vandeleur, L.; Fullston, T.; Easton, D.F.; Boyle, J.; Partington, M.; Hackett, A.; Field, M.; Skinner, C.; Stevenson, R.E.; Bobrow, M.; Turner, G.; Schwartz, C.E.; Gecz, J.; Raymond, F.L.; Futreal, P.A.; Stratton, M.R.

    2009-01-01

    Large-scale systematic resequencing has been proposed as the key future strategy for the discovery of rare, disease-causing sequence variants across the spectrum of human complex disease. We have sequenced the coding exons of the X chromosome in 208 families with X-linked mental retardation (XLMR),

  7. Partitioning Heritability of Regulatory and Cell-Type-Specific Variants across 11 Common Diseases

    Science.gov (United States)

    Gusev, Alexander; Lee, S. Hong; Trynka, Gosia; Finucane, Hilary; Vilhjálmsson, Bjarni J.; Xu, Han; Zang, Chongzhi; Ripke, Stephan; Bulik-Sullivan, Brendan; Stahl, Eli; Ripke, Stephan; Neale, Benjamin M.; Corvin, Aiden; Walters, James T.R.; Farh, Kai-How; Holmans, Peter A.; Lee, Phil; Bulik-Sullivan, Brendan; Collier, David A.; Huang, Hailiang; Pers, Tune H.; Agartz, Ingrid; Agerbo, Esben; Albus, Margot; Alexander, Madeline; Amin, Farooq; Bacanu, Silviu A.; Begemann, Martin; Belliveau, Richard A.; Bene, Judit; Bergen, Sarah E.; Bevilacqua, Elizabeth; Bigdeli, Tim B.; Black, Donald W.; Børglum, Anders D.; Bruggeman, Richard; Buccola, Nancy G.; Buckner, Randy L.; Byerley, William; Cahn, Wiepke; Cai, Guiqing; Campion, Dominique; Cantor, Rita M.; Carr, Vaughan J.; Carrera, Noa; Catts, Stanley V.; Chambert, Kimberly D.; Chan, Raymond C.K.; Chen, Ronald Y.L.; Chen, Eric Y.H.; Cheng, Wei; Cheung, Eric F.C.; Chong, Siow Ann; Cloninger, C. Robert; Cohen, David; Cohen, Nadine; Cormican, Paul; Craddock, Nick; Crowley, James J.; Curtis, David; Davidson, Michael; Davis, Kenneth L.; Degenhardt, Franziska; Del Favero, Jurgen; DeLisi, Lynn E.; Demontis, Ditte; Dikeos, Dimitris; Dinan, Timothy; Djurovic, Srdjan; Donohoe, Gary; Drapeau, Elodie; Duan, Jubao; Dudbridge, Frank; Durmishi, Naser; Eichhammer, Peter; Eriksson, Johan; Escott-Price, Valentina; Essioux, Laurent; Fanous, Ayman H.; Farrell, Martilias S.; Frank, Josef; Franke, Lude; Freedman, Robert; Freimer, Nelson B.; Friedl, Marion; Friedman, Joseph I.; Fromer, Menachem; Genovese, Giulio; Georgieva, Lyudmila; Gershon, Elliot S.; Giegling, Ina; Giusti-Rodrguez, Paola; Godard, Stephanie; Goldstein, Jacqueline I.; Golimbet, Vera; Gopal, Srihari; Gratten, Jacob; Grove, Jakob; de Haan, Lieuwe; Hammer, Christian; Hamshere, Marian L.; Hansen, Mark; Hansen, Thomas; Haroutunian, Vahram; Hartmann, Annette M.; Henskens, Frans A.; Herms, Stefan; Hirschhorn, Joel N.; Hoffmann, Per; Hofman, Andrea; Hollegaard, Mads V.; Hougaard, David M.; Ikeda, Masashi; Joa, Inge; Julià, Antonio; Kahn, René S.; Kalaydjieva, Luba; Karachanak-Yankova, Sena; Karjalainen, Juha; Kavanagh, David; Keller, Matthew C.; Kelly, Brian J.; Kennedy, James L.; Khrunin, Andrey; Kim, Yunjung; Klovins, Janis; Knowles, James A.; Konte, Bettina; Kucinskas, Vaidutis; Kucinskiene, Zita Ausrele; Kuzelova-Ptackova, Hana; Kähler, Anna K.; Laurent, Claudine; Keong, Jimmy Lee Chee; Lee, S. Hong; Legge, Sophie E.; Lerer, Bernard; Li, Miaoxin; Li, Tao; Liang, Kung-Yee; Lieberman, Jeffrey; Limborska, Svetlana; Loughland, Carmel M.; Lubinski, Jan; Lnnqvist, Jouko; Macek, Milan; Magnusson, Patrik K.E.; Maher, Brion S.; Maier, Wolfgang; Mallet, Jacques; Marsal, Sara; Mattheisen, Manuel; Mattingsdal, Morten; McCarley, Robert W.; McDonald, Colm; McIntosh, Andrew M.; Meier, Sandra; Meijer, Carin J.; Melegh, Bela; Melle, Ingrid; Mesholam-Gately, Raquelle I.; Metspalu, Andres; Michie, Patricia T.; Milani, Lili; Milanova, Vihra; Mokrab, Younes; Morris, Derek W.; Mors, Ole; Mortensen, Preben B.; Murphy, Kieran C.; Murray, Robin M.; Myin-Germeys, Inez; Mller-Myhsok, Bertram; Nelis, Mari; Nenadic, Igor; Nertney, Deborah A.; Nestadt, Gerald; Nicodemus, Kristin K.; Nikitina-Zake, Liene; Nisenbaum, Laura; Nordin, Annelie; O’Callaghan, Eadbhard; O’Dushlaine, Colm; O’Neill, F. Anthony; Oh, Sang-Yun; Olincy, Ann; Olsen, Line; Van Os, Jim; Pantelis, Christos; Papadimitriou, George N.; Papiol, Sergi; Parkhomenko, Elena; Pato, Michele T.; Paunio, Tiina; Pejovic-Milovancevic, Milica; Perkins, Diana O.; Pietilinen, Olli; Pimm, Jonathan; Pocklington, Andrew J.; Powell, John; Price, Alkes; Pulver, Ann E.; Purcell, Shaun M.; Quested, Digby; Rasmussen, Henrik B.; Reichenberg, Abraham; Reimers, Mark A.; Richards, Alexander L.; Roffman, Joshua L.; Roussos, Panos; Ruderfer, Douglas M.; Salomaa, Veikko; Sanders, Alan R.; Schall, Ulrich; Schubert, Christian R.; Schulze, Thomas G.; Schwab, Sibylle G.; Scolnick, Edward M.; Scott, Rodney J.; Seidman, Larry J.; Shi, Jianxin; Sigurdsson, Engilbert; Silagadze, Teimuraz; Silverman, Jeremy M.; Sim, Kang; Slominsky, Petr; Smoller, Jordan W.; So, Hon-Cheong; Spencer, Chris C.A.; Stahl, Eli A.; Stefansson, Hreinn; Steinberg, Stacy; Stogmann, Elisabeth; Straub, Richard E.; Strengman, Eric; Strohmaier, Jana; Stroup, T. Scott; Subramaniam, Mythily; Suvisaari, Jaana; Svrakic, Dragan M.; Szatkiewicz, Jin P.; Sderman, Erik; Thirumalai, Srinivas; Toncheva, Draga; Tooney, Paul A.; Tosato, Sarah; Veijola, Juha

    2014-01-01

    Regulatory and coding variants are known to be enriched with associations identified by genome-wide association studies (GWASs) of complex disease, but their contributions to trait heritability are currently unknown. We applied variance-component methods to imputed genotype data for 11 common diseases to partition the heritability explained by genotyped SNPs (hg2) across functional categories (while accounting for shared variance due to linkage disequilibrium). Extensive simulations showed that in contrast to current estimates from GWAS summary statistics, the variance-component approach partitions heritability accurately under a wide range of complex-disease architectures. Across the 11 diseases DNaseI hypersensitivity sites (DHSs) from 217 cell types spanned 16% of imputed SNPs (and 24% of genotyped SNPs) but explained an average of 79% (SE = 8%) of hg2 from imputed SNPs (5.1× enrichment; p = 3.7 × 10−17) and 38% (SE = 4%) of hg2 from genotyped SNPs (1.6× enrichment, p = 1.0 × 10−4). Further enrichment was observed at enhancer DHSs and cell-type-specific DHSs. In contrast, coding variants, which span 1% of the genome, explained <10% of hg2 despite having the highest enrichment. We replicated these findings but found no significant contribution from rare coding variants in independent schizophrenia cohorts genotyped on GWAS and exome chips. Our results highlight the value of analyzing components of heritability to unravel the functional architecture of common disease. PMID:25439723

  8. Identification and annotation of genetic variants (SNP/Indel) in Danish Jutland cattle

    DEFF Research Database (Denmark)

    Das, Ashutosh; Panitz, Frank; Holm, Lars-Erik

    We sequenced the whole-genome of a Danish Jutland bull to identify genetic variants (SNP/indel). Using UnifiedGenotyper from the Genome Analysis Toolkit (GATK), we identified 6,812,198 SNPs and 804,453 indels. There were 2,598,000 (38.1%) novel SNPs and 607,923(75.6%) novel indels while the remai......,122 indels in coding sequences, 832 predicted to cause frame shift, 89 predicted to be inframe insertion and 115 to be inframe deletion. We detected a higher level of genetic variation in the Jutland bull compared to similar data from Holstein cattle......We sequenced the whole-genome of a Danish Jutland bull to identify genetic variants (SNP/indel). Using UnifiedGenotyper from the Genome Analysis Toolkit (GATK), we identified 6,812,198 SNPs and 804,453 indels. There were 2,598,000 (38.1%) novel SNPs and 607,923(75.6%) novel indels while...... the remaining was annotated in dbSNP build 133. In-depth annotation of the variants revealed that 45,776 SNPs affected the coding sequences of 11,538 genes, 221 SNPs predicted to cause a premature stop codon, 17 to cause a gain in coding sequence and 20,828 predicted to be non-synonymous. We identified 1...

  9. Variant Computer Aided Process Planning System for Rotational Parts

    Institute of Scientific and Technical Information of China (English)

    AHMED Hassan; YAO Zhen-qiang; CAI Jian-guo

    2005-01-01

    The amount of material must be removed away to produce the final product should minimize, excess stock will increase not only the material cost, but also processing cost, fixture cost, tooling cost, and increases machine cycle times.Noticing in recent years that the world is running out of mineral resources, and the price of engineering materials will continually rise in the future, the percentage of the cost of manufactured part that is due to the cost of materials is also rising. This paper proposed a variant CAPP system for rotational parts based on the concept of group technology,this system accepts part features characteristics code number as an input and provides operation details for manufacturing route with the suitable primary processes required to produce the blank work piece as an output.

  10. Different Variants of Fundamental Portfolio

    Directory of Open Access Journals (Sweden)

    Tarczyński Waldemar

    2014-06-01

    Full Text Available The paper proposes the fundamental portfolio of securities. This portfolio is an alternative for the classic Markowitz model, which combines fundamental analysis with portfolio analysis. The method’s main idea is based on the use of the TMAI1 synthetic measure and, in limiting conditions, the use of risk and the portfolio’s rate of return in the objective function. Different variants of fundamental portfolio have been considered under an empirical study. The effectiveness of the proposed solutions has been related to the classic portfolio constructed with the help of the Markowitz model and the WIG20 market index’s rate of return. All portfolios were constructed with data on rates of return for 2005. Their effectiveness in 2006- 2013 was then evaluated. The studied period comprises the end of the bull market, the 2007-2009 crisis, the 2010 bull market and the 2011 crisis. This allows for the evaluation of the solutions’ flexibility in various extreme situations. For the construction of the fundamental portfolio’s objective function and the TMAI, the study made use of financial and economic data on selected indicators retrieved from Notoria Serwis for 2005.

  11. Chemokine gene variants in schizophrenia.

    Science.gov (United States)

    Dasdemir, Selcuk; Kucukali, Cem Ismail; Bireller, Elif Sinem; Tuzun, Erdem; Cakmakoglu, Bedia

    2016-08-01

    Background Chemokines are known to play a major role in driving inflammation and immune responses in several neuroinflammatory diseases, including multiple sclerosis, Alzheimer's disease and Parkinson's disease. Inflammation has also been implicated in the pathogenesis of schizophrenia. Aim We aimed to investigate a potential link between chemokines and schizophrenia and analyze the role of MCP-1-A2518G, SDF-1-3'A, CCR5-delta32, CCR5-A55029G, CXCR4-C138T and CCR2-V64I gene polymorphisms in the Turkish population. Methods Genotyping was conducted by PCR-RFLP based on 140 patients and 123 unrelated healthy controls to show the relation between chemokine gene variants and schizophrenia risk. Results Frequencies of CCR5-A55029G A genotypes and CCR5-A55029G AG genotypes were found higher in patients than the controls and even also CCR2-V64I WT: CCR5-A55029G A and CCR2-V64I 64I: CCR5-A55029G A haplotypes significantly associated according to Bonferroni correction. However, no significant association was found for any of the other polymorphisms with the risk of schizophrenia. Conclusions Our findings suggest that CCR5-A55029G polymorphisms and CCR2-V64I WT: CCR5-A55029G A and CCR2-V64I 64I: CCR5-A55029G A haplotypes might have association with schizophrenia pathogenesis.

  12. Convolutional coding techniques for data protection

    Science.gov (United States)

    Massey, J. L.

    1975-01-01

    Results of research on the use of convolutional codes in data communications are presented. Convolutional coding fundamentals are discussed along with modulation and coding interaction. Concatenated coding systems and data compression with convolutional codes are described.

  13. Code Flows : Visualizing Structural Evolution of Source Code

    NARCIS (Netherlands)

    Telea, Alexandru; Auber, David

    2008-01-01

    Understanding detailed changes done to source code is of great importance in software maintenance. We present Code Flows, a method to visualize the evolution of source code geared to the understanding of fine and mid-level scale changes across several file versions. We enhance an existing visual met

  14. Code flows : Visualizing structural evolution of source code

    NARCIS (Netherlands)

    Telea, Alexandru; Auber, David

    2008-01-01

    Understanding detailed changes done to source code is of great importance in software maintenance. We present Code Flows, a method to visualize the evolution of source code geared to the understanding of fine and mid-level scale changes across several file versions. We enhance an existing visual met

  15. Mitochondrial variants in schizophrenia, bipolar disorder, and major depressive disorder.

    Directory of Open Access Journals (Sweden)

    Brandi Rollins

    Full Text Available BACKGROUND: Mitochondria provide most of the energy for brain cells by the process of oxidative phosphorylation. Mitochondrial abnormalities and deficiencies in oxidative phosphorylation have been reported in individuals with schizophrenia (SZ, bipolar disorder (BD, and major depressive disorder (MDD in transcriptomic, proteomic, and metabolomic studies. Several mutations in mitochondrial DNA (mtDNA sequence have been reported in SZ and BD patients. METHODOLOGY/PRINCIPAL FINDINGS: Dorsolateral prefrontal cortex (DLPFC from a cohort of 77 SZ, BD, and MDD subjects and age-matched controls (C was studied for mtDNA sequence variations and heteroplasmy levels using Affymetrix mtDNA resequencing arrays. Heteroplasmy levels by microarray were compared to levels obtained with SNaPshot and allele specific real-time PCR. This study examined the association between brain pH and mtDNA alleles. The microarray resequencing of mtDNA was 100% concordant with conventional sequencing results for 103 mtDNA variants. The rate of synonymous base pair substitutions in the coding regions of the mtDNA genome was 22% higher (p = 0.0017 in DLPFC of individuals with SZ compared to controls. The association of brain pH and super haplogroup (U, K, UK was significant (p = 0.004 and independent of postmortem interval time. CONCLUSIONS: Focusing on haplogroup and individual susceptibility factors in psychiatric disorders by considering mtDNA variants may lead to innovative treatments to improve mitochondrial health and brain function.

  16. Allele-specific methylation occurs at genetic variants associated with complex disease.

    Directory of Open Access Journals (Sweden)

    John N Hutchinson

    Full Text Available We hypothesize that the phenomenon of allele-specific methylation (ASM may underlie the phenotypic effects of multiple variants identified by Genome-Wide Association studies (GWAS. We evaluate ASM in a human population and document its genome-wide patterns in an initial screen at up to 380,678 sites within the genome, or up to 5% of the total genomic CpGs. We show that while substantial inter-individual variation exists, 5% of assessed sites show evidence of ASM in at least six samples; the majority of these events (81% are under genetic influence. Many of these cis-regulated ASM variants are also eQTLs in peripheral blood mononuclear cells and monocytes and/or in high linkage-disequilibrium with variants linked to complex disease. Finally, focusing on autoimmune phenotypes, we extend this initial screen to confirm the association of cis-regulated ASM with multiple complex disease-associated variants in an independent population using next-generation bisulfite sequencing. These four variants are implicated in complex phenotypes such as ulcerative colitis and AIDS progression disease (rs10491434, Celiac disease (rs2762051, Crohn's disease, IgA nephropathy and early-onset inflammatory bowel disease (rs713875 and height (rs6569648. Our results suggest cis-regulated ASM may provide a mechanistic link between the non-coding genetic changes and phenotypic variation observed in these diseases and further suggests a route to integrating DNA methylation status with GWAS results.

  17. A Large French Case-Control Study Emphasizes the Role of Rare Mc1R Variants in Melanoma Risk

    Directory of Open Access Journals (Sweden)

    Hui-Han Hu

    2014-01-01

    Full Text Available Background. The MC1R gene implicated in melanogenesis and skin pigmentation is highly polymorphic. Several alleles are associated with red hair and fair skin phenotypes and contribute to melanoma risk. Objective. This work aims to assess the effect of different classes of MC1R variants, notably rare variants, on melanoma risk. Methods. MC1R coding region was sequenced in 1131 melanoma patients and 869 healthy controls. MC1R variants were classified as RHC (R and non-RHC (r. Rare variants (frequency < 1% were subdivided into two subgroups, predicted to be damaging (D or not (nD. Results. Both R and r alleles were associated with melanoma (OR = 2.66 [2.20–3.23] and 1.51 [1.32–1.73] and had similar population attributable risks (15.8% and 16.6%. We also identified 69 rare variants, of which 25 were novel. D variants were strongly associated with melanoma (OR = 2.38 [1.38–4.15] and clustered in the same MC1R domains as R alleles (intracellular 2, transmembrane 2 and 7. Conclusion. This work confirms the role of R and r alleles in melanoma risk in the French population and proposes a novel class of rare D variants as important melanoma risk factors. These findings may improve the definition of high-risk subjects that could be targeted for melanoma prevention and screening.

  18. Bias of selection on human copy-number variants.

    Directory of Open Access Journals (Sweden)

    2006-02-01

    Full Text Available Although large-scale copy-number variation is an important contributor to conspecific genomic diversity, whether these variants frequently contribute to human phenotype differences remains unknown. If they have few functional consequences, then copy-number variants (CNVs might be expected both to be distributed uniformly throughout the human genome and to encode genes that are characteristic of the genome as a whole. We find that human CNVs are significantly overrepresented close to telomeres and centromeres and in simple tandem repeat sequences. Additionally, human CNVs were observed to be unusually enriched in those protein-coding genes that have experienced significantly elevated synonymous and nonsynonymous nucleotide substitution rates, estimated between single human and mouse orthologues. CNV genes encode disproportionately large numbers of secreted, olfactory, and immunity proteins, although they contain fewer than expected genes associated with Mendelian disease. Despite mouse CNVs also exhibiting a significant elevation in synonymous substitution rates, in most other respects they do not differ significantly from the genomic background. Nevertheless, they encode proteins that are depleted in olfactory function, and they exhibit significantly decreased amino acid sequence divergence. Natural selection appears to have acted discriminately among human CNV genes. The significant overabundance, within human CNVs, of genes associated with olfaction, immunity, protein secretion, and elevated coding sequence divergence, indicates that a subset may have been retained in the human population due to the adaptive benefit of increased gene dosage. By contrast, the functional characteristics of mouse CNVs either suggest that advantageous gene copies have been depleted during recent selective breeding of laboratory mouse strains or suggest that they were preferentially fixed as a consequence of the larger effective population size of wild mice. It

  19. Histological variants of cutaneous Kaposi sarcoma

    Directory of Open Access Journals (Sweden)

    Pantanowitz Liron

    2008-07-01

    Full Text Available Abstract This review provides a comprehensive overview of the broad clinicopathologic spectrum of cutaneous Kaposi sarcoma (KS lesions. Variants discussed include: usual KS lesions associated with disease progression (i.e. patch, plaque and nodular stage; morphologic subtypes alluded to in the older literature such as anaplastic and telangiectatic KS, as well as several lymphedematous variants; and numerous recently described variants including hyperkeratotic, keloidal, micronodular, pyogenic granuloma-like, ecchymotic, and intravascular KS. Involuting lesions as a result of treatment related regression are also presented.

  20. Ultrasonographic imaging of papillary thyroid carcinoma variants

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Jung Hee [Dept. of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2017-04-15

    Ultrasonography (US) is routinely used to evaluate thyroid nodules. The US features of papillary thyroid carcinoma (PTC), the most common thyroid malignancy, include hypoechogenicity, spiculated/microlobulated margins, microcalcifications, and a nonparallel orientation. However, many PTC variants have been identified, some of which differ from the classic type of PTC in terms of biological behavior and clinical outcomes. This review describes the US features and clinical implications of the variants of PTC. With the introduction of active surveillance replacing immediate biopsy or surgical treatment of indolent, small PTCs, an understanding of the US characteristics of PTC variants will facilitate the individualized management of patients with PTC.

  1. Identification of Claudin 1 Transcript Variants in Human Invasive Breast Cancer

    Science.gov (United States)

    Zelinski, Teresa; Xie, Jiuyong; Cooper, Steven; Penner, Carla; Leygue, Etienne; Myal, Yvonne

    2016-01-01

    Background The claudin 1 tight junction protein, solely responsible for the barrier function of epithelial cells, is frequently down regulated in invasive human breast cancer. The underlying mechanism is largely unknown, and no obvious mutations in the claudin 1 gene (CLDN1) have been identified to date in breast cancer. Since many genes have been shown to undergo deregulation through splicing and mis-splicing events in cancer, the current study was undertaken to investigate the occurrence of transcript variants for CLDN1 in human invasive breast cancer. Methods RT-PCR analysis of CLDN1 transcripts was conducted on RNA isolated from 12 human invasive breast tumors. The PCR products from each tumor were resolved by agarose gel electrophoresis, cloned and sequenced. Genomic DNA was also isolated from each of the 12 tumors and amplified using PCR CLDN1 specific primers. Sanger sequencing and single nucleotide polymorphism (SNP) analyses were conducted. Results A number of CLDN1 transcript variants were identified in these breast tumors. All variants were shorter than the classical CLDN1 transcript. Sequence analysis of the PCR products revealed several splice variants, primarily in exon 1 of CLDN1; resulting in truncated proteins. One variant, V1, resulted in a premature stop codon and thus likely led to nonsense mediated decay. Interestingly, another transcript variant, V2, was not detected in normal breast tissue samples. Further, sequence analysis of the tumor genomic DNA revealed SNPs in 3 of the 4 coding exons, including a rare missense SNP (rs140846629) in exon 2 which represents an Ala124Thr substitution. To our knowledge this is the first report of CLDN1 transcript variants in human invasive breast cancer. These studies suggest that alternate splicing may also be a mechanism by which claudin 1 is down regulated at both the mRNA and protein levels in invasive breast cancer and may provide novel insights into how CLDN1 is reduced or silenced in human breast

  2. Exome sequencing identifies a rare HSPG2 variant associated with familial idiopathic scoliosis.

    Science.gov (United States)

    Baschal, Erin E; Wethey, Cambria I; Swindle, Kandice; Baschal, Robin M; Gowan, Katherine; Tang, Nelson L S; Alvarado, David M; Haller, Gabe E; Dobbs, Matthew B; Taylor, Matthew R G; Gurnett, Christina A; Jones, Kenneth L; Miller, Nancy H

    2014-12-12

    Idiopathic scoliosis occurs in 3% of individuals and has an unknown etiology. The objective of this study was to identify rare variants that contribute to the etiology of idiopathic scoliosis by using exome sequencing in a multigenerational family with idiopathic scoliosis. Exome sequencing was completed for three members of this multigenerational family with idiopathic scoliosis, resulting in the identification of a variant in the HSPG2 gene as a potential contributor to the phenotype. The HSPG2 gene was sequenced in a separate cohort of 100 unrelated individuals affected with idiopathic scoliosis and also was examined in an independent idiopathic scoliosis population. The exome sequencing and subsequent bioinformatics filtering resulted in 16 potentially damaging and rare coding variants. One of these variants, p.Asn786Ser, is located in the HSPG2 gene. The variant p.Asn786Ser also is overrepresented in a larger cohort of idiopathic scoliosis cases compared with a control population (P = 0.024). Furthermore, we identified additional rare HSPG2 variants that are predicted to be damaging in two independent cohorts of individuals with idiopathic scoliosis. The HSPG2 gene encodes for a ubiquitous multifunctional protein within the extracellular matrix in which loss of function mutation are known to result in a musculoskeletal phenotype in both mouse and humans. Based on these results, we conclude that rare variants in the HSPG2 gene potentially contribute to the idiopathic scoliosis phenotype in a subset of patients with idiopathic scoliosis. Further studies must be completed to confirm the effect of the HSPG2 gene on the idiopathic scoliosis phenotype.

  3. What Froze the Genetic Code?

    National Research Council Canada - National Science Library

    Lluís Ribas de Pouplana; Adrian Gabriel Torres; albert Rafels-Ybern

    2017-01-01

    The frozen accident theory of the Genetic Code was a proposal by Francis Crick that attempted to explain the universal nature of the Genetic Code and the fact that it only contains information for twenty amino acids...

  4. Decoding Xing-Ling codes

    DEFF Research Database (Denmark)

    Nielsen, Rasmus Refslund

    2002-01-01

    This paper describes an efficient decoding method for a recent construction of good linear codes as well as an extension to the construction. Furthermore, asymptotic properties and list decoding of the codes are discussed.......This paper describes an efficient decoding method for a recent construction of good linear codes as well as an extension to the construction. Furthermore, asymptotic properties and list decoding of the codes are discussed....

  5. The path of code linting

    CERN Document Server

    CERN. Geneva

    2017-01-01

    Join the path of code linting and discover how it can help you reach higher levels of programming enlightenment. Today we will cover how to embrace code linters to offload cognitive strain on preserving style standards in your code base as well as avoiding error-prone constructs. Additionally, I will show you the journey ahead for integrating several code linters in the programming tools your already use with very little effort.

  6. Multiple LDPC decoding for distributed source coding and video coding

    DEFF Research Database (Denmark)

    Forchhammer, Søren; Luong, Huynh Van; Huang, Xin

    2011-01-01

    Distributed source coding (DSC) is a coding paradigm for systems which fully or partly exploit the source statistics at the decoder to reduce the computational burden at the encoder. Distributed video coding (DVC) is one example. This paper considers the use of Low Density Parity Check Accumulate...... (LDPCA) codes in a DSC scheme with feed-back. To improve the LDPC coding performance in the context of DSC and DVC, while retaining short encoder blocks, this paper proposes multiple parallel LDPC decoding. The proposed scheme passes soft information between decoders to enhance performance. Experimental...

  7. Code stroke in Asturias.

    Science.gov (United States)

    Benavente, L; Villanueva, M J; Vega, P; Casado, I; Vidal, J A; Castaño, B; Amorín, M; de la Vega, V; Santos, H; Trigo, A; Gómez, M B; Larrosa, D; Temprano, T; González, M; Murias, E; Calleja, S

    2016-04-01

    Intravenous thrombolysis with alteplase is an effective treatment for ischaemic stroke when applied during the first 4.5 hours, but less than 15% of patients have access to this technique. Mechanical thrombectomy is more frequently able to recanalise proximal occlusions in large vessels, but the infrastructure it requires makes it even less available. We describe the implementation of code stroke in Asturias, as well as the process of adapting various existing resources for urgent stroke care in the region. By considering these resources, and the demographic and geographic circumstances of our region, we examine ways of reorganising the code stroke protocol that would optimise treatment times and provide the most appropriate treatment for each patient. We distributed the 8 health districts in Asturias so as to permit referral of candidates for reperfusion therapies to either of the 2 hospitals with 24-hour stroke units and on-call neurologists and providing IV fibrinolysis. Hospitals were assigned according to proximity and stroke severity; the most severe cases were immediately referred to the hospital with on-call interventional neurology care. Patient triage was provided by pre-hospital emergency services according to the NIHSS score. Modifications to code stroke in Asturias have allowed us to apply reperfusion therapies with good results, while emphasising equitable care and managing the severity-time ratio to offer the best and safest treatment for each patient as soon as possible. Copyright © 2015 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  8. MHD Generation Code

    OpenAIRE

    Frutos-Alfaro, Francisco; Carboni-Mendez, Rodrigo

    2015-01-01

    A program to generate codes in Fortran and C of the full Magnetohydrodynamic equations is shown. The program used the free computer algebra system software REDUCE. This software has a package called EXCALC, which is an exterior calculus program. The advantage of this program is that it can be modified to include another complex metric or spacetime. The output of this program is modified by means of a LINUX script which creates a new REDUCE program to manipulate the MHD equations to obtain a c...

  9. Cinder begin creative coding

    CERN Document Server

    Rijnieks, Krisjanis

    2013-01-01

    Presented in an easy to follow, tutorial-style format, this book will lead you step-by-step through the multi-faceted uses of Cinder.""Cinder: Begin Creative Coding"" is for people who already have experience in programming. It can serve as a transition from a previous background in Processing, Java in general, JavaScript, openFrameworks, C++ in general or ActionScript to the framework covered in this book, namely Cinder. If you like quick and easy to follow tutorials that will let yousee progress in less than an hour - this book is for you. If you are searching for a book that will explain al

  10. Code Optimization in FORM

    CERN Document Server

    Kuipers, J; Vermaseren, J A M

    2013-01-01

    We describe the implementation of output code optimization in the open source computer algebra system FORM. This implementation is based on recently discovered techniques of Monte Carlo tree search to find efficient multivariate Horner schemes, in combination with other optimization algorithms, such as common subexpression elimination. For systems for which no specific knowledge is provided it performs significantly better than other methods we could compare with. Because the method has a number of free parameters, we also show some methods by which to tune them to different types of problems.

  11. Topological code Autotune

    CERN Document Server

    Fowler, Austin G; McInnes, Angus L; Rabbani, Alimohammad

    2012-01-01

    Tailoring a fault-tolerant quantum error correction scheme to a specific physical architecture can be a laborious task. We describe a tool Autotune capable of analyzing and optimizing the classical processing for an arbitrary 2-D qubit architecture making use of arbitrary circuits implementing either the surface code or progressively generated slices of a 3-D topological cluster state with arbitrary stochastic error models for each quantum gate. Autotune is designed to facilitate precise study of the performance of real hardware running topological quantum error correction.

  12. Code Generation with Templates

    CERN Document Server

    Arnoldus, Jeroen; Serebrenik, A

    2012-01-01

    Templates are used to generate all kinds of text, including computer code. The last decade, the use of templates gained a lot of popularity due to the increase of dynamic web applications. Templates are a tool for programmers, and implementations of template engines are most times based on practical experience rather than based on a theoretical background. This book reveals the mathematical background of templates and shows interesting findings for improving the practical use of templates. First, a framework to determine the necessary computational power for the template metalanguage is presen

  13. Memory Code©

    OpenAIRE

    Gómez-Londoño, Ana María

    2013-01-01

    El proyecto Memory Code© pertenece al ámbito de las cosmopolíticas del arte contemporáneo porque se ocupa de una relación singular de lo humano (mujer) con lo no-humano (caballo y técnicas)5. Específicamente enmarca el estudio del Binomio Ecuestre: caballo-jinete en el marco de una relación afectiva y de adiestramiento (doma clásica). Dicha relación estuvo compuesta por los siguientes operadores : a) Elementos de con-tacto entre jinete-caballo: espuelas, estribus, fustas b) Sistemas rítmicos ...

  14. Wavefront coding with adaptive optics

    Science.gov (United States)

    Agbana, Temitope E.; Soloviev, Oleg; Bezzubik, Vitalii; Patlan, Vsevolod; Verhaegen, Michel; Vdovin, Gleb

    2015-03-01

    We have implemented an extended depth of field optical system by wavefront coding with a micromachined membrane deformable mirror. This approach provides a versatile extension to standard wavefront coding based on fixed phase mask. First experimental results validate the feasibility of the use of adaptive optics for variable depth wavefront coding in imaging optical systems.

  15. Authorship Attribution of Source Code

    Science.gov (United States)

    Tennyson, Matthew F.

    2013-01-01

    Authorship attribution of source code is the task of deciding who wrote a program, given its source code. Applications include software forensics, plagiarism detection, and determining software ownership. A number of methods for the authorship attribution of source code have been presented in the past. A review of those existing methods is…

  16. Strongly-MDS convolutional codes

    NARCIS (Netherlands)

    Gluesing-Luerssen, H; Rosenthal, J; Smarandache, R

    2006-01-01

    Maximum-distance separable (MDS) convolutional codes have the property that their free distance is maximal among all codes of the same rate and the same degree. In this paper, a class of MDS convolutional codes is introduced whose column distances reach the generalized Singleton bound at the earlies

  17. Improved code-tracking loop

    Science.gov (United States)

    Laflame, D. T.

    1980-01-01

    Delay-locked loop tracks pseudonoise codes without introducing dc timing errors, because it is not sensitive to gain imbalance between signal processing arms. "Early" and "late" reference codes pass in combined form through both arms, and each arm acts on both codes. Circuit accomodates 1 dB weaker input signals with tracking ability equal to that of tau-dither loops.

  18. On Maximum Lee Distance Codes

    OpenAIRE

    Alderson, Tim L.; Svenja Huntemann

    2013-01-01

    Singleton-type upper bounds on the minimum Lee distance of general (not necessarily linear) Lee codes over ℤq are discussed. Two bounds known for linear codes are shown to also hold in the general case, and several new bounds are established. Codes meeting these bounds are investigated and in some cases characterised.

  19. Coding Issues in Grounded Theory

    Science.gov (United States)

    Moghaddam, Alireza

    2006-01-01

    This paper discusses grounded theory as one of the qualitative research designs. It describes how grounded theory generates from data. Three phases of grounded theory--open coding, axial coding, and selective coding--are discussed, along with some of the issues which are the source of debate among grounded theorists, especially between its…

  20. The Weights in MDS Codes

    CERN Document Server

    Ezerman, Martianus Frederic; Sole, Patrick

    2009-01-01

    The weights in MDS codes of length n and dimension k over the finite field GF(q) are studied. Up to some explicit exceptional cases, the MDS codes with parameters given by the MDS conjecture are shown to contain all k weights in the range n-k+1 to n. The proof uses the covering radius of the dual code

  1. Coding Issues in Grounded Theory

    Science.gov (United States)

    Moghaddam, Alireza

    2006-01-01

    This paper discusses grounded theory as one of the qualitative research designs. It describes how grounded theory generates from data. Three phases of grounded theory--open coding, axial coding, and selective coding--are discussed, along with some of the issues which are the source of debate among grounded theorists, especially between its…

  2. Order functions and evaluation codes

    DEFF Research Database (Denmark)

    Høholdt, Tom; Pellikaan, Ruud; van Lint, Jack

    1997-01-01

    Based on the notion of an order function we construct and determine the parameters of a class of error-correcting evaluation codes. This class includes the one-point algebraic geometry codes as wella s the generalized Reed-Muller codes and the parameters are detremined without using the heavy...

  3. Order functions and evaluation codes

    DEFF Research Database (Denmark)

    Høholdt, Tom; Pellikaan, Ruud; van Lint, Jack

    1997-01-01

    Based on the notion of an order function we construct and determine the parameters of a class of error-correcting evaluation codes. This class includes the one-point algebraic geometry codes as wella s the generalized Reed-Muller codes and the parameters are detremined without using the heavy...... machinery of algebraic geometry....

  4. A class of constacyclic BCH codes and new quantum codes

    Science.gov (United States)

    liu, Yang; Li, Ruihu; Lv, Liangdong; Ma, Yuena

    2017-03-01

    Constacyclic BCH codes have been widely studied in the literature and have been used to construct quantum codes in latest years. However, for the class of quantum codes of length n=q^{2m}+1 over F_{q^2} with q an odd prime power, there are only the ones of distance δ ≤ 2q^2 are obtained in the literature. In this paper, by a detailed analysis of properties of q2-ary cyclotomic cosets, maximum designed distance δ _{max} of a class of Hermitian dual-containing constacyclic BCH codes with length n=q^{2m}+1 are determined, this class of constacyclic codes has some characteristic analog to that of primitive BCH codes over F_{q^2}. Then we can obtain a sequence of dual-containing constacyclic codes of designed distances 2q^2 2q^2 can be constructed from these dual-containing codes via Hermitian Construction. These newly obtained quantum codes have better code rate compared with those constructed from primitive BCH codes.

  5. ON CLASSICAL BCH CODES AND QUANTUM BCH CODES

    Institute of Scientific and Technical Information of China (English)

    Xu Yajie; Ma Zhi; Zhang Chunyuan

    2009-01-01

    It is a regular way of constructing quantum error-correcting codes via codes with self-orthogonal property, and whether a classical Bose-Chaudhuri-Hocquenghem (BCH) code is self-orthogonal can be determined by its designed distance. In this paper, we give the sufficient and necessary condition for arbitrary classical BCH codes with self-orthogonal property through algorithms. We also give a better upper bound of the designed distance of a classical narrow-sense BCH code which contains its Euclidean dual. Besides these, we also give one algorithm to compute the dimension of these codes. The complexity of all algorithms is analyzed. Then the results can be applied to construct a series of quantum BCH codes via the famous CSS constructions.

  6. New quantum codes constructed from quaternary BCH codes

    Science.gov (United States)

    Xu, Gen; Li, Ruihu; Guo, Luobin; Ma, Yuena

    2016-10-01

    In this paper, we firstly study construction of new quantum error-correcting codes (QECCs) from three classes of quaternary imprimitive BCH codes. As a result, the improved maximal designed distance of these narrow-sense imprimitive Hermitian dual-containing quaternary BCH codes are determined to be much larger than the result given according to Aly et al. (IEEE Trans Inf Theory 53:1183-1188, 2007) for each different code length. Thus, families of new QECCs are newly obtained, and the constructed QECCs have larger distance than those in the previous literature. Secondly, we apply a combinatorial construction to the imprimitive BCH codes with their corresponding primitive counterpart and construct many new linear quantum codes with good parameters, some of which have parameters exceeding the finite Gilbert-Varshamov bound for linear quantum codes.

  7. Structured error recovery for code-word-stabilized quantum codes

    Science.gov (United States)

    Li, Yunfan; Dumer, Ilya; Grassl, Markus; Pryadko, Leonid P.

    2010-05-01

    Code-word-stabilized (CWS) codes are, in general, nonadditive quantum codes that can correct errors by an exhaustive search of different error patterns, similar to the way that we decode classical nonlinear codes. For an n-qubit quantum code correcting errors on up to t qubits, this brute-force approach consecutively tests different errors of weight t or less and employs a separate n-qubit measurement in each test. In this article, we suggest an error grouping technique that allows one to simultaneously test large groups of errors in a single measurement. This structured error recovery technique exponentially reduces the number of measurements by about 3t times. While it still leaves exponentially many measurements for a generic CWS code, the technique is equivalent to syndrome-based recovery for the special case of additive CWS codes.

  8. On (Partial) Unit Memory Codes Based on Gabidulin Codes

    CERN Document Server

    Wachter, Antonia; Bossert, Martin; Zyablov, Victor

    2011-01-01

    (Partial) Unit Memory ((P)UM) codes provide a powerful possibility to construct convolutional codes based on block codes in order to achieve a high decoding performance. In this contribution, a construction based on Gabidulin codes is considered. This construction requires a modified rank metric, the so-called sum rank metric. For the sum rank metric, the free rank distance, the extended row rank distance and its slope are defined analogous to the extended row distance in Hamming metric. Upper bounds for the free rank distance and the slope of (P)UM codes in the sum rank metric are derived and an explicit construction of (P)UM codes based on Gabidulin codes is given, achieving the upper bound for the free rank distance.

  9. Histone variants in plant transcriptional regulation.

    Science.gov (United States)

    Jiang, Danhua; Berger, Frédéric

    2017-01-01

    Chromatin based organization of eukaryotic genome plays a profound role in regulating gene transcription. Nucleosomes form the basic subunits of chromatin by packaging DNA with histone proteins, impeding the access of DNA to transcription factors and RNA polymerases. Exchange of histone variants in nucleosomes alters the properties of nucleosomes and thus modulates DNA exposure during transcriptional regulation. Growing evidence indicates the important function of histone variants in programming transcription during developmental transitions and stress response. Here we review how histone variants and their deposition machineries regulate the nucleosome stability and dynamics, and discuss the link between histone variants and transcriptional regulation in plants. This article is part of a Special Issue entitled: Plant Gene Regulatory Mechanisms and Networks, edited by Dr. Erich Grotewold and Dr. Nathan Springer.

  10. TCM Differential Treatment of Cough Variant Asthma

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhong-de; DENG Yi-qi; ZHANG Yu; HAN Yun; LIN Lin; CHAO En-xiang

    2010-01-01

    @@ Cough variant asthma (CVA), also called latent asthma or cough asthma, is a special type of asthma. With gradually deepened understanding of CVA in recent years, good curative effect has been achieved in TCM treatment of CVA.

  11. Bisalbuminemia. A new molecular variant, albumin Vancouver.

    Science.gov (United States)

    Frohlich, J; Kozier, J; Campbell, D J; Curnow, J V; Tárnoky, A L

    1978-11-01

    Of 18 members of a Fiji Indian family investigated, eight of the 12 males and two of the six females had an electrophoretically slow-type bisalbuminemia (alloalbuminemia). The albumin was characterized by the hiterto unique ratio of the two bands (Al A 35%: variant 65%), and by dye-binding studies and electrophoretic mobility in different media. The data suggest that this is a new variant, which we propose to call albumin Vancouver (Al Va).

  12. Another new variant of Bouveret's syndrome

    Institute of Scientific and Technical Information of China (English)

    Seong-Heum Park; Sang-Woo Lee; Tae-Jin Song

    2009-01-01

    Although Bouveret's syndrome, i.e. gastric outlet obstruction by a large gallstone impacted in the proximal duodenum secondary to a cholecystoduodenal fistula,is rare, its pathogenesis and clinical features are well characterized. However, existence of variant forms of the syndrome are not well known, and as far as we have been described in the English-language literature.We present a case of another new variant of Bouveret's syndrome in a 54-year-old Korean woman.

  13. Investigation of the role of rare TREM2 variants in frontotemporal dementia subtypes.

    Science.gov (United States)

    Thelen, Mathias; Razquin, Cristina; Hernández, Isabel; Gorostidi, Ana; Sánchez-Valle, Raquel; Ortega-Cubero, Sara; Wolfsgruber, Steffen; Drichel, Dmitriy; Fliessbach, Klaus; Duenkel, Tanja; Damian, Marinella; Heilmann, Stefanie; Slotosch, Anja; Lennarz, Martina; Seijo-Martínez, Manuel; Rene, Ramón; Kornhuber, Johannes; Peters, Oliver; Luckhaus, Christian; Jahn, Holger; Hüll, Michael; Rüther, Eckart; Wiltfang, Jens; Lorenzo, Elena; Gascon, Jordi; Lleó, Alberto; Lladó, Albert; Campdelacreu, Jaume; Moreno, Fermin; Ahmadzadehfar, Hojjat; Fortea, Juan; Indakoetxea, Begoña; Heneka, Michael T; Wetter, Axel; Pastor, Maria A; Riverol, Mario; Becker, Tim; Frölich, Lutz; Tárraga, Lluís; Boada, Mercè; Wagner, Michael; Jessen, Frank; Maier, Wolfgang; Clarimón, Jordi; López de Munain, Adolfo; Ruiz, Agustín; Pastor, Pau; Ramirez, Alfredo

    2014-11-01

    Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous disorder. Rare TREM2 variants have been recently identified in families affected by FTD-like phenotype. However, genetic studies of the role of rare TREM2 variants in FTD have generated conflicting results possibly because of difficulties on diagnostic accuracy. The aim of the present study was to investigate associations between rare TREM2 variants and specific FTD subtypes (FTD-S). The entire coding sequence of TREM2 was sequenced in FTD-S patients of Spanish (n = 539) and German (n = 63) origin. Genetic association was calculated using Fisher exact test. The minor allele frequency for controls was derived from in-house genotyping data and publicly available databases. Seven previously reported rare coding variants (p.A28V, p.W44X, p.R47H, p.R62H, p.T66M, p.T96K, and p.L211P) and 1 novel missense variant (p.A105T) were identified. The p.R47H variant was found in 4 patients with FTD-S. Two of these patients showed cerebrospinal fluid pattern of amyloid beta, tau, and phosphorylated-tau suggesting underlying Alzheimer's disease (AD) pathology. No association was found between p.R47H and FTD-S. A genetic association was found between p.T96K and FTD-S (p = 0.013, odds ratio = 4.23, 95% Confidence Interval [1.17-14.77]). All 6 p.T96K patients also carried the TREM2 variant p.L211P, suggesting linkage disequilibrium. The remaining TREM2 variants were found in 1 patient, respectively, and were absent in controls. The present findings provide evidence that p.T96K is associated with FTD-S and that p.L211P may contribute to its pathogenic effect. The data also suggest that p.R47H is associated with an FTD phenotype that is characterized by the presence of underlying AD pathology.

  14. Brief Analysis of Regional Variants in English%Brief Analysis of Regional Variants in Enghsh

    Institute of Scientific and Technical Information of China (English)

    张炳科

    2008-01-01

    It is universally acknowledged that regional variants exist in each language, for it is impossible that people always employ the same pronunciation or vocabulary or even grammar to express the same meaning no matter how large the scope in which a language is used may be. The author of this paper is just to exemplify some regional variants in English and to analyze the factors that account for the variants ,with the purpose of teaching English well in the most efficient way.

  15. Physical Layer Network Coding

    DEFF Research Database (Denmark)

    Fukui, Hironori; Yomo, Hironori; Popovski, Petar

    2013-01-01

    Physical layer network coding (PLNC) has the potential to improve throughput of multi-hop networks. However, most of the works are focused on the simple, three-node model with two-way relaying, not taking into account the fact that there can be other neighboring nodes that can cause/receive inter......Physical layer network coding (PLNC) has the potential to improve throughput of multi-hop networks. However, most of the works are focused on the simple, three-node model with two-way relaying, not taking into account the fact that there can be other neighboring nodes that can cause....../receive interference. The way to deal with this problem in distributed wireless networks is usage of MAC-layer mechanisms that make a spatial reservation of the shared wireless medium, similar to the well-known RTS/CTS in IEEE 802.11 wireless networks. In this paper, we investigate two-way relaying in presence...

  16. Security Embedding Codes

    CERN Document Server

    Ly, Hung D; Blankenship, Yufei

    2011-01-01

    This paper considers the problem of simultaneously communicating two messages, a high-security message and a low-security message, to a legitimate receiver, referred to as the security embedding problem. An information-theoretic formulation of the problem is presented. A coding scheme that combines rate splitting, superposition coding, nested binning and channel prefixing is considered and is shown to achieve the secrecy capacity region of the channel in several scenarios. Specifying these results to both scalar and independent parallel Gaussian channels (under an average individual per-subchannel power constraint), it is shown that the high-security message can be embedded into the low-security message at full rate (as if the low-security message does not exist) without incurring any loss on the overall rate of communication (as if both messages are low-security messages). Extensions to the wiretap channel II setting of Ozarow and Wyner are also considered, where it is shown that "perfect" security embedding...

  17. Supervised Transfer Sparse Coding

    KAUST Repository

    Al-Shedivat, Maruan

    2014-07-27

    A combination of the sparse coding and transfer learn- ing techniques was shown to be accurate and robust in classification tasks where training and testing objects have a shared feature space but are sampled from differ- ent underlying distributions, i.e., belong to different do- mains. The key assumption in such case is that in spite of the domain disparity, samples from different domains share some common hidden factors. Previous methods often assumed that all the objects in the target domain are unlabeled, and thus the training set solely comprised objects from the source domain. However, in real world applications, the target domain often has some labeled objects, or one can always manually label a small num- ber of them. In this paper, we explore such possibil- ity and show how a small number of labeled data in the target domain can significantly leverage classifica- tion accuracy of the state-of-the-art transfer sparse cod- ing methods. We further propose a unified framework named supervised transfer sparse coding (STSC) which simultaneously optimizes sparse representation, domain transfer and classification. Experimental results on three applications demonstrate that a little manual labeling and then learning the model in a supervised fashion can significantly improve classification accuracy.

  18. Histone variants: key players of chromatin.

    Science.gov (United States)

    Biterge, Burcu; Schneider, Robert

    2014-06-01

    Histones are fundamental structural components of chromatin. Eukaryotic DNA is wound around an octamer of the core histones H2A, H2B, H3, and H4. Binding of linker histone H1 promotes higher order chromatin organization. In addition to their structural role, histones impact chromatin function and dynamics by, e.g., post-translational histone modifications or the presence of specific histone variants. Histone variants exhibit differential expression timings (DNA replication-independent) and mRNA characteristics compared to canonical histones. Replacement of canonical histones with histone variants can affect nucleosome stability and help to create functionally distinct chromatin domains. In line with this, several histone variants have been implicated in the regulation of cellular processes such as DNA repair and transcriptional activity. In this review, we focus on recent progress in the study of core histone variants H2A.X, H2A.Z, macroH2A, H3.3, and CENP-A, as well as linker histone H1 variants, their functions and their links to development and disease.

  19. A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk.

    Science.gov (United States)

    Manning, Alisa; Highland, Heather M; Gasser, Jessica; Sim, Xueling; Tukiainen, Taru; Fontanillas, Pierre; Grarup, Niels; Rivas, Manuel A; Mahajan, Anubha; Locke, Adam E; Cingolani, Pablo; Pers, Tune H; Viñuela, Ana; Brown, Andrew A; Wu, Ying; Flannick, Jason; Fuchsberger, Christian; Gamazon, Eric R; Gaulton, Kyle J; Im, Hae Kyung; Teslovich, Tanya M; Blackwell, Thomas W; Bork-Jensen, Jette; Burtt, Noël P; Chen, Yuhui; Green, Todd; Hartl, Christopher; Kang, Hyun Min; Kumar, Ashish; Ladenvall, Claes; Ma, Clement; Moutsianas, Loukas; Pearson, Richard D; Perry, John R B; Rayner, N William; Robertson, Neil R; Scott, Laura J; van de Bunt, Martijn; Eriksson, Johan G; Jula, Antti; Koskinen, Seppo; Lehtimäki, Terho; Palotie, Aarno; Raitakari, Olli T; Jacobs, Suzanne B R; Wessel, Jennifer; Chu, Audrey Y; Scott, Robert A; Goodarzi, Mark O; Blancher, Christine; Buck, Gemma; Buck, David; Chines, Peter S; Gabriel, Stacey; Gjesing, Anette P; Groves, Christopher J; Hollensted, Mette; Huyghe, Jeroen R; Jackson, Anne U; Jun, Goo; Justesen, Johanne Marie; Mangino, Massimo; Murphy, Jacquelyn; Neville, Matt; Onofrio, Robert; Small, Kerrin S; Stringham, Heather M; Trakalo, Joseph; Banks, Eric; Carey, Jason; Carneiro, Mauricio O; DePristo, Mark; Farjoun, Yossi; Fennell, Timothy; Goldstein, Jacqueline I; Grant, George; Hrabé de Angelis, Martin; Maguire, Jared; Neale, Benjamin M; Poplin, Ryan; Purcell, Shaun; Schwarzmayr, Thomas; Shakir, Khalid; Smith, Joshua D; Strom, Tim M; Wieland, Thomas; Lindstrom, Jaana; Brandslund, Ivan; Christensen, Cramer; Surdulescu, Gabriela L; Lakka, Timo A; Doney, Alex S F; Nilsson, Peter; Wareham, Nicholas J; Langenberg, Claudia; Varga, Tibor V; Franks, Paul W; Rolandsson, Olov; Rosengren, Anders H; Farook, Vidya S; Thameem, Farook; Puppala, Sobha; Kumar, Satish; Lehman, Donna M; Jenkinson, Christopher P; Curran, Joanne E; Hale, Daniel Esten; Fowler, Sharon P; Arya, Rector; DeFronzo, Ralph A; Abboud, Hanna E; Syvänen, Ann-Christine; Hicks, Pamela J; Palmer, Nicholette D; Ng, Maggie C Y; Bowden, Donald W; Freedman, Barry I; Esko, Tõnu; Mägi, Reedik; Milani, Lili; Mihailov, Evelin; Metspalu, Andres; Narisu, Narisu; Kinnunen, Leena; Bonnycastle, Lori L; Swift, Amy; Pasko, Dorota; Wood, Andrew R; Fadista, João; Pollin, Toni I; Barzilai, Nir; Atzmon, Gil; Glaser, Benjamin; Thorand, Barbara; Strauch, Konstantin; Peters, Annette; Roden, Michael; Müller-Nurasyid, Martina; Liang, Liming; Kriebel, Jennifer; Illig, Thomas; Grallert, Harald; Gieger, Christian; Meisinger, Christa; Lannfelt, Lars; Musani, Solomon K; Griswold, Michael; Taylor, Herman A; Wilson, Gregory; Correa, Adolfo; Oksa, Heikki; Scott, William R; Afzal, Uzma; Tan, Sian-Tsung; Loh, Marie; Chambers, John C; Sehmi, Jobanpreet; Kooner, Jaspal Singh; Lehne, Benjamin; Cho, Yoon Shin; Lee, Jong-Young; Han, Bok-Ghee; Käräjämäki, Annemari; Qi, Qibin; Qi, Lu; Huang, Jinyan; Hu, Frank B; Melander, Olle; Orho-Melander, Marju; Below, Jennifer E; Aguilar, David; Wong, Tien Yin; Liu, Jianjun; Khor, Chiea-Chuen; Chia, Kee Seng; Lim, Wei Yen; Cheng, Ching-Yu; Chan, Edmund; Tai, E Shyong; Aung, Tin; Linneberg, Allan; Isomaa, Bo; Meitinger, Thomas; Tuomi, Tiinamaija; Hakaste, Liisa; Kravic, Jasmina; Jørgensen, Marit E; Lauritzen, Torsten; Deloukas, Panos; Stirrups, Kathleen E; Owen, Katharine R; Farmer, Andrew J; Frayling, Timothy M; O'Rahilly, Stephen P; Walker, Mark; Levy, Jonathan C; Hodgkiss, Dylan; Hattersley, Andrew T; Kuulasmaa, Teemu; Stančáková, Alena; Barroso, Inês; Bharadwaj, Dwaipayan; Chan, Juliana; Chandak, Giriraj R; Daly, Mark J; Donnelly, Peter J; Ebrahim, Shah B; Elliott, Paul; Fingerlin, Tasha; Froguel, Philippe; Hu, Cheng; Jia, Weiping; Ma, Ronald C W; McVean, Gilean; Park, Taesung; Prabhakaran, Dorairaj; Sandhu, Manjinder; Scott, James; Sladek, Rob; Tandon, Nikhil; Teo, Yik Ying; Zeggini, Eleftheria; Watanabe, Richard M; Koistinen, Heikki A; Kesaniemi, Y Antero; Uusitupa, Matti; Spector, Timothy D; Salomaa, Veikko; Rauramaa, Rainer; Palmer, Colin N A; Prokopenko, Inga; Morris, Andrew D; Bergman, Richard N; Collins, Francis S; Lind, Lars; Ingelsson, Erik; Tuomilehto, Jaakko; Karpe, Fredrik; Groop, Leif; Jørgensen, Torben; Hansen, Torben; Pedersen, Oluf; Kuusisto, Johanna; Abecasis, Gonçalo; Bell, Graeme I; Blangero, John; Cox, Nancy J; Duggirala, Ravindranath; Seielstad, Mark; Wilson, James G; Dupuis, Josee; Ripatti, Samuli; Hanis, Craig L; Florez, Jose C; Mohlke, Karen L; Meigs, James B; Laakso, Markku; Morris, Andrew P; Boehnke, Michael; Altshuler, David; McCarthy, Mark I; Gloyn, Anna L; Lindgren, Cecilia M

    2017-07-01

    To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2. © 2017 by the American Diabetes Association.

  20. Sub-Transport Layer Coding

    DEFF Research Database (Denmark)

    Hansen, Jonas; Krigslund, Jeppe; Roetter, Daniel Enrique Lucani

    2014-01-01

    Packet losses in wireless networks dramatically curbs the performance of TCP. This paper introduces a simple coding shim that aids IP-layer traffic in lossy environments while being transparent to transport layer protocols. The proposed coding approach enables erasure correction while being...... oblivious to the congestion control algorithms of the utilised transport layer protocol. Although our coding shim is indifferent towards the transport layer protocol, we focus on the performance of TCP when ran on top of our proposed coding mechanism due to its widespread use. The coding shim provides gains...

  1. The Art of Readable Code

    CERN Document Server

    Boswell, Dustin

    2011-01-01

    As programmers, we've all seen source code that's so ugly and buggy it makes our brain ache. Over the past five years, authors Dustin Boswell and Trevor Foucher have analyzed hundreds of examples of "bad code" (much of it their own) to determine why they're bad and how they could be improved. Their conclusion? You need to write code that minimizes the time it would take someone else to understand it-even if that someone else is you. This book focuses on basic principles and practical techniques you can apply every time you write code. Using easy-to-digest code examples from different languag

  2. Three Paradigms for Mixing Coding and Games: Coding in a Game, Coding as a Game, and Coding for a Game

    OpenAIRE

    2015-01-01

    Games for teaching coding have been an educational holy grail since at least the early 1980s. Yet for decades, with games more popular than ever and with the need to teach kids coding having been well-recognized, no blockbuster coding games have arisen (see Chapter 2). Over the years, the research community has made various games for teaching computer science: a survey made by shows that most do not teach coding, and of the ones that do teach coding, most are research prototypes (not produc...

  3. Remarks on generalized toric codes

    CERN Document Server

    Little, John B

    2011-01-01

    This note presents some new information on how the minimum distance of the generalized toric code corresponding to a fixed set of integer lattice points S in R^2 varies with the base field. The main results show that in some cases, over sufficiently large fields, the minimum distance of the code corresponding to a set S will be the same as that of the code corresponding to the convex hull of S. In an example, we will also discuss a [49,12,28] generalized toric code over GF(8), better than any previously known code according to M. Grassl's online tables, as of July 2011.

  4. Rotated and Scaled Alamouti Coding

    CERN Document Server

    Willems, Frans M J

    2008-01-01

    Repetition-based retransmission is used in Alamouti-modulation [1998] for $2\\times 2$ MIMO systems. We propose to use instead of ordinary repetition so-called "scaled repetition" together with rotation. It is shown that the rotated and scaled Alamouti code has a hard-decision performance which is only slightly worse than that of the Golden code [2005], the best known $2\\times 2$ space-time code. Decoding the Golden code requires an exhaustive search over all codewords, while our rotated and scaled Alamouti code can be decoded with an acceptable complexity however.

  5. On constructing disjoint linear codes

    Institute of Scientific and Technical Information of China (English)

    ZHANG Weiguo; CAI Mian; XIAO Guozhen

    2007-01-01

    To produce a highly nonlinear resilient function,the disjoint linear codes were originally proposed by Johansson and Pasalic in IEEE Trans.Inform.Theory,2003,49(2):494-501.In this paper,an effective method for finding a set of such disjoint linear codes is presented.When n≥2k,we can find a set of[n,k] disjoint linear codes with joint linear codes exists with cardinality at least 2.We also describe a result on constructing a set of [n,k] disjoint linear codes with minimum distance at least some fixed positive integer.

  6. Orthogonal coding of object location.

    Science.gov (United States)

    Knutsen, Per Magne; Ahissar, Ehud

    2009-02-01

    It has been argued whether internal representations are encoded using a universal ('the neural code') or multiple codes. Here, we review a series of experiments that demonstrate that tactile encoding of object location via whisking employs an orthogonal, triple-code scheme. Rats, and other rodents, actively move the whiskers back and forth to localize and identify objects. Neural recordings from primary sensory afferents, along with behavioral observations, demonstrate that vertical coordinates of contacted objects are encoded by the identity of activated afferents, horizontal coordinates by the timing of activation and radial coordinates by the intensity of activation. Because these codes are mutually independent, the three-dimensional location of an object could, in principle, be encoded by individual afferents during single whisker-object contacts. One advantage of such a same-neuron-different-codes scheme over the traditionally assumed same-code-different-neurons scheme is a reduction of code ambiguity that, in turn, simplifies decoding circuits.

  7. New Codes for Spectral Amplitude Coding Optical CDMA Systems

    Directory of Open Access Journals (Sweden)

    Hassan Yousif Ahmed

    2011-03-01

    Full Text Available A new code structure with zero in-phase cross correlation for spectral amplitude coding optical code division multiple access (SAC-OCDMA system is proposed, and called zero vectors combinatorial (ZVC. This code is constructed in a simple algebraic way using Euclidean vectors and combinatorial theories based on the relationship between the number of users N and the weight W. One of the important properties of this code is that the maximum cross correlation (CC is always zero, which means that multi-user interference (MUI and phase induced intensity noise (PIIN are reduced. Bit error rate (BER performance is compared with previous reported codes. Therefore, theoretically, we demonstrate the performance of ZVC code with the related equations. In addition, the structure of the encoder/decoder based on fiber Bragg gratings (FBGs and the proposed system have been analyzed theoretically by taking into consideration the effects of some noises. The results characterizing BER with respect to the total number of active users show that ZVC code offers a significantly improved performance over previous reported codes by supporting large numbers of users at BER≥ 10-9. A comprehensive simulation study has been carried out using a commercial optical system simulator “VPI™”. Moreover, it was shown that the proposed code managed to reduce the hardware complexity and eventually the cost.

  8. Making your code citable with the Astrophysics Source Code Library

    Science.gov (United States)

    Allen, Alice; DuPrie, Kimberly; Schmidt, Judy; Berriman, G. Bruce; Hanisch, Robert J.; Mink, Jessica D.; Nemiroff, Robert J.; Shamir, Lior; Shortridge, Keith; Taylor, Mark B.; Teuben, Peter J.; Wallin, John F.

    2016-01-01

    The Astrophysics Source Code Library (ASCL, ascl.net) is a free online registry of codes used in astronomy research. With nearly 1,200 codes, it is the largest indexed resource for astronomy codes in existence. Established in 1999, it offers software authors a path to citation of their research codes even without publication of a paper describing the software, and offers scientists a way to find codes used in refereed publications, thus improving the transparency of the research. It also provides a method to quantify the impact of source codes in a fashion similar to the science metrics of journal articles. Citations using ASCL IDs are accepted by major astronomy journals and if formatted properly are tracked by ADS and other indexing services. The number of citations to ASCL entries increased sharply from 110 citations in January 2014 to 456 citations in September 2015. The percentage of code entries in ASCL that were cited at least once rose from 7.5% in January 2014 to 17.4% in September 2015. The ASCL's mid-2014 infrastructure upgrade added an easy entry submission form, more flexible browsing, search capabilities, and an RSS feeder for updates. A Changes/Additions form added this past fall lets authors submit links for papers that use their codes for addition to the ASCL entry even if those papers don't formally cite the codes, thus increasing the transparency of that research and capturing the value of their software to the community.

  9. Molecular prioritization strategies to identify functional genetic variants in the cardiovascular disease-associated expression QTL Vanin-1

    Science.gov (United States)

    Kaskow, Belinda J; Diepeveen, Luke A; Michael Proffitt, J; Rea, Alexander J; Ulgiati, Daniela; Blangero, John; Moses, Eric K; Abraham, Lawrence J

    2014-01-01

    There is now good evidence that non-coding sequence variants are involved in the heritability of many common complex traits. The current ‘gold standard' approach for assessing functionality is the in vitro reporter gene assay to assess allelic differences in transcriptional activity, usually followed by electrophoretic mobility shift assays to assess allelic differences in transcription factor binding. Although widely used, these assays have inherent limitations, including the lack of endogenous chromatin context. Here we present a more contemporary approach to assessing functionality of non-coding sequence variation within the Vanin-1 (VNN1) promoter. By combining ‘gold standard' assays with in vivo assessments of chromatin accessibility, we greatly increase our confidence in the statistically assigned functional relevance. The standard assays revealed the −137 single nucleotide variant to be functional but the −587 variant to have no functional relevance. However, our in vivo tests show an allelic difference in chromatin accessibility surrounding the −587 variant supporting strong functional potential at both sites. Our approach advances the identification of functional variants by providing strong in vivo biological evidence for function. PMID:24045843

  10. Intronic rs2147363 variant in ATP7B transcription factor-binding site associated with Alzheimer's disease.

    Science.gov (United States)

    Bucossi, Serena; Polimanti, Renato; Ventriglia, Mariacarla; Mariani, Stefania; Siotto, Mariacristina; Ursini, Francesca; Trotta, Laura; Scrascia, Federica; Callea, Antonio; Vernieri, Fabrizio; Squitti, Rosanna

    2013-01-01

    Copper homeostasis abnormalities have been shown to be associated with Alzheimer's disease (AD), possibly by accelerating amyloid-β toxicity and plaque formation. The ATP7B gene plays a key role in controlling body copper balance. Our previous studies showed an association between ATP7B variants and AD risk. Among these variants, an intronic single nucleotide polymorphism, rs2147363, was associated with AD risk. In order to understand this intronic association, we screened a population of 286 AD patients and 283 healthy controls, and verified the presence of other functional coding variants in linkage disequilibrium (LD). Then we searched for a regulatory function region close to rs2147363. An LD analysis revealed the presence of an LD between rs2147363 and a Wilson's disease-causing variant, rs7334118. However, this mutation did not explain the observed genetic association. Conversely, in silico analyses of rs2147363 functionality highlighted that this variant is located in a binding site of a transcription factor, and is, consequently, associated with regulatory function. These data suggest that the genetic variation in cis-regulatory elements located in non-coding regions can have a role in determining ATP7B functionality and account for some of the AD missing hereditability.

  11. Rare variants in MYD88, IRAK4 and IKBKG and susceptibility to invasive pneumococcal disease: a population-based case-control study.

    Directory of Open Access Journals (Sweden)

    Magda K Ellis

    Full Text Available Although rare variants within the Toll-like receptor signalling pathway genes have been found to underlie human primary immunodeficiencies associated with selective predisposition to invasive pneumococcal disease (IPD, the contribution of variants in these genes to IPD susceptibility at the population level remains unknown. Complete re-sequencing of IRAK4, MYD88 and IKBKG genes was undertaken in 164 IPD cases from the UK and 164 geographically-matched population-based controls. 233 single-nucleotide variants (SNVs were identified, of which ten were in coding regions. Four rare coding variants were predicted to be deleterious, two variants in MYD88 and two in IRAK4. The predicted deleterious variants in MYD88 were observed as two heterozygote cases but not seen in controls. Frequencies of predicted deleterious IRAK4 SNVs were the same in cases and controls. Our findings suggest that rare, functional variants in MYD88, IRAK4 or IKBKG do not significantly contribute to IPD susceptibility in adults at the population level.

  12. Exome-based Variant Detection in Core Promoters.

    Science.gov (United States)

    Kim, Yeong C; Cui, Jian; Luo, Jiangtao; Xiao, Fengxia; Downs, Bradley; Wang, San Ming

    2016-07-28

    Core promoter controls the initiation of transcription. Core promoter sequence change can disrupt transcriptional regulation, lead to impairment of gene expression and ultimately diseases. Therefore, comprehensive characterization of core promoters is essential to understand normal and abnormal gene expression in biomedical studies. Here we report the development of EVDC (Exome-based Variant Detection in Core promoters) method for genome-scale analysis of core-promoter sequence variation. This method is based on the fact that exome sequences contain the sequences not only from coding exons but also from non-coding region including core promoters generated by random fragmentation in exome sequencing process. Using exome data from three cell types of CD4+ T cells, CD19+ B cells and neutrophils of a single individual, we characterized the features of core promoter-mapped exome sequences, and analysed core-promoter variation in this individual genome. We also compared the core promoters between YRI (Yoruba in Ibadan, Nigeria) and the CEU (Utah residents of European decedent) populations using the exome data generated by the 1000 Genome project, and observed much higher variation in YRI population than in CEU population. Our study demonstrates that the EVDC method provides a simple but powerful means for genome-wile de novo characterization of core promoter sequence variation.

  13. Post-mortem testing; germline BRCA1/2 variant detection using archival FFPE non-tumor tissue. A new paradigm in genetic counseling.

    Science.gov (United States)

    Petersen, Annabeth Høgh; Aagaard, Mads Malik; Nielsen, Henriette Roed; Steffensen, Karina Dahl; Waldstrøm, Marianne; Bojesen, Anders

    2016-08-01

    Accurate estimation of cancer risk in HBOC families often requires BRCA1/2 testing, but this may be impossible in deceased family members. Previous, testing archival formalin-fixed, paraffin-embedded (FFPE) tissue for germline BRCA1/2 variants was unsuccessful, except for the Jewish founder mutations. A high-throughput method to systematically test for variants in all coding regions of BRCA1/2 in archival FFPE samples of non-tumor tissue is described, using HaloPlex target enrichment and next-generation sequencing. In a validation study, correct identification of variants or wild-type was possible in 25 out of 30 (83%) FFPE samples (age range 1-14 years), with a known variant status in BRCA1/2. No false positive was found. Unsuccessful identification was due to highly degraded DNA or presence of large intragenic deletions. In clinical use, a total of 201 FFPE samples (aged 0-43 years) were processed. Thirty-six samples were rejected because of highly degraded DNA or failed library preparation. Fifteen samples were investigated to search for a known variant. In the remaining 150 samples (aged 0-38 years), three variants known to affect function and one variant likely to affect function in BRCA1, six variants known to affect function and one variant likely to affect function in BRCA2, as well as four variants of unknown significance (VUS) in BRCA1 and three VUS in BRCA2 were discovered. It is now possible to test for germline BRCA1/2 variants in deceased persons, using archival FFPE samples from non-tumor tissue. Accurate genetic counseling is achievable in families where variant testing would otherwise be impossible.

  14. Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks.

    Science.gov (United States)

    Decker, Brennan; Allen, Jamie; Luccarini, Craig; Pooley, Karen A; Shah, Mitul; Bolla, Manjeet K; Wang, Qin; Ahmed, Shahana; Baynes, Caroline; Conroy, Don M; Brown, Judith; Luben, Robert; Ostrander, Elaine A; Pharoah, Paul Dp; Dunning, Alison M; Easton, Douglas F

    2017-08-04

    Breast cancer (BC) is the most common malignancy in women and has a major heritable component. The risks associated with most rare susceptibility variants are not well estimated. To better characterise the contribution of variants in ATM, CHEK2, PALB2 and XRCC2, we sequenced their coding regions in 13 087 BC cases and 5488 controls from East Anglia, UK. Gene coding regions were enriched via PCR, sequenced, variant called and filtered for quality. ORs for BC risk were estimated separately for carriers of truncating variants and of rare missense variants, which were further subdivided by functional domain and pathogenicity as predicted by four in silico algorithms. Truncating variants in PALB2 (OR=4.69, 95% CI 2.27 to 9.68), ATM (OR=3.26; 95% CI 1.82 to 6.46) and CHEK2 (OR=3.11; 95% CI 2.15 to 4.69), but not XRCC2 (OR=0.94; 95% CI 0.26 to 4.19) were associated with increased BC risk. Truncating variants in ATM and CHEK2 were more strongly associated with risk of oestrogen receptor (ER)-positive than ER-negative disease, while those in PALB2 were associated with similar risks for both subtypes. There was also some evidence that missense variants in ATM, CHEK2 and PALB2 may contribute to BC risk, but larger studies are necessary to quantify the magnitude of this effect. Truncating variants in PALB2 are associated with a higher risk of BC than those in ATM or CHEK2. A substantial risk of BC due to truncating XRCC2 variants can be excluded. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. Differential association of two PTPN22 coding variants with Crohn's disease and ulcerative colitis

    NARCIS (Netherlands)

    Diaz-Gallo, Lina-Marcela; Espino-Paisán, Laura; Fransen, Karin; Gómez-García, María; van Sommeren, Suzanne; Cardeña, Carlos; Rodrigo, Luis; Mendoza, Juan Luis; Taxonera, Carlos; Nieto, Antonio; Alcain, Guillermo; Cueto, Ignacio; López-Nevot, Miguel A; Bottini, Nunzio; Barclay, Murray L; Crusius, J Bart; van Bodegraven, Adriaan A; Wijmenga, Cisca; Ponsioen, Cyriel Y; Gearry, Richard B; Roberts, Rebecca L; Weersma, Rinse K; Urcelay, Elena; Merriman, Tony R; Alizadeh, Behrooz Z; Martin, Javier

    2011-01-01

    BACKGROUND: The PTPN22 gene is an important risk factor for human autoimmunity. The aim of this study was to evaluate for the first time the role of the R263Q PTPN22 polymorphism in ulcerative colitis (UC) and Crohn's disease (CD), and to reevaluate the association of the R620W PTPN22 polymorphism w

  16. Differential Association of Two PTPN22 Coding Variants with Crohn's Disease and Ulcerative Colitis

    NARCIS (Netherlands)

    Diaz-Gallo, Lina-Marcela; Espino-Paisan, Laura; Fransen, Karin; Gomez-Garcia, Maria; van Sommeren, Suzanne; Cardena, Carlos; Rodrigo, Luis; Mendoza, Juan Luis; Taxonera, Carlos; Nieto, Antonio; Alcain, Guillermo; Cueto, Ignacio; Lopez-Nevot, Miguel A.; Bottini, Nunzio; Barclay, Murray L.; Crusius, J. Bart; van Bodegraven, Adriaan A.; Wijmenga, Cisca; Ponsioen, Cyriel Y.; Gearry, Richard B.; Roberts, Rebecca L.; Weersma, Rinse K.; Urcelay, Elena; Merriman, Tony R.; Alizadeh, Behrooz Z.; Martin, Javier

    2011-01-01

    Background: The PTPN22 gene is an important risk factor for human autoimmunity. The aim of this study was to evaluate for the first time the role of the R263Q PTPN22 polymorphism in ulcerative colitis (UC) and Crohn's disease (CD), and to reevaluate the association of the R620W PTPN22 polymorphism w

  17. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm.

    Science.gov (United States)

    Kumar, Prateek; Henikoff, Steven; Ng, Pauline C

    2009-01-01

    The effect of genetic mutation on phenotype is of significant interest in genetics. The type of genetic mutation that causes a single amino acid substitution (AAS) in a protein sequence is called a non-synonymous single nucleotide polymorphism (nsSNP). An nsSNP could potentially affect the function of the protein, subsequently altering the carrier's phenotype. This protocol describes the use of the 'Sorting Tolerant From Intolerant' (SIFT) algorithm in predicting whether an AAS affects protein function. To assess the effect of a substitution, SIFT assumes that important positions in a protein sequence have been conserved throughout evolution and therefore substitutions at these positions may affect protein function. Thus, by using sequence homology, SIFT predicts the effects of all possible substitutions at each position in the protein sequence. The protocol typically takes 5-20 min, depending on the input. SIFT is available as an online tool (http://sift.jcvi.org).

  18. A Genetic Variant (COMT) Coding Dopaminergic Activity Predicts Personality Traits in Healthy Elderly.

    Science.gov (United States)

    Kotyuk, Eszter; Duchek, Janet; Head, Denise; Szekely, Anna; Goate, Alison M; Balota, David A

    2015-08-01

    Association studies between the NEO five factor personality inventory and COMT rs4680 have focused on young adults and the results have been inconsistent. However, personality and cortical changes with age may put older adults in a more sensitive range for detecting a relationship. The present study examined associations of COMT rs4680 and personality in older adults. Genetic association analyses were carried out between the NEO and the targeted COMT rs4680 in a large, well-characterized sample of healthy, cognitively normal older adults (N = 616, mean age = 69.26 years). Three significant associations were found: participants with GG genotype showed lower mean scores on Neuroticism (p = 0.039) and higher scores on Agreeableness (p = 0.020) and Conscientiousness (p = 0.006) than participants with AA or AG genotypes. These results suggest that older adults with higher COMT enzymatic activity (GG), therefore lower dopamine level, have lower Neuroticism scores, and higher Agreeableness and Conscientiousness scores. This is consistent with a recent model of phasic and tonic dopamine release suggesting that even though GG genotype is associated with lower tonic dopamine release, the phasic release of dopamine might be optimal for a more adaptive personality profile.

  19. Beta-glucosidase variants and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Wogulis, Mark; Harris, Paul; Osborn, David

    2017-06-27

    The present invention relates to beta-glucosidase variants, e.g. beta-glucosidase variants of a parent Family GH3A beta-glucosidase from Aspergillus fumigatus. The present invention also relates to polynucleotides encoding the beta-glucosidase variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the beta-glucosidase variants.

  20. On Bounded Weight Codes

    CERN Document Server

    Bachoc, Christine; Cohen, Gerard; Sole, Patrick; Tchamkerten, Aslan

    2010-01-01

    The maximum size of a binary code is studied as a function of its length N, minimum distance D, and minimum codeword weight W. This function B(N,D,W) is first characterized in terms of its exponential growth rate in the limit as N tends to infinity for fixed d=D/N and w=W/N. The exponential growth rate of B(N,D,W) is shown to be equal to the exponential growth rate of A(N,D) for w <= 1/2, and equal to the exponential growth rate of A(N,D,W) for 1/2< w <= 1. Second, analytic and numerical upper bounds on B(N,D,W) are derived using the semidefinite programming (SDP) method. These bounds yield a non-asymptotic improvement of the second Johnson bound and are tight for certain values of the parameters.

  1. Homomorphic encryption from codes

    CERN Document Server

    Bogdanov, Andrej

    2011-01-01

    We propose a new homomorphic encryption scheme based on the hardness of decoding under independent random noise from certain affine families of codes. Unlike in previous lattice-based homomorphic encryption schemes, where the message is hidden in the noisy part of the ciphertext, our scheme carries the message in the affine part of the transformation and applies noise only to achieve security. Our scheme can tolerate noise of arbitrary magnitude, as long as the noise vector has sufficiently small hamming weight (and its entries are independent). Our design achieves "proto-homomorphic" properties in an elementary manner: message addition and multiplication are emulated by pointwise addition and multiplication of the ciphertext vectors. Moreover, the extremely simple nature of our decryption makes the scheme easily amenable to bootstrapping. However, some complications are caused by the inherent presence of noticeable encryption error. Our main technical contribution is the development of two new techniques for...

  2. Semiconductor Whole Exome Sequencing for the Identification of Genetic Variants in Colombian Patients Clinically Diagnosed with Long QT Syndrome.

    Science.gov (United States)

    Burgos, Mariana; Arenas, Alvaro; Cabrera, Rodrigo

    2016-08-01

    Inherited long QT syndrome (LQTS) is a cardiac channelopathy characterized by a prolongation of QT interval and the risk of syncope, cardiac arrest, and sudden cardiac death. Genetic diagnosis of LQTS is critical in medical practice as results can guide adequate management of patients and distinguish phenocopies such as catecholaminergic polymorphic ventricular tachycardia (CPVT). However, extensive screening of large genomic regions is required in order to reliably identify genetic causes. Semiconductor whole exome sequencing (WES) is a promising approach for the identification of variants in the coding regions of most human genes. DNA samples from 21 Colombian patients clinically diagnosed with LQTS were enriched for coding regions using multiplex polymerase chain reaction (PCR) and subjected to WES using a semiconductor sequencer. Semiconductor WES showed mean coverage of 93.6 % for all coding regions relevant to LQTS at >10× depth with high intra- and inter-assay depth heterogeneity. Fifteen variants were detected in 12 patients in genes associated with LQTS. Three variants were identified in three patients in genes associated with CPVT. Co-segregation analysis was performed when possible. All variants were analyzed with two pathogenicity prediction algorithms. The overall prevalence of LQTS and CPVT variants in our cohort was 71.4 %. All LQTS variants previously identified through commercial genetic testing were identified. Standardized WES assays can be easily implemented, often at a lower cost than sequencing panels. Our results show that WES can identify LQTS-causing mutations and permits differential diagnosis of related conditions in a real-world clinical setting. However, high heterogeneity in sequencing depth and low coverage in the most relevant genes is expected to be associated with reduced analytical sensitivity.

  3. Natural genetic variation impacts expression levels of coding, non-coding, and antisense transcripts in fission yeast

    DEFF Research Database (Denmark)

    Clément-Ziza, Mathieu; Marsellach, Francesc X.; Codlin, Sandra

    2014-01-01

    Our current understanding of how natural genetic variation affects gene expression beyond well-annotated coding genes is still limited. The use of deep sequencing technologies for the study of expression quantitative trait loci (eQTLs) has the potential to close this gap. Here, we generated...... to be affected by eQTLs as protein-coding RNAs. We identified a genetic variation of swc5 that modifies the levels of 871 RNAs, with effects on both sense and antisense transcription, and show that this effect most likely goes through a compromised deposition of the histone variant H2A.Z. The strains, methods...... the first recombinant strain library for fission yeast and conducted an RNA-seq-based QTL study of the coding, non-coding, and antisense transcriptomes. We show that the frequency of distal effects (trans-eQTLs) greatly exceeds the number of local effects (cis-eQTLs) and that non-coding RNAs are as likely...

  4. LDGM Codes for Channel Coding and Joint Source-Channel Coding of Correlated Sources

    Directory of Open Access Journals (Sweden)

    Javier Garcia-Frias

    2005-05-01

    Full Text Available We propose a coding scheme based on the use of systematic linear codes with low-density generator matrix (LDGM codes for channel coding and joint source-channel coding of multiterminal correlated binary sources. In both cases, the structures of the LDGM encoder and decoder are shown, and a concatenated scheme aimed at reducing the error floor is proposed. Several decoding possibilities are investigated, compared, and evaluated. For different types of noisy channels and correlation models, the resulting performance is very close to the theoretical limits.

  5. Improved lossless intra coding for next generation video coding

    Science.gov (United States)

    Vanam, Rahul; He, Yuwen; Ye, Yan

    2016-09-01

    Recently, there have been efforts by the ITU-T VCEG and ISO/IEC MPEG to further improve the compression performance of the High Efficiency Video Coding (HEVC) standard for developing a potential next generation video coding standard. The exploratory codec software of this potential standard includes new coding tools for inter and intra coding. In this paper, we present a new intra prediction mode for lossless intra coding. Our new intra mode derives a prediction filter for each input pixel using its neighboring reconstructed pixels, and applies this filter to the nearest neighboring reconstructed pixels to generate a prediction pixel. The proposed intra mode is demonstrated to improve the performance of the exploratory software for lossless intra coding, yielding a maximum and average bitrate savings of 4.4% and 2.11%, respectively.

  6. The maximal C(3) self-complementary trinucleotide circular code X in genes of bacteria, eukaryotes, plasmids and viruses.

    Science.gov (United States)

    Michel, Christian J

    2015-09-07

    In 1996, a set X of 20 trinucleotides is identified in genes of both prokaryotes and eukaryotes which has in average the highest occurrence in reading frame compared to the two shifted frames (Arquès and Michel, 1996). Furthermore, this set X has an interesting mathematical property as X is a maximal C(3) self-complementary trinucleotide circular code (Arquès and Michel, 1996). In 2014, the number of trinucleotides in prokaryotic genes has been multiplied by a factor of 527. Furthermore, two new gene kingdoms of plasmids and viruses contain enough trinucleotide data to be analysed. The approach used in 1996 for identifying a preferential frame for a trinucleotide is quantified here with a new definition analysing the occurrence probability of a complementary/permutation (CP) trinucleotide set in a gene kingdom. Furthermore, in order to increase the statistical significance of results compared to those of 1996, the circular code X is studied on several gene taxonomic groups in a kingdom. Based on this new statistical approach, the circular code X is strengthened in genes of prokaryotes and eukaryotes, and now also identified in genes of plasmids. A subset of X with 18 or 16 trinucleotides is identified in genes of viruses. Furthermore, a simple probabilistic model based on the independent occurrence of trinucleotides in reading frame of genes explains the circular code frequencies and asymmetries observed in the shifted frames in all studied gene kingdoms. Finally, the developed approach allows to identify variant X codes in genes, i.e. trinucleotide codes which differ from X. In genes of bacteria, eukaryotes and plasmids, 14 among the 47 studied gene taxonomic groups (about 30%) have variant X codes. Seven variant X codes are identified with at least 16 trinucleotides of X. Two variant X codes XA in cyanobacteria and plasmids of cyanobacteria, and XD in birds are self-complementary, without permuted trinucleotides but non-circular. Five variant X codes XB in

  7. Selection of Code and Interleaver for Turbo Coding

    DEFF Research Database (Denmark)

    Andersen, Jakob Dahl

    1998-01-01

    The selection of component codes for turbo coding has often been based on the performance at high SNR's. However, we will argue that the selection mainly should be based on the performance at low SNR's, i.e. the convergence properties. Further, we will present a way to construct interleavers...... that significantly improve the performance of the turbo coding scheme at high SNR's, i.e. lowers the error floor...

  8. Superimposed Code Theorectic Analysis of DNA Codes and DNA Computing

    Science.gov (United States)

    2010-03-01

    Bounds for DNA Codes Based on Fibonacci Ensembles of DNA Sequences ”, 2008 IEEE Proceedings of International Symposium on Information Theory, pp. 2292...5, June 2008, pp. 525-34. 32 28. A. Macula, et al., “Random Coding Bounds for DNA Codes Based on Fibonacci Ensembles of DNA Sequences ”, 2008...combinatorial method of bio-memory design and detection that encodes item or process information as numerical sequences represented in DNA. ComDMem is a

  9. Analysis of protein-coding genetic variation in 60,706 humans.

    Science.gov (United States)

    Lek, Monkol; Karczewski, Konrad J; Minikel, Eric V; Samocha, Kaitlin E; Banks, Eric; Fennell, Timothy; O'Donnell-Luria, Anne H; Ware, James S; Hill, Andrew J; Cummings, Beryl B; Tukiainen, Taru; Birnbaum, Daniel P; Kosmicki, Jack A; Duncan, Laramie E; Estrada, Karol; Zhao, Fengmei; Zou, James; Pierce-Hoffman, Emma; Berghout, Joanne; Cooper, David N; Deflaux, Nicole; DePristo, Mark; Do, Ron; Flannick, Jason; Fromer, Menachem; Gauthier, Laura; Goldstein, Jackie; Gupta, Namrata; Howrigan, Daniel; Kiezun, Adam; Kurki, Mitja I; Moonshine, Ami Levy; Natarajan, Pradeep; Orozco, Lorena; Peloso, Gina M; Poplin, Ryan; Rivas, Manuel A; Ruano-Rubio, Valentin; Rose, Samuel A; Ruderfer, Douglas M; Shakir, Khalid; Stenson, Peter D; Stevens, Christine; Thomas, Brett P; Tiao, Grace; Tusie-Luna, Maria T; Weisburd, Ben; Won, Hong-Hee; Yu, Dongmei; Altshuler, David M; Ardissino, Diego; Boehnke, Michael; Danesh, John; Donnelly, Stacey; Elosua, Roberto; Florez, Jose C; Gabriel, Stacey B; Getz, Gad; Glatt, Stephen J; Hultman, Christina M; Kathiresan, Sekar; Laakso, Markku; McCarroll, Steven; McCarthy, Mark I; McGovern, Dermot; McPherson, Ruth; Neale, Benjamin M; Palotie, Aarno; Purcell, Shaun M; Saleheen, Danish; Scharf, Jeremiah M; Sklar, Pamela; Sullivan, Patrick F; Tuomilehto, Jaakko; Tsuang, Ming T; Watkins, Hugh C; Wilson, James G; Daly, Mark J; MacArthur, Daniel G

    2016-08-18

    Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of predicted protein-truncating variants, with 72% of these genes having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human 'knockout' variants in protein-coding genes.

  10. Bit-Interleaved Coded Multiple Beamforming with Perfect Coding

    CERN Document Server

    Li, Boyu

    2010-01-01

    When the channel state information is known by the transmitter as well as the receiver, beamforming techniques that employ Singular Value Decomposition (SVD) are commonly used in Multiple-Input Multiple-Output (MIMO) systems. Without channel coding, when a single symbol is transmitted, these systems achieve the full diversity order. Whereas, this property is lost when multiple symbols are simultaneously transmitted. Full diversity can be restored when channel coding is added, as long as the code rate Rc and the number of employed subchannels S satisfy the condition RcS =< 1. Moreover, by adding a proper constellation precoder, full diversity can be achieved for both uncoded and coded SVD systems, e.g., Fully Precoded Multiple Beamforming (FPMB) and Bit-Interleaved Coded Multiple Beamforming with Full Precoding (BICMB-FP). Perfect Space-Time Block Code (PSTBC) is a full-rate full-diversity space-time code, which achieves maximum coding gain for MIMO systems. Previously, Perfect Coded Multiple Beamforming (P...

  11. Practices in Code Discoverability: Astrophysics Source Code Library

    CERN Document Server

    Allen, Alice; Nemiroff, Robert J; Shamir, Lior

    2012-01-01

    Here we describe the Astrophysics Source Code Library (ASCL), which takes an active approach to sharing astrophysical source code. ASCL's editor seeks out both new and old peer-reviewed papers that describe methods or experiments that involve the development or use of source code, and adds entries for the found codes to the library. This approach ensures that source codes are added without requiring authors to actively submit them, resulting in a comprehensive listing that covers a significant number of the astrophysics source codes used in peer-reviewed studies. The ASCL now has over 340 codes in it and continues to grow. In 2011, the ASCL (http://ascl.net) has on average added 19 new codes per month. An advisory committee has been established to provide input and guide the development and expansion of the new site, and a marketing plan has been developed and is being executed. All ASCL source codes have been used to generate results published in or submitted to a refereed journal and are freely available ei...

  12. Pseudomonas aeruginosa induces pigment production and enhances virulence in a white phenotypic variant of Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Antonic V

    2013-11-01

    Full Text Available Vlado Antonic,1–3 Alexander Stojadinovic,3–5 Binxue Zhang,1–3 Mina J Izadjoo,1–3,5 Mohammad Alavi1–3 1Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; 2Diagnostic and Translational Research Center, Gaithersburg, MD, USA; 3Combat Wound Initiative Program, Bethesda, MD, USA; 4Walter Reed National Military Medical Center, Bethesda, MD, USA; 5Uniformed Services University of the Health Sciences, Bethesda, MD, USA Abstract: Staphyloxanthin is a virulence factor which protects Staphylococcus aureus in stress conditions. We isolated two pigment variants of S. aureus and one strain of Pseudomonas aeruginosa from a single wound infection. S. aureus variants displayed white and yellow colony phenotypes. The sequence of the operons for staphyloxanthin synthesis indicated that coding and promoter regions were identical between the two pigment variants. Quorum sensing controls pigment synthesis in some bacteria. It is also shown that P. aeruginosa quorum-sensing molecules affect S. aureus transcription. We explored whether the co-infecting P. aeruginosa can affect pigment production in the white S. aureus variant. In co-culture experiments between the white variants and a selected number of Gram-positive and Gram-negative bacteria, only P. aeruginosa induced pigment production in the white variant. Gene expression analysis of the white variant did not indicate upregulation of the crtM and other genes known to be involved in pigment production (sigB, sarA, farnesyl pyrophosphate synthase gene [FPP-synthase], hfq. In contrast, transcription of the catalase gene was significantly upregulated after co-culture. P. aeruginosa-induced pigment synthesis and catalase upregulation correlated with increased resistance to polymyxin B, hydrogen peroxide, and the intracellular environment of macrophages. Our data indicate the presence of silent but functional staphyloxanthin synthesis machinery in a white phenotypic variant

  13. A novel variant of aquaporin 3 is expressed in killifish (Fundulus heteroclitus) intestine.

    Science.gov (United States)

    Jung, Dawoon; Adamo, Meredith A; Lehman, Rebecca M; Barnaby, Roxanna; Jackson, Craig E; Jackson, Brian P; Shaw, Joseph R; Stanton, Bruce A

    2015-05-01

    Killifish (Fundulus heteroclitus) are euryhaline teleosts that are widely used in environmental and toxicological studies, and they are tolerant to arsenic, in part due to very low assimilation of arsenic from the environment. The mechanism of arsenic uptake by the intestine, a major route of arsenic uptake in humans is unknown. Thus, the goal of this study was to determine if aquaglyceroporins (AQPs), which transport water and other small molecules including arsenite across cell membranes, are expressed in the killifish intestine, and whether AQP expression is affected by osmotic stress. Through RT-PCR and sequence analysis of PCR amplicons, we demonstrated that the intestine expresses kfAQP3a and kfAQP3b, two previously identified variants, and also identified a novel variant of killifish AQP3 (kfAQP3c) in the intestine. The variants likely represent alternate splice forms. A BLAST search of the F. heteroclitus reference genome revealed that the AQP3 gene resides on a single locus, while an alignment of the AQP3 sequence among 384 individuals from eight population ranging from Rhode Island to North Carolina revealed that its coding sequence was remarkably conserved with no fixed polymorphism residing in the region that distinguishes these variants. We further demonstrate that the novel variant transports arsenite into HEK293T cells. Whereas kfAQP3a, which does not transport arsenite, was expressed in both freshwater (FW) and saltwater (SW) acclimated fish, kfAQP3b, an arsenic transporter, was expressed only in FW acclimated fish, and kfAQP3c was expressed only in SW acclimated fish. Thus, we have identified a novel, putative splice variant of kfAQP3, kfAQP3c, which transports arsenic and is expressed only in SW acclimated fish.

  14. Altered endoribonuclease activity of apurinic/apyrimidinic endonuclease 1 variants identified in the human population.

    Directory of Open Access Journals (Sweden)

    Wan Cheol Kim

    Full Text Available Apurinic/apyrimidinic endonuclease 1 (APE1 is the major mammalian enzyme in the DNA base excision repair pathway and cleaves the DNA phosphodiester backbone immediately 5' to abasic sites. APE1 also has 3'-5' DNA exonuclease and 3' DNA phosphodiesterase activities, and regulates transcription factor DNA binding through its redox regulatory function. The human APE1 has recently been shown to endonucleolytically cleave single-stranded regions of RNA. Towards understanding the biological significance of the endoribonuclease activity of APE1, we examined eight different amino acid substitution variants of APE1 previously identified in the human population. Our study shows that six APE1 variants, D148E, Q51H, I64V, G241R, R237A, and G306A, exhibit a 76-85% reduction in endoribonuclease activity against a specific coding region of the c-myc RNA, yet fully retain the ability to cleave apurinic/apyrimidinic DNA. We found that two APE1 variants, L104R and E126D, exhibit a unique RNase inhibitor-resistant endoribonuclease activity, where the proteins cleave c-myc RNA 3' of specific single-stranded guanosine residues. Expression of L104R and E126D APE1 variants in bacterial Origami cells leads to a 60-80% reduction in colony formation and a 1.5-fold increase in cell doubling time, whereas the other variants, which exhibit diminished endoribonuclease activity, had no effect. These data indicate that two human APE1 variants exhibit a unique endoribonuclease activity, which correlates with their ability to induce cytotoxicity or slow down growth in bacterial cells and supports the notion of their biological functionality.

  15. Altered endoribonuclease activity of apurinic/apyrimidinic endonuclease 1 variants identified in the human population.

    Science.gov (United States)

    Kim, Wan Cheol; Ma, Conan; Li, Wai-Ming; Chohan, Manbir; Wilson, David M; Lee, Chow H

    2014-01-01

    Apurinic/apyrimidinic endonuclease 1 (APE1) is the major mammalian enzyme in the DNA base excision repair pathway and cleaves the DNA phosphodiester backbone immediately 5' to abasic sites. APE1 also has 3'-5' DNA exonuclease and 3' DNA phosphodiesterase activities, and regulates transcription factor DNA binding through its redox regulatory function. The human APE1 has recently been shown to endonucleolytically cleave single-stranded regions of RNA. Towards understanding the biological significance of the endoribonuclease activity of APE1, we examined eight different amino acid substitution variants of APE1 previously identified in the human population. Our study shows that six APE1 variants, D148E, Q51H, I64V, G241R, R237A, and G306A, exhibit a 76-85% reduction in endoribonuclease activity against a specific coding region of the c-myc RNA, yet fully retain the ability to cleave apurinic/apyrimidinic DNA. We found that two APE1 variants, L104R and E126D, exhibit a unique RNase inhibitor-resistant endoribonuclease activity, where the proteins cleave c-myc RNA 3' of specific single-stranded guanosine residues. Expression of L104R and E126D APE1 variants in bacterial Origami cells leads to a 60-80% reduction in colony formation and a 1.5-fold increase in cell doubling time, whereas the other variants, which exhibit diminished endoribonuclease activity, had no effect. These data indicate that two human APE1 variants exhibit a unique endoribonuclease activity, which correlates with their ability to induce cytotoxicity or slow down growth in bacterial cells and supports the notion of their biological functionality.

  16. The genetic code as a periodic table: algebraic aspects.

    Science.gov (United States)

    Bashford, J D; Jarvis, P D

    2000-01-01

    The systematics of indices of physico-chemical properties of codons and amino acids across the genetic code are examined. Using a simple numerical labelling scheme for nucleic acid bases, A=(-1,0), C=(0,-1), G=(0,1), U=(1,0), data can be fitted as low order polynomials of the six coordinates in the 64-dimensional codon weight space. The work confirms and extends the recent studies by Siemion et al. (1995. BioSystems 36, 231-238) of the conformational parameters. Fundamental patterns in the data such as codon periodicities, and related harmonics and reflection symmetries, are here associated with the structure of the set of basis monomials chosen for fitting. Results are plotted using the Siemion one-step mutation ring scheme, and variants thereof. The connections between the present work, and recent studies of the genetic code structure using dynamical symmetry algebras, are pointed out.

  17. Maisonneuve-hyperplantarflexion variant ankle fracture.

    Science.gov (United States)

    Hinds, Richard M; Tran, Wesley H; Lorich, Dean G

    2014-11-01

    Maisonneuve fractures are rare ankle injuries, accounting for up to 7% of all ankle fractures. They consist of a proximal third fibula fracture, syndesmotic disruption, and medial ankle injury (either a deltoid ligament disruption or a medial malleolus fracture), and are often successfully managed with nonoperative treatment of the proximal fibula fracture and open reduction and internal fixation (ORIF) of the medial ankle injury and syndesmotic disruption. The hyperplantarflexion variant ankle fracture comprises approximately 7% of all ankle fractures and features dual posterior tibial lip fractures featuring a posterolateral fragment and a posteromedial fragment. Good functional results have been reported in the literature after ORIF of both the posterolateral and posteromedial fragments of this variant fracture that is not described by the Lauge-Hansen classification. In this report, the authors present the unique case of an isolated ankle fracture demonstrating characteristics of both a Maisonneuve fracture and a hyperplantarflexion variant ankle fracture. They also highlight the diagnostic imaging characteristics, including magnetic resonance imaging (MRI) and preoperative radiograph findings, surgical treatment, and postoperative clinical outcome for this patient with a Maisonneuve-hyperplantarflexion variant ankle fracture. To the authors' knowledge, this unique fracture pattern has not been reported previously in the literature. The authors conclude that although good results were seen postoperatively in this case, the importance of ORIF of both the posteromedial and posterolateral fragments of variant fractures cannot be overstated. They also found MRI to be a particularly helpful adjunct in formulating the correct diagnosis and treatment plan.

  18. Word Variant Identification in Old French

    Directory of Open Access Journals (Sweden)

    Peter Willett

    1997-01-01

    Full Text Available Increasing numbers of historical texts are available in machine-readable form, which retain the original spelling, which can be very different from the modern-day equivalents due to the natural evolution of a language, and because the concept of standardisation in spelling is comparatively modern. Among medieval vernacular writers, the same word could be spelled in different ways and the same author (or scribe might even use several alternative spellings in the same passage. Thus, we do not know,a priori, how many variant forms of a particular word there are in such texts, let alone what these variants might be. Searching on the modern equivalent, or even the commonest historical variant, of a particular word may thus fail to retrieve an appreciable number of occurrences unless the searcher already has an extensive knowledge of the language of the documents. Moreover, even specialist scholars may be unaware of some idiosyncratic variants. Here, we consider the use of computer methods to retrieve variant historical spellings.

  19. Elements of algebraic coding systems

    CERN Document Server

    Cardoso da Rocha, Jr, Valdemar

    2014-01-01

    Elements of Algebraic Coding Systems is an introductory textto algebraic coding theory. In the first chapter, you'll gain insideknowledge of coding fundamentals, which is essential for a deeperunderstanding of state-of-the-art coding systems.This book is a quick reference for those who are unfamiliar withthis topic, as well as for use with specific applications such as cryptographyand communication. Linear error-correcting block codesthrough elementary principles span eleven chapters of the text.Cyclic codes, some finite field algebra, Goppa codes, algebraic decodingalgorithms, and applications in public-key cryptography andsecret-key cryptography are discussed, including problems and solutionsat the end of each chapter. Three appendices cover the Gilbertbound and some related derivations, a derivation of the Mac-Williams' identities based on the probability of undetected error,and two important tools for algebraic decoding-namely, the finitefield Fourier transform and the Euclidean algorithm for polynomials.

  20. Functional Assessment of Disease-Associated Regulatory Variants In Vivo Using a Versatile Dual Colour Transgenesis Strategy in Zebrafish

    Science.gov (United States)

    Bhatia, Shipra; Gordon, Christopher T.; Foster, Robert G.; Melin, Lucie; Abadie, Véronique; Baujat, Geneviève; Vazquez, Marie-Paule; Amiel, Jeanne; Lyonnet, Stanislas; van Heyningen, Veronica; Kleinjan, Dirk A.

    2015-01-01

    Disruption of gene regulation by sequence variation in non-coding regions of the genome is now recognised as a significant cause of human disease and disease susceptibility. Sequence variants in cis-regulatory elements (CREs), the primary determinants of spatio-temporal gene regulation, can alter transcription factor binding sites. While technological advances have led to easy identification of disease-associated CRE variants, robust methods for discerning functional CRE variants from background variation are lacking. Here we describe an efficient dual-colour reporter transgenesis approach in zebrafish, simultaneously allowing detailed in vivo comparison of spatio-temporal differences in regulatory activity between putative CRE variants and assessment of altered transcription factor binding potential of the variant. We validate the method on known disease-associated elements regulating SHH, PAX6 and IRF6 and subsequently characterise novel, ultra-long-range SOX9 enhancers implicated in the craniofacial abnormality Pierre Robin Sequence. The method provides a highly cost-effective, fast and robust approach for simultaneously unravelling in a single assay whether, where and when in embryonic development a disease-associated CRE-variant is affecting its regulatory function. PMID:26030420

  1. Characterization of a novel five-transmembrane domain cholecystokinin-2 receptor splice variant identified in human tumors.

    Science.gov (United States)

    Sanchez, Claire; Escrieut, Chantal; Clerc, Pascal; Gigoux, Véronique; Waser, Beatrice; Reubi, Jean Claude; Fourmy, Daniel

    2012-02-26

    The cholecystokinin-2 receptor (CCK2R), is expressed in cancers where it contributes to tumor progression. The CCK2R is over-expressed in a sub-set of tumors, allowing its use in tumor targeting with a radiolabel ligand. Since discrepancies between mRNA levels and CCK2R binding sites were noticed, we searched for abnormally spliced variants in tumors from various origins having been previously reported to frequently express cholecystokinin receptors, such as medullary thyroid carcinomas, gastrointestinal stromal tumors, leiomyomas and leiomyosarcomas, and gastroenteropancreatic tumors. A variant of the CCK2R coding for a putative five-transmembrane domains receptor has been cloned. This variant represented as much as 6% of CCK2R levels. Ectopic expression in COS-7 cells revealed that this variant lacks biological activity due to its sequestration in endoplasmic reticulum. When co-expressed with the CCK2R, this variant diminished membrane density of the CCK2R and CCK2R-mediated activity (phospholipase-C and ERK activation). In conclusion, a novel splice variant acting as a dominant negative on membrane density of the CCK2R may be of importance for the pathophysiology of certain tumors and for their in vivo CCK2R-targeting.

  2. BILINEAR FORMS AND LINEAR CODES

    Institute of Scientific and Technical Information of China (English)

    高莹

    2004-01-01

    Abraham Lempel et al[1] made a connection between linear codes and systems of bilinear forms over finite fields. In this correspondence, a new simple proof of a theorem in [1] is presented; in addition, the encoding process and the decoding procedure of RS codes are simplified via circulant matrices. Finally, the results show that the correspondence between bilinear forms and linear codes is not unique.

  3. Error correcting coding for OTN

    DEFF Research Database (Denmark)

    Justesen, Jørn; Larsen, Knud J.; Pedersen, Lars A.

    2010-01-01

    Forward error correction codes for 100 Gb/s optical transmission are currently receiving much attention from transport network operators and technology providers. We discuss the performance of hard decision decoding using product type codes that cover a single OTN frame or a small number...... of such frames. In particular we argue that a three-error correcting BCH is the best choice for the component code in such systems....

  4. High performance scalable image coding

    Institute of Scientific and Technical Information of China (English)

    Gan Tao; He Yanmin; Zhu Weile

    2007-01-01

    A high performance scalable image coding algorithm is proposed. The salient features of this algorithm are the ways to form and locate the significant clusters. Thanks to the list structure, the new coding algorithm achieves fine fractional bit-plane coding with negligible additional complexity. Experiments show that it performs comparably or better than the state-of-the-art coders. Furthermore, the flexible codec supports both quality and resolution scalability, which is very attractive in many network applications.

  5. Code Speed Measuring for VC++

    Science.gov (United States)

    2015-10-01

    UNCLASSIFIED AD-E403 688 Technical Report ARWSE-TR-14025 CODE SPEED MEASURING FOR VC++ Tom Nealis...TYPE Final 3. DATES COVERED (From – To) 4. TITLE AND SUBTITLE CODE SPEED MEASURING FOR VC++ 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c...ABSTRACT It’s often important to know how fast a snippet of code executes. This information allows the coder to make important decisions

  6. ACE spectrum of LDPC codes

    Directory of Open Access Journals (Sweden)

    Vukobratović Dejan

    2006-01-01

    Full Text Available Construction of short-length LDPC codes with good, both waterfall and error-floor, behavior is still an attractive research problem. Recently proposed construction algorithms in this field are based on remarkably simple ideas, but yet, their effectiveness can still be questioned. In this paper we investigate a novel measure of goodness of a given LDPC code namely its ACE spectrum, based on a previously introduced ACE metrics associated with each cycle in LDPC code graph.

  7. QR code for medical information uses.

    Science.gov (United States)

    Fontelo, Paul; Liu, Fang; Ducut, Erick G

    2008-11-06

    We developed QR code online tools, simulated and tested QR code applications for medical information uses including scanning QR code labels, URLs and authentication. Our results show possible applications for QR code in medicine.

  8. Modulation of Malaria Phenotypes by Pyruvate Kinase (PKLR) Variants in a Thai Population.

    Science.gov (United States)

    van Bruggen, Rebekah; Gualtieri, Christian; Iliescu, Alexandra; Louicharoen Cheepsunthorn, Chalisa; Mungkalasut, Punchalee; Trape, Jean-François; Modiano, David; Sirima, Bienvenu Sodiomon; Singhasivanon, Pratap; Lathrop, Mark; Sakuntabhai, Anavaj; Bureau, Jean-François; Gros, Philippe

    2015-01-01

    Pyruvate kinase (PKLR) is a critical erythrocyte enzyme that is required for glycolysis and production of ATP. We have shown that Pklr deficiency in mice reduces the severity (reduced parasitemia, increased survival) of blood stage malaria induced by infection with Plasmodium chabaudi AS. Likewise, studies in human erythrocytes infected ex vivo with P. falciparum show that presence of host PK-deficiency alleles reduces infection phenotypes. We have characterized the genetic diversity of the PKLR gene, including haplotype structure and presence of rare coding variants in two populations from malaria endemic areas of Thailand and Senegal. We investigated the effect of PKLR genotypes on rich longitudinal datasets including haematological and malaria-associated phenotypes. A coding and possibly damaging variant (R41Q) was identified in the Thai population with a minor allele frequency of ~4.7%. Arginine 41 (R41) is highly conserved in the pyruvate kinase family and its substitution to Glutamine (R41Q) affects protein stability. Heterozygosity for R41Q is shown to be associated with a significant reduction in the number of attacks with Plasmodium falciparum, while correlating with an increased number of Plasmodium vivax infections. These results strongly suggest that PKLR protein variants may affect the frequency, and the intensity of malaria episodes induced by different Plasmodium parasites in humans living in areas of endemic malaria.

  9. Modulation of Malaria Phenotypes by Pyruvate Kinase (PKLR Variants in a Thai Population.

    Directory of Open Access Journals (Sweden)

    Rebekah van Bruggen

    Full Text Available Pyruvate kinase (PKLR is a critical erythrocyte enzyme that is required for glycolysis and production of ATP. We have shown that Pklr deficiency in mice reduces the severity (reduced parasitemia, increased survival of blood stage malaria induced by infection with Plasmodium chabaudi AS. Likewise, studies in human erythrocytes infected ex vivo with P. falciparum show that presence of host PK-deficiency alleles reduces infection phenotypes. We have characterized the genetic diversity of the PKLR gene, including haplotype structure and presence of rare coding variants in two populations from malaria endemic areas of Thailand and Senegal. We investigated the effect of PKLR genotypes on rich longitudinal datasets including haematological and malaria-associated phenotypes. A coding and possibly damaging variant (R41Q was identified in the Thai population with a minor allele frequency of ~4.7%. Arginine 41 (R41 is highly conserved in the pyruvate kinase family and its substitution to Glutamine (R41Q affects protein stability. Heterozygosity for R41Q is shown to be associated with a significant reduction in the number of attacks with Plasmodium falciparum, while correlating with an increased number of Plasmodium vivax infections. These results strongly suggest that PKLR protein variants may affect the frequency, and the intensity of malaria episodes induced by different Plasmodium parasites in humans living in areas of endemic malaria.

  10. Modulation of Malaria Phenotypes by Pyruvate Kinase (PKLR) Variants in a Thai Population

    Science.gov (United States)

    van Bruggen, Rebekah; Gualtieri, Christian; Iliescu, Alexandra; Louicharoen Cheepsunthorn, Chalisa; Mungkalasut, Punchalee; Trape, Jean-François; Modiano, David; Sodiomon Sirima, Bienvenu; Singhasivanon, Pratap; Lathrop, Mark; Sakuntabhai, Anavaj; Bureau, Jean-François; Gros, Philippe

    2015-01-01

    Pyruvate kinase (PKLR) is a critical erythrocyte enzyme that is required for glycolysis and production of ATP. We have shown that Pklr deficiency in mice reduces the severity (reduced parasitemia, increased survival) of blood stage malaria induced by infection with Plasmodium chabaudi AS. Likewise, studies in human erythrocytes infected ex vivo with P. falciparum show that presence of host PK-deficiency alleles reduces infection phenotypes. We have characterized the genetic diversity of the PKLR gene, including haplotype structure and presence of rare coding variants in two populations from malaria endemic areas of Thailand and Senegal. We investigated the effect of PKLR genotypes on rich longitudinal datasets including haematological and malaria-associated phenotypes. A coding and possibly damaging variant (R41Q) was identified in the Thai population with a minor allele frequency of ~4.7%. Arginine 41 (R41) is highly conserved in the pyruvate kinase family and its substitution to Glutamine (R41Q) affects protein stability. Heterozygosity for R41Q is shown to be associated with a significant reduction in the number of attacks with Plasmodium falciparum, while correlating with an increased number of Plasmodium vivax infections. These results strongly suggest that PKLR protein variants may affect the frequency, and the intensity of malaria episodes induced by different Plasmodium parasites in humans living in areas of endemic malaria. PMID:26658699

  11. Astrophysics Source Code Library Enhancements

    CERN Document Server

    Hanisch, Robert J; Berriman, G Bruce; DuPrie, Kimberly; Mink, Jessica; Nemiroff, Robert J; Schmidt, Judy; Shamir, Lior; Shortridge, Keith; Taylor, Mark; Teuben, Peter J; Wallin, John

    2014-01-01

    The Astrophysics Source Code Library (ASCL; ascl.net) is a free online registry of codes used in astronomy research; it currently contains over 900 codes and is indexed by ADS. The ASCL has recently moved a new infrastructure into production. The new site provides a true database for the code entries and integrates the WordPress news and information pages and the discussion forum into one site. Previous capabilities are retained and permalinks to ascl.net continue to work. This improvement offers more functionality and flexibility than the previous site, is easier to maintain, and offers new possibilities for collaboration. This presentation covers these recent changes to the ASCL.

  12. Multiple Beamforming with Perfect Coding

    CERN Document Server

    Li, Boyu

    2011-01-01

    In Singular Value Decomposition (SVD) beamforming, without channel coding, there is a trade-off between full diversity and full multiplexing. Adding channel coding, full diversity and full multiplexing can be both achieved, as long as the code rate Rc and the number of subchannels S satisfy RcS1. Recently discovered Perfect Space-Time Block Codes (PSTBCs) are full-rate full-diversity space-time codes, achieving maximum coding gain. In this paper, two novel techniques, Perfect Coded Multiple Beamforming (PCMB) and Bit-Interleaved Coded Multiple Beamforming with Perfect Coding (BICMB-PC), are proposed, employing PSTBCs. PCMB achieves full diversity, full multiplexing, and full rate simultaneously, and its performance is close to PSTBC and FPMB, while the decoding complexity is significantly less than PSTBC and much lower than FPMB of dimensions 2 and 4. On the other hand, BICMB-PC achieves both full diversity and full multiplexing, and its performance is similar to BICMB-FP, but provides much lower decoding com...

  13. Automatic code generation in practice

    DEFF Research Database (Denmark)

    Adam, Marian Sorin; Kuhrmann, Marco; Schultz, Ulrik Pagh

    2016-01-01

    -specific language to specify those requirements and to allow for generating a safety-enforcing layer of code, which is deployed to the robot. The paper at hand reports experiences in practically applying code generation to mobile robots. For two cases, we discuss how we addressed challenges, e.g., regarding weaving...... code generation into proprietary development environments and testing of manually written code. We find that a DSL based on the same conceptual model can be used across different kinds of hardware modules, but a significant adaptation effort is required in practical scenarios involving different kinds...

  14. Should you learn to code?

    CERN Document Server

    Team, The Hyperink

    2013-01-01

    On May 15, 2012 Jeff Atwood (co-founder of Stack Overflow) published a blog post titled "Please Don't Learn to Code" in response to Mayor Mike Bloomberg's resolution to learn how to code in 2012. In that post he argues against "learning to code just for the sake of learning how to code," a sentiment that sparked an active online debate. This book is a compilation of several different perspectives on that debate. Should programming be taught to every student as part of their core curriculum, similar to mathematics, reading, and writing? Should every working professional take time to learn a

  15. Grassmann codes and Schubert unions

    DEFF Research Database (Denmark)

    Hansen, Johan Peder; Johnsen, Trygve; Ranestad, Kristian

    2009-01-01

    We study subsets of Grassmann varieties over a field , such that these subsets are unions of Schubert cycles, with respect to a fixed flag. We study such sets in detail, and give applications to coding theory, in particular for Grassmann codes. For much is known about such Schubert unions...... with a maximal number of -rational points for a given spanning dimension. We study the case and give a conjecture for general . We also define Schubert union codes in general, and study the parameters and support weights of these codes....

  16. Semi-supervised sparse coding

    KAUST Repository

    Wang, Jim Jing-Yan

    2014-07-06

    Sparse coding approximates the data sample as a sparse linear combination of some basic codewords and uses the sparse codes as new presentations. In this paper, we investigate learning discriminative sparse codes by sparse coding in a semi-supervised manner, where only a few training samples are labeled. By using the manifold structure spanned by the data set of both labeled and unlabeled samples and the constraints provided by the labels of the labeled samples, we learn the variable class labels for all the samples. Furthermore, to improve the discriminative ability of the learned sparse codes, we assume that the class labels could be predicted from the sparse codes directly using a linear classifier. By solving the codebook, sparse codes, class labels and classifier parameters simultaneously in a unified objective function, we develop a semi-supervised sparse coding algorithm. Experiments on two real-world pattern recognition problems demonstrate the advantage of the proposed methods over supervised sparse coding methods on partially labeled data sets.

  17. Identification of minority resistance mutations in the HIV-1 integrase coding region using next generation sequencing

    DEFF Research Database (Denmark)

    Fonager, Jannik; Larsson, Jonas T; Hussing, Christian

    2015-01-01

    BACKGROUND: The current widely applied standard method to screen for HIV-1 genotypic resistance is based on Sanger population sequencing (Sseq), which does not allow for the identification of minority variants (MVs) below the limit of detection for the Sseq-method in patients receiving integrase......: raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG). STUDY DESIGN: NGS and Sseq were used to analyze RT-PCR products of the HIV-1 integrase coding region from six patients and in serial samples from two patients. NGS sequences were assembled and analyzed using the low frequency variant detection...

  18. Next-gen sequencing identifies non-coding variation disrupting miRNA-binding sites in neurological disorders.

    Science.gov (United States)

    Devanna, P; Chen, X S; Ho, J; Gajewski, D; Smith, S D; Gialluisi, A; Francks, C; Fisher, S E; Newbury, D F; Vernes, S C

    2017-03-14

    Understanding the genetic factors underlying neurodevelopmental and neuropsychiatric disorders is a major challenge given their prevalence and potential severity for quality of life. While large-scale genomic screens have made major advances in this area, for many disorders the genetic underpinnings are complex and poorly understood. To date the field has focused predominantly on protein coding variation, but given the importance of tightly controlled gene expression for normal brain development and disorder, variation that affects non-coding regulatory regions of the genome is likely to play an important role in these phenotypes. Herein we show the importance of 3 prime untranslated region (3'UTR) non-coding regulatory variants across neurodevelopmental and neuropsychiatric disorders. We devised a pipeline for identifying and functionally validating putatively pathogenic variants from next generation sequencing (NGS) data. We applied this pipeline to a cohort of children with severe specific language impairment (SLI) and identified a functional, SLI-associated variant affecting gene regulation in cells and post-mortem human brain. This variant and the affected gene (ARHGEF39) represent new putative risk factors for SLI. Furthermore, we identified 3'UTR regulatory variants across autism, schizophrenia and bipolar disorder NGS cohorts demonstrating their impact on neurodevelopmental and neuropsychiatric disorders. Our findings show the importance of investigating non-coding regulatory variants when determining risk factors contributing to neurodevelopmental and neuropsychiatric disorders. In the future, integration of such regulatory variation with protein coding changes will be essential for uncovering the genetic causes of complex neurological disorders and the fundamental mechanisms underlying health and disease.Molecular Psychiatry advance online publication, 14 March 2017; doi:10.1038/mp.2017.30.

  19. Coding, cryptography and combinatorics

    CERN Document Server

    Niederreiter, Harald; Xing, Chaoping

    2004-01-01

    It has long been recognized that there are fascinating connections between cod­ ing theory, cryptology, and combinatorics. Therefore it seemed desirable to us to organize a conference that brings together experts from these three areas for a fruitful exchange of ideas. We decided on a venue in the Huang Shan (Yellow Mountain) region, one of the most scenic areas of China, so as to provide the additional inducement of an attractive location. The conference was planned for June 2003 with the official title Workshop on Coding, Cryptography and Combi­ natorics (CCC 2003). Those who are familiar with events in East Asia in the first half of 2003 can guess what happened in the end, namely the conference had to be cancelled in the interest of the health of the participants. The SARS epidemic posed too serious a threat. At the time of the cancellation, the organization of the conference was at an advanced stage: all invited speakers had been selected and all abstracts of contributed talks had been screened by the p...

  20. Polymatroids with Network Coding

    CERN Document Server

    Han, Te Sun

    2010-01-01

    The problem of network coding for multicasting a single source to multiple sinks has first been studied by Ahlswede, Cai, Li and Yeung in 2000, in which they have established the celebrated max-flow mini-cut theorem on non-physical information flow over a network of independent channels. On the other hand, in 1980, Han has studied the case with correlated multiple sources and a single sink from the viewpoint of polymatroidal functions in which a necessary and sufficient condition has been demonstrated for reliable transmission over the network. This paper presents an attempt to unify both cases, which leads to establish a necessary and sufficient condition for reliable transmission over a noisy network for multicasting all the correlated multiple sources to all the multiple sinks. Furthermore, we address also the problem of transmitting "independent" sources over a multiple-access-type of network as well as over a broadcast-type of network, which reveals that the (co-) polymatroidal structures are intrinsical...

  1. Consensus Convolutional Sparse Coding

    KAUST Repository

    Choudhury, Biswarup

    2017-04-11

    Convolutional sparse coding (CSC) is a promising direction for unsupervised learning in computer vision. In contrast to recent supervised methods, CSC allows for convolutional image representations to be learned that are equally useful for high-level vision tasks and low-level image reconstruction and can be applied to a wide range of tasks without problem-specific retraining. Due to their extreme memory requirements, however, existing CSC solvers have so far been limited to low-dimensional problems and datasets using a handful of low-resolution example images at a time. In this paper, we propose a new approach to solving CSC as a consensus optimization problem, which lifts these limitations. By learning CSC features from large-scale image datasets for the first time, we achieve significant quality improvements in a number of imaging tasks. Moreover, the proposed method enables new applications in high dimensional feature learning that has been intractable using existing CSC methods. This is demonstrated for a variety of reconstruction problems across diverse problem domains, including 3D multispectral demosaickingand 4D light field view synthesis.

  2. Variants of Monteggia Type Injury: Case Reports

    Directory of Open Access Journals (Sweden)

    Kamudin NAF

    2015-03-01

    Full Text Available Background: Monteggia fracture-dislocation is rare in children. Various reports attest to its rarity, while recording the many variant of this injury. It is, therefore, easy to miss the diagnosis in the absence of proper clinical examination and radiographs. Case Report : This report highlights two rare variants of Monteggia fracture-dislocation seen in children. The first case was a 12-year old girl alleged to have fallen from a 15-feet tall tree and sustaining a combined type III Monteggia injury with ipsilateral Type II Salter-Harris injury of distal end radius with a metaphyseal fracture of the distal third of the ulna. The second case was a 13-year old who had sustained a closed fracture of atypical Type I Monteggia hybrid lesion, in a road traffic accident. Conclusion: This report highlights the rare variants of Monteggia fracture dislocation which could have been missed without proper clinical examinations and radiographs.

  3. Variants of Monteggia Type Injury: Case Reports

    Science.gov (United States)

    Firdouse, M; Han, CS; M Yusof, A

    2015-01-01

    Background Monteggia fracture-dislocation is rare in children. Various reports attest to its rarity, while recording the many variant of this injury. It is, therefore, easy to miss the diagnosis in the absence of proper clinical examination and radiographs. Case Report This report highlights two rare variants of Monteggia fracture-dislocation seen in children. The first case was a 12-year old girl alleged to have fallen from a 15- feet tall tree and sustaining a combined type III Monteggia injury with ipsilateral Type II Salter-Harris injury of distal end radius with a metaphyseal fracture of the distal third of the ulna. The second case was a 13-year old who had sustained a closed fracture of atypical Type I Monteggia hybrid lesion, in a road traffic accident. Conclusion This report highlights the rare variants of Monteggia fracture dislocation which could have been missed without proper clinical examinations and radiographs. PMID:28435591

  4. Genetics in psychiatry: common variant association studies

    Directory of Open Access Journals (Sweden)

    Buxbaum Joseph D

    2010-03-01

    Full Text Available Abstract Many psychiatric conditions and traits are associated with significant heritability. Genetic risk for psychiatric conditions encompass rare variants, identified due to major effect, as well as common variants, the latter analyzed by association analyses. We review guidelines for common variant association analyses, undertaking after assessing evidence of heritability. We highlight the importance of: suitably large sample sizes; an experimental design that controls for ancestry; careful data cleaning; correction for multiple testing; small P values for positive findings; assessment of effect size for positive findings; and, inclusion of an independent replication sample. We also note the importance of a critical discussion of any prior findings, biological follow-up where possible, and a means of accessing the raw data.

  5. A case of reninoma with variant angina

    Directory of Open Access Journals (Sweden)

    Hyung Ah Jo

    2014-06-01

    Full Text Available Reninoma is a tumor of the renal juxtaglomerular cell apparatus that causes hypertension and hypokalemia because of hypersecretion of renin. We present a case of a 29-year-old female patient with reninoma and concomitant variant angina. The patient had uncontrolled hypertension and elevated plasma renin activity and aldosterone levels. Imaging studies revealed a mass in the left kidney, which was further confirmed as a renin-producing lesion via selective venous catheterization. During the evaluation, the patient had acute-onset chest pain that was diagnosed as variant angina after a provocation test. After partial nephrectomy, the plasma renin activity and plasma aldosterone levels decreased and blood pressure normalized. We report a case of reninoma with variant angina.

  6. Hemoglobin variants: biochemical properties and clinical correlates.

    Science.gov (United States)

    Thom, Christopher S; Dickson, Claire F; Gell, David A; Weiss, Mitchell J

    2013-03-01

    Diseases affecting hemoglobin synthesis and function are extremely common worldwide. More than 1000 naturally occurring human hemoglobin variants with single amino acid substitutions throughout the molecule have been discovered, mainly through their clinical and/or laboratory manifestations. These variants alter hemoglobin structure and biochemical properties with physiological effects ranging from insignificant to severe. Studies of these mutations in patients and in the laboratory have produced a wealth of information on hemoglobin biochemistry and biology with significant implications for hematology practice. More generally, landmark studies of hemoglobin performed over the past 60 years have established important paradigms for the disciplines of structural biology, genetics, biochemistry, and medicine. Here we review the major classes of hemoglobin variants, emphasizing general concepts and illustrative examples.

  7. Decoding of concatenated codes with interleaved outer codes

    DEFF Research Database (Denmark)

    Justesen, Jørn; Høholdt, Tom; Thommesen, Christian

    2004-01-01

    Recently Bleichenbacher et al. proposed a decoding algorithm for interleaved (N, K) Reed-Solomon codes, which allows close to N-K errors to be corrected in many cases. We discuss the application of this decoding algorithm to concatenated codes....

  8. The KIDTALK Behavior and Language Code: Manual and Coding Protocol.

    Science.gov (United States)

    Delaney, Elizabeth M.; Ezell, Sara S.; Solomon, Ned A.; Hancock, Terry B.; Kaiser, Ann P.

    Developed as part of the Milieu Language Teaching Project at the John F. Kennedy Center at Vanderbilt University in Nashville, Tennessee, this KIDTALK Behavior-Language Coding Protocol and manual measures behavior occurring during adult-child interactions. The manual is divided into 5 distinct sections: (1) the adult behavior codes describe…

  9. Evidence for differences in the binding of drugs to the two main genetic variants of human alpha 1-acid glycoprotein.

    Science.gov (United States)

    Herve, F; Gomas, E; Duche, J C; Tillement, J P

    1993-09-01

    1. Human alpha 1-acid glycoprotein (AAG), a plasma transport protein, has three main genetic variants. F1. S and A. Native commercial AAG (a mixture of almost equal proportions of these three variants) has been separated by chromatography into variants which correspond to the proteins of the two genes which code for AAG in humans: the A variant and a mixture of the F1 and S variants (60% F1 and 40% S). Their binding properties towards imipramine, warfarin and mifepristone were studied by equilibrium dialysis. 2. The F1S variant mixture strongly bound warfarin and mifepristone with an affinity of 1.89 and 2.06 x 10(6) l mol-1, respectively, but had a low affinity for imipramine. Conversely, the A variant strongly bound imipramine with an affinity of 0.98 x 10(6) l mol-1. The low degree of binding of warfarin and mifepristone to the A variant sample was explained by the presence of protein contaminants in this sample. These results indicate specific drug transport roles for each variant, with respect to its separate genetic origin. 3. Control binding experiments performed with (unfractionated) commercial AAG and with AAG isolated from individuals with either the F1/A or S/A phenotypes, agreed with these findings. The results for the binding of warfarin and mifepristone by the AAG samples were similar to those obtained with the F1S mixture: the mean high-affinity association constant of the AAG samples for each drug was of the same order as that of the F1S mixture: the decrease in the number of binding sites of the AAG samples, as compared with the F1S mixture, was explained by the smaller proportion of variants F1 and/or S in these samples. Conversely, results of the imipramine binding study with the AAG samples concurred with those for the binding of this basic drug by the A variant, with respect to the proportion of the A variant in these samples.

  10. A Splice Variant of Bardet-Biedl Syndrome 5 (BBS5 Protein that Is Selectively Expressed in Retina.

    Directory of Open Access Journals (Sweden)

    Susan N Bolch

    Full Text Available Bardet-Biedl syndrome is a complex ciliopathy that usually manifests with some form of retinal degeneration, amongst other ciliary-related deficiencies. One of the genetic causes of this syndrome results from a defect in Bardet-Biedl Syndrome 5 (BBS5 protein. BBS5 is one component of the BBSome, a complex of proteins that regulates the protein composition in cilia. In this study, we identify a smaller molecular mass form of BBS5 as a variant formed by alternative splicing and show that expression of this splice variant is restricted to the retina.Reverse transcription PCR from RNA was used to isolate and identify potential alternative transcripts of Bbs5. A peptide unique to the C-terminus of the BBS5 splice variant was synthesized and used to prepare antibodies that selectively recognized the BBS5 splice variant. These antibodies were used on immunoblots of tissue extracts to determine the extent of expression of the alternative transcript and on tissue slices to determine the localization of expressed protein. Pull-down of fluorescently labeled arrestin1 by immunoprecipitation of the BBS5 splice variant was performed to assess functional interaction between the two proteins.PCR from mouse retinal cDNA using Bbs5-specific primers amplified a unique cDNA that was shown to be a splice variant of BBS5 resulting from the use of cryptic splicing sites in Intron 7. The resulting transcript codes for a truncated form of the BBS5 protein with a unique 24 amino acid C-terminus, and predicted 26.5 kD molecular mass. PCR screening of RNA isolated from various ciliated tissues and immunoblots of protein extracts from these same tissues showed that this splice variant was expressed in retina, but not brain, heart, kidney, or testes. Quantitative PCR showed that the splice variant transcript is 8.9-fold (+/- 1.1-fold less abundant than the full-length transcript. In the retina, the splice variant of BBS5 appears to be most abundant in the connecting cilium

  11. Regulatory element-based prediction identifies new susceptibility regulatory variants for osteoporosis.

    Science.gov (United States)

    Yao, Shi; Guo, Yan; Dong, Shan-Shan; Hao, Ruo-Han; Chen, Xiao-Feng; Chen, Yi-Xiao; Chen, Jia-Bin; Tian, Qing; Deng, Hong-Wen; Yang, Tie-Lin

    2017-08-01

    Despite genome-wide association studies (GWASs) have identified many susceptibility genes for osteoporosis, it still leaves a large part of missing heritability to be discovered. Integrating regulatory information and GWASs could offer new insights into the biological link between the susceptibility SNPs and osteoporosis. We generated five machine learning classifiers with osteoporosis-associated variants and regulatory features data. We gained the optimal classifier and predicted genome-wide SNPs to discover susceptibility regulatory variants. We further utilized Genetic Factors for Osteoporosis Consortium (GEFOS) and three in-house GWASs samples to validate the associations for predicted positive SNPs. The random forest classifier performed best among all machine learning methods with the F1 score of 0.8871. Using the optimized model, we predicted 37,584 candidate SNPs for osteoporosis. According to the meta-analysis results, a list of regulatory variants was significantly associated with osteoporosis after multiple testing corrections and contributed to the expression of known osteoporosis-associated protein-coding genes. In summary, combining GWASs and regulatory elements through machine learning could provide additional information for understanding the mechanism of osteoporosis. The regulatory variants we predicted will provide novel targets for etiology research and treatment of osteoporosis.

  12. VaRank: a simple and powerful tool for ranking genetic variants

    Directory of Open Access Journals (Sweden)

    Véronique Geoffroy

    2015-03-01

    Full Text Available Background. Most genetic disorders are caused by single nucleotide variations (SNVs or small insertion/deletions (indels. High throughput sequencing has broadened the catalogue of human variation, including common polymorphisms, rare variations or disease causing mutations. However, identifying one variation among hundreds or thousands of others is still a complex task for biologists, geneticists and clinicians. Results. We have developed VaRank, a command-line tool for the ranking of genetic variants detected by high-throughput sequencing. VaRank scores and prioritizes variants annotated either by Alamut Batch or SnpEff. A barcode allows users to quickly view the presence/absence of variants (with homozygote/heterozygote status in analyzed samples. VaRank supports the commonly used VCF input format for variants analysis thus allowing it to be easily integrated into NGS bioinformatics analysis pipelines. VaRank has been successfully applied to disease-gene identification as well as to molecular diagnostics setup for several hundred patients. Conclusions. VaRank is implemented in Tcl/Tk, a scripting language which is platform-independent but has been tested only on Unix environment. The source code is available under the GNU GPL, and together with sample data and detailed documentation can be downloaded from http://www.lbgi.fr/VaRank/.

  13. Guaranteeing Syntactic Correctness for All Product Line Variants: A Language-Independent Approach

    Science.gov (United States)

    Kästner, Christian; Apel, Sven; Trujillo, Salvador; Kuhlemann, Martin; Batory, Don

    A software product line (SPL) is a family of related program variants in a well-defined domain, generated from a set of features. A fundamental difference from classical application development is that engineers develop not a single program but a whole family with hundreds to millions of variants. This makes it infeasible to separately check every distinct variant for errors. Still engineers want guarantees on the entire SPL. A further challenge is that an SPL may contain artifacts in different languages (code, documentation, models, etc.) that should be checked. In this paper, we present CIDE, an SPL development tool that guarantees syntactic correctness for all variants of an SPL. We show how CIDE’s underlying mechanism abstracts from textual representation and we generalize it to arbitrary languages. Furthermore, we automate the generation of plug-ins for additional languages from annotated grammars. To demonstrate the language-independent capabilities, we applied CIDE to a series of case studies with artifacts written in Java, C++, C, Haskell, ANTLR, HTML, and XML.

  14. The Impact of PPARγ Genetic Variants on IBD Susceptibility and IBD Disease Course

    Directory of Open Access Journals (Sweden)

    Jessica Mwinyi

    2012-01-01

    Full Text Available PPARγ is a nuclear receptor that regulates numerous pathways including cytokine expression and immune responses and plays an important role in controlling colon inflammation. We aimed at determining the occurring PPARγ SNPs, at predicting the haplotypes, and at determining the frequency outcome in inflammatory bowel disease (IBD patients in comparison with healthy controls. We determined genetic variants in the coding exons and flanking intronic sequences of the NR1C3 gene in 284 IBD patients and 194 controls and predicted NR1C3 haplotypes via bioinformatic analysis. We investigated whether certain NR1C3 variants are associated with susceptibility to IBD or its disease course. None of the detected 22 NR1C3 variants were associated with IBD. Two variants with allelic frequencies over 1% were included in haplotype/diplotype analyses. None of the NR3C1 haplotypes showed association with IBD development or disease course. We conclude that NR1C3 haplotypes are not related to IBD susceptibility or IBD disease activity.

  15. VaRank: a simple and powerful tool for ranking genetic variants.

    Science.gov (United States)

    Geoffroy, Véronique; Pizot, Cécile; Redin, Claire; Piton, Amélie; Vasli, Nasim; Stoetzel, Corinne; Blavier, André; Laporte, Jocelyn; Muller, Jean

    2015-01-01

    Background. Most genetic disorders are caused by single nucleotide variations (SNVs) or small insertion/deletions (indels). High throughput sequencing has broadened the catalogue of human variation, including common polymorphisms, rare variations or disease causing mutations. However, identifying one variation among hundreds or thousands of others is still a complex task for biologists, geneticists and clinicians. Results. We have developed VaRank, a command-line tool for the ranking of genetic variants detected by high-throughput sequencing. VaRank scores and prioritizes variants annotated either by Alamut Batch or SnpEff. A barcode allows users to quickly view the presence/absence of variants (with homozygote/heterozygote status) in analyzed samples. VaRank supports the commonly used VCF input format for variants analysis thus allowing it to be easily integrated into NGS bioinformatics analysis pipelines. VaRank has been successfully applied to disease-gene identification as well as to molecular diagnostics setup for several hundred patients. Conclusions. VaRank is implemented in Tcl/Tk, a scripting language which is platform-independent but has been tested only on Unix environment. The source code is available under the GNU GPL, and together with sample data and detailed documentation can be downloaded from http://www.lbgi.fr/VaRank/.

  16. Coded Path Protection: Efficient Conversion of Sharing to Coding

    CERN Document Server

    Avci, Serhat Nazim

    2011-01-01

    Link failures in wide area networks are common and cause significant data losses. Mesh-based protection schemes offer high capacity efficiency but they are slow and require complex signaling. Additionally, real-time reconfiguration of a cross-connect threatens their transmission integrity. On the other hand, coding-based protection schemes are proactive. Therefore, they have higher restoration speed, lower signaling complexity, and higher transmission integrity. This paper introduces a coding-based protection scheme, named Coded Path Protection (CPP). In CPP, a backup copy of the primary data is encoded with other data streams, resulting in capacity savings. This paper presents an optimal and simple capacity placement and coding group formation algorithm. The algorithm converts the sharing structure of any solution of a Shared Path Protection (SPP) technique into a coding structure with minimum extra capacity. We conducted quantitative and qualitative comparisons of our technique with the SPP and, another tec...

  17. Cryptanalysis of SIMON Variants with Connections

    DEFF Research Database (Denmark)

    Alizadeh, Javad; Alkhzaimi, Hoda A.; Aref, Mohammad Reza

    2014-01-01

    SIMON is a family of 10 lightweight block ciphers published by Beaulieu et al. from the United States National Security Agency (NSA). A cipher in this family with K-bit key and N-bit block is called SIMONN/K. We present several linear characteristics for reduced-round SIMON32/64 that can be used...... the presented observations do not directly yield an attack, but provide a basis for further analysis for the specific SIMON variant. Finally, we exploit a connection between linear and differential characteristics for SIMON to construct linear characteristics for different variants of reduced-round SIMON. Our...

  18. Histone variants and melanoma: facts and hypotheses.

    Science.gov (United States)

    Konstantinov, Nikifor K; Ulff-Møller, Constance J; Dimitrov, Stefan

    2016-07-01

    Melanoma is the most aggressive form of skin cancer with rising incidence and morbidity. Despite advances in treatment, the 10-yr survival for patients with metastatic disease is less than 10%. During the past few years, ongoing research on different epigenomic aberrations in melanoma has catalyzed better understanding of its pathogenesis and identification of new therapeutics. In our review, we will focus on the role of histone variants, key epigenetic players in melanoma initiation and progression. Specifically, incorporation of histone variants enables additional layers of chromatin structure, and here, we will describe how alterations in this epigenetic behavior impact melanoma.

  19. Allele coding in genomic evaluation

    Directory of Open Access Journals (Sweden)

    Christensen Ole F

    2011-06-01

    Full Text Available Abstract Background Genomic data are used in animal breeding to assist genetic evaluation. Several models to estimate genomic breeding values have been studied. In general, two approaches have been used. One approach estimates the marker effects first and then, genomic breeding values are obtained by summing marker effects. In the second approach, genomic breeding values are estimated directly using an equivalent model with a genomic relationship matrix. Allele coding is the method chosen to assign values to the regression coefficients in the statistical model. A common allele coding is zero for the homozygous genotype of the first allele, one for the heterozygote, and two for the homozygous genotype for the other allele. Another common allele coding changes these regression coefficients by subtracting a value from each marker such that the mean of regression coefficients is zero within each marker. We call this centered allele coding. This study considered effects of different allele coding methods on inference. Both marker-based and equivalent models were considered, and restricted maximum likelihood and Bayesian methods were used in inference. Results Theoretical derivations showed that parameter estimates and estimated marker effects in marker-based models are the same irrespective of the allele coding, provided that the model has a fixed general mean. For the equivalent models, the same results hold, even though different allele coding methods lead to different genomic relationship matrices. Calculated genomic breeding values are independent of allele coding when the estimate of the general mean is included into the values. Reliabilities of estimated genomic breeding values calculated using elements of the inverse of the coefficient matrix depend on the allele coding because different allele coding methods imply different models. Finally, allele coding affects the mixing of Markov chain Monte Carlo algorithms, with the centered coding being

  20. Civil Code, 11 December 1987.

    Science.gov (United States)

    1988-01-01

    Article 162 of this Mexican Code provides, among other things, that "Every person has the right freely, responsibly, and in an informed fashion to determine the number and spacing of his or her children." When a marriage is involved, this right is to be observed by the spouses "in agreement with each other." The civil codes of the following states contain the same provisions: 1) Baja California (Art. 159 of the Civil Code of 28 April 1972 as revised in Decree No. 167 of 31 January 1974); 2) Morelos (Art. 255 of the Civil Code of 26 September 1949 as revised in Decree No. 135 of 29 December 1981); 3) Queretaro (Art. 162 of the Civil Code of 29 December 1950 as revised in the Act of 9 January 1981); 4) San Luis Potosi (Art. 147 of the Civil Code of 24 March 1946 as revised in 13 June 1978); Sinaloa (Art. 162 of the Civil Code of 18 June 1940 as revised in Decree No. 28 of 14 October 1975); 5) Tamaulipas (Art. 146 of the Civil Code of 21 November 1960 as revised in Decree No. 20 of 30 April 1975); 6) Veracruz-Llave (Art. 98 of the Civil Code of 1 September 1932 as revised in the Act of 30 December 1975); and 7) Zacatecas (Art. 253 of the Civil Code of 9 February 1965 as revised in Decree No. 104 of 13 August 1975). The Civil Codes of Puebla and Tlaxcala provide for this right only in the context of marriage with the spouses in agreement. See Art. 317 of the Civil Code of Puebla of 15 April 1985 and Article 52 of the Civil Code of Tlaxcala of 31 August 1976 as revised in Decree No. 23 of 2 April 1984. The Family Code of Hidalgo requires as a formality of marriage a certification that the spouses are aware of methods of controlling fertility, responsible parenthood, and family planning. In addition, Article 22 the Civil Code of the Federal District provides that the legal capacity of natural persons is acquired at birth and lost at death; however, from the moment of conception the individual comes under the protection of the law, which is valid with respect to the