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2. Derivations in Codifferential Categories

Author

Blute, Richard, Lucyshyn-Wright, Rory B. B., and O'Neill, Keith

Subjects
Mathematics - Category Theory, Mathematics - Commutative Algebra, Mathematics - Logic, 18D10, 13N15, 03B47
Abstract

Derivations provide a way of transporting ideas from the calculus of manifolds to algebraic settings where there is no sensible notion of limit. In this paper, we consider derivations in certain monoidal categories, called codifferential categories. Differential categories were introduced as the categorical framework for modelling differential linear logic. The deriving transform of a differential category, which models the differentiation inference rule, is a derivation in the dual category. We here explore that derivation's universality. One of the key structures associated to a codifferential category is an algebra modality. This is a monad $T$ such that each object of the form $TC$ is canonically an associative, commutative algebra. Consequently, every $T$-algebra has a canonical commutative algebra structure, and we show that universal derivations for these algebras can be constructed quite generally. It is a standard result that there is a bijection between derivations from an associative algebra $A$ to an $A$-module $M$ and algebra homomorphisms over $A$ from $A$ to $A\oplus M$, with $A\oplus M$ being considered as an infinitesimal extension of $A$. We lift this correspondence to our setting by showing that in a codifferential category there is a canonical $T$-algebra structure on $A\oplus M$. We call $T$-algebra morphisms from $TA$ to this $T$-algebra structure Beck $T$-derivations. This yields a novel, generalized notion of derivation. The remainder of the paper is devoted to exploring consequences of that definition. Along the way, we prove that the symmetric algebra construction in any suitable symmetric monoidal category provides an example of codifferential structure, and using this, we give an alternative definition for differential and codifferential categories., Comment: 25 Pages

Published
2015

3. A phase I trial of lenalidomide and radiotherapy in children with diffuse intrinsic pontine gliomas or high-grade gliomas

Author

Hipp, Sean J., Goldman, Stewart, Kaushal, Aradhana, Krauze, Andra, Citrin, Deborah, Glod, John, Walker, Kim, Shih, Joanna H., Sethumadhavan, Hema, O’Neill, Keith, Garvin, James H., Glade-Bender, Julia, Karajannis, Matthias A., Atlas, Mark P., Odabas, Arman, Rodgers, Louis T., Peer, Cody J., Savage, Jason, Camphausen, Kevin A., Packer, Roger J., Figg, W. Douglas, and Warren, Katherine E.

Published
2020
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4. Epidermal Growth Factor Receptor Activation in Glioblastoma through Novel Missense Mutations in the Extracellular Domain.

Author

Lee, Jeffrey C, Vivanco, Igor, Beroukhim, Rameen, Huang, Julie H Y, Feng, Whei L, Debiasi, Ralph M, Yoshimoto, Koji, King, Jennifer C, Nghiemphu, Phioanh, Yuza, Yuki, Xu, Qing, Greulich, Heidi, Thomas, Roman K, Paez, J Guillermo, Peck, Timothy C, Linhart, David J, Glatt, Karen A, Getz, Gad, Onofrio, Robert, Ziaugra, Liuda, Levine, Ross L, Gabriel, Stacey, Kawaguchi, Tomohiro, O'neill, Keith, Khan, Haumith, Liau, Linda M, Nelson, Stanley F, Rao, P Nagesh, Mischel, Paul, Pieper, Russell O, Cloughesy, Tim, Leahy, Daniel J, Sellers, William R, Sawyers, Charles L, Meyerson, Matthew, and Mellinghoff, Ingo K

Abstract

BACKGROUND: Protein tyrosine kinases are important regulators of cellular homeostasis with tightly controlled catalytic activity. Mutations in kinase-encoding genes can relieve the autoinhibitory constraints on kinase activity, can promote malignant transformation, and appear to be a major determinant of response to kinase inhibitor therapy. Missense mutations in the EGFR kinase domain, for example, have recently been identified in patients who showed clinical responses to EGFR kinase inhibitor therapy. METHODS AND FINDINGS: Encouraged by the promising clinical activity of epidermal growth factor receptor (EGFR) kinase inhibitors in treating glioblastoma in humans, we have sequenced the complete EGFR coding sequence in glioma tumor samples and cell lines. We identified novel missense mutations in the extracellular domain of EGFR in 13.6% (18/132) of glioblastomas and 12.5% (1/8) of glioblastoma cell lines. These EGFR mutations were associated with increased EGFR gene dosage and conferred anchorage-independent growth and tumorigenicity to NIH-3T3 cells. Cells transformed by expression of these EGFR mutants were sensitive to small-molecule EGFR kinase inhibitors. CONCLUSIONS: Our results suggest extracellular missense mutations as a novel mechanism for oncogenic EGFR activation and may help identify patients who can benefit from EGFR kinase inhibitors for treatment of glioblastoma.

Published
2006

6. Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing

Author

Thomas, Roman K, Nickerson, Elizabeth, Simons, Jan F, Janne, Pasi A, Tengs, Torstein, Yuza, Yuki, Garraway, Levi A, LaFramboise, Thomas, Lee, Jeffrey C, Shah, Kinjal, O'Neill, Keith, Sasaki, Hidefumi, Lindeman, Neal, Wong, Kwok-Kin, Borras, Ana M, Gutmann, Edward J, Dragnev, Konstantin H, DeBiasi, Ralph, Chen, Tzu-Hsiu, Glatt, Karen A, Greulich, Heidi, Desany, Brian, Lubeski, Christine K, Brockman, William, Alvarez, Pablo, Hutchison, Stephen K, Leamon, J H, Ronan, Michael T, Turenchalk, Gregory S, Egholm, Michael, Sellers, William R, Rothberg, Jonathan M, and Meyerson, Matthew

Abstract

The sensitivity of conventional DNA sequencing in tumor biopsies is limited by stromal contamination and by genetic heterogeneity within the cancer. Here, we show that microreactor-based pyrosequencing can detect rare cancer-associated sequence variations by independent and parallel sampling of multiple representatives of a given DNA fragment. This technology can thereby facilitate accurate molecular diagnosis of heterogeneous cancer specimens and enable patient selection for targeted cancer therapies. NOTE:: In the version of this article initially published, it should have been acknowledged that Jan F. Simons, in addition to Roman K. Thomas and Elizabeth Nickerson, contributed equally to this work. The error has been corrected in the HTML and PDF versions of the article., Author(s): Roman K Thomas [1, 2, 12]; Elizabeth Nickerson [3, 12]; Jan F Simons [3, 11, 12]; Pasi A Janne [1]; Torstein Tengs [1, 2]; Yuki Yuza [1]; Levi A [...]

Published
2006
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7. Analysis of the DNA sequence and duplication history of human chromosome 15

Author

Zody, Michael C., Garber, Manuel, Sharpe, Ted, Young, Sarah K., Rowen, Lee, O'Neill, Keith, Whittaker, Charles A., Kamal, Michael, Chang, Jean L., Cuomo, Christina A., Dewar, Ken, FitzGerald, Michael G., Kodira, Chinnappa D., Madan, Anup, Qin, Shizhen, Yang, Xiaoping, Abbasi, Nissa, Abouelleil, Amr, Arachchi, Harindra M., Baradarani, Lida, Birditt, Brian, Bloom, Scott, Bloom, Toby, Borowsky, Mark L., Burke, Jeremy, Butler, Jonathan, Cook, April, DeArellano, Kurt, DeCaprio, David, Dorris, III, Lester, Dors, Monica, Eichler, Evan E., Engels, Reinhard, Fahey, Jessica, Fleetwood, Peter, Friedman, Cynthia, Gearin, Gary, Hall, Jennifer L., Hensley, Grace, Johnson, Ericka, Jones, Charlien, Kamat, Asha, Kaur, Amardeep, Locke, Devin P., Madan, Anuradha, Munson, Glen, Jaffe, David B., Lui, Annie, Macdonald, Pendexter, Mauceli, Evan, Naylor, Jerome W., Nesbitt, Ryan, Nicol, Robert, O'Leary, Sinead B., Ratcliffe, Amber, Rounsley, Steven, She, Xinwei, Sneddon, Katherine M. B., Stewart, Sandra, Sougnez, Carrie, Stone, Sabrina M., Topham, Kerri, Vincent, Dascena, Wang, Shunguang, Zimmer, Andrew R., Birren, Bruce W., Hood, Leroy, Lander, Eric S., and Nusbaum, Chad

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Michael C. Zody (corresponding author) [1]; Manuel Garber [1]; Ted Sharpe [1]; Sarah K. Young [1]; Lee Rowen [2]; Keith O'Neill [1]; Charles A. Whittaker [1, 6]; Michael Kamal [...]

Published
2006
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8. DNA sequence and analysis of human chromosome 8

Author

Nusbaum, Chad, Mikkelsen, Tarjei S., Zody, Michael C., Asakawa, Shuichi, Taudien, Stefan, Garber, Manuel, Kodira, Chinnappa D., Schueler, Mary G., Shimizu, Atsushi, Whittaker, Charles A., Chang, Jean L., Cuomo, Christina A., Dewar, Ken, FitzGerald, Michael G., Yang, Xiaoping, Allen, Nicole R., Anderson, Scott, Asakawa, Teruyo, Blechschmidt, Karin, Bloom, Toby, Borowsky, Mark L., Butler, Jonathan, Cook, April, Corum, Benjamin, DeArellano, Kurt, DeCaprio, David, Dooley, Kathleen T., Dorris, III, Lester, Engels, Reinhard, Glockner, Gernot, Hafez, Nabil, Hagopian, Daniel S., Hall, Jennifer L., Ishikawa, Sabine K., Jaffe, David B., Kamat, Asha, Kudoh, Jun, Lehmann, Rudiger, Lokitsang, Tashi, Macdonald, Pendexter, Major, John E., Matthews, Charles D., Mauceli, Evan, Menzel, Uwe, Mihalev, Atanas H., Minoshima, Shinsei, Murayama, Yuji, Naylor, Jerome W., Nicol, Robert, Nguyen, Cindy, O'Leary, Sinead B., O'Neill, Keith, Parker, Stephen C. J., Polley, Andreas, Raymond, Christina K., Reichwald, Kathrin, Rodriguez, Joseph, Sasaki, Takashi, Schilhabel, Markus, Siddiqui, Roman, Smith, Cherylyn L., Sneddon, Tam P., Talamas, Jessica A., Tenzin, Pema, Topham, Kerri, Venkataraman, Vijay, Wen, Gaiping, Yamazaki, Satoru, Young, Sarah K., Zeng, Qiandong, Zimmer, Andrew R., Rosenthal, Andre, Birren, Bruce W., Platzer, Matthias, Shimizu, Nobuyoshi, and Lander, Eric S.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Chad Nusbaum (corresponding author) [1]; Tarjei S. Mikkelsen [1]; Michael C. Zody [1]; Shuichi Asakawa [2]; Stefan Taudien [3]; Manuel Garber [1]; Chinnappa D. Kodira [1]; Mary G. Schueler [...]

Published
2006
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9. Genome sequence, comparative analysis and haplotype structure of the domestic dog

Author

Lindblad-Toh, Kerstin, Wade, Claire M., Mikkelsen, Tarjei S., Karlsson, Elinor K., Jaffe, David B., Kamal, Michael, Clamp, Michele, Chang, Jean L., Kulbokas, III, Edward J., Zody, Michael C., Mauceli, Evan, Xie, Xiaohui, Breen, Matthew, Wayne, Robert K., Ostrander, Elaine A., Ponting, Chris P., Galibert, Francis, Smith, Douglas R., deJong, Pieter J., Kirkness, Ewen, Alvarez, Pablo, Biagi, Tara, Brockman, William, Butler, Jonathan, Chin, Chee-Wye, Cook, April, Cuff, James, Daly, Mark J., DeCaprio, David, Gnerre, Sante, Grabherr, Manfred, Kellis, Manolis, Kleber, Michael, Bardeleben, Carolyne, Goodstadt, Leo, Heger, Andreas, Hitte, Christophe, Kim, Lisa, Koepfli, Klaus-Peter, Parker, Heidi G., Pollinger, John P., Searle, Stephen M. J., Sutter, Nathan B., Thomas, Rachael, Webber, Caleb, Baldwin, Jennifer, Abebe, Adal, Abouelleil, Amr, Aftuck, Lynne, Ait-zahra, Mostafa, Aldredge, Tyler, Allen, Nicole, An, Peter, Anderson, Scott, Antoine, Claudel, Arachchi, Harindra, Aslam, Ali, Ayotte, Laura, Bachantsang, Pasang, Barry, Andrew, Bayul, Tashi, Benamara, Mostafa, Berlin, Aaron, Bessette, Daniel, Blitshteyn, Berta, Bloom, Toby, Blye, Jason, Boguslavskiy, Leonid, Bonnet, Claude, Boukhgalter, Boris, Brown, Adam, Cahill, Patrick, Calixte, Nadia, Camarata, Jody, Cheshatsang, Yama, Chu, Jeffrey, Citroen, Mieke, Collymore, Alville, Cooke, Patrick, Dawoe, Tenzin, Daza, Riza, Decktor, Karin, DeGray, Stuart, Dhargay, Norbu, Dooley, Kimberly, Dooley, Kathleen, Dorje, Passang, Dorjee, Kunsang, Dorris, Lester, Duffey, Noah, Dupes, Alan, Egbiremolen, Osebhajajeme, Elong, Richard, Falk, Jill, Farina, Abderrahim, Faro, Susan, Ferguson, Diallo, Ferreira, Patricia, Fisher, Sheila, FitzGerald, Mike, Foley, Karen, Foley, Chelsea, Franke, Alicia, Friedrich, Dennis, Gage, Diane, Garber, Manuel, Gearin, Gary, Giannoukos, Georgia, Goode, Tina, Goyette, Audra, Graham, Joseph, Grandbois, Edward, Gyaltsen, Kunsang, Hafez, Nabil, Hagopian, Daniel, Hagos, Birhane, Hall, Jennifer, Healy, Claire, Hegarty, Ryan, Honan, Tracey, Horn, Andrea, Houde, Nathan, Hughes, Leanne, Hunnicutt, Leigh, Husby, M., Jester, Benjamin, Jones, Charlien, Kamat, Asha, Kanga, Ben, Kells, Cristyn, Khazanovich, Dmitry, Kieu, Alix Chinh, Kisner, Peter, Kumar, Mayank, Lance, Krista, Landers, Thomas, Lara, Marcia, Lee, William, Leger, Jean-Pierre, Lennon, Niall, Leuper, Lisa, LeVine, Sarah, Liu, Jinlei, Liu, Xiaohong, Lokyitsang, Yeshi, Lokyitsang, Tashi, Lui, Annie, Macdonald, Jan, Major, John, Marabella, Richard, Maru, Kebede, Matthews, Charles, McDonough, Susan, Mehta, Teena, Meldrim, James, Melnikov, Alexandre, Meneus, Louis, Mihalev, Atanas, Mihova, Tanya, Miller, Karen, Mittelman, Rachel, Mlenga, Valentine, Mulrain, Leonidas, Munson, Glen, Navidi, Adam, Naylor, Jerome, Nguyen, Tuyen, Nguyen, Nga, Nguyen, Cindy, Nguyen, Thu, Nicol, Robert, Norbu, Nyima, Norbu, Choe, Novod, Nathaniel, Nyima, Tenchoe, Olandt, Peter, O'Neill, Barry, O'Neill, Keith, Osman, Sahal, Oyono, Lucien, Patti, Christopher, Perrin, Danielle, Phunkhang, Pema, Pierre, Fritz, Priest, Margaret, Rachupka, Anthony, Raghuraman, Sujaa, Rameau, Rayale, Ray, Verneda, Raymond, Christina, Rege, Filip, Rise, Cecil, Rogers, Julie, Rogov, Peter, Sahalie, Julie, Settipalli, Sampath, Sharpe, Theodore, Shea, Terrance, Sheehan, Mechele, Sherpa, Ngawang, Shi, Jianying, Shih, Diana, Sloan, Jessie, Smith, Cherylyn, Sparrow, Todd, Stalker, John, Stange-Thomann, Nicole, Stavropoulos, Sharon, Stone, Catherine, Stone, Sabrina, Sykes, Sean, Tchuinga, Pierre, Tenzing, Pema, Tesfaye, Senait, Thoulutsang, Dawa, Thoulutsang, Yama, Topham, Kerri, Topping, Ira, Tsamla, Tsamla, Vassiliev, Helen, Venkataraman, Vijay, Vo, Andy, Wangchuk, Tsering, Wangdi, Tsering, Weiand, Michael, Wilkinson, Jane, Wilson, Adam, Yadav, Shailendra, Yang, Shuli, Yang, Xiaoping, Young, Geneva, Yu, Qing, Zainoun, Joanne, Zembek, Lisa, Zimmer, Andrew, and Lander, Eric S.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Kerstin Lindblad-Toh (corresponding author) [1]; Claire M Wade [1, 2]; Tarjei S. Mikkelsen [1, 3]; Elinor K. Karlsson [1, 4]; David B. Jaffe [1]; Michael Kamal [1]; Michele Clamp [...]

Published
2005
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10. The ner gene of Photorhabdus: effects on primary-form-specific phenotypes and outer membrane protein composition

Author

O'Neill, Keith H., Roche, Declan M., Clarke, David J., and Dowds, Barbara C.A.

Subjects
Symbiosis -- Genetic aspects, Nematoda -- Genetic aspects, Cell cycle -- Physiological aspects, Phenotype -- Analysis, Biological sciences
Abstract

Results reveal that the endogenous ner gene is not involved in the secondary phenotype switching but inactivation of the primary form ner affects outer membrane protein profile in Photorhabdus. Data show accumulation of outer membrane proteins in the stationary phase.

Published
2002

11. Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans

Author

Haas, Brian J., Kamoun, Sophien, Zody, Michael C., Jiang, Rays H. Y., Handsaker, Robert E., Cano, Liliana M., Grabherr, Manfred, Kodira, Chinnappa D., Raffaele, Sylvain, Torto-Alalibo, Trudy, Bozkurt, Tolga O., Ah-Fong, Audrey M. V., Alvarado, Lucia, Anderson, Vicky L., Armstrong, Miles R., Avrova, Anna, Baxter, Laura, Beynon, Jim, Boevink, Petra C., Bollmann, Stephanie R., Bos, Jorunn I. B., Bulone, Vincent, Cai, Guohong, Cakir, Cahid, Carrington, James C., Chawner, Megan, Conti, Lucio, Costanzo, Stefano, Ewan, Richard, Fahlgren, Noah, Fischbach, Michael A., Fugelstad, Johanna, Gilroy, Eleanor M., Gnerre, Sante, Green, Pamela J., Grenville-Briggs, Laura J., Griffith, John, Grünwald, Niklaus J., Horn, Karolyn, Horner, Neil R., Hu, Chia-Hui, Huitema, Edgar, Jeong, Dong-Hoon, Jones, Alexandra M. E., Jones, Jonathan D. G., Jones, Richard W., Karlsson, Elinor K., Kunjeti, Sridhara G., Lamour, Kurt, Liu, Zhenyu, Ma, LiJun, MacLean, Daniel, Chibucos, Marcus C., McDonald, Hayes, McWalters, Jessica, Meijer, Harold J. G., Morgan, William, Morris, Paul F., Munro, Carol A., O’Neill, Keith, Ospina-Giraldo, Manuel, Pinzón, Andrés, Pritchard, Leighton, Ramsahoye, Bernard, Ren, Qinghu, Restrepo, Silvia, Roy, Sourav, Sadanandom, Ari, Savidor, Alon, Schornack, Sebastian, Schwartz, David C., Schumann, Ulrike D., Schwessinger, Ben, Seyer, Lauren, Sharpe, Ted, Silvar, Cristina, Song, Jing, Studholme, David J., Sykes, Sean, Thines, Marco, van de Vondervoort, Peter J. I., Phuntumart, Vipaporn, Wawra, Stephan, Weide, Rob, Win, Joe, Young, Carolyn, Zhou, Shiguo, Fry, William, Meyers, Blake C., van West, Pieter, Ristaino, Jean, Govers, Francine, Birch, Paul R. J., Whisson, Stephen C., Judelson, Howard S., and Nusbaum, Chad

Published
2009
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13. Smoothness in Codifferential Categories

Author

O'Neill, Keith

Subjects
Mathematics::K-Theory and Homology, Mathematics::Quantum Algebra, Category Theory, Mathematics::Algebraic Topology, Smoothness
Abstract

The Hochschild-Kostant-Rosenberg theorem, which relates the Hochschild homology of an algebra to its modules of differential $n$-forms, can be considered a benchmark for smoothness of an algebra. This notion is used here in the search for a conception of smoothness formulated in the context of codifferential categories, both commutative and noncommutative. Since it is desirable to adapt such a conception to the noncommutative context, the theory of this domain is developed considerably; a significant result in this direction establishes a connection between noncommutative codifferential categories and commutative ones. This investigation necessitates, then, both the formulation of a notion of smoothness for $T$-algebras in codifferential categories and an adaptation of the Hochschild-Kostant-Rosenberg theorem to a wide variety of contexts which includes noncommutative ones. The former consideration fosters both the notion of a smooth monad, and a formulation of Andr\'e-Quillen homology in codifferential categories; the latter engenders a highly adaptable version of the Hochschild-Kostant-Rosenberg theorem. Specifically, it is shown that for any algebra modality there exists a corresponding Hochschild-Kostant-Rosenberg theorem. This includes a version of the theorem for the free associative algebra monad, the conclusion of which is satisfied by noncommutative smooth algebras.

Published
2017
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14. Glad to be vegan

Author

O'Neill, Keith

Subjects
General interest, News, opinion and commentary, Political science
Abstract

Sir: James Delingpole trots out the usual criticisms of veganism (8 September). I have been vegetarian since the 1980s and vegan for about ten years. The food I eat is [...]

Published
2018

15. A bit parky

Author

O'Neill, Keith

Subjects
Festivals, Literature/writing, Political science
Abstract

Hundreds of revellers will take over woodland in Kent this weekend for the three-day Flamefest. People will pay around 600 [pounds sterling] for sex with 'like-minded people' at the event, [...]

Published
2017

16. Assembly of polymorphic genomes: Algorithms and application to Ciona savignyi

Author

Vinson, Jade P., Jaffe, David B., O'Neill, Keith, Karlsson, Elinor K., Stange-Thomann, Nicloe, Anderson, Scott, Mesirov, Jill P., Satoh, Nori, Satou, Yutaka, Nusbaum, Chad, Birren, Bruce, Galagan, James E., and Lander, Eric S.

Subjects
Genetic polymorphisms -- Research, Haplotypes -- Research, Health
Abstract

A method for assembling highly polymorphic diploid genomes that involves assembling the two haplotypes separately and then merging them to obtain a reference sequence is presented. This method represented loci in a single copy more reliably and achieved greater contiguity than a conventional whole-genome assembly method.

Published
2005

17. Analysis of the DNA sequence and duplication history of human chromosome 15

Author

Zody, Michael, Garber, Manuel, Sharpe, Ted, Young, Sarah, Rowen, Lee, O'Neill, Keith, Whittaker, Charles, Kamal, Michael, Chang, Jean, Cuomo, Christina, Dewar, Ken, FitzGerald, Michael, Kodira, Chinnappa, Madan, Anup, Qin, Shizhen, Yang, Xiaoping, Abbasi, Nissa, Abouelleil, Amr, Arachchi, Harindra, Baradarani, Lida, Birditt, Brian, Bloom, Scott, Bloom, Toby, Borowsky, Mark, Burke, Jeremy, Butler, Jonathan, Cook, April, DeArellano, Kurt, DeCaprio, David, Dorris, Lester, Dors, Monica, Eichler, Evan, Engels, Reinhard, Fahey, Jessica, Fleetwood, Peter, Friedman, Cynthia, Gearin, Gary, Hall, Jennifer, Hensley, Grace, Johnson, Ericka, Jones, Charlien, Kamat, Asha, Kaur, Amardeep, Locke, Devin, Madan, Anuradha, Munson, Glen, Jaffe, David, Lui, Annie, Macdonald, Pendexter, Mauceli, Evan, Naylor, Jerome, Nesbitt, Ryan, Nicol, Robert, O'Leary, Sinéad, Ratcliffe, Amber, Rounsley, Steven, She, Xinwei, Sneddon, Katherine, Stewart, Sandra, Sougnez, Carrie, Stone, Sabrina, Topham, Kerri, Vincent, Dascena, Wang, Shunguang, Zimmer, Andrew, Birren, Bruce, Hood, Leroy, Lander, ic, Nusbaum, Chad, Zody, Michael, Garber, Manuel, Sharpe, Ted, Young, Sarah, Rowen, Lee, O'Neill, Keith, Whittaker, Charles, Kamal, Michael, Chang, Jean, Cuomo, Christina, Dewar, Ken, FitzGerald, Michael, Kodira, Chinnappa, Madan, Anup, Qin, Shizhen, Yang, Xiaoping, Abbasi, Nissa, Abouelleil, Amr, Arachchi, Harindra, Baradarani, Lida, Birditt, Brian, Bloom, Scott, Bloom, Toby, Borowsky, Mark, Burke, Jeremy, Butler, Jonathan, Cook, April, DeArellano, Kurt, DeCaprio, David, Dorris, Lester, Dors, Monica, Eichler, Evan, Engels, Reinhard, Fahey, Jessica, Fleetwood, Peter, Friedman, Cynthia, Gearin, Gary, Hall, Jennifer, Hensley, Grace, Johnson, Ericka, Jones, Charlien, Kamat, Asha, Kaur, Amardeep, Locke, Devin, Madan, Anuradha, Munson, Glen, Jaffe, David, Lui, Annie, Macdonald, Pendexter, Mauceli, Evan, Naylor, Jerome, Nesbitt, Ryan, Nicol, Robert, O'Leary, Sinéad, Ratcliffe, Amber, Rounsley, Steven, She, Xinwei, Sneddon, Katherine, Stewart, Sandra, Sougnez, Carrie, Stone, Sabrina, Topham, Kerri, Vincent, Dascena, Wang, Shunguang, Zimmer, Andrew, Birren, Bruce, Hood, Leroy, Lander, ic, and Nusbaum, Chad

Abstract

Here we present a finished sequence of human chromosome 15, together with a high-quality gene catalogue. As chromosome 15 is one of seven human chromosomes with a high rate of segmental duplication, we have carried out a detailed analysis of the duplication structure of the chromosome. Segmental duplication in chromosome 15 are largely clustered in two regions, on proximal and distal 15q; the proximal region is notable because recombination among the segmental duplications can result in deletions causing Prader-Willi and Angelman syndromes. Sequence analysis shows that the proximal and distal regions of 15q share extensive ancient similarity. Using a simple approach, we have been able to reconstruct many of the events by which the current duplication structure arose. We find that most of the intrachromosomal duplications seem to share a common ancestry. Finally, we demonstrate that some remaining gaps in the genome sequence are probably due to structural polymorphisms between haplotypes; this may explain a significant fraction of the gaps remaining in the human genome.

Published
2006
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18. Strain Characteristics ofStreptococcus pneumoniaeCarriage and Invasive Disease Isolates during a Cluster‐Randomized Clinical Trial of the 7‐Valent Pneumococcal Conjugate Vaccine

Author

Lipsitch, Marc, primary, O’Neill, Keith, additional, Cordy, Derrick, additional, Bugalter, Boris, additional, Trzcinski, Krzysztof, additional, Thompson, Claudette M., additional, Goldstein, Richard, additional, Pelton, Stephen, additional, Huot, Heather, additional, Bouchet, Valerie, additional, Reid, Raymond, additional, Santosham, Mathuram, additional, and O’Brien, Katherine L., additional

Published
2007
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20. Corrigendum: DNA sequence and analysis of human chromosome 18

Author

Nusbaum, Chad, Zody, Michael C., Borowsky, Mark L., Kamal, Michael, Kodira, Chinnappa D., Taylor, Todd D., Whittaker, Charles A., Chang, Jean L., Cuomo, Christina A., Dewar, Ken, FitzGerald, Michael G., Yang, Xiaoping, Abouelleil, Amr, Allen, Nicole R., Anderson, Scott, Bloom, Toby, Bugalter, Boris, Butler, Jonathan, Cook, April, DeCaprio, David, Engels, Reinhard, Garber, Manuel, Gnirke, Andreas, Hafez, Nabil, Hall, Jennifer L., Norman, Catherine Hosage, Itoh, Takehiko, Jaffe, David B., Kuroki, Yoko, Lehoczky, Jessica, Lui, Annie, Macdonald, Pendexter, Mauceli, Evan, Mikkelsen, Tarjei S., Naylor, Jerome W., Nicol, Robert, Nguyen, Cindy, Noguchi, Hideki, O'Leary, Sinead B., O'Neill, Keith, Piqani, Bruno, Smith, Cherylyn L., Talamas, Jessica A., Topham, Kerri, Totoki, Yasushi, Toyoda, Atsushi, Wain, Hester M., Young, Sarah K., Zeng, Qiandong, Zimmer, Andrew R., Fujiyama, Asao, Hattori, Masahira, Birren, Bruce W., Sakaki, Yoshiyuki, and Lander, Eric S.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Chad Nusbaum; Michael C. Zody; Mark L. Borowsky; Michael Kamal; Chinnappa D. Kodira; Todd D. Taylor; Charles A. Whittaker; Jean L. Chang; Christina A. Cuomo; Ken Dewar; Michael G. [...]

Published
2005
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21. Erratum: Corrigendum: DNA sequence and analysis of human chromosome 18

Author

Nusbaum, Chad, primary, Zody, Michael C., additional, Borowsky, Mark L., additional, Kamal, Michael, additional, Kodira, Chinnappa D., additional, Taylor, Todd D., additional, Whittaker, Charles A., additional, Chang, Jean L., additional, Cuomo, Christina A., additional, Dewar, Ken, additional, FitzGerald, Michael G., additional, Yang, Xiaoping, additional, Abouelleil, Amr, additional, Allen, Nicole R., additional, Anderson, Scott, additional, Bloom, Toby, additional, Bugalter, Boris, additional, Butler, Jonathan, additional, Cook, April, additional, DeCaprio, David, additional, Engels, Reinhard, additional, Garber, Manuel, additional, Gnirke, Andreas, additional, Hafez, Nabil, additional, Hall, Jennifer L., additional, Norman, Catherine Hosage, additional, Itoh, Takehiko, additional, Jaffe, David B., additional, Kuroki, Yoko, additional, Lehoczky, Jessica, additional, Lui, Annie, additional, Macdonald, Pendexter, additional, Mauceli, Evan, additional, Mikkelsen, Tarjei S., additional, Naylor, Jerome W., additional, Nicol, Robert, additional, Nguyen, Cindy, additional, Noguchi, Hideki, additional, O'Leary, Sinéad B., additional, O'Neill, Keith, additional, Piqani, Bruno, additional, Smith, Cherylyn L., additional, Talamas, Jessica A., additional, Topham, Kerri, additional, Totoki, Yasushi, additional, Toyoda, Atsushi, additional, Wain, Hester M., additional, Young, Sarah K., additional, Zeng, Qiandong, additional, Zimmer, Andrew R., additional, Fujiyama, Asao, additional, Hattori, Masahira, additional, Birren, Bruce W., additional, Sakaki, Yoshiyuki, additional, and Lander, Eric S., additional

Published
2005
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23. Epidermal Growth Factor Receptor Activation in Glioblastoma through Novel Missense Mutations in the Extracellular Domain

Author

Vivanco, Igor, Feng, Whei L, Yoshimoto, Koji, King, Jennifer C, Nghiemphu, Phioanh, Yuza, Yuki, Xu, Qing, Thomas, Roman K, Peck, Timothy C, Linhart, David J, Glatt, Karen A, Getz, Gad, Onofrio, Robert, Ziaugra, Liuda, Levine, Ross L, Gabriel, Stacey, Kawaguchi, Tomohiro, O'Neill, Keith, Khan, Haumith, Liau, Linda M, Nelson, Stanley F, Rao, P. Nagesh, Mischel, Paul, Pieper, Russell O, Cloughesy, Tim, Leahy, Daniel J, Sellers, William R, Sawyers, Charles L, Mellinghoff, Ingo K, Lee, Jeffrey C., Beroukhim, Rameen, Huang, Julie, DeBiasi, Ralph Michael, Greulich, Heidi E., Paez, J. Guillermo, and Meyerson, Matthew Langer

Subjects
genetics and genomics, oncology
Abstract

Background: Protein tyrosine kinases are important regulators of cellular homeostasis with tightly controlled catalytic activity. Mutations in kinase-encoding genes can relieve the autoinhibitory constraints on kinase activity, can promote malignant transformation, and appear to be a major determinant of response to kinase inhibitor therapy. Missense mutations in the EGFR kinase domain, for example, have recently been identified in patients who showed clinical responses to EGFR kinase inhibitor therapy. Methods and Findings: Encouraged by the promising clinical activity of epidermal growth factor receptor (EGFR) kinase inhibitors in treating glioblastoma in humans, we have sequenced the complete EGFR coding sequence in glioma tumor samples and cell lines. We identified novel missense mutations in the extracellular domain of EGFR in 13.6% (18/132) of glioblastomas and 12.5% (1/ 8) of glioblastoma cell lines. These EGFR mutations were associated with increased EGFR gene dosage and conferred anchorage-independent growth and tumorigenicity to NIH-3T3 cells. Cells transformed by expression of these EGFR mutants were sensitive to small-molecule EGFR kinase inhibitors. Conclusions: Our results suggest extracellular missense mutations as a novel mechanism for oncogenic EGFR activation and may help identify patients who can benefit from EGFR kinase inhibitors for treatment of glioblastoma.

Published
2006
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24. Changing Places: Narratives of Spiritual Conversion during the First College Year

Author

O'Neill, Keith Brendan

Subjects
Higher Education, Higher Education Administration, Spirituality, spiritual conversion, religious conversion, college students, student development, spiritual development, higher education, college student development, first-year college students, conversion narrative, student affairs, student affairs administration
Abstract

A student's first year of college study is marked by the transition of leaving a familiar routine of academic, social, and family commitments. Upon arrival at college, a student can learn how to negotiate personal responsibility for intellectual and community development during the first year. New college students are primed for such immense intellectual, intrapersonal, and interpersonal development, and it may include consideration of religious practice and spiritual values, their meaning and relevance, and determination of religious habits and spiritual identity.This study explored the experiences of spiritual conversion among first-year college students, and how the college environment may contribute to such experiences. Religious and spiritual conversion experiences may reflect a creation, diminishment, strengthening, or transformation of a student's spiritual identity, and this exploratory study sought to include any of these forms of conversion and the factors that challenge and encourage them. By studying the nature of these experiences in the postsecondary environment, educators may learn more about how the experience of college can affect students before, during, and beyond conversion experiences.Students were invited to share their stories to illustrate how their spiritual lives were created, diminished, strengthened, or transformed during their first college year. They shared insights into the related challenges and opportunities encountered through feelings of loneliness, community inclusion and exclusion, academic achievements in the midst of personal turmoil, and environmental influences that may have shaped their journeys.The findings of this inquiry suggested the need for additional opportunities for training for personnel in higher education and student affairs to be more attentive to and better able to support students who are searching spiritually and who may experience a spiritual conversion during the first year of college. These findings demonstrated educators' need to focus on ways in which the college environment can best support safe and healthy student journeys to, through, and beyond the campus. Educators must shape the college environment academically, socially, and spiritually to be a place of change that welcomes and challenges students for success.

Published
2014

25. DNA sequence and analysis of human chromosome 18.

Author

Nusbaum C, Zody MC, Borowsky ML, Kamal M, Kodira CD, Taylor TD, Whittaker CA, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Yang X, Abouelleil A, Allen NR, Anderson S, Bloom T, Bugalter B, Butler J, Cook A, DeCaprio D, Engels R, Garber M, Gnirke A, Hafez N, Hall JL, Norman CH, Itoh T, Jaffe DB, Kuroki Y, Lehoczky J, Lui A, Macdonald P, Mauceli E, Mikkelsen TS, Naylor JW, Nicol R, Nguyen C, Noguchi H, O'Leary SB, O'Neill K, Piqani B, Smith CL, Talamas JA, Topham K, Totoki Y, Toyoda A, Wain HM, Young SK, Zeng Q, Zimmer AR, Fujiyama A, Hattori M, Birren BW, Sakaki Y, and Lander ES

Subjects
Aneuploidy, Animals, Conserved Sequence genetics, CpG Islands genetics, Exons genetics, Expressed Sequence Tags, Genes genetics, Genome, Human, Humans, Introns genetics, Molecular Sequence Data, Sequence Analysis, DNA, Synteny, Chromosomes, Human, Pair 18 genetics, DNA genetics
Abstract

Chromosome 18 appears to have the lowest gene density of any human chromosome and is one of only three chromosomes for which trisomic individuals survive to term. There are also a number of genetic disorders stemming from chromosome 18 trisomy and aneuploidy. Here we report the finished sequence and gene annotation of human chromosome 18, which will allow a better understanding of the normal and disease biology of this chromosome. Despite the low density of protein-coding genes on chromosome 18, we find that the proportion of non-protein-coding sequences evolutionarily conserved among mammals is close to the genome-wide average. Extending this analysis to the entire human genome, we find that the density of conserved non-protein-coding sequences is largely uncorrelated with gene density. This has important implications for the nature and roles of non-protein-coding sequence elements.

Published
2005
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