The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation

Florencia Pereyra; Xiaoming Jia; Paul J. McLaren; Amalio Telenti; Paul I.W. de Bakker; Bruce D. Walker; Stephan Ripke; Chanson J. Brumme; Sara L. Pulit; Mary Carrington; Carl M. Kadie; Jonathan M. Carlson; David Heckerman; Robert R. Graham; Robert M. Plenge; Steven G. Deeks; Lauren Gianniny; Gabriel Crawford; Jordan Sullivan; Elena Gonzalez; Leela Davies; Amy Camargo; Jamie M. Moore; Nicole Beattie; Supriya Gupta; Andrew Crenshaw; Noël P. Burtt; Candace Guiducci; Namrata Gupta; Xiaojiang Gao; Ying Qi; Yuko Yuki; Alicja Piechocka-Trocha; Emily Cutrell; Rachel Rosenberg; Kristin L. Moss; Paul Lemay; Jessica O’Leary; Todd Schaefer; Pranshu Verma; Ildiko Toth; Brian Block; Brett Baker; Alissa Rothchild; Jeffrey Lian; Jacqueline Proudfoot; Donna Marie L. Alvino; Seanna Vine; Marylyn M. Addo; Todd M. Allen; Marcus Altfeld; Matthew R. Henn; Sylvie Le Gall; Hendrik Streeck; David W. Haas; Daniel R. Kuritzkes; Gregory K. Robbins; Robert W. Shafer; Roy M. Gulick; Cecilia M. Shikuma; Richard Haubrich; Sharon Riddler; Paul E. Sax; Eric S. Daar; Heather J. Ribaudo; Brian Agan; Shanu Agarwal; Richard L. Ahern; Brady L. Allen; Sherly Altidor; Eric L. Altschuler; Sujata Ambardar; Kathryn Anastos; Ben Anderson; Val Anderson; Ushan Andrady; Diana Antoniskis; David Bangsberg; Daniel Barbaro; William Barrie; J. Bartczak; Simon Barton; Patricia Basden; Nesli Basgoz; Suzane Bazner; Nicholaos C. Bellos; Anne M. Benson; Judith Berger; Nicole F. Bernard; Annette M. Bernard; Christopher Birch; Stanley J. Bodner; Robert K. Bolan; Emilie T. Boudreaux; Meg Bradley; James F. Braun; Jon E. Brndjar; Stephen J. Brown; Katherine Brown; Sheldon T. Brown; Jedidiah Burack; Larry M. Bush; Virginia Cafaro; Omobolaji Campbell; John Campbell; Robert H. Carlson; J. Kevin Carmichael; Kathleen K. Casey; Chris Cavacuiti; Gregory Celestin; Steven T. Chambers; Nancy Chez; Lisa M. Chirch; Paul J. Cimoch; Daniel Cohen; Lillian E. Cohn; Brian Conway; David A. Cooper; Brian Cornelson; David T. Cox; Michael V. Cristofano; George Cuchural; Julie L. Czartoski; Joseph M. Dahman; Jennifer S. Daly; Benjamin T. Davis; Kristine Davis; Sheila M. Davod; Edwin DeJesus; Craig A. Dietz; Eleanor Dunham; Michael E. Dunn; Todd B. Ellerin; Joseph J. Eron; John J.W. Fangman; Claire E. Farel; Helen Ferlazzo; Sarah Fidler; Anita Fleenor-Ford; Renee Frankel; Kenneth A. Freedberg; Neel K. French; Jonathan D. Fuchs; Jon D. Fuller; Jonna Gaberman; Joel E. Gallant; Rajesh T. Gandhi; Efrain Garcia; Donald Garmon; Joseph C. Gathe; Cyril R. Gaultier; Wondwoosen Gebre; Frank D. Gilman; Ian Gilson; Paul A. Goepfert; Michael S. Gottlieb; Claudia Goulston; Richard K. Groger; T. Douglas Gurley; Stuart Haber; Robin Hardwicke; W. David Hardy; P. Richard Harrigan; Trevor N. Hawkins; Sonya Heath; Frederick M. Hecht; W. Keith Henry; Melissa Hladek; Robert P. Hoffman; James M. Horton; Ricky K. Hsu; Gregory D. Huhn; Peter Hunt; Mark J. Hupert; Mark L. Illeman; Hans Jaeger; Robert M. Jellinger; Mina John; Jennifer A. Johnson; Kristin L. Johnson; Heather Johnson; Kay Johnson; Jennifer Joly; Wilbert C. Jordan; Carol A. Kauffman; Homayoon Khanlou; Robert K. Killian; Arthur Y. Kim; David D. Kim; Clifford A. Kinder; Jeffrey T. Kirchner; Laura Kogelman; Erna Milunka Kojic; P. Todd Korthuis; Wayne Kurisu; Douglas S. Kwon; Melissa LaMar; Harry Lampiris; Massimiliano Lanzafame; Michael M. Lederman; David M. Lee; Jean M.L. Lee; Marah J. Lee; Edward T.Y. Lee; Janice Lemoine; Jay A. Levy; Josep M. Llibre; Michael A. Liguori; Susan J. Little; Anne Y. Liu; Alvaro J. Lopez; Mono R. Loutfy; Dawn Loy; Debbie Y. Mohammed; Alan Man; Michael K. Mansour; Vincent C. Marconi; Martin Markowitz; Rui Marques; Jeffrey N. Martin; Harold L. Martin; Kenneth Hugh Mayer; M. Juliana McElrath; Theresa A. McGhee; Barbara H. McGovern; Katherine McGowan; Dawn McIntyre; Gavin X. Mcleod; Prema Menezes; Greg Mesa; Craig E. Metroka; Dirk Meyer-Olson; Andy O. Miller; Kate Montgomery; Karam C. Mounzer; Ellen H. Nagami; Iris Nagin; Ronald G. Nahass; Margret O. Nelson; Craig Nielsen; David L. Norene; David H. O’Connor; Bisola O. Ojikutu; Jason Okulicz; Olakunle O. Oladehin; Edward C. Oldfield; Susan A. Olender; Mario Ostrowski; William F. Owen; Eunice Pae; Jeffrey Parsonnet; Andrew M. Pavlatos; Aaron M. Perlmutter; Michael N. Pierce; Jonathan M. Pincus; Leandro Pisani; Lawrence Jay Price; Laurie Proia; Richard C. Prokesch; Heather Calderon Pujet; Moti Ramgopal; Almas Rathod; Michael Rausch; J. Ravishankar; Frank S. Rhame; Constance Shamuyarira Richards; Douglas D. Richman; Berta Rodes; Milagros Rodriguez; Richard C. Rose; Eric S. Rosenberg; Daniel Rosenthal; Polly E. Ross; David S. Rubin; Elease Rumbaugh; Luis Saenz; Michelle R. Salvaggio; William C. Sanchez; Veeraf M. Sanjana; Steven Santiago; Wolfgang Schmidt; Hanneke Schuitemaker; Philip M. Sestak; Peter Shalit; William Shay; Vivian N. Shirvani; Vanessa I. Silebi; James M. Sizemore; Paul R. Skolnik; Marcia Sokol-Anderson; James M. Sosman; Paul Stabile; Jack T. Stapleton; Sheree Starrett; Francine Stein; Hans-Jurgen Stellbrink; F. Lisa Sterman; Valerie E. Stone; David R. Stone; Giuseppe Tambussi; Randy A. Taplitz; Ellen M. Tedaldi; William Theisen; Richard Torres; Lorraine Tosiello; Cecile Tremblay; Marc A. Tribble; Phuong D. Trinh; Alice Tsao; Peggy Ueda; Anthony Vaccaro; Emilia Valadas; Thanes J. Vanig; Isabel Vecino; Vilma M. Vega; Wenoah Veikley; Barbara H. Wade; Charles Walworth; Chingchai Wanidworanun; Douglas J. Ward; Daniel A. Warner; Robert D. Weber; Duncan Webster; Steve Weis; David A. Wheeler; David J. White; Ed Wilkins; Alan Winston; Clifford G. Wlodaver; The International HIV Controllers Study; Angelique van’t Wout; David P. Wright; Otto O. Yang; David L. Yurdin; Brandon W. Zabukovic; Kimon C. Zachary; Beth Zeeman; Meng Zhao

doi:10.1126/science.1195271

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The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation

Journal article

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The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation

Florencia Pereyra, Xiaoming Jia, Paul J. McLaren, Amalio Telenti, Paul I.W. de Bakker, Bruce D. Walker, Xiaoming Jia, Paul J. McLaren, Stephan Ripke, Chanson J. Brumme, …

Science, Vol.330(6010), pp.1551-1557

10/12/2010

DOI: https://doi.org/10.1126/science.1195271

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https://hdl.handle.net/10523/32656

Abstract

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA–viral peptide interaction as the major factor modulating durable control of HIV infection.

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Record Identifier: 9926517707601891
Title: The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation
Creators: Florencia Pereyra
Xiaoming Jia
Paul J. McLaren
Amalio Telenti
Paul I.W. de Bakker
Bruce D. Walker
Xiaoming Jia
Paul J. McLaren
Stephan Ripke
Chanson J. Brumme
Sara L. Pulit
Mary Carrington
Carl M. Kadie
Jonathan M. Carlson
David Heckerman
Paul I.W. de Bakker
Florencia Pereyra
Paul I.W. de Bakker
Robert R. Graham
Robert M. Plenge
Steven G. Deeks
Bruce D. Walker
Lauren Gianniny
Gabriel Crawford
Jordan Sullivan
Elena Gonzalez
Leela Davies
Amy Camargo
Jamie M. Moore
Nicole Beattie
Supriya Gupta
Andrew Crenshaw
Noël P. Burtt
Candace Guiducci
Namrata Gupta
Xiaojiang Gao
Ying Qi
Yuko Yuki
Florencia Pereyra
Alicja Piechocka-Trocha
Emily Cutrell
Rachel Rosenberg
Kristin L. Moss
Paul Lemay
Jessica O’Leary
Todd Schaefer
Pranshu Verma
Ildiko Toth
Brian Block
Brett Baker
Alissa Rothchild
Jeffrey Lian
Jacqueline Proudfoot
Donna Marie L. Alvino
Seanna Vine
Marylyn M. Addo
Todd M. Allen
Marcus Altfeld
Matthew R. Henn
Sylvie Le Gall
Hendrik Streeck
David W. Haas
Daniel R. Kuritzkes
Gregory K. Robbins
Robert W. Shafer
Roy M. Gulick
Cecilia M. Shikuma
Richard Haubrich
Sharon Riddler
Paul E. Sax
Eric S. Daar
Heather J. Ribaudo
Brian Agan
Shanu Agarwal
Richard L. Ahern
Brady L. Allen
Sherly Altidor
Eric L. Altschuler
Sujata Ambardar
Kathryn Anastos
Ben Anderson
Val Anderson
Ushan Andrady
Diana Antoniskis
David Bangsberg
Daniel Barbaro
William Barrie
J. Bartczak
Simon Barton
Patricia Basden
Nesli Basgoz
Suzane Bazner
Nicholaos C. Bellos
Anne M. Benson
Judith Berger
Nicole F. Bernard
Annette M. Bernard
Christopher Birch
Stanley J. Bodner
Robert K. Bolan
Emilie T. Boudreaux
Meg Bradley
James F. Braun
Jon E. Brndjar
Stephen J. Brown
Katherine Brown
Sheldon T. Brown
Jedidiah Burack
Larry M. Bush
Virginia Cafaro
Omobolaji Campbell
John Campbell
Robert H. Carlson
J. Kevin Carmichael
Kathleen K. Casey
Chris Cavacuiti
Gregory Celestin
Steven T. Chambers
Nancy Chez
Lisa M. Chirch
Paul J. Cimoch
Daniel Cohen
Lillian E. Cohn
Brian Conway
David A. Cooper
Brian Cornelson
David T. Cox
Michael V. Cristofano
George Cuchural
Julie L. Czartoski
Joseph M. Dahman
Jennifer S. Daly
Benjamin T. Davis
Kristine Davis
Sheila M. Davod
Edwin DeJesus
Craig A. Dietz
Eleanor Dunham
Michael E. Dunn
Todd B. Ellerin
Joseph J. Eron
John J.W. Fangman
Claire E. Farel
Helen Ferlazzo
Sarah Fidler
Anita Fleenor-Ford
Renee Frankel
Kenneth A. Freedberg
Neel K. French
Jonathan D. Fuchs
Jon D. Fuller
Jonna Gaberman
Joel E. Gallant
Rajesh T. Gandhi
Efrain Garcia
Donald Garmon
Joseph C. Gathe
Cyril R. Gaultier
Wondwoosen Gebre
Frank D. Gilman
Ian Gilson
Paul A. Goepfert
Michael S. Gottlieb
Claudia Goulston
Richard K. Groger
T. Douglas Gurley
Stuart Haber
Robin Hardwicke
W. David Hardy
P. Richard Harrigan
Trevor N. Hawkins
Sonya Heath
Frederick M. Hecht
W. Keith Henry
Melissa Hladek
Robert P. Hoffman
James M. Horton
Ricky K. Hsu
Gregory D. Huhn
Peter Hunt
Mark J. Hupert
Mark L. Illeman
Hans Jaeger
Robert M. Jellinger
Mina John
Jennifer A. Johnson
Kristin L. Johnson
Heather Johnson
Kay Johnson
Jennifer Joly
Wilbert C. Jordan
Carol A. Kauffman
Homayoon Khanlou
Robert K. Killian
Arthur Y. Kim
David D. Kim
Clifford A. Kinder
Jeffrey T. Kirchner
Laura Kogelman
Erna Milunka Kojic
P. Todd Korthuis
Wayne Kurisu
Douglas S. Kwon
Melissa LaMar
Harry Lampiris
Massimiliano Lanzafame
Michael M. Lederman
David M. Lee
Jean M.L. Lee
Marah J. Lee
Edward T.Y. Lee
Janice Lemoine
Jay A. Levy
Josep M. Llibre
Michael A. Liguori
Susan J. Little
Anne Y. Liu
Alvaro J. Lopez
Mono R. Loutfy
Dawn Loy
Debbie Y. Mohammed
Alan Man
Michael K. Mansour
Vincent C. Marconi
Martin Markowitz
Rui Marques
Jeffrey N. Martin
Harold L. Martin
Kenneth Hugh Mayer
M. Juliana McElrath
Theresa A. McGhee
Barbara H. McGovern
Katherine McGowan
Dawn McIntyre
Gavin X. Mcleod
Prema Menezes
Greg Mesa
Craig E. Metroka
Dirk Meyer-Olson
Andy O. Miller
Kate Montgomery
Karam C. Mounzer
Ellen H. Nagami
Iris Nagin
Ronald G. Nahass
Margret O. Nelson
Craig Nielsen
David L. Norene
David H. O’Connor
Bisola O. Ojikutu
Jason Okulicz
Olakunle O. Oladehin
Edward C. Oldfield
Susan A. Olender
Mario Ostrowski
William F. Owen
Eunice Pae
Jeffrey Parsonnet
Andrew M. Pavlatos
Aaron M. Perlmutter
Michael N. Pierce
Jonathan M. Pincus
Leandro Pisani
Lawrence Jay Price
Laurie Proia
Richard C. Prokesch
Heather Calderon Pujet
Moti Ramgopal
Almas Rathod
Michael Rausch
J. Ravishankar
Frank S. Rhame
Constance Shamuyarira Richards
Douglas D. Richman
Berta Rodes
Milagros Rodriguez
Richard C. Rose
Eric S. Rosenberg
Daniel Rosenthal
Polly E. Ross
David S. Rubin
Elease Rumbaugh
Luis Saenz
Michelle R. Salvaggio
William C. Sanchez
Veeraf M. Sanjana
Steven Santiago
Wolfgang Schmidt
Hanneke Schuitemaker
Philip M. Sestak
Peter Shalit
William Shay
Vivian N. Shirvani
Vanessa I. Silebi
James M. Sizemore
Paul R. Skolnik
Marcia Sokol-Anderson
James M. Sosman
Paul Stabile
Jack T. Stapleton
Sheree Starrett
Francine Stein
Hans-Jurgen Stellbrink
F. Lisa Sterman
Valerie E. Stone
David R. Stone
Giuseppe Tambussi
Randy A. Taplitz
Ellen M. Tedaldi
William Theisen
Richard Torres
Lorraine Tosiello
Cecile Tremblay
Marc A. Tribble
Phuong D. Trinh
Alice Tsao
Peggy Ueda
Anthony Vaccaro
Emilia Valadas
Thanes J. Vanig
Isabel Vecino
Vilma M. Vega
Wenoah Veikley
Barbara H. Wade
Charles Walworth
Chingchai Wanidworanun
Douglas J. Ward
Daniel A. Warner
Robert D. Weber
Duncan Webster
Steve Weis
David A. Wheeler
David J. White
Ed Wilkins
Alan Winston
Clifford G. Wlodaver
The International HIV Controllers Study
Angelique van’t Wout
David P. Wright
Otto O. Yang
David L. Yurdin
Brandon W. Zabukovic
Kimon C. Zachary
Beth Zeeman
Meng Zhao
Publication Details: Science, Vol.330(6010), pp.1551-1557
Academic Unit: Pathology and Molecular Medicine (UOC)
Publisher: American Association for the Advancement of Science
Grant note: U01 AI069495-06 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069484-06 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069477-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069428-06 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069511-06 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID R01 AI077505-04 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069556-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069432-06 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID UL1 RR024975-05 || RR / National Center for Research Resources : NCRR U01 AI069484-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069465-06 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069495-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID K24 AI069994-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID R01 MH071205-05 || MH / National Institute of Mental Health : NIMH U01 AI069424-06 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069472-06 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069511-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069432-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI034853-12 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069424-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069471-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069450-06 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069450-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069472-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069556-06 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069477-06 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID R01 AI030914-17 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI032782-13 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI046370-04 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID UM1 AI068636-06 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069513-06 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069502-06 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID UL1 RR024975-04 || RR / National Center for Research Resources : NCRR U01 AI069471-06 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069419-06 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069532-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID R01 AI028568-20 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID P30 AI027763-19 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069467-06 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069423-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069452-06 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069434-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI046370-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069502-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID R01 AI030914-16 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069513-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069467-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069501-06 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069428-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069474-06 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID P30 AI027763-20 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069465-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID R01 AI087145-02 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 MH085520-01 || MH / National Institute of Mental Health : NIMH U01 AI069532-06 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069419-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069501-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069452-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069423-06 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID U01 AI069474-05 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID
Date published ; e-published: 10/12/2010
Language: English
Resource Type ; Subtype: Journal article