help button home button Genetics J Bacteriology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yang, Z.
Right arrow Articles by Pedersen, A.-M. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yang, Z.
Right arrow Articles by Pedersen, A.-M. K.
Genetics, Vol. 155, 431-449, May 2000, Copyright © 2000

Codon-Substitution Models for Heterogeneous Selection Pressure at Amino Acid Sites

Ziheng Yanga, Rasmus Nielsenb, Nick Goldmanc, and Anne-Mette Krabbe Pedersend
a Department of Biology, University College London, London NW1 2HE, United Kingdom,
b Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138,
c Department of Genetics, University of Cambridge, Cambridge CB2 3EH, United Kingdom
d Department of Ecology and Genetics, University of Århus, Ny Munkegade, DK-8000 Århus C, Denmark

Corresponding author: Ziheng Yang, Department of Biology, 4 Stephenson Way, London NW1 2HE, United Kingdom., z.yang{at}ucl.ac.uk (E-mail)

Communicating editor: W. STEPHAN

Comparison of relative fixation rates of synonymous (silent) and nonsynonymous (amino acid-altering) mutations provides a means for understanding the mechanisms of molecular sequence evolution. The nonsynonymous/synonymous rate ratio ({omega} = ) is an important indicator of selective pressure at the protein level, with {omega} = 1 meaning neutral mutations, {omega} < 1 purifying selection, and {omega} > 1 diversifying positive selection. Amino acid sites in a protein are expected to be under different selective pressures and have different underlying {omega} ratios. We develop models that account for heterogeneous {omega} ratios among amino acid sites and apply them to phylogenetic analyses of protein-coding DNA sequences. These models are useful for testing for adaptive molecular evolution and identifying amino acid sites under diversifying selection. Ten data sets of genes from nuclear, mitochondrial, and viral genomes are analyzed to estimate the distributions of {omega} among sites. In all data sets analyzed, the selective pressure indicated by the {omega} ratio is found to be highly heterogeneous among sites. Previously unsuspected Darwinian selection is detected in several genes in which the average {omega} ratio across sites is <1, but in which some sites are clearly under diversifying selection with {omega} > 1. Genes undergoing positive selection include the ß-globin gene from vertebrates, mitochondrial protein-coding genes from hominoids, the hemagglutinin (HA) gene from human influenza virus A, and HIV-1 env, vif, and pol genes. Tests for the presence of positively selected sites and their subsequent identification appear quite robust to the specific distributional form assumed for {omega} and can be achieved using any of several models we implement. However, we encountered difficulties in estimating the precise distribution of {omega} among sites from real data sets.




This article has been cited by other articles:


Home page
 GeneticsHome page
Q. Xu, X. Wen, and X. Deng
Genomic Organization, Rapid Evolution and Meiotic Instability of Nucleotide-Binding-Site-Encoding Genes in a New Fruit Crop, "Chestnut Rose"
Genetics, April 1, 2008; 178(4): 2081 - 2091.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
C. P. Burridge, D. Craw, D. Fletcher, and J. M. Waters
Geological Dates and Molecular Rates: Fish DNA Sheds Light on Time Dependency
Mol. Biol. Evol., April 1, 2008; 25(4): 624 - 633.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
R. H. Y. Jiang, S. Tripathy, F. Govers, and B. M. Tyler
RXLR effector reservoir in two Phytophthora species is dominated by a single rapidly evolving superfamily with more than 700 members
PNAS, March 25, 2008; 105(12): 4874 - 4879.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
S. E. LaPatra, C. Evilia, and V. Winston
Positively selected sites on the surface glycoprotein (G) of infectious hematopoietic necrosis virus
J. Gen. Virol., March 1, 2008; 89(3): 703 - 708.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
J. L. Kelley and W. J. Swanson
Dietary Change and Adaptive Evolution of enamelin in Humans and Among Primates
Genetics, March 1, 2008; 178(3): 1595 - 1603.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
A. Wong, M. C. Turchin, M. F. Wolfner, and C. F. Aquadro
Evidence for Positive Selection on Drosophila melanogaster Seminal Fluid Protease Homologs
Mol. Biol. Evol., March 1, 2008; 25(3): 497 - 506.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
Z. Yang and R. Nielsen
Mutation-Selection Models of Codon Substitution and Their Use to Estimate Selective Strengths on Codon Usage
Mol. Biol. Evol., March 1, 2008; 25(3): 568 - 579.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
D. Hoffmann, J. Seebach, A. Cosma, F. D. Goebel, K. Strimmer, H. M. Schatzl, and V. Erfle
Therapeutic vaccination reduces HIV sequence variability
FASEB J, February 1, 2008; 22(2): 437 - 444.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
T. Yuri, R. T. Kimball, E. L. Braun, and M. J. Braun
Duplication of Accelerated Evolution and Growth Hormone Gene in Passerine Birds
Mol. Biol. Evol., February 1, 2008; 25(2): 352 - 361.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
M. D. Dean, J. M. Good, and M. W. Nachman
Adaptive Evolution of Proteins Secreted during Sperm Maturation: An Analysis of the Mouse Epididymal Transcriptome
Mol. Biol. Evol., February 1, 2008; 25(2): 383 - 392.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
K. M. Wong, M. A. Suchard, and J. P. Huelsenbeck
Alignment Uncertainty and Genomic Analysis
Science, January 25, 2008; 319(5862): 473 - 476.
[Abstract] [Full Text] [PDF]

Home page
 BioinformaticsHome page
N. Rodrigue, H. Philippe, and N. Lartillot
Uniformization for sampling realizations of Markov processes: applications to Bayesian implementations of codon substitution models
Bioinformatics, January 1, 2008; 24(1): 56 - 62.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
M. Karlsson, K. Nygren, and H. Johannesson
The Evolution of the Pheromonal Signal System and Its Potential Role for Reproductive Isolation in Heterothallic Neurospora
Mol. Biol. Evol., January 1, 2008; 25(1): 168 - 178.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
S. A. Ramm, P. L. Oliver, C. P. Ponting, P. Stockley, and R. D. Emes
Sexual Selection and the Adaptive Evolution of Mammalian Ejaculate Proteins
Mol. Biol. Evol., January 1, 2008; 25(1): 207 - 219.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
M. A. Streisfeld and M. D. Rausher
Relaxed Constraint and Evolutionary Rate Variation between Basic Helix-Loop-Helix Floral Anthocyanin Regulators in Ipomoea
Mol. Biol. Evol., December 1, 2007; 24(12): 2816 - 2826.
[Abstract] [Full Text] [PDF]

Home page
 J HeredHome page
H. C. Miller, M. Andrews-Cookson, and C. H. Daugherty
Two Patterns of Variation among MHC Class I Loci in Tuatara (Sphenodon punctatus)
J. Hered., November 21, 2007; (2007) esm095v1.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
S. Glemin
Mating Systems and the Efficacy of Selection at the Molecular Level
Genetics, October 1, 2007; 177(2): 905 - 916.
[Abstract] [Full Text] [PDF]

Home page
 Genome Res.Home page
H. Ogata and J.-M. Claverie
Unique genes in giant viruses: Regular substitution pattern and anomalously short size
Genome Res., September 1, 2007; 17(9): 1353 - 1361.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
H. L. Zaaijer, F. J. van Hemert, M. H. Koppelman, and V. V. Lukashov
Independent evolution of overlapping polymerase and surface protein genes of hepatitis B virus
J. Gen. Virol., August 1, 2007; 88(8): 2137 - 2143.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
M. F. Ducatez, C. M. Olinger, A. A. Owoade, Z. Tarnagda, M. C. Tahita, A. Sow, S. De Landtsheer, W. Ammerlaan, J. B. Ouedraogo, A. D. M. E. Osterhaus, et al.
Molecular and antigenic evolution and geographical spread of H5N1 highly pathogenic avian influenza viruses in western Africa
J. Gen. Virol., August 1, 2007; 88(8): 2297 - 2306.
[Abstract] [Full Text] [PDF]

Home page
 MicrobiologyHome page
R. H. Orsi, D. R. Ripoll, M. Yeung, K. K. Nightingale, and M. Wiedmann
Recombination and positive selection contribute to evolution of Listeria monocytogenes inlA
Microbiology, August 1, 2007; 153(8): 2666 - 2678.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
X. Maside and B. Charlesworth
Patterns of Molecular Variation and Evolution in Drosophila americana and Its Relatives
Genetics, August 1, 2007; 176(4): 2293 - 2305.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
R. A. Subramanian, P. Arensburger, P. W. Atkinson, and D. A. O'Brochta
Transposable Element Dynamics of the hAT Element Herves in the Human Malaria Vector Anopheles gambiae s.s.
Genetics, August 1, 2007; 176(4): 2477 - 2487.
[Abstract] [Full Text] [PDF]

Home page
 Plant CellHome page
J. Win, W. Morgan, J. Bos, K. V. Krasileva, L. M. Cano, A. Chaparro-Garcia, R. Ammar, B. J. Staskawicz, and S. Kamoun
Adaptive Evolution Has Targeted the C-Terminal Domain of the RXLR Effectors of Plant Pathogenic Oomycetes
PLANT CELL, August 1, 2007; 19(8): 2349 - 2369.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
J. L. Thorne, S. C. Choi, J. Yu, P. G. Higgs, and H. Kishino
Population Genetics Without Intraspecific Data
Mol. Biol. Evol., August 1, 2007; 24(8): 1667 - 1677.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
Z. Yang
PAML 4: Phylogenetic Analysis by Maximum Likelihood
Mol. Biol. Evol., August 1, 2007; 24(8): 1586 - 1591.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
S. C. Choi, A. Hobolth, D. M. Robinson, H. Kishino, and J. L. Thorne
Quantifying the Impact of Protein Tertiary Structure on Molecular Evolution
Mol. Biol. Evol., August 1, 2007; 24(8): 1769 - 1782.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
J. Tarraga, I. Medina, L. Arbiza, J. Huerta-Cepas, T. Gabaldon, J. Dopazo, and H. Dopazo
Phylemon: a suite of web tools for molecular evolution, phylogenetics and phylogenomics
Nucleic Acids Res., July 13, 2007; 35(suppl_2): W38 - W42.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
A. Stern, A. Doron-Faigenboim, E. Erez, E. Martz, E. Bacharach, and T. Pupko
Selecton 2007: advanced models for detecting positive and purifying selection using a Bayesian inference approach
Nucleic Acids Res., July 13, 2007; 35(suppl_2): W506 - W511.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
V. A. Arankalle, S. Shrivastava, S. Cherian, R. S. Gunjikar, A. M. Walimbe, S. M. Jadhav, A. B. Sudeep, and A. C. Mishra
Genetic divergence of Chikungunya viruses in India (1963-2006) with special reference to the 2005-2006 explosive epidemic
J. Gen. Virol., July 1, 2007; 88(7): 1967 - 1976.
[Abstract] [Full Text] [PDF]

Home page
 BioinformaticsHome page
I. Mayrose, A. Doron-Faigenboim, E. Bacharach, and T. Pupko
Towards realistic codon models: among site variability and dependency of synonymous and non-synonymous rates
Bioinformatics, July 1, 2007; 23(13): i319 - i327.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
C. Kosiol, I. Holmes, and N. Goldman
An Empirical Codon Model for Protein Sequence Evolution
Mol. Biol. Evol., July 1, 2007; 24(7): 1464 - 1479.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. T. Ranjith-Kumar, W. Miller, J. Sun, J. Xiong, J. Santos, I. Yarbrough, R. J. Lamb, J. Mills, K. E. Duffy, S. Hoose, et al.
Effects of Single Nucleotide Polymorphisms on Toll-like Receptor 3 Activity and Expression in Cultured Cells
J. Biol. Chem., June 15, 2007; 282(24): 17696 - 17705.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
L. Abi-Rached, K. Dorighi, P. J. Norman, M. Yawata, and P. Parham
Episodes of Natural Selection Shaped the Interactions of IgA-Fc with Fc{alpha}RI and Bacterial Decoy Proteins
J. Immunol., June 15, 2007; 178(12): 7943 - 7954.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
V. Ruano-Rubio and M. A. Fares
Testing the Neutral Fixation of Hetero-Oligomerism in the Archaeal Chaperonin CCT
Mol. Biol. Evol., June 1, 2007; 24(6): 1384 - 1396.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
S.-Y. Wang, J.-C. Wu, T.-Y. Chiang, Y.-H. Huang, C.-W. Su, and I-J. Sheen
Positive Selection of Hepatitis Delta Antigen in Chronic Hepatitis D Patients
J. Virol., May 1, 2007; 81(9): 4438 - 4444.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
M. Anisimova and Z. Yang
Multiple Hypothesis Testing to Detect Lineages under Positive Selection that Affects Only a Few Sites
Mol. Biol. Evol., May 1, 2007; 24(5): 1219 - 1228.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. C.-C. Shih, T.-C. Hsiao, M.-S. Ho, and W.-H. Li
Simultaneous amino acid substitutions at antigenic sites drive influenza A hemagglutinin evolution
PNAS, April 10, 2007; 104(15): 6283 - 6288.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
G. Venturi, M. Ciccozzi, S. Montieri, A. Bartoloni, D. Francisci, L. Nicoletti, C. Fortuna, L. Marongiu, G. Rezza, and M. G. Ciufolini
Genetic variability of the M genome segment of clinical and environmental Toscana virus strains
J. Gen. Virol., April 1, 2007; 88(4): 1288 - 1294.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
S. Jagadeeshan and R. S. Singh
Rapid Evolution of Outer Egg Membrane Proteins in the Drosophila melanogaster Subgroup: A Case of Ecologically Driven Evolution of Female Reproductive Traits
Mol. Biol. Evol., April 1, 2007; 24(4): 929 - 938.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
C. Seoighe, F. Ketwaroo, V. Pillay, K. Scheffler, N. Wood, R. Duffet, M. Zvelebil, N. Martinson, J. McIntyre, L. Morris, et al.
A Model of Directional Selection Applied to the Evolution of Drug Resistance in HIV-1
Mol. Biol. Evol., April 1, 2007; 24(4): 1025 - 1031.
[Abstract] [Full Text] [PDF]

Home page
 Genome Res.Home page
B. Hurle, W. Swanson, NISC Comparative Sequencing Program, and E. D. Green
Comparative sequence analyses reveal rapid and divergent evolutionary changes of the WFDC locus in the primate lineage
Genome Res., March 1, 2007; 17(3): 276 - 286.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
Z. Zhao, J. H. Thomas, N. Chen, J. A. Sheps, and D. L. Baillie
Comparative Genomics and Adaptive Selection of the ATP-Binding-Cassette Gene Family in Caenorhabditis Species
Genetics, March 1, 2007; 175(3): 1407 - 1418.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
P. K. Ingvarsson
Gene Expression and Protein Length Influence Codon Usage and Rates of Sequence Evolution in Populus tremula
Mol. Biol. Evol., March 1, 2007; 24(3): 836 - 844.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
O. G. Pybus, A. Rambaut, R. Belshaw, R. P. Freckleton, A. J. Drummond, and E. C. Holmes
Phylogenetic Evidence for Deleterious Mutation Load in RNA Viruses and Its Contribution to Viral Evolution
Mol. Biol. Evol., March 1, 2007; 24(3): 845 - 852.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
R. J. P. Brown, A. W. Tarr, C. P. McClure, V. S. Juttla, N. Tagiuri, W. L. Irving, and J. K. Ball
Cross-genotype characterization of genetic diversity and molecular adaptation in hepatitis C virus envelope glycoprotein genes
J. Gen. Virol., February 1, 2007; 88(2): 458 - 469.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
A. Doron-Faigenboim and T. Pupko
A Combined Empirical and Mechanistic Codon Model
Mol. Biol. Evol., February 1, 2007; 24(2): 388 - 397.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
L. Bofkin and N. Goldman
Variation in Evolutionary Processes at Different Codon Positions
Mol. Biol. Evol., February 1, 2007; 24(2): 513 - 521.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
T. Hernandez-Hernandez, L. P. Martinez-Castilla, and E. R. Alvarez-Buylla
Functional Diversification of B MADS-Box Homeotic Regulators of Flower Development: Adaptive Evolution in Protein-Protein Interaction Domains after Major Gene Duplication Events
Mol. Biol. Evol., February 1, 2007; 24(2): 465 - 481.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
R. Nielsen, V. L. Bauer DuMont, M. J. Hubisz, and C. F. Aquadro
Maximum Likelihood Estimation of Ancestral Codon Usage Bias Parameters in Drosophila
Mol. Biol. Evol., January 1, 2007; 24(1): 228 - 235.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
M. L. Porter, T. W. Cronin, D. A. McClellan, and K. A. Crandall
Molecular Characterization of Crustacean Visual Pigments and the Evolution of Pancrustacean Opsins
Mol. Biol. Evol., January 1, 2007; 24(1): 253 - 268.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. Harlin-Cognato, E. A. Hoffman, and A. G. Jones
Gene cooption without duplication during the evolution of a male-pregnancy gene in pipefish
PNAS, December 19, 2006; 103(51): 19407 - 19412.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
G. A. Bazykin, J. Dushoff, S. A. Levin, and A. S. Kondrashov
Bursts of nonsynonymous substitutions in HIV-1 evolution reveal instances of positive selection at conservative protein sites
PNAS, December 19, 2006; 103(51): 19396 - 19401.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
L. Rohmer, M. Brittnacher, K. Svensson, D. Buckley, E. Haugen, Y. Zhou, J. Chang, R. Levy, H. Hayden, M. Forsman, et al.
Potential Source of Francisella tularensis Live Vaccine Strain Attenuation Determined by Genome Comparison
Infect. Immun., December 1, 2006; 74(12): 6895 - 6906.
[Abstract] [Full Text] [PDF]

Home page
 Integr. Comp. Biol.Home page
S. Cohen, J. Tirindelli, M. Gomez-Chiarri, and D. Nacci
Functional implications of Major Histocompatibility (MH) variation using estuarine fish populations
Integr. Comp. Biol., December 1, 2006; 46(6): 1016 - 1029.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
P. R. Marri, W. Hao, and G. B. Golding
Gene Gain and Gene Loss in Streptococcus: Is It Driven by Habitat?
Mol. Biol. Evol., December 1, 2006; 23(12): 2379 - 2391.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
M. R. Pie
The Influence of Phylogenetic Uncertainty on the Detection of Positive Darwinian Selection
Mol. Biol. Evol., December 1, 2006; 23(12): 2274 - 2278.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
Z. Yang
On the Varied Pattern of Evolution of 2 Fungal Genomes: A Critique of Hughes and Friedman
Mol. Biol. Evol., December 1, 2006; 23(12): 2279 - 2282.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. E. Aagaard, X. Yi, M. J. MacCoss, and W. J. Swanson
Rapidly evolving zona pellucida domain proteins are a major component of the vitelline envelope of abalone eggs
PNAS, November 14, 2006; 103(46): 17302 - 17307.
[Abstract] [Full Text] [PDF]

Home page
 BioinformaticsHome page
K. Scheffler, D. P. Martin, and C. Seoighe
Robust inference of positive selection from recombining coding sequences
Bioinformatics, October 15, 2006; 22(20): 2493 - 2499.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
T. H. M. Mes and M. Doeleman
Positive Selection on Transposase Genes of Insertion Sequences in the Crocosphaera watsonii Genome.
J. Bacteriol., October 1, 2006; 188(20): 7176 - 7185.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
Y. Liu, J. McNevin, J. Cao, H. Zhao, I. Genowati, K. Wong, S. McLaughlin, M. D. McSweyn, K. Diem, C. E. Stevens, et al.
Selection on the Human Immunodeficiency Virus Type 1 Proteome following Primary Infection
J. Virol., October 1, 2006; 80(19): 9519 - 9529.
[Abstract] [Full Text] [PDF]