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The large amount of solar flux at the visible and IR bands implies that small flux differences may induce important terrestrial consequences. The impact of the 110 variability of these bands on the Earth's climate is expected Relative contribution of the UV (200-400 nm), visible (400-700 nm), near-IR (700-1000 nm) and ...
10.5194/acp-13-3945-2013
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Earth and Planetary Sciences
https://openalex.org/fields/19
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Variability out-of-phase with solar activity is indeed predicted by some SSI models in the NIR, but with a sig-135 nificantly lower magnitude than found by SORCE/SIM. Details are provided in the following. The inverse variability observed by SIM in a wide integrated band in the visible was, however, unexpected. It can ...
10.5194/acp-13-3945-2013
article
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2,013
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Earth and Planetary Sciences
https://openalex.org/fields/19
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g. Haigh et al. , 2010; Merkel et al. , 2011) , it should be noted that the SIM measurements employed for the analysis covered less than one solar cycle and required extrapolation over a full cycle, and therefore, added uncertainty (Garcia, 2010). Also the transition altitude from in-phase (lower and middle stratosphe...
10.5194/acp-13-3945-2013
article
en
2,013
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Earth and Planetary Sciences
https://openalex.org/fields/19
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e. a study involving the coordinated work of various research communities, which is part of the COST Action ES1005 1 to which most of the authors of this paper belong. This paper summarises and compares, for the first time, a large number of SSI observations and models, and discusses the impact of these data on Earth's...
10.5194/acp-13-3945-2013
article
en
2,013
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false
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Earth and Planetary Sciences
https://openalex.org/fields/19
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Moreover, the values above are relative to annual changes. Therefore, they can be assumed valid for short-term variations, but on longer time scales, the instrument stability could be considerably lower. It is worth mentioning that the SORCE public Level 3 data include the SOLSTICE data up to 308 nm and SIM data above ...
10.5194/acp-13-3945-2013
article
en
2,013
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false
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Earth and Planetary Sciences
https://openalex.org/fields/19
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The studies have been concentrated on SSI instrument observations, capabilities, and estimated spectral irradiance uncertainties, methods of correcting for degradation, and refinement of estimated uncertainties. It has been understood that all detectors and optics suffer some degradation in space, largely due to exposu...
10.5194/acp-13-3945-2013
article
en
2,013
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false
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Earth and Planetary Sciences
https://openalex.org/fields/19
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For the first time Major efforts, however, are still needed in each of the three research areas covered in this study. Resolving differences in existing long-term time series of solar measurements is a 2055 major challenge; forthcoming initiatives for merging these measurements into single homogenous databases will be ...
10.5194/acp-13-3945-2013
article
en
2,013
true
false
false
false
Earth and Planetary Sciences
https://openalex.org/fields/19
cc-by
Acknowledgements. This work is the outcome of a workshop funded by the COST Action ES1005 TOSCA (http://www. tosca-cost. eu). We thank J. Lean , J. Fontenla , 2075 and G. Thuillier for helpful comments and kind collaboration. The authors are grateful to W. Ball , S. Criscuoli , S. Oberländer and M. Kun...
10.5194/acp-13-3945-2013
article
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2,013
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Earth and Planetary Sciences
https://openalex.org/fields/19
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0 Cycle Sequencing ready reaction Kit (life Technologies), and 5 % DMSO on the ABI3730Xl capillary genetic analyzer (life Technologies). genotyping assay Two primers (forward primer, 5′-CAg CgC TgC CTg AAA CTC-3′; reverse primer, 5′-gTC CTg CCC CTT CAC CTT C-3′) were designed to amplify a 163-bp product encompassing C2...
10.1007/s00401-013-1198-2
article
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2,013
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Medicine
https://openalex.org/fields/27
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Statistical analysis Survival time according to TERT mutational status was assessed using the Kaplan-Meier estimate and a log-rank test. Comparisons of binary and categorical patient characteristics between subgroups and cohorts were performed using the two-sided Fisher's exact test or Chi-squared test. Continuous vari...
10.1007/s00401-013-1198-2
article
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2,013
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true
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Medicine
https://openalex.org/fields/27
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Acknowledgments We thank Susan Archer for technical writing, and Nick Downey from Integrated DNA Technologies for support with probe/primer design. We acknowledge CrB HCl-Neurobiotec tumor bank ( Hospices Civils de lyon, lyon, France ). MDT is supported by a CIHr Clinician Scientist Phase II award , funds from...
10.1007/s00401-013-1198-2
article
en
2,013
false
false
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Medicine
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Discussion The data presented here are, to our knowledge, the first direct evidence of intracellular vitrification in a cell suspension under ecologically relevant conditions, that is in a dilute aqueous medium and the absence of external cryoprotectants. Vitrification was observed in all cell types examined, and intra...
10.1371/journal.pone.0066207
article
en
2,013
true
false
false
false
Environmental Science
https://openalex.org/fields/23
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Acknowledgments We thank Sarah Acton and Stephanie Gibbons for reading the typescript and Stephanie Cenard for cell cultures. We also thank Nick Lane and three anonymous referees for valuable and perceptive comments that improved the paper significantly.
10.1371/journal.pone.0066207
article
en
2,013
false
false
true
false
Environmental Science
https://openalex.org/fields/23
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Both Kir6. x and SUR subunits participate in the metabolic regulation of channel activity by nucleotides, with binding of ATP to Kir6. 2 closing the channel and binding of Mg-nucleotides (MgATP, MgADP) to SUR stimulating channel opening [15] [16] [17]. Structural information on the K ATP channel is still limited. The ...
10.1111/febs.12097
article
en
2,012
true
false
false
false
Medicine
https://openalex.org/fields/27
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Electron microscopy and image processing Images were recorded on Kodak SO 163 film using a Philips CM120 electron microscope operating at 120 kV under low dose conditions with a nominal magnification of 45 000 9 (actual magnification 41 000 9). Images were digitized with a step size of 12. 5 lm on a Nikon Super Coolsca...
10.1111/febs.12097
article
en
2,012
false
true
false
false
Medicine
https://openalex.org/fields/27
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Modelling of SUR2B A homology model of human SUR2B was built using MOD-ELLER 9v5 [54] and the ADP-bound crystal structure of Sav1866 (PDB ID 2HYD) as template. A multiple sequence alignment of SUR2B, SUR1 and Sav1866 was created with CLUSTALX 2. 1 [53] by aligning the half-transporters of SUR (TMD1-NBD1 and TMD2-NB...
10.1111/febs.12097
article
en
2,012
true
false
false
false
Medicine
https://openalex.org/fields/27
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Fitting of structures and models into the projection map Crystal structures of Sav1866 (PDB ID 2HYD), P-glycoprotein (PDB ID 3G5U) and a homology model of SUR2B (based on the Sav1866 structure) were fitted to the EM maps using SPIDER [52]. In this process, the 3D structures were first converted into 3D density maps us...
10.1111/febs.12097
article
en
2,012
true
false
false
false
Medicine
https://openalex.org/fields/27
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The resulting rotations and shifts were also applied to the PDB file itself, resulting in positions and orientations that correspond to the best fits. This enabled the best fit of the x and y orientations of the structures/ model to the SUR2B projection map to be obtained. For display purposes, in the figures the 2D SU...
10.1111/febs.12097
article
en
2,012
true
false
false
false
Medicine
https://openalex.org/fields/27
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Acknowledgements We dedicate this paper to the memory of Dr Michael Mikhailov , who passed away during the course of this work. We thank the Wellcome Trust , the Royal Society and the European Union (EDICT: 201924 ) for support. JA held a Wellcome Trust Structural Biology Studentship. CV-B held a Wellcome Trus...
10.1111/febs.12097
article
en
2,012
false
false
true
false
Medicine
https://openalex.org/fields/27
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This finding is particularly important because it directs biological studies to understand the mechanisms that lead to this chronic life-long inflammatory disease. junction variants) with 56% of these already reported in dbSNP version 132, a non-synonymous/synonymous ratio of 1. 7 and a transition/transversion ratio of...
10.1371/journal.pgen.1003723
article
en
2,013
true
false
false
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Biochemistry, Genetics and Molecular Biology
https://openalex.org/fields/13
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Follow-up genotyping and association analyses After removal of variants that did not validate, variants observed only once in our sequencing dataset (singletons) and variants from the MHC region, 84 non-synonymous coding variants (missense, non-sense and splicing variants), were used for subsequent analyses. Following ...
10.1371/journal.pgen.1003723
article
en
2,013
true
false
false
false
Biochemistry, Genetics and Molecular Biology
https://openalex.org/fields/13
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Using GEO public microarray datasets, we pursued a systematic follow-up analysis of expression profiles of epithelial cells in response to bacterial products, PAMPs/pathogens. We found that RNF186 gene expression was significantly up-regulated in small intestine epithelium and induced by Shigella infection in mice (P =...
10.1371/journal.pgen.1003723
article
en
2,013
true
false
false
false
Biochemistry, Genetics and Molecular Biology
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e. missense, nonsense or splice junction variants) in the NOD2, ATG16L1, IL23R, MST1, CARD9, IL18RAP and RNF186 genes, and at least suggestive evidence for causal variation in the CUL2, C1orf106, PTPN22, MUC19, CEP72, LAMB1, CCR6, JAK2, and STAC2 genes (Current study and references [4, 5, 7, 11, 31] ). While only a sm...
10.1371/journal.pgen.1003723
article
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2,013
true
false
false
false
Biochemistry, Genetics and Molecular Biology
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Moreover, should this observation not be limited to risk loci identified by GWA studies, this has implications with respect to future efforts for discovering risk loci. Specifically, if the occurrence of rare variants with large effects sizes is relatively infrequent, then this may favor the current paradigm of locus d...
10.1371/journal.pgen.1003723
article
en
2,013
true
false
false
false
Biochemistry, Genetics and Molecular Biology
https://openalex.org/fields/13
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Target selection and design Target exonic sequences were selected based on the coding exons of 55 genes in 14 UC-associated regions and 7 regions identified in CD with nominal replication in our recent UC GWAS study, as well ECM1 identified from recent candidate-gene study in UC [6, [8] [9] [10] 34]. Specifically, amp...
10.1371/journal.pgen.1003723
article
en
2,013
false
true
false
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Biochemistry, Genetics and Molecular Biology
https://openalex.org/fields/13
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Sequencing and variant discovery The combined PCR products from each pooled DNA group were concatenated using the NotI adapters and sheared into fragments as previously described [36]. Libraries were constructed according to Illumina single-end library protocol, with 150-200 bp gel size selection and PCR enrichment us...
10.1371/journal.pgen.1003723
article
en
2,013
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false
Biochemistry, Genetics and Molecular Biology
https://openalex.org/fields/13
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Genotyping, validation and follow-up genotyping We randomly selected 237 high quality variants for validation in our 350 discovery DNAs samples using Sequenom MassARRAY iPlex200 chemistry. Genotyping assay designs were obtained from the Assay Designer v. 3. 1 software, and genotyping oligonucleotides were synthesized a...
10.1371/journal.pgen.1003723
article
en
2,013
true
true
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false
Biochemistry, Genetics and Molecular Biology
https://openalex.org/fields/13
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We then evaluated these variants in an independent cohort of North-American individual of European descent from the NIDDK IBD genetics consortium (754 cases and 1008 controls); only variants detected in this independent cohort were kept for follow-up genotyping. Following assay design, 42 SNPs were genotyped using Sequ...
10.1371/journal.pgen.1003723
article
en
2,013
true
false
false
false
Biochemistry, Genetics and Molecular Biology
https://openalex.org/fields/13
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(A) Table of gene expression fold change statistics from comparison of PBMC transcriptional profiles in healthy subjects and patients with ulcerative colitis (UC) (GSE3365). Only top 10 genes and RNF186 are shown. The rank column refers to the rank of the gene for signal to noise ratio in the specific study (1061 signi...
10.1371/journal.pgen.1003723
article
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2,013
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false
Biochemistry, Genetics and Molecular Biology
https://openalex.org/fields/13
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Summary of Pooled Sequencing Experiment. (XLSX)Table S4 Details of sequencing and follow-up genotyping results, as well as association analyses for each SNP tested in this study. (XLSX) Table S5 Power calculations for each SNP tested with observed minor allele frequency greater than 0. 0001. (XLSX) Table S6 Sequencing ...
10.1371/journal.pgen.1003723
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false
Biochemistry, Genetics and Molecular Biology
https://openalex.org/fields/13
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Acknowledgments The authors would like to acknowledge the important contributions of the Quebec IBD Genetics Consortium , the NIDDK North American IBD Genetics Consortium and the International IBD Genetics Consortium for sample collection and for the Immunochip genotype data used in replication. data: PG MB GB KSL...
10.1371/journal.pgen.1003723
article
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2,013
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false
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false
Biochemistry, Genetics and Molecular Biology
https://openalex.org/fields/13
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Research in Sweden was supported by the Swedish Society of Medicine, Ihre Foundation, O ¨rebro University Hospital Research Foundation , Karolinska Institutet , the Swedish National Program for IBD Genetics , the Swedish Organization for IBD , and the Swedish Medical Research Council. RKW is supported by a clinica...
10.1371/journal.pgen.1003723
article
en
2,013
false
false
true
false
Biochemistry, Genetics and Molecular Biology
https://openalex.org/fields/13
cc-by
(A) Table of gene expression fold change statistics from comparison of PBMC transcriptional profiles in healthy subjects and patients with ulcerative colitis (UC) (GSE3365). Only top 10 genes and RNF186 are shown. The rank column refers to the rank of the gene for signal to noise ratio in the specific study (1061 signi...
10.1371/journal.pgen.1003723
article
en
2,013
true
false
false
false
Biochemistry, Genetics and Molecular Biology
https://openalex.org/fields/13
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A consortium newsletter was developed and circulated widely. An open access website (www. menafricar. org) was established as well as a separate, password protected site, accessible only to consortium members, which holds all operational documents and which hosts a discussion forum. Each centre established a crisis man...
10.1111/tmi.12125
article
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2,013
false
false
false
true
Immunology and Microbiology
https://openalex.org/fields/24
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The 7. 5 mM MgCl 2 master mix was adjusted to 11 mM MgCl 2 to optimise the technique. Prior to the introduction of PCR testing as a routine procedure, each site underwent cross-validation of the technique, comparing results of approximately 50 samples with results obtained at the University of Oxford. On arrival in Oxf...
10.1111/tmi.12125
article
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false
false
Immunology and Microbiology
https://openalex.org/fields/24
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Data management Various systems for data management that required construction of local and a central database were considered, including manual double entry, the open-source electronic data capture system Open Clinica (Paulsen et al. 2012) and TeleForm, an automated form processing system for data management (TeleFo...
10.1111/tmi.12125
article
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2,013
true
true
false
false
Immunology and Microbiology
https://openalex.org/fields/24
cc-by
For harmonisation purposes and to facilitate technical support, centres were provided with similar scanning and computing equipment pre-loaded with TeleForm. To ensure that all centres used the same study forms, were developed centrally in both English and TeleForm French. A label form was designed, which could be popu...
10.1111/tmi.12125
article
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2,013
true
true
false
false
Immunology and Microbiology
https://openalex.org/fields/24
cc-by
The TeleForm data management adopted for the study was new to most centres and because of lack of time for training and frequent changes in form design at the start of the project, completion errors and poor optical character recognition were initially common. However, this situation improved as form design became stab...
10.1111/tmi.12125
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false
Immunology and Microbiology
https://openalex.org/fields/24
cc-by
Acknowledgements The authors thank members of the MenAfriCar Advisory Committee (Fred Binka , Mamoudou Djingarey , Robert Heyderman , Marie-Paule Kieny , Marie-Pierre Preziosi , David Stephens and Marcel Tanner [chairman]) for their sound advice and support and the following who provided clinical monitoring: ...
10.1111/tmi.12125
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false
false
true
false
Immunology and Microbiology
https://openalex.org/fields/24
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Acknowledgments We are grateful to A. Barroso , M. Krawczyk and R. Santos for useful discussions. S. D. acknowledges partial support from the EU FP7 ITN INVISIBLES (MC actions , PITN-GA-2011-289-442 ) and the Lyon Institute of Origins. The work of R. G. F. and J. P. S. was partially supported by FCT -Fundaçã...
10.1007/jhep11(2013)100
article
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false
false
true
false
Physics and Astronomy
https://openalex.org/fields/31
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Data collection, laboratory measurements, and follow-up WC was measured in the standing position, using a tape placed midway between the lower ribs and iliac crests on the midaxillary line. BMI (kg/m 2 ) was calculated from the measured height and body weight. Supine blood pressure was measured in the right arm using a...
10.2147/vhrm.s49922
article
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2,013
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false
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false
Medicine
https://openalex.org/fields/27
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An adjustment for hypertension, lipid level, and diabetes, which reflect possible mechanisms by which obesity increases mortality, was made in separate, subsequent steps. For these analyses, hypertension was defined as systolic BP. 140 mmHg, diastolic BP. 90 mmHg, or ongoing antihypertensive treatment, and diabetes was...
10.2147/vhrm.s49922
article
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true
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false
Medicine
https://openalex.org/fields/27
cc-by
Acknowledgments This study was supported by the Caisse Nationale d'Assurance Maladie des Travailleurs Salariés ( CNAMTS, Paris, France ) and the Caisse Primaire d'Assurance Maladie de Paris (CPAM-Paris, France ).
10.2147/vhrm.s49922
article
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false
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false
Medicine
https://openalex.org/fields/27
cc-by
Sequence assembly Reads were assembled using Trinity [33]. The longest assembled sequences were referred to as contigs. The reads were then mapped back to contigs with paired-end reads to detect contigs from the same transcript and the distances between these contigs. Finally, sequences were obtained that lacked Ns an...
10.1371/journal.pone.0058914
article
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false
Environmental Science
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Orientation and protein coding region prediction (CDS) of sequences having no hits in BLAST were predicted using ESTScan [34]. Original transcript sequences (59-. 39) were provided if their orientations could be determined. Other sequences were provided by the assembler outputs.
10.1371/journal.pone.0058914
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false
Environmental Science
https://openalex.org/fields/23
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Sequence annotation Unigene annotations provide functional annotations for all unigenes, along with their expression levels. Functional annotations of unigenes were analyzed using protein sequence similarity, KEGG Pathway, COG and GO analysis. All unigene sequences were against the protein databases (Nr, SwissProt, KEG...
10.1371/journal.pone.0058914
article
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false
Environmental Science
https://openalex.org/fields/23
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All unigenes were aligned to the COG database to predict and classify their possible functions. GO functional annotation was obtained from Nr annotation. GO annotation comprises three ontologies, i. e. , a molecular function, a cellular component and a biological process. The basic GO unit is a GOterm, and every GO-ter...
10.1371/journal.pone.0058914
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false
Environmental Science
https://openalex.org/fields/23
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Annotation of predicted proteins For annotation, distinct gene sequences were first searched using BLASTx against the non-redundant (Nr) NCBI nucleotide database, with a cut-off E-value of 10 25. Using this approach, 25,239 genes (87. 39% of all distinct sequences) returned an above cut-off BLAST result (Table S1 ). T...
10.1371/journal.pone.0058914
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2,013
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Environmental Science
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The percentages of infected cells and viability were assessed by GFP expression and propidium iodide, respectively, using a FACSCalibur flow cytometer (BD Biosciences). The CELLQuest TM software (BD Biosciences) was used for data acquisition and analysis. For rescue experiments, PANC-1 cells stably expressing HA-tagged...
10.1074/jbc.m113.473348
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false
Medicine
https://openalex.org/fields/27
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Each individual fraction was desalted and concentrated prior to phosphopeptide enrichment by solid phase extraction using Waters Oasis reversed-phase HLB cartridges (Waters). The eluted samples were lyophilized and reconstituted in a solution containing 80% acetonitrile with 2. 5% TFA. The phosphopeptides were enriched...
10.1074/jbc.m113.473348
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Medicine
https://openalex.org/fields/27
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Singly charged ions with unassigned charge state were also excluded from MS/MS. The mass spectrometry data were processed using Proteome Discoverer 1. 3 (Thermo Scientific). The MS/MS peak lists were extracted and searched by Mascot against a concatenated forward and reversed version of the Swiss-Prot human database. T...
10.1074/jbc.m113.473348
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Medicine
https://openalex.org/fields/27
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MSQuant calculated the ratio average over the peptide elution time, and the assignments used for quantification were visually displayed and validated. To minimize the false discovery rate, all phosphopeptide identifications were filtered by Mascot score. We accepted peptides based on the criterion that the number of fo...
10.1074/jbc.m113.473348
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Medicine
https://openalex.org/fields/27
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Water containing 0. 1% (v/v) formic acid was used as eluent A, and acetonitrile containing 0. 1% (v/v) acid formic was used as eluent B with a linear gradient from 5 to 60% B in 25 min and from 50 to 100% B in 3 min. MS/MS analysis was performed in positive ionization mode using an ion spray voltage of 5500 V. Analyst ...
10.1074/jbc.m113.473348
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Medicine
https://openalex.org/fields/27
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The collision energy, declustering potential, and collision cell exit potential were optimized for each chosen MRM transition by infusion of a standard peptide obtained from chemical synthesis. The MRM transitions were monitored and acquired with a dwell time of 50 ms to ensure 25 and 30 data points per chromatographic...
10.1074/jbc.m113.473348
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Medicine
https://openalex.org/fields/27
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5 nM to 1 M was preincubated with PRP4 for 30 min at room temperature before the reaction was initiated with PAK4 protein substrate. Compound dilution (3-fold) was prepared in 100% DMSO and diluted 1:100 into the final reaction. After a 60-min incubation at room temperature, the reaction was terminated with formic acid...
10.1074/jbc.m113.473348
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Medicine
https://openalex.org/fields/27
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2 M ammonium sulfate, 20 -30% PEG 3350, and 0. 1 M HEPES, pH 7. 0 at 18 °C in the presence or absence of ligand. Crystals were cryoprotected by addition of glycerol or PEG 400. For the reported complexes of PRP4 with ADP, AMPPNP, and Compound A, apo crystals were soaked for longer times in cryoprotectant solution in th...
10.1074/jbc.m113.473348
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Medicine
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Subsequent structures were solved using apo-PRP4 as the starting point. Model building was done using Coot (24). Refinement was carried out using CNX (25) with NCS constraints released in the last refinement cycles (apo) or BUSTER (all complexes) (26). The final coordinates for all discussed structures have been de...
10.1074/jbc.m113.473348
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Medicine
https://openalex.org/fields/27
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In parallel, we initiated a SILAC-based quantitative global phosphoproteomics profiling experiment and confirmed the resulting candidate list using an AIMS approach. PRP4 binders revealed from the interactome studies were then cross-referenced with the data obtained from the phosphoproteomics profiling effort, resultin...
10.1074/jbc.m113.473348
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Medicine
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3C and supplemental Table 4). A representative example of the identified spectrum for PAK4 is shown in Fig. 3D. To examine the existence of a PRP4 consensus motif, we analyzed a 13-amino acid sequence surrounding the central phosphorylated residue with Motif-X software for the phosphopeptides that were down-regulated ...
10.1074/jbc.m113.473348
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Medicine
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To further validate candidates obtained from SILAC-based phosphoproteomics profiling, we performed AIMS in the Orbitrap MS system. Data for m/z and charge state were collected based on a user-defined inclusion list, which consists of 153 phosphopeptides selected based on the -fold change and the reliability of the pept...
10.1074/jbc.m113.473348
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Medicine
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The apo data set resolution is 2. 44 Å, and its space group is C2 with cell parameters a ϭ 73. 27 Å, b ϭ 75. 29 Å, c ϭ 148. 00 Å, ␣ ϭ ␥ ϭ 90°, and ␤ ϭ 97°. ADP, AMPPNP, and Compound A complex data sets were processed in P1 space group with cell parameters around a ϭ b ϭ 52 Å, c ϭ 79 Å, ␣ ϭ 103°, ␤ ϭ 105°, and ␥ ϭ 93°an...
10.1074/jbc.m113.473348
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false
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Medicine
https://openalex.org/fields/27
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Cells cultured in heavy medium were treated with doxycycline for 72 h to induce knockdown of endogenous PRP4, whereas those cultured in light medium were left untreated. Both batches of cells were combined in a ratio of 1:1 followed by nuclear protein extraction, protein digestion, affinity enrichment of phosphopeptide...
10.1074/jbc.m113.473348
article
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Medicine
https://openalex.org/fields/27
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Apo To investigate the possibility of generating PRP4-specific inhibitors, we dissected structural differences between PRP4 and its closely related kinases, namely DYRK2 and CLK2, for which structural information is currently available. To this end, we superimposed the structures of PRP4 with those of apo-DYRK2 (Protei...
10.1074/jbc.m113.473348
article
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2,013
true
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Medicine
https://openalex.org/fields/27
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Pro 769 in PRP4 at this position is highly unusual. The residue preceding the DFG is shown in green. Cys 833 in PRP4 at this position is unusual as well. F, structural alignment between apo-PRP4 (yellow), DYRK2 (red), and CLK2 (orange). Detail of the differences at the G-rich loop is shown. Note that although the entir...
10.1074/jbc.m113.473348
article
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Medicine
https://openalex.org/fields/27
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5F ). To further explore the feasibility of generating more potent and selective PRP4 kinase inhibitors, a complex between PRP4 and Compound A was examined by co-crystallization. Compound A is a small molecule identified from a high throughput compound screen and shown to be active in MS-based biochemical assay using P...
10.1074/jbc.m113.473348
article
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2,013
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Medicine
https://openalex.org/fields/27
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PRP4 kinase is a large protein that possesses an RS domain at its N terminus. This domain serves as an essential platform for interaction with other RS domain-containing proteins. The potential significance of the PRP4 kinase adaptor function therefore cannot be overlooked. However, it is apparent from the data present...
10.1074/jbc.m113.473348
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Medicine
https://openalex.org/fields/27
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Acknowledgments-We thank Christopher Arendt and Asher Zilberstein for early contributions and Ying Zhang for help with PRP4 expression and purification.
10.1074/jbc.m113.473348
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Medicine
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Acknowledgments We acknowledge financial support from the European Research Council Advanced Grant DYNamo ( ERC-2010-AdG-267374 ), Spanish Grants ( 2010-21282-C02-01 and PIB2010US-00652 ), Grupos Consolidados UPV/EHU del Gobierno Vasco ( IT578-13 ) and European Commission projects CRONOS (Grant number 280879...
10.1088/1367-2630/15/12/125005
article
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2,013
false
false
true
false
Materials Science
https://openalex.org/fields/25
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e. , they both reentered the cell cycle and formed microcolonies) and because CATMA microarrays are based on the Col-0 genome, we performed our transcript analyses using Col-0 material. Massive (8984) transcriptomic changes took place during the first week of protoplast culture, corresponding to 5276 different genes be...
10.1105/tpc.113.109538
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Agricultural and Biological Sciences
https://openalex.org/fields/11
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27 and 3. 23 normed frequencies, respectively) and in genes encoding plastid components (4. 23 normed frequency). The Pliv/Pls transcript profile comparison reflected adaptations of the photosynthetic apparatus, cell walls, and chromatin composition in plantlets cultured in vitro. Among the downregulated genes, we iden...
10.1105/tpc.113.109538
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Agricultural and Biological Sciences
https://openalex.org/fields/11
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The GLK2 TF, which coordinates photosynthesis; HEMA1, the glutamyl-tRNA reductase gene involved in tetrapyrrole synthesis; and genes that regulate the stability of chloroplastencoded transcripts (HCF152 and 173) were downregulated in protoplasts (see Supplemental Data Set 1 online). However, chloroplast degradation was...
10.1105/tpc.113.109538
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Agricultural and Biological Sciences
https://openalex.org/fields/11
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Further investigation of the expression of ribosome transacting factors, such as SWA1 (Shi et al. , 2005) (absent from the CATMA microarray), that regulate division would facilitate the characterization of RP regulation in our system. Regulation of protein translation also modulates the protein content of a cell duri...
10.1105/tpc.113.109538
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Agricultural and Biological Sciences
https://openalex.org/fields/11
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Cell Wall Reestablishment during the First Week of Culture Cell wall reorganization is essential for protoplast survival and adaptation to the external medium. This complex process is regulated by numerous enzymes and relies on interactions with the cytoskeleton, which determines microfibril orientation (Szymanski and...
10.1105/tpc.113.109538
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Agricultural and Biological Sciences
https://openalex.org/fields/11
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Progression of Transcriptional Control Based on knowledge of the role of TFs in animal stem cells (Takahashi and Yamanaka, 2006) , we analyzed TF expression in the protoplast cultures. We extracted lists of TFs and their family annotations from previous reviews (Mitsuda and Ohme-Takagi, 2009; Lu et al. , 2012). Of th...
10.1105/tpc.113.109538
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Agricultural and Biological Sciences
https://openalex.org/fields/11
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RNA Extraction and Microarray Data RNAs from 3-week-old seedlings, protoplasts, and PdCs after 24, 48, 96, and 168 h of culture were extracted using the RNAeasy mini kit (Qiagen). RNA integrity was tested with an Agilent Bioanalyzer. For each biological replicate, 4. 5 3 10 7 protoplasts were isolated: 10 7 of freshly ...
10.1105/tpc.113.109538
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Agricultural and Biological Sciences
https://openalex.org/fields/11
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, 2008) (see Supplemental Methods 1 online). After statistical validation, variations in transcript abundance were expressed as the log 2 of the ratio of hybridization intensities between biological materials and/or successive steps. The microarray data sets were deposited into the Gene Expression Omnibus (http://www....
10.1105/tpc.113.109538
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Agricultural and Biological Sciences
https://openalex.org/fields/11
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Transcriptome Analysis Supplemental Data Set 1 online lists the 8206 genes differentially expressed in at least one of the nine conditions tested in our experimental design. The various publicly available data sets used in this study, such as the chromatin-related genes (ChromDB; http://chromdb. org/), the lists of TFs...
10.1105/tpc.113.109538
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Agricultural and Biological Sciences
https://openalex.org/fields/11
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ACKNOWLEDGMENTS This work was supported by the Institut National de la Recherche Agronomique, France. We thank John Celenza for afl4-1 seeds, Hervé Vaucheret for ago4-4 seeds and fruitful discussions, and all technicians in charge of the Institut Jean-Pierre Bourgin greenhouses , with special mention to Bruno Le...
10.1105/tpc.113.109538
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Agricultural and Biological Sciences
https://openalex.org/fields/11
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ACKNOWLEDGMENTS This work was supported by the Institut National de la Recherche Agronomique, France. We thank John Celenza for afl4-1 seeds, Hervé Vaucheret for ago4-4 seeds and fruitful discussions, and all technicians in charge of the Institut Jean-Pierre Bourgin greenhouses , with special mention to Bruno Le...
10.1105/tpc.113.109538
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Agricultural and Biological Sciences
https://openalex.org/fields/11
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Genomic selection (GS) offers breeders the possibility of using historic data and unbalanced breeding trials to form training populations for predicting the performance of new lines. However, when using datasets that are unbalanced over time and space, there is increasing exposure to different genotype environment comb...
10.1016/j.fcr.2013.07.020
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Biochemistry, Genetics and Molecular Biology
https://openalex.org/fields/13
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Using the International Center for Maize and Wheat Improvement's (CIMMYT) Semi-Arid Wheat Yield Trials (SAWYT) we assessed the accuracy of genomic predictions and the potential to subset these nurseries using the concept of mega-environments (ME) adapted to a genomic selection context. We found that there was no differ...
10.1016/j.fcr.2013.07.020
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Biochemistry, Genetics and Molecular Biology
https://openalex.org/fields/13
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Potential of genomic data to improve the utility of unbalanced historical datasets The ubiquity of unbalanced historic datasets in plant breeding programs is a longstanding challenge. Breeding lines are selected and promising lines are advanced to a point where enough seed is available for multi-locational trials of ca...
10.1016/j.fcr.2013.07.020
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Biochemistry, Genetics and Molecular Biology
https://openalex.org/fields/13
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, 2011; Poland and Rife, 2012). Software and database tools have become available that make it possible to keep track of phenotypic, genotypic and pedigree records for thousand of individuals over many years. Because of improvements in genotyping and statistical methods that can handle this type of data, genomic select...
10.1016/j.fcr.2013.07.020
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Biochemistry, Genetics and Molecular Biology
https://openalex.org/fields/13
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National breeding programs could greatly benefit from using data from other programs with similar environmental conditions, combined with their own historical data and the international center data, in order to increase their power to detect superior lines for their target environments. The objective of this study was ...
10.1016/j.fcr.2013.07.020
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Biochemistry, Genetics and Molecular Biology
https://openalex.org/fields/13
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Genotypic data The wheat genotypes included in SAWYT 1-17, indexed by their genotypic identification number (GID), were characterized using genotyping-by-sequencing following the same procedure as described in Poland et al. (2012). A total of 45,818 SNP markers were obtained, and 34,843 were retained with a maximum of...
10.1016/j.fcr.2013.07.020
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Biochemistry, Genetics and Molecular Biology
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Data curation Phenotypic data for the SAWYT was obtained from the CIMMYT bioinformatics unit after initial data cleaning to remove outliers. Yield was the most complete trait; out of a total of 723 trials in the dataset, yield was measured in 611 individual trials and 237 unique locations over 17 years (planted in yea...
10.1016/j.fcr.2013.07.020
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Biochemistry, Genetics and Molecular Biology
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Two criteria were used to identify and eliminate trials with errors in matching genotypes and phenotypes. The ratio V a /(V a + V e ), the proportion of variance due to additive genetic effects, was used to eliminate trials where genotypes did not match phenotypic data. Trials with this ratio less than 0. 01 were consi...
10.1016/j.fcr.2013.07.020
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Biochemistry, Genetics and Molecular Biology
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This ratio is referred to as the repeatability or broad-sense heritability, the proportion of variance due to all genetic variance effects, calculated with variance components assuming independent genotypes. This step was used only to eliminate trials that must have had errors in data reporting, and thus near-zero valu...
10.1016/j.fcr.2013.07.020
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Biochemistry, Genetics and Molecular Biology
https://openalex.org/fields/13
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Clustering methods for grouping similar locations Because global genomic predictions may not be the most relevant to individual breeding programs in particular environments, several methods were used to attempt to group locations into similar environmental clusters to improve the accuracy of genomic predictions within ...
10.1016/j.fcr.2013.07.020
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Biochemistry, Genetics and Molecular Biology
https://openalex.org/fields/13
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ME 3, with acidic soil, was only present in two years at one location in the SAWYT dataset and so was eliminated. The remaining ME were represented in at least 16 of the 17 years. ME 2/4, alternating high and low rainfall, was considered to be part of ME 2 to balance the ME representation across years, and the subsets ...
10.1016/j.fcr.2013.07.020
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Biochemistry, Genetics and Molecular Biology
https://openalex.org/fields/13
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Because of the unbalanced nature of the SAWYT dataset, typical clustering analyses could not be used with individual locations, as neither locations nor genotypes were balanced over years. Cluster analysis requires a complete distance matrix calculated from genotypic performance among the locations to be clustered, whi...
10.1016/j.fcr.2013.07.020
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Biochemistry, Genetics and Molecular Biology
https://openalex.org/fields/13
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Details of these clustering methods are presented in Appendix. Ward's hierarchical clustering method and the complete linkage method were implemented with the function hclust and the K means method was implemented with the function kmeans in the R package stats (R Development Core Team, 2012). Model based clustering wa...
10.1016/j.fcr.2013.07.020
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Biochemistry, Genetics and Molecular Biology
https://openalex.org/fields/13
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BLUPs based on yield phenotypes in the validation dataset were used to calculate the accuracy of genomic predictions. Details on calculation of validation yield estimates are in Appendix A. GS accuracies are reported as the correlation between the genomic prediction and the validation values, corrected by the average s...
10.1016/j.fcr.2013.07.020
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Biochemistry, Genetics and Molecular Biology
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, 2012). The dataset was divided at random into 16 equal sets, or folds, and the model was developed using 15 of these golds and validated on the 16th. This was repeated 16 times so that each fold was used for validation once. We also evaluated the accuracy of global and environmentspecific predictions for the CIMMYT M...
10.1016/j.fcr.2013.07.020
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Biochemistry, Genetics and Molecular Biology
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Data-driven clustering using all four methods was done separately for each training dataset before models were fit. 1) global (GL): makes one genomic prediction over all clusters for each genotype: yield = block(rep) + rep(trial) + trial + cluster + loc(cluster) + GID + error 2) interaction (IN): fits a main effect of ...
10.1016/j.fcr.2013.07.020
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Biochemistry, Genetics and Molecular Biology
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For each validation year, all years up to but not including the validation year were used as the training dataset. Locations in the validation dataset were matched to locations in the training dataset for assignment to clusters. ASReml (Butler, 2009) was used to make genomic predictions for each genotype using all ye...
10.1016/j.fcr.2013.07.020
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Biochemistry, Genetics and Molecular Biology
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Simulation of multi-environment trial data Because of the high level of unbalance in the SAWYT dataset and the low ratio of genetic to environmental variance, the effectiveness of dividing the data into target clusters in the SAWYT may not be representative of other breeding programs across multiple target environments...
10.1016/j.fcr.2013.07.020
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Biochemistry, Genetics and Molecular Biology
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Every prediction was based on 80% of the lines, corresponding to four years of simulated data, and validated using simulated true breeding values from the remaining year. All five years were used for validation, so for every combination of parameters in the simulation there were five validation experiments and 50 repli...
10.1016/j.fcr.2013.07.020
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Biochemistry, Genetics and Molecular Biology
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Clustering of similar locations Clustering based on the correlation of genomic predictions across locations grouped different locations together and did not correlate with the CIMMYT ME. A year by year analysis of the SAYWT data showed that the interaction between genotype and ME or cluster component of variance was al...
10.1016/j.fcr.2013.07.020
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Biochemistry, Genetics and Molecular Biology
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3 ). Correlations between the ME-specific yield estimates and the global yield estimates were fairly high for the 6 validation years (Table 3 ), other than ME 6 in 2006, which was unusually low. ME4 has the highest number of locations and trials in the dataset, which contributes to its high correlation to the global y...
10.1016/j.fcr.2013.07.020
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Biochemistry, Genetics and Molecular Biology
https://openalex.org/fields/13