dataesr/scientific-paragraphs-categorization huggingface dataset:
Acknowledgements This work was supported by the  French National Agency for Research (ANR)  under the Jugurta programme, directed by  Philippe Gervais-Lambony. I express my appreciation to  IFRA-Nairobi  and to its former Director Bernard Calas, who welcomed me during my field work. I am very grateful to  Hélène Charton  and  Sam Owuor  who invited me to the launching of their CORUS research programme (" Governance, informality and identity in Nairobi and Dar as Salaam "). I thank  Winnie Mitullah  and  Sam Owuor  from the  University of Nairobi  (who also participated in the Jugurta programme),  Lydia Muthuma ,  Anne Bousquet  and  Quentin Mercurol  who helped me to find my intellectual way around Nairobi. This paper owes a lot to the discussions I had with  Sophie Didier  and to our work on Cape Town.
DNA methylation levels were assessed by bisulfite sequencing for non-autonomous short interspersed element (SINEs) individual copies that have numerous p4-siRNAs matching their genomic sequence. No significant variation is obtained for SB2-2, SB3-35 and AtSN1 (SB4-8) SINE copies in the drb2 mutant (Additional file 2: Figures  S2e, f  and g ), while the nrpe1 mutation, included here as a control, clearly affects CHG and CHH methylation as well as CG methylation to some extent. We also investigated the possibility that the drb2 mutation results in changes in TE RNA levels. No reproducible change in RNA accumulation was observed for a diverse set of TEs in the drb2 background compared to the wild type situation (data not shown). We also generated drb2 x ddm1 lines, taking advantage of the ddm1 background, known to accumulate several TE transcripts  [54] [55] [56].
Similarly, a specific signal for DRB2-FlagHA is obtained after a GFP IP with both MSI4-eGFP and eGFP-MSI4 proteins, while no signal is observed when only DRB2-FlagHA is present in the crude extract (Figure  2c ). This interaction is also observed when both proteins are transiently expressed in Nicotiana benthamiana (Additional file 4: Figure  S4 ). However, using a similar IP protocol on extracts from plants co-expressing DRB2-FlagHA and MBD10-Cmyc, we were not able to confirm in planta the DRB2-MBD10 interaction suggested by the mass spectrometry data (not shown). To further characterize the complex formed by DRB2 and its partners, we performed gel filtration on the same Superose 6 column for all the epitope tagged interacting proteins. Consistent with an interaction with DRB2, PRMT4B-Cmyc, HDA19-GFP and MSI4-eGFP all elute in the same maximal fraction, around 2 MDa, as it is the Table summarizing the multiple proteins specifically found in the DRB2-CMyc purified extract.
Bands were then dried in a speed-vac at room temperature and destained in 7% hydrogen peroxide, washed in 100% acetonitrile and ultra-pure water. Resulting samples were trypsin digested and analysed using a nanoLC-MS/MS LTQ-Orbitrap XL (Thermo Fisher Scientific) in a 40 minutes run/sample. Raw data analysis was performed using MASCOT and further analysis was done using the 'compare to dataset' option of Galaxy (https://usegalaxy. org/) to remove unspecific hits that appeared in both the test and control sample. Each peptide was manually checked by BLASTp to obtain a final candidate list, with unique and unambiguous peptides.
Acknowledgments We thank  Thierry Lagrange ,  Dominique Pontier  and  Jacinthe Azévédo-Favory  for the  NERD-FlagHA ,  NRPD1-Flag ,  NRPE1 -Flag seed stocks, for her help in the crosslinking experiments and for critical reading of the manuscript. We thank  Pr. Jeffrey Chen  for the HDA19-GFP line and  Sabrina Jung Romero  for the eGFP-MSI4 and MSI4-eGFP constructs. This work was supported by the  CNRS , by the  Université de Perpignan (UPVD)  and by the  ANR   SVSE6 EpiRNase 000703  for CC salary.
ACKNOWLEDGMENTS We acknowledge support from the  European Research Council  under  ERC  Grants No. 637756   STARLIGHT , No. 227355  ELYCHE, and No. 290853 XCHEM, from  LASERLAB-EUROPE  (Grant Agreement No. 284464 ,  EC's Seventh Framework Programme ), from  European COST Action   CM1204 XLIC , the  MICINN  Project  FIS2013-42002-R , the  ERA- Chemistry  Project  PIM2010EEC-00751 , the European Grant MC-ITN CORINF. Calculations were performed at the  Centro de Computación of the Universidad Autónoma de Madrid (CC-UAM ) and the  Barcelona Supercomputing Center (BSC). G. S. acknowledges the Italian Ministry of Research Project FIRB No. RBID08CRXK. R. L. and M. H. acknowledge a  Marie Curie International Research Staff Exchange Scheme Fellowship  (Grant Agreement No. PIRSES-GA-2012-31754 ,  EC's Seventh Framework Programme ) and the  COST Action   CM1405  MOLIM.
Gene trees All gene families sequences were then aligned using Prank  [34]  and one gene tree per family was computed using PhyML (100 bootstraps, otherwise default parameters). Because we are aligning recently diverged strains of the same organisms  [35] , the sequences often have not Figure  2  Dotplot between the sequence of two extant strains of Yersinia pestis: CO92 and KM10. Both strains are descendants of the ancestor we focus on. Data was obtained by aligning the sequence of strain KIM10 on the sequence of strain CO92 using megablast (default parameters, only hits with a length >10 2. 5 were kept). diverged enough to allow an unambiguous tree reconstruction. So we collapsed all branches with a support lower than 99 and then used ProfileNJ  [36]  to solve the created polytomies. ProfileNJ reconstructs species tree branches instead of collapsed branches and chooses among several solutions with a Neighbor-Joining formula.
Distances for the Neighbor-Joining part were computed with bppdist, a Bio++ suite software  [37]  (GTR + Γ(4) model). ProfileNJ also roots the gene trees according to "Last Common Ancestor" reconciliation method, annotating internal nodes with duplications or speciations, and choosing a root minimizing the number of duplications. Reconciled gene trees depict the history of the gene family, including all ancestral genes, uniquely defined by the reconciliation. This step corresponds to part C in Figure  3.
Both strains are descendants of the ancestor we focus on. Data was obtained using the extant adjacency graphs of strains KIM10 and CO92 and concerns genes order. Vertical and horizontal lines separate the different molecules (here the chromosome and the plasmids). A) dotplot between the gene orders of the two extant strains KIM10 and CO92. B) dotplot between the gene orders of the ancestral genome and the extant strain CO92. C) dotplot between the gene orders of the ancestral genome and the extant strain KIM10. outgroup species) sequences bear the same allele and thus the reconstructed ancestral sequence bears it too. However, the ancient contig bears another allele at that position. If we consider the ancient contig as correct, then this difference would be an original mutation on the ancient strain.
Acknowledgements This work is funded by the  Agence Nationale pour la Recherche ,  Ancestrome  project  ANR-10-BINF-01-01. Publication charges for this work were funded by the  Agence Nationale pour la Recherche ,  Ancestrome  project  ANR-10-BINF-01-01. This article has been published as part of  BMC Genomics Volume 16 Supplement 10 , 2015: Proceedings of the 13th Annual Research in  Computational Molecular Biology (RECOMB) Satellite Workshop on Comparative Genomics: Genomics. The full contents of the supplement are available online at http://www. biomedcentral. com/bmcgenomics/supplements/ 16/S10.
6% of the collection (24/1475). Subsequently, to distinguish possible additive effects from more specific interactions, all selected UYi lines were crossed with vg-GAL4. Only wild type wing phenotypes were observed, ruling out an additive effect of UYi and bax transgenes, and thus revealing the specificity of the genetic interactions between bax and the 24 insertions. To define if the wing phenotype suppression could be due to a gain of function (GOF) or a LOF, we identified the insertion point and orientation of each of the 24 insertions. PCR rescue experiments were performed and their products were sequenced. We compared the recovered sequence of the flanking genomic DNA to the Drosophila full-genome sequence database  [32]. We were unable to obtain unambiguous flanking sequence information for 7 isolated UYi lines, i.
Molecular characterization of UYi lines To characterize the genes identified by screening for bax-induced phenotype modifiers, the DNA flanking the P[Mae-UAS. 6. 11]  element was isolated by inverse polymerase chain reaction (PCR), essentially according to the Berkeley Drosophila Genome Project (BDGP) protocol (http://www. fruitfly. org/about/methods/inverse. pcr. html) and sequenced. The following primers were used in this study: 5'-GCAGTTGATTTACTTGGTTGCTGG-3', 5'-GGTAAGCTTCGGCTATCGAC-3', 5'-GCTTTCGCTTAGCGACGTGT-3', 5'-GCTTTCGCTTAGCGACGTG-3', 5'-GTATACTTCGGTAAGCTTCG-3', 5'-CTCTCAACAAGCAAACGTGC-3', 5'-ACACAACCTTTCCTCTCAACAA-3', 5'-GAATTGAATTGTCGCTCCGT-3', 5'-ATTGATTCACTTTAACTTGCAC-3'. Sequencing was performed by Genecust (Genopole, Evry, France). Sequences were submitted to BLAST search in the BDGP database to identify nearby genes.
ACKNOWLEDGEMENTS This work was supported in part by grants from the  Ligue Nationale Contre le Cancer (Comité des Yvelines). Jessie Colin ,  Cécile Milet  and  Amandine Clavier  held a support from the  Ministère de l'Enseignement Supérieur et de la Recherche. Jessie Colin ,  Julie Garibal ,  Cécile Milet  and  Amandine Clavier  were supported by the  Ecole Pratique des Hautes Etudes. We thank  Laurent Théodore ,  Helena Richardson  and the  Bloomington Drosophila stock center  for providing Drosophila strains. We thank  François Juge  and  Martine Simonelig  for precious information about the UY1131 strain and  Magali Lecourtois  for P[UY1615] localization.
MD simulation setup The initial apo hAgo2 conformation was taken from the crystal structure of hAgo2 in complex with miR-20a (PDB ID: 4F3T)  [32] , and the missing residues were added using MODELLER  [70] [71] [72] [73]. The apo hAgo2 protein was solvated in a dodecahedron box containing 42,847 SPC water molecules  [74]  with 129 Na + ions and 159 Cl -ions to neutralize the charge. All the MD simulations were performed using the GROMACS 4. 5. 4 package  [75]  and the Amber99S-B-ILDN force field  [76]. Long-range electrostatic interactions were treated with the Particle-Mesh Ewald method  [77]. Both short-range electrostatic interactions and van der Waals interactions used a cutoff of 10Å. All bonds were constrained by the LINCS algorithm  [78]. Velocity-rescaling thermostat  [79]  and the Parrinello-Rahman barostat  [80]  were used for temperature and pressure coupling respectively.
Next, we extracted ~170,000 conformations from the first two rounds of MD simulations and built an MSM containing 553 microstates that were further lumped into 9 macrostates. However, the 553-microstate MSM predicted kinetics inconsistent with the original MD simulations, indicating the necessity of additional sampling (see S13 Fig). We thus seeded the third round of MD simulations from conformations taken from each of the 9 macrostate in the initial MSM with the number proportional to their predicted equilibrium populations. In this round, we performed 30 150-ns MD simulations with a saving interval of 20ps. Combining MD simulations from all three rounds, we obtained a dataset containing over 394,000 conformations extracted from ~8μs MD simulations.
We also performed a cross validation of the MFPTs calculated from our MSM by evenly dividing the dataset into two non-overlapping sub-datasets. MFPTs predicted from MSMs built from these two subdatasets are in reasonable agreement with each other, and are also consistent with the MFPTs reported using the whole dataset (see S15 Fig). Protein-RNA docking with HADDOCK Protein-RNA docking simulations were performed with HADDOCK 2. 1  [62, 63]. Since the RNA binding groove is completely blocked or largely hindered by the PIWI loops in the closed or partially open hAgo2 conformations (see S4 Fig for representative conformations), these conformations are unlikely to allow the direct miRNA binding. Therefore, we selected hAgo2 conformations that are as open as possible (with PAZ-PIWI loops c. o. m.
distance > 25Å) and obtained 15 microstates. From each of these 15 microstates, we randomly selected 10 conformations for docking. The input miRNA structure was modeled using ModeRNA  [83]  based on miRNA fragments in the crystal structure (PDB ID: 4F3T). We defined both Ambiguous Interaction Restraints (AIR) and unambiguous distance restraints to drive the docking simulations. For AIR, the "active" protein residues were defined according to the hAgo2-miRNA interactions suggested by Elkayam et al. [32] : R179, S180, A221, T222, H271, K278, R280, F294, Y311, H316, R351, G524, K525, T526, Y529, K533, Q545, C546, Q548, N551, S561, K566, K570, D597, R635, D669, R710, Q757, R761, R792, S798, Y804, H807, and R812. All RNA nucleotides were set to be "active". We also imposed unambiguous distance restraints to guide the docking simulations (see S2 Table ).
Funding: XH acknowledges the support from  National Science Foundation of China  (no. 21273188 ),  Hong Kong Research Grants Council   ECS 60981 ,  AoE/M-09/12 , and  T13-607/12R. XG acknowledges the support from  King Abdullah University of Science and Technology (KAUST). The work is also supported by a grant from the  PROCORE-France/Hong Kong Joint Research Scheme  sponsored by the  Research Grants Council  funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Plasmids The plasmid expressing the full-length HCV core protein (pVax1-core ), corresponding to 1b genotype (GenBank: AF176573), was described previously  [29]. To generate the constructs encoding aa 1-36 and aa 37-191 truncated forms of HCV core, the respective fragments were amplified from the plasmid pVax1-core(1-191) using oligonucleotides core1-For (5 -TTTGGATCCGATATGAGCACGAATCCTAAACC-3 ), core36-Rev (5 -TTTGAATTCTTACAGGTAAACTCCACCGAC-3 ), core37-For (5 -TTTGGATCCGATATGTTGCCGCGCAGGGGC-3 ), and core191-Rev (5 -TTTGAATTCTTAAGCGGAAGCTGGGATG-3 ). The PCR products were cloned into BamHI and EcoRI sites of pVax1 vector (Invitrogen, Waltham, MA, USA). The structure of all plasmids was confirmed by sequencing.
Statistical Analysis Statistical analysis was performed with BioStat 2009 software (AnalystSoft, Vancouver, BC, Canada). All data are presented as mean ± SD. Differences between two groups were compared using two-tailed unpaired Student's t-test. For comparison between multiple groups, ANOVA followed with a Tukey-Kramer posttest applied. p values < 0. 05 were considered statistically significant if not stated otherwise. Viruses 2015, 7 2751 3. Results.
To assess this, Huh7 cells were transfected with the respective siRNA and a mixture of plasmids expressing core(1-191) and HyPer-cyto sensor; mean fold increase in HyPer-cyto fluorescence (E) and the % of fluorescent cells (F) was quantified by flow cytometry. Alternatively, Huh7 cells were transfected with the plasmid expressing core(1-191) and a mixture of respective siRNA; the induction of ROS was assessed by the DCFH assay (G). Fluorescence was expressed as a fold-increase compared to the fluorescence measured in mock-treated Huh7 cells transfected with the empty vector pVax1. For experimental details, see Materials and Methods. All data represent the means ± S. D. from triplicate measurements done in three independent experiments. * p < 0. 01; ** p < 0. 001.
To assess this, Huh7 cells were transfected with the respective siRNA and a mixture of plasmids expressing core and HyPer-cyto sensor; mean fold increase in HyPer-cyto fluorescence (E) and the % of fluorescent cells (F) was quantified by flow cytometry. Alternatively, Huh7 cells were transfected with the plasmid expressing core and a mixture of respective siRNA; the induction of ROS was assessed by the DCFH assay (G). Fluorescence was expressed as a fold-increase compared to the fluorescence measured in mock-treated Huh7 cells transfected with the empty vector pVax1. For experimental details, see Materials and Methods. All data represent the means ± S. D. from triplicate measurements done in three independent experiments. * p < 0. 01; ** p < 0. 001.
Huh7 cells transfected with the empty vector pVax1 or a plasmid encoding HCV NS5B served as negative controls. Fluorescence was expressed as a fold-increase compared to the fluorescence measured in mock-treated Huh7 cells transfected with the empty vector pVax1. For experimental details, see Materials and Methods. All data represent the means ± S. D. from triplicate measurements done in three independent experiments. * p < 0. 01; ** p < 0. 001. N. S. , not significant.
Acknowledgments The authors are grateful to  Prof. R. Bartenschlager  for his kind gift of Huh7 cells. They are also grateful to  Francesco Negro  and  Saleem Kamili  for thoughtful discussion and comments on the manuscript. This work was supported by  Skoltech University , the  Russian Foundation for Basic Research  ( 13-04-01837a ,  13-04-40307-H , and  13-04-01523a ), the  Program of the Presidium of the Russian Academy of Sciences  (" Molecular and Cellular Biology "), and the  Thematic Partnership Program of the Swedish Institute  (grant  09272/2013 ). Maria Isaguliants  was supported by  BALTINFECT  project contract nr 316275.
In both cases, one observes  13  C multiplets that do not obey the usual binomial 1:2:1 intensity distribution of  13  CH 2 groups. The proton and carbon-13 signals arise because cross-relaxation converts the invisible TSI into observable population differences across allowed transitions. The nonbinomial peak patterns have the same sign regardless if one saturates either the positive or negative lobes of the microwave DNP response. The enhancements ε are determined by comparison to Boltzmann's polarization in thermal equilibrium, as reported in Table  1. Simulations were carried out using the Mathematica package SpinDynamica. 25 The initial state consisted of a pure TSI, and the relaxation superoperator accounted for dipole-dipole (DD) interactions, the chemical shift anisotropies (CSAs) of both 1 H and  13  C, and DD/CSA cross-correlation effects.
This forms a continuous spectrum in which the diagnosis of especially atypical cases can be particularly difficult to establish. However, establishing an early diagnosis and thus initiating a specific immunotherapy treatment is a real challenge. In severe cases, the Cochrane Database recommends intravenous immunoglobulin. 25 In this case, the first course of immunoglobulin was only administrated on days 5 and 6, although it started before the electromyogram confirmation, which points to the difficulties met to find the diagnosis. The intravenous immunoglobulin treatment did not contribute to make significant improvements. Because of the severity of such atypical forms, and due to the guarded neurological prognosis in such cases, the authors decided to administer a second course 3 weeks later.
Statistics All data in bar graphs are means Ϯ SEMs. Sample sizes are indicated within each bar in all graphs. Data were analyzed using the Student's t test for comparisons between two groups, and one-way and two-way ANOVA followed by indicated post hoc tests for multiple analyses. P Յ 0. 05 was considered statistically significant. Analyses were performed using Excel 2011 (Microsoft) with add-in software and Prism version 6. 0 (GraphPad).
DNA sequencing of 40 nt-tags was performed on a Solexa genome analyzer GA-IIx or Hi-Seq using the procedures recommended by the manufacturer (Illumina). Input DNA and DNA from ChIP with an untagged strain were used as negative controls. Mediator ChIP-seq analysis was performed only for the Med15 subunit. Low ChIP signals were obtained for the Med8-HA subunit. High background levels in the ChIP-seq experiments for Med5-HA and Med6-HA subunits precluded accurate enrichment detection. It should be noted that Mediator enrichment levels in ChIP experiments are relatively low, depending on the Mediator subunit used, possibly due to the low efficiency of formaldehyde crosslinking and/or the dynamic association of Mediator to chromatin. The ChIP-seq data have been deposited to the Array Express under accession numbers E-MTAB-2961 for the mutant strains and E-MTAB-1595 for the wild-type (WT) strain.
d. × 15 cm, 2 m, 100 Å). Peptide separation was performed with a 5-35% solvent B gradient for 40 min. Solvent A was 0. 1% formic acid in water, and solvent B was 0. 1% formic acid in 100% acetonitrile. The nanoLC-MS/MS experiments were conducted using the data-dependent acquisition method by selecting the 20 most intense precursors for CID fragmentation with Q1 quadrupole set at low resolution for better sensitivity. Raw data were processed using MS Data Converter software (AB Sciex) for generating. mgf data files and protein identification was performed using the MASCOT search engine (Matrix science, London, UK) against the Swissprot database (release 2014 08) with carbamidomethylation of cysteines and oxidation of methionines set as fixed and variable modifications, respectively. Peptide and fragment tolerance were respectively set at 20 ppm and 0.
Data analysis ChIP-seq data were analyzed as described previously  (45). The sequences were aligned on the S. cerevisiae genome (UCSC version sacCer3) using Bowtie version 0. 12. 7  (49). Only uniquely mapped tags were used and a maximum of two mismatches was allowed. Conversions to different file formats were performed using Samtools version 0. 1. 16. To avoid possible sequencing artifacts, reads with the bestquality scores were conserved for each position. The number of mappable tags for each ChIP-seq experiment is indicated in Supplementary Table  S4. To calculate ChIP-seq density, reads were extended to an assumed fragment length of 150-180 nt, and a count of reads was determined per 1-bp bin using Bedtools version 2. 15. 0. ChIP-seq density profiles were displayed using the Integrated Genome Browser (IGB) yeast genome browser.
The normalization values for untagged strain sample before subtraction are indicated in Supplementary Table  S5. The significantly enriched regions were identified using peak calling MACS2 software version 2. 0. 10. 20120703 (50). To avoid possible sequencing artifacts, reads beyond five repetitions at the same position of the genome were removed. A minimum false discovery rate (q-value) cutoff peak detection of 0. 01 was used for Med15 and 0. 05 for Pol II, Rad3, Kin28 and TBP. This step was followed using the PeakSplitter step of PeakAnalyzer software for the subdivision of ChIP-seq regions into discrete peaks  (51). The significantly enriched regions were also identified in the control ChIP sample with an untagged strain using Bayespeak version 1. 10. 0 (52) with a threshold of 0. 9. Around 200 peaks were identified by this method in the control sample and they were used to correct peakcalling data from Med15, Rad3, Kin28 and TBP ChIP-seq.
GTFs, Mediator and Pol II significantly enriched peaks were annotated relative to the intergenic region or the ORF in which they were detected using BedTools version 2. 15. 0. The nomenclature used for the intergenic regions was as follows: tandem regions were named relative to the downstream-located gene, divergent and convergent regions were named relative to the two genes surrounding the region. To compare read counts in WT and med17 mutant ChIPseq data, a count of reads was determined on promoter regions of Pol II-transcribed genes for Rad3, Kin28, TBP and Med15, and on Pol II-transcribed gene ORFs for Pol II, using Bedtools. For ChIPseq data analysis, promoter regions were defined as corresponding intergenic regions on the yeast genome. For this step, all mapped reads were conserved to allow quantitative comparison between the different samples.