dataesr/scientific-paragraphs-categorization huggingface dataset:
Acknowledgements The authors thank the patients of the  Centre de santé Elizabeth Diouf ,  Ndeye Fatou Diop  and  Maurice Gomis  from the  Hôpital Principal de Dakar ,  Marie-Louise Senghor ,  Fatou Bintou Badji ,  Joseph Faye  and  Baba Diakhaby  from  Institut Pasteur de Dakar  and  Thiaba Sene Ndour  and  Fatou Seck  from the  Centre de Santé Elizabeth Diouf  for technical support. This work was supported by the  Etat Major des Armées Françaises  (grant schéma directeur paludisme LR 607).
In our experimental model the inhibition of cdc2 in LCLs by the chemical inhibitor roscovitine slightly affected DNp73a levels (data not shown). JNK-1 could also induce DNp73 transcription by an alternative mechanism via activation of the proto-oncogene c-Jun. It has been shown that p73 acts in synergistic manner with c-Jun in promoting Figure  5. JNK-1 is involved in LMP-1-mediated activation of DNp73a expression. (A) BJAB cells were transfected with JNK-1 expression vector or empty pcDNA3 construct as control. After 36 hours cells were collected and processed for RNA extraction. The levels of DNp73, JNK-1 and GAPDH transcripts were determined by quantitative RT-PCR. The data are the mean of three independent experiments. The difference of DNp73a mRNA levels in mock cells (BJAB) and BJAB expressing JNK-1 is statistically significant (p value = 0.
022). (B) LCLs were treated with JNK-1 inhibitor (SP600125) at 20 mM. After the indicated times cells were collected and processed for RNA extraction. DNp73 mRNA levels were determined by quantitative RT-PCR. The data are the mean of three independent experiments. The difference of DNp73a mRNA levels in LCLs cultured in presence (7 hours) or absence (DMSO) of JNK-1 inhibitor is statistically significant ((p value = 0. 015). (C and D) Scrambled siRNA and siRNA for JNK-1 (siJNK-1) was transfected in LCLs. Thirty-six hours after transfection, cells were collected and processed for RNA or total cells proteins extraction. (C) DNp73 and JNK-1 transcript levels were determined by quantitative RT-PCR. The data are the mean of three independent experiments. The difference of JNK-1 or DNp73a mRNA levels in LCLs transfected with scramble siRNA or siJNK-1 is statistically significant (p value = 0.
008 and p value = 0. 0002, respectively). (D) Forty mg of whole cell lysate was analyzed by immunoblotting for the levels of DNp73a, JNK-1 or b-actin proteins (left panel). DNp73a and JNK-1 protein signal was quantified by Quantity one (Biorad), normalized on the levels of b-actin, and the values obtained were reported in the histogram (right panel). The data are the mean of three independent experiments. The difference of DNp73a mRNA levels in LCLs transfected with scramble siRNA or siJNK-1 is statistically significant (p value = 0. 01). (E and F) SaOS-2 cells were transfected with different pcDNA3 constructs in the indicated combinations. After 36 hours, cells were collected and fixed for ChIP experiments performed with a HA antibody and followed by quatitative PCR (E) or analysed by immunoblot for the indicated proteins (F).
It is worth noting that we found PLK2 gene strongly upregulated upon inhibition of DNp73a in LCL. It is well known that PLK2 promoter is positively regulated by p53. Thus, it is highly likely that DNp73a induces PLK2 down-regulation by altering the p53 transcriptional function. For the first time, our data provide evidence for a link between PLK2 expression silencing and DNp73a in EBV-infected cells. Our findings also suggest that Figure  6. EBV infection of B cells determines epigenetic changes on the p2 promoter. (A and B). Primary B cells were infected and immortalized with EBV (LCL). At the day of the extraction and 2-weeks post infection, primary and immortalized B cell respectively, were fixed and processed for quantitative ChIP analysis. (A) ChIP was carried out using EZH2, Histone 3 Trimethylated Lysine 27 (H3K27), Histone 3 acetylated Lysine 9 (H3K9Ac) antibodies and IgG antibody as negative control.
01 for H3K27Met, p value = 0. 002 for H3K9Ac). (C) Primary B cells or primary B cells infected with wild-type EBV (EBV) or EBV lacking the entire LMP-1 gene (EBVDLMP-1) were fixed and processed for EZH2 ChIP by using the LowCell ChIP Kit (Diogenode). Quantitative ChIP analysis was performed according to the manufacturers' protocol. The data are the mean of two independent experiments. The difference between the % of EZH2 binding to p2 in primary and LCL is significant (p value = 0. 01). (D) RPMI-pLXSN (pLXSN) and RPMI-pLXSN-LMP-1 (LMP-1), RPMI EBV and RPMI EBVDLMP-1 were fixed and processed for ChIP for EZH2 as described in figure  6C. The difference in the levels of EZH2 recruited to DNp73a promoter in the different conditions is significant (pLXSN vesus LMP-1 p value = 0. 038, EBVDLMP-1 versus EBV p value = 0.
The data are the mean of three independent experiments. The difference in the percentage of H4Ac or p73 binding to DNp73a promoter in the different conditions is significant (DMSO versus JNK-1 inhibitor p value = 0. 004 for H4Ac and p value = 0. 001 for p73). (G) Primary B cells and EBV-positive B cells were analyzed by immunoblotting for the levels of the indicated proteins. (H) Forty mg of total extract from RPMI-EBVDLMP-1 pLXSN and pLXSN-LMP-1 cells were analyzed by immunoblotting for the levels of the indicated proteins. (I) Nuclear and cytoplasmic fractions from RPMI-EBVDLMP-1 pLXSN and pLXSN-LMP-1 were analyzed by immunoblotting for the levels of LMP-1, EZH2, b-actin and PARP. (J) Cellular localization of EZH2 was determined by immunofluorescent in Primary B cells and LCLs. Fluorescent signal was visualized using Axioplan2 microscope from Zeiss laser microscopy.
RNA seq data analysis The secondary and tertiary analyses was done with LifeScope software v. 2. 5. 1 from Life Technologies (Build ID:LifeScope-v2. 5. 1-r0_102906_20120406100430) The raw data (xsq files) from each lane were grouped per sample (based on the barcodes) before launching the standard RNA seq workflow on the 3 samples (EBV_sense, EBV_antisens1, EBV_antisens2). We kept all the standard parameters as advised by Life Technologies. This workflow includes 3 modules: the ''mapping analysis'' for which we used hg19 as reference genome, the ''coverage analysis'' and the ''count known genes and exons analysis''. After reads mapping, the R/Bioconductor package edgeR (empirical analysis of digital gene expression data in R) was used to study differential gene expression  [72]. After fitting a negative binomial model, data obtained from antisense samples were grouped before applying the ''common dispersion'' function in edgeR.
Safety data on ustekinumab Safety data concerning ustekinumab came from Phase II and III studies in the different chronic IMDs. 11, 28 All trials were designed to have a placebo-controlled phase, but some were followed by long-term therapy through 5 years (PHOENIX 1). 21 The safety of ustekinumab has thus been evaluated in more than 3000 patients overall. Safety findings were largely documented in patients with moderate to severe psoriasis and available through week 36 (Phase II trial),  20  week 52 (PHOENIX 2),  22  week 64 (ACCEPT),  23  and week 76 (PHOENIX 1). 21 In patients with PsA, CD, or MS, safety findings were limited to follow-up periods ranging from 12 to 37 weeks. 25, 31, 32 During the placebo-controlled period in the psoriasis trials, adverse events were reported in 50. 4% of patients in the placebo group and between 51.
Parasite quantitation and statistical analysis To qualitatively and quantitatively assess the permissiveness of A. funestus to P. berghei, intact mosquitoes and dissected mosquito tissues were examined at 7 days post-feeding to assay midgut stages of infection and at 18-20 days post-feeding to assay sporozoite migration and salivary gland invasion. Oocyst infection prevalence is defined as the percentage of mosquitoes that become infected with oocysts, and oocyst intensity is the mean and median number of oocysts in the midguts of infected mosquitoes  [24]. The data presented in this study represent the results from two independent field collections and laboratory experiments. For comparison, parallel infections were carried out by feeding mosquitoes of the sympatric species, A. gambiae (G3 colony) on the same P.
Cell imaging Visual observations were done under bright field illumination, differential-interference-contrast (DIC), and GFP epi-fluorescence using a Nikon Eclipse E600 upright microscope connected to a CoolSNAPES digital camera (Photometrics, Tucson, AZ). Digital images were taken using MetaVue Imaging Software (Universal Imaging Corporation, Downingtown, PA), bright field images HiGauss filtered using Image-Pro Plus (Media Cybernetics, Silver Spring, MD), and histogram stretches, stitching, and overlays done using Adobe Photoshop (Adobe Systems, San Jose, CA).
ACKNOWLEDGEMENT We are sincerely grateful to Dr Albert Deisseroth and Professor Farzin Farzaneh for their valuable input to the construction of this manuscript. Dr. Rossi's NIH grant should have been acknowledged in both papers: NIH R01 HL074704. (A) Liver tumour nodules were visibly reduced in C/EBPα-saRNA injected rats when compared to both PBS control and Scramble-saRNA control groups. (B) Tumour burden was assessed by the volume of all tumour nodules with a diameter in excess of 3 mm. C/ EBPα-saRNA injected rats had significantly reduced tumour burden after two weeks of treatment when compared to both control groups. Data represents mean ± SD. (C) 2 µm liver sections from PBS control, scramble-saRNA-dendrimer control and C/EBPα-saRNAdendrimer injected rats were immunostained for expression of placenta-form glutathione-Stransferase (GST-p).
Non adherent cells were removed by 4 washes. Adherent monocytes were incubated in RPMI medium with 10% FCS, glutamine, and antibiotics in the presence of 10 ng/ml rhM-CSF (10 ng/ml) to differentiate to macrophages, as previously described  [41]. The relative concentration of rhM-CSF improve cell viability and maintained a neutral environment with respect to activation marker quantitative expression (HLA-DR, CD14, CD16), which remained similar to that of MDM cultured in medium alone  [41]. Half of the medium, including all supplements, was replaced every 3 days. After 7 days of culture, adherent cells corresponding to the macrophages-enriched fraction were harvested, washed, and used for subsequent experiments  [41, 42]. At the time of collection, MDM were more than 90% pure, expressing by flow cytometry analysis (CellQuest software, Becton Dickinson) CD4 + , CXCR4 low , CCR5 high+ , CD14 (73%) and CD11b (70%) (data not shown).
The HT-29 human colorectal epithelial cells line was provided by the AmericanType Culture Collection (ATCC HTB-38, Manassas, VA, USA). Cells were grown in RPMI 1640 medium complemented with 10% FCS, penicillin (100 IU/ml) and streptomycin (100 mg/ml). The HT-29 cells were CD4 2 , DC-SIGN 2 , CXCR4 high+ , CCR5 low+ and GalCer high+ (data not shown).
Statistical Analysis Levels of immunoglobulins, Lf, HIV-specific antibody SA, and RRE were expressed as mean6standard error. Functional tests were expressed as percentage 6 standard error. The nonparametric Mann-Whitney U test was used for statistical analyses, using GraphPad Prism 5. 0 (San Diego, California, US) statistical software. A P-value ,0. 05 was considered as significant.
Functional Activities Against HIV-1 of Immunoglobulins Purified from Pooled Stools Samples of Children Breastfed by HIV-1-infected Milk Two pools of stools samples from children of group I and from group II were constituted, in order to be subjected to immunoaffinity purification of total immunoglobulins. Resulting purified pooled stools immunoglobulins contained F(ab')2 to gp160 (data not shown), showed similar SA [F(ab')2 to gp160 purified from pooled stools of group I, 2. 660. 6 AU/mg, and of group II, 3. 261. 0 AU/mg; P. 0. 05)], and were used for further functional experiments. The capability of purified pooled stools immunoglobulins to inhibit the attachment of HIV-1 on HT29 cells and on MDM was first evaluated. As shown in Figure  3A , pooled stools immunoglobulins(30 mg/ml) purified from group I and group II inhibited the attachment of HIV-1NDKon HT29 cells by 58.
Acknowledgments We are grateful to all the women and their children who consented participating in the study. We also thank the staff of the maternity clinics of Castors,  Boy-Rabe ,  Begoua and Hopital Communautaire in Bangui , where the study was conducted and the staff of the  Complexe Pediatrique of Bangui. We are also very thankful to  Dr. Antoinette Gody ,  Ministry of Public Health, Bangui, as well as Pulcherie Pelembi  and  Julienne Ipero  from the  Laboratoire des Retrovirus, Institut Pasteur de Bangui , for their precious contributions. Finally, we are particularly grateful to the association  ARI, Paris, France ,  Dr Hakim Hocini ,  Vaccine Research Institute, Creteil, France , and  Mary Requena ,  INSERM, UMR1043, Toulouse, France , for their contributions.
The staining was analyzed using a Leica SP5 confocal microscope. To perform the bioplex to detect the phosphorylated signaling proteins, 3 ϫ 10 6 NK cells per test were cultured in culture tubes for 30 min or 1 h in the presence or absence of the IL-15, IL-18, IL-15/IL-18 (10 ng/ml), and/or CpG-ODN (1 M). Cells were then resuspended and homogenized in 50 l of radioimmune precipitation assay buffer. Cell lysates were kept at Ϫ80 °C until analysis. NK cell surface antigens were labeled in staining buffer (PBS, 2 mM EDTA, and 0. 5% FCS) with antibodies at the concentration suggested by the manufacturers. Intracellular staining was performed after fixation and permeabilization of the cells using the Inside Stain kit (Myltenyi Biotec), according to the manufacturer's instructions. All flow cytometry data were acquired and analyzed on a MACSQuant flow cytometer (Myltenyi Biotec).
Study Sites and Sampling We studied 16 populations of house sparrow in France along a gradient of urbanization (Fig. 1 , Table  1 ). Habitat characteristics were obtained from the CORINE (Coordination of information on the environment) Land Cover database using the geographical information system package ArcView 3. 2  (ESRI 2000). This is a European geo-referenced land-cover database, based on satellite digital images, that allows classifying landscape units, according to a list of environmental classes  [39]. It provides consistent localized geographical information on the land cover of 12 Member States of the European Union. We used the data for year 2000 (http:// www. eea. europa. eu/themes/landuse/interactive/clc-download). All the details about the program and the complete methodology can be found in the following internet site: http://www.
We used the package lme4  [45] , implemented in R 2. 15. 0 to run all LMMs. We used the information-theoretic (IT) approach as it has recently been suggested as being more appropriate for observational studies  [46]. Model support was assessed using the corrected version of Akaike Information Criterion (AICc) for small sample sizes, and DAIC was used to infer support for models in the candidate set  [47]. We calculated the Akaike weights (v) for each model, which is the probability that a model is selected as the best model in a model set  [46]. We deemed that there was essentially no evidence in support to a model when its DAIC value was greater than 10  [46]. It is also worth noting that when a fitted parameter was added to a model, a penalty of 2 is added to the model's AIC value  [46].
Acknowledgments We thank all the volunteers from the  National Museum of Natural History of Paris  for their help on the field and for providing samples:  F. Baroteau ,  J. Besnault J. Birard ,  L. Brucy ,  P. Bulens ,  P. Cannesson ,  G. Chaussi ,  P. Fiquet ,  C. Girard ,  D. Lavogiez ,  J. Marion ,  F. Martayan ,  G. Massez ,  P. Ollivier ,  V. Ternois , and  M. Zucca. We are grateful to  David Bru  for his assistance with the quantitative PCR analyses and to  Nadia Crini ,  Simon Belle  and for their help in metal analyses. We thank also  Anne Besson  and  Bruno Faivre  for their comments, and  Isabelle Leviol  for her help with GIS analyses.
Multi locus sequence typing The seven target loci as well as the PCR and sequencing protocols are listed in Additional file 2. The sequences were assembled using Phred/Phrap/Consed  [30] , verified manually to ensure high quality, and deposited in Genbank (GenBank:KC203886-KC204683). In keeping with MLST standards  [31, 32] , arbitrary numbers served for unambiguous identification of the AT (particular alleles at particular loci) and ST (unique combinations of AT at the seven loci). To facilitate large scale studies the following changes were made compared to the initial study  [17] : PCR amplification was performed with an optimized touchdown protocol; 5' extensions were added to the PCR primers to allow sequencing of the 7 loci with the same pair of primers; and AT attribution was based on slightly shortened sequences.
The data, including the genotypes from  [17, 26] , are made available in a new version of the F. psychrophilum MLST database  [33]  which uses the BIGSdb system  [34]. A tree depicting AT-sharing between ST was built by hierarchical clustering with R; the function "hclust" using the single link aggregation method and drawn with the R package "ape". The eBURSTv3 software with default settings  [35]  was used to obtain a "population snapshot" highlighting the relationships between closely related ST. Clonal complexes (CC) were defined using the criterion of single locus variant (SLV) connections between ST. Analyses of nucleotide diversity, including analysis of molecular variance  [36] , were coded in R. Nucleotide diversity was computed on pairwise comparisons between unique ST rather than between isolates to minimize the impact of sampling biases; as a consequence, the values were slightly higher than those initially reported in Nicolas et al.
However, at least two other factors may contribute to this difference: a temporal evolution of relative frequencies, since most isolates sampled at the country level were collected years before the sampling of the model river; and the fish sampling strategy, since sampling in the model river was performed irrespectively of disease symptoms and CC-ST52 seems less virulent  [14]. Seven ST (ST59, ST60, ST61, ST62, ST63, ST64, and ST66) not connected to those found in ayu were retrieved from river water, a case of caddisfly, and several local fish. These strains were isolated in November 2005, November 2006 and December 2006, when ayu are absent from the river due to their one-year life cycle ending after spawning in the autumn. Six of these strains (no data available on ST66) showed no pathogenicity against ayu  [14].
Acknowledgements We are grateful to the organizations listed in Additional file 1 for providing F. psychrophilum strains. We also wish to thank  Dr K. Sugahara ,  J. Ikeda , and  A. Fukuda  for help with field sampling and technical assistance and  Dr Keith Jolley  at  University of Oxford  for hosting the F. psychrophilum MLST database. This work received the support of a  Grant-in-Aid for Young Scientists, KAKENHI (B)  ( 18780153 ) and a  Grant-in-Aid  from the  Global Center of Excellence (COE) Program, Japan. EFN was also supported by  Research Fellowships  from the  Japan Society for the Promotion of Science for Young Scientists  and PN, CCD, JFB and ED by  ANR  ( ANR-07-GMGE-004  Flavophylogenomics) and  EU EMIDA ERA-NET  ( ANR 2010-EMID-006-01 Pathofish ).
Production of recombinant viruses The production of vesicular stomatitis virus (VSV)-pseudotyped pNL4-3-based recombinant viruses that contain a deletion in env, that express Renilla luciferase in place of Nef, and whose Gag-PR sequences were derived from clinical isolates (NRC2, NRC3, NRC10) or from NL4-3 has been described previously  [16, 34]. The recombinant NL4-3-based provirus carrying the RT sequence from a clinical isolate BV34 (accession number JQ994264), which contains numerous mutations associated with resistance to both nucleoside and non-nucleoside RT inhibitors, has been previously described  [35]. To transfer this RT sequence to a luciferaseexpressing provirus, this plasmid was digested with ClaI and SnaBI, and the fragment was ligated into pNL4-3-DENV-lucR-XC  [34]  cleaved with the same enzymes.
T cell repertoire diversity and clonotype follow-up in vaccination, cancer, infectious and immune diseases represent a major challenge owing to the enormous complexity of the data generated. Here we describe a next generation methodology, which combines 5 0 RACE PCR, 454 sequencing and, for analysis, IMGT, the international ImMunoGeneTics information system (IMGT), IMGT/HighV-QUEST web portal and IMGT-ONTOLOGY concepts. The approach is validated in a human case study of T cell receptor beta (TRB) repertoire, by chronologically tracking the effects of influenza vaccination on conventional and regulatory T cell subpopulations. The IMGT/HighV-QUEST paradigm defines standards for genotype/ haplotype analysis and characterization of IMGT clonotypes for clonal diversity and expression and achieves a degree of resolution for next generation sequencing verifiable by the user at the sequence level, while providing a normalized reference immunoprofile for human TRB.
Results Workflow results. A model immune challenge was provided by vaccinating a healthy volunteer with a H1N1 influenza vaccine. Three T cell subpopulations ('CD4 À ' , 'CD4 þ ' and 'Treg'  [27] [28] [29] [30]  ) were isolated by flow cytometry, at four time points (baseline and days 3, 8 and 26 post vaccination) (Fig. 1a ). Twelve amplicon libraries of the corresponding TR trancripts were prepared using anchored 5 0 RACE PCR  12  and a TRBC gene-specific reverse primer  1, 31  (Supplementary Table  S1 ). Sequencing was performed using 454 technology, which is appropriate for 4400 nt long sequences. During the platform-specific data processing, 160,944 reads passed the 454 pipeline filter (the pass rate was 46. 73%), but 7,405 of these were later discarded owing to missing or incomplete barcodes.
S1 ). The nb of sequences of 'More than 1' for each '1 copy' assigned to an IMGT clonotype (AA) is finally included (795 sequences). Thus, by proceeding stepwise to assign sequences, the high quality and specific characterization of the 'IMGT clonotype (AA)' remain unaltered. For the first time, for NGS antigen receptor data analysis, our standardized approach allows a clear distinction and accurate evaluation between clonal diversity (nb of 'IMGT clonotypes (AA)') and clonal expression (nb of sequences assigned, unambiguously, to a given 'IMGT clonotype (AA)'). In our study, the 22,234 'IMGT clonotype (AA)' (clonal diversity) corresponded to 50,234 sequences (clonal expression), which represented 78. 2% of the filtered-in sequences (Supplementary Fig. S1 ). These assignments are clearly described and visualized in detail, so the user can check clonotypes, individually.
1b ). Sequencing and initial data processing. Sequencing was performed on a  1 4  PicoTiterPlate by the Australian Genome Research Facility using the 454 Genome Sequencer FLX (GSFLX) Titanium (Roche). Initial data processing was performed using the manufacturer's software, which included the removal of low quality and erroneous sequences as determined by the standard filters of the Roche amplicon signal-processing pipeline. Sequences were assigned to samples based on incorporated barcodes, and read orientation was determined by the presence or absence of the sequence corresponding to the TSO used in the SMARTer RACE. Sequence segments corresponding to the adapters, barcodes and TSO were removed during this process. Quality control was conducted by spiking the amplicon library using classical cloning and sequencing methods  7, 11.