dataesr/scientific-paragraphs-categorization huggingface dataset:
Acknowledgements We are grateful to the villagers of Ndiop for their active participation and continued collaboration in the project. We thank  Dr Shirley Longacre  for providing MSP1 antigen and substantial contribution to this work. We thank  Drs M Jouan  and  J Salomon  from  Division International (Institut Pasteur, Paris)  for their help to initiate and sustain this work from the very early steps. This study was supported by grants from  Institut Pasteur   ACIP N°25_2012  and from the  Rotary International  associated with  Rotary Paris Alliance and Rotary Dakar Almadies. was also supported by the 7th European Framework Programme, FP7/2007-2013, (http://cordis. europa. eu/fp7/home_en. html)contract 242095 Evimalar, and by a grant from the  Symphasis Foundation, Zurich, Switzerland.
General Protein Response of Sponge Primmorphs to 10 26 M 3-oxo-C 12 -HSL 2. 3. 1 Total protein fraction. The analysis of 24 h-treated primmorph proteins showed that 12 proteins were over-expressed in the presence of 10 26 M 3-oxo-C 12 -HSL (Figures  3 A, B  and C ). After characterization and data bank analyses, 7 proteins matched with EST sequences: 5 with S. domuncula EST sequences and 2 with A. queenslandica EST sequences (Table  1 ). The alignment of these sequences with the GenBank data base led to the identification of 5 proteins according to their function. Three proteins corresponded to the a and b subunits of a lysosomal ATPase (spots 104, 154 and 157). a actinin (spot 99) and the a subunit of tubulin (spot 169) were also over-expressed in the presence of 10 26 M 3-oxo-C 12 -HSL. Two EST sequences, not identified, were translated and submitted to the Prosite software (spot 17 and 121).
After centrifugation at 800 g for 10 min at 4uC, the supernatant was removed and replaced by 200 mL DMSO. The plate was shaken in the darkness and then sonicated to promote the cell lysis. The production of formazan, which is related to cell viability  [24] , was determined by measuring its absorbance at 540 nm with a spectrophotometric 96-well plate reader (Tecan, France). A U-Mann Whitney test was performed as a statistical test with the following hypothesis: the results are different between the controls and the samples (p,0. 05) using the Statistica software (StatSoft, France).
Image Analysis Gels were scanned using the Molecular Imager G800 Calibrated Densitometer (Bio-Rad Laboratories, France) at 400 dpi by Quantity One software (Bio-Rad Laboratories, France). The gels were then analyzed with the Melanie software (GE Healthcare, France). Manual editing and normalization were applied after automated spot detection and matching. Spot quantification was based on spot density as a percentage of the total spot density of the gel to normalize for possible staining differences between gels. Gel annotations and matching fidelity were checked manually to eliminate matching errors caused by the software. All spots selected for MS analyses presented statistically significant variations (p,0. 05) using the U-Mann Whitney test (Statistica software, (StatSoft, France).
A laser intensity of 3,000 A was typically used for ionizing. MS spectra were acquired in the positive reflector mode by summarizing 1000 single spectra (56200) in the m/z 700-4,000 range. MS/MS spectra were acquired in the positive MS/MS reflector mode by summarizing a maximum of 2,500 single spectra (106250) with a laser intensity of 3,900 A. For the tandem MS experiments, the acceleration voltage applied was 1 kV, and air was used as the collision gas. The fragmentation pattern was used to determine the sequence of the peptide. Database searching was performed using the Mascot 2. 3. 02 program (Matrix Science, USA). Two Expressed Sequence Tags (EST) databases corresponding to updated compilation downloaded from the NCBI database were used with the demosponges S. domuncula and A. queenslandica as selected species (including 13,684 and 30,060 entries respectively).
The variable modifications allowed were as follows: N-terminal acetylation, methionine oxidation, and dioxidation. ''Trypsin'' was selected as enzyme, and three miscleavages were also allowed. Each matching cDNA sequence was submitted to the NCBI protein data base (blastx) to find a potential homology with known proteins of other species. Homologous proteins possessing an Evalue lower than 10 210 were considered to possess the same identity as the studied protein. The sequences of unknown proteins were then analyzed by Scanprosit (expasy. org/tools/scanprosite) to predict putative functions for the proteins under study.
The mRNAs of interest were quantified by real-time PCR amplification of their cDNAs. The relative mRNA transcript change of each gene was studied for immune markers: Toll-like receptor, TRAF 6-like and MPEG-like protein, and for apoptotic markers: caspase 3/7-like, BHP 1 and BHP 2. Primers (Table  2 ) were designed with Primer Express 3 software (Applied Biosystems, USA) in order to have a melting temperature (Tm) between 58 and 60uC. Each primer pair was validated by verifying that the PCR efficiency E was above 0. 95, and that a single PCR product with the expected Tm was obtained. PCR reactions were performed in triplicate with the 7300 Real Time PCR System apparatus (Applied Biosystems, USA). The 20 mL reactions contained 10 mL SYBR Green PCR Master Mix (including AmpliTaq Gold DNA Polymerase) (Applied Biosystems, USA), 2 mL of each primer (3 mM) and 8 mL of cDNAs.
JG was the recipient of a PhD fellowship from the  Ministere de la Recherche et de l'Enseignement Superieur, France. This project was funded by the  Axis 1 (Genomics and Blue Chemistry)  of the  GIS Europole Mer. The LBCM is supported by the  Region Bretagne and European FEDER. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Evolutionary conservation of the PFD region in various fungal species Previous studies have analyzed the evolutionary conservation of the b-solenoid fold  [21, 35, 36, 37, 38]. Due to the rapid increase in the number of fully sequenced fungal genomes, many additional HET-S homologs sequences have become recently available, we have thus conducted a database search for HET-s/HET-S homologs in current fungal genome sequences. We could identify a total of 51 het-s/het-S homologs (file S1). Based on residues found at 33 of the Helo domain which is known to define HET-s and HET-S allele specificities  [51, 52] , the homologs found in the other species are of the HET-S, rather than HET-s-type (Figure  S1 ), as suggested previously  [18, 21, 30, 37]. Some species like Nectria haematococca and some strains of the Fusarium oxysporum species complex contained up to 4 het-S paralogs.
Each experiment has been measured three times starting in part from different sample preparations. The analysis and extraction of the DG and m-value was done by the software package MATLAB following the mathematical formula and procedures of Santoro and Bolen  [61]. As stated above the samples were incubated before the OD 500 measurement at the various concentrations of GuHCl for one day in order to reach equilibrium conditions. Longer incubation periods such as one week did either not alter the measurements as demonstrated for the V267A variant in Figure  S5 , or a flattening of the denaturation curve was observed as shown for the V264A variant (Figure  S5 ). The flattening of the curve is interpreted as a restructuring of the amyloid aggregate during the long incubation time of one week, which let us concentrate on the use of the denaturation measurements with one day incubation for the quantitative analysis.
Sequence analysis HET-S homologs were recovered from available genome databases at ncbi (http://blast. ncbi. nlm. nih. gov/Blast. cgi) and jgi (http://genome. jgi-psf. org/) using BLAST searches. Multiple alignments were performed with CLUSTALW2 at http://www. ebi. ac. uk/Tools/msa/clustalw2/. The consensus sequence of the R1 and R2 repeats were generated using MEME at meme. nbcr. net/, [53]. The MEME output gives a graphical representation of the consensus sequence as a weighted consensus in which the size of the letter designating a given amino acid is proportional to the conservation of the residue in the different sequences used to generate the motif. The size of the character reflects the information content measured in bits. (H33 in HET-S and P33 in HET-s), no sequence is of the HET-s type and most sequences are of the HET-S type.
Model building Modeling was carried out starting from the HIV TAR RNA/SELEX RNA kissing-loop complex (PDB ID 2RN1) (44) using the program Coot  (46). Residues of the stem and the loop were mutated to match the DIS sequence and each stem length was extended to seven base pairs. Stem/loop junctions were opened in order to insert flanking adenines 5 and 3 of the loop, without changing the angle between each stem. Adenines 280 were modeled stacked inside the helix whereas adenines 272 and 273 were placed outside the helix and stacked on each other, similarly to their respective conformation observed in the HIV DIS kissing-loop complex crystal structure (PDB ID 1XPF)  (32). After model building, several cycles of geometrical regularization were carried out with Coot.
Magnesium ions are required to form the bent intermediate To assess the effect of monovalent and divalent ions on the folding pathway, we determined the fraction of each observed state (KC, intermediate bent conformation and extended) with varying [K + ] and [Mg 2+ ] in the presence of saturating concentrations of free DIS2. The Mg 2+ titration was performed at 150 mM background K + ions, while the K + titration was performed in a 5 mM background of Mg 2+ ions. At low [Mg 2+ ], ∼75% of molecules adopt the KC conformation, and only 10-20% form the intermediate or the ED conformation. Increasing the [Mg 2+ ] to 50 mM (Figure  4b , left panel) shifts the KC population to the intermediate state, making both fractions equally populated (40%). This data suggest that Mg 2+ ions promote conversion of KC into the bent intermediate.
ACKNOWLEDGMENTS We would like to thank  P. Dumas  and  C. Chow  for helpful discussions and for commenting on the manuscript. FUNDING  National Institute of Health  [ R01 GM085116 ];  National Science Foundation CAREER Award  [ MCB-0747285  to D. R. ]. Agence Nationale pour la Recherche  ( ANR-12-BS07-0007-03  "ClickEnARN" to E. E. ). Source of open access funding:  Imperial College London.
Methods Ten members of the French HIV 2013 expert group were appointed to write the project of guidelines on antiretroviral therapy (ART). This subgroup included five clinicians, two virologists, one pharmacologist, and two patient representatives. They systematically reviewed the more recent literature. Data presented at scientific conferences were also considered. Two additional experts were questioned about specific fields of interest. The chairman of the subgroup was responsible for writing and harmonizing the guidelines. Each of the following specific sections was assigned to one of the subgroup members. All members of the subgroup met several times, either physically or by teleconference over a sixmonth period. The draft guidelines that resulted from this process were presented to, discussed within and finalized by the whole expert group over three in-person meetings to obtain a consensus.
Blank (no serum, secondary antibody only), negative controls (anti-HMGCR Ab-negative serum), and positive controls (highly positive human anti-HMGCR Ab serum) were included in every assay. Mean fluorescence intensity (MFI) was determined on a Bio-Plex apparatus using the Bio-Plex Manager Software 4. 0 (Bio-Rad Laboratories, Hercules, CA). Anti-HMGCR Ab titers were determined at a 1/D dilution using the following formula: [MFI serum/MFI calibrator] Â [titer of calibrator] Â D/500. The calibrator is a highly positive human anti-HMGCR Ab serum (the same throughout the study) whose titer was arbitrarily set to 100 arbitrary units (AU/mL). We tested the first 37 sera that were found positive with this assay, and all 37 sera also scored positive for anti-HMGCR aAb using the recently developed Myositis Euroline 7 line immunoassay from Euroimmun (Lübeck, Germany).
Patients and Data Collection We tested first the sera of 23 patients having the diagnosis of NAM based on clinical and histologic criteria. These patients were recruited by clinicians (YA, AR, AB, PL, TS, BE, SH, and OB) from the neuromuscular diseases reference center of East Paris. The positive first results were communicated to the French Myositis Network. Sera of 183 patients (including 8 pediatric patients) selected by clinicians of the network were sent to what was until June 2013 the sole French immunology laboratory able to detect anti-HMGCR. These 183 patients had a suspicion of NAM based on clinical and/or pathologic criteria. All these patients were also selected because of their negativity for myositis-specific aAb anti-Jo-1 and anti-SRP using a commercial kit (dTek or Euroimmun).
BIOINFORMATIC ANALYSIS FOR THE TLR2 POLYMORPHISM rs5743704 The TLR2 protein information was obtained from Swissprot accession code O60603, and OMIM accession code 603028, using the MRS server 1. We used the PROSITE server 2 to retrieve information about the TLR2 protein domains. No protein structure is available for the complete TLR2 protein at the moment. However, the cytoplasmic TIR domain is known and can be found as PDBfile 1O77  (Tao et al. , 2002). This structure in this file contains a mutation on position 713 and misses one loop, but the remaining residues are 100% identical to the sequence of TLR2. The extracellular domain up to residue 509 is 100% identical to the protein in PDB file 2Z7X  (Jin et al. , 2007). The Pro631His polymorphism is located in the region linking the TIR domain with the intracellular domain.
We used the automatic modeling script in the YASARA & WHAT IF Twinset  (Krieger et al. , 2002)  to extend the known structures and to model missing loops in these structures. As a result, we produced models of the N-and of the C-terminal domain, which are both accurate, because they are based on the known structure of that protein. These structures are extended with residues of the linking region. Additionally, we used HOPE 3 , a next generation bioinformatics web server that performs automatic mutant analysis  (Venselaar et al. , 2010). Besides this, an analysis of the pathogenicity of the Pro631His polymorphism in TLR2 was performed using conservation and structural information. The Polyphen-2, SIFT, PANTHER, snps3D, and the SNAP servers where employed for this analysis.
STATISTICAL ANALYSIS For the analysis of the polymorphisms in the PRRs, statistical comparisons of frequencies were made between RVVC versus control subjects. We used SPSS 16. 0 software to perform Chi-square tests and the 5% Confidence Intervals Odds ratio to calculate the risk. Furthermore, for the analysis of the effect of the TLR2 genotype on the in vitro cytokine production, a non-parametrical Kruskal-Wallis analysis was performed, and for the circulatory MBL measurement we used the Mann-Whitney U -test. Both analyses were done using GraphPad Prism version 4. 00 for Windows, GraphPad Software, San Diego, CA, USA.
The amino acid change for the Pro631His polymorphism affects an amino acid residue that is located near the TIR domain (residue 639-784). To visualize the Pro631His polymorphism on the 3D structure of the TIR domain, we evaluated the homology model using the YASARA software. A screenshot of the 3D homology model is shown in Figure  1. The amino acid change is situated between the intracellular domain and the TIR domain, and might introduce a loss in rigidity when substituting proline by histidine. Finally, the HOPE server predicted that due to the fact that the polymorphism introduces an amino acid with different www. frontiersin. org characteristics, this would affect the function of the molecule. The wild-type residue proline is rigid, resulting in a characteristic backbone conformation that might be required at this position.
ACKNOWLEDGMENTS Diana C. Rosentul  was funded by the  European Commission  through the  FINSysB Marie Curie Initial Training Network  ( PITN-GA-2008-214004 ). Theo S. Plantinga was supported by a  Veni grant  of the  Netherlands Organization for Scientific Research (NWO). Mihai G. Netea  was supported by a  European Research Council   Consolidator Grant  ( ERC -StG-310372 ). All authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Despite of these changes in the dynamics of circulating pDC, longitudinal analysis of HLA-DR and CCR7 expression levels (MFI) did not reveal any activation of circulating pDC (Figure  1F ), IFNa remained undetectable by intracellular staining (Figure  1G ), and IFNa mRNA expression measured be RT-qPCR in PBMC did not change at any time (data not shown). These data show that despite dynamic changes in pDC numbers in primary infection these cells do not show any activation in the blood. Plasmacytoid DC strongly contribute to IFNa production in peripheral lymph nodes (PLN) during acute infection PLN were studied in the nine SIV-infected macaques of the longitudinal study. All were sampled at baseline, three on days 7, 8 and 9 p. i. , and six on days 8, 9, 35 and month 3 (M3). As pDC are the best candidates for the IFNa production observed, we analyzed pDC dynamics in PLN.
IFNa production rapidly decreased as a consequence of both activation-induced exhaustion of pDC, and their replacement by pDC precursors with no IFNa production ability. Our data indicate that pDC renewal contributes to the rapid contraction of pDC-derived IFNa production during primary infection, which may favor the transition from acute-to-chronic infection by limiting the efficacy of innate immunity. by pDC, vRNA in PLN was assayed by qRT-PCR. Viral RNA peaked on day 8-9 p. i. and was significantly lower by day 35 than on day 9 (p = 0. 031) (Figure  S3 A ). IFNa mRNA levels in LN correlated with viral RNA in PLN (R = 0. 88, p = 0. 003) (Figure  S3  B). These results are consistent with the IFNa response being driven by viral components, and suggest that pDC in PLN are directly triggered by SIV vRNA.
(data not shown). We also observed a significant reduction of CD123 expression on pDC in LN on day 9 p. i. (Figure  7C ): this may reflect either pDC activation, as we observed decreased CD123 expression after TLR-7/8 stimulation in vitro (data not shown), or increased proportions of late-stage pDC precursors  [35]  that have lost Ki67 expression before homing to LN. To better study the complexity of pDC dynamics in LN, we performed a principal component analysis (APS: Automated Population Separator, using Infinicyt software) of merged files from baseline and day 9 p. i. APS allowed a 2D-plot of pDC events based on the expression levels (MFI) of three markers: CCR7, CD123 and HLA-DR. Three distinct sub-populations in LN were individualized, and named pDC-a, pDC-b and pDC-c (Figure  7D ). These populations had distinct phenotypes (Figure  7E ): pDC-a displayed a steady-state immature pDC phenotype at baseline (CCR7 low HLA-DR int CD123 high ), pDC-b was CCR7 low HLA-DR low CD123 low resembling BM pDC, and pDC-c was CCR7 high HLA-DR high C-D123 low/high , and was most likely activated/matured pDC.
For intra-cellular IFNa labeling, cells isolated from 500 ml of blood or 2-4610 6 LN cells were incubated at 37uC for 30 min with 10 mg/mL of Brefeldin A (Sigma-Aldrich). Fc receptor saturation and dead cell staining were performed as described above before intracellular labeling of IFNa. All steps were as previously described  [47]. A BD LSRII apparatus equipped with four lasers (355, 405, 488 and 633 nm) was used to acquire data, and data was analyzed with FlowJo v7. 6 (Tree Star, Ashland, OR) or Infinicyt v1. 6 (Cytognos, Salamanca, Spain) software. For longitudinal follow-up, acquisition was performed after calibrations with fluorochrome-tagged beads (BD cytometer setup and tracking beads) and using automated application settings. Additionally, fluorescence minus one controls were performed at each time point as intra assay control.
Acknowledgments We thank  Dr. Christophe Joubert , DVM, and the staff of the animal care facility of  Mircen (CEA, Fontenay-aux-Roses ) for assistance in animal care and housing, and  Claire Torres ,  Benoit Delache ,  Naya Sylla ,  Patricia Brochard  and  Sebastien Langlois  for expert technical assistance. We thank  Dr. Michaela Muller-Trutwin  and  Dr. Beatrice Jacquelin  for helpful comments on this work and  Dr Isabelle Mederle-Mangeot  for project assistance.
This work was supported by the  French National Agency for AIDS Research and Viral Hepatitis-(ANRS ; www. anrs. fr). TB was funded by the  PhD program  for life sciences of the  CEA (Irtelis-INSTN ) and SD was supported by a postdoctoral fellowship from the  ANRS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
ACKNOWLEDGMENTS The  Institute of Liver Studies (KCL)  is supported by the  Medical Research Council (MRC) Centre for Transplantation, King's College London, UK  - MRC  grant no. MR/J006742/1  and by the  National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the  NHS , the  NIHR  or the Department of Health. This work was realized in the context of the  IHU-Cesti  project which received French government financial support managed by the  National Research Agency  via the investment of the future program  ANR-10-IBHU-005. The  IHU-Cesti  project is also supported by  Nantes Metropole  and the  Pays de la Loire Region. Richard Danger  was supported by the " Fondation Centaure " (RTRS; http://www.
Design and data collection The ALTADIH Cohort is a prospective hospital-based cohort of symptomatic PHID patients  [1] , initiated at the Bordeaux University Hospital and five other public hospitals (Agen, Dax, Limoges, Pau and Toulouse) in Aquitaine, South-Western France. First patients were enrolled in 2007. Patients included were over eighteen years old with primary hypogammaglobulinemia (serum IgG level < 5 g/L for CVID, or IgG subclass deficiency or Good's syndrome). They were already followed for symptomatic or newly diagnosed PHID (Ig level determined before substitution therapy). Differential diagnoses of hypogammaglobulinemia have been excluded and the reduction in the level of the seric gammaglobulins was confirmed at least 3 times at 3-month intervals for each patient, thus excluding transient hypogammaglobulinemia.
A standardized questionnaire was filled by physicians at each hospital contact, according to routine clinical management procedures, generally every 6 months. Clinical data collected focused on infections and PHID complications while biological data focused on innate and adaptive markers. The ALTADIH Cohort was approved by the Bordeaux University Institutional Review Board on December 20th, 2006. Each patient gave informed written consent before participating in the study. Some PHID patients were also enrolled in the French national prospective Cohort DEFI  [7]. In this paper, the study is cross-sectional. We only deal with inclusion measurements.
Events were acquired with the dedicated CXP-1 software. In these settings, we did not use any viability staining. Unless specified, all monoclonal antibodies were purchased from Beckman-Coulter (France) whose catalog references are reported below and in Additional file 1: Table  S1. We used the following panel of monoclonal antibodies (Mab): T and B-cell subpopulation counts were obtained using the flow count beads kit from Beckman-Coulter Flow Count (ref: 7547053) following a lyse and no wash procedure according to the manufacturer's recommendations. Markers of CD4+ T-cell differentiation were not performed in this study. -B Results are expressed as percentages of total circulating lymphocytes or of CD19+, CD3+, CD4+ or CD8+ lymphocytes as appropriate, and/or absolute counts in cells/ mm3 as appropriate.