dataesr/scientific-paragraphs-categorization huggingface dataset:
(b) Hypothetical model of E2 sequence mutations on HCV B cell tropism. (c) The HCV E2 amino acids sequences are variable. Red arrows indicate the different amino acid positions between SB and other HCV strains. 1b strain is from sequence accession number P29846. 3. (d) Variations of E2 sequences change HCV tropism (*Po0. 05; **Po0. 01; ***Po0. 001, ANOVA, n ¼ 3). Error bars represent s. d.
Error bars represent s. d. (d) Correlation plot between B7. 2 levels and relative infectivity. (e) Time course of the blocking effects of anti-B7. 2 and anti-CD81 on HCVpp(SB) infection. Synchronized infections were performed on Raji or Huh7. 5. 1 cells. Values (percent entry) are relative to the signal seen when the antibody was added at 4 h post temperature shift. Cellular HCV RNA levels were detected in Raji cell cultures treated with isotype-matched or anti-B7. 2 or anti-CD81 antibody. Fits of t ¼ 0 and later data points represent a one-phase exponential association and sigmoidal dose-response (variable slope) for anti-B7. 2 (50 mg ml À 1 ) or anti-CD81 (50 mg ml À 1 ) antibody (mean of n ¼ 3; error bars, s. d. ). (f) Both B7. 2 IgV and cytoplasmic regions are required for efficient HCV entry.
Acknowledgements We thank  Dr S. M. T. ( USC ) for critical reading,  Mr Jian-Chang Liu  ( USC ) for technical assistance,  Dr Steven Foung  ( Stanford University ) for providing anti-E2 neutralizing antibody,  Dr Rice  ( Rockefeller University ) for Huh7. 5 cells,  Dr Chisari  ( Scripps Research Institute ) for Huh7. 5. 1 cells,  Dr Bartenschlager  ( University of Heidelberg ) for HCV Con1 replicons,  Dr Aizaki  and other  Lai lab members  for invaluable suggestions,  Dr Melvin Trousdale  for electron microscopic analysis,  Dr Nathaniel R. Landau  for a luciferase construct,  Dr Weeraratna  from the  National Institutes of Health (NIH)  for Claudin-1 expression vector,  Dr Ernesto Barron  and  Mr Anthony Rodriguez  for Electron microscopy analysis,  Mr Emmanuel V. Dimacali  from  University of Southern California  for FACS analysis and  Mr Chad Nakagawa  ( USC ) for critical reading.
d. (b) Hypothetical model of E2 sequence mutations on HCV B cell tropism. (c) The HCV E2 amino acids sequences are variable. Red arrows indicate the different amino acid positions between SB and other HCV strains. 1b strain is from sequence accession number P29846. 3. (d) Variations of E2 sequences change HCV tropism (*Po0. 05; **Po0. 01; ***Po0. 001, ANOVA, n ¼ 3). Error bars represent s. d.
Plant material, isolation of essential oil The essential oil samples have been isolated by hydro distillation using a Clevenger-type apparatus from different parts of individual tree (500 g; yields given in table 1) harvested on the experimental forest plot, in which each planted tree is individually numbered, of l'Ospedalesoutheast of the Corsica (P. menziesii, P. ponderosa, S. giganteum, C. japonica), and the managed natural forests of Vizzavona-center of Corsica (P. menziesii) and Verde -center of Corsica (L. decidua) (Figure  S1 ). Plant material was identified by Ms J. Gross, G. Paolacci and J. M. Morin foresters from the ONF (National Forestry Office) in charge of the sampled forests. Voucher specimens have been deposited at the Conservatoire Botanique National de Corse, (Corte, France), under accession numbers: GG2770 (P.
Gas Chromatography Analyses were performed on a Clarus 500 PerkinElmer (PerkinElmer, Courtaboeuf, France) system equipped with a FID and two fused-silica capillary columns (50m x 0. 22 mm, film thickness 0. 25 mm), BP-1 (polydimethylsiloxane) and BP-20 (polyethylene glycol). The oven temperature was programmed from 60 °C to 220 °C at 2 °C/min and then held isothermal at 220 °C for 20 min; injector temperature: 250 °C; temperature detector: 250 °C; carrier gas: helium (0. 8 mL/min); split: 1/60; injected volume: 0. 5 L (50 L in 350 L of CHCl 3 ). The relative amounts of the oil constituents were expressed as percentages obtained by peak-area normalisation, without using correcting factors. Retention indices (RI) were determined relative to the retention times of a series of n-alkanes with linear interpolation (Target Compounds software from PerkinElmer).
METHODS/DESIGN Study design The study will be a multicentre, randomised controlled trial, using a two-stage modified Zelen design (figure  1 ). 16 17 he experimental group will consist of toddlers with ASD receiving 12 hours per week ESDM and the control group will consist of toddlers with ASD receiving care available in the community. Core trial information is presented in table 1 (WHO Trial Registration Data Set).
Allocation sequence generation and randomisation All eligible toddlers, whose parents have provided consent for them to participate, will be randomised using stratified minimisation at a ratio 1:2 in favour of the control group (one toddler assigned to the intervention group for two toddlers assigned to the control group). A random element will be used, so that children will be assigned to the treatment arm which will minimise the imbalance with 90% probability. The minimisation factors will be the centre, the children's age, the DQ score on the MSEL and the severity of the ADOS score at inclusion. Randomisation will be performed using a computer program generated in the statistical software SAS by the centre for clinical research of the university teaching hospital of Lyon (Hospices Civils de Lyon, France).
Outcome measures and tools All outcomes will be assessed at baseline, 12 and 24 months of follow-up (figure  2 ). Additionally, demographic and socioeconomic data will be obtained at the same times points for descriptive purposes. The primary outcome will be the change in DQ measured using the MSEL, scored from baseline to 24 months. Secondary outcome measures will focus on child development and autism symptoms, quality of life of parents and healthcare resource use. To assess child cognitive level -The MSEL is a direct observation tool measuring cognitive levels for children from birth to 68 months. 22 It is a reliable, validated test widely used to evaluate the paediatric ASD population. 23 24 As most of the children are likely to score too low to use the Early Learning Composite Score of the MSEL manual, we will calculate the DQ score (ie, developmental age equivalents divided by chronological age).
National unit costs for care and interventions will be applied to estimate direct costs. Parental employment changes related to ASD will be recorded and valued using the human capital approach. Analysis of socioeconomic data will be adapted to trial results and to the nature and diversity of toddlers' care in the control group, which are unknown to date, and will therefore be exploratory in nature. The costconsequences framework will allow concomitant publication of all relevant costs and outcomes, avoiding overemphasis on any of them. 40 rticipant enrolment Toddlers will be enrolled by psychiatrists of the centres. The number of toddlers usually in care in the participating centres should be sufficient for the recruitment required. Nevertheless, in order to facilitate inclusions, healthcare professionals, usually meeting with children with ASD ( paediatricians, speech language therapists and occupational therapists), will be contacted by postal mail to inform them of the study, or informed by specific meetings.
Data collection and management The study data will be collected on a secure electronic case report form (eCRF) that will be available at each centre through an internet portal. No personal identifying information will be mentioned on the eCRF. Each subject included in the study will be assigned a unique identification number that will consist of the identification number of the investigational centre, the initials of the patient and the chronological inclusion number of the patient. Multiple external validation checks will be applied: examination of the source documents and crosschecking with the data recorded in the eCRF as to its accuracy, the presence of missing data and the consistency of data. The eCRF will only include the data necessary for the analysis to be reported in a scientific publication.
Concerning the analysis of the primary outcome, descriptive statistics will be presented for each group as the mean change (SD, 95% CIs) in DQ score from baseline to 24 months after randomisation. The longitudinal association between ESDM intervention and DQ scores over the 24-month study period will be estimated using a linear mixed-effects regression model. 46 Mixed models have the advantage of dealing with missing values because they use all of the available data from a patient over the study period. The DQ score at each follow-up visit will be defined as the dependent variable. The first model will include the following as independent variables: study group, time. The group will be coded as a dichotomous variable. Time will be treated as a continuous variable to account for the variability of the point in time at which the measurements are obtained.
Additional covariates can be included if they are significant at 0. 05 level according to the likelihood ratio test or if they alter the coefficient of the intervention effect >10%, when removed from the analysis. All models will be performed with the SAS MIXED procedure. Model assumptions will be verified according to residual analysis. If most of the assumptions are not met, After the 1st step, a total of 132 patients (44:88) are required to detect a difference between groups under assumptions. After the 2nd step, a total of 159 patients (53:106) are required to correct the 20% dilution bias due to the cross-over effect. To maintain the 1:2 ratio, we rounded the sample size up to the next whole number (27 patients rather than 26). After randomisation, all patients will be then followed up during 24 months.
After the 3rd step, a total of 180 patients (60:120) are to be included to account for ∼10% drop-out rate during the 24-month follow-up. Again, we rounded the sample size up to the next whole number to keep the 1:2 ratio between groups. DQ, developmental quotient. other alternatives such as transformation for DQ score or generalised linear mixed model will be examined. For the secondary outcomes, change in other scores from baseline to 24 months after randomisation will be analysed in the same way as the primary outcome. All tests will be two sided and carried out at the 5% level of significance. Statistical analyses will be performed using SAS 9. 3 (SAS Institute, Cary, North Carolina, USA) by the centre for clinical research of the teaching hospital of Lyon (Hospices Civils de Lyon, France).
Acknowledgements The authors would like to thank  Sally Rogers ,  Elizabeth Fulton ,  Cynthia Zermut  and  Marie Rocha  for their training in ESDM. They are grateful to  Catherine Lord  and  Rebecca Grzadzinski  for use of the BOSCC. Particular acknowledgements are addressed to  Jonathan Green  for his expert advice and to  Catherine Aldred  for her training in DCMA methodology. They thank all teams of the different study sites for their ongoing support of this project. Thanks also to  Paul Belhouchat , a member of the  Centre for Autism Resources of Lyon (Rhône-Alpes)  who provided references. The authors are grateful to  Philip Robinson  for his help with manuscript preparation and  Isabelle Bluche ,  Translator-Editor ,  Translands Traductions , for editing this paper Collaborators Lyon-CH du Vinatier: MMG, NG,  Stéphane Grisi ,  Stéphanie Marignier ,  Jean-Marc Useo ,  Alain Pourrat ,  Chloé Peter ,  Flavia Mengarelli ,  Natacha Gallifet ,  Fanny Rumillat ,  Gaelle Tenant ;.
Exclusion criteria: serious neurological or physical condition, diagnosis of Rett syndrome, family unavailable for a regular follow-up and intervention. Data category Information Primary registry and trial clinicaltrials. gov NCT02608333 identifying number Date of registration in primary 11 May 2015 registry Secondary identifying numbers French institutional review board (2015-013B) sponsor (69HCL15_0278) Source of monetary or material French Ministry of Health (Programme de Recherche sur la Performance du Système de support soins) Fondation de France (member of the Network of European Foundations for Innovative Cooperation) Primary sponsor Centre Hospitalier Le Vinatier, Bron, France Secondary sponsor Not applicable Contact for public queries Marie-Countries of recruitment France and Belgium Health condition or problem Autism spectrum disorder (ASD) studied Study type Interventional Allocation: randomised 1:2; parallel assignment; blinding: assessor blind; two-stage modified Zelen design Date of first enrolment NA Target sample size 180 Recruitment Status NA Primary outcome Change in developmental quotient (DQ) measured using the MSEL, scored at 24 months Key secondary outcomes Child development, autism symptoms, quality of life of parents, healthcare resource use.
Its main purpose is to provide a standard framework for the description, identification, and classification of "natural" taxa, which may provide a more solid basis for reconstructing the evolution of the order. An annotated version of the matrix (NEXUS-formatted) is included in the Supplemental Data Archive (SDA;  Grimm, Bomfleur & McLoughlin (2017)  available from Dryad Digital Repository http://dx. doi. org/10. 5061/dryad. 270gs) and included in Supplemental Information linked to this paper.
Numerical phylogenetic framework The all-inclusive matrix (S00, all Osmundales + outgroup) provides partly incompatible signals accompanied by substantial intertaxonomic diversity. The maximum pairwise distance found in the Osmundales matrix is 0. 81; the matrix Delta Value (mDV) is relatively high with 0. 38 (File S3), but is within the range expected for morphological matrices including mainly fossil taxa (Guido W. Grimm, 2005 onwards, personal observation; Table  S2 ; see Go ¨ker  & Grimm, 2008). In general, a tree derived from a matrix with a mDV > 0. 2 (Table  S2 ) can be assumed to represent the signal in the underlying dataset only inadequately, occasionally including clades that are incompatible with molecular data  (Denk & Grimm, 2005; Denk, Grimm & Hemleben, 2005; Manos et al. , 2007; Friis et al.
14 ), and the same holds true for support consensus networks  (Grimm, Bomfleur & McLoughlin (2017)  available from Dryad Digital Repository http://dx. doi. org/10. 5061/dryad. 270gs), illustrating the lack of consistent sorting signals in the underlying matrix. The traditional subdivision based on the degree of stele perforation (informal groups as in the listing below) is, therefore, not supported by any further evidence. Furthermore, the data compiled here show that imperforate and highly perforate steles are end members of a complete transformation series in Osmundoideae and, thus, provide a poor basis for classification above species level. A much deeper understanding of character conservation and evolution in the Osmundoideae would be necessary to propose a finer subdivision. Moreover, it is conspicuous that the network (Fig.
e. , more or less horseshoe-shaped). Stipe sclerenchyma ring heterogeneous: differentiation typically initiating in the stipe base with the formation of an abaxial arch of particularly thick-walled fibers. Status: Holophyletic (cf. Bomfleur, Grimm & McLoughlin, 2015) , extant with fossil representatives. Known geochronologic range: Triassic to present. Comments: In analyses of molecular datasets that are based also on conserved coding chloroplast and mitochondrial genes, the outgroup-inferred root is consistently placed between Osmundastrum and a clade comprising all remaining extant Osmundaceae  (Yatabe, Nishida & Murakami, 1999; Metzgar et al. , 2008). Combining several lines of evidence, such as detailed analysis of the signal from molecular data, fossilized birth-death dating using frond fossils, rhizome anatomical evidence, and hybridization capacity,  Bomfleur, Grimm & McLoughlin (2015)  argued that this is an outgroup-ingroup (long) branching artefact.
16; or Osmundeae: Figs. 11, 13 and 15). Claytosmunda is more or less equally similar to all other members of Osmundeae and shows no apparent preference toward any extant species. Accordingly, no member of Claytosmunda, including the extant Claytosmunda claytoniana, would be supported as a member of a clearly defined clade (BS ML/LS/MP 10; File S3; see the BS support networks in  Grimm, Bomfleur & McLoughlin (2017)  available from Dryad Digital Repository http://dx. doi. org/10. 5061/dryad. 270gs). Although Claytosmunda nathorstii from the Paleogene of Svalbard is known only from isolated stipes and was thus excluded from the phylogenetic analyses owing to it lacking too many characters, the species is clearly allied with Claytosmunda based on its characteristic stipe structure with two lateral masses of thick-walled fibers in the heterogeneous with an abaxial arch or mass and two opposite, separate or thinly connected lateral masses of particularly thick-walled fibers.
Hence, we include it in this holophyletic genus, even though it lacks the fiber patch adaxial to each leaf trace that is characteristic of the modern members. The intermediate, bridging nature of this fossil is also apparent in the neighbour-nets provided here, where it consistently occupies a position between modern Osmundastrum and early representatives with putatively primitive axis anatomy as seen in early Claytosmunda. This placement underscores its great similarity to its more derived congeners (MD ! 0. 08) and to early members of the Claytosmunda-Osmunda (-Plenasium) lineage (MD ! 0. 10). If forced into a tree, Osmundastrum pulchellum would be placed close to modern Osmundastrum (Table  3 ; see also BS support networks in  Grimm, Bomfleur & McLoughlin (2017)  available from Dryad Digital Repository http://dx.
doi. org/10. 5061/dryad. 270gs), as expected for an early member of this lineage. Molecular dating using the frond fossil record confirms a Triassic split between Osmundastrum and the remainder of the Osmundinae  (Bomfleur, Grimm & McLoughlin, 2015; Grimm et al. , 2015). Triassic Osmundaceae fossils include Osmundinae rhizomes with a heterogenous sclerenchyma ring in the leaf traces, usually exhibiting the pattern typical of many Jurassic Osmundinae and the extant Claytosmunda claytoniana. An exception is Australosmunda indentata  (Hill, Forsyth & Green, 1989) , which has the typical Osmundastrum configuration. In other aspects (e. g. , stele dissection), this species is most similar to the Jurassic Claytosmunda embreii, and to a lesser degree, Claytosmunda sinica and Claytosmunda preosmunda; corresponding clades would receive low but consistent support based on our matrices (Table  3 ).
CONCLUSION AND OUTLOOK This study provides a comprehensive comparative dataset and the methodological tool-kit to describe, identify and classify fossil osmundalean axes. A phylogenetic framework assigns explicit biological meaning to the names of fossil and extant taxa. The design of our character matrix is optimized for these purposes. Information on the anatomy of forthcoming finds of fossil osmundalean axes can easily be incorporated into the matrix in order to facilitate systematic placement, comparisons, and character analysis. We propose natural groups that can be identified based on diagnostic character suites, and we aim to reconcile the extensive fossil record of the group in the form of anatomically preserved axes with modern phylogenies and systematic treatments of extant taxa based on molecular data.
ACKNOWLEDGEMENTS We thank the editor  William DiMichele (Washington, D. C. , USA)  and two anonymous reviewers for detailed and constructive criticism on an earlier version of this manuscript;  Harald Schneider  ( London/Xishuangbanna ) for helpful discussion on the recently revised classification of modern Osmundaceae (PPG I, 2016);  Weston Testo (Burlington)  for providing complete documentation of the phylogenetic analyses in Testo & Sundue (2016); and  Ignacio H. Escapa  (Trelew),  Juan Garcia Massini  ( La Rioja ),  Ning Tian (Shenyang) ,  Ezequiel I. Vera  ( Buenos Aires ), and  Yongdong Wang  ( Nanjing ) for kind help in obtaining literature.
Images were analysed with SR-Tesseler software to perform a precise and automatic segmentation and quantification of protein organization  32. This further demonstrated the organization of CD147 in clusters (mean size: 37,700 ± 2,715 nm 2 ), whereas only few clusters were detected in non-infected cells (Supplementary Fig. 8 ). Similar results were obtained using different fluorophores, STORM imaging buffers or image reconstruction systems (Supplementary Fig. 9A-C,E ). Furthermore, this cluster organization was not observed for receptors that do not accumulate at bacterial adhesion sites, such as CD71 (Supplementary Fig. 9D ), demonstrating the specific organization of these clusters for receptors recruited at bacterial adhesion sites. The small variation in CD147 cluster sizes, together with their regular organization (Fig.
Briefly, after transfection with the indicated siRNA or plasmids, HBMECs were grown on IBIDI chambers for 48 h and then submitted to laminar flow (0. 04 dynes cm À 2 ) under an inverted microscope. GFP-expressing bacteria were introduced in the flow chamber for 10 min, then the medium was introduced under flow for 10 min to get rid of non-adherent bacteria and fixed. Adhesion of bacteria was recorded using an Olympus CKX41 inverted microscope with a Â 40 objective. The total number of adhesion events (that is, GFP-expressing meningococci adhering in single diplococci or in aggregates) and the average size of the bacterial aggregates (measured in mm 2 ; one diplococci ¼ 3 mm 2 ) were quantified using the ImageJ Software. Proteomic analysis. Analysis was performed by the 3P5 proteomics facility of the UniversiteParis Descartes, as follows: In-gel trypsin digestion: In-gel digestion with trypsin was carried out as described  57  using a digester/spotter robot (Tecan, Ma ¨nnedorf, Germany) at all steps.
Spectra acquisition and processing were performed using the 4,000 Series Explorer Software (ABSciex) version 3. 5. 28193 build 1011 in positive reflectron mode at fixed LASER fluency with low mass gate and delayed extraction. External plate calibration was performed using Pepmix1 peptides from ABSciex. For each fraction, steps of 50 spectra in the range of 850 to 4,000 Da were acquired. Five hundred spectra per sample were summed, processed to obtain monoisotopic values from isotopes clusters with a raw spectra signal-to-noise ratio of 20. MS spectra generated by each nLC fraction were treated automatically, allowing the 12 most abundant precursors to be selected for fragmentation starting with the least abundant unless its intensity was higher in a neighbouring fraction. A cutoff was applied at a minimum s/n of 15.
Neighbouring precursors within 200 resolutions were excluded. One thousand MS/MS spectra per precursor were summed by increment of 50 and were subjected to baseline subtraction and Savitsky-Golay smoothing (with a polynomial order of 4 and 15 point across peak). Protein identification: Extracted MS/MS peaklists were submitted to an in-house mascot (Matrix Science) version 2. 2 search engine  58. The Swiss-prot database (May 2007, 267,354 sequences; 98,158,671 residues) was used restricted to the Homo sapiens subset of sequences (16,529 sequences). Parent and fragment mass tolerances were, respectively, set to 100 p. p. m. and 0. 3 Da, partial modification (oxidization) of methionines was allowed. Carbamidomethylation of cysteins by iodoacetamide were considered as complete. Missed trypsin cleavage sites were limited to 1.