dataesr/scientific-paragraphs-categorization huggingface dataset:
Supplementary material The supplementary files are available at http://bds. sagepub. com/content/3/2 3. This roughly summarised process has been extensively addressed through my interviews. 4. Collecting data about existing chemicals, i. e. about their physicochemical properties and toxicity, is an important goal of REACH regulation. 5. http://www. lhasalimited. org/products/derek-nexus. htm (last accessed 13 April 2016). 6. http://oasis-lmc. org/ (last accessed 13 April 2016). 7. The detailed analysis of these specifications would not fit in this paper. However, the interested reader can refer to the reference guidance document from the OECD (2007). 8. REACH specifies a more restrictive series of conditions in order for QSAR results to be used instead of classical testing. The following conditions are cumulative: (1) results are derived from a (Q)SAR model whose scientific validity has been established, (2) the substance falls within the applicability domain of the (Q)SAR model, (3) results are adequate for the purpose of classification and labelling and/or risk assessment, and (4) adequate and reliable documentation of the applied method is provided, see European  Commission (2006: 202) , Annex XI, 1.
Duplication of unc-29 Cloned cDNA sequences available in Genbank  [17]  and genomes available in the Wormbase ParaSite WBPS2 database  [18]  were used to identify homologs of the C. elegans unc-29 gene in different nematode species representing clades III and V  [6, 8]. These also appear to be present in A. cantonensis but its genome assembly is not sufficiently complete to identify the copies unambiguously. An independent duplication of unc-29. 7 produced unc-29. 5 and unc-29. 6, shared by O. dentatum, A. caninum and A. ceylenicum. N. brasiliensis possessed four copies derived from unc-29. 7 that were found only within this species. A similar quadruplication of unc-29. 7 is inferred to have occurred in the Trichostrongyloidea following divergence from Nippostrongylus but prior to diversification of the trichostrongylid group to produce unc-29.
Phylogeny and substitution rate analysis Coding sequence orthologous to Cel-unc-29 was identified from genome data available from the ParaSite WBPS2 release for clade III and clade V nematodes  [6, 8]. These were A. suum (Asu), T. callipaeda (Tzc), B. malayi (Bma), L. loa (Llo), D. immitis (Dim), O. volvulus (Ovo), L. sigmodontis (Lsi), A. viteae (Avi) and P. pacificus (Ppa), P. exspectatus (Pex), C. tropicalis (Ctr), C. japonica (Cjp), C. remanei (Cre), C. brigsgae (Cbr), C. elegans (Cel), H. contortus (Hco), T. colubriformis (Tco), T. circumcincta (Tci), A. costaricensis (Acs), D. viviparus (Dvi), O. dentatum (Ode), A. caninum (Aca), A. ceylanicum (Ace) and N. brasiliensis (Nbr). Sequences were aligned as codons using the MAFFT plugin (v1. 3. 3) of Geneious (v7. 1. 2, Biomatters Ltd)  [57].
Accession numbers cDNA clones used in this study correspond to sequences, Cel-lev-1 (NP_502534), Cel-lev-8 (NP_509932), Cel-unc-29 (NP_492399), Cel-unc-38 (NP_491472) and Cel-unc-63 (NP_491533); Hco-unc-29. 1 (GU060980), Hco-unc-29. 2 (GU060981), Hco-unc-29. 3 (GU060982), Hco-unc-29. 4 (GU060983), Hco-unc-38 (GU060984), Hco-unc-63a (GU060985), Hco-acr-8 (EU006785), Hco-unc-50 (HQ116822), Hco-unc-74 (HQ116821), Hco-ric-3. 1 (HQ116823).
Glass electrodes were filled with 3M KCl and checked for resistance between 1 and 3 MO. The oocyte bath was connected to the ground through a 3 M KCl agar bridge. Agonist and antagonists were dissolved or diluted in recording solution (100 mM NaCl, 2. 5 mM KCl, 1 mM CaCl 2 , 5 mM HEPES, pH 7. 3). All measurements were performed using a Geneclamp 500B amplifier and Digidata 1322M (Axon Instruments), oocytes were voltage-clamped at -60 mV. Drug solutions were applied to oocytes by gravity flow using perfusion syringes directly connected to the chamber. Data were collected and analyzed using Clampex 9. 2 and Clampfit 9. 2 (Axon Instruments, Sunnyvale, CA, USA). Traces were filtered at 30 Hz and analyzed using GraphPad Prism 5. 0 software (GraphPad Software, San Diego, CA, USA). Final results are presented as means ± SE.
C. elegans paralysis assay Three day old adult fluorescent worms were transferred onto unseeded NGM plates, equilibrated at 20°C, containing 200 μM LEV. Drug induced paralysis was determined by visual inspection every 15 min. Worms were defined as paralyzed if no movement was observed within five seconds after prodding the tail with a hair tip  [52]. Statistics. Experimental data are shown as mean ± S. D. Statistical comparisons between the unc-29 (e1072) mutant strain and the transformed lines were done using two-way ANOVA with Bonferroni's multiple comparison post test. A level of p < 0. 05 was considered significant.
Final washes were performed 2 times with AbD and 2 times with 1X PBS/0. 1% (v/v) Triton X-100. The membrane of the oocytes was observed using a Zeiss LSM710 confocal microscope (Carl Zeiss Inc. , Canada) equipped with the Zeiss Zen 2010 software. Negative controls were either waterinjected oocytes or AChR-expressing oocytes but omitting the primary antibodies.
Acknowledgments We would like to thank  R. J. Martin ,  L. Rufener ,  V. Dufour ,  K. Keller ,  M. Kaji  and  J. Agostinone  for technical support. The C. elegans L-AChR subunit plasmids were kindly provided by  T. Boulin  ( Institut NeuroMyoGène-INMG CNRS UMR 5310-INSERM U1217-Université Claude Bernard Lyon 1, Villeurbanne, France ).
Data Collection To test our prediction, we needed data on a group of organisms with a large number of controlled infection experiments and where both the infective dose and the number of surviving individuals at the age of reproduction could be quantified. We would also prefer to have a data set consisting of species from several different hosts and with a wide range in age at maturity. Nematodes from the intestinal system of mammals fulfilled all these criteria. We made up a list of all known intestinal nematode species observed in experimental mammalian hosts, using  Anderson (2000)  as a source. We then used the ISI database to search for these species by typing the species name in the "title" field. We restricted the search to the 20-year period from 1987 to 2006, assuming that all relevant data from this period would give us a representative and unbiased sample.
All nematode species that produced 30 hits or more in such a search were selected for further analysis. We included the information from a paper in our data set if it complied with the following criteria: (1) Experimental infections must have been given in a single dose. (2) Hosts must have been slaughtered and worms counted at the start of reproduction for the nematode species studied. In order to get a sufficient number of data points, we allowed the time of observation to deviate 125% from the prepatency times found in  Taylor et al. (2007). (3)  In studies where parasite mortality or developmental rates were manipulated, for example, by anthelmintics, diet, or immune suppressants, only the control animals were used. (4) Parasites must have been naturally adapted to the hosts used in the experiments; that is, only nematodes that are naturally occurring in these hosts were included.
These search criteria produced data from 77 different published papers including 202 independent observations (experiments) on 10 different species of nematodes (see the appendix, available online). Most of the experiments in this data set were what we call "homologous infections," that is, infections where the parasite infective stages were isolated from the same host species as the one used in the experiment. In these experiments, we assume that the parasite was adapted to the experimental host, which is a basic assumption for any optimality model. However, there were also data where the parasite strain was obtained from a host species other than the one used in the experiment-these we refer to as "heterologous infections. " In these experiments, we cannot expect the parasite to be optimally adapted to its experimental host.
Phylogenetic signal and analyses Prior conducting any phylogenetic inferences based on the 7 MLST gene fragments (argH, Cya, glpK, gnd, murC, pta, and purH), we inferred the quality of the phylogenetic information contained in these sequences by plotting transition and transversion rates as a function of genetic distances (Additional file 1: Figure  S1 ). This graph shows that neither transitions nor transversions are saturated but, rather, both rise linearly with increasing genetic distance. We then measured substitution saturation using the Xia index  [47]  for all three codon positions. The observed I ss. c value of 0. 808 was significantly higher than the I ss value of 0. 019, thus confirming that little saturation occurs at these sites. The evaluation of the phylogenetic content of the dataset was performed with likelihood mapping analyses.
Bacterial strains collection and sequence dataset A total of 280 strains belonging to the MAB were chosen from multiple clinical sources in diverse geographical areas in an attempt to study the genetic diversity of this bacterial species from an evolutionary perspective (Additional file 5: Table  S1 ). In order to verify that all strains belonged to MAB, RpoB typing was performed, and phylogenetic trees of each of the seven housekeeping genes used for MLST analysis (argH, Cya, glpK, gnd, murC, pta, and purH), were checked (see Additional file 9: Figure  S8 ). We also assessed that the associated housekeeping genes were under strong purifying selection (Additional file 10: Figure  S9 ). To estimate the level of gene conservation, pairwise dN/dS ratio ω (dN: non-synonymous mutation substitution rate, dS: synonymous mutation substitution rate) were calculated using the program CODEML provided by the PAML (Phylogenetic Analyses by Maximum Likelihood) package version 4  [58].
Data were retrieved from the French CF registry (CNIL authorisation No 1,202,233), and an internal review board approved the study. Samples were analyzed for NTM identification at each center, using approved techniques and all data analysed were anonymized. CF patients were considered as infected if MAB was associated with "nontuberculous mycobacterial lung disease" (NTMLD), if the cases: i) fulfilled the bacteriological American Thoracic Society criteria for mycobacterial lung infections  [61] , and ii) presented clinical (e. g. , functional deterioration such as fever, asthenia and emaciation) and/or radiographic signs of mycobacterial disease. Each CF patient was periodically investigated for pulmonary MAB isolation between 1996 and 2009. If MAB was no more identified after previous positive tests, and without any anti-MAB treatment, this was considered as a 'transient colonisation'.
Gene fragments sequencing Eight gene fragments were amplified and sequenced from all isolates using the primers and PCR protocols presented in  Macheras et al. 2011. Both strands were sequenced using an Applied Biosystems Prism 3700 automated sequencer with dRhodamine-labeled terminators (PE Applied Biosystems). Sequences were aligned and trimmed using SEQLAB and PILEUP (Wisconsin Package 9. 1, GCG, Madison, WI) and then concatenated. All sequence type profiles and nucleotide sequences are publicly available at (http://bigsdb. web. pasteur. fr/mycoabscessus/ mycoabscessus. html).
MLST and minimum spanning-trees In order to define the relationships between strains at the microevolution level, we performed allelic profile-based comparisons using a minimal spanning tree (MST) analysis with the BIONUMERICS v5. 10 software (Applied-Maths, Sint Maartens-Latem, Belgium). The minimal spanning tree is calculated by Prim's algorithm, modified to choose between otherwise equivalent, alternative subtrees at each step by implementing priority rules that incorporate aspects of the EBURST algorithm  [62]. The highest priority is given to STs with the largest numbers of single locus variants. Any ties were resolved by choosing the ST (or a random ST) with the largest number of isolates. The first node in the network is the ST with the highest priority according to these rules and subsequent links are chosen by a recursive strategy.
Phylogenetic analyses In order to gain an overview of the phylogenetic signal, we plotted pairwise transition and transversion distances against the total genetic distances using the DAMBE software package  [63] , and we also tested our set of molecular sequences for substitution saturation. The phylogenetic signal of the dataset was also investigated with the likelihood mapping method implemented in TREE-PUZZLE  [64]  by analysing 10,000 random quartets. This method proceeds by evaluating, using maximum likelihood, groups of four randomly chosen sequences (quartets). The three possible unrooted tree topologies, for each quartet, are weighted and the posterior weights are then plotted using triangular coordinates, such that each corner represents a fully resolved tree topology. Therefore the resulting distribution of the points shows whether the data are suitable for a phylogenetic reconstruction, or not.
The best-fit model of DNA substitution and the parameter estimates used for tree reconstruction were chosen by performing hierarchical likelihood ratio tests implemented in JMODELTEST 2. 1. 3 [65]. Phylogenetic trees were estimated for each data set with PHYML incorporating the best-fit model of evolution. Alternatively, we also implement the Bayesian Markov chain Monte Carlo (MCMC) method available in the BEAST 1. 8. 1 package  [17]  to generate a phylogeny of MAB. The general time reversible (GTR) substitution model was implemented under a constant population size scenario and five independent runs were generated. Convergence was then evaluated with ESS values and trace plots were explored with the software TRACER 1. 5. Runs were combined using LOGCOMBINER and trees were plotted using FIGTREE v1.
Recombination and mutation We tested for recombination within the 3 subspecies for all loci independently, as well as for the concatenated MLST loci using the software LDHAT v2. 2  [49]. LDHAT employs a coalescent-based method to estimate the population-scaled mutation (θ = 2N e μ) and recombination (ρ = 2N e r) rates, where N e is the effective population size, r the rate at which recombination events separate adjacent nucleotides and μ is the mutation rate per nucleotide. The ratio r/μ were calculated as (ρ/L)/θ, where L is the gene length (sequence length). This r/μ ratio ranges from 0, which indicates full clonal reproduction, to > > 1, which is expected under free recombination. Significance of the evidence for recombination was tested using nonparametric, permutation-based tests implemented in LDHAT (Lkmax and G4 tests).
To avoid strains overrepresentation, the analysis was conducted on the sole STs. Concatenated sequences recombination rates confidence intervals were calculated using likelihood curve method. M. bolletii and M. massiliense reference strains DNA sequencing and genome assembly The genomic DNAs of Mycobacterium abscessus subsp bolletii reference strain CIP 108541 and Mycobacterium abscessus subsp bolletii CIP 108297 (former M. massiliense reference strain) were sequenced at the Genopole of the Institut Pasteur by using the Genome Analyzer IIx (Illumina Inc. , San Diego, USA) with a coverage rate of 175X and 170X, respectively. 36 bp single-end reads were generated and aligned against the reference genome of M. abscessus (EMBL accession number: CU458896) [41] by using MAQ  [71]. In order to prevent the presence of potential amplification contaminants, duplicated reads were removed from the alignment maps.
Two reads were considered as a duplicate if they shared the same mapping position, stemmed from the same DNA strand and possessed exactly the same sequence. In the case of duplicates, the read having the best quality sum was preserved. The resulting alignment maps were then analysed by using SNIFER (https://bitbucket. org/clafooty/tango/wiki/Home) for the SNP calling, which is based on a comparison of aligned read sequences to the reference genome from mapping positions. Mismatches detected were then filtered according to 5 stringent criteria: (i) a coverage sum > 10; (ii) a substitution frequency of at least 0. 89; (iii) a mean quality of mapped bases > 20 according to the Sanger format; and both mean (iv) coverage and (v) quality >20 for the 10 bases surrounding the variant (-5/+5). So as to investigate large insertion-deletion events, each short-read data set was de novo assembled using the perl script VelvetOptimiser, provided with the VELVET package  [72].
All reads were pre-processed to remove low quality or artefactual nucleotides. First, all nucleotides occurring at 5′ and 3′ ends and supported by a Phred quality score < 28 were trimmed off using SICKLE (https://github. com/najoshi/sickle). Second, contaminant oligonucleotides (i. e. , library adaptors) were detected and trimmed off using ALIENTRIMMER  [73]. Third, reads shorter than 45 nt after the aforementioned cleaning steps were discarded, as were those containing more than 5 % nucleotides with Phred score < 28. Finally, the program FQDUPLICATE (ftp://ftp. pasteur. fr/pub/gensoft/projects/ fqtools) was used to discard every duplicate single-or paired-ends reads. A de novo assembly of the remaining reads was built with CLC Genomics Workbench version 3 (CLC Bio, Cambridge, MA). Contigs were then reordered using the MUMMER software.
The contigs of the three "hybrid" strains were compared with the three reference strains previously assembled (M. abscessus subspecies, M. massiliense subspecies, and M. bolletii subspecies) using NUCMER  [74]  and the deltafilter command (90 % minimum identity threshold on at least 400 nucleotides). The Show-Tilling script was then used to determine the order of the contigs (minimum 10 % coverage, maximal gap length 100,000 bp). The rejected contigs were manually checked and reintegrated in the final assembly if they had at least 96 % identity on > 1500 bp regions. The assembled genomes of strains M139, 23 and 137 are very similar to the reference strains (4,916,028 bp, 4,834,006 bp, and 5,011,043 bp, respectively), and represent at least 95 % of the size of the longest reference M. abscessus subsp.
abscessus strain chromosome, that was sequenced by the Sanger method  [41]. Mycobacterium abscessus 23 genomic sequence was deposited on NCBI whole genome shotgun project with accession number JRMD00000000. Mycobacterium abscessus subsp. bolletii 137 was deposited on NCBI whole genome shotgun project with accession number JRME00000000. Additionally, the 6 analysed genomes were uploaded on the Genoscope MAGE database. Core and accessory genomes were identified using a Bidirectionnal Best Hit Method, with 50 % protein identity threshold. Manual gene annotation was performed for the genetic loci of interest using global information given by this platform (Interproscan domains, SwissProt similarities, FigFam) for each gene. All regions that were identified as putative genomic islands (strain specific genetic loci of more than 8 kb) were all blasted on the NCBI NR nucleotide database, and results showing more than 80 % identity on more than 75 % of the sequence were retrieved.
Acknowledgments We are grateful to  Guillaume Achaz  from the  Atelier de Bio-informatique de Jussieu  for statistical expertise; to  Ghislaine Guigon  from  Genotyping of pathogens and Public health (Institut Pasteur ) for bioinformatics expertise; to  Laurence Ma  for Illumina library preparation and sequencing; to  Claudine Medigue  and  Stephane Cruveiller  and  David Roche  from the Genoscope for the MAGE platform facilities and for technical assistance in genome scaffolding. We are grateful to the association " Vaincre la Mucoviscidose " for initial support for this work. We would also like to thank 3 anonymous reviewers for their comments that helped us to improve the manuscript.
Improved methodologies could also advance research and decision making by shedding light on where the data are sufficiently strong to inform policy decisions and where new data are needed. In Section III we present a framework for the systematic review of EDC studies. The framework we have developed can be used to identify substances as EDCs according to the IPCS/WHO definition. This process also assesses the strength of evidence associating an EDC with a health or environmental outcome. Each stream of evidence (mechanistic in vitro, laboratory animal, ecotoxicology, epidemiology) is evaluated first individually and then collectively, using the principles of toxicology, epidemiology and endocrinology  [41]. EDC data are often derived from multiple lines of evidence, and these different types of data need to be evaluated and integrated carefully.
2 ). It maps out the number of included and excluded records identified, and the primary reasons for exclusions at the full text level  [61]. Step 3A: Performing searches The goal of the search strategy is to provide a systematic, objective, reproducible and comprehensive search of the literature relevant to the objective of the review. This is a key feature in clinical systematic reviews and a key step in reducing bias in the overall evaluation  [27]. The goal and steps of the search strategy are defined in the protocol. Decisions about the scope of the search are also made, including the databases to be searched and the types of data that will be considered. For example, during the database search stage, decisions should be made about what type of literature should be considered, e. g. peer-reviewed articles, agency reports, consultancy and industry studies, and other proprietary data.
Other sources of information may come from publicly available databases, such as the US National Toxicology Program (NTP)'s Tox21 and US EPA's ToxCast high-throughput screening platforms. These results may be very relevant to EDCs so they should be considered for inclusion in the protocol. The literature search should be developed and performed in consultation with a specialist, in particular a trained librarian or a person experienced in systematic review. Others involved in this process include the evaluation team and, as needed, subject matter experts. Typically, the search strategy is developed by: (1) identifying PubMed's Medical Subject Headings (MeSH) for relevant and appropriate terms,  (2)  extracting key terminology from relevant reviews and a set of previously identified primary data studies that are known to be relevant to the topic, identified in consultation with the expert team, and (3) reviewing search strategies presented in other reviews.
The search strategy may be tailored to make it suitable to other non-PubMed databases such as Web of Science, Scopus, etc. In these circumstances a number of related search strategies might exist, each designed for a specific database. The search strategy, date of search, and publication dates included in the search should be documented with sufficient detail so that the search can be reproduced, although replication of the exact search results may not be possible as databases change over time. It may be useful to update the literature search at a specified time interval during the evaluation, to capture literature published during the course of the evaluation. This should be defined in the study protocol, perhaps conditionally (e. g. if the review is not completed within 12 months of the search, a further search will be performed).