dataesr/scientific-paragraphs-categorization huggingface dataset:
The first U. S. indel strain, named OH851, was described in January 2014  (10) , and another PEDV indel variant named USA/Indiana 12. 83/2013 was described in June 2013, suggesting that highly pathogenic strains and indel strains were introduced at the same time in the United States  (7). According to our results, it appears that the French and German PEDV isolates are more related to the USA/Indiana 12. 83/2013 strain than to the USA/OH851/2014 isolate. This might suggest that indel strains circulate in Europe for a longer time than was previously hypothesized, a time that might even be contemporary to the introduction of PEDV to the United States around mid-2013. Nucleotide sequence accession number. The PEDV FR/001/ 2014 genome sequence has been deposited in GenBank under the accession no.
Sequencing and Phylogenetic Analysis Sequencing was performed with an ABI PRISM 3100-Avant Genetic Analyzer (PE Applied Biosystems, Foster City, CA, USA) using the ABI PRISM BigDye ® Terminator v 3. 1 Cycle Sequencing Kit (PE Applied Biosystems, Foster City, CA, USA). Sequences were checked for possible chimeric origin using the Bellerophon software  [34]. Initial alignment of amplified sequences and close relatives identified with BLAST  [35]  were performed using the SILVA alignment tool  [36]  and manually inserted in ARB  [37]. After alignment, the neighbour-joining algorithm and the Jukes-Cantor distance matrix of the ARB package were used to generate the phylogenetic trees based on distance analysis for 16S rRNA. One thousand bootstrap re-samplings were performed to estimate the robustness of the tree.
Statistical Analysis For statistical analysis, the clones from each library were considered to define phylotypes at 97% similarity  [40, 41]. The presence of library-specific phylotypes was further analysed by a total alignment. Clustering of sequences, rarefaction analysis, taxa, total clones, singletons, dominance, Shannon (H), equitability (E) and Simpson (D) chao1-2 indexes for each clone library were performed using the Dotur program  [42]. Coverage values (C) were calculated to determine the efficiency of the different clone libraries. The coverage value is given as C = 1 -(n1/N), where n1 is the number of clones that occurred only once in the library (singletons )  [43]. To study the influence of depth on prokaryotic biodiversity at the three different sampling depths, the Primer 6 ecological software package  [44]  was employed to obtain the ANalysis Of SIMilarities (ANOSIM) test from DNA-RNA distance matrix  [45].
, 2012). The second dimension was carried out using the Criterion Dodeca system (Biorad). A minimum of four gels loaded with biological replicates was used for each condition. Criterion any kD TGX gels (Biorad) were run at 10 • C in Laemmli buffer system  (Laemmli, 1970)  at 100 V for 2 h  (Cherrad et al. , 2012). 2Dgels were stained with silver nitrate as described  (Catusse et al. , 2008)  then scanned and analyzed with the software SameSpots v. 5 (Non-linear Dynamics Progenesis). A t-test of the spot volumes was calculated to compare the different treatments. Variations in spot volumes with p < 0. 02 and fold-change >4 were considered significant.
In-gel Digestion of Proteins and Sample Preparation for MS Analysis: Data Acquisition and Database Searching Spots were destained in 25 mM ammonium bicarbonate (NH 4 HCO 3 ), 50% (v/v) acetonitrile (ACN; VWR Chemicals) and shrunk in ACN for 10 min. After ACN removal, gel pieces were dried at room temperature. Proteins were digested by incubating each gel spot with 10 ng/µL of trypsin (T6567, Sigma-Aldrich) in 40 mM NH 4 HCO 3 , 10% (v/v) ACN, rehydrated at 4 • C for 10 min, and finally incubated overnight at 37 • C. The resulting peptides were extracted from the gel in three steps: a first incubation in 40 mM NH 4 HCO 3 , 10% (v/v) ACN for 15 min at room temperature and two incubations in 47. 5% (v/v) ACN, 5% (v/v) formic acid (Sigma) for 15 min at room temperature. The three collected extractions were pooled with the initial digestion supernatant, dried in a vacuum centrifuge (SpeedVac; Eppendorf), and resuspended with 25 µL of 0.
The mass spectrometer operated in positive ion mode at a 1. 9-kV needle voltage and a 4-V capillary voltage. Data acquisition was performed in a data-dependent mode alternating in a single run, a MS scan survey over the range m/z 300-1700 and three MS/MS scans with Collision Induced Dissociation (CID) as activation mode. MS/MS spectra were acquired using a 2-m/z unit ion isolation window, a 35% relative collision energy, and a 0. 5 min dynamic exclusion duration. Mascot and Sequest algorithms through Proteome Discoverer 1. 4 Software (Thermo Fisher Scientific Inc. , USA) were used for protein identification against the Broad Institute Botrytis cinerea database (http://www. broadinstitute. org/annotation/ genome/botrytis_cinerea/MultiHome. html; 16,448 entries;  Amselem et al. , 2011). Two missed enzyme cleavages were allowed.
Mass tolerances in MS and MS/MS were set to 2 Da and 1 Da, respectively. Oxidation of methionine and carbamidomethylation on cysteine were searched as dynamic and static modifications, respectively. Peptide validation was performed using Target Decoy PSM Validator and only "high confidence" peptides were retained corresponding to a 1% false positive rate at peptide level. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium  (Vizcaíno et al. , 2014)  via the PRIDE partner repository (http:// www. ebi. ac. uk/pride/help/archive/about) with the dataset identifier PXD002873.
Bioinformatics The Fungal Secretome Database 3. 0  (Choi et al. , 2010)  was used to collect annotations and signal peptide prediction programs  (Bendtsen et al. , 2004b; Emanuelsson et al. , 2007; Caccia et al. , 2013). SecretomeP 2. 0 (http://www. cbs. dtu. dk/services/ SecretomeP/) was also used to provide information related to non-classical secretory proteins  (Bendtsen et al. , 2004a). Secreted proteins were classified into functional categories as described  (Espino et al. , 2010; Cherrad et al. , 2012).
ACKNOWLEDGMENTS We thank  Marie-Pascale Latorse  ( Bayer CropScience, Lyon ),  Nathalie Poussereau  ( UMR5240 , Lyon),  Cécile Ribot  ( UMR5240 , Lyon) and  Catherine Sirven  ( Bayer CropScience, Lyon ) for helpful discussions. We are grateful to the Reviewers for their helpful comments that have led to important improvements of the original manuscript.
INTRODUCTION Tiotropium (SPIRIVA, Boehringer Ingelheim Pharma & Co KG, Ingelheim am Rhein, Germany) is a once-daily, long-acting, anticholinergic bronchodilator available in two formulations: dry powder via HandiHaler (18 μg once daily) and as an aqueous solution via the Respimat Soft Mist Inhaler (5 μg (two puffs of 2. 5 μg once daily)). 1, 2 Tiotropium HandiHaler 18 μg and tiotropium Respimat 5 μg have demonstrated similar improvements in lung function, symptoms and quality of life  [3] [4] [5] [6]  and have similar pharmacokinetic profiles in patients with chronic obstructive pulmonary disease (COPD). 7 ueries around the safety of Respimat  [8] [9] [10]  were addressed in the TIOtropium Safety and Performance In Respimat (TIOSPIR; NCT01126437) trial  11  -the largest long-term, randomised, doubleblind trial in patients with COPD performed to date.
Interpretation of findings in relation to previously published work COPD is a heterogeneous disease comprising a wide range of clinical phenotypes that may respond differently to treatment. 16 ot all of these phenotypes (particularly patients with mild COPD) are represented within populations included in RCTs. ] [14]  In a comparison of primary care data from the Uncovering and Noting Long-term Outcomes in COPD (UNLOCK) database with six large RCTs of patients with COPD, significant differences were observed with respect to baseline characteristics. 13 Patients included in the RCTs tended to be younger, were predominantly male and had significantly worse lung function and quality-of-life scores than primary care patients. Disparities were also observed with respect to exacerbations: a lower mean exacerbation rate per year and lower number of patients with ⩾ 1 or ⩾ 2 exacerbations Abbreviations: CI, confidence interval; GOLD, Global Initiative for Chronic Obstructive Lung Disease.
On-treatment analysis (from randomisation to drug stop+1 day). Six patients (Respimat 2. 5 μg, one patient; Respimat 5 μg, three patients; HandiHaler 18 μg, two patients) from sites with data irregularities were excluded. being observed in the UNLOCK population. 13 A further interesting observation from the UNLOCK analysis is that patients with GOLD stage I or II COPD comprised 20. 7% and 53. 3%, respectively, of the total UNLOCK population. 13 This compares with a complete absence of patients at GOLD stage I and 45% of patients at GOLD stage II in the combined RCTs, normally caused by exclusion criteria for mild patients. In the TIOSPIR anticholinergic-naive subpopulation, 0. 3% patients were at GOLD stage I (because of the inclusion of patients with an FEV 1 percent predicted of o70%) and 48.
Conclusions In this post hoc analysis, patients with COPD who were naive to anticholinergic treatment had similar efficacy and safety profiles when treated with tiotropium Respimat or HandiHaler in the TIOSPIR trial. This study provides further data that addresses prior safety concerns regarding tiotropium Respimat and provides additional evidence that tiotropium Respimat treatment is also safe for patients who were not previously treated with an anticholinergic, including patients with mild disease more commonly seen in primary care.
ACKNOWLEDGEMENTS Editorial and writing assistance was provided by  Carol A Richter  and  Sarah J Petit  at PAREXEL (funded by  Boehringer Ingelheim ). The TIOSPIR trial and this subsequent post hoc analysis were funded by  Boehringer Ingelheim. support from  AstraZeneca ,  Boehringer Ingelheim ,  Forest Laboratories ,  GlaxoSmithKline  and  Novartis , and grant support to the  University of Texas Health Science Centre from GlaxoSmithKline ; NM, AF and AM are employees of  Boehringer Ingelheim.
Importantly, the molecular studies described herein can greatly benefit from the analysis of public databases. In the recent years, bioinformatic platforms have been developed in order to aid in the analysis of publicly available genomic, epigenomic, transcriptomic and proteomic studies. These platforms now allow quickly browsing through tens of studies (which imply thousands of samples) looking at a gene or pathway of interest. Two outstanding examples of this effort are Oncomine (www. oncomine. org) [26]  and cbioportal (www. cbioportal. org) [27, 28]. These sites allow the researcher to get information about the status of a gene or genes of interest in a given cancer, the mutational landscape throughout different cancers, the epigenetic modifications regulating its expression and the clinical variables associated with its expression.
Acknowledgments Apologies to those whose related publications were not cited due to space limitations. We thank  Paolo Nuciforo ,  Maurizio Scaltriti  and  Pau Castell  for technical advice. David Gil  and  Sandra Delgado  from electron microscopy CIC bioGUNE platform for their technical assistance in the cryo-TEM analysis of EVs. The work of AC is supported by the  Ramón y Cajal award , the  Basque Department of Industry, Tourism and Trade (Etortek) ,  Health  (2012111086) and Education ( PI2012-03 ),  Marie Curie  ( 277043 ),  Movember Foundation  ( GAP1 ),  ISCIII  ( PI10/01484 ,  PI13/00031 ) and  ERC  ( 336343 ). N. M. -M. is supported by the  Spanish Association Against Cancer (AECC). A. A. -A and L. V. -J are supported by the  Basque Government of education. RB is supported by  ISCIII  ( PT13/ 0010/0052 ) and A.
Mobile measurements Due to the high frequency of local contamination events, mobile data was postprocessed by examining video footage recorded at the driver's cabin of the mobile laboratory, based on Drewnick et al. (  2012 ). Measurement periods were omitted from analysis if traffic was identified less than 150 m from the platform; if human activities (e. g. cooking, heating) were spotted; when driving at low speed caused a possible contamination by the vehicle's own exhaust; and when travelling inside tunnels. In order to reduce the amount of contaminated data major roads were avoided. More details concerning the conditioning of mobile measurements presented in this study can be found in von der  Weiden-Reinmüller et al. (2014a). Further analysis of the mobile dataset was conducted based on results from the particle dispersion model FLEXPART performed in forward mode  (Stohl et al.
11. During the summer campaign air ion bursts (of both polarities) for particles of sizes between 2 and 5 nm were picked up by the AIS at SIRTA on a daily basis (Fig. 11 ) with the exception of 29 July. Concentrations of negatively charged particles between 2 and 10 nm were higher by one order of magnitude compared to positively charged. In Fig. 11  we present the NPF categorization based on the negative ions which provided a more sensitive way of identifying nucleation events. During the summer campaign we observed 14 events at SIRTA, 14 at LHVP and 7 at GOLF based on SMPS, DMPS and EAS measurements, respectively. When NPF was identified at SIRTA it also took place at the city center (Fig. 11 ) with one exception (7 July). Due to technical issues of the DMPS, data for five days are not available at the LHVP site.
Supplement related to this article is available online at doi:10. 5194/acpd-15-5663-2015-supplement. Acknowledgements. Parts of the research leading to these results have received funding from the European Union's Seventh Framework Programme FP7 within the project MEGAPOLI, grant agreement no. 212520 and the FP7 IDEAS project ATMOPACS. The research conducted by MPIC was supported by internal funds. Support from the French ANR project MEGAPOLI -PARIS (ANR-09-BLAN-0356) and from the CNRS-INSU/FEFE via l'ADEME (no. 0962c0018) is acknowledged. We are grateful for the logistical support in the field by IPSL/SIRTA, by Labo-Discussion Paper | Discussion Paper | Discussion Paper | ratoire d'Hygiène de la Ville de Paris (LHVP) and by the staff of the Golf Départemental de la Poudrerie. The SAFIRE team is acknowledged and thanked for performing ATR-42 flights and measurementsDiscussion Paper | Discussion Paper | Discussion Paper |.
The Supplement related to this article is available online at doi:10. 5194/acpd-15-5663-2015-supplement. Acknowledgements. Parts of the research leading to these results have received funding from the European Union's Seventh Framework Programme FP7 within the project MEGAPOLI, grant agreement no. 212520 and the FP7 IDEAS project ATMOPACS. The research conducted by MPIC was supported by internal funds. Support from the French ANR project MEGAPOLI -PARIS (ANR-09-BLAN-0356) and from the CNRS-INSU/FEFE via l'ADEME (no. 0962c0018) is acknowledged. We are grateful for the logistical support in the field by IPSL/SIRTA, by Labo-Discussion Paper | Discussion Paper | Discussion Paper | ratoire d'Hygiène de la Ville de Paris (LHVP) and by the staff of the Golf Départemental de la Poudrerie. The SAFIRE team is acknowledged and thanked for performing ATR-42 flights and measurementsDiscussion Paper | Discussion Paper | Discussion Paper |.
For all mammoth samples, the other half of each DNA library was subjected to two more independent rounds of PCR amplification and shipped to the Kurtchatov Institute, Moscow, Russia for sequencing on the GAIIx platform. For the Palaeo-Eskimo Saqqaq sample, both halves of the DNA libraries were amplified independently and sequenced in Denmark. The first position of both pair-ended reads generated in Russia was trimmed due to base calling issues at that position, after checking for DNA damage signature profiles with mapDamage 2  27. All sequence information generated in this study is available for download at the Short Read Archive (Accession Nb. PRJNA260386). Sequence alignment. Sequencing reads were aligned against reference genomes using the PALEOMIX pipeline  49. Seeding was disabled while mapping and two different alignment files were obtained per sample, one without applying a mapping quality threshold (MQ0) and one filtering for a mapping quality above 25 (MQ25 filter).
For equine samples, sequencing reads were aligned against the nuclear chromosomes from the horse reference genome EquCab2  50  and against the horse mitochondrial reference genome (Accession Nb. NC_001640. 1)  51. The sequence data from the Palaeo-Eskimo Saqqaq individual was aligned to the GRCh37/hg19 assembly of the human genome and to the rCRS sequence (Accession Nb. NC_012920) for the mtDNA  52, 53. The scaffolds from the African elephant genome loxAfr3 (Accession Nb. GCA_000001905. 1) and the Mammuthus primigenius mitochondrial sequence from Rogaev and colleagues  54  (Accession Nb. DQ316067) were used for aligning mammoth reads. For mammoth and equine specimens, we used standard mapping parameters, except that the -n option from BWA was relaxed to 0. 03 to compensate for the evolutionary distance to the genomes used as reference.
We also evaluated whether MBD+ and MBDfractions differed in their amount of DNA damage using the two-sample t-test on the posterior means of the damage parameters δ d , δ s and λ. All statistical tests were implemented in R version 3. 0. 1  57. Tests were carried out as three independent statistical comparisons between MBD+ and MBD-fractions on samples carrying at least 2,000 reads and on species with a minimum of three samples: Homo sapiens (HSSR), Mammuthus primigenius (Khroma, Zhenya), Ursus maritimus (PB9, PB25, PB44), and Equus ferus (EQ26, EQ34, EQ36). Read size, GC content and CpG densities. We performed a linear mixed effect analysis to compare MBD+ and MBD-fractions for their size distribution, %CG and CpG densities, all calculated using seqtk comp (available at https://github. com/lh3/seqtk) on collapsed reads.
We used a linear mixed effect model, with the overall mean μ and the fraction type covariate τ i as fixed effects: = µ + τ + ν + ε H : y 1 ijk i j ijk = µ + ν + ε H : y 0 ijk j i jk The within-sample dependence is modeled as the random factor ν j ; furthermore the error ε ijk and the ν j terms are independent and identically distributed, respectively. Mixed effects model fitting was achieved by applying the lmer function (option REML = FALSE) in the R package lme4 (http://cran. r-project. org/ package= achieved lme4). The asymptotic chi-square test was used to assess the statistical significance of the likelihood difference. Linear mixed models were restricted to samples carrying a minimum of 2,000 collapsed reads in each MBD+ and MBD-fractions (one Homo sapiens -the Palaeo-Eskimo Saqqaq individual, twelve samples of Mammuthus primigenius, three samples of Ursus maritimus, three samples of Equus ferus and one sample of Equus lambei).
MBD+ and MBD-microbial profiling. We compared MBD+ and MBD-fractions for their distribution of microbial taxonomic groups and their respective relative abundances. Microbial profiles were obtained using MetaPhlAn (version 1. 7. 7  60  ) as implemented within the metagenomic module of PALEOMIX  49  and as described in Der Sarkissian and colleagues  5  and Schubert and colleagues  49. To limit the impact of false positive identification in downstream analyses, low-abundance taxa (less than 1%) were disregarded. The Shannon diversity index of each microbial profile was computed using genus relative abundance data and the function diversity of the vegan package in R (http://cran. r-project. org/package= vegan). Principal Coordinate Analysis (PCoA) of Bray-Curtis distances among profiles was performed at the genus level using the R function pcoa.
Manhattan distance-based relationships amongst profiles were assessed at the genus level by hierarchical clustering using the R package pvclust  61. The support for each cluster was estimated through p-values (Approximately Unbiased and Bootstrap Probabilities) estimated from 10,000 bootstrap pseudo-replicates. Further statistical comparisons between the microbial profiles of MBD+ and MBD-fractions were carried out using the program LEfSe 30. Consistent differences in taxon abundances were tested using the non-parametric Kruskal-Wallis sum-rank test and the unpaired Wilcoxon test. A linear discriminant analysis also estimated the effect size of taxonomical covariates at the origin of the fraction differences (threshold on logarithmic linear discriminant analysis score for discriminative features = 2.
Acknowledgements This work was supported by the  Danish Council for Independent Research, Natural Sciences (FNU) ; the  Danish National Research Foundation  ( DNRF94 ); " Chaires d' Attractivité 2014 "  IDEX, University of Toulouse ; a  Marie-Curie Career Integration grant  ( FP7 CIG-293845 ); the  International Research Group Program  ( IRG14-08 ),  Deanship of Scientific Research (King Saud University, Saudi Arabia ). CG and LE were supported by  Marie-Curie Intra-European Fellowships  ( FP7-IEF-328024  and  FP7 IEF-302617 ). BS was supported by the  Gordon and Betty Moore Foundation. Equid samples were obtained from the  GNL Quintero  project and the  Natural and Cultural History Museum of the Atacama Desert (Museo de Historia Natural y Cultural del Desierto de Atacama). We thank the  Smithsonian Institution  for allowing us to sample Equus lambei and use its data for this study;  S.
Field Collections and Measurements We obtained blood samples and morphometric data for white-eyes that inhabit the Loyalty Islands Archipelago, 110 km northeast of New Caledonia (fig. 1b ). We collected individuals from the three white-eye taxa of Lifou (167 30 0 E, 20 45 0 S), all of which are endemic to the island: The Lifou silvereye (Z. lateralis melanops), the small Lifou white-eye (Z. minutus), and the large Lifou white-eye (Z. inornatus). We additionally collected a different subspecies of silvereye (Z. lateralis nigrescens) found in Ouvea Island (166 30 0 E, 20 30 0 S) and also in the Loyalty Islands. Birds were caught using mist nets during October-December 2011; blood samples were taken via venipuncture from the subbrachial wing vein of each bird and stored either in 95% ethanol, Queen's lysis buffer, or RNAlater.
Genome Annotation Repetitive sequences in the Zosterops genome were identified and masked with RepeatMasker 4. 0. 5  (Smit et al. 2010)  and RepBase  (Jurka et al. 2005 ) using repeat regions from the chicken genome as a reference. The MAKER 2. 10 pipeline  (Cantarel et al. 2008)  was used for genome annotation with a combined strategy of homology-based and ab initio gene prediction approaches. For the homology-based approach, we aligned protein sequences from chicken, turkey, and zebra finch to the translated nucleotide sequences from Zosterops using TBLASTN  (Kent 2002)  and Exonerate  (Slater and Birney 2005). For the ab initio approach, the SNAP software  (Korf 2004 ) was used to generate a consensus gene set with evidence-based quality values. Only genes with Annotation Edit Distance (AED) score less than 1 were extracted for further analysis.
The final list of genes was then annotated using BLASTP  (Camacho et al. 2009 ) against the NCBI (National Center for Biotechnology Information) nonredundant protein database with matches restricted to the four avian species used for comparative genomics (chicken, turkey, zebra finch, peregrine falcon) with an e-value threshold of 1 Â 10 À5. BLAST2GO  (Conesa et al. 2005)  was then used to extract gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes annotations for our genes.