dataesr/scientific-paragraphs-categorization huggingface dataset:
After culturing the bacteria in liquid medium supplemented with ampicillin, the plasmids were extracted using the Gene JET Plasmid Miniprep Kit (ThermoScientific, Waltham, MA, USA) following the manufacturer's instructions and sequenced. Sequencing was performed using M13 primers, as well as specific internal primers designed from the isolates sequenced in 2015. The sequences determined in this work have been deposited in the NCBI database with accession numbers MH644778 to MH644788 and MH680947 to MH680958.
Analysis of Sequences A search for complete sequences in the NCBI database was performed using the BLAST tool  [52]. Nucleotide identities between sequence pairs were calculated using the SDT program v1. 2  [32]. In this analysis, we included sequences from the seven strains that make up the TYLCV species, and a sequence from a Spanish isolate of the TYLCSV species. A set of 60 complete sequences was generated including the complete sequences determined in this work and representative sequences of the TYLCV strains, which was edited manually and aligned with the MUSCLE tool included in MEGA7  [53]. In addition, a second set of sequences was generated with those obtained in this work, which was also edited and aligned with MEGA7  [53]. A phylogenetic analysis was carried out with both sets of sequences for which maximum likelihood phylogenetic trees were constructed using the Tamura-Nei TN93 + G model  [54] , chosen as the best nucleotide substitution model according to MEGA7  [53]  and a bootstrap of 1000.
Trees were edited using the TreeGraph2 program  [55] , where the branches with a bootstrap value lower than 50% were collapsed. An additional alignment was made with Spanish partial sequences available in the databases  [16] , the sequences obtained in this article, using MEGA7  [53]. With this set of 61 sequences, another phylogenetic analysis was carried out in which a phylogenetic tree of maximum likelihood was constructed with the Tamura-3 parameters T92 + G model  [56] , chosen in this case as the best model of nucleotide substitution by MEGA7  [53]  and a bootstrap of 1000. A tree of partial sequences was constructed with the same model of phylogenetic reconstruction but including only the sequences determined in this work. A Bayesian analysis was performed using the Beast v. 1. 8. 4 program  [57].
4. 3. Genetic distances between and within populations were estimated using the Kimura 2-parameter method  [59]  implemented in MEGA7  [53] , and the calculation of the ratio of synonymous and nonsynonymous substitutions between sequence pairs was carried out using the Pamilo-Bianchi-Li method  [35, 36]. For both calculations, the associated standard error was computed with the bootstrap method with 500 replicates. An analysis was also carried out to find out possible recombination patterns in the new sequences with the RDP program  [60] , using the default program parameters.
(2016)   [27]. The optimal concentration was determined for the pair that amplified the TYLCV-Mu15 DNA, which was also 300 nM. PCR conditions: Initial denaturation of 10 min at 95 • C, followed by 40 cycles of 10 s at 95 • C, 40 s at 63 • C for TYLCV-IL and TYLCV-Mu15, 20 s at 60 • C for TYLCV-IS76 and 25S, and 15 s at 72 • C. The viral genome copy number was calculated from standard curves made with dilutions of the plasmids in base 10 (10 9 -10 2 copies). The fluorescence data obtained were analyzed with the LinReg program  [63] , which calculates the initial concentration of the target per sample (N o ) from the fluorescence threshold for each target (F t ), the average of the efficiency of the PCR (E mean ) and the number of cycles necessary to reach that threshold (C t ). The N o values were transformed from fluorescence values to DNA copy number.
Statistical Analyses Statistical analyses were performed using the Statgraphics plus 5. 1 program (Manugistics, Inc. , Rockville, MD, USA). To determine the statistical significance of the virus accumulation data between treatments at 10 and 30 dpi, expressed as the logarithm of no. of copies, and the measurements of the plants made at 30 dpi, the Kluskal-Wallis test was used. To determine the statistical significance of the differences between treatments for the same clone (simple and mixed infections), the Wilcoxon test was used.
Figure5. Maximum clade credibility tree reconstructed from the Spanish, Moroccan, and selected Tomato yellow leaf curl virus strain Israel (TYLCV-IL) nucleotide sequences dataset. The genomic region recombined in TYLSV-IS76 isolates was excluded from the alignment. Each taxon was named according to the GenBank accession number of its sequence except the taxa identified in this study, which were named with their sequence codes (Table1). The time-scale is indicated below the tree. Node labels correspond to posterior probability support values (values below 40% are not shown). The branches supporting the El Jadida/Murcian Group 2 clade are colored in red. Node B corresponds to the most recent common ancestor of the parental genome of El Jadida/Murcian Group 2 and node A to the most recent common ancestor of TYLCV-IS76 Moroccan recombinants and El Jadida/Murcian Group 2.
Acknowledgments: We thank  Pedro Gómez  and  Cristina Alcaide  ( CEBAS-CSIC, Murcia, Spain ) for their help with the RCA-HTS analysis of 2015 samples,  Maria del Carmen Montesinos  ( CEBAS-CSIC, Murcia, Spain ) and  Yesica Navarro  ( Abiopep S. L. , Murcia, Spain ) for their technical assistance and  Mario Fon  (mariogfon@gmail. com)for editorial assistance.
Research in M. A. A. , C. U. and M. P labs was funded by the  Ministry of Economy, Industry, and Competitiveness of Spain , grant number  PCIN-2017-055 , and  Agence Nationale de la Recherche of France , respectively, both within the  ERANET-ARIMNet2 (ref. 302) program. J. A. and C. G. -A. were recipients of grants  PTQ-13-05882  and  PTQ-15-07646 , respectively, from the  Torres-Quevedo program (Ministry of Economy, Industry and Competitiveness; Spain) , and C. T. of fellowship  DI-14-06825  from the  Industrial Doctoral program  ( Ministry of Economy, Industry, and Competitiveness, Spain).
Acknowledgements. This research is supported by the  National Research Foundation of Singapore  under its  Campus for Research Excellence and Technological Enterprise programme. The Center for Environmental Sensing and Modeling is an interdisciplinary research group of the  Singapore-MIT Alliance for Research and Technology. This research is also supported by the  U. S. National Science Foundation  ( AGS-1339264 ) and the  U. S. Department of Energy, Office of Science  ( DE-FG02-94ER61937 ). The  CESM  project is supported by the  National Science Foundation  and the  Office of Science (BER)  of the  U. S. Department of Energy. We acknowledge high-performance computing support from Cheyenne (https://doi. org/10. 5065/D6RX99HX )provided by  NCAR's Computational and Information Systems Laboratory , sponsored by the  National Science Foundation.
Code and data availability. CESM 1. 2. 2 is available via http://www. cesm. ucar. edu/models/cesm1. 2/ (last access: 29 October 2018). The version of MARC used in this study is MARC v1. 0. 4, archived at https://doi. org/10. 5281/zenodo. 1117370 (Avramov et al. , 2017). Model Namelist files, configuration scripts, and analysis code are available via https://github. com/grandey/p17c-marc-comparison/, archived at https://doi. org/10. 5281/zenodo. 1346707 (Grandey, 2018a). The MARC input data and the model output data analysed in this paper are archived at https://doi. org/10. 6084/m9. figshare. 5687812 (Grandey, 2018b).
Data were acquired and analyzed using Chemstation software (Agilent, Les Ulis, France). Do taxel and paclitaxel typical retention times were 11 and 13. 5 minutes, respectively. Encapsulation rate for docetaxel was calculated using the following formula: Encapsulation rate mg DOCE HPLC measured mg DOCE initially = u used × 100. Entrapment efficiency for docetaxel was calculated using the following formula: Entrapment efficiency mg DOCE HPLC measured mg DOCE present = before centrifugation × 100.
Acknowledgments The authors would like to thank the platform  Amuticyt (VRCM) de la faculté de Pharmacie La Timone  and the  Service Commun de Microscopie Électronique de la Faculté de Médecine La Timone  for their technical expertise. The authors would also like to thank the  Ligue Contre le Cancer  who generously provided a grant to AR. Additionally, we thank the  French Institut Roche  who partly supported this study and  Genentech  who kindly provided trastuzumab.
Consultation by the editorial board or interested researchers may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations. To transfer the data to another structure, a specific request for authorization must be made to the CNIL (https://www. cnil. fr/fr/ declarer-un-fichier). To be more precise, the path to follow is: 1-Interested researchers request the unit responsible for data processing: kevin. zarca@aphp. fr or secretariat@urc-eco. fr 2-URC Eco fills a request for modification of the initial authorization for the new recipient to the CNIL 3-URC Eco gets the authorization and sends the data to the new recipient This process is accessible for both reviewers and other interested researchers after publication.
Effectiveness Data were collected in both centers (CHSF and Port-Royal) during both periods (before and after). The following variables were recorded: sex, birth date, GA, birth weight, height and head circumference, dates of entry and discharge from NICU, date of eye examination, procedure (tele-expertise or usual care) and destination at hospital discharge (transfer to another center, return home, death). The primary outcome was the proportion of infants having a ROP screening within the guidelines of the American Academy of Pediatrics  [4]. We considered that examination satisfied the primary outcome if it occurred at the theoretical recommended date +/-6 days. The secondary endpoint was deviation from guidelines computed as the interval between recommended and effective date of examination.
Trial registration and ethics approval Clinicaltrials. gov: NCT02157727 The ethics approval was given by the "ComiteConsultatif sur le Traitement de l'Information en matière de Recherche dans le domaine de la Sante" (CCTIRS), number 15. 162. It approved the lack of parent or guardian consent in the decision, as every effort has been made to provide information to parents. Data were fully unidentified prior access to authors.
Patient perspective Data on pain during examination were collected for 56 infants (13 in Port-Royal and 43 in the CHSF center). For 2 infants, data were missing. Characteristics of infants according to the center are detailed in Table  5. No significant differences regarding distributions by GA at birth, or birth and weight at examination date observed between the Port-Royal and the CHSF medical centers (Table  2 ). Drug and non-drug treatments were almost systematically administrated for eye examination with the RETCAM. Median pain score evaluated during examination was.
The selected time points represent sub-lethal proteotoxic stress conditions, at which the cell viability is not yet compromised (Fig. S2A ). Before mRNA purification, the knock-out phenotype was confirmed with immunoblotting (Fig. S2B ). Notably, stress-inducible hyperphosphorylation of HSF1  [47]  and increased HSP70 expression were observed in both WT and 2KO cells (Fig. S2B ). To identify the HSF2-dependent target genes, we first compared the inducible gene expression profiles between WT and 2KO cells in response to 6 h and 10 h BTZ treatment (Fig. 2A ). Differentially expressed (DE) genes were determined with the Bioconductor R package Limma  [48] , with fold change ≥ 3 and false discovery rate (FDR) < 0. 001, from quadruplet samples that correlated well to each other (Fig. S2C ). According to the analysis, BTZ treatment resulted in a significant upregulation and downregulation of genes in WT (> 600 and > 300, respectively) and 2KO (> 500 and > 200, respectively) cells (Fig.
2B , Table  S1 ). The complete dataset is available at Gene Expression Omnibus under accession number: GSE115973. The HSF-regulated heat shock response is one of the main cellular survival pathways induced by proteotoxic stress and it is characterized by simultaneous upregulation of multiple genes essential for maintaining the correct protein folding environment  [1, 4]. To examine whether the heat shock response is compromised in 2KO cells, we analyzed the inducible expression patterns of all human molecular chaperone genes  [49] , in WT and 2KO cells treated with BTZ. Intriguingly, the chaperone expression profiles of WT and 2KO cells were nearly identical, and only HSPB2, DNAJC1,2 and DNAJC18 exhibited clearly distinct expression patterns in 2KO cells (Fig. 2C ). A closer examination of the RNA-seq data for the expression of selected chaperone genes, i.
CRISPR-Cas9 Guide RNAs (gRNA) targeting the exon 1 of HSF2 were designed using CRISPOR software (http://crispor. tefor. net/) and cloned into pMLM3636 gRNA expression plasmid (a gift from Keith Joung, Addgene plasmid #43860). U2OS cells were transfected with Cas9 and gRNA expression plasmids using Amaxa electroporation as recommended by the manufacturer (Lonza). The hCas9 plasmid was a gift from George Church (Addgene plasmid #41815). One week after transfections, cells were seeded at single cell density. Clones were genotyped by DNA sequencing of PCR products spanning the targeted region of the HSF2 gene. The selected U2OS clones presented 3 different outframe mutations on HSF2 exon 1, each corresponding to a different allele (Table  S2 ). Guide RNA sequence targeting the 1 st AUG of the HSF2 exon 1: 5´-UGCGCCGCGUUAACAAUGAA-3´.
Bioinformatic analysis The quality of the raw sequencing reads was confirmed with FastQC version 0. 20. 1 and aligned against the hg38 human genome assembly using TopHat2 version 2. 1. 0. Subreads version 1. 5. 0 was used to calculate gene level expression counts according to RefSeq-based gene annotations. The downstream analysis was carried out with R and Bioconductor. The data was normalized with TMM normalization method on the edgeR package. In all sample groups, the Spearman´s correlation value was above 0. 97, indicating high reproducibility. Statistical testing between the sample groups was carried out using Bioconductor R package Limma  [48]  and the differentially expressed genes were filtered using fold change ³ 3 and false discovery rate (FDR) of 0. 001 as cutoff. Enrichment analysis for the differentially expressed (DE) filtered genes was performed with topGO and GOstats packages.
For immunofluorescence, spheroids were washed with 40 µl of PBS and fixed with 25 µl of 4 % PFA for 20 min at room temperature, followed by three washes with 40 µl of PBS. Spheroids were stained with 25 µl of 0. 7 % Triton X-100, 1:500 Alexa Fluor 488 Phalloidin (#A12379, #A22287, Thermo Fisher Scientific), 300 nM DAPI in PBS at room temperature for 1 h. The stained spheroids were stored in PBS at 4 °C until imaging. The spheroids were imaged as z-stacks with a 3i CSU-W1 spinning disc confocal microscope (Intelligent Imaging Innovations) using the same settings between the repeats. Spheroid volume was calculated based on the phalloidin staining using ImageJ v1. 51n  [64]  software with the 3D Object Counter v2. 0 (Bolte and Cordelieres, 2006) plugin. The threshold for background and object voxels was manually adjusted for each image in order to capture the whole volume of each spheroid.
Visualization of the data Heatmaps were generated with GraphPad Prism 7 Software (GraphPad Prism Software, La Jolla California USA, http://www. graphpad. com). Venn diagrams were generated with BioVenn web application (http://www. cmbi. ru. nl/cdd/biovenn/). DAVID Bioinformatic Resources 6. 7 (https://david-d. ncifcrf. gov/home. jsp) was used for functional annotation clustering.
Statistical analysis All statistical analyses were performed with GraphPad Prism 7 Software (GraphPad Prism Software, La Jolla California USA, http://www. graphpad. com). The statistical significance was analyzed with two-way ANOVA and Holm-Sidak's post-hoc test unless indicated differently. Cluster enrichment score for upregulated gene cluster: 4. 39; for downregulated gene cluster: 9. 71. FIGURE LEGENDS Figure Supplement 3.
50 mM HEPES, pH 7. 4, 150 mM NaCl, 1 mM EDTA, 2 mM MgCl2, 1 % Triton X-100, 10 % glycerol, 1 x completeÔ Protease Inhibitor Cocktail (04693159001, Roche Diagnostics), 50 mM NaF, 0. 2 mM Na3VO4]. Protein concentration of the lysates was determined with Bradford assay. Equal amounts of cell lysates were resolved on 4-20 % or 7. 5 % Mini-PROTEAN ® TGX precast gels (Bio-Rad) and the proteins were transferred to a nitrocellulose membrane. For HSF2 detection, membranes were boiled for 15 min in MQ-H2O and blocked in 3 % milk-PBS-Tween20 solution for 1 h at RT. Primary antibodies were diluted in 0. 5 % BSA-PBS-0. 02 % NaN3 and the membranes were incubated in respective primary antibodies overnight at 4 °C. The following antibodies were used: anti-GAPDH (ab9485, Abcam), anti-HSC70 (ADI-SPA-815, Enzo Life Sciences), anti-HSF1 (ADI-SPA-901, Enzo Life Sciences), anti-HSF1 pS326 (ab76076, Abcam), anti-HSF2 (HPA031455, Sigma-Aldrich), anti-HSP70 (ADI-SPA-810, Enzo Life Sciences), N-cadherin (04-1126, Millipore or ab76057, Abcam), anti-PARP-1 (F-2, sc-8007, Santa Cruz Biotechnology), anti-PanPCDHgA (75-178, NeuroMab), and anti-β-Tubulin (T8328, Sigma-Aldrich).
Secondary 16 antibodies were HRP-conjugated and purchased from Promega, GE Healthcare or Abcam. All immunoblotting experiments were performed at least three times. Immunofluorescence 2 x 10 5 U2OS WT cells were plated on coverslips or MatTek plates (P35GC-. 5-14-C, MatTek Corporation) 24 h before treatments. Cells were fixed with 4 % paraformaldehyde (PFA) for 15 min, permeabilized in 0. 1 % Triton-X-100 in PBS and washed three times with PBST (PBS-0. 5 % Tween20). Cells were blocked with 10 % FBS in PBS for 1 h at room temperature and incubated overnight at 4 °C with a primary anti-HSF2 antibody (HPA031455, Sigma-Aldrich), which was diluted 1:20 in 10 % FBS-PBS. Secondary goat anti-rabbit Alexa Fluor 488 (R37116, Invitrogen) was diluted 1:500 in 10 % FBS-PBS and the cells were incubated for 1 h in RT.
ACKNOWLEDGEMENTS We are grateful to  Joshua Weiner  ( University of Iowa, Iowa, US ) for helpful discussions and advice and for providing us with the anti-PanPCDHgA antibody. All members of the  Sistonen laboratory  and  Véronique Dubreuil  from the  Mezger  laboratory are thanked for their valuable comments and critical review of the manuscript. Imaging was performed at the  Cell Imaging Core, Turku Centre for Biotechnology, University of Turku  and  Åbo Akademi University. The instruments used in this project belong to the infrastructure of  Biocenter Finland. We especially thank  Markku Saari  and  Jouko Sandholm  from the  Cell Imaging Core of Turku Centre for Biotechnology  for technical assistance and advice. The  Bioinformatics unit of Turku Centre for Biotechnology  is acknowledged for their expert assistance with the RNA-sequencing data analysis.
FUNDING This study has been funded by The  Academy of Finland (LS) ,  Sigrid Juselius Foundation (LS) ,  Turku Doctoral Network in Molecular Biosciences  (JJ, AJDS, JCL),  Finnish Cultural Foundation (JJ) ,  Cancer Foundation Finland sr (JJ, LS) ,  Åbo Akademi University Research Foundation  (JJ, MB), Tor, Joe and  Pentti Borg Memory Foundation (JJ) ,  Ida Montin´s Foundation (JJ) ,  Otto A. Malm Foundation (JJ) , the  Medical Research Foundation Liv och Hälsa (JJ), K. Albin Johansson´s Foundation (JJ, AJDS) ,  Center for International Mobility (AJDS) ,  Agence Nationale Recherche  ( Program SAMENTA   ANR-13-SAMA-0008-01 ) (ADT, VM, DSD),  Short Researcher Mobility France Embassy/MESRI-Finnish Society of Science and Letters (VM) , and  CNRS/Project International de Coopération Scientifique  PICS 2013-2015 (ADT, VM, DSD).
[ 50 mM HEPES, pH 7. 4, 150 mM NaCl, 1 mM EDTA, 2 mM MgCl2, 1 % Triton X-100, 10 % glycerol, 1 x completeÔ Protease Inhibitor Cocktail (04693159001, Roche Diagnostics), 50 mM NaF, 0. 2 mM Na3VO4]. Protein concentration of the lysates was determined with Bradford assay. Equal amounts of cell lysates were resolved on 4-20 % or 7. 5 % Mini-PROTEAN ® TGX precast gels (Bio-Rad) and the proteins were transferred to a nitrocellulose membrane. For HSF2 detection, membranes were boiled for 15 min in MQ-H2O and blocked in 3 % milk-PBS-Tween20 solution for 1 h at RT. Primary antibodies were diluted in 0. 5 % BSA-PBS-0. 02 % NaN3 and the membranes were incubated in respective primary antibodies overnight at 4 °C. The following antibodies were used: anti-GAPDH (ab9485, Abcam), anti-HSC70 (ADI-SPA-815, Enzo Life Sciences), anti-HSF1 (ADI-SPA-901, Enzo Life Sciences), anti-HSF1 pS326 (ab76076, Abcam), anti-HSF2 (HPA031455, Sigma-Aldrich), anti-HSP70 (ADI-SPA-810, Enzo Life Sciences), N-cadherin (04-1126, Millipore or ab76057, Abcam), anti-PARP-1 (F-2, sc-8007, Santa Cruz Biotechnology), anti-PanPCDHgA (75-178, NeuroMab), and anti-β-Tubulin (T8328, Sigma-Aldrich).
RNA-Seq pipeline The pipelines used for the analysis of the RNA-Seq data are available on GitHub (https://github. com/kerrimalone). Computational analyses were performed on a 32-node Compute Server with Linux Ubuntu [version 12. 04. 2]. Briefly, pooled libraries were deconvoluted, adapter sequence contamination and paired-end reads of poor quality were removed using cutadapt [v1. 13] (Phred > 28) 40 and the filterbytile. sh script from the BBMap package 41. At each step, read quality was assessed with FastQC [v0. 11. 5] 42. Paired-end reads were aligned to the Bos taurus reference genome (B. taurus UMD 3. 1. 1) with the STAR software  43. Read counts for each gene were calculated using featureCounts, set to unambiguously assign uniquely aligned paired-end reads in a stranded manner to gene exon annotation (B.
taurus UMD 3. 1. 1 GCF_000003055. 6)  44. Differential gene expression analysis was performed using the edgeR Bioconductor package that was customised to filter out all bovine ribosomal RNA (rRNA) genes, genes displaying expression levels below one count per million (CPM) in at least four individual libraries and identify differentially expressed (DE) genes correcting for multiple testing using the Benjamini-Hochberg method with a log 2 fold change (log 2 FC) greater than 1/less than -1 and a False-Discovery Rate (FDR) threshold of significance ≤ 0. 05 45. DE gene expression was evaluated between M. bovis and M. tuberculosis infected animals for unstimulated blood samples (unpaired statistics) for each time point in addition to between unstimulated and PPD-B-stimulated blood samples for the M.
05) (*). (C) Pathway enrichment analysis results for 658 genes that are significantly differentially expressed (-1 > log 2 FC < 1, FDR < 0. 05) in PPD-B stimulated whole blood samples from both M. bovis AF2122/97-and M. tuberculosis H37Rv-infected animals at both 14 and 42 days post infection in comparison to unstimulated whole blood samples. The graph depicts the association of each pathway with the differentially expressed gene list based on the SIGORA successes metric (circle size) and the number of genes annotated within the pathway ("#genes in pathway") while the colour bar depicts the significance of the association (Bonferroni < 0. 05). (D) The relative expression (transcripts per million, TPM, "log(TPM +1)") and the relative change in expression (log 2 fold change ("Log 2 FC")).
Funding Sources We gratefully acknowledge funding from: the  European Commission 's  Seventh Framework Programme  ( FP7 ,  2007 ( FP7 , -2013) )  Research Infrastructures Action  under the grant agreement No. FP7-228394  ( NADIR  project);  EC H2020 program  grant number  643381  ( TBVAC2020 );  Wellcome Trust  grant number  075833/A/04/Z  under their "Animal health in the developing world" initiative;  Wellcome Trust  PhD awards  097429/Z/11/Z  (K. R-A. ) and  102395/Z/13/Z  (A. S. );  Science Foundation Ireland   Investigator Award   08/IN. 1/B2038 (SG).