dataesr/scientific-paragraphs-categorization huggingface dataset:
IMGT/2Dstructure-DB uses the IMGT/3Dstructure-DB informatics frame and interface which allow one to analyse, manage and query IG, TR and MH, as well as other IgSF and MhSF and engineered proteins (FPIA, composite proteins for clinical applications (CPCA)), as polymeric receptors made of several chains, in contrast to the IMGT/LIGM-DB sequence database that analyses and manages sequences individually  (7). The AA sequences are analysed with the IMGT R criteria of standardized identification  (44) , description  (45) , nomenclature  (46)  and numerotation  (47) (48) (49) (50) (51) (52). The current IMGT/2Dstructure-DB entries include AA sequences of antibodies from Kabat (70) (those for which there were no available nucleotide sequences), and AA sequences of mAb and FPIA from the WHO-INN programme  (12, 39, 40).
IMGT/mAb-DB. A new database and interface, IMGT/mAb-DB  (12) , http://www. imgt. org, has been developed to provide an easy access to therapeutic antibody AA sequences (links to IMGT/2Dstructure-DB) and structures (links to IMGT/3Dstructure-DB, if 3D structures are available) (Figure  2 ). IMGT/mAb-DB data include monoclonal antibodies (mAb, INN suffix -mab) (a -mab is defined by the presence of at least an IG variable domain) and fusion proteins for immune applications (FPIA, INN suffix -cept) (a -cept is defined by a receptor fused to a Fc) from the WHO-INN programme  (39, 40). This database also includes a few CPCA (e. g. protein or peptide fused to a Fc for only increasing their half-life, identified by the INN prefix ef-) and some RPI used, unmodified, for clinical applications.
The IMGT R databases and tools, and implicitly IMGT R reference directories, are widely used in clinical applications. Thus, IMGT/V-QUEST is frequently used by clinicians for the analysis of IG somatic hypermutations in leukemia, lymphoma and myeloma, and more particularly in chronic lymphocytic leukemia (CLL)  (16, 71)  in which the percentage of mutations of the rearranged IGHV gene in the VH of the leukemic clone has a prognostic value for the patients. For this evaluation, IMGT/V-QUEST is the standard recommended by the European Research Initiative on CLL for comparative analysis between laboratories  (71). The sequences of the V-(D)-J junctions determined by IMGT/JunctionAnalysis  (19, 20)  are also used in the characterization of stereotypic patterns in CLL and for the synthesis of probes specific of the junction for the detection and follow-up of minimal residual diseases (MRD) in leukemias and lymphomas.
A new era is opening in hemato-oncology with the use of NGS for analysis of the clonality and MRD identification, making IMGT R standards use more needed as ever. More generally, the IMGT/HighV-QUEST web portal is a paradigm for identification of IMGT clonotype diversity and expression in NGS immune repertoire analysis of the adaptive immune response in infectious diseases, in vaccination and for next generation repertoire immunoprofiling  (24). The IMGT R reference directory databases behind these tools are key to provide standardized results. The therapeutic monoclonal antibody engineering field represents the most promising potential in medicine  (64). A standardized analysis of IG genomic and expressed sequences, structures and interactions is crucial for a better molecular understanding and comparison of the mAb D420 Nucleic Acids Research, 2015, Vol.
43, Database issue specificity, affinity, half-life, Fc effector properties and potential immunogenicity. IMGT-ONTOLOGY concepts have become a necessity for IG loci description of newly sequenced genomes, antibody structure/function characterization, allotypes in relation with molecular and structural analysis  (72) (73) (74) , antibody engineering (single chain Fragment variable (scFv), phage displays, combinatorial libraries) and antibody humanization (chimeric, humanized and human antibodies)  (32, 33, 35, (63) (64) (65) (66). IMGT R standardization allows repertoire analysis and antibody humanization studies to move to novel high-throughput methodologies with the same high-quality criteria. The CDR-IMGT lengths are now required for mAb INN applications and are included in the WHO-INN definitions  (40) , bringing a new level of standardized information in the comparative analysis of therapeutic antibodies.
ACKNOWLEDGEMENTS We are grateful to all the previous members of the  IMGT R team , for their expertise and constant motivation. We thank  Cold Spring Harbor Protocol Press  for the pdf of the IMGT Booklet available in IMGT references. IMGT R is a registered trademark of CNRS. IMGT R is member of the  International Medical Informatics Association (IMIA). FUNDING IMGT R was funded in part by programmes of the  European Union (EU) :  BIOMED1 [BIOCT930038]; Biotechnology BIOTECH2 [BIO4CT960037 ]; 5th  PCRDT Quality of Life and Management of Living Resources  [ QLG2-2000-01287 ]; 6th  PCRDT Information Science and Technology [ImmunoGrid ,  FP6 IST-028069 ]. IMGT R is currently supported by the  Centre National de la Recherche Scientifique (CNRS) ; the  Ministère de l'Enseignement Supérieur et de la Recherche (MESR) ; the  Université de Montpellier, France ; the  Agence Nationale de la Recherche (ANR)   Labex MabImprove  [ ANR-10-LABX-53-01 ];  BioCampus Montpellier ;  Région Languedoc-Roussillon  ( Grand Plateau Technique pour la Recherche (GPTR) ).
This corresponds well with the response of S. cerevisiae, where. 2,000 genes have altered expression in anaerobic conditions  [60]. We used DAVID (Database for Annotation, Visualization and Integrated Discovery) to identify enrichment of specific categories among the differentially expressed genes  [61]. DAVID applies several categorization tools, incorporating annotation categories that include Gene Ontology assignments, KEGG metabolic pathways, and InterPro database of protein families and domains. Genes upregulated in hypoxia are enriched for categories associated with membrane structure, ion binding and oxidoreductase activity (Table  1 ). Notably, transcription factors are also significantly overrepresented in genes upregulated in hypoxia (Table  1 , Table  S6 ). Expression of 78 genes with potential transcription factor activity is upregulated, including both YlUPC2 and YlSRE1 (Table     [58, 62] , is among the genes with the highest fold induction.
Calcofluor White staining For liquid cultures, cells from a single colony on SC medium were incubated in 10 ml YPD or SC media and 1% Tween 80-EtOH (vol:vol = 1:1) where indicated, and incubated at 28uC and 21% O 2 or 1% O 2 overnight. The cultures were washed, resuspended in PBS and 5 ml was mixed with 5 ml of 0. 2 mM Calcofluor White (dissolved in 10 mM NaOH) and mounted on a glass slide with coverslip. Cells from colonies on solid media after 2 days growth were washed in PBS, resuspended in 100 ml PBS, and stained as above. Cells were observed under UV fluorescence and photographed using a ColorView II camera mounted on a Zeiss AxioImager M1 fluorescent microscope using axiovision software.
One of 3 index adaptors (i6, i10 or i11, Table  S4 ) was ligated to the samples to allow multiplexing. Adapters were ligated by mixing 25 ml of 26 Quick DNA Ligase Buffer (NEB), 1 ml (15 mM) of the specific adaptor mix, and 3 ml Quick T4 DNA Ligase with library samples. Ligations were carried out for 15 min at 20uC. The DNA was purified with a QIAquick PCR purification kit and MinElute column. The DNA was eluted with 10 ml EB. Sequencing was carried out in-house on an Illumina Genome Analyzer IIx according to manufacturer's instructions, resulting in read lengths of approximately 42 bases. For four samples (Table  S5 ) libraries were generated and sequenced by GATC using an Illumina HiSeq 2000. All data has been submitted to Gene Expression Omnibus and is available at accession number GSE47433.
Read mapping and expression analysis Gene annotations were obtained from Genolevures and manually curated using RNAseq data by the Neuveglise group. In-house reads were processed according to version 1. 8 of Illumina's Genome Analysis Pipeline. Multiplexed samples were separated using a Perl script and quality was tested using FASTQC (http://www. bioinformatics. babraham. ac. uk/projects/ fastqc/). Each sample dataset was aligned to the 6 Y. lipolytica chromosomes using TopHat  [86]. Reads mapped to two or more locations were removed from analysis. Data were visualized using the Artemis genome browser  [87]. Raw counts of reads mapped to genes were calculated using HT-Seq. These were used as input for differential gene expression analysis using DESeq, with a P-value cutoff of , = 0. 05 and LogFC cut off of.
= 1  [59]. Differentially expressed gene lists were analyzed using the online DAVID functional annotation tool  [61]  with the Y. lipolytica gene background and default settings (Classification Stringency: Medium). Gene Ontology (GO) FAT terms, KEGG Pathways, InterPro and Swiss-Prot databases were selected for functional annotation clustering. Hierarchical cluster analysis implemented in R was used to identify genes with shared and different expression patterns in the wild type, Ylsre1 deletion and Ylupc2 deletion when exposed to hypoxia. Genes that were differentially expressed in at least one comparison were clustered, using the log 2 fold change values generated from DESeq analysis. Hierarchical cluster analysis implemented in R (http://www. R-project. org) was used to identify genes with shared and different expression patterns in the wild type, Ylsre1 deletion and Ylupc2 deletion when exposed to hypoxia.
Promoter motif analysis The Upc2 binding site motif  [89]  was downloaded from the JASPAR database (http://jaspar. genereg. net/) [90]  and used as input for tffind (http://globin. cse. psu. edu/dist/tffind/) to scan promoter regions from each genome (Table  2 ) using a cut off of 0. 95 (95% confidence). A one-tailed Fisher exact test was performed to compare the enrichment among ergosterol pathway genes relative to the background group (rest of promoter regions in genome containing a motif). The number of binding sites per promoter was not considered. Fisher exact tests were calculated using the R Statistics package (http://www. r-project. org).
Phylogenetic analysis SREBP-like proteins were retrieved from the NCBI protein database using BLASTP with human SREBPF1, Schizosaccharomyces pombe Sre1, and Cryptococcus neoformans CNJ02310 as queries. Only proteins containing the atypical Tyr residue were retained. Sequences were imported into SeaView  [91]  for downstream analyses. Sequences from orthologous clades were aligned using MUSCLE  [92] , after which these clades were profile-aligned with each other using ClustalW2  [93]. Phylogenetic trees were constructed from the bHLH region of the alignment with PhyML, using the LG substitution model with four rate classes. Similar methods were used to construct phylogenetic trees for Upc2 and Scap proteins. Transmembrane helices were predicted using the TMHMM server (http://www. cbs. dtu. dk/services/TMHMM/) [94]  and protein domains were predicted using Pfam  [41].
rouxii. The sterol-sensing domain of SCAP has been lost in all species of the CTG clade including C. albicans. The Scap gene is also missing from the Eurotiomycetes within the Pezizomycotina. (PDF) Figure  S6  Details of the phylogenetic tree in Figure  1C. The tree has been rooted using the human SREBPF1/2 sequences. Protein sequences are identified by their NCBI gene identifier (gi) numbers except for sequences that were taken directly from the CGOB and YGOB databases  [95]. Branch support values are aLRT (approximate likelihood ratio test) values from PhyML as implemented in SeaView  [91]. (PDF).
Moreover, dasatinib is being investigated in diffuse large B-cell lymphoma (DLBCL) and other NHL, multiple myeloma (MM) and in CLL in combination with chemotherapy (fludarabine) or anti-CD20 mAb (rituximab) (Phase 1/2 clinical trials NCT00949988 and NCT01173679, respectively). CD20 is a membrane protein expressed on the surface of normal and malignant B-cells. It is an excellent molecular target for mAbs that are widely used in the treatment of NHL and CLL. Anti-CD20 mAbs are successfully and widely used therapeutic mAbs. They are routinely incorporated in cyclophosphamide-or fludarabine-containing combination regimens into all phases of conventional treatments, including first-line, maintenance and salvage treatment. Nonetheless, the overall response rates to rituximab have been reported to be 46-67%, and are even lower in patients relapsing after initial rituximab treatment.
Global gene expression analysis upon chemical inhibition of SFKs A transcriptional profiling of Raji cells incubated with 100 nM dasatinib (a clinically-available multi-target tyrosine kinase inhibitor) or 10 mM PP2 (a more selective inhibitor of BCR-associated SFKs) was performed to characterize molecular changes in lymphoma cells incubated with SFKs inhibitors. The unpaired t test with Benjamin-Hochberg FDR <5% (false discovery rate) correction (with P value cut-off <0. 01) revealed 28 upregulated and 86 downregulated (with at least 3-fold change) genes in cells incubated with either dasatinib or PP2 (Fig. 1A ). The analysis of microarray data has been deposited in NCBI's Gene Expression Omnibus and is accessible via GEO Series accession number GSE50929. Compared with untreated cells, these up/downregulated genes were common for each treatment examined individually.
Red spots represent genes for which expression changed significantly (p < 0. 01, Fold Change > 3, unpaired t test and Benjamin-Hochberg FDR < 5% correction) due to dasatinib or PP2 treatment, gray spots represent genes for which expression was not significantly changed. Arrow indicates MS4A1 gene (blue spot). The plot was made using GeneSpring (Agilent) software. (B) GeneSpring (Agilent, USA) cluster of genes (containing MS4A1 gene) for which expression changed similarly in cells upon incubation with dasatinib or PP2. All genes with a fold change cut-off > 3. 0 (p value < 0. 01 in unpaired t test and Benjamin-Hochberg FDR < 5% correction) were considered as significantly regulated and are presented in a matrix format: each row represents a single gene, and each column represents an experimental sample.
Gene expression microarray RNA was isolated using a Universal RNA Purification Kit (EurX) according to the manufacturer's protocol. The samples were treated with DNaseI to eliminate a possibility of DNA contamination and subsequently purified using RNeasy MiniElute Cleanup Kit (Qiagen). Labeling, hybridization, acquisition and analysis were performed as described in Supplementary Information. The unpaired t test with Benjamin-Hochberg FDR <5% (false discovery rate) correction was applied (with P value cut-off <0. 01). Only genes with at least a 3-fold change in the expression level in all the examined samples were further analyzed. The data has been deposited in NCBI's Gene Expression Omnibus and is accessible via GEO Series accession number GSE50929.
p. ) with d-luciferin (150 mg/kg), and after 5 min were anaesthetized with isoflurane and visualized using IVIS Ò Imaging System (Xenogen, Alameda, CA, USA). Images were analyzed with the Living Image 4. 2 software package (Caliper Life Science, Hopkinton, MA, USA). To quantify the bioluminescence (BLI) of mice, the regions of interest (ROIs) were drawn on the whole body and the results were used to generate the growth curve of EL4 lymphoma. Luminescence data were presented as average radiance (photons/sec/cm 2 / steradian). All in vivo experiments were performed in accordance with the guidelines and approved by the local Ethics Committee.
Funding The work was supported by National Science Center grant 2012/07/B/NZ6/03498 (MW), Polish Ministry of Science grant NN402352938 (MW), the European Commission 7th Framework Programme FP7-REGPOT-2012-CT2012-316254-BAS-TION (JG) and the Medical University of Warsaw grant 1M19/ PM12D/13 (KB).
(B) GeneSpring (Agilent, USA) cluster of genes (containing MS4A1 gene) for which expression changed similarly in cells upon incubation with dasatinib or PP2. All genes with a fold change cut-off > 3. 0 (p value < 0. 01 in unpaired t test and Benjamin-Hochberg FDR < 5% correction) were considered as significantly regulated and are presented in a matrix format: each row represents a single gene, and each column represents an experimental sample. In each sample, the ratio of the abundance of transcripts of each gene to the median abundance of the gene's transcript across all sample, is represented by the color of the corresponding cell in the matrix.
Four of these sampling sites are located offshore in Prony Bay at water depths up to 50 m (ST07, ST09, ST11 and ST12), one (Bain des Japonais, noted below as BdJ spring) is also in Prony Bay but uncovered at low tide and one, set up as a spa by the local touristic administration (Rivière des Kaoris, shortened below as Kaoris spring), is on land slightly above the seawater level at high tide. Furthermore, we present the chemical composition of gases emitted at these last two sites. No such gas bubbling has been observed at the deeper offshore sites (namely ST07, ST09, site ST11 and ST12). These data show that mixing of the alkaline hydrothermal endmember with local seawater produces large ranges and very sharp gradients of pH, salinity and dissolved element concentrations. We then calculated the mineral saturation indices to investigate the conditions of the formation of brucite and Mg-Ca carbonates in this peculiar environment.
Acknowledgements. We deeply acknowledge the efficient work of the scuba divers  Eric Folcher ,  Bertrand Bourgeois  and  John Butscher , of the  IRD Center in Nouméa , with the help of  Régis Hocdé  (who also provided a key administrative and logistical support), who collected the samples in dark waters in a shark inhabited environments. We thank  Captain Jean-François Barazer  and his crew on board the  R/V Alis. Anne-Marie Cousin  skillfully designed the sketch of the PHF. CM warmly thanks  Dominique Cluzel ,  Margot Godard  and  Julien Collot  for this glorious day at the springs in the Prony Bay in April 2013. The HYDROPRONY cruise would not have taken place without the full support of the  Direction Scientifique de l'IRD. This project was financially supported by  IRD  and by the  French national CNRS  programs  EC2CO-Biohefect/Ecodyn/Dril/MicrobiEn (MicroProny).
© 2014 Enders et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/licenses/by/4. 0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons. org/publicdomain/zero/1. 0/) applies to the data made available in this article, unless otherwise stated.
D30-and D30+ indicate that cells were cultured without DMSO for 30 days or without DMSO for 15 days and then with 2% DMSO for 15 days, respectively. Quantitative RT-PCR and microarray analysis DNA and RNA were purified with commercial kits (Qiagen). Quantitative RT-PCR and its data analysis were performed as previously described  [24]. TaqMan gene expression assays (hs99999901_s1 and hs01021084m1, Applied Biosystems) were used to analyze 18S and PI4KA expression, respectively. The last assay detected both PI4KA mRNA variants referenced in GenBank (NM_058004. 3 = Variant 1, NM_002650. 2 = Variant 2) with no amplification of pseudogene products. The probe hybridizes at the exon-exon junctions 39-40 and 7-8 of variants 1 and 2, respectively. For absolute quantification, a plasmid (pCMV-SPORT6-hPI4KA, Open Biosystems) containing the PI4KA cDNA (BC018120) was used for calibration.
Statistics Continuous data were compared using the non-parametric Mann-Whitney Test (two groups) or Kruskal-Wallis Test (more than two groups). Spearman or Pearson tests were used for correlation analysis according to sample size. We used the Mantel Cox log rank test and Kaplan Meier method to assess post-resection survival. Disease-specific survival is defined by the tumor-related death and patients who died of another etiology were censored. Recurrencefree survival was defined as the length of time after hepatectomy for HCC during which a patient survives with no sign of HCC. The last recorded follow-up visit was in February 2011. Univariate analysis using Cox models was performed to identify variables associated with disease-specific survival. Variables with a P value < 0. 05 in the univariate analysis were entered into a Cox multivariate model.
Acknowledgements We thank  Dr. Francis Chisari  ( Scripps Research Institute, La Jolla, CA, USA ) for the Huh-7. 5. 1 cells and the  Biological Resource Centre of Rennes  for providing the normal human liver specimens. This work was supported by the  Institute National de la Santé et de la Recherche Médicale (INSERM) , the  University of Rennes 1 , the  Comité Grand-Ouest de la Ligue contre le Cancer , the  Ligue Nationale contre le Cancer  (" Cartes d'identité des tumeurs" program ),  IntegraGen (OSEO) ,  HEPTROMIC  ( FP7 ), the  PAIR-CHC  project  NoFLIC  (funded by  INCa and Association pour la Recherche contre le Cancer, ARC) , the  Réseau national CRB Foie, INCa (WntHCC)  and  BioIntelligence (OSEO). AI is supported by a fellowship from the  Ministère de l′Education  and from the  ARC.
cheopis (2/199, 1%), with a Ct of 32. 6 and 34. 5, from 2 sites (Bokossi Tokpa and Dedokpo). Bartonella spp. were detected in 69/199 (34. 6%) of the fleas (Ct, 31. 81, +/22. 97) (24#Ct#35) collected from all studied sites (Table  1 ). DNA sequence analyses of the PCR products of the gltA gene of 8 representative samples (with high Ct values) showed 100% similarity with the Uncultured Bartonella sp. clone Pd5700t (GenBank no. FJ851115. 1, 334/334 bp) detected in Praomys delectorum rodents in Mbulu district, northern Tanzania  [19]. More information about the Ct value and localization of each positive flea is reported in Supplementary data S1.
United Republic of Tanzania A total of 3821 fleas (rodent fleas and free-roaming fleas present in the environment) were collected from localities of the Lushoto district (United Republic of Tanzania) and were distributed into 23 species. A total of 94 fleas belonging to six common species were screened (Supplementary data S2) (20 Ct. f. strongylus, 7 Ct. canis, 20 Ctenophthalmus calceatus calceatus, 20 X. brasiliensis, 20 Pulex irritans and 7 Nosopsyllus incisus. All tested fleas were negative for Y. pestis and Bartonella spp. DNA. However, R. typhi DNA was detected in 10% (2/20) of X. brasiliensis collected from 2 villages (Magamba and Manolo). R. felis DNA was also detected in 20. 2% (23/94) of analyzed fleas, including 65% (13/20) of Ct. f. strongylus, 71. 4% (5/7) of Ct. canis and 25% (5/20) of Ct.
Democratic Republic of the Congo In 2007, in the Linga and Rethy health zones, Ituri district, 1190 fleas captured in households, belonging to 6 species (394 P. irritans, 153 Tunga penetrans, 280 Ct. f. strongylus, 89 Echidnophaga gallinacea, 88 L. a. aethiopica and 186 X. brasiliensis). A total of 123 fleas were conveniently selected for this work (Supplementary data S3). qPCR for R. typhi and Bartonella spp. was negative for all 123 fleas; however, 4. 8% (6/ 123), namely 19. 2% (5/26) of Ct. f. strongylus and 4. 7% (1/21) of E. gallinacea, contained R. felis DNA (Table  1 ). Y. pestis DNA was detected in 3. 8% (1/26) of Ct. f. strongylus and 10% (3/30) of P. irritans from 2 villages (Wanyale and Zaa). DNA sequence analyses of the PCR products targeting the glpD gene showed 100% similarity with Yersinia pestis Angola isolated from Angola (GenBank accession no.