dataesr/scientific-paragraphs-categorization huggingface dataset:
Multiple sequence alignments were performed using MEGA 5. 05 with other previously published rabies virus sequences, and alignments were checked manually. Phylogenetic trees were inferred from the aligned nucleotide sequences. The MrModeltest2. 3 program  [51]  was used to determine the optimal model of nucleotide evolution for the two genes. The GTR model, with a gamma distribution shape parameter (G) and invariable sites (I), was identified and used for the Bayesian approach, which was performed with Mr. Bayes 3. 2. 2 to infer phylogenetic relationships  [52]. Markov Chain Monte Carlo (MCMC) simulations were run for 10,000,000 generations, with four simultaneous chains, using a sample frequency of 100 and a burn-in of 25,000. Majority rule consensus trees were obtained from the output. Validation of the inference was assessed based on the standard deviation of split frequencies, which was less than the expected threshold value of 0.
Molecular detection of RABV and phylogenetic relationships The molecular survey realized on 995 healthy bats captured between 2005 and 2013, identified one positive common vampire bat Desmodus rotundus for RABV (Table  1 ). This animal was a female adult, not pregnant, that was captured in September 2010, on the Approuague River, North-East of French Guiana. RABV RNA was detected in blood, saliva and heart tissue (the brain was not tested). This animal was also positive by serology, with a low titer (0. 6 IU/ml). Sequences of this RABV-positive sample (AT6) were obtained for the G and N genes and deposited in GenBank (accession numbers KT023100 and KT023101, respectively). Furthermore, the only other bat (Artibeus planirostris, specimen 09035FRA) detected as positive by the NRC for Rabies was found in a sublethal condition in Rémire-Montjoly, close to Cayenne in 2009.
All the sequences obtained by the NRC were deposited in GenBank (accession numbers KT276358 and KT276360 to KT2763688 for domestic species; KT276359 for the Artibeus). For the N gene, all sequences isolated from bats, dogs and cattle in French Guiana belong to the haematophagous bat-related strains. They cluster in three different groups according to their isolation date. The first group, composed of strains isolated between 1989 and 2003, shows a high percentage of sequence identity within the group (between 98. 5% and 100%). They are related to strains identified in Trinidad and Ecuador between 1995 and 2007. The second group of sequences is made up of strains isolated between 1997 and 1999. They show between 99. 5 and 100% identity within the group. These strains have a basal position within the clade to which the two sequences identified from bats (AT6 and 09035FRA) belong.
This study was conducted within the ViRUSES and CAROLIA programs supported by  European funds (ERDF/FEDER)  and assistance from  Région Guyane and Direction Régionale pour la Recherche et la Technologie. It also received a  European commission "REGPOT-CT-2011-285837-STRonGer" grant  within the  FP7  and " Investissement d'Avenir " Grants managed by  Agence Nationale de la Recherche  ( CEBA, Ref. ANR-10-LABX-25-01 ; defaunation. ECOFECT, Ref. ANR-11-The authors thank the (http://www. invs. sante. fr/)and the  Institut Pasteur  for their financial contribution to the National Reference Centre for Rabies that made this work possible. This research was also funded by the  European Union Seventh Framework Programme  ( FP7/2007-2013) PREDEMICS grant 278433. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Study population The study population consisted of all malaria cases reported by hospitals of the CNR located in Ile-de-France (Paris area) in order to ensure a greater degree of homogeneity in terms of population, access to health care and case management. First, the population is more homogeneous in this region of 12 million inhabitants, with a high proportion of African migrants. Moreover, 45 % of the 44 hospitals are academic hospitals, 25 % have infectious disease units, and others are major hospitals with expertise in the management of malaria cases. Finally, a large proportion of imported malaria cases are reported by the hospitals located in Ile-de-France (54 % of imported malaria cases in 2013, CNR database, data not published). Data were collected prospectively and in a consistent manner, regardless of severity or type of care pathway.
Statistical analysis All data were analyzed by SPSS v11. 5 and "R" v3 softwares. Both SNPs were tested for Hardy-Weinberg disequilibrium to check for stratification. In order to calculate the Šidák multiple testing correction, we first evaluate the effective number of independent tests (called Meff ) in the analysis by using the methodology proposed by Li and Ji  [34]. This method aims to prevent from overcorrection due to possible linkage disequilibrium (LD) between the SNPs. Power calculation has been based on the frequency of the variant allele in the control population as proposed by Hattersley et al. [35]. Hence, for an incidence of the variant allele of 11 % in the control population and a power at 90 %, a 50 % increase in the case population with a type I error of 5 %, 886 individuals in each group appear to be sufficient to detect genetic susceptibility to SS (http://www.
REL genotypes and septic shock susceptibility Hardy-Weinberg proportions were comparable to expected percentages regarding REL variants: REL rs842647 (p = 0. 9) and REL rs13031237 (p = 0. 7) in favor of homogeneity of population ethnicity. To determine whether REL rs842647 and rs13031237 SNPs were associated with septic shock susceptibility, genotype frequencies were determined for SS and C patients. As reported in Table  1 , no significant difference was found between the two groups. Moreover, these incidences were similar to those reported in the HapMap database-reported genotype distribution for European population (http:// www. ncbi. nhm. nih. gov/projects/SNP/snp_viewTable. cgi?pop=1409).
Acknowledgements This study was supported by national grant from the  Ministry of Health  ( PHRC 2003 ), grant from  CARISMA  ( Cochin Association for Research in inflammation, Sepsis and Molecular Advances ), grant from  SRLF  ( Société de Réanimation de Langue Française ) and grant from  SFAR (Société Française Anesthésie Réanimation. These funding organizations played no role in the design, execution and publication of the study.
Amplicon was sequenced with 3130-XL sequencer (Applied Biosciences, Saint Aubin, France). Strain KHD2 exhibited a 98. 2% sequence similarity with Peptoniphilus harei (GenBank NR_026358. 1), the phylogenetically closest validated species (Fig. 1 ). This value is lower than the 98. 7% 16S rRNA sequence threshold recommended to delineate a new species in the phylum Firmicutes without carrying out DNA-DNA hybridization  [5]. Hence, the strain KHD2 may be classified as the representative strain of a novel species within the genus Peptoniphilus in the Peptoniphilaceae family. Created in 2001 by Ezaki et al. , after the subdivision of the genus Peptostreptococcus into three genera (Anaerococcus, Peptoniphilus and Gallicola), the genus Peptoniphilus contains only strictly anaerobic bacteria  [6]. Besides, this genus currently includes 13 species that have been identified in diverse human clinical specimens like sacral ulcer, vaginal discharge, and ovarian, peritoneal and lachrymal gland abscesses  [7].
ulcerans and M. marinum were incubated at 30 °C in ambient air. Plates were checked by visual inspection weekly for colonies for 4 weeks. Colonies were counted regardless of their size and counting was considered interpretable when >10 3 colonies were observable on the control (0 %-NaCl) Middlebrook 7H10 medium plates. A strain was considered salt tolerant when more than 50 colonies developed on the 7H10-NaCl supplemented media. Image J program  [10]  was used to measure the average size of colonies after 50 colonies were randomly chosen from each plate. The morphology of colonies was observed by the naked-eye. Ziehl-Neelsen staining was conducted to confirm the identity of the colonies.
Genome analyses The whole genome and proteome of 15 mycobacterial species under investigation were downloaded from Genbank (Table  1 ). The proteins were clustered into orthologous groups using orthoMCL  [11]  with a conservative parameter value of 60 % sequence identity. Homologous sequences were selected using the all-against-all BlastP algorithm  [12]  with an E value of <10 -5. Clustering of the orthologous sequences was then analyzed using the Markov Cluster algorithm  [13]. Determination of the different unique core genomes was based on the homology clusters found by orthoMCL. The resulting orthologous groups were used to construct a whole-genome tree using the Neighbor-Net algorithm based on a gene content matrix using splitree  [14]. The similarity between two species was defined as the number of genes in common divided by the total number of genes of the two species  [15].
of CDS N° of CDS in groups Unique core genes Core genome Core genes Pan genome Pan genes Genome C % N° Group 1 (Sensi-GenBank acces-sion N°G 290 1563 37,132 6043 70,580 tive) M. tuberculosis NC_00962 65. 6 3906 3863 45 H37Rv M. tuberculosis NC_021054 66 4110 1969 141 str. Beijing/ NITR203 M. tuberculosis NC_20559 65. 6 4245 3960 285 str. Erd- man = ATCC 35801 M. canettii CIPT NC_015848 66 3861 3796 81 140010059 M. bovis BCG str. NC_008769 66 3949 3884 67 Pasteur 1173P2 M. marinum M NC_010612 66 5423 5092 349 M. ulcerans NC_008611 65 4160 4070 310 Agy99 Group 2 (Interme- 0 diate) M. avium 104 NC_00859 69 5120 4817 311 M. intracellulare NC_016946 68 5144 4777 380 ATCC 13950 M. massiliense str. NC_018150 64 4558 4446 112 GO06 Group 3 (resistant) 0 M. abscessus T NC_010397 64 4920 4701 223 M. abscessus AHAS01000000 64 4923 4657 268 subsp.
5B, D ) and compiled MFIs data (Fig. 5C, E ). To gain further insights, we quantified by qPCR the expression level of several genes known to influence the differentiation and/or effector function of T cells. Although no difference was observed in Nfat, Ap-1, and Gata3 expression in all tested groups, a decrease in T-bet and RORC (encoding for RORct) transcript levels was detected in T cells derived from rIL-21-treated aged mice compared to aged PBS control mice (Fig. S4 ). Foxp3 expression level, on the other hand, was equivalent between PBS-and rIL-21-treated aged mice but significantly higher than younger mice (Fig. S4 ). These qPCR results are consistent with the observed decrease in IFNc (T-bet) and IL-17 (RORC) secretion levels and are particularly interesting as several investigations have associated IL-21 to autoimmune diseases  (Korn et al.
Western blots Splenocytes were first isolated to sort total CD3 + T cells. Whole T-cell extracts were obtained through using the Cell Lytic M reagent (Sigma). Extracts were separated by electrophoresis, transferred onto Hybond-ECL membrane, and probed using primary antibodies. Densitometry analysis was conducted by first imaging the chemiluminescent blots with the ImageQuant LAS 4000 imager (GE Healthcare Life Sciences, Mississauga, ON, Canada) followed by analysis using the ImageQuant TL software (GE Healthcare Life Sciences).
Acknowledgments We are grateful to  Dani ele Gagn  e and Serge S en echal (for sorting and flow cytometry assistance),  Rapha€ elle Lambert  (for qPCR studies), and to the staff of the IRIC histology and animal care facility for their assistance. This work was supported by a  Cancer Research Society (CRS)  operating grant. Moutih Rafei  holds a  Fonds de la Recherche en Sant e du Qu ebec Junior 1 award.
Statistics For multiple group comparisons, one-way ANOVA, two-way ANOVA, or Kruskal Wallis nonparametric tests were applied. For single comparisons of independent groups, the Student's t test or the Mann-Whitney test was performed. For single comparisons of matched groups, the paired Student's t test or the Wilcoxon matched pairs test was performed depending on the sample size and distribution. For comparisons of qualitative variable, the Fisher's exact t test was performed. In the relevant figures, n. s. indicates not significant; ***p < 0. 001; **p < 0. 01; and *p < 0. 05. Analyses were performed using GraphPad software.
ACKNOWLEDGMENTS We would like to acknowledge  Christelle Retie  `re for kindly providing the 1F12 antibody. We thank  Jean-Laurent Casanova  and  Bernard Malissen  for critical reading of the manuscript. This work was supported by grants from the  Swedish Research Council , the  Swedish Children's Cancer Society , the  Swedish Cancer Society , the  Tobias Foundation , the  Swedish Foundation for Strategic Research , the  Karolinska Institutet , the  Wenner-Gren Foundation ,.
the  KG Jebsen Center for Cancer Immunotherapy. J. T. and J. A. T. are supported by the  MRC  and the  Welcome Trust  with partial funding from the  National Institute for Health Research Cambridge Biomedical Research Centre. V. B. is supported by the  French National Research Agency (ANR)  (grant no. NKIR-ANR-13-PDOC-0025-01 ).
Thousands of continuous epitopes listed in epitope databases have been identified only on the basis of their ability to cross-react with protein antibodies in a variety of immunoassays and not by showing that each residue in the peptide made contact with residues of a paratope  [76, 77]. Since the criterion used for identifying a continuous epitope is only its binding activity, the exact structure of the epitope is never clearly defined  [78]  (pp. When epitopes are defined structurally by crystallography they comprise about 15 residues whereas if they are defined functionally by binding assays, they appear to be much smaller  [79]. When peptides of decreasing size are tested for binding activity, the smallest peptide that retains a significant level of reactivity is sometimes given the status of epitope although it may be as short as a pentapeptide or a tripeptide  [69, 80, 81]  (pp.
Statistics Data was analyzed with GraphPad Prism 5. 04 (La Jolla, USA). After testing for normal distribution using the D'Agostino and Pearson's tests, the appropriate methods of analysis were determined. For non-normally distributed data, non-parametric testing (Mann-Whitney U / Kruskal-Wallis test) followed by Dunn's multiple comparison's test was employed. For normally distributed data, student's t-test or one-way ANOVA was performed. P values < 0. 05 were considered significant. Interrater reliability of histopathologic assessment was confirmed using Cohen's κ. As described by Landis and Koch 1977, Cohen's κ was interpreted as "slight agreement" for the range of 0-0. 20, "fair agreement" for the range of 0. 21-0. 40, "moderate agreement" for the range of 0. 41-0. 60 and "substantial agreement" for the range of κ = 0.
61-0. 80 [18]. Smooth muscle contractility, as measured in a dose-response curve using the muscarinic agonist betanechol in a standard organ bath, was compared by fitting the normalized data to a logistic curve (four-parameter sigmoidal model) and comparing the fitted midpoint (logEC 50 ) and slope, using the F test and Graph Pad Prism 5. 04. All data relevant to reach the conclusions drawn in the manuscript with related metadata and methods, and any additional data required to replicate the reported study findings in their entirety is found in the manuscript and supporting information files.
Viability Assay and doubling time Drug-induced changes in cell viability after 24 h, 48 h and 72 h treatment were assessed by flow cytometry after propidium iodide (PI) staining (Sigma-Aldrich, 81845). To assess relative changes in the viable cell number, an automated cell viability analyzer was used according to standard procedures. Both parameters were analysed using a FACSVerse flow cytometer and FACSuite software (Becton Dickinson). The software program Graph Pad Prism was used to plot viability curves. Doubling time (DT) was calculated using the formula: DT = (t-t 0 )log2 / (logA-logA 0 ), in which t and t 0 are the times at which the cells were assessed and A and A 0 are the absorbance at times t and t 0 , respectively.
Cell Cycle Analysis Melanoma cells were treated with pentoxifylline at 10 mM for 24 h. After incubation cells were collected and fixed with 70% (w/v) ethanol at -20°C. Cells were washed twice with PBS and resuspended in PI Staining Buffer containing RNase (Becton Dickinson, 550825). Following incubation for 30 min at room temperature, cells were analysed using a FACSVerse flow cytometer. ModFit LT 3. 0 software was used to calculate the percentages in each cell cycle phase.
Flow Cytometric Analysis of Apoptosis Detection of cell death was carried out by dual staining with Annexin V-FITC and PI (Roche Diagnostics, Manheim, Germany). Melanoma cells were seeded into 12-well plates and treated with 10 mM pentoxifylline for 24 h. After treatment, cells were collected, centrifuged at 400 x g for 5 min and stained with Annexin V-FITC and PI for 15 min at room temperature in the dark. 30,000 events were analyzed for each sample by flow cytometer FACSVerse (Becton Dickinson), and results were processed by using FACSuite software (Becton Dickinson).
TCF/LEF reporter assay Cell lines were transduced with Cignal TCF/LEF Reporter (GFP) or negative control (GFP reporter construct with a minimal promoter) (Qiagen, CCS-018G) by nucleofection (Lonza). Three hours after transfection, cells were treated with 5 mM and 10 mM Pen for 24 h. Cells were harvested, trypsinized and washed with PBS. Pellet was resuspended in PBS and incubated with 7-aminoactinomycin D (7-AAD) (eBioscience, 00-6993-50) for 10 min at 4°C. Acquisition of 30,000 cells was performed using FACSVerse flow cytometer and data were analysed with FACSuite software.
The analysis of the immunofluorescence data were performed on images that were acquired using the following parameters: magnification 400x, exposure time for 15 ms (DAPI) and for 20 ms (Alexa Flour 555). It was conducted with ZEN microscope software (Carl Zeiss). Localisation of β-catenin in nucleus was performed as combined display of two channels in colour overlay mode. The pixel of red channel (Alexa Fluor 1 555) was plotted against blue channel (DAPI) in the diagram and each pixel pair with the same X/Y coordinates was displayed as a point. Regions in which both fluorescent dyes (DAPI and Alexa flour 555) were co-localised were displayed in a rose colour. Histograms of Alexa flour 555 fluorescence intensities (co-localised with DAPI) have been shown to demonstrate decreased intensity of fluorescence of β-catenin after Pen treatment.
Enzyme-linked Immunosorbent Assay (ELISA) of DKK1 The ELISA kit Quantikine Human DKK1 Immunoassay (R&D Systems, DKK100) was used to determine the concentrations of DKK1 in the culture media. The optical density of each well was determined with a microplate reader (Infinite M200Pro). A standard curve and the concentrations of DKK1 in the samples were obtained by reducing the data using a four-parameter logistic curve fit.
It has been demonstrated that inhibition of CTGF, either genetically or with a specific monoclonal antibody FG-3019, reduces melanoma growth and prevents the formation of distant metastases in the lungs of SCID mice  [45]. Anti-CTGF therapy using monoclonal antibody has entered a clinical trial in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (NCT01181245. ). Our results indicate that CTGF can be also downregulated pharmacologically by a small molecule pentoxifylline in β-catenin high /CTGF high melanoma cells. Our study also clearly demonstrates that pentoxifylline inhibits MITF-M expression and activity. MITF-M is a melanocyte-specific transcription factor that has a critical role in the pathogenesis of melanoma  [46] [47] [48] [49]. The close relationship between the WNT/ β-catenin signalling and MITF expression and stability has already been demonstrated  [29, 50, 51].
Acknowledgments We thank  Dr. M. Sztiller-Sikorska  for melanoma cell isolation and their propagation and  E. Lewandowska  for her excellent administrative and technical support. This work was financially supported by  2012/06/M/NZ2/00109  from  National Science Centre (Poland). SC was supported by a grant " Equipe labellisée par la Ligue Contre le Cancer " ( EL2015. LNCC/SaC ).
4G-I ). Renal function as measured by plasma creatinine and urea, due to contralateral filtration, was not affected (data not shown). Percentage of circulating Ly6C/Gr-1 high granulocytes (A) and Ly6C/Gr-1+ F4-80 low monocytes (B) of total leukocytes, 1 day after IR (the gating strategy can be found as Supplementary Fig. S2 ). Membrane TREM-1 expression on granulocytes (C) and monocytes (D) as displayed by mean fluorescence intensity (MFI) (n = 5-8/group). Circulating TREM-1 soluble protein in sham and one day after IR, measured by ELISA (n = 7/group) (E). Values are expressed as mean ± SEM. *P < 0. 05 vs sham. **P < 0. 005 versus sham. Because the potential therapeutic significance of LP17 treatment has been extensively shown by many other groups and especially in sterile inflammation settings  12, 20  , we tested whether the neutral results obtained were dependent on the degree of damage.
Flow cytometry. Peripheral blood was drawn via a cardiac puncture and red blood cells were lysed (Erythrocyte lysis solution: 160 mM NH 4 Cl, 10 mM KHCO 3 and 0. 1 mM EDTA, pH 7. 4). Cell suspensions were stained with FITC-labeled anti-mouse Ly6C/Gr-1 (BD Pharmingen) and Alexa Fluor 647-labeled anti mouse F4/80 (eBioscience) to determine granulocytes and monocyte populations. PE-labeled rat anti-mouse TREM-1 (R&D) was used to determine TREM-1 positive cells within the identified leukocyte populations. Stained cells were acquired on FACS Calibur (BD Biosciences). Data analysis was performed using FlowJo v10 (FlowJo LLC). mRNA purification and reverse transcriptase PCR. Total RNA was isolated from 10-15 renal frozen tissue slides (20 μ M) using Trizol reagent (Invitrogen) according to manufacturer's protocol.
Genotype clustering and calling were performed using BeadStudio Data Analysis Software (Illumina). Renal transplantation study outcomes. The primary outcome used in this study was DGF, defined as the requirement for dialysis within the first week after transplantation (patients with primary non-function of the graft  53  , were excluded, since these cases most probably represent arterial and venous thrombosis instead of IR). Secondary outcomes were time-to-first episode of biopsy-proven acute rejection (BPAR) and death-censored graft survival (DCGF: defined as the need for indefinite dialysis or re-transplantation).
Statistical analyses. In the murine studies, differences between groups were analysed using non-parametric Mann-Whitney (2 groups) or Kruskal-Wallis tests (> 2 groups) followed by Mann Whitney (treatment compared to control) using Prism (GraphPad Software). Results are expressed as mean ± SEM. Values of P < 0. 05 were considered significant. For the human renal transplantation study, deviation from Hardy-Weinberg equilibria were tested with PLINK  54. Differences in allele frequencies between donors and recipients were tested by logistic regression analyses in a genetic additive model construction. Results were adjusted for age and donor-recipient relatedness with the DFAM algorithm. Minor allele frequencies between the HapMap-CEU (a population from Utah with Northern and Western European ancestry) that was genotyped in the context of the 1000 Genomes study were compared by Fisher exact tests or χ 2 tests where appropriate.