dataesr/scientific-paragraphs-categorization huggingface dataset:
Additionally, a large screening study of 833 cells lines from the database of Cancer Genome Project, Sanger Institute, focused on frequently mutated genes (six suppressor gene and five oncogenes), has identified NRAS homozygous mutation in 10% of cell lines  [29]. However, the zygosity status was only determinate by manual examination of sequencing electropherograms. Interestingly, in vitro studies of mutant RAS family members had demonstrated a high oncogenic potential of increased mutant allele frequency. The oncogenic potential of NRAS G12D/G12D was highly increased as compared to heterozygous or hemizygous NRAS cells in NRASdriven hematopoietic transformation  [30]. Additionally, progenitors of hematopoietic cells expressing the highest levels of NRAS G12D demonstrated cytokine-independent CFU-GM colony growth and exhibited an increased level of pAkt, pErk and pS6 proteins.
B ovine coronavirus (BCoV) belongs to the Nidovirales order, the Coronaviridae family, the Coronavirinae subfamily, and the Betacoronavirus (https://talk. ictvonline. org/ ICTV/proposals/2008. 085-122V. v4. Coronaviridae. pdf). Its genome is a single-stranded, linear, and nonsegmented RNA of around 31 kb. BCoV is responsible for respiratory and enteric diseases in cattle, particularly during winter (1, 2). To date, the 19 complete BCoV genome sequences available in GenBank databases (consulted on 17 January 2017) originated from the United States or Asia. Here, we report the first complete genome sequence of a BCoV detected in France. The BCoV/FRA-EPI/CAEN/2014/13 strain was obtained from a fecal sample collected from a 1-week-old calf in Normandy in 2014. The presence of BCoV in the fecal sample was assessed using an in-house reverse transcription-PCR (RT-PCR) targeting the M gene (3).
A cDNA library was synthesized using SuperScript III (Invitrogen, Carlsbad, CA, USA) and hexamers. The complete genome sequencing of overlapping PCR products was carried out in both directions, using original primers and Sanger's dideoxy sequencing. Sequencing reactions were performed as previously described (3). Sequences were assembled and annotated using the Geneious software (version 5. 1. 6). We obtained a sequence counting 30,847 nucleotides. The orf1ab, HE, S, ns5, E, M, and N genes of the obtained BCoV were submitted to a Blastn analysis. According to these analyses, the orf1ab (20kb nucleotides, located at the 5= side of the genome) gene is closely related to the Dromedary camel coronavirus (DcCoV) HKU23-23-362F strain from the United Arab Emirates (accession no. KF906251), with a nucleotide identity of 99.
Acknowledgments This work was supported by grants from the  Agence Nationale de Recherche (ANR , No  11 BSV3 025 01 ), the  Agence National de Recherche sur le SIDA et les Hepatitis Virales (ANRS) ,  Institut Pasteur ,  CNRS  and  INSERM. JB has been supported by  ANRS  and  Roux--Institut Pasteur postdoctoral fellowships. IdRI is a scholar in the Pasteur -- Paris University  ( PPU )  International PhD program  and is funded by the  People Programme  ( Marie Curie Actions ) of the European Union's  Seventh Framework Programme FP7 /2007--2013/ under the  REA  grant agreement n°  317057 HOMIN.
Transient absorption setup The laser system and frequency-conversion apparatus employed to excite samples were the same as for time-resolved fluorescence measurements. White light continuum (360-1000 nm) pulses generated in a 5 mm methanol cell were used as a probe. The variable delay time between excitation and probe pulses was obtained by using a delay line with 0. 1 mm resolution. The solutions were placed in a 1 mm circulating cell. White light signals and reference spectra were recorded using a two-channel fiber spectrometer (Avantes Avaspec-2048-2). A home-written acquisition and experiment-control program in LabView made it possible to record transient spectra with an average error of less than 10 À4 times the optical density for all wavelengths. The temporal resolution of our setup was better than 60 fs.
The quantum yields j A-B and j B-A were determined using the numerical solution of the corresponding differential equations using the primarily specified value and the ratio of quantum yields of the forward and backward reactions preliminarily measured using the Fisher method. The quantum yield values were optimized by the iteration method using the program in the Visual Basic language incorporated into Microsoft Excel. The absolute light intensity I 0 was measured using a ferrioxalate actinometer  41, 42  before each photolysis experiment (for details also see the ESI †). The measurement accuracy does not exceed 20%.
X-ray diffraction analysis The crystals suitable for X-ray analysis were prepared by slow evaporation of solutions of compounds NI1-3 in solvent mixtures benzene-dichloromethane (v/v = 1 : 1), ethanol-ethyl acetate (v/v = 1 : 1) and DMF, respectively. The measurements were carried out using a SMART APEX II CCD diffractometer (MoKa irradiation, graphite monochromator, o-scanning). The structures were solved by the direct method and refined by the full-matrix leastsquares technique against F hkl 2 in the anisotropic approximation. Hydrogen atoms were placed in calculated positions and refined in the riding model using isotropic approximation. The main crystallographic parameters can be found in the ESI † (Table  S1 ). All calculations were performed using SHELX software package. 43 he X-ray data of NI1-3 have been deposited with the Cambridge Crystallographic Data Centre as supplemental publications CCDC 1037166-1037168.
Computational details Quantum chemical calculations were carried out by the MOPAC 2012 program package using the PM6 semiempirical method. 44 I calculations were performed at optimized geometries, which reached gradient variations less than 0. 01 kcal mol À1. The solvent effect was included in geometry optimizations following the ''COnductorlike Screening Model'' (COSMO) implemented in MOPAC 2012. A dielectric constant of e = 20 and a refraction index of solvent (n) such that n 2 = 2 were used for geometry optimization and calculations of electron distribution of the HOMO and the LUMO in compounds NI1-3. The CI included eight occupied and eight unoccupied MOs.
A little difference between t 1 and t 2 can be explained by the fact that the time t 1 is affected to some extent by the dynamic solvation of the twisted form which shifts the TICT absorption band to longer wavelengths on a timescale of the excited state relaxation map. Dynamic solvation effects were very easily detectable when polar solvents with low viscosity (like acetonitrile) were used. The full data on TRABS spectral maps, TRABS spectra at different time delays and time profiles of the signals are presented in the ESI † (Fig. S77-S94 ). A very interesting particularity was found in the TRABS spectra of NI1 and NI2 recorded in diethyl ether. In these cases, the residual signals of LE states were not completely quenched during the lifetime of TICT forms. This observation allows us to conclude that a quasi-equilibrium between twisted and planar forms is possible, which could be a result of a low TICT-LE energy gap due to relatively weak solvation in Et 2 O.
3-16. 0 Hz. After the irradiation, the signals of the E-isomer decreased, whereas a new set of signals with a lower 3 J H18-H17 constant (12. 3-12. 4 Hz) corresponding to the Z-isomer was detected. As an example, Fig. 7  shows the 1 H NMR spectra of compound NI3 before and after irradiation at 436 nm. The spectra of E-isomers and corresponding photostationary states of NI1 and NI3 can be found in the ESI † (Fig. S10 ). The spectral characteristics of phototransformation products (Z-isomers) were investigated by the Fisher method  39  from the absorption spectra of two photostationary states obtained at irradiation wavelengths 436 and 365 nm and the spectra of E-isomers. Also, the quantum yields of the forward (E -Z) and backward (Z -E) photoreactions were determined. The data are summarized in Table  3.
Quantification of cell surface Markers by Flow cytometry For phenotypic analysis, PBMC were resuspended at a density of 200,000 cells in 50 µl of 1% BSA, 0. 1% NaN3 in PBS (+20% human serum to block Fc receptors), and incubated for 30 min on ice with mAbs specific for CD3, CD4, CD8, CD80, CD86, CD95/Fas, and HLA-DR and corresponding isotype controls (BD Biosciences). For total Fas surface quantification and apoptosis, a minimum of 100,000 events/sample were stained and acquired with FACSort and FACSCanto II flow cytometers (BD Biosciences) and analyzed using CellQuest and Diva software, respectively.
, submitted). This Fas hi proliferating and chemotherapy-resistant leukemic phenotype is in agreement with the recently discovered CD4 T stem cell memory (Tscm) hierarchical apex of ATL. The same FAS -670 polymorphism also determined CD4 Tscm levels in a genome-wide twin study, confirming our hypothesis (Khouri et al. , submitted). Therefore, a genetically determined interferon (IFN)/STAT1/FAS axis might help explain the proliferative, non-apoptotic phenotype in HAM/TSP suggesting CD4 Tscm as a pivotal factor not only in ATL but also in HAM/TSP pathogenesis. Considering STAT1 and FAS are in the HAM/TSP gene signature, our data further refine the data of Tattermusch et al. (7) It is not unexpected that a Tscm phenotype is absent from the disease signature, since Tscm are rare (2-3%) (45)  and their genome-wide expression profile is intermediate between naïve and central memory T cells.
a moderated t-test, resulting p-values were corrected for genomewide testing (5% FDR). All microarray raw data are available at Gene Expression Omnibus database (GEO, http://www. ncbi. nlm. nih. gov/geo/) series accession number GSE82160. statistical analysis The use of parametric (t-test, Pearson correlation) or non- parametric (Mann-Whitney or Spearman rank correlation) tests was based on normal distribution as determined by Kolmogorov-Smirnov test (all GraphPad Prism v5. 0 or v6. 0). A p-value of <0. 05 was considered significant for all statistical tests. Transcriptome-wide correlation of FAS mRNA expression levels was calculated using Spearman rank correlation test, with stringent correction for multiple testing (5% FDR).
Selection of SNPs and genotyping Genomic DNA was obtained from peripheral blood samples. Extraction was performed using the Qiagen DNA extraction kit (QIAamp DNA Blood Midi Kit) according to the manufacturer's instructions and quantified by Nanodrop assay. DNA was stored at -20˚C until analysis. Ninety-six SNPs were genotyped in IL1, IL4, IL4R, IL6, IL8, IL10, IL12, IL12R, TNFA, INFG, MIF, HPR, CFH, APOL1, HLA-A, and HLA-G. The SNPs were selected by two strategies: 1) SNP in IL4, IL6, IL8, HLAG and IFNG were designed as markers for linkage disequilibrium (LD) scans of each gene  [46] , 2) SNPs in other genes were selected based on reports in the literature that they were associated with trypanosomiasis or other infectious diseases. The LD scans were designed using 1000 Genomes Project data  [47] , merged with low fold coverage (8-10x) whole genome shotgun data generated from 230 residents living in regions (DRC, Guinea Conakry, Cote d'Ivoire and Uganda) where trypanosomiasis is endemic (TrypanoGEN consortium, European Nucleotide Archive study EGAS00001002482).
Loci with minor allele frequency < 5% in the reference data were excluded and an r 2 of 0. 5 was used to select SNP in LD. DNA was genotyped by two commercial service providers: INRA-Site de Pierroton, Plateforme Genome Transcriptome de Bordeaux, France and ii-LGC genomics Hoddesden UK. At INRA multiplex design (two sets of 40 SNPs) was performed using Assay Design Suite v2. 0 (Agena Biosciences). SNP genotyping was achieved with the iPLEX Gold genotyping kit (Agena Biosciences) for the Mass Array iPLEX genotyping assay, following the manufacturer's instructions. Products were detected on a Mass Array mass spectrophotometer and data were acquired in real time with Mass Array RT software (Agena Biosciences). SNP clustering and validation was carried out with Typer 4. 0 software (Agena Biosciences).
Statistical analysis All statistical analyses were performed using the Plink 1. 9 and R v 3. 2. 1 software. Individuals were excluded who had > 10% missing SNP data. SNP loci were excluded that > 10% missing genotypes or if the control samples were not in Hardy-Weinberg equilibrium (p<0. 001). Case-control association analysis using SNP alleles/genotypes was undertaken using Fisher's exact test. The difference between the ethnic groups was estimated using the F ST , with values potentially varying from zero (no population differentiation) to one (complete differentiation)  [47]. Ethnicity was not used as a risk factor for HAT because we observed no significant differences in F ST between ethnic groups (F ST maximum 0. 015) or clustering by linguistic group by multidimensional scaling in Plink.
Acknowledgments We thank subjects who generously donated their specimens and the field workers from the  Ivorian HAT  foci for their dedication in collecting and processing these specimens. TrpanoGEN Research Group:  Bernadin Ahouty ,  Mathurin Koffi ,  Vincent Jamonneau ,  Harry Noyes ,  Hamidou Ilboudo ,  Julius Mulindwa ,  Magambo Phillip Kimuda ,  Justin Windingoudi Kabore ,  Dieudonne Mumba Ngoyi ,  Olivier Fataki ,  Gustave Simo ,  Elvis Ofon ,  John Enyaru ,  John Chisi ,  Kelita Kamoto ,  Martin Simuunza ,  Vincent P. Alibu ,  Veerle Lejon ,  Annette MacLeod ,  Mamadou Camara ,  Bruno Bucheton ,  Christiane Hertz-Fowler ,  Issa Sidibe ,  Enock Matovu.
Liquid chromatography tandem mass spectrometry (LC-MS/MS) and data analyses BAL supernatants (hereafter called BAL) containing 20 μg total protein, determined using the Bradford assay (BioRad), were diluted to contain 50 mM ammonium bicarbonate. The samples were reduced with dithiothreitol (DTT) and alkylated with iodoacetamide. Trypsin was added in a trypsin:protein ratio of 1:20 and digestion was performed overnight. Thereafter the samples were purified by Pierce C18 Spin Columns (Thermo Scientific), dried and resolved in 60μL 0. 1% formic acid, and analysed by tandem mass spectrometry. Analyses were performed in a blind manner using peptide separation by reversed phase liquid chromatography and an QExactive Plus Orbitrap mass spectrometer (Thermo Fisher Scientific, Bremen, Germany) equipped with a nano electrospray ion source, as detailed in  [12] , with the following modifications: Protein identification was performed against a FASTA database containing proteins from Bos Taurus extracted from the SwissProt database (release Oct 2016, 44366 entries).
Search parameters included a maximum of 4. 5 ppm and 20 ppm error tolerances for the survey scan and MS/MS analysis, respectively. For protein identification, only peptides with a minimum of 7 amino acids were considered. A total label free intensity analysis was performed for each individual sample. Pathway analyses were carried out in Reactome v59  [13] , (www. reactome. org). Proteins were classified as detected at calf treatment group level if identified in at least 4 out of 5 calves and venn diagrams were designed using the Interactivenn software  [14] , (www. interactivenn. net). Protein functions were analysed in Panther v11. 1  [15] , (www. pantherdb. org/).
Statistical analyses Statistical analyses were carried out in Minitab1 software, version 17. For comparisons of label free quantification (LFQ) of intensities for relative protein expression level in BAL, a twotailed student's T-test was used, with assumed unequal variance. For correlations, the Spearman's rank and Pearson product moment correlation coefficients were used for data with non-normal and normal distribution, respectively (determined using the Anderson-Darling test). Samples from all animals were included in all analyses, if not otherwise specified.
Pathway analysis confirmed increased neutrophil degranulation and reduced detoxification of reactive oxygen species associated with BRSV infection The four quantitative datasets, containing the 57 and 35 proteins identified at statistically significantly higher expression levels in BRSV-infected, susceptible calves (Table  2 , Quantitative), as well as the 95 and 101 proteins identified at statistically significantly lower expression levels in these animals compared to those in their vaccinated or non-infected controls, in experiment I and II, respectively (S3 Table ), were submitted to Reactome  [13]. The numbers of proteins that were recognized and mapped were as follows: 29/57 (higher, experiment I), 10/35 (higher, experiment II), 56/95 (lower, experiment I) and 52/101 (lower, experiment II).
Overall, there was a significant correlation between severity of clinical signs, pathology and viral load and the presence of neutrophils in alveolar septa (Spearmans rho 0. 71, p = 0. 02, for extent of lung lesions; 0. 63, p = 0. 05 for clinical score; and 0. 87, p = 0. 001 for virus shedding). Two of these correlations were also statistically significant within just the group of five BRSV-infected, susceptible_I animals, i. e. those for lung lesions (Pearson's r: 0. 89, p = 0. 04) and virus shedding (Pearson's r: 0. 93, p = 0. 02), but not for clinical score (Pearson's r: 0. 72, p = 0. 17). To confirm these data and to validate the mass spectrometric results for neutrophil-related proteins, the relative expression level of selected proteins detected by LC-MS/MS in BAL was analysed in relation to the degree of BRSV-induced gross pathology, clinical score, virus shedding and degree of neutrophils in alveolar septa.
Acknowledgments We thank the technical staff at  Swedish University of Agricultural Science (SLU)  and the  National Veterinary Institute, Sweden , for maintaining the animals and preparation of histological samples. A. Rikberg ,  A. Svensson  and  K. Selin-Wretling  at  SLU  are acknowledged for logistic support and  K. Ho  ¨rneus,  A. Falk  and  G. Shevchenko  at the  Science for Life Laboratory, Mass Spectrometry Based Proteomics Facility, Uppsala, Sweden , for technical assistance. We also wish to thank  M. Andersson Franko ,  SLU , for his feedback on statistical analyses, and  Pr. L. E. Larsen ,  DTU, Denmark , for generously sharing the BRSV isolate no. 9402022.
2015a). Molecular statics calculations are carried out at P = 120 GPa and constant volume using the program package LAMMPS  (Plimpton 1995) , which relies on Ewald summation methods for Coulombic interactions. Energy minimization is performed using a conjugate-gradient algorithm followed by a Hessian-free truncated Newton algorithm until the maximum force on an atom drops below 10 -9 eV/Å (1. 602 × 10 -18 N).
For the latter group of patients, for example, these include monoclonal antibodies that have shown to be effective or are currently investigated in combination with other drugs. Results from the Swedish population-based Lymphoma Registry Study showed a significant survival improvement in patients diagnosed with Follicular Lymphoma between 2000 and 2010. This improvement correlated with the increasing use of first-line rituximab over time and with regional differences in firstline rituximab use  [2]. The Swedish observation is in line with dramatic improvements of relative survival in the last decade for NHL patients as recently reported from the SEER database  [4]. Despite the changing landscape of treatment of lymphoproliferative disorders and in contrast to the large number of quality of life (QoL) studies in patients with solid tumours, relatively few studies have reported QoL in patients with haematological malignancies  [7].
Also, the American Society of Hematology (ASH) has voiced concern about the lack of data in this area, advocating urgent efforts to raise the standards of QoL research  [8]. Likewise, international recommendations for various hematologic diseases are also now paying greater attention to QoL assessment  [8] [9] [10] [11] [12]. Studies investigating effects and complications after haematological cancer treatment have identified problems in several domains, including eye, oral, endocrine, neurosensory and cardiopulmonary impairments  [13] [14] [15] [16] [17] [18] [19] [20]. The FACT-Lymphoma questionnaire has been developed more than a decade ago to assess QoL in the broad group of all subtypes of lymphoma cancer patients. From a pool of 69 items, following expert relevancy ratings (n = 17), patient input (n = 75) and item correlations, a lymphoma subscale of 15 items was constructed  [21].
Data analyses and criteria for item selection Results from phase 1 and 3 interviews were analysed using descriptive statistics according to the EORTC guidelines and data were analysed per tumour group. Analyses were performed with IBM SPSS statistics version 19. Phase 1 issues were retained if patients reported a mean score of ≥ 1. 75 (range 1-4) for the relevance question and > 15% of patients considered the item a priority, and HCPs reported a mean score of ≥ 2. 00 for the relevance question and > 25% considered it a priority. For patients, two points were assigned for every criterion that was met and for HCPs, one point was assigned. This was done to give more importance to the results of patients. Subsequently, issues that had a score of 4, 5 or 6 points for at least one of the four tumour groups were selected for inclusion in the provisional phase 3 item questionnaire.
Phase 1: generation of issues Extensive literature searches through PUBMED and PsychINFO (January 2011) resulted in thirteen studies  [13] [14] [15] [16] [17] [18] [19] [20] [27] [28] [29] [30] [31]  performed between 1998 and 2011 that formed the basis of the provisional list as no new issues came out of further searches of other databases. Also, previous work that had been conducted by EORTC QoL group members on the development of the EORTC QLQ-CLL16 was included and updated in the module development process.
Acknowledgements LP, SO and FE designed the study, SO, AB, CK, MS, SP, LD, CC, KC, SM, GC, WC and FE collected the data. LP and SO analysed the data, while AB, CK, MS, SP, LD, CC, KC, SM, GC, WC and FE interpreted findings. LP, SO wrote the paper, AB, CK, MS, SP, LD, CC, KC, SM, GC, WC and FE revised it critically. All authors approved the submitted version.
NMR measurements 1 H-NMR spectra were recorded at 300 K on a Bruker Avance 500 MHz NMR spectrometer (Bruker, Karlsruhe, Germany) operating at a proton NMR frequency of 500. 13 MHz for 1 H, using a triple BBI probe. Deuterated methanol was used as the internal lock. 128 scans of 32 K data points with a spectral width of 10,330 Hz were recorded with the following parameters: pulse width (PW) = 30°, and relaxation delay (RD) = 1. 0 s. The acquisition time was 3. 17 s. FIDs were Fourier transformed with LB = 0. 3 Hz. The resulting spectra were manually phased and calibrated to 0. 00, using the internal standard TMSP and topspin software (version 3. 9, Bruker). Two replicates were measured for each plant material studied. The optimised 1 H-NMR spectra were automatically baseline corrected and reduced to ASCII files using AMIX software (version 3.
DNA sequencing PCR amplicons were purified using Fermantas PCR purification kits following the manufacturers' instructions. DNA sequencing reactions were done using a Big Dye Terminator v. 3. 1 Cycle Sequencing Kit (Applied Biosystems) following the protocol outlined by the manufacturers. Sequencing products were purified by ExoSAP method  (Werle et al. , 1994). All DNA sequences were determined with an ABI 3500 DNA sequencer (Applied Biosystems) at Inqaba Biotechnical Industries (Pty) Ltd. , South Africa. 2. 6. Phylogenetic analysis 2. 6. 1. Sequence editing and alignment Forward and reverse sequences were assembled and edited using CLC Main Workbench Version 7. 6 (https://www. qiagenbioinformatics. com/). All sequences were deposited in GenBank (Table  2 ). DNA sequences were aligned using the online version of MAFFT 5.