dataesr/scientific-paragraphs-categorization huggingface dataset:
The optimal tree with the sum of branch length = 0. 28572580 is shown. The tree is drawn to scale, with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic tree. The evolutionary distances were computed using the Maximum Composite Likelihood method  [39]  and the unit is the number of base substitutions per site. Codon positions included were 1st+2nd+3rd+Noncoding. All positions containing gaps and missing data were eliminated from the dataset (Complete deletion option). There were a total of 500 positions in the final dataset. Phylogenetic analyses were conducted in MEGA4  [40]. For the recipient, viruses from PBMC-derived DNA ( N ) and plasma RNA (#) are represented. For the donor, strains from PBMC-derived DNA (. ) and plasma RNA (=) are represented.
Acknowledgments We thank all patients and their physicians for their participation in the  ANRS PRIMO cohort study  (http://u822. kb. inserm. fr. gate2. inist. fr/COHAD/participantsPRIMO. htm), and  Francis Barin  ( French National Reference Center for HIV, Tours, France ) and  Stephane Le Vu  ( Institut National de Veille Sanitaire ) for technical assistance and continuous helpful discussions. ANRS  PRIMO Cohort Study Group: -Bruno ABRAHAM ,  Service de Medecine interne, Centre hospitalier de Brive, Brive, France. - Thierry ALLEGRE, Service d'Hematologie, Centre hospitalier du pays d'Aix, Centre hospitalier intercommunal Aix-Pertuis , Aix-en-Provence, France. - Odile ANTONIOTTI ,  Service de Dermatologie , Centre hospitalier, Montlucon, France.
IgG-mediated hydrolysis of PFR-MCA IgG (66. 67 nM) were mixed with 100 mM PFR-MCA (Peptide Institute, Inc. ) in 40 ml of catalytic buffer containing 5 mM CaCl2 (pH 7. 7) in white 96-well U-bottom plates (Thermo Scientific) and incubated in the dark for 24 h at 37uC. Hydrolysis of the PFR-MCA substrate was determined by the fluorescence of the leaving group (aminomethylcoumarin; lem 465 nm, lex 360 nm) using a spectrofluorometer (GENios; Tecan Trading). Fluorescence values were compared with a standard curve of free MCA and the corresponding quantities of released MCA were computed. At each time point, background release of MCA, measured in wells containing the substrate alone, was subtracted from the value observed in the presence of the Abs. Data are expressed as the quantity of released MCA computed at time 0 subtracted from the quantity of released MCA computed at a given time point per amount of time per amount of IgG.
Acknowledgments We wish to thank  Madame Marie-Noe ¨lle Blandel-Halley  and  Madame Marie Bouclier  ( Service de Transplantation Renale et de Soins Intensifs, Hopital Necker, APHP, Paris, France ) for assistance in the follow-up of the patients and for technical support. We particularly thank late  Sophie Lechaton  for her help in organizing the cohort and patients recruitment ( Service de Transplantation Renale et de Soins Intensifs, Hopital Necker, APHP, Paris, France ). The present work is dedicated to her.
This work was supported by  Centre National de la Recherche Scientifique , by  Institut National de la Santeet de la Recherche Medicale , by  Universite Ṕierre et Marie Curie , and by grants from the  Indo-French Center for Promotion of Advanced Research  (Reference No:  4103-2 ), from  Agence Nationale de la Recherche  ( ANR-09-GENO-028 ), from the  Japan Sciences and Technology Agency (Tokyo, Japan ) and from the  Agence de la Biomedecine. OT and CL are members of the  CENTAURE Transplantation Research Network. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
However, clinical data suggest that patients rapidly acquire immunity that protects against severe disease  [14, 15, 16, 17]  and varying degrees of cross-reactivity have been demonstrated on a serological level using either sera from malaria infected individuals on heterologous parasites or sera from PfEMP1-immunized animals on heterologous PfEMP1 proteins or parasites  [23, 24, 25, 26, 27, 28, 29]. By studying the var gene transcription profiles of fresh clinical P. falciparum isolates of 93 Ugandan children we have previously demonstrated a correlation between different degenerate PfEMP1-DBL1a amino acid motifs and different states of malaria  [30]. The collected sequences were examined with a novel method of region alignment of homology areas (MOTIFF) to identify degenerate sequence motifs correlated with specific disease states.
S1. These motifs were chosen because of predicted surface availability employing prediction program Phyre  [53]  and visualized by PyMOL (The PyMOL Molecular Graphics System, Version 1. 3, Schro ¨dinger, LLC). We further selected specific sequences from the pool that represent each degenerate motif based on the availability of in vitro adapted parasites predicted to express the specific motif. From the choice of specific sequences representing the motifs, we decided to extend the sequences in order to increase the likelihood of mimicking the native secondary structures that these motifs would have in the full-length protein. For this purpose, we used the Phyre webserver  [53]  to model the 3D structures of the DBL1a domains from which the sequences originated. Most sequences were part of a-helical structures: we therefore extended our selected sequences to include the fulllength predicted a-helices.
Tertiary Structure Modeling of NTS-DBL1a The 3D structures of the NTS-DBL1a domains of R29 were modeled using the Phyre2 server with intensive settings  [53]. The crystal structure of the NTS-DBL1a domain of Palo Alto varO (Protein Data Bank accession code 2XUO)  [42]  was used as a template and had the highest sequence and secondary structure alignment score. Structural visualizations and high resolution images were made using PyMOL.
After a 30 min incubation with a goat antirat/rabbit IgG antibody coupled to ALEXA488 (dilution 1:100), the pRBCs were washed thrice with FCS/PBS. Ethidium bromide was added at a final concentration of 2. 5 mg/ml after the last wash and the pRBCs were resuspended in FCS/PBS after two additional washes. The cell acquisition was done using flow cytometry (FACSCalibur, BD Bioscience, Franklin Lakes, NJ USA) where 5000 pRBCs were counted. The analysis was performed using the FlowJo software (Tree Star, Inc. Ashland, Oregon, USA). All assays were done in duplicates. Reactivity of the pRBCs was scored as geometric mean fluorescence intensity as described previously  [56]. In order to compare the different FACS acquisitions, the mean fluorescence of the pRBCs was calculated with the following formula, taking into account the background reactivity of unparasitized RBCs: (pRBC immune /pRBC non-immune ) -(RBC immune /RBC non-immune ).
22 mm filter. The slides were then incubated with a 1:500 dilution of goat anti-rat-or goat anti-rabbit Cy5-conjugated secondary antibodies (Jackson ImmunoResearch) for two hours at RT in a humid chamber, followed by the five washing steps (see above). The microarrays slides were scanned at wavelength of 635 nm using a GenePix 4000B microarray scanner (Axon Instruments, Sunnyvale, CA, USA). The images were analyzed using GenePixPro 7. 0 software in combination with the. GAL file provided by JPT. The mean of fluorescence intensity given by the difference between the foreground and the local background were used to measure the IgG response. The data represent the average of the three subarrays. Anova test and Bonferroni post test were applied to identify peptides that were differentially recognized by the immunized animals compared to their controls (pre-immune serum or purified non-immune IgG).
13 hose results suggested that cyclophosphamide used as first-line therapy could be an interesting alternative to methotrexate. In this letter, we describe the encouraging results of cyclophosphamide used in a series of 45 previously untreated LGL leukemia patients. Patients suffering from LGL leukemia and treated with cyclophosphamide as first-line therapy were included in this retrospective study. Patients were screened from the Italian, French and USA Penn State registries. Patients gave their informed consent for data collection. The diagnosis of LGL leukemia was based on a chronic LGL peripheral blood expansion (40. 5 Â 10 9 /l), usually lasting for more than 6 months. Criteria for T-LGL leukemia included expression of LGL surface markers compatible with a typical T-cell (commonly using flow cytometry.
ACKNOWLEDGEMENTS We thank all clinicians for providing patient data to US, Italian and French LGL Leukemia registry. This work was supported in part by the  National Institutes of Health  grants  CA094872 ,  Associazione Italiana per la Ricerca sul Cancro (AIRC) ,  Cariparo, Cariverona and ADHO (association pour le developpement de l'hematologie-Oncologie ).
STATISTICAL ANALYSIS Non-parametric Mann-Whitney or Kruskal-Wallis tests were used to correlate the effect of different clinical parameters on TREC counts. Since data did not have a normal distribution, a logarithmic transformation was performed. Difference in cumulative incidence of relapse was estimated using univariate Kaplan-Meier analysis. P-values <0. 05 were considered to be statistically significant. All analyses were performed using SPSS Statistics 20 Software.
ACKNOWLEDGMENTS The authors would like to thank  Rita Maccario  for her helpful contribution. This work was supported by research grants from  AIRC  ( Associazione Italiana Ricerca sul Cancro , special grant 5 per  1. 000 ) to  Franco Locatelli ,  Cancéropôle Ile-de-France  and  AP-HP  "contrat de recherche translationelle en biologie 2010" #  RTB1002.
Peripheral T-cell lymphoma, not otherwise specified is a heterogeneous group of aggressive neoplasms with indistinct borders. By gene expression profiling we previously reported unsupervised clusters of peripheral T-cell lymphomas, not otherwise specified correlating with CD30 expression. In this work we extended the analysis of peripheral T-cell lymphoma molecular profiles to prototypical CD30 + peripheral T-cell lymphomas (anaplastic large cell lymphomas), and validated mRNA expression profiles at the protein level. Existing transcriptomic datasets from peripheral T-cell lymphomas, not otherwise specified and anaplastic large cell lymphomas were reanalyzed. Twenty-one markers were selected for immunohistochemical validation on 80 peripheral T-cell lymphoma samples (not otherwise specified, CD30 + and CD30 -; anaplastic large cell lymphomas, ALK + and ALK -), and differences between subgroups were assessed.
Gene expression analyses In order to compare the expression profiles of 16 PTCL, NOS (6 CD30 + and 10 CD30 -) and 35 ALCL (25 ALK + and 10 ALK -) from our two previously published datasets (de Leval et al. 19  ; Lamant et al. 7  ), the RMA normalized matrices were averaged per gene symbol, concatenated and quan-tile-normalized. The four PTCL categories were compared for the expression of two gene sets, referred to as "CD30 neg. signature" (Table  S4  of de Leval et al. 19  ) and "ALK neg. signature" (Table  S3  of Lamant et al. 7  ). For each gene set, the mean expression across genes was calculated per sample and compared using Welch t tests. The "ALK neg. signature" was also used for gene set enrichment analysis (GSEA), as previously described. 19, 20.
CD30 -PTCL, NOS were all essentially negative for CD30. Approval for the study was obtained from the Ethics Committee of the University Hospital of Liège. For immunohistochemical validation of GEP findings, the selection of markers was based on: (i) the most differentially expressed genes across distinct PTCL subgroups, according to our GEP datasets and other publicly available sources;  6, 7, 13, 19, [21] [22] [23] [24]  (ii) their involvement in relevant cellular pathways; and (iii) availability of primary antibodies suitable for paraffin-embedded tissues. S2. explored are depicted in Figure  1  and listed in Online Supplementary Table  S2. The immunolabeled sections were evaluated semi-quantitatively, using a scoring scale based on extent and intensity of the stainings. 25 The extent score and the intensity score were multiplied to provide a unique global score, ranging from 0 to 12, for each immunostain.
Statistical analyses of clinical and immunohistochemical data Differences in clinical features and immunostaining scores between the PTCL subgroups were assessed by means of the chi-square, Mann-Whitney and Kruskal-Wallis tests (GraphPad Prism software, San Diego, CA, USA). Distributions of overall and progression-free survival were analyzed by the Kaplan and Meier method and compared using the log-rank test (GraphPad Prism software). 27, 28 ierarchical cluster analysis was conducted on all immunohistochemical data (average linkage clustering, Cluster and TreeView softwares, http://www. eisenlab. org). 29, 30.
Interestingly however, when we excluded these "borderline" samples from the analyses, only the score of pSTAT3 was significantly different between CD30 + PTCL, NOS and ALK -ALCL (data not shown), enabling us to exclude the hypothesis of an eventual bias introduced by the inclusion of these six cases. Moreover, when applying the molecular classifiers developed by Piva et al. 13  and Agnelli et al. 14  to discriminate ALCL from PTCL, NOS, we found that the levels of mRNA expression of three of the four genes which could be analyzed in our dataset (TMOD1, PERP, TNFRSF8) were significantly lower in CD30 + PTCL, NOS than in ALK -ALCL, while one of the genes (BATF3) was expressed at similar levels in CD30 + PTCL, NOS and ALCL. Interestingly, the levels of expression of TMOD1, PERP and TNFRSF8 were also significantly different between CD30 -and CD30 + PTCL, NOS, being lower in the CD30 -subgroup (data not shown).
20 2] [23]  In Phase I studies subcutaneous sarilumab was generally well tolerated and, in patients with RA,  24 25  reduced acute phase reactants including C reactive protein (CRP). 24 26 esults from the dose ranging study, Part A of the MOnoclonal antiBody to IL-6Rα In RA patients: A pivotal Trial with X-raY (MOBILITY) seamless-design Phase II/III study (NCT01061736), are reported here. The primary objective was to demonstrate that sarilumab dosed qw or q2w plus MTX is effective in reducing the signs and symptoms of RA at week 12 in patients with active RA who have inadequate response to MTX, and to select one or more dose regimens to be evaluated in the pivotal Phase III MOBILITY Part B study. Key secondary objectives were to assess the safety of sarilumab in combination with MTX, and to document its pharmacokinetic (PK) and pharmacodynamic (PD) profile.
Statistical analysis Primary efficacy The primary endpoint, the ACR20 response rate at Week 12, was assessed in the intent-to-treat population, which included all randomised patients, and was analysed according to the treatment group allocated by randomisation. ACR20 response rate was analysed using the two-sided Cochran-Mantel-Haenszel test stratified by prior biological use and geographical region. Pairwise comparisons for the response rates between each dose of sarilumab and placebo were derived by testing each active dose group versus placebo separately. The Mantel-Haenszel estimate of the OR and the corresponding 95% CI were derived by testing each active dose group versus placebo separately. Details of data handling for patients who discontinued study treatment, correction for the multiplicity that arose from testing multiple doses of sarilumab against placebo, and sensitivity analysis are provided in the online supplement.
Statistical analysis The model that predicts the activity of NK cells was applied as follows: a) KIR2DS1 and/or KIR2DS2 with homozygous HLA-Cw for group 1 or 2 (combination of susceptibility -excessive activation); b) KIR2DS1 and/or KIR2DS2 with heterozygous HLA-Cw group; c) lack of KIR2DS1 or KIR2DS2 with homozygous HLA-Cw group (relatively neutral combination -balance); Rev Bras Reumatol 2013;53(1):66-74 and d) lack of KIR2DS1 or KIR2DS2 with heterozygous HLA-Cw group (combination of protection -excessive inhibition). The results were assessed by use of Pearson's chi-square test and the SPSS 16. 0 software. Statistical signi cance was adopted as a P value 0. 05.
Fluorescent profiles were recorded using a FACSCalibur (BD), and results were analyzed using the CellQuest Pro software (BD). Adhesive potential and inner foreskin explants. Adhesion in vitro to fibronectin (Sigma-Aldrich)-coated plates (5,000 MDLCs/well) was performed as we described previously  (Ganor et al. , 2007). For conjugate formation in vitro, 10 5 MDLCs were labeled according to the manufacturer's instructions with CellTracker green (Molecular Probes), pretreated with CGRP, washed, and incubated with 3 × 10 5 CellTracker orange-labeled T cells for 1 h. Untreated and labeled MDLCs were also incubated with labeled T cells in the presence of mouse anti-human CD50 (ICAM-3) or CD54 (ICAM-1) mAbs (ImmunoTools) at 20 µg/ml. The percentage of doublepositive conjugates was measured by flow cytometry.
RNAi and infection assays RNAi silencing of TEP1 by double-stranded RNA injection into the thorax of adult mosquitoes and mosquito infections on mice carrying Plasmodium berghei GFP-con 259cl2 were performed as described  [22]. To semi-automatically quantify the number of oocysts in photographs of dissected mosquito midguts, we used the "watershed segmentation" and "analyze particles" plugins of the ImageJ software after digital subtraction of the image background and smoothing of the signal. Oocyst counts obtained by this method are consistent with those obtained by manual counting of oocysts.
This study was funded by an  Agence Nationale de la Recherche (ANR)  young researcher grant to  E. M. (project  GEMM ), by the  European Commission   FP7  projects  INFRAVEC  (grant agreement no. 228421 ) and  EVIMalar  (grant agreement no. 242095 ), by the  Institut National de la Santé et de la Recherche Médicale (INSERM)  and by the  Centre National de la Recherche Scientifique (CNRS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Gene expression profiling of rosiglitazone-treated trophoblasts Gene profiling of EVCTs isolated from first-trimester human placenta, with comparisons of rosiglitazone-treated and control cells from the same placenta, was performed with an Affymetrix GeneChip analyzing 14 500 genes with 22 000 probe sets. The microarray data are available in the gene expression omnibus database (http://www. ncbi. nlm. nih. gov/geo, 2012 GSE28426). Mean results are shown for rosiglitazone-treated cells from five different placentas vs their paired controls (SAM scatter plot in Figure  2 , heat map in Figure  3  and Figure  S1 ). Five independent EVCT cultures yielded similar results in four cases and a slightly different pattern for culture 1. A total of 139 genes (175 probe sets, 117 unique genes) were identified as having significantly different expression (p,0.
Functional network analyses Expression profiles were analyzed with Ingenuity Pathway Analysis software. The top seven functional networks showing altered gene expression in rosiglitazone-treated EVCTs are shown in Figure  5. Functional areas included cell signaling, molecular transport and small-molecule biochemistry, cell growth, lipid metabolism, cell cycling, tissue morphology, skeletal and muscular system development and function, cancer, and cell death. The LOX gene was found to be part of networks 2, 5 and 7 (Figure  5 ). The transcriptome data were confirmed for selected genes, namely those found here to be strongly regulated or known to be involved in placental development. RT-qPCR was applied to treated and paired control EVCT cultures distinct from those used for the microarray experiments (Figure  S2 ).
There was no effect of 0. 1% ethanol (vehicle) on EVCT cultures (data not shown). Rosiglitazone-treated and control cells were trypsinized 24 h later for RNA assays or 48 h later for protein assays. Experiments were carried out on PFA-fixed sections of 8-WA placental villi, using specific antibodies; non-specific rabbit IgG was used as a control. Immunostaining was performed with an universal streptavidinperoxidase kit (Dako). doi:10. 1371/journal. pone. 0079413. g008.
Microarray analysis EVCT primary cultures from first-trimester placentas (rosiglitazone-treated and matched vehicle controls, n = 5 placentas) were obtained as described above. RNA was extracted using the TRIzolH reagent (Invitrogen) as described for RT-PCR, and then purified using the RNeasyH Mini kit (Quiagen S. A. , Courtaboeuf, France). RNA integrity and purity were checked using a 2100 Bioanalyzer with the RNA 6000 LabChip kit (Agilent Technologies, Massy, France). The GeneChip (U133A 2. 0, Affymetrix, Inc. , Santa Clara, CA), which analyzes 14 500 genes with 22 000 probe sets, was used according to the manufacturer's instructions. Data were processed with the Expression Analysis algorithm of the Affymetrix Microarray suite (version 4. 0). CEL files were imported into BRB Array Tools software (http://linus.
Images were captured with a Hamamatsu C4742-95 CCD camera and VisionStageH software (Alliance Vision, Montelimar, France). Ten representative fields were photographed for each filter. Cells and pseudopods were counted manually and the number of migrating cells was divided by the total number of nuclei (DAPI stain). The numbers of invasive cells in treated cultures are expressed as a percentage of control cultures, and are the mean of four separate experiments performed in duplicate.
Acknowledgments We thank the  department of Obstetrics and Gynecology of Broussais and Saint Vincent de Paul Hospitals (Paris, France)  for providing placental tissues,  Audrey Chissey  for trophoblast primary cultures and placental tissue sectioning,  Mickae ¨l Guesnon  and  Jasmine Ouatara  for technical assistance, and  David Young  for editorial assistance.
Identification of Phylogenetic Clusters within non-Sg1 L. pneumophila Clinical Isolates To identify prevalent population based clusters of non-Sg1 L. pneumophila clinical strains in Ontario, we conducted a phylogenetic analysis on 73 clinical isolates recovered between 1980 and 2009 using sequence based typing (SBT) and multiple-locus variable number tandem repeat analysis (MLVA). SBT based phylogenetic comparisons between different strains is accomplished by observing sequence variations of 7 allelic markers including house-keeping genes and known virulence factors  [43, 44]. MLVA takes advantage of the polymorphisms of 9 tandemly repeated DNA sequences  [45]. The UPGMA analysis based on a matrix of pairwise allelic differences between all the sequence types (ST) of our dataset identified a large cluster (n = 40) comprising most of the Sg6 isolates of our repository.
Isolates of this large cluster showed less phylogenetic diversity compared with other clusters and it encompassed 2 two main subclusters (Figure  S1 ). The phylogenetic subcluster 1 included 17 isolates of Sg6 and ST 187 (Figure  S1 ), while the phylogenetic subcluster 2 included 9 isolates who were all identified as Sg6 ST 68 (Figure  S1 ). MLVA typing of this dataset, identified a large phylogenetic cluster as well, comprising two subclusters, where cluster 1 grouped 20 isolates, and included Sg6 ST 187 and Sg6 ST 68, along with Sg4, Sg8 and Sg10 strains (Figure  S2 ). Interestingly, cluster 2 had 10 isolates, out of which 8 were Sg6 ST 187, 1 was a Sg6 ST242 and 1 was a Sg3 ST93 (Figure  S2 ). To further increase the discriminatory power of the molecular typing methods  [46] , we next constructed a phylogenetic tree combining SBT and MLVA profiles (Figure  1 ).