dataesr/scientific-paragraphs-categorization huggingface dataset:
E-F: Analysis of wild-type, MX-1-deficient C57BL/6 mice after infection with S. mansoni and influenza A virus (strain PR8). A, Relative weight loss of mice with chronic schistosomiasis (10 wks; red) and control animals (black) at indicated times after challenge with 60 pfu/mouse of hvPR8. Some control mice received 50. 000 U IFN-a, given one day before challenge with hvPR8 (green). Data points were cumulatively acquired from 3-4 mice in each group in one experiment. Error bars represent SEM; B, Survival curves of mice in Fig. 6A. C, Relative weight loss of mice with chronic schistosomiasis (10 wks, red) and control animals (black) at indicated time points after challenge with 200 pfu/mouse of hvPR8. Some control mice received 50. 000 U IFN-a, given one day before challenge with hvPR8 (green).
Study population and design The Department of Infectious and Tropical Diseases at Croix-Rousse Hospital in Lyon, France, follows approximately 2,500 HIV-infected patients yearly. The Department provides care to patients from the diagnosis of HIV infection to complications from AIDS, leading to a high retention rate. This hospital cohort is included in the French Hospital Database on HIV and follows the protocols described elsewhere  [16]. Patients' files are registered in a computerized database after the patient provides written informed consent. The database is registered by the French Commission Nationale de l'Informatique et des Libertés under the reference CNIL 1599796. The study was performed in accordance with The ICHGCP guidelines and the Declaration of Helsinki. Every treatment-naïve adult patient, initiating cART from January 2000 to December 2010, and for whom baseline and 12-month data were available (or deceased before month 12) were included.
After univariate analysis, independent variables and potential confounders were entered in multivariate models if their P value was ≤. 15; a backward stepwise process was then implemented and models were compared with the Wald test. Baseline CD4 count was forced in the predictive model of CD4 count variation at 12 months. Baseline HIV viral load was forced in the predictive model of undetectable HIV viral load at 12 month. All statistical tests were 2-tailed, and P <. 05 was considered statistically significant. The viral suppression rate at 12 months was analyzed in an intention to treat (ITT) way (i. e. that all switches were counted as failures). The data were analyzed by Stata software 11. 0 (StataCorp LP 2009, College Station, TX). Missing data were avoided by complete case analysis. A B C+ 3 T C+d d I A l t.
Finally, not following the "whatto-start" guidelines was independently associated with a worse virological response. Contrary to the Swiss Cohort study  [14] , age, HIV risk factors, and baseline CD4 counts were not associated with 12-month outcomes. Differences in populations and the selection of variables can explain such discrepancies between the study results. However, our study is the first to report a clear association between following the "what-to-start" guidelines and the virological response at 1 year using the universally accepted cut-off of <50 copies/mL, irrespective of the degree of immunodeficiency. Limitations of this study include the follow-up that was voluntarily limited to 1 year in order to assess the effect of the first line of cART. Data on adherence and compliance were not collected, as well as associated comorbidities, which could have influenced the timing of cART initiation or the choice of drugs.
Patients Immune reconstitution was monitored as part of routine follow up in all 410 patients undergoing allogeneic stem cell transplantation at our center between June 2005 and November 2009. Blood samples were collected prior to transplant and at three, six, 12 and 24 months after transplant. 3, 6, 12 All patients provided written informed consent in accordance with the Declaration of Helsinki. The present study focuses on patients with immune reconstitution profiling available at twelve months from transplant, regardless of indication, conditioning regimen, and stem cell source of HSCT; 190 patients met these criteria. Kinetics of reconstitution was studied in a smaller cohort of 77 patients with data at all other study points. Characteristics of both cohorts are shown in Table  1. Definition of clinical variables, including    conditioning regimen intensity, GvHD grading and CMV replication, is described in the Online Supplementary Methods.
Statistical analysis Statistical analyses are detailed in the Online Supplementary Methods. All lymphocyte subsets were studied as proportions of the patient's total lymphocyte count at the time of sampling. Multivariate analysis was performed by correspondence analysis (CA), which is conceptually analogous to principal component analysis. 17 imilarity between patients' and controls' datasets was evaluated with the 'RV' coefficient, which measures the relationship of two sets of variables defined for the same individuals. 18 ne-way analysis of variance according to categorical variables was performed with the Kruskall-Wallis test. When two variables were each significantly impacting a single dimension, two-way analysis of variance (ANOVA) accounting for interaction were performed. Non-relapse mortality (NRM) and cumulative incidence of relapse (CIR) were defined with a landmark at 12 months considering relapse and death as competing events.
There was no significant difference, except for a greater proportion of CMV seronegative recipients in the 12-month study population (P=0. 02). We performed CA on this global dataset. The first 5 dimensions accounted for a cumulative 75. 5% of the total variance of the dataset [dimension (DIM) 1: 33. 2%; DIM2: 15. 5%]. Dimensions resulting from CA display the similarity between patients ('rows' in our dataset), but can also be used to analyze the similarity between immune populations ('columns') across the patient populations. We performed a supervised 'between-group' clustering of immune populations, which uncovered the distinct reconstitution of B and NK cell populations, and to a lesser extent of CD4 + and CD8 + T-cell subsets. Expectedly, Tregs were closer to CD4 + T cells (Figure  2 ).
We also performed unsupervised clustering analysis on the resulting dataset. This analysis uncovered 6 statistically significant clusters (P<0. 05 by approximately unbiased tests) (Online Supplementary Figure  S2 ): B-cell subpopulations (naïve, memory and CD5 + B cells) formed a cluster, as did NK-cell subpopulations. As further validation, naïve (CD45RA + / CCR7 + ) and 'early differentiated' (CD28 + ) CD8 + T cells were found to significantly cluster. Interestingly, within the CD8 + T-cell compartment, HLA-DR + activated cells clustered with 'late effector memory' (CD45RA + / CCR7 -) cells, whereas activated T cells characterized by CD25 expression instead clustered with 'central memory' (CD45RA -/ CCR7 + ) cells. Of note, such distinct clustering of CD25 + and HLA-DR + activated CD8 + T cells was also noted in patients studied at six months after transplant (data not shown).
The kinetics of global immune reconstitution was first studied sequentially until two years. The profile of 16 lymphocyte subpopulations as compared to healthy controls was significantly abnormal at all times, including before transplant, possibly because of underlying malignancy and previous treatments, and reached a nadir six months after transplant, before beginning to become near to normal. However, immune populations were still overall significantly different from controls at two years after transplant. 1] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33]  We next focused on patients alive at one year and analyzed global immune reconstitution of 25 lymphocyte subsets, and performed a correspondence analysis on this global dataset. This late time point was chosen to allow sufficient lymphocyte count recovery and significant cumulative incidence of cGvHD for analysis.
Both study populations were defined on the basis of prolonged survival and thus include selected patients. However, their base-line characteristics were comparable to that of the global population transplanted at our center during the same period, except for an overrepresentation of CMV seronegative recipients, which is in keeping with the role of CMV replication on NRM after HSCT. 34 The first 5 dimensions accounted for two-thirds of the total variance of the dataset. Analyses uncovered the distinct reconstitution of B -and NK-cell populations, and to a lesser extent of CD4 + and CD8 + T-cell subsets. Tregs were closer to CD4 + and CD8 + T cells. Within the CD8 + DR + T-cell clustered with late effector memory, whereas CD8 + CD25 + T cells clustered with central memory cells. To determine which factors influence the pattern of immune reconstitution we performed non-parametric analysis of variance.
Sequencing Whole genome sequencing was performed by the CNRS sequencing facility in Gif sur Yvette (IMAGIF) using the Illumina platform (Illumina Genome Analyzer IIx). Assembly of short sequence reads was performed using BioNumerics tools (Applied Maths, Sint-Martens-Latem, Belgium) as described  [14]. The phage genome was annotated automatically using the BaSyS annotation tools  [23]. Bacterial genome contigs were annotated using BioNumerics annotation tools. Detailed methods are available on the website http://bacteriophages. igmors. u-psud. fr. The annotated Ab31 phage sequence has been deposited at EMBL-EBI under accession number HG798806. Total reads of bacterial genome sequences have been deposited at EMBL-EBI under accession number PRJEB5001.
Therefore we were not able to determine the position of the first nucleotide, and we decided to assign it by comparison with the related phage AF. In the Ab31 genome, 69 putative ''open reading frames'' (ORFs) were identified. Thirty five ORFs were transcribed on the positive strand (Fig. 4 ). On the basis of sequence similarity comparisons in the GenBank database, 25 ORFs could be assigned to putative functions. The majority of the other ORFs exhibited similarity to uncharacterized bacterial or phage proteins. No tRNA genes were predicted. Nucleotide position 1 was 60 bp upstream of the ATG codon of a putative protein containing a Helix Turn Helix domain, and sharing similarities with the small terminase subunit encoded by Escherichia coli phage phiv10  [32]  and Salmonella enterica phage epsilon 15  [33].
aeruginosa Tr60 genome as compared to that of PA14. The first deletion encompassed approximately 22 kbp (coordinates 1919495 to 1941370). It started with 2. 5 kbp of DNA of unknown function and ended inside a gene encoding a pirin-like protein (ORF PA14_22080 to ORF PA14_22280), and also contained genes for a resolvase and a recombinase. The second deletion encompassed approximately 11 kbp, and covered exactly the sequence of the Pf1 prophage of P. aeruginosa PA14 (Genbank: AY324828). Both deletions were identified in Tr60, in all Tr60 variants that were sequenced and in the genome of reference strain PAO1. The existence of the two deletions was confirmed by PCR in Tr60 and its Ab31-resistant variants using primers localised in the flanking regions (Table  1 ; Fig. 6 ). The deletions were also observed in Tr162 and in PAO1, as expected.
7B ). In order to check whether the deletion was pre-existing in a subpopulation of the Tr60 culture before phage infection, 94 bacterial colonies were picked and PCR was performed on thermolysates with the Flank 234 and porin primers. The results showed that none of the isolates were deleted for the 234 kbp region (data not shown). Compared to Tr60, Tr60-10A and Tr60-100A showed approximately the same amount of SNPs (respectively 29 and 26). The mutations occurred in the same coding sequences for both resistant bacteria. In particular, mutations were found in a transcriptional regulator, in the NADH dehydrogenase I subunit F, the pyoverdine biosynthesis protein PvcA, phenazine biosynthesis protein PhzD, C32 tRNA thiolase and in an MFS transporter. Specific mutations in a gene for an Usher protein and in a gene for a lipase chaperone, were detected in Tr60-10A and Tr60-100A, respectively.
In each essay, three samples with known genotypes together with three no-DNA blanks were included. After PCR amplification, sample genotypes were attributed by measuring the allele-specific fluorescence using an ABI Prism 7700 Sequence Detection System, using SDS 1. 7 software for allele discrimination (Applied Biosystems Foster City, CA, USA). Four VDR SNPs (Fok T/C [rs10735810], Apa T/G [rs7975232], Taq C/T [rs731236], and Bsm A/G [rs1544410]) were genotyped using restriction fragment length polymorphism analysis. The primers used for this procedure are provided in Table  1. PCR amplified products were digested overnight with ApaI, TaqI, FokI, and BsmI restriction endonucleases (New England BioLabs, Beverly, MA, US) and visualized in 2. 5% agarose gel electrophoresis. The presence of a restriction site was assigned a lowercase letter and its absence an uppercase letter, according to convention (i.
Acknowledgements This work was supported by institutional funding to INSERM UMRS 940 and  Assistance Publique des Hôpitaux de Paris (AP-HP)  under the cadre of the  French-Moroccan (INSERM-CNRST ) bilateral cooperation. The support of the  Hassan II Academy of Science and Technology  and the  National Institute of Hygiene of Morocco  is gratefully acknowledged. We thank the study subjects for their willingness to participate in the study. We thank the doctors and other employees of the  Pulmonary Department of Moulay-Youssef Hospital  and the blood bank Center in Rabat, in particular,  Dr Mokrei ,  Dr Cherkaoui  and  Dr Marwan.
Acknowledgments This work would have been impossible without the help of the professionals of the Taupgreen network (http:// www. taupegreen. com/). We especially thank:  J Dormion ,  JF Barbot ,  F Burgot ,  F Cairey ,  M Derosier ,  Y Dupont ,  JM Georgeon ,  M Giroud ,  JL Laclamette ,  EJ Laffont ,  G Moncel ,  B Pradier ,  L Quemener  and  R Fons  for their help in mole capture. Molecular analyses were performed at the " Service de Systématique Moléculaire " ( UMS 2700 ) of the MNHN. This work was also supported in part by grant number  R01AI075057  from the  National Institute of Allergy and Infectious Diseases, National Institutes of Health.
MS data deposition The mass spectrometry data from this publication have been submitted to the ProteomeXchange Consortium  (Vizcaino et al, 2014)  via the PRIDE partner repository (http://www. ebi. ac. uk/ pride) with the data set identifier PXD001410. shRNA-mediated gene knock-down in human CD4 + T cells For each shRNA construct, lentiviral supernatants from three 100-mm dishes of HEK293 cells (10 ml each) were pooled at 48 h posttransfection, filtered through a 0. 45-lm syringe filter and subjected to ultracentrifugation at 23,000 × g (SW28 rotor) for 90 min at 4°C. Viral pellets were gently resuspended in 300 ll serum-free DMEM medium and either used immediately for transductions or snapfrozen in liquid nitrogen and stored at À80°C for future use. Briefly, human peripheral CD4 + T cells were isolated from blood by negative selection using the Dynabeads Untouched Human CD4 T-cell isolation kit (Life Technologies Corp.
For plate-bound stimulations, biotinylated 6V monomers were immobilized at the indicated concentrations on Streptavidin-coated 96-well plates (Thermo Scientific) at 4°C overnight in PBS. Plates were washed twice with PBS, and 10 5 1G4-CD8 cells/well were incubated ON at 37°C in RPMI with 10% FCS. Cells were harvested, washed in PBS and stained with Annexin-V-Alexa647 (Life Technologies) in 100 mM HEPES, 140 mM NaCl, 25 mM CaCl 2 , pH 7. 4. Flow data were analysed as described above.
Data were analysed with Diva software (BD Biosciences), and overlayed plots were constructed with FlowJo software. OVA peptides and tetramers OVA peptide variants and a null peptide VSV were synthesized and purified as described  (Daniels et al, 2006). Biotinylated, soluble peptide-MHC monomer involving the H-2K b molecule and OVA peptide variants were tetramerized with streptavidin as described  (Daniels et al, 2006).
Acknowledgments We thank  Dr. Ge Baoxue  for providing plasmid pcDNA3. 1-HA-SHP1and Drs. Ji-Li Chen  and  Vincenzo Cerundolo  for initial help with the Jurkat 1G4 system. We thank  Ben Thomas ,  Svenja Hester  and  Philip Charles  for help with mass spectrometry data analysis and all members of the  T Cell Signalling Laboratory  for helpful discussions. We are grateful for the support of the PRIDE team in depositing our proteomics data set. We thank  Ed Palmer  for providing peptide-MHC monomers in the frame of the 'Sybilla' project and the  Centre d'Immunophénomique  for blastocyst injection. This work was supported by:  Wellcome Trust  grant  WT094296MA  (to O. A) and  EU - FP7 'Sybilla'  grant  201106  to O. A. and B. M. ,  NIH  grants  AI073870  and  GM065230  to N. R. J. G. ; grants from  Centre National de la Recherche Scientifique , from the  Institut National de la Santé et de la Recherche Médicale ; from  Agence Nationale de Recherche  (projects 'ADAPT' and 'BASILIC', to B.
M. ), and from the  European Research Council  (project ' Integrate ' to B. M. ); grants  EU - FP7 'Targetbinder'  and from  Breast Cancer Campaign  (to S. M. F. ); P. C. S. is further supported by the  Rosetrees Trust. O. D. was supported by a  Sir Henry Dale Fellowship jointly  funded by the  Wellcome Trust  and the  Royal Society  ( 098363 ). A. M. B. was supported by a Case- MRC  fellowship.
The rarity of PTCs worldwide may be explained by the fact that only a very small proportion (approx. 2%) of patients in the French Hospital Database on HIV who were identified during primary infection initiated early cART and experienced a treatment interruption  [17]. Indeed, in the absence of a reliable marker to predict the outcome, therapy discontinuation, even if started early, is not recommended outside clinical structured protocols. Non-controlled infection after treatment interruption increases risks of morbidity and mortality  [24]  and also of infection transmission. PTCs were able to control viral replication in the long term and, in some cases, even exhibited a progressive decrease in viral reservoir  [17]. This may be at least partially related to the weak contribution of long-lived cells, such as central memory CD4þ T cells (T CM ), to the total circulating reservoir in these individuals.
Statistical analysis The differences between experimental groups were analyzed (unless otherwise stated) with one-way ANOVA with Tukey's post hoc test, two-way ANOVA Dunnett's post hoc test or t-test as indicated in the figure legends. P < 0. 05 was considered as statistically significant. We used the statistical software GraphPad PRISM 6. 0 (San Diego, CA, USA). Data is represented as mean ± S. E. M. A minimum of 3 different independent experiments were performed for all the in vitro experiments.
Acknowledgements We thank  Dr. Sara Linse  from  Lund University  for providing the α-synuclein plasmid construct. This work was supported by grants from the  Swedish Research Council  ( 2012-2229 ,  2012-4100 ),  A. E. Berger ,  Gyllenstiernska Krapperup ), the  Royal Physiographic Society, Crafoord, Wiberg, G&J Kock , Stohnes foundation, by  Swedish governmental agency for innovation systems, VIN-NOVA , grant No. 2009-00236. By the  European Research Council   Advanced Award  ( PRISTINE-PD ) to P. B. , the  Swedish Parkinson Foundation (Sweden) , the  Swedish Brain Foundation , the  Human Frontier Science Program. Grant from  Spanish Ministerio de Economia y Competitividad  ( SAF2012-39029 ). A. B. -S. , J. F. R. , N. L. R. , P. B. and T. D. are active in Bagadilico (Linné consortium sponsored by the  Swedish Research Council ) and the  Strong Research Environment Multipark (Multidisciplinary research in Parkinson's disease at Lund University ).
Inclusion Consecutive patients with symptomatic AF referred to our department for ablation during the year 2013 were included in this study. Exclusion criteria included all non-cardiac conditions with expected elevated Gal-3 levels, such as liver cirrhosis, pancreatitis or chronic inflammatory disease. Patients with a history of ablation procedure for AF were also excluded. Collected clinical data included symptoms (EHRA classification) and history of arrhythmia, presence of thromboembolic risk factors (according to CHADS 2 and CHA 2 DS 2 -VaSC scores), and past and current medications. Trans-thoracic echocardiography and cardiac magnetic resonance imaging were performed to assess left ventricular function and left atrial diameter and volume. The local ethics committee for human research approved the study protocol.
Galectin-3 in atrial fibrillation Although clinical data are still lacking, animal models of cardiac fibrosis have been shown to harbor an upregulation of Gal-3. Ho et al. have shown in a large cohort that higher Gal-3 levels were associated with increased risk of developing AF in the general population, although not after accounting for other risk factors  [22]. In that study, the mean value of Gal-3 in patients developing AF was 15. 0. In our study, we used for the first time a selected population of patients referred for AF ablation, in which such markers may have therapeutic implications. Patients with reduced left ventricular ejection fraction were included, but to gain specificity, clinical conditions known to be associated with elevated Gal-3 levels, such as cirrhosis, pancreatitis, or chronic inflammatory disease, were excluded.
Acknowledgements. We thank  A. Alcaı  ¨s,  S. Boisson-Dupuis ,  J. Bustamante  and all members of the  Necker branch and Rockefeller branch of the laboratory of Human Genetics of Infectious Diseases. Funding statement. This work was supported by grants from the  European Research Council  ( ERC-2010-AdG-268777 ), the  French National Agency for Research (ANR , grant no. ANR-08-MIEN-014-02 ),  EU-grant HOMITB (HEALTH-F3-2008-200732 ), the  Canadian Institutes of Health Research (CIHR) , the  St. Giles Foundation , the  Rockefeller University  grant no. 8ULTR000043  from the  National Center for Research Resources  and the  National Center for Advancing Sciences (NCATS)  of the  National Institutes of Health , the  Rockefeller University , the  National Institute of Allergy and Infectious Diseases  grant no.
CD4 + T cell count were assumed to be measured every three months and when it dropped below 500 cells/mL a cycle of IL-7 administration was simulated (one injection per week for 3 weeks). The dynamics were therefore based in part on fit to observed data and in part on a predicted response to repeated therapy. We analyzed two primary outcomes: the time spent above 500 cells/mL and the number of cycles (including the first cycle) needed to maintain CD4 + T cell counts above 500 cells/mL over 2 years. A secondary outcome was the median time between two successive cycles. Simulations were performed according to several scenarios varying from a constant effect after each cycle and decreasing effects on loss and proliferation rates. At each cycle, we assumed that the effect of IL-7 on the loss rate of CD4 + T cells started to decrease 3 (or 9) months after the last injection and disappeared after 1 (or 2) year.
Acknowledgments This work was presented in part at the 17th Conference of Retroviruses and Opportunistic Infections in San Francisco, California,  USA , on February 27-March 2, 2010, and at the 50th  Interscience Conference on Antimicrobial Agents and Chemotherapy in Boston, Massachusetts, USA , on September  12-15 ,  2010. We would like to thank  Michele Di Mascio  for his valuable comments on an earlier draft of the manuscript. Parallel computing was used thanks to the computing facilities  MCIA  ( Mesocentre de Calcul Intensif Aquitain) of the Universitede Bordeaux and of the Universitede Pau et des Pays de l'Adour.