dataesr/scientific-paragraphs-categorization huggingface dataset:
GWAS and replication studies on LA We performed a GWAS of 49 LA and 92 non-LA HIV patients. Demographic data on these 141 patients are summarized in Table  1. In our previous study, treatment with d4T was significantly associated with earlier onset of LA. 10  Therefore, we intentionally enrolled more non-LA patients treated with d4T-containing regimens in order to exclude the possibility that levels of potential LA risk were lower in control patients than in LA patients. We also selected non-LA patients treated for longer periods. Except for the duration of the LA-free period and the drug regimen, there was no difference in demographic data between LA and non-LA patients (Table  1 ). When we compared allele frequencies of SNPs between validated 47 LA and 89 non-LA patients, no SNP was significantly associated with the disease ( p < 10 -7 ).
Acknowledgments We thank the HIV patients for their kind participation in the study. We thank  Tippawan Rattanatham  and  Siriluk Feangvad  for their excellent assistance. We also thank  Drs. Wisit Prasithsirikul ,  Agostino Riva ,  Massimo Galli , and  Patrice Debre  for critical discussions. This study was supported by grants from the  Ministry of Education, Culture, Sports, Science, and Technology , the  Ministry of Health, Labour, and Welfare, Japan , and those from  ANRS, France. S. U. was a recipient of the  Royal Golden Jubilee Ph. D. Program  (grant  PHD/0094/2551 ) of the  Thailand Research Fund. We dedicate this research communication to  Siriluk Feangvad , who passed away on November 30, 2013.
Antigen design Consensus clade B 15-mer peptides (123 total) overlapping by 11 amino acids (aa) for HIV-1 Gag were obtained through the NIH AIDS Reagent Program (catalog #8117). In our unbiased approach, we used ASP sequences obtained from the transmitted founder virus of an acute patient (WITO_TF1, Genbank Acc. # JN944938. 1) and a HIV-1 lab strain, NL4. 3 (Genbank Acc. # M19921), to design 85 overlapping ASP peptides (OLPs; 14 to 18mers overlapping by 10 residues) using the Los Alamos National Lab's PeptGen tool (http://www. hiv. lanl. gov/content/sequence/PEPTGEN/peptgen. html; Additional file 2: Figure  S1 ). Peptides were synthesized in a 96 well array format by New England Peptide  [68]. Individual OLPs were combined into a single Gag or ASP pool. ASP subpools of no more than 10 peptides were used in a matrix format.
Acknowledgments The authors are grateful to  Pierre-Gregoire Coulon  for discussions and technical assistance. We would like to thank  NIH AIDS Reagent Program  for providing reagents. This work was supported by the  National Institute of Allergy and Infectious Diseases (NIAID ;  RO1 A1 084772 ), the  Agence Nationale de Recherche sur le SIDA et les hepatitis virales (ANRS) , and  Sidaction. S. Cardinaud is supported by  Sidaction  and the European consortium  FP7 Cuthivac. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
They have been sampled either in Cameroon or in France, at time points ranging from 1994 to 2012, showing that they are not associated to a particular sampling time or location (see S2 Text and S2C and S2D Fig). Selection pressure analysis also showed that H strains were submitted to lower negative selection pressure than T strains and evolved faster. It has also been proposed that the 181C residue in the RT could represent a fitness advantage  [20] , even though this has been demonstrated in vitro only using mutants viruses from a H strain backbone. The reasons why H strains became predominant could thus be linked to favourable biological properties of these strains and/or different opportunities for diffusion. The two phases may also reflect a two-step geographic expansion of the virus in Cameroon, but the absence of a geolocalized dataset does not allow us to investigate this hypothesis further.
The ML trees were visualised using FigTree (http://tree. bio. ed. ac. uk/software/figtree/). Distribution of the natural Y181C mutation. Among the 190 concatenated sequences, 11 were sampled from patients who received or had received NNRTIs and 100 were NNRTInaïve at the time of sampling. The information about NNRTI treatment was not available for the other 79 patients. To investigate the distribution of the natural 181C resistance mutation, we used the sequences from the 100 NNRTI-naïve patients and studied the association between clade and Y181C residue by using a chi-squared test. Evolutionary analyses. Out of the 190 concatenated sequences described above, 154 were used for tMRCA inference and analysis of evolutionary dynamics. These were the sequences for which all three regions had been sequenced from the same sample, meaning a unique time of sampling.
All the positions in the protease and RT regions known to be involved in drug resistance for group M according to the ANRS algorithm (http://www. hivfrenchresistance. org/) were removed from the alignment. SIV sequences sampled from gorillas (accession numbers: FJ424863, FJ424864, FJ424865, FJ424866, FJ424871) were included to be used as an outgroup, and evolutionary analysis was performed in a Bayesian framework using BEAST  [44]. A GTR +Γ model allowing for invariant rates among sites was used, with a log-normal relaxed molecular clock model and analysis performed using various tree priors, including constant size, exponential growth, logistic growth and Bayesian Skyline. Bayesian analysis was calibrated by setting priors on the tip nodes of the tree, referring to the year in which sequences were sampled.
Flow cytometry Lymph node cells were surface stained with the following primary monoclonal antibodies (mAb): mAb IL-A11 (IgG2a) for CD4 (VMRD, USA). Macrophages were stained with mAb IL-A156 for CD40, and mAb IL-A159 for CD80 (all IgG1 isotype from AbD Serotec, UK). Cells were then washed and stained with fluorochrome-conjugated, isotype-specific antibodies. Debris and dead cells were excluded from analysis based on granularity and size and, for lymphocytes, based on inclusion of 7-amino-actinomycin D (7-AAD) as a viability dye (BD Biosciences, USA). Multiple color analyses were performed with a flow cytometer (FACScanto; Becton-Dickinson) equipped with the FACSDiva software (BD Biosciences) after the acquisition of at least 5000 events. Control isotype antibodies (AbD Serotec, UK) were used to evaluate nonspecific binding and to set gates and quadrants delineating positive populations.
Acknowledgements This work was supported by the  Centre National de la Recherche Scientifique (CNRS) , by the  Agence Nationale de la Recherche (ANR)  through the  LabEx  project  Chemistry of Complex Systems  ( ANR-10-LABX-0026_CSC ), the  EC-ERC  project  SUPRAFUNCTION  ( GA-257305 ) and by the  International Center for Frontier Research in Chemistry  (icFRC). BD wishes to thank support by the  ANR  project  Nanomultisens  ( ANR-13-BS10-0003-02 ). MS wishes to acknowledge for support by the  EC  project  MSCA-SYNCHRONICS  ( GA-643238 ). The authors wish to acknowledge  Cathy Royer  and  Valérie Demais  for TEM and SEM analyses at the " Plateforme Imagerie in Vitro " at the  Center of Neurochemistry (Strasbourg, France). Rajendra Kurapati  is acknowledged for fruitful discussions during the manuscript preparation.
Moreover, besides the possibility of resident APCs to pick-up Figure  1  Dual effect of tick saliva in vivo on the recruitment of leukocyte infiltrates to skin and dendritic cells to draining lymph nodes. A surgical monofilament suture was positioned on the back of a C57BL/6 mouse and tick saliva or a control solution was intradermally injected once a day for 3 days into the suture area. The skin at the sutured area was then stained with FITC solution and mice were killed 24 h later to analyze the skin and lymph nodes. Data were obtained from two independent experiments including three mice per condition. (A) Representative hematoxylin and eosin staining (H&E) of histological sections of skin biopsies. B Density of infiltrated leukocytes in skin biopsies was estimated by counting the total number of nuclei within histological samples of skin sections, of similar size and including the sutured-damaged area, using Image J software (two mice per condition, 10 sections per mouse).
Acknowledgments We are very grateful to  Dr Naomi Taylor  ( IGMM, Montpellier ) for helpful discussions, advice regarding experiments and for correcting the manuscript. We thank  Dr Valérie Dardalhon  ( IGMM, Montpellier ) for helpful discussions, advice and for help regarding in vivo experiments and cytometry. We thank  Marc Plays  ( IGMM, Montpellier ) for help regarding in vivo experiments. We acknowledge support from the animal facilities of  CIRAD Guadeloupe  and the animal facilities of IGMM.
Results Transcriptome analysis of DC challenged with BCG and Mtb recombinant strains. To investigate whether the RD1 locus and specifically the ESX-1 secretion system may impact the global gene expression profile in DC, a comparative microarray analysis was performed in primary human DC infected with parental Mtb or Mtb and BCG recombinant strains, expressing the RD1 region (MtbΔ RD1::RD1 and BCG::RD1, respectively) or lacking the RD1 genetic locus (MtbΔ RD1::B412 and BCG::B412, respectively) (for further details on strain characteristics and virulence see Supplementary Table  S1 ). Total RNA was isolated, hybridized on the HumanHT-12 v4 Expression BeadChips (Illumina) and analyzed with the oneChannelGUI Bioconductor package  17. Among the significantly expressed genes, the top upand down-regulated transcripts with a minimum fold change of 2.
To validate the transcriptome analysis data, quantitative real time PCR experiments were conducted in DC infected with Mtb and BCG recombinants. A robust induction of IFNB1 and IL29 (also known as IFNL1) was observed in DC infected with either wt Mtb or MtbΔ RD1::RD1 (Fig. 3 ) and correlated with the gene expression data demonstrating ISG up-regulation (Fig. 2  and Table  1B ). Interestingly, the   1A ). This observation prompted us to extend our analysis to other subunits of the heterodimeric cytokines IL-23 and IL-27: IL12B (also known as IL12p40) that pairs with IL23p19 to constitute IL-23, and EBI3 that associates with IL27p28 to form IL-27  25. Expression of both IL12p40 and EBI3 subunits was induced by RD1 in the Mtb background, as occurs in response to Mtb infection (Supplementary Fig.
Transcriptomic analysis. DC cultures from 2 healthy donors were infected for 8 h with parental Mtb and the indicated Mtb and BCG recombinants. RNAs were extracted with mirVana isolation kit (Ambion, Life Technologies) according to the manufacturer's instructions. RNA quantification and integrity was inspected by bioanalyzer analysis (Agilent Technologies). cRNAs were generated and hybridized on HumanHT-12 v4 Expression BeadChips according to the Illumina TotalPrep RNA Amplification Protocol (Illumina). The chips were then scanned with the Illumina scanner to generate the digitized image data files. Data were analyzed using the BeadStudio software package to generate a probe-level profile without background subtraction. Data were further analyzed with oneChannelGUI bioconductor package  17.
Specifically data were normalized by loess  55  and the number of genes evaluated was reduced by applying an interquartile filter (IQR > 0. 25) to remove the non significant probe sets (i. e. not expressed and those not changing)  56  (http://www. bepress. com/bioconductor/). To assess differential expression, we used an empirical Bayes method  57  together with a false discovery rate correction of the p-value  58. Hierarchical clustering (ST, Euclidean distance, average clustering) was performed using TMEV 4. 8 software (http://www. tigr. org/software/). The genes annotated in the Ingenuity knowledge database were analyzed using the data-mining tool IPA 7. 0 (www. ingenuity. com). Each treatment was subjected to IPA 4. 0 analysis, and subsequently, the results were subjected to a comparative analysis to identify functional classes associated with differentially expressed genes in response to different treatments.
Gene expression data have been deposited in the NCBI's Gene Expression Omnibus (GEO, http: http://www. ncbi. nlm. nih. gov/geo, GEO Series accession number GSE62423), according to the MIAME standards. Flow cytometry analysis. Cells (10 5 ) were washed once in PBS containing 2% FBS and incubated with monoclonal Abs at 4 °C for 30 min. After washing the cells were fixed in 4% formaldehyde (PanreacQuimica) before analysis on a FACSCan using CellQuest software (Becton Dickinson). A total of 20,000 cells were analyzed per sample. The viable DC were gated by forward and side scatter and then the expression of cell surface molecules was evaluated using the median fluorescence intensity (MFI) after subtraction of the values of the isotype Ab controls. Only cells comprised in viable cell gate were considered for the analysis.
A total of 30,000 cells were analyzed per sample. Data were analyzed by FlowJo software (TreeStar Inc. , Ashland, OR). MLR experiment. MLR was conducted as previously described  33. Briefly, CD4 + T cells were purified by indirect magnetic sorting with a CD4 + T-cell isolation kit (Miltenyi) from allogeneic PBMC. Immature DC and DC infected for 24 h with wild type Mtb or Mtb and BCG recombinant strains described previously were re-suspended in 10% FBS complete medium prior to co-culture with total CD4 + T cells. Supernatants from T cell/DC co-culture (ratio 10:1) were harvested at day 5 and analyzed for IFN-γ production.
Acknowledgements This work was supported by grant  RF-2010235199  from the  Italian Ministry of Health  (to EMC). We acknowledge  Eugenio Morassi  for figure preparation. We thank  Prof. John Hiscott  ( Istituto Pasteur-Fondazione Cenci Bolognetti, Rome ) and  Dr. Fabrizio Mattei  ( Istituto Superiore di Sanità, Rome ) for helpful discussion of the data and critical reading of the manuscript.
A foremost worldwide network employing such principles is PulseNet International, a molecular subtyping network for foodborne and waterborne disease surveillance (http://www. pulsenetinternational. org/). The primary bacterial subtyping technique used by PulseNet is PFGE analysis. PulseNet Africa is operational and active  [27, 28] , with an established database of PFGE patterns for V. cholerae O1 isolated in sub-Saharan Africa  [7, 11, 29]. Therefore, for molecular subtyping of V. cholerae O1, PFGE analysis using PulseNet methodology is currently the most functional choice for data sharing and inter-laboratory comparisons. The ultimate genotypic method for analysis and comparison of bacterial isolates would be whole-genome sequencing (WGS) analysis. WGS of V. cholerae O1 El Tor strains from sub-Saharan Africa have shown clonal relatedness to O1 El Tor strains isolated elsewhere in the world.
Acknowledgments We acknowledge Africhol focal points, country coordinators, and data managers of  Côte d'Ivoire, Guinea, Mozambique ,  DRC , and Togo who oversaw work in their respective country and organized surveillance for Africhol on behalf of the Ministries of Health. We also acknowledge the following Africhol staff at AMP:  Mr Leonard Heyerdahl  (Project operations manager),  Miss Delphine Sauvageot  (Africhol coordinator-West Africa),  Dr Bekithemba Mhlanga  ( Africhol coordinator-East Africa ) and  Souleymane Sakande  (Africhol data manager). More generally, we would like to acknowledge the assistance of numerous staff at the countries National Ministry of Health as well as district medical officers whose cooperation was highly helpful for data and specimen collection, and shipment.
Data variables, sources, and statistical analysis Data was sourced from the Khayelitsha RR-TB database and cross checked with medical records for confirmation of data specific to this study. The Khayelitsha RR-TB database was established in 2008 for evaluation of the decentralized model of care and all data was collected prospectively from 2008  [6]. The STROBE guidelines on the reporting for observational studies were followed  [26]. Data meeting the inclusion criteria were extracted into an Excel database (Microsoft, Redmond, WA, USA). CD4 count was defined as CD4 result available at time at RR-TB diagnosis or within one month of RR-TB treatment start. Final RR-TB treatment outcomes were defined according to the South African National Guidelines, which are in line with the World Health Organization outcome definitions, with the exception of treatment failure, where failure to convert positive cultures to negative within 6-8 months constitutes failure of treatment  [22, 27, 28].
The time from RR-TB treatment start to start of ART was calculated in days and then categorised as 2 weeks, 2-8 weeks and > 8 weeks; time windows were derived from the guidelines described in Table  1. Data was analysed using STATA/IC 12 software (Stata Corp, College Station, TX, USA) and descriptive statistics were used to report demographic, clinical, and immunological characteristics of patients. Final treatment outcome proportions were compared by chi-square tests; a pvalue < 0. 05 was considered significant. Time to ART initiation was shown using a Kaplan Meier curve. To assess the impact of time to ART initiation on mortality, a multivariate Cox regression analysis was performed. Censoring for both analyses was done at loss from RR-TB treatment (previously defined as lost to follow-up) and transfer out.
Acknowledgments This research was conducted through the  Structured Operational Research and Training Initiative (SORT IT ), a global partnership led by the  Special Programme for Research and Training in Tropical Diseases at the World Health Organization (WHO/TDR ). The model is based on a course developed jointly by the  International Union Against Tuberculosis and Lung Disease  ( The Union ) and Médecins sans Frontières. The specific SORT IT programme which resulted in this publication was jointly developed and implemented by: the  Operational Research Unit (LUXOR) ,  Médecins Sans Frontières, Brussels Operational Centre, Luxembourg ; the  Centre for Operational Research, The Union, Paris, France; the Centre for International Health, University of Bergen, Norway ; the  Institute of Tropical Medicine, Antwerp, Belgium ; the  University of Nairobi ,  Kenya  and the  University of Chester ,  United Kingdom.
Thus, courses of saturation time dependency must be used to infer the initial velocities of saturation  [47]. Also, the relaxation of ligand-saturated spins during the irradiation time, when the ligand is not bound to the protein, should also be taken into account  [48] [49] [50]. Recently, we have applied a kinetic model based on the DynaFit software  [51]  that explicitly includes the rebinding and relaxation of already saturated ligand in one analysis of the experimental STD values  [52]. Herein, we present the extension of this kinetic model to include, in an individualized way, the presence of the Į and ȕ anomers as two competing ligands in equilibrium.
Kinetic Model The program DynaFit  [51]  was used to process the experimental data within the model. As follows, we describe the components, chemical equations (Equations 1-17), kinetic constants, concentrations and experimental data sets (Equations 18 and 19) that were used: 2. 4. 1. Components Ligand, 2FDM; [Į]total + [Į]total = [2FDM]total R, receptor (ConA); R*, steady-state saturated receptor during on-resonance irradiation time Į, unsaturated Į anomer; ȕ, unsaturated ȕ anomer Į*, saturated Į anomer; ȕ*, saturated ȕ anomer 2. 4. 2. Equations R* + Į R*Į koffĮ/kon = KDĮ (konĮ Ł konȕ Ł kon) (1) R* + ȕ R*ȕ koffȕ/kon = KDȕ (konȕ Ł konĮ Ł kon) (2) R*Į ĺ R*Į* km (kmĮ Ł kmȕ) (3) R*ȕ ĺ R*ȕ* km (kmȕ Ł kmĮ) (4) Į* ĺ Į krĮ (5) ȕ* ĺ ȕ krȕ (6) R* + Į* R*Į* koffĮ/kon (KDĮ* Ł KDĮ) (7) R* + ȕ* R*ȕ* koffȕ/kon (KDȕ* Ł KDȕ) (8) 2.
In our case, the two anomers interact with ConA, albeit with different affinities (see Figure  4 ). The calculated saturated concentrations of both anomers from the experimental STD percentages at every concentration and saturation time were globally fitted to a series of kinetic differential equations corresponding to the above model using the DynaFit software  [51]  (Figure  4 ). Instead of directly using the equilibrium dissociation constants (KDĮ and KDȕ), the kinetic dissociation constants (koffĮ and koffȕ) were used as adjustable parameters. First, the association constant kon was considered to be constant and fixed to the diffusion-limited encounter at 10 8 M í1 •s í1. This is a reasonable approximation of the kinetics of binding monosaccharides to ConA. Interestingly, it has been shown that, when analyzing STD data in processes that are not diffusion-controlled, the kinetics of the association must be considered  [55].
Image analysis Images were analyzed by in-house macros based on ImageJ software (http://imagej. nih. gov/ij/). MF/microglial cell density was determined as the number of positive pixels for CD68 divided by the total tumor area. MF density was differentiated from that of microglia by the ratio of CD14 positive pixels to CD68 positive pixels. M1 and M2 MF densities were characterized by the number of either iNOS or Arg1 positive pixels, respectively, within the population of CD68 positive pixels. Bone marrow-derived MF culture and activation Bone marrow was isolated from femora and tibiae of nude mice (20-25 g, Charles River Laboratory) by flushing the bones with 1 mL of Iscove's Modified Dulbecco's Media (IMDM, Sigma) containing 60% Fetal Clone II (FCII, Thermo Scientific) and 1 mg/mL P/S (Sigma).
Statistical analyses All data are presented as the mean § standard deviation (SD). Statistical analyses were performed with the JMP Ò program (SAS institute, USA) and, unless otherwise stated, significances were calculated by nonparametric Kruskall-Wallis for multiple comparisons or Mann-Whitney U tests. Statistical significance was achieved when p < 0. 05 (*) or p < 0. 01 (**), otherwise they were not significant (NS).
Introduction: To assess the safety and immunogenicity of MAGE-A3 immunotherapeutic in patients with stage IB-III MAGE-A3-positive non-small-cell lung cancer (NSCLC) who were or were not undergoing standard cisplatin/vinorelbine chemotherapy. Methods: This open, prospective, multicenter, parallel-group phase I study (NCT00455572) enrolled patients with resected (cohorts 1-3) or unresectable (cohort 4) MAGE-A3-positive NSCLC. MAGE-A3 immunotherapeutic (300 μg recombinant MAGE-A3 formulated with AS15) was administered (eight doses, 3 weeks apart) concurrent with (cohort 1), after (cohort 2), or without (cohort 3) standard-adjuvant chemotherapy, or after standard radiotherapy and/or chemotherapy (cohort 4). Results: Sixty-seven patients received greater than or equal to 1 dose of MAGE-A3 immunotherapeutic.
Study Design The clinical study (NCT00455572) was an open, nonrandomized phase I/II study conducted at 18 centers in five European countries (Belgium, France, Germany, Italy, and United Kingdom) and Canada. The study was conducted in accordance with good clinical practice guidelines and all applicable regulatory requirements, including the Declaration of Helsinki (1996). The protocol was approved by the review boards at all participating institutions, and all patients gave written informed consent. Eligible patients had pathological stage IB, II, or III (but not III/N2-3  47  ) NSCLC, which was MAGE A3-positive (determined by reverse-transcriptase polymerase chain reaction [PCR] on paraffin-embedded primary tumor sample; Supplementary Methods, Supplemental Digital Content 1, http://links. lww.
Statistics This was the first study of MAGE-A3 immunotherapeutic in a target population of MAGE A3-positive NSCLC patients who were receiving, or had recently received, chemotherapy after tumor resection. The sample size was, therefore, typical of studies of this kind and was based on general experience rather than any formal estimate or hypothesis. It was anticipated that out of 18 patients enrolled in a cohort, 15 patients would be evaluated for immunogenicity. Appropriate descriptive statistics were applied to demographic and other baseline characteristics. SAS (version 9. 2, SAS Institute Inc. Cary, NC) was used for all computations.