dataesr/scientific-paragraphs-categorization huggingface dataset:
Southern blot For Southern blot analysis, a 597 bp probe corresponding to endogenous SERA5 coding sequence lying just upstream of the targeting sequence in constructs pHH1SERA5chimWT, pHH1_A_DC_mock and pHH1_3A_H + B_DH/E_SERA5 (which was identical in all cases) was produced by PCR amplification from P. falciparum 3D7 genomic DNA with primers SERA5_US_F and SERA5_US_R (Table  S1 ). Radiolabelling of the probe and hybridization to HindIII/EcoNIdigested genomic DNA from parasite clones of interest was performed as described previously  (Ruecker et al. , 2012). Quantification of the conversion of the signal corresponding to the non-excised modified SERA5 locus to the excised form was performed by phosphorimager analysis on a STORM 860 Molecular Imager (GE Healthcare) using ImageQuant software.
Acknowledgements The authors are grateful to  Malcolm Strath  ( NIMR ) for excellent technical assistance with this work, and thank  Andy Osborne ,  University College London, UK , for the gift of plasmid pA289-attP-BSD. This work was supported by the  UK Medical Research Council  ( U117532063  to M. J. B. ), and the  European Community Seventh Framework Programme  ( FP7/2007-2013)  under grant agreement No. 242095. C. R. C. was supported by a  Wellcome Trust   Project Grant  ( 086550/Z/08/Z ), and S. M. and M. M. by  Wellcome Trust Senior Fellowships  ( WT061173MA  and  087582/Z/08/Z  respectively). S. D. was in receipt of a PhD studentship from the  European Union   Framework Programme 7-funded Network of Excellence EviMalAR.
Acknowledgements The present paper summarises presentations made at a satellite symposium held at the 11th European Nutrition Conference, 28 October 2011, which was made possible by an unrestricted grant from  Danone Institute International. Writing and editorial assistance were provided by  Lisa Buttle , of  Chill Pill Media. This was contracted and funded by  Danone Research. The authors have declared that they have no conflicting interests. I. L. -W. is an employee of Danone Research.
▸ Short ordinal data are described by median and IQR and analysed using non-parametric statistical techniques. As originally described by Kiresuk and Sherman, the GAS T-score provides a composite score (the sum of the attainment levels×the relative weights (optional) for each goal) transformed into a standardised measure with a mean of 50 and an SD of 10. Several different scoring methods are currently used in the literature to account for partial achievement of goals in GAS. 22 In this study, baseline scores were rated as -1='some function' and -2='no function' with respect to the goal. T-scores were calculated with weighting (importance), and partial achievement was rated as -1 to conserve the normal distribution of scores. 22 AS scores were recorded for the shoulder, elbow, wrist, fingers and thumb joints.
Acknowledgements This work was supported by  Ipsen Pharma. The authors thank all the investigators and patients who participated in this trial and, in particular, to  Thierry Deltombe ,  Belgium  and  Steven Faux  and  Ian Baguley ,  Australia. The authors would like to acknowledge the editorial assistance of  Ogilvy Healthworld  and  Watermeadow Medical. Ipsen Pharma  provided financial support for this assistance. Financial support for manuscript preparation was also provided through the  Dunhill Medical Trust. The authors would like to thank  Benjamin Zakine  who was involved in the concept and design and data analysis for this study. Contributors LT-S wrote the first draft of this manuscript. LT-S, KF and JJ were involved in data collection and assembly of data, manuscript review and critique and final approval of the manuscript.
ACKNOWLEDGEMENTS We thank the patients and their families, and would also like to extend our thanks to those who provided editorial assistance. We thank the staff of their  Clinical Research Unit of the Oscar Lambret Centre  for the trial management and monitoring:  Yvette Vendel ,  Muriel Chapoutier ,  Emilie Decoupigny ,  Laurence Delannoy  and  Sandrine Ducornet. This is an investigator-initiated trial supported financially by  Novartis France. This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution-NonCommercial-Share Alike 3. 0 Unported License.
This study was registered in the European Clinical Trials Register(EudraCT No. 2008-004212- 12). Informed consent was obtained from each patient. Ethical considerations. (A) Patients undergoing simultaneous therapy with other anticancer agents (B) Patients with any prior allergy to cyclophosphamide or IM (C) Patients with concurrent illness such a congestive heart failure, active serious infection, etc. (D) Patients not able to stop during the first 2 weeks of treatment (PK phase) any medication that may interfere with PK of either treatments (E) Patients not able to swallow and absorb the oral investigational agents À 3 (L) Total bilirubin within normal limits (M) Serum creatinine within normal limits (N) Normal left ventricular ejection fraction (by MUGA scan or echocardiogram or NT-proBNP dosage) (O) Negative pregnancy test within the 7 days before the study (P) Using effective contraceptive measures and national regulations (Q) Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial (R) Before patient registration, written informed consent must be given according to ICH/GCP Abbreviations: ECOG ¼ Eastern Cooperative Oncology Group; ICH/GCP ¼ International Conference on Harmonisation/Good Clinical Practice; IM ¼ imatinib mesylate; MUGA ¼ multigated acquisition; NT-proBNP ¼ N-terminal probrain natriuretic peptide; PK ¼ harmacokinetic; RECIST ¼ Response Evaluation Criteria In Solid Tumours.
Illumina Infinium Human Methylation450 Bead Arrays We performed an epigenome-wide association study (EWAS) on peripheral whole blood from 100 AMD (GA and NV) case-control trios (a subset of the Michigan AMD-MMAP cohort; dbGaP phs000182) using the HM450 platform (unpublished data). Each trio (1 patient with bilateral GA, 1 patient with bilateral NV, 1 control) was matched for sex and for age (< 1 year difference between the 3 individuals in each trio). The sample group comprised 63% females, with a mean ± SD age of 79. 3 ± 5. 6. There was no significant difference in age between the AMD (79. 3 ± 5. 5, N=200) and control (79. 3 ± 5. 7, N=100) groups (P=0. 93; unpaired Student's t-test). We utilized this dataset to examine the methylation of IL17RC in a cohort independent of that previously described  (Wei et al.
10% ± 0. 05  [SEM] ) and control groups (0. 17% ± 0. 03; P=0. 34; unpaired Student's t-test) using this restriction enzyme-based approach (Figure  3 ). Furthermore, all samples examined showed <1% methylated DNA using the EpiTect Methyl II PCR Assay for IL17RC. These results were entirely consistent with our bisulfite pyrosequencing data from this region. Incomplete digest by the methylation-dependent enzyme was excluded as a potentially confounding factor in the observation of hypomethylation by the inclusion of the methylation-dependent control assay (Table  S3 ).
Illumina Infinium Human Methylation450 Bead Array data preprocessing We normalized the intensity data using a modified version of quantile normalization in the minfi Bioconductor package (http://bioconductor. org/packages/devel/bioc/html/minfi. html), which, briefly, forces the distribution of type I and type II probes on the Illumina 450K microarray to be the same. Quantile normalization is performed on the type II probes and then interpolated to a reference distribution to which the type I probes are normalized. This normalization is performed separately on the methylated (M) and unmethylated (U) channel intensities. The logit-transformed DNA methylation (DNAm) is y=log2(M/U), and the proportion methylation ("beta" scale, as reported by Illumina) can be obtained by: 2^y/ (1+2^y). The "beta" values for probes in and around IL17RC (N=35) were selected for subsequent statistical analyses.
Bisulfite pyrosequencing of the IL17RC promoter Bisulfite pyrosequencing is widely considered the gold-standard approach for quantitatively measuring DNA methylation across targeted regions (<400 bp) of the genome. Pyrosequencing assays were designed using algorithms built into the PyroMark Assay Design Software (Version 2. 0. 1, Qiagen, Maryland USA). Briefly, primers designed to target specific CpG sites within the IL17RC promoter were chosen from a list generated by the software on the basis of the algorithms' predicted assay quality. Genomic DNA (500 ng) was bisulfite converted using the EZ DNA Methylation Gold kit (Zymo Research) according to the manufacturer's instructions. Following bisulfite treatment all previously unmethylated cytosine residues are converted to uracil, whereas methylated cytosine residues remain unconverted.
, 2006). Pyrosequencing was performed on a PyroMark 24 Pyrosequencing System (Qiagen, Maryland USA) as per the manufacturer's instructions. Data were analyzed on the PyroMark Q24 software (Qiagen, Maryland USA). This software calculates the C peak as a percentage of the T plus C peak at each CpG site taking into account sequence length and signal strength. The mean methylation for each individual was calculated. Initially eight CpG sites overlapping the region specifically targeted previously  (Wei et al. , 2012)  were investigated in the Baltimore and Australian cohorts. To further explore additional regions at the locus an additional 25 CpGs were sequenced in the Baltimore cohort alone. An unpaired Student's t-test was used to compare the methylation difference between the matched case-control groups.
Acknowledgments The authors gratefully acknowledge the technical advice provided by  Dr David Chandler , the assistance of the  Western Australian DNA Bank  and the  Center for Inherited Disease Research (CIDR, Johns Hopkins University ). This work was supported by funding from the  Ophthalmic Research Institute of Australia (ORIA)  and the  American Health Assistance Foundation  to AWH as well as from an  Australian National Health and Medical Research Council (NHMRC) Centres of Research Excellence  Grant  1023911 (2012 )(2013)(2014)(2015)(2016) to JEC, DAM and AWH. CERA receives operational infrastructure support from the  Victorian government. Collection of the Michigan AMD-MMAP cohort was enabled by funding from the  National Eye Institute (NEI)  ( EY016862 ) to AS and JRH. Funding from the  NEI  ( X01HG006605 ) to SLM, VFO, AEJ, KEB, JRH, AS and DJZ was used for the analysis of samples on the Illumina Human Methylation 450K platform at CIDR.
Alkylated proteins were compared in mass spectrometry before and after oxidation. CD-CD spectra were measured with a 100-m path length from 260 -178 nm at 10 -70 °C on a JASCO J-810 spectropolarimeter. Data were collected at 0. 5-nm intervals using a step auto response procedure (JASCO). CD spectra were presented as ⌬⑀ per amide. Protein concentration was 1 mg/ml in 20 mM phosphate buffer, pH 4. 5, for MIMOOX and Tat OYI. The CD data were analyzed with VARSELEC software to determine the secondary structure content according to the method of Manavalan and Johnson (38) using a set of 32 reference proteins and an average of 4960 calculations. Transactivation Activity-Transactivation was performed with HIV LTR-transfected HeLa cells (HeLa-P4) and analyzed by monitoring the production of ␤-gal as described previously  (13).
These results confirmed the establishment of a disulfide bond between the cysteine at position 22 and the C-terminal cysteines. CD spectra of MIMOOX and Tat OYI were similar (Fig. 2C ). According to the method of Manavalan and Johnson  (38) , mostly ␤ turn structures were deduced from CD spectra analysis, but no ␣ helix was found. The transactivation activity of MIMOOX and MIMO was tested with Tat OYI with a cysteine in position 22 as a positive control and without Tat as a negative control. A basal level of transactivation similar to the negative control was observed with MIMOOX and MIMO (data not shown). MIMOOX Is Recognized by the mAb 7G12-An ELISA-based method was used to measure antigen/antibody association rate constants in solution. Antigen and antibody were mixed and aliquots were withdrawn at different time intervals to determine the amount of free antibodies.
B, mass spectrometry after alkylation with iodoacetamide of MIMO (black), MIMOOX in oxidation conditions at T ϭ 0 h (dashed lines) and at T ϭ 6 h (gray). In C, CD spectra of MIMOOX and Tat OYI were measured from 260 to 178 nm with a 50-mm path length in 20 mM phosphate buffer (pH 4. 5). The same percentage of secondary structures of MIMOOX and Tat OYI was determined from the CD data analysis with no ␣ helix, 23% extended structure, 30% ␤ turns, and 47% of other structures. The absence of the ␣ helix in MIMOOX is in accordance with a similar structure of the conserved surface of Tat variants that contain only ␤ turn secondary structure. Furthermore, MIMOOX having 56 residues, 30% ␤ turns correspond to four ␤ turns. This is compatible with the presence of at least ␤ turns in the MIMOOX structure.
Clinical trials with Tat OYI were begun in France in February 2013. The protocol is entitled "Evaluation on seropositive patients of a synthetic vaccine targeting the HIV Tat protein" with the acronym: "EVA TAT. " The protocol was declared in the European Clinical trial database (EudraCT) under ID no. 2012-000374-36. The protocol received favorable advice from an ethics committee (CPP SudMed 2) on November 9th, 2012 and an authorization from the French drug agency (Agence Nationale de Securitedu Medicament) on January 14th, 2013. It is a phase I/II clinical trial to test the Tat OYI vaccine. It is a randomized double-blinded clinical trial with anonymous syringes containing either the vaccine or placebo. Phase I/IIa will be carried out on four groups of 12 patients with an undetectable viremia (inferior to 40 copies/ml) and a level of CD4 cells superior to 350/mm3 for at least one year.
HCVcc and HCVpp production and infection HCVcc (Luc-Jc1 and Jc1)  [18]  and HCVpp (H77, HCV-J, JFH1, UKN3A1. 28, UKN4. 21. 16, UKN5. 14. 4, UKN6. 5. 340, P02VJ)  [8, 41]  were produced as described  [8, 25]. Patient-derived HCVpp were produced from serum of a patient undergoing LT using full-length E1E2 expression constructs generated from circulating HCV as described  [8, 36]. The study was approved by the Strasbourg University Hospital Institutional Review Board and written informed consent was obtained from all patients (ClinicalTrial. gov Identifier: NCT00213707). Huh7. 5. 1 cells were pre-incubated with antibodies for 1 h and then incubated with HCVpp or HCVcc for 4 h at 37uC. Analysis of viral infection was performed by detection of luciferase activity as described  [18, 24, 25]. For combination experiments, anti-CD81 (QV-6A8-F2-C4) mAb was tested individually or in combination with the second antibody.
Acknowledgments We thank  R. Bartenschlager  ( University of Heidelberg, Germany ),  F. -L. Cosset  ( Inserm U758, ENS Lyon, France ) and  J. Ball  ( University of Nottingham, UK ) for providing plasmids for production of HCVcc and HCVpp,  C. M. Rice  (The  Rockefeller University ) and  F. V. Chisari  ( The Scripps Research Institute, La Jolla, CA ) for Huh7. 5 and Huh7. 5. 1 cells, respectively,  A. Patel  ( University of Glasgow, UK ) for Huh7. 5-GFP+cells,  S. K. H. Foung  ( Stanford University,Palo Alto, CA ) for anti-E2 mAb CBH23,  D. Trono  ( Ecole Polytechnique Federale de Lausanne, Switzerland ) and  T. Pietschmann  ( TWINCORE, Centre for Experimental and Clinical Infection Research, Germany ) for lentiviral expression constructs. We acknowledge excellent technical assistance of  L.
This work was supported by  Inserm ,  University of Strasbourg , the  European Union  ( ERC-2008-AdG-233130-HEPCENT ,  INTERREG-IV-Rhin Superieur-FEDER-Hepato-Regio-Net 2009 and 2012 ), the chair of excellence program of the  Agence Nationale de la Recherche France  ( ANR-05-CEXC-008 ),  ANRS  ( 2009/183 ,  2011/132 ,  2012/239 ),  Laboratoire d'excellence LabEx HEPSYS (Investissement d'Avenir ;  ANR-10-LAB-28 ), the  Direction Generale de l'Offre de Soins  ( A12027MS ) and  Aldevron (Pro Inno II  ( KA0690901UL8) ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. FG and JT are employees of  Aldevron GmbH ,.
Reports from each OPD were consolidated into a central database. Coordination and sharing of urgent information was conducted by regular telephone contact with health facilities and their medical coordinators, and weekly meetings. Regular data and information on outbreak alerts were transmitted daily (subsequently weekly) to the Internally Displaced Persons Surveillance System (IDPSS) set up by the MSPP with the support of the United States Centers for Disease Control and Prevention (CDC). The IDPSS collated information from a larger number of reporting sites throughout Haiti, operated by various health agencies, of whom MSF was the largest in terms of geographic coverage and average number of sites reporting each week. Each OPD reported the number of consultations among children under 5 years old and among older persons due to any of the reportable diseases, with all other diagnoses grouped into the category "others" (Table  2 ).
The frequency of reporting was initially daily at the request of the Ministère de la Santé Publique et de la Population (MSPP), and weekly starting in week 12. Reports from each OPD were consolidated into a central database. Coordination and sharing of urgent information was conducted by regular telephone contact with health facilities and their medical coordinators, and weekly meetings. Regular data and information on outbreak alerts were transmitted daily (subsequently weekly) to the Internally Displaced Persons Surveillance System (IDPSS) set up by the MSPP with the support of the United States Centers for Disease Control and Prevention (CDC). The IDPSS collated information from a larger number of reporting sites throughout Haiti, operated by various health agencies, of whom MSF was the largest in terms of geographic coverage and average number of sites reporting each week.
Each OPD reported the number of consultations among children under 5 years old and among older persons due to any of the reportable diseases, with all other diagnoses grouped into the category "others" (Table  2 ). The frequency of reporting was initially daily at the request of the Ministère de la Santé Publique et de la Population (MSPP), and weekly starting in week 12. Reports from each OPD were consolidated into a central database. Coordination and sharing of urgent information was conducted by regular telephone contact with health facilities and their medical coordinators, and weekly meetings. Regular data and information on outbreak alerts were transmitted daily (subsequently weekly) to the Internally Displaced Persons Surveillance System (IDPSS) set up by the MSPP with the support of the United States Centers for Disease Control and Prevention (CDC).
Data collection Surveillance of death rates and malnutrition prevalence was community-based and exhaustive within two specific sites served by MSF-France: Delmas24, a neighbourhood of Port-au-Prince consisting of mixed residential layout (houses, tents, and small camps) and Champs de Mars, a dense community of displaced persons. Surveillance of Delmas 24 was established by week 12, while surveillance of Champs de Mars was established by week 17, six and three weeks after MSF-France began operating these OPDs, respectively. In each site, during the first week of data collection, the baseline size of the population under surveillance was estimated. In Delmas24, a team of home visitors counted all households, while an estimate of mean household size, necessary to compute the total population, was obtained through a stratified cluster survey, which was also used to assess basic needs (results not shown).
Data analysis & reporting Data were entered in EpiData (EpiData Association, Odense, Denmark) between Monday and Wednesday of the week following data collection, and analysed using Microsoft Excel, with a short bulletin written each Thursday. Bulletins reported crude and under-5y death rates (CDR and U5DR, respectively) per 10,000 person-days, as warranted. Aggregate case data were analysed using Microsoft Excel. A bulletin was created for each reporting period providing an overview of the situation, with special reference to suspected cases of conditions requiring immediate notification, and to changing trends in any condition under surveillance. While a single case of any immediately reportable condition was sufficient to generate an alert, for other, more frequent conditions (e. g. acute respiratory infection) we plotted trends in incident cases and proportional morbidity so as to detect important changes.
Data analysis & reporting Data were entered in EpiData (EpiData Association, Odense, Denmark) between Monday and Wednesday of the week following data collection, and analysed using Microsoft Excel, with a short bulletin written each Thursday. Bulletins reported crude and under-5y death rates (CDR and U5DR, respectively) per 10,000 person-days, as well as estimates of severe (MUAC < 115mm and/or bilateral oedema) and global (MUAC <125 mm and/or bilateral oedema) acute malnutrition (SAM and GAM, respectively) among children aged 6-59 months, and descriptions of population movements.
Acknowledgements The authors would like to thank  Melissa McRae ,  Marie Noelle Rodrigues ,  Yann Diplo ,  Rosa Chrestani ,  Marie-Christine Ferir ,  Laurent Sury ,  Lisabeth List , the changing medical coordinators of all MSF sections and  Todd Swarthout  who supported the establishment of the surveillance systems and facilitated sharing the intersectional data. Kate Alberti  and  Leslie Shanks  provided valuable guidance in the drafting of the final text of the article.
POTENTIAL AND GENOMIC REPERTOIRES: A QUESTION OF ONTOLOGY AND ORTHOLOGY Immune repertoires sensu stricto are expressed by lymphocyte clones, each carrying a single receptor for the antigen. Such receptors comprise IG and TR in jawed vertebrates  (8, 9)  and VLR in Agnathans  (145). The sequences of these receptors are available in databases such as GenBank or EMBL, which are difficult to use for transversal studies due to inconsistent annotation. The IMGT® information system (see below) has largely solved this problem setting standardized gene nomenclatures, ontologies and a universal numbering of the IG/TR V and C domains, thus giving a common access to standardized data from genome, proteome, genetics, two-dimensional, and three-dimensional structures  (146). The accuracy and the consistency of the IMGT® data are based on IMGT-ONTOLOGY, the first, and so far, unique ontology for immunogenetics and immunoinformatics  (147).
With the development of high-throughput sequencing, large numbers of new sequences of antigen receptor genes have become available, which can be classified into different categories: genomic sequences of IG or TR (in germline configuration in genome assemblies) or fragments of IG/TR transcripts, containing the CDR3 or not. Also, these datasets can be produced from species newly sequenced, as well as from new haplotypes of well-described species. The annotation of such sequences remains an open question. Manual annotation is not applicable, and no good automated approach has been validated yet. A relevant annotation of these massive datasets will require the integration of genomic and expression data with existing standardized description charts, as offered by IMGT®. A standardized annotation is an important issue since it facilitates the re-utilization of datasets and comparison of analyses.