dataesr/scientific-paragraphs-categorization huggingface dataset:
Availability of supporting data Data supporting the results of this article are available in the NCBI Sequence Read Archive (SRA) repository. This includes whole genome sequence data for the Silkie and Taiwan L2 chickens [SRA:PRJNA202483]; whole genome sequence data for the Red Jungle Fowl [SRA:SRX043655, SRA:SRX043656]; and BAM alignments to the LTR of the EAV-HP genome [GenBank:NC_005947] for the Pirbright lines and Ethiopian village chickens [SRA:SRP062207]. Availability of data and materials Not applicable.
Characteristics of the mitochondrial CDS cohort This study reports the results of 101 individual RNAi knockdowns performed in procyclic forms (PCF) of T. brucei and targeting proteins for which the mitochondrial localization was predicted "with high confidence" in a previous study  [17] , and for (most of ) which the annotation in the T. brucei genome database GeneDB  [6]  was "Hypothetical protein, conserved" at the start of the study. At the time of writing, new annotations have been proposed for a number of these CDSs (See Additional file 1). All the targeted proteins belong to the mitochondrial protein inventory 'MitoCarta'  [18] ). Moreover, all 101 CDSs but two (Tb10. 61. 1810 and Tb927. 7. 2990, code name in our study: T217 and T320) were also included in a global approach of "high-throughput phenotyping using parallel sequencing of RNA interference targets" (RIT-seq) developed after the start of our study  [8].
One possible source of these discrepancies is that our PCFs were cultivated in vitro for a long time whereas in the RIT-seq study, Alsford et al. used induced PCFs directly deriving from BSFs. Discrepancies were significantly lower when we compared our data to those obtained from individual RNAi knockdowns in the literature  [9, [19] [20] [21] [22] [23] [24] [25] [26]. Indeed, this comparison showed a concordance between both datasets in 8/ 11 cases (see Additional file 1); whereas for three genes (T223/ Tb927. 4. 1660, mitochondrial carrier protein; T171/ Tb927. 1. 1160 and T179/ Tb927. 1. 2990), conflicting results were obtained. As regard Tb927. 4. 1660, in spite of several attempts, Colasante et al. [22]  could not obtain a viable null mutant by double knock-out, nor could they obtain it using RNAi knockdown, even in non-induced condition.
Protocol and criteria for growth reduction definition The criteria chosen to assess cell growth dynamics used here were as described previously  [7]. Briefly, growth of the induced and uninduced culture was followed for up to 8 days after induction, with cell number determined daily using a Z2 Coulter counter (Beckman Coulter®). The numerical data obtained for growth were analyzed according to the following criteria: a defect was recorded if, during the 4 days following induction, cell number in the induced culture was <75% (mild) or <50% (severe) of the uninduced culture for two consecutive days.
Protocol and criteria for definition of cell cycle defects At day 5 post-induction, cells were fixed in 4% paraformaldehyde and stained with 4′,6-diamidino2-phenylindole (DAPI), air-dried on microscope immunofluorescence slides, and then analysed on a Zeiss Axioplan 2 microscope with a 100× objective equipped with a Photometrics CoolSNAP charge-coupled device camera (Roper Scientific®) driven by Metamorph Software (Molecular Devices®). The numbers of nuclei (N) and kinetoplasts (K) per cell were then counted in 200 cells, allowing determining the position of these cells in the cell cycle progress. Morphological abnormalities of the nuclei and/or kinetoplasts, as well as of the whole cell, were also recorded. All primary phenotypic data were collected blind. These data were then compared to those obtained for the reference cell line described above (T280), where DAPI analysis indicated ~68% cells with one nucleus (N) and one kinetoplast (K) (1N1K cells), ~20% 1N2K cells, and ~7% 2N2K cells, i.
DNA content To determinate the DNA content, a PI staining method was used. For this purpose, cells were washed with PBS, resuspended in 500 μl of iced 70% ethanol, vortexed 1 min and incubated at 4°C. After centrifugation, cells were resuspended in PBS and 10 mg/ml RNAse, placed 20 min at 37°C, centrifuged, incubated 10 -30 min on ice with 2. 5% PI and immediately analysed with a FACSCalibur flow cytometer (Becton Dickinson, San Jose, CA, USA) with the BD CellQuest™ Pro software.
Acknowledgments We thank  Frédéric Bringaud  ( Université Victor Segalen Bordeaux 2 ) for generously providing the T. brucei 29-13 cell line and T. brucei expression vectors. We were able to get the RNAi vector thanks to TrypanoFAN, the T. brucei functional genomics website, which is supported by the  Wellcome Trust  and published in Subramaniam et al. [7] (director Mark Field). We gratefully acknowledge  Vicky Diakou  and  Julien Cau  ( RIO Imaging in Montpellier/BioCampus Montpellier ) for expert advice and assistance in fluorescence microscopy. DEM was a recipient of a PhD grant from the  Fondation Infectiopole Sud  (http://www. infectiopolesud. com). This work received specific financial support from the  MIE (Emerging Infectious Diseases) program  of the CNRS, from the  University Montpellier 1 (Bonus Qualité Recherche , 2009) and from the  Agence Nationale de la Recherche  within the frame of the " Investissements d'avenir" program  ( ANR-11-LABX-0024-01 , "ParaFrap"), the  French Ministry of Research  and the  Centre Hospitalier Universitaire of Montpellier.
6 in 37ºC for 1 hour. Washing steps were performed in triplicate with 250 µl of TBS supplemented with 5mM CaCl2 (TBSCa) and 0. 1% Tween 20 between each step. The plates were quenched with 5% fish gelatine in TBSCa for 3 hours at room temperature. Protein S was titrated (0-1000nM) in 5% fish gelatine and incubated for 1. 5 hours at room temperature. Bound protein S was detected using biotinylated monoclonal anti-protein S (15nM, HTI), followed by HRP-conjugated streptavidin/biotin complexes, both diluted in TBSCa with 0. 5% fish gelatine and incubated for 1 hour at room temperature. Also higher concentrations of the detection antibody was added giving similar results. The assay was developed by addition of OPD, terminated with H2SO4 and the absorbance was read at 492nm. The data from all binding curves were fitted using nonlinear regression for the equation Y=Bmax×X/(Kd+X), where Y is the absorbance; Bmax, the maximal binding; X, protein S concentration, and Kd is the concentration of ligand required to reach half maximal binding.
APC and TFPI cofactor function in thrombin-generation assays determined by CAT Calibrated automated thrombography (CAT) was performed in protein S depleted plasma (Enzyme Research Laboratories) using a Fluoroscan Ascent FL plate reader (Thermo Labsystem) and Thrombinoscope software (Synapse BV), essentially as described previously  (4, 5, 18, 27). The protein S-depleted plasma was also deficient in protein S-C4BP complexes, which allowed specific studies of TFPI and APC cofactor functions without influence of effects caused by altered C4BP binding, as protein S-C4BP complexes have previously been shown to have limited TFPI-and APC-cofactor functions  (1, 18, 45). In the CAT assay, protein S (0-120nM) was added to plasma (80 µl/well) in the presence or absence of 9nM of APC (Haematologic Technologies Inc.
The APC cofactor function of the four protein S variants was studied in plasma and in assays with pure component. All four variants were fully functional as APC cofactors in both settings. All protein S variants also bound to FVa similarly to WT protein S. Taken together, these data suggests that the substituted residues were of little importance for the protein/protein interactions involved in this function of protein S. In conclusion, we have targeted potential PPI sites in the SHBG-like region of protein S by clustered mutagenesis in four recombinant protein S variants. Two of the protein S variants (SHBG2 and SHBG3) showed decreased binding and enhancement of TFPI, thereby confirming the importance of the LG1 domain in the TFPI cofactor function of TFPI. Combining experimental and in silico data we propose possible models of the protein S SHBG/TFPI Kunitz domain 3 complex.
Remaining FVa activity was analysed in a prothrombinase assay. D) Protein S enhancement of APC in the inactivation of FVIIIa was measured using a FVIIIa inactivation assay. Protein S (0-50nM) was incubated with 200 mU/mL FVIIIa, 5nM FIXa, 2. 5nM APC, 2. 5nM FV and 50μM phospholipids for 2. 5 minutes. The remaining FVIIIa activity was measured in a Xase assay. Data are presented as mean±SD; n=3. FIGURE LEGENDS.
Results and Discussion 3. 1. HPTLC. HPTLC, combined with chemical detection, is an effective technique for the phytochemical screening of plant extracts. Detection of different phenol is attempted using different stationary and mobile phases and using specific derivation system. Presence and/or absence of specific molecules were identified by matching the colors of spots after development and after derivatisation. Nuzheinide and oleuropein were used as references. The HPTLC fingerprints (data not shown) exhibit a good separation which allows a qualitative analysis of the studied extarct. Ethyl acetate, methanol, and methanol/water extracts were rich in phenolic compounds. Indeed, they showed fluorescent spots with different colors in the corresponding plates (white, blue, pink, brown, yellow-orange, and yellow-green color).
Research methods The main research method was a programme of forty semi-structured interviews of individuals at all levels of the organisation. Thirteen of these were waged and twenty seven unwaged. Three interviewees were female and thirty-seven were male. Depth data were sought and so interviews were semi-structured and open-ended in order to allow respondents to expand on those issues which they felt were most significant and meaningful. Interviews took a 'life history' approach  (Musson, 1998; Kirton, 2006)  and began by asking participants to trace back their involvement with the RNLI, how and when they had come to join the RNLI and what happened when they joined. Interviews took place at local stations (for coxswains, launch authorities, LOM's, mechanics and crew members), at RNLI headquarters (for directors and senior managers of the RNLI) and at RNLI divisional base (for divisional management and staff) and lasted from fifteen minutes to three hours in length, with an average of fifty minutes per interview.
All interviews were digitally recorded and transcribed. Further data were collected through participant observation (undertaking an exercise in the simulator) and non-participant observation (sitting-in on a five day management communications and command training course aimed at station management personnel) at the Lifeboat Training College co-located with RNLI headquarters in Poole. These research visits were used as 'an opportunity to see the organization at work and to 'feel' the organization'  (Parker, 2000: 238) , and observations were recorded in a research diary. Data were also derived from approximately 850 pages of organizational documents. After all interviews were transcribed and field notes and the research diary were written up, the primary data ran to 514 single-spaced pages.
Patient population and study designs For RA, the pooled CZP safety database included 4049 patients with RA from 14 studies (including randomised controlled trials (RCTs) and open label extensions (OLEs); figure  2A ), with maximum CZP exposure of 7. 6 years as previously described. 21 The first patient was enrolled by the end of 1998 and the safety cut-off date was 30 November 2011. Safety data were also assessed in 528 patients with RA enrolled in two Japanese CZP RCTs and their OLEs ( J-RAPID (NCT00791999, NCT00851318), HIKARI (NCT00791921, NCT00850343)) from 19 November 2008 up to 6 June 2013 (figure  2B ). In addition, safety data were assessed for psoriasis phase 2 CZP studies conducted between October 2005 and May 2007 (N=117 patients; C87040 (NCT00245765) and C87044 (NCT00329303)). Safety data were also assessed for the RAPID-PsA 15 (N=393 patients; NCT01087788) and RAPID-axSpA 18 studies (N=315 patients; NCT01087762) initiated in March 2010, using the new TB screening cut-off criteria of ≥5 mm induration for PPD positivity, up to the cut-off date of 16 November 2012 (figure  2B ).
For the majority of RA studies, and for RAPID-PsA and RAPID-axSpA, a loading dose of CZP 400 mg was administered subcutaneously at weeks 0, 2 and 4, followed by CZP 200 mg every 2 weeks (Q2W) or CZP 400 mg every 4 weeks (registered doses). During RAPID1 and RAPID2 RCTs (NCT00152386, NCT00160602), and for ≥6 months during their OLEs (NCT00175877, NCT00160641), CZP was also administered at 400 mg Q2W (twice the registered dose) for all patients. Across trials, patients were exposed to CZP either as a monotherapy or in combination with methotrexate and/or other DMARDs.
TB screening and protocol amendment All patients were screened for TB at study baseline. The safety database was manually reviewed retrospectively by independent experts ( JC, RvV, XM, KW, LC for RA; JC, RvV, XM, KW, LC, JV, JG-R, MW, OL for psoriasis, PsA and axSpA). All cases of suspected TB (PPD positive or exhibiting signs/symptoms compatible with TB) were classified as active TB, LTBI or PPD positive, or as nonevaluable. Active TB cases reported in this paper were confirmed according to the WHO or Centers for Disease Control and Prevention (CDC) criteria for TB. 22 n CZP studies before 2007, TB screening was conducted according to respective national guidelines of the recruiting study centre (cut-off for PPD positivity ranged from ≥5 up to ≥20 mm). Since 2007, patients were screened for PPD positivity ≥5 mm at baseline and subsequently received INH treatment for LTBI if they tested PPD positive.
Stratification of RA studies Data from the pooled RA safety database  21  (which excluded the Japanese RA trials) were assessed for trials initiated prior to 2007 (2367 patients) in two subgroups: (1) original trials (837 patients), completed prior to TB screening protocol amendment; and (2) intermediate trials (1530 patients from the RAPID1 and RAPID2 trials), which were initiated using PPD positivity cut-off from ≥5 to ≥20 mm but amended retrospectively. Group (3), current trials (1682 patients), were initiated after protocol amendment in 2007 and any patient was subsequently treated for LTBI if they tested PPD positive at study baseline.
Statistical analyses Safety assessments included all confirmed TB events that occurred after the first dose of CZP or placebo (PBO), and up to 84 days after the last study dose or patient withdrawal. Total exposure to CZP, as used in the IR calculation, was defined as the time from the first dose until the date that the TB event was reported. Exposure-adjusted IRs per 100 patient-years (PY), with 95% CI, are presented in this analysis. In some instances, data are also presented as the percentage of patients with events divided by the total number of patients. All statistics were performed using SAS V. 9. 1 or a later version.
Incidence of TB in CZP-treated patients across indications The incidence of TB was assessed in a total of 5402 CZP patients treated for RA, psoriasis, PsA and axSpA, with an overall IR of 0. 42/100 PY (95% CI 0. 31 to 0. 57). For RA, 4049 patients were included in the pooled safety database (9277 PY; mean CZP exposure 782 days, median exposure 267 days). 21 Up to 30 November 2011, 44 confirmed TB cases were reported in CZP-treated patients with RA (IR 0. 47/100 PY (0. 34 to 0. 64); also, there were 30 cases of pulmonary TB and 14 cases of non-pulmonary (including isolated lymph node TB) or disseminated TB (occurring in two or more noncontinuous organs)). No TB cases were reported in PBO patients during RCTs; however, the total exposure time was relatively short (total exposure 373 PY; mean exposure 110 days), mainly due to mandatory early escape to active CZP treatment for non-responders at weeks 12 and 14 in the RAPID1 and RAPID2 studies, as compared to CZP exposure (total exposure 9277 PY; mean exposure 782 days).
Separate analysis of safety data from 528 patients with RA enrolled in Japanese CZP trials ( J-RAPID and HIKARI and their OLEs) conducted up to 6 June 2013 confirmed no cases of TB (figure  3 ). Incidence of TB was also assessed in 117 study patients with psoriasis (85 PY; mean CZP exposure 206 days) up to 9 May 2007 and confirmed one case of disseminated TB after 61 days of CZP exposure (IR 1. 18/100 PY (0. 03 to 6. 58)). The incidence of TB was also assessed in 393 RAPID-PsA patients (612 PY; mean CZP exposure For current trials initiated with the standardised 5 mm PPD cut-off after protocol amendment was enforced, the IR was 0. 18/100 PY (0. 02 to 0. 66) (2/1682 patients). In total, 11/44 TB cases in RA trials were diagnosed after protocol amendment (9 from intermediate trials [RAPID1 and RAPID2] and 2 from current trials; figures 3 and 4).
Incidence of TB in relation to geographic location The geographic distribution of CZP-treated patients in the pooled RA safety database was 19. 8% from Western Europe, 20. 0% from Central Europe, 12. 4% from Eastern Europe, 41. 3% from North America and 6. 5% from the Rest of the World. United Nations statistics for the lower bound incidence of TB in the general population report a higher risk in Eastern and Central Europe (table  2 ). Consistent with this, the majority of TB cases observed with CZP originated in Eastern Europe (21 cases; IR 1. 02/100 PY (0. 63 to 1. 56)) and Central Europe (18 cases; IR 0. 58/100 PY (0. 34 to 0. 92)). 29/32 TB cases in patients with RA with PPD<5 mm at baseline were reported in patients from Eastern or Central Europe. Nevertheless, the rate of TB in patients with RA was far below the expected rate observed in the general population in each respective country (table  2 ).
One patient who developed TB received INH administration. INH treatment started 393 days after the first CZP dose was administered and 517 days before the onset of TB. †One patient with unknown PPD who developed TB was administered INH treatment before study baseline; INH was administered 141 days prior to the first CZP dose and 340 days before the onset of TB. TB cases in CZP-treated patients with RA in the pooled RA safety database (N=4049) by region and country (risk vs incidence).
Acknowledgements The authors would like to thank  John J Cush  (Dallas),  Kevin Winthrop  (Portland) and  Leonard Calabrese (Cleveland)  for their contribution to the external medical review of suspected TB cases. The authors acknowledge ' Matladi N. Ndlovu, PhD ,  UCB Pharma, Brussels, Belgium , for publication coordination and Costello Medical Consulting, UK, for writing and editorial assistance, which was funded by  UCB.
AC K N OW L E D G E M E N T S CF acknowledges support by the Beckwith Trust. MF acknowledges support by FONDECYT grant 1130521. RS acknowledges support from Brain Korea 21 Plus Program (21A20131500002) and the Doyak Grant (2014003730). RS also acknowledges support support from the EC through an ERC grant  StG-257720, and Fondecyt (project number 3120135). GC acknowledges support by FONDECYT grant 3130480. BKG acknowledges the support of the UK Science & Technology Facilities Council (ST/J001341/1), and the generous visitor support provided by FONDECYT and the Universidad de Concepcion.
Recently, WHO updated its HPV vaccines position paper  [24]  to recommend a two-dose regimen with increased flexibility in the interval between doses (see below). The evidence on HPV vaccination was updated in the European Code Against Cancer using the methodology described in greater detail in this issue (see  Minozzi et al. , 2015). The Medline, Embase, PsycINFO and Cochrane Library databases were searched to identify systematic reviews (SRs) on the efficacy and safety of HPV vaccines in women; two SRs were selected  [25, 26]. Additional scientific publications identified by the experts were also included (as detailed below) to complete the evidence. Due to the relatively low number of RCTs on efficacy and safety of HPV vaccines in men, individual studies on this topic were directly searched using the Cochrane Central Register of Controlled Trials (CENTRAL), and six articles  [27] [28] [29] [30] [31] [32]  were selected from the publications retrieved.
The evidence on efficacy and safety of HBV vaccination was updated with a systematic search of the Medline, Embase, PsycINFO and Cochrane Library databases up to January 2013; two SRs  [99, 100]  were selected based on the European Code Against Cancer methodology. Neither of these reviews reported chronic hepatitis B, liver cirrhosis or HCC incidence or mortality outcomes but reported either anti-HB level  [99]  or occurrence of hepatitis B infection  [100]. Ortqvist's SR  [99]  showed efficacy, but no meta-analysis was performed. Mathew's SR  [100]  showed contradictory results on efficacy depending on the method used to perform data analysis. The evidence available since the last WHO position paper is therefore summarized below using individual studies. Effectiveness studies have been performed in highly HBV endemic countries or regions with high rates of HCC.
Objectives The objective of this study is to provide a detailed description of BVOC mixing ratios in and above the canopy and their diurnal fluctuations, which can indicate heterogeneous sources and sinks within the canopy, and can be related to the exchange between the Amazonian forest and the atmosphere under dry and wet seasonal conditions. Measurements were performed on an 80 m tower at the site of the Amazonian Tall Tower Observatory (ATTO), and therefore represent a new data set from this very pristine area. Several (two) field campaigns enabled the determination of seasonal, diel, and vertical variation of BVOCs. This new information allows for a more comprehensive understanding of BVOC emissions and interactions within the central Amazon rainforest.
Acknowledgements. We thank the  Max Planck Society  and the  Instituto Nacional de Pesquisas da Amazonia  for continuous support. Furthermore, we acknowledge the support by the  ATTO project (German Federal Ministry of Education and Research, BMBF  funds  01LB1001A ;  Brazilian Ministério da Ciência, Tecnologia e Inovação FINEP/MCTI  contract  01. 11. 01248. 00 ); UEA  and  FAPEAM, LBA/INPA  and  SDS/CEUC/RDS-Uatumã. We would like to especially thank all the people involved in the logistical support of the  ATTO  project, in particular  Reiner Ditz  and  Hermes Braga Xavier. We acknowledge the Micrometeorological group of the  INPA/LBA  for their collaboration concerning the meteorological parameters, with special thanks to  Marta Sá ,  Antonio Huxley  and  Leonardo Oliveira. We are grateful to  Tracey W.
, 2013). To date, at least four first-inman phase 1 clinical trials considering anti-CD47 humanized mAbs are underway, according to clinicaltrials. gov website (identifiers NCT02216409, NCT02447354, NCT02488811, and NCT02367196). Given the ubiquitous expression of CD47, systemically administered anti-CD47 mAbs will inevitably come across a huge number of CD47 copies on red blood cells (RBCs). To avoid phagocytic-induced excessive reduction in erythrocytes count, it has been suggested to use a primingdose of anti-CD47 that would result in "aged" RBCs removal and subsequent erythropoiesis stimulation  (McCracken et al. , 2015). Such suggestion is obviously questionable, as many other clearance mechanisms are known to be preponderant in triggering removal of senescent RBCs  (Lutz and Bogdanova, 2013).
ACKNOWLEDGMENTS The authors acknowledge supports from  Centre National de la Recherche Scientifique (CNRS) ,  Région Champagne-Ardenne  and  SATT Nord. AJ was recipient of grants from the  Ministère de l'Enseignement Supérieur et de la Recherche  ( 2010-13 ). The authors acknowledge  A. Thomachot  and  D. Blackwell  for editorial assistance.