dataesr/scientific-paragraphs-categorization huggingface dataset:
Statistical analysis We pooled data by using RevMan 5. 1 and random-effects models, applying inverse variance weighting and the methods of DerSimonian and Laird  [22]. We generated summary estimates of relative risk (RR) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, each with associated 95% confidence intervals (CIs). To investigate the effect of treatment on oxygenation, we analyzed early changes in PaO 2 /FiO 2 at 24, 48, and 72 hours after randomization. To assess for effects on duration of ventilation, we planned to compare VFDs at day 28. Because of the controversy surround VFDs as an outcome, we conducted post hoc comparisons of duration of ventilation in survivors, and all patients. We assessed for heterogeneity between studies by using the Mantel-Haenszel χ 2 statistic (P < 0.
01 indicating substantial heterogeneity) and the I 2 statistic (> 50% indicating substantial heterogeneity). We had too few studies to assess for publication bias by using a funnel plot or conventional statistical methods  [23]. The review protocol stipulated a number of exploratory analyses to assess potential reasons for differing results (if any) across studies. We hypothesized that two factors might generate estimates of greater benefit: high or unclear risk of bias (versus low), and more-severe hypoxemia at baseline (PO 2/ /FiO 2 < 100, versus 100 to 200). To inform current guidelines, we also sought to estimate the effect of NMBA specifically among sepsis patients. With RevMan 5. 1 software, subgroup analyses were conducted by pooling RRs for subgroups in each trial. Last, we planned to test the robustness of our primary (mortality) results in sensitivity analyses by using fixed-effects models and by using two alternative statistical metrics: odds ratios and risk differences.
Results After screening 740 titles and abstracts, we found three trials eligible for this review (Figure  1 ). All three trials originated from the same group of investigators, including a total of 431 patients, and one trial was conducted in 20 centers in France. The trials were specifically designed to investigate the effects of cisatracurium besylate, a benzylisoquinoline compound, on gas exchange  [12] , inflammatory markers  [13] , and clinically important outcomes  [14] , respectively. In each trial, cisatracurium besylate was infused for 48 hours, by using weight-based dosing in two trials  [12, 13] , and a fixed high dose (15 mg bolus, followed by a continuous infusion of 37. 5 mg per hour) in the other (Table  1 )  [14]. All three trials reported 28-day mortality, barotraumas, and ICU-acquired weakness; and these data were supplemented by additional, previously unpublished data from the study investigators.
Phenotype of the E478 xenografts E478 xenografts characteristically grow to diffuse infiltrative tumors in the mouse brain (Figure  2A, B ) with proliferation indices of 34 +/-2% as determined by Ki67 IHC staining (Figure  2C  and not shown). Apoptotic cells, as determined by IHC for activated caspase 3A, were hardly detected (<0. 1%; data not shown). Blood vessels were often abnormal with signs of endothelial hyperplasia and microvascular proliferation with prominent CD34 staining (Figure  2D ), reminiscent of typical high grade glioma pathology. The presence of extravascularly deposited mouse IgG indicated focal disruption of the blood brain barrier (BBB; Figure  2E ). The tumor vasculature was positive for the BBB-marker GLUT-1 throughout the tumor (Figure  2F ). However, tumor cellassociated GLUT-1 or monocarboxylate transporters MCT1 and MCT4 were not present (Figure  2F  and data not shown).
Array comparative genomic hybridization (aCGH) aCGH was carried out with DNA of the originating patient tumor and several passages of the derived xenografts. DNA was digested using the restriction enzymes RsaI and AluI, followed by labeling using the Bio Prime CGH Genomic Labeling Kit (Invitrogen, Carlsbad, CA) and Cy3 and Cy5 dyes (GE Healthcare, Buckinghamshire, UK), according to standard protocols for Agilent CGH. Commercially available female DNA pooled from multiple donors (Promega Cat:G1521) was used as reference. Labeled DNA was competitively hybridized to SurePrint G3 Human 2×400k CGH microarrays (G4448A, Agilent Technologies, Amstelveen, The Netherlands) following standard protocols. The slides were scanned at 3 μm resolution using the Agilent High-Resolution Microarray scanner and the image data were extracted with Feature Extraction software (Agilent Technologies).
In situ metabolite quantification by LESA-nano ESI-FTICR In a separate set of experiments, we quantified D-2HG and α-KG levels via LESA (Liquid Extraction Surface Analysis, Nanomate, Advion) coupled to ESI-FTICR (Fourier transform ion cyclotron resonance, Solarix 7T, Bruker Daltonics, Bremen) and Quantinetix Software (ImaBiotech, France) allowing very sensitive detection and quantification of metabolites in small tissue plugs taken from 10 μm thick cryostat brain sections (Cryostat HM560, Microme). The Nanomate system was used in LESA mode with a 400 μm diameter surface extraction. Sample plates were cooled down to 12°C during analyses. Spray parameters were set as follows: Voltage to apply 1. 30 kV and gas pressure 0. 40 psi. Extraction solvent consisted of 65:15:20 MeOH:IPA:Water + 5 mM ammonium acetate using LCMS quality solvents.
0. 6 μL extraction solvent was used to extract analytes from the surface and was injected then into the nano-electrospray source. Tissue suppression was calculated using Quantinetix to address matrix effect and to normalize signals of 2-HG and α-KG. A dilution range of pure metabolites mixed with brain tissue was applied next to the samples for absolute quantification and data for each LESA spot were analyzed using Quantinetix™ (ImaBiotech, France) taking 10 mDa mass tolerance around theoretical m/z of 2-HG and α-KG. Data were normalized against a standard included in the extraction solvent (m/z 141. 019). Mass spectrometry was performed using the negative mode with the nano-electrospray source and CASI mode (isolation of m/z 150 +/-50 Da in the quadrupole) in the mass range 71-160 Da. Each acquisition was a result of 80 accumulated spectra.
Acknowledgements This work was supported by a grant from the  Hersenstichting  (grant  2010(1)-01 ) and by the  CORE grant ESCAPE  ( C10/BM/784322 ) from the  FNR in Luxembourg. ACN was supported by a  RUNMC grant. We thank  Jeroen Mooren  for excellent technical assistance with xenograft transplantations and  Nathalie Nicot  from the  Genomics Research Unit of CRP-Santé  for expert technical assistance in genomics analysis.
Importantly, our challenge will incorporate a new GWAS data set, which will be used in the validation phase, in which models built in the discovery phase are tested. The data set of ~1,100 patients with RA treated with anti-TNF therapy will be made available though a public-private partnership between the Consortium of Rheumatology Researchers of North America, Inc. (CORRONA) and the Pharmacogenomics Research Network (PGRN) sponsored by the National Institute of General Medical Sciences (NIGMS) and the US National Institutes of Health (NIH). A unique component of our Rheumatoid Arthritis Responder Challenge is the diversity of participation across a number of groups from academic institutions, private foundations and for-profit companies. In addition to support from CORRONA and PGRN, we received funding from pharmaceutical companies (see complete list on our website; link below) and a private foundation (the Arthritis Foundation) to support the public We also received support from the Arthritis Internet Registry (AIR) and the Broad Institute to generate new genomic data sets, as well as in-kind support from a large number of academic collaborators from across the world to make GWAS data available in the discovery phase.
In a model of open collaboration, participants will use Synapse to post code, share insights and engage in rapid learning prepublication. In phase 2 (validation), models will be posted, tested and scored in an independent GWAS data set of ~1,100 patients with RA treated with anti-TNF therapy. To complement challenge-assisted peer review (which occurs in both the discovery and validation phases), conventional peer review will have access to Synapse to understand the iterative process of model building. Synapse will allow study investigators to respond to peer-review critiques and resubmit versions of their models and studies.
Lower levels of detection were 0. 010 ng/mL, 0. 039 pg/mL, and 0. 125 mg/mL for hsCRP, IL-6, and sCD14, respectively. Sociodemographic characteristics and clinical, virological, and biological data from patients were assessed using descriptive statistical methods. We assessed the correlation between inflammatory biomarkers and FibroScanH values as continuous variables using Spearman's rank test. We also used a logistic regression model, as a dichotomous variable, to determine if there was an association between the level of inflammatory biomarkers and METAVIR stage of liver fibrosis (F0-F2 vs. F3-F4). Then we adjusted the model for those factors found, in univariate analyses, to be associated with METAVIR fibrosis stage (F0-F2 vs. F3-F4). We applied a forward-selection procedure for those variables with a univariate P-value of #0.
Acknowledgments We are indebted to the following for their assistance in data collection:  E. Bouvet ,  S. Matheron ,  P. Yeni ,  S. Lariven ,  C. Rioux ,  M. Caseris ,  N. Dournon ,  H. Ferrand ,  M. Pichon ,  M. Ahouanto ,  E. Casalino ,  G. Castanedo ,  A. Dia ,  X. Duval ,  Z. Eid ,  S. Fegueux ,  V. Gregoire ,  F. Guiroy ,  S. Harent ,  C. Jestin ,  K. Jidar ,  M. A. Khuong ,  N. Landgraf ,  Y. Latorre ,  C. Leport ,  A. Lepretre ,  F. Lheriteau ,  P. Longuet ,  F. Michard ,  G. Morau ,  G. Pahlavan ,  E. Papot ,  B. Phung ,  M. H. Prevot ,  S. Puget ,  P. Ralaimazava ,  H. Rousselot ,  F. Louni ,  C. Godard ,  Z. Julia ,  M. Chansombat ,  G. Hamet.
This study was supported by  French National Agency for Research on AIDS and viral hepatitis (Agence Nationale de Recherches sur le SIDA  et les hepatites virales [ANRS]) and from the  European Community 's  Seventh Framework Programme  ( FP7/2007-2013 ) under the project '' Collaborative HIV and Anti-HIV Drug Resistance Network (CHAIN)' ' (grant no. 223131 ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
(2009). The eight other systems are not known to harbour any circumstellar disc. Archival data was collected for each TWA member in our target list, including Johnson, Tycho, 2-Microns All-Sky Survey (2MASS), InfraRed Array Camera (IRAC), Wide-Field Infrared Explorer (WISE), AKARI, Multiband Imaging Photometer for Spitzer (MIPS), Sub-Millimeter Array (SMA) and Submillimetre Common-User Bolometer Array (SCUBA) photometry. Spitzer-MIPS values are taken from  Low et al. (2005). TWA23 and TWA25 MIPS flux densities are not included in  Low et al. (2005). For these two stars, we computed our own photometry for the 24 µm MIPS band, using an aperture of 13 arcsec, and a sky annulus between 20 arcsec and 32 arcsec, and applying the appropriate aperture corrections (as described in the Spitzer Data Analysis Cookbook 1  ).
Stellar parameters To model the stars' SEDs, we need knowledge of their stellar properties (specifically, their temperature and luminosity), to choose the correct photosphere models. For each star in the sample, we selected the photometric data that do not show excess above the stellar photosphere, i. e. those data points in agreement with pure photospheric emission. Typically, this includes Johnson, Stromgren, and 2MASS data. Then we compared this photospheric emission with a grid of theoretical stellar photosphere models using the Virtual Observatory SED Analyzer (VOSA,  Bayo et al. 2008) , which provides the best-fitting model based on a χ 2 minimisation. We used the grid of Phoenix models from  Hauschildt et al. (1999). The values for T eff and L * from each best-fitting model are summarised in Table  1.
Spectroscopic data reduction Nine TWA stars were observed with PACS in LineScan spectroscopic mode. The line targeted with the LineScan observations was [OI] at 63. 18 µm. PACS spectra were reduced using HIPE 8 with the latest version of the pipeline and the proper calibration files. Spectra were extracted from the central spaxel when the observations were well centred there. When the observations were not properly centred on the source, we extracted the spectrum from the spaxel with the highest continuum signal. The extracted spectrum was then aperture corrected to account for flux loss in the surrounding spaxels. The line spectra from PACS typically show higher noise levels near the spectrum edges. To account for that effect, we exclude from the 63 µm spectra any wavelength shorter than 63.
6 mJy flux density at 70 µm. But  Plavchan et al. (2009)  showed that the 70 µm emission is coincident with a background galaxy and not with TWA 13A. Our combined images for TWA 13A do not show any source at the nominal position of the star, therefore we agree with  Plavchan et al. (2009)  that there is no excess associated with TWA 13A. However there is a background galaxy that could have polluted the  Low et al. (2005)     In Fig. 3 , we show a comparison of the photometry at 70 µm from MIPS with that from PACS for the remaining sources. We see that the agreement between MIPS and PACS for detected objects is good; both datasets are in agreement within the calibration uncertainties, and sources are therefore not variable. Any discrepancy can be due to problems in the calibration of the instruments, to the larger beam size in MIPS or to real variability.
Models of dust discs For every star in the sample, we built the SED including the new Herschel-PACS data and aiming to compare the observed data with modified blackbody models to estimate basic dust properties in the TWA association. We are aware that this approach may be very simplistic for some of these targets, but it is a good starting point for estimating dust temperatures. In any case, each individual object is discussed in the next sections. Figure  7  includes SEDs for TWA members detected with Herschel. The disc models were built using the NextGen models from Sec. 2. 1 plus a modified blackbody to describe the dust emission, defined as F continuum = B ν (T dust ) × (λ 0 /λ) β (1) with λ 0 = 2πa min and β=0 for λ < λ 0 , where B ν is the Planck function. The choice for a min depends on the target.
Acknowledgements. This research has been funded by  Spanish  grants  AYA 2010-21161-C02-02 ,  AYA2012-38897-C02-01 ,  AYA2011-26202 CDS2006-00070 , and  PRICIT-S2009/ESP-1496. We also acknowledge support from  ANR  (contract  ANR-07-BLAN-0221 ) and  PNPS of CNRS/INSU, France. C. Pinte  acknowledges funding from the  European Commission 's 7 th Framework programme (contract  PERG06-GA-2009-256513 ) and from  Agence Nationale pour la Recherche (ANR) of France  under contract  ANR-2010-JCJC-0504-01. WFT thanks the  CNES  for a post-doctoral position. WFT, FM and IK acknowledge funding from the  EU   FP7-2011  under Grant Agreement nr. 284405  ( DIANA  project). JCA acknowledges the  PNP-CNES  for financial support. FM acknowledge support from the  Millennium Science Initiative (Chilean Ministry of Economy ), through grant " Nucleus   P10-022-F".
Scenario Execution Engine This module is responsible of translating the attack scenario from formal level to the implementation level. It ensures the association between abstract messages and concrete ones, stored in the Data Store module. Operation execution is held with the functionality provided by the Primitive Holder. Primitive Holder Our execution environment works at the implementation level. The exchanged messages are real network messages. Therefore, we have to relate abstract messages with actual messages and operations. This is the main role of the Scenario Execution Handler. We can classify the attack scenario instructions into three categories: To do this, we use cryptographic primitives (crypt, pair and unpair) and network primitives (send and receive). In fact, we define all the needed cryptographic operations in the Primitive Holder Module.
Exit with success The last case of Algorithm 1 is the message construction or decomposition. In both cases the Handler invokes the Data Store and the Primitive Holder modules Consider for instance the instruction X1 = Crypt(X2, X3). First, the Scenario Execution Handler collects the arguments by requesting them from the Data Store through the data buffer. Then, it requests the Primitive Holder to construct the message. Finally, the latter's response is stored at the result position X1 in the Data Store. At the end of the attack scenario execution, the Scenario Execution Engine sends a "finish" message. This means that the attack works on the tested implementation.
DNA Vaccine Plasmids The construction of Bx08 gp140 (Genbank JX473289) plasmid used codons from highly expressed human genes as described earlier  [18, 33, 34]  and two other primary Envs from Danish patients, ctl21 (JX473290) and ctl27 (JX473291), were similarly codon optimized. Seven different clade B env constructs were synthesized (syn. ) and used (syn. gp140 Bx08 , syn. gp150 Bx08 , syn. gp140 ctl21 , syn. gp140 ctl27 , syn. gp140Bx08 SOSIP. R6-IZ-H8 , syn. gp140 ctl21 SOSIP. R6-IZ-H8 or syn. gp140 ctl27 SOSIP. R6-IZ-H8 ). We have previously described the construction of synthetic env Bx08 plasmids encoding secreted gp140 and membrane-bound gp150 from HIV-1 Bx08  [18, 33, 34]. The two primary env ctl21 and env ctl27 were PCR-amplified from isolated patient virus, cloned, sequenced and then synthesized using only codons from highly expressed human genes (completely codon exchanged)  [34, 35].
The constructs were control sequenced and tested for successful in vitro expression of functional envelope glycoproteins (CD4 binding) (data not shown). # The DK1 isolate is an A1D intersubtype recombinant form with a clade A envelope gene  [47]. <5 ctl20 5 >5 >5 <5 <5 ctl46 >5 >5 >5 <5 <5 ctl26 >5 >5 >5 <5 <5 ctl36 >5 <5 12 >5 <5 ctl22 <5 >5 >5 <5 >5 ctl34 >5 <5 >5 <5 <5 ctl45 >5 <5 >5 <5 <5 ctl28 >5 <5 >5 <5 <5 ctl32 >5 <5 <5 <5 <5 ctl35 <5 >5 211 <5 <5 ctl13 <5 >5 >5 <5 <5 ctl16 <5 >5 >5 <5 <5 § Four of the HIV-1 panel isolates are R5 clade B. Guinea pig and rabbit groups were immunized with a trivalent mix encoding syn. gp140 Bx08 , syn. gp140 ctl21 and syn. gp140 ctl27 to facilitate heterotrimer formation (referred to as syn. gp140 mix ). Guinea pigs were also immunized with the same single DNA construct, syn.
Though, in the rabbit model the two constructs yielded similar neutralizing activity for the six different viruses tested (compared in Figure  4D , and Supplementary Table  1 ). Only two of the six viruses used could be neutralized to 50% by syn. gp140 mix SOSIP. R6-IZ-H8 antisera at the IgG concentrations tested, and they were both clades B pseudotype virus. These data indicate that neutralizing activity can be improved by use of DNA vaccines encoding for modified Env immunogens, syn. gp140 mix SOSIP. R6-IZ-H8 , but the increased activity in guinea pigs is non-HIV specific. IgG was purified from a few selected guinea pig serum samples and tested in the TZMbl assay (data not shown). The guinea pig IgG displayed very low neutralizing activity. The unspecific neutralizing activity of modified constructs was only observed in immunized guinea pigs, while rabbit IgG resulting from the modified trivalent vaccine displayed similar neutralizing activity as non-modified.
Acknowledgments The authors gratefully acknowledge  Jan Gerstoft  for providing the serum samples from Danish HIV patients at the  University Hospital of Copenhagen (Rigshospitalet). The project was sponsored by the  European Community  under EC-FP7-grant -Next Generation HIV-1 Immunogens inducing broadly reactive Neutralizing antibodies‖ NGIN_201433. Other members of the  NGIN Consortium  are  Mauro Malnati  and  Lucia Palco ,  Fondazione Centro San Raffaele del Monte Tabor, Milan, Italy ;  Hanneke Schuitemaker ,  AMC  at the  University of Amsterdam , the  Netherlands ;  Luigi Buonaguro ,  Istituto Nazionale Tumori -Fond. G. Pascale‖, Naples, Italy ;  Philippe Saudan ,  Cytos Biotechnology AG, Zurich-Schlieren, Switzerland ;  Mario Clerici ,  Milano University Medical School, Italy ;  Anna-Lena Spetz ,  Karolinska Institut, Stockholm, Sweden ;  Jan Albert ,  Francesca Chiodi  and  Britta Wahren ,  SMI/MTC, Stockholm, Sweden ;  Guido Vanham ,  Institute of Tropical Medicine, Antwerp, Belgium; Meghna Ramaswamy, National Institute for Biological Standards & Control, Herfordshire, UK ;  Sylvan Fleury  and  Anick Chalifour ,  Mymetics Corporation , Epalinges, Switzerland;  Eva-Maria Fenyo ,  Lund University, Lund, Sweden ; and  Morgane Bomsel ,  Institut Cochin, Paris, France.
Acknowledgements Jordi Camps ,  Luis Alberto Perez Jurado  and  Lorna Brocksopp  for technical help. The  Spanish Government  for grants  BFU2010-14839  to JLG-S,  Spanish Government  and  FEDER  for grants  BFU2009-13409-C02-02  and  BFU2012-38236  to AN and JP-M,  BFU2012-39482  to IM, and  BFU2011-28549  to TM-B The Andalusian Government for grants  CSD2007-00008  and  CVI-3488 , supported by  FEDER  to  JLG-S The Barcelona Zoo (Ajuntament de Barcelona)  for an award to JP-M. EEE is an investigator with the  Howard Hughes Medical Institute. The  European Community  for an  ERC Starting Grant  ( StG_20091118 )) to TM-B.
Lithology and Chronology The lower parts of the core (270-300 cm) were lacustrine organic muds, overlain by a peat deposit from around 230 cm upwards. Three radiocarbon dates were performed on bulk sediment (Table  1 ). The age calibrations were done in Calib 5. 0. 2 software  (Stuiver et al. 1998 ) and the age-depth model was constructed in the software package CLAM  (Blaauw 2010)  run in the software R (R Development Core Team 2010).
Sample Processing Pollen Pollen extraction was carried out following  Moore et al. (1994)  and using successive treatments with HCl, HF and acetolysis. For pollen identifications, we used the pollen reference collection of IMBE including reference slides of Iranian flora as well as the pollen atlases of Europe and N. Africa  (Reille 1992 (Reille , 1995 (Reille , 1998;; Beug 2004 ) and also pollen morphological data in van  Zeist and Bottema (1977). A total of 20 samples were analysed. New samples will be analysed in the near future to improve the time resolution. Hygrophilous and aquatic plants (in particular Cyperaceae, which are over-represented) as well as non-pollen palynomorphs (NPPs), among them fungal spores, algal cysts and animal microremains, have been excluded from the pollen sum (PS).
Beetles The sedimentary profile was cut into 25 samples for insect analysis. Each sample was 10-cm thick and ca. 140 cm 3 in volume. The 25 insect samples numbered from 1 (bottom) to 25 (top of the sequence) span continuously the entire sedimentary profile (250 cm), from the surface to the rocky bottom of the lake. The fossils were extracted using the method recommended by  Coope (1986) , and identifications were made by direct comparison with specimens from a modern reference collection. Ecological interpretation and biogeographical data are derived from  Koch (1989a Koch ( , 1989b Koch ( , 1992)) ,  Böhme (2005) , and  Löbl and Smetana (2003-2010).