dataesr/scientific-paragraphs-categorization huggingface dataset:
From observations We retrieved from the Canada-France-Hawaii Telescope (CFHT) archive 5 the spectrum of HIP 93511, obtained with the ESPaDOnS spectrograph on 2010, May 28 in spectroscopic mode. The spectrum, reduced with the Libre-ESpRIT package 6  (Donati et al. 1997) , covers the 3700-10 400 Å spectral range with a resolving power of about 80 000. We looked for the presence of the secondary star in the ESPaDOnS spectrum by comparing the least-squared deconvolution (LSD) profile (Fig. 2 , bottom panel  Donati et al. 1997; Kochukhov et al. 2010)  with that of a Gaussian concluding that the LSD profile is symmetric with no visible presence of the secondary star, therefore HIP 93511 is a single-line spectroscopic binary (SB1). The line bisector as well did not show the presence of the secondary star.
From the stellar parameters of the two stars (in particular temperature, gravity, and radius) recovered by photometric means, we were able to conclude that the lines of the secondary star should be present in the spectrum and therefore they blend completely with the spectral lines of the primary star. To estimate the metallicity of the two stars, we computed synthetic spectra with the atmospheric parameters of the two stars, combined them according to their luminosity ratio and compared to the observed spectrum. We calculated synthetic spectra with SYNTH3  (Kochukhov 2007)  on the basis of line lists extracted from the Vienna Atomic Line Database (VALD) 1 The WIYN Observatory is a joint facility of the University of Wisconsin-Madison, Indiana University, the National Optical Astronomy Observatory and the University of Missouri.
Time series and power spectra Kepler observations were obtained in two different operating modes: long cadence (LC) and short cadence (SC;  Gilliland et al. 2010; Jenkins et al. 2010). This work is based on SC data. For the brightest stars (down to Kepler magnitude K p ≈ 12), SC observations could be obtained for a limited number of stars (up to 512 at any given time) with sampling cadence of 58. 84876 s (Nyquist frequency of ∼8. 5 mHz), which permits a more precise exoplanet transit timing and improves the performance of asteroseismology for main sequence and sub-giants stars. Kepler observations are divided into three-month-long quarters (Q). The binary system was observed during quarters Q7 to Q15. Therefore, the length of data gives a frequency resolution of about 14. 3 nHz. The light curves were concatenated and high-pass filtered using a triangular smoothing with full-width-at-half-maximum of one day, to minimise the effects of long-period instrumental drifts.
Stellar ages from a proxy Using large frequency separation. Lundkvist et al. (2014)  showed that a stellar age can be derived from the measurement of Δν and of the stellar mass: this is asteroseismology made easy or AME. The relation they derived is based upon a grid of stellar evolutionary models that cover masses ranging from 0. 7 M to 1. 6 M , and metallicities from -0. 3 dex to +0. 3 dex. For deriving the stellar age for our two stars, we used the data made available on the AME web site 7. Using data from Fig. A. 10 and Fig. A. 11 of Lundkvist et al. (2014) , we derived the age of the stars from the measured large frequency separations and the seismic masses: Age A = 4. 0 ± 0. 7 Gyr and Age B = 2. 2 ± 0. 9 Gyr. The error bars were derived from a Monte-Carlo simulation taking the errors quoted above into account for Δν and the seismic mass for a fixed metallicity of -0.
Metcalfe et al. (2009, their Fig. 5 ) performed a sensitivity analysis considering seismic data for the Sun and showed the theoretical correlations that exist between initial helium abundance and mass. Baudin et al. (2012)  found a similar result in a red giant star observed by CoRoT. Lebreton & Goupil (2014)  examined in detail the correlation between model input parameters of the CoRoT target HD 52265. They quantified the anti-correlation of the mass with the initial helium abundance to be ΔY 0 ΔM = -0. 58 and also suggested a correlation of the age with the mixing length parameter of ΔAge Δα = +0. 13. The ΔY 0 ΔM anti-correlation can account for the mass difference between Verma and Lebreton but not for the mass difference between Ball and Creevey since their initial helium abundance is the same.
Conclusions We use Kepler data for measuring the seismic mode parameters of two spatially unresolved stars in a single time series. We provide the seismic mode frequencies, mode linewidths, and mode heights of the two stars and derived using scaling relations the mass, the radius, and the age of the two stars in a binary system. We also derive the orbit characteristics using speckle interferometry which gives an independent measurement of the total mass of the system. We also model the stars using the mode frequencies and four different stellar model pipelines. The seismic mass of the binary system derived with the models is consistent with that determined with astrometry. For 3 models, the age of the binary system is in the range 3. 4-3. 9 Gyr while for another model the age is about 2. 7 Gyr.
Acknowledgements. T. A. gratefully acknowledges the financial support of the  Centre National d'Etudes Spatiales (CNES)  under a  PLATO grant. T. L. C. , W. J. C. , and G. R. D. acknowledge financial support from the  UK Science and Technology Facilities Council (STFC). W. B. and L. G. acknowledge support from the  Deutsche Forschungsgemeinschaft   SFB 963  " Astrophysical Flow Instabilities and Turbulence " (Project  A18 ). L. G. acknowledges research funding from the  Center for Space Science, NYU Abu Dhabi Institute, UAE. Funding for the  Stellar Astrophysics Centre  is provided by The  Danish National Research Foundation. We are indebted to  Ian Roxburgh  for extensively commenting on the paper and for his timely contribution. We are grateful to  Sébastien Salmon  for commenting on an earlier version of the paper.
a b s t r a c t Parasite interactions have been widely evidenced experimentally but field studies remain rare. Such studies are essential to detect interactions of interest and access (co)infection probabilities but face methodological obstacles. Confounding factors can create statistical associations, i. e. false parasite interactions. Among them, host age is a crucial covariate. It influences host exposition and susceptibility to many infections, and has a mechanical effect, older individuals being more at risk because of a longer exposure time. However, age is difficult to estimate in natural populations. Hence, one should be able to deal at least with its cumulative effect. Using a SI type dynamic model, we showed that the cumulative effect of age can generate false interactions theoretically (deterministic modeling) and with a real dataset of feline viruses (stochastic modeling).
model to investigate the impact of the cumulative effect of age in the detection of pairwise parasite interactions. Second, we propose a method to correct for this mechanical effect. We adapt a statistical method previously proposed to account for identified confounding factors in the search for parasite interactions ('the corrected chi-square',  (Hellard et al. , 2012) ). This approach is applied to a real serological dataset of four feline viruses obtained in natural populations of domestic cats.
Bias introduced in a real dataset: an empirical approach The stochastic version of the model was then applied to a real serological dataset obtained in natural populations of domestic cats to study the influence of the cumulative effect of age in the search for interactions between feline viruses in the field. Data for four viruses were available: the Feline Immunodeficiency Virus (FIV), the Feline Herpesvirus (FHV), the Feline Calicivirus (FCV), and the Feline Parvovirus (FPV). Details on the studied viruses, on the protocols and on the model can be found in Appendix A1 and in previous papers  (Hellard et al. , 2011; Fouchet et al. , 2009). As the value of the antibodies' disappearance rates of the studied viruses varied a lot between studies, we tested different scenarios: (1) both viruses induce long lasting antibodies, (2) one virus induces long lasting antibodies and the other induces short-lasting antibodies, (3) both viruses induce short lasting antibodies (see Appendix A1 for more details).
Using likelihood maximization we can calculate the coefficients a x k for each parasite x, which estimate the coefficients a k x for the parasite x. The third step consists of calculating the theoretical table, giving the expected number of individuals positive to none, one, or two parasites, assuming no interaction between the parasites. Four states are possible according to the status (St) to both parasites: neg/neg (St1 = neg, St2 = neg), neg/pos (St1 = neg, St2 = pos), pos/neg and pos/pos. The probability that individual i is in each of the four states is obtained from the formula: P i (St1, St2|A) = a1(A) a2(A) P i (St1|a) P i (St2|a) da (14) The solution of this equation is given in Appendix A2 (see Eqs. A13-A15). By summing the probabilities over all individuals when they are in their observed age-class (A obs ), we obtain the corrected expected number of individuals (C k,l ) in each of the four states: C k,l = i P i (St1 = k, St2 = l|A obs (i)) (15) The corrected chi 2 is simply the Pearson chi 2 that compares the expected and the observed tables: 2 = 1 k=0 1 l=0 (O k,l -C k,l ) 2 C k,l (16) In the last step, K in silico data sets are generated under H0: 'the two parasites are independent' in order to estimate the distribution of the corrected chi 2 under H0.
First, for each individual, a serological status to both parasites is sampled assuming the probability of infection given in Eq. (  9 ) by replacing for each parasite the coefficients a x k by their estimates ( a x k ). Then the in silico data set is reanalyzed and the associated corrected chi 2 is calculated. For each of the K in silico data sets, we obtain one estimate of the corrected chi 2 leading to K independent realizations of the corrected chi 2 statistic under H0. The p-value is calculated as follows. Since the chi 2 quantifies the deviation from theoretical quantities, we consider an unilateral p-value. If H0 is true, the observed chi 2 combined with the K simulated values provide K + 1 independent realizations of the same distribution. The probability of observing a value as extreme as the one observed is simply given by the number of in silico chi 2 that are above the observed corrected chi 2 plus one, divided by K + 1.
Bias introduced in a real dataset: an empirical approach (stochastic modeling) If the cumulative effect of age was not taken into account (i. e. , using a classical Pearson's chi 2 ), five out of the six pairs of feline viruses appeared significantly associated with a type I error of 5% (  (Hellard et al. , 2012) , Table  A1  in Appendix A1). Using the dynamic stochastic model, we found that four of these associations could in fact be explained by the cumulative effect of age when both viruses induced long-lasting antibodies (scenario 1; Table  A1  in Appendix A1). It was not the case anymore however if at least one virus induced short immunity (scenarios 2 and 3; Table  A1  in Appendix A1). The stochastic modeling confirmed that antibodies persistence was of premium importance. The simulated chi 2 distribution was very strongly shifted compared to the distribution of a Pearson's.
Discussion The bias introduced by the cumulative effect of age in the search for parasite interactions in the field has long been suspected  (Courchamp et al. , 2000; Cross et al. , 2009) , without providing a theoretical background explaining how this cumulative effect works nor a proper way to take this phenomenon into account into a statistical framework. Intuitive solutions have been proposed, such as the restriction of the dataset to a narrow age-class, most often the young, in which the cumulative effect of age is less important  (Kuris and Lafferty, 1994). Age-stratification of the data has also been used as an alternative strategy (e. g. ,  (Farrington et al. , 2001) ). Using deterministic and stochastic versions of an epidemiological model, this paper provides a theoretical background to study the degree of false interactions (i.
e. , statistical associations) that can be generated by the cumulative effect of age. Its effect was indeed important, i. e. , found to generate apparent interactions between independent parasites, especially when forces of infection were high (i. e. , strong transmission, high prevalence) and when antibodies persisted for a long time within hosts (i. e. , long immunity). The maximal risk was when parasites were both transmitted with a similar force of infection. When stochastic modeling was applied to a real dataset of feline viruses, we showed that this mechanical effect of age could be strong in realistic conditions. The method we propose here is an extension of the corrected chi 2 method proposed in  (Hellard et al. , 2012) , which enabled the correction for other potential confounding risk factors such as sex, way of life or the population of origin.
Acknowledgments We would like to thank the anonymous reviewers for their valuable inputs on the manuscript;  Lyon-Biopôle  ( FIV-VAX program ) for financial support;  Guillaume Leblanc  for data collection in the field and  Hervé Poulet ,  Béatrice Tarin ,  Vincent Badol  and  Christine Coupier  for serological analyses. This work was performed within the framework of the  LABEX ECOFECT  ( ANR-11-LABX-0048 ) of  Université de Lyon , within the program " Investissements d'Avenir"  ( ANR-11-IDEX-0007 ) operated by the  French National Research Agency (ANR).
Previous studies have suggested that procalcitonin is a reliable marker for predicting bacteremia. However, these studies have had relatively small sample sizes or focused on a single clinical entity. The primary endpoint of this study was to investigate the diagnostic accuracy of procalcitonin for predicting or excluding clinically relevant pathogen categories in patients with suspected bloodstream infections. The secondary endpoint was to look for organisms significantly associated with internationally validated procalcitonin intervals. We performed a cross-sectional study that included 35,343 consecutive patients who underwent concomitant procalcitonin assays and blood cultures for suspected bloodstream infections. Biochemical and microbiological data were systematically collected in an electronic database and extracted for purposes of this study.
Study Population The ''Nancy Biochemical Database'' is an electronic database that included consecutive patients hospitalized in 67 healthcare departments at the University Hospital of Nancy and underwent concomitant blood procalcitonin assays and blood cultures for suspected bloodstream infections between January 1, 2006 and December 31, 2012 (Supplemental Digital Content: Figure  1 , http://links. lww. com/MD/A504). Blood cultures and procalcitonin assays were considered concomitant if the time between the 2 tests was less than 12 hours. All investigations were conducted at the discretion of the physicians of each health care department as part of a standard assessment for bloodstream infection suspicion. For each patient, biochemical and microbiological data were systematically collected in the electronic database and were retrospectively extracted for the purposes of the study using the GLIMS general laboratory information management system, version 8.
11. 6 (MIPS France S. a. r. l. , Paris, France). The following data were available in the electronic database: patient identification number, patient age at the time of blood collection, date and time of blood sampling for blood culture and procalcitonin assay, patient health care department, blood culture result (positive or negative), microorganism genus and species in case of positive blood culture, blood procalcitonin concentration (ng/mL), and blood C-reactive protein concentration (mg/L). The following data were not available in the electronic database: clinical diagnosis of SIRS, sepsis, severe sepsis, or septic shock; the presence or absence of a central venous catheter, final clinical diagnosis, and infection source in patients with positive blood culture; and antibiotic use. The ''Nancy Biochemical Database'' was reported to the French National Commission for Data Protection and Liberties (CNIL No 1763197v0), which supervises the protection of individuals with regard to the processing of personal data.
Nalmefene is the first drug approved for reduction of alcohol consumption. The aim of this study was to evaluate the clinical relevance of treatment with nalmefene in alcohol-dependent patients with a high drinking risk level from two randomised placebo-controlled 6-month studies (NCT00811720 and NCT00812461). Response criteria were based on alcohol consumption, Clinical Global Impression, and Short Form Health Survey mental component summary scores at month 6, analysed using logistic regression. The proportion of responders was higher in the nalmefene group than in the placebo group with odds ratios significantly in favour of nalmefene for all responder criteria; numbers-needed-to-treat ranged from 6 to 10. Significant differences from placebo in clinician-rated and patient-reported outcomes, and liver enzymes further supported the clinical relevance of the treatment effect.
Patients This paper includes data from the pooled sub-group of patients with a high or very high drinking risk level at screening and randomisation (target population as defined in  [10]  ) from the identically designed 6-month studies ESENSE1 (NCT00811720)  [2]  and ESENSE2 (NCT00812461)  [3]. Briefly, the studies included adult patients with a primary diagnosis of alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders  [11]  , assessed with the Mini-International Neuropsychiatric Interview  [12]. Patients were excluded if they had comorbid psychiatric disorders or an average alcohol consumption below a medium drinking risk level (men: ≤ 40 g alcohol/day; women ≤ 20 g alcohol/day) according to the World Health Organization  [5]. The full list of selection criteria is published elsewhere  [2, 3].
For sites which belong to flexible regions of ubiquitin (V5-K11, Q41, L67, L69, and V70),  19, 20  no mediumor long-range 13 C-13 C correlations could be detected [Fig. 2(c) ]. Especially the reduced number of long range correlations for the hairpin b1-b2 is consistent with previous studies  8, 9  (cf. Fig. S8  and Table  SVII , Supporting Information). Figure  2 (d) illustrates the distance distribution of the 59 unambiguous distance restraints as backcalculated from the X-ray structure (PDB ID: 3ONS). The majority of the observed correlations were found to correspond to distances between 4. 5 and 7 A ˚(by comparison to the X-ray structure). Dihedral angle restraints were calculated from backbone chemical shift information using the program TALOS1 (Supporting Information Fig. S9 ). 21 urther details on the structure calculation can be found in the Supporting Information.
9  (cf. Fig. S8 , Supporting Information). Those regions of structural heterogeneity also show increased  15  N chemical shift differences of the main conformation to the solution NMR structure (PDB code 1d3z) and the solid state NMR structure (PDB code 2JZZ) indicating structural differences of the backbone in those regions, while  13  Ca and 13 C 0 appear very similar (cf. Tables SV and SVI, Supporting Information). Previous work  8, 9  did not report on multiple conformations. We explain the occurrence of multiple conformations by slightly different crystallization conditions compared to Zech et al. 9  The observed structural polymorphism coincides with regions that are known to be dynamic, as investigated by solution NMR  15  N relaxation  23  and RDC-based measurements  20, 24  as well as recent high-resolution NMR relaxometry.
Activation of BoNT/E3 BoNT/E3 was purchased as a single chain, and therefore proteolytic activation was performed prior to use to generate the active form. This also minimized the risk of denaturation of the activated BoNT/E3. Pure BoNT/E3 holotoxin (Metabiologics Inc. ), 3 μg at a concentration of 1 μg/μL in PBS, was incubated for 30 min at 37°C with 0. 15 μg trypsin (T1426, Sigma Aldrich). The cleavage reaction was stopped by adding 0. 3 μg (100 μg/mL) trypsin inhibitor (T9003, Sigma Aldrich) and by incubating the reaction mixture for 30 min at 37°C. The extent of activation was assessed by capillary electrophoresis under reducing conditions where migration of a band corresponding to the uncleaved toxin (150 kDa) and the appearance of a 50 kDa and a 100 kDa band (data not shown) were monitored (Experion, Bio-Rad, Hercules, USA).
Antibody affinity was determined by surface plasmon resonance spectroscopy using a BIAcore 3000 instrument (GE Healthcare-Biacore, Uppsala, Sweden). ScFv were coated at a maximum of 800 RU on a CM5 chip (BR100012, GE Healthcare-Biacore) via amine coupling according to the manufacturer's instructions. A flow rate of 30 μL/min was maintained during each measurement and volumes of 100 μL of at least ten dilutions of activated BoNT/E3 (250 nM to 0. 03 nM) dissolved in HBS-EP buffer (BR100188, GE Healthcare-Biacore) were tested. After each dilution, the chip was regenerated with 1. 5 μM glycine buffer (BR100354, GE Healthcare-Biacore) injected for 30 s at 10 μL/min. Affinities were calculated using the BIAevaluation software (GE Healthcare-Biacore) according to the Langmuir 1:1 adsorption model and were verified by internal consistency test  [48].
Isolation of BoNT/E3-L specific scFv A multi-step panning of four rounds was performed against BoNT/E3 holotoxin with 5, 10, 20 and 40 washes, respectively. After the third round of panning 1. 6 x 10 6 scFv-phage were isolated. After each round of panning, the reactivity of the eluted phage against BoNT/E3 was assessed by phage-ELISA and the signal increased 1. 5-fold between round 1 and 4. In addition, no reactivity against trypsin and trypsin inhibitor, nor against BSA, KLH and LF was observed (data not shown). After the fourth round of panning, one hundred scFv-clones were randomly chosen, the scFv encoding DNA was extracted and sequenced. Only five sequences appeared to be recombined and the corresponding clones were discarded. Of the 95 remaining scFv, 78 sequences were identified in a single copy and seven were identified in two or more copies, resulting in a total of 85 different scFv sequences.
The Germinality Index (GI) of each scFv (VH and VL) was calculated using IMGT/DomainGapAlign. doi:10. 1371/journal. pone. 0139905. t001 for each VH and VL was calculated using IMGT/DomainGapAlign and provided an indication of the identity between framework regions of the selected scFv and those encoded by the most similar human germline genes, as a percentage. The average GI-values for all 38 scFv were 86. 9% (VH) and 89. 4% (VL). In vitro endopeptidase immunoassay   2 ) (The raw data for Figs 2-5 are given in S1 File). The most potent inhibitor, ELC76, inhibited the endopeptidase activity of BoNT/E3 at a molar ratio of scFv to toxin of 14,765:1 (IC 50 of 33. 8 nM) (Table  2 ). The scFv inhibiting toxin endopeptidase activity were selected for further analyses using the ex vivo mouse phrenic nerve-hemidiaphragm assay and affinity measurement.
Affinity measurement The affinity of the four scFv that inhibited the endopeptidase activity of BoNT/E3 was determined by surface plasmon resonance spectroscopy. All affinities were in the sub-nanomolar range from 0. 01 nM (ELC77) to 9. 16 nM (ELC51) (Table  3 ). The four selected scFv did not react against trypsin or trypsin-inhibitor (data not shown). These antigens were used as controls as they were part of the antibody selection process for toxin activation. No correlation was observed between affinity and IC 50.
Acknowledgments We acknowledge funding from the  European Community 's  Seventh Framework Program  ( FP7/2007-2013 ) under agreement no. 241832  granted to the  AntiBotABE  project (http:// www. antibotabe. com). We thank  Olivier De Bardoneche  ( Vitamib/Absiskey ) for his excellent project management office work in the  AntibotABE  project.