dataesr/scientific-paragraphs-categorization huggingface dataset:
S2 ). This finding in addition to the complement data shows that Mfd is required for B. cereus virulence in an insect model of infection. We assessed the survival of the strains during infection by crushing the insects and dilution plating. In sharp contrast to the wild type stain, the ∆mfd mutant was unable to grow in vivo and no bacteria were recovered 24 h after infection (Fig. 1B ). Thus, Mfd is required for bacterial survival during the infectious process.
3A ). The ∆mfd mutant did not survive following incubation of cells in the absence of NMMLA. By contrast, in the presence of the inhibitor, the survival rates of ∆mfd and wild-type strains were similar (P > 0. 26) strongly suggesting that Mfd plays a role in NO resistance. In a second type of experiment, bacteria were exposed directly to chemically generated acidified nitrite in a cell-free system (Fig. 3B ). The wild-type strain survived, whereas survival of the ∆mfd mutant was impaired (P < 0. 005). The concentration of NO able to reduce by 50% the survival of the strains (IC 50) was measured by dose-response experiments. The NO-IC 50 required for the wild type strain was of 4. 12 ± 1. 2 mM and was thus 2. 5 times higher that the IC 50 for the mfd mutant, which was 1. 61 ± 1. 3 mM. These data implicate Mfd in the resistance to NO, a critical mediator of the host innate immune response.
Cultures were then diluted to 10 4 cfu/ml in RPMI-1640 medium (Invitrogen) at acidic pH (pH 5. 4) in the presence of 0 to 10 mM sodium nitrite (Walco Pure Chemical Industries Ltd); under these acidic conditions, NO+ is generated from the sodium nitrite by a chemical reaction  51. The bacteria were then cultured at 37 °C for 0 to 4 h, harvested and plated on agar plates to evaluate bacterial survival. Using this cell free assay, the NO+ concentration required to decrease by 50% the survival rate of each strain (IC 50 ) was calculated using the GraphPad PRISM software (version 6. 0, GraphPad Software, San Diego, CA) with non-linear regression. Data are means of at least 5 independent experiments. To inhibit the nitrogen response in cellular assay, the NO inhibitor NMMLA N G -monomethyl-L-arginine (Sigma) was used at 1 mM.
Acknowledgements We are indebted to the  Unité d'Infectiologie Experimentale des Rongeurs et Poissons (IERP) ,  INRA ,  Jouy en Josas, France , for performing the experiments with mice and to  J. C. Jeanny  for generously providing the NOS-KO mice. We thank  A. Moris  and  Dr. Benaroch  for the gift of the PLB cells. We thank  S. Perchat  for helpful discussions and technical assistance. We thank  R. Dervyn  for helpful technical assistance. We thank  E. Dervyn  and  N. Jacques  for their help in the pulsed field experiments. We are indebted to  B. Michel ,  MA. Petit  and  I. Matic  for very helpful discussions and proofreading of the manuscript.
Rationale and objective: Incidence of thyroid cancer (TC) is rapidly increasing worldwide, but little is known about the TC burden in Central and South America (CSA). We describe the geographic patterns and trends of TC by sex in CSA. Methods: We obtained regional-and national-level incidence data from 48 population-based cancer registries in 13 countries and nationwide cancer deaths from the WHO mortality database for 18 countries. We estimated world population age-standardized incidence rates (ASRs) and agestandardized mortality rates (ASMRs) per 100,000 person-years. We calculated ASRs by histological subtype. We estimated the annual percentage change (EAPC) to describe time trends. Results: Between CSA countries, TC incidence and mortality rates varied from 8-fold to 12-fold and from 2-fold to 5-fold, respectively.
Methods The present analysis includes thyroid cancer (C53), as coded by the 10th edition of the International Classification of Diseases for Oncology (ICD-10). The data sources and methods are described in detail in an earlier article in this supplement issue. In brief, we obtained regional-and national-level incidence data from 48 population-based cancer registries in 13 countries and nationwide cancer deaths from the World Health Organization mortality database for 18 countries. We estimated age-standardized incidence rates (ASRs) and age-standardized mortality rates (ASMRs) per 100,000 person-years using the direct method and the world standard population  [13, 14]. We estimated national ASRs by aggregating the data from the available cancer registries using a weighted average of local rates.
Acknowledgements The authors would like to thank sincerely all of the cancer registry directors and their staff (listed in the Appendix to the Introduction of this Supplement) for their considerable efforts in collecting the data presented in this paper, together with members of the  IARC Section of Cancer Surveillance , especially  Sebastien Antoni ,  Murielle Colombet  and  Mathieu Laversanne , for their collaboration. The authors also wish to acknowledge  Drs Esther de Vries ,  Enrique Barrios  and  Carina Musetti  for their valuable comments in reviewing earlier drafts of the manuscript.
8 l, resulting in a final molar ratio of 2. 2:1 (taHef:taPCNA). Measurements with 1. 23 mM hsFANCM peptides (purchased from Gen-Script) as the titrant and recombinant 120 M hsPCNA in the cell were conducted in 20 mM Tris/HCl, 50 mM KCl, 5 mM MgCl2, pH 7. 5 under the same conditions as mentioned before. The signal of the first injection was discarded. The data were fitted to a single binding site model using the MicroCal ITC data evaluation software with no fixed parameters.
Ten individual frames were collected for every exposure, each 2 s in duration using the Pilatus 1M detector (Dectris). Individual frames were processed automatically and independently within the EDNA framework, yielding individual radially averaged curves of normalized intensity versus scattering angle s = 4SIN/. Additional data reduction within EDNA utilizes the automatic data processing tools of the EMBL-Hamburg ATSAS package, to combine timeframes, excluding any data points affected by aggregation induced by radiation damage, yielding the average scattering curve for each exposure series  (41). Matched buffer measurements taken before and after every sample were averaged and used for background subtraction. Merging of separate concentrations and further analysis steps were performed manually using the tools of the ATSAS package.
In solution model of the taHef-taPCNA complex To gain structural insight into the taHef-taPCNA interaction we utilized SAXS. As control experiments, we also analyzed apo taPCNA (Figure  2B ) via SAXS to facilitate modeling and interpretation of the taHef-taPCNA complex (Figure  2C ). The first step was to verify that the taPCNA ring can be approximated as a single rigid body. Since there is no crystal structure of taPCNA available, we utilized the structure of human PCNA (hsPCNA; PDB entry 1VYM) which matched the experimental data reasonably well (chi 4. 9), though systematic deviations consistent with a small amount of flexibility were observed (Figure  2B )  (56). This flexibility was visualized in the superposition of the ab initio model with hsPCNA, which appeared slightly bent and more elliptical, indicating the possibility of twisting, expansion and contraction of the ring (Figure  2B ).
Although taPCNA displays some flexibility, the data show that the hsPCNA structure is a reasonable approximation of the average position in solution. Moreover, any effects caused by the flexibility of taPCNA will be minor compared to the possible movement of taHef relative to taPCNA due to a linker region comprising 26 amino acids N-terminal to the PIP motif in taHef. Thus the hsPCNA structure was also used for the modeling of the taHef-taPCNA complex. For modeling of taHef within the complex we utilized the crystal structure of the pfHef helicase entity (PDB entry 1WP9)  (57). We analyzed the possibility of one, two or three taHef monomers bound to taPCNA using CORAL, with no symmetry applied. The best fit was obtained with 3 Hef molecules bound, followed closely by 2 Hef molecules, whereas 1 Hef provided a very poor fit (chi 1.
0 and the taPCNA ab initio model (blue) with a corresponding chi value of 3. 7 indicating that the shape of the structure is compatible with the solution data but suggesting some flexibility. Overlay of the ab initio model with the human PCNA structure (PDB entry 1VYM) indicating that the PCNA ring is likely to bend slightly and expand and contract leading to a more oval average structure. (C) Experimental SAXS data for the taHef-taPCNA complex (grey) with indicated error (light grey) and CORAL rigid body fit for one (blue; chi = 361. 93), two (red; chi = 13. 62), and three (green; chi = 1. 47) Hef proteins bound to the taPCNA trimer. SAXS rigid body model of the complex containing three Hef monomers (green) bound to the PCNA trimer (grey). For PCNA modeling the human crystal structure (PDB entry 1VYM) and for taHef the Pyrococcus furiosus (pfHef) structure (PDB entry 1WP9) was used.
We also introduced Flag-tagged FANCM into HeLa cells, and performed PLA using antibodies against Flag and PCNA; and obtained similar results (Figure  3A  and C ). These data indicate that FANCM and PCNA can form a complex in vivo, and formation of this complex is considerably enhanced when cells are under replication stress. To further analyze the FANCM-PCNA complex, we introduced Flag-FANCM into HEK293 cells and performed immunoprecipitation with the Flag antibody coupled by Western blotting. We detected the presence of PCNA in the FANCM immunoprecipitate only in cells treated with HU, but not in untreated cells (Figure  3D ). These findings are consistent with the PLA data, indicating that FANCM and PCNA form a complex in response to HU-induced replication stress. We failed to detect the presence of PCNA in the Flag-FANCM immunoprecipitate from cells treated with MMC (Figure  3D ), a DNA interstrand crosslinking drug that can block progression of replication forks.
Overlay of the ab initio model with the human PCNA structure (PDB entry 1VYM) indicating that the PCNA ring is likely to bend slightly and expand and contract leading to a more oval average structure. (C) Experimental SAXS data for the taHef-taPCNA complex (grey) with indicated error (light grey) and CORAL rigid body fit for one (blue; chi = 361. 93), two (red; chi = 13. 62), and three (green; chi = 1. 47) Hef proteins bound to the taPCNA trimer. SAXS rigid body model of the complex containing three Hef monomers (green) bound to the PCNA trimer (grey). For PCNA modeling the human crystal structure (PDB entry 1VYM) and for taHef the Pyrococcus furiosus (pfHef) structure (PDB entry 1WP9) was used. (D) Isothermal titration calorimetry measurements of peptides representing the N-terminal 17 amino acids of hsFANCM in its wildtype or mutated state (see also Figure1C) and hsPCNA.
MEA Recordings. Extracellular recordings from cultured CMs were performed by using a PC-based data acquisition system consisting of the MEA, preamplifiers, filter amplifiers (Multi Channel System, Reutlingen, Germany), data acquisition boards (ADInstruments, Dunedin, New Zealand), and software: Lab chart (ADInstruments) and MATLAB (MathWorks, Natick, MA, USA). The MEA was fabricated on a 50 × 50 mm glass substrate. 60 titanium-nitride electrodes with a diameter of 30 m and distance of 200 m were organized in a 1. 4 × 1. 4 mm matrix in the center of substrate. Cultures were stimulated using one of the electrodes. The MEA with CMs was taken from the incubator and placed on a hotplate controlled by a temperature controller maintained at 37 ∘ C. Data were recorded at 20 kHz with 16-bit precision and were digitally filtered by a low pass arithmetic filter to obtain zero phase distortion with a cut-off frequency of 2 kHz.
The filtered signal was differentiated digitally to determine the local activation time (LAT) at each electrode, and the activation map was constructed by interpolating the LAT values for the sites between the electrodes within the MEA matrix. The amplitude, QT interval, T-wave recording ratio, and beating rate were determined by analyzing the waveform of the CM field potential. The corrected QT interval (cQT interval) was calculated by normalization to the CM beating rate by using the Fridericia correction formula: cQT interval = QT interval/ Shinku Device, Sagamihara, Japan). The angular distributions and fiber diameters were evaluated using ImageJ software (National Institutes of Health, Bethesda, MD, USA). For transmission electron microscopy (TEM), the samples were fixed with 2% glutaraldehyde (Distilled EM Grade, Electron Microscopy Sciences, Hatfield, PA, USA) in NaHCa buffer (100 mM NaCl, 30 mM HEPES, 2 mM CaCl 2 , adjusted to pH 7.
Acknowledgments Funding was provided by the  Japan Society for the Promotion of Science (JSPS) :  Grants-in-Aid for Scientific Research Stem Cells International 9 (B) ( 15H03948 ,  26289065 ),  Grants-in-Aid for Scientific Research (C)  ( 15K08270 ),  Challenging Exploratory Research  ( 26630096 ), and  Grants-in-Aid for JSPS Fellows  ( 26. 04046 ). Funding was also provided by the  Center of Innovation (COI) Program  from  MEXT  and  JST , the  European Commission  through contract no. 604263  (Neuroscaffolds) and the  French National Research Agency (ANR)  through contract no. ANR-12-RPIB-0015  ( Cardiac Patch ). The  WPI-iCeMS  is supported by the  World Premier International Research Centre Initiative (WPI) ,  MEXT, Japan.
Instrumentation Structural elucidation of derivatives of steroids in solutions of high concentration was performed on a LC triple quadrupole mass spectrometer, a TSQ Quantum Discovery MS (Thermofisher, Waltham, USA) and operated using Xcalibur software version 2. 0. Confirmation of accurate mass was performed by direct infusion into a 12 T SolariX dual source Fourier Transform Ion Cyclotron Resonance MS (FT-ICR MS; Bruker Daltonics, MA, US), operated with SolariX control v1. 5. 0 (build 42. 8) software. High-sensitivity quantification was performed on a QTrap 5500 (AB Sciex, Warrington, UK) coupled to an Acquity™ Ultra Performance LC (Waters Corporation, Milford, USA), operated using Analyst software v1. 5. 1.
Acknowledgments The authors acknowledge the Mass Spectrometry Core of the  Edinburgh Clinical Research Facility  for technical support. The  Royal Embassy of Saudi  (Grant no. S5019/2 ) Arabia, the  British Heart Foundation  (Grant no. RG-05-008 ),  Wellcome Trust  (Grant no. 090937 ) and the  Society for Endocrinology  provided scholarships for AF, DC, FG and TM, respectively.
Long-term stability studies Long-term stability studies for evaluating suitable storage conditions were conducted as isochronous stability studies  [18]  and were carried out for the two SEA-containing materials (IRMM-359b, IRMM-359c). For the study running over 1 year, two units were selected per time/temperature point, and from each unit, three subsamples were analysed. Storage temperatures were 4 and -20 °C, and the reference temperature was set to -70 °C. The storage times were 0, 4, 8 and 12 months. After the indicated storage periods, samples were transferred to storage at -70 °C until analysis. Measurements had to be split over five days to perform the 42 analyses. The ESM/VIDAS was used for analysis. Data were checked for outliers using the Grubbs test (99 % confidence level), and linear regression analysis as a function of time was performed.
Slopes were tested for significance using a t test at the 95 % confidence level. In addition, a 2-year study was performed, for temperatures 4 and -20 °C and a reference temperature of -70 °C. Seen the excellent results for the 1 year stability study, only samples with storage times of 0 and 24 months were finally analysed. Two units per storage time and temperature were selected, and three replicate analyses were performed from each unit using the ESM/VIDAS as described above. Measurements had to be split over 3 days to perform the analysis. Data were evaluated as described above.
Interlaboratory comparison to acquire data for reference material certification A laboratory intercomparison was organised. Laboratories were selected based on their technical competence and experience to apply the ESM. Having the method operated under ISO/IEC 17025 accreditation was not mandatory, but considered as an asset. In total, 13 laboratories participated in the characterisation study: six laboratories used the ESM/VIDAS, five laboratories used the ESM/Ridascreen and two laboratories applied both ESM/VIDAS and ESM/ Ridascreen. For those two laboratories, it shall be noted that independent samples were prepared for analysis using either detection step. Each laboratory received three sets of IRMM-359 (one set consists of one sachet of IRMM-359a (blank), one sachet of IRMM-359b (very low level SEA) and one sachet of IRMM-359c (low level SEA).
One-year stability study The data were evaluated individually for each temperature. The results were screened for outliers using the single and double Grubbs tests at a confidence level of 99 %. For SEA in IRMM-359b, one outlier was found (4 °C, 12 months, value 1. 00). As no technical reason for this outlier could be found, the result was retained for statistical analysis. For SEA in IRMM-359c, one outlier was found and excluded from further data evaluation for technical reasons (part of sample lost during extraction). The data were evaluated against storage time and regression lines of test values versus time were calculated (Electronic supplementary material Fig. S1 ). The slopes of the regression lines were tested for statistical significance. For SEA in IRMM-359b, a statistically significant trend was obtained at 4 °C (95 % confidence level).
Two-year stability study An isochronous study was scheduled over a period of 2 years. However, seen the excellent results of study over 1 year (suitable material stability at 4 and -20 °C), it was decided to only measure at time points 0 and 24 months. The data were evaluated as described for the one-year study. No outlier for SEA in IRMM-359b and IRMM-359c was found. The slopes of the regression lines were tested for statistical significance (Electronic supplementary material Fig. S2 ). For SEA in IRMM-359b and IRMM-359c, the slopes of the regression lines were not significantly different from zero (95 % confidence level) at both 4 °C and -20 °C. It was confirmed that the material can be stored at -20 °C. The stability of the materials will be regularly monitored throughout their lifetime (time span from material release to material being sold out) in the frame of IRMMs regular CRM stability monitoring programme.
Secondly, when comparing mean values produced by analyst when analysing CRM and spiked samples for a given SEA level, an overlap of datasets is obtained, indicating equivalence of results among samples spiked before analysis and CRM samples. In all cases however, the obtained recovery values for CRM samples were somewhat higher than those of the spiked samples (52 ± 4 % for IRMM-359b (low level), 42 ± 3 % for IRMM-359c (high level)). To further elaborate on the obtained results, extracts were prepared from blank cheese powder and spiked postextraction with SEA at the 0. 1 ng/g level (n = 6) and the 0. 25 ng/g level (n = 6). The obtained recoveries of 97 ± 3 % (interval 94-102 %) for the lower level and 86 ± 10 % (interval 72-101 %) for the higher level indicate that the loss of SEA is not primarily caused by matrix effects in the extract.
Characterisation study and value assignment Fifteen datasets (eight ESM/VIDAS and seven ESM/ Ridascreen) were received and first checked for compliance with the requested analysis protocol and for their validity based on technical reasons. The criteria considered during the evaluation were the adherence to the prescribed masses of cheese powder and water to be used for reconstitution, the pH value after acidification of the sample to be in the interval 3. 5-4. 0; the pH value after centrifugation to be <4. 5 in the supernatant; the pH value after neutralisation to be in the interval 7. 4-7. 6, and the final mass of the sample to be in the interval 5. 0-5. 8 g. Table  1  lists the individual results that had to be discarded due to non-compliance with the prescribed procedure. Both assays deliver quantity values (so-called test values for the VIDAS assay; optical density values for the Ridascreen assay, see above).
However, the results of analysis are finally expressed as SEs A-E not detected (Bnegative^, Babsent^) or SEs A-E detected (Bpositive^, Bpresent^), which is accomplished by comparison of the obtained value with the respective cutoff (threshold) of the assay (the discriminator between presence and absence, in practice a limit of detection). A summary of the obtained raw data (test values; OD values) is presented in Table  2. It shall be noted that these values are meant as information values for the laboratories when comparing the results they obtain with the results of the assays used for the characterisation of the reference materials. For establishing the certified values, however, these values were converted into presence/ absence classifications as outlined above. The following results were thus obtained: IRMM-359a, 112 valid results, all classified as BSEs detected^; IRMM-359b, 122 valid results, all classified as SEs detected; IRMM-359c, 125 valid results, all classified as SEs detected.
Conclusions One blank and two SEA-containing cheese materials could be successfully certified for testing of the presence/absence of SEA. The certified values, expressed as either diagnostic specificity (blank) or diagnostic sensitivity (SEA-containing materials), are traceable to the International System of units (SI). The materials are intended to be used for method performance  The presence/absence certification (see text for explanation and details) is expressed in either diagnostic specificity (blank material) or diagnostic sensitivity (SEA-containing materials) a As defined in the formula depicted in the text and in  [18]  b As determined using the European screening method (ESM) with the VIDAS SET2 detection step and the Ridascreen SET Total detection step. The certified value is based on eight accepted datasets of the ESM with the VIDAS SET2 detection step and seven accepted datasets of the ESM with the Ridascreen SET Total detection step.
Kepler-78 is host to a transiting 8. 5-hour orbit super-Earth. In this paper, the rotation and magnetic properties of the planet host star are studied. We first revisit the Kepler photometric data for a detailed description of the rotation properties of Kepler-78, showing that the star seems to undergo a cycle in the spot pattern of ∼1,300 day duration. We then use spectropolarimetric observations with CFHT/ESPaDOnS to measure the circular polarization in the line profile of the star during its rotation cycle, as well as spectroscopic proxies of the chromospheric activity. The average field has a strength of 16 G. The magnetic topology is characterized by a poloidal and a toroidal component, encompassing 60% and 40% of the magnetic energy, respectively. Differential rotation is detected with an estimated rate of 0.
The rocks composing the telluric planet would be molten on the dayside, and condensed on the nightside, generating a desequilibrium of the planet structure and other extreme physical phenomena as first described by  Léger et al (2011)  for the so-called "lava-ocean planets". In this paper, we present an observational follow up of this interesting system. In Section 2, we revisit the Kepler observations of this star. In Section 3, we present new observational data and analyses to constrain the magnetic properties of the planet host Kepler-78, obtained with ESPaDOnS at the Canada-France-Hawaii Telescope. In Section 4, we describe the results obtained by Zeeman Doppler Imaging on the magnetic topology of the stellar surface and differential rotation. In Section 5, we report the analysis of activity proxies from this data and search for potential planetary signatures.