dataesr/scientific-paragraphs-categorization huggingface dataset:
2d ): mucosa (Fig. 5a-d ), lymphoid follicles (Fig. 5e-h ) and tumors (Fig. 5i-l ). To facilitate cell detection, the algorithm was first set to recognize cell nuclei and cellular membranes and, finally, to simulate cells using the "Inside cytoplasmic stain" mode. This mode was optimal for precise cell delimitation despite the blurry DAPI signal resulting from the high cellular density in the lymphoid follicles as shown in Fig. 5e ; and in tumors as shown in Fig. 5i. We successfully programmed the algorithm to recognize different cell types on whole colon tissue, with the same settings for the DAPI fluorescence range and mean nuclear area value. We tested several combinations of these parameters. In this step, the grey value level of DAPI was converted into arbitrary units by Tissue Studio software.
Composer Reclassification Region ( = Automatic reclassification of fragmented ROI by conditional rules see Supplementary Figure  4 ) To manage with the complexity of a whole organ slide, we implemented three analysis steps, named composers. First composer is "Initialization", a mandatory composer in Tissue Studio software to detect ROI. It allows automatic recognition of ROIs by software, using a stock of representative areas, selected on colon section during algorithm development. Second composer is "Reclassification region" based 65,536 g. v. l). Thus, CD45 + cells could be automatically and correctly detected in each iROI for all slides (Fig. 5d : mucosa, 5h: lymphoid follicle, 5l: tumor; yellow cells).
Furthermore, thanks to the development of our algorithm, its step by step description, and its troubleshooting guide (Table  1 ), it is easier to analyse data than to perform mass spectrometry imaging. If necessary, our algorithm can be easily applied to the Definiens software interface using the Tissue Studio User guide  29. Additionally, obtaining numerical data is faster than with mass spectrometry or classical IHC. Thus, we developed a fast and simple way to robustly quantify and localize immune cells on numerous tissue samples without the requirement of complex bioinformatics expertise. Moreover, our method allows the cell density to be determined from microscopic structures, such as lymphoid follicles and small neoplastic lesions, which are not accessible with FC. Because of the Definiens CNT used in our algorithm, we can implement specific settings to detect these structures within the colon and count the associated cells.
Accession code. Algorithm codes for digital image analysis of whole colon slide, and more precisely for ROI classification and leucocytes and T cells quantification are available on Scientific Report website, in dax format. This format must be opened in Tissue Studio Software. Structures and all any details of algorithm code are available in. pdf format in article figures (Figs  1a, 2  and 4d ) and in Supplementary information (Supplementary Figs  2  and 3 ).
(c) We implemented a third step, "ROI Classification", to discriminate the various colon regions of interest (ROI). To manage with the complexity of a whole organ slide, we implemented three analysis steps, named composers. First composer is "Initialization", a mandatory composer in Tissue Studio software to detect ROI. It allows automatic recognition of ROIs by software, using a stock of representative areas, selected on colon section during algorithm development. Second composer is "Reclassification region" based.
Acknowledgements We are grateful to  Mr. P. Ripaille  for his great help in statistical analysis in order to calculate the number of available coded action possibilities in Tissue Studio software. This study was supported by the  Ministère de la Recherche et de la Technologie ,  Inserm  and  Université Clermont-Auvergne  ( UMR1071 ),  INRA  ( USC-2018 ). A. Lopès was supported by a  CIFRE  grant with  Sanofi   R&D (2015/622 ).
FUNDiNG NG was supported by the  French "Fondation pour la Recherche Médicale FRM " award number  SPE20130326582 , the  Société Française de Dermatologie (SFD) , the  Société Française l' Allergologie (SFA) , the  European Commission  ( Marie Skłodowska-Curie Individual Fellowship   H2020-MSCA-IF-2016 749629 ), and the  French "Institut National de la Santé et de la Recherche Médicale " (INSERM); TM is a Research Associate of the F. R. S. -FNRS and is supported by an  "Incentive Grant for Scientific Research " of the  F. R. S. -FNRS  (F. 4508. 18),by the  FRFS-WELBIO  under grant  CR-2017s-04  and by the  Acteria Foundation ; SJG is supported by  NIH  Grants  U19 AI104209 ,  R01 AR067145 , and  R01 AI32494 ; the  United States-Israel Binational Science Foundation  (Grant  2013263 ); the  University of California , Tobacco- Related Disease Research Program ; and the  Sean N.
2 Abs. Data are expressed as arbitrary units (AU). Bars show the mean ± SD of four independent transfections. Anti-HA western blotting were performed on total lysates (insert panel). c-f Human primary CD4 + T cells were stimulated for 6 h with isotype control mAb (Ig) or 2 μg ml -1 crosslinked agonistic CD28. 2 (c, d) or superagonistic ANC28. 1 Abs (e), or 2 μg ml -1 crosslinked anti-CD3 (UCHT1) plus anti-CD28 (CD28. 2) Abs (f) in the presence of 10 μM cytochalasin D or DMSO, as vehicle control. IL-8 (c), IL-6 (d, e), and IL-2 (f) mRNA levels were measured by real-time PCR and values, normalised to GAPDH, expressed as arbitrary units (AU). Lines represent mean values ± SD. g NF-AT luciferase activity of hCD28 WT cells transfected with empty vector or HA-Nck R311K mutant and stimulated with medium (Med) or 5-3.
Uncropped version of all Western blots can be found in Supplementary Figs. 14  and 15. Cytokine production. Secretion of IL-8 was measured from the supernatants of CD4 + T cells cultured for 24 h in flat bottom 48 culture wells (3 × 10 5 cells per well) either unstimulated or stimulated with crosslinked anti-CD28. 2 Ab (2 μg ml -1 ) or adherent Dap3/B7 cells fixed with paraformaldehyde to avoid detachment and secretion. A cytometric bead-based immunoassay (#558277, CBA FLEX SET, BD Biosciences) was used to measure IL-8. Data were analysed with the FCAP Array v3. 0. 1 software (Soft Flow Hungary Ltd. ). Real-time PCR. Total RNA was extracted using Trizol (Thermo Fisher Scientific, CA, USA) from 2 × 10 6 cells and RNeasy MicroKit (#74004, Qiagen) from 5 × 10 5 cells according to the manufacturer's instructions and was reverse-transcribed into cDNA by using Moloney murine leukaemia virus reverse transcriptase (Invitrogen).
However, no data are available for species other than C. parvum and C. hominis. Cell-culture assays have been used to assess the exposure of humans to infective Cryptosporidium spp. oocysts in various types of environmental water samples (Table  1 ), although in the most recent large waterborne outbreaks of cryptosporidiosis, they do not appear to have been applied  [22, 50]. This approach also seems relevant to assess the efficacy of control measures that can be used in food industries (i. e. oxidants, organic acids, heating or storage at 2-8 °C) in simple matrices and in fruit juices, but it has not been extensively applied in foods (Table  1 ).
For Cryptosporidium and Giardia, determination of the species and the genetic assemblages respectively, is part of the exposure assessment. These important taxonomic details can be determined by DNA-based assays and directly address the infectious potential for humans. ii) Characterize the efficacy of treatments in place to control parasites using a combination of techniques. Simple vital dye inclusion/exclusion methods may be the preliminary approach, providing initial data on the inactivation potential of different treatments. To determine inactivation levels, which are the reference measure for food operators (log 10 viability reduction), RT-qPCR-based assays could be applied. They will overestimate the level of infective protozoa (quantification of live and infectious, live and non-infectious, and possibly dead (oo)cysts), leading to an underestimation of the efficacy of the treatments.
Acknowledgements. This work was funded by the  UMT ACTIA PROTORISK  and the  University of Reims Champagne-Ardenne , in the framework of a PhD thesis with a CIFRE agreement between ACTALIA and the  French Ministry of Higher Education, Research and Innovation. This work was also supported by the  French National Research Agency  (grant  ANR-17-CE21-0005-07 ). This review is based upon collaboration within the framework of Working Group 3 of  COST Action FA1408 "A European Network for Foodborne Parasites: Euro-FBP ", supported by  COST (European Cooperation in Science and Technology).
Statistical analysis Data analyses were performed using the SAS version 9. 3 software package (SAS Institute, USA). Due to the absence of normal distribution, continuous variables were described as median and inter-quartile range (IQR) and were compared with Wilcoxon Mann-Whitney tests and Chi-square test was used to compare percentages. The Spearman correlation coefficients were calculated to determine the relationship between continuous variables. The results with corresponding P-values < 0. 05 were considered to be statistically significant.
Enumeration of spontaneous circulating ASCs directed against Cut4 and CFP21 Circulating cells secreting spontaneously IgG antibodies (Abs) directed against Cut4 or CFP21 were explored by ELISpot assays. Immunospots corresponding to the footprint of cells secreting Abs directed against Cut4 or CFP21 were enumerated after overnight culture without polyclonal activation (Fig  1    B cells, was enumerated in subjects of TB negative and LTB groups. There was no correlation when comparing Cut4 IgG immunospots with PPD IgG immunospots results (ρ = -0. 030; p = 0. 909) but a weak positive correlation was found, between CFP21 IgG immunospots and PPD IgG immunospots (ρ = 0. 457; p = 0. 065; data not shown).
All flow cytometry data were collected using a FACSCalibur (BD Biosciences, San Jose, CA), and analyzed using Flowjo 7. 6. 1 software (TreeStar, Ashland, OR). For all samples, monocytes and lymphocytes were identified using a SCC/FSC cell gating strategy, then the following cell populations were considered: gamma/delta (γ/δ)T-cells (CD3 + /γ/δ + ), alpha/beta (α/β)T-cells (CD3 + /α/β + ), NK T-cells (NKT as CD3 + /CD56 + ); NK cells (CD3 -/CD56 + ), CD8 + T-cells (CD3 + /CD8β + ), B-cells (CD3 -/CD19 + ), CD4 + T-cells (CD3 + /CD4 + ), regulatory (Tregs) T-cells (CD3 + / CD4 + /CD25 high /CD127 low/-), and finally monocytes (CD3 - CD14 + ) in a monocyte gate. The lymphocyte population was validated by CD45 expression (Figure  1 ). Only the median percentage (%) compared to total lymphocytes was considered for all lymphocytes subsets between days 0-30 because of profound lymphopenia in patients.
The efficiency of the hybridization was monitored by a green fluorescence labeled probe within the hybridization buffer, which hybridizes to specific DNA sequences on the chip. The chip coated with 39 species-specific probes can detect 41 mycoplasma species that are found in more than 99% of all reported contaminated samples. Each mycoplasma species was detected and identified by five measuring points on the DNA chips. Following the hybridization step, the chips were washed to remove unbound PCR products. Hybridized and fluorescently labeled DNA was detected by monochromatic light using the CheckScanner™ (Greiner Bio-One), and the results were analyzed using CheckReport™ Software (Greiner Bio-One). The results were expressed as either mycoplasma positive (specific signal detected by the CheckReport™ Software indicating DNA amplification by PCR) or mycoplasma negative (no specific signal detected by the CheckReport™ Software indicating the absence of mycoplasma DNA in the PCR).
Each mycoplasma species is detected by five measuring points on the chip. A universal probe, also on the chip, broadens the spectrum of detectable species. 3. Inadequately bound PCR products and excess of PCR products are removed by washing. Monochromatic light is used to excite the bound, labeled probes which are then analyzed using the CheckReport™ Software. materials used during the production or freeze-drying of the modified live vaccine. We demonstrated the specificity of the CytoInspect™ Test Kit since the mycoplasma species were detected individually in assays of the spiked tested vaccine containing all five species and no mycoplasmas were detected in the non-spiked vaccine. Although our results showed that the LOD for M. hyorhinis strain was > 10 CFU/mL in the presence of the other four strains, the results from a complementary study showed that, when the vaccine was spiked with M.
Acknowledgements The authors thank  T. Bonnevay  and  L. Mallet  ( Sanofi Pasteur, Marcy-L'étoile, ARD Department ) for providing highly characterized mycoplasma strains and technical support and  Annett Kilic  ( Greiner Bio-One Company ) for her helpful review of this manuscript. The authors would like to acknowledge medical writing and editorial assistance provided by  Margaret Haugh ,  MediCom Consult , Villeurbanne, France, funded by  Merial. The research described did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors. SM, VG, SB, JL, HP, and BSV are employed by  Merial  (now  Boehringer Ingelheim ) and EA and SF are employed by  Sanofi Pasteur.
METHOD DETAILS Flow Cytometry-Cells were stained as previously described  (Bankoti et al. , 2017)  with the antibodies listed in the Key Resources Table. A rabbit anti-GFP antibody was used to stain Blimp1 YFP or Foxp3 GFP reporter cells in some experiments. Foxp3 staining was done with eBioscience Foxp3 staining kit or BioLegend's FOXP3 Fix/Perm Buffer Set. Samples were acquired on a LSRII analyzer and FACSymphony (BD Biosciences). FACS data was analyzed with FlowJo software. Antibiotic treatment-Mice were treated (6 wks) with a cocktail of 1mg/ml vancomycin, 0. 5mg/ml metronidazole, 1mg/ml neomycin, 1mg/ml ampicillin and 0. 5mg/ml Fluconazole in their drinking water. Cytokine measurement-Cytokine production was measured in the supernatant of cell culture using eBioscience kits (IL10; IL17A).
0 software. Genomic sequences were obtained from Ensembl. Luciferase reporter assays-A 2 kb fragment containing the Il17a promoter was cloned into the PGL4. 10 luciferase reporter plasmid with or without the CNS7 region. Full length wild-type Blimp-1 (Blimp-Full) or a DNA-binding-lacking construct (Blimp-ΔZF) was clone into pcDNA3. 1(+) expression vector (Invitrogen, Waltham, MA). All primers used for cloning listed in the Key Resources Table. EL4 LAF T cells (5 × 10 6 ) were transfected with luciferase reporter plasmids (5 μg), Blimp1-expression plasmids (5 μg) and phRL-TK(2 μg) (Promega) as internal control plasmid. Transfections were performed with BTX ECM830 Square Wave Electroporation System (BTX, Holliston, MA). Total DNA amount was adjusted with the empty pcDNA3. 1(+) vector. Transfected cells were incubated 18 h, and then stimulated, lysed and luciferase activity measured with a dual luciferase assay system.
ACKNOWLEDGMENTS We are grateful to members of the  Martins laboratory  for discussions; to  Drs. V. Kuchroo  ( Harvard Medical School ) and  E. Meffre  ( Yale School of Medicine ) for Foxp3 GFP and Blimp1 YFP single reporter mice, respectively; and to  Dr. M. Fukata  ( CSMC ) for IL17 GFP Foxp3 RFP dual reporter mice. We thank  Drs. M. Tone ,  T. Araki , and  T. Watanabe  ( CSMC ) for help with luciferase assays; the  CSMC Flow cytometry core  ( A. Lopez  and  Dr. J. Suda ); and the Fred Hutchinson CCEH vector production core ( Dr. M. Wohlfahrt ). Funding for this work was provided by  NIH  research grant  R01AI103542  and  R01AI127406  (to G. A. M. ) and by  IBIRI-CSMC  (to G. A. M. ).
The mutant strain RA-CH-1ΔB739_1343 exhibits reduced iron utilization in iron-starved conditions To identify the function of B739_1343, the mutant strain RA-CH-1ΔB739_1343 was constructed and verified as described in the "Materials and Methods" section. After the B739_1343 gene was knocked out, its ability to affect the growth of R. anatipestifer CH-1 in tryptone soy broth (TSB) liquid medium was evaluated. As shown in Fig  1 , disruption of B739_1343 did not damage the growth of R. anatipestifer CH-1 in TSB liquid medium. Moreover, the addition of the iron chelator 2,2'-dipyridyl at a final concentration of less than 80 μM impaired the optimal growth of both RA-CH-1ΔB739_1343 and the wild-type strain at the same level (data not shown). However, the addition of the iron chelator 2,2'-dipyridyl at a final concentration of 120 μM impaired the maximal growth rate, e.
Sequence analysis The homology of the B739_1343 sequences was analyzed using the Basic Local Alignment Search Tool (BLAST) algorithm (http://blast. ncbi. nlm. nih. gov/). Prediction of protein structure was performed using Phyre 2 programme online (http://www. sbg. bio. ic. ac. uk/phyre2/ html/page. cgi?id=index)  [38]. Multiple sequence alignments of the B739_1343 sequences were performed using the program Clustal W2  [39].
The next day, the cells were washed five times with PBS, and the fluorescent secondary antibodies (anti-IgG (HϩL), Alexa Fluor conjugates, Thermo Scientific), diluted 1:1000 in 1% BSA, were applied for 1 h. The coverslips were washed again with PBS and incubated for 5 min with Hoechst dye diluted in PBS at a final concentration of 4 g/ml. The coverslips were mounted on slides using ProLong Gold Antifade (Invitrogen). Images were captured using an inverted confocal microscope (LSM 710 META, Zeiss) and processed with Zeiss Axiovision software.
This work was supported by  Fondation Innovations en Infectiologie , the  Foundation for the Development of Internal Medicine in Europe , and the  Groupama Foundation  (to Y. J. ),  EC Seventh Framework Programme  ( FP7)  Grants  311542  (to T. H. ) and  281996  (to F. M. ); the  Société Nationale Française de Médecine Interne , and by a poste d'accueil from  INSERM  (to Y. J. ). The authors declare that they have no conflicts of interest with the contents of this article. Acknowledgments-We thank  Dr. Manfredo Quadroni  and the proteomics facility of the  University of Lausanne  for help with MS and analysis.
Amplifications were performed on an Applied Biosystems ® 7500 Real-Time PCR system (Thermo Fisher Scientific, Villebon-sur-Yvette, France). Data were analyzed using the 7500 software v2. 0. 6. E2, E6, and β-globin copy numbers in UCS were determined by absolute quantification using standard curves. These curves were generated from serial dilutions of plasmids containing E2, E6, and β-globin's relevant sequences (ten-fold range). β-globin amplification allowed cell load quantification (copy number divided by two, as each cell contains two copies of the β-globin gene). Total and episomal HPV16 VLs were determined using E6 and E2 cell load normalized DNA quantifications. Integrated VL was calculated by subtracting episomal VL from total VL.
Wilcoxon non parametric test was used to test statistical significance of VLs regarding proper classification of lesion grades. p-values ≤0. 05 were considered statistically significant. Clinical performances such as sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were expressed in percentages (95% confident intervals). Statistical calculations were performed using SAS V9. 4 software (SAS Institute Inc. , Cary, NC, USA).
05). Regarding DNA VLs, only the total DNA VL increase was statistically significant for CIN3+ lesions. These data suggest that E6/E7 mRNA VLs are relevant biomarkers to discriminate patients harboring high grade cervical lesions from patients with low grade lesions regardless of high or low E6/E7 mRNA expression level. In order to measure the effectiveness of HPV16 DNA and E6/E7 mRNA VLs quantification assays for proper identification of high grade CIN2+ and CIN3+ cervical lesions, we performed a ROC analysis. ROC curves obtained for detection of CIN2+and CIN3+ lesions are shown in Figure  2A  for DNA VLs and Figure  2B  for E6/E7 mRNA VLs. The AUC value calculated for each VL reflects its accuracy in discriminating high grade lesions from low grade ones. For both CIN2+ and CIN3+ lesions, quantification of SP-E6/E7 mRNA VL exhibited the best performance with an AUC of 0.
Surprisingly, in the two invasive CC samples of our cohort, the integration of HPV16 is weak which supports the current controversy about the role of HPV integration in the onset and progression of CC. In addition, although the integration of the HPV genome has long been considered a late event in cervical oncogenesis, recent controversial results showing early detection of HPV integration and poor performance of this biomarker suggest a more complex interplay  [27, 42]. Our data clearly demonstrate that E6/E7 mRNA VLs in UCS represent useful biomarkers to identify women harboring high grade cervical lesions. Indeed, we showed that expression of E6/E7 mRNA is significantly increased in UCS obtained from women developing CIN2+ and CIN3+ lesions. We performed E6/E7 mRNA VL quantification using an in-house qRT-PCR assay involving three primer/probe sets designed to amplify various E6/E7 mRNA isoforms.
This paper examines the national and international growth of prehistoric archaeology in Italy from 1875 to 2000. A bibliometric approach is proposed for a case study of a scientific discipline, language and period that are poorly represented in current bibliographic databases. These constraints led to the generation of a data set with articles from 5 journals (2842 articles and 1221 unique authors). Publication language and author nationalities were manually included in the data set. Journal internationality measures and co-authorship network analyses showed: 1) that internationalisation was not the most striking change over the study period: it was one of a number of features that journal editors addressed in their own way; 2) results confirm a change in the social organisation of scientific production in archaeology, with the emergence of co-authorship and reflect the differentiation of local research trends.
LIMITATIONS OF BIBLIOMETRIC STUDIES OF THE (DE)NATIONALIZATION OF SCIENCES As in others scientific disciplines aiming to produce a universal knowledge, prehistoric archae-ology includes an international aim. There are, however, three specific points which make it of particular interest when studying internationalisation in science. First, in general, archaeological practises are closely related to international issues, being a practise made by a cosmopolitan elite or being an aspect of the cultural diplomacy between states. 1  Second, considering the methodological aspects of historical investigation, archaeology -and specifically archaeology written in a non-English languageis a scientific discipline that is rarely included in the main bibliographic databases (e. g. Scopus, Web of Science).
These authors also argued, however, that analysing the relationships between national frameworks and scientific activities on a broader time-scale shows that: 1) trends of (de)nationalisation occurred periodically throughout the history of science; 2) that these processes were achieved by various methods including the emergence of spontaneous associations, state bureaucracy policies, the migration of scientists, and the creation of "locally-grounded transnational research sites". 7 uch insights suggest that the main problem is not the investigation of contrasting national and international scientific practises, but the empirical examination of the various forms of (inter) nationalisation. Concerning the latter, for decades, sociologists and historians of science have used a wide range of specific data set to examine scientific activities, including: scientific production (actors' involvement in fieldwork, publication languages, patents and publications), socialisation (affiliation to institutions, participation in conferences), reception or visibility (citations).