dataesr/scientific-paragraphs-categorization huggingface dataset:
Accordingly, it is possible to generate an epitope list, including sequence, antigen name (GenBank) and name of the organisms (NCBI) of origin. Similarly, details from specific assays, host organisms or a references list can be retrieved and also downloaded by clicking on the Excel icon at the top of the data table. A total of 15 antigens reported in the IEDB account for 88% of the references and the near totality of the data (94%) (Table  2 ). GAD and insulin alone make up 62% of the curated assay data. The top seven antigens associated with more than 100 different curated assays (GAD, insulin, IA-2/PTPRN, ZnT8, HSP, IGRP and ICA-1 also known as ICA69), account for nearly 90% of the data. Additional antigens include MHC, glial fibrillary acidic protein (GFAP), serum albumin, islet amyloid polypeptide precursor (IAPP), insulin-like growth factor (IGF), TCR and chromogranin A.
These epitopes are derived from GAD, insulin, IA-2 and ZnT8 using antibodies from human subjects with disease. The Homology Mapping tool visualizes conformational epitopes by mapping each residue onto a given antigen sequence and highlights its position in the 3D structure of the protein  [28]. For example, a list of IA-2 epitopes was generated through Excel download. Next, from the 'Tools' menu we selected 'Epitope Analysis Tools' and then Homology Mapping. All IA-2 epitope residues reported (multiple records) were pasted in sequentially. The FASTA sequence of the GenBank ID (4506321) for IA-2 was then entered as source antigen, to generate the three-dimensional image shown in Figure  8.
The diabetes related data contained in the IEDB can be seamlessly linked to the IEDB analysis resource, [34], which includes class I, class II and B cell epitope prediction tools, and other epitope analysis tools such epitope clustering, homology mapping, conservancy analysis and population coverage tools. Moreover, the IEDB provides links to more than 50 other relevant databases/resources, including NCBI, GenBank, PDB, ChEBI, DO, etc. This combination of data, features and tools housed in one location makes the IEDB unique among immunological web-based resources. Herein we demonstrate the use of the IEDB to access and analyze diabetes-specific epitope data generated from humans and animal models. Our ultimate objective is to increase the awareness of the IEDB resource in the diabetes research community, and encourage feedback, which is key to ensuring the accuracy and continued enhancement of the data housed therein.
Data inclusion criteria This analysis includes available data for antibody and T cell epitopes associated with diabetes, based either on the clinical status of the host or on the association of the antigen with diabetes. We followed the process of Davies et al  [7]  to identify diabetes related data derived from peer-reviewed literature (PubMed), as well as data directly submitted to the IEDB (instructions can be obtained on the IEDB main page Solutions Center under 'Data Submissions. '). Epitope definitions (length and mass restrictions) and IEDB inclusion criteria can be found at [http://tools. immuneepitope. org/wiki/index. php/ Curation_Manual2. 0#Prevailing_Rules]. For the purpose of this report, epitopes represents the unique molecular structures (minimal sequences, linear and discontinuous regions, as well as key residues) experimentally shown to react with a B cell or T cell receptor (the database only curates experimental data and does not include predictions).
IEDB Queries and Analysis Queries were performed using the IEDB [www. iedb. org] search interfaces. Unless otherwise specified, results were analyzed by downloading them into Excel format. In some cases, query results were captured as still images. All other figures and/or tables were produced in Excel. The Response frequency score (RFscore) is calculated as described previously  [27]. To query for epitopes defined for GAD in mice, the Host Organism field was used to enter 'Mouse. ' The auto-complete feature will display the top ten hits and by choosing 'Mus musculus (ID 10090 common name: mouse' the query will retrieve epitopes defined in mice for the specified antigen (in this example GAD). The Disease Finder feature selects data defined in hosts (both human and non-human) affected by a naturally-occurring or experimentally induced disease, excluding data derived from healthy controls and non-relevant data.
Islet auto-antigen 2 (protein tyrosine phosphatase-like auto-antigen 2); IGF, insulin-like growth factor 1; LPS/LOS, lipopolysaccharide/ lipooligosaccharides; GFAP, glial fibrillary acidic protein isoform 2. A total of 405 references were identified [using method described in  Davies 2009 ] as being associated with 'diabetes' as of September 2012. Enumeration of total assays: these data were generated from the SQL download. A spreadsheet of all data (all ref IDs = diabetes from Davies 2009) was first filtered for 'qualitative_measure' = positive. Then using the 'structure_source_ag' field each individual auto antigen was selected and the total number of 'struc_id's (unique epitopes) were enumerated using advanced filter to retrieve only unique IDs. Then Bcell_id, Tcell_id, MHC_id and elution_ids were enumerated.
Acknowledgments We gratefully acknowledge  Drs Howard Grey  ( La Jolla Institute for Allergy and Immunology ) and  Alison Deckhut  ( National Institute of Allergy and Infectious Diseases ) for review of this manuscript. The Immune Epitope Database is supported by the  National Institutes of Health National Institute of Allergy and Infectious Diseases , contract number  HHSN272201200010C.
cancer. gov/clinicaltrials) are evaluating the efficacy of the combination of HCQ with cytotoxic drugs in a variety of cancers. Importantly, many of the aforementioned pharmacological agents have been shown to be effective in the treatment of cardiovascular disorders, including cardiomyopathy, and heart failure in which AP is involved  [184]. For example, reduction of infarct size has been demonstrated in mice treated with rapamycin  [185]. Rapamycin, AICAR, and metformin improve cardiac function, reduce cardiac hypertrophy, and delay the onset of heart failure during overload pressure  [186, 187]. On the other hand, a strong activation of AP, due to Beclin 1 upregulation, is observed in response to severe pressure overload, and this could be responsible for the transition from compensatory ventricular hypertrophy to pathological remodeling  [188].
The ITS and 16S rRNA of strain R4T exhibited nucleotide sequence similarities of 63. 8% and 99. 4% with those of Bartonella tribocorum strain CIP 105476, respectively (GenBank accession number AF312505 and NR_074354, respectively) strain CIP 105476, respectively; 94. 4% with Bartonella birtlesii strain IBS 325 for ftsZ (AM690313), 92. 6% with Bartonella acomydis strain KS2-1 for rpoB (AB529942) and 90. 7% with Bartonella taylorii strain M6 for gltA (Z70013). Phylogenetically, strain R4 T formed a separate branch among the rodent-associated species (Figure  1 ). Different growth temperatures (32, 37, 42°C) were tested. Growth only occurred at 37°C in 5% CO 2 atmosphere. Colonies were gray, opaque and 0. 3 mm to 1 mm in diameter on blood-enriched Columbia agar. Cells grown on agar are Gramnegative and have a mean length and width of 1.
Each smear was overlaid with 2 μL of matrix solution (a saturated solution of alphacyano-4-hydroxycinnamic acid) in 50% acetonitrile/2. 5% trifluoroacetic acid, and allowed to dry for five minutes. The twelve R4 T spectra were imported into the MALDI BioTyper software (version 2. 0, Bruker) and analyzed by standard pattern matching (with default parameter settings) against the main spectra of 4,613 bacteria, including 241 spectra from 20 validly named Bartonella species, used as reference data in the BioTyper database. A score enabled the presumptive identification and discrimination of the tested species from those in a database: a score > 2 with a validated species enabled the identification at the species level; and a score < 1. 7 did not enable any identification. For strain R4 T , no significant score was obtained, suggesting that our isolate was not a member of any known species (Figures  3  and 4 ).
Genome project history The organism was selected for sequencing on the basis of the similarity of its 16S rRNA, ITS, ftsZ, gltA and rpoB to other members of the genus Bartonella. Nucleotide sequence similarity levels of these genes suggested that strain R4 T represents a new species within the genus Bartonella. It was the eleventh genome of a Bartonella species and the first genome of Bartonella florenciae sp. nov. A summary of the project information is shown in Table  2. The GenBank accession number is CALU00000000 and consists of 62 contigs (14 scaffolds). Table  3  shows the project information and its association with MIGS version 2. 0 compliance. [27]. If the evidence is IDA, then the property was directly observed for a live isolate by one of the authors or an expert mentioned in the acknowledgements.
Genome annotation Coding sequences (CDSs) were predicted using PRODIGAL with default parameters  [35] , but predicted ORFs were excluded if they spanned a sequencing gap region. The functional annotation of protein sequences was performed against the non-redundant GenBank database using BLASTP and functional categories of these proteins was searched against the Clusters of Orthologous Groups (COG) database using COGNITOR  [36]. The prediction of RNAs genes, i. e. , rRNAs, tRNAs and other RNAs was carried out using RNAmmer  [37]  and ARAGORN  [38]  algorithms. The transmembrane helices and signal peptides were identified using TMHMM [39] and SignalP  [40]  tools, respectively.
The G+C content is 38. 5%. Sequences from the ITS, 16S rRNA, ftsZ, rpoB and gltA genes, and the genome are deposited in GenBank under accession numbers HM622140, HM622139, HM622141, HM622143, HM622142 and CALU00000000, respectively. The type strain R4 T (DSM 23735, CSUR B627) was isolated from a C. russula shrew found dead in calanque d'En-Vau near Marseille, France.
Acknowledgements We are grateful to  Denis Pyak ,  Audrey Borg , and  Geetha Subramanian  for their technical help. The present work was funded by the  Agence Nationale de Recherche  grant  2010   MALEMAF  (research on emergent patho-gens in Africa) and the  Mediterranée-Infection Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Positions related to promoter are coincident with panel A. C. Functional analysis of Ccl20-luc in vivo. BALB/c mice were transfected for 48 h by hydrodynamic shock with Ccl20-luc and TK-renilla plasmids, treated next i. v. for 8 h (5 mg flagellin or PBS), and liver luciferase activity was determined. Results are expressed as relative luciferase activity using PBS-treated mice as reference and renilla activity as normalizer for transfection efficiency. Data are given as mean 6 SD (n = 8; * p,0. 05 Mann-Whithney test) and are representative of two experiments. D. NF-kB site but not Ets1 site is required for the activation of transcriptional fusion by flagellin. Experiments were conducted as described in C using different luciferase reporter Ccl20-luc [2299-+6] plasmids harboring deletions or mutations as shown in B.
Experiments were conducted as described in C using Ccl20-luc-IRES-eyfp. Data are given as mean 6 SD (n = 8; * p,0. 05 Mann-Whithney test) and are representative of two experiments. doi:10. 1371/journal. pone. 0078447. g001 activity in differen organs (see below). Classical genotyping of mice was performed on tail genomic DNA using the following set of primers for control (Cpxm1-F: ACTGGGATCTTC-GAACTCTTTGGAC and Cpxm1-R: GATGTTGGGG-CACTGCTCATTCACC), 59-amplification of construct (D-F: GTGACAGGATGAGGCAGATTAATCAATGGG and D-R: CTTTACCAACAGTACCGGAATGCCAAG), and 39-amplification of construct (F-F: GCCCAGAAGGTACCCCATTG-TATG and F-R: GTTTACGTCGCCGTCCAGCTC). In some assays, genomic DNA was assessed using real time quantitative PCR with the following primers specific for luc (LUC-F: TGAGTACTTCGAAATGTCCGTTC and LUC-R: GTATT-CAGCCCATATCGTTTCAT) and Actb (Actb-F: CGTCATC-CATGGCGAACTG and Actb-R: GCTTCTTTGCAGCTCCTTCGT).
The fusion expression in liver was also assessed at different times after flagellin stimulation. We observed a fast induction of luciferase activity (200650 fold) 4 h post-treatment associated to a gradual decrease at later time points (Figure  2C ). This rapid activation correlates with a rise in Ccl20 mRNA levels of around 150 fold at 4 h posttreatment that return to basal levels at 24 h (Figure  2D ). Interestingly, qPCR analysis of genomic DNA derived from F1 to F7 generations revealed that the transgene copy number is stable as defined by relative levels of genomic DNA specific for luciferase and beta actin genes (data not shown). Altogether, our data show that the Ccl20-luc reporter mice represent an appropriate model to monitor in real time the activity of Ccl20 promoter. As CCL20 can be induced at various mucosal sites in response to pro-inflammatory stimuli  [14] , the activation of the reporter in lung mucosa after intranasal and systemic flagellin administration was compared.
LVM, DC, JT and JCS were funded by  Institut national de la santeet de la recherche medicale ,  Institut Pasteur de Lille, Region Nord Pas de Calais (Ph. D. fellowship) , the  European Community  ( STREP ''SavinMucoPath'' INCO-CT-2006-032296 ), and the  Institut Clinique de la Souris  (Projet  IM1340 ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
For each of these four countries, information was collected on Q fever in humans and farm animals based on a detailed review of relevant peer reviewed and non-peer reviewed literature. Relevant literature was identified following interrogation of two publication databases, ISI Web of Knowledge and PubMed, using defined qualifiers for infection and disease (C. burnetii infection, Q fever), host (humans, farm animals), location (Bulgaria, France, Germany and the Netherlands)) and issue (epidemiology, diagnostics, control, review). The search was limited to literature published from 2005 to 2010, but relating to the period from 1982 to 2010. Additional national literature (both peer reviewed and non-peer reviewed) was obtained by working group members, and complemented with their expert knowledge and opinion, noting that EFSA working group included national experts on these issues from Bulgaria, France, Germany and the Netherlands  [2].
9%  [16]. In 2009, 2,354 new Q fever cases were registered in the national infectious disease notification database, with a hospitalisation rate of 19. 7%, comparable to the situation in 2008  [16]. In 2010, 504 cases were notified, of which 406 had a known day of onset of illness in 2010, indicating that the peak of the epidemic had been reached in 2009. In this epidemic, most cases were found in the province of Noord-Brabant (Table  3 ).
Acknowledgments We thank  G. Michlewski  and  D. Santhakumar  for comments on the manuscript. This work was financially supported by a  VIDI fellowship  (Project Number  864. 08. 003 ) from the  Netherlands Organization for Scientific Research  to RvR, by a PhD fellowship from  Radboud University Nijmegen Medical Centre  to PM. Research in AHB's lab is supported by the  BBSRC  ( BB/ J001279 ) and a  Wellcome Trust RCDF  ( WT097394A1A ). Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
In the present study, commune size ranged from 191 to 14,000 ha; these data were from the National Institute of Statistics and Economic Studies (http://www. insee. fr/). Each commune in which at least one cat was collected was characterised by its local landscape composition, farm density and local climate. Landscape composition in these communes was assessed with the CORINE Land Cover (CLC) France databases (25 ha resolution) that were produced by the European Environmental Agency (http://www. stats. environnement. developpement-durable. gouv. fr/clc/CORINE_Land_Cover_-_Saisie_ Demande. jsp, accessed June, 2012) and the geographical informa-tion system ArcGIS 10 (ESRI; http://www. esrifrance. fr, accessed June, 2012). Land cover data from the CLC 2000 database were applied to cats collected from 1996 to 2000, whereas data from CLC 2006 were used for cats collected from 2001 to 2006.
Each twelve month period of the study was divided into two: 21 December to 20 March, and 21 March to 20 December. Using this timetable, the value of the NAO winter index was recorded for the winter preceding the sampling of each cat. For example, for cats sampled between 21 December, 2000 and 20 March, 2001, the 1999-2000 winter was used, and for cats sampled between 21 March and 20 December, 2001, the 2000-2001 winter was used. The variable NAO was attributed differently for juveniles and adults. For juvenile cats the NAO winter index for one previous year was used, and for adult cats the mean NAO index for two and three previous winters. This was done because as T. gondii antibodies are lifelong, seropositivity could be related to a seroconversion that occurred several years ago. Since the precise age of cats is unknown in our dataset, we considered the median age of 2-3 years old estimated in previous studies conducted in owned or stray domestic cats living in rural or non anthropized areas  (Afonso et al.
Statistical analysis A logistic regression was used to relate the logit of the probability of infection for a cat to the predictor variables. Because the variable NAO was calculated differently for juveniles and adults, analyses were performed by considering two separate datasets according to age class. A forward selection was used to build the final equation; only some predictor variables were included per model to avoid confusion and over-parameterisation (see Appendix 2 in Supplementary data). At each analysis step, a series of models were built and compared according to the procedure described below. Individual characteristics (gender, type, and body condition) were considered in the logistic equation, and all models that included one or two variables such as gender, type and body condition with one two-order interaction were compared.
9). The probability of T. gondii seropositivity increased 2. 6-fold (95% CI: 1. 1-6. 4) with each increase of 1 farm/km 2 (Fig. 3b ). The farm density per commune ranged from 0. 1 to 6. 9 farms/km 2 (mean = 0. 86, median = 0. 68); however, communes with farm densities >2 farms/km 2 were rare in this dataset (3. 8% of the 160 communes). Finally, the probability of infection was related to large-scale meteorological fluctuations; seropositivity correlated positively with the NAO winter index (DAICc = 2. 2). NAO winter index values retained for adults were the mean of the three winters preceding the sampling. As expected, cats were more often seropositive when NAO was high. The probability of seropositivity increased 2. 0-fold (95% CI: 1. 1-4. 0) with each increase of one NAO winter index unit.
, 2008) , the range of one cat can overlap two communes). We assumed that farm densities within the communes reflected local agricultural management and therefore the importance of cat exposure to farm surroundings that are potential hyperendemic areas. Because farms are favourable areas for the presence of domestic cats  (Warner, 1985; Turner and Bateson, 2000) , wildlife (including wildcats and hybrids) that hunt in the vicinity of farms could be exposed to T. gondii oocysts that are present in the environment, or to infected intermediate hosts. These results suggest that T. gondii exposure may be more affected by the presence of highly localised areas supportive of parasite transmission (hyperendemic areas), for example farm building, than by a particular type of land cover. However, in our dataset, farm density correlated positively with grassed farmland areas (permanent grasslands and pastures; R 2 = 0.
Such a high geographical resolution approach could be used in studies of relationships between landscapes and T. gondii infection; however, map resolutions should be precise enough to clearly delimit the land cover around farms, which is not true of the geographical information currently available at the commune scale that was used for this study. The variations of seroprevalence in our dataset correlated with large-scale meteorological variations. Because T. gondii antibodies are life-long, old, seropositive individuals may have been infected long before the study period, in which case their serological status should not depend on the conditions in the years of the study. As a consequence, at the population level, the correlation between yearly conditions and seroprevalence should be attenuated when the proportion of old individuals is high.
These results reinforce the hypothesis of a general effect of meteorological variations on parasite transmission. One way to explore these results would be an investigation of the relationship between large-scale index values (NAO, El Niño) and primary productivity that influences small mammal abundance  (Stenseth et al. , 2002b) ; for example, the Normalised Difference Vegetation Index (NDVI) database could be used in a study of seroconversion data, which represent the number of individuals who seroconverted during a defined period of time. Our results suggest that areas with high farm density and years with high NAO values are, respectively, high-risk places and highrisk periods for T. gondii infection in the three types of cats and thus for environmental contamination (oocyst spread in the soil or water).
Acknowledgements The authors thank all persons who participated in the trapping, collection and necropsies of cats, particularly  François Léger  from the  Office National de la Chasse et de la Faune Sauvage. The authors also thank  Régine Geers  for performing serological tests. Thanks to the anonymous referees who significantly improved an earlier version of the manuscript. This study was financially supported by the  Office National de la Chasse et de la Faune Sauvage , the  Agence National de Sécurité Sanitaire de l'alimentation, de l'environnement et du travail (ANSES) ,  Grünenthal France Laboratory , the  Région Champagne-Ardenne , the  Communauté de Communes de l'Argonne Ardennaise  and the  Zoo d'Amnéville (Moselle, France). We have no indication that there may be a conflict of interest.
To measure T. gondii tachyzoite position relative to the host cell, we adapted the assay previously described  27. HeLa cells were plated on poly-lysine-coated glass coverslips in a 6-well plate, transfected with 1 mg of plasmid-encoding mCherry in the pDisplay Vector (Invitrogen) and used 20 h later for a 5-min invasion assay. Cells were fixed in PBS-4% PFA (20 min, room temperature) and stained with anti-SAG-1 antibodies followed by Alexa-Fluor anti-mouse antibodies to label extracellular parasites. Samples were scanned on the confocal Nikon Ti Eclipse microscope and images were captured and analysed with Metamorph software (using the 4D viewer application). For each zoite, an ellipsoid was fit to measure the longitudinal axis, whereas the cell surface contacting the tachyzoite centres of mass was affected to all the isosurfaces.
After incubating for 6 days, the HFF monolayer was washed in PBS and fixed in ice-cold methanol for 20 min. Afterwards, the HFF cells were stained with Giemsa. The area of ten plaques was assessed using Image J 1. 34r software. T. gondii egress assay. 4 Â 10 5 parasites were grown in HFF monolayers on coverslips for 36 h. Media were exchanged for pre-warmed, serum-free DMEM supplemented with calcium ionophore 2 mM (A23187 in DMSO)  56. After incubation for 5 min at normal growth conditions (37 °C; 5% CO 2 ), cells were fixed and stained with anti-GAP45 primary antibody and Alexa-Fluor secondary antibody. Two hundred vacuoles were scored in each experiment. T. gondii motility assay. Freshly egressed tachyzoites were allowed to glide for 30 min on glass coverslips coated with 50 mg ml À 1 heparin in PBS.