dataesr/scientific-paragraphs-categorization huggingface dataset:
Our tools are currently used in HSCT: first, for unrelated donors search using HLA-Upgrade to update an old typing in a donor database, and second, for haplo-identical transplantation using HLA-2-Haplo to predict haplotypes. Our tools have also been used in biomedical research: using HLA-Upgrade, we have updated 2 large solidorgan transplantation cohorts from low-resolution to high-resolution genotypes, hence empowering us to now carry out allele, haplotype and immunogenetic data (HLA-2-Haplo additional functionalities) associations with graft survival. In conclusion, Easy-HLA (freely available online at: https://hla. univnantes. fr) facilitates large-scale analyses and promotes the multi-faceted HLA expertise beyond allelic associations. Our tool perfectly illustrates how computational and statistical modelling can relay and upgrade highvalue experimental data to better enlighten clinical practice and sustain research.
1A )  (34, 35). The activation loop in the catalytic domain is particularly short in CstK, and the DFG motif is substituted by a GLG motif. Interestingly, the transmembrane domain usually presents in classical prokaryotic STPKs is lacking in CstK, thus it is a so-called cytoplasmic STPK. CstK is a Dot/Icm effector protein. Bioinformatics analysis using the prediction software S4TE2  (36)  indicated that CstK harbors features corresponding to secreted effector proteins, including a promoter motif typically found in effector proteins from intra-vacuolar bacterial pathogens and a putative C-terminal E-block domain  (37) , suggesting that CstK is indeed a Coxiella effector protein (Fig. 1A ). Consistently, previous studies by Chen and colleagues have shown that CstK is secreted in a T4SS-dependent manner by the surrogate host L.
TBC1D5 is recruited at TBC1D5 is not phosphorylated in vitro by recombinant CstK. Next, we assessed whether CstK might phosphorylate the recombinant Hs-TBC1D5. Despite the in silico prediction of several Ser/Thr and Tyr phosphorylatable residues in Hs-TBC1D5, we failed to detect Hs-TBC1D5 phosphorylation using several in vitro kinases assays (data not shown). In addition, Hs-TBC1D5 phosphorylation status was also investigated upon transfection with CstK or its inactive derivative (K55M) followed by Hs-TBC1D5 immunoprecipitation. No phosphorylation could be detected in our conditions, though a sensitivity issue regarding the detection cannot be ruled out.
Mass spectrometry analysis. For mass spectrometry analysis, CstK was phosphorylated as described above, excepted that [γ-33 P]ATP was replaced with 5 mM cold ATP. Subsequent mass spectrometry analyses were performed as previously reported  (31) (32) (33) (34). Spectra were analyzed with the paragon algorithm from the ProteinPilot® 2. 0 database-searching software (Applied Biosystems) using the phosphorylation emphasis criterion against a homemade database that included the sequence of CstK.
ImageJ, ICY, and CellProfiler software were used for image analysis and quantifications. Phenotypic profiles (expressed as z-scores) were calculated following median based normalization of 96-well plates. Plates effects were corrected by the median value across wells that are annotated as control. Beta-lactamase translocation assay. Effector proteins translocation assays were performed as previously described  (38). Briefly, Coxiella burnetii Tn1832 (wt) and dotA::Tn were transformed either with pXDC-Blam (negative control), pXDC-Blam-CvpB (positive control) or pXDC-Blam-CstK. Each strain was used to infect U2OS epithelial cells. After 24, 48 or 72 hours of infection, cells were loaded with the fluorescent substrate CCF4/AM (LiveBLAzer-FRET B/G loading kit; Invitrogen) in HBSS (20 mM HEPES pH 7.
3) containing 15 mM probenecid (Sigma). Cells were incubated in the dark for 1 h at room temperature and imaged using an EVOS inverted fluorescence microscope. Images were acquired using DAPI and GFP filter cubes. The image analysis software CellProfiler was used to segment and identify all cells in the sample (GFP), positive cells (DAPI) and to calculate the intensity of fluorescence in each channel. The percentage of positive cells versus the total number of infected cells was then calculated and used to evaluate effector translocation.
ACKNOWLEDGMENTS The wish to thank the Montpellier RIO imaging facility at the  University of Montpellier 2. This work was supported by grants from the  ATIP/AVENIR Program  for V. M. and M. B. , the  Region Languedoc-Roussillon  for S. B. , a  Marie Curie CIG  to E. M. (grant n. 293731), the  Agence Nationale de la Recherche (ANR)  Grant  ANR-14-CE14-0012-01  (project  AttaQ ) to M. B.
05) (Figure  3C ). Conversely, a significant improvement of median survival was measured for U87-shST8SIA3-bearing mice of 72 days (range 69-75) compared to 42. 5 days in U87-MG-ones (p < 0. 05), and as expected, median survival was higher when compared to U87-ST8SIA3 mice (32 days, p = 0. 02). It is worth noting that in the U87-shST8SIA3 group, only two out of eight mice developed a tumor. The data unambiguously demonstrate that in vivo, the A2B5 expression level negatively correlates with overall survival. Histologically, tumors did not differ between the three groups of mice (Figure  3D ). They were dense and mostly circumscribed. However, a clear difference was revealed by cleaved caspase 3 immunohistochemistry. The U87-shST8SIA3 tumors showed significant higher staining as compared to U87-MG or U87-ST8SIA3 tumors (Figure  3D ).
Flow Cytometry Flow cytometry was performed using FACS Calibur (BD Biosciences) on dissociated cells to quantify the number of cells expressing A2B5 (APC (Allophycocyanin)-labelled IgM, clone 105, Miltenyi Biotec, Bergisch Gladbach, Germany) using a previously described standard procedure  [14, 21]. Data were analyzed using FlowJo software (Tree Star, Inc. , Ashland, OR, USA).
Images of the explants were captured every 10 min for periods of 72 h using a 5× objective in order to obtain a quantitative analysis of the cell migration. Quantifications of the area core and the total area of explants were performed using ImageJ software (National Institutes of Health). Quantifications are represented by the (total area)/(core area) ratio and data were standardized using the H0 ratio. Data from three distinct GBM samples are presented and expressed as mean ± SEM.
Statistical Analyses The non-parametric Wilcoxon-Mann-Whitney test was conducted using XLSTAT 2013 software (Addinsoft, Paris, France) to analyze cell migration and proliferation rates, flow cytometry, DNA fragmentation, and clonogenicity. Overall survival curves of intracranial xenografted mice were obtained according to the Kaplan-Meier method and compared using the Log-rank test using GraphPad Prism4 software (GraphPad, Inc. , San Diego, CA, USA). All statistical tests were two-sided, and the threshold for statistical significance was p < 0. 05. Significances are denoted as follows: *** p < 0. 001, ** p < 0. 01, * p < 0. 05.
Acknowledgments: We would like to thank  Mylène Cayol  for mice handling,  Philippe Morando  and  Jessica Cappai  for tissue samples sections. Sylvie Mathieu  and  Assou El Battari  are acknowledged for their expertise in lentiviral infection and  Geneviève Rougon  for carefully reading the manuscript. We also thank the  Canceropôle PACA.
Acknowledgments We thank  Natacha Bessis  and  Jérôme Biton  ( University of Paris 13, Inserm UMR 1125, Bobigny, France ) for critical reading of the manuscript and statistical support,  Mylène Petit  and  Nathalie Saidenberg  ( Avicenne Hospital, Rheumatology Department, Bobigny, France ) for patient recruitment and organizing collection of clinical data,  Magali Breckler ,  Delphine Lemeiter  and  Katarzyna Matyja  ( University of Paris 13, Inserm UMR 1125, Bobigny, France ) as well as  Dennis Lindau  ( Radboud University, Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands ) for technical support, and  Nathalie Bendriss-Vermare (Cancer Research Center Lyon, UMR Inserm   1052 CNRS 5286 ,  Centre Leon Berard, Lyon, France ) for providing LL-37 ELISA.
(C) Compstatin, and APL-2 are inhibitors of activation of C3. The crystal structure of C3c (PDB ID: 2QKI) (147), a major proteolytic fragment of C3, is shown in complex with compstatin (yellow stick model). Both inhibitors bind to a site (shaded in blue) formed by the macroglobulin domains 4 and 5 (MG4, MG5). All illustrations were prepared with PyMOL (148).
The C5a/C5aR model is based on PDB ID: 6C1R (146). (C) Compstatin, and APL-2 are inhibitors of activation of C3. The crystal structure of C3c (PDB ID: 2QKI) (147), a major proteolytic fragment of C3, is shown in complex with compstatin (yellow stick model). Both inhibitors bind to a site (shaded in blue) formed by the macroglobulin domains 4 and 5 (MG4, MG5). All illustrations were prepared with PyMOL (148).
The purification of PCR products was performed using NucleoFast 96 PCR plates (Macherey-Nagel EURL, Hoerdt, France) according to the manufacturer's instructions. The amplicons were sequenced using the Big Dye Terminator Cycle Sequencing Kit (Perkin Elmer Applied Biosystems, Foster City, CA) with an ABI automated sequencer (Applied Biosystems). The electrophoregrams obtained were assembled and edited using the ChromasPro software (ChromasPro 1. 7, Technelysium Pty Ltd. , Tewantin, Australia).
Data analysis Unique haplotypes were defined by using DnaSPv5. 10 to obtain head lice cytb sequences, then, compared and combined (Additional file 1: Table  S1 ), with the cytb haplotypes previously reported  [12]. In order to investigate the possible relationships between the haplotypes, the median-joining (MJ) network using the method of Bandelt was constructed with the program NETWORK4. 6 (http://www. fluxu s-engin eerin g. com/share net. htm) using equal weights for all mutations  [31]. Phylogenetic analyses and tree reconstruction were performed using MEGA software v. 6. 06  [32]. Phylogenetic analysis was performed using maximum likelihood (ML) approach. To generate the best ML tree, Modeltest v. 3. 7  [33]  was used to examine model of nucleotide substitution and choose a best-fit model of sequence evolution.
The model that provides the best approximation of the data using the fewest parameters was chosen for the analysis according to the Akaike information criterion  [34, 35]. Tree reconstruction was conducted using MEGA software v. 6. 06 under HKY+I+G model with 500 bootstrap replicates. All obtained sequences of Acinetobacter spp. were analyzed using BLAST (www. ncbi. nlm. nih. gov/blast /Blast. cgi) and compared with sequences in the GenBank database. A maximum-likelihood method was used to infer the phylogenetic analyses and the best-fit model was chosen as described for cytb sequences above. The tree reconstruction was performed using the TrN+ G model for nucleotide sequences under 500 bootstrap replicates in MEGA software v. 6. 06  [32].
The most closely-related species is A. guillouiae (GenBank: FJ754439) with 94. 9% similarity (337 of 355 base positions in common). The remaining five of 33 sequences (15. 1%) presented also some similarities with Acinetobacter. However, the sequences were of poor quality, which is assumed to be due to co-infection with several Acinetobacter species. The distribution of Acinetobacter species according to lice clades are presented in Table  4. The phylogenetic positions of all Acinetobacter species identified in this study are presented in Fig. 3. The partial rpoB sequences obtained in this study were deposited in the GenBank database under the accession numbers: MH230910-MH230920.
Acknowledgements We thank medical staff involved in this study and patients who agreed to participate. This study was supported by the  Institut Hospitalo-Universitaire (IHU) Méditerranée Infection , the  National Research Agency  under the program « Investissements d'avenir », reference  ANR-10-IAHU-03 , the  Région Provence Alpes Côte d' Azur and European funding FEDER PRIMI.
5 EGTA  (pH 7. 3, 290 mOsm). Recordings were performed in the presence of the following glutamatergic receptors blockers: 10 mM 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium salt (NBQX; Hellobio) and 50 mM D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5; Hellobio). IPSCs recorded in layer 4 PC were optogenetically evoked at 0 mV by driving the ChR2 activity in PV interneurons with 470 nm blue light (0. 9 mW/mm 2 ) delivered by a LED (Cairn Research, OptoLED) through the 40X water-immersion objective (Olympus). We used a 100 mm diameter light field (i. e. about the size of one barrel) and light stimulations of 5 ms were delivered at 0. 05 Hz. In pilot experiments, the light intensity was adjusted to 1. 5 times the threshold for eliciting one action potential in FS cells and we verified that this threshold did not differ among the different experimental groups (data not shown).
Electrophysiological data acquisition and analysis Whole-cell patch-clamp recordings were obtained using either Axopatch 200B or 700B amplifiers (Molecular Devices). Currents and potentials were low-pass filtered at 5 kHz or 6 kHz, collected at a 10 kHz frequency, and analyzed offline using pClamp 10. 7 (Molecular Devices) for voltage-clamp recordings, or using a custom written procedure in IGOR Pro 6. 0 (Wavemetrics) for current-clamp recordings. For all recordings performed with K-gluconate or Cs-gluconate in the pipette, potentials were corrected for a junction potential of À10 mV. Series resistances (Rs) were not compensated but continuously monitored using 5 or 10 mV hyperpolarizing pulses. Recordings were discarded if Rs increased by > 20% during the whole experiment. For all experiments, the amplitude of EPSCs and IPSCs were quantified from the average of 15-30 consecutives responses.
For paired-recording analysis, the peak responses to each stimulation were measured and then averaged over all trials. The paired-pulse ratio was calculated as the average peak amplitude of the second response divided by that of the first one. In current clamp experiments aiming at characterizing basic membrane properties, a series of hyperpolarizing and depolarizing current steps were applied for 1 s in 25-50 pA increments at 5 s intervals. Pairs obtained with presynaptic cells displaying low firing rate or adaptation ratio (< 0. 6) or small AHP (< 10 mV) were discarded. Voltage-sensitive dye data acquisition and analysis Using a CMOS-based camera (MiCam Ultima, SciMedia), sequences of images of 1 s were acquired at 500 Hz, with or without (blank trials) whisker stimulation, alternately, every 20 s.
Variations of the light intensity were initially recorded as variations over the resting light intensity (first acquired frame). Acquisition and data preprocessing were done using in-house software (Elphy, G. Sadoc, UNIC-CNRS), further analyses were made using custom written routines in IgorPro (WaveMetrics, USA). Subtraction of a pixel by pixel bestfit double-exponential from the averaged unstimulated sequence was used to correct for photobleaching. For each averaged whisker evoked response (n = 20 trials), a 2D-Gaussian fit of the evoked signal at 12 ms following the start of the whisker stimulus was used to localize the center of a first region of interest (ROI) defined as a 100 mm-diameter circle. A second, more distal ROI, was defined as a 50 mm-wide ring placed at 575 mm from the center of the first ROI.
Statistical Analysis All data are presented as mean ± SEM. Non-parametric two-sided Mann-Whitney U-tests were used to compare two distributions. If the normality test was statistically significant, two-sided Student's t tests were used to compare two distributions. Two-way ANOVA with Sidak post hoc test were used to compare groups of data. All graphs and statistical analyses were generated using GraphPad Prism software. *p < 0. 05, **p < 0. 01, ***p < 0. 001.
ACKNOWLEDGMENTS We are grateful to members of the  Garel and Audinat labs  for discussions and critical comments on the manuscript. We thank the  IBENS Imaging Facility (France BioImaging , supported by  ANR-10-INBS-04 ,  ANR-10-LABX-54  MEMO  LIFE , and  ANR-11-IDEX-000-02 PSL Research University , ''Investments for the future''). We are grateful to  C. Auger ,  A. Delecourt ,  E. Touzalin ,  D. Valera ,  C. Le Moal ,  A. David , and  M. Omnes , for excellent technical assistance. This work was supported by grants from  INSERM ,  CNRS , the  ERC Consolidator Grant NImO   616080  to S. G. , and by grants from  INSERM , the  Fondation pour la Recherche Medicale  (FRM:  DEQ20140329488 ),  European Commission  ( H2020-MSCA-722053   EU-GliaPhD)  to E. A. C. -A. M. was supported by the  Region Île-de-France  ( DIM Cerveau et Pensee ) and by the  FRM  ( FDT20170739030 ).
PCR entailed the use of Phire Green Hot Start II PCR Master Mix (Thermo Scientific) in a 20 lL reaction volume containing 500 nM of each primer. Thermal cycling entailed 98 °C for 5 min followed by 45 cycles of 98 °C for 5 s, 68 °C for 5 s, and 72 °C for 30 s, followed by a final elongation at 72 °C for 1 min. PCR products were analysed using agarose gel electrophoresis and results were documented. A PCR product of approximately 567 bp indicated the presence of the B. rossi rDNA target region in the sample. Positive, negative, no template, as well as internal amplification controls were included in each run. The PCR setup and conditions used in this study resulted in a minimum detection sensitivity of !5 target copies per PCR, and no cross-reaction with B. canis and B. vogeli DNA could be detected (data not shown).
In all suspected cases, stained blood smears were positive for intra-erythrocytic forms of Babesia rossi. The PCR exam on blood provided the exact same results, and all infected dogs became seropositive within three weeks after tick challenge. The acaricidal treatment assessed in this experiment was an oral formulation, meaning that ticks need to attach and start to feed before being killed. No data were available in regards to the efficacy of afoxolaner against Haemaphysalis elliptica, but only Dermacentor reticulatus  [3, 7]. This study demonstrated 100% acaricidal efficacy of NexGard Ò against Haemaphysalis elliptica within 48 h (thumb counts) for 28 days. The sustained efficacy made it possible to prevent transmission of Babesia rossi in all treated dogs after two infective challenges, on Days 2 and 28, respectively.
The control group (i. e. , PBS injected) (E0) was sampled prior to onset of the study. The VHSV used for vaccination (i. m. injection, 10 4 pfu/fish) and boost (i. m. injection, 10 6 pfu/fish) was the attenuated 25-111 variant of strain 07-71  (28). The IPNV virus, IPNV-TA (rNVI-015), a clone derived from the Norwegian Sp strain NVI015 (Genbank accession No. AY379740) was used for immunization. It is highly virulent and immunogenic to Atlantic salmon  (29, 30). IPNV-TA is named after its VP2-capsid amino acid residues T 217 and A 221 , a virulence marker in Atlantic salmon, while this strain is not pathogenic to rainbow trout (O. E. , own observations). Fish immunized with IPNV-TA received an intraperitoneal injection of 1 × 10 4 PFU/fish (Figure  1 ). Trout were sacrificed by overexposure to 2-phenoxyethanol diluted 1/1000.
Fingerprints of IPNV Vaccination in Selected VH/C Repertoires The prime goal in this study was to find out whether a secondary immunization with IPNV (heterologous) administered post primary VHSV vaccination would modify the response to the primary antigen. Therefore, we first characterized the repertoire post IPNV immunization (group E7) and focused on the VH/C combinations characterized earlier in VHSV immunized fish: VH4/Cµ, VH5/Cµ, VH8/Cµ for IgM and VH4/Cτ and VH5/Cτ for IgT were included. IgH repertoires in IPNV-immunized fish (E7) were compared to control (E0). Random subsampling of 7000 MIDs per individual fish datasets obtained for each VH/C combination without replacement was done, allowing quantitative comparisons despite variations of the total MID count per group. We focused on the most expressed clonotypes of each fish and for each VH/C ("Top 50" clonotypes), checking their sharing by different individuals within the control group (E0) and in IPNV-immunized fish (group E7) as in Magadan et al.
ACKNOWLEDGMENTS We acknowledge  Louis Du Pasquier ,  John Hansen ,  Rosario Castro  and  Pierre-André Cazenave  for helpful discussions, and the  INRA  fish facilities (IERP). This work has benefited from the facilities and expertise of the IMAGIF platform at I2BC. We are grateful to the  GENOTOUL bioinformatics platform Toulouse Midi-Pyrenees (Bioinfo GENOTOUL)  for providing help, computing, and storage resources.
FUNDING This work was supported by the  Institut National de la Recherche Agronomique , by the  European Commission  under the Work Program 2012 of the 7th  Framework Program for Research and Technological Development of the European Union  (Grant Agreement 311993 TARGETFISH), and by the  ANR-16-CE20-0002-01  (FishRNAVax). SN has been supported by a  NMBU PhD program  and from the  Research Council of Norway (RCN)  projects no. 237315  and ØE received part funding from  RCN  project no. 239140.
Within-and between-day accuracy (bias) and precision Within-and between-day accuracy (bias) and precision were examined by performing replicate analyses (n = 6) for all IQC standards. Between-day accuracy and precision were assessed with the same IQCs by repeated injection (n = 6) over six days. The data were analyzed by several analysts and calculated as the percentage deviation of the average calculated concentration from the nominal concentration. Precision was expressed as the coefficient of variation (CV). The acceptance limits were < 15% for precision and within ± 15% of the nominal value for accuracy, except for the lowest concentration of the IQC, for which < 20% for precision and within ± 20% of the nominal value for accuracy were accepted.
Study design This was a monocentric retrospective study. Plasma samples (n = 90) from CD patients (n = 71), followed from October 2016 to May 2018 for routine care in the Division of Hepatology and Gastroenterology at the Grenoble-Alpes University Hospital, were included (Supplemental Figure  1 ). Blood samples were collected at outpatient care just before ADM administration. Demographic, clinical, and biological data were collected from electronic medical records. Demographic data included age, sex, weight, and height. Clinical data included disease localization, date of diagnosis, CDrelated surgery, date of treatment initiation, co-medication, last administered doses of ADM, and time since the last dose. Biological data included the number of ADM Cmin measurements per patient, plasma C-reactive protein (CRP) level, ferritin and albumin concentrations, fecal calprotectin levels, and the presence of anti-drug antibodies (ADA).
IF labeling of ex vivo cysts Five percent of the brain homogenate was stained with rhodamine-conjugated DBA lectin, fixed in 4% PFA for 10 min at room temperature (RT) and permeabilized in PBS -0. 2% Triton™ X100 (Sigma-Aldrich). Samples were then incubated with a custom-made rabbit anti-SIINFEKL (1/300, Biotem) or anti-OVA (1/500, Sigma) and a mouse anti-GRA2 (1/3000, Biotem) diluted in PBS BSA 3 % (Dutscher), followed by incubation with AF555-coupled anti-rabbit Immunoglobulin G (IgG) or AF488-coupled anti-rabbit (1/500) and AF647-coupled anti-mouse IgG (1/500, Life Technologies, Thermo Fisher) diluted in PBS-BSA 3 %. Samples were mounted using ProLong TM Diamond Anti-Fade containing DAPI (Life Technologies, Thermo Fisher scientific) and imaged using a Zeiss LSM710 confocal microscope. Quantifications of the GRA6-OVA signal were performed using ImageJ software (NIH).