dataesr/scientific-paragraphs-categorization huggingface dataset:
The 50-level vertical discretization retained for this system has 1 m resolution at the surface decreasing to 450 m at the bottom, and 22 levels within the upper 100 m. The bathymetry used in the system is a combination of interpolated ETOPO1 (Earth TOPOgraphy 1 arcmin) and GEBCO8 (GEneral Bathymetric Chart of the Oceans, version 8) databases. The system was initialized on 11 October 2006 based on the temperature and salinity profiles from the EN4 monthly gridded climatology. The atmospheric fields forcing the ocean model are taken from the ECMWF (European Centre for Medium-Range Weather Forecasts) Integrated Forecast System. A 3 h sampling is used to reproduce the diurnal cycle. The system does not include tides nor pressure forcing. The monthly runoff climatology is built with data on coastal runoffs and 100 major rivers from the  Dai et al.
(2009)  database  (Lellouche et al. , 2018). Altimeter data, in situ temperature and salinity vertical profiles, and satellite sea surface temperature data are jointly assimilated to estimate the initial conditions for numerical ocean forecasting. Moreover, satellite sea ice concentration data are now assimilated in the system in a mono-variate or mono-data mode. More information can be found in  Lellouche et al. (2018).
Partial bottom cell representation of the bathymetry (a composite of ETOPO2 and GEBCO8) allows an accurate representation of the steep slopes characteristic of the area. The model grid is a subset of the Global 1/12 • ORCA tripolar grid used by the parent system (the CMEMS GLOBAL system) that provides initial and lateral boundary conditions (west -the Atlantic Ocean, east -the Western Mediterranean Sea), but refined at 1/36 • horizontal resolution. The IBI run is forced every 3 h with up-to-date highfrequency (1/8 • horizontal grid resolution) meteorological forecasts (10 m wind, surface pressure, 2 m temperature, rel- Hydro" datasets. Further details can be found in  Sotillo et al. (2015). Originally, the operational IBI system was based on a periodic reinitialization from the GLOBAL parent solution.
Afterwards, IBI has steadily evolved: by April 2016, an upgrade of the downscaling methodology was implemented, substituting the periodic reinitialization by a spectral nudging technique in order to avoid temporal discontinuity inherent to the periodic reinitialization and to minimize dependency from the GLOBAL parent solution on the shelf. The spectral nudging aims at forcing the regional child model solution (IBI) to be close to the parent system (GLOBAL) in those areas where the latter is supposed to be accurate thanks to data assimilation, mainly in deep waters outside the continental shelf  (Herbert et al. , 2014). After each forecast cycle of IBI, the increment between the parent model analysis X p and the child model forecast X c is calculated for a chosen state variable X (typically currents, temperature, and salinity).
Such an increment consists of a space and time low-pass filter of the differences X p -X c in order to keep the characteristic scales so the parent GLOBAL system can properly resolve (from large scale to mesoscale). After each forecast cycle of the child IBI system, a new cycle (called analysis) is relaunched where X c is nudged to X p at each time step by the weekly mean of the daily increments previously computed in the parent system grid during the forecast cycle. The 1-week time smoothing window was imposed as this is the typical timescale associated with mesoscale structures. Furthermore, the nudging is spatially limited in those areas where the parent system can not improve the regional model (e. g. where there is no data assimilation of altimetry or where the physics is missing, for instance on the shelf) or where the spatial filtering processes are potentially detrimental (close to the bottom or the open boundaries).
In the vertical dimension, SAMPA has 46 unevenly spaced z levels with maximum resolution of 5 m near the surface, exponentially decaying towards the seafloor. The shallower level is at 2. 5 m depth. The bathymetry is derived from a combination of the GEBCO bathymetry dataset and fine-resolution bathymetric charts of the Strait of Gibraltar and the continental shelf of the Gulf of Cádiz and northern coast of the Alboran Sea. The bottom topography is represented as partial vertical cells. In the two lateral open boundaries (west -the Atlantic Ocean, east -the Western Mediterranean Sea) the model is partially forced by daily mean temperature, salinity, and velocity fields from CMEMS IBI regional model  (Sotillo et al. , 2015). Since such frequency is not suitable to resolve barotropic flows through the strait either  (García-Lafuente et al.
eu/, last access: 1 July 2019). Complementarily, opportunistic inter-comparisons are conducted in the frame of diverse EU-funded projects such as MEDESS-4MS  (Sotillo et al. , 2016a) : 35 satellite-tracked drifters were released on both sides of the Strait of Gibraltar and the quality-controlled in situ data of sea surface temperature and currents were collected to build the MEDESS-GIB database  (Sotillo et al. , 2016b) , hence providing a complete Lagrangian view of the surface inflow of Atlantic waters through the GIBST and the Alboran Sea. Such valuable oceanographic information was subsequently used to compare IBI and SAMPA forecast products to identify strengths (realistic simulation of the Atlantic Jet and the Algerian Current) and shortcomings (position and intensity of the Alboran gyres, especially the western one) in both model performances.
Recent work relying on this HFR system has successfully investigated the water exchange between Algeciras Bay and the Strait of Gibraltar  (Chioua et al. , 2017) , the impact of the atmospheric pressure fluctuations on the mesoscale water dynamics of the Strait of Gibraltar and the Alboran Sea  (Dastis et al. , 2018) , the dominant modes of spatio-temporal variability in the surface circulation  (Soto-Navarro et al. , 2016) , or the characterization of the Atlantic surface inflow into the Mediterranean Sea  (Lorente et al. , 2018). In the present work, quality-controlled hourly HFR current measurements collected during the entire 2017 were used as benchmark to elucidate the skill of a number of OOFSs. The data availability was significantly high: almost 100 % in the selected transect (solid black longitudinal line shown in Fig.
Temperature The CMEMS L3 satellite-derived daily data were used to validate the SST fields predicted by both GLOBAL and IBI systems. The map of annual availability of this remote-sensing product for 2017 (Fig. 2a ) reveals that the highest percentages of available observations (above 80 %) were found in the south of Canary Islands, the Gulf of Cádiz, and in the Western Mediterranean Sea. Equally, there was also a significant data provision in the west coast of the Iberian Peninsula and Morocco, although it decreased to 70 % in nearshore areas over the shelf such as the Iberian and African upwelling or the Strait of Gibraltar. By contrast, the lowest data availability (below 40 %) was detected in the northernmost latitudes, including the Irish and North seas. Maps of annual mean absolute differences (MADs) were firstly computed in open water where the spectral nudging technique was applied (Fig.
At this point it is worth recalling that GLOBAL includes a data assimilation scheme, whereas IBI takes realistic ocean conditions from weekly global analyses. This fact shows up the possible benefits of the observational data assimilation in these areas, at least in terms of surface variables. Furthermore, a fraction of observed model-buoy discrepancies in SST can be explained in terms of disparate depth scales. Whereas IBI and GLOBAL daily outputs are representative of the temperature in the upper 1 m of the water column, moored buoys provide temperature estimations at a deeper nominal depth (between 1 and 3. 5 m, depending on the brand). Future validation exercises should include the interpolation of model outputs to both the exact buoy location and also to the specific depth level in order to more accurately assess the model skilfulness.
Salinity As pointed out in the introduction, the enhancement of riverine forcing is still a priority in ocean modelling as the estuarine circulation is mainly driven by horizontal density gradients which are ultimately modulated by freshwater inputs. In this context, previous work has investigated the potential benefits of replacing old climatologies by data from hydrological model predictions  (O'Dea et al. , 2017). Here we provide a specific example to illustrate the discrepancies between GLOBAL and IBI performances in the Galician coast (NW Spain), as a consequence of the different horizontal resolution and distinct runoff forcing implemented in the operational chain. While both model performances are rather similar in open water (according to the results derived from the validation against 3-D Argo-float profiles and exposed in the QUID), higher discrepancies are expected to arise in coastal and shelf areas as they are governed by small-scale processes such as land-sea breezes, runoff (and the resulting stratification and buoyancy-driven circulation), and transport materials (nutrients, sediments, pollutants, etc.
). As shown in Fig. 6a , hourly in situ SSS data collected by B4 buoy during March 2018 experienced an abrupt decrease from a standard value around 36 PSU down to almost 33 PSU in just a few hours during 20 March, likely due to a noticeable filament of freshwater discharged by Miño River. IBI outputs at the closest grid point appeared to properly capture both the sharp drop in SSS values and the persistent low salinity values for the next 4 d period. By the end of the month, the modelled salinity field seemed to steadily recover to usual levels in the range of 35. 5-35. 8 PSU, whereas in situ observations revealed a steeper rise to 34. 8 PSU by 23 March. Nevertheless, the skill metrics confirmed the rather accurate IBI performance, with a correlation coefficient of 0. 92 and a RMSD of 0. 33 PSU.
, 2016). Since the atmospheric pressure forcing is missing in the GLOBAL sea level outputs, this system only considers the barotropic response to wind forcing. In the case of IBI system, both atmospheric forcings are taken into account but the inverted barometer approximation is solely imposed over the Western Mediterranean Sea (not over the entire basin). Therefore, only a portion of the subtidal variability in the flow through the Strait of Gibraltar can be adequately explained  (García-Lafuente et al. , 2002b). Additional statistical indicators were computed: two histograms illustrated the number of hourly zonal (U ) and meridional (V ) velocity data per class interval (Fig. 9a  and b ). HFR-derived zonal velocity estimations exhibited a Gaussian-like shape clustered around 84 cm s -1 and slightly shifted to lower values in the case of SAMPA coastal model (79 cm s -1 ).
Both datasets show similar positive skew and variability, with the standard deviation around 56-57 cm s -1 for 2017 (Fig. 9a ). IBI and GLOBAL presented narrowed histograms, with distributions positively shifted and constrained to zonal velocities above 0 and 40 cm s -1 , respectively. In the case of meridional currents, each distribution exhibits a nearly symmetrical Gaussian-like shape but shifted towards different values (Fig. 9b ). Whilst SAMPA and IBI exhibited a similar distribution (and moderately similar to that revealed for HFR estimations), GLOBAL histogram emerged again dramatically shortened and restricted only to positive values, revealing a recurrent predominance of the AJ to flow northeastwards. Based on the QQ plot for the zonal velocity component (Fig. 9c ), it can be concluded that SAMPA estimations were consistent despite the slight overestimation observed for the highest velocities (95th-100th percentiles).
Finally, refined mixing schemes might also produce notable improvement in the representation of water masses, re-sulting in a substantial reduction of temperature and salinity bias relative to model solution. Data availability. The CMEMS IBI and GLOBAL modelling products are publicly available on the CMEMS web portal (http: //marine. copernicus. eu/, last access: 1 July 2019). Equally, in situ and satellite-derived observations used in this work are also freely accessible on the CMEMS web portal. SAMPA coastal model outputs and HFR-derived surface current data can be downloaded from Puertos del Estado's public catalogue (http://opendap. puertos. es/ thredds/catalog. html, last access: 1 July 2019). Author contributions. PL, MGS, and EAJ contributed scientific expertise and text drafting. AAB, RA, AdPC, and CT contributed technical support and expertise in IBI forecast system.
The role of ANA in the diagnostic work-up of idiopathic inflammatory myopathies Detection of anti-nuclear antibodies (ANA), as detected by an indirect immunofluorescence assay (IIFA) on HEp-2 cells, is considered the most optimal screening assay for autoantibodies in the SARD  [61]. Whether this also holds for the IIM is more than questionable for several reasons. First, in the international recommendations on ANA testing, as issued by a combined effort of the International Union of Immunological Societies (IUIS) and the EASI, it is recognized that the ANA IIFA is not sufficiently sensitive for the spectrum of MSA, in particular for the anti-ARS autoantibodies  [62]. This has recently been confirmed in a large dataset obtained in a routine setting  [63]. Second, there is no consensus on whether autoantibodies to cytoplasmic components of the HEp-2 cells are to be considered as ANA positive  [64].
More comparative data between assays are needed  [78]. A screening ELISA (MESACUP anti-ARS test, MBL, Nagoya, Japan) has been developed for the detection of anti-ARS autoantibodies. In addition to Jo-1, also PL-7, PL-12, EJ, and KS are included as autoantigen. This assay is not to be considered a multispecific immunoassay because the antigen-specificity is not unequivocally determined. This ELISA kit has a good sensitivity and specificity when compared to IP. Besides, the assay has also been validated both in patients with IIM as well as in patients with ILD  [79]. Commercial ELISAs are also available for anti-TIF-1γ, anti-Mi-2 and anti-MDA-5 for DM, with almost 100% sensitivity and specificity when compared to IP  [80, 81]. Anti-Mi-2 can also be detected by FEIA, but no comparative data to IP is available.
Cells were incubated at 37 °C for 2 h in the presence of pHrodo ® Red E. coli BioParticles ® (Thermofisher) at a ratio of 100 µg/10 6 cells. Negative control samples were incubated on ice. Cells were analyzed using the BD LSR Fortessa flow cytometer. Dead cells were identified and excluded based upon DAPI uptake. Flow cytometry. Cells were analyzed by flow cytometry using standard procedures. Inhibition of non-specific binding was achieved by incubating the cells for 30 min on ice in purified anti-CD16/32 (1 µg/mL, BioLegend, 101302) or hybridoma 2. 4G2 supernatant. All antibodies are listed in Supplementary Table  2. Where indicated, cells were fixed and permeabilized prior to staining using the Leucoperm TM kit (BioRad). Blood was processed using the Uti-Lyse reagent (Agilent). Data analysis was performed in FlowJo ® v10.
A 0. 5 mm aluminum filter and two frame averaging were used to optimize the scan. After scanning, the data was reconstructed using Skyscan software NRecon v1. 6. 9 (Bruker). The reconstruction thresholding window was optimized to encapsulate the target image, with the same values used for all bones. Reconstructed bones were oriented around their vertical axis using DataViewer v1. 5. 2. 4 (Bruker). The trabecular region of bone 200 µm thick starting 100 µm proximal to the primary spongiosa was identified, and volumetric analysis to determine the microarchitecture of this region was performed using CTAn v1. 16. 4. Histology and immunohistochemistry. Tissues were fixed in 10% neutral buffered formalin and processed into paraffin using standard procedures. For examination of tissue architecture, sections were stained with hematoxylin and eosin (H&E) or Luxol fast blue.
Samples were washed five times for 1 h at RT in TBS containing 0. 02% Tween 20 (Fisher Scientific) (TBST) followed by incubation overnight at RT with anti-goat and anti-rat Alexa Fluour secondary antibodies (Life Technologies) diluted 1:500 in PB. After washing four times for 1 h in TBST, epidermal sheets were counterstained with DAPI (Sigma) and mounted in Prolong Gold (Life Technologies). Frozen sections of 4% PFA perfused adult brains were processed and stained with rabbit anti-IBA1 (1:500, Wako, 019-19741), rabbit anti-P2RY12 (Sigma, 1:125, HPA013796), and Alexa Fluor ® conjugated secondary antibodies using standard procedures. Dura mater were removed into ice-cold PBS, fixed for 1 h in 4% PFA, treated for 30 min at 37 °C in PBS containing 20 mM EDTA and then blocked in 3% BSA, 0. 3% Triton X100 in PBS for 30 min.
Whole mount staining steps were performed in blocking buffer containing rabbit anti-IBA1 overnight (1:1000, Wako, 019-19741), goat anti-rabbit Alexa Fluor ® 594 1 h (1:400, Life Technologies, A-11012), Alexa Fluor ® 647 anti-mouse CD169 1 h (Clone Siglec-1, 1:200, BioLegend, 142408), with washes in buffer in between incubations. Stained tissues were then mounted onto glass slides with mounting medium and cover-slipped. Slides were imaged via a LSM710 confocal microscope (Zeiss) using Zen software. Image acquisition and quantification. Whole-slide bright field images were acquired using the NanoZoomer slide scanner. Image analysis was performed with the NDP. view software v2. 4. 26 (Hamamatsu) and with ImageJ v1. 46h. For spleen and liver, 10 regions of interest (ROI) were exported per sample as jpg format from the NDP.
view files. Signal was quantified from the whole area corresponding to each ROI (i. e. each jpg file). For analysis of small intestine, individual villi were set as a ROI in the jpg file derived from PAS-staining. Villus perimeter, as well as the area and the number of Goblet cells (PAS + cells) were quantified. Measurement of villus length was performed in H&E images where 30 villi were measured per sample, from the mucosal base adjacent to the crypts to the apex, using the "ruler" function of the NDP. view v2. 4. 26 software. Entire brain tissue sections were imaged using a Zeiss AxioScan SlideScanner and visualized with Zen2 software. Epidermal tail sheets were imaged with a Zeiss LSM 710 confocal microscope and ZEN software. For astrocyte analysis the images were obtained by z-stacks using a Zeiss Axio Scan.
Z1 (10× objective) and an Olympus 3i Spinning Disk confocal microscope (30× silicone objective) using SlideBook software. For astrocytes counts, tiff files from max projections were imported to Image J, and the images were converted to 8-bit fluorescence RGB tiff and thresholded. For nuclear counts, watershed segmentation on binary images was used to separate objects and then images were analyzed. Two fields of view were quantified and then the mean was calculated and converted to mm 2. To count the proportion of GFAP-positive cells, the number of GFAP + cells was divided by the number of SOX9 + nuclei. Blood analysis. Blood was isolated through cardiac puncture, using syringe and needle coated with 2% EDTA. Blood was collected into 2 mL EDTA tubes (BD Vacutainer ® ) containing 1. 8 mg of EDTA per mL of blood.
Analysis of hippocampi microarray data. These data were interrogated with sets of genes whose expression is highly enriched in specific cell types of the brain (astrocytes, oligodendrocytes, microglia, neurons, brain endothelial cells). These sets were curated from published RNA-seq data (GEO, accession number GSE73721) describing the transcriptome of astrocytes, oligodendrocytes, microglia, neurons, and brain endothelial cells  60. The inclusion criteria consisted of (a) being expressed at least five-fold higher in the cell type of interest than all other cell types and (b) being expressed at least 50 FPKM to enable robust detection in the mixed cell type environment of a whole hippocampus. cDNA synthesis and quantitative real-time PCR. Complementary DNA (cDNA) was synthesized from RNA using the SuperScript III.
First-Strand Synthesis System and remaining template was removed by incubation with RNase H (Invitrogen). Oligonucleotides were designed in Primer3 v4. 0. 0 (available at http://bioinfo. ut. ee/ primer3/). Real-time qPCR reactions were performed using the Fast SYBR green master mix and the 7500 Fast System (Applied Biosystems). Analysis was performed with 7500 software v2. 0. 6 (Applied Biosystems, Life Technologies Corporation). For analysis of relative changes in gene expression, data were normalized according to the 2 -ΔΔCT method. Hypoxanthine guanine phosphoribosyl transferase (Hprt) was used as a loading control/housekeeping gene. Oligonucleotide sequences are listed in Supplementary Table  3. Reporting summary. Further information on research design is available in the Nature Research Reporting Summary linked to this article.
Acknowledgements This work was supported by the medical research council (MRC)  UK grant   MR/ M019969/1. R. R. was supported by a doctoral scholarship (application number:  314413 , file number:  218819 ) granted by  CONACyT Nuevo Leon-I2T2 , Mexico. J. A. was supported by  Wellcome Trust  grant  201531/Z/16/Z. D. A. H. and K. M. S. are supported by The  Mater Foundation. P. H. was supported by the  biotechnology and biological sciences research council (BBSRC)  grant  BB/P013732/1. D. D. O. was supported by  MRC  grant  MR/M010341/1. C. P. is supported by the  Simons Foundation Autism Research Initiative. Flow cytometry data was generated with support from the  Queen's Medical Research Institute (QMRI)  and  Roslin Institute Flow Cytometry  and cell sorting facility,  University of Edinburgh.
Ultrasonic vocalizations (USVs) in pups. USVs were assessed in response to a 6min isolation on PND7-8 (in the afternoon, 4 hours after the end of the MS episode). Pups were gently removed from the homecage and placed in a glass crystallizer bedded with thick cotton in a different room. USVs (range 60-80 kHz, threshold -50 dB) were recorded using an ultrasound microphone coupled with the Recorder USGH software (Avisoft, Glienicke, Germany) and automatically quantified using the whistle tracking mode of the SAS LabPro software (Avisoft Bioacoustics).
Ex vivo measurement of colonic motility (males only). Ex vivo neuromuscular transmission was evaluated as previously described  (Suply et al. , 2012). Segments of distal colon were placed in cold oxygenated (5% CO2-95% O2) Krebs solution containing (in mM) 117. 0 NaCl, 4. 7 KCl, 1. 2 MgCl2, 1. 2 NaH2 PO4, 25. 0 NaHCO3, 2. 5 CaCl2, and 11. 0 glucose. Segments were placed in the longitudinal direction in a 7-ml organ bath containing oxygenated Krebs solution (37°C) and were stretched with a preload tension of 10 mN. Preparations were equilibrated for 60 min. Isometric contractions were recorded with force transducers (No. TRI202PAD, Panlab, Cornellã, Spain) coupled to a computer equipped with the PowerLab 8/30 System and the Labchart data analysis software (AD Instruments, Spechbach, Germany).