dataesr/scientific-paragraphs-categorization huggingface dataset:
ACKNOWLEDGMENTS We thank  Maria Grazia Biferi  for kindly providing NSC34 cells and  Evelyne Gicquel-Zouida  for kindly providing human myoblast cells. This work was supported by  Genethon  and the  French Muscular Dystrophy Association  (A. F. M. ). It was also supported by the  European Union Research and Innovation Program  under grant agreements  667751  (to F. M. ) and  658712  (to F. M. ), a  European Research Council   consolidator grant  under grant agreement  617432  (to F. M. ), and an  ASTRE Laboratories of the Essonne General Council  grant (to F. M. ).
The ANTARES neutrino telescope has an energy threshold of a few tens of GeV. This allows to study the phenomenon of atmospheric muon neutrino disappearance due to neutrino oscillations. In a similar way, constraints on the 3+1 neutrino model, which foresees the existence of one sterile neutrino, can be inferred. Using data collected by the ANTARES neutrino telescope from 2007 to 2016, a new measurement of ∆m 2 32 and θ23 has been performed -which is consistent with world best-fit values -and constraints on the 3+1 neutrino model have been derived.
The formalism given in Eq. 1 is further modified by matter effects  [5, 6, 7]  as the neutrinos propagate through the Earth. Throughout the paper, oscillation probabilities are calculated with the OscProb package  [8]  which treats matter effects for an arbitrary number of neutrino families numerically without approximations. The ANTARES neutrino telescope  [9]  has been designed and optimised for the exploration of the high-energy Universe by using neutrinos as cosmic probes. However, its energy threshold of about 20 GeV is sufficient, even if at the edge, to be sensitive to the first atmospheric oscillation minimum, making also the study of neutrino oscillations possible. As neutrinos and antineutrinos are indistinguishable on an event-by-event basis in neutrino telescopes, in the following muon (electron) neutrinos are refered to the sum of contributions from both neutrinos and antineutrinos.
In this paper, the results of an investigation aiming to constrain the mixing angles θ 24 and θ 34 of the 3+1 neutrino model are also reported. [GeV] The paper is organised as follows: in Section 2 the ANTARES neutrino telescope is briefly described and its detection principle is illustrated; the ANTARES data sample as well as the Monte Carlo (MC) chain are presented in Section 3, while the event reconstruction is discussed in Section 4. Section 5 is dedicated to the event selection and the minimisation procedure. The results are presented in Section 6, while conclusions are given in Section 7.
ANTARES data and Monte Carlo samples ANTARES data collected from 2007 to 2016 have been considered in the analysis. After excluding data acquired under adverse conditions, a total of 2830 days of live time has been evaluated. The aim of the MC production is to reproduce in the most realistic way the events expected at the detector, as well as the response of the apparatus when recording these events. In order to account for changes of the environmental conditions, as well as for the different operational status of the detector and its components over time, a run-by-run MC approach is applied  [21]. A typical run lasts few hours. Several time dependent conditions are taken from real data and applied to the run-by-run MC. First, temporarily or permanently non-operational OMs are masked in the simulation.
It allows to reproduce neutrino interactions in the GeV to multi-PeV energy range. MC neutrino events can be weighted to reproduce different physical expectations. For atmospheric neutrinos with E ν ∈ [20 -100] GeV, a MC sample almost three hundreds times larger than the data sample is available. The model by Honda et al. [24]  for the Fréjus site is used in this work. Even though the sub-marine location of ANTARES provides a good shielding against atmospheric muons, still a large amount of them will reach the detector. The event generator used in ANTARES to simulate atmospheric muons is MUPAGE  [25] ; the energy and angular distributions, as well as the multiplicity of muons propagating in sea water are parameterised. The contribution from this background is also evaluated from the data itself.
Conclusions Ten years of ANTARES data have been analysed to provide a measurement of the atmospheric neutrino oscillation parameters. The analysis chain has been optimised with respect to our previously published study, by combining two track reconstruction algorithms and introducing a more elaborate treatment of various sources of systematic uncertainties. The results, ∆m  For the analysis presented in this paper, oscillation probabilities are evaluated with the software package OscProb  [8]. However, in this Appendix some common approximations are applied, to derive analytical formulae. These are NOT used for the analysis itself but allow to get a better understanding of the interplay between different parameters. The ν µ survival probability in vacuum in the 3 + 1 model can be simplified with the following two hypotheses  [43, 15] : first, it is assumed, that the first generation decouples completely, i.
(2. 0 +0. 4 -0. 3 )×10 -3 eV 2 and θ 23 = (45 +12 -11 ) • , are consistent with what has been published by other experiments. The non-oscillation hypothesis is discarded with a significance of 4. 6σ. Exploiting the same analysis chain and the same data set, a further study has allowed to constrain, for the first time with ANTARES, the parameter space of the 3+1 neutrino model, which foresees the existence of one sterile neutrino. ANTARES excludes values of the parameter space not yet excluded by other experiments. Européenne (FEDER fund and Marie Curie Program), Institut Universitaire de France (IUF), IdEx program and UnivEarthS Labex program at Sorbonne Paris Cité (ANR-10-LABX-0023 and ANR-11-IDEX-0005-02), Labex OCEVU (ANR-11-LABX-0060) and the A*MIDEX project (ANR-11-IDEX-0001-02), Région Île-de-France (DIM-ACAV), Région Alsace (contrat CPER), Région Provence-Alpes-Côte d'Azur, Département du Var and Ville de La Seyne-sur-Mer, France; Bundesministerium für Bildung und Forschung (BMBF), Germany; Istituto Nazionale di Fisica Nucleare (INFN), Italy; Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), the Netherlands; Council of the President of the Russian Federation for young scientists and leading scientific schools supporting grants, Russia; Executive Unit for Financing Higher Education, Research, Development and Innovation (UEFISCDI), Romania; Ministerio de Economía y Competitividad (MINECO): Plan Estatal de Investigación (refs.
2 32 = 32 (2. 0 +0. 4 -0. 3 )×10 -3 eV 2 and θ 23 = (45 +12 -11 ) • , are consistent with what has been published by other experiments. The non-oscillation hypothesis is discarded with a significance of 4. 6σ. Exploiting the same analysis chain and the same data set, a further study has allowed to constrain, for the first time with ANTARES, the parameter space of the 3+1 neutrino model, which foresees the existence of one sterile neutrino. ANTARES excludes values of the parameter space not yet excluded by other experiments. Européenne (FEDER fund and Marie Curie Program), Institut Universitaire de France (IUF), IdEx program and UnivEarthS Labex program at Sorbonne Paris Cité (ANR-10-LABX-0023 and ANR-11-IDEX-0005-02), Labex OCEVU (ANR-11-LABX-0060) and the A*MIDEX project (ANR-11-IDEX-0001-02), Région Île-de-France (DIM-ACAV), Région Alsace (contrat CPER), Région Provence-Alpes-Côte d'Azur, Département du Var and Ville de La Seyne-sur-Mer, France; Bundesministerium für Bildung und Forschung (BMBF), Germany; Istituto Nazionale di Fisica Nucleare (INFN), Italy; Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), the Netherlands; Council of the President of the Russian Federation for young scientists and leading scientific schools supporting grants, Russia; Executive Unit for Financing Higher Education, Research, Development and Innovation (UEFISCDI), Romania; Ministerio de Economía y Competitividad (MINECO): Plan Estatal de Investigación (refs.
Seven hours post treatment, a transcriptomic analysis was performed, and twenty four hours after stress, proteomic analysis were performed with HPLC-MS/MS. The transcriptome and proteome datasets were analyzed for activation of signaling pathways and upstream regulatory factors. The newly identified regulatory factor NUPR1 was then functionally assessed by siRNA mediated knockdown in KC. localized NUPR1 in nuclei of epidermal keratinocytes and found, that exposure of recombinant NUPR1 to oxidized PAPC affected its electrophoretic mobility, potentially by modifying and crosslinking the protein. Our data thus suggest a novel role for NUPR1 in the skin, as transcriptional regulator of redox responses, lipid metabolism and the cell cycle of epidermal keratinocytes under stress evoked by UV light and bioactive oxidized lipids.
A high-resolution MS method identifies uncharted UV-generated phospholipids Besides these identified species, the bulk of the UV regulated lipid signals could however not be unambiguously identified by our screening method. Thus, 20 analytes were selected for further analysis based on the criteria that they were highly inducible by UVA at 0 h or 24 h and that they were detectable also in human epidermis or in dermal fibroblasts. We used an independent high-resolution MS/MS approach combining data from positive and negative ionization modes. Precursor ions corresponding to the previously identified SRM transitions and collision-induced dissociation (CID) analysis in positive ion Fig. 2. Lipidomic analysis of UVA and UVPAPC exposed keratinocytes. Polar lipids were isolated from human primary keratinocytes immediately and after 24 h post stress treatment with UVA (40 J/cm 2 ) and UVPAPC (25 µg/ml), respectively.
4A ) which together with the heatmap (Fig. 4A ) confirmed reproducibility within-and clear separation between the treatment groups. We used "Ingenuity Pathways Analysis" software (IPA, Qiagen) to investigate whether the regulated gene groups would allow predicting activation or inhibition of canonical signaling pathways. The pathway analysis indicated that both stressors, UVA (Fig. 4C ) and UVPAPC (Fig. 4D ), significantly induced the oxidative stress response controlled by NRF2 (Gene Heatmaps Supplementary Fig. 4B ). Additionally, UVA significantly induced the unfolded protein response (UPR; Supplementary Fig. 4C )-and the endoplasmic reticulum (ER) stress pathway and inhibited interleukin 17 A and -F signaling (Fig. 4C ). UVPAPC treatment activated, in addition to NRF2, genes attributed with functions in glutathione biosynthesis or methylglyoxal degradation and reduced the "role of tissue factor in cancer" and the "inhibition of angiogenesis by TSP1" pathways (Fig.
4D ). We verified regulation of NRF2 dependent gene expression by qPCR for HMOX1 (Fig. 4E ), the autophagy adaptor sequestosome 1 (SQSTM1, p62; Fig. 4F ) and AKR1C3 (Fig. 4G ), and for the UPR marker ATF4 (Fig. 4H ). As the dynamic changes in the oxidized phospholipidome over time suggest the involvement of inducible lipid metabolizing enzymes, we screened for candidates carrying the string "lipid" in their gene ontology (GO) database entry for biological function (Supplementary Table  2A ,B). Exemplary lipid metabolism genes that were induced both by UVA and UVPAPC were aldo-keto reductase 1C family genes (AKR1C3), patatin-like phospholipase domain containing 8 (PNPLA8, calcium-independent phospholipase A2) and the oxysterol binding protein (OSBP) with potential roles in the signaling, detoxification and degradation of reactive oxidatively modified (phospho) lipids (Fig.
Identification of NUPR1 as transcriptional upstream regulator While the NRF2 pathway was thereby confirmed as shared regulator of UV-and lipid responses, we used the "upstream regulators" feature of Fig. 4. UVA and UVPAPC effects on the KC transcriptome. Human primary keratinocytes were treated with UVA ("U"; 40 J/cm 2 ), UVPAPC ("L"; 25 µg/ml) or were sham treated ("C"). 7 h after the stress treatment total RNA was isolated from biological triplicates and global gene expression was analyzed with microarray technology. Genes that showed significant regulation (p < 0. 05; moderated t-statistics (LIMMA) with Benjamini-Hochberg correction) of > 2fold were used for further analysis. the IPA software to predict further regulators potentially implicated in KC redox stress responses (Fig. 6A ). The algorithm indeed predicted NRF2 as an activated upstream regulator, also ATF4, which regulates UPR-dependent transcription was predicted activated, especially in the UVA treated cells, in line with the previous findings.
Immunofluorescence analysis Human skin obtained from plastic surgery was fixed with 10% formalin, paraffin embedded and microtome sections (4 µm) were immuno-stained. Primary keratinocytes were fixed with 4% paraformaldehyde (10 min rt) and the permeabilized with PBS containing 0,1% Trition X-100 (Sigma-Aldrich; MO, USA). Sections were incubated overnight at 4 °C in phosphate-buffered saline (pH 7. 2, 2% BSA) with the primary antibody Nupr1 (bs-7106R Bioss; 1:500; rb) or Nrf2 (ab62352 Abcam; 1:200; rb). As secondary antibody goat anti-rabbit IgG (H+L), conjugated with Alexa Fluor dyes (Molecular Probes Eugene, OR, USA) were used at a dilution of 1:500. For imaging, an Olympus (Tokyo, Japan) AX 70 was used. All image analyses were performed under the same parameter settings. Nuclear intensity of NRF2 was quantified using ImageJ software.
Cell cycle analysis Cell cycle analysis was performed using the BrdU cell-cycle kit (containing the reagents below; BD Biosciences, Franklin Lakes, NJ) according to the manufacturer's instructions. 48 h post transfection, cells were incubated with BrdU (10 µM) for 4 h. After fixation with 100 μL of BD Cytofix Cytoperm Buffer for 15 min at 4 °C cells were stained with a fluorescein isothiocyanate (FITC) conjugated anti-BrdU antibody for 30 min and stained with 7-AAD and immediately analyzed on a FACS-Calibur (BD Biosciences). Gates were set according to the manufacturer's instructions and data were evaluated using FlowJo software (Tree Star, Ashland, OR).
7 µm) and eluted with linear gradients from 50% to 90% eluent B (30 min) and to 99% B (1 min, and held for 10 min). Column temperature was set to 50 °C and the flow rate to 60 μL/min. Sampling cone voltage was set to 40 V, source offset to 60 V, source temperature to 120 °C, cone gas flow to 30 L/h, desolvation gas flow to 650 L/h, desolvation temperature to 250 °C, nebuliser gas pressure of 6 bar, and an ion spray voltage of -2. 0 kV. Data were acquired in negative and positive ion data-dependent (DDA) resolution modes. Precursor ion survey scans (scan time 0. 5 s) were acquired for m/z 200-1200. Tandem mass spectra (ramp collision energy: LM CE start/ end 10-40 and HM CE start/end 20-60) were recorded (scan time 0. 25 s) for the 12 most intense signals in each survey scan using a dynamic exclusion for 30 s.
Microarray Total RNA cleanup and concentration was performed using the RNeasy MinElute Cleanup Kit (Qiagen) according to the manufacturer's recommendations. 200 ng of each sample were used for gene expression analysis with Affymetrix (Sta. Clara, CA) human PrimeView 3`IVT. Hybridization and scanning were performed according to manufacturer's protocol (http://www. affymetrix. com). The experiment was performed on biological triplicate samples. The full microarray data was uploaded to the Gene Expression Omnibus (GEO) with the identifier GSE104870. 4. 12. Quantitative PCR 400 ng of isolated RNA was reverse transcribed using iScript cDNA Synthesis Kit (Bio-Rad, Hercules, CA) and was diluted 1:5 for further quantitative PCR (qPCR). LightCycler 480 and the LightCycler 480 SYBR Green I Master (Roche, Basel, Switzerland) was used with a standard protocol described before  [32]  for qPCR.
Protein liquid chromatography tandem mass spectrometry Samples were injected onto a Dionex Ultimate 3000 system (Thermo Fisher) coupled to a Q-Exactive Plus mass spectrometer (Thermo Fisher). Software versions used for the data acquisition and operation of the Q-Exactive were Tune 2. 8. 1. 2806 and Xcalibur 4. HPLC solvents were as follows: solvent A consisted of 0. 1% formic acid in water and solvent B consisted of 0. 1% formic acid in 80% acetonitrile. From a thermostated autosampler, 10 μL that correspond to 1 µg of the peptide mixture was automatically loaded onto a trap column (PM100-C18 3 µm, 75 µm × 20 mm, ThermoFisher) with a binary pump at a flow rate of 5 μL/min using 2% acetonitrile in 0. 1% TFA for loading and washing the pre-column. After washing, the peptides were eluted by forward-flushing onto a 50 cm analytical column with an inner diameter of 75 µm packed with 2 µm-C18 reversed phase material (PepMap-C18 2 µm, 75 µm × 500 mm, ThermoFisher).
Protein identification and label free quantitation The acquired raw MS data files were processed in MaxQuant 1. 5. 3. 30 [18]  and searched against the human SwissProt protein database version v 2015. 11. 11 (42,097 sequences, including isoforms). The search parameters were as follows: two tryptic missed cleavage sites, mass tolerances of 5 ppm and 20 ppm for the precursor and fragment ions, respectively. Oxidation of methionine and N-terminal protein acetylation were set as variable modification, whilst carbamidomethylation of cysteine residues were set as fixed modifications. The data was also matched against a decoy reverse database. Peptides and protein identifications with 1% FDR are reported. Protein identifications requiring a minimum of two peptides sequences were reported. The mass spectrometry proteomics data have been deposited to the Proteo-meXchange Consortium via the PRIDE partner repository with the dataset identifier PXD008050.
The peak intensity was log2-transformed and compared between each condition for timepoints 0 h and 24 h using R version 3. 2. 2/ Bioconductor software package Limma. A linear model was applied for each peak and moderated t-tests were computed. In the model, the "condition" was defined as a factor of 3 levels (shame, UVA and UVPAPC). The Benjamini and Hochberg (BH) procedure was applied to adjust the raw p-values into false discovery rate (FDR). A FDR < 0. 05 was chosen as the cut-off value. To see the proximities among the conditions in terms of lipids, a Principal Component Analysis was conducted with the conditions in lines and the peaks in columns. Then a heatmap, a double Hierarchical Classification Analysis (HCA) centered and reduced) with Euclidean Distance and the Ward's method, was performed.
Affymetrix array Robust multi-array average (RMA) signal extraction and normalization were performed using custom chip description file at timepoint 7 h. After exclusion of all Gene IDs with a RMA value of less than 50 in all conditions, log2 transformation was applied. Differential expression between the three conditions (sham, UVA and UVPAPC) was tested using moderated t-tests as described above (R version 3. 2. 2/ Bioconductor software package Limma) with a BH multiple testing correction. Gene identifiers covering annotated genes or annotated variants (with eleven probes per set) are referred to as "genes" throughout the manuscript. Genes that were regulated more than 2-fold with a p-value < 0. 05 were used for principal component analysis. Heatmaps were used to visualize double HCA of the mRNAs (center and reduced) based on euclidian distance with Ward's method.
Proteins Protein identifications and LFQ intensities from MaxQuant were analyzed using Perseus statistical package (version 1. 5. 1. 6) [75]. The LFQ intensity values were log2-transformed and zero-intensities were imputed-replaced by normal distribution. Statistical significance of differences in protein levels between groups were evaluated using twosided t-test with p < 0. 05 with Permutation based-FDR. PCA and hierarchical clustering analysis using Euclidean distance method for both rows and columns with average linkage and k-mean pre-processing.
Gene network and pathway analyses Regulated genes and proteins were analyzed with the software QIAGEN's Ingenuity® Pathway Analysis (IPA®, QIAGEN Redwood City, USA, www. qiagen. com/ingenuity) which allowed prediction of activated signaling pathways and upstream regulatory events that were likely to cause the observed gene expression changes, both based on literature evidence. Heatmaps and activation z-scores were calculated within the IPA software package and modified for better presentation as recently described  [70].
Acknowledgments We thank  Prof. Ralf Hoffmann  ( Institute of Bioanalytical Chemistry, University of Leipzig ) for providing access to his laboratory and mass spectrometers. We thank  Wolfgang Bicker  from  FTC FORENSISCH-TOXIKOLOGISCHES LABOR BETRIEBSGMBH  for his additional support. We thank  Markus Jeitler  from the  MUW Core Facility Genomics  for his support. The financial support of the  Federal Ministry for Digital and Economic Affairs (BMWFW) of Austria  and the  National Foundation for Research, Technology, and Development of Austria  to the  Christian Doppler Laboratory for Biotechnology of Skin Aging  is gratefully acknowledged. The support of the  Herzfelder'sche Familienstiftung ,  Austria  is gratefully acknowledged. These funding bodies do not issue grant numbers. Financial support from the  German Federal Ministry of Education and Research (BMBF)  within the framework of the e: Med research and funding concept for  SysMedOS  project is gratefully acknowledged.
Fcgr2b is on the same chromosome than the Ly5 locus, making it very difficult to obtain FcγRIIb KO mice bearing the congenic marker CD45. 1. The mHEL (membrane-bound HEL transgenic) and ML5 (soluble HEL transgenic) mice have been described previously  2, 5. We crossed the mHEL strain with the Rag2 -/-(here called RAG2KO) strain to obtain the mHEL × RAG2KO strain, expressing one allele of the mHEL transgene. For all experiments, the number of animals included in each experiments was determined based on our previous expertise using mouse models with different expression level of FcγRIIb and by using the G*Power software for a priori power calculation. To generate bone marrow chimeras, recipient mice were irradiated lethally (1000 Gy for WT, mHEL and mL5 recipients) or sub-lethally (500 Gy for RAG2KO and mHEL × RAG2KO recipients) and reconstituted by intravenous injection of fresh bone marrow cells.
FACS analysis was performed on a BD LSR Fortessa (BD biosciences) and data were analysed with the Flowjo software (TreeStar, Ashland, OR). All antibodies used are described in Supplementary Table  2. ELISA and ELISPOT. Serum HEL-specific IgG1 were detected by ELISA using a modified version of the protocol previously described  44. Briefly, plates were coated with 5 μg/ml of HEL in PBS overnight at 4 °C. Sera were added to the saturated plates and were incubated for 2 h at 37 °C. Pooled sera from hyperimmune mice (immunised with SRBC-HEL twice) were used as a standard. Plates were developed with the BD Opteia kit (BD Biosciences). Serum dsDNA-specific IgG1 was detected by ELISA as previously described  65. For detection of HEL-specific antibody-forming cells (AFCs) ELISPOT plates (Millipore) were coated with 5 μg/ml of HEL in PBS overnight at 4 °C.
Universal barcoded regions were identified in reads and orientated to read from V-primer to constant region primer. The barcoded region within each primer was identified and checked for conserved bases (i. e. the T's in NNNNTNNNNTNNNNT). Primers and constant regions were trimmed from each sequence, and sequences were retained only if there was >80% sequence certainty between all sequences obtained with the same barcode, otherwise discarded. The constant region allele with highest sequence similarity was identified by 10-mer matching to the reference constant region genes from the IMGT database  69  , and sequences were trimmed to give only the region of the sequence corresponding to the variable (V-D-J) regions. Isotype usage information for each IgH was retained throughout the analysis hereafter.