dataesr/scientific-paragraphs-categorization huggingface dataset:
8426 was used to calibrate MS data and the fragment ion [M + H] + at m/z 684. 3469 was used to calibrate MS/MS data during the analysis. For tandem MS experiments, the system was operated with automatic switching between MS (0. 5 s/scan on m/z range [150;1700]) and MS/MS modes (0. 5 s/scan on m/z range  [50;2000] ). The two most abundant peptides (intensity threshold 20 counts/s), preferably doubly and triply charged ions, were selected on each MS spectrum for further isolation and CID fragmentation using collision energy profile. Fragmentation was performed using argon as the collision gas. Mass data collected during analysis were processed and converted into pkl files using ProteinLynx Global Server 2. 3 (Waters Corporation, Milford, MA, USA). Normal background subtraction type was used for both MS and MS/MS with 5% threshold and polynomial correction of order 5.
Smoothing was performed on MS/MS spectra (Savitsky-Golay, 2 iterations, window of 3 channels). Deisotoping was applied for MS (medium deisotoping) and for MS/MS (fast deisotoping). The TripleTOF 5600 was operated in positive mode, with the following settings: ionspray voltage floating (ISVF) 2300 V, curtain gas (CUR) 10, interface heater temperature (IHT) 150, ion source gas 1 (GS1) 2, declustering potential (DP) 80 V. Information-dependent acquisition (IDA) mode was used with Top 10 MS/MS scans. The MS scan had an accumulation time of 250 ms on m/z [400;1250] range and the MS/MS scans 100 ms on m/z [150;1800] range in high sensitivity mode. Switching criteria were set to ions with charge state of 2-4 and an abundance threshold of more than 500 counts, exclusion time was set at 4 s. IDA rolling collision energy script was used for automatically adapting the CE.
Mass calibration of the analyser was achieved using peptides from digested BSA. The complete system was fully controlled by AnalystTF 1. 7 (Sciex) Raw data collected were processed and converted with MSDataConverter in mgf peak list format. For protein identification, MS/MS data were interpreted using a local Mascot server with MASCOT 2. 5. 1 algorithm (Matrix Science, London, UK) against UniProtKB/SwissProt (version 2018_11, 558,898 sequences), without taxonomical restrictions. Spectra were searched with a mass tolerance of 15 ppm for MS and 0. 05 Da for MS/MS data, allowing a maximum of one trypsin missed cleavage. Carbamidomethylation of cysteine residues and oxidation of methionine residues were specified as variable modifications. Protein identifications were validated with at least two peptides with Mascot ion score above 30.
This allowed to take into account coordinated but low amplitude changes that can be highly significant, as shown before  [74]. The proteins were then identified by mass spectrometry. The results are shown on Figures  3 4 5 , the raw images, quantitative data and identification data being supplied in Supplementary Figures  1 2 3 , Supplementary Tables  1  and 2 , respectively. Global analysis of the proteomic experiment by hierarchical clustering. All the spots that showed a p-value <0. 25 in either the hydroxyquinoline vs. control or the copper complex vs. control comparisons in the proteomic experiments were used for the calculation of the clustering tree. The PAST software package was used for the calculations, using a Euclidean distance and the Ward's algorithm. This tree indicates the similarity between the various experimental groups (the higher the distance of the branching point between groups, the more dissimilar they are).
Ctrl: unexposed cells. OHQ: cells exposed to 4 µM 8-hydroxyquinoline. QCu: cells exposed to 4 µM 8-hydroxyquinoline +2 µM copper sulfate. 3. 2. Detailed Analysis of the Proteomic Results. We then selected the spots modulated by at least one of the treatments, on the strict basis of the statistical tests, without any fold change threshold. This allowed to take into account coordinated but low amplitude changes that can be highly significant, as shown before  [74]. The proteins were then identified by mass spectrometry. The results are shown on Figures  3 4 5 , the raw images, quantitative data and identification data being supplied in Supplementary Figures  S1-S3 , Supplementary Tables  S1  and S2 , respectively. The same conditions as described in Figure  3  were applied to this figure The proteins involved in mitochondria, central metabolism, protein production, as well as unclassified proteins are shown in this figure In order to take into account the multiple testing issue, we submitted the modulated protein lists to statistical tests as the Benjamini-Hochberg FDR test  [59]  and the sequential goodness of fit tests  [60, 61].
Questionnaires A questionnaire survey was conducted during the data collection stage to determine the knowledge, attitudes, beliefs and opinions of the local people about anthrax that may help to explain the disease recurrence. A total of 113 questionnaires were distributed in villages within the study area that had had a history of the disease and those without any history. This ensured that there was an unbiased evaluation of the levels of awareness about anthrax. The target population included all cattle farmers in the upper Zambezi basin and the study population comprised simple randomly selected villages with cattle farmers. The sampling unit of interest was a village and the secondary sampling unit was a simple randomly selected individual cattle farmer in each of the selected villages.
Data collection Evaluation of the candidates for CRT implantation, except those undergoing rescue-CRT, had to be performed in our center within three months before the procedure, and included a 12-lead electrocardiogram and a standard two-dimensional echocardiogram performed with the IE 33™ or Epic 5™ system (Philips Healthcare, Amsterdam, Netherlands) with the measurement of LVEF using Simpson's biplane method. Clinical, biological, electrocardiogram and echocardiographic data were anonymously collected.
Statistical analysis Categorical variables were expressed as numbers and percentages and compared using Pearson's chi-squared test or Fisher's exact test depending on whether the data met the criteria for a given test. Continuous variables were expressed as the mean and standard deviation if the data were normally distributed or the median and interquartile range if the data were not normally distributed. The data were then compared using Student's t-test or the Mann-Whitney U test. The association between the baseline characteristics and the occurrence of clinical events was evaluated by univariate analysis. Variables with p values ≤0. 20 in univariate analysis were then introduced in multivariate analysis using a binary logistic regression model with Wald's step-by-step method. The survival time for the primary endpoint was defined as the number of days between implantation and the first event.
The Data Set The data used in this study were collected as part of the longitudinal research project "Cultural Formation of Responsibility in Caregiver-Child Interaction, " which focuses on developmental transitions wherein children's innate behavioral preferences are shaped into coordinated patterns of interaction to meet the expectations of both caregiver and child  (Takada et al. , 2016). The author directed this project from 2007 to 2012 and supported follow-up projects 5. The data were collected in the Kansai region of Japan. Commencing in 2007, the research team began to visit 17 middle-class families with children aged 0-5 years with the aim of collecting data. The families were chosen from among those who expressed interest in the Kyoto University Child Development Research Group 6.
All families used the Kansai dialect for daily communication. A researcher and a videographer visited each family at home for approximately 2 h per month to record the interactions between the child(ren) and caregiver(s) in their natural settings in that family. Most families consisted of caregivers and more than one child, as one of the project's objectives was to elucidate how older siblings developed a sense of responsibility. Some mothers who participated in this study were pregnant at the time the data were collected. This is relevant to the analysis because an unborn child may be the subject of conversation and a participant in an interaction. In total, approximately 410 h of video were recorded, and all basic verbal and non-verbal behaviors were transcribed to yield the data set. Although there was no intention of creating a balanced sampling, the data set nevertheless reflect the everyday life of ordinary Japanese families with young children.
Hazukashii as Teasing In our dataset, the term hazukashii also frequently occurred in the context of teasing a child or saying that certain action(s) carried out by the child are inappropriate in relation to social norms (i. e. , shameful or something to be embarrassed/ashamed about). In the next example, the girl A, 2 years and 9 months old, is watching a video, taken while A was still an infant, with her mother (M) in her last month of pregnancy (on the TV screen, children, including baby A, and a woman, who appears to be the nursery teacher, are seen). M cautions A to take a step back. A turns to M, rising up on her knees, and tries to move back as instructed. The excerpt begins from there. A loses her balance and her hands strike the floor. A immediately begins to pretend to cry like a baby (line 1; Figure  4 ).
Background: Immune checkpoint therapies (ICTs) targeting the programmed cell death-1 (PD1)/programmed cell death ligand-1 (PD-L1) pathway have improved outcomes for patients with non-small cell lung cancer (NSCLC), particularly those with high PD-L1 expression. However, the predictive value of manual PD-L1 scoring is imperfect and alternative measures are needed. We report an automated image analysis solution to determine the predictive and prognostic values of the product of PD-L1+ cell and CD8+ tumor infiltrating lymphocyte (TIL) densities (CD8xPD-L1 signature) in baseline tumor biopsies. Methods: Archival or fresh tumor biopsies were analyzed for PD-L1 and CD8 expression by immunohistochemistry. Samples were collected from 163 patients in Study 1108/NCT01693562, a Phase 1/2 trial to evaluate durvalumab across multiple tumor types, including NSCLC, and a separate cohort of 199 non-ICT-patients.
Digital images were automatically scored for PD-L1+ and CD8+ cell densities using customized algorithms applied with Developer XD™ 2. 7 software. Results: For patients who received durvalumab, median overall survival (OS) was 21. 0 months for CD8xPD-L1 signature-positive patients and 7. 8 months for signature-negative patients (p = 0. 00002). The CD8xPD-L1 signature provided greater stratification of OS than high densities of CD8+ cells, high densities of PD-L1+ cells, or manually assessed tumor cell PD-L1 expression ≥25%. The CD8xPD-L1 signature did not stratify OS in non-ICT patients, although a high density of CD8+ cells was associated with higher median OS (high: 67 months; low: 39. 5 months, p = 0. 0009) in this group. Conclusions: An automated CD8xPD-L1 signature may help to identify NSCLC patients with improved response to durvalumab therapy.
However, their clinical utility has been questioned, as some PD-L1-low/ negative patients show a therapeutic response and some PD-L1-high patients fail to respond  [15]. Durvalumab is a selective, high-affinity, engineered human IgG1 monoclonal antibody that blocks PD-L1 binding to PD1 and CD80  [16]. Consistent with other immunotherapies targeting the PD1/PD-L1 axis, greater response rates and longer survival have been observed in durvalumab-treated NSCLC patients with biopsy specimens that express ≥25% membranous PD-L1 TC compared to those with < 25% PD-L1 TC. This was shown in two separate trials: a nonrandomized Phase 1/2 trial evaluating durvalumab in advanced NSCLC and other solid tumors (Study 1108/NCT01693562) and PACIFIC, a randomized Phase 3 trial of durvalumab after chemoradiotherapy in stage III, locally advanced, unresectable NSCLC (NCT02125461)  [7, 10].
Patient cohorts To assess the predictive potential of the CD8xPD-L1 signature, baseline archival or fresh tumor samples were analyzed from NSCLC patients enrolled in Study 1108/ NCT01693562. The primary endpoints were the safety profile across various tumor types and antitumor activity of durvalumab in NSCLC and urothelial carcinoma. Secondary study endpoints were assessment of antitumor activity for all other investigated tumor types, as well as pharmacokinetics and immunogenicity. Assessments of antitumor activity included objective response rate (ORR), disease control rate, duration of response, and progression-free survival (PFS) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1. 1 guidelines  [38] , as well as overall survival (OS). Eligible patients had histologically or cytologically confirmed advanced squamous or non-squamous NSCLC and had failed, were intolerant of, ineligible for, or had refused an approved first-line treatment.
For stage I disease, all patients underwent surgery and rarely received adjuvant chemotherapy. For stage II-IIIA disease, patients underwent surgery followed by adjuvant chemotherapy. For stage IIIB disease, patients received neo-adjuvant chemotherapy or if they did not respond to chemotherapy, they underwent radiotherapy, followed by surgery, followed by adjuvant chemotherapy. Baseline patient characteristics from both sample cohorts are shown in Additional file 2: Table  S1. Immunohistochemistry 4-μm histological sections were prepared from formalin-fixed, paraffin-embedded tumors and mounted on positively-charged glass slides. Baseline tumor biopsies from Study 1108/NCT01693562 were immunostained separately for PD-L1 (clone SP263, Ventana Medical Systems, Inc. , Tucson, AZ, USA) and for CD8 (clone SP239, Spring Bioscience, Pleasanton, CA, USA), both performed on the Ventana BenchMark ULTRA staining platform (Ventana Medical Systems, Inc.
Image analysis Rule-based methods combined with machine learning were used to segment and classify cells and nuclei of acquired images  [40]  using Developer XD™ 2. 7 software (Definiens AG, Munich, Germany). The pathologists' expert knowledge was translated into automated image analysis solutions to detect CD8+ and PD-L1+ cells in single marker images as shown in Fig. 1 , or multiplex IHC images (Additional file 1: Figure  S1 ). Image variability caused by histological quality and immunostaining variability across different samples was accounted for by unmixing the three-color red-green-blue image into marker-specific colors (brown-blue/purple-brown-blue) before analysis (Additional file 1: Figure  S2 ). The readouts used for this study were based on positive cells that were detected in pathologist-annotated tumor regions as previously described  [37].
The nested model of fitted objects was compared using an analysis of variance (ANOVA), giving an estimate of the difference between the respective models, indicated by the p-value. The p-values for the covariates in the Cox model and the ANOVA were considered significant if ≤0. 05. Statistical calculations were performed using R version 3. 4. 2 with the Survival package 2. 41-3  [44]  and the Statistics package 3. 4. 2 [45].
Acknowledgments We thank the patients and their families and the caregivers for their participation in clinical trial NCT01693562. We also thank  Anmarie Boutrin ,  Holly Koelkebeck ,  Samantha Knockaert , and  Nathalie Jupiter  for histology,  Charles Brown  for immunohistochemistry,  Karma Dacosta  for digital slide scanning,  Dr. Audrey Mansuet-Lupo  for providing clinical data of those patients not part of study  NCT01693562 , and  Professor Dr. Gerd Binnig ,  Dr. Johannes Zimmermann , and  Professor Dr. Ralf Huss  for image mining and discussions on biological insights.
Funding This study was sponsored by  AstraZeneca , and was supported by the  Institut National de la Santé et de la Recherche Médicale (INSERM) ,  Pierre and Marie Curie University  ( Sorbonne University ),  Paris Descartes University  ( Sorbonne Paris Cité University ). Dr. H. Kaplon received a doctoral fellowship from  La Ligue nationale contre le Cancer. Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by  Craig Turner , MSc, of  Cirrus Communications (Macclesfield, UK ) and was funded by  AstraZeneca (Gaithersburg, MD, USA ).
Acknowledgements This study was funded by the  BGF program ,  France  (project  DISTIMACC , Ecofor  2014-23 ) and supported by the  GIS-Coop, France  ( E 12/2016 ). This work was also partially funded by the Chair '' Modélisation Mathématique et Biodiversité " of VEOLIA-Ecole Polytechnique-MNHN-F. X. LESSEM is part of  Labex ,  France OSUG@2020  ( ANR10 LABX56 ).
The recordings were randomly selected from a set of four stories (readers' sex ratio: 1:1) obtained from a French audiobook database (http://www. litteratureaudio. com) after written authorization from the readers. Children and adults listened to different stories adapted to their age to maximize their implication in the task and their comprehension of the stories. This approach was particularly important for stories used in children as it has been previously demonstrated that reading stories aloud from books exposes children to a linguistic and cognitive complexity typically not found in child-directed or adult-directed speech  (Massaro, 2017). Special care was therefore taken to select stories with comprehensible vocabulary and content. Phrasal, word, and syllable rates, assessed as the number of phrases, words, or syllables divided by the corrected duration of the audio recording, were comparable in children (mean phrasal, word, and syllable rates across different stories 0.
Data acquisition Cortical neuromagnetic signals were recorded at CUB Hopital Erasme using a whole scalp-covering, 306-channel MEG device (for 15 adults and 12 children; Elekta Neuromag Vectorview, Elekta Oy; and otherwise Elekta Neuromag Triux, MEGIN) installed in a lightweight magnetically shielded room (Maxshield, MEGIN), the characteristics of which have been described previously (De  Tiege et al. , 2008; Carrette et al. , 2011). The MEG device has 102 sensor chipsets, each comprising one magnetometer and two orthogonal planar gradiometers. MEG signals were bandpass filtered through 0. 1-330 Hz and sampled at 1 kHz. Four headtracking coils monitored subjects' head position inside the MEG helmet. The locations of the coils and at least 150 head surface (on scalp, nose, and face) points with respect to anatomical fiducials were digitized with an electromagnetic tracker (Fastrack, Polhemus).
Coherence analyses in source space Individual MR images were first segmented using Freesurfer software (Martinos Center for Biomedical Imaging, Boston, MA; RRID: SCR_001847;  Reuter et al. , 2012). MEG and segmented MRI coordinate systems were then coregistered using the three anatomical fiducial points for initial estimation and the head-surface points to manually refine the surface coregistration. The MEG forward model was computed for triplets of orthogonal current dipoles, placed on a homogeneous 5 mm grid source space covering the whole brain, using MNE suite (Martinos Centre for Biomedical Imaging; RRID:SCR_005972;  Gramfort et al. , 2014). The forward model was then reduced to its two first principal components. This procedure is justified by the insensitivity of MEG to currents radial to the skull, and hence, this dimension reduction leads to considering only the tangential sources.
This study and the MEG project at the  CUB Hopital Erasme  were financially supported by the  Fonds Erasme  (research convention " Les Voies du Savoir ,"  Fonds Erasme, Brussels, Belgium ). M. V. G. and M. N. were supported by a research grant from the  Fonds Erasme (Brussels, Belgium). M. B. was supported by the program  Attract of Innoviris  (Grant  2015-BB2B-10 ), by the  Spanish Ministry of Economy and Competitiveness  (Grant  PSI2016-77175-P ), and by the  Marie Skłodowska-Curie Action of the European Commission  (Grant  743562 ). V. J. was supported by a research grant from the  Institut d'Encouragement de la Recherche Scientifique et de l'Innovation de Bruxelles ("Brains back to Brussels," Brussels, Belgium). X. D. T. is Postdoctorate Clinical Master Specialist at the  Fonds de la Recherche Scientifique (FRS- FNRS, Brussels, Belgium ).
4, which were used for the measurements. TEM measurements. Carbon-coated copper-rhodium electron microscopy grids with a 300 mesh (Euromedex) were surfacetreated with a glow discharge in amylamine atmosphere (0. 45 mbar, 4-5 mA, 40 s) in an Elmo glow discharge system (Cordouan Technologies). Then, 5 μ l of the TPE polymeric NPs were deposited onto the grids and left for 1 min. The grids were washed with milli Q water followed by stained with a 2% uranyl acetate solution for 1 min. The measurements were taken on a Philips CM120 transmission electron microscope equipped with a LaB6 filament and operating at 100 kV. Areas of interest of all the TPE polymeric NPs were recorded at different magnifications on a Peltier cooled CCD camera (Model 794, Gatan). The obtained raw images were analyzed using Fiji software.
6 W cm -2 power density). The presented images were an average of the first 20 frames (recorded at 200 ms integration time), whereas the time lapse data were recorded for 10 s with 100 ms integration time. The single-particle analysis was performed using Fiji software. Cell culture and imaging. HeLa cells (ATCC® CCL-2™) were grown in DMEM (without phenol red) at 37 °C under a humidified atmosphere containing 5% CO2, supplemented with 10 % heat inactivated fetal bovine serum (FBS), L-Glutamine, Penicillin and Streptomycin. Further, cells were seeded onto an ibidi treated glass petridish and incubated for 24 hours. For imaging, the culture medium was removed and the attached cells were washed two times with PBS and one time with Opti-MEM (Gibco-Invitrogen). Then, a freshly prepared solution of TPE polymeric NPs (at 30-fold dilution of the original formulation) Opti-MEM was added to the cells and incubated for 3 h.
Acknowledgements N. A. acknowledge  Marie Curie post-doctoral research grant  ( MSCA-H2020-IF , NanoOxySens) by  European Union. This work was supported by  ERC   Consolidator grant  BrightSens  648528. We thank  A. Reisch  for fruitful discussions and  J. Valanciunaite  for technical support. The authors also thank  C. Ruhlmann  and  C. Crucifix  from the  FRISBI platform  ( ANR-10-INBS-05 ) for help with electron microscopy.
The cells were washed twice with 0. 1%BSA-PBS and were then suspended in 0. 5 mL of 0. 1% BSA-PBS for analysis with a Macs Quant (Miltenyi Biotec ® ; Paris; France). More than 10,000 events were acquired for each sample and were analyzed. Data retrieved from the sorting were analyzed with FlowJo software (FlowJo LLC/ Miltenyi Biotec ® ; Paris, France ).
Methylation Assays by Pyrosequencing Genomic DNA (1 µg) was treated with sodium bisulfite using EpiTect ® 96 Bisulfite (Qiagen ® ) according to the manufacturer's instructions. Quantitative DNA methylation analysis of the bisulphite-treated DNA was performed by pyrosequencing, or, in the case of several sequencing primers, by serial pyrosequencing on a PSQ 96MD system with the PyroGold SQA reagent kit (Biotage AB ® ), and results were analyzed using Q-CpG software (V. 1. 0. 9, Biotage ® ; Uppsala, Sweden) as previously described  [23].
Statistical Analysis Statistics were computed with GraphPad Prism 5. 0 software (GraphPad Software, Inc; San Diego, US. ). Values are reported as the mean and SD or the mean and SEM according to the experiments. Differences between groups were considered significant when p < 0. 05 (* p < 0. 05; ** p < 0. 01; *** p < 0. 001). According to the size of the experiment, parametric or nonparametric tests were chosen (t test, one-way or two-way ANOVA, and post hoc tests).