dataesr/scientific-paragraphs-categorization huggingface dataset:
Data were acquired using the Xcalibur software (v 2. 0. 7). For all full scan measurements with the Orbitrap detector, a lock-mass ion from ambient air (m/z 445. 120024) was used as an internal calibrant as described  (Olsen et al. , 2005). Analysis of MS data was performed using the MaxQuant software package (v 1. 5. 5. 1)  (Cox and Mann, 2008). Tandem mass spectra (MS/MS) were searched by the Andromeda search engine  (Cox et al. , 2011)  against the UniProtKB Reference Proteome UP000000589 database for the Mus musculus taxonomy (release 2017_08, 22277 canonical entries) and the specific sequence of interest using the following parameters: enzyme specificity was set as Trypsin/P, and a maximum of two missed cleavages and a mass tolerance of 0. 5 Da for fragment ion were applied. A second database of known contaminants provided with the MaxQuant suite was also employed.
The 'match between runs' and 'iBAQ' options were checked. Oxidation (M) was specified as variable modification. Database searches were performed with a mass tolerance of 20 ppm for precursor ion for mass calibration, and with a 4. 5-ppm tolerance after calibration. The maximum false peptide and protein discovery rate was specified as 0. 01. Seven amino acids were required as minimum peptide length. The MaxQuant software generates several output files that contain information about identified peptides and proteins. The 'proteinGroups. txt' file is dedicated to the identified proteins: each single row collapses into protein groups all proteins that cannot be distinguished based on identified peptides. An in-house bioinformatics tool has been developed to automatically select a representative protein ID in each protein group.
Bioinformatics and network analysis Only proteins with a fold enrichment of six (based on the MS/MS ratio) and a minimum of two unique peptides per protein were considered as potential interactors of the carboxyl terminus of the mGlu1 receptor (Supplementary Table  S1 ). Protein-protein interactions of these 173 proteins have been downloaded from the IntAct database  (Orchard et al. , 2014 ) (October 12, 2017)  and filtered based on an edge score set to 0. 6 (high confidence). Protein network analysis was performed using Cytoscape  (Shannon et al. , 2003)  (version 3. 5. 1) and the ClueGO application  (Bindea et al. , 2009) (v2. 3. 4 ) was used to handle GO annotations (from EBI-QuickGO-GOA, September 6-October 16, 2017). A focus was made on proteins annotated to the 'intracellular transport' GO term, GO:0046907 (29/173 proteins; 9/29 with known PPI in IntAct).
For quantitative measurements, coverslips were transferred in 24-well microplates and processed for in-cell western assay (Odyssey, LI-COR Biosciences). Briefly, cells were blocked with gelatin, washed, incubated with anti-GFP antibodies, washed again and finally incubated with IRDye800CW-conjugated donkey anti-rabbit polyconal antibodies (Rockland). Infrared fluorescence was determined using the 700 nm channel of the Odyssey Infrared Imaging System (LI-COR Biosciences). Fluorescence intensity was measured using Image J software from circular gates placed in the middle of the wells. Background values measured in wells containing mocktransfected cells were subtracted from the signal. All measurements were performed in triplicate and expressed as mean ± SEM.
Funding This work was supported by the  European Research Council (ERC)  under the European Union's  Horizon 2020 research and innovation programme  (grant agreement no. 646788  to J. P. ), the  Agence Nationale de la Recherche  ( ANR-13-JSV4-0005-01  to J. P. ), and the  Region Languedoc-Roussillon  ( Chercheur d'Avenir 146090  to J. P. ).
In addition, the short wavelength in which laser scanners operate provides high-resolution data and the capability to acquire details of the target reinforcing recognition applications. These appealing features can enhance the probability of detection and reduce the false alarm rate of future LIDAR seeker missiles with ATR capabilities. Driven by the appealing advantages of 3D ATR, we propose a missile seeker architecture based on a dual role pipeline that incorporates extensive pre and post-processing operations combined with the Signatures of Histograms (SHOT) descriptor  [18]. Since real military data are classified, we apply SHOT on a number of simulated but highly credible air-to-ground and maritime missile engagement scenarios. It should be noted that although SHOT is a high performing descriptor, the dataset we use is very challenging as it is highly realistic, cluttered, occluded, and incorporates sensor noise while the target scene is generated under various obliquities (viewing angles) and resolutions.
The difficulty to achieve a successful ATR is such that just applying the SHOT algorithm on its own is ineffective and thus the proposed architecture has a very important contribution to the overall ATR performance. From a military and aerospace industry point of view, we consider our contribution as highly appealing. Indeed this paper demonstrates that an existing 3D descriptor from the computer vision domain, after properly processing the data obtained from a LIDAR sensor and refining the matching process, can provide an appealing military ATR solution. In addition, the military dataset exploited is much more challenging compared to the ones used in the current open source literature because ours combines more parameters. The rest of the paper is organized as follows: Section 2 presents a literature review of the existing 3D ATR algorithms in a military context.
For the remaining clusters, the transformation hypothesis (pose) is refined via the Iterative Closest Point (ICP) surface registration technique. Finally, a geometrical cue verification task is included to reject false transformation hypotheses while retaining the correct ones. During this stage, the template and the scene are aligned using the transformation hypothesis that passed all the intermediate consistency and outlier tests, on the subsampled full 3D template that is stored in the database during the offline stage. We note that during the hypothesis verification phase the un-processed scene is subsampled with different.
Oktal SE synthetic environment Real military LIDAR point clouds are classified, hence we create a number of simulated but highly credible air-to-ground and maritime missile engagement scenarios using the Oktal Synthetic Environment (SE)  [29]. Oktal SE is a widely used highly realistic simulation software, capable of creating accurate active laser fingerprints that can be converted into point clouds for further processing. Models include both military and non-military objects to support the creation of a variety of scenes.
Experiments We train the suggested ATR architecture by splitting the runs of each scenario into a training and an evaluation subset with a ratio of 1:9. The overall performance attained is Pd=88%, Pfa=9%, TPR=93% and F1-SCORE=92% while detailed performance per scenario is presented in Fig. 4. Trials are implemented in MATLAB on Windows 7 on an AMD QL-64 CPU with 4GB RAM.
Objective: The aim of this study was to identify factors that influence treatment adjustments and adoption of a treat-to-target (T2T) strategy in patients with rheumatoid arthritis (RA) in European practices. Methods: Cross-sectional data were drawn from the Adelphi 2014 RA Disease Specific Programme. Treatment patterns and clinical characteristics were investigated in patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) vs non-bDMARDs. For the T2T analysis, patients were subdivided into two subsets (RA diagnosis ,2 or $2 years) and compared according to the approach used (no target = no T2T approach; pragmatic = target different from remission; and aspirational = target set as remission). Results: Data from 2,536 patients were analyzed (mean age: 52. 76 years and mean time since RA diagnosis: 6.
Study design This was an analysis of cross-sectional data drawn from the Adelphi 2014 RA Disease Specific Programme (DSP), a point-in-time survey of rheumatologists and their patients with RA. The DSP aims to provide impartial observations of realworld clinical practice from a physician and matched patient viewpoint without consideration of current guidelines, but with the intention of providing a view on contemporary RA management. The survey was conducted in France, Germany, Italy, Spain, and the UK from January to August 2014. Patients provided written informed consent for use of their anonymized and aggregated data for research and publication in scientific journals. For each patient meeting the eligibility criteria, the physicians filled out a patient record form (PRF), which included questions on demographics, symptoms, past and current treatments, compliance, and general patient management.
Data were collected in such a way that patients and physicians could not be identified directly; all data were aggregated and de-identified before receipt. Data collection was undertaken in line with the European Pharmaceutical Marketing Research Association (EPhMRA) guidelines and as such it did not require ethics committee approval. 15 The survey was performed in full accordance with relevant legislation at the time of data collection, including the Health Insurance Portability and Accountability Act,  16  a cornerstone of the EPhMRA guidelines relating to data privacy. Local fieldwork teams identified and invited rheumatologists to participate in the study upon fulfillment of the inclusion criteria listed subsequently. Compensation was set according to time spent on the study at fair market rates.
Live cell imaging For imaging cells were plated on 25 mm glass coverslips, pre-coated with 120 mg/mL of collagen type I of rat-tail (Institut de Biotechnologie Jacques Boy), and placed in an observation chamber (Pecon, Meyer Instruments). Imaging was performed at 37 ˚C and 5% CO2 in a heating chamber (Pecon, Meyer Instruments) on an inverted microscope Olympus IX71 equipped with a 100X objective with NA 1. 45. The microscope was controlled with the software Metamorph (Molecular Devices). Differential interference contrast (DIC) imaging was performed with a far-red filter (cutoff 550 nm, BLP01-635R-25, Semrock) in the illumination path to avoid CRY2 activation. Total internal reflection fluorescence (TIRF) images were acquired using an azimuthal TIRF module (ilas2, Roper Scientific). Localized stimulation was performed with the FRAP system at low laser power (~5%) with both 491 nm and 401 nm wavelength light lasers (Stradus), 2-3 100 ms pulses, every 10-15 s.
Imaging of Cherry and iRFP was done with 561 nm and 642 nm laser (Stradus), respectively. For image processing and data analysis, after background subtraction, the mean fluorescence over the time inside the blue light activated region (ROI) was measured using Metamorph software. The mCherry and iRFP recruitment curves obtained from TIRF images were expressed as fold increase of fluorescence: the value of fluorescence for each time point was normalized by the pre-illumination fluorescence (mean of the first frames without light activation). For cell edge morphodynamics and recruitment analysis, a custom-built ImageJ plugin, named 'Recruitment Edge Dynamics', was used  (Paul-Gilloteaux et al. , 2018).
5 ml of serum-free medium inside a 12-well plate (lower chamber); 230 ml of 10% FBS-DMEM supplemented with 25 ng/ml EGF were added inside the transwell (upper chamber). The cells were then allowed to invade upward into the bovine collagen and toward the gradient of serum/EGF for 4 days at 37 ˚C and 5% CO 2. Cells were live stained with CellTrace yellow (Thermofisher) for 1 hr at 37 ˚C and rapidly imaged by confocal microscopy (Zeiss LSM880, 10x objective, excitation at 545 nm and emission at 605 nm). Optical sections were captured at 5 mm intervals, starting from the underside of the transwell membrane and moving upward in the direction of cell invasion. The resulting fluorescence images were quantified using ImageJ software. For each independent experiment, data were generated from two duplicate transwells, and optical sections were acquired from two areas of each transwell.
Rac1 and RalB activity measurements Rac1 activity was measured using the 'Rac1 Pull-down Activation Assay Biochem Kit' (# BK035, Cytoskeleton), which is based on beads-coupled GST-Pak1GBD. A similar pull-down assay was used for RalB activity but using home-made beads-coupled GST-Sec5GBD. For RalB activity measurement by FRET, cells were transfected with a validated FRET-based RalB biosensor  (Martin et al. , 2014)  and imaged with an Olympus IX71 microscope equipped with a FRET filter set (86002v1JP4, Chroma Technology) and a 63x oil-immersion objective. YFP/CFP images were generated using Metamorph and ImageJ software.
Antibodies were: anti-RalB (#WH0005899M4, clone 4D1, Sigma-Aldrich), anti-RalA (#610222, BD Transduction Laboratories). H-scores were calculated using the following formula: stained cell percentage x stain intensity/100. Analysis of human samples was performed in accordance with the French Bioethics Law 2004-800, the French National Institute of Cancer (INCa) Ethics Charter, and after approval by the Institut Curie review board and ethics committee (Comitede Pilotage du Groupe Sein) that waived the need for written informed consent from the participants. Women were informed of the research use of their tissues. Data were analyzed anonymously.
Statistics Results are as mean ± standard deviation (SD) or standard error of the mean (SEM). Statistical analysis was performed using Graphpad Prism (v5. 0) and R Software v. 3. 3. 2 (R Core  Team, 2016). Comparisons between two groups were assessed using Student t-test. Comparisons between more than two groups were assessed using one-way ANOVA test. Comparisons between paired data were assessed using Wilcoxon signed-rank test. For breast cancer H-score analysis, Shapiro-Wilk normality test and non-parametric Mann-Whitney tests and Wilcoxon signed-rank test for paired data were used. p values less than 0. 05 were considered significant.
Acknowledgements We thank the staff of  Flow Cytometry Core Facility of Institut Curie  for their excellent assistance, the Cell and  Tissue Imaging  ( PICT-IBiSA ),  Institut Curie , member of the  French National Research Infrastructure France-BioImaging  ( ANR10-INBS-04 ),  Chiara Vicario  for discussion and analysis help, and  Hiroaki Kajiho  and  Giorgio Scita  for very kindly sharing their detailed protocols. This work was supported by  Fondation ARC pour la Recherche sur le Cancer  ( PJA 20151203371  to MCP, fellowship to GZ),  Institut national de la Santeet de la Recherche medicale (INSERM ITMO Plan Cancer   2014-2018 ,  PC201530  to MC and MCP),  Association Christelle Bouillot ,  French National Research Agency (ANR) Paris-Science-Lettres Program  ( ANR-10-IDEX-0001-02 PSL ).
Calcium imaging Myotubes grown on glass coverslips were loaded with 4 μM Fura 2-AM for 30 min at 37°C. Cells were incubated in Ringer buffer (125 mM NaCl, 5 mM KCl, 6 mM glucose, 2 mM CaCl 2 , 1. 2 mM MgSO 4 and 25 mM HEPES, pH 7. 4) for 20 min at room temperature to remove non-hydrolyzed fluorophore and complete de-esterification of the dye. Experiments were performed at 37°C under continuous perfusion (2 ml/min) with Ringer buffer using an ECLIPSE Ti-S/L100 microscope (Nikon) equipped with a 20X S-Fluor objective and attached to a lambda-DG4 illumination system. Image acquisition was performed using an Orca-Flash 2. 8 camera (Hamamatsu) with the Nis-Elements AR software. Variations in Ca 2+ levels over time are determined by the ratio between the fluorescence intensities at 340 and 380 nm excitation wavelengths.
05). Finally, effect of ECM overlays on myotube survival was quantified at 5, 7, and 10 dpd by measuring lactate dehydrogenase (LDH) released to the medium from dying myotubes. We found that addition of an ECM overlay significantly increased cell viability at 7 dpd compared to standard conditions (p < 0. 05). At 10 dpd, most of the myotubes are detached in standard cultures, whereas myotubes differentiated under ECM overlays retained ~80% cell viability compared to levels at 5 dpd (100%; p < 0. 001, Figure  1D ). These data support our theory that providing an appropriate protein scaffold to human myotube cultures results in higher attachment and survival and, as a consequence, it produces a significant increase in the maturation levels of these myotubes, which develop spontaneous contractile capacity.
Data expressed as mean ± SEM. 200-500 myotubes were analyzed from at least N = 3 independent experiments; *p < 0. 05 vs. shCtrl. Scale bar = 25 μm. A Novel Functional In Vitro Model that Recapitulates Human Muscle Disorders http://dx. doi. org/10. 5772/intechopen. 75903 our model. Indeed, we observed overexpression of SR-stress-related genes such as GRP78, CHOP, HERP, and spliced XBP1 in shCapn3 myotubes (Figure  4B )  [44] [45] [46]. SR stress leads to the activation of the unfolded protein response (UPR), which involves splicing of X-box binding protein-1 (XBP1) mRNA. After sustained UPR, the transcriptional factor CCAAT/enhancer-binding protein homologous protein is induced, which leads to caspase activation and apoptosis  [47]. Our results indicate that Capn3 deficiency results in significant SR stress that leads to activation of programmed cell death, which is likely caused by reduced protein levels of RyR1 and SERCAs.
Acknowledgements We thank  Dr. Cristina Sánchez  ( Inbiomed ) for lentiviral particles. We thank members of the  Neuromuscular Diseases Research Group at Biodonostia Institute and Dr. Jacobo Paredes (Tecnun)  for helpful discussions and  Dr. Virginia Arechavala-Gomeza  ( BioCruces Health Research Institute, Barakaldo, Spain ) for comments on the chapter. We dedicate this work to all muscular dystrophy patients and their relatives.
Funding This work was supported by the  Carlos III Institute of Health, Ministry of Economy, and Competitiveness in Spain  and co-funded with  European Union ERDF  funds (A. V-I,  PI14/01499 ,  PI17/00676 ), ( A. LdM ,  PI14/00436 ,  PI17/01841 ), the  Basque Government  (A. V-I. , 2016111091),  Diputación Foral de Gipuzkoa  ( A. LdM ,  114/17 );  Duchenne Parent Project España (A. V-I) ;  Asociación Ayuda Enfermedades Raras Solidaridad y Esperanza ; and by an  AFM-Telethon Grant  (A. V-I. , 19125). J. L-E, I. T-O. and G. A. hold PhD fellowships from the  Basque Government ; H. L-F holds a PhD fellowship from  UPV/EHU ; and A. V-I. holds a Ramón y Cajal contract funded by the  Spanish Ministry of Economy and Competitiveness.
Results Over the 4-year study period, 113 cases were reported to hospital emergency departments and 123 cases were reported to the ARS, ie a total of 234 cases. Sixteen cases were excluded, 5 from Saint-Martin/Saint-Barthélémy and 11 duplicate cases derived from the two data sources. These 234 cases comprised 99 cases of isolated poisoning and 46 cases of collective poisoning (an average of 1. 6 ± 1. 5 people [range: 1 to 14] were poisoned during the same meal), i. e. a total of 145 cases of poisoning.
3% of patients. Significant differences in terms of symptoms and signs were observed between the two data sources (hospital emergency departments and private physicians/ARS reports). Cardiovascular symptoms were predominant in emergency department cases, as 70. 7% of cases presented bradycardia (heart rate ≤ 60 bpm) and 33. 7% presented hypotension (systolic blood pressure < 90 mmHg). Cardiovascular symptoms were essentially observed when the patient attended the emergency department within 12 hours after eating ciguatera fish (87. 8%). Nevertheless, cardiovascular symptoms were also observed in one-third of patients who attended the emergency department more than 24 hours after their toxic meal (Fig. 1 ). Severe bradycardia (heart rate ≤ 40 bpm) was observed in 16. 3% of patients (n = 15), and atropine was used in 14 patients.
1% of cases when the patient was seen between 12 and 24 hours and in 36. 8% of cases when the patient was seen more than 24 hours after food intake. The frequency of hypothermia decreased with observation time (73. 5%, 62% and 42%, respectively). Neurological symptoms were more often reported when the patient attended the emergency department more than 24 hours after food intake (95. 2% of cases). "dysesthesia", "paresthesia", "abdominal pain", "vomiting", "nausea", "itching", "malaise", "fever", "vertigo" or a free field concerning the other clinical signs observed. In parallel, a search for ciguatera cases was carried out during the same period in the emergency department databases of the two public hospitals using key words ("cigua", "fish") or ICD-10 code T61. 0: "Ciguatera fish poisoning".
Duplicate cases between ARS reports derived from hospital physicians and cases extracted from hospital emergency department databases were deleted on the basis of date, sex, age and the type of fish incriminated. All cases were taken into account (ARS cases and emergency department cases) to assess the overall incidence of ciguatera and the species involved. Only cases with a complete emergency report or an individual ARS declaration form (indicating the clinical signs) were used to evaluate the clinical characteristics of poisoning. Quantitative variables were expressed as mean ± standard deviation, and qualitative variables were expressed as percentage and relative risk, together with the 95% confidence interval. Spearman's correlation coefficient was used to analyze associations between heart rate, blood pressure and body temperature.
A limit of p < 0. 05 was considered to be significant. All analyses were performed with R v. 3. 0. 2 software. All methods were carried out in accordance with STROBE recommendations. The CIRE and the two hospitals determined it to be in accordance with the French regulations (CNIL authorization obtained) and that the criteria for waived patient authorization had been met. All cases of ciguatera must be reported to ARS in Guadeloupe for investigations. The database created for this study has been anonymised.
Measurements Sociodemographic characteristics, such as sex, age, marital status, educational level, employment, and sexual orientation; and behavioral data, such as previous HIV tests, reason for testing, and number of sexual partners, were obtained from the routine HTC data collection form. Unit of analysis was the individual and not the test, in order to avoid biases due to clients who had undergone more than one test during the study period. For these multi-testers, data from the most recent test was used for analysis. The outcome variable, i. e. , collecting or not collecting the test result was obtained from HTC follow-up data. Non-collection was defined as failing to return for the HIV test results within 30 days after the test. For the telephone survey, a semistructured questionnaire was used.
Procedures Data from the HTC form was collected and anonymized for the analysis. For the telephone survey, data for clients who met the inclusion criteria was copied to a separate list. The list included contact information that a trained health care worker used to try to contact the client at four time-points (May, July, December 2016 and January 2017). At each timepoint, a maximum of two attempts were made per client at two different times during the day. If the individual was located and accepted the interview, the semi-structured questionnaire was applied. Two specialized health researchers categorized the answers to the openended question regarding failure to collect results.