dataesr/scientific-paragraphs-categorization huggingface dataset:
pHH3 labeling Sections obtained as outlined above were kept in 2-M HCl at 50 °C for 30 min, then transferred to 10-mM citrate buffer pH6 at 90 °C for 30 min, chilled in PBT for 20 min and incubated in anti pHH3 rabbit polyclonal antibody (Santa Cruz, sc8656-R; 1:50) for 4 days at 4 °C. The final PBS washes, incubation with secondary antibody using the labeled streptavidin-biotin, DAPI staining, and mounting were performed as described above. Data were collected from eight randomly selected histological sections of the intestines of two animals (n = 2). For comparison, immunofluorescence was also performed in histological sections of the epidermis. The percentages of positive nuclei were obtained independently for each intestinal layer, i. e. , mucosa, submucosa, and serosa, as well as for epidermis tissue.
Each wave lasted approximately 1 min (data not shown). After 1 week of settlement, the four juvenile ampullae were resorbed, and the tunic of the juvenile continued to thicken. Simultaneously, the siphons opened and the cilia in the gill slits of the branchial basket started to beat. Shortly after these events, the first heartbeats were observed. Hemocytes with heterogeneous morphologies and sizes were already present at this stage (Fig. 6e, g ). Thus, by the first week after fertilization, the circulatory system was clearly functional.
Acknowledgements The authors thank  Stefania Gutierrez ,  Luiza Saad ,  Taynan Portal  and  David Soares  for their valuable comments and help. Thanks to  Prof. Regina P. Markus  for availability of the FlowSight cytometer (grant number  FAPESP Temático Multiusuário 2014/20809-1 ). Many thanks to the  CEBIMar  staff for support in the field, and  Sandra Muxel  for technical support with flow cytometry. We also thank  José Marián  and  Fernando Carbayo  for their valuable comments during histological procedures. The authors are also indebted to the  Rudolph Barth Electron Microscopy Platform of the Oswaldo Cruz Institute/Fiocruz.
Funding This work was supported by  FAPESP   2016/07607-6 Grant  to  J. J. ,  FAPESP   JP 2015/50164-5  and  BPE 2019/06927-5  Grants to F. D. B. ,  FAPESP   2018/05923-3  and  2015/14052-8  to L. S. H. ,  ANR-14-CE02-0019-01  and  PICS-CNRS  Grants to S. T. ,  FAPERJ   E-26/111. 705/2011 , E-26/201. 434/2014 , E-26/010. 001823/2015 , E-26/202. 762/2017 ,and  CNPq  Grants  471250/2011-2 , c to S. A. ,  FAPERJ   E-26/203. 021/2018Grant  to C. M. B.
Designing peptides to generate anti-protein abs The 'One Specific Peptide Design' section of the PEPOP 2. 0 web site is dedicated to the prediction of one peptide at a time. This section already existed in the previous version of PEPOP 2. 0 but was updated and enriched with new methods. This section allows defining only a small number of peptides. The peptide is progressively built through 4 steps: the reference segment, the method of extension, the area of extension and the peptide length. At each step, a choice is selected by default so that at the end the peptide can be built automatically. Instead, the user may control the choices and the parameters (the 5 physicochemical and structural criteria: hydrophobicity, accessibility, segment length, β-turn content, WRYP content) at any step. Using this section of PEPOP, we designed a peptide from the 3D structure of the LMW (low molecular weight) form of adiponectin (PDB code: 1C3H).
Each method predicts all the possible peptides. For example, in the case of the prime, ALA, SA, and SAS methods, all the segments determined by Fig. 2  Reactivity of mouse immune serum raised using a "discontinuous" peptide against trimeric full length adiponectin (LMW adiponectin) and a control protein (HSA). The segments composing the peptide are displayed on the surface of the protein PEPOP 2. 0 are individually selected as the reference segment. Thus, the method predicts as many peptides as segments. In this way, the entire surface of the protein is explored. Moreover, using several methods allows the testing of different arrangements of the same segments in peptides. Indeed, as we do not really know what governs the antigenic rules, we do not really know how some peptide characteristics, such as the peptide conformation, the aa position, the aa spacing, or the aa order influence the interaction with the Ab.
The predicted peptides can be visualized on the 3D structure of the protein one or several at a time. Using this methodology we map discontinuous epitopes either recognized by a pAbs on Amm8  [35]   Figure  4  shows three more studies mapping discontinuous epitopes on LiD1 recognized by LimAb7 mAb  [39, 40]  and GAD65 recognized by DPC mAb and Ab54 mAb. Using prime, ALA, and SA methods with a requested peptide length of 10 aa, 456, and 648 peptides were predicted from the 3D model of LiD1  [41]  and the 3D structure of GAD65 (PDB code: 2OKK) respectively. Peptides shorter than 7 aa have been eliminated because it is considered that the peptide is too short to well mimic the discontinuous epitope. Peptides longer than 24 aa have been eliminated due to synthesis performance limitations. Peptides have been synthesized using the SPOT method and their immune reactivities were tested with their respective mAb.
The fourth pair of aa consists of one of the two aa of the second pair and the most distance of all the surface-accessible aa of the protein. The fifth pair of aa is the most distant pair where one is one of the two aa of the third pair and the other is found among all the surface-accessible aa of the protein. Web interface PEPOP 2. 0 has been implemented on a virtualized Linux server kernel 2. 6 running the Apache web server version 2. 2. 15. The tool has been implemented in object-oriented PHP and JavaScript, and uses scripts and software developed in PERL, C, and C++. Segments, clusters, and peptides identified by PEPOP 2. 0 can be directly visualized on the 3D structure of the Ag thanks to jsmol. PEPOP 2. 0 is available at https://www. sys2diag. cnrs. fr/index. php?page=pepop.
Funding This work was supported by grants from the  Ministry of Research (France) ;  University Paris Diderot ,  Sorbonne Paris Cité (France) ; the  National Institute for Blood Transfusion (INTS, France) ; the  Brazilian institutions CAPES ,  FAPEMIG  and CNPQ; the  Institute for Health and Medical Research (INSERM, France) ; and a  Labex GR-Ex grant (France)  to  Alexandre G. de Brevern. The  Labex GR-Ex , reference  ANR-11-LABX-0051 , is funded by the program " Investissements d'avenir " of the  French National Research Agency , reference  ANR-11-IDEX-0005-02. The funding body had no role in the design and collection of the study, experiments, analyses and interpretations of data, and in writing the manuscript.
It is worth noting that Tspan15knockout cells are not the perfect negative control for ADAM10 detection in this experiment, because ADAM10 expression is reduced by 60% in these cells. Hence, in Fig. 5 , the 400-fold ADAM10 enrichment in the WT cells may be a slight overestimation. These data are consistent with two previous studies in which GFP-tagged Tspan15 was expressed in U2OS or HepG2 cells, which were lysed in relatively nonstringent 1% Brij97 and Tspan15 immunoprecipitated via the GFP tag  (12, 20). For example, MS identified ADAM10 as 15-fold more abundant than any other Tspan15-interacting proteins  (12). However, interpretation was complicated in these two studies because of the use of less stringent detergent and the resulting large number of tetraspanin-associated proteins identified, the majority of which are likely to be indirectly associated with Tspan15.
The findings of our study lead us to speculate that Tspan15 may be promoting cancer via ADAM10, most likely due to cleaving of specific substrates that enhance the cancer phenotype. Interestingly, gene expression data suggest that Tspan15 is strongly up-regulated in cholangiocarcinoma and pancreatic adenocarcinoma  (38)  and is a marker of poor prognosis in pancreatic, renal, and liver cancer  (18). Moreover, Tspan15 has been recently implicated in oral squamous cell carcinoma  (19)  and hepatocellular carcinoma  (20). The generation of mAbs to certain tetraspanins is a recognized difficulty in the tetraspanin field; there are no mAbs to many of the 33 human tetraspanins. To initiate this study, we generated the first Tspan15 mAbs using a novel strategy. Mice were immunized with ADAM10-knockout MEFs stably overexpressing human Tspan15, with the aim of focusing the mAb response on Tspan15 and preventing the larger ADAM10 from masking epitopes or preventing mAb binding by steric hindrance.
Nevertheless, our data are comparable with the previously reported inhibitory activity of a Tspan5 mAb toward ADAM10/Tspan5 in Notch activation  (15). TspanC8 mAbs therefore have potential as therapeutics to treat human diseases promoted by ADAM10. To conclude, our findings strongly suggest that Tspan15 exists as an ADAM10/Tspan15 scissor complex, which may be a general theme for the other five TspanC8s. We therefore propose that ADAM10 be studied in the context of its associated TspanC8. This has implications for future work that should aim to determine how ADAM10/TspanC8 complexes are triggered to cleave specific substrates and whether ADAM10/TspanC8 complexes can be therapeutically targeted to treat human disease.
Generation of CRISPR/Cas9-knockout cell lines Two guide RNA sequences were selected for each of human ADAM10 and Tspan15 using the Wellcome Trust Sanger Institute's CRISPR Finder tool  (47). The following primer pairs were used to encode these sequences: ADAM10 guide 1 (5Ј-CACC-GCGTCTAGATTTCCATGCCCA-3Ј and 5Ј-AAACTGGGC-ATGGAAATCTAGACGC-3Ј); ADAM10 guide 2 (5Ј-CACC-GATACCTCTCATATTTACAC-3Ј and 5Ј-AAACGTGTAA-ATATGAGAGGTATC-3Ј); Tspan15 guide 1 (5Ј-CAC-CGGCGCGCGCTTCTCCTACCTC-3Ј and 5Ј-AAACGAGG-TAGGAGAAGCGCGCGCC-3Ј); Tspan15 guide 2 (5Ј-CAC-CGAGCGCCCAGGATGCCGCGCG-3Ј and 5Ј-AAACCG-CGCGGCATCCTGGGCGCTC-3Ј). Each primer pair was annealed and cloned into the pSpCas9 (BB)-2A-Puro (PX459) plasmid (a gift from Feng Zhang, Addgene plasmid 62988)  (48). Cells were transfected with either of the guide constructs; clonal transfectants were selected using 1, 2.
Protein structure prediction and computational modeling The structure of human Tspan15 (UniProt accession number O95858) was predicted and modeled using Phyre2 (51) under intensive mode and visualized with PyMOL. The model generated yielded 100% confidence for 78% of the total protein length, based on the crystal structure of human CD81 (Protein Data Bank code 5TCX)  (5). In particular, residues 16 -190 and 209 -261 were built with 100% confidence, whereas the remainder of the residues, primarily located on the loops, were built ab initio, corresponding to lower-confidence regions.
Data analysis and label-free quantification The raw data were analyzed by Maxquant software (Max-Planck Institute Munich) version 1. 6. 6. 0  (53). The MS data were searched against a fasta database of Homo sapiens from UniProt (download: June 12, 2019; 20,962 entries). Trypsin was defined as the protease. Two missed cleavages were allowed for the database search. The option first search was used to recalibrate the peptide masses within a window of 20 ppm. For the main search, peptide and peptide fragment mass tolerances were set to 4. 5 and 20 ppm, respectively. Carbamidomethylation of cysteine was defined as static modification. Acetylation of the protein N terminus and oxidation of methionine were set as variable modifications. The false discovery rate for both peptides and proteins was adjusted to less than 1%.
Label-free quantification of proteins required at least two ratio counts of unique peptides. Only unique peptides were used for quantification. The option "match between runs" was enabled with a matching time of 1 min. The protein label-free quantification intensities were log 2 -transformed, and a two-sided Student's t test was applied to evaluate the significance of proteins with changed abundance between the TSPAN15 immunoprecipitation from WT samples and the control immunoprecipitation from Tspan15-knockout samples. Additionally, a permutationbased false discovery rate estimation was used  (54). The MS data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository  (55)  with the data set identifier PXD016508.
Molecular brightness of complexes was determined using PCH analyses carried out on the same fluctuation traces as used for autocorrelation analyses using Zen 2012. Traces were binned at 100 s and fitted to either a one-or two-component PCH model with the first-order correction fixed at 0. 3, as determined from the calibration read. Data are shown as values obtained from individual cell membranes, obtained over n independent transfections.
Edited by Peter Cresswell This work was funded by a  British Heart Foundation   Ph. D. Studentship Grant   FS/18/9/33388  and  COMPARE  (to C. Z. K. ),  Biotechnology and Biological Sciences Research Council  Project Grant  BB/P00783X/1  (to N. H. ),  British Heart Foundation  Project Grant  PG/13/92/30587  (to P. J. N. ),  Biotechnology and Biological Sciences Research Council Ph. D. Studentships  (to J. S. and A. L. M. ), and a  Biochemical Society Summer Vacation Studentship  (to H. T. H. N. ). This work was also supported by the  Deutsche Forschungsgemeinschaft (German Research Foundation ) within the framework of the  Munich Cluster for Systems Neurology (EXC 2145 SyNergy , project  ID 390857198 ) and by the  BMBF  through CLINSPECT-M (to S. F. L. ). Further support was provided by  Deutsche Forschungsgemeninschaft  Grant  DFG-SFB877-A3  (to P.
E. S. S. J1745-303  [24] , and a diffuse emission extending along the Galactic plane  [25, 26]. The rich observational dataset obtained from deep observations of the GC region by the H. E. S. S. phase-I instrument has been used to look for continuum and line signals from DM annihilations. Standard analyses of H. E. S. S. -I observations of the GC region provided about 250 hours of live time in the inner 1 • of the GC. H. E. S. S. searches have been performed with 10 years of data of the 4-telescope array towards the GC for the continuum  [27]  and mono-energetic gamma line  [3]  channels, respectively, using a 2-dimensional likelihood ratio test statistics to look for any possible excess over the measured background. In order to avoid modeling the complex standard astrophysical background in the GC region, a region of ±0.
p9MSSM scanning setup and constraints We apply the projected sensitivity reach of CTA as calculated in Sec. 2 to the case of the MSSM parametrized by 9 free input parameters. The parameters that we scan over and their ranges are shown in Table  2. We employ the Multinest v. 2. 7  [42, 43]  package for the scan, using flat priors. In order to ensure the best coverage of the parameter space of the model, several independent scans with 20, 000 live points each have been performed and the resulting points have been combined when presenting the results. The supersymmetric spectrum is calculated with SPheno v4. 0. 3  [44, 45]. We allow the bino mass M 1 and the µ parameter to assume negative values in order to accommodate blind spots in DM direct detection  [46, 47] , which stem from the vanishing hχχ coupling for certain combinations of parameters (see also  [48]  for a recent discussion).
At present, the only public code that gives the relic density with the SE included for a generic neutralino and all possible co-annihilation partners in the general MSSM is DarkSE -a package written for DarkSUSY v5  [63]. 2  A complete numerical treatment of the SE is very CPU-expensive and thus cannot be handled automatically in a scan. Therefore, we have adopted a two-step approach: 1) in the scan we use micrOMEGAs and include the SE by rescaling the result using a grid of the enhancements in the M 2 -µ plane following the procedure of  [10] ; 2) the final points are then post-processed with the accurate SE treatment using full DarkSE code. Sommerfeld enhancement is also included in the computation of the present-day σv 0 , as well as for σv γγ and σv Zγ. 3 Ideally, one could use an approximate simplified treatments of the SE for the first step, as in, e.
In order to accommodate such scenarios, we additionally present results for the aforementioned case 2 but without rescaling σv 0. Dark matter direct detection The steady progress observed in recent years in direct detection (DD) searches for DM in underground liquid noble gas detectors has led to strong upper limits on the spin-independent cross section of the neutralino scattering off nucleons. We include the most recent DD bounds here. For this we employ SuperIso Relic v4. 0 [86] and the DDCalc v. 2. 0. 0 package  [87] , assuming the Standard Halo Model (SHM) and the following values for the relevant astrophysical parameters: ρ 0 = 0. 39 GeV/cm 3 , v rot = 220 km/s, v esc = 544 km/s. We note that slight modifications to the SHM that might be suggested by e. g. recent data release by the GAIA Collaboration  [88] , see e.
E. S. S. and in dSphs by Fermi-LAT (see  [13]  for recent discussion). A recent determination  [133]  of the bounds on the neutralino annihilation cross section from AMS-02 antiproton cosmic-ray (CR) data  [134]  has proven to be competitive with H. E. S. S. diffuse γ-ray searches in the ∼ TeV mass range. We have verified that this is in general true also in the context of our scans using SuperIso Relic v4. 0  [86]  that employs a semi-analytic approach to solving the propagation equations following  [135]. However, the limits that one derives from the AMS-02 data depend on the assumed CR propagation model and suffers from large astrophysical uncertainties (see, e. g. , Refs. [136, 137] ). For this reason, we do not discuss them in details in the following section, which focuses on DM-induced γ-ray signal.
Acknowledgments We would like to thank  Alexander Pukhov  for providing a refined micrOMEGAs module that calculates annihilation cross section to monochromatic photons. We would like to thank  Martin Vollmann  for useful discussions. This research has made use of the CTA instrument response functions provided by the  CTA Consortium and Observatory , see http://www. cta-observatory. org/science/cta-performance/(version prod3b-v1) for more details. K. J. ,  L. Rosz. and S. T. are supported by the  National Science Centre (NCN)  research grant No. 2015/18/A/ST2/00748. L. Rosz. is also supported by the  National Science Centre  research grant No. 2016/22/M/ST9/00583  and by " Astro-CeNT: Particle Astrophysics Science and Technology Centre  project that is carried out within the  International Research Agendas programme of the Foundation for Polish Science co -financed by the  European Union  under the  European Regional Development Fund.
The large database generated by this study also enables exploration of the symptom itch in the group of all skin patients, as well as the assessment of the distribution of itch in different skin diseases. Moreover, the data allows the comparison of the occurrence, chronicity and intensity of itch between patients with skin diseases and healthy-skin controls. The aims of the study are: (i) to describe the occurrence of current (acute) and chronic itch (itch lasting longer than 6 weeks) as well as the intensity of current itch in skin patients compared with healthy-skin controls; (ii) to describe the occurrence of current (acute) and chronic itch (itch lasting longer than 6 weeks) as well as the intensity of current itch among patients with different skin diseases; (iii) to determine whether skin patients with itch differ from skin patients without itch and healthyskin controls regarding age, sex and the occurrence of physical comorbidities.
Study design A secondary analysis of data that have already been published (13) was conducted. However, it should be emphasized that data on the occurrence, chronicity and intensity of itch from this database have not been published previously. The investigation was an observational cross-sectional multicentre study with 15 sites in 13 European countries  (13). Out-patients in secondary and tertiary care were recruited from 15 dermatological clinics between November 2011 and February 2013. The study protocol was that, at each clinic, consecutive patients were invited to participate in the study until 250 patients were included (for the exact numbers recruited in each country, see  (13) ). The participation rate was 79. 9%  (13). The inclusion criteria were age at least 18 years and being able to read and write the local language.
Statistical analyses Data were entered into a database at each site and sent to the Statistical Center in Giessen, Germany. The data were consolidated into a single file. SPSS version 22 software (IBM Corp, released 2013) was used to process and analyse the data. To characterize the sample, we report numbers, percentages with 95% confidence interval (CI), or mean values with standard deviation (SD). To compare patients and healthy-skin controls, we used t-tests for continuous variables and χ 2 tests for dichotomous or categorical variables. We describe the occurrence of physical comorbidities with number and percentages with 95% CI. Multivariate logistic regression analyses were conducted to study the associations between the occurrence, chronicity and groups, adjusted for sex and age. Odds ratios (ORs) were calculated using the regression coefficients β from the regression models.
ACKNOWLEDGEMENTS Funding. South-Eastern Norway Regional Health Authority granted scholarship for the study to FJD, but had no influence on the study design, in the collection of data and data analysis, and interpretation of data, in the writing of the report, and in the decision to submit the paper for publication. Conflicts of interest. LM report  Astellas ,  Celgene ,  Expanscience ,  Johnson&Johnson ,  Novartis ,  Pierre Fabre ,  Sanofi. FS has been a consultant for  Janssen and Abbvie. FP has been consultant for  Leo-Pharma. AYF has received honoraria for consultancy with travel expenses from  Galderma ,  Novartis ,  Napp ,  Sanofi ,  Archimedes ,  Amgen. GBEJ is a consultant and investigator for  AbbVie and Novartis , has received unrestricted grants from  AbbVie ,  Leo Pharma  and Novartis; sits on  Advisory Boards of AbbVie ;  InflaRx, LEO Pharma ,  Novartis ,  Janssen Pharmaceuticals, Pierre Fabre , and  UCB ; and is Investigator for AbbVie,  InflaRx ,  Novartis ,  Regeneron ,  Sanofi  and  UCB.
Results and discussion Figure  1  presents the weight range within each packaged dozen. It appears that none of the dozens respects the weight specification given by the manufacturer. The analysis of weight range of the shafts within a same size highlights the difference of 11. 64 grains between the lighter and heavier 380 shaft. For all the other stiffness, the overall ranges values went from 1. 96 to 3. 69 grains. From Equation (3), for equal bow energy, the velocity of the arrow after release decreases if its mass increases. Moreover, Equation (  7 ) show that the arrow mass will also affect its acceleration on both axes. The equations are solved with Matlab basic ordinary differential equations solver ode45 to give the trajectory of the arrow in the plane (x, y). Realistic parameters are selected for the computation.
Scientific Observations Seismicity. During the fifty years since the 1963 eruption, almost no local earthquakes were recorded on the CVGHM network at Mount Agung, and seismic energy was dominated by cultural noise from the south flank of the mountain. As of 2017, the seismic monitoring network consisted of two short-period stations on the south and southwest flanks of Mount Agung ~4 and 5 km from the summit and four short-period stations in the Batur Caldera (Fig. 1A ). Throughout the crisis, the primary data streams used to monitor unrest were realtime seismic data from the CVGHM network and earthquake hypocenters from the Indonesian Meteorology, Climatology, and Geophysics authority (BMKG). The CVGHM network was used to make visual observations, conduct daily earthquake counts, and compute RSAM (Real-time Seismic Amplitude Measurement).