dataesr/scientific-paragraphs-categorization huggingface dataset:
Contribution to the UGGp Conception The conduction of the GIS database reinforces four relevant issues in the conception of an UGGp: cooperation, territorial unity, visibility and corporate identity. The cooperation was promoted by the collaborations among the UGGp staff, scientists, local administrations, companies and local people during the initial data acquisition, involving information from local and regional actions (e. g. , Bioblitz Courel project, micro-reserves project). This networking agrees to the bottom-up approach of the UGGp and reinforces the participation and understanding between the actors involved in the UGGp. The territorial unity was reinforced by the creation of a unique database for the entire UGGp, homogenising information along the area. This result is key to blur the limits between municipalities and villages, strengthening the UGGp as a unified geographical area.
Another contribution of the GIS database is the promotion of the visibility of the UGGp, creating new maps for outreach activities, including dissemination, publications and online resources. In the future, the database can supply information for the development of web visors and mobile applications of the UGGp  (Luo 2015; Hartoko et al. 2018; Nurpandi et al. 2020). For that, the UGGp is well-equipped to edit its own maps adapted to final purposes and users, showing an end product whose main authorship already belongs to the UGGp. In addition, the silhouette of UGGp maps is already part of the singular identity of the Courel Mountains. Altogether, the GIS database and the produced maps promote the corporate identity of the UGGp, reinforced by its territorial unit and visibility.
Conclusions A GIS database has been developed to assist the management of the Courel Mountains UGGp. The database includes 66 coverages storing technic, geoscientific, ecological and cultural data based on open sources, works, fieldwork, photointerpretation and GIS analyses. The methodological procedure implies an efficient acquisition, homogenization and validation of the archived data, which can be easily updated in the future. The combination of selected coverages allows for the elaboration of thematic maps showing specific relationships between Earth processes, biodiversity and human history. The maps are adapted to different final purposes and users, from general audiences to specialists. In addition, the GIS maps reinforce the territorial unity, visibility and corporative identity of the UGGp, as well as the cooperation between managers, scientists and local administrations, companies and people.
The GIS coverages contain the necessary knowledge for the successful development of educational, tourism and geoconservation programmes of the UGGp, representing also useful support for scientific research. The design of educative and touristic actions is assisted by a database related to all the topics of the Courel Mountains, including Global Change, geological hazards, Earth resources and local and indigenous knowledge. The GIS facilitates the geoconservation strategy based on protected areas, land use practices, geological hazards and natural and cultural heritage. Altogether, the database is key for the identification and evaluation of potential alternatives undertaken during the policy-making for the development of the UGGp.
Our results show that the application of the GIS database is a powerful tool to implement scientific knowledge into the education, tourism, research and conservation programmes of the UGGp, which are the four pillars of UGGp management (e. g. , Zouros 2016). GIS maps provide an overview of thematic features of the Courel Mountains and constitute easy-to-understand resources employed in outreach activities, interpretation centres, scholar projects and training workshops for guides. As shown in the 'Results' section, a large variety of themes can be performed, including common topics relevant to UGGps, like global change, geological hazards, Earth resources, and local and indigenous knowledge (Henriques et al. 2012; Álvarez 2020 ).
Acknowledgements This work was developed in the framework of the  Scientific Program  of the Courel Mountains UGGp with the cooperation of tourism agents ( A. M. Arza  and  A. López ), roofing slate quarries ( Pizarras de Villarbacú ,  Pizarras de Quiroga ) and local people ( M. Reinosa ,  G. Díaz ,  O. Álvarez ). We are deeply grateful to  J. R. Martínez Catalán  ( Universidad de Salamanca ),  A. Pérez-Alberti  and  J. Guitián  (both from  Universidade de Santiago de Compostela ), J. R. Gutiérrez-Marco  ( ICOG, Universidad Complutense de Madrid/CSIC ),  J. Vegas  ( IGME-CSIC ),  L. González-Menéndez  ( IGME-CSIC ),  J. M. García Queijeiro  ( Universidade de Vigo ),  L. Santos  and  A. Grandal-D'Anglade  (both from  Universidade da Coruña ) for their assistance supplying information involved in the database.
Current population hand scanning The data for the modern sample was taken during practical workshops in Primary and Secondary Schools, College and cultural activities (Sup. 3). In total, 545 participants took part in the process, all of them from Spain. Hands of 545 individuals were scanned with an Epson Stylus SX125 contact image scanner to which was added a scale, thus acquiring real and proportional measurements. Each participant was asked for his/ her biological sex and age for the subsequent classification. For underage individuals a written permit was asked by tutors or parents. No other personal data was asked or registered. Although both of the hands were scanned for each participants only the left ones were taken into account in the study. This experiment has been approved by the Ethics Committee of Cantabria University following all the values and regulations asked and having the informed consent of all the participants and/or their legal guardians.
For the hand, we have connected the most external part of the middle finger in its central axis with the union point between the palm and the wrist on the thumb side. AutoCAD® was chosen to measure the sample of modern hands, as it allowed each sample to be scaled with a physical scale introduced in the scanner, as well as because of the precision of its calculations. Together with it, Blender® software was the tool used to take measurements from the photogrammetric models of the archaeological sample. The statistical study was performed with the freeware programmes JMP Pro 14® and PAST®. First, the modern sample was characterised, as it formed the reference framework into which the archaeological record would be inserted. In this way, this sample was studied by univariate and multivariate analysis and also by Principal Component Analysis (PCA).
Accuracy of the biometric parameters in the modern population A key step in the statistical study was to determine the efficacy of the parameters being used. This has tested the appropriateness of the potential parameters for the study: length and width of the hand and fingers in order to classify the individuals in their correct age stage. First the featured intervals were calculated for each age group based on their hand and fingers length and width, with the values between 25 and 75 percentiles (Sup. 4). Then this modern sample was reclassified with the data obtained for the parameters and the real and suggested results were compared. These intervals will later be used to classify the archaeological data. Traditional studies focusing on establishing the sex of an individual have focused attention on specific body parts that have been shown to confer a high degree of accuracy quantified at well over 80%.
Acknowledgements The authors would like to express their gratitude to the project " Handpas. Hand from the past" (Create Europe  Project  2014-2016  of the  European Commission ) for facilitating access to their documentation by the present study, and especially to  H. Collado , co-director of the project. They also thank  I. Libano ,  M. Á. Medina  and  I. Intxaurbe  and  Before Art  members for their collaboration in the archaeological experimentation, and  Colegio Atalaya (Santander)  for helping with the biometric modern data used. The author V. Fernández-Navarro is beneficiary of a "Concepción Arenal "  2020-21  pre-doctoral contract at the  University of Cantabria  for research towards the doctoral thesis titled "From the hand to the mind: demography and semiotics of Palaeolithic artists through the representation of hands", of which the present study forms part.
E. Camarós is recipient of a grant from the  Marie Curie Fellowship (IF)   2020-21  programme and  D. Garate  has a research contract within the  "Ramón y Cajal" programme  of the  Ministry of Science and Innovation of the Government of Spain. The present study has been conducted as part of the research project " Before art: social investment in symbolic expressions during the Upper Palaeolithic (B-Art )" (PID  2019-107262 GB-I00 ), funded by the  Ministry of Science, Innovation and Universities  ( MCIN/ AEI /10. 13039/ 501100011033 ), PI:  Diego Garate. This study is also a part of the research project " From the Mind to the Wall: Tracing Sign Language in Palaeolithic Hand Stencils (MIND2WALL) " ( ANR-21-CE27-0005 ), funded by the  French Ministry of Culture , PI:  Aritz Irurtzun.
S1 ). Viruses were cultured in the presence of RDV at 0-1. 0 μM final concentration for 48 hours and luciferase activity was measured and normalized against control without RDV treatment (0 μM final concentration). The 50% effective concentration (EC50) was calculated using the drc package (v3. 0-1; R Project for Statistical Computing). All tested mutant viruses showed greater EC50 than WT virus, although the difference between WT and F480L mutant was small, indicating that the mutations observed in NSP12 led to decreased viral sensitivity to RDV.
Virus-infected cells were harvested and fixed from 12-72 hpi and subjected to immunofluorescent assay using anti-SARS-CoV-2 NP antibody and DAPI. The virus infection rates were then calculated. All the mutant viruses demonstrated equivalent or significantly lower virus infection rates compared with WT virus in the absence of RDV. These data suggested that the number of cells infected with mutant viruses increased more slowly compared with WT virus in the absence of RDV treatment, consistent with the data on production of infectious virus particles. Meanwhile, the infection rates of the presumed RDV-resistant mutant viruses, except for D484Y, were higher or significantly higher (R10/E796G/C799F at 48 and 72 hpi, and R10/C799F at 72 hpi) than those of WT virus at 48 and 72 hpi in the presence of RDV, indicating that these mutant viruses can spread more efficiently than WT virus in the presence of RDV.
Antiviral effect of RDV on the presumed RDV-resistant mutants, analyzed by mathematical modeling To quantify the kinetic parameters of SARS-CoV-2 and the antiviral effect of RDV on WT and RDV-resistant viruses, we developed a mathematical model for SARS-CoV-2 infection under RDV treatment. We examined the growth rate of HEK293-C34 cells up to 48 hours after seeding (Fig. S2A ), the degradation rate of SARS-CoV-2 at 37°C (Fig. S2B ), the infectious virus production rate for 96 hours (Fig. 2A  and B ), and the rate of infection in susceptible cells (Fig. 2C  and D ). These estimated parameters were fixed and used here. To consider the variability of kinetic parameters and model predictions, we performed Bayesian estimation for the whole dataset using Markov chain Monte Carlo (MCMC) sampling, and simultaneously fit equations (1-4) with RDV (𝜺 > 𝟎) and without RDV (𝜺 = 𝟎) to the concentrations of target cells, infected cells, and infectious virus (see Method and Fig.
Immunopositive signals were confirmed under a FluoView FV1000 confocal laser scanning microscope (Olympus), with appropriate barrier and excitation filters. Quantitative imaging data were obtained using a CellVoyager CQ1 benchtop high-content analysis system (Yokogawa Electric Corporation) and analyzed with CellPathfinder high content analysis software (Yokogawa Electric Corporation). The number of SARS-CoV-2-infected cells stained by anti-SARS-CoV-2 NP antibody and the number of cell nuclei stained by DAPI were counted. The infection rates were then calculated by dividing the number of SARS-CoV-2-positive cells by the total number of cell nuclei.
Theoretical predictions and analyses of the effects of amino acid mutations The WT NSP12 structure used as a reference was created based on the crystal structure (PDB ID: 6XEZ)  (40). From this crystal structure, only the NSP12 protein and 28 bases of the binding RNA (binding site) were extracted. The target mutant structures were constructed by substituting amino acids in the above WT structure. Based on the crystal structure (PDB ID: 7BV2) (41), the terminal nucleotides of each predicted structure were replaced with RDV. To neutralize the charge of these complex structures, counter ions were placed, and sufficient water molecules were placed around them. Each structure was stabilized by the energy minimization method and used as the initial structure for molecular dynamics simulations. The composite structure was thermally stabilized by raising the temperature from 0 K to 310 K (in vivo temperature, approximately 36.
85°C) over 500,000 steps with Δt = 0. 2 fs. The structural changes during this temperature increase process were structurally sampled for each complex at every 1000 steps. These sampling structures were superimposed, and the RMSD for each protein was calculated. In addition, to observe the extent to which the structural properties differed between WT and mutants, we superimposed them in various substructures and calculated and compared the RMSD differences. These energy minimizations and molecular dynamics simulations were performed with the AMBER18 program package  (42). The "AMBER99 (43)", "GAFF (44)" and "TIP3P (45)" force fields for the "proteins and nucleic acids", "RDV", and "water molecules" were employed, respectively.
Statistical analysis Results are indicated as the means ± standard deviations or standard errors. Statistical significances were determined by the one-way ANOVA with Dunnett's test or the Kruskal-Wallis test with the two stage linear step-up procedure of Benjamini, Kreiger, and Yekutieli, which was performed using GraphPad Prism (Software ver. 9. Virus-infected cells were fixed and stained with antibodies for SARS-CoV-2 and cell nuclei. Infection rates were calculated by dividing the numbers of virus-positive cells by the numbers of nuclei. Statistical significances were determined by one-way ANOVA with Dunnett's test. Significant differences compared with WT virus are indicated by asterisks (***p<0. 001).
Acknowledgments We thank  M. Tomiyama  for her secretarial work,  M. Ishibashi  and  K. Toyoda  for their technical assistance. We also thank  Dr. Dr. Masayuki Shimojima  at  NIID  for providing SARS-CoV-2 strain JPN/TY/WK-521 and Bio Matrix Research for providing anti-SARS-CoV-2 NP monoclonal antibodies. This study was supported in part by a  Grant-in-Aid for JSPS Scientific Research (KAKENHI)   B 21H02736  (to T. F. ),  18KT0018  (to  S. Iwami ),  18H01139  (to  S. Iwami ),  16H04845  (to S. Iwami),  20H04281  (to T. S. ),  Scientific Research in Innovative Areas   20H05042  (to S. Iwami),  19H04839  (to S. Iwami),  18H05103  (to S. Iwami),  20H04841  (to T. S. );  AMED   CREST 19gm1310002  (to S. Iwami);  AMED Japan Program for Infectious Diseases Research and Infrastructure ,  20wm0325007h0001  (to  S.
Real-Time Quantitative RT-PCR Total RNA was extracted using the RNeasy minikit (QIAGEN, Valencia, CA, USA) and reverse transcription was carried out using the high capacity kit (Applied Biosystems, Foster City, CA, USA) according to the manufacturer's instructions. The 7900HT Fast Real-Time PCR System (Applied Biosystems) and SYBR-green labeling were used for quantitative RT-PCR (RT-qPCR). The comparative ∆∆cycle threshold method was used to determine the relative quantities of mRNA using ACTB (ß-actin) mRNA as reference gene for normalization. Each RNA sample was analyzed in triplicate. The results are presented in histograms showing the relative expression of the studied marker with standard error of mean (sem). The sequences of oligonucleotides used with SYBR-green detection were designed with Primer Express Software and are illustrated in Supplementary Table  S1.
Single Cell RNA Seq Two sets of 25 EBs at day 4 were washed in PBS and dissociated with TrypLE Express for 30 to 60 min at 37 • c with repeated flushing, and the reaction was stopped with medium plus KSR, and cells were centrifuged at 300× g for 15 min and resuspended into PBS-BSA 0. 05%. Single-cell suspensions from day 4 EBs were pooled before Hoescht 33258 staining. Total viable cells were flow-sorted, the cells were counted and 4. 000 were loaded onto the Chromium 3 chip. Reverse transcription, library preparation and sequencing were performed according to the manufacturer's recommendations (10× Genomics, Pleasanton, CA, USA). Two replicates were performed for the scRNAseq study. Samples were sequenced on a single run with the NovaSeq 6000 system (Illumina, San Diego, CA, USA). Data were preprocessed with Cell Ranger software v6.
1. 2 from 10× Genomics. For analysis of scRNA-seq data, Seurat package v4. 0. 4 was used in R version 4. 1. 1 [23]. Separate preprocessed data sets were merged into one Seurat object and analyzed. Data were log-normalized and scaled. Principal component analysis (PCA) was performed based on the 3000 most variable genes, selected using the vst method and 20 PCA dimensions were used for graph-based clustering with a resolution of 0. 8. Clusters were visualized with a UMAP algorithm. When zooming in, 20 PCA dimensions were used for graph-based clustering. A cluster of cells with higher level of mitochondrial genes, low count of genes and no POU5F1 expression (cluster 3) was removed before reclustering using a resolution of 0. 5 and 20 PCA dimensions. The cluster of PGC-like cells was used for subclustering with a resolution of 0.
Sections were then blocked either in 2% horse serum, and the slides were mounted with the Vectashield 4,6-diamidino-2-phenylindole (DAPI) medium (Vector Laboratories, Newark, CA, USA). Imaging was performed using a Leica DM5500 B epifluorescence microscope (Leica Microsystems, Wetzlar, Germany) equipped with a CoolSNAP HQ 2 camera (Photometrics) and Leica MMAF software (Metamorph). Images were processed with Image J software.
In order to isolate PGC-LC, we searched for a specific membrane-bound antigen and therefore assessed PDPN, which was detected on the mRNA level through scRNA-seq analysis. In day 4 EBs, the PDPN protein was detected at the surface of cells resembling hPGC-LCs by IHC (Figure  3D ). Of interest, more than 90% of PDPN-positive cells were also stained for POU5F1, confirming the PGC-like identity of these cells (Figure  3E ). On the other hand, very few somatic-like cells presented a staining for PDPN (1. 01 ± 0. 20% of POUF1-negative cells were PDPN-positive, n = 4), indicating a specific presence of the protein at the membrane of hPGC-LC and contrasting with scRNA-seq data (62. 8% of somatic-like cells expressing the PDPN mRNA, Figure  2E ). The same PDPN antibody was used for hPGC-LCs sorting from day 4 dissociated EBs.
Altogether, these data show that the hanging drop culture system allows the further differentiation of hPGC-LCs with transcriptional levels of late PGC and meiotic genes expression similar to the human fetal ovary control (7. 8 to 10 GW). Since little difference was observed between +D6 HD and +D8 HD with or without RA in terms of late PGC and meiotic genes expression, the +D6 HD was selected as the optimal condition for the following experiments. To confirm that induced hPGC-LCs gained further differentiation in hanging drop EBs, the presence of DDX4 and SYCP3 proteins was investigated by immunofluorescence. In PB12 hiPSCs-derived EBs, DDX4 and SYCP3 were completely absent at day 4 of culture (Figure  7A ). However, after an additional 6-day culture in the hanging drop (+D6 HD) we retrieved DDX4-positive cells in EBs without any detection of the SYCP3 protein (Figure  7A ).
Acknowledgments: We thank  Alexandra Plancheron  from iSTEM for technical training in iPS culture method and  Aurélie Gouret  for her secretarial assistance. We are indebted to  Kazuyuki Ohbo  for generously providing OCT4-GFP mice. We also thank  Clémentine Lapoujade  and the iRCM platforms, notably the animal housing and experimentation facilities, and particularly  Véronique Neuville ,  Vilma Barroca  and C,  Guillaume Piton  from the Genetic engineering and protein biochemistry platform and the  Flow Cytometry Shared Resource , headed by  Jan Bayer. We greatly acknowledge  Tracy Dagher  and  Dana Alawie  for English language correction.
Funding: This research was funded by  Institut Universitaire de France  (GL),  Electricité de France ,  Agence nationale de sécurité sanitaire de  l'alimentation, de l'environnement et du travail ( BODY EST-2017-43/2 ) and  Université Paris Cité. B. A. holds a fellowship from  DIM Biothérapies Région Ile de France  ( DIMBIO 2014 , # 14011253 ). Institutional Review Board Statement: Animal studies were conducted in accordance with the  French Ministry of Agriculture  guidelines for the care and use of laboratory animals and human fetal gonad protocol was approved by the  French Biomedicine Agency  (authorization number  PFS12-002 , 2012, last modified 2021). Informed Consent Statement: Informed consent was obtained from all women involved in the study.
Study Design The data from this study were collected within the "dsd-LIFE" study, a European multicenter cross-sectional study funded by the European Commission (7th Framework Program, FP7). From February 2014 to September 2015 participants were recruited in 14 specialized clinical centers in 6 countries (France (n = 4), Germany (n = 4), Poland (n = 2), the Netherlands (n = 2), Sweden (n = 1) and the United Kingdom (n = 1)). Patients were enrolled if they had a medically confirmed clinical or genetic diagnosis of DSD, were at least 16 years of age, and presented to a study center at least once during the course of the study. Patients who did not fulfill the diagnostic criteria or could not consent nor answer the questionnaire by themselves, were excluded. A total of 1040 patients met the inclusion criteria and of these, 203 were females diagnosed with CAH and were therefore included in the study.
Ethical approval was received for each study center and all participants gave written informed consent. The study consisted of 2 parts: the first part took place at the respective study center and consisted of a medical interview and an optional medical examination; the second part consisted of a digital patient-reported outcome (PRO) questionnaire and was filled out online. If necessary, a paper pencil form was available. All medical data were pseudonymized and reviewed regarding accuracy of statement. Further information on the theoretical and methodological background of the study can be found elsewhere  [41]. Sociodemographic data were collected using the European Social Survey (ESS Round 7, 2015) as well as self-constructed items. The educational status of the participants was measured by the ES-ISCED as a part of the ESS.
Statistical Analysis In order to compare body image and QoL of women with CAH to a healthy reference population Welch's tests were conducted as recommended  [43]. The Bonferroni-Holm correction was used for multiple testing. To assess psychosocial determinants, 38 items were included in the statistical analysis. As these items were not part of a validated instrument but either self-constructed or taken from different measuring instruments, they could not be summed up by predetermined criteria. Therefore, to reduce data for further analysis, an explorative factor analysis was performed. The data's eligibility for a factor analysis was tested as recommended  [44]  and based on the results a principal component analysis with oblique promax rotation was carried out extracting 2 factors. In total, the 2 factors explained 45.