dataesr/scientific-paragraphs-categorization huggingface dataset:
The molecular lipophilicity potential was calculated using the default fauchere method of the mlp function in ChimeraX based on MLPP program  [37]. The electrostatic interactions between were calculated in ChimeraX of the Asn 101 residue of each protomer in the central channel of the trimer at the region of domain 2. The electrostatic potential of the beta-sheet-forming residues at the domain 2 region was calculated according to Coulomb's law using the Coulombic surface coloring tool in ChimeraX. The constrained range corresponds to the average distance between stakes ±1 nm. At this distance the stakes have predominantly only 1 to 2 neighbors for both datasets. The whole range of distance is needed to obtained more NN and even in this case the majority of stakes has 3 to 4 NN. (d) STA maps of nearest neighbor pairs at distances 6.
5 nm to 7. 5 nm (left), 7. 5 to 8. 5 nm (middle) and 8. 5 to 9. 5 nm (right) from the in vitro dataset. The top row shows cross section from the top part of the domain 1, the bottom row is the cross section from the domain 2. Despite narrow distance ranges, the stakes do not have a form of a trimer as this shape was averaged out due to lack of strong preferred orientation among the pairs. At the distance from 8. 5 to 9. 5 nm a strong density connects the pair of stakes at the top of domain 1 (violet arrowhead) which corresponds to the observed threads from.
Acknowledgments We thank  Stefanie Boehm  ( MPI of Biophysics ) for critical reading of the manuscript and helpful discussion. We thank  Sylvia Panitz  and  Regina Eberle , microscopy facility  Paul Ehrlich   Institute , for excellent technical assistance. We also acknowledge support by  Cornelia Cazey ,  Ulrike Laugks , and  Carolin Seuring , for access to the Cryo-EM multi-user facility at CSSB and providing time for sample preparation, screening, and data collection;  Wolfgang Lugmayr  for help and support in using the CSSB partition on the DESY computer cluster for cryo-EM data processing. Part of this work was performed at the Cryo-EM multi-user Facility at CSSB, headed by K. G. and supported by the  UHH and DFG  (grants  INST 152/772-1 ,  774-1 ,  775-1  and  776-1 ). In the framework of this project, E.
Data availability The electron microscopy density maps of the A10 trimers have been deposited in the Electron Microscopy Data Bank under accession codes: EMD-XXXX, EMD-YYYY, EMD-ZZZZ (loose and tight conformation from the in vitro dataset, trimer from the in situ data). The raw tilt series of the in vitro dataset together with representative tomograms from both in vitro and in situ datasets were deposited at EMPIAR-QQQQ. The python scripts developed for core picking and contextual analysis will be publicly available on github at the time of the publication.
The positions are shown in 2D for xy dimension, which corresponds to the top view of the map. Although minor clustering, corresponding to the hexagonal arrangement, can be observed in the in vitro dataset, the majority of stakes do not form any regular arrangements. (c) Distribution of number of NN with the distance constrained to the range of 7 nm to 9 nm (left) and the whole range, i. e. 6 nm to 11 nm (right). The constrained range corresponds to the average distance between stakes ±1 nm. At this distance the stakes have predominantly only 1 to 2 neighbors for both datasets. The whole range of distance is needed to obtained more NN and even in this case the majority of stakes has 3 to 4 NN. (d) STA maps of nearest neighbor pairs at distances 6. 5 nm to 7. 5 nm (left), 7. 5 to 8. 5 nm (middle) and 8.
5 to 9. 5 nm (right) from the in vitro dataset. The top row shows cross section from the top part of the domain 1, the bottom row is the cross section from the domain 2. Despite narrow distance ranges, the stakes do not have a form of a trimer as this shape was averaged out due to lack of strong preferred orientation among the pairs. At the distance from 8. 5 to 9. 5 nm a strong density connects the pair of stakes at the top of domain 1 (violet arrowhead) which corresponds to the observed threads from Fig 1. Scale bar 10 nm.
Acknowledgments We would like to thank  Dr. Sarah Kaakai  for her help in transposing our initial simulation Python codes into the IBMPopSim framework,  Dr. Allon Weiner  for a few hours of "naive" discussion that helped explore the interpretations of this model's impact on our perception of ageing  Dr. André Klarsfeld  for his numerous useful comments on the manuscript and  Dr. Bastian Greshake Tsovaras  for helping with setting up the mybinder. orgimplementations of the simulations' codes. This work was granted access to the  GENCI -sponsored HPC resources of TGCC@CEA under allocation  A0090607519. This work has been supported by the Chair " Modélisation Mathématique et Biodiversité" of Veolia Environnement-Ecole Polytechnique-Museum National  d'Histoire Naturelle-Fondation X.
204 in ZMA to 0. 255 in SHK). More interestingly, the F IS estimated within the TAF sample was found to be significantly negative indicating an excess of heterozygotes in the sample relative to the Hardy-Weinberg equilibrium expectation, although the 18 samples from the 1992 and 2006 35  (Gautier et al. , 2009)  Table  1 : Sample description with country of origin and population type (i. e. EUT=European Taurines, AFT=African Taurines, AFZ=African Zebus, ZEB=Zebus of Indian origin, or HYB=Hybrids); the country of sampling; the GPS coordinate (in decimal degrees) used to retrieve environmental covariates; the number of individuals genotyped on the BovineSNP50 Illumina assay and included in the W50K dataset; and the number of individuals sequenced (WGS) with associated reference. GPS coordinates specifying the environment of each population were taken as the birthplace of the breed including for GIR and NEL in Brazil  (Gautier et al.
, 2010). Individuals from the Jersey (EUT) breed were divided into two distinct groups corresponding to i) 21 individuals (coded JE2) sampled in northwestern France  (Maine-et-Loir county)  and born between 1982 and 1990  (Gautier et al. , 2010) ; and ii) 28 individuals (coded JER) sampled in the USA  (Matukumalli et al. , 2009). The newly genotyped (n=49) and sequenced (n=24) individuals are highlighted in bold. All genotyped data (including the new ones) are available from the WIDDE repository  (Sempéré et al. , 2015)  and the newly generated whole genome sequence data are publicly available in the NCBI SRA repository (project PRJNA1010533).
Relationship with other worldwide populations The global F S T estimated on the W50K dataset was found to be 21. 5% (CI95%=  [21. 1%; 21. 8%] ) while the global F IS remained negligible (CI95%=[0. 04%; 0. 26%]). As shown in Figure  S2 , the estimated pairwise F S T values ranged from 0. 0247 for the MAY/ZMA pair to 0. 472 for the LAG/NEL pair (median of 0. 203). For pairs including the TAF, values ranged from 0. 208 (TAF/PMT) to 0. 436 (TAF/NEL), consistent with a presumably high amount of drift in this population following an intense founding bottleneck. In addition, the TAF appeared more closely related to breeds of EUT origin. However, clustering based on pairwise F S T must be interpreted cautiously and cannot be safely used to infer population origins as it is highly sensitive to drift and admixture.
For example, the TAF may appear as an outgroup of the EUT cluster in Figure  S2  due to drift and the TAF/PMT pair is likely to display the lowest pairwise F S T because, like the TAF, the PMT breed has some amount of ZEB ancestry (see Figure  S4  and  Gautier et al. , 2010). Finally, note that the F S T between the TAF and the newly genotyped MOK sample was 0. 275, i. e. , in the upper range of values estimated for pairs involving this population sample, which varied from 0. 0578 for the MOK/ZMA pair to 0. 303 for the MOK/LAG pair. To refine the exploration of the overall structuring of genetic diversity on the W50K dataset, we computed allelesharing distances between all pairs of individuals and used the resulting matrix to build the neighbor-joining tree shown in Figure  S3. In agreement with previous observations (e.
g. Gautier et al. , 2010)  and the results above, the obtained tree showed a clear clustering of individuals according to their population of origin, except to some extent for the MOK individuals, which were more dispersed with two apparent outliers. At a higher level, the EUT, AFT and ZEB populations were also well separated, as were the AFZ and MOK populations, both of which branched between ZEB and AFT. Finally, the TAF population was clearly isolated from the other populations and branched close to the EUT populations. A similar pattern was recovered using principal component analysis (PCA) of the W50K dataset (Figure  1C ). Interestingly, in the first factorial plan, TAF and MOK individuals are positioned on an axis connecting the ZMA and EUT populations, suggesting ZEB and EUT ancestry for both populations, with TAF individuals closer to EUT and MOK closer to ZMA and MAY.
Inferring the demographic history of the TAF population We relied on the f -statistics based framework  (Patterson et al. , 2012)  as implemented in the R package poolfstat  (Gautier et al. , 2022)  to infer the origin of the TAF population using the W50K dataset. We first performed a formal test of admixture based on the F 3 statistic computed for all the 465 population triplets with TAF as the target admixed population, but none of the resulting statistics were found to be (significantly) negative. In fact, this can be explained by the high amount of drift due to the extreme founding effect in the TAF history. Conversely, 100 of the 465 population triplets with MOK as the target population showed significantly negative f 3 (at the 5% threshold), with the lowest value observed for the (MOK;GIR,NDA) and (MOK;BPN,ZMA) configurations (both with Z = -21.
7). We also used f -statistics to construct an admixture graph construction as detailed in Figure S5  (Patterson et al. , 2012; Gautier et al. , 2022). This allowed us to demonstrate the admixed origin of the TAF and MOK populations with closely related EUT ancestral sources contributing to 75% and 22% of their genome composition, respectively, and another source closely related to ZMA. Positioning the MOK population resulted in a poorer fit suggesting a more complex origin (i. e. , three-way EUTxZMAxZEB admixture) difficult to capture with the W50K dataset (Figure  S5 ). Nevertheless, the inferred graph suggests that MOK may not be considered as the closest proxy for the source populations from which TAF originated. Figure  2A  shows the results for the best-fitting graph among all possible ways of positioning TAF and the JE2 Jersiaise breed sample (Table  1 ) on a scaffold graph previously inferred to describe the history of the Indian Ocean island populations MAY and ZMA  (Magnier et al.
Timing of admixture of the TAF source population We further estimated the timing of this admixture event using the alder program, which is based on modeling the exponential decay of admixture-induced Linkage Disequilibrium (LD) with genetic distance  (Loh et al. , 2013). Using TAF as the target admixed population in one-reference tests (i. e. , using an LD measure weighted by allele frequencies observed in a single source population proxy), a significant weighted LD curve was found with all the 31 other breeds of the W50K dataset, except MOK and ZFU, confirming the admixture signal. We further fitted the TAF two-reference weighted LD curves (i. e. , using an LD measure weighted by the allele frequencies observed in two source proxies) for all 406 possible pairs of the 29 populations that passed the one-reference tests.
Genetic Offset In order to assess the potential environmental challenges that the bioclimatic condition of Amsterdam Island may represent for different (adapted) cattle populations originating from different regions, i. e. their relative maladaptation or pre-adaptation, we used the Genetic Offset (GO) statistic  (Capblancq et al. , 2020). For this purpose, we relied on the BayPass GEA model  (Gautier, 2015)  to summarize the relationship between seven bioclimatic PCs (resulting from a PCA of 19 bioclimatic covariates) and the genomic composition of the 32 populations represented in the W50K dataset. We then estimated the GO between the Amsterdam island environment and the birthplace environment of each of the 31 (non-TAF) populations (Figure  5A ), following  Gain et al. (2023). Interestingly, the lowest GO was obtained for the environment associated with the birthplace of JE2 (and JER), which was also the one with the smallest environmental distance, i.
To improve mapping resolution, we analyzed a dataset combining high-density (>770,000 SNPs) SNP genotyping data from the Illumina BovineHD assay for 23 ZMA and 30 JER individuals  (Magnier et al. , 2022; Sempéré et al. , 2015)  with the subset of 50K SNP data (most of which are shared with the BovineHD assay) for the 18 TAF individuals. We then imputed (or directly genotyped for the 8 sequenced TAF individuals) the missing BovineHD genotypes in the TAF using the available WGS data (see M&M section). After filtering and phasing, the analyzed data set consisted of 142 haplotypes (36 TAF, 46 ZMA and 60 JER) per autosome, totaling 530,769 SNPs (ranging from 8,842 to 33,710 for chromosomes 25 and 1, respectively). In total we could identify 21 significant regions, 12 (ranging from 76. 90 to 1,355 kb in length) associated with the within TAF iHS, and two and eight with the Rsb T AF/JER (83.
Detecting footprints of selection on a dense haplotype data set The remaining 20 candidate genes were then subjected to functional annotation using the Ingenuity Pathway Analysis (IPA) software (Ingenuity Systems, Inc. , 2023). Three genes (i. e. , LOC112448598, TRNAY-AUA and LOC132345997) that were not recognized in the IPA database (IPKB) were removed from the analysis. The top five diseases and biological functions significantly enriched by the analysis of the 17 annotated candidate genes (Table  S9 ) were related to the nervous system (i. e. , Neurological Disease and Nervous System Development and Function), and to tissue, organ and organism development (i. e. , Organismal Injury and Abnormalities, Cell Morphology and Tissue Morphology). More specifically, 15 of the 17 genes (i. e. , ADGRG6, AGL, BLOC1S5, GCM1, HSPB3, MAPK10, SYNE2, USH1C, UTRN, OR8B8, PKHD1, SLC36A3, SYNE2, SYT16, TRPS1) are involved in nervous system function and/or its development.
(2022)  and  Gautier et al. (2009). Thirteen (8 MAY and 5 ZMA) were paired-end sequenced on a HiSeq 2500 (n=5 with 2×125 nt) or a NovaSeq 6000 (n=8 with 2×150 nt) Illumina sequencer at the MGX platform (Montpellier, France). The three remaining ZMA individuals were paired-end sequenced (2×150 nt) on a NovaSeq 6000 Illumina sequencer at the Genoscope platform (Evry, France) (Tables  S3  and 1 ). All the newly generated sequencing data for the 8 TAF, the 8 MAY and the 8 ZMA individuals were deposited in the NCBI Sequence Read Archive repository under the BioProject accession number PRJNA1010533 (Table  S3 ).
The 50K SNP genotyping dataset (W50K) representative of worldwide cattle genetic diversity To explore the genetic relationship of the TAF population with other bovine population and infer its origin, the newly generated data obtained with the BovineSNP50 assay were combined with publicly available data from populations representating the worldwide cattle diversity  (Gautier et al. , 2010; Matukumalli et al. , 2009)  and that are stored in the WIDDE database  (Sempéré et al. , 2015). As detailed in Table  1  and represented in Figure  3A , the resulting W50K data set finally consists of 876 individuals from 32 different populations. Genotyping data were filtered using WIDDE utilities  (Sempéré et al. , 2015) , only retaining individuals with a SNP genotyping call rate > 95%. Likewise, we only retained SNPs with an individual genotyping call rate > 75% in all population samples (leading to an overall genotyping call rate > 90%) and that mapped to the latest ARS-UCD1.
, 2022)  and were extracted from the Widde database  (Sempéré et al. , 2015). We used genotypes from 24 the individuals (8 TAF, 8 MAY and 8 ZMA) that were both sequenced and genotyped to assess the genotype concordance rate. Among their 8,843,201 genotypes available from both WGS data (with a GQ > 20) and the genotyping array, only 0. 42% were found to be different. For those, we chose to keep the SNP assay genotype in the combined data set further excluding five individuals (3 ZMA and 2 MAY) that remained poorly genotyped. Likewise, we only retained the 547,214 SNPs that were genotyped on more than 90% of the individuals in each of the four population samples. We then proceeded with the imputation of missing genotypes for the 10 TAF individuals that were only genotyped on the 50K SNP assay (corresponding to the targets).
Acknowledgments We wish to thank  Hubert Levéziel  ( INRA , retired),  Cécile Grohs  ( GABI, INRAE, Jouy-en-Josas, France ) and  Roberta Ciampolini  ( Università di Pisa, Pisa, Italy ) for their help during DNA extraction and management of the bovine samples from Amsterdam island collected in 1992. The genotyping of individuals from the Amsterdam island cattle breed and from the Moka cattle breed was supported by the  National Institute of Agronomic Research (INRA, Animal Genetics Division, France ; " SNPDOM " and " PERSAFRICA " projects). The sequencing was supported by  EU  ( FORWARD RITA DEFI-ANIMAL  project,  2015-2020 ) and  France Génomique (CEA ,  Evry-Courcouronnes, France ;  High impact project  funded " CAHWA "). MGX acknowledges financial support from  France Génomique National infrastructure , funded as part of " Investissement d'Avenir" program  managed by  Agence Nationale pour la Recherche  (contract  ANR-10-INBS-09 ).
Trial design and population The trial was designed as a prospective, bi-centric, randomized, open-label interventional trial. This clinical study is referenced in clinical trial with the number: NCT04539899. This French trial was conducted at the Rennes Family Planning Centre and the Rennes University Hospital Abortion Centre from September 2020 to April 2022. The health professions that performed the IUD insertion were either doctors, midwives, medical interns or student midwives supervised, that had been trained in the use of the VR device and in the procedure for insertion of the IUD. All adult women presenting for a contraceptive consultation and that chose an IUD as contraceptive were eligible for the trial. Women younger than 18 years of age, under legal guardianship, and not affiliated to a national social security system were not eligible.
Data collection During the trial, data from participants were collected using two selfadministered questionnaires and from healthcare professionals using one questionnaire. The questionnaires were modified by adding new parameters during the course of the study. This was done in order to optimize our study and it is the reason for the number of missing data for some parameters. The first questionnaire was completed by the participants before the IUD insertion procedures. This first questionnaire collected relevant socio-demographic (age), gynaecological history (births, type of deliveries [vaginal versus Caesarean], abortions, miscarriages), medical history (endo-uterine procedures and history of dysmenorrhea), IUDrelated data (prior use and failures of IUD, perception of and reason for choosing an IUD), and the use of pharmacological substances before the IUD insertion.
Participants were also asked to indicate their level of anxiety prior to the procedure and the expected level of pain during the procedure. The second questionnaire was completed the participants immediately after the consultation. The second questionnaire collected data concerning the levels of anxiety and pain experienced during the IUD insertion procedure and the levels experienced a few minutes after the procedure had been completed. The women were also asked their satisfaction with the procedure, and whether they would choose to repeat the procedure in the future. Women allocated the VR therapy were asked if they would recommend the VR therapy to their families and friends. After the consultation, the healthcare professional completed a questionnaire. The questionnaire collected data concerning the type of IUD used, the insertion technique, the use of single-tooth tenaculum, success or failure of the insertion, and relevant details concerning the healthcare professional (profession, medical experience, and previous number of IUD performed).
Acknowledgements We would like to thank all the women who consented to participate in the trial as well as healthcare professionals who performed the procedure. Thanks to the association  IME (Institut Mère enfant, CHU de Rennes)  for their support, and the company  Butterfly Therapeutics (Laval, France)  for participating by lending us the virtual reality medical device Bliss DTx. Thanks also to the clinical research assistants,  Ms Gervais Marie Laure  and  Ms Quibel Anne-Lyse  for their contribution throughout this study, and  Trevor Stanbury  ( Pro-Pens ) for medical writing services.
Peptides were loaded with solvant A and separated on an Aurora analytical column (ION OPTIK, 25 cm × 75 m, C18, 1. 6 m) with a gradient of 0-35% of solvent B for 30 minutes. Solvent A was 0. 1% formic acid and 2% acetonitrile in water and solvent B was acetonitrile with 0. 1% formic acid. MS and MS/MS spectra were recorded from m/z 100 to 1700 with a mobility scan range from 0. 6 to 1. 4 V s/cm2. MS /MS spectra were acquired with the PASEF (Parallel Accumulation Serial Fragmentation) ion mobility-based acquisition mode using a number of PASEF MS/MS scans set as 10. MS and MSMS raw data were processed and converted into mgf files with DataAnalysis software (Bruker). Peptide and protein identifications were performed using the MASCOT search engine (Matrix Science, London, UK) against a homemade database (the unknown amino acid at stop codon is represented by « X » in the readthrough GST sequence).
Database searches were performed using LysC cleavage specificity with two possible missed cleavages. Carbamidomethylation of cysteines was set as fixed modification and oxidation of methionines and tryptophan as variable modifications. Peptide and fragment tolerances were set at 10 ppm and 0. 05 Da, respectively. Only ions with a score higher than the identity threshold and a false-positive discovery rate of less than 1% (Mascot decoy option) were considered. The XIC-based relative quantification of readthrough peptides was corrected by dividing the XIC peak areas of endogenous peptides by their heavy isotope labeled counterparts.
Acknowledgments We acknowledge the proteomic facility of I2BC for mass-spectrometry expertise and analysis. This work was funded to ON by  Vaincre la Mucoviscidose  funded to ON ( N°RF20180502275 ), by  ANR  (grant  Actimeth  ( 19-CE12-0004-02 )) and by  AFM-Telethon  (grant  19660  and translectin N°  20531 ). SK is supported by  Vaincre la Mucoviscidose funded  to ON ( N°RF20180502275 ). Vaincre la Mucoviscidose had no involvement in the design, analysis or interpretation of the data.
Interestingly, several of these studies highlighted that the transcriptional variations tended to be buffered when looking at the translational variations  (13) (14) (15) (16). This phenomenon is known as post-transcriptional buffering and has also been observed when comparing transcriptomic and proteomic datasets  (18, 19). However, despite recurring observations, the mechanisms underlying this post-transcriptional buffering are still poorly understood. Moreover, while transcription and protein abundance have been extensively monitored, translation itself has been considerably less studied, and no clear description of the phenomenon has been made at this level. More globally, translational variation remains largely unexplored, and several known sources of expression variation, such as accessory ORFs (Open Reading Frames), have yet to be investigated at the translational layer.