dataesr/scientific-paragraphs-categorization huggingface dataset:
2011)  and in order to avoid possible contamination from a neighboring point source. However, in both observations the source was adjacent to a chip gap and we note that when part of the PSF lies in a chip gap, effective exposure and encircled energy fraction may be affected. We followed the standard filtering and extraction practices provided by the XMM-Newton Science Analysis System (SAS). The source spectrum was extracted using SAS task evselect, and the standard filtering flags (#XMMEA_EP && PATTERN<=4 for pn). For the background region we considered a 40 ′′ circle located in the same region of the chip as the source center, avoiding the copper ring and OoT events. SAS tasks rmfgen and arfgen were respectively employed to produce the redistribution matrix and ancillary file. For the analysis of the NuSTAR data we used the version 1.
We applied standard PSF, alignment, and vignetting corrections. For the χ 2  analysis, all spectra were regrouped so as not to oversample the instrument energy resolution by more than a factor of 3 and to have at least 25 counts per bin. For the Bayesian analysis (see Sect. 4) the spectra were unbinned and Cash statistics (Cash 1979) was employed. The analysis was performed using the Xspec spectral fitting package, version 12. 9. 0 (Arnaud 1996)  and the Bayesian Xray analysis package  (Buchner et al. 2014). We restricted the NuSTAR spectra to energies below 30. 0 keV as above this range the signal-to-noise ratio (S/N) 2 fell below a value of 5. We also ignored all NuSTAR channels below 3 keV. Data-to-model ratio vs energy plot for the phaseaveraged broadband (XMM-Newton plus NuSTAR) spectrum of NGC 300 ULX1.
Modeling of the phase-averaged continuum Below we report on the two modeling approaches when applied to the pulse-phase averaged X-ray spectrum. AC model: The XMM-Newton EPIC-pn and NuSTAR (FPMA and FPMB) phase-averaged spectra were fitted together with a constant multiplicative factor to account for inter-calibration uncertainties between the two instruments and any minor intensity changes between the two XMM-Newton observations. The spectral continuum was modeled with an MCD with a temperature of ∼0. 29 keV ( Xspec model diskbb) and a power law with a spectral slope of ∼0. 5 and an e-folding energy of the exponential roll-off at E f old ∼4. 2 keV ( Xspec model cutoffpl, "Full (no line)" model in Table  1 ). The interstellar absorption was modeled using the improved version of the tbabs code 4   (Wilms et al.
In Bayesian model selection, prediction diversity distant from the observed data is punished. The Bayesian approach is appealing because it does not assume the true value to be equal to the best fit and takes into account the uncertainties and the model complexity. While priors need to be specified on all parameters, primarily the priors on parameters that are different between models are influential. To compute the evidence Z we used the Bayesian X-ray analysis package (BXA). The BXA package 5  (Buchner et al. 2014) connects the nested sampling  (Skilling 2004 ) algorithm MultiNest  (Feroz et al. 2009)  with Xspec. It explores the parameter space and can be used for parameter estimation (probability distributions of each model parameter and their degeneracies) and model comparison (computation of Z).
Acknowledgements. The authors would like to thank the anonymous referee whose contribution, significantly improved our manuscript. FK acknowledges support from the  CNES. JB acknowledges support from the  CONICYT-Chile grants Basal-CATA   PFB-06/2007 ,  FONDECYT Postdoctorados 3160439 , and the  Ministry of Economy, Development, and Tourism's Millennium Science Initiative  through grant  IC120009 , awarded to  The Millennium Institute of Astrophysics, MAS.
The study carried out in this paper aims to analyze the fatigue behaviour of prestressed bolts involved in a so-called tee-stub bolted assembly that is subjected to variable loads. A multiaxial fatigue post-processing tool using two multiaxial fatigue approaches (integral approach and critical plan approach) is developed and implemented on Matlab software in order to assess the bolt fatigue damage and then its fatigue life through an iterative process. The tool is validated by fatigue test results on bolted assemblies found in the literature, which are additionally compared with those obtained by standards (Eurocode, VDI). A parametric study on the tee-stub is then performed.
Introduction Metal structures essentially consists of a set of elements such as columns and beams. To ensure the correct transmission of forces between these elements, links are made between components according to different methods as bolting. Bolted assemblies are probably the most widely used mechanical connections. In order to clearly understand the fatigue behaviour of bolted connections, a tee-stub where bolts are submitted to a pretension force is numerically studied by the use of Finite Element Model on Salome-Meca software. Then, a fatigue post-treatment tool is implemented on Matlab software and uses two multiaxial fatigue approaches. It allows to assess the fatigue damage and the fatigue life of material or structures under multiaxial constant amplitude cyclic stress states. Two multiaxial fatigue criteria were implemented; they are related to the so called critical plane approach (Dang Van criterion) and to the integral approach (Zenner criterion).
Bolt material S-N curves As the bolt material S-N curves are not precisely known, some fatigue data are taken from the literature (as CES edupack 2018) to analyze the influence of some parameters on the fatigue behaviour of the tee-stub bolts. The considered S-N curve (figure  4b ) derives from the Wöhler model and gives the fatigue lifetime N under fully reversed tensile load (R = -1) by: 𝝈-1 (N) = 720 -60 log (N) ( 8 ) The material is the AISI 4037 alloy steel which can be used for heavy duty shafts, connecting rods and also high tensile bolts. The other S-N curves (fully reversed torsion load -1, repeated tension 0 and torsion 0) that are necessary for the criteria calibration are derived from this S-N curve according to the following assumptions:  𝜎 -1 (𝑁) 𝜏 -1 (𝑁) = √3 , according to Harald Zenner and al.
Results The experimental setup. Data were acquired from February 19th to February 24th, 2018, on a 41. 5 km long electro-optic telecommunication cable from Alcatel, which is deployed offshore Toulon in the south of France. This cable is the backbone of the MEUST-NUMerEnv project  17  (Mediterranean Eurocentre for Underwater Sciences and Technologies-Neutrino Mer Environnement) (Fig. 1 ). The cable straddles several oceanic domains of the north Mediterranean margin: a shallow continental shelf, a steep continental slope, and a 2500 m-deep oceanic plain. The main purpose of the cable is to collect data from the KM3NeT/ ORCA (Oscillation Research with Cosmics in the Abyss) neutrino detector deployed at its seafloor termination point  18. The MEUST cable was installed in 2014  19  and, as it is often the case with telecommunication cable, was simply laid on the seafloor.
In our experiment, the gauge length was fixed to 19. 2 m. The data set used in this study consists of strainrate value sampled every 6. 4 m in space and 0. 5 ms in time yielding ~6500 acoustic sensors with an effective recording frequency of 1 kHz (more details available in the Methods section). Along its entire length, the OF cable continuously records a background signal made of periodic oscillations. These oscillations have different properties on the continental shelf and on the abyssal plain. We describe them sequentially hereafter, starting with observations near the coast. Ocean surface gravity wave detection in the coastal environment. The signals in the first 8 km of underwater cable are dominated by periodic oscillations with frequencies between 0. 1 and 0. 25 Hz, which propagate landward with increasing amplitude (Fig.
Data availability The fiber optic DAS recordings of the earthquake and microseism signals are available in the following OSF repository: https://osf. io/x6awb/. Open Access This article is licensed under a Creative Commons Attribution International License, which permits use, sharing, adaptation, distribution reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
Acknowledgements We thank the team from the  Centre de Physique des Particules de Marseille  who facilitated the access to the MEUST infrastructure. The MEUST infrastructure is financed with the support of the  CNRS/IN2P3 , the  Region Sud, France (CPER the State (DRRT) , and the  Europe (FEDER). This work was supported by the  SEAFOOD  project, funded in part by grant  ANR-17-CE04-0007  of the  French Agence Nationale de la Recherche  and in part by  Université   Côte d'Azur IDEX program UCA JEDI   ANR-15-IDEX-0001.
Acknowledgements M. A. C. M. and L. C. contributed equally to this work. This project received funding from the  European Union 's  Horizon 2020 research and innovation program  under grant agreement No  736937. Numerical simulations were supported by the  Russian Foundation for Basic Research  (grant No. 18-32-20115 ). Manufacturing and testing of ceramic resonators was supported by the  Russian Science Foundation  (project No. 18-79-10167 ). The authors thank  Erwan Selinge  for extracting and fixing the spinal cord and  Christophe Craeye  for his help in the analytical part.
Several working groups and expert panels were created within ClinGen, including gene-and disease-specific Variant Curation Expert Panels (VCEPs). 9, 10 Moreover, the ClinGen Sequence Variant Interpretation (SVI) Working Group (https://clinicalgenome. org/working-groups/sequence-variant-interpretation/) aims to provide general recommendations for the refinement and evolution of the ACMG/AMP guidelines, which are then specialized further by the gene-specific VCEP. The publicly available ClinVar database (https://www. ncbi. nlm. nih. gov/clinvar/), launched in 2013, serves as a valuable centralized resource for documenting the clinical significance of genetic variants submitted by clinical and research laboratories and databases such as OMIM (Online Mendelian Inheritance in Man) and GeneReviews.
11 ClinVar uses the ACMG-recommended 5level scoring system to indicate the level of evidence supporting the assertion of clinical significance of a variant. Human variant data curated by ClinGen expert panels are submitted to ClinVar with a 3star status (reviewed by expert panel) including a designation that the ClinGen VCEP process has been recognized by the US Food and Drug Administration (FDA). The general workflow of a VCEP is to define its leadership/ membership and scope of focus as well as conflicts of interest. 9 ce approved, this group develops disease-specific variant classification rules, based on curation of gene-specific features, published literature, and evidence thresholds that are consistent with gene-disease associations. ACMG and AMP have defined 28 codes that address specific evidence, including population data, segregation data, functional data, computational predictions, and allelic data.
3 Each code is weighted according to the strength of the evidence: stand-alone, very strong, strong, moderate, or supporting. Codes are also designated as defining the direction of clinical significance: benign (BEN) or pathogenic (PATH). These evidence codes applied to variants are then combined to arrive at a single designation of clinical significance: PATH, likely pathogenic (LPATH), variant of uncertain significance (VUS), likely BEN (LBEN), or BEN. Once preliminary rules are specified, they are pilot tested on a collection of variants with existing assertions of clinical significance, and based on the results of this preliminary testing, the VCEP may adjust some of its rules to optimize variant classification. Once final rules have been approved, they are published and implemented, with VCEP-curated assertions disseminated via the ClinVar database.
0] [21]  More than one-half of germline RUNX1 variants are reported in single probands/families,  13  leading to a high allelic heterogeneity that restricts the collection of data from segregation analyses and functional analyses across several affected families. Individuals with a hematologic malignancy are often candidates for hematopoietic stem cell transplantation. [24] [25] [26]  Here, we present the RUNX1-specific guidelines generated by the MM-VCEP. The MM-VCEP adapted the ACMG/AMP framework for RUNX1 variant classification with the aim of improving consistency in variant classification and curating RUNX1 variants for 3-star submission to ClinVar. We used multiple lines of evidence, showing the rationale and data supporting each criterion's modification, and the results from pilot testing the criteria on variants with BEN/LBEN, PATH/LPATH, VUS, and conflicting (CONF) ClinVar assertions.
ClinGen MM-VCEP The MM-VCEP is sponsored by the American Society of Hematology through its partnership with ClinGen and is described at https:// (3) optimization of rules using pilot variants; and (4) MM-VCEP approval by ClinGen, implementation of rules in the ClinGen Variant Curation Interface, and submission of curated variants to the ClinVar database. For step two, members were divided into 3 subgroups that focused on the modification of functional/computational/splicing criteria (Team F), population/phenotypic criteria (Team P), and segregation/allelic/de novo criteria (Team S). All members disclosed potential conflicts of interest as required by ClinGen.
ACMG/AMP specifications for RUNX1 MM-VCEP members proposed and discussed changes to the existing ACMG/AMP classifications for RUNX1 germline variants and arrived at consensus decisions via teleconference calls and e-mail. Criteria modifications included gene-or disease-specific modifications, strength-level adjustments, general recommendations, and certain criteria being deemed "not applicable. " Publicly available databases, predictive software, and published data obtained from relevant papers were used for criteria specifications. For BA1/BS1 RUNX1-specific population MAF, calculations were made assuming Hardy-Weinberg equilibrium using the recently published Whiffin/Ware online calculator. 6 Additional efforts included identification of key functional domains and mutational hotspots within RUNX1, definition of informative functional assays, and characterization of phenotypic criteria.
26, 30, 36, 37 There are rare case reports of patients with germline RUNX1 variants and mixed myeloproliferative syndromes/MDS such as chronic myelomonocytic leukemia,  26, 38  as well as case reports of patients with B-cell ALL  39  and hairy-cell leukemia. 40 pulation data (BA1, BS1, PM2, PS4, PS4_moderate, PS4_supporting, and BP2) FPD/AML is a rare disorder. The prevalence of the diseaseassociated RUNX1 variants is unknown, with an estimated 5515 families worldwide based on a population incidence generated from a survey of centers with FPD/AML patients (A. L. B. , written communication, 10 June 2019), which is likely an underestimate of the true prevalence. Among the 3 phenotypic features seen in individuals with germline RUNX1 variants (Table  2 ), thrombocytopenia is the most common. We conservatively estimated the prevalence of thrombocytopenia for use in the BA1/BS1 calculations.
To obtain an RUNX1-specific population MAF threshold for BA1, we used the Whiffin/Ware calculator 6 (http://cardiodb. org/allelefrequencyapp/) with a prevalence of 1 in 40, a conservative unascertained penetrance estimate of 85%, an allelic heterogeneity of 100%, and a maximum genetic heterogeneity of 10%. The MM-VCEP also adopted the SVI recommendation that the variant be present in any general continental population dataset with a minimum number of 2000 alleles and the variant present in $5 alleles. 42 A 95% confidence interval was used to develop the thresholds. The threshold developed for application of BA1 as a stand-alone criterion is a MAF $0. 0015 (0. 15%). For BS1, a maximum genetic heterogeneity contribution of 1% (1 magnitude lower) was used, which led to a range of 0. 00015 (0.
015%) to 0. 0015 (0. 15%) for application of BS1. Because we used conservative values for the calculation, we allow a variant to reach an LBEN classification based on BS1 alone if there is no contradictory evidence supporting pathogenicity (as outlined in a recent SVI revision). 29 For this work, the gnomAD population database was mostly used, although other databases with a minimum of 2000 alleles are also sufficient. However, we encourage the use of a large dataset such as gnomAD, ExAC, or ESP. Because most RUNX1 variants are unique to probands or families,  13  it was determined that the variant must be completely absent from all population databases to apply PM2. The MM-VCEP tested pilot PATH/LPATH variants with this rule and validated this determination. The MM-VCEP further recommends that the mean coverage of exome and genome sequencing data for RUNX1 in the population databases used should be at least 203.
This code has a sliding weight scale to account for the number of unrelated probands who meet the RUNX1-phenotypic criteria. PS4 is applied with $4 probands (OR, 100. 6), PS4_moderate with 2 to 3 probands (OR, 50. 3-75. 5), and PS4_supporting with 1 proband (OR, 25. 1) (supplemental Table  1 ). BP2, supporting evidence for a BEN code, can be applied in the context of autosomal dominant FPD/AML when the variant is found in trans with a known PATH variant. Because there is no evidence in the literature of probands with a homozygous PATH RUNX1 variant, and lack of Runx1 is embryonically lethal in mice, the MM-VCEP recommends that BP2 also be applied when a variant is found in a confirmed homozygous state in population databases or internal laboratories. 43, 44 gregation data (PP1_strong, PP1_moderate, PP1, and BS4) Segregation with disease (PP1) is used as evidence for pathogenicity, and with increasing number of meioses, a stronger level of evidence can be applied.
PS2_moderate is reached with a score of 1 point (two or more proven de novo occurrences), and PS2_supporting is used when reaching a score of 0. 5 point (one proven de novo occurrence). Likewise, PM6_moderate is met when 4 assumed de novo occurrences are present (score of 1), and PM6_supporting is applicable with 2 to 3 assumed de novo cases (score of 0. 5). Combining these 2 criteria (eg, in the case of the same variant having both confirmed and assumed de novo evidence) is possible with the recognition that the maximum allowable value is still 1 point, which effectively leads to the application of 1 moderate or 2 supporting rules (supplemental Table  2 ). Computational and predictive data (PVS1, PVS1_strong, PVS1_moderate, PS1, PS1_moderate, PM1, PM1_supporting, PM4, PM4_supporting, PM5_strong, PM5, PM5_supporting, PP3, BP4, and BP7) RUNX1 germline variants have been well described as being dominant-negative, loss-of-function, or hypermorphic.
PP3 cannot be used for canonical splice site variants. The BEN criterion BP4 should be applied for missense variants if all of the following criteria apply: the variant's REVEL score is ,0. 15, SSF and MES predict either an increase in the canonical splice site score or a decrease in the canonical splice site score by no more than 10%, and no putative cryptic splice sites are created. BP4 should also be applied for synonymous, intronic, and noncoding variants for which SSF and MES predict either an increase in the canonical splice site score or a decrease in the canonical splice site score by no more than 10%, and no putative cryptic splice sites are created. The original PM1 code can be applied for variants affecting mutational hotspots and/or functional domains without BEN variation. The RHD, spanning from AA 77-204, has been established as a highly conserved DNA-binding domain without any BEN variation in ClinVar.
The MM-VCEP agreed to extend BP7 (synonymous variant with no splicing effect and position is not highly conserved) to apply to intronic/noncoding variants at or beyond positions  which SSF and MES predict either an increase in the canonical splice site score or a decrease in the canonical splice site score by no more than 10%, no putative cryptic splice sites are created, and the position is not conserved (eg, PhyloP score ,0. 1 75 ) or the variant is the reference nucleotide in 1 primate and/or 3 mammal species. 76 nctional data (PS3, PS3_moderate, PS3_supporting, BS3, and BS3_supporting) The evolutionarily conserved 128 AA RHD, present in most of the RUNX1 isoforms (Figure  1B ), is involved in DNA binding and heterodimerization with core binding factor (CBF) b. Heterodimerization of RUNX1 with CBFb promotes DNA binding by stabilizing the interaction of the complex with the DNA.
RUNX1 regulates the activity of several important hematopoietic genes, such as the granulocytemacrophage colony-stimulating factor,  77, 78  T-cell receptor,  79, 80  myeloperoxidase,  81, 82  and neutrophil elastase,  82  by binding to a core sequence (TGTGGT) found in their promoters or enhancers. Transactivation assays showing altered transactivation compared with wild type are often performed as functional studies to evaluate the pathogenicity of a RUNX1 variant. ] [85] [86] [87]  Data from secondary assays are frequently used to evaluate an altered function of mutant RUNX1. Electrophoretic mobility shift assays  31, [87] [88] [89] [90]  and yeast hybrid assays  88, 89  are performed to show decreased DNA-binding affinity, and coimmunoprecipitation assays,  85, 87, 90  fluorescence resonance energy transfer assays,  88  and affinity assays  31  can illustrate the diminished heterodimerization ability of mutant RUNX1 with CBFb.
The MM-VCEP further stipulates that PS3 cannot be applied if the variant meets PVS1. If the variant meets PVS1_strong and PS3, we recommend applying either PVS1_strong and PS3_moderate or upgrading PVS1_strong to PVS1 without applying PS3. PS3_moderate is applied when data from transactivation assays exhibit reduced transactivation (,20% of wild type and/or reduced to levels similar to wellestablished PATH variants such as R201Q or R166Q) or 2 or more secondary assays show altered function. PS3_supporting can be applied for transactivation assays exhibiting enhanced transactivation (. 115% of wild type), as has been reported previously for the hypermorphic RUNX1 mutant, S388X. 52 kewise, the BS3 requirements (functional studies show no damaging effect on protein function) are a normal transactivation (80%-115% of wild type) and data from a secondary assay that exhibit normal function.
Incomplete penetrance, an average age of onset of 33 years for hematologic malignancies,  [19] [20] [21]  and the lack of sufficient clinical data to exclude an RUNX1-related phenotype render BS2 (observed in a healthy individual with full penetrance at an early age) not applicable. Both missense and truncating variants have been described as causative in FPD/AML, making BP1 (missense variant in a gene with primarily truncating variants) not applicable. Similarly, BP3 is not applicable, as RUNX1 lacks repetitive regions of unknown function. BP5 can be applied when the variant is found in a case with an alternate molecular basis for disease. The MM-VCEP concluded that this rule is not applicable because in rare circumstances, a patient can carry variants in 2 genes predisposing to hematologic malignancies, as has been described in case reports.