dataesr/scientific-paragraphs-categorization huggingface dataset:
Ethics approval and consent to participate Not applicable. d'Avenir #ANR-11-BINF-0002 Institut de Biologie Computationnelle (young investigator grant to C-H. L. ) and GEM Flagship project funded from Labex NUMEV (ANR-10-LABX-0020). FANTOM5 was made possible by the following grants: Research Grant for RIKEN Omics Science Center from MEXT to Y. H. ; Grant of the Innovative Cell Biology by Innovative Technology (Cell Innovation Program) from the MEXT to Y. H. ; Research Grant from MEXT to the RIKEN Center for Life Science Technologies; Research Grant to RIKEN Preventive Medicine and Diagnosis Innovation Program from MEXT to Y. H. This work was further supported by a Research Grant from MEXT to the RIKEN Center for Integrative Medical Sciences. Motif discovery around CAGE peakmax. HOMER [23] was used to find 21bp-long motifs in 21bp-long sequences centered around the peak summit of FANTOM5 CAGEs.
Acknowledgements We thank  Cédric Notredame ,  Anthony Mathelier ,  Oriol Fornes Crespo ,  Philip Richmond ,  Jean-Christophe Andrau ,  Diego Garrido Martin ,  Dimitri D. Pervouchine ,  Roderic Guigo ,  Charles Plessy  and  Chung Hon  for their help in analyzing the data and for insightful suggestions. We are indebted to the researchers around the globe who generated experimental data and made them freely available. C-H. L. is grateful to  Marc Piechaczyk  and  Edouard Bertrand  for continued support. The work was supported by funding from  CNRS  ( International Associated Laboratory "miREGEN" ),  INSERM-ITMO Cancer project  " LIONS "  BIO2015-04 ,  Plan d'Investissement.
org/10. 1038/nmeth. 2019). Deconvolution was performed using the Huygens software to optimize the signal-to-noise ratio. Measurements of invagination depth. Invagination depth was measured with respect to the vitelline membrane in the ventral-most region of the embryo. For the comparison of central and anterior regions, depth was measured in the center of these respective regions. Cell segmentation. Confocal image stacks were preprocessed with Zen (Zeiss) and 3D-median-filtered with ImageJ. Segmentation and shape extraction were performed using MorphoGraphX 32 (http://www. MorphoGraphX. org). First, the images were cut using clipping planes to remove most of the artifact from the acquisition. Then, a solid shape was created to follow the global shape of the embryo by edge detection. A meshwork was generated on this solid shape using the marching cube surface algorithm.
The apico-basal is exerted between j and j′. After each iteration, a new energy minimum is searched through a gradient descent strategy using the Broyden-Fletcher-Goldfarb-Shanno bound constrained minimization algorithm from the scipy library  33. Results are displayed using the Matplotlib (https://doi. org/10. 5281/zenodo. 1202077) and Ipyvolume libraries (https://doi. org/10. 5281/zenodo. 1286976). For cell dynamics in the tissue, we used the following: cells can undergo different processes: apical contractility increase, apico-basal traction, apical relaxation. At each iteration, the respective tasks are stored in an "event manager" in order to be executed at the following iteration. At each iteration, before execution of any task, tasks are shuffled to ensure a random ordering of their execution.
5b , e, red rectangle). Invagination depth was measured with respect to the vitelline membrane and the corresponding transversal sections (in the center or in the anterior part of the embryo, see figure legends) are presented in Figs. 7 8 9 , Supplementary Figs. 4  and 5. Morphometric analysis is the same for both the segmented microscopy data and the simulations. The analysis starts with the 3D positions of the cell boundaries. The cell area is determined as the area of the polygon enclosed by the boundary. Cell areas were measured when the embryo adopts a curved shape, i. e. , at the time step when the invagination depth corresponds to the in vivo depth of curved-shaped embryos (4. 9 ± 1. 1 µm). In order to account for in vivo variability, cell area was normalized to the average cell area at the end of cellularization for each data set.
Acknowledgements We thank  Arnaud Besson ,  Eric Theveneau ,  Bruno Monier ,  Daniela Roellig ,  Juan Carlos Lopez  and  Malek Djabali  for comments on the manuscript. We thank the  Imaging (LITC)  and  Drosophila  facilities of the  CBI. M. S. 's lab  is supported by grants from the  European Research Council (ERC)  under the  European Union   Horizon 2020 research and innovation program  (grant number  EPAF: 648001 ), the  Fondation Arc pour la Recherche sur le Cancer  ( CA 09-12-2014 ) and from the  Institut National de la Santé et de la Recherche Médicale  (Inserm, Plan cancer 2014-2019). M. G. has been supported by the  Ligue Nationale contre le Cancer  and the  Fondation pour la Recherche Medicale ; ST by the  ANRT  during their Ph. D.
Data availability Results obtained from the vertex model are displayed using the Matplotlib (https://doi. org/10. 5281/zenodo. 1202077) and Ipyvolume libraries (https://doi. org/10. 5281/ zenodo. 1286976). The data that support all experimental findings of this study are available from the corresponding authors upon reasonable request. Correspondence and requests should be addressed to M. S. and C. B. (magali. suzanne@univ-tlse3. fr and corinne. ben-assayag@univ-tlse3. fr) for biology and materials and to G. G. (guillaume@morphogenie. fr) for modeling. The source data underlying Figs. 2e, 5c, 7d, 8c, f, 9e and Supplementary Figs. 2c-e , 4a-c, 5c, f are provided as a Source Data file.
, 2018). SLP and Z500 yield similar properties during the winter. One of the caveats of this reanalysis dataset is the lack of homogeneity of assimilated data, in particular before the satellite era. This can lead to breaks in pressure related variables, although such breaks are mostly detected in the Southern Hemisphere and the Arctic regions  (Sturaro, 2003) , and it marginally impacts the eastern North Atlantic region. Since Z500 values depend on temperature, we detrend the Z500 daily field by removing a seasonal average linear trend from each grid point. This preprocessing is performed to ensure that the results do not depend on atmospheric trends. All the analogue computations of this paper were performed on detrended and raw Z500 data, in order to verify the robustness of the results to Z500 trends.
Temperature observations We took daily averages (TGs) of temperatures from the European Climate Assessment & Dataset (ECA & D) project  (Klein-Tank et al. , 2002). We extracted data from Berlin, De Bilt, Toulouse, Orly and Madrid (Fig. 1 ). We consider data from June-July-August (JJA). Those five stations cover a large longitudinal and latitudinal range in western Europe. These datasets were also chosen because they start before 1948 and end after 2018. This allows the computation of analogue temperatures with the Z500 from the NCEP reanalysis, which includes that period; they contain less than 10 % of missing data. These two criteria allow keeping 528 of the 11 422 ECA&D stations that are available in 2018. The five daily TGs are then averaged in order to provide a daily European temperature index.
Circulation analogues Analogues of circulation are computed on Z500 data from reanalysis data of the NCEP reanalysis (Sect. 2. 1) on the region outlined in red in Fig. 1. The reason to use this field rather than SLP is linked to the heat low of SLP during heat waves  (Jézéquel et al. , 2018). SLP and Z500 yield similar properties during the winter. For each day between 1 January 1948 and 31 December 2018, the best 20 analogues (with respect to a Euclidean distance) in a different year and within 30 cal-endar days are searched. This follows the procedure of  Yiou et al. (2013). The small region (20 • W-25 • E; 40-70 • N) is used to compute analogues of Z500, to simulate continental temperatures, following the domain recommendations of the analysis of  Jézéquel et al. (2018). We compute analogues on "raw" daily Z500 data and detrended Z500.
(2017). The major algorithmic difference is that importance sampling "eliminates" trajectories with "poor" properties of the observable, while the analogue importance sampling "favors" the trajectories with the "best" properties. The analogue importance sampling uses a self-coherent dataset as a basis (here: observations for temperature and a reanalysis for Z500 analogues), ensuring that the simulated trajectories bear physical consistence between temperature and the atmospheric circulation. The physical relevance also requires that simulations follow a seasonal cycle. If one is interested in simulating a perpetual summer, then the weight value α cal on the calendar day is not very important. For physically realistic simulations, the value of α cal can be chosen to be the smallest for which the temperature simulation median yields a seasonality.
This methodology simulates ensembles of extreme heat waves that are possible in present-day conditions. We emphasize that no hypothesis on climate change is made to simulate events that are more intense than the record of 2003. One parameter of the simulations controls the weight to be given to the hottest analogues. This parameter also controls the return period of simulation ensembles, similarly to the control parameter of  Ragone et al. (2017). Thus, the simulated ensembles are associated with a return period (or a range of return periods). This methodology is relatively easy to implement and does not require running a high-resolution climate model because it uses already existing datasets. It was tested on rather restricted cases of summer warm temperatures. It can be adapted to simulate other types of extreme events: -Temperature extremes in other seasons.
The examples in this paper exclusively used NCEP reanalysis  (Kistler et al. , 2001) data and ECA & D (Klein-Tank et al. , 2002)  observations for present-day climate conditions. Simulations could use the CMIP model database  (Taylor et al. , 2012)  for analogue computation, and hence it would be possible to investigate changes in extremes for scenario simulations, relative to control simulations. Therefore, we consider that this paper paves the way for many types of studies of impacts of extreme events and risk assessment for extremes  (Sutton, 2019). www. geosci-model-dev. net/13/763/2020/ Geosci. Model Dev. , 13, 763-781, 2020.
Acknowledgements. We thank  Freddy Bouchet  and  Francesco Ragone  for enlightening discussions on importance sampling. We thank  Juliette Legrand ,  Natacha Legrix ,  Jason Markantonis ,  Peter Pfleiderer  and  Edoardo Vignotto  for discussions on the implementation of the computing code. The two anonymous reviewers greatly helped improve the paper. Financial support. This work was supported by  ERC  grant no. 338965-A2C2  and the  CoCliServ  project, which is part of  ERA4CS , an  ERA-NET  initiated by  JPI  Climate and co-funded by the  European Union  (grant no. 690462  from the  H2020-EU. 3. 5. 1. research and innovation program ). Review statement. This paper was edited by  Leena Järvi  and reviewed by two anonymous referees.
Code availability. The R code for simulations is available from Yiou (2019) under a free CeCILL licence. The analogues are computed with the "blackswan" WPS  (Hempelmann et al. , 2018). Data availability. NCEP reanalysis and ECA&D data are available on open web sites. Sample input temperature and Z500 analogue files are provided by  Yiou (2019). Sample availability. A sample file for Orly temperature simulations is available from  Yiou (2019).
Structural information of GH3 enzymes is available through 36 unique entries in the Protein Data Bank (PDB) from all phyla, although there is only one plant structure available (that of HvExoI), notably in complex with a variety of oligosaccharide substrate analogues and mimics  [7] [8] [9]. HvExoI folds in an (α/β) 8 barrel (domain 1) and an (α/β) 6 sandwich (domain 2) that at their interface cradle a 13 Å-deep pocket-or crater-shaped active site. This site accommodates the catalytic nucleophile Asp285 and catalytic acid/base Glu491 in the -1 subsite, while the aromatic clamp of Trp286 and Trp434 indole moieties constitutes the neighbouring +1 subsite  [6] [7] [8] [9]. HvExoI releases a single Glc from non-reducing termini of oligo-and polymeric β-D-glucosides to support seed germination and plant development  9.
5-2. 7 Å between Oδ1 and Oδ2 of Asp95, and the C6-OH and C4-OH groups of the Glc moiety. We attempted to position into the electron density other skew boat conformers of Glc ( 3 S 5 , 1 S 5 ) with various occupancies, however, convergence in the refinement was reached with those of  4  C 1 and 1 S 3. We concluded that during maturation in P. pastoris, Glc cannot be entrapped and thus observed, because the intracellular concentration in this host is not high enough during enzyme maturation or secretion. To demonstrate that Glc was not displaced from the active site by the cryoprotectant, data were collected from recombinant crystals at ambient temperatures without applying vitrification solutions. Here, no Glc was observed in the active site, but was readily observable after perfusion of crystals with Glc.
Enzyme inactivation was monitored at 30 °C by incubating 8 μmoles of the enzyme in 100 mM sodium acetate buffer, pH 5. 25, containing 0. 8-6. 6 mM 4NPGlc as a substrate, 160 μg/ml BSA, and 3dGlc, 4dGlc, octyl-O-Glc, octyl-S-Glc and G2SG-OMe. Each inhibitor was tested at six concentrations at 0. 4-3 times the K i values in duplicate. We used the v = V max S / [K M × (1 + I/K i ) + S] equation to calculate K i constant; K i is defined as a dissociation constant of the enzyme-inhibitor complex. The enzyme activity was monitored at 410 nm and Dixon plots were used to determine K i under the pseudo-first-order rate limiting conditions by a non-linear regression analysis, as described previously  22. Expression and crystallisation of recombinant HvExoI. The optimised HvExoI cDNA (GenBank Accession GU441535; was subcloned into the pPICZαBNH 8 vector, from which the protein was expressed in Pichia pastoris strain SMD1168H (Invitrogen, Carlsbad, CA, USA).
The final concentrations of ligands were between 5-20 mM and perfusion proceeded during 5-720 min. Alternatively, the crystals were deposited in a solution A with the concentration of PEG increased to the 35% (v/v). After various perfusion times at 4 ± 2 °C crystals were cryo-protected with 15% (v/v) glycerol in the solution A and mounted on a synchrotron goniometer in a stream of N 2 gas at 100 K (Oxford Instruments, UK). X-ray diffraction data (native, and with 3dGlc and 4dGlc) were collected on the undulator beamline BioCARS 14-ID-B at the University of Chicago Advanced Photon Source (USA) equipped with a bent cylindrical Si-mirror (Rh coating) Diamond(111) double-bounce monochromator and focussing to the MARCCD-165 detector. X-ray diffraction data sets of crystals with PEG and with octyl-O-Glc and octyl-S-Glc were collected using the multipole wiggler beamline BL5 at the Photon Factory (Japan), which was fitted with a collimating mirror, double-crystal Si(111) monochromator and a focusing to the ADSC Quantum 315 CCD detector.
X-ray diffraction data from recombinant WT and variants were collected at the MX1 and MX2 beamlines of the Australian Synchrotron (Australia) at 100 K (Oxford Instruments) or at ambient temperature (291 K) with a collimating mirror, double-crystal Si(111) monochromator 03BM1 dipole/bending magnet and ADSC Quantum 210r Detector. In the latter case, crystals were mounted using transparent polymer capillaries from the RT Screening kit (MiTeGen). All data were collected at 0. 5-1°oscillations throughout 180-720°. Data were processed using the DENZO/SCALEPACK HKL 2000 suite of programmes  61. Autoindexing determined that space group P4 3 2 1 2 of crystals were consistent with the tetragonal space group P43212 in all instances. The structures of the enzyme-ligand complexes were refined using CCP4 REFMAC5  62  and PHENIX  63.
We used the solved structures (PDB accessions: 1EX1, 1IEQ, 1IEV, 1IEW, 1IEX and 1J8V) without ligands, ions, glycerol and water molecules, as starting models for refinements of HvExoI in complex with ligands  7, [15] [16] [17]. The iterative model building using XtalView/MIFIT  64  , Coot  65  and refinements with REFMAC5  62  allowed tracing of all the residues. Following convergence in a standard refinement, a further improvement of about 2% in the Rwork/Rfree factors ratio was achieved by refining domain 1, (residues 1-357) and domain 2, (residues 374-559), as two independent anisotropic entities with translation-librationscrew (TLS) motion  66, 67. Electron densities for the ligands were well-defined in the active site regions at 3σ level in m|F o |-|F c | maps and water molecules were located automatically with CCP4 ARP at levels higher than 3σ.
The protein contained Glc at the -1 subsite, and G2OG or G3OG attached at +1 and putative +2 subsites. GaudiMM  20  (https://github. com/insilichem/gaudi), a recently developed modular multi-objective genetic algorithm platform allows conformational exploration of defined genes (defined below) with multiple evaluation operators of fitness or objectives. The GPathFinder extension was used, defining as genes protein and substrates molecules, rotational bonds of ligands and rotamers of the protein, and as objectives, minimisation of van der Waals contacts and maximisation of separations between Glc geometric centres at the -1 subsite. This afforded the lowcost computational pre-identification of putative exit channels. The ProDy (Protein Dynamics)  92  Normal Mode Algorithm (NMA) was used to generate alternative starting structures for the GPathFinder.
Normal mode calculations were performed with Tangram implementation on the UCSF Chimera suite  93  , using residues grouped in clusters of 100 (to avoid protein distortion and achieve acceptable conformations), generating 10 modes with a cut-off of 15. 0 Å and a Gamma LJ of 1. 0. In the case of the crystal structure (PDB 3WLH), the second frame of the mode with frequency 31. 2 cm -1 was chosen, while the second frame of the mode with frequency 28. 7 cm -1 was selected for complex 3. In both cases, the displacement parameter in the Tangram interface was set to 150. PELE calculations. The PELE software (https://pele. bsc. es)  21, 94 was used to simulate Glc displacement and to identify the Glc migration route from the -1 subsite. PELE is a Monte Carlo based algorithm that generates configurations along a path through a sequential ligand and protein geometric perturbation scheme, side-chain conformational prediction and minimisation steps.
Acknowledgements We thank  M. Raab  ( Slovak Academy of Sciences ),  B. J. Smith  ( La Trobe University ) and  G. B. Fincher  ( University of Adelaide ) for interest in this research. H. Tong  ( Advanced Photon Source ),  N. Matsugaki  and  S. Wakatsuki  ( Photon Factory ), and  F. Pettolino  ( University of Melbourne ) are thanked for advice and  S. Pradeau  for technical assistance. Funding was supported by the  Huaiyin Normal University  and the  Australian Research Council  ( DP120100900 ) to M. Hrmova. , the  Australian Synchrotron  (MX1 and MX2 beamlines) to M. Hrmova. and V. A. S. , the  Advanced Photon Source  ( 14-ID-B beamline ) to J. N. V. and  M. Hrmova. , the  Photon Factory  (BL5 beamline) to V. A. S, the  Suranaree University of Technology  and the  Thailand Research Fund  ( BRG5980015 ) to J.
S. F. was supported by  Glyco@Alps  ( ANR-15-IDEX-02 ),  Carnot Institut PolyNat ,  Labex ARCANE  and  CBH-EUR-GS  ( ANR-17-EURE-0003 ), and thanks to  Chimie Moléculaire de Grenoble  for access to facilities. M. A. -P. and C. R. acknowledge  MareNostrum and Minotauro and BSC-CNS  ( RES-QCM-2017-2-001 ) resources. Use of synchrotrons was supported by the  Australian Synchrotron Research Program , which is funded by the  Commonwealth of Australia  under the  Major National Research Facilities Program.
Data availability The atomic coordinates and structure factors were deposited in the Protein Data Bank (www. pdb. org) with the PDB accessions: native HvExoI, and in complex with 3dGlc, 4dGlc, octyl-O-Glc, octyl-S-Glc and PEG400 are 3WLH, 3WLJ, 3WLK, 3WLM, 3WLN and 3WLL, respectively. The PDB accessions of WT recombinant ligand-free HvExoI and in complex with Glc, G2SG-OMe and G6SG-OMe are 3WLI, 3WLO, 6MD6 and 3WLP, respectively. The PDB accessions of recombinant R158A/E161A ligand-free HvExoI and in complex with Glc and G6SG-OMe, are 3WLQ, 3WLR and 6MI1, respectively. A reporting summary for this Article is available as a Supplementary Information file. All other data generated and/or analysed during the current study are available from the corresponding author upon reasonable request.
All genomes were annotated using MicroScope's automatic annotation pipeline, and manual curation was carried out on the genome of UBOCC-A-315001 using the same pipeline  [39, 40]. The superior, manual annotation was spread to all genes using a similarity criterion (> 90% identity, > 70% similarity, alignment > 80% of CDS length) to supersede the automatic annotation on a gene by gene basis. The newly sequenced genomes range from 1. 79 to 1. 92 Mb in size, which is in the range of O. oeni genomes reported to date (from 1. 69 to 2. 55 Mb according to data in Genbank). The two full genomes contain only two sets of rRNA operons, which seems to be universal in this species. The count of coding regions (CDS) is fairly stable through the assemblies at a mean of 1905 ± 48, though high numbers of contigs in several assemblies may inflate the CDS count when genes are counted more than once.
Phylogenetic clustering of the newly sequenced strains To identify the phylogeny of the newly sequenced strains, phylogenetic trees were constructed using the 14 obtained genome sequences as well as 212 O. oeni genome assemblies from NCBI's Genbank. Genome sequences of O. kitaharae, O. alcoholitolerans and Leuconostoc mesenteroides were used as outgroups. A phylogenetic tree was constructed using the Average Nucleotide Identity (ANI) method, using a combination of BLAST and MUMmer to find the optimal distances inside and between the species, respectively. ANIm and ANIb distance matrices were used to reconstruct a hybrid tree by using Neighbor Joining (Fig. 1a ). The previously identified A and B groups were well separated in this tree and subgroups are clearly visible in A as reported in previous studies  [12, 13].
This survivor bias could be a cause of undersampling, whereas the less restrictive cider environment allows a higher diversity of strains to grow. It has been suggested that O. oeni strains are not generally constrained by geography  [33] , so we did not consider that the divergence was due to the fact that these strains evolved independently due to geographical partitioning. To confirm the existence of the two newly defined groups C and D by another analytical method, we calculated distance matrices from the presence of Single Nucleotide Polymorphisms (SNPs). The core genome of all new and public O. oeni strains (n = 226) was calculated and aligned by ClustalOmega. 210,180 SNPs were identified and used to reconstruct phylogenetic trees using Maximum Parsimony (data not shown) and Maximum Likelihood showing evolutionary distances (Fig.
Synteny and variable regions in full genomes of C and D group strains To determine if C and D group strains shared the same genome organization as that of group A strains, we circularized the genomes of one representative strain from each group: CRBO_1381 (group C) and UBOCC-A-315001 (group D). They are the first fully completed O. oeni genomes since PSU-1 (group A), although another full genome has been uploaded to the NCBI's database during the preparation of this manuscript (strain "19", GCA_003264795. 1). The new genomes are 1,834,577 and 1,876,981-bp long, respectively, and contain two sets of rRNA operons, which is somewhat similar to PSU-1's genome (Table  1 ). Genomic rearrangements amongst group A, C and D strains were investigated using the SyMap algorithm  [42] , but no rearrangements or inversions were found (Additional file.