dataesr/scientific-paragraphs-categorization huggingface dataset:
, 2016) , corresponding to smoothing (from the O 3 profile), interfering species and retrieval parameters in Table  2. The m is derived from the SNR. The systematic uncertainties of both O 3 and interfering species a priori profiles are set to 10 %, and their random uncertainties are derived from the WACCM data. According to the ATM2019 line list, the systematic uncertainties of O 3 line intensity, air broadening and pressure broadening are 10 %-20 %, 5 %-10 % and 5 %-10 %, respectively. In this study, we set 15 %, 7. 5 % and 7. 5 % for the systematic uncertainties of the O 3 line intensity, air broadening and pressure broadening, respectively, and we assume that there are no random uncertainties. The uncertainties for temperature and H 2 O are derived from the difference between NCEP reanalysis data and the European Centre for Medium-Range Weather Forecasts (ECMWF) ERA5 reanalysis data, where the mean difference is set as the systematic uncertainty, and the standard deviation (SD) of the differences is set as the random uncertainty.
Note that we have applied the pressure pump efficiency corrections to the IAP ozonesonde  (Zheng et al. , 2018). The IAP ozonesonde measurements used in this study cover the period between June 2018 and February 2019, after which the ozonesonde measurements stopped. The ozonesonde data performed at Gillot, Réunion (20. 89 • S, 55. 53 • E; 8 m a. s. l. ), are affiliated with NDACC  (De Mazière et al. , 2018)  and the Southern Hemisphere ADditional OZonesondes (SHADOZ) network  (Thompson et al. , 2003). Detailed information about the ozonesonde measurements at Gillot can be found in  Thompson et al. (2014)  and  Witte et al. (2017) , where the ozonesonde measurements are applied to understand the tropospheric ozone increases over the southern Africa region. Gillot is about 26 km away from Maïdo and is considered representative for the ozone concentrations at Maïdo  (Duflot et al.
The profiles of the FTIR retrievals and ozonesonde measurements, together with their relative differences at Xianghe and Maïdo, are shown in Fig. 4. In general, the relative difference profiles at these two sites are similar: within ±15 % below 20 km and between -30 % and 10 % between 20 and 40 km. The total column observed by ozonesonde is 6. 4±6. 0 (1σ ) % and 9. 0 ± 4. 3 % larger than the FTIR (3040 cm -1 ) retrievals at Xianghe and Maïdo, respectively. To check the impact of the O 3 columns above the maximum height of Table  3. The mean and SD ("mean/SD") of the relative differences between the FTIR O 3 (3040 cm -1 ) retrievals with other datasets (ozonesonde, TROPOMI and FTIR O 3 (1000 cm -1 retrievals)) in total column and two partial columns (surface-20 km and 20-40 km) at Xianghe and Maïdo.
Datasets Xianghe Maïdo mean/SD mean/SD (%) (%) Total column Ozonesonde -6. 4/6. 0 -9. 0/4. 3 FTIR (1000 cm -1 ) -8. 4/1. 1 TROPOMI -5. 5/2. 0 -6. 1/1. 3 Surface-20 km Ozonesonde -0. 3/6. 0 -2. 4/6. 6 FTIR (1000 cm -1 ) 0. 8/4. 4 20-40 km Ozonesonde -10. 3/7. 8 -10. 1/6. 5 FTIR (1000 cm -1 ) -10. 8/1. 8 the ozonesonde, we also compare the FTIR column between the surface to the maximum altitude of each co-located ozonesonde profile, where the ozonesonde measurements are 6. 2 ± 6. 1 % and 9. 7 ± 7. 0 % larger than the FTIR retrievals at Xianghe and Maïdo, respectively. As a result, the impact of extending the ozonesonde profile to higher altitude with the FTIR a priori profile is relatively small compared to the large uncertainty. The comparisons between the total and partial columns (surface-20 km and 20-40 km) retrieved from the FTIR and the ozonesonde measurements are listed in Table  3.
In order to reduce the influence of different a priori profiles, we substitute the satellite a priori profile for the ground-based FTIR a priori profile when comparing both datasets: x r = x r + (I -A) x s, a -x F, a , (5) where x r is the adapted FTIR profile by using the satellite a priori profile as the a priori profile, x r is the original FTIR retrieved profile, and x s, a and x F, a are the satellite and FTIR a priori profiles. TROPOMI provides the column averaging kernel (A s ) together with the total column; therefore, we applied the smoothing correction to the adapted FTIR profile: TC r = TC s, a + A s P C dry, air x r -x s, a , (6) where TC s, a is the TROPOMI a priori total column and TC r is the FTIR retrieved total column after a priori profile substitution and taking TROPOMI vertical sensitivity into account.
The time series of the hourly-mean retrieved O 3 total column and partial columns (surface-20 and 20-40 km) in the 3040 and 1000 cm -1 spectral ranges, together with their differences and correlations, are shown in Fig. 7. Both O 3 datasets show the same seasonal variations in the total column and the two partial columns. The mean and SD of their relative differences are also listed in Table  3. The O 3 (3040 cm -1 ) total columns have a negative bias of 8. 4±1. 1 % compared to the O 3 (1000 cm -1 ) total columns. For the lower partial column (surface-20 km), the two FTIR O 3 retrievals are close to each other, with a mean relative difference of 0. 8±4. 4 %. The O 3 upper partial column (20-40 km) retrieved in the 3040 cm -1 spectral range is 10. 8 ± 1. 8 % smaller than the one retrieved in the 1000 cm -1 spectral range.
The FTIR (3040 cm -1 ) retrievals at Xianghe and Maïdo show the same seasonal and synoptic O 3 variations as seen by the TROPOMI satellite measurements and the NDACC standard FTIR O 3 retrievals at Maïdo. The ongoing FTIR O 3 total and partial columns (surface-20 km and 20-40 km) data at Xianghe can provide useful information on O 3 synoptic and seasonal variations and longterm trends. Based on the successful and consistent O 3 retrieval results at Xianghe and Maïdo, the retrieval strategy used in this study can be extended to other FTIR sites recording the 3040 cm -1 spectral range.
Acknowledgements. This research was supported by the  National Key R&D Program of Chin  and the  National Natural Science Foundation of China. The FTIR site at Réunion is operated by the  BIRA-IASB  and locally supported by LACy /UMR8105 ,  Université de La Réunion. We would like to thank  Weidong Nan ,  Qun Cheng  and  Rongshi Zou  ( IAP ) for the FTIR maintenance at Xianghe;  Geoffrey C. Toon  ( JPL, NASA ) for sharing the ATM2019 spectroscopy;  Daan Hubert  ( BIRA-IASB ) for useful discussion about the ozonesonde measurements;  James Hannigan  ( NCAR ) for providing the WACCM data at Xianghe; and  Ball William  ( ETH Zürich ) for useful discussions. We also acknowledge the  NDACC-IRWG  network for providing the retrieval code and  ESA  for providing the TROPOMI products. Financial support.
Data availability. The NDACC standard FTIR O 3 (1000 cm -1 ) retrievals at Maïdo and the ozonesonde measurements are publicly available at the NDACC archive (http://www. ndacc. org, last access: 20 January 2019, InfraRed working Group, 2020). The TROPOMI offline data are publicly available at the ESA Copernicus Open Access Hub (https://scihub. copernicus. eu/, last access: 20 September 2020, Copernicus Open Access Hub, 2020). The FTIR O 3 (3040 cm -1 ) retrievals at Xianghe used in this study are available via https://github. com/zmq814/O3_xianghe. git (last access: 17 August 2020, Zhou, 2020).
Both cases reveal that the shorter the hydrogen bond, the larger the chemical-shift difference between the H Z and H E protons  (Barfield, 2002). We speculate that the scenario described in Figure  4  is more likely reflecting the situation in asparagine ladders, although not only the hydrogen bond length effects the strength of the hydrogen bond and thus the proton chemical-shift values observed experimentally, but also the bond angle certainly has an influence. Experimentally, for N226 we find a large difference between the two proton resonances resonating at 8. 4 and 6. 5 ppm. For N262 the less-shielded value is 7. 6 ppm compared to 6. 8 ppm for the more-shielded one. The two NH 2 protons are thus shifted in different directions with respect to their average chemical-shift values over all deposited asparagine residues as extracted from the BMRB database (7.
0 ms and τ N = 1. 2 ms). homo for N279 is even larger (543 ± 140 Hz). All these values are significantly larger than the corresponding values of the backbone amide protons, which have been reported before, showing on average 22 ± 1 Hz at 100 kHz MAS for DUL HET-s(218-289)  (Smith-Penzel, 2019). The glutamine side-chains which are easily observed in INEPT-hNH have, as expected, a smaller homo value (<50 Hz). As an additional reference we also measured the homogeneous proton linewidths for asparagine and glutamine side-chains in DnaB. In accordance with the experimental observation of glutamine side-chains in INEPT spectra, the homo are indeed smaller and amount on average to 31 ± 5 Hz (Supplementary Figure  S10 ). To investigate whether the larger-than-expected homo values observed for the asparagine side-chains are related to coherent broadening mechanisms, we have numerically simulated the 1 H solid-state NMR spectrum using the geometry of the six NH 2 proton spins of N262-N226-N262 taken from the PDB file (Figure  1 , PDB accession number 2KJ3, the chosen geometry is taken from structure 16 in which the asparagine ladder N226/N262 is most clearly visible, see also Supplementary Figure  S11A ).
Whether this observation is a general feature of N/Q ladders has to be investigated on further amyloid fibrils in future work, it is however interesting that the glutamine sidechains in  do not show these effects, and their homogeneous linewidths are roughly by a factor of three smaller. Characterization of Glutamine Side-Chains and the Orientation of Q240 For the two glutamine side-chains of , no ladder formation is possible from the structure  (Van Melckebeke et al. , 2010). Both glutamine side-chain NH 2 are observed in the CP and INEPT-spectra (Figures  2A, 3D ). For Q240, one proton is shifted to the more shielded region (4. 8 ppm), the other one is at 7. 8 ppm, slightly less shielded compared to the average chemical shift values taken from the BMRB database (7. 22/7. 04 ppm). The increased shielding of one of the NH 2 proton of Q240 might be associated with ring-current effects, since Q240 points toward a hydrophobic pocket constituted by aromatic residues (F286 and W287, Figure  2D ;  Van Melckebeke et al.
Solid-State NMR Solid-state NMR spectra were acquired at 20. 0 T static magnetic-field strength using a Bruker 0. 7 mm probe. The MAS frequency was set to 110 kHz. The 2D spectra were processed with the software TOPSPIN (version 3. 5, Bruker Biospin) with a shifted (3. 0) squared cosine apodization function and automated baseline correction in the indirect and direct dimensions. The sample temperature was set to 293 K  (Böckmann et al. , 2009). All spectra were analyzed with the software CcpNmr  (Fogh et al. , 2002; Vranken et al. , 2005; Stevens et al. , 2011)  and referenced to 4,4-dimethyl-4-silapentane-1-sulfonic acid (DSS). Site-specific relaxationrate constants were extracted from the 2D hNH relaxation experiments, using the INFOS software  (Smith, 2017)  (see Supplementary Figures S14, S15 for the mono-exponential fits of all relaxation decay curves for DUL HET-s).
Numerical Simulations The numerical simulations of 1 H MAS spectra were performed with SIMPSON  (Bak et al. , 2000)  using six proton spins in the geometry extracted from the pdb file 2JK3 (structure 16). The spin-echo decay curves were obtained using the same proton six-spin system with and without three nitrogen spins. The simulations were performed in the GAMMA spin simulations environment  (Smith et al. , 1994). The program code for the simulations is provided in the Supplementary Material.
Overview of asparagine and glutamine side-chain spectral and relaxation properties. Determined on protonated HET-s fibrils in 13 C-detected MAS experiments (BMRB accession code 11064). Differences to the values derived from 1 H-detected experiments are related to temperature differences in the experiments. bThe average value over the relaxation rate constants for both resonances is given. The error is derived by error propagation of the individual experimental errors (a 2σ error is given). c homo is calculated according to R 2 '/π = 1/(πT 2 ').
FUNDING This work was supported by the  ETH Career   SEED-69 16-1  (TW) and the  ETH Research Grant   ETH-43 17-2  (TW), an  ERC Advanced Grant  (BM, Grant No. 741863 , Faster), by the  Swiss National Science Foundation  (BM, Grant Nos. 200020_159707  and  200020-188711 ,  ME , Grant No. 200020_188988 ), the  French Agence Nationale de Recherche  ( AB ,  ANR-14-CE09-0024B ), and the  LABEX ECOFECT (AB ,  ANR-11-LABX-0048 ) within the  Université de Lyon program Investissements d'Avenir (AB ,  ANR-11-IDEX-0007 ).
Description of data collection Radioactivity counts retained on GF/C filters were counted on a γ -counter. Filtered luminescence readings of BRET experiments were recorded in endpoint readout using a multimode plate reader equipped with a BRET2 filter set. Optical density (absorbance) of the colorimetric reaction for cell-surface ELISA was recorded in endpoint readout using a multimode plate reader using a 450 nm filter. Western blots for phosphorylation of p42/p44 were revealed using an enhanced chemiluminescence detection with high sensitivity films. ( continued on next page ) Remaining intact peptide in plasma stability assay was quantified using an internal standard and UPLC/MS system. Graphs, data normalization, and non-linear regression fits were done using GraphPad Prism v7. 0a. Western blots for phosphorylation of p42/p44 were revealed using an enhanced chemiluminescence detection with high sensitivity films.
Radioligand binding experiments Binding experiments were carried out on freshly prepared membrane homogenates as previously described  [4]. Competition radioligand binding experiments were performed by incubating cell membranes with 125 I-[T yr 3 ]-NT (specific activity of 2200 Ci/mmol) and different concentrations of ligands (ranging from 10 -11 to 10 -5 M) for a hour at room temperature. All binding data were plotted and fitted by using the One site -Fit Log(IC 50 ) of Prism v7. 0a (GraphPad, La Jolla, CA, USA) and represent the mean ± SEM of three separate determinations.
The cells were then stimulated with 5 μM of coelenterazine 400A (GoldBio, St-Louis, MO, USA), incubated at 37 °C for 5 minutes, and read on a GENios Pro plate reader (Tecan, Durham, NC, USA) using a BRET 2 filter set (410 nm and 515 nm emission filters). For each well, a BRET2 ratio was determined by dividing the GFP10-associated light emission by RlucII-associated light emission. The data was subsequently normalized relative to NT(8-13); values for non-treated cells were set as 0% pathway activation, and those for cells treated with 1 μM NT(8-13) were set as 100% pathway activation.
JMV2009-induced NT receptors internalization Receptor internalization using CHO-K1 cells transiently transfected with either HA-NTS1 or HA-NTS2 was carried out as previously described in details  [9] [10] [11]. Before ELISA detection, cells were washed with PBS and stimulated using 1 μM of NT or JMV2009 for 60 min at 37 °C in serum-free media. Cells were then washed with PBS and remaining ELISA steps form the detailed protocol were followed and unchanged. Absorbance was read at 450 nm and data were normalized according to the protocol. of the Canadian Council on Animal Care, the ARRIVE recommendations  [12]  , and the National Institutes of Health guide for the care and use of Laboratory animals (NIH Publications No. 8023).
Acknowledgments ÉBO is the recipient of a  Fond de recherche du Québec -Santé  ( FRQ-S, grant   255989 ) and a  Canadian Institutes for Health Research (CIHR , grant  MFE-164740 ) research fellowships. PT is the recipient of a post-doctoral fellowship from the  CIHR  (grant  MFE-135472 ). RLB is the recipient of a Ph. D. Scholarship from the  FRQ-S  and the  Faculty of Medicine and Health Sciences  of the  Université de Sherbrooke. PS is the recipient of a Tier 1  Canada Research Chair in Neurophysiopharmacology of Chronic Pain  and a member of the  FRQ-S-funded Québec Pain Research Network (QPRN). This research was supported by grants from the  Canadian Institutes for Health Research  (grants  MOP-74618 ,  FDN-148413 ).
Small angle x-ray scattering experiments Small angle x-ray scattering (SAXS) data were collected at the BioSAXS beamline (ID14-3) of the ESRF  (57). The scattering from the buffer alone was measured before and after each sample measurement and used for background subtraction. All data analyses were performed using the program PRIMUS from the ATSAS 3. 0. 0 package  (58).
NMR spectroscopy The spectral assignment of the different constructs of NiV P protein (P 1-100 , P  , P 173-240 , P 223-319 , P 300-401 , P 387-479 , P 588-650 , and P XD (residues 655-709)) at 25 C in buffer B was determined using BEST-type triple resonance experiments  (59). The NMR experiments were acquired at a 1 H frequency of 600 or 800 MHz (Agilent spectrometers). Six experiments were acquired for each construct: HNCO, intraresidue HN(CA)CO, HN(CO)CA, intraresidue HNCA, HN(COCA)CB, and intraresidue HN(CA)CB. All spectra were processed in NMRPipe  (60)  and analyzed in Sparky  (61) , and automatic assignment of spin systems was done using MARS  (62) , followed by manual verification. The assigned chemical shifts have been deposited in the BMRB database under accession numbers 50098, 50099, 50100, 50101, 50102, 50103, and 50105.
X-ray crystallography Initial crystallization conditions for the tetramerization domain (aa 471-580) were identified at the High Throughput Crystallization platform of the Partnership for Structural Biology (https://htxlab. embl. fr). The crystals used for data collection were obtained in 7% PEG 3350, 1 M LiCl, 0. 1 M sodium citrate, 0. 1 M arginine, 4% hexanediol, and 0. 001% NaN3 at pH 5. 0 and were frozen with 15% glycerol as cryoprotectant. X-ray diffraction data were collected at the ID29 beamline of the ESRF at a wavelength of 0. 9793 A ˚and at the Proxima1 beamline of SOLEIL at a wavelength of 0. 97895 A ˚and a temperature of 100 K and were processed with the XDS package  (64). Initial phases were obtained using the anomalous scattering from selenium atoms by the SAD method with the program HKL2MAP  (65).
A model was initially constructed with the Autobuild program (66) from the phenix suite (67) and subsequently refined with the phenix. refine program  (68)  and Coot  (69). The geometry of the final model was checked with MolProbity (70). In the model, 98. 04% of residues had backbone dihedral angles in the favored region of the Ramachandran plot, 1. 83% fall in the allowed regions, and 0. 13% were outliers. Figures were generated with PYMOL (71) and Chimera  (72). high-resolution three-dimensional structures of the tetramerization domain (P MD ) and a homology model of the C-terminal X domain based on the known HeV P XD structure (74) by using Modeler  (75). To accurately model the disordered N-terminal region, the ASTEROIDS selection algorithm  (76)  was first applied to each of the subconstructs of the phosphoprotein to obtain an ensemble of conformers of these regions in agreement with experimental 1 H N , 15 N, 13 C a , 13 C b , and 13 C 0 chemical shifts.
Briefly, in successive rounds of selection, 5 Â 200 pairs of (f, j) dihedral angles were selected for each residue from a pool of 10,000 conformers assembled by Flexible-Meccano such that the difference between ensemble-averaged 1 H, 15 N, and 13 C chemical shifts predicted by the program SPARTA  (77)  and corresponding experimental values was minimized. The selected dihedral angles were then used in generation of a new set of 10,000 conformers for the next round of selection. The (f, j) databases for each subconstruct of the phosphoprotein thus obtained after four rounds of selection were combined and used by Flexible-Meccano to build conformations of fulllength protein. Residues in the linker region between the tetramerization domain and the X domain were stochastically assigned amino-acid-specific backbone dihedral angles in agreement with random coil statistics.
In the disordered regions, side chains were constructed using the program SCCOMP  (78). Scattering curves were calculated with CRYSOL (ATSAS 3. 0. 0) (79) and ensemble selections were performed using ASTEROIDS (80) by combining both the experimental NMR and SAXS data. To account for conformational heterogeneity within different regions of the full-length protein, the ASTEROIDS target function combined SAXS data from three constructs: P FL , P 1-580 , and P 471-709 , representing the full-length tetramer and the tetramerization domain with the N-terminal and C-terminal parts of the protein, respectively.
ITC ITC experiments for characterizing the interaction between the five fragments P 92-190 (WT, Y116A, G120E, G125E, H117A/Q118A/H1119A) and STAT1 132-683 were performed with a MicroCal iTC200 system (Northampton, MA). The STAT1 solution at a concentration of 100 mM in buffer C was loaded in the calorimetric cell and titrated at 25 C, typically by performing 16 injections of 2. 5 mL of the wild-type (WT) P 92-190 solution or of one of the variants (at concentrations ranging between 1. 5 and 2. 5 mM) in the same buffer. Protein samples and buffers were degassed before data collection. The heat generated for each injection was obtained by integrating the calorimetric signal. The heat resulting from the binding reaction between the two proteins was obtained as the difference between the heat of the reaction and the corresponding heat of dilution.
S5 E ), as shown previously  (34, 37). The N-terminal region and the C-terminal linker are globally disordered Several fragments of $100 amino acids covering the entire N-terminal region but also the linker in the C-terminal part (P CT-LINK ), which is predicted to be at least partially disordered (IDR3 in Fig. 1 A ), and the X domain were produced as 13 C, 15 N-labeled proteins and purified (Fig. 1 C ). Each fragment from the N-terminal region has a hydrodynamic radius (R h ) significantly larger than that expected for a globular protein of the same molecular mass and slightly smaller than that expected for a fully unfolded protein in a good solvent (Table  1 ). SAXS data recorded for these fragments revealed no concentration dependence. For the different N-terminal fragments and for the fragment corresponding to the C-terminal linker (P 588-650 ), the experimental radius of gyration (R g ) values determined using the Guinier approximation were close to the R g -values calculated for a random coil according to Flory's power-law dependence on chain length using parameters for chemically unfolded proteins  (87)  or for intrinsically disordered proteins (Table  1;  (88)), in line with the proposal that these regions are disordered.
ACKOWLEDGMENTS We thank  Dr. Rob W. Ruigrok  ( Institute de Biologie Structurale, Grenoble, France ) for helpful discussions and  Dr. Daniel Panne  ( European Molecular Biology Laboratory, Grenoble, France ) for the gift of a plasmid coding for human STAT1. We thank the biosafety team members for their support in conducting experiments. F. Y. was supported by a predoctoral fellowship from the  R egion Rhone-Alpes. The work was supported by grants from the  French Agence Nationale de la Recherche  to M. J. and  M. B. ( ANR BSV8-2012-NNViPol ) and to M. J. and  V. Volchkov  ( ANR-18-CE11-0014-02 ), from the  Fond de la Recherche M edicale  (grant '' Equipe 2017 ''  DEQ20170336754 ) to M. J. and from the  Fondation Innovations en Infectiology (FINOVI)  to M. J. and V. Volchkov We acknowledge the  European Synchrotron Radiation Facility  for the allocation of beamtime on ID14-3 and ID23-1 and the  Synchrotron SOLEIL  for the allocation of beamtime on Proxima 1.