dataesr/scientific-paragraphs-categorization huggingface dataset:
The vertical resolution in the UTLS is ∼ 0. 5 km. WACCM6 uses comprehensive troposphere, stratosphere, mesosphere and lower thermosphere chemistry (TSMLT;  Gettelman et al. , 2019). Anthropogenic emissions are from the global CAMS (Copernicus Atmosphere Monitoring Service) emission data set version 4, downloaded from the ECCARD data page: http://www. igacproject. org/sites/default/files/2018-03/ Issue_61_FebMar_2018. pdf (last access: 21 January 2021). Fire emissions are based on the FINN inventory Version 1. 5  (Wiedinmyer et al. , 2011). The WACCM6 simulation used in this study has been performed with observed sea-surface temperature and sea-ice conditions. Atmospheric winds and temperatures are nudged towards NASA GMAO GEOS5. 12 meteorological analysis with a Newtonian relaxation of 50 h below 50 km using a smooth transition to no nudging at higher model levels from 50 to 60 km.
Conclusions In situ observations of CO, O 3 and N 2 O were collected during two aircraft campaigns near the edge and near the centre of the ASM anticyclone. CO and N 2 O are tropospheric tracers with short and long photochemical lifetimes, respectively, while O 3 is a mainly stratospheric tracer. Analysis of these observations helps us to further fill in the emerging picture of vertical transport in the ASM anticyclone, confirming and extending earlier studies: -A "fast convective chimney" lifts polluted boundary layer air to the ASM upper troposphere, with the main outflow below 370 K. -Inside the ASM anticyclone, above the level of main convective outflow, upward transport of air continues at slower rates roughly consistent with vertical velocities and heating rates from reanalysis data and on timescales largely consistent with photochemical removal and production of CO and O 3 , respectively (Figs.
It is not associated with a conference. Acknowledgements. We would like to thank the Myasishchev Design Bureau team operating the M55 Geophysica aircraft for the successful deployments and their support with instrument integration and operation and provision of avionic data. We thank the local airport and ATC (air traffic control) staff in Kalamata and Kathmandu for their support. We also thank Johannes Wintel, Valentin Lauther, Thorben Beckert, Emil Gerhardt and Lydia Eppert, who supported HAGAR operations and data analysis, as well as Nicole Spelten for preparing time-synchronized merged files that were used for our analyses. Special thanks to Fred Stroh for the tremendous spadework he put in to actually make the campaigns and flights in these locations possible and to Dipak Kumar Kharki for diplomatic support in Nepal.
Campaign planning and logistics as well as the scientific interpretation was largely covered by the StratoClim project funded by the EuropeanCommission's Seventh Framework Programme (FP7/2007-2013)under grant agreement no. 603557. Additional support for this work was obtained from the German Bundesministerium für Bildung und Forschung (BMBF) under the ROMIC-SPITFIRE project (BMBF-FKZ: 01LG1205), from a joint research project funded by the National Natural Science Foundation of China (NSFC project number 41761134097) and the German Research Foundation (DFG project number 392169209). The GEOS data used in the WACCM6 run have been provided by the Global Modeling and Assimilation Office (GMAO) at NASA Goddard Space Flight Center through the online data portal in the NASA Center for Climate Simulation.
Felix Ploeger was funded by the Helmholtz Association under grant no. VH-NG-1128 (Helmholtz Young Investigators Group A-SPECi). Corinna Kloss was partly funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) -409585735. We thank Michelle Santee, an anonymous reviewer, Rolf Müller and Bärbel Vogel for constructive comments on the article that helped to significantly improve this paper. Financial support. This research has been supported by the European Commission, Seventh Framework Programme (Stra-toClim (grant no. 603557)), the Bundesministerium für Bildung und Forschung (grant no. BMBF-FKZ: 01LG1205), the National Natural Science Foundation of China (grant no. 41761134097), the Deutsche Forschungsgemeinschaft (grant nos. 392169209, 409585735) and the Helmholtz Association (grant no.
Code availability. CESM2 WACCM6 software is available for download at https://escomp. github. io/CESM/versions/cesm2. 1/ html/downloading_cesm. html (US National Science Foundation, 2020). Data availability. All data will soon be accessible via the HALO database at https://halo-db. pa. op. dlr. de/mission/101 (German Aerospace Center, 2021). In the meantime, they can be provided by the principal investigators (MvH for AMICA; VY and FR for FOZAN; CMV for HAGAR) upon request.
Hence, it is essential to unveil the initial structural response of HbI upon the photodissociation of the ligands. Femtosecond TRXSS (fs-TRXSS) at X-ray free-electron lasers (XFELs) is one of the promising experimental methods to study the initial structural response of HbI in the solution phase. Indeed, fs-TRXSS has been used to disclose the ultrafast structural dynamics of small molecules  [19] [20] [21] [22] [23] [24] [25]  and proteins  26, 27. In spite of its strong potential, however, fs-TRXSS has been applied to a limited number of model protein systems such as myoglobin (Mb) and photosynthetic reaction center unlike time-resolved serial femtosecond X-ray crystallography (TR-SFX), which has been used for various protein systems  [28] [29] [30] [31] [32] [33] [34]. Moreover, the interpretation of fs-TRXSS data is still under debate.
In the present work, we studied the initial structural response of HbI upon photoexcitation via fs-TRXSS, covering both SAXS Amplitude (arb. units) Fig. 1  TRXSS data of HbI and temporal oscillation of the signal. a A crystal structure of HbI(CO) 2 (bottom) and an enlarged view of the heme group and the His101 residue (top) (PDB entry: 3sdh). The C helix with the CD loop, the E helix, and the F helix are indicated with green, red, and blue colors, respectively. The CO ligand molecules are indicated with spheres. The photodissociation of a ligand molecule that is bound to a heme group induces the structural transition of the heme and the overall protein, called the R-T transition. b The experimental femtosecond TRXSS data (black) and calculated curves (red) from -4. 5 to 100 ps. The calculated curve at each time delay shown in red was generated by taking a linear combination of the theoretical difference scattering curves of the reaction intermediates (I 0 , I 1 , I 0 U , and I 0 D ) obtained from the structural refinement.
For each species, the scattering curves of the candidate structures obtained from structure refinement were averaged to generate the corresponding theoretical difference scattering curve (see the Supplementary Information for detailed information). The coefficients for the linear combination were determined by the concentrations of the reaction intermediates at each time delay. For clarity, the high q region with q ≥ 0. (0. 06 ≤ q ≤ 0. 1 (Å -1 )) and WAXS (0. 13 ≤ q ≤ 1. 0 (Å -1 )) regions and compared the global structural changes obtained by analyzing the two regions. The kinetic and structural analyses on the WAXS region of fs-TRXSS data of wild-type HbI(CO) 2 revealed the existence of an earlier reaction intermediate (I 0 ) and the subsequent thermal transition to I 1 that was reported in the previous TRXSS study  16.
I 0 exhibits ultrafast coherent motion in addition to the transition to I 1. The detailed structural changes related to the formation of I 0 , the coherent motion, and the subsequent evolution to I 1 were clarified via the experimentrestrained rigid-body (ERRB) structure refinement aided by Monte Carlo (MC) simulations  16. The structural dynamics analysis using the SAXS region of fs-TRXSS data was performed via the Guinier analysis. The global structural change elucidated via analyzing the WAXS region has strikingly different features compared to that revealed by the Guinier analysis. These results indicate that the femtosecond SAXS (fs-SAXS) data does not originate solely from the bare protein, whereas the femtosecond WAXS (fs-WAXS) data is relatively free from the influence of the hydration shell.
To confirm this finding and check whether the observation of the long-lived vibration depending on the q range is limited to the HbI case, we revisited the fs-TRXSS data on Mb. The same analysis used for the HbI data was applied to the Mb data, and the results show that the analysis using the WAXS region and the Guinier analysis yielded different features as in the case of HbI, revealing similar dependency on the scattering angle used for the analysis. The fact that two different proteins exhibit similar dependency of the analysis results on the scattering angle used for the analysis indicates that the effect of the hydration shell on fs-SAXS data is a common phenomenon.
4 )  16. Hence, we assigned the second intermediate to I 1. The ultrafast dynamics of HbI could not be described solely by the exponential kinetics. The first right singular vector (rSV) exhibits a deviation from the exponential fit in the early time domain (<3 ps). The TRXSS data encrypts the information of both structural change and population kinetics of the protein. The oscillatory feature in addition to the exponential kinetics indicates that a non-thermal motion is involved in the dynamics since the thermally induced dynamics generally exhibit a simple exponential behavior. The SVD on the q range from 0. 2 to 1. 0 Å -1 does not exhibit such an oscillatory deviation, and only the small q range (0. 13 ≤ q ≤ 0. 2 (Å -1 )) of the entire WAXS range contributes to this deviation (Supplementary Fig.
3a   13. In the previous TRXSS study, similar structural changes of HbI in the solution and crystalline phases were identified in the late time domain (>100 ns)  16. Our fs-TRXSS data reveals that the intrasubunit helix movement similar to that in the crystalline phase at a much later time delay (5 ns) was already developed even within a picosecond. For example, the Pearson correlation coefficient between the intra-subunit DDMs of I 0 and the crystal structure at 5 ns using the region from the B helix to the F helix is 0. 77, which falls into a range typically indicating a strong correlation between For clarity, the high q region with q ≥ 0. 2 Å -1 is scaled up by 5. d The SADS of I 0 (black) and the theoretical difference scattering curves of 108 candidates (other colors). For clarity, the high q region with q ≥ 0.
2 Å -1 is scaled up by 5. e Displacement plots of initial structures used for the ERRB structure refinement aided by MC simulations (left) and candidate structures obtained from the structure refinement (right). For each subunit, the displacement was calculated as the changes in the distance from the iron atom to the Cα atom of each residue with respect to the carboxy structure. The displacements of the same residues in the two subunits were averaged. For the displacement plots of the initial structures, 108 initial structures were selected randomly out of the total 270 initial structures used for the structure refinement. The labels of the helices are shown at the top of the plots. The helix labels follow the helix identification in the carboxy structure (PDB entry: 3sdh). two variables (see Supplementary Information for detailed information on the calculation of Pearson correlation coefficient).
The movements of the C helix and CD loop region can be induced by the rearrangement of the E helix during the formation of I 0 since the E helix is connected to the CD loop region. The flexibility of the CD loop region may be responsible for the large movement. The negative intra-subunit distance changes of the C helix and CD loop indicate that they moved toward the center of the protein. The movement of the C helix and CD loop toward the center of the Fig. 3  Ultrafast structural dynamics of HbI obtained from the analysis of TRXSS data in the WAXS region. a Averaged difference distance maps (DDMs) of I 0 (left) and the crystal structure at 5 ns after photolysis (right, PDB entry: 2grz). The carboxy structure (PDB entry: 3sdh) was used as the reference structure. The upper triangle and the lower triangle of the DDM are inter-subunit and intra-subunit DDMs, respectively.
In contrast, in HbI, the movement of the C helix and CD loop region is apparent up to 100 ps with the formation of I 1 , whereas the movement of the E helix is not large. We note that the D helix of HbI is not well structured and exists as a part of the CD loop. The difference in the structural change observed between Mb by TR-SFX and HbI by fs-TRXSS may arise from the crystal packing and the different rigidity of the C and D helices in HbI and Mb. Comparison of the structural dynamics of HbI and Mb in the solution phase. For comparison with HbI, we analyzed the WAXS region of the previously reported TRXSS data on Mb using the same approach used for HbI (see Supplementary Information and Supplementary Figs. 13 and 14 for detailed information). As expected from the structural similarity between Mb and HbI, the structure refinement results indicate that Mb exhibits similar global structural change to HbI.
Since CRYSOL, the program used to calculate the scattering curve, describes the hydration shell as a layer with a thickness of 3 Å 49 , the density change dependent on the distance from the protein surface is approximated as a constant density of a single hydration shell instead of the density changes of multiple shell layers. To check the effect of this approximation, we performed a series of simulations considering the effect of multiple shell layers and their density changes (see "Single-layer model vs. multiple-layer model to describe the density change in the hydration shell" section of Supplementary Information for detailed information). The simulations confirm that the difference scattering curve due to the density changes of multiple shell layers can be approximated with the difference scattering curve due to the density change of a single shell layer, confirming that this approximation should still capture the general density change (Supplementary Fig.
For example, ΔV SAXS and the change of the electron density of the hydration shell exhibit a similar rising time (Supplementary Fig. 16a ), indicating that the delayed rise of ΔV SAXS may originate from the change of hydration shell and the SAXS region is dominantly affected by the change of the hydration shell. In contrast, the time profile of ΔR g WAXS resembles the first rSV obtained from the SVD analysis on the WAXS region, which implies that the structural change of bare protein largely influences the WAXS region (Supplementary Fig. 16b ). To confirm the generality of the effects of the hydration shell on the SAXS region, we analyzed the WAXS region of fs-TRXSS data of Mb and compared the results with the results of the Guinier analysis. In a previous fs-TRXSS study on Mb using the SAXS region, a long-lived underdamped vibration was identified by the Guinier analysis.
We analyzed the WAXS region of the same data of Mb (0. 17 ≤ q ≤ 1. 0 (Å -1 )). In contrast to the Guinier analysis results, the rSVs obtained from the analysis of the WAXS region do not exhibit oscillatory features (Supplementary Fig. 13 ), indicating that the long-lived underdamped vibration is absent when the WAXS region is analyzed. The different analysis results obtained from the WAXS and SAXS regions of the Mb data show good agreement with the results obtained from the analysis on HbI. The fact that two different proteins exhibit similar dynamics dependence supports that the effect of non-protein factors on the SAXS region of fs-SAXS data is a general phenomenon. Meanwhile, unlike the case of HbI, the rSVs of the WAXS region of the Mb data do not indicate the emergence of a coherent motion manifested as an oscillatory deviation in the early time domain.
Considering the existence of the coherent motion of HbI, which is a similar heme protein, it seems that the coherent motion of Mb dampens within the time resolution rather than it does not undergo any coherent motion  50. For example, the TR-SFX study on Mb reported the coherent motion corresponding to some inter-residue distances  28. A possible explanation for the ultrafast damping can be the larger ratio between surface area and volume in Mb. The surface area relative to the volume is larger in Mb since Mb and HbI have monomeric and dimeric structures, respectively. The larger relative surface area may lead to faster damping of a coherent motion via larger interaction with the hydration shell so that the coherent motion was not detected with the experimental time resolution. The dependence of the temporal behavior on the SAXS and WAXS regions implies that the fs-SAXS data is dominantly affected by non-protein factors, such as the hydration shell.
Here we experimentally demonstrated that ultrafast time-resolved SAXS data encrypts the additional factors as well as the structural change of the protein molecule itself by comparing the structural dynamics decoded from the SAXS and WAXS regions of HbI and Mb. Furthermore, we tracked the change of the hydration shell and protein structure over time using an analysis method that refines the latter using the WAXS region and the former using the SAXS region. The initial response of HbI upon ligand dissociation revealed by the analysis of both the WAXS and SAXS regions is summarized in Fig. 5. The earliest reaction intermediate identified in this study, I 0 , is formed within our time resolution (~800 fs) and evolves to I 1 with a time constant of 8. 7 ps. The oscillatory deviation from the exponential kinetics appeared during the early time domain (<3 ps).
Methods Data acquisition. The fs-TRXSS data for wild-type HbI(CO) 2 were collected at the X-ray Pump-Probe endstation of Linac Coherent Light Source using a pump-probe scheme. A flow cell system was exploited for the measurement. In the flow cell system, the HbI(CO) 2 sample with a concentration of ~0. 6 mM was flowed through a capillary back and forth using a syringe pump. The whole flow cell system was saturated with carbon monoxide to maintain the concentration of the ligated form of HbI. At the center of the capillary, the sample was excited using a circularly polarized femtosecond laser pulse with a 532-nm center wavelength. At the sample position, the laser was focused on 200 × 200 μm 2 , and the fluence of the laser was ~0. 5 mJ/mm 2. A femtosecond X-ray pulse with 9. 5 keV photon energy and 100 × 100 μm 2 size at the sample position followed the laser pulse to investigate the structural dynamics of HbI(CO) 2 after photoexcitation.
SVD can decompose time-resolved experimental data into three components, which are left singular vectors (lSVs), right singular vectors (rSVs), and the singular values. For TRXSS data, lSVs are the time-independent difference scattering curves and rSVs are the time profiles of the lSVs. Each singular value indicates the relative contribution of each singular vector to the experimental signal. From the SVD results, two SVD components were classified as the major components as they predominantly contribute to the experimental signal (Supplementary Fig. 2a-c ). According to the number of the major SVD components, two reaction intermediates were identified. The time constant for the transition between these two intermediates was obtained by fitting the reconstructed experimental data of the SVD results to the original experimental data.
Even though we observed clear deviations at 0. 5 and 1. 5 ps from the exponential behavior, the kinetic parameters related to the deviations could not be determined accurately due to the limited number of time points during the deviation. To increase the number of the time points during the deviation and determine the kinetic parameters related to the deviation more accurately, we re-binned the original fs-WAXS data from -0. 5 to 2. 5 ps with 500-fs time bins and 333-fs time bins. For the kinetic analysis, the first rSVs of the two re-binned datasets were simultaneously fitted with a sum of an exponential function and a damped cosine function convoluted with the IRF of 800-fs full width half maximum (FWHM), as shown in Fig. 1c, d. We note that only the first rSVs were used for the kinetic fit due to insufficient SNR of the second rSVs of 500-fs-binned data and 333-fsbinned data, as shown in Supplementary Fig.
2. During the fitting, all parameters related to the exponential decay were fixed to the values obtained from the prior exponential decay fit of the original 1-ps binned data. Similar to the case of prior SVD fitting, the SVD fitting was performed so that the sum of the differences between the original data and reconstructed data of two re-binned datasets was minimized. All the fittings and error analyses were performed using the MINUIT software packages provided by CERN  52. We note that, since the original 1-ps binned data have better SNR, they were used for the structure refinement to improve the quality of the structural analysis.
Acknowledgements This work was supported by the  Institute for Basic Science  ( IBS-R004 ). We acknowledge LCLS staff including  T. Sato ,  T. van Driel ,  D. Zhu ,  S. Nelson ,  Z. L. Lentz ,  J. Robinson ,  P. Walter , and  M. Chollet  for experimental support and helpful discussion. Use of the Linac Coherent Light Source (LCLS),  SLAC National Accelerator Laboratory , is supported by the  U. S Department of Energy, Office of Science, Office of Basic Energy Sciences  under Contract No. DE-AC02-76SF00515  (proposal Nos. LO66  and  LP06 ).
Identification of differential genes for COPD sub-phenotypes in males. The EvA study has used CT image analysis to define emphysema-dominant (E) and airway disease-dominant (A) sub-phenotypes of COPD  3. Using the RNAseq data on bronchial brush samples from these cases we analysed controls (n = 145 males) versus E-dominant (n = 50 males) and controls versus A-dominant cases (n = 32 males) and controls versus Eextreme (Eex, n = 22 males) and versus Aextreme (Aex, n = 16 males). Eex and Aex are the cases with the most pronounced CT-phenotype, which were selected by rank order of the CT measures of lung density and airway wall thickness  3. The Eex and Aex samples are included in the E and A samples, respectively (see also under Supplement: Strategy for identification of DEGs for step by step explanation of data analysis).
Our data in females give support to the gender specific gene expression in COPD sub-phenotypes. A notable finding in female E-dominant COPD is the expression of mast cell associated genes like tryptase B2, tryptase AB1 and the peptidase CPA3, suggesting a role for mast cells in the pathophysiology of emphysema dominant COPD in females. Limitations. At this point there is no sizable data set on a bronchial brush transcriptome in COPD available, such that our findings cannot be analyzed in an external validation cohort. In the present study we have used an internal confirmation group, which was able to confirm several of the findings. This confirmation group has limitations, since it lacks the CT image data and there is no separate control group to go along with this patient group. RNA sequencing data have been confirmed for selected genes by RT-PCR, but these transcript data have not been confirmed at the protein level.
Acknowledgements This work was supported by the  European Union ,  FP7  project #  200506. We acknowledge the helpful discussions with  Emanuele Raineri ,  Barcelona, Spain  and with  Wilfried Karmaus ,  Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, Tennessee, USA. CNAG-CRG  lab is a member of the  Spanish National Bioinformatics Institute (INB) ,  PRB2-ISCIII  and is supported by grant  PT13/0001  of the PE I+D+i 2013-2016, funded by  ISCIII  and  FEDER. Work by CB at Leicester and by LZH at Munich was also supported the  European Union   FP7  project #  270194.