dataesr/scientific-paragraphs-categorization huggingface dataset:
5 µM, 30 µl/ min, 120 s) using a dual injection command. All binding curves were fitted and analysed using the Biacore Insight Evaluation Software. ITC binding experiments. ITC experiments were performed according to Peter et al. 21 on a MicroCal PEAQ-ITC device from Malvern Panalytical, using corresponding MicroCalPEAQ-ITC software (version 1. 21) for experiment design, measurement, and analysis. Sialic acid (Carbosynth) was dissolved in the P-domain standard buffer (50 mM Tris, 50 mM NaCl (pH 8)). Each mutant was at least measured three times and the mean values are given. Cryo-EM-sample preparation, data collection, processing, structure modelling. The cryo-EM structural studies were performed with HiSiaQM in MSP1D1-H5 nanodiscs with DMPC lipids. For the selection of HiSiaQM-containing nanodiscs, the purified Mb3 was loaded onto Ni-NTA beads, equilibrated with HiSiaQM buffer C, for 1 h at 4 °C.
The fractions that corresponded to the main protein peak were combined and used for cryo-EM experiments. The grid preparation was performed on a Vitrobot (Thermo Fisher Scientific) at 4 °C and 100% humidity by using Quantifoil R1. 2/1. 3 grids. The blot time was set to 6 s and the blot force to 0. The grids were stored in liquid nitrogen until data collection at a Titan Krios microscope (Table  S1 ). A dataset of 5004 movies was collected using a Cs-corrected Titan Krios electron microscope (Thermo Fisher Scientific) operated at 300 kV, and equipped with a Gatan K3 camera and a BioQuantum imaging filter (Gatan). Images were recorded over 2. 264 s with the camera operating in counting mode, with a dose rate of 22. 179 e -/Å 2 /s for a total dose of 50. 213 e/Å 2 over 50 frames. After patch motion correction and CTFestimation with cryoSPARC  35  , 2.
33 million particles were automatically picked using a blob-picker job and subjected to multiple rounds of 2D classification. Representative 2D classes are shown in Fig. S3  and clearly show the megabody-HiSiaQM complex in the top views. The 2D classes and the movies were used as inputs for a template picker job resulting in 2. 55 million particles that were subjected to one round of 2D classification. The remaining 2. 29 million particles were exported from cryoSPARC using the csparc2star. py script by Daniel Asarnow (https://doi. org/10. 5281/zenodo. 3576630) and imported into RELION  36  to construct an ab initio model and to perform two rounds of 3D classifications. The first round (regularization parameter T = 4) revealed one good 3D class with a clearly visible transporter consisting of 790 K particles.
The maximum linking distance was set to 1 μm. Each track is considered as a single interaction of the P-domain with the bilayer. Three independently prepared samples were measured 30 times each, resulting in a total of 90 individual movies for each condition. Normalization of interactions per second was achieved by first dividing the total number of interactions by the summed total duration of all measured movies in the respective condition. Then, the positive control value was set to 1 and all other values were adjusted accordingly. Structural predictions with AlphaFold. The source code of the AlphaFold 37 algorithm was downloaded from https://github. com/deepmind/alphafold and installed as described https://github. com/deepmind/alphafold. The pLDDTs scores were mapped onto the structures with PyMOL (www.
Acknowledgements This project was financed by the  German Research Foundation (Deutsche Forschungsgemeinschaft, DFG)  in project nos. HA 6805/4-1  and  HA 6805/5-1  and a  Method Development Grant  by the  TRA Life and Health (University of Bonn, Germany)  as part of the  Excellence Strategy  of the federal and state governments (to G. H. and P. A. K. ). M. F. P. acknowledges a Ph. D. fellowship from  Konrad Adenauer Stiftung. U. K. received funding by the  Deutsche Forschungsgemeinschaft (DFG) -Project-ID 398967434-TRR 261. M. G. is funded by the  DFG  under Germany's Excellence Strategy-EXC2151-390873048. We thank  Elif Tokmak  for technical assistance with the cloning of the HiSiaQM mutants. We thank  Jan M. P. Tödtmann  of the  Core Facility Nanobody (CFN)  at the  Medical Faculty of the University of Bonn  for cloning the nanobody library, selecting nanobodies by phage display, identification of hits, and their initial characterization by ELISA.
Data availability The coordinate and map data generated in this study have been deposited in the PDB and EMDB databases under accession codes 7QE5 and EMD-13930. The movie data generated in this study are provided as Supplementary Movies 1-4. The models of the outward and inward-facing tripartite complex are provided in Supplementary Data 1 and 2. Data underlying all plots are provided as Source data. The coordinate data used in this study are available in the PDB database under accession codes 5UL9, 2CEY, 3B50, 5NVA, 2HZL, 2ZZV). Source data are provided with this paper.
FUNDING DL and TK-F were supported by  Thomas Jefferson Fund , a program of  FACE Foundation  launched in collaboration with the French Embassy. MC was supported by the  "Ecole Doctorale des Sciences de la Vie et de la Santé -ED414". TK-F was supported by the  National Institutes of Health  ( R01AI155611  and  R21AI149115 ). DL was supported by the  "Agence Nationale de la Recherche " ( ANR-20-CE12-0021 ). The work of the  Interdisciplinary Thematic Institute IMCBio , as part of the  ITI 2021-2028 program  of the  University of Strasbourg ,  CNRS  and INSERM, was supported by  IdEx Unistra  ( ANR-10-IDEX-0002 ), by  SFRI-STRAT ' US  project ( ANR 20-SFRI-0012 ), and by  EUR IMCBio (IMCBio   ANR-17-EURE-0023 ) under the framework of the  French Investments for the Future Program as well as from the previous Labex NetRNA  ( ANR-10-LABX-0036 ).
In vivo and ex vivo biodistribution analysis of  64  Cu by whole-body PET imaging and gamma counter measurements in Atp7b -/-, WT, and VTX-801-treated Atp7b -/-mice at 18 weeks of age PET analysis was performed 90 min and 24 and 48 h post-64 Cu injection. Ex vivo biodistribution analysis was performed at sacrifice, 72 h after 64 Cu administration. (A) Representative PET coronal slices obtained 48 h after the injection of the radiotracer are shown. The VOIs)containing the entire liver (dashed line) were used to obtain quantitative data. (B) Graphical representation of hepatic concentration of 64 Cu (SUV) at 90 min and 24 and 48 h post-injection and ratio of 24 h/90 min and 48 h/90 min hepatic SUV values derived from PET data analysis is shown. (C) Ex vivo biodistribution data of selected organs are shown.
Biological sampling After [ 64 Cu]CuCl 2 injection, several biological samples were collected and radioactivity (Bq) was counted on a gamma counter (Hidex Automatic Gamma Counter). Blood samples were collected and weighted. The % injected dose (ID)/g of blood was calculated considering the decay of copper-64, and data were represented in the graph as the fold change ratio relative to 1 h. Urine and feces were harvested throughout 24 h from individual animals using metabolic cages, and data were expressed as the % ID correcting the radioactive decay of copper-64. In vivo PET imaging and ex vivo copper-64 biodistribution All PET scans were obtained in a dedicated small-animal imaging tomograph (Mosaic, Philips), with an axial and transaxial field of view of 11. 9 and 12. 8 cm, respectively, and a full width at half maximum resolution of 2.
1 mm. At 1. 5, 24 and 48 h post-injection, mice were placed prone on the PET scanner under continuous anesthesia with isoflurane (2% in 100% O 2 gas) to acquire a static image (sinogram) within 15 min. All the images were reconstructed in a 128 Â 128 matrix with a 1 Â 1 Â 1 mm 3 voxel size using the 3D Ramla algorithm with two iterations and a relaxation parameter of 0. 024. Dead time, decay, random, and scattering corrections were applied during the reconstruction process. All the studies were exported and analyzed using the PMOD software (PMOD Technologies, Adliswil, Switzerland). Images were expressed in SUV units, using the formula SUV = h tissue activity concentrationðBq=cm 3 Þ injected dose ðBqÞ i Â body weightðgÞ. A spherical VOI containing the entire liver was drawn over PET images to obtain semi-quantitative data.
parents together, including new union situations), along with the number of siblings (including those from the previous or current union of each of the parents, recoded into 2 modalities: only child vs. presence of sibling(s)). The main setting of the study was the UTD, within the University Hospital Centre (CHU) of Pointeà-Pitre (n = 75) or, for patients who came from the Basse-Terre area, and depending on another hospital structure, the Basse-Terre Hospital Centre, CHBT (n = 5). For the control group, data was collected at convenient places for the subjects, mainly at home. Data was entirely collected using an eCRF. 4   Analysis Statistical analyses were conducted using Statistica and R 3. 6. 1 software. Discrete and continuous variables were compared using Khi2 test and Student's t-test (for two groups) or ANOVA (for more than 2 groups) respectively.
Concerning the positive perception of socio-health services, this result could reveal evidence of a social desirability bias among patients, as the assessment was made in a hospital context, in a specific care unit dedicated to SCD. In many cases, the investigator (social sciences researcher) was confusedly assimilated to a member of the medical staff. Data is not detailed in the current work, but our study design also included a qualitative axis with biographical interviews, often conducted at the home of patients and family, which provided more information, and qualified the quantitative data collected with questionnaires. Results relating to socio-demographic characteristics also demonstrated that among the SCD group, only the occupational category of the family unit (and more precisely, the absence of a professional activity), had an impact on their perception of environmental factors, particularly social factors.
Finally, additional analyses will complete this data by considering the dynamic interaction between environmental and individual factors (e. g. , clinical manifestations of SCD, neuropsychological disorders) when examining the social participation of individuals with SCD. These conclusions will stimulate reflection concerning the challenges and opportunities offered by the transdisciplinarity of this project and its conceptual rooting in a complex model such as the DCP, issues that are the focus of an ongoing discussion  (Ruffié et al. , 2020).
i Average responses of the mutant channels evoked by different stimuli as indicated. Residues in the linker S4-S5 of TRPV1 were individually mutated to the corresponding residues of TRPV2. Whole-cell currents were recorded from transiently transfected HEK293 cells at -60 mV, and current densities were determined by dividing the peak current amplitudes by membrane capacitance. j Whole-cell recordings were made at -60 mV from HEK293 cells showing that 1,4-dioxane (2%), 1,3-dioxane (2%), and tetrahydrofuran (2%) failed to activate V1(M572V), while the response to capsaicin (1 μM) was retained. k Summary data of current densities at -60 mV evoked by capsaicin (1 μM), 1,4-dioxane (2%), 1,3-dioxane (2%), and 1,3,5-trioxane (2%) and tetrahydrofuran (2%) obtained by whole-cell recordings to 1,4-dioxane (Fig.
Statistics and reproducibility Data were processed with Qstudio developed by Dr. Feng Qin at State University of New York at Buffalo, Clampfit (Molecular Devices, Sunnyvale, CA), IGOR (Wavemetrics, Lake Oswego, OR, USA), SigmaPlot (SPSS Science, Chicago, IL, USA), and OriginPro (Origi-nLab Corporation, MA, USA). For concentration response analysis, the modified Hill equation was used: Y = A1 + (A2-A1)/[1 + 10 ^(logEC 50 -X) * n H ], in which EC 50 is the half maximal effective concentration, and n H.
champanellensis, termed Cel9A-r that has the exact same modular composition (see Fig. 1  and Additional file 1: Table  S2 ). Interestingly, the result for Cel9A-r, that also contains a CBM3c module tightly tethered to the catalytic module (Fig. 2b ), is an exception to the proportionality of D max and R g of dockerin-containing enzymes vs. their mass (Table  1 ), since the overall shape is more compact than Cel8A-b or Cel48S-t as illustrated by the Kratky-plots (Fig. 2c ), even though Cel9A-r is larger and has a longer linker region  (29 residues ). An atomic model could be built, since crystal structures for all individual modules of Cel9A-r are available, and, using CRYSOL  [40] , the compact form of the model was calculated to fit the experimental scattering curve with a poor χ 2 of 4. 1.
SAXS measurements of scaffoldin variants For all three scaffoldin variants, ScaA, ScaH and ScaK, no crystallographic structures are available, we have thus analyzed and compared their compactness by Kratky plots  [42, 43]  and ab initio envelope calculations using DAMMIN  [44]. To verify their compact and globular character, we have collected SAXS curves for the individual X-module of ScaA and of SGNH present in ScaH (see Additional file 1 and Additional file 4: Fig. S3 ). ScaA is a 68-kDa protein, which is composed of an X-module, two cohesins and a dockerin (Fig. 1 , Additional file 1: Table  S2 ). SAXS data of good quality (Additional file 5: Fig. S4a ) were acquired for this construct (Fig. 3a , orange curve), which allowed determination of R g as 60. 9 Å and D max = 282 ± 11 Å (Table  1 ).
As is highlighted by the Kratky plot (Fig. 4a , orange curve), the obtained scattering curve is consistent with a non-globular, elongated and partially flexible protein. We then calculated ab initio envelopes in multiple independent runs using DAMMIN  [44]  as described in the Methods section. Despite some apparent partial unfolded parts, identified in the Kratky plot at high Q values, the normalized spatial discrepancy (NSD) obtained over 10 calculations is 0. 84 < 1, which indicates that the shape of the envelopes is rather conserved. All shapes display the same kinks (Fig. 3b ) consistent with the presence of four distinct modules, but the relative orientation of the individual modules remains ambiguous. ScaH (Fig. 1 , Additional file 1: Table  S2 ) is composed of a catalytic domain, consisting of an SGNH homologue of a lipase or an esterase, a cohesin and a dockerin.
An unidentified 103-residue stretch precedes the cohesin at the N terminus (Additional file 1: Table  S2 ), which could indicate the presence of an additional small domain or module. The SAXS data (Fig. 3e , light green curve) indicate R g of 45 Å and D max of 184 ± 6 Å, which is significantly more globular and compact than ScaH. This is also illustrated by the Kratky-plot (Fig. 4a , light green curve), where the maximum of the bell shape is shifted to lower values as compared to ScaH and notably ScaA. Repeated DAMMIN  [44]  calculations yielded conserved envelopes (NSD = 0. 73) that fit the experimental curve, as exemplified in Fig. 3e , with similar χ 2 values, the best being 3. 1. Nevertheless, these SAXS data measured on ScaK do not allow us to identify the relative positions of the domains within the molecular envelopes with confidence, even if a more globular shape in the middle of most envelopes would suggest that the GH25 adopts a central position (Fig.
c. Experimental scattering curve (light blue points) of ScaH fitted by DAMMIN (black line)  [73]. d ScaH; representation of 5 examples out of 10 fitted DAMMIN envelopes (colored magenta, blue, yellow, cyan and green); the overall mean NSD calculated with DAMAVER for the 10 independent envelopes is 0. 72 with a variation of 0. 01, a value that indicates conservation of the shapes. The various envelopes highlight the modular composition of the scaffoldin, but locating individual modules within the shape is not possible. e ScaK; Experimental scattering curve of ScaK (green points) fitted by DAMMIN (black line)  [73]. f ScaK; representation of 5 examples out of 10 fitted DAMMIN envelopes (colored blue, red, green, yellow and magenta); the overall mean NSD calculated with DAMAVER for the 10 independent envelopes is 0.
Small angle X-ray scattering at SWING beamline The SAXS data were collected at the Synchrotron SOLEIL on the SWING beamline, using an AVIEX170170 CCD detector. Frames were recorded at 12 keV. The sample-to-detector distance was set to 1799 mm for all samples and also to 4000 mm for CipA and its complexes, leading to scattering vectors q ranging from 0. 0005 to 0. 5 Å -1. For all scattering curves, the scattering vector is defined as q = 4π/λ sin θ, where 2θ is the scattering angle. The protein samples were loaded onto a size-exclusion column (Agilent Bio SEC-3 or Bio SEC-5, 4. 6 × 300 mm, 3 μm) using the online purification system that delivers the eluted fractions directly into the measurement cell, developed at the SWING beamline  [69]. After equilibrating the column with the protein buffer supplemented with 2-5% of radio-protectant (glycerol), 50 µL of protein sample, concentrated at 8 to 15 mg/mL, were injected.
Subsequently, and triggered by the elution procedure, a first series of 180 successive frames of 750 ms were recorded on buffer solution (before the column's void volume) to measure the background. In the next step, 250 frames were collected continuously during the elution, with a frame duration of 1. 5 s and a dead time between frames of 0. 5 s. In contrast to classical SAXS experiments that are conducted in batch using several protein concentrations within a standard range (e. g. , 0. 1-10 mg/mL -1 ), here data collection is coupled to a size-exclusion column so that analysis of the required multiple concentrations of the protein occurs within a single experiment. This is because many different positions within the elution peak are sampled during the course of the measurement (typically 50-100 frames are acquired).
The averaged buffer scattering curve was then subtracted from the protein signal. R g (radius of gyration) values were calculated for each frame during the measurement and those that exhibit the same R g were averaged (Additional file 9: Fig. S8 ). Data reduction to absolute units, frame averaging, and subtraction were performed using the program FOXTROT (Xenocs). All subsequent data treatment and analysis were performed using Scatter  [70]  or PRIMUS from the ATSAS suite  [71]. The forward scattering I(0) and the radius of gyration R g were derived by the Guinier approximation I(q) = I(0) exp(-q 2 R g 2/3 ) roughly for qR g < 1. 1 or 1. 2 using Scatter. The distance distribution function P(r) and the maximum particle dimension D max were calculated by Fourier inversion of the scattering intensity I(q) using GNOM  [72].
Protein shapes were derived from the experimental SAXS data using the bead-modeling program DAMMIN  [44]  or GASBOR  [73]. At least 20 different calculations were carried out and then aligned with SUPCOMB  [74]. The models that had the same shape were averaged using the DAMAVER and DAMFILT packages  [71, 75]. The quality of the 3D modeling was determined using the discrepancy χ 2 , defined according to Konarev et al. [76]. Values lying in the range of 0. 9-1. 1 are accepted to indicate a good fit between the models and the data. However, the calculation of χ 2 is inversely proportional to the measurement error. Using the low-error detector at SOLEIL, higher χ 2 values were obtained  [77, 78]. Coarse-grain molecular models were then fit into the ab initio envelopes using SUPCOMB  [74].
Acknowledgements This work was supported by the  European Union ,  Area NMP. 2013. 1. 1-2:Self-assembly of naturally occurring nanosystems: CellulosomePlus Project number:  604530. Additional support to EAB was provided by an  Israel Science Foundation  Grant (No. 1349 ), and by an  ADEME   ERANET IB Grant  to MC (No. 1201C0104 ). The authors strongly acknowledge the regular access to the small angle X-ray scattering beamline SWING at synchrotron SOLEIL ( St Aubin , France) through the  BAG MX-20170744  and  MX-20181002 , and are grateful for the expert technical support provided by beamline staff:  Javier Perez  for help with data treatment and  Blandine Pineau  for sample preparation. B. R. acknowledges the support received from the  PL-Grid Infrastructure  and from the  National Science Centre, Poland , Grant no  2016/21/B/NZ1/00006.
Study design and participants We implemented a cross-sectional survey to assess the presence of wheeze among participants included in the longitudinal monitoring cohort (LMC) of the DeWorm3 study, which took place between August 26th and October 25th, 2020. In the LMC, a total of 6000 individuals were included. We conducted the study described here in a subset of participants aged 6-14 years of age, whose households were located and who were present during the third LMC survey in 2020. A total of 1,130 participants met these criteria. We used data collected at baseline to define STH infection status.
The questionnaire was administered in the local language by a team of five interviewers. Our study questionnaire combined the wheezing module of ISAAC questionnaire, a module on allergy predisposing factors and a module on participants's exposure to indoor air pollution. Data were collected using Kobocollect software deployed on smartphones and stored in password-protected data sets in secured servers. The wheezing questionnaire database was subsequently merged with the baseline DeWorm3 LMC survey database by the DeWorm3 central data manager. To blind the data, the household, individual, village and cluster identifiers were anonymized and all other identifiers removed.
Helminth infection Data on helminth infection were from the baseline study of the DeWorm3 longitudinal cohort, conducted in April 2018. Participants' stool samples were screened for the presence of STH using the Kato-Katz technique  [38]. The parasite intensity was calculated from a Kato-Katz smear made with 41. 7 mg of stool, by multiplying the egg count from the slide by a factor of 24 (24 × 41. 7 mg ≈ 1 g) to get the number of eggs per gram of stool (EPG).
Study population Among the 1113 participants aged 6-14 years from the DeWorm3 LMC database considered for the wheezing survey, there were 81 participants who had permanently migrated, forty had travelled, eight with households not located and one deceased (Fig. 1 ). Among the 974 participants we asked for, seven refused to participate, leading to a 99. 3% (967/974) participation rate. We excluded from the database observations with missing information for questions concerning current wheezing (n = 6), cooking fuels (n = 11) and STH infection status (n = 55). The descriptive analysis concerned 895 participants. The median age was 9. 2 years (IQR 7. 2-11. 8), with 46. 2% females. Household size ranged from 2 to 20 individuals with a median of 6 (IQR 5-7). Most participants (98. 1%) had a normal BMI, i.
Acknowledgements We give our heartfelt thanks to the population of the commune of Comé for their enthusiastic participation in our studies, and in particular the children who agreed to take part in the wheezing study. We are also extremely grateful to both the health and municipal authorities of the commune for their confidence and for their continuous and generous support of our research efforts in Comé. We gratefully acknowledge the dedication and motivation of all members of the wheezing study survey team, namely,  Fidèle Houngbégnon ,  Linda Kitivo ,  Gildas Avokpaho ,  Sylvestre Lokossou ,  Corneille Agbo ,  Malicka Ibikounlé.
Acknowledgments: We would like to thank Mayka Sanchez (D•IRON & IJC, Barcelona, Spain) for exploration of IRE elements in ATP4A and ATP4B genes. We also thank Nicolas Sorhaindo, Olivier Thibaudeau, Christopher Prochasson, Samira Laouirem and Miguel Albuquerque for their technical help. The authors also thank Galien Health Publishing who provided editorial assistance.