dataesr/scientific-paragraphs-categorization huggingface dataset:
Gene Annotation and Statistical Analysis. ABCC2, RyR, AChE, and VGSC were annotated by aligning protein sequences obtained from NCBI and reference genomes using exonerate 2. 2. 0  [38]  with the protein2genome model. The accession numbers of these genes were QGS83596, XP_022819835, MK226188, and KC435025, for ABCC2, AChE, RyR, and VGSC, respectively. Genetic variations within these genes were identified from the resequencing data  [31]  using IGV tools  [39]. P450 genes were identified from the gene annotation files generated in our previous study (OGS7. 0) [31]. The identification of the P450 clan was performed by blasting against OGS2. 2 [9], which includes manually annotated P450 genes, with 98% cutoff using ncbiblast-2. 10. 0+ [40]. The Fisher's exact test was performed using the R package to test a statistical significance of increased gene duplication of P450 genes.
Gene Annotation and Statistical Analysis ABCC2, RyR, AChE, and VGSC were annotated by aligning protein sequences obtained from NCBI and reference genomes using exonerate 2. 2. 0  [38]  with the protein2genome model. The accession numbers of these genes were QGS83596, XP_022819835, MK226188, and KC435025, for ABCC2, AChE, RyR, and VGSC, respectively. Genetic variations within these genes were identified from the resequencing data  [31]  using IGV tools  [39]. P450 genes were identified from the gene annotation files generated in our previous study (OGS7. 0) [31]. The identification of the P450 clan was performed by blasting against OGS2. 2 [9], which includes manually annotated P450 genes, with 98% cutoff using ncbiblast-2. 10. 0+ [40]. The Fisher's exact test was performed using the R package to test a statistical significance of increased gene duplication of P450 genes.
Funding: This work ( ID 1702-018 , given to K. N. ) was publicly funded through  ANR  (the  French National Research Agency)  under the " Investissements d'avenir" program  with the reference  ANR-10-LABX-001-01 Labex Agro  and coordinated by  Agropolis Fondation  under the frame of I- SITE MUSE  ( ANR-16-IDEX-0006 ). In addition, a grant from the  department of Santé des Plantes et Environnement at Institut  national de la recherche agronomique was awarded to K. N. (adaptivesv). This work was also financially supported by  EUPHRESCO  (FAW-spedcom, given to  Anne-Nathalie Volkoff ) and by  CSIRO Health & Biosecurity  (given to W. T. T. , T. W. , and K. G. ). S. Y. was supported by a  CIRAD-INRAE  PhD fellowship. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable.
Statistical analysis SPSS v. 24 (IBM; Armonk, NY) was employed for analyzing the results, which were presented as means and + -SD (normally distributed continuous data), or percent total (categorical parameters). Student's t test and Pearson's χ 2 test were used for assessing mean differences in or differences in proportions, respectively. All analyses were conducted under the additive genetic model using SNPStats (bioinfo. iconcologia. net/snpstats/). Haploview 4. 2 (http://broad. mit. edu/mpg/haploview) was utilized for HWE assessment of the distribution of LEPR genotypes in control women, and calculation of the study power was determined using GAS Power Calculator (http://csg. sph. umich. edu/abecasis/ gas power calculator/index. html). After considering sample size (cases and controls), disease allele frequency, and genotype relative risk, and significance level, the overall study power (average of three variants) was calculated at 0.
, 2013; Thirel et al. , 2015b). When run under changing climate conditions, they sometimes reveal an unwanted sensitivity to the data used to conceive or calibrate them  (Coron et al. , 2011). The diagnostic tool most widely used to assess the robustness of hydrological models is the split-sample test (SST)  (Klemeš, 1986) , which is considered by most hydrologists as a "good modelling practice"  (Refsgaard and Henriksen, 2004). The SST stipulates that when a model requires calibration (i. e. when its parameters cannot be deduced directly from physical measurements or catchment descriptors), it should be evaluated twice: once on the data used for calibration and once on an independent dataset. This practice has been promoted in hydrology by  Klemeš (1986) , who did not invent the concept  (Arlot and Celisse, 2010; Larson, 1931; Mosteller and Tukey, 1968) , but who formalized it for hydrological modelling.
Catchment set We employed the dataset previously used by  Nicolle et al. (2014) , comprising 21 French catchments (Fig. 3 ), extended up to 2020. Catchments were chosen to represent a large range of physical and climatic conditions in France, with sufficiently long observation time series (daily streamflow from 1974 to 2020) in order to provide a diverse representation of past hydroclimatic conditions. Streamflow data come from the French HYDRO database  (Leleu et al. , 2014)  and with quality control performed by the operational hydrometric services. Catchment size ranges from 380 to 4300 km 2 and median elevation from 70 to 1020 m. The daily precipitation and temperature data originate from the gridded SAFRAN climate reanalysis  (Vidal et al. , 2010)  over the 1959-2020 period. More information about the catchment set can be found in  Nicolle et al.
7. Upon recommendation by one of the reviewers, we tried to assess the possible impact of the quality of the precipitation forcing on RAT results (see https://doi. org/10. 5194/hess-2021-147-AC5) and found that the type of forcing used does have an impact on RAT results (interestingly, the climatic dataset yielding the best simulation results was also the dataset yielding the fewer catchments failing the robustness test). It seems unavoidable that forcing data quality will impact the results of RAT, but we would argue that it would similarly have an impact on the results of a differential split sample test. We believe that there is no way to avoid entirely this dependency and that evaluating the quality of input data should be done before looking at model robustness. 8. Last, we could mention that a model showing a small overall annual bias (but linked to a climate variable) could still be preferred to one showing a large overall annual bias (but independent of the tested climate variables): the RAT should not be seen as the only basis for model choice.
We would not advise to use RAT with time series of less than 20 years. These differences can be quantitatively measured by computing the RMSD (see Eq. 1) between the annual bias obtained with the RAT procedure and with the SST for different calibration period lengths (see Fig. A5 ). The RMSD tends to increase when the number of years available to calibrate the model decreases, but it seems to be stable for periods longer than 20 years. Code and data availability. The gridded SAFRAN climate reanalysis data can be ordered from Météo-France. Observed streamflow data are available on the French HYDRO database (http://www. hydro. eaufrance. fr/, last access: 1 September 2021). The GR models, including GR4J, are available from the airGR R package. Supplement. The supplement related to this article is available online at: https://doi.
Acknowledgements. The authors gratefully acknowledge the comments of  Jens-Christian Refsgaard  and  Nans Addor  on a preliminary version of the note, as well as the reviews by  Bettina Schäfli  and by two anonymous reviewers. Financial support. This research has been supported by the project  AQUACLEW , which is part of  ERA4CS , an ERA-NET initiated by  JPI Climate , and  FORMAS (SE) ,  DLR (DE) ,  BMWFW (AT) , IFD (DK),  MINECO (ES)  and  ANR (FR) , and the  European Commission ,  Horizon 2020  ( ERA4CS  (grant no. 690462 )). Review statement. This paper was edited by  Bettina Schaefli  and reviewed by two anonymous referees.
Data analysis strategy All analyses were performed using R (R Core Team, 2019). The dataset on which our analyses were based, as well as the R script used, are contained in an open-access file available at https://osf. io/p36fe/?view_only=0e959c59bf734c2d9d904d38490f5d7e. All the analyses reported below involved linear mixed-effects models fitted with maximum likelihood estimation. Four characteristics were shared by all these models. First, they all contained one random intercept per participant, to take into account the hierarchical nature of the data (i. e. , several assessment points nested within several individuals). Second, all these models contained the same sociodemographic control variables as predictors, namely sex (dichotomous variable), age (grand-mean-centered numeric variable), education level (grand-mean-centered ordinal variable with four modalities indicating whether the participant had no diploma, a vocational high-school diploma, a general high-school diploma, or one or more completed years of higher education), and duration of unemployment (grand-mean-centered ordinal variable with five modalities indicating whether the participant had been unemployed for less than 1 week, 1-4 weeks, 1-6 months, 6-12 months, or longer).
Trial Design and Setting DHANI (effect of n-3 fatty acid (DHA) supplementation during pregnancy on newborn birth weight and gestational age in India) was established as a randomized, double-blinded, placebo-controlled trial to assess the effect of 400 mg/day algal prenatal DHA consumption by healthy Indian women from ≤20 weeks of singleton gestation till delivery on their offspring's size (weight, length, and head circumference) at birth. The detailed trial protocol has been published elsewhere  [23]. DHANI is registered on the CTRI website as CTRI/2013/04/003540 and at clinical trials. gov as NCT01580345. Ethical clearance was obtained from institutional review boards (IRBs) of all participating institutions: Center for Chronic Disease Control (CCDC-IEC_04_2015), Public Health Foundation of India (PHFI) (TRC-IEC-261/15), and Jawaharlal Nehru Medical College (MDC/IECHSR/2016-17/A-85).
Information on sociodemographic characteristics, obstetric and medical history, dietary intake (with a pre-piloted semi-quantitative food frequency questionnaire focusing on n-3 LC-PUFArich Indian foods), anthropometric measurements, a non-fasting blood draw, and vital signs were obtained at enrollment. The women were then given the supplements in the form of coded bottles (each bottle had a 2 week supply) matching the allotted code for the participant. Further supplements were either collected by the women from the study site or were delivered to the women's homes every fortnight by fieldworkers. Research staff maintained contact with all women, especially during the last trimester, and visited the woman in the delivery ward within 24 h of delivery to collect data on gestational age at delivery, type of delivery, complications (if any), pregnancy outcome, APGAR (Appearance, Pulse, Grimace, Activity, Respiration) score, newborn anthropometry (weight, length, and head circumference), and maternal and cord blood samples.
Randomization, Masking, and Intervention The randomization list for 1200 women was generated using a permuted block design (randomly allocating 600 women to DHA or placebo). The assignment code list was placed in a sealed envelope at the beginning of the study and in a secure location at PHFI by a staff member not involved in the trial. Study participants and research staff (including those at the study site) remained blinded to the treatment allocation throughout the duration of fieldwork. After obtaining due approval from the Data Safety Monitoring Board (DSMB) of the study, full analyses were carried out. Unblinding of the treatment group was done only after the generation of the primary tables. The details of the intervention have been published already  [23] , but briefly, the intervention was comprised of 635 mg soft gel capsules having either 200 mg/day algal DHA or a placebo (soy/corn oil in a 50:50 ratio), identical in taste and appearance.
Outcomes The primary outcome for the DHANI trial was newborn anthropometry (birth weight, birth length, head circumference). Secondary outcomes included gestational age, APGAR scores at 1 and 5 min, still births, LBW, and preterm. All research staff at the study site were apprised of the data collection methods before the start of the trial and were provided regular refresher training every 6 months. Abstracted data included gestational age, pregnancy outcome (live birth, sex of baby, type of delivery), and APGAR score at 1 min and 5 min. Gestational age at delivery was calculated in weeks by noting the number of days from the last menstrual period (LMP) until delivery. Preterm delivery was defined as delivery after 20 weeks and before 37 completed weeks. Anthropometric data were collected by a trained research assistant within 24 h of delivery.
Acknowledgments: The  Department of Obstetrics and Gynecology at KAHER's JN Medical College (JNMC) Belagavi  is deeply acknowledged. The  Unit Chiefs (M. B. Bellad ,  Anita Dalal ,  Yeshita Pujar , and  M. C. Metgud ) deserve a special mention in providing valuable inputs and support during each phase of this study. We are indebted to the  JNMC's Blood Bank  in the charge of  Shrikant Viragi  and his whole team for facilitating all on site biochemical work in the study. We are truly grateful to the resource and support teams at the  Centre for Chronic Disease Control (CCDC)  and  Public Health Foundation of India (PHFI) ,  Delhi. This trial is funded by  Wellcome Trust-DBT India Alliance  (December 2015-December 2020). The  Young Scientist Award  by  DST SERB India  ( 2013-16 ) helped us establish the DHANI trial.
SARS-CoV-2 appears to also favour endocytosis through reduced cleavage efficiency of spike impairing TMPRSS2 mediated entry. Indeed, the accumulated mutations in omicron include multiple additional basic amino acids leading to an increase in the overall charge of the S protein. This change may make S more sensitive to low-pH induced conformational changes, and be an adaptation that facilitates use of the low-pH endosomal entry route, and/or to entry in the lower pH environment in the upper airway. Analysis of scRNA-seq datasets and qPCR measurements on our own human respiratory tissue samples suggest that lung cells have higher TMPRSS2 mRNA as compared to cells found in the upper airway. Recent findings from Hong Kong suggest lower replication in ex vivo lung tissue as compared to upper airway tissue for Omicron, but not for Delta (HKU website).
Sequencing Spike genomes for the original Wuhan strain, and Omicron VOC were obtained from GISAID EpiCoV database accessed on 30 th November 2021. A consensus Spike genome was created from all complete and high coverage genomes, excluding all sequences with >5% Ns using Geneious Prime v2022. The consensus genome was translated to poly-proteins and the Spike gene was aligned to the original Wuhan strain using mafft v7. 490  38  with the -globalpair --maxiterate 1000 flags.
Data availability: The above structural models used in this study for Delta and Omicron variants are available at https://github. com/CSB-Thukral-Lab/Spike_structural_models_Delta_and_Omicron 3D structural models of the spike homotrimer protein complex were alternatively also generated using Alphafold v2. 1. 1  39. In its validation at the 14th edition of the Critical Assessment of protein Structure Prediction (CASP14) the predictions generated were demonstrated to be comparative to experimental structures. When a close homolog structure is available to Alphafold the predictions it generates for those positions are within typical experimental error. Required databases were downloaded on 02/12/2021. The program was run with the parameters --max_template_date=2021-12-01 --model_preset=monomer --db_preset=full_dbs --is_prokaryote_list=false.
Protein structures were visualised in ChimeraX v1. 3 40. As predicted structures for the whole spike protein include poorly resolved chains at the terminal ends, these residues were identified by overlaying structures on PDB entry 6ZP2, then selected and removed from PDB files using the delete atoms/bonds action. Two further monomers were overlayed on 6zp2 to generate a homotrimer structure. Mutated residues were then coloured in red and labelled manually with respect to the Wuhan strain. To model interactions between the omicron spike RBD and REGN 10933 and 10987, 6XDG was downloaded from PDB and aligned to the alphafolded omicron spike using the matchermaker function in ChimeraX v1. 3. Predicted hydrogen bonds were plot within ChimeraX using a relaxed distance of 0. 400Å and are shown as dashed green and blue lines.
Alternatively, we also performed the capturehybridization method. The RNA isolated from saliva was treated with DNase I (Takara, Cat# EN0521) and the sequencing library was prepared using Twist library preparation kit (Twist Bioscience, Cat# 101058). The capture-hybridization was conducted using xGen COVID-19 capture panel and xGen hybridization and wash kit (Integrated DNA Technologies, Cat# 1080578) according to the manufacturer's instruction. Illumina sequencing was performed using MiSeq reagent kit v2 (300 cycles) and a MiSeq sequencer (Illumina). For the data analysis, trimmomatic-0. 39 (reference  42  ) was used to remove the adaptors and low-quality reads from the raw sequence data. The trimmed paired-end reads were aligned to the human genome hg38 using bowtie2 v2. 3. 4. 3 (reference  43  ) and unmapped reads were mapped to the original SARS-CoV-2 genome (strain Wuhan-Hu-1, GenBank accession no.
Analysis of single-nuclei and single-cell RNA sequencing datasets. Normalised and log-transformed expression values per cell were obtained from human lung single-nuclei and epithelial non-small cell lung carcinoma cell lines. scanpy 1. 7. 1 was used to process the data. For the tissue data  24  , only single-nuclei RNA-seq were selected. From the cancer cell lines study, only mock samples were selected. ACE2 and TMPRSS2 expression was plotted with violin plot function in scanpy. Plasmids for split GFP system to measure cell-cell fusion pQCXIP BSR GFP11 and pQCXIP GFP1 10 were from Yutaka Hata 49 Addgene plasmid #68716; http://n2t. net/addgene:68716; RRID:Addgene_68716 and Addgene plasmid #68715; http://n2t. net/addgene:68715; RRID:Addgene_68715).
Cell-cell fusion assay Cell-cell fusion assays were carried out as previously described  13, 50, 51. Briefly, 293T GFP1-10 and Vero-GFP11 cells were seeded at 80% confluence in a 1:1 ration in 48 multiwell plate the day before. Cells. were co-transfected with 0. 5 µg of spike expression plasmids in pCDNA3 using Fugene 6 and following the manufacturer's instructions (Promega). Cell-cell fusion was measured using an Incucyte and determined as the proportion of green area to total phase area. Data were then analysed using Incucyte software analysis. Graphs were generated using Prism 8 software. To measure cell surface spike expression HEK293 cells were transfected with S expression plasmids and stained with rabbit anti-SARS-CoV-2 S S1/S2 polyclonal antibody (Thermo Fisher Scientific, Cat# PA5-112048, 1:100).
Normal rabbit IgG (SouthernBiotech, Cat# 0111-01, 1:100) was used as a negative control, and APCconjugated goat anti-rabbit IgG polyclonal antibody (Jackson ImmunoResearch, Cat# 111-136-144, 1:50) was used as a secondary antibody. Surface expression level of S proteins was analysed using FACS Canto II (BD Biosciences) and FlowJo software v10. 7. 1 (BD Biosciences). Gating strategy for flow cytometry is shown in Supplementary Figure  8.
SARS-CoV-2 live virus isolation, preparation and titration for hNEC experiments To isolate an Omicron variant (BA. 1 lineage, strain TY38-873; GISAID ID: EPI_ISL_7418017), saliva was collected from a traveller arrived at Japan, and quantitative RT-PCR testing for SARS-CoV-2 was performed in an airport quarantine station, Japan. The sample was subjected to whole genome sequencing based on a modified ARTIC Network protocol  41  , and the near full-length SARS-CoV-2 genome sequence (GISAID ID: EPI_ISL_6913953) was deposited in GISAID. Virus isolation was performed as previously described  52. In brief, the saliva was inoculated into VeroE6/TMPRSS2 cells and cytopathic effect (CPE) was observed 4 days after inoculation. The supernatant was then harvested and stored at -80°C as an original virus (GISAID ID: EPI_ISL_7418017).
After one more passage in VeroE6/TMPRSS2 cells, the virus was obtained from National Institute of Infectious Diseases, Japan. A D614G-bearing early pandemic isolate (B. 1. 1lineage, strain TKYE610670; GISAID ID: EPI_ISL_479681) and a Delta isolate (B. 1. 617. 2 lineage, strain TKYTK1734; GISAID ID: EPI_ISL_2378732) were used in the previous study  3. Virus preparation and titration was performed as previously described  3, 53. To prepare the working virus stock, 100 μl of the seed virus was inoculated into VeroE6/TMPRSS2 cells (5 × 10 6 cells in a T-75 flask). One hour after infection, the culture medium was replaced with Dulbecco's modified Eagle's medium (low glucose) (Wako, Cat# 041-29775) containing 2% FBS and 1% PS. At 3 days postinfection, the culture medium was harvested and centrifuged, and the supernatants were collected as the working virus stock.
Antiviral drug assay with live virus One day prior to infection, HOS-ACE2-TMPRSS2 cells (10,000 cells) were seeded into a 96well plate. The cells were infected with SARS-CoV-2 (100 TCID 50 ) at 37°C for 1 h. Then, the cells were washed with DMEM and cultured in DMEM supplemented with 10% FCS and 1% PS and the serially diluted Remdesivir (Selleck, Cat# S8932) or beta-d-N4hydroxycytidine (a derivative of Molnupiravir; Cell Signaling Technology, Cat# 81178S). At 24 h postinfection, the culture supernatants were harvested and viral RNA was quantified by real-time RT-PCR (see above). The assay of each compound was performed in quadruplicate, and the 50% neutralization titre was calculated using Prism 9 (GraphPad Software).
Entry Inhibitors in A549-ACE2-TMPRSS2-based luminescent reporter cells using live virus Quantification of viral replication in A549-ACE2-TMPRSS2-based luminescent reporter cells was performed as previously described  55  and Gerber et al. , manuscript in preparation). In according to the manufacturer's instructions. % inhibition was calculated relative to the maximum luminescent signal for each condition, then analysed using the Sigmoidal, 4PL, X is log(concentration) function in GraphPad Prism.
To construct the plasmids expressing anti-SARS-CoV-2 monoclonal antibodies (Casirivimab and Imdevimab), the sequences of the variable regions of Casirivimab and Imdevimab were obtained from KEGG Drug Database (https://www. genome. jp/kegg/drug/) and were artificially synthesized (Fasmac). The obtained coding sequences of the variable regions of the heavy and light chains were cloned into the pCAGGS vector containing the sequences of the human immunoglobulin 1 and kappa constant region [kindly provided by Dr. Hisashi Arase (Osaka University, Japan)].
flask was then filled with 20 mL of complete growth medium and incubated for 4 days. The viral supernatant (passage 2 (P2) stock) was used for experiments. ,M:D3G,M:Q19E,M:A63T,N:P13L,N:R203K,N:G204R,ORF1a:K856R,ORF1a:L2084I ,ORF1a:A2710T,ORF1a:T3255I,ORF1a:P3395H,ORF1a:I3758V,ORF1b:P314L,ORF1b:I15 66V,ORF9b:P10S,S:A67V,S:T95I,S:Y145D,S:L212I,S:G339D,S:S371L,S:S373P,S:S375F,S :K417N,S:N440K,S:G446S,S:S477N,S:T478K,S:E484A,S:Q493R,S:G496S,S:Q498R,S:N50 1Y,S:Y505H,S:T547K,S:D614G,S:H655Y,S:N679K,S:P681H,S:N764K,S:D796Y,S:N856K, S:Q954H,S:N969K,S:L981F. Sequence was deposited in GISAID, accession: EPI_ISL_7886688.