dataesr/scientific-paragraphs-categorization huggingface dataset:
Docking of 3'-sialyllactose to SARS-CoV-2 NTD We docked 3'-sialyllactose to NTD with version 2. 4 of the HADDOCK webserver. (39, 40)  The binding site on NTD was defined by comparison with PDB entry 6q06 (5), a complex of MERS-CoV spike protein and 2,3-sialyl-N-acetyl-lactosamine. The binding site could not directly be mapped because of conformational differences between the NTDs of MERS-CoV and SARS-CoV-2, but by inspection a region with similar properties (aromatics, methyl groups and positively charged residues) could be identified. We defined in HADDOCK the sialic acid as 'active' and residues  18, 19, 20, 21, 22, 68, 76, 77, 78, 79, 244, 254, 255, 256, 258  and 259 of NTD as 'passive', meaning the sialic acid needs to make contact with at least one of the NTD residues but there is no penalty if it doesn't contact all of them, thus allowing the compound to freely explore the binding pocket.
Cryo-EM analysis. SARS-CoV-2 spike protein, purified as previously described  (44) , in 1. 1 mg /ml was incubated with 10mM ethylbenzamide-tri-iodo Siallyllactose (please check) over night at 4 ˚C 3. 5 µl sample was applied to glow-discharged Quantifoil gold R1. 2/1. 3 300-mesh grids and blotted for ~ 3 s at 100% humidity and 6 ˚C before vitrification in liquid ethane using Vitrobot (FEI). Two datasets were collected on Titan Krios equipped with K2 direct electron detector at cryo-EM facility (OPIC) in the Division of Structural Biology, University of Oxford. Both datasets were collected by SerialEM, at a magnification of × 165,000 with the physical pixel size 0. 82 Å/pixel. Defocus range was -0. 8 µm to -2. 4 µm. Total dose for two datasets were 60 e/Å 2 (5492 movies) and 61 e/Å 2 (8284 movies) respectively.
The k-fold cross-validation provided the partition of the dataset into k batches, then exploited k -1 batches for the training and the remaining test batch as a test, by repeating this procedure k times. In the grid search method, a cross validation procedure was carried out for each value of the regularization hyperparameter in the range [10 -4 ,. , 10 6 ]. Specifically, the optimal regularization parameter is chosen by selecting the most parsimonious parameter whose cross-validation average accuracy falls in the range of the best one along with its standard deviation. During the fitting procedure, the class unbalancing was tackled by penalizing the mis-classification of minority class with a multiplicative factor inversely proportional to the class frequencies. For the RFE, the number of excluded at each steps of the algorithm well as the final number of features was fixed at 100.
Acknowledgments Upgrades of the 600 MHz and 950 MHz spectrometers were funded by the  Wellcome Trust  (Grant Ref:  095872/Z/10/Z ) and the  Engineering and Physical Sciences Research Council  (Grant Ref:  EP/R029849/1 ), respectively, and by the  University of Oxford Institutional Strategic Support Fund , the  John Fell Fund , and the  Edward Penley Abraham Cephalosporin Fund. We thank the  Wellcome Trust  for support ( 20289/Z/16/Z  and  100209/Z/12/Z ). IB is an Investigator of the  Wellcome Trust  ( 106115/Z/14/Z ). EM time was funded by a philanthropic gift to support COVID-19 research at the  University of Oxford. The  Rosalind Franklin Institute  is supported by the  EPSRC. AMJJB and PIK acknowledge financial support from the  European Union Horizon 2020 projects BioExcel  ( 823830 ) and  EOSC-Hub  ( 777536 ) and the  IMI-CARE  project ( 101005077 ) We would like to thank  Professor Xi Chen  at the  University of California at Davis  for providing the plasmid encoding Pd2, 6ST ;  Professor John Mascola  at the  NIH  for the plasmids encoding influenza A virus (IAV)  NC99  ( H1N1 ) haemagglutinin (HA) variants;  Mikhail Kutuzov  and  Omer Dushek  for useful discussions and assistance with SPR experiments;  Dr Andrew Quigley  and  Nadisha Gamage  ( Diamond Light Source ) for help with thermal stability assays;  Professor Christina Redfield  for assistance with high field Bruker instrumentation;  Dr Lindsay Baker  for insights into the structural models.
Data Availability Statement Raw spectral data for Figures 1, 2, 3, and 4 , the data used to plot Figures  4A, B , C and relevant uSTA code have been deposited on the University of Oxford ORAdata server at https://ora. ox. ac. uk/objects/uuid:121699de-68d5-4b6f-b77e-cee85895da6c All associated spectral data is also shown in Supplementary Table  S7. HADDOCK datasets and results for this work can be found at https://github. com/haddocking/SARS-COV2-NTD-SIAmodelling and https://doi. org/10. 5281/zenodo. 4271288. All associated clinical data have been supplied in Supplementary Tables S1-S6, conducted under trial (NCT04549831, www. clinicaltrial. org). The uSTA software is free for academic use.
Based on a full model (all simple terms +the interactions between site identity and kDNA concentration and between renal lesions and kDNA concentration), we used an information-theoretic approach (based on the small-sample size corrected Akaike Information Criterion, AICc) to identify the most likely model(s)  (Burnham & Anderson, 2002)  using the MuMIn package  (Barton, 2019).
ACK N OWLED G M ENTS We warmly thank the employees and volunteers from the Fédération Départementale de pêche de l'Ariège for the sampling, Frédéric Martins and Emeline Lhuillier from the Genotoul laboratory for their help with ddPCR at the Genotoul laboratory. We thank Hanna Hartikainen and an anonymous reviewer for their very relevant and detailed comments on the first version of this manuscript. This work was funded by the French Office for Biodiversity (OFB) and the French Water Agency (Agence de l'Eau Adour-Garonne AEAG). This work was carried out within the framework of the "Laboratoire d'Excellence" (LABEX) TULIP (ANR-10-LABX-41).
Histology Testes and ovaries were fixed overnight in Bouin's fixative at 4 °C, washed in PBS, dehydrated in ethanol series, and stored in 70% ethanol at 4 °C. The fixed organs were embedded in paraffin, sectioned (5 μm), and mounted on glass slides. Sections were then deparaffinized using xylene and rehydrated with ethanol series. For PAS-H staining, sections were incubated with 0. 5% periodic acid (Sigma) for 10 min, washed in tap water for 3 min, and stained with Schiff's reagent (Sigma) for 20 min. Sections were counterstained with Harris hematoxylin (Sigma) for 15 s, washed in tap water for 10 min, and dehydrated with ethanol series and xylene. Whole slides were scanned and digitized with the Zeiss Axioscan. Z1 Slide Scanner with a 20× 0. 8 NA objective (Carl Zeiss). The open-source software QuPath  [71]  was used for analyzing digital histology images of testes sections manually.
For immunofluorescent labeling of acrosome and nucleus after TUNEL detection, slides were treated with Peanut Lectin from Arachis hypogaea (peanut) conjugated with Alexa Fluor 568 (PNA; Invitrogen) and Hoechst 33342 (Sigma) as described  [63]. TUNEL-PNA-Hoechst slides were scanned with the Zeiss Axioscan. Z1 Slide Scanner with a 20× 0. 8 NA objective (Carl Zeiss) and analyzed using QuPath software  [71]. Single-strand DNA sequencing (SSDS) DMC1 ChIP-SSDS to assess genome-wide DSB distribution using snap-frozen adult testes and its analyses were done as described previously  [72, 73]. Sequencing reads were aligned to the rat rn5 genome using a modified version of bwa (0. 7. 12) and ssDNA-derived fragments were identified using a bespoke ssDNA identification pipeline. DSB hotspots were called using a default hotspot calling pipeline and using only uniquely mapping ssDNA type 1 fragments with an alignment Q-score for both paired-end reads with values over 30.
Rat-mouse hotspot conservation and annotation Coordinates of B6 and B6-Prdm9 KO/KO hotspots (HSs) were obtained from published SSDS ChIP-seq data (GEO acc. nos. GSM1954835 and GSM1954864,  [39] ). For detection of HSs conserved between B6-Prdm9 KO/KO and SHR-Prdm9 KO/KO , we applied previously described criteria  [15] , considering two HSs as taking place at the same location only when overlapping within ± 200 bp distance from the HS centers. For comparative analysis of Prdm9-independent rat versus mouse HS, coordinates of the ± 200 bp central HS regions were converted (remapped) from rn5 to mm10 genome assembly using UCSC LiftOver binary tool  [74]  with default parameters, -minMatch = 0. 1, and the chain rn5ToMm10. over. chain. gz. Totally, 94% of SHR-Prdm9 KO/KO (34,313 of 36, 687) and 87% of SHR-Prdm9 wt/wt (18,678 of 21,589) central 400 bp HS regions were remapped.
HS containing extremely long gaps after conversion were excluded from the analysis (specifically, 717 SHR Prdm9 wt/wt and 791 SHR-Prdm9 KO/KO HS with central region above 800 bp after coordinate conversion). Overlapping rat/mouse HS (central 400 nt) coordinates were merged and considered as one conserved region. HSs revealing no overlaps within central 400 nt regions were considered non-conserved, B6-Prdm9 KO/KO -or SHR-Prdm9 KO/KOspecific. Coordinates of rat and mouse promoters of coding genes, taken as 2000 bp upstream and 200 bp downstream from the transcription start site, were extracted from the Ensembl Genes via biomaRt R package  [75]. Coordinates of rat promoters were converted from rn6 to mm10 with a chain rn6ToMm10. over. chain. gz. The overlapping rat/mouse promoter ranges were merged and considered as one conserved promoter.
Acknowledgements thank  A. Musilová ,  E. Linhartová ,  L. Šebestová ,  M. Fickerová , and  K. Křivánková  for technical assistance,  Drs. O. Šimoník  and  K. Komrsková  for PNA, as well as  Drs. J. Forejt ,  B. de Massy ,  K. Paigen ,  M. Jasin ,  S. Keeney ,  J. C. Schimenti ,  P. Svoboda , and anonymous reviewers for comments. Some data were produced at the  Microscopy Centre of the Institute of Molecular Genetics in Prague.
Materials and Methods We performed a national retrospective study of all adult patients who received at least one dose of cefiderocol from 2 November 2018 to 5 November 2019. Standardized questionnaires were sent to the prescribers to collect patients' baseline characteristics, infections type and management, microbiological data, reasons for cefiderocol use, doses and duration of cefiderocol treatment, concomitant antibiotic treatments, adverse events, and outcome. The research was conducted in accordance with the Declaration of Helsinki, and national and institutional standards. Patients were informed that cefiderocol was provided within a compassionate use program, and that their clinical data could be used, after anonymization, for research purposes. Immunosuppression was defined as asplenia, neutropenia, agammaglobulinemia, organ transplant, hematologic malignancies, HIV infection with CD4 cells count <400/mm 3 , or end-stage liver disease.
Cefiderocol MICs were also determined by BMD using iron-depleted and cation-adjusted Mueller-Hinton broth (Ther-moFisher, Waltham, MA, USA) as recommended by CLSI guidelines  [3]. The breakpoints used were those defined by the CLSI, 2019 update. All bacterial isolates were sequenced using Illumina technology as previously described  [4]. Resfinder server v3. 2 (https://cge. cbs. dtu. dk/services/ResFinder/) and CARD database (https://card. mcmaster. ca) were used to identify the antimicrobial resistance genes. The MLST (MultiLocus Sequence Typing) was performed using the MLST 2. 0 server (http://www. genomicepidemiology. org/). Quantitative variables are presented as mean ± standard deviation (SD), or median and interquartile range (IQR). Qualitative variables are presented as number of occurrences and relative frequencies.
Acknowledgments: The authors acknowledge as co-authors all of the following Cefiderocol French study group members:  Philippe Ichai  ( Intensive care unit, Paul Brousse Hospital, Paris-Saclay University, Villejuif, France );  Jérôme Robert  ( Microbiology laboratory, Pitié-Salpétrière University Hospital, Paris, France );  Laurène Deconinck  ( Infectious disease department, Bichat University Hospital, Paris, France );  Raphaël Lepeule  ( Infectious disease unit ),  Paul-Louis Woerther  ( Microbiology laboratory ),  Clement Ourghanlian (Pharmacy department)  ( Mondor University Hospital, Créteil, France );  Soline Siméon  ( Infectious disease unit ),  Latifa Noussair  ( Microbiology laboratory ),  Frédérique Bouchand  ( Pharmacy department ), and  Jean-Louis Gaillard  ( Microbiology laboratory) (Raymond-Poincaré University Hospital, Paris-Saclay University, Garches, France ).
Exploratory end points in both DLL3-high and randomized patients included PFS by investigator, ORR and clinical benefit rate (CBR) per CRAC and investigator (on the basis of RECIST v. 1. 1), and duration of response (DOR) per CRAC and investigator. The study was approved by local institutional review boards of all participating centers, and all patients provided written informed consent. The study was designed according to Good Clinical Practice Guidelines and the Declaration of Helsinki. The trial is registered at www. clinicaltrials. gov (NCT03033511).
1. 1. CBR was defined as the proportion of patients with a BOR of CR or PR or stable disease by investigator assessment according to RECIST v. 1. 1. DOR was defined from the day the patient met the criteria for confirmed CR or PR per investigator assessment (whichever is recorded first) to the date of progressive disease or death, whichever comes first. An unblinded interim analysis was conducted and reviewed by the Independent Data Monitoring Committee. A futility analysis was planned when approximately 160 deaths in patients with DLL3-high ES-SCLC (approximately 50% of the planned deaths) were observed. If the estimated Cox HR for OS analysis of Rova-T to placebo exceeded 0. 9, the trial would be stopped early. The safety of Rova-T was evaluated through study drug exposure and adverse events assessed by NCI CTCAE version 4.
Acknowledgments AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Rovalpituzumab tesirine has been developed by  AbbVie, Inc. Medical writing support was provided by  Swati Ghatpande, PhD , of  Bio Connections, LLC , funded by  AbbVie, Inc. The authors thank all the trial investigators and the patients who participated in this clinical trial. Validation (verification of the overall replication/reproducibility of results/experiments and other research outputs) was by  Drs. Komarnitsky  and  Sun. Formal  analysis (application of statistical, mathematical, computational, or other formal techniques to analyze or synthesize study data) was by  Drs.
We found that the level of fl-mAPP was significantly reduced after 4 hr of Wnt5a treatment, as shown by western blot (Figure  3F, G ), with no effect on mApp mRNA levels (Figure  3H ). The results of immunofluorescence (IF) and western blot (WB) suggest that the decrease of the mAPP upon Wnt5a treatment is caused by lysosomal degradation. To Source data 3. Western blots for mAPP and Actin after Wnt5a treatment on DIV7 primary cortical neurons. Source data 4. Western blots for mAPP and Actin after adding Bafilomycin followed by Wnt5a treatment on DIV7 primary cortical neurons. Figure supplement 1. Rapid turnover of fl-mAPP in culture mouse primary cortical neurons. Figure supplement 1-source data 1. Western blots for time course (0. 5 hr, 1 hr, 2 hr, 4 hr) of fl-mAPP expression after Cycloheximide (50 mg/ml) treatment on DIV7 primary cortical neurons.
(K and L) Quantification of the western blots results for figure I and J. (n=three biological independent repeat, t-test). (M) Western blots for mAPP expression 4 hr after Wnt3a and Wnt5a treatment at the same time on DIV7. PBS/BSA group acted as control group. (N) Quantification of the western blots results for figure M. (n=three biological independent repeat, t-test). (O) qPCR results for mApp mRNA expression in mApp knockout neurons (negative control), PBS/BSA treated control group neurons and Wnt3a+Wnt5a-treated group neurons. (n=three biological independent repeat, one-way ANOVA). Bars represent the mean ± S. E. M. Samples collected from at least two independent experiments. *p<0. 05, **p<0. 01. The online version of this article includes the following source data and figure supplement(s) for figure  4 : Source data 1.
In contrast, in neurons transduced with mAPPDCRD those effects were eliminated (Figure  5B, D ). Finally, we performed IF to trace mAPP and mAPPDCRD localization. Neurons transduced with wild type mAPP showed the same results as wild-type neurons with more mAPP in the TGN upon 4 hr of Wnt3a treatment and more mAPP in lysosomes upon 2 hr (Figure  3 -figure  supplement 2B, E, H ) and 4 hr of Wnt5a treatment (Figure  5 -figure supplement 2A-D). Similarly, there was no effect on Source data 1. Western blots for APP and Actin after lenti-virus transduction followed by Wnt3a or Wnt5a treatment on DIV7 primary cortical neurons. Source data 2. Western blots for APP-deltaCRD and Actin after lenti-virus transduction followed by Wnt3a or Wnt5a treatment on DIV7 primary cortical neurons. In summary, these data show that the CRD of mAPP is critical for Wnt3a/5a binding and mediates the effects of Wnts on mAPP trafficking and expression.
At this early stage, the ACI showed a tendency to increase in mAPP knockout neurons that was not significant (Figure  6 -figure supplement 2D), likely because both primary and secondary branches show a similar level of increase. Together these data suggest an overall increase in axonal growth. In contrast to axonal growth, we found no significant alterations in dendritic length or branching (Figure  6 -figure  supplement 2E-G ) consistent with the fact that the spur in dendritic outgrowth is largely initiated at DIV4  (Polleux and Snider, 2010; Barnes and Polleux, 2009). To further analyze neurite outgrowth, we examined axonal and dendritic growth at DIV7. By this stage, mAPP knockout neurons showed an increased ACI (Figure  7A, B ). In contrast, total axonal length, longest axon length, and the total number of branch tips was not significantly different (Figure  7C-E ).
(K and L) Quantification of the western blots result for figure I and J. (n=three biological independent repeat, t-test). Bars represent the mean ± S. E. M. Samples collected from at least two independent experiments. *p<0. 05, **p<0. 01. The online version of this article includes the following source data and figure supplement(s) for figure 3: Source data 1. Co-immunoprecipitation (co-IP) of Wnt5a-Myc with full-length proteins mAPP-flag or mAPP-delatCRD-flag. Source data 2. Western blots for mAPP and Actin after Wnt5a treatment on DIV7 primary cortical neurons. Figure 3 continued on next page.
(n=three biological independent repeat, t-test). (O) qPCR results for mApp mRNA expression in mApp knockout neurons (negative control), PBS/BSA treated control group neurons and Wnt3a+Wnt5a-treated group neurons. (n=three biological independent repeat, one-way ANOVA). Bars represent the mean ± S. E. M. Samples collected from at least two independent experiments. *p<0. 05, **p<0. 01. The online version of this article includes the following source data and figure supplement(s) for figure4:.
Acknowledgements We thank  Dr. Radoslaw Ejsmont  for writing the co-localization macro,  Natalia Danda  for the construction of the plasmids used in this work,  Drs. Ariane Ramaekers ,  Natalia Mora Garcia ,  Gerit Linneweber ,  Simon Weinberger  and  Guangda Liu  for helpful discussions. We thank  Drs. Zeynep Kalender Atak  and  Marina Naval Sanchez  for support on the statistical analysis of the data and  Dr. Jean-Maurice Dura  for fly lines. Mouse breeding work was conducted at the  PHENO-ICMice facility. The Core is supported by 2  Investissements d'Avenir grants  ( ANR-10-IAIHU-06  and  ANR-11-INBS-0011-Neu-rATRIS ) and the  'Fondation pour la Recherche Medicale'. Primary  neuron culture work was carried out at the CELIS core facility with support from  Program Investissements d'Avenir  ( ANR-10-IAIHU-06 ).
Light microscopy was carried out at the ICM. Quant facility. We thank all core technical staff involved. We thank  Philippe Ravassard  for providing the pSYN lentiviral vector backbone and  Blandine Bonnamy  and  Clementine Ripoll  from iVECTOR core facolity for technical assistance and production of the lentiviral vectors. This work was supported by  Fonds Wetenschappelijke Onderzoeks (FWO)  grants  G. 0543. 08, G. 0680. 10, G. 0681. 10  and  G. 0503. 12 ,  the program 'Investissements d'avenir'   ANR-10-IAIHU-06 , the  Einstein-BIH program , the  Neuro-Glia Foundation , a  Sorbonne Universite Émergence grant , an  Allen Distinguished Investigator Award  and the  Roger De Spoelberch Foundation Prize  (to  BAH ),  ANR-12-MALZ-0004  grant (to MCP), the  Vlaams Instituut voor Biotechnologie  and the Methusalem grants from  KU Leuven  (to BDS and BAH), the  Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO; ZonMw TOP  grant  40-00812-98-10058 ) and the  Hersenstichting Nederland  [ HS 2011(1)À46 ] (to LGF), a  doctoral fellowship  from the  Centre National de Recherche Scientifique Libanais  (to MN) and  Chinese Scholarship Council fellowships  (to TZ and TL).
| Genomic characterisation of populations (Illumina 60K SNP) DNA isolation from tissues was performed using the Qiagen DNeasy 96 Blood & Tissue Kit (QIAGEN GmbH Valencia, CA, USA) following manufacturer's instructions. To discriminate hybrids from Southern Italy we applied three approaches: coat colour observation, MC1R sequence (useful to discriminate F1 hybrids), and single nucleotide polymorphisms (SNPs) analysis (using the Illumina 60 K SNP). The latter was used both to discriminate hybrid individuals with greater accuracy compared with the other methods and to analyse the genomic relationships between the studied forms. We genotyped 96 pig samples (Table  1 ) using the Illumina 60 K SNP  (Ramos et al. , 2009) , and pooled them to 97 external samples (Table  2 ;  Yang et al. , 2017). The quality of raw data was assessed using PLINK  (Purcell et al.
, 2007). We removed genotypes with a minor allele frequency (MAF) lower than 0. 05, resulting in a final data set of 39,605 SNP). These were used to construct neighbour joining (NJ) trees, obtained using the R package ape  (Paradis et al. , 2004)  and visualised in figtree v1. 4. To compute support for each node we bootstrapped our ped file 100 times and recomputed a NJ tree each time. Furthermore, SNPs were useful for identifying signatures of selection (SOS) on genomes and for the assessment of runs of homozygosity (ROHs). Long ROHs usually indicate intense selection pressures  (Metzger et al. , 2015)  and/or recent inbreeding  (Al-Mamun et al. , 2015) , whereas short ROHs are often caused by more ancient bottleneck effects  (Al-Mamun et al. , 2015)  and/or inbreeding events  (Howrigan et al.
, 2011). We then removed data in high linkage disequilibrium (r 2 > 0. 2) resulting in 15,531 SNPs for principal component (PCA) and admixture analyses. PCA was carried out in PLINK and visualised by R programming language (R Core Team, 2013) using the ggplot2 package  (Wickham, 2016)  in order to position feral pigs within Suidae family. To detect SOS in the Sardinian system, we calculated the fixation index (F ST )  (Weir & Cockerham, 1984)  as measure of group differentiation per locus following the pipeline proposed by Porto-Neto et al. (  2013 ) and comparing the value for each population with that of the meta-population. We divided SNP data into genic (cisregulatory 5' and 3' UTR regions, nonsynonymous SNPs that would experience increased selective pressure) and nongenic  (Barreiro et al.