dataesr/scientific-paragraphs-categorization huggingface dataset:
For wine separation, PCA was performed and followed by OSC-PLS-DA to create a more reasonable regression model. Orthogonal signal correction is a PLS-based data filtering technique that removes the uncorrelated information, and consequently it is more exclusively focussed on the variables of interest  (Gavaghan, Wilson, & Nicholson, 2002). In addition, the model predictivity was evaluated by internal leave one-out cross validation (LOOCV). In the LOOCV procedure, each training set is created by randomly taking all the samples except one and the test set is the sample left out. Thus, for N samples, N different training sets and N different test sets are created. Each sample is predicted once, which provides a conservative estimate of the prediction ability of the PCA model  (Forina, Lanteri, Casolino, & Oliveri, 2004).
Wine aging and vintages To observe the effects of vintage and wine evolution during bottle aging, the NMR-data of the Bordeaux red wines (n=127) obtained from thirteen different vintages (2004 to 2016) were analysed. First, to observe the influence of wine aging independently of vintage, the youngest wines (n=28, vintages 2013 to 2016) were compared to the oldest wines (n=37, vintages 2004 to 2007) by OSC-PLS-DA (Figure  4 ). The analysis revealed a clear separation among the two groups with R 2 Y and Q 2 values of 0. 75 and 0. 78, respectively. The main compounds responsible for these differences are xylose, epicatechin, catechin, tyrosine and citric acid which are more present in young wines, and ethyl acetate, ethyl lactate, fructose, caffeic acid, syringic acid, succinic acid and shikimic acid which are more present in older wines (Figure  4C ).
Conclusion In this study, 224 commercial wines produced in the six major French wine regions were analysed using 1 H NMR experiments and multivariate analysis. Forty compounds were quantified by conventional targeted analysis. Advanced data analysis and chemometrics allowed the discrimination of wines on different levels. Bordeaux wines present a singular brand in comparison to the five other major French producing areas. Despite the differences within each geographical designation, NMR spectrometric analyses coupled to multivariate approaches allows the discrimination of a specific area. In addition, the analysis shows that it is possible to discriminate the two major Bordeaux sub-regions Libournais and Médoc. The grape variety composition alone does not explain all the differences observed.
Elodie Guittard and Caroline Baz are warmly thanked for their collaboration in the sample collection. This work was supported by the  Bordeaux Metabolome Facility and MetaboHUB  ( ANR-11-INBS-0010  project), the  Conseil Régional d'Aquitaine, Conseil Interprofessionnel du Vin de Bordeaux (CIVB) and FranceAgriMer program  (grant number  2014-0785 ).
Dengue virus type 2 is the most prevalent one of all serotypes in Malaysia. 9  our search for bioactive compounds from Endiandra species against dengue virus, we carried out a phytochemical study of the bark of E. kingiana. A new benzofuranone (1), along with 6 known compounds (-)-epicatechin (2),  10  (+)-catechin (3),  10  methyl orsellinate (4),  11  vanillic acid (5),  12  vanillin (6),  13  and cinnamtannin B1 (7),  14  was characterized by comparison of the spectroscopic data with that in the literature (Figure  1 ). These compounds were evaluated against dengue virus type 2 NS2B/NS3 serine protease. In addition, molecular docking simulations were implemented to probe the binding modes of the active ligands to the amino acids in the active site of serine protease. Herein, we report the isolation and structural elucidation of these compounds, their dengue inhibitions, and their molecular docking.
Molecular Docking A homology model of the DENV2 NS2B/NS3 protease was obtained from the Research Collaboratory for Structural Bioinformatics-Protein Data Bank (RCSB-PDB) database for structure-based design purposes. The selected 3D structure was downloaded in a PDB format file. The enzyme was then prepared under the protein preparation protocol implemented in Discovery Studio 2. 5 (Accelry Inc. , CA, United States) suite of program. After that, the geometry optimization and energy minimization of DENV2 NS2B/NS3 protease was conducted by removing the water molecules. Then, the protonation of the DENV2 NS2B/NS3 protease was done through "Protonate 3D" feature, followed by optimization of the partial charge and energy minimization. The optimized, minimized 3D structure of DENV2 NS2B/NS3 protease was saved in the.
pdbqt format. For the ligands, the two-dimensional structure of 1 to 3 was built using Hyperchem 8 and subjected to energy minimization with a convergence criterion of 0. 05 kcal/(mol A). Nonpolar hydrogens and lone pairs were then merged, and each atom was assigned with Gasteiger partial charges. A grid box was generated at the center of the active site gorge with 60 × 60×60 points along the x, y, and z axes. The remaining parameters were at default setting. The molecular docking simulation of DENV2 NS2B/NS3 protease and the ligands used Autodock 3. 0. 5 software. The docking simulation process began by selecting "Dock" feature from "Compute" panel. The remaining parameters were at default setting. After the docking control, parameters and models to display were set to the receptor and ligand molecule.
Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was financial supported by University of Malaya research grant, PPP PG137-2013A, High Impact Research -Ministry of Education (HIR-MOE), UM. C/625/1/HIR/MOE/SC/37 and International Funding, the French Embassy in Malaysia on Collaborative Projects On Phytochemical Analysis On Malayan Flora, project number 57-02-03-1007.
k cat in s -1 and K m in g/L. The K m and V max values were obtained by Lineweaver-Burk plots and the k cat calculated from the V max values. The program OriginPro was also used to fit the Michaelis-Menten representation. The acetyl-xylan esterase activity was measured using washed WAXY-I at the concentration of 17. 5 g/L. GH62-CE6-1240 at the final concentration of 1 µM was incubated with 4 mL of substrate, at 37 °C under mild shaking (70 rpm). At specific intervals, aliquots of 500 µL were cooled on ice and centrifuged at 4 °C for 5 min at 15,000g. 0. 2 mL of soluble products released were mixed with 50 μL of 25 mM H 2 SO 4 and analyzed using an IOTA 2 Differential Refractometer and an HPX-87H HPLC column (Bio-Rad) preceded by the corresponding guard column (Micro-Guard HPLC column protection system).
Three-dimensional structure modeling We used various servers for the construction of 3D models. Each α-l-ABF characterized was modeled using each program (SWISS-MODEL, Phyre2, and RaptorX). The identification of structural template(s) comes from the initial protein primary structures from the KEGG SSDB Database [cce:Ccel_1229, cce:Ccel_1233, cce:Ccel_1234, and cce:Ccel_1240]. The SWISS-MODEL server was used to build protein models, using a template structure and target-template sequences alignments. For each selected template, a 3D protein model was automatically generated and the assessment of the model's quality: the GMQE score and QMEAN score were calculated. GMQE (Global Model Quality Estimation) score and QMEAN score provided a quality estimation of the structural features observed for the model.
GMQE score is expressed as a number between 0 and 1. QMEAN scores around zero indicate good agreement between the model structure and experimental structures. The Phyre2 (Protein Homology/AnalogY Recognition Engine) server was also used to generate 3D models after searching for homologous sequences in the HHblits database (HMM-HMM-based lightning-fast iterative sequence search). For each model constructed, the ProQ2 quality assessment was checked  [20, 21]. RaptorX was generally used to generate models for protein sequences without close homology (less than 30% sequence identity in PDB). It assigns confidence scores to evaluate the quality of the predicted 3D model: P value for the relative global quality (the smaller the P value, the higher quality the model), GDT (global distance test), and uGDT (un-normalized GDT) for the absolute global quality.
Modular organization and putative function of Xyl-Doc enzymes The 14 putative cellulosomal proteins (called Xyl-Doc enzymes) encoded by the xyl-doc gene cluster (Ccel_1229 to Ccel_1242) all display a modular organization (Table  1 ) and are predicted to be involved in hemicellulose degradation. The xyl-doc gene cluster was specifically expressed when arabinoxylan, arabinose, or xylose was used as substrates, and Xyl-Doc enzymes were consequently detected by proteomic analysis in the cellulosomes produced by R. cellulolyticum grown in these specific culture conditions  [18, 19]. Some of them, which have a catalytic module belonging to families GH43 and GH62, are annotated as α-l-arabinofuranosidases (Table  1 ). In the CAZy database, GH43 family contain β-xylosidases, α-l-arabinofuranosidases, arabinanases, xylanases, galactan 1,3-β-galactosidases, exo-α-1,5-larabinofuranosidases, exo-α-1,5-l-arabinanases, and β-1,3-xylosidases.
In the structural models generated with SWISS-MODEL, Phyre2, and RaptorX, these residues occupy the center of the cavity as expected. The additional X19 module of the protein GH43 10 -1233 (encompassing amino-acids 344 to 533) displays a canonical β-sandwich fold (Fig. 1 ). The structure of a GH43 β-xylosidase from Geobacillus stearothermophilus showed that the cleft of the active site.
WAXY-I insoluble wheat-flour arabinoxylan insoluble, OSX oat spelt xylan. ND means not determined due to insufficient activity or lack of detectable activity NA not active a Specific activities from Table  2  b Specific activity in IU/µmol. The data show the mean and standard deviation of 6 independent experiments Araf is α-1,3-linked, the decorated Xylp residue is noted A 3. If the xylodextrin contains a double decoration, the substituted xylose residue substituted is noted: A 2+3. GH43 16 -1229 is totally inactive on the tested AXOS (Table  4 ), despite the high enzyme concentration used (5 µM). The Araf decorations located on the non-reducing Xylp residue or penultimate Xylp residue from the non-reducing end in these AXOS, are not cleaved by GH43 16 -1229. We can hypothesize that this enzyme is an α-l-ABF specific of the decorations located at the reducing end of the main chain.
Three-dimensional structure modeling Computational methods for protein structure modeling (SWISS-MODEL, Phyre2 and RaptorX) were used to shed some light on our biochemical results. The 3D structure of the catalytic module of the protein GH43 16 -1229 (residues 33-314 based on KEGG SSDB Database, cce:Ccel_1229) was modeled to refine the understanding of its mode of action. Structural models were built using the 3D structure of Ct43Araf (PDB ID: 5a8d. 1. A) (subfamily 16) from Clostridium thermocellum, which shares 64% sequence identity.
According to the narrowness of the catalytic pocket, GH43 16 -1229 could be specific of Araf mono-substitutions. GH43 16 -1229 and Ct43Araf act only on arabinoxylans and are unable to cleave off arabinose decorations from arabinan. These biochemical results are consistent with the structure of Ct43Araf which reveals the presence of a substrate-binding cleft designed to interact with arabinoxylan but unable to accommodate the nonlinear backbone of arabinan  [33, 34]. A 3 X: α-l-Araf-(1 → 3)-β-d-Xylp-(1 → 4)-d-Xylp A 2 XX: α-l-Araf-(1 → 2)-β-d-Xylp-(1 → 4)-β-d-Xylp-(1 → 4)-d-Xylp XA 3 XX: β-d-Xylp-(1 → 4)-[α-l-Araf-(1 → 3)]-β-d-Xylp-(1 → 4)-β-d-Xylp-(1 → 4)-d-Xylp A 2+3 XX: [α-l-Araf-(1 → 2)][α-l-Araf-(1 → 3)]-β-d-Xylp-(1 → 4)-β-d-Xylp-(1 → 4)-d-Xylp XA 2+3 XX: β-d-Xylp-(1 → 4)-[α-l-Araf-(1 → 2)][α-l-Araf-(1 → 3)]-β-d-Xylp-(1 → 4)-β-d-Xylp-(1 → 4)-d- The N-terminal part of GH43 10 -1233, composed of two modules (GH43: residues 35 to 300 and X19: residues 344 to 533), was modeled using the 3D structure of HiAXHd3 (PDB ID: 3zxl.
A) (subfamily 36) from Humicola insolens which shares 37% identity with the GH43-X19 part of GH43 10 -1233 (Figs. 1  and 4b ). HiAXHd3 is, like GH43 10 -1233, highly specific for substrates containing double Araf substitutions  [27]. The structure of the catalytic cavity of GH43 10 -1233 shows a shallow but extended pocket able to accommodate two Araf residues. The three putative catalytic amino-acids (D46, D156, and E207) are localized, according to our model, around the groove inside which Araf decorations might interact (Fig. 4b ). Like other GH43 proteins carrying an additional X19 module, the 3D model shows structural connections between these two modules. The primary structures of the two GH62 catalytic modules from GH62-1234 (residues 35 to 295 based on KEGG SSDB Database, cce:Ccel_1234) and GH62-CE6-1240 (residues 35 to 294 based on KEGG SSDB Database, cce:Ccel_1240) are strictly identical except for one residue located at position 236.
For both GH62 catalytic modules, the template used was the GH62-α-l-ABFs from Coprinopsis cinerea (PDB ID: 5b6s. 1. A)  [35]. The three-dimensional modeling revealed, as expected  for an enzyme belonging to the clan F, a structure in five-bladed β-propeller with a narrow pocket, carrying the three putative catalytic amino-acids, identified by multiple alignment. GH62-α-l-ABFs from C. cinerea accommodates a single Araf residue  [35]. The narrowness of the catalytic cavities of both GH62-1234 and GH62-CE6-1240 also suggests an interaction with a single Araf substitution, in agreement with the enzymatic characteristics described above (Fig. 4c ). The serine-histidineglycine (SHG) motif conserved within the GH62 family  [8, 36, 37]  and in some GH43 members was also found in the four R. cellulolyticum α-l-ABFs described in this paper.
Presently, the CAZy database contains 16 CE families. The family CE6 is composed of only few characterized enzymes, all of them having an acetyl-xylan esterase activity. According to its mode of action, GH62-1234 was renamed RcAbf62A m2,3 and GH62-CE6-1240 was renamed RcAbf62B m2,3 Axe6. The recently characterized bifunctional enzyme from R. josui RjAbf62A-Axe6A harbors an acetyl-xylan esterase activity with a specific activity of 0. 0170 ± 0. 0002 IU/µmol on WAXY-I  [24]. Although the two enzymes show 91% of identity, this activity is relatively low compared to the acetylxylan esterase activity of the homologous R. cellulolyticum RcAbf62B m2,3 Axe6 determined to be 2. 83 ± 0. 21 IU/ µmol. Nevertheless, the GH62 module of RjAbf62A-Axe6A is around 50-fold more active on insoluble arabinoxylan and this enzyme is, in addition, polyspecific.
Acknowledgements The authors would like to thank  Goetz Parsiegla  from the  laboratoire Bioénergétique et Ingénierie des Protéines (BIP) Research group: Enzymology of Supramoleculaires Systems  ( Aix-Marseille Université ) for helpful discussions concerning the 3D modeling. The authors would also like to thank  Athel Cornish-Bowden  from the  laboratoire Bioénergétique et Ingénierie des Protéines (BIP ) a native English speaker for the correction of the manuscript.
Acknowledgements We thank  O. Cotto  and  V. Llaurens  for discussion and suggestions on the manuscript. T. G. A. was funded by a PhD scholarship from the  French Ministry of Higher Education and Research. This research was supported by grants from the  Doctoral School GAIA  (to T. G. A. ), the  French National Agency for Research  ( ANR-12-JSV7-0005-01-Hybevol  and  ANR-18-CE02-0019-01-Supergene ) (to M. J. ) and the  Swiss National Science Foundation  (to H. K. ).
Canada is one of the only countries to have developed a national method for estimating N 2 O emissions (IPCC Tier 2 method). The data used to develop this method were acquired on rotations dominated by wheat cultivation. The increase in rapeseed acreage in Canada justifies the question of the effect of the crop on emissions. Lemke et al. 1 studied the effect of the crop and of the preceding crop. Their conclusions agree with the results obtained in France: protein pea emissions are at the same level as those of wheat not receiving N fertilizer and lower than nitrogen-fertilized crops, with no difference between wheat and rapeseed receiving the same amount of N fertilizer, and higher emissions after the rapeseed crop without possibility to attribute this difference to the soil nitrate content or the amount of nitrogen in the residues or the amount of fertilizer added to the following crop.
Räbiger et al. 1 focused on indirect emissions of N 2 O in Germany (emissions caused by nitrogen enrichment of natural environment due to losses from cultivated plots). Their work is based on the use of models to estimate nitrate leaching and NH 3 volatilization. The calculated emissions are lower than those obtained with the IPCC Tier 1 method based on emission factors. More global assessments than the contribution to global warming were also presented. In France, a public database has been designed to allow life cycle analyzes (Dauguet et al. ) 1 , as part of the AgriBalyse project. The presentation focused on the data sources and on the use of the database to calculate 4 environmental indicators of French rapeseed production: GHG emissions, fossil energy consumption, eutrophication and acidification.
Growth assays-drug sensibility test Drug sensitivity was assessed by monitoring the inhibition of yeast cell proliferation. Yeast were grown in 5 mL culture medium YP10 or YPEth with increasing concentrations of drugs. Cultures were inoculated at an OD 600nm of 0. 2 and incubated at 28°C with (YPEth) or without (YP10) vigorous shaking for three days. OD 600 nm were then measured. Data are presented for each strain and culture condition as the percentage of growth relative to control, i. e. untreated by drugs. The experiments were repeated at least twice and the data averaged. The final OD 600nm of the untreated cultures of WT and mutant strains were similar. Measurement of the components of the respiratory chain in yeast mitochondria. Mitochondria were prepared as in  [15]. Protein concentration was determined by Bradford method.
This clearly indicates that PD growth inhibitory activity is highly exacerbated in cells with lower oxidative stress defence, and thus that PD could act, at least in part, via the generation of oxidative stress. This is coherent with previous data showing a more oxidizing glutathione-dependent redox potential in intact living parasites treated with PD  [5]. As a comparison, we observed that deletions of SOD1, SOD2 and CTT1 had no or minor effect on the sensitivity to ART in the same conditions (not shown). Second, we tested the effect of PD treatment on aconitase activity. This enzyme of the tricarboxylic acid (TCA) cycle is located in the mitochondrial matrix and contains a [4Fe-4S] (Fe-S) cluster that is exposed to solvent and easily damaged by oxidative stress. As a control, we monitored the activity of fumarase, a TCA enzyme that is not sensitive to oxidative damage.
The rate of NADH oxidation was measured at 340 nm. Mitochondria were added at 60 to 240 g protein per mL. The reaction was initiated by the addition of 100 M decylubiquinone. Experiments were repeated at least twice and data averaged. The error bars represent standard deviation. **, p < 0. 005; ***, p < 0. 001 according to two-tailed Student's t test. (D) Effect of the over-expression of flavoprotein encoding genes on PD sensitivity in a nde1 background. Deletion mutant nde1 and derived strains over-expressing NDE1 (pNDE1), NDE2 (pNDE2), GLR1 (pGLR1), LPD1 (pLPD1) or MCR1 (pMCR1) were grown in YPEth medium with increasing concentration of PD. OD 600nm were measured after three days. For each strain, the data are presented as percentage of the OD 600nm of the untreated culture. The experiments were repeated at least twice and the data averaged.
Strains were grown in YPEth medium with various concentrations of PD derivatives. OD 600nm were measured after three day culture. For each strain, the data are presented as percentage of the OD 600nm of the untreated culture. The experiments were repeated at least twice and the data averaged. The error bars represent standard deviation. Figure  7 : Effect of plasmodione and its putative metabolites PDO, PD-bzol and 7-OH-PD on purified aconitase activity. mitochondrial aconitase (33 ng. mL -1 ) was incubated for 20 min at room temperature with drugs at different concentrations. The reaction was started by addition of cis-aconitate and activity was monitored spectrophotometrically at 240 nm at 37°C. The activity is expressed as percentage of the activity obtained after incubation of the enzyme in the absence of drugs.
Acknowledgements The work was supported by the  French National Research Agency (ANR)  ( PlasmoPrim  project to B. M, E. D. -C. , M-P. G-C. and S. A. B. ), by the  Laboratoire d'Excellence (LabEx) ParaFrap  (grant  LabEx ParaFrap   ANR-11-LABX-0024  to E. D. -C. and S. A. B. ), by the  ERC Starting  Grant  Nº260918  to S. A. B. , and by funding from  CNRS (E. D. -C. and S. A. B) ,  Inserm (S. A. B) , and the  University of Strasbourg  (E. D. -C. and S. A. B). We are grateful to  N. Fisher  for his comments on the manuscript.
In 2011, we developed a tool for fast and accurate frequency estimation of reference TE insertions called T-lex  (Fiston-Lavier et al. , 2011). The first update of this software, T-lex2  (Fiston-Lavier et al. , 2015) , allowed the user to work with individual strain and pooled whole genome sequencing data. In addition, we added a TE-TSD detection module that allowed us to correct the genome annotations for 65 Drosophila melanogaster reference TE insertions. We also showed that T-lex2 provides accurate TE calls in D. melanogaster, with 99. 14% specificity and 89. 58% sensitivity, and in the human genome, with 97. 65% specificity and 93. 26% sensitivity. In this work, we implemented a new version of this broadly applicable and flexible tool, which can now be used with the latest short-read high-throughput sequencing technologies.
We have redesigned the T-lex algorithm to integrate the BWA-MEM short-read aligner: one of the most accurate short-read mappers available  (Li and Durbin, 2009). This aligner has no read length limitation, is currently being maintained by its developers, and it is easy to install as the package is available for most Linux distributions and OSX. In addition, we have added extra filtering steps and parameters, and fixed some bugs present in T-lex2. We demonstrate that T-lex3, now available at Github (https://github. com/GonzalezLab/T-lex3), can provide accurate TE genotyping and frequency estimation using D. melanogaster, human and Oryza sativa datasets.
Materials and methods T-lex3, as its previous version, is composed of five modules. Briefly, the TE-analysis module analyses whether the sequences flanking each reference TE insertion are part of a segmental duplication, or whether they contain repetitive regions, as both features are known to affect the accuracy of TE calls. The TE-presence detection module and the TE-absence detection module are two independent modules that detect both the presence and the absence of the reference TE based on the analysis of the junction sequences of the TE insertion. When the requirements to call a TE as present or absent are not met, these modules return a no data call. The TE-combine module combines the results of the two detection modules to determine whether the TE insertion is present, absent, polymorphic or no data.
Finally, the TE-TSD detection module analyzes the read alignments of the TEabsence detection module to identify the Target Site Duplication (TSD) of the TE insertion. In the new version of T-lex described here, T-lex3, we have updated and improved three of these modules (Fig. 1 ), and we have also implemented other more general changes as described below. All these changes have been summarized in Table  2.